Abstract
This chapter discusses the epidemiology of infertility and the importance of the initial assessment of the infertile individual. Profound changes in society over the last two decades challenge previously agreed on norms in our understanding of the nature of parenthood and family. Defining infertility in a contemporary context has thus also changed as the profile of those seeking advice has evolved. Nevertheless it remains essential that efficient mechanisms for referral and investigation are established for those involved in the planning of fertility services. These must involve good liaison between primary care providers and medical, nursing and diagnostic laboratory staff in specialist centres. Adherence to agreed on protocols will facilitate appropriate and timely investigation along standardised paths, thereby minimising risk of delay and repetition of tests which those seeking assistance find particularly demoralising. Once a diagnosis is reached it should be possible to offer people with infertility an accurate prognosis and the opportunity to consider the issues relevant to treatment choices for their particular situation.
1.1 Introduction
This chapter discusses the epidemiology of infertility and the importance of the initial assessment of people with infertility. Profound changes in society over the past two decades challenge previously agreed upon norms in our understanding of the nature of parenthood and family. Defining infertility in a contemporary context has thus also changed as the profile of those seeking advice has evolved. Nevertheless, it remains essential that efficient mechanisms for referral and investigation are established for those involved in the planning of fertility services. These must involve a good liaison between primary care providers and medical, nursing and diagnostic laboratory staff in specialist centres. Adherence to agreed upon protocols will facilitate appropriate and timely investigation along standardised paths, thereby minimising risk of delay and repetition of tests which those seeking assistance find particularly demoralising. Once a diagnosis is reached it should be possible to offer people with infertility an accurate prognosis and the opportunity to consider the issues relevant to treatment choices for their particular situation.
1.2 Epidemiology
The International Glossary on Infertility and Fertility Care (2017) [1] highlighted the importance of rigour in using terms and definitions relevant to fertility care. It is now acknowledged that infertility is a disease of the reproductive system which in some instances leads to significant disability. Acceptance of this has, in many countries, been a major driver in establishing equity of access to care, though in the United Kingdom this remains an as yet unmet challenge.
Fecundity is a term describing the natural capacity of a woman to have a live birth. Fecundability refers to the chance of a pregnancy being established during a single menstrual cycle, in a woman with adequate exposure to sperm and who is not using contraception, which leads to a live birth. In population studies fecundability is usually measured as a monthly probability.
The Total Fertility Rate (TFR) refers to the average number of live births a woman will have in the totality of her reproductive life. This may be determined in retrospect to an individual through observed data. If applied to a group of women, for example, all women in a certain year, it is referred to as a Cohort Total Fertility Rate (CTFR) and is determined after all women have completed their reproductive years. In England and Wales the TFR in 2017 was 1.76 births per woman. This represented the fifth year in succession in which the rate had declined. In 2012 the level was 1.94 (Figure 1.1).
The Age-Specific Fertility Rate (ASFR) describes the number of live births per woman in a particular age group in a specific calendar year expressed per 1,000 women in that age group. This has declined in every age group in recent years except for women older than 40 years, in whom there has been an increase, with levels now at their highest since 1949. Delaying childbirth and the impact of fertility treatments in older women are major influences on these interesting trends.
The TFR can also be estimated for a population of women over a defined period of time. The Period Total Fertility Rate (PTFR) is the number of children who would be born per woman (or per 1,000 women) if she/they were to pass through the childbearing years bearing children according to a current schedule of age-specific fertility rates. The figure is obtained by adding up the single-year ASFRs over the defined period.
Another concept which bears consideration is that of the TFR level required to sustain population levels in particular countries. This ‘replacement fertility rate’ in the developed world is of the order of 2.1, though in developing countries the figure may be much higher due to increased mortality rates, particularly among children.
Analysis of global population trends shows a decline in TFR in many developed countries. In the United Kingdom in 2017 the rate was 1.7 whereas in 1950 this figure was 4.7. In sub-Saharan Africa the figures for TFR are higher, for example, Uganda 5.2. In many other areas of the world the TFR is very low and much below that required to sustain population levels. Three key factors are involved in these trends – fewer deaths in childhood mean women today have fewer babies; men and women have greater access to contraception; and more women are in education and working. Age at first birth is rising in many countries and in the United Kingdom is now approaching 30 years. Among women born in 1972 the average age at first birth is 31 years. For women born in 1945 the figure was 23–24 years. The consequence of these trends will have a significant effect on the demography of populations, with fewer young people available to resource the care of an increasingly aged population. Migration may to a degree mitigate against these trends but the problems for some countries will have very profound implications for society in the future.
In any population, not all women without children at the end of their reproductive life are infertile. Voluntary childlessness is not an uncommon lifestyle choice. Involuntary childlessness, however, may be a consequence of not establishing a life partnership with a member of the opposite sex, or where a person has had the misfortune of all children having died. A major cause of involuntary childlessness, however, is infertility. Same-sex relationships are an established societal norm in many parts of the world and thus infertility as a term now has to take account of the potential use of third-party reproductive techniques in assisting those seeking to have a child and where, after exposure to treatment over a defined period of time, pregnancy has failed to establish and no live birth has ensued.
In practice the term ‘infertility’ can be interchangeable with ‘subfertility’ although it is debatable as to whether the term subfertility is useful. Sterility should be regarded as a permanent state of infertility. The Glossary defines infertility as ‘a disease characterised by the failure to establish a clinical pregnancy after 12 months of regular unprotected intercourse, or due to impairment in a person’s capacity to reproduce either as an individual or with his/her partner’.
The use of the specific time frame is both necessary and based on sound epidemiological data. The length of exposure time considered is determined by the observation that in the general population, which would include a proportion of couples with infertility, one would expect the chance of a woman becoming pregnant in any individual cycle (fecundability) to be around 20%. By 1 year of exposure about 85% of couples would have established a pregnancy and by the time 2 years has elapsed this figure will have reached 92% [2]. For couples presenting with more than 4 years’ unwanted childlessness the prospects for becoming pregnant without assistance are very low. In practical terms the failure to achieve pregnancy causes enormous distress to those affected. For people with fertility problems, using a definition of a year to describe infertility is usual and most will have sought medical advice or assistance by that time.
Age-specific fertility rates for women decline in association with increasing age, though in an ultimately fertile group of women it is not certain that their monthly fecundability (% chance of establishing a pregnancy leading to a live birth) is any less than in younger cohorts. It may be sensible to consider specialist referral of women over the age of 35 years in advance of 1 year. However, it should be recognised that in many instances pregnancy will be established without medical assistance in these cases, since it can be assumed that a proportion will not be infertile.
Infertility is often categorised as either primary or secondary. Primary female infertility refers to a woman who has never been diagnosed with a clinical pregnancy. Primary male infertility refers to a man who has never initiated a clinical pregnancy. In both instances women and men should meet the criteria for the definition of infertility. Secondary female infertility refers to a woman unable to establish a clinical pregnancy who has previously been diagnosed with a clinical pregnancy. Secondary male infertility refers to a man who has previously initiated a clinical pregnancy but is now unable to do so. A clinical pregnancy refers to a pregnancy diagnosed by ultrasonographic visualisation of one or more gestation sacs within the uterus or definitive clinical signs of pregnancy or a clinically documented ectopic pregnancy.
Estimates of the prevalence of infertility in the population are influenced by the duration of infertility used in the definition and the setting of the population studied, for example, primary care or hospital clinics. Community-based data will give the most accurate reflection of prevalence within the general population but these studies are few in number. Published prevalence studies suggest a range of lifetime risk of infertility varying from 6.6% to 32.6%. One population-based study in the north east of Scotland which took account also of pregnancies resulting in miscarriage and ectopic pregnancy found a prevalence of 14% using a 2-year definition.
In global terms the prevalence of infertility seems to have changed little in the last 20 years. In the United Kingdom setting a number of factors have been a matter of concern with respect to their potential impact on the prevalence of infertility. These include the incidence of sexually transmitted infection (STI) such as Chlamydia trachomatis in the young. In addition, there have been suggestions that environmental factors may affect male fertility. As alluded to earlier, profound questions have been raised about the effects on female fertility of delayed childbearing as determined by changes in lifestyle and working patterns. Despite these legitimate concerns, when the population-based study was repeated [3] the observed prevalence of infertility had not increased in north east Scotland in the succeeding 20 years.
Data from a review of worldwide prevalence studies, using a 5-year definition and live birth as the outcome, suggest that nearly 50 million couples worldwide are infertile. This includes 1.9% of couples wishing to have a first child who have primary infertility and 10.5% of those who have previously had a live birth experiencing secondary infertility. Regional variations were noted in this study in the overall prevalence, particularly in relation to secondary infertility with, in some Eastern European; South-East Asian; and West, Central and Southern African countries, more than 20% of couples affected (Figure 1.2). This is most likely due to the prevalence of infective complications following miscarriage, abortion or childbirth as well as the acquisition of sexually transmitted infections in these settings. A previous study using a shorter duration of infertility as the definition suggested the worldwide figure could be as high as 80 million couples. This review also suggested that the overall prevalence of infertility changed very little worldwide between 1990 and 2010.
Figure 1.2 Prevalence of secondary infertility among women who have had a live birth previously and seek another, in 2010.
A lack of observed change in prevalence should not encourage complacency in respect of public health responsibilities. Opportunities to prevent infertility are limited, and encouragement to the young to engage in safe sexual practices limiting exposure to risk of STI is clearly important. For teenage girls, rubella immunisation programmes should be in place. HPV vaccination programmes are now established. Education of the public about the known decline in fertility which occurs with age, particularly in women older than 35 years of age, is also important. Furthermore, the need for folic acid supplementation for women to reduce the risk of neural tube defect should be promoted as well as the need to make certain lifestyle adjustments on issues such as the potential need to moderate levels of smoking and alcohol consumption as well as achieving optimal weight. There is convincing evidence that smoking, active or passive, affects reproductive performance in women, and men, as well as increasing the risks in pregnancy of small for gestational age infants, stillbirth and infant mortality. Referral to a smoking cessation programme to support efforts in stopping smoking should be available to those who find giving up the habit difficult. Chronic high stress may also have deleterious effects on the biology of reproduction in both men and women as well as have an impact on sexual frequency and performance.
Our public health responsibilities as reproductive medicine specialists thus lie not just in providing fertility care but also in providing people with information and support in planning families and avoiding pregnancy where wished. We also have a professional responsibility to ensure that women are provided with safe services in relation to unwanted pregnancy and miscarriage as well as safe care in pregnancy and childbirth.
1.3 Initial Assessment
1.3.1 Primary Care
In our UK setting the role of the general practitioner is crucial. Infertility represents a deeply personal problem, and many individuals will prefer to discuss intimate matters with someone they know and trust. The support that the GP can provide in terms of counselling and preliminary investigations is an excellent foundation for provision of care. Not infrequently the man and woman may be registered with different GPs. One should always consider that infertility is a problem affecting both parties and each may contribute to the pathogenesis. Once referral is made to a specialist clinic the stresses imposed on couples may increase, with demands on their time for attendance, the indignity of some of the investigations carried out and the invasion of privacy that occurs. Since it is well recognised that infertility investigation and treatment pose real threats to domestic stability, it is the GP, through knowledge of the couple and their families, who may be in the best position to provide support for those struggling to come to terms with continued disappointment.
All patients should be seen as couples in appropriate surroundings. Facilities should be available to permit examination of both partners and with sufficient time, usually half an hour, set aside to make an adequate overall assessment of the problem.
It may be helpful for the local fertility clinic to employ dedicated liaison staff to assist with the referral process and guideline dissemination. In some instances, tubal assessment might be organised in primary care, though before committing to intrusive investigation it would be wise to have information on semen quality beforehand. This can be difficult where the male partner has a different GP than the female partner, but improved communication within primary care can resolve this issue. Bearing in mind the statutory requirement in offering licensed treatment to take account of the welfare of the potential child or existing children it is essential that GPs give this some thought at this early stage to avoid difficulties in later management.
1.3.2 Specialist Centre Care
This should be provided in a setting under the clinical direction of a consultant gynaecologist with a special interest in infertility. Patients should be seen in a dedicated infertility clinic with appropriate appointment times to permit thorough evaluation. A team system should be established involving medical, nursing, laboratory (endocrine and andrology) and counselling personnel to facilitate a consistent and co-ordinated approach to care. The level of treatment options available will depend on the expertise of, and the facilities available to, staff at each centre.
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