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RHO archives : Topics : Infertility

Annotated Bibliography

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General

Family Health International (FHI). Preserving fertility. Network. 2003;23(2):1–24.Available at: www.fhi.org/en/RH/Pubs/Network/v23_2/index.htm.
This issue of Family Health International’s (FHI) quarterly publication, Network, is devoted to articles that discuss a range of topics related to defining and preserving infertility. Articles focus on issues such as contraception and the return to fertility, assisted reproductive technologies, the link between sexually transmitted infections (STIs) and infertility, men’s experiences, and programmatic efforts to reduce infertility through the management of STIs.

PATH (Program for Appropriate Technology in Health). Infertility in developing countries. Outlook 15(3):1–6 (November 1997). Available at: www.path.org/outlook/html/15_3.htm#infert).
This article, available on-line at www.path.org/html/15_3_fea.htm, reviews data on the prevalence, causes, and management of infertility in developing countries. Its discussion of the common causes of infertility, especially infection, leads to recommendations on how infertility can be prevented and its prevalence reduced. The article also discusses how to evaluate and treat infertile couples where resources are limited. It emphasizes the need for systematic work-ups to establish accurate diagnoses and the importance of considering costs and probable results in treatment decisions. The author recommends thorough counseling to help infertile couples understand and cope with their situation. Also discussed is the role family planning clinics can play in educating couples about infertility and in offering basic evaluations and treatments.

Ralph, S.G. et al. Influence of bacterial vaginosis on conception and miscarriage in the first trimester: cohort study. British Medical Journal 319:220–23 (1999). Available at: www.bmj.com/cgi/content/full/319/7204/220).
This study compared the rates of conception and miscarriage among women with bacterial vaginosis and those with normal vaginal flora. Vaginal samples were collected from 867 consecutive women undergoing an in vitro fertilization in Britain; 25 percent proved to have bacterial vaginosis. There was no difference in conception rates between women with and without bacterial vaginosis. However, women with bacterial vaginosis had twice the risk of miscarrying during the first trimester, after adjusting for age, smoking, previous live births and miscarriages, and polycystic ovaries. Of the 237 women who conceived, 18.5 percent of women with normal vaginal flora miscarried during the first 13 weeks of gestation, compared with 23.3 percent of those with intermediate flora, and 36.1 percent of those with bacterial vaginosis. Pre-existing endometritis affecting implantation or early embryonic development is the most likely reason; this could also affect naturally conceived pregnancies.

Rowe, P.J. et al., eds. WHO Manual for the Standardized Investigation and Diagnosis of the Infertile Couple. Cambridge University Press, Cambridge, England (1993).
This book presents a standard protocol for the evaluation and diagnosis of infertile couples. It was developed by a WHO Task Force and tested in 25 countries during the investigation of more than 9,000 infertile couples. The goal of the protocol is to provide more efficient, systematic, and economic care for infertile couples by ensuring that all essential information is collected and by improving the accuracy of diagnoses. The book provides clear guidelines and a logical sequence of steps for clinicians to follow in evaluating both men and women. It also includes diagnostic charts and explanations of essential clinical tests.

Sciarra, J. Infertility: an international health problem. International Journal of Gynecology & Obstetrics 46:155–163 (1994).
This article summarizes available data on the prevalence of infertility in both developed and developing countries; important etiological factors, especially infection; and surgical and medical therapies for tubal disease, uterine adhesions, uterine fibroids, and spontaneous abortions. It also reviews the success, expense, and ethical considerations surrounding in vitro fertilization (IVF) and assisted reproductive technology. The author concludes that the most important steps physicians can take to reduce infertility are the prevention and early management of PID and conservative surgery for tubal ectopic disease.

Sciarra, J. Sexually transmitted diseases: global importance. International Journal of Gynecology & Obstetrics 58:107–119 (1997).
This article reviews the impact of Chlamydia, gonorrhea, Syphilis, and HIV/AIDS, on the health of women and the prevalence of each disease in developed and developing countries. It also reviews the evidence for a relationship between STI infection, pelvic inflammatory disease (PID), ectopic pregnancy, and infertility. The author recommends the expansion of STI prevention programs using four different approaches: (1) educating physicians and patients about risks of STIs; (2) developing simple, inexpensive, rapid tests for routine screening and early diagnosis of asymptomatic infections; (3) developing vaginal contraceptives that protect against STIs; and (4) creating vaccines against Chlamydia and HIV.

WHO Scientific Group. Recent Advances in Medically Assisted Conception. WHO Technical Report Series, Number 820 (1992).
This report was produced by an international group of experts who met in 1990 under the auspices of the World Health Organization. It discusses a wide range of infertility treatments, including in vitro fertilization, intrauterine and intrafallopian transfer techniques, and artificial insemination. In addition to reviewing when these techniques are appropriate and how they should be performed, the report also discusses psychological, social, ethical, and legal issues surrounding medically assisted conception.

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Geographic and ethnic variations in the prevalence of infertility

Ericksen, K. and Brunette, T. Patterns and predictors of infertility among African women: a cross-national survey of twenty-seven nations. Social Science and Medicine 42(2):209–220 (1996).
Data from World Fertility Surveys and Demographic and Health Surveys are used to calculate and compare infertility rates for 27 countries in sub-Saharan Africa. Infertility ranged from 10 percent to 20 percent, with lower rates concentrated in eastern Africa and higher rates in southern Africa. Low childlessness rates indicate little primary infertility, except in Cameroon and Madagascar, but data on birth intervals suggest that many African women experience extended periods of subfecundity during their lives. Risks of infertility are greater for sexually experienced women who are currently unmarried, have had multiple partners, or began having sex at a early age. Infertility is also higher in urban than rural areas. The analysis also found large variations in infertility rates between cultural groups that were independent of sexual risk factors and geographic location.

Fuentes, A. and Devoto, L. Infertility after 8 years of marriage: a pilot study. Human Reproduction 9(2):273–278 (1994).
To investigate the prevalence of infertility over time, this study examined the reproductive histories of 474 women married in Santiago, Chile in 1982 during the first eight years of their marriages. Over the course of the eight-year period, 26 percent of the women had experienced an episode of infertility (defined as the inability to conceive after trying for a year), averaging 24 months in length. At the end of the eight-year period, however, only 4 percent of the women had never conceived. The authors conclude that the inability to conceive after one year may be too strict a definition of infertility, since many women eventually do conceive without treatment. The majority of the women themselves did not consider a one-year delay in conception to be a medical problem.

Greenhall, E. and Vessey, M. The prevalence of subfertility: a review of the current confusion and a report of two new studies. Fertility and Sterility 54(6):978–983 (1990).
The authors discuss the methodological problems in defining infertility and measuring its prevalence, especially the difficulty of obtaining information from an unbiased sample of women. They analyze the strengths and weaknesses of census and population surveys, retrospective studies of women receiving antenatal or postnatal care, studies of women seeking medical treatment, and prospective studies of women trying to conceive. Two new approaches to studying subfertility are presented. The authors conclude that it is important to distinguish between different types of subfertility (e.g., whether the delay is in conceiving a first or subsequent child, and whether or not the problem has been resolved) when analyzing data on infertility.

Larsen, U. Infertility in Central Africa. Tropical Medicine and International Health 8(4):354–367 (April 2003).
In this article, the author examines DHS-III data for four Central African countries to assess levels of primary and secondary infertility. Data from Cameroon, Chad, Central African Republic, and Gabon show rates of primary infertility ranging from 3.1 percent in Chad to 6.9 percent in Central African Republic. Secondary infertility rates ranged from 18.9 percent in Chad to a high of 26.3 percent in Central African Republic, suggesting that there still is an "infertility belt" in the Central African region. Risk factors associated with primary and secondary infertility for women include women being married more than once and living with the husband. In addition, women born after 1970 had a higher risk of primary infertility and women born after 1960 had a higher risk of secondary infertility than older women (born before 1960).

Larsen, U. Primary and secondary infertility in sub-Saharan Africa. International Journal of Epidemiology 29:285–291 (2000).
This study measured the prevalence of infertility in Africa among women aged 20 to 44 based on data from nationally representative Demographic and Health Surveys and World Fertility Surveys. Primary infertility was defined as the proportion of women who remain childless at least seven years after their first marriage. Secondary infertility was defined as the proportion of women with no live births for at least five years after the birth of last their last child. The prevalence of primary infertility is low throughout sub-Saharan Africa, ranging from 1 percent to 6 percent. In contrast, the prevalence of secondary infertility varies widely between countries, from a low of 5 percent in Togo, to a high of 23 percent in Central African Republic. Age patterns of infertility also vary widely between countries. The author concludes that the prevalence of infertility of pathological origins is so high that infertility should be considered a public health problem.

Larsen, U. Childlessness, subfertility, and infertility in Tanzania. Studies in Family Planning 27(1):18–28 (1996).
This study examined trends and geographic variations in childlessness, subfertility (measured by open birth intervals of more than five years), and infertility in Tanzania based on data from the 1973 National Demographic Survey and the 1991–1992 Demographic and Health Survey. Infertility was markedly higher in urban than in rural areas, and in the coast and northwest highlands than in the northeast highlands. Childlessness declined by more than 60 percent and subfertility by 40 percent-50 percent between the two surveys. The author suggests that the decline in infertility may be due primarily to effective campaigns against malaria and the improvement of midwifery practices, rather than to any decline in the incidence of STIs.

Thonneau, P. and Spira, A. Prevalence of infertility: international data and problems of measurement. European Journal of Obstetrics & Gynecology and Reproductive Biology , 38:43–52 (1990).
This article compares alternative methodologies to measure the prevalence of infertility, including national surveys, regional studies, and health center based studies. Because national surveys are population-based and include infertile women who do not seek treatment, they can estimate the prevalence of infertility and its trends accurately, but they provide little information on causes and risk factors. Regional studies that attempt to identify all infertile women in a limited population exclude infertile women who do not seek treatment. However, these studies can provide good data on the causes, distribution, and risk factors of primary and secondary infertility. Retrospective studies of a series of infertile patients treated at a facility can provide information on risk factors and treatments, but not prevalence.

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Investigation of the causes of female infertility

Cates, W. et al. Worldwide patterns of infertility: is Africa different? Lancet 596–598 (September 14, 1985).
This landmark article reports the results of the most comprehensive study of infertility to date: a multinational WHO investigation of 5,800 infertile couples seeking help at 33 medical centers in 22 developed and developing countries between 1979 and 1984. It concludes that Africa exhibits a different pattern of infertility from the rest of the world, a pattern that is driven by high rates of infection. Data show that infertile women in Africa are younger, more likely to suffer from secondary infertility, and more likely to have a history of STIs and pregnancy complications than women in other regions. Over 85 percent of infertile African women had a diagnosis which could be related to infection, compared with 39 percent in Asia, 44 percent in Latin America, and 36 percent in developed countries. African men were more likely than men elsewhere to have a varicocele or accessory gland infection. The authors argue that public health programs to reduce infection in Africa are critically important for reducing infertility.

Cates, W. et al. Pelvic inflammatory disease and tubal infertility: the preventable conditions. Annals of the New York Academy of Sciences 709:179–195 (1994).
This article traces a causal pathway from lower genital tract STIs to upper genital tract PID, scarring, and tubal infertility. It reviews the magnitude, etiology, and risk factors for each condition. Risk factors for tubal occlusion include the number and severity of episodes of PID; the woman's age, contraceptive choice, and smoking history; and the pathogen. Since antibiotic treatment of symptomatic PID has little impact on a woman's subsequent fertility, the authors conclude that efforts should be focused on preventing STIS and on treating them before they reach the fallopian tubes.

Chigumadzi, P. et al. Infertility profile at King Edward VIII Hospital, Durban, South Africa.Tropical Doctor 28:168–172 (1998).
This study reports on a series of 100 infertile black African women seeking treatment at a South African hospital where one in eight gynecology patients presents with infertility. The mean duration of infertility was 7.2 years. While 49 percent of the women had been evaluated before, most had never received treatment. Sixty-one percent of the women had histories suggesting PID, 16 percent were sero-positive for syphilis, and 16 percent were HIV-positive. Tubal factors were the leading cause of infertility, present in 77 percent of couples, followed by ovulatory factors in 21 percent, uterine factors in 21 percent, and male factors in 21 percent. The authors conclude that preventing infection (both STIs and septic abortions) should be a public health priority. They also discuss problems in the way infertility patients are treated and recommend the establishment of a dedicated infertility service with standard protocols to ensure appropriate and efficient infertility work-ups and continuity in patient management.

Favot, I. et al. HIV infection and sexual behavior among women with infertility in Tanzania: a hospital-based study. International Journal of Epidemiology 26(2):414–419 (1997).
This case-control study compared 154 women attending an infertility clinic in northwestern Tanzania with 259 women coming to deliver in the same facility from 1994–1995. The infertile women were two and half times more likely to have HIV than the pregnant women. Infertile women also had higher levels of sexual activity as indicated by marital instability, number of sexual partners, age at first intercourse, and evidence of past STIs. There were no significant differences in current levels of STI infection. The authors argue that while it is possible that HIV reduces fertility, it is equally possible that infertility causes a pattern of marital breakdown, multiple sexual partnerships, and subsequent HIV infection, or that patterns of sexual behavior lead to reproductive tract infections, subsequent infertility, and HIV. The article recommends that sentinel surveillance and voluntary screening for HIV should include infertility clinics as well as antenatal clinics.

Greenlee, A.R. et al. Risk factors for female infertility in an agricultural region. Epidemiology 14(4):429–436 (July 2003).
In 1997 the Fertility Risk Factor Study was initiated to examine the risk of female infertility associated with exposure to various agricultural products. The study was carried out in an area of Wisconsin where the majority of occupations are in farming and manufacturing. Cases (626 infertile women) and controls (558 fertile women) were interviewed about home and occupational exposures and other activities in the 2-year period prior to their attempt to become pregnant. The survey results showed an increased risk of infertility for women involved in mixing and applying herbicides during the 2-year period as compared to controls (adjusted OR = 27, 95% confidence interval = 1.9-383.8), although the number of women exposed was too small to isolate the risks associated with individual chemicals. Other exposures and behavioral factors such as exposure to fungicides, alcohol consumption, smoking, smoke exposure, and steady weight gain were also associated with modest increased risks, although the odds ratios and confidence intervals did not appear statistically significant.

Inhorn, M.C. and Buss, K.A. Ethnography, epidemiology, and infertility in Egypt. Social Science and Medicine 39(5):671–686 (1994).
This article combines ethnographic and epidemiological research to investigate risk factors for infertility in Egypt. It reports the results of a case-control study of 190 women living in Alexandria who visited a clinic for infertility treatment, family planning, or prenatal care. The women were interviewed in-depth on potential risk factors identified by the epidemiological literature and during ethnographic field research. The study found higher risks of infertility for: (1) women who were treated with cervical electrocauterization, which is an overused therapeutic technique in Egypt that can permanently damage the cervix, (2) men exposed to heat, pesticides, chemicals, and/or schistosomiasis during their work, (3) men who smoke a traditional waterpipe, and (4) marriages between close cousins, which over multiple generations may increase the risk of immunological-factor infertility. The authors conclude that local ethnographic factors are important for understanding the etiology and patterns of infertility.

John, M. and Kukkady, Z. Genital tuberculosis and infertility. International Journal of Gynecology & Obstetrics 64:193–194 (1999).
Infertility is the most common initial symptom of tuberculosis. The reported prevalence of genital tuberculosis in infertility clinics varies widely, but may range as high as 19 percent in some countries. In this brief communication from the United Arab Emirates, the authors report that four patients at their infertility clinic who were discovered to have genital tuberculosis conceived spontaneously 2–9 months after beginning anti-tuberculosis therapy.

Leke, J.I. et al. Regional and geographical variations in infertility: effects of environmental, cultural, and socioeconomic factors. Environmental Health Perspectives Supplements 101 (Suppl. 2):S73–S80 (1993).
This article examines the etiology of infertility in three different parts of the world. In sub-Saharan Africa, it looks at the impact of traditional practices, including polygamy, illegal abortion, female circumcision, and unassisted labor and delivery. In Mexico, it reviews socio- economic and environmental factors affecting health, especially the effects of arsenic pollution in the drinking water of Comarca Lagunera, a region in north-central Mexico. In Brazil, it describes the impact of changes in government priorities on women's health care services in state of So Paulo.

Longombe, A.O. and Geelhoed, G.W. Iodine deficiency disorders and infertility in northeast Zaire. Nutrition 13(4):342–343 (1997).
This article presents data on the prevalence of sterility and goiter by subregion in northeast Zaire. It speculates that iodine and selenium deficiencies may contribute to high rates of infertility in this area. The authors discuss possible mechanisms for iodine deficiency to reduce female fertility and for selenium deficiency to reduce male fertility.

Mayaud, P. "The Role of Reproductive Tract Infections." In: Boerma, J.T. and Mgalla Z., eds. Women and Infertility in sub-Saharan Africa: A Multi-disciplinary Perspective. Amsterdam: KIT Publishers (2001).
This chapter reviews the factors associated with male and female infertility in sub-Saharan Africa. Particular attention is given to the impact of untreated or poorly treated STIs and the subsequent development of PID. PID is considered the main cause of infertility in women in Africa, due mostly to tubal scarring. Other factors associated with the development of PID, such as cesarean sections, unclean birthing practices, unsafe abortions, IUD insertions when STIs are present, and trans-cervical procedures, are discussed. Authors suggest implications for policy and programs, including an emphasis on the appropriate screening and management of STIs and higher quality obstetric and gynecology practices in developing countries, to help reduce the incidence of infertility.

Parikh, F.R. et al. Genital tuberculosis—a major pelvic factor causing infertility in Indian women. Fertility and Sterility 67(3):497–500 (1997).
This study examines the effect of tuberculosis on female fertility in India. Tuberculosis is widespread in India and spreads to the genital areas early in the course of the disease. Of 300 women with tubal infertility treated between 1993–1994, 39 percent had pelvic tuberculosis, either currently or in the past. Laparoscopy found tubal involvement in 54.7 percent of the women with tuberculosis, tubo-ovarian masses in 15.4 percent, and a frozen pelvis in 23.9 percent. Three-quarters of these women complained of menstrual irregularities, which can be caused by endometrial tuberculosis. The authors conclude that tuberculosis is a major etiologic factor of female tubal infertility in India.

Shahara, F. et al. Environmental toxicants and female reproduction. Fertility and Sterility 70(4):613–622 (1998).
This article reviews evidence from both human and animal studies on how exposure to chemicals in the workplace and at home may affect women's fertility and reproductive outcomes. It also discusses possible mechanisms of action. Among the chemicals considered are endocrine disruptors, heavy metals, solvents, pesticides, industrial chemicals, and cigarette smoke. While studies suggest that a wide range of chemicals may affect women's reproductive functioning, methodological shortcomings limit the strength of their conclusions. The authors recommend that women's exposure to known toxicants, such as dioxins and cigarette smoke, be limited and that further research on other chemicals be conducted.

Stewart, A.G. Iodine deficiency disorders and infertility. Tropical Doctor :36–37 (January 1991).
A physician working in a Pakistani clinic relates his experience in treating infertility in this letter to the editor. The clinic has limited capabilities for diagnosing and treating infertility. Because goiter is common in this region, however, all infertile patients are routinely given iodized oil intramuscularly, whether or not they have a goiter. Although the author is still collecting data on the patients treated, this treatment appears to be successful in many cases. The author speculates about whether low iodine levels alone can explain infertility or whether the presence of a goitrogen contributes to the problem.

Tuntiseranee, P. et al. Are long working hours and shiftwork risk factors for subfecundity? A study among couples from southern Thailand. Occupational and Environmental Medicine 55:99–105 (1998).
This study investigated the effect of work patterns on the fecundity of 907 working women with planned pregnancies who sought antenatal care at two clinics in Thailand. Women who worked more than 70 hours a week were 1.6 times as likely as other women to experience a 9.5 month delay in conception, after adjusting for age, education, body mass index, menstrual regularity, medical history, coital frequency, and exposure to toxic agents. Long working hours had an even greater impact on fecundity among women conceiving for the first time (OR = 2.3) and among couples where both husband and wife worked long hours (OR = 2.0). Neither sexual activity nor menstrual disturbances explained the association.

Westrom, L.V. Sexually transmitted diseases and infertility. Sexually Transmitted Diseases 21(2, Suppl.):S32–S36 (1994).
This exhaustive review of the evidence linking STIs with infertility covers both male and female infertility. For men, there are no firm conclusions because a host of small, non-comparable studies have produced conflicting results. For women, the author summarizes the results of the 25-year landmark study of PID in Lund, Sweden, which enrolled more than 3,000 women who underwent routine laparoscopy from 1960-1984. The study found that women with PID had a higher risk of infertility and ectopic pregnancy than those with a normal laparoscopy, and that risk increased with the number and severity of PID episodes. Twelve percent of women with PID and 0.9 percent of controls had tubal factor infertility. The author argues for evaluating, diagnosing, and treating STIs more promptly in order to lower the incidence of PID.

World Health Organization. Infections, pregnancies, and infertility: perspectives on prevention. Fertility and Sterility 47(6):964–968 (1987).
This analysis of the data from the WHO multinational study of infertility examines whether regional differences in rates of bilateral tubal occlusion are related to differences in levels of STIs, PID, and postpartum/postabortion infection. A history of any of these infections was associated with an increased risk of bilateral tubal occlusion and other infection-related infertility diagnoses in every region studied. The percentage of women diagnosed with bilateral tubal occlusion generally increased if they had ever been pregnant, had an abortion, or a live birth. However, the number of previous abortions had more of an impact on infertility risks in developed countries and in Asia, while the number of live births was more important in Africa and in Latin America. The authors conclude that public health programs aimed at reducing STIs, PID, and postpartum and postabortion infections may reduce the incidence of infertility.

World Health Organization Task Force on the Prevention and Management of Infertility. Tubal infertility: serologic relationship to past chlamydial and gonococcal infection. Sexually Transmitted Diseases 22(2):71–77 (1995).
This case-control study of women attending infertility centers in Thailand, Slovenia, and Hungary examines the link between STIs and infertility. Seventy-eight infertile women with bilateral tubal occlusion (BTO) were compared with 155 infertile women without BTO and 466 pregnant women. A striking difference was found in the likelihood of past, but not current, STI infections: 93 percent of the women with BTO had antibodies to Chlamydia and/or gonorrhea, compared with only 40 percent of the pregnant women. Most of these episodes had gone unrecognized by the women: two-thirds of the women with BTO who had STI antibodies did not report any prior symptoms of PID. Surprisingly, the prevalence and levels of Chlamydia antibodies were also elevated in infertile women with tubal abnormalities other than BTO. This suggests that Chlamydia may contribute to a wider range of female infertility than previously suspected.

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