Defining infertility: what infertility means for clinicians and clients.

KEY POINTS

* Infertility often involves both members of a couple.

* STIs are the primary preventable causes of infertility.

* Postpartum and postabortion infections are also associated with infertility.

* Contraceptive use does not cause infertility.

Infertility is complex. It has multiple causes and consequences depending on the gender, sexual history, lifestyle, society, and cultural background of the people it affects.

Partly due to its complexity and to difficulty preventing, diagnosing, and treating it, infertility is a global public health concern. More than 80 million people--about 8 percent to 12 percent of all couples worldwide (1)--are or have been infertile. Although infertility is considered by some to be primarily a woman's problem, men often contribute to and are also affected by it (see article, page 17).

"Infertility is not really an issue of either partner," says Dr. Timothy Farley, previously a member of the World Health Organization (WHO) Task Force on Diagnosis and Treatment of Infertility and currently coordinator of the Department of Reproductive Health and Research at WHO. "Infertility is an issue of the couple."

Infertility arises when either one or both members of a couple are sterile or have severely reduced fertility. Sterility of one partner will always render the couple infertile. But subfertility, or reduced fertility, is more complicated. Subfertility in both partners is likely to lead to infertility, but subfertility in one partner may or may not, depending on the overall combined fertility of the couple.

A couple is considered clinically infertile only when pregnancy has not occurred after at least 12 months of regular sexual activity without the use of contraceptives. At the teaching hospital at the University of Ibadan in Nigeria, gynecologist and senior lecturer Dr. Ayodele Arowojolu, who is also a former FHI fellow, says that clients are discouraged from seeking infertility services until they have failed to conceive for an entire 24 months.

"Clinicians implement these waiting times because otherwise they would be inundated with people who have subfertility problems for which little or nothing needs to be done," says Dr. Farley. Research has shown that many couples seeking infertility treatment are actually subfertile and may eventually become pregnant without any intervention. In an evaluation and two-year follow-up of 455 couples attending an infertility clinic in Chandigarh, India, 14 percent of the couples became pregnant before treatment even started and another 10 percent before treatment was completed. (2) Two studies from developed countries have shown even higher rates of pregnancy--35 percent in one (3) and 72 percent in the other (4)--among 548 and 342 untreated subfertile couples, respectively.

Preventable causes

Many factors--infectious, environmental, genetic, and even dietary in origin--can contribute to infertility (see table, below). (5) But this list includes factors that produce subfertility, which may not ultimately prevent conception or may subside. An important question, then, is which of these are the major causes of infertility that likely will not reverse without clinical intervention.

Between 1979 and 1984, the WHO Task Force on Diagnosis and Treatment of Infertility supported an evaluation of 5,800 couples who completed a standard diagnostic work-up for infertility at 33 medical centers in 25 countries throughout the developed and developing world. (6) Although the results may not be applicable to all populations, this was the largest epidemiological study of its kind, providing unparalleled data on the major causes of infertility.

Results showed no known cause for up to 14 percent of the couples. But in all regions of the world, the largest proportion of remaining diagnoses could be attributed to infection. In particular, women who reported a history of sexually transmitted infections (STIs) had higher rates of infertility than women who did not. (7)

In fact, STIs are recognized as the most common preventable cause of tubal infertility (see article, page 12). Such STIs as chlamydial infection or gonorrhea in the lower genital tract can ascend into the upper genital tract, causing pelvic inflammatory disease (PID) that can produce inflammation, scarring, and eventual blockage of the fallopian tubes. (8)

The WHO study also showed that in every region of the world, a history of postpartum or postabortion complications was associated with blockage of both fallopian tubes. In addition, the percentage of women with both fallopian tubes blocked generally increased if the women had even ever been pregnant, given birth, or had an abortion, regardless of whether complications occurred. (9)

Unsafe obstetric practices during delivery or abortion could introduce new infections that can lead to PID or other problems that hinder conception. Many cases of infertility after delivery or abortion may, however, still be due to STIs. If a woman has gonorrhea or chlamydial infection during pregnancy, her estimated risk of PID increases 50 percent to 100 percent if she either gives birth or has an abortion. (10) In these cases, instruments used during obstetric procedures could carry existing infections into the upper genital tract.

Knowledge and misconceptions

In many cultures, infertility is considered a shameful condition, something that is not freely discussed. So, not surprisingly, many men and women either do not know or still have misconceptions about the true causes of infertility.

Dr. Silke Dyer is the director of infertility services at Groote Schuur Hospital, a large public tertiary care hospital in Cape Town, South Africa. "I've begun asking almost all of my patients 'Now why do you think you're infertile?' and many of them just shrug their shoulders," she says. "So I think they truly do not know."

Dr. Arowojolu, the gynecologist from the University of Ibadan, Nigeria, agrees that many patients do not understand what is causing their fertility problems. "There is also a lot of mystique surrounding infertility," he says. Because childbearing is viewed as a natural part of adult life, some have explained infertility as supernatural. It has been labeled an act of God, a punishment from unhappy ancestors, or the result of witchcraft. In an urban slum area of Bangladesh, nearly half of 120 men and women surveyed said evil spirits caused female infertility. (11)

Another common misconception--that some forms of contraception cause infertility--may be a powerful disincentive to contraceptive use. (12) Group interviews with men and women in Cameroon's North West Province revealed that contraception was thought to "spoil the womb" and that young, less-educated women were particularly unlikely to use contraception as long as they felt susceptible to infertility. (13) In southwest Nigeria, study participants also suggested that contraceptives can damage the uterus, leading to infertility. (14)

Even family planning providers sometimes misunderstand the effects of contraceptives on fertility. In an FHI study in Ghana, many of 97 providers interviewed said they used age or parity requirements to ensure that only women of proven fertility obtained contraceptives, mainly because they believed that hormonal methods delay fertility or cause infertility. (15)

Because contraceptives prevent pregnancy, they may mask underlying fertility problems, but they do not cause infertility. The risk of long-term impaired fertility after using any contraceptive method is low, and fertility usually returns immediately or shortly after contraceptive discontinuation (see table, this page). (16) In fact, by preventing unintended pregnancy and thus the potential for either postpartum or postabortion infections, all contraceptives can help prevent infertility and improve the chances that women will become pregnant when they choose to do so.

Expectations

While many couples do not know the true causes of infertility, the consequences are often apparent, especially for women in the developing world. Grief and frustration, guilt, stigmatization and ridicule, abuse, marital instability, economic deprivation, and social ostracism are just some of the consequences that have been reported in various parts of Asia and Africa. (17)

Many of these consequences are personal, but others are societal. Throughout the world women are expected to bear children, but these social pressures can be particularly intense in parts of the developing world where voluntary childlessness is rare and opportunities for women, aside from motherhood, are few. In hopes of becoming pregnant, some women who consider themselves infertile may even engage in extramarital relations, a behavior that places them at risk of STIs, including HIV. (18)

Clinicians should be aware that infertile couples also have their own expectations. Dr. Dyer and colleagues from Groote Schuur Hospital, the University of Cape Town, and South Africa's Medical Research Council recently conducted research aimed in part to identify clients' expectations of infertility clinics. The research included a quantitative study of 120 women and a qualitative study of 30 women. All were visiting the Groote Schuur Hospital's infertility clinic for the first time. (19)

When the women were asked about their expectations, three main themes emerged: hope to conceive; hope to receive information about if, when, and how they could conceive; and uncertainty about what to expect. Some women also had unrealistic expectations. Nearly half of the 120 women in the quantitative study thought they would definitely conceive by attending the clinic, and more than one woman from the qualitative study thought that she would be pregnant by the end of her first visit.

"Very often infertility services focus mostly on pregnancy rates, but this research shows us there is a definite role of infertility care beyond achieving pregnancy," says Dr. Dyer. "Not everyone is going to conceive, and not everyone will ultimately be able to access the kind of therapy they want. So, particularly in communities like ours, there is a separate aim. And that is providing information, counseling, and empathy."

Factors Contributing
to Infertility

Anatomical problems
Endocrinological problems
Genetic problems
Immunological problems
Increasing age
Infectious and parasitic diseases
  Genital tuberculosis
  Malaria
  Schistosomiasis
Malnutrition
Potentially harmful substances
  Aflatoxins
  Arsenic
  Pesticides
  Tobacco, alcohol, or caffeine
Reproductive tract infections
  Postabortion infections
  Postpartum infections
  Sexually transmitted infections

Contraception and Return to Fertility

Contraceptive Method                        Time to Return of Fertility

Abstinence                                  immediate
Condoms (male and female)                   immediate
Female barrier methods,other than condoms   immediate
Implants                                    immediate
Injectables
  Combined monthly                          immediate
  Progestin-only
    Depot-medroxyprogesterone acetate       average 10 months
      (DMPA)
    Norethisterone enanthate (NET-EN)       average 6 months
Intrauterine devices                        immediate
Oral contraceptives *                       immediate
Sterilization                               no return to fertility

* Although return to fertility may be immediate, a delay of a few
months has been observed in several studies.

Note: Because all contraceptives protect against pregnancy, they also
protect against postpartum and postabortion infections that are
associated with infertilty.

Source: World Health Organization. Improving Access to Quality Care in
Family Planning. Medical Eligibility Criteria for Contraceptive Use.
Geneva, Switzerland: World Health Organization, 2000.

References

(1) Program for Appropriate Technology in Health (PATH). Infertility. Overview/lessons learned. Reproductive Health Outlook 2002. Available: http://www.rho.org/html/infertility.htm.

(2) Khaliwal LK, Khera KR, Dhali GI. Evaluation and two-year follow-up of 455 infertile couples--pregnancy rate and outcome. Int J Fertil 1991;36(4):222-26.

(3) Collins JA, Wrixon W, Janes LB. Treatment-independent pregnancy among infertile couples. N Engl J Med 1983;309(20):1201-6.

(4) Snick HK, Snick TS, Evers JL, et al. The spontaneous pregnancy prognosis in untreated subfertile couples: the Walcheren primary care study. Hum Reprod 1997;12(7):1582-88.

(5) Program for Appropriate Technology in Health (PATH). Infertility in developing countries. Outlook 1997;15(3):1-6; Mascie-Taylor CGN. Endemic disease, nutrition and fertility in developing countries. J Biosoc Sci 1992;24(3): 355-65; Hassan MA, Killick SR. Effect of male age on fertility: evidence for the decline in male fertility with increasing age. Fertil Steril 2003;79(Suppl 3):1520-27.

(6) Cates W, Farley TM, Rowe PJ. Worldwide patterns of infertility: is Africa different? Lancet 1985;2(8455):596-98.

(7) World Health Organization. Infections, pregnancies, and infertility: perspectives on prevention. Fertil Steril 1987;47(6):964-68.

(8) Cates W Jr, Rolfs RT, Aral SO. Sexually transmitted diseases, pelvic inflammatory disease, and infertility: an epidemiological update. Epidemiol Rev 1990;12:219-20.

(9) World Health Organization.

(10) McFalls JA, McFalls MH. Disease and Fertility. London, England: Academic Press, 1984.

(11) Papreen N, Sharma A, Sabin K, et al. Living with infertility: experiences among urban slum populations in Bangladesh. Reprod Health Matters 2000;8(15):33-44.

(12) Inhorn MC. Global infertility and the globalization of new reproductive technologies: illustrations from Egypt. Soc Sci Med 2003;56(9): 1837-51; Okonofua F. The case against new reproductive technologies in developing countries. Br J Obstet Gynaecol 1996;103(10):957-62.

(13) Richards SC. "Spoiling the womb": definitions, aetiologies and responses to infertility in North West Province, Cameroon. Afr J Reprod Health 2002;6(1):84-94.

(14) Okonofua FE, Harris D, Odebiyi A, et al. The social meaning of infertility in southwest Nigeria. Health Transit Rev 1997;7(2):205-20.

(15) Stanback J, Twum-Baah KA. Why do family planning providers restrict access to services? An examination in Ghana. Int Fam Plann Perspect 2001;27(1):37-41.

(16) Huggins GR, Cullins VE. Fertility after contraception or abortion. Fertil Steril 1990;50(5): 451-60; Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology, Seventeenth Revised Edition. New York, NY: Ardent Media, Inc., 1998.

(17) Papreen; Okonofua; Dyer SJ, Abrahams N, Hoffman M, et al. "Men leave me as I cannot have children": women's experiences with involuntary childlessness. Hum Reprod 2002;17(6):1663-68; Gerrits T. Social and cultural aspects of infertility in Mozambique. Patient Educ Couns 1997;31(1):39-48.

(18) Gerrits.

(19) Dyer SJ, Abrahams N, Hoffman M, et al. Infertility in South Africa: women's reproductive health knowledge and treatment-seeking behavior for involuntary childlessness. Hum Reprod 2000;17(6):1657-62.

One Couple's Story: The Uncertainty of Infertility

Each case of infertility is unique in its causes, consequences, and outcomes. One such individual story comes from Jamaica, where 36-year-old Maria (fictitious name) and her husband are trying to conceive.

"My family was asking how come I am married so long and have no children," says Maria. After seven years of having unprotected sexual intercourse with her husband without becoming pregnant, she finally decided to visit her gynecologist.

Maria says that, before the visit, she had no idea what could be causing her infertility. But a series of tests revealed that she is an ovulatory (that her ovaries are not producing and releasing eggs).Her husband also went to the clinic to have his semen analyzed and discovered that he is oligospermic (has a suboptimal number of sperm in his semen).So in this case, as in many throughout the world, the couple's infertility can be attributed to both partners. But when asked about the causes of the couple's infertility, Maria never mentions that her husband is also contributing to the problem. "It seems to me that she has assumed full responsibility for the infertility," says Maria's gynecologist, who prefers to remain anonymous to protect Maria's privacy.

In many countries, infertility is perceived as a woman's problem, perpetuated by community beliefs. Maria's gynecologist says that in some areas of Jamaica, a woman who does not conceive within a defined period is considered a "mule," the name for the usually sterile offspring of a donkey and a horse. "Some communities do not accept that a man is sterile until they have proof," she says. "Once, when I shared with a woman the results of her partner's semen analysis, she asked for a copy of the results so that she could show his family that she was not the mule."

Because of Maria's personal characteristics--Christian, Caucasian, and middle class--she may not suffer the same social consequences of infertility that women of many other backgrounds experience. In fact, she says she is coping with infertility "satisfactorily."

Since her diagnosis, Maria has been taking medicine to stimulate ovulation, and she has now been referred for assisted reproduction (see article, page 7). Her husband has been referred to a urologist.

Results from a study of more than 2,000 infertile couples from Canada estimate that about 42 percent of women who are treated for ovulation disorders and almost 30 percent of wives of men who are treated for oligospermia will eventually give birth to a live infant. (1) But additional research has also predicted that couples who have been infertile for three or more years are less likely than others to conceive, and that women who are at least 30 years old and have never been pregnant are less likely to eventually have a live birth. (2)

So what does this mean for this Jamaican couple?

"I am still being treated," Maria says. Meanwhile, like many infertile couples, she and her husband will continue waiting in an emotional limbo, harboring the hope that they will eventually have the good fortune to conceive.

* Kerry L. Wright

References

(1) Collins J, Burrows E, Willan A. Infertile couples and their treatment in Canadian Academic Infertility Clinics. In Royal Commission on New Reproductive Technologies. Treatment of Infertility: Current Practices and Psychosocial Implications. Volume 10. (Ottawa, Ontario: Minister of Supply and Services, 1993)233-329.

(2) Hunault CC, Eijkemans MJ, te Velde ER, et al. Validation of a model predicting spontaneous pregnancy among subfertile untreated couples. Fertil Steril 2002;78(3):500-6.

The Possibility of Assisted Reproduction.

Infertility management is an important component of reproductive health services. When infertility occurs, couples should not be denied treatment, including assisted reproductive technologies.

Assisted reproductive technologies are most often used to treat infertility caused by damage to or blockage of a woman's fallopian tubes, male infertility, and persistent infertility for which other treatments have not worked. One of the best-known and most common technologies is in vitro fertilization (IVF), a procedure in which a man's sperm and a woman's egg are fertilized in a laboratory and the resulting embryo is transferred into the woman's uterus. Other technologies include intracytoplasmic sperm injection (ICSI), in which a single sperm is injected into a single egg during IVF, and gamete intrafallopian transfer, an alternative to IVF in which sperm and unfertilized eggs are surgically placed in a woman's fallopian tubes.

Global demand for such help is undeniable. But some experts are concerned about the cost and difficulty of providing such interventions in the developing world. (1) In Nigeria, for instance, one cycle of IVF is estimated to cost between U.S. $2,000 and U.S. $2,700, but the minimum wage in Nigeria is typically no more than U.S. $720 a year. (2)

Nonetheless, examples from Africa demonstrate that assisted reproductive technologies are feasible and successful in low-resource settings where staff are trained and equipment is available. In Mombasa, Kenya, an IVF center was created in 1995, and nearly 50 patients had attended by early 2003, according to Dr. Abdallah Kibwana, an obstetrician/gynecologist from Mombasa's Coast General Hospital. At a regional obstetrical and gynecological conference, he reported that 19 of the patients seen at the IVF center have conceived with the help of simple ovarian stimulation, and two babies have been born using IVF. (3)

Also, two cases of successful ICSI have recently been reported from a private IVF clinic in Lagos, Nigeria. (4) In one case, a man had no sperm in his semen, so sperm were extracted from his testes. ICSI and transfer of the resulting embryo into the uterus of his 38-year-old wife resulted in the birth of a healthy baby boy. In the other instance, a 31-year-old woman who had tubal infertility and whose husband had low sperm counts delivered twins after ICSI was performed.

* Kerry L.Wright

References

(1) Inhorn MC. Global infertility and the globalization of new reproductive technologies: illustrations from Egypt. Soc Sci Med 2003;56(9):1844; Okonofua F. New reproductive technologies and infertility treatment in Africa. Afr J Reprod Health 2003;7(1):7-11.

(2) Giwa-Osagie OF. ART in developing countries with particular reference to sub-Saharan Africa. In Vayena E, Rowe PJ, Griffin PD, eds. Current Practices and Controversies in Assisted Reproduction. Geneva, Switzerland: World Health Organization, 2002.

(3) Kibwana AK. Assisted reproductive technology (ART): experience, current and future status. The 5th International Scientific Conference of the East, Central and Southern African Association of Obstetrical and Gynaecological Societies, Mombasa, Kenya, February 23-27, 2003.

(4) Ajayi RA, Parsons JH, Bolton VN. Live births after intracytoplasmic sperm injection in the management of oligospermia and azoospermia in Nigeria. Afr J Reprod Health 2003;7(1):121-24.

Web Resources

http://www.who.int/reproductivehealth/ infertility/index.htm

Current Practices and Controversies in Assisted Reproduction is the report of an expert meeting on "Medical, Ethical and Social Aspects of Assisted Reproduction" held at World Health Organization headquarters in Geneva, Switzerland, in September 2001. This 31-chapter book examines these issues and presents experts' recommendations for clinical practice and research.

Harmful Traditional Practices Can Hinder Conception

Various traditional practices can lead to a narrowing of the vagina, also known as acquired vaginal stenosis (gynetresia), that makes it difficult for some couples to conceive a child, decades of research from Nigeria indicate.

Scarring from female genital cutting was the leading cause of vaginal narrowing among 78 women with vaginal stenosis who took part in a retrospective study conducted between 1980 and 1989 at the University of Nigeria Teaching Hospital in Enugu. (1) In a second retrospective study, conducted from 1967 to 1996 among 126 women with vaginal stenosis at the University College Hospital in Ibadan, most cases were due to chemical vaginitis from insertion of vaginal pessaries (suppositories) that are caustic, a common practice promoted by traditional healers. (2)

Stenosis, if left untreated, can make sexual intercourse uncomfortable or even impossible. In both studies, infertility was recorded as a symptom of the condition for about a quarter of the women.

Authors of both studies emphasized that acquired vaginal stenosis is a public health concern requiring community-based education programs to teach couples about these harmful traditional practices. The lead author of one of these studies and also a former FHI fellow, Dr. Ayodele Arowojolu of Nigeria, reports that obstetricians and gynecologists in that country are using the media to warn members of the public about some of these harmful practices and inform them of modern medical programs to manage infertility.

* Kerry L. Wright

References

(1) Ozumba BC. Acquired gynetresia in eastern Nigeria. Int J Gynecol Obstet 1992;37(2):105-9.

(2) Arowojolu AO, Okunlola MA, Adekunle AO, et al. Three decades of acquired gynaetresia in Ibadan: clinical presentation and management. J Obstet Gynaecol 2001; 21(4):375-78.