Reproductive health research: the new directions: biennial report: 1996-1997
Publication date: 1998
I I the nel directio s " ~ t World Health Organization ~ Geneva 1998 UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP) Reproductive health research: the new directions Biennial Report 1996-1997 Edited by J. Khanna P.F.A. Van Look .~ ~." ~ ~ 'II§ -~ World Health Organization Geneva 1998 I In order to ensure prompt distribution, this Report is being issued without the usual detailed editorial revision by the WHO Office of Publications. WHO Library Cataloguing in Publication Data UNDP/UNFPNWHOlWorld Bank Special Programme of Research, Development and Research Training in Human Reproduction. Repro- ductive health research: the new directions biennial report 1996-1997/ edited by J. Khanna, P. F. A. Van Look. 1.Reproduction 2.Research-trends 3.Contraception 4.Fertility 5.Family planning 6. Reproductive health I.Khanna, J.II. Van Look, P.F.A. Ill. 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Contents Preface . 3 Part 1: The work of the Programme in 1996-1997 Understanding people's reproductive health needs and perspectives . 9 Developing new methods of fertility regulation . 22 Expanding family planning options . 41 Evaluating reproductive health care . 46 Assessing and improving reproductive health services . 58 Building national research capability in reproductive health research . 71 Part 2. Reproductive health research after Cairo and Beijing Rethinking sexual and reproductive health research: new priorities and approaches in the post-ICPD era (Cynthia Myntti, Francis Webb, Paul Van Look) . 97 Fertility regulation: still a core research issue (Steven w. Sinding) . 105 Current status of knowledge on maternal health-facts and gaps (Vivian Wong) . 111 Reducing the impact of reproductive tract and sexually transmitted infections (/sabelle de Zoysa) . 117 The role of men in improving reproductive health: the direction research should take (Axel Mundigo) . 124 Research needs in adolescent sexual and reproductive health (Pramilla Senanayake) . 132 Implications of domestic violence for women's reproductive health: what we know and what we need to know (Shireen Jejeebhoy) . 138 Annex 1. Funding during 1996-1997 . 150 Annex 2. Centres collaborating with the Programme duril1g 1996-1997 . 153 Annex 3. Staff of the Programme (December 1997) . 160 Preface The year 1997 marked the 25th anniversary of the Programme. It also marked a new turning point in the Programme's rich and distinguished history in several other ways. First, with the convening of a WHO Scientific Group Meeting on Cardiovascular Disease and Steroid Hormone Contraception in November 1997 the Programme concluded a series of landmark studies on the safety and efficacy of fertility regulating methods. Initiated in 1985 with the establishment of a dedicated task force of experts from developing and developed countries, this initiative has produced a wealth of scientific information that has already had a significant impact on family planning policies and practices. A poll among a panel of 20 international experts, due to be published soon in the Lancet, illustrates the impact that the Programme has had in this field. Out of the ten most important advances in knowledge about safety or efficacy of fertility regulating methods listed by the panel, seven are subjects in which the Programme's task force played a major role. They include: the benefits and risks of oral contraceptives in relation to cancer; oral contraceptives and cardiovascular disease; the relation between oral contraceptives and breast cancer and between depot- medroxyprogesterone acetate and breast cancer; IUDs and pelvic inflammatory disease; suitability of copper-bearing IUDs for long-term use; and the issue of venous thromboembolism in users of third-generation oral contraceptives. An additional topic among the top ten identified by the panel was the safety and efficacy of the anti progestogen mifepristone, an area in which the Programme has also been at the cutting edge through the work of one of its other task forces. A score of eight out of ten is an achievement to be proud of and a tribute to the hundreds of collaborators in some 50 countries around the world who have had the vision, skills and stamina to make it possible. Second, the fertile initiative on safety and efficacy of fertility regulating methods has amply demonstrated the power of imaginatively conceived, carefully designed and meticulously executed mission-oriented research. It has also confirmed, once again, the Programme's adage that, where research is concerned, collaboration is key to success. Multicentre research studies in the biomedical and epidemiological spheres and calls for proposals for social science research on defined high-priority topics have traditionally constituted the backbone of the Programme's research endeavours. This is likely to remain so for the years to come. But the traditional concept of interaction between the Programme and its worldwide network of collaborating institutions on a one-to-one basis, as between the hub and rim of a wheel, is changing in important ways. Many of the collaborating centres have reached the stage of maturity and sustainable independence and this, together with the revolutionary advances in electronic communication, is creating untold opportunities for people, institutions and countries to develop their own networks for collaborative research on common problems of regional or interregional scope. As you will discover in Part 1 of this Report several such networks addressing issues such as female genital mutilation, knowledge and attitudes with respect to emergency contraception and the (mis )use of caesarean section have started functioning in Africa and Latin America in the last year or two and more are expected to emerge shortly. The third, and perhaps the most significant, reason why 1997 is likely to be recorded as a memorable year in the Programme's history relates to events that took place during 1994-1995. During that biennium, two major United Nations conferences-the International Conference on Population and Development (ICPD) and the Fourth World Conference on Women- were held in Cairo, Egypt, and Beijing, China, respectively. The nations of the world present at these meetings firmly endorsed the concepts of sexual and reproductive health and rights and their implications for the delivery of services and for research. Already prior to these conferences, the Programme and its highest governing body, the Policy and Coordination Committee (PCC), had been studying the implications of the reproductive health paradigm for the Programme's mandate and focus of its research. During the 1996-1997 biennium, this study was extended and led to the report "Sexual and Reproductive Health Research Priorities for WHO for the Period 1998-2003". The report proposes that, in line with the ICPD Programme of Action, the Programme address, in a focused manner, an expanded array of priorities in sexual and reproductive health, building on its work and achievements in fertility regulation. The research agenda would encompass, in addition to fertility regulation, high-priority research on unsafe abortion, maternal health, reproductive tract infections (including cervical cancer), and planning and programming in reproductive health. Aspects of research on adolescent reproductive health, harmful practices and violence against women, which are relevant to the Programme's mandate, would also be incorporated. This proposal for a focused expansion of the research agenda in the Programme will be submitted for consideration by PCC at its meeting in June 1998. Part 2 of this Biennial Report includes individual chapters on some of the topics that were highlighted at Cairo and Beijing as requiring intensified research efforts by governments, agencies and organizations active in the field. Written mainly by experts outside the Programme in their personal capacity, these essays provide a glimpse of the challenges in research that must be addressed if reproductive health for all is to become more than mere rhetoric. In her acceptance speech on 13 May 1998, Dr Gro Harlem Brundtland, the first woman to become WHO's Director-General, observed "The Cairo Summit put population and reproductive health on the agenda but there is still so much to do. We must help doing W. The Programme and its worldwide web of collaborators and supporters stand ready to answer that call. Paul F.A. Van Look, MD PhD Director Part 1 The work of the Programme in 1996-1997 Understanding people's reproductive health needs and perspectives Highlights • Much unmet need for family planning persists, even in settings where knowledge of contraceptive methods is high. Studies suggest that many potential users choose not to use more reliable methods due to misperceptions and concerns about health-related risks. For example, a study in the Maldives found that knowledge of family planning was universal, but only 30% of couples were using a contraceptive method. Several studies, including one from Malaysia, found that non-use of contraceptives was linked to fears about side-effects. This research highlights the continuing need for information, education and communication (IEC) campaigns to dispel misconceptions and allay fears about modern methods. • Research on vasectomy demonstrated that concerns and misperceptions about the procedure's impact on health and virility are important reasons why many men do not choose this method. Furthermore, research from Mexico among men who underwent vasectomy found that some believed vasectomy would protect them against HIV infection. These studies stress the need to provide better information and counselling regarding vasectomy, especially to men. There may also be a need for prevention efforts with respect to sexually transmitted diseases (STDs) and HIV among men who undergo vasectomy. • Studies have found that despite health education campaigns and counselling, condom use among married couples remains stigmatized because of its association with infidelity. Research continues on: the acceptability of male and female condoms; the effectiveness of condom promotion; high-risk sexual behaviour in several countries; and men's views on sexuality and STD transmission. A new research initiative was launched on the dual risk of unplanned pregnancy and STDs, including HIV/AIDS. Research already completed suggests that promoting condom use among couples for dual protection against both pregnancy and STDs may be more successful than for prevention of STDs alone. The newly launched initiative will try to identify ways to address the need for dual protection against unplanned pregnancy and STDs in different sociocultural contexts. • Unsafe abortion may persist even when family planning and legal abortion services are available. This was demonstrated by research in Turkey which found that many women tried to self-induce abortion before seeking legal abortion services. Despite the availability of family planning services, recourse to abortion remained high due to non-use of contraception and the failure of the widely practised traditional method of withdrawal. Research on abortion has many implications for programmes and policies. For instance, it highlights the need to dispel fears regarding the negative health consequences of contraception and ensure an easy access to services. It also illustrates the key role of providing information and counselling regarding prevention of unplanned pregnancy and of the involvement of men in strategies to increase contraceptive use and reduce unwanted pregnancies. • Research on gender roles, sexuality and contraception has been carried out in several countries. In Thailand, a study found that, while there was little acceptance of wives' extramarital affairs, male visits to sex workers were considered the norm. In Mexico, research documented the belief that women should take primary responsibility for contraception, but men should be experts on sexuality and birth control. Research in Nigeria found that the decision to have a child was made by the husband alone in 17% of cases, and 30% of couples did not discuss whether to have another child. Programme planners, policy-makers and researchers need to understand gender roles and socio- cultural norms in order to design appropriate IEC campaigns and plan more effective family planning programmes. This research also highlights the need to provide better family planning information to men. Biennial Report 1996-1997 • Research from several countries, including China, Malaysia and Nigeria, documented the belief that wider access to contraceptive methods for young people would lead to promiscuity or "moral decay." Yet many studies have shown that despite lack of access to family planning services, many unmarried young people are already sexually experienced. In China, for example, a study found that many unmarried (but engaged) young women reported sexual activity, without access to formal family planning services. Few of these women used contraception during the first sexual encounter because they did not know where to obtain a method or because they were embarrassed to seek advice from family planning outlets for fear of disclosing their premarital sexual behaviour. These studies point to the need for information and services for young people and a need to overcome social disapproval of such services throUgh culturally sensitive public education campaigns. Research on adolescent sexual behaviour provides information necessary for developing appropriate programmes and policies to promote safer sex and prevent unintended pregnancies and transmission of STDs, including HIV/AIDS, among young people. • Studies from several countries documented the serious consequences of unprotected sex among adolescents, especially for female adolescents. In the Republic of Korea, over 20% of male industrial workers and 10% of male students reported having made their partner pregnant. A study among male adolescents in Nigeria found that 13% had made their partner pregnant and that 67% of these pregnancies had been aborted. Among Nigerian female students, 10% reported abnormal vaginal discharge during the previous year and among male students, 8% reported a history of STDs, primarily gonorrhoea. Information about the extent of unwanted pregnancy and STDs among young people is critical for drawing policy-makers' attention to the problem. • Studies among adolescents show that knowledge about sexuality, reproduction, and contraception does not necessarily lead to the practice of safer sex. Nor does lack of knowledge result in young people abstaining from sexual intercourse. Programmes targeted at adolescents need to go beyond providing factual information to young people. Effective education programmes for adolescents should include negotiation techniques and life skills. Biennial Report 1996-1997 People's perspectives on fertility and contraceptive use The Programme is involved in research to identify so-cial, cultural, and behav- ioural factors, and problems in seNice delivery which limit ac- cess to, and impede the improve- ment of, reproductive health. This research focuses on the percep- tions, fears, and concerns of po- tential users about the health-as- sociated risks of contraceptive methods. It also examines the role of men in reproductive health and helps identify shortcomings in family planning seNices which may limit the choice of contracep- tives available. Malaysia A study carried out among three ethnic groups in Malaysia found that poor uptake of some family planning methods was linked to fears and misconcep- tions about their possible side- effects. The study was designed to identify differences in attitudes to- wards family planning among women from three ethnic groups: Chinese, Indian, and Malay. The research found that women from the Malay group favoured a larger family size than Chinese or Indian women and used contraception mainly for spacing births rather than for limiting family size. The Malay women reported generally low use of contraceptive meth- ods-partly due to a lack of knowl- edge about modern contraceptive methods and partly due to a de- sire for larger families. They also disapproved of intrauterine de- vices (IUDs) because they require insertion by medical personnel, who are often men. The Chinese women wanted to have fewer children than women from the other groups-mainly be- cause they wanted to ensure that their children received a good edu- cation. Women from the Indian community reported using contra- ception both for birth spacing and for limiting family size. The study also found some convergence in attitudes. All three groups reported a fear of side- effects as the most important rea- son for not using contraceptives and said there was little open dis- cussion about contraception. All groups expressed concern that wider access to contraceptive methods would lead to "moral decay" among adolescents. Ma/dives A study carried out in the Maldives investigated whether attitudes to the sex composition of families (usually a preference for sons) had any affect on family size. Of the approximately 400 couples involved, 75% said they had no sex preference, and that the ideal family size was four children. Although knowledge of family planning was universal, only 30% of couples were using a method of contraception-signal- ling an unmet need for family planning seNices. Nigeria A study in Nigeria on beliefs and attitudes about sexual behav- iour and contraceptive decision- making highlighted the need for information and education pro- grammes on the use of contra- ceptive methods. The study, con- ducted in Oyo State, involved 4000 men and women aged 18-50 years. The decision about whether or when a woman should become pregnant was often a joint deci- sion (47% of couples), but about 30% of couples never discussed it, and in 17% of cases the deci- sion was taken by the male part- ner alone. The study also found that modern contraceptive meth- ods were little used and that many respondents believed family size was determined by "God's will". Providers' perspectives Views of health care providers on different contraceptive methods and reproductive health technology can have key implica- tions for service delivery and policy change. However, the role of pro- viders in contraceptive acceptabil- ity and continuation of use has seldom been studied. Thus, research was carried out in Nigeria on the attitudes of almost 300 traditional and reli- gious healers (both Christian and Muslim) towards fertility and the family planning services they pro- vide. While most of those inter- viewed maintained that traditional healers and western practitioners should work together in family plan- ning, 26% of the traditional heal- ers and 30% of religious healers opposed the use of modern con- traceptive methods such as the pill. However, in advocating more "natural" forms of contraception, such as periodic abstinence, they demonstrated a poor understand- ing of the fertile period during the menstrual cycle. The findings un- derscored the importance of in- volving and training traditional and religious leaders who play an im- portant role as service providers Biennial Report 1996-1997 in areas where modem health serv- ices are less accessible. People's perspectives on spe- cific contraceptive methods There are important lessons I for programme planners and policy-makers in how people se- lect, use, and discontinue a con- traceptive method. Research is ongoing to determine some of the complex factors involved. Vasectomy A study in Mexico on the fac- tors that influence men to undergo vasectomy documented the un- expected finding that some men believed the procedure would pro- tect them against HIV/AIDS. This finding has led to detailed recom- mendations for an information campaign in Mexico about male sterilization and the need for HIVI AIDS prevention efforts among men who have undergone vasec- tomy. The Mexico study involved 50 men planning to undergo a vasec- tomy, 100 men who had already undergone the procedure, and 50 men with no intention of having a vasectomy. The study found that men undergoing vasectomy re- ported they and their partners had more experience with "natu- ral" and hormonal methods of con- traception (including withdrawal, rhythm method, periodic absti- nence, and the pill) and less expe- rience with barrier methods than those who did not choose vasec- tomy. In addition, they reported a higher level of communication with their partners about sexuality and contraception. The most impor- tant factor in the choice of vasec- tomy was accessibility, including Biennial Report 1996-1997 the view that vasectomy is a sim- ple procedure that does not in- volve "unpleasant feelings" after the operation. Another study carried out among 1000 couples in China found that attitudes towards va- sectomy were largely influenced by fears and misconceptions about the procedure. Respondents be- lieved that vasectomy was not as simple or effective as female steri- lization and that potential side- effects included negative effects on physical strength. While dis- cussion between both partners was a key factor in the choice of contraceptive method, the cou- ples did not have enough informa- tion about vasectomy to make an informed decision. One ofthe main conclusions of this study was that, since, in China, husbands gener- ally have a higher level of educa- tion than their wives and are the main decision-makers, informa- tion about vasectomy should be targeted directly to men, rather than through their wives. The diaphragm A study in Turkey looked into the reasons why women choose to use the diaph ragm as a method of birth control. Researchers are also investigating the use-effec- tiveness of this method and as- sessingthe reqUirements forserv- ice delivery. The Turkish study is part of an interagency initiative involving comparative studies overseen by Family Health Inter- national (in the Philippines) and The Population Council (in Co- lombia). Initial findings from the study in Turkey suggest that, in general, women who chose the diaphragm tend to be older and that both they and their husbands were better educated than women who choose other methods. The main reasons cited by diaphragm users for choosing the method were safety and the lack of side-effects. In addition, some women chose the diaphragm because they wanted to have control over con- traception. The majority of other method users said they selected the method because of its effec- tiveness. A higher percentage of dia- phragm users reported having in- tercourse more than four times a week as compared to users of other methods. Patterns of uri- nary tract infections were similar for both diaphragm users and women using other methods. The final results from this study are due in early 1998. Pregnancy prevention in the era of H IV I AI OS and STOs In 1997, the Programme launched a new research initia- tive that will focus on the dual risk of unplanned pregnancy and STDs, including HIV/AIDS. The new initiative marks a shift away from the previous approach which focused exclusively on either pre- vention of STDs or pregnancy. The aim is to understand what sexually active individuals believe about the dual risk of HIVlAIDS and unwanted pregnancy, and what they consider as appropri- ate and effective protective meas- ures against these risks. Family planning and HIVlSTD pre- vention In Africa, a regional study will investigate the interface between Cl) w > i= o w 0. Cl) (I; w 0. -~ .J § ~ Biennial Report 1996-1997 family planning and HIV/STD pre- tural, psychological,andsocialfac- vention. It will be carried out in tors, as well as the ability of women Kenya, South Africa, Uganda, the to negotiate with their sexual part- United Republic of Tanzania, ner. Zambia, and Zimbabwe, and pos- One of the key findings was sibly Botswana and Ethiopia. that-despite health education A decline in fertility is reported campaigns and counselling---con- in an increasing number of coun- tries in this region-driven by a desire for smaller families and by an increase in the use of contra- ceptives. However, despite high levels of infection with HIV and other STDs in many countries, few people use condoms or other barrier methods, preferring to use mainly hormonal methods instead. During the study, sexually ac- tive individuals will be asked how they evaluate the risks of unwanted pregnancy and STDs, including HIV/AIDS, and what strategies they use to avoid those risks. The project will examine possible ways of changing behaviour, with a par- ticular focus on partner communi- cation. The study is due to be completed by the end of 1999. Prevention of STOs The Programme is supporting a number of studies on the pre- vention of STDs. They include research on: the acceptability of male and female condoms (sev- eral countries); the effectiveness of condom promotion (China); high-risk sexual behaviour (Ni- geria); male attitudes to transmis- sion of STDs (Brazil); and the use of condoms among men (in five border towns in Nepal). In Argentina, a Programme- supported study was carried out in a low-income district on beliefs and attitudes towards the preven- tion and treatment of STDs. The study explored the impact of cul- dom use among married couples remains stigmatized because it is associated with infidelity. This find- ing suggests that the promotion of condom use for dual protection against pregnancy and STDs may be more successful than for pre- vention of STDs alone. The study also found thatthere was a need to ensure that people had access to accurate informa- tion on sexual and reproductive health. Those taking part in the study had little knowledge of STDs and of how they are transmitted, apart from HIV/AIDS. It was more common for men than women to discuss STDs and men were also more aware of STD symptoms. Some men believed that women are responsible for the spread of STDs because it is more difficult to knowwhetherthey are infected. Determinants and conse- quences of induced abortion I\. bout 20 million unsafe abor- I"'\tions are carried out every year. Performed by unskilled per- sonnel or in unhygienic condi- tions, or both, these 20 million unsafe abortions are estimated to be responsible for the deaths of some 70000 women, or about 13% of the nearly 600 000 mater- nal deaths that occur each year. The Programme has funded a series of research projects aimed at determining the reasons and consequences of the widespread recourse to unsafe abortions. Most Biennial Report 1996-1997 of these studies have now been completed and a book describing the findings is in press. However, a series of new projects in Argen- tina, Bangladesh, China, and Sri Lanka has been initiated to ex- plore remaining gaps in knowl- edge. China In China, a study on pregnancy before marriage compared the in- dividual characteristics of young women who opted to have an abortion with those who went on to marry and give birth. The study found that almosttwo-thirds of the women-regardless of the out- come of the pregnancy-had never used contraception. The main reasons cited for this were lack of knowledge about meth- ods, fear of side-effects, and not knowing where to obtain contra- ception. Women with higher education and higher status occupations were more likely to choose abor- tion than marrying and having babies, as well as migrant women in uncommitted relationships, women with negative feelings about pregnancy, and women under2Q-the minimum legal age of marriage in China. These findings underscore the need for wider access to informa- tion and services related to family planning, regardless of age or marital status. The finding that many young people are sexually active before marriage, often in uncommitted relationships, has important implications for prevent- ing pregnancy as well as the spread of STDs. Turkey A study carried out in Turkey, where abortion has been legal since 1983, showed that the le- galization of abortion does not necessarily lead to the disappear- anceofunsafeabortion. The study found that before seeking medi- cal help many women attempted :E I o "D I ~ o ~ ?= :t> Z :t> Z o m z Biennial Report 1996-1997 a self-induced abortion using approved in 1997 in Brazil, China, methods such as taking an over- Jamaica, Senegal, and Turkey. dose of medicine (aspirin or qui- A study involving over 400 mar- nine) or intrauterine insertion of ried couples in Thailand focused soap, marshmallows, chicken on the impact of sex roles and feathers, matches, or needles. partner communication on the risk Another common method was to of STDs. The study examined ask a health care providerto insert an ILlD. The Turkish women involved in the survey wanted fewer chil- d ren so they coul d be bette r cared for and educated. Although most women considered abortion to be a woman's right, it was neverthe- less considered a "sin", and in- creasingly sinful the longer the pregnancy. All the women believed that abortion has an adverse ef- fect on a woman's health. Although women in the survey had access to family planning methods, very few were using modern contraceptive methods. Most either used traditional meth- ods (mainly withdrawal), delivered unwanted children, or had repeat abortions. Despite major efforts by the Turkish family planning pro- gramme, recourse to abortion re- mains high-due to non-use of contraception or the failure of tra- ditional methods. The role of men in reproductive health M any ofthe Programme's re-cent research projects have focused on the impact of gender roles and status, the empower- ment of women, and interspousal communication on sexual and re- productive health issues. In 1995, the Programme launched a re- search initiative on the role of men in reproductive health. Many of th~se studies are still under way. Meanwh ile five new projects were gender-based attitudes and be- haviour in relation to extramarital sex, use of female sex workers, sex roles within marriage, and pre- vention of STDs. Although the study found there was little ac- ceptance of wives' extramarital affairs, male visits to sex workers were considered the norm. Over 80% of husbands interviewed and almost 70% of wives did not con- sider it "strange" for husbands to visit sex workers. Almost 80% of husbands reported having had sex with a commercial sex worker at least once in their life, but only 5% had done so during the previous three months. The researchers found signifi- cant differences between the views of husbands and wives on the sexual role of women. Over 90% of husbands did not consider it shameful for a wife to initiate sexual intercourse, while less than 70% of wives felt the same. In several instances there were wide variations in attitudes depending on the occupational status of the individual. For example, among blue-collar workers, 64% of wives and 40% of husbands maintained that men should get more pleas- ure from sexual intercourse than women, while only 28% and 14% of white-collarwives and husbands thought the same. Asked whether they had changed their sexual behaviour after learning about HIVlAIDS, only about 20% of husbands and Biennial Report 1996-1997 17% of wives said they had. Of the husbands who reported a change in behaviour, about half said they had stopped visiting commercial sex workers. Meanwhile, about 20% of wives reported having tried to stop their husbands from visit- ing sex workers. Although most couples reported talking with their partner about sexual mat- ters, the study found that dis- cussion about extramarital sex, use of sex workers, and the use of condoms within marriage was difficult or impossible. Birth spacing and maternal health Aver the past decade, there has been an increasing fo- cus on maternal health issues, especially on maternal deaths. However, maternal ill-health and its psychological and social con- sequences have received little attention so far. A study in Thailand assessed the influence of information and reproductive health education on mothers' beliefs about breast- feeding. The study involved women of childbearing age from both ru ral and urban areas, all with at least one child aged under two years. Researchers found that contraceptive uptake was high during the first two months after giving birth. Almost 60% of pill users and nearly70% of injectable users started using the method at that time. Although health work- ers in Thailand recommend that babies be exclusively breast-fed for the first three months, less than 50% were found to be exclu- sively breast-fed after one month, 34% after two months, and only 6% after three months. Knowl- edge of breast-feeding as a con- traceptive method was found to increase with age. The researchers concluded that there was a need to promote breast-feeding for the first three months both for the sake of the child's health and as a contracep- tive method. This recommenda- tion is important in view of con- cerns about the use of combined oral contraceptives while breast- feeding. Elsewhere, a study carried out in Morocco investigated social and cultural factors that interfere with access to care and communica- tion between women and health care providers. Researchers found that the women were ashamed and embarrassed about illnesses of the reproductive tract. Most women would not discuss the sub- ject in public or even with their husbands. They had developed their own way of describing dif- ferent forms of reproductive ill- health, although they used bio- medical descriptions as well. Access to medical care was limited by financial constraints and by women's acceptance of the decision-making authority of their husbands. While most of the women preferred private sector medical care, traditional medicine was used more often. Reproductive health of adolescents A dolescents are at high risk of /"'\unintended pregnancy and STDs, including HIV/AIDS, be- cause of their sexual behaviour, their lack of information, and lim- ited access to sexual and repro- ductive health services. About 12 million babies are born to adoles- I cent mothers every year-endan- gering the health of both mother and infant. Most sexual and reproductive health services fail to make provi- sion for the special needs of ado- lescents. In response, the Pro- gramme has conducted research on the extent of unmet need for sexual and reproductive health in- formation and services among adolescents. This research is critical for developing appropri- ate programmes and policies to promote safer sex and prevent unintended pregnancies and transmission of STDs including HIV/AIDS. Adolescent sexuality Studies completed in Nigeria, the Philippines, the Republic of Korea,Thailand, and Viet Nam in- dicate that a high proportion of male adolescents are sexually ex- perienced. They include over70% Biennial Report 1996-1 997 of male adolescents in the Nigeria study and over 75% of factory workers in the Republic of Korea and Thailand. A study in the Republic of Ko- rea, involving over 800 school and university students aged 15-23, found that two-thirds of sexually experienced males and one-third of sexually experienced females reported more than one lifetime sexual partner. Meanwhile, an- other study involving male stu- dents and male industrial workers found that over 75% of the indus- trial workers were sexually active, compared to fewer than 40% of the students. Elsewhere, a study on the re- productive behaviour of university students in Viet Nam, found that 98% of women and over 75% of men believed that sexual inter- course should only take place within marriage. The study also found gender differences in the longevity of partnerships, with 90% of sexually experienced females staying with theirfirst partner com- pared to only 55% of males. A similar study involving over 1000 students in the Philippines found that 18% were sexually active, of whom the majority were monoga- mous and with thei r original sexual partner. A study in Nigeria involving 4000 men and women aged 18- 50 found that over a third of re- spondents became sexually ac- tive during adolescence (11-18 years). Experience of rape during adolescence was reported by 4% of males and 7% offemales. Some respondents (5%) also reported having sexual intercourse between the ages of six and 10, while 2% reported having been sexually Biennial Report 1996-1997 abused (forced intercourse) atthat age. The Nigerian study also found that adolescent sexuality was a controversial issue. Some partici- pants opposed the provision of sex education and contraception for adolescents on the grounds that it would lead to promiscuity. This suggests there is a need for community education about the benefits of reproductive health services for adolescents and that such education should also be targeted to community leaders and opinion leaders. Gender roles among adolescents Perceptions of gender roles are a key determinant of expecta- tions of male and female sexual- ity. A study in rural areas of Thai- land, involving 1200 men and women aged 15-24, found that premarital sex was more accept- able for men than for women. While 25% of men and 60% of women believed that men should not have sex before marriage, as many as 95% of women and 60% of men said it was unacceptable for women to do so. Also, of those who had ever been married, al- most 90% of the men but less than 30% of the women reported having premarital sexual inter- course. Almost half of the men who had never been married and about a third of the married men reported having their first sexual encounter with a sex worker. Meanwhile, another study in Thailand, involving male and fe- male adolescent factory workers, found that, whilefor85%ofwomen theirhusbandwastheirfirstsexual partner, on Iy 6% of males reported marrying their first sexual partner. Contraceptive use A study on sexual behaviour and contraceptive use among over 2500 unmarried but engaged couples in Shanghai, China, found that premarital sexual inter- course was higher in rural coun- ties (86%) than in urban Shanghai (60%). This finding contradicts the assumption that greater expo- sure to the media and rapid mod- ernization in urban areas com- pared to rural areas invariably leads to higher levels of premarital sex. The researchers suggest that the difference may be a reflection of better living conditions in rural areas and the ability of unmarried rural men and women to live to- gether once engaged. Although sexual activity is high among this population, only one in five sexually experienced women reported using a contra- ceptive method during the first sexual encounter. Furthermore, about 40% of those who reported using a contraceptive method used less reliable methods such as the rhythm method and with- drawal. Contraceptive use was higher among sexually experi- enced women in urban areas (24%) than in rural areas (17%). As a result of strict limitations on family size in China, and the social stigma attached to a child born out of wedlock, most premari- tal pregnancies (90%) were re- ported to have ended in abortion, and only few women opted to marry early. Some women said they did not use contraception during the first sexual encounter because they did not know where to obtain a contraceptive method. Others were embarrassed to seek advice I from family planning outlets for fear of disclosure of their premari- tal sexual behaviour. These find- ings point to a need for informa- tion and services to be provided for unmarried men and women in China, especially couples who have recently become engaged. Elsewhere, in the Philippines, over 50% of sexually experienced students interviewed reported us- ing contraception during their first sexual encounter, mainly (75%) the rhythm method or withdrawal. However, 50% of sexually experi- enced students said they were now using effective contraceptive methods compared to 5% at their first sexual encounter. The consequences of adolescent sexuality Unsafe sex among adoles- cents and young adults can have serious consequences, especially for young women. In a study in- volving sexually experienced male industrial workers in the Republic of Korea, over 20% reported hav- ing made their partner pregnant; the corresponding figure for stu- dents was 10%. Although most of these pregnancies were aborted, 13% of the industrial workers and 11 % of the students had fathered a child. A similar study among male adolescents in Nigeria found that 13% had made their partner preg- nant and that 67% of these preg- nancies had been aborted. Among female adolescents, almost 10% reported having had at least one pregnancy. Most (77%) ended in abortions, 7% miscarried, and 16% resulted in the birth of unintended babies. In southwest Nigeria, over 40% of sexually active female Biennial Report 1996-1997 adolescents reported having had at least one abortion. Unsafe sex among adoles- cents can also lead to the trans- mission of STDs, including HIVI AIDS. A study in Nigeria among students aged 15-24 found that 10% of young women reported abnormal vaginal discharge dur- ing the previous year and 25% said they were unsure if their part- ner might have a STD during the previous year. Among the male students, 8% reported a history of STDs, primarily gonorrhoea (93%). Relationship between knowledge and behaviour Studies among adolescents have shown that knowledge about sexuality, reproduction, and con- traception does not necessarily lead to the practice of safer sex. Nor does a lack of knowledge result in young people abstaining from sexual intercourse. In a study in rural Thailand, where 80% of adolescents knew about HIV/AIDS, condoms were seen as a means of preventing transmission of STDs and not for use within marriage. Of the sexu- ally experienced males, 76% re- ported usingacondomduringtheir first encounter with a commercial sex worker, although only 23% of those who had sex with commer- cial sex workers used a condom every time. Nearly half of those who visited sex workers main- tained the sex workers were free of STDs because they underwent regular medical checks. Among male factory workers in Thailand, 20% reported using a condom during their first sexual encounter with women who were Biennial Report 1996-1997 not commercial sex workers, while 54% used one during the initial encounter with a sex worker. Meanwhile, 24% of young mar- ried men who reported extramari- tal sex during the last 12 months said they did not consistently use condoms. Among the young women involved in the study, 88% maintained that men should use condoms with casual partners, while only 46% believed they should use them with wives or regular partners. In the Republic of Korea, a study among male students and industrial workers found almost universal knowledge that H IV can be transmitted by having sex with an infected person, and many of the young men knew that STDs could be prevented by using con- doms. However, the study also found misconceptions about the transmission of STDs including HIV/AIDS. Over half of the indus- trial workers and over 60% of the students believed that STDs could be transmitted by kissing. Among those who were sexually experi- enced, 80% of industrial workers and 73% of college students re- ported having had sex with a com- mercial sex worker. However, con- dom use was low: 23% of indus- trial workers and 40% of students reported using a condom during their first visit to a sex worker and 39% and 48%, respectively, at their most recent visit. A similar study among adoles- cents in Nigeria found that, al- though all those involved had heard of HIVlAIDS, 44% ofthe men and 17% of the women reported hav- ing sex with a casual partner or sex worker without consistently using a condom. I Developing new methods of fertility regulation Highlights • In November 1997, the Scientific Review Committee for Technology Development and Assessment reviewed the Programme's existing research portfolio and reprioritized the product leads. Since the previous review in 1995, work had been either completed or terminated on several potential products. The new list contains seven high-priority leads-five for methods for women and two for male methods. The research portfolio of the Programme in the area of development of new methods is reviewed every two years to ensure that research efforts are sharply focused on leads that are most promising for product development. • Research was undertaken on the anti progestogen mifepristone to see if it could be developed as an oral contraceptive that could be taken either daily or weekly. Daily doses of 0.5-1 mg and a weekly dose of 5 mg mifepristone produced changes in the lining of the womb that could potentially prevent implantation of a fertilized egg. Encouraged by these findings the Programme conducted studies in small numbers of women to test whether these doses would be effective in preventing pregnancy. The final results from these studies will not be available until later in 1998. Interim results indicate that dosage levels that do not disrupt the menstrual cycle apparently do not produce a reliable contraceptive effect. Since the aim of these studies was to find out if mifepristone could be used for contraception without disturbance of the menstrual cycle, these results are considered disappointing and hence research in this area will not be continued. • Progress continues to be made in the work to develop levonorgestrel butanoate as a new injectable hormonal contraceptive. Since 1996, research has focused on reformulating the product to prevent clumping of the suspension during prolonged storage and on optimizing the sterilization method. Initial results suggest that particle aggregation and adhesion can be solved by modifying the formula and by switching from a glass ampoule to a prefilled single-use syringe. Levonorgestrel butanoate would provide contraceptive protection for up to three months with a single 10 mg dose. Such a low-dose preparation would expose a woman to a lesser amount of synthetic hormone than does depot-medroxyprogesterone acetate (DMPA}-the currently available three- monthly injectable. The lower dose would also result in less suppression of the ovaries, which in turn would result in fewer women experiencing amenorrhoea. In addition, fertility would be restored more rapidly after stopping the injections than is the case with DMPA. • In ongoing research to develop two new methods of emergency contraception using the anti progestogen mifepristone and the progestogen levonorgestrel, the Programme has established that, when administered within 120 hours of unprotected intercourse, mifepristone dosages of 10 mg and 50 mg appear to be as effective as the 600 mg dose in preventing pregnancy. Programme studies have also shown that levonorgestrel is more effective than the Yuzpe method for emergency contraception and has considerably fewer side-effects. The most commonly used method of emergency contraception today is the Yuzpe method. It involves the use of four high-dose oral contraceptive pills administered with an interval of 12 hours. Apart from the inconvenience of the 12-hour regimen, this method fails to prevent pregnancy in about 25% of cases. In addition, it often involves unpleasant side-effects ranging from nausea and dizziness to headaches and vomiting. The new methods being developed by the Programme are intended to be more effective than the Yuzpe method, with fewer side-effects. • The Programme was the first to show that the use of a prostaglandin 36-48 hours after the administration of mifepristone was more effective in terminating an early pregnancy than the use of mifepristone alone. The Programme is now conducting studies to find out if misoprostol-a commonly available and inexpensive prostaglandin that can be administered orally-can be used in combination with mifepristone for early termination of pregnancy. A one-year study, Biennial Report 1996-1997 involving over 2000 women in 14 centres, will determine the optimum dose of misoprostol needed to ensure a complete abortion up to 63 days after the last menstrual period. Studies suggest that many women undergoing an induced abortion would prefer a safe and effective non-surgical method. Developing a method that is based on a drug that can be taken orally is expected to have special advantages. Misoprostol is currently marketed in over 60 countries forthe prevention and treatment of gastric ulcers. It has a good safety record, is inexpensive, can be stored at room temperature, and has the advantage of being orally active. The study will compare the effectiveness of different regimes of oral and vaginal administration of misoprostol after pretreatment with mifepristone. • The Programme is supporting research on the development of prototype hormonal contraceptives for men. The new products are either a combination of two synthetically produced hormones-a progestogen (Ievonorgestrel butanoate) and an androgen (testosterone buciclate}- or the androgen alone. They will act by stopping the production of sperm in the testes. The aim is to reduce the amount of sperm in semen to undetectable or very low levels incompatible with fertility. The method would involve three-monthly injections and would be reversible. At present, men have access to only three forms of contraception-the condom, withdrawal, and vasectomy. Calls have been made at various international fora to increase contraceptive choices for men in order to enable them to take greater responsibility for fertility regulation. • Encouraging results have been achieved in research conducted over the past 6-7 years on a new non-surgical method of vasectomy. This method involves the percutaneous injection of liquid silicone to block the two ducts (vasa deferentia) that carry sperm from the testes. The plugs can be removed easily suggesting that this approach may be readily reversible. The liquid silicone contains a hardener which enables it to set quickly and form a tight seal or plug within the vas deferens thereby blocking the passage of sperm from the testes. There is a need for a non-surgical and reversible alternative to vasectomy for men who want a non- hormonal, long-lasting but non-permanent method of contraception. Results of a study carried out some years ago in Indonesia indicated greater than 90% efficacy of this approach. A similar study conducted recently in Europe yielded a disappointingly low level of efficacy, about 5%-10%. Further animal studies are proposed to see if the method can be improved. • In 1990 the Programme had concluded a licensing agreement with a pharmaceutical company for the manufacture and distribution of a levonorgestrel-releasing vaginal ring. But following reports of vaginal lesions among women involved in Phase III clinical trials, it was decided to redesign the ring. A trial of a redesigned placebo ring suggests that it does not produce lesions and that it would be suitable for further development. In 1997, the Programme's pharmaceutical partner decided to withdraw from the project and return the licence to the Programme. The Programme is now considering the possible development of a new higher-dose version of the redesigned vaginal ring in collaboration with the Contraceptive Research and Development Program (CONRAD). The Programme is pursuing this lead in response to women's expressed need for long-acting, effective methods of contraception which are under their own control. Acceptability studies done by the Programme suggest that many women will find this method suitable for their contraceptive needs. I In response to the need for new methods of fertility regulation to meet varied and changing individual reproductive needs, the Programme is continuing to sup- port research on the development of a range of new or improved technologies. In December 1995, the Programme convened a meet- ing of biomedical and social sci- entists, drug development ex- perts, health care planners and women's health advocates to re- view its technology development activities. The Scientific Review Committee ranked the activities as high, medium or low priority (see Table 1) according to four criteria: user needs and prefer- ences; feasibility of development into a product; feasibility of serv- ice delivery; and commercial in- terest and potential. In November 1997, the Scientific Review Committee reconsidered the existing re- search portfolio and reprioritized the product leads (see Table 2). During the intervening two years, work was either completed or terminated (owing to unfavour- able results) on several potential products. For example, research on the development of an antipro- gestogen-only daily oral contra- ceptive is no longer being pursued by the Programme following unpromising results from initial trials. During 1996, work was also discontinued on a progesterone- releasing vaginal ring, and on two oral contraceptive products which failed to produce promising re- sults: a once-weekly and a once- monthly pill, both using the antiprogestogen mifepristone. Meanwhile, a comparative study Biennial Report 1996-1997 of the copper intrauterine device (IUD) (TCu380A) and a prototype frameless IUD (FlexiGard) was closed down in 1997 after the Flexigard failed to fulfil expecta- tions of lower expulsion and re- moval rates. Highest priority is now being given to continued research on the development of seven new prod- ucts. They include several forms of long-acting hormonal contraception for both men and women, emer- gency contraception, non-surgical abortion, and non-surgical revers- iblevasectomy. Otherproduct leads have been accorded medium or low priority. This chapter docu- ments the work undertaken by the Programme prior to the No- vember 1997 review of priorities. High-priority leads An anti progestogen-only daily pill (mifepristone) Current hormonal contracep-tives sometimes have side- effects which women find unac- ceptable. Data suggest that up to 20% of women who start using oral contraceptive pills or inject- able contraceptives discontinue their use within the first year be- cause of unacceptable side-ef- fects or health concerns. Scien- tists have therefore been on the lookout for compounds that can produce the same antifertility ef- fectasthe current hormonal meth- ods but without the associated side-effects. Antiprogestogens- compounds that block the activ- ity ofthe hormone progesterone- hold that promise. It has been shown in studies, for example, that in humans, depending on the dose given, daily administration of the anti progestogen Biennial Report 1996-1997 I (J) o o I f- w ::l; ~ Z ~ . 0:; .• ~ . .w :0 mifepristone results either in inhi- bition of ovulation or in changes in the lining of the womb (en- dometrium) such that implanta- tion of a fertilized egg cannot take place. In 1995, studies were initiated by the Programme to determine the feasibility of using mifepristone as a minipill. Two approaches were adopted: (a) to identify the dose of mifepristone which disturbs the development of the endometrium but does not inhibit ovulation and hence does not cause disturbance of the menstrual cycle; and (b) to evalu- ate the biological effects of those doses of antiprogestogens wh ich block ovulation. A two-centre study was car- ried out in Santiago (Chile) and Szeged (Hungary) to assess the effects on the menstrual cycle of continuous daily administration of 1 mg of mifepristone for 150 consecutive days (five months). Overall, the results indicated that continuous treatment with 1 mg of mifepristone interferes with en- dometrial development. However, in the treated women up to half of the menstrual cycles were dis- rupted, with suppression of ovu- lation. This suggested that the daily dose would need to be lower than 1 mg if disruption of the menstrual cycle is to be avoided. The Programme's Collaborat- ing Centre in Stockholm (Swe- den) looked atthe effects on ovar- ian and endometrial functions of three months'treatmentwith daily doses of 0.1 mg and 0.5 mg of mifepristone. The results indi- cated that both these doses would not cause any disturbances in the menstrual cycles. However, Biennial Report 1996-1997 the 0.1 mg dose was too low even to cause any changes in the en- dometrium. The 0.5 mg dose appeared to interfere with the development ofthe endometrium . A study was then conducted in 1997 in Stockholm and Szeged to see if the 0.5 mg dose was sufficient to prevent pregnancy. Both centres were planning to recruit 20 women who would use the daily mifepristone pill as their only method of contraception for a period of six months. The women would record bleeding patterns, the timing of menstrual periods and side-effects during the treatment period. Although the final results of the above study will only be avail- able in 1998, interim findings are disappointing. Thus, until other leads emerge in this area-e.g. experience with other antiprogestogens or new infor- mation about other routes of ad- ministration-the Programme has decided not to pursue this lead further. An antiprogestogen-only weekly pill (mifepristone) Studies carried out in mon- keys suggest that a twice weekly dose of mifepristone could be identified that had no effect on the sex hormones or ovulation or the length of the menstrual cycle but that impaired endometrial de- velopment and prevented preg- nancy. Encouraged by this, the Programme initiated studies in 1995 to determine if in women infrequent (weekly) administra- tion of a relatively low dose of an antiprogestogen could suppress endometrial development without suppressing ovarian function. I Biennial Report 1996-1997 The first study was carried out by the Programme's Collaborat- ing Centre in Stockholm (Swe- den) to evaluate the feasibility of weekly administration of mifepristone in women with nor- mal cycles. Fourteen women were recruited in this trial and two treatment cycles were followed. reliable contraceptive effect with a 5 mg dose of mifepristone. As more frequent administration, for example every three days, is not practical, there are no plans to carry out any further studies of the intermittent administration of mifepristone in women. During the treatment cycles the Three-monthly injectable women received either 2.5 mg (nine women) or 5 mg (five women) of mifepristone at weekly intervals for eight weeks. Results showed that both doses did not affect the length of the cycle and there was no spotting or other side-effects. Changes in the de- velopment of the endometrium were observed with both doses, although they were less pro- nounced with the lower dose. In 1996, to evaluate whether the changes seen with the 5 mg dose were sufficient to prevent pregnancy, a study was planned in which 20 women would use the weekly dose of 5 mg as their only method of contraception for up to six months. By the end of Sep- tember 1996 all 15 women had been recruited for the study, and 13 had completed at least one month of treatment. A total of 39 months of exposure was ob- tained. One woman becamepreg- nant in the second month of treat- ment, but several women suc- cessfully used the method for 4- 6 months. However, by the end of October 1996, another woman had become pregnant and, as required by the protocol, the study had to be discontinued. The data obtained in this study are currently being analysed. However, it seems thatthe weekly interval is too long to achieve a (levonorgestrel butanoate) As many as 15 million women worldwide now use injectable con- traceptives-one injection provid- ing protection from 1-3 months depending on the product used. Of these, about 12 million women use depot-medroxyprogesterone acetate (DMPA), a three-monthly injectable based on a progestogen. Although highly effective, this prod- uct can cause irregular bleeding and amenorrhoea. It is estimated that 50% . 80% of women who give up using DMPA do so because of menstrual problems. Another dis- advantage is that the return to fertility is often delayed once in- jections are stopped. The Programme is supporting research on the development of a new kind of injectable contracep- tive (Ievonorgestrel butanoate) designed to protect women for three months with fewer side-ef- fects than DM P A. Because the new contraceptive contains a lower dosage of synthetic steroid hor- mone than other injectable con- traceptives, it is expected to cause less suppression of the ovaries, less amenorrhoea, and a quicker return to fertility once the injec- tions are stopped. Levonorgestrel butanoate was initially tested to determine its ef- fectiveness in blocking ovulation and the duration of protection at various doses. Next, the product was tested in a multicentre com- parative study involving another injectable contraceptive already on the market, norethisterone enantate (NET-EN), both given in the form of an injection lasting two months. Both products had the same high contraceptive efficacy and both caused some steroid- related side-effects. However, af- tera year, NET-EN caused greater weight gain and more erratic bleed- ing patterns than levonorgestrel butanoate. Animal studies have also been carried out, involving monkeys, to determine the optimum particle size for the compound, which is formulated as a crystalline sus- Biennial Report 1996-1997 pension. The studies showed that by increasing the size of the par- ticles, the release of the product could be slowed down, the dura- tion of protection extended, and the amount of steroid needed re- duced. An optimal particle size was then determined and a manu- facturing process established. Meanwhile, a one-year toxicology study in animals did not reveal any unexpected side-effects. Since 1996, research has fo- cused on reformulating the prod- uct to prevent clumping of the suspension during prolonged stor- age. Although the product has been shown to have good chemi- cal stability after several years' storage at different temperatures, Biennial Report 1996-1997 overtime, the crystal particles tend the blood that block a crucial stage to aggregate and stick to the sides in the reproductive process. of the glass ampoule-making it The method is likely to be of difficult to resuspend. Initial re- interest to women who want a suits suggest that this problem contraceptive that is free of the can be solved by modifying the side-effects associated with exist- formula and the manufacturing ing hormonal methods (including process, and by switching from a glass ampoule to a prefilled sin- gle-use syringe. It was also found that sterilization by gamma-irra- diation induced up to 4% impuri- ties. Thus, work is ongoing to optimize the sterilization proce- dure for this preparation.This in- vestigative work is being carried out with technical input from the Contraceptive Research and De- velopment Program (CONRAD) in the USA. Once these studies have been completed, clinical tri- alswill resume-probably in 1999. When the optimum dosage has been determined, a multicentre study will be carried out to com- pare the new injectable with DIVIPA. In the meantime, the Pro- gramme is negotiating with phar- maceutical companies to ensure the continued development and eventual manufacture ofthe prod- uct-togetherwith guarantees that it will be made available at a low price for use in the public sector in developing countries. Because the product is easy to synthesize, it is expected that production costs will be low. Immunocontraceptives The Programme has been sup- porting the development of an immunocontraceptive since 1973. This new form of contraception protects against pregnancy by stimulating the body's immune system to produce antibodies in contraceptive pills, injectables, and implants), does not require inser- tion of a device (such as an IUD), and is relatively long-lasting but not permanent. The immunocontraceptive be- ing developed by the Programme works by preventing the implanta- tion of a fertilized egg in the womb. It produces antibodies that bind to and neutralize the action of a hor- mone, human chorionic gonado- trophin (hCG), which is produced by a fertilized egg. This prevents pregnancy and menstruation oc- curs at or around the expected time, and the fertilized egg is ex- pelled. The antifertility effect ceases when the level of hCG antibodies in the blood drops at the end ofthe period of protection. The first clinical trial with the Programme's prototype hCG immunocontraceptive (Phase I safety trials) was carried out in Australia during 1986-1988, and involved 43 volunteers who had previously chosen to be sterilized and were therefore not at risk of pregnancy. No serious adverse effects were reported. However, a subsequent clinical trial (Phase 11 efficacy trial) launched in Sweden in 1993and involving fertile women was halted when the injection was found to cause an unacceptable reaction atthe injection site, which had not occurred during the Phase I trial. The prototype product is now being reformulated to avoid these I side-effects and preclinical safety studies and Phase I and Phase 11 clinical trials are due to resume in 1998. If the planned clinical trials are successful, the way would be open for the development of an initial product which may require a series of two or three injections in order to provide protective cover for six months. However, research- ers are also working on the devel- opment of an improved version which will provide the same dura- tion of protection with a single injection, and on a version which will provide a longer duration of protection (12 months). Studies are also being carried out on the possibility of producing the immunocontraceptive in a form that can be taken orally. Although the antifertility effect of the immunocontraceptive will end after the six- or 12-month period, research is under way to determine ways of safely inter- rupting and reversing its effect for women who may change their mind and wish to become preg- nantpriortothis.lnthe meantime, women who opt for this kind of contraception will be counselled to ensure that they understand the long-acting nature of the prod- uct, and that its action cannot be reversed before the end of the specified duration of effect. It is estimated that a further 5- 7years of clinical testing and prod- uct improvement will be needed before a first-generation product will be available. Meanwhile, a second-generation synthetic, bioengineered product is also un- der development, in collaboration with industry, and could be avail- able within the same or a slightly extended time-frame. Biennial Report 1996-1997 A licensing agreement for eventual manufacture of the prod- uct has been concluded between Ohio State University and an in- dustrial partner. This agreement, together with a collaborative re- search and product supply agree- ment between the company and WHO, will ensure that the immunocontraceptive is made available to the public sector in developing countries atthe lowest possible price. Emergency contraception Until recently, the Programme was the only international body involved in the research and de- velopment of emergency contra- ception. For almost a decade, the Programme has supported efforts to develop two alternative meth- ods of emergency contraception- one using the antiprogestogen mifepristone, and the other using the progestogen levonorgestrel. Both mifepristone and levonorgestrel have been on the market for some time: what is new is their proposed use as emer- gency contraceptives. Emergency contraception was first used in the 1960s to prevent pregnancy in rape victims. Since then it has been used by women in the event of unprotected inter- course or recognized contracep- tive failure. However, emergency contraception is not yet widely available. In many countries, fam- ily planning service providers have not been trained in this method of contraception and many women do not even know it exists. The most commonly used method of emergency contracep- tion today, the Yuzpe method, involves the use of an elevated Biennial Report 1996-1997 dose of an oral contraceptive. An initial dose of two pills (comprising estrogen and progestogen) is fol- lowed by two more to be taken 12 hours later. Apart from the incon- venience of the 12-hour regimen, which may entail taking pills in the middle of the night, this method fails to prevent about25% of preg- nancies. In addition, it often in- volves unpleasant side-effects ranging from nausea and vomit- ing to headaches and dizziness. The new products being devel- oped by the Programme are in- tended to be more effective than the Yuzpemethod, withfewerside- effects. Efforts to ensure that emer- gency contraception is available at the lowest possible price to women in developing countries are being spearheaded by the Interagency Consortium on Emer- gency Contraception (see page 42), of which the Programme is a member. 1. Mifepristone Research on the use of mifepristone as an emergency contraceptive began in 1989 fol- lowing the discovery that the com- pound can be used to block ovu- lation or to prevent the implanta- tion of a fertilized egg in the lining of the uterus-depending on the stage of the menstrual cycle at the time of administration. The earli- est trials involved almost 1200 women who had sought emer- gency contraception following un- protected intercourse or contra- ceptive failure. A single dose of mifepristone was given within 72 hours after intercourse and found to be more effective than the Yuzpe method, with fewer side-effects. However, women using mifepristone were more likely to have delayed menstruation than those using the Yuzpe method. A follow-up study-involving over 1700 women in Australia, China, Finland, Georgia, the United Kingdom, and the USA- compared the effectiveness of the original dose (600 mg) with two lower doses (50 mg and 10 mg) to determine the lowest effective dose required. All three were found to be equally effective. In this study, mife-pristone was given up to five days after intercourse but it ap- peared to be less effective once 72 hours had passed. Overall, the drug prevented 85%-90% of pregnancies that would have oc- curred without emergency contra- ception. 2. Levonorgestrel Since 1990, the Programme has been investigating the possi- bility of using levonorgestrel for emergency contraception. Levonorgestrel has a long-estab- lished safety record as a compo- nent of oral contraceptive pills and as the active ingredient in Norplant, the contraceptive implant. An early comparative study in Hong Kong, Special Administra- tive Region of China, involving over 800 women, found that levonorgestrel was as effective as the Yuzpe method, with fewer side- effects. In each case, treatment was initiated within 48 hours of intercourse and a second dose given 12 hours later. A follow-up study involving about 2000 women in 14 countries was launched in 1995. The aim was to confirm the findings of the earlier study and determine whether it was possible I to delay the start of emergency contraception up to 72 hours after intercourse. Initial results from this study suggest that levonorgestrel is more effective than the Yuzpe method with considerably fewer side-effects. The study was com- pleted in 1997 and the results are due to be published in the second half of 1998. This trial has already had a major impact in the field. On the basis of the interim results, the Interagency Consortium for Emergency Contraception se- lected levonorgestrel as the method to be introduced in family planning services through model introduction programmes in Indo- nesia, Kenya, Mexico, and Sri Lanka. During 1998-1999, a multicentre study involving almost 4200 women will compare the ef- fectiveness and side-effects of a single 1 0 mg dose of mifepristone with levonorgestrel given both as a single dose and in two doses. Meanwhile, a parallel study in Hong Kong, involving about 2000 women, will look at the effective- ness of giving levonorgestrel in two doses each 24 hours apart- a more convenient time interval than the 12-hour regimen used in earlier trials. 3. Emergency insertion of an IUD In some cases, insertion of a copper IUD can be used as an altemative form of emergency con- traception. One advantage is that an IUD can be inserted up to 5 days after ovulation, i.e. up to the estimated time of the start of im- plantation-which is 48 hours later than hormonal methods. Once in place, the IUD provides immedi- ate contraception and can be used BiennIal Report 1996-1997 for up to 10 years. However, this method is not recommended for women who have never given birth or those who are at risk of STDs. An analysis of 19 studies of postcoital insertion of IUDs re- vealedafailure rateofonlyO.1 %- suggesting that this method is 15 times more effective than the Yuzpe method. However, only one of these studies compared the actual and expected numbers of pregnancies. And while no stud- ies reported side-effects or illness after ILlD insertion for emergency contraception, emergency inser- tion is carried out at a later stage in the menstrual cycle than rou- tine insertion and therefore may be more difficult. The Programme has launched a new study in China involving 2000 women which will investi- gate the efficacy, acceptability, side-effects, and possible compli- cations of emergency insertion of an ILlD. Non-surgical abortion Globally, an estimated 150000 unwanted pregnancies end in abortion every day. Of these, as many as 55 000 are carried out in unsafe conditions-involving 200 deaths a day. In countries where abortion is legal but not widely available due to a shortage of medical facilities and trained man- power, the availability of non-sur- gical abortion could help reduce the number of unsafe abortions and maternal deaths. For many women, non-surgical abortion ap- pears to be more acceptable than surgical methods. However, non- surgical abortion can only be safely carried out in those areas where surgical back-up facilities are avail- Blenmal Report 1996-1997 able in the event of occasional failure. The Programme has been in- volved in the development of non- surgical methods of abortion us- ing antiprogestogens since 1983. It was the fi rst to demonstrate that an antiprogestogen pill (mifepristone) followed 36-48 hours later by administration of a prostaglandin could terminate an early pregnancy. This method is now registered for use in China, France, Sweden, and in the United Kingdom. However, gemeprost, the prostaglandin initially em- ployed most commonly, is ex- pensive and is not stable at room temperature. The Programme is therefore now studying the use of another prostaglandin, misoprostol, as a replacementfor gemeprost. Misoprostol-currently mar- keted as Cytotec in over 60 coun- tries for the prevention and treat- ment of gastric ulcers-has a good safety record, is less expensive, can be stored at room tempera- ture, and has the advantage of being active when given orally. Initial studies involving the use of mifepristone and misoprostol indicated thatthis combination was effective in terminating pregnan- cies of up to 49 days. However, a 1993 study carried out at the WHO Collaborating Centre in Edinburgh, United Kingdom, indicated that the use of oral misoprostol was less effective than vaginal admin- istration of gemeprost in pregnan- cies of longer than seven weeks. These findings were confirmed by follow-up studies which showed that increasing the initial dose of mifepristone (from 200mg to 600 mg) did not improvethe efficacy of this method beyond 49 days of pregnancy-indicating that the dosage and method of adminis- tration of misoprostol are critical in ensuring the termination of preg- nancy up to 63 days. If the method were highly effective only within the first seven weeks of preg- nancy, it would not be a useful choice for women in developing countries, as many fail to contact health services early enough. The Programme is now sup- porting a further one-year study, involving over 2000 women in 14 centres. The aim is to determine the optimum dose of misoprostol needed to ensure an effective abortion up to 63 days after the last menstrual period. The study will also compare the effective- ness of different regimes of oral and vaginal administration of misoprostol.lnitiallY,allthewomen volunteers will be given the same dose (200mg) of oral mifepristone. Two days later-the time required for mifepristone to take full ef- fect-different regimens of misoprostol will be started. A disadvantage of non-surgi- cal abortion is the amount and duration of bleeding that occurs afterwards, which lasts twice as long as bleeding after surgical abortion involving vacuum aspira- tion. This could have an adverse effect on women's health-espe- cially in countries where anaemia is prevalent. The Programme is therefore seeking to find ways of reducing blood loss and thereby further improve the acceptability of non-sugical abortion. Although the Programme has not provided support for research on the termination of second tri- mester pregnancies, it provides I I >%,:~ _,'~',<r'_; technical advice as well as mifepristone and placebo tablets for some of the studies. One com- pleted study involved the use of mifepristone to prime the cervix prior to induction of abortion with different prostaglandin regimens. The aim was to find a way of reducing the long and painful process of abortion at this stage of pregnancy. The study involved 98 women who were given a 200mg dose of mifepristone followed by oral or vaginal administration of misoprostol every three hours up to a maximum of five doses. Among those given misoprostol vaginally, the average time in- volved in achieving abortion was nine hours and 90% of the women aborted within 24 hours. The cor- responding figu res forthose given oral misoprostol were 13 hours and 69%. Although the vaginal route was more effective, most women preferred the oral route. A follow-up study will examine whether effectiveness of adminis- tration could be improved by in- creasing the dose of misoprostol. Meanwhile, the Programme is also supporting a study investi- gating the use of misoprostol as a preoperative treatment for soften- ing and dilating the cervix before a surgical abortion is carried out by vacuum aspiration. In order to determine the lowest effective dose of misoprostol and the short- est time interval needed before surgery, different doses of misoprostol, administered orally or vaginally, are being assessed. The study, involving 225 women with pregnancies of 8-12 weeks' duration, is due to be completed by mid-1998. Bienn ial Report 1996-1997 Three-monthly injectable for men At present, men have access to only three forms of contracep- tion-thecondom, withdrawal,and vasectomy. To increase the choice available, the Programme is sup- porting research on the develop- ment of a prototype hormonal con- traceptive for men. The new prod- uct is a combination of two syn- thetically produced hormones-a progestogen (Ievonorgestrel butanoate) and an androgen (tes- tosterone buciclate). The new contraceptive, which is being de- veloped in collaboration with the US National Institutes of Health (NIH) and the Contraceptive Re- search and Development Program (CONRAD), acts by stopping the production of sperm in the testes. The aim is to reduce the amount of sperm in semen to very low or undetectable levels. The method would involve three-monthly in- jections and the contraceptive ef- fectwouldendwithinafewmonths after the injections were discon- tinued. In recent multicentre trials, a similar product that involved weekly injections was rated as highly acceptable by the men in- volved-although many ex- pressed interest in a longer-last- ing contraceptive that would re- quire fewer injections. In the two- year study using weekly injec- tions of testosterone enantate (a synthetic derivative of the male hormone testosterone), the method was found to be 98.6% effective-at par with the effec- tiveness of hormonal methods for women, including oral contracep- tives. When the injections were stopped, the average times taken for men to return to normal fertile -:3' . ·''------------------------------ Biennial Report 1996-1997 levels of sperm production, or to reach pre-treatment levels, were 112 and 201 days, respectively. And all ofthe 33 babies so far born to couples who had taken part in the study, were healthy and of normal weight. The four-continent trials involved over 399 couples aged 21-45from9 countries. Most had volunteered because of dis- satisfaction with existing forms of male and female contraception. However, the use of testoster- one alone has two major draw- backs: the frequency of injections needed to maintain suppression of sperm production and the un- predictable effect of raised levels of testosterone on behaviour and prostate changes over time. Be- cause of this, the Programme is supporting the use of a combina- tion comprising a progestogen (levonorgestrel butanoate) to sup- press sperm production, together with a smaller dosage of testo- sterone (testosterone buciclate) to ensure maintenance of normal levels of testosterone. Although preliminary small- scale trials with testosterone buciclate were promising, the start of clinical trials of the combined product has been delayed be- cause of production problems. It was discovered that, in its current microcrystalline form, the testo- sterone buciclate clumps together and adheres to the side of the glass vial. The solution is difficult to resuspend and there is a 10% reduction in the concentration. An additional concern is that the for- mation of small particles could clog up syringes and alter the intended duration of effect. Simi- lar problems have also been en- countered in the formulation of levonorgestrel butanoate. During the past year ,24 prepa- rations-involving different con- centrations of testosterone buciclate and types and levels of flocculating agents-have been developed and stored at different temperatures in Hypack syringes. The main modification has been the addition of a flocculating agent to maintain the dispersal of the steroid microcrystals and avoid clumping. Preliminary results indi- cate that all the test preparations can be readily suspended and easily expelled from the syringe. Although the least concentrated suspension had the best flow characteristics, a concentration higher than previously thought possible appears to be stable and can be readily expelled from the syringe. Once the reformulated prod- uct is ready, preclinical studies and clinical trials will be resumed. While the clinical trials are under way, studies involving both male volunteers and their partners will be carried out to assess the ac- ceptability of this new form of con- traception. In the meantime, discussions are under way with industry to ensure the continued development and eventual manufacture of the three-monthly injectable for men, and guarantee its availability at low cost to the public sector in developing countries. Non-surgical reversible vasec- tomy Although about 40-50 million couples today have opted to use vasectomy as their preferred method of contraception, chang- ing family circumstances prompt I I z w o .Z <t Z <t I >- aJ g o I CL o I 3: many to seek a reversal of the procedure. But reversal involves skilled microsurgery and fertility is successfully restored in only about 30%-40% of cases. An added deterrent for many men is the surgical intervention and perceived discomfort involved in undergoing a vasectomy. Al- though the availability today of less-invasive "no-scalpel" vasec- tomy is encouraging an increas- ing number of men to opt for this form of permanent contraception, there is a need for a non-surgical and a more easily reversible method of sterilization for men who want a long-lasting method of contraception. The new sterilization tech- nique-developed in the Nether- lands-involves the injection of liquid silicone to block the two ducts (vasa deferentia) that carry sperm from the testes. The liquid silicone contains a hardener which enables it to set quickly and form a tight seal or plug within the vas deferens-thereby blocking the passage of sperm from the testes. The plug can stay in place indefi- Biennial Report 1996-1997 nitely or be removed by a minor incision. Programme-supported Phase I trials carried out in China and Indonesia overthe past 6-7 years provided encouraging preliminary data on the effectiveness of the silicone plug method. However, they also highlighted the need to determine the exact volume of liquid silicone needed and the cor- rect injection pressure required to ensure that the sperm ducts were securely sealed off. Ifthe injection pressure is too low, the liquid may not be in contact with the interior wall of the duct before the plug forms-leaving gaps through which sperm can pass. But if the injection pressure is too great, this can cause a small tear in the side of the duct, some leakage of sperm, and the formation of scar tissue. During 1995 and 1996, the New York-based AVSC International and the manufacturer carried out Phase I trials in the Netherlands to assess the effectiveness and any complications associated with the silicone plug method. The study Biennial Report 1996-1997 involved 74 men who had re- quested vasectomy-49 using the silicone plug method and a control group of 25 who underwent rou- tine vasectomies. This study was halted after follow-up sperm- counts revealed that, although all the men with silicone plugs had reduced sperm counts, only 5%- 10% had undetectable levels of sperm in their semen (Le. were azoospermic). However, there was less incidence of leakage of sperm through the outer wall of the duct than in the earlier trials carried out in Indonesia. These findings suggest that a slightly larger volume of silicone may be needed and possibly a greater injection pressure. Other possible adaptations could include reducing the viscosity of the sili- cone to make it more fluid and quickerto disperse before setting. During 1997 the Programme did not support any research on the silicone plug method. How- ever, if an improved injection pro- cedure is developed and future company-funded studies produce promising results, the Programme may consider supporting further trials in developing countries. A consultation meeting will be held during the first half of 1998 to review the available data. In the meantime, a Memorandum of Un- derstanding has been agreed with the manufacturer to ensure that, if it proves successful, the even- tual product will be made avail- able at the lowest possible price to the public sector in develop- ing countries. The Programme has also con- tinued to fund two long-term fol- low-up studies in China on the efficacy and reversibility of two other methods of vas occlusion. One study involved an assess- ment of return to fertility among 56 men who had undergone micro- surgery to reverse a vasectomy, and a further 75 men who had undergone removal of vas occlud- ing medical-grade polyurethane (MPU) plugs. During the three- year follow-up after the reversals, all the men in both groups had sperm in their semen and there was no significant difference be- tween the concentration of sperm after one month. However, from three months onward, the sperm concentration was significantly higher in the plug-removal group. The pregnancy rate was almost 99% in the plug-removal group, compared with 66% in the micro- surgery group. Also in China, the Programme continued to support a prospec- tive 10-centre study to compare the effectiveness of reversal of three methods of vasectomy, us- ing microsurgery: no-scalpel va- sectomy; vas occlusion with methyl cyanoacrylate (MCA); and vas occlusion with medical-grade polyurethane (MPU) plugs. The reversal was found to be easiest in the no-scalpel group and most difficult in the MCA group, as a result of morphological changes induced in the vas. The highest concentration of sperm and the largest number of pregnancies occurred among the no-scalpel group, followed by the MCA plug- removal group, and the MPU plug -removal group. Medium-priority leads Hormone-releasing vaginal ring In response to women's ex-pressed need for long-acting, effective methods of contracep- tion which are under their own control, the Programme is con- tinuing to support the develop- ment of a hormone-releasing vagi- nal ring. Following collaboration with in- dustry in testing a series of differ- ent progestogens released from vaginal rings, a prototype ring re- leasing a small daily dosage of levonorgestrel was selected for development. In 1990, after the completion of tests for safety, ef- ficacy, and acceptability, the Pro- gramme concluded a licensing agreement with a company based in the United Kingdom for the manufacture and distribution of the product. However, following reports of vaginal lesions among women involved in Phase III clini- cal trials, it was decided to rede- sign the ring into a thinner, more flexible device that would exert less pressure on the vaginal wall. Results from a subsequent multicentre trial of a redesigned placebo ring suggest that the ring does not produce lesions and that it would be suitable for future de- velopment. In 1997, the company to which the ring was licensed decided to withdraw from the project and fo- cus instead on the development of a combined contraceptive ring releasing a progestogen and an estrogen. As a result, negotia- tions have been initiated for the return of the licence to the Pro- gramme. Because of concern at the lim- ited efficacy of the current dosage of levonorgestrel-especially for heavier women-the Programme is now considering to develop a new, higher-dose version of the Biennial Report 1996-1997 redesigned vaginal ring in collabo- ration with CONRAD. Natural family planning Although surveys indicate that the rhythm or calendar method is the most extenSively used method of natural family planning world- wide, there has been little or no scientific evaluation of any of the suggested calendar-based rules for determining the period of absti- nence. The Programme is collaborat- ing with the Institute for Repro- ductive Health (I RH) at Georgetown University in the USA in studies to determine how cou- ples identify the fertile period. The studies reveal key differences in knowledge of how to use the method between people in devel- oping countries and elsewhere. In Peru, the Philippines, and Sri Lanka the women interviewed had generally been taught about the method by a relative or friend and had only a limited understand- ing of how it worked. Some tried to increase the reliability of the method by extending the period of abstinence-sometimes inappro- priately. There was a strong de- mand among these users for in- formation and counselling on the calendar-based rules. Their rea- sons for choosing this method of contraception included its low cost, availability, and freedom from side- effects. On the other hand, in Hungary, all those interviewed re- ported the appropriate use of a combination of cervical mucus observations, body temperature monitoring, and/or use of the cal- endar method. Couples reported having chosen the method after experiencing side-effects from Biennial Report 1996-1997 other contraceptive methods and said they considered it a healthier and more natural method. They appreciated the closeness thatthe method encouraged between sexual partners as well as the freedom of sexual expression dur- ing the non-fertile period. During 1998-1999, the Pro- gramme intends to collaborate with IRH in supporting a multicentre trial to assess the effi- cacy and acceptability of a simpli- fied calendar method. Lactational amenorrhoea method Since 1984 the Programme has supported research on the contraceptive effect of breast- feeding. The aim is to determine the duration of infertility, the indi- cators for the end of infertility, and the mechanism involved in sup- pression of the ovaries during the breast-feeding period. The infor- mation will especially benefit women who have no other means of contraception as well as coun- tries with limited resourcesforfam- ily planning. In 1988, a group of interna- tional scientists meeting in Bellagio, Italy, issued a consen- sus statement on the effect of breast-feeding on fertility. In what became known as the Bellagio Consensus, they concluded that women who are fully or almost fully breast-feeding and amenor- rhoeic have a less than two per cent risk of becoming pregnant during the first six months after delivery. Guidelines issued in 1989 pOint out that, once women no longer meet all three criteria, they should adopt another family plan- ning method if they wish to avoid pregnancy. In December 1995, a second Bellagio conference confirmed the earlierfindings and concluded that it may be possible to reduce the criteria without comprising the ef- fectiveness of the method. While amenorrhoea remains a key re- quirement for ensuring low risk of pregnancy, it may be possible to relax the requirement of full or almost full breast-feeding and to extend the duration of use beyond six months. Additional research is now needed to establish the condi- tions under which the modified requirements can be adopted. However, funds for this area of research have deciined-despite the revived interest in breast-feed- ing in many countries as a result of the UNICEF/wHO baby-friendly hospital initiative. No new research was initiated by the Programme during the 1996-1997 biennium and no further studies are planned during the 1998-1999 biennium. Low-priority leads Estrogen-free oral contraceptives The most common reasons I for discontinuation of com- bined oral contraceptives are hor- monal side-effects-mainly due to the estrogen component in the pills-and the fear of long-term adverse effects such as the risk of cardiovascular complications or breast cancer. The emergence of antiprogestogens, which interfere with the normal development of maturing follicles in the ovaries, has opened the way for develop- ment of a new type of estrogen- free sequential pill. The replace- ment of estrogen by an antiprogestogen would avoid the estrogen-induced side-effects and I possibly lower the risk of certain types of cancer. To investigate the feasibility of this approach, the Programme has carried out a study involving the use of 5 mg of mifepristone during the first 15 days of the menstrual cycle, followed by 10 mg of med roxyprogesterone acetate (MPA) up to the 28th day of the cycle. The study, involving 10 steri- lized women volunteers overthree menstrual cycles, found that men- struation was fairly regular and that 50% of the women did not OVUlate during the three cycles. Endometrial biopsies taken dur- ing the third menstrual cycle showed eitherdelayed or irregular development. Levonorgestrel-releasing IUD Previous studies have demon- strated that IUDs that release a regular dosage of a progestogen are effective in preventing preg- nancy and in reducing menstrual blood loss. However, a major draw- back of these IUDs was their short life span (12-18 months) which is too short for most family planning programmes. Biennial Report 1996-1997 A higher-dose levonorgestrel- releasing IUD, developed with sup- port from The Population Council, was found to have a pregnancy rate of 1.1 per 100 woman-years after five years. However, by then, one in five users had discontinued the method because of persistent amenorrhoea. Between 1993 and 1997, the Programme launched a series of studies, involving over 3000 women in 20 centres, to compare the use of a copper IUD (TCu380A) and the higher-dose levonor- gestrel-releasing IUD. Initial find- ings show that, while failure rates were almost identical after three years, use of the levonorgestrel- releasing IUD resulted in signifi- cantly higher rates of removal for medical reasons, bleeding (with or without pain), amenorrhoea, and hormone-related reasons. By the third year, there were only two removals for amenorrhoea for the TCu380A device compared to 146 for the levonorgestrel-releasing IUD. These comparative studies will continue throughoutthe 1998- 1999 biennium. Expanding famUy planning options Highlights • The Programme continu",s to play a major role within the interagency Consortium on Emergency Contraception, providing technical input to ensure the availability of emergency contraception in developing countries. In its efforts to introduce emergency contraception, the Consortium has adopted the strategic approach developed by the Programme. The aim is to ensure that the new method is introduced within a broad range of contraceptive methods and not promoted as a primary method of contraception. Emergency contraception was first used in the 1960s, but it is not yet widely known or available. Wider use of this method could prevent millions of unwanted pregnancies and abortions. • In support of efforts to introduce the female condom in developing countries, the Programme is coordinating a female condom working group, in collaboration with WHO's Division of Reproductive Health (Technical Support) and the Joint United Nations Programme on HIVlAIDS (UNAIDS). The working groulp has produced information materials, initiated research, and provided assistance in making the product available. An information pack has been produced for policy- makers, programme managers, and others involved in reproductive health care. The female condom is a woman-controlled method and the only contraceptive for women that can protect against both pregnancy and sexually transmitted diseases (STDs). However, the method-like emergency contraception-;-is virtually unknown to both providers and potential users. Its use in developing countries shoulo help to prevent the transmission of STDs (including HIV) and pregnancy. • Work has continued on making Cyclofem and Mesigyna-the once-a-month injectables devel- oped by the Programme-available to developing countries. The Concept Foundation-a Bang- kok-based non-governmental organization committed to making reproductive health technology available to developing countries-has closely monitored the quality of Cyclofem produced in Indonesia and Mexico, and obtained registration of the product in 15 countries. An application has been made in the USA for registration of Cyclofem and registration in the European Union is also being sought. Registration of Cyclofem irn the USA would allow it to be distributed in developing countries by the US Agency for International Development (USAID). I (/) z o t o The strategic approach used to increase contra-ceptive choice by ensur- ing a mix of existing methods (see Chapter on Assessing an improv- ing reproductive health services) is also being applied for methods which are new or unknown to po- tential users and providers. The aim is to establish awareness of the availability of new methods within the existing mix of meth- ods. Initial trials are focusing on two methods: emergency contra- ception and the female condom. Emergency contraception Emergency contraception-in-volving the use of a high dose of estrogen-was first used in the 1960s to prevent pregnancy in rape victims. In the early 1980s the high-dose estrogen treatment was replaced by a modified regi- men of combined oral contracep- tive pills known as the Yuzpe regimen after its inventors. Since then emergency contraception has been used by women in the event of unprotected intercourse or recognized contraceptive fail- ure. However, emergency contra- ception is not yet widely known or available. Wider use of this method 'The member organizations of the Consortium are: The Concept Foundation (Bangkok), the Interna- tional Planned Parenthood Federa- tion (London), the Pacific Institute for Women's Health (Los Angeles), Pathfinder International (Boston), The Population Council (New York), the Program for Appropriate Tech- nology in Health (Seattle), and the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Train- ing in Human Reproduction (Ge- neva). Biennial Report 1996-1997 could prevent millions of unwanted pregnancies and abortions. The Programme continues to play a major role within the inter- agency Consortium on Emer- gency Contraception 1, providing technical inputto ensure the avail- ability of emergency contracep- tion in developing countries. In its efforts to introduce emergency contraception, the Consortium has adopted the strategic approach developed by the Programme. The aim is to ensure that the new method is introduced within a broad range of contraceptive meth- ods and not promoted as a pri- mary method of contraception. Careful planning is essential to ensure that the public, including religious and political leaders, are aware that this method is not a form of abortion. Emergency con- traception should be available in the event of contraceptive failure and promoted as a bridge to other contraceptive services, especially for young people. In addition, it should be readily available on de- mand for those who need it. Preliminary studies are focus- ing on user perspectives on con- traceptive methods and service delivery, and determine what changes are needed in both serv- ice delivery and management to provide quality emergency con- traception services. The Consor- tium is currently focusing on the introduction and availability of the emergency contraceptive Postinor-2, comprising two 750 mcg tablets of levonorgestrel, available in a blister pack. The Programme and The Population Council are the lead agencies for the research and evaluation involved in the studies Biennial Report 1996-1997 on the introduction of emergency contraception in Indonesia and Sri Lanka (the Programme) and in Kenya and Mexico (The Popula- tion Council). Initial assessments carried out in Indonesia and Sri Lanka in early 1997 revealed little or no awareness of emergency contraception as well as many misconceptions about the method. These findings were used in the design of introductory studies, in- formation materials, and training for providers. Limited service pro- vision of Postinor-2 began in both countries in 1997. In Sri Lanka, where an emergency contracep- tion hotline was set up, demand has been Significant, while in In- donesia there has been only a small uptake so far. An evaluation of the provision and uptake of Postinor-2 in both countries will be carried out in late 1998. Introductory studies are also due to begin in Pakistan and Tan- zania in 1998. Elsewhere, the Yuzpe method of emergency con- traception is being introduced in South Africa and Zambia. The Consortium, which was established in late 1995, has pro- duced a package of information and advocacy materials, includ- ing service delivery guidelines, a framework for introduction, as well as information material for clients, providers, and decision-makers. A model training curriculum is also available. The female condom The female condom is a woman-controlled method and the only contraceptive for women that can protect against both pregnancy and sexually transmitted diseases (STDs). However, the method-like emer- gency contraception-is virtually unknown to both providers and potential users. Acceptability studies carried out in several countries have Biennial Report 1996-1997 (f) shown that the method is accept- make the female condom more z 0 i= able to some women and men, widely available, UI\IAIDS and CL 0 including first-time family planning WHO have negotiated a public users. The method would also be sector price of about US$ 0.60 suitable for women at high risk of and are continuing to monitor cost- contracting ortransmitting H IV and related issues. other STDs and for those seeking alternative contraceptive methods. Monthly injectable In support of efforts to intro- contraceptives duce the female condom, the Pro- I njectable contraceptives have gramme is coordinating a female been in use for over 20 years condom working group, in col- and are now used by about 15 laboration with WHO's Division of million women worldwide. The Reproductive Health (Technical most widely used products are Support) (RHT) and the Joint DMPA (depot-medroxyproges- United Nations Programme on terone acetate) which provides HIV/AIDS (UNAIDS). The work- contraceptive protection for three ing group has produced informa- months after a single injection, tion materials, initiated research, and NET-EN (norethisterone and provided assistance in mak- enantate) which protects for two ing the product available. An in- months. Although these methods formation pack has been produced are highly effective, the pro- for policy-makers, programme gestogen content causes irregu- managers, and others involved in lar menstrual bleeding-a factor reproductive health care. Mean- that has limited their more wide- while, the working group is con- spread use. tinuing to review information on In efforts to provide a suitable the use of the female condom as alternative, the Programme has well as the outcome of research developed two injectable products studies. Guidelinesforprogramme for use on a monthly basis: managers on the introduction of Cyclofem and Mesigyna. Both this method are now being devel- products contain an estrogen as oped. well as a progestogen, thus en- The Programme is also sup- suring a regular monthly bleeding porting research on the contra- pattern for most women who use ceptive efficacy and acceptability them. of the female condom. Pro- Over the past two years, work gramme-supported studies are has continued on making once-a- also under way in South Africa to month injectables available to de- determine whetherthe female con- veloping countries. The Concept dom can be safely re-used. It is Foundation-a Bangkok-based antiCipated that, because of its non-governmental organization relatively high price, the product committed to making reproduc- will be used more than once. If the tive health technology available to studies show this to be safe and developing countries-has closely viable, guidelines will be devel- monitored the quality of Cyclofem oped for the safe re-use of the produced in I ndonesia and Mexico, product. Meanwhile, in an effort to and obtained registration of the I Biennial Report 1996-1997 product in 15 countries. In Mexico, production of Cyclofem in a non- reusable syringe (Uniject) has been delayed and is now due to begin in the second half of 1998. In the USA, an application has been made for registration of the product with the US Food and Drug Administration (FDA), which would allow distribution by the US Agency for International Develop- ment (USAI D). Registration in the European Union is also being sought. Mesigyna is available in the private sector in Latin America and the manufacturer is now plan- ning to make it available in Paki- stan. I Evaluating reproductive health care Highlights • A WHO Scientific Group reviewed the results ofthe Programme's study as well as other studies on the effect of the use of hormonal contraceptives and other risk factors on the risk of cardiovascular disease and whether the risk of cardiovascular disease varies between different compositions of combined oral contraceptives. The Group concluded that for women of reproduc- tive age the overall incidence and death rate from cardiovascular disease is very low, and that any heightened risk for women who use oral contraceptives is very small if they do not smoke or have other cardiovascular risk factors. However, the risk of heart attack and stroke among women who smoke or have high blood pressure is further increased by the use of combined oral contraceptives. This expert opinion has important implications forthe use and prescription of hormonal contraceptives. • A study has found that the use of depot-medroxyprogesterone acetate (DMPA) has a strong protective effect against uterine myoma. The protective effect appears to last for more than 10 years after the last DMPA injection. The over 12 million users of DMPA and past users will find these results reassuring. • A study is under way to determine the effect of oral contraceptives on women with a history of gestational diabetes (diabetes during pregnancy). Another study is examining the relationship between the use of hormonal contraceptives and bone mass. The use of oral contraceptives can lead to changes in blood sugar levels as well as in the level of insulin and glucose in the body. The study will provide new knowledge on the safety of oral contraceptives for women who had impaired glucose tolerance during a previous pregnancy. Osteoporosis affects an estimated 75 million people in Europe, Japan, and the USA, including one in three postmenopausal women and most elderly people. The study on bone mass in users of oral contraceptives will contribute new knowledge about the safety of hormonal contraceptives. • Data collection for a major five-year collaborative study involving post-marketing surveillance of women using the contraceptive implant Norplant was completed in 1997. The aim was to discover any major short- or medium-term side-effcts that may not have been identified in clinical trials. This study will provide information on the safety of Norplant under normal conditions of use. • To assess the feasibility of carrying out a study of the possible effects of non-surgical abortion on future births, surveys were carried out in Beijing, Chengdu, and Shanghai on the prevalence of previous non-surgical abortions among pregnant women attending antenatal clinics. The preva- lence was found to be almost 10% in Beijing, over 17% in Chengdu, and 3% in Shanghai. The main study will begin in these cities during 1998. This study will provide information on the effect of non-surgical abortion on the outcome of subsequent pregnancies. • Analysis of data from the WHO Collaborative Study on Neoplasia and Steroid Contraception has provided reassuring evidence that the risk of endometrial cancer is not increased by use of the intrauterine device (IUD). These findings were not affected by the duration of use or by the age of the user when the device was inserted or removed. Over 110 million women use the IU D for contraception. This finding further strengthens the knowledge on the safety of copper-bearing modern IUDs. • A study-the first of its kind-is being conducted to determine the effect of steroid hormone contraceptives on the progression of HIV infection. The study will include two groups of women who are HIV-positive but have not yet developed AIDS: women using steroid hormone contracep- tives, and those using non-hormonal methods of contraception. The findings from this study are expected to have major implications for the care and family planning practice of HIV-positive women. Biennial Report 1996-1997 • A study was launched to determine whether the use of hormonal contraceptives by HIV-positive women increases the amount of HIV shed in the lower genital tract. Another study is examining whether the use of hormonal contraceptives leads to thinning of the lining of the vagina and whether this affects local immunity and modifies susceptibility to HIV and other sexually transmitted infections. The findings of the first study will have important implications for prescription of hormonal contraceptives to HIV-positive women. The second study will provide the basic physiological information needed to understand the relationship between the use of hormonal contraceptives and transmission of STDs (including HIV). • Recruitment is nearing completion for the first multicentre trial to evaluate the impact of a new antenatal care programme on the health of mothers and newborns. The new programme consists of four antenatal visits, and it limits antenatal tests, clinical procedures, and follow-up actions to those scientifically proved to be effective in improving the health of mothers and newborns. This study is expected to have major implications for optimizing the use of resources in reproductive health care services. • A multicentre trial of misoprostol was launched to evaluate the drug's effectiveness when used to reduce blood loss during the third stage of labour. The study, involving 20000 women in nine countries, will compare rates of severe postpartum haemorrhage among women given oral misoprostol and those given injected oxytocics. If misoprostol is found to be effective, this is expected to lead to large-scale trials of the prostaglandin in rural areas where medically trained staff are not available. • The Programme is planning to conduct a series of studies on the prevalence of genital tract infections in selected populations and epidemiological studies on lower genital tract infection and the effect of male chlamydial infection on sperm function. These studies are important because there is little information available on the prevalence of STDs in developing countries. Moreover, most available information is based on limited data from selected samples involving high-risk groups in geographically disparate regions. I Steroid hormone contracep- tives and the risk of cardiovas- cular disease The main work has now been completed on a WHO collaborative study to determine whether the use of steroid hormone contraceptives increases the risk of cardiovascu- lar disease (heart attack, strokes, and venous thromboembolism). Currently used, low-dose com- bined oral contraceptives (con- taining an estrogen and a pro- gestogen) were developed after the earlier generation of higher dose combined pills used in the 1960s and 1970s was found to increase the risk of cardiovascu- lar diseases. By 1985, combined pills contained a third less estrogen and a tenth of the progestogen dose of the pills in use in the 1960s. In addition, some of the current brands contain newer progestogens. The introduction of low-dose pills led to an apparent reduction in the risks associated with the earlier combined pills. But the in- formation was based almost ex- clusively on data from developed countries and it was unclear to what extent otherfactors may have contributed to this. The aim of the WHO study was to examine the risk from cur- rently available oral contracep- tives and to assess to what extent the apparently lower risk was as- sociated with: • more careful screening by doc- tors to avoid use of the pills by women at risk of cardiovascular disease • improved diagnosis for these diseases • the new pill formulations. Biennial Report 1996-1997 An additional objective was to assess the risk of cardiovascular disease associated with pro- gestogen-only contraceptives. The study, involving almost 3800 women under the age of 45 years with cardiovascular dis- ease and a control group of 11 200 women, was carried out in 17 countries in Africa, Asia, Europe, and Latin America. The study, which was coordinated by the Department of Epidemiology and Public Health, University College Medical School, London, was the first of its kind to focus mainly on women in developing countries. The findings relating to venous thromboembolism were published in 1995, those on stroke in 1996, and the findings on heart attacks in 1997. The results relating to cardiovascular risk and the use of other hormonal methods, includ- ing progestogen-only pills and injectables, and combined injectables, are due to be pub- lished in the journal Contracep- tion. In November 1997, WHO con- vened a Scientific Group Meeting on Cardiovascular Disease and Steroid Hormone Contraception to review the results of the WHO study and other available scien- tific data on: • the overall incidence of cardio- vascular disease among women of reproductive age • the impact of the use of hormo- nal contraceptives and other risk factors (including high blood pres- sure, diabetes, and smoking) on the risk of cardiovascular disease • whether the risk of cardiovas- cular disease varies between dif- ferent compositions of combined oral contraceptives. Biennial Report 1996-1997 The Scientific Group con- cluded that for women of repro- ductive age the overall incidence and death rate from cardiovas- cular disease are very low, and that any heightened risk for women who use oral contraceptives is very small if they do not smoke or have other cardiovascular risk factors. However, the risk of heart attack and stroke among women who smoke or have high blood pressure is further in- creased by the use of combined oral contraceptives. The Scientific Group also as- sessed the possible links be- tween the use of oral contracep- tives and specific forms of car- diovascular disease: Heart attack For women with no risk factors for cardiovascular disease, there is no increase in the relative risk of heart attack, regardless of age. Nor is there any increased risk for former users of combined oral contraceptives. Ischaemic stroke (involving a blood clot or restricted blood flow) Forwomen with no risk factors for cardiovascular disease, the risk of ischaemic stroke is increased by about 1 .5-fold. The level of risk does not increase with prolonged use of oral contraceptives, and there is no increased risk for women who had used oral con- traceptives in the past. Haemorrhagic stroke (involving a burst blood vessel) For women under 35 who are non-smokers and do not suffer from hypertension, the use of oral contraceptives does not in- crease the risk of haemorrhagic stroke, regardless of the duration of use.And there is no increased risk for past users. However, there is a 2-fold increase in risk among users of oral contraceptives who are over age 35. Venous thromboembolism While current users of com- bined oral contraceptives have a low absolute risk of venous throm- boembolism, it is 3-6 times higher than that of non-users. The risk is probably greatest in the first year of use. Although the risk declines with continued use, it persists until discontinuation. Formulations con- taining desogestrel and gestodene probably carry a small increased risk of venous thromboembolism beyond that attributable to for- mulations containing levo- norgestrel. The IUD and endometrial cancer Analysis of the large amount of data from the WHO Col- laborative Study on Neoplasia and Steroid Contraception has pro- vided reassuring evidencethatthe risk of endometrial cancer is not increased by use of an intrauter- ine device (IUD). These findings were not affected by the duration of use or by the age of the user when the device was inserted or removed. DMPA and uterine myoma A hospital-based study involv-ing over 3500 women in Thailand has been assessing the relationship between the use of the 3-monthly injectable contra- ceptive depot-medroxyproges- terone acetate (DMPA)-used by I about 12 million women world- wide-and the development of uterine myoma. The study found that the use of DM PA had a strong protective effect against uterine myoma (fibroids) and that it was even greater for women who had used DMPA for longer than five years. The study also found that the protective effect lasts for more than 10 years after the last DMPA injection. The authors of the study estimated that the number of sur- gical interventions for uterine myoma would have been 7% higher without the current level of DMPA use in Thailand. An unexpected finding of this study was that the risk of uterine myoma was higher among women who had been sterilized using the tubal ligation method. Oral contraceptives and diabetes The Programme is supporting a study in Venezuela to de- termine the effect of oral contra- ceptives on women with a history of diabetes during pregnancy. The use of oral contraceptives can lead to changes in the blood sugar level as well as in the levels of insulin and glucagon in the body. The study compares carbohydrate metabolism in women using a standard oral contraceptive con- taining ethinylestradiol and levonorgestrel and in those using non-hormonal contraceptive meth- ods. Data collection is expected to be completed by the end of 1998. Hormonal contraceptives and bone density AstudY on the relationship between the use of hormo- Biennial Report 1996-1997 nal contraceptives and bone den- sity is now nearing completion. Loss of bone mass leads to devel- opment of osteoporosis, com- monly known as "brittle bone dis- ease". Osteoporosis affects an estimated 75 million people in Europe, Japan, and the USA, in- cluding one in three postmeno- pausal women and most elderly people. The disease is rare in Africa, common in India, and oc- curs most frequently in Europe and North America. Osteoporosis and associated fractures are a major cause of Sickness, death, and medical expense worldwide. The study was carried out in seven centres in Bangladesh, Bra- zil, China, Egypt, Mexico, Thai- land, and Zimbabwe and involved over 2500 women aged 30-34. Bone mass was compared be- tween women who had used hor- monal contraceptive methods for at least 24 months and a control group of women with no or less than six months' experience of using hormonal methods. The data are now being analysed. Post-marketing surveillance of Norplant Data collection for a major collaborative study involving post-marketing surveillance of women using the contraceptive implant Norplant was completed in 1997. The study, which was carried out by Family Health Inter- national. The Population Council, and the Programme, involved over 16 000 women in 32 family plan- ning clinics in eight developing countries. The aim was to discover any major, short- or medium-term side- effcts that may not have been I Biennial Report 1996-1997 identified in clinical trials. The study compared rates of complications and disease among Norplant us- ers with those for women who chose an IUD or sterilization. The women were followed up for five years, even if they switched to another contraceptive method. The overall follow-up rate was over 96%-far higher than expected. The study was coordinated by the Programme, which supported the studies in Egypt, Indonesia, Sri Lanka, and Thailand. Partici- pating centres in Bangladesh were supported by Family Health International, while The Popula- tion Council supported those in China and Colombia. The findings of the study were reported at a meeting at the Washington DC- based Institute of Medicine and at the XV FIGO World Congress of Gynecology and Obstetrics in Den- mark. Further analysis of the re- sults is now under way. Safety and efficacy of intrauterine devices (IUDs) Aseries of major studies on the safety and efficacy of IUDs has produced a mass of data of key importance for family planning services and women. The I U D is currently used by about 11 0 million women-mainly in devel- oping countries. It is the second most widely used form of contra- ception after sterilization. The multicentre studies, launched by the Programme be- tween 1978 and 1982, focused on three copper IUDs-TCu220C, TCu380A, and the Multiload- which were at that time being introduced into family planning programmes in developing coun- tries. The results of the studies on the use of TCu220C and TCu380A by women at 9,11, and 13 years were published in 1997. The preg- nancy rate for women using the TCu380A was significantly lower at every stage than for those us- ing the TCu220C. However, after 11 and 13 years of use, the TCu220C had a significantly lower rate of removal due to pain, bleed- ing, or both. For both devices, most removals after 11 years WHO PHOTO BY CARLOS GAGGERO were for non-medical reasons. After 13 years, 51% of women using the TCu220C and 57% of those using the TCu380A had stopped using it for non-medical reasons. The most frequently cited reasons were the intention to be- come pregnant and "no further need". Pregnancy rates for both devices were consistently higher, for unknown reasons, in the Chi- nese participating centres than in non-Chinese centres. Meanwhile, another ongoing multicentre study, involving over 3500 women in eight countries, is comparing the safety and efficacy ofthe Multiload 375 and TCu380A devices. Results after seven years show that women using the Multiload 375 had higher rates of pregnancy and expulsion than those using the TCu380A. The difference in the rate of pregnancy is seen after two years but only becomes significant after four years. In this study, the data from the Chinese centres involved does not vary from the findings else- where. Condoms Contraceptive efficacyofcondoms Although studies have con-firmed that the use of con- doms is effective in preventing transmission of sexually transmit- ted diseases (STDs), including HIV/AIDS, findings on their con- traceptive efficacy have shown wide variations. It is believed that most failures are the result of in- correct use rather than method failure. The Programme is supporting a study in two centres in China to determine the comparative effec- tiveness (of both the method and Biennial Report 1996-1997 its use) between using the con- dom alone and using the condom together with hormonal emer- gency contraception. The study is due to be completed by late 1998. Non-latex and standard latex male condoms New non-latex male condoms have now been developed which have a longer shelf-life than stand- ard latex condoms and may be more acceptable to users. How- ever, acceptability has only been evaluated so far among couples using other forms of contracep- tion, and there is little information on the relative effectiveness of the two kinds of condoms in prevent- ing pregnancy. A new comparative research study will examine pregnancy rates among 3000 volunteers from sev- eral countries using two types of non-latex condoms and standard latex condoms. Volunteers will be asked to keep a diary, recording acts of sexual intercourse and details of condom usage over a six-month period-enabling re- searchers to distinguish between user and method effective-ness. In addition, continuation rates for all three types of condom will be examined. The study will also determine breakage and slippage rates for the three types of condom and assess whether this can be used to simplify premarketing testing of new condoms for approval by regulatory authorities. vasectomy and prostate cancer Although most studies have shown that vasectomy is a safe contraceptive method with I I Biennial Report 1996-1997 no adverse consequences for health, two studies from the USA in 1993 suggested that 20 years after vasectomy there was an in- creased risk of developing pros- tate cancer. While other studies fromtheUSAandtheUnited King- dom did not support these find- ings, recently published work from China and India also indicates an elevated risk of prostate cancer in men who have undergone vasec- tomy. In view of these conflicting findings, the Programme launched a hospital-based study in China, Nepal, and the Repub- lic of Korea-countries where vasectomy is widely used. The study included over 400 men with prostate cancer, and a con- trol group of over 1200 men with- out the disease. Data collection has now been completed in all three countries and analysis is due to start in early 1998. The Programme has also provided technical assistance to the In- dian Council of Medical Re- search, New Delhi, India, to fa- cilitate a similar multi-centre study in India, and is also sup- porting a multicentre study in New Zealand. Abortion Unsafe abortions WHO estimates that 20 mil-lion unsafe abortions are carried out every year-95% of them in developing countries. In an effort to dete rm ine the extent of complications and deaths arising from unsafe abortions, and the health care costs involved, the Programme launched a series of hospital-based studies in nine countries where access to safe abortion is limited. The studies, carried out in Bangladesh, Benin, Brazil, Chile, Ethiopia, Guatemala, Senegal, Thailand, and Uganda, have highlighted the severe con- sequences (including death) of unsafe abortions for women's health (see also page 14). Impact of induced abortion on fu- ture pregnancies Since many women who ter- minate an unwanted pregnancy intend to have a child at a later date, it is important to establish whether induced abortion will have any adverse effects on a future pregnancy. An abortion performed by skilled personnel and carried out by vacuum aspiration during the first three months of pregnancy has been amply demonstrated to be a safe procedure, with few, if any, long-term adverse effects. However, there is a need to deter- mine the possible consequences of multiple abortions and abortion in young women who have never given birth. Since 1994, the Programme has been supporting a hospital- based study in China, where about 10 million legally induced abor- tions are carried out every year. The study involves following a group of women from the eighth week of pregnancy through to the birth to determine any differences in the outcome of pregnancy be- tween those who previously had an abortion and those who had not. The study focuses on events such as illnesses during preg- nancy, spontaneous abortion, pre- mature births, low birth weight, and infant deaths and illnesses at or near the time of the birth. The findings are due to be published in late 1998 or early 1999. Non-surgical abortion In China, the use of non-surgi- cal abortion to terminate earlypreg- nancies (up to 63 days) is increas- ing rapidly.This abortion method involves taking an antiprogestogen pill (mifepristone) followed 36-48 hours later by oral vaginal admin- istration of a prostaglandin ana- logue. There is, at the present time, no scientific information on the effect of non-surgical abortion on the outcome of subsequent pregnancies. To assess the feasibilityof car- rying out a study of the possible effects of non-surgical abortion on future births, surveys were car- ried out in Beijing, Chengdu, and Shanghai on the prevalence of non-surgical abortions among pregnant women attending ante- natal clinics. The prevalence was found to be almost 10% in Beijing, over 17% in Chengdu, and 3% in Shanghai. The main study will begin in these cities during 1998, involving 4500 women with a history of non- surgical abortion, 4500 women with a history of surgically-induced abortion during the first three months of pregnancy, and 4500 women with no history of induced abortion. The women will be en- rolled at their first antenatal care visit and followed up until one month after giving birth. Contraception and HIV Use of contraceptive steroids by women infected with HIV MOSt women infected with HIV are of reproductive age. Since HIV infection does not Biennial Report 1996-1997 appear to affect fertility, women who are HIV-positive continue to need a reliable method of contra- ception. However, some of the most effective methods of contra- ception involve the use of steroid hormones and it is not known whether these will have an effect on the progression of HIVlAIDS- either by interacting with the virus itself or indirectly through their ef- fect on the immune system. The Programme is now carry- ing out a study-the first of its kind-to determine the effect of steroid hormone contraceptives (including oral contraceptives, the injectable contraceptive DMPA, and the contraceptive implant Norplant) on the progression of HIV/AIDS. The comparative study will include two groups of women who are HIV-positive but have not yet developed AIDS: women us- ing steroid hormone contracep- tives, and those using non-hor- monal methods of contraception (sterilization, barrier methods), or no contraception. Women will be recruited from four centres in Bra- zil, Thailand, and Zambia, includ- ing 660 using hormonal methods and 340 using non-hormonal or no methods. They will be followed up every six months over four years to assess the progression of HIV/AIDS. The findings are expected to have major implica- tions for the care and family plan- ning practice of HIV-positive women. Steroid hormone contraception and shedding of HIV The Programme has launched a study to determine whether the use of hormonal contraceptives by H IV-positive women increases I Biennial Report 1996-1997 the amount of HIV shed in the lower genital tract. The findings of this study will have important im- plications for prescription of hor- monal contraceptives to HIV -posi- tive women. Four groups of HIV-positive women will be enrolled in the study: current users of the contraceptive implant Norplant, the contracep- tive injectable DMPA, oral contra- ceptives, and non-hormonal meth- ods. The tests will include speci- mens taken from the lower genital tract as well as regular blood tests to determine the level of HIV infec- tion and measure hormone levels. Effect of steroid hormones on vagina/lining The Programme is supporting a study to determine whether the use of hormonal contraceptives leads to thinning ofthe lining ofthe vagina and changes in local im- munity, and whether these inturn modify susceptibility to HIV infec- tion, as well as other sexually transmitted agents including hu- man papillomavirus (HPV). The study is being done in response to recent data from animal studies showing that the monkey equiva- lent of HIV, simian immunodefi- ciency virus (SIV), can be trans- mitted through the vaginal lining (epithelium). Research has also shown that administering pro- gesterone to monkeys leads to thinning of the vaginal lining and increased susceptibility to SIV infection. The study is being carried out in Sweden and includes women using combined oral contracep- tives, the contraceptive inject- able DMPA, and the contracep- tive implant Norplant, as well as a group of women using non- hormonal methods. Vaginal bi- opsy specimens will be used to measure the effect of hormonal contraceptives on the thickness of the vaginal epithelium in com- parison with that of women using non-hormonal methods. New antenatal care programme D ecruitment is nearing com- ~Ietion forthe first multicentre trial to evaluate the impact of a new antenatal care programme on the health of mothers and their newborns. The new programme consists of four antenatal visits, and limits antenatal tests, clini- cal procedures, and follow-up actions to those scientifically proved to be effective in improv- ing the health of mothers and newborns. The study is being carried out in collaboration with WHO's Divi- sion of Reproductive Health (Tech- nical Support) at four centres in Argentina, Cuba, Saudi Arabia, and Thailand. It will involve about 25 000 women recruited at ante- natal clinics over an 18 month period. Since recruitment began in May 1996, almost 22 000 women have been enrolled in the study. Recruitment in Cuba, Saudi Arabia, and Thailand was com- pleted by the end of 1997 and will end in Argentina in April 1998. The study will focus on key indicators for maternal and new- born health including: preeclampsia (high blood pres- sure accompanied by protein in the urine, and fluid retention) and life-threatening eclampsia, anaemia following childbirth, severe urinary tract infection, and low birth weight babies. Use of misoprostol in third stage of labour Postpartum haemorrhage is a leading cause of maternal death in both developing and de- veloped countries. Although the use of oxytocics in the manage- ment of the third stage of labour reduces the amount of bleeding and the need for blood transfu- sions, these agents can produce side-effects, are administered by injection, and have to be kept un- der refrigeration. Some prostaglandin prepara- tions have proved to be potentially effective in preventing postpar- tum haemorrhage but these are expensive and have to be admin- istered by injection. There is a need for a cheap, effective, oral preparation which could be rou- tinely used during the third stage of labour in places where refrig- eration is not available and there is a shortage of medically trained staff. Misoprostol-a prostaglandin currently marketed as Cytotec in over 60 countries for use in the prevention and treatment of gas- tric ulcers-has attracted wide- spread attention because of its ability to trigger strong uterine contractions. Misoprostol remains effective after storage for long pe- riods at room temperature and is rapidly absorbed after oral admin- istration. In 1997, the Programme launched a multicentre trial of misoprostol to evaluate its effec- tiveness when used to reduce blood loss during the third stage of labour. The study, involving20 000 women in nine countries (Argen- tina, China, Egypt, Ireland, Ni- geria, South Africa, Thailand, and Bienntal Report 1996-1997 Viet Nam), will compare rates of severe postpartum haemorrhage among women given misoprostol and those given oxytocics. If misoprostol is found to be effec- tive, this is expected to lead to large-scale trials of the drug in rural areas where medically trained staff are not available. Prevalence of sexually trans- mitted diseases The Programme is planning to conduct a series of studies on the prevalence of genital tract in- fections in selected populations, epidemiological studies on lower genital tract infection, and the ef- fect of male chlamydial infection on sperm function. Chlamydiallower genital tract In- fection There is little information avail- able on the prevalence of STDs in developing countries. Most avail- able information is based on lim- ited data from selected samples involving high-risk groups in geo- graphically disparate regions. However, studies on the preva- lence of active chlamydial and gonococcal lower genital tract in- fections among both low- and high- risk populations can give some indication of epidemiological pat- terns. A series of Programme- supported studies on the preva- lence of lower genital tract infec- tions has been launched and oth- ers are planned in several coun- tries. In China, although STDs are not as common as in other Asian countries, surveys carried out in STD clinics suggest thatthe preva- lence of STDs is increasing. Stud- ies are being carried out in three Biennial Report 1996-1997 provinces involving women un- dergoing an induced abortion and others attending family planning clinics. Both groups are being tested forchlamydial infection and other STDs. Meanwhile, a multicentre study in China, which has now been completed, indi- cated that STD prevalence among the groups studied was related to the non-use of condoms, the number of induced abortions, mul- tiple sexual partners, and low so- cioeconomic status. In Malaysia, a study has been completed in a STD clinic in Kuala Lumpur on the detection of chlamydia infection in men, using urine samples. The main finding of this study is that, in a population with a high incidence of chlamydial infection, urine analysis is a suit- able alternative to analysis of male urethral swabs. There is also evi- dence that, for women, a urine test could replace a cervical swab. A similar study is now under way in Zimbabwe. Elsewhere, the Programme has launched a study in Indonesia to determine the prevalence of gonorrhoea and chlamydial infec- tion in both partners of infertile couples, patients with ectopic pregnancy, antenatal women, men and women attending a STD clinic, and a group of 300 commercial sex workers. The study, which is being funded by AusAID, is due to be completed by late 1998. Prevalence of chlamydial infec- tion in male adolescents A consequence of the lower- ing of the age of first sexual inter- course, especially among male adolescents in many societies, has been an increase in the number of young men contracting chlamydial urethritis. Because this infection may produce no symptoms in up to 80% of cases, this group is probably a major source of chlamydial genital tract infection in adolescent or young women. In Chiang Mai, Thailand, a study on the prevalence of chlamydial urethritis in adolescent males was completed in 1996. The study involved interviews with over 800 male vocational school students, of whom over 60% com- pleted a questionnaire and pro- vided a urine sample. The overall prevalence of chlamydia was 11 %. The students who provided urine samples tended to have less sexual experience but a higher rate of previous STDs or urethritis than those who did not give a urine sample. The findings sug- gest that, while the prevalence of chlamydia I urethritis may be high compared to studies in developed countries, it may be overestimated due to overrepresentation of stu- dents with a history of STDs or urethritis. Assessing and improving reproductive health services Highlights • Stage I activities involve an assessment of family planning and other reproductive health services. Assessments were conducted in Burkina Faso, Chile, Ethiopia, and Myanmar. In Burkina Faso strengthening the management and quality of reproductive health services, including information, education and communication activities, logistics, human resources, issues related to HIV/AIDS and services for adolescents, was recommended. The Chilean assessment identified the need to broaden contraceptive options by improving the quality of care for existing methods as well as introducing injectable contraceptives. It also highlighted the need for involving men and meeting the reproductive health needs of youth. In Ethiopia a broad range of reproductive health issues was addressed with emphasis given to operationalizing reproductive health, improving quality of care and broadening contraceptive choice. The Myanmar assessment identified the need to expand access to and availability of public sector reproductive health services, to strengthen the capacity of the community and the private sector to provide services, and to improve the quality of care for a range of reproductive health issues, including contraception, management of reproductive tract infections, prevention of unsafe abortion and management of its complications. • Stage 11 activities develop appropriate strategies to introduce or reintroduce new and/or existing but underutilized methods while improving the overall quality of care for all methods and reproductive health services more generally. Stage 11 activities were conducted in Bolivia, Brazil, Myanmar, South Africa, Viet Nam and Zambia. In Bolivia the research focused on improving quality of care and developing a strategy to introduce injectable contraceptives. In Brazil the project developed a municipality-level model for operational and management changes to improve quality of reproductive health services and to broaden contraceptive choice. In Myanmar the Stage 11 project will develop a district-level model for strengthening family planning and other reproductive health services provided by the public and private sectors, and the community. The South African study aims to expand contraceptive choice by developing a strategy for introducing male and female condoms, emergency contraception and referral systems for sterilizations. In Viet Nam the Stage 11 study is assisting the Government in developing a strategy for depot-medroxy progesterone acetate (DMPA) introduction within the context of improved quality of care in the provision of all family planning methods. The Zambia project aims at broadening contraceptive options by introducing emergency contraception and DMPA, while strengthening the provision of other methods. • Stage III activities apply Stage 11 research findings to policy development and wider programme development and implementation. Stage III activities are under way in Brazil and will soon commence in Viet Nam. The lessons learned in the Stage II project in one municipality in Brazil have been applied to restructure reproductive health services in other municipalities in the country. I Biennial Report 1996-1997 Stage I Assessments Bhutan A preliminary review was carried out in Bhutan to assess the current avai- lability of contraceptive methods and the need to introduce new methods, in particular the feasibility of introducing the the workshop concluded that, while there has been some improve- ment in women's health care in Bolivia over recent years, most managers and health workers as well as the public have little under- standing of the concept of repro- ductive health. Obstetrical services, including contraceptive implant Norplant. antenatal care and delivery, are A wide range of contraceptive underused because they are too methods is already available in Bhutan, including combined con- traceptive pills, the contraceptive injectable depot-medroxyproges- terone acetate (DMPA), IUDs, condoms, no-scalpel vasectomy, and tubal ligation. However, ac- cess and availability remain con- strained and improved quality of lEG materials and strengthened technical and managerial support for family planning services are required. Although Norplant would pro- vide an additional option as a long- term reversible method, major programmatic challenges would be faced in its introduction. It was recommended there- fore that a full assessment of con- traceptive availability and the need for introduction of new methods should be carried out before a decision was made on the possi- ble introduction of Norplant orother new methods. Support for this assessment will be requested as part of the 1998 United Nations Population Fund (UNFPA) coun- try programme. Bolivia In Bolivia, a workshop was held in mid-1996 to review the findings of the assessment carried out in 1995 and to develop a plan of action. The report presented at Biennial Report 1996-1997 expensive, difficulttoaccess, cul- Other problems highlighted by turally inappropriate, and the pub- the Stage I assessment include lic has little confidence in them. shortages of drugs, equipment, Despite improvements in fam- and other supplies due to an inad- ily planning services, access re- equate distribution system; poor mains restricted in many areas monitoring and evaluation of both due to a shortage of adequately obstetrical and family planning trained personnel, lack of sup- services; and a failure to involve plies, high cost, and poor location women in decision-making on the of services. The range of contra- design and implementation of re- ceptive options available in the productive health services. public health sector is largely re- In response to these findings, stricted to condoms, pills, and the the Ministry of Health has devel- intrauterine device (IUD). Access oped a Stage II proposal de- to sterilization (tubal ligation) is scribed later. difficult and injectables are only available in the private sector. Lack Burkina Faso of access to reproductive health An assessment was carried services in the public sector leads out in Burkina Faso in late 1996 many women to use private prac- by the Cellule de la Recherche titioners, traditional medicine, and en Santa de la Reproduction other health care institutions. (CRESAR) with support from The quality of care in contra- UNFPA and technical assistance ceptive services is poor, espe- from The Population Council's re- cially in counselling and free choice gional office for Africa. of methods. On the other hand, The conclusions and recom- there is a need to take some con- mendations of the assessment traceptive products off the mar- report focus on: management and ket, including those with an un- quality of services; IEC and other proven safety record and those strategies for the development of for which safer, lower-dose sub- reproductive health; gender and stitutes are available. sociocultural factors in reproduc- Political developments in Bo- tive health; young people and re- livia, especially implementation of productive health; logistics and the Law of Popular PartiCipation, human resources; reproductive have opened the way for improve- rights; and issues relating to HIVI ments in the quality of health care. AIDS. The findings are now being However, local government lead- studied with a view to making ers lack the skills needed to iden- plans for Stage II research activi- tify the most urgent needs or to ties. plan and execute programmes which benefit the population. Chile Meanwhile, at the central level, A limited assessment was car- initiatives are delayed by the slow ried out in Santiago, Chile follow- machinery of government, and ing a proposal by the Ministry of quality of care is compromised by Health to introduce injectable con- a high turnover of personnel, es- traceptives into family planning pecially physicians. services. ';;:>;'<0<1,.) .,;/<;" I / "" '/ ''',' '~,t <J<; I -,;", ;,?" /'( ;!~,<'~>':;;;'~t:'; f:j:;,-i:0;:;C: ;-/~;~;:;: I Biennial Report 1996-1997 The assessment team re- ported that, while some aspects of reproductive health care were good, largely due to the availabil- ity of trained midwives, the con- cept of reproductive health is not widely understood and therefore not implemented at the primary health care level. Care is largely restricted to antenatal care, fertil- ity control, and breast-feeding. Among the unmet needs iden- tified were: reproductive health of adolescents; better advice on fam- ily planning; wider contraceptive choice; greater focus on the diag- nosis, treatment, and prevention of sexually transmitted diseases (STDs) including HIVlAIDS; and care of women beyond their re- productive years. The assess- ment also found that health edu- cation and health promotion were not considered a high priority and that many health care providers failed to take account of clients' perspectives of service delivery. The range of contraceptive methods available was limited to one brand of combined oral con- traceptives and the IUD. Moreo- ver, some midwives were not well informed about other methods. Condoms are provided as a tem- porary method, without any infor- mation forthe men who use them. Tubal ligation is considered not as a voluntary form of contracep- tion but as a preventive measure in cases where pregnancy would involve a high medical risk. Va- sectomy is almost non-existent. Although the staff in family plan- ning clinics have the expertise to provide injectable contraceptives, the availability of disposable sy- ringes and needles is limited and they have to be purchased by the clients themselves. None of the clinics visited by the assessment team had gynae- cologists but all had an adequate number of highly professional mid- wives. However, many ofthe mid- wives had not received post-cur- riculartraining to update theirtech- nical skills, and they spent too much time on administrative is- sues or doing work that could be carried out by less specialized staff. The assessment team found evidence of a continuing reduc- tion in the number of births, an increase in the number of repro- ductive tract infections (RTls), a rise in mortality rates from gynae- cological cancers, and an increase in the percentage of women over 50 years of age requesting health care. These findings were discussed at a workshop in Santiago in Au- gust 1996, and it was recom- mended that research should be carried out to determine ways of improving reproductive health services including: shifting the emphasis from maternal care to the broader concept of reproduc- tive health; ensuring a free and informed choice of a broader range of contraceptive methods includ- ing injectables; improving the re- lationship between users and pro- viders; giving greater priority to health education activities; encour- aging the participation of men in reproductive health care; and ad- dressing the reproductive needs of young people. Ethiopia A Stage I assessment was carried out in Ethiopia to identify the need for new contraceptive I nancy, appropriate pain control, inspection of placental tissue, post- abortion monitoring and counsel- ling, management of abortion com- plications, and treatment of RTls. The team recommended that new technical guidelines on abor- tion should be widely disseminated and backed up by refresher train- ing courses for providers on all aspects of abortion service deliv- ery and by regular supervision to reinforce technical skills and prac- tices in the field. The Ministry of Health is con- sidering the introduction of non- surgical abortion, using mifepristone and misoprostol. However, the assessment team recommended that priority should be given to improving the quality of surgical abortion services in- stead. They pOinted out that un- der current service delivery ca- pabilities non-surgical abortions could only be provided saefly in national and provincial hospitals- thereby limiting availability to a relatively small number of women. Further research concerning ap- propriate approaches to service delivery of non-surgical abortion is required. The findings and recommen- dations of the assessment were discussed at a national workshop in September 1997 and a national technical working group on abor- tion was established to oversee implementation ofthe recommen- dations. Zambia The Stage I assessment in Zambia has had a major impact on reproductive health services. Information from the assessment, together with WHO's Medical EH- Biennial Report 1996-1997 gibility Criteria for Contraceptive Use formed the basis for a new policy document, entitled Family Planning in Reproductive Health: Policy Framework and Guidelines, which is the first component of a new national reproductive health policy and action plan. The na- tional plan will also draw on the findings of a safe motherhood needs assessment carried out in 1996. Review of Stage I assessments A review of all Stage I assessments carried out to date found that, despite signifi- cant differences in the range and availability of contraceptive meth- ods, as well as in geographical, social and political systems, many of the conclusions are common to all the countries involved. They include the need to: • broaden contraceptive choice • improve quality of care in family planning and reproductive health services • give higher priority to helping increase the take-up of existing methods than to introducing new ones. The review also notes that management capacity is gener- ally not strong enough to suc- cessfully introduce new methods on a wide scale and with an ad- equate level of care. In addition, the assessments: • identified issues in the provision offamily planning and other repro- ductive health services which re- quire policy or programme action; • identified other research, espe- cially health systems research, required in reproductive health; and • acted as a catalyst for improved I Biennial Report 1996-1997 coordination with donors. Also highlighted was the need to take some contraceptives off the market. These include formu- lations comprising unacceptably high dosages of hormones and products inadequately tested for safety. These problems under- line the fact that many developing countries have inadequate drug regulatory mechanisms and lim- ited control over methods avail- able through the private sector. Also, the assessments pointed to the need to link the introduction of new contraceptive methods to improvements in overall quality of care in reproductive health serv- ices. The aim is to use the intro- duction of new methods as a cata- lyst for upgrading the quality of care with which all methods are delivered. In some countries, social atti- tudes to contraception were found to be heavily influenced by race, ethnicity, class, religion, and gen- der. In Bolivia, for example, the low uptake in public sector family planning services was partly at- tributed to ethnic and class differ- ences between clients and pro- viders, while in South Africa, dur- ing the apartheid era, a racially motivated family planning pro- gramme focused on the use of injectables for African women, while denying them the right of informed choice. Elsewhere, reli- gious and traditional cultural be- liefs have impeded the use of both modern services and spe- cific methods. Meanwhile, all as- sessments found evidence of the effect of gender imbalances on contraceptive choice as well as the influence of family, peers, and even neighbours on decisions about contraceptive use. Thethree underlying principles of country-ownership, participa- tion of all stakeholders, and an open, transparent process have proved critical to both conduct of the assessment and acceptance of the findings. The difficult chal- lenge of bringing together policy- makers, programme managers, and researchers with community and district-level providers, wom- en's health groups, and young people has proved successful in countries as different as Brazil and Viet Nam. The involvement of WHO as a technical partner has helped validate the conclusions of the country-based and country- owned report. Stage 11 research Bolivia A study was launched in Bo-livia in early 1997 to steer the introduction of injectable con- traceptives and improve the over- all quality of care in family plan- ning services. A situational analy- sis has been completed in two districts, La Paz and Santa Cruz, and the data are now being ana- lysed. Initial results indicate that overall health care is weak and they point to major problems in the provision of services such as difficulty in access; extremely long waiting times; lack of clinic records; physicians arriving late; and poor interpersonal relations between clients and providers. There is very little training for providers in family planning and choice is largely restricted to IUDs. Research began by determi n- ing users' and providers' perspec- tives on contraceptive methods and available services and on the I to determine why women choose to use DMPA, their continuation rates, and the reasons for con- tinuing or discontinuing this method. The service delivery sys- tem is also being investigated to determine what technical and managerial adaptations are needed to ensure an improved quality of care in the delivery of DMPA and other methods. A workshop was held in early 1997 to assess progress prior to expansion of DMPA delivery to the level of communes. One out- come of the workshop was a de- cision to introduce DMPA in se- lected districts in eight additional provinces a faster pace than originally envisaged. The Stage 11 study is due to be completed in mid-1998 and will be followed by a workshop. Stage III activities are expected to begin soon afterwards. Zambia The Stage II research study began with a review of the experi- ence of CARE International in the provision of DM PA and other con- traceptive methods in 26 govern- ment clinics in Livingstone and Lusaka. The findings were used to finalize a training curriculum for providers. A situation analysis was then carried out at 11 health centres and hospitals at the three study sites, i.e. rural districts in the Copperbelt area. During 1997, staff atthe study sites were trained in the use of all available contra- ceptive methods: combined oral contraceptives, male and female condoms, DM P A, and emergency contraception, as well as referral for IUD insertion and sterilization Biennial Report 1996-1997 using tubal ligation. The availability of a broader choice of methods has led to a significant increase in the uptake of contraceptive methods, with 50% of clients choosing DMPA.ln addition, several women used emergency contraceptive pills in the month after providers had been trained in their use. In early 1998, the research project will be broadened to in- clude other aspects of reproduc- tive health such as obstetric care and safe motherhood activities as well as the training of staff in STD diagnosis and management. Stage III expansion Brazil In Brazil, a Stage III project is continuing to apply the lessons from the Stage II project in Santa Barbara to help improve contra- ceptive choice and other repro- ductive health services in two groups of municipalities. The two have both been motivated by the success of the Santa Barbara project and are pursuing a similar participatory approach. but are receiving different levels of tech- nical support. VietNam Planning is under way for a Stage III project designed to pro- vide strategic support to making DMPA more widely available in Viet Nam. The study is expected to be implemented in the second half of 1998. Evaluation of the strategic approach An independent evaluation of the strategiC approach for introduction of contraceptive meth- I Biennial Report 1996-1997 ods will be carried out during the first half of 1998. The aims are to: • assess the impact of the strat- egy, its abilityto improve quality of care in the delivery of all methods being provided, and its feasibility in relation to time, costs, and hu- man resources; • refine the design and implemen- tation of the strategy to enhance feasibility and impact as well as its application to other reproductive health issues; and • guide future Programme activi- ties in the area oftechnology intro- duction and transfer. Case studies of activities in Bolivia, Brazil, Myanmar, South Africa, Viet Nam, and Zambia will be used to: illustrate how the stra- tegic approach and its core princi- ples were applied in different re- gions and programme settings; highlight the key lessons learned; provide a basis for Stage III imple- mentation; and make recommen- dations on the future application of the strategy by the Programme and others. The evaluation team, compris- ing two independent external con- sultants, will review the case stud- ies and visit Brazil, Viet Nam, and Zambia. The report on the evalu- ation will be considered at a meet- ing of the Scientific Review Com- mittee in June 1998. Assuring quality of contraceptive methods Since the quality of contracep-tive products is fundamental to usersatisfaction and confidence in family planning services, the Programme is making efforts to determine how widespread is the problem of poor-quality contra- ceptive products and to identify the cause. In Bangladesh, for example, quality-related problems have been identified involving a range of contraceptive products avail- able in the public sector. They include: sticky and crumbling oral contraceptive pills; non- suspendability of injectable con- traceptives, including vials that had been opened and tampered with; ILlDs that were tarnished and/or missing strings; and con- doms that did not meet procure- ment specifications. The Programme is continuing ~ ::c o "0 ::c @ ;:c » z m z o m z I I Biennial Report 1996-1997 (LOCs), the emphasis will be on reproductive health needs assessments and on definition of research priorities, together with efforts to strengthen research capabilities through training, core support, and intraregional partnerships . • Between 1990 and 1997, the Programme provided technical support and financial assistance to 22 institutions in 11 countries in the Asia and Pacific regions, including five least developed countries. In the coming years efforts to strengthen research capacity will build on the existing momentum of intra- regional cooperation through regional research initiatives, regional networking mechanisms and appro- priate designation of WHO Collaborating Centres. The Programme will also develop appropriate strategies and support programmes-ensuring the right mix between research training, core support, research project funding, and intraregional support for research and technical support. • In AUgust 1997, a special session at the XV World Congress of the International Federation of Gynaecology and Obstetrics (FIGO) in Copenhagen, Denmark, focused on reproductive health in Eastern Europe. The papers presented at this session will be published during 1998. Eastern Europe urgently needs to strengthen its capacity to conduct reproductive health research. The special session at the FIGO World Congress was designed to highlight reproductive health problems in that region and to generate increased interest in research to solve those problems . • A survey involving 1200 readers of the Programme's newsletter Progress in human reproduction research has found that most readers find it interesting and useful-both for themselves and for the organizations for which they work. Most respondents (over 90%) indicated that the level of technical language and amount of detail included is "about right" and that the readability is "good" or "very good." Progress remains the flagship of the Programme's communication materials aimed at policy-makers, scientists and the general public. The impact of this publication extends beyond its readers, with nearly 20% of respondents saying that they disseminate to others the information they get through Progress, 19% saying that they use it for teaching, and 10% saying that they use it for initiating new research projects. ~;~~~!---------------------------- Biennial Report 1996-1997 The Programme continues to support research capa-bility strengthening in de- veloping countries in an effort to enable these countries to: • carry out research aimed at pro- moting the reproductive health of their populations; and • participate in global research on reproductive health problems. Since 1994, there has been a convergence in the interests of global and national research on reproductive health. The common research agenda has grown out of a recognition of the need to ad- dress research issues in the broader context of reproductive health, thus narrowing the gap between the focus of global and national research agendas. An added factor is the increasing ca- pacity of the Programme's net- work of over 1 00 research centres to initiate research of national and global relevance which is comple- mentary to Programme-initiated research activities. During 1996-1997, research training grants were awarded to 48 scientists, of whom 10 were women. Table 1 shows the break- down of the grants by discipline. During 1997, Long-term Insti- tutional Development (U D) grants were awarded to a total of 22 institutions: five in the Africa/East- ern Mediterranean regions; six in the Americas; and 11 in the Asia/ Pacific regions. Emphasis was placed on the conduct of research, and infrastructure support was designated for the identified re- search programmes. In addition, resource maintenance grants were given to 17 institutions: three in the Africa/Eastern Mediterranean regions; eight in Latin America; Table I. Research training grants awared during the biennium 1996- 1997. by discipline Andrology 3 Clinical management 2 Clinical trials 2 Epidemiology I I Laboratory techniques 2 Medical demography I Medical records 2 Microbiology Molecular biology Operations research Public health 5 Reproductive endocrinology 2 Reproductive medicine Research management 2 Sexually transmitted diseases 4 Social sciences 4 Statistics Toxicology Total 3 48 and six in the Asia/Pacific regions. Small grants were awarded to 27 institutions, including 17 in the Africa/Eastern Mediterranean re- gions, seven in the Americas, and three in the Asia/Pacific regions. In many cases, these are used for the purchase of scientific journals in countries where foreign ex- change is difficult to secure. The grants are also used to purchase laboratory supplies. During 1997, two of the newly established Regional Advisory Panels met for the first time in Cuba (forthe Americas) and Thai- land (forthe Asia/Pacific regions). The Panels bring to the Pro- gramme's work a thorough un- derstanding of reproductive health issues, problems, and priorities in the relevant region and thus pro- videabasisforplanning, research, research capability strengthening, and the dissemination of research results. The new Panels have been established to replace the former Committee on Resources for Re- Biennial Report 1996-1997 >- grammes in their areas. One out- During 1997, four research I-(5 ~ come was a recommendation to projects were under way: two on « .0 include family life education in the maternal and infant health, one on school curriculum. abortion, and a fourth on repro- ductive health services. In addi- Cameroon tion, the Cellule continued its col- The Centre for Human Repro- laboration with the Programme by duction Research at the Univer- initiating a process to determine sity of Yaounde, Cameroon, re- reproductive health research pri- ceived LID grant support from orities. 1987-1996, followed by a resource maintenance grant in 1997. Democratic Republic of Congo During 1997, the Centre had In 1995, a research Cellule 23 ongoing research projects: eight was established in the former Za- in the field of reproductive biology, ire to compile a data bank on eight on maternal and infant health, reproductive health and plan ac- one on abortion, four on contra- tivities outside the capital, Kin- ception, one on infertility, and one shasa. In 1996, small grants were on STDs. Five of these were awarded to the Cellules in Kin- funded by the Programme, 12from shasa and Lumumbashi to start national sources, and the restfrom these activities, and three mem- other international groups. The bers ofthe Cellules attended work- research included studies on a shops and courses organized by rationalized approach to anaes- the Programme. thetic care in reproductive health, the cost of premature baby care, Ethiopia effects of steroid contraception on The Department of Obstetrics liver function tests for hepatitis B and Gynaecology at the Univer- carriers, and a comparative study sity of Addis Ababa was awarded of the use of misoprostol and oxy- a LI D grant from 1990-1994, a tocin to induce labour. resource maintenance grant in 1995, and annual small grants Cote d'lvoire since 1996 for library support. Since 1995, the Nationallnsti- During 1996, the results of a tute of Health in Abidjan has hosted five-year U NFPA-supported study the 48-member National Research on the return of fertility after re- Cellule on Reproductive Health, moval of an IUD were published. which was established in 1989 as Ongoing research studies-none part of the African Network on of them Programme-funded-in- Research on Reproductive Health. cluded: the management and out- An application by the Cellule for a come of multiple pregnancies, LID grant has been put on hold gestational trophoblastic disease, until the Programme's financial the use of the contraceptive im- situation improves. In the mean- plant Norplant, and the use of time, a pre-LlD grant in 1996 ena- contraception following an abor- bled the Cellule to carry out a tion or birth. review of reproductive health care In 1997, a Reproductive Health in Cote d'lvoire. Research Unit was established Biennial Report 1996-1997 and a number of clinical research diagnosis and treatment of cervi- CD c::: i'" studies initiated, mainly on mater- cal cancer, mother-to-child trans- Q z nal and infant health. mission of HIV, semen quality, Cl :;0 m and the prevention and manage- en rtl » Kenya mentofSTDs, including HIV/AIDS, :;0 () ;:c In Kenya, the Programme is among street children. () »> "U collaborating with four institutions ):> 0 which together comprise the Na- Mozambique ~ tional Centre for Research in Re- The Department of Obstetrics production (NCRR). NCRR has and Gynaecology at the National proved successful in providing University of Maputo has received opportunities for a comprehen- a LID grant since 1989. During sive human reproduction training 1996, ongoing research included and research programme that has studies on: eclampsia during preg- benefited not only Kenyans but nancy; use of the prostaglandin also scientists from other parts of misoprostol in induced abortion; Africa. In addition to a steady flow the impact of genital infection on of research results from its four the outcome of pregnancy; and constituent institutions, the estab- premature detachment of the pla- lishment of a Programme-sup- centa. ported Master's Degree pro- Meanwhile, the results were gramme at Nairobi University in published of a comparative study 1993, under the auspices of of over 2000 caesarean deliveries NCRR, has helped broaden its undertaken by assistant medical role as a regional training centre. officers trained for surgery (46.3% During 1997, 20 research of deliveries) and by specialist projects were ongoing at the I nsti- gynaecologists and obstetricians tute of Primate Research at the (53.7% of deliveries). The study National Museums of Kenya. They found no significant differences- included 11 studies on reproduc- regardless of who performed the tive biology, including five on con- caesarian operation-in the traception, one on maternal and number of maternal deaths or infant health, one on infertility, and duration of postoperative hospital two on STDs. Elsewhere, the Uni- stay. And the total number of versity of Nairobi's Reproductive wound ruptures was similar in both Biology Unitwascarrying out eight groups. However, there was a basic science research projects slightly increased incidence of involving animal models. And the superficial infection of the wound University Department of Obstet- in the group operated on by medi- rics and Gynaecology was con- cal assistants. ducting six research projects- During 1997, the Department six of them with support from the was conducting research projects Programme. Meanwhile, the on neonatal deaths, intrauterine Kenya Medical Research Institute, adhesions, the psychological as- which received a small grant from pects ofteenage pregnancies, and the Programme, was involved in the role of men in contraceptive four research studies on: the early decision-making. I I I Nigeria The Programme is collaborat- ing with a number of institutions in Nigeria. The Department of Ob· stetrics and Gynaecology at the University of Ibadan, which re- ceives small grants for library fa- cilities and laboratory support, is carrying out mainly clinical and epidemiological research, with in- creasing input from social scien- tists. Projects under way in 1997 included a study on the introduc- tion of the emergency contracep- tive pill, efficacy studies on differ- ent dosage oral contraceptives, contraceptive method switching, and abortion in rural areas. The Department of Obstetrics and Gynaecology at the Univer- sityof Benin, Benin City, a former recipient of a LID grant, currently receives a small grant for labora- tory supplies and joumal subscrip- tions. During 1997, the main re- search was a community-based study on determinants of infertility in both rural and urban areas. Elsewhere, researchers at Ogun State University are involved in four Programme-supported studies: a comparative study of the effectiveness of the Yuzpe and levonorgestrel methods of emergency contraception; a com- parative study of the contracep- tive effectiveness of latex and non- latex condoms; determination of normal ranges of reproductive hor- mones; and trials of misoprostol and oxytocics in the management of the third stage of labour. Senegal The Department of Obstetrics and Gynaecology at Le Dantec Hospital, University of Dakar, has collaborated with the Programme Biennial Report 1996-1997 in a range of projects since 1981. In November 1996, the Intema- tional Centre for Training and Research in Reproductive Health (CEFOREP), which is attached to the Department, started to func- tion as a national NGO. Due to its financial difficulties, the Pro- gramme was unable to approve a LI D grant for the Centre for the period 1996-2000. However, a small grant was awarded to sup- port the Department's documen- tation centre and journal subscrip- tions during 1996 and 1997. During 1996, the Department hosted an international workshop on the role of men in fertility, fam- ily planning, and reproductive health, and collaborated with the Programme in organizing a na- tional-level course on epidemio- logical methods for reproductive health research. And in 1997, the Department hosted the regional workshops on protocol develop- ment for the studies on reproduc- tive health services for adoles- cents and on improving antenatal care. South Africa Following the readmission of South Africa to WHO in May 1994, the Programme has expanded its links with researchers and institu- tions in the country. In 1997, the Programme organ ized a research training workshop in Durban to finalize the protocol for a multicountry study on family plan- ning and sexual behaviour in the era of HIV/STDs. Collaboration with the Repro- ductive Health Research Unit at the Soweto-based Baragwanath Hospital has steadily increased since 1993. In 1997, the Unit was Biennial Report 1996-1997 involved in nine ongoing research WHO Collaborating Centre for Re- O) c j= projects, including three supported search in Human Reproduction in 0 z Cl by the Programme. They included 1973. Support for institution :D m studies on: the acceptability of strengthening included a LID grant CJl m :t> non-latex condoms; reasons for from 1987-1991. Since then, the :D (") I discontinuation of contraceptive Centre has received small grants (") :t> -0 methods; re-use of the female for library facilities and laboratory :t> (") ::::j condom; and the involvement of supplies. -< men in reproductive health. In Research has included a com- addition, the Unitcontinued to pro- parative study of the effective- vide support to the National De- ness of copper IUDs, mother-to- partment of Health, the Directo- child transmission of HIV, and stud- rate of Maternal, Child and Wom- ies on infertility, maternal health, en's Health, and the AIDS Direc- and adolescent reproductive health. torate, as well as provincial health The Stage I assessment for departments. contraceptive introduction carried out in 1995 has had a major im- Uganda pact and resulted in the develop- The Department of Obstetrics ment of the first phase of a na- and Gynaecology at Makerere Uni- tional reproductive health policy versity in Kampala has had a LID and plan of action in 1996. grant since 1989. The main lines of research include epidemiologi- Zimbabwe cal studies of fertility, contracep- The University of Zimbabwe tion, and maternal and perinatal Department of Obstetrics and Gy- health, as well as clinical research naecology has had a LID grant on the role of hormones in infertil- since 1988. The Department has ity and contraception. Projects carried out a wide range of re- under way during 1997 included search including studies on: male studies on infertility, testicularfunc- sexuality and H IV/STD risk aware- tion in H IV -positive men, and trials ness; unplanned pregnancy; epi- of the efficacy of several drugs in demiology of HIV; mother-to-child preventing mother-to-child trans- transmission of HIV; diabetes dur- mission of H IV. ing pregnancy; pelvic inflamma- A wide range of research tory disease; cervical cancer; and projects have been supported post-abortion counselling on fam- under the current LID grant. They ily planning. include studies on: the use of dif- ferent contraceptive methods, Other countries in Africa male infertility, and teenage preg- Elsewhere in Africa, the Pro- nancy, as well as a rural commu- gramme is continuing to support: nity-based study on reproductive a study in Botswana on sexual health needs. behaviour and the risk of HIV among adolescent girls; a study in Zambia Ghana on the sexual behaviour of The Department of Obstetrics commercial sex workers and "free and Gynaecology at the Univer- women"; and a study in Togo on sity of Zambia was designated a fertility transition in rural Africa. I Biennial Report 1996-1997 >- Eastern Mediterranean Region lished reproductive health re-I-(J 4: Egypt search networks in six provinces, Cl. 4: () ~he University of Alexandria with a separate reproductive health Department of Obstetrics and research committee located in Gynaecology, one of the Pro- each of the country's 30 universi- gramme's long-term partners, was ties. deSignated a WHO Collaborating During 1997, eight research Centre for Research in Human projects were under way, none of Reproduction in 1972. The Pro- them supported by the Pro- gramme's institutional support gramme. They include three on for the Centre ended in 1980 but contraception, two on maternal it continues to receive grants for and infant health, and one each the maintenance of library and on unwanted pregnancy, post- laboratory facilities. During 1997, menopausal problems, and infer- a total of 77 research projects tility. were under way: 24 on infertility, 42 on maternal and infant health, Pakistan and 11 on contraception. The The National Research Insti- Centre also organized 24 training tute of Fertility Control has been a courses, workshops, and semi- WHO Collaborating Centre for nars. Research in Human Reproduc- The Egyptian Fertility Care So- tion since 1976. During 1997, it ciety (EFCS), established in 1972, received a small grant for library has a research network including resources and laboratory supplies. all university and Ministry of Health The Centre has been involved in teaching hospitals involved in re- research studies on contracep- search on issues related to family tion (including the introduction of planning. EFCS has been receiv- Norplant in Pakistan) and mater- ing a LI D grant since 1992. During nal and infant health. 1997, the Centre completed sev- erallarge-scale research projects Sudan on unmet needs in contraception The University of Khartoum and reproductive health care in Department of Obstetrics and Gy- Egypt and on female genital muti- naecology has received a LI D grant lation. EFCS has also been since 1989. The Department has awarded grants to analyse the carried out research on maternal data from studies on fertility pat- and infant health, abortion, con- terns among migrant populations traception, and adolescent health. in Egypt and on the use of mater- During 1997, research studies nal health services by pregnant were under way on screening for women. rubella antibodies among preg- nantwomen, contraceptive aware- Islamic Republic of Iran ness and usage among educated The National Research Cen- women, the relation between tre for Reproductive Health is re- physical growth during puberty and ceiving a small grant from the the start of menstruation, and the Programme for library support. effect of a desogestrel oral con- During 1996, the Centre estab- taining low-dose contraceptive pill I I Biennial Report 1996-1997 on lipid metabolism in Sudanese women. Tunisia The Tunis-based Centre for Research in Human Reproduc- tion is a large government clinic providing services for family plan- ning and the management of in- fertility. It also acts as a reference centre for the scientific evaluation of existing and new methods of contraception. The Centre has been supported by the Programme for over 20 years and currently receives a small grant for library and laboratory support. In 1997, a resource maintenance grant was also awarded. During 1997, the Centre was involved in four research projects-two of them funded from national sources. They included studies in the areas of reproduc- tive biology, abortion, STDs, and contraception. One of the major interests of the Centre is to con- tinue the ongoing study on cervi- cal cancer screening on a nation- wide scale. The Centre also held a workshop during 1997 to lay the groundwork for the establishment of a Maghrebian research net- work. The workshop was attended by 19 researchers from Algeria, Morocco, and Tunisia. Meanwhile, the Tunisian En- docrine Society is continuing to publish a journal on endocrinology and reproductive health re- search-launched in 1995 with financial support from the Pro- gramme. The aim of the journal is to disseminate in French impor- tant research findings of particular relevance to Africa. The journal has also included French transla- tions of articles from the Pro- gramme's newsletter Progress in human reproduction research. Other countries in the Eastern Mediterranean region The Programme is seeking ways of extending its collabora- tion to other countries in the East- ern Mediterranean region. Two collaborative research projects have been launched in Saudi Ara- bia: one on evaluation of a new model of antenatal care and the other on diabetes during preg- nancy. Elsewhere, in Morocco, the Programme is supporting a research project on women's atti- tudes towards, and perceptions of, reproductive health. Eastern Europe In January 1994, a Scientific Working Group on Reproduc- tive Health Research in Eastern Europe was established to pro- mote and coordinate research and trainingthroughoutthe region. The first six research proposals were developed that year, but some research has been delayed due to the lack of donor support. The research is designed to address three major problems in reproduc- tive health in eastern and central Europe: family planning and con- traceptive choice; the health con- sequences of abortion; and peri- natal care. The use of modern contracep- tive methods remains low in most countries in the region and abor- tion is a major method of fertility regulation. Three of the research proposals are designed to investi- gate the reasons for this and sug- gest possible solutions. The first of these, which is under way, is investigating why few people use Biennial Report 1996-1997 i:: modern contraceptive methods cine and reproductive biology at u « despite the existence of family the University of Geneva, Swit-CL « () planning services. The second zerland, which included several study is a comparative clinical trial participants from Eastern Europe. on the safety, efficacy, and ac- Meanwhile, a Scientific and Tech- ceptability of once-a-month and nical AdviSOry Group on Training three-monthly injectable contra- in Reproductive Health has been ceptives-methods not widely established by the WHO Reg ional available in the region. The third Office for Europe to coordinate study, planned to start in 1998, training in Eastern Europe. In ad- investigates the acceptance and dition to the need for additional continuation rates of different con- funding, there is a need to build up traceptive methods by women who capacity for social science re- have already given birth. search and to increase the in- Elsewhere, a perinatal audit volvement of scientists from the project is under way in Latvia, Central Asian Republics. Lithuania and Russia to deter- mine why the countries of Eastern The Americas Region Europe have perinatal mortality I n the Americas region, collabo rates two to four times higher than rating institutions supported by in western Europe. the Programme are involved in a Two additional research pro- large number of research projects posals on the use of medical abor- on topiCS relating to national and tion in early pregnancy and on regional reproductive health prob- abortion-related morbidity and lems. They include studies car- mortality are still under review. ried out by the three regional re- While financial difficulties have search networks-clinical/epide- prevented the initiation of further miological, social sciences, and studies, the Programme's proto- basic sciences-as well as by in- colon standardized management stitutions at the national level. of infertility was adapted in During 1996, five regional re- Yerevan, Armenia, in a study to search initiatives were under way. investigate the causes of infertil- Three centres in Brazil, Chile, and ity. Mexico are investigating the ac- In August 1997, a special ses- ceptability of emergency contra- sion at the XV World Congress of ception in Latin America. In an- the International Federation of other research study-still at the Gynaecology and Obstetrics in review stage-institutions from Copenhagen, Denmark, focused Argentina, Bolivia, Cuba, and Peru on reproductive health in Eastern are planning to investigate men's Europe. The papers presented at perceptions and behaviour in the this session will be published dur- sexual and reproductive decision- ing 1998. making process. Another recently During 1996-1997, the Pro- approved regional study, involv- gramme continued to provide ing institutions from Argentina, technical and financial support for Brazil, Cuba, Guatemala, and the annual postgraduate course Mexico with funding from the Eu- for training in reproductive medi- ropean Union, will investigate the Biennial Report 1996-1997 problem ofthe increasing number four were rejected and two with- of caesarian deliveries in Latin drawn by the principal investiga- America. Elsewhere, women's tors. Ofthe remaining 12 projects, views on the quality of antenatal four were approved and one re- care will be evaluated in a jected by the Programme's Sci- multicentre study involving cen- entific and Ethical Review Group, tres in Argentina and Cuba as well and eight are still under review. as Saudi Arabia and Thailand. In During 1996-1997, the Pro- addition, four centres in Argen- gramme collaborated with 25 in- tina, Chile and Mexico have iden- stitutions in 12 countries in Latin tified the need for a new regional America. Of these, 13 received research initiative on the biologi- major support for institutional cal processes involved in emer- streng~hening or research grants, gency contraception using hor- 11 received small grants, and one monal methods. Preliminarywork a Technical Cooperation between was undertaken in 1997 to draw Developing Countries grant. up a detailed plan of activities to be initiated in 1998. Argentina At the same time, the centres The Programme continues to are involved in research projects support the Rosario-based Cen- that address national priorities. Of tre for Perinatal Studies (CREP) the216studiesunderwayin 1996, and the Department of Obstetrics 33 projects (15%) were supported and Gynaecology at the Centre by the Programme through ca- for Medical Education and Clinical pacity-building grants and 82 Investigation (CEMIC) in Buenos projects (38%) were funded from Aires. CREP carries out research national sources. in the areas of maternal and infant The involvement of regional health, adolescent health, and centres in the global research ef- reproductive health epidemiology, fort is underscored by the 25 and also serves as a training and projects (12%) supported by other research methodology referral Programme components and the centre both at the national and 76 studies (35%) funded by other regionallevels. It is one ofthe four international agencies. centres involved in the antenatal In an effort to improve the links care research project and is due between capacity-building grants to take part in the misoprostol trial and research implementation, it and in the regional study on cae- was required that grant applica- sari an deliveries. CEMIC is in- tions reviewed during the 1996- volved in a regional Reagent Pro- 1997 biennium should be linked to duction Programmeforthedevel- specific research proposals. The opment of reproductive hormone proposals were subjected to the assay kits. full scientific and ethical review Elsewhere, the Buenos Aires- process which was carried out, based Centre for Population Stud- for the first time, by external re- ies is the coordinator as well as viewers. During 1997, 94 external one of the study sites for the re- reviewers were asked to review gional study on men's percep- 18 grant-funded projects. Of these, tions and behaviour in the sexual I I I and reproductive decision-mak- ing process. In addition, the Insti- tute for Experimental Biology and Medicine was awarded a LI D grant in 1997 for research on basic sci- ence aspects of male fertility and infertility. Research in reproductive epi- demiology and endocrinology was supported through small grants to the Centre for Endocrinology at the Children's Hospital and the Laboratory of Growth and Devel- opment Research at the National Pediatric Hospital, both in Buenos Biennial Report 1996-1997 regional coordinating centre for introductory trials of the Pro- gramme's once-a-month inject- able contraceptive, Cyclofem, in Latin America-helping coun- tries develop national capacity for research and data manage- ment. In addition, the Programme provides a small grant to the Cen- tre of Reproductive Biology in Juiz de Fora. This centre is mainly involved in reproductive biology studies involving monkeys. Aires, as well as the Centre for Chile Applied and Experimental In Chile, the Programme is Endocrinology in La Plata. continuing to support three institu- Bolivia Researchers from Bolivia helped plan, and will implement, the regional social sciences re- search initiative on men's percep- tions and behaviour in sexual and reproductive decision-making. This study is due to start in 1998. Brazil The Campinas Centre for Re- search and Control of Maternal and Infant Disease (CEMICAMP) at the University of Campinas is the main recipient of Programme support in the country. The grants are being used for training in re- search methodology as well as for research on contraceptive intro- duction and other aspects of wo m- en's reproductive health. CEMICAMP is one of three study sites implementing the regional study on acceptability of emer- gency contraception. In addition, it is conducting one of the three regional projects on informed con- sent. CEMICAMP also acts as the tions in Santiago: the Chilean In- stitute of Reproductive Medicine, the Unit of Reproductive Biology and Development at the Catholic University of Chile, and the Insti- tute for Maternal and Child Health Research. All three centres par- ticipate in Programme-supported institutional development activities and act as regional training cen- tres. The University of Chile also continued to receive a small grant for support of research on basic reproductive biology. In addition to its research on reproduction in monkeys, the Unit of Reproductive Biology and De- velopment has taken the leader- ship to establish and coordinate the regional basic sciences net- work that will study the mode of action of emergency contracep- tion using oral contraceptives. Meanwhile, the Institute of Repro- ductive Medicine is coordinating and participating in the regional study on acceptability of emer- gency contraception, which got under way in early 1997. Biennial Report 1996-1997 Colombia on caesarian deliveries, due to Since 1980, the University of begin in 1998. Valle, in Cali, has collaborated with the Programme in implement- ing the national programme in human reproduction. The Centre, which iscurrently receiving a small grant from the Programme, is in- volved in plansto reduce mate mal mortality in Colombia. The aims are to: develop operational re- search to improve delivery of ma- temal health services; support epi- demiological studies on the devel- opment of risk models for the pri- mary causes of maternal morbid- ity and mortality in Colombia; and improve the network conducting research on maternal care. Cuba In Cuba, research in reproduc- tive health is conducted by the National Coordinating Networkfor Research in Human Reproduc- tion, in coordination with other public health programmes. The Network also collaborates exten- sively in various multicentre trials of the Programme. The Institute of Endocrinology continues to conduct basic sci- ences research on reproductive immunology and is involved in the Regional Reagent Production Pro- gramme conducted in coordina- tion with the Institute of Nutrition in Mexico City and CEMIC in Bue- nos Aires. Meanwhile, the Insti- tute will implement the regional research initiative on men's per- ceptions and behaviour in sexual and reproductive decision-mak- ing. Elsewhere, the America Arias Hospital is taking part in the ongo- ing multicentre antenatal care project and in the regional study Guatemala The Guatemalan Research Group in Reproductive Health re- ceives support to develop a repro- ductive health research unit for epidemiological and health serv- ice studies. Research projects in- clude a large follow-up study of mothers and their children which began 1 ° years ago when the women were still pregnant. The aim is to evaluate the reproduc- tive health experience of women from urban areas with different sociocultural backgrounds. Other key projects include the develop- ment of Spanish language soft- ware for perinatal and maternal mortality surveillance pro- grammes, and the implementa- tion of new technology to evaluate quality of care within mother and infant health care systems in ur- ban areas. Mexico The_Department of Reproduc- tive Biology at the Mexico City- based National Institute of Nutri- tion is the main recipient of Pro- gramme support in the country. The I nstitute maintains a very high standard of research and plays a key role in collaborating with the Programme and other research centres in the region, as well as participating in the regional pro- gramme for the production of rea- gents for reproductive hormones. The Department is also one of four centres which comprise the regional basic sciences network. In 1997, the Department contin- ued to receive grants for resource maintenance and training. >-I-(3 0: (3 I Q Cl: « ill (f) ill Cl: The Programme also supports the Reproductive Biology Depart- ment at the University of Coahuila in Torreon, which is involved in research on contraception and the impact of environmental pollution Biennial Report 1996-1997 CERI is involved in a twinning venture with the Centre for Popu- lation Studies (CENEP), Buenos Aires, Argentina. The twinning arrangement aims to enhance CERI's research capability in so- on reproductive health. A grant is cial science research. also provided forthe M.Sc.course in reproductive biology run by the National Institute of Health in Cuernavaca. Over the past six years, graduate students have included 12 young scientists from Programme-supported centres in Argentina, Chile, Cuba, Guate- mala, Mexico, Panama, Peru, and Venezuela. Also, the Programme is supporting activities at the Insti- tute for Scientific Research at the University of Durango. The Insti- tute is collaborating with centres in Brazil and Chile in implement- ing the regional study on the ac- ceptability of emergency contra- ception. Panama The Centre for Research in Human Reproduction has carried out research in areas such as sickle cell anaemia and the use of contraceptives, reproductive health of adolescents,
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