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Infertility is a global problem, but the highest prevalence is in low resource countries, particularly in sub-Saharan Africa where infection-related tubal damage is the commonest cause. Most infections causing tubal damage are preventable and assisted conception can treat the infertility. However, assisted conception, despite being available for nearly three decades is either unavailable or inaccessible to most residents of resource poor countries. Infertility has social, economic and personal effects, which go beyond childlessness, and women bear the major brunt of the burden. There is urgent need for a comprehensive sexual and reproductive healthcare initiative involving maternal and child health, safe abortions, family planning and infertility prevention and management. The provision of low cost assisted reproduction for couples in poorly resourced countries also needs to be revisited.
Health has been described as a state of complete physical, mental and social well being and not just absence of disease. This definition also applies to the reproductive system and its functions. Reproductive health implies an individual’s right to reproduce and freedom to decide when and how often.1 This right has been enshrined in United Nations Declaration of Humans Rights, Article 16:1, which states that ‘Men and women of full age, without any limitation due to race, nationality or religion have the right to marry and found a family’.2 Infertility, however, continues to be a major worldwide problem, affecting an estimated 60–80 million women and men, the vast majority of whom live in low resource countries.
As achieving parenthood is the most basic and desired goal in adulthood,2 infertility is more than a physical problem. It has adverse social and psychological implications, especially for women in developing countries. Even when the man is at fault, in many cases, the childless woman is made to feel inferior and may be abused or even tortured by the family.3 Not all couples who try for pregnancy will achieve their goal without some medical intervention. Alleviation of infertility therefore becomes a necessity on many levels and it has been declared a public health issue by the World Health Organization (WHO).4
It is therefore important that efforts are made to develop simple, low cost and effective instruments for the prevention, evaluation and treatment of infertility in resource-poor countries. In this review, we aim to look at the current state of infertility, its prevalence, management and controversies in low resource countries.
The UK National Institute for Clinical Excellence (NICE)5 describes infertility as the inability to conceive after 2 years of unprotected intercourse. According to this definition, it is estimated that 8–10% of couples in the UK5 or 8–12% worldwide6 experience some form of infertility. These figures, however, disguise a widely varying prevalence both between and within countries. In a major survey of sub-Saharan countries, the national average for prevalence ranged from 12.5 to 16%.7 Inhorn has described areas of central and southern Africa as ‘the infertility belt’ with prevalences as high as 32% in Namibia.8 Other Southern African countries (Botswana, Zimbabwe, Lesotho) report a prevalence of 15–22%, significantly higher than the rates of 8–13% found in three Eastern African countries and Egypt.8 Other studies suggest that the rate in Nigeria is also very high at 20–30%.9
In India, eight to ten million couples are estimated to be childless. According to the Delhi IVF Fertility Research centre, infertility affects one in six couples in India10 and the recent National Family Health Survey data estimated that 3.8% of currently married women between 40 and 44 years are childless.11 But this overall rate hides variations according to social class. In a population study in three Indian states, for example, the overall prevalence in 7000 couples was 24% in low socio-economic groups and 31% in higher classes.12
In addition to the higher prevalence of overall infertility in developing countries, there are significant differences in the primary and secondary infertility rates. Secondary infertility is much more common in resource poor countries, especially in Africa and Latin America and among middle and high income couples (Figure 1).12–14 In India, primary infertility is high in the early reproductive years and reduces as women got older, while the secondary infertility prevalence continues to increase with age.12
Boivin et al. (2007)4 in the most recent survey of more than 25 countries from all parts of the world found a remarkable similarity in infertility prevalence with estimates of 5–15%. The study also found comparable rates of preventable sexually transmitted diseases. In North America and Western Europe, the prevalence of sexually transmitted diseases was 1.9 and 2.0% of the population, respectively, compared with 2.1 and 0.7% in North Africa and East Asia. In certain Central African countries, this figure has fallen from a high of 30–40% in the 1960s and 1970s to the current 6%. These comparable infertility rates across the world are in sharp contrast with the earlier WHO survey,13 which showed significantly higher rates in parts of Africa, Asia and Latin America. This discrepancy could be due to sampling differences, with the collection of data from either unrepresentative parts of the country or exclusion of countries with higher prevalence rates. For example, sub-Saharan Africa was not studied despite its very high prevalence of sexually transmitted diseases (11.9% of the population) and infertility.
The use of varied definitions to describe infertility (typically 12 months, 24 months or lifetime infertility) also makes comparisons difficult.15 For example, Boivin’s estimates derive from two studies with a 12-month interval, two with 24 months duration, five studies using lifetime infertility and a further four studies which used 5–7 years.4
Even though NICE in the UK uses 24 months as the denominator, 5 other Western countries have used only 12 months. Many studies from developing countries do not give either the definition or the prevalence rates.2,6,8,9 Furthermore, much as there is a reported variation in prevalence both within the countries and in different parts of the world, there are two additional factors, which need to be considered before firm conclusions can be drawn. First, data collection in resource poor countries is commonly deficient. Prevalence calculations rely on both an accurate diagnostic process and pre-registration of procedures, both of which are frequently absent or unreliable.16 Analyses of the collected data needs sophisticated public health infrastructure which is often lacking in low resource countries. The second problem is that most studies from developing countries extrapolate fertility data to get infertility rates, a process that can underestimate prevalence rates.13
Despite this, there is a broad consensus that prevalence rates for infertility are significantly higher in resource poor countries than in developed nations.
Aetiology of infertility
Causes of infertility can be put in two broad groups. The first group includes anatomic, genetic, hormonal and immunological problems. These have been described as the ‘core’ causes of infertility. The core group is responsible for about 5% of the prevalence and this rate is similar throughout the world.2 The second group includes causes that are preventable and their rates therefore differ widely in the world. The preventable causes are largely infection-related and iatrogenic. In Africa, nearly 85% of women had a diagnosis of infertility caused by infection, a figure which is more than double that of the rest of the world13 (Table 1). The type and mode of infection varies from country to country depending on the social factors, health infrastructure, healthcare practices and environmental factors.6 Iatrogenic causes of infertility constitute approximately 5% of all causes in Western Europe compared to 15.5% in Africa.6,17
Table 1. Cause of infertility in different regions
Data is % of couples and is taken from Cates13. Not all categories are listed and some patients had more than one diagnosis.
No demonstrable cause
No demonstrable cause
Most preventable infertility in couples results from one of four factors.
Reproductive tract infections
In sub-Saharan Africa, sexually transmitted diseases (STDs) are responsible for more than 70% of cases of pelvic infections, with most being caused by Chlamydia and N. gonorrhoea. Of these two organisms, N. gonorrhoea causes an acute form of infection of the fallopian tubes requiring immediate treatment, even hospitalisation, making diagnosis easier. Chlamydia however is indolent and the infection may remain unrecognised until the investigations for infertility are undertaken. They also cause male factor infertility,18 as well as being associated with postpartum and post-abortal infections.
HIV infected individuals are also at risk for infertility both through tubal damage in women and through altered spermatogenesis in men. These effects happen both directly and through increased susceptibility to other sexually transmitted infections.
Tuberculosis is another major cause of infertility in both men and women in the Indian subcontinent.19,20 Genital tuberculosis appears to be an important and common cause of Asherman’s syndrome in India, causing oligomenorrhoea or amenorrhoea with infertility. In a study of women with infertility and amenorrhoea/oligomenorrhoea, there was past history of tuberculosis in 68% of women21 while the prevalence of genital tuberculosis in tubal factor infertility was 49% in women requesting assisted reproduction.22 Genital tuberculosis therefore appears to be a major contributor to both primary and secondary infertility in India.23
Other infections associated with infertility in developing countries include Lepromatous leprosy, schistosomiasis and malaria.6,18
Despite being preventable, unsafe abortion is one of the biggest public health issues faced by women worldwide.24 The WHO report of 200625 estimated that in 1995, there were 26 million legal and 20 million illegal abortions performed worldwide. Of all the abortions performed in developing countries, 97% were unsafe and of these, 55% were in south Asian countries. Unsafe abortions can have severe consequences: 20–50% of women will have immediate complications (e.g. haemorrhage, sepsis or trauma) and 20–30% will get upper genital tract infection and infertility. Unsafe abortions contribute about 2% to all the causes of infertility.26,27
Unhygienic obstetric practices in developing countries are also major contributors to infertility. In parts of sub-Saharan Africa, only 40% of births are attended by trained birth attendants and long-term complications including postpartum infection is common.18,26,28,29 Other iatrogenic causes include the use of outdated treatments like dilatation and curettage, and cauterisation of cervix for the treatment of infertility, and traditional therapies where herbs and chemicals are inserted into the vagina.30 A lack of trained health personnel, poor laboratory and support facilities and the unavailability of drugs further add to the overall negative effects.18,30
Alcohol, tobacco and caffeine consumption have all been shown to compromise fertility and all of these are widely used in developing countries.6 Dietary deficiencies of iodine and selenium have been linked to infertility as has been exposure to dietary aflatoxine.8 (Conversely, although not true, contraceptives are rejected in certain developing countries on the basis that they may result in infertility.31)
According to a 2005 WHO report,32 100–140 million young girls/women in Africa and certain parts of the Middle East between have undergone some form of genital mutilation. This procedure has traditionally been performed by local midwives without any understanding of antisepsis or anatomy and is associated with haemorrhage, sepsis, dyspareunia, obstructed labour and infertility.
Cultural beliefs like early marriage, polygamy, an aversion to female education and antagonism to condoms further contribute indirectly towards infertility. There is also a disparity between rural and urban areas in the number of healthcare facilities and access to health care.33 Societies in which fertility is given a very high value can lead to women undergoing all kinds of unproven treatments to get a child, and these may result in further damage to reproductive potential.35
Evaluation of infertility
There are certain basic principles, which should be followed to minimise the time spent on investigations and treatment. These include evaluation of the couple, history and examination of both partners and the use of evidence-based investigations.5 It is important that couples are discouraged from seeking help from multiple units that a clinical diagnosis is made without delay, and that interventions are both appropriate and evidence-based.6
An accurate personal and medical history from the couple along with a simple semen analysis is generally sufficient to make a clinical diagnosis.18 These simple measures alone can suggest anovulatory infertility and male factor problems, as well as helping in the diagnosis of tubal infertility. Healthcare workers in low resource countries need also to remember the endemic infections like tuberculosis, shistosomiasis, malaria and HIV, which may be either direct or indirect contributors to infertility.
A previous history of STD, RTI, abortion or delivery-related complications combined with hysterosalpingography can achieve a diagnosis of tubal infertility with a high degree of sensitivity. These are simple and inexpensive measures, which do not rely on extensive and expensive infrastructure of laboratory, operation theatre and high tech training of personnel.35,36
Laparoscopy as a second line investigation complements the initial HSG for tubal infertility and endometriosis.35–38 A simplified laparoscopic technique has been examined in a multicentre trial and has been found to be reliable and practical.35
The use of a systemic approach with standardised guidelines and training of dedicated healthcare workers can provide effective and reliable care.35 However, despite recommendations to simplify the evaluation of infertility, low resource countries continue to have problems. This is partly because of the low priority given to infertility services by national reproductive health services programmes. This results in poor organisation, inadequate referral systems and a fragmented preventative strategy. In addition, there is also a lack of laboratory facilities.34
The treatment of infertility needs to be evidence-based, and the UK-based RCOG and NICE have produced exhaustive guidelines.5 In low resource countries, these recommendations need to be balanced against the requirements of safety, simplicity and cost effectiveness.
Awareness of fertility principles by the patients and staff working in the infertility clinics is important within a treatment programme and has been shown to be effective.39 This awareness includes the importance of timing intercourse to different cervical secretions and the harm caused by smoking and alcohol.
For ovulatory dysfunction with no other abnormality (normal semen analysis and patent fallopian tubes), ovulation induction is the initial treatment. Clomiphene citrate achieves about 70% ovulation and combining it with timed intercourse will achieve pregnancy of up to 25% per cycle.18 This treatment is simple to administer, safe and achieves a reasonable degree of success. Paramedical staff and nurses can be trained to give the treatment with little training. In India, ovulation induction drugs are frequently used without any investigations or prescription, even within a few months of marriage to enhance fertility. There is, however, risk of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) especially at high doses and with unmonitored cycles.18
Controlled stimulation can be achieved with a number of agents. Simplicity, safety and cost make clomiphene the first line of treatment. The next step in the treatment after clomiphene will be ovulation induction with gonadotrophins, which can be combined with intra uterine insemination (IUI).40 IUI is a very effective treatment, but it requires an advanced infrastructure, monitoring of treatment and training of personnel. Treatment with gonadotrophins puts the woman at risk of OHSS, a potentially life-threatening complication, which, along with multiple pregnancies, is common in poorly monitored cycles. Monitoring of cycles involves follicle tracking with the help of ultrasound. Treatment therefore becomes expensive as it includes the drug costs, the need for the laboratory facilities, the cost of ultrasound machine and trained staff.18 Management of complications further add to the cost of the whole healthcare system.
Surgical techniques for tubal infertility have been tried and have success rates of around 50%, but depend on the severity of damage, associated abnormalities, technique of surgery (open versus microsurgery versus laparoscopic) and training of the surgeon.41–43
The next logical step in infertility treatment would be some form of assisted reproductive treatment. Assisted Reproductive Techniques (ARTs) are defined as the techniques used where there is need for in-vitro preparation or manipulation of gametes. The commonest ARTs are intra-uterine insemination (IUI), in-vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI). IVF would be the logical treatment for tubal infertility. The indications for ART include unexplained infertility, tubal damage, male factor infertility and premature ovarian failure.
All assisted conception treatments require significant investment in infrastructure, training of personnel and a reliable supply of drugs and other resources. This makes the cost of ARTs prohibitive for most patients. Despite the cost, ART clinics have started to come up in developing countries although mostly in the private sector.17 Efforts have also been made to develop simplified and low-cost assisted conception techniques, for example natural cycle IVF and intra-vaginal culture. However, so far none of these techniques has been evaluated in clinical trials.41,42
Assisted reproductive technologies in low resource countries
It is estimated that of all the couples who embark on infertility treatment, up to 10% will require some form of ART. There is no reason to believe that the indications for ART would be different in low resource countries, but there is likely to be an increased requirement for IVF because of the high tubal infertility rates.
Indications for ARTs are increasing in parallel with advances in the reproductive technology. Relatively new technologies are egg and embryo donation, pre-implantation genetic diagnosis and possibly in vitro maturation.
In vitro fertilisation (IVF) is the logical treatment for tubal infertility. However, the establishment of high technology ART programmes in low resource countries is not only extremely difficult but also contentious because of the limited healthcare budgets. ART services are expensive to set up and have high recurring costs. Furthermore, there are indirect costs to the health system, which arise from complications (OHSS and multiple pregnancies33,35) and the need to monitor the safety and effectiveness of ART clinics.
The high cost of ARTs is a reality the world over. In the U.S. women who did not pursue a second IVF cycle cited expense as the main cause—and that is despite developed countries spending between 9–12% of their gross domestic product on health compared to 4–6% in resource poor countries.17,18 It is estimated that an ART unit in Nigeria would use up to 50% of that health facility’s budget.9 For healthcare providers, therefore, the priority is justifiably healthcare programmes, which address issues of high maternal mortality and overpopulation.30
Despite this, private clinics have come up in most countries and now present a problem regarding equality of access. As most patients are from a low socio-economic background, there is a severe inequality in the use of these services, Government subsidy of these services may be an answer but may lead to resentment among people who do not have to use these expensive treatments.20
In India, ART services were first introduced in 1980. By 2002, there were 60 clinics and today they are frequent throughout the country. A similar picture emerges from Egypt and Latin America17,20,30 and other countries in economic transition. In most developing countries, however, ARTs are either unavailable or inaccessible. The quality of available services is also wanting in such cases.44 The need for alternatives to ARTs or cheap IVF cannot be overstated.42
Infertility: social and political context
Infertility has a profound effect on women and men worldwide. Infertility management therefore takes on an added dimension which is beyond the physical and organic and which is firmly embedded in the social and cultural environment of that region. In developing countries, it is a devastating burden on the social, economic and personal well being of those affected, a burden that is disproportionately borne by the women.42 Psychological stress, economic hardship, stigma, isolation, mental and physical violence have all been described as consequences of infertility,2,30,46,47 Women not only suffer because they are mostly blamed for infertility, but they lose a very important chance to enhance their status.46,47,49 In the Southern Indian state of Andhra Pradesh, 70% of infertile women admitted to receiving physical violence as a consequence of their infertility.48,49
Despite this, there has been no political will to directly address the problems associated with infertility. Attention has focused almost exclusively on the extremely high maternal mortality rates and overpopulation.50 The overpopulation argument contends that there already is a problem of excessive population growth in the world. As population growth is exclusively confined to developing countries, any treatment for infertility would not only add to the world overpopulation but will also divert funds from more important primary health needs.2,46,47,50,51 It is clear, however, that with the expense and psychological trauma of ART treatment combined with a ‘take home baby’ rate of only around 20%, there is unlikely to be a significant effect on the population size.50
The limited resource argument is valid as health planners from poor countries have to provide equitable expenditure of the available funds. However, the effect of infertility on an individual’s quality of life is immense and disproportionately affects women and the poor.52,53 Infertility treatment should therefore not be given a lower priority than other medical conditions. India has recognised this and now includes infertility in the comprehensive reproductive and child health programme following ICPD recommendations.54
Infertility treatments including ARTs are expensive and their availability is limited even in developed countries. It therefore makes sense to focus on developing a robust preventative strategy, especially as preventable infections play such a major role in the aetiology.
Post abortion infections are the major cause of pelvic infections and tubal damage; therefore, elimination of unsafe abortions and early recognition and treatment of post abortion complications is extremely important. In countries where termination is legal but relatively inaccessible, increased access to safe pregnancy termination services will reduce the morbidity and mortality associated with unsafe practices.24,25,33,35,36,52,53
WHO have suggested that improving maternal and child health programmes is an important first step.2 Simple steps like introducing hygienic obstetrics techniques and early recognition and referral of maternal infections could significantly reduce the risk of tubal blockage. Furthermore, the provision of high quality and accessible family planning services (especially condoms) will not only help in reducing STIs, terminations and their complications, but also help with associated gynaecological morbidity e.g. pelvic inflammatory disease and cancers.
Suggestions for improvement
WHO has been at the forefront of conducting epidemiological studies in infertility in low resource countries and producing recommendations.2,36,53 The 2002 document ‘Medical Ethical and Social Aspects of Assisted Conception’ not only suggested a focus on preventative strategies but also recommended the collection, collation and interpretation of population-derived data.2 This is now integrated into WHO strategy with the 2006 document including safe terminations and the control and elimination of reproductive tract infections as main parts of a broad-based sexual and reproductive health policy.53 There is also a need to develop culturally sensitive evidence-based guidelines.30
But above all, there is a need for political willingness to treat infertility as a public health issue, both as an issue in its own right and as a part of a broader sexual and reproductive health strategy.
Infertility is a significant problem in developing countries. And women bear the major brunt of this devastating social, medical and economic burden.
In tackling infertility, the focus needs to be on the prevention of infection. But there remains a role for ARTs in low resource countries. The crippling effects of infertility on women are so profound that treatment should neither be denied because of other healthcare demands nor be inaccessible because of cost. Governments should work with the medical community to develop low cost treatments, including affordable assisted reproductive technology.
Disclosure of interests
We declare that there are no competing interests.
Contribution to authorship
SS conceived and wrote the initial and final drafts. These were reviewed by SM and PA who contributed to the evaluation and treatment segments in general and all the references to the Indian sub-continent in particular.
Details of ethics approval
We would like to thank Michael Mason for his help in the literature research. Carol Beck was instrumental in keeping continuity and her help was invaluable.