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Female fertility: hostage to affluence, age and the search for self-fulfilment In modern industrialized societies female fertility is compromised due to a perfect storm of social, economic, educational and political factors that far outweigh any attempt by Governments to encourage women to have more children. In affluent societies, there is no need to have a large family. Infant and childhood mortalities are low and children are not needed in the workforce to facilitate survival of the family unit. As a result of the reduction in family size, women are freed to pursue their educational and professional goals. This ultimately means that childbearing is postponed to the point that fertility goes into age-dependent decline, around the age of 35. Many women in this situation will look to the IVF industry for salvation, however live births decline with age following assisted conception just as they do in natural cycles. Oocyte donation and/or cryopreservation are the only realistic methods to address age-dependent female infertility at the present time, although even these techniques are far from infallible. As societies engage in the long march to affluence, we shall inevitably witness repeated collisions between the tectonic plates of female biology and our prosperity-driven quests for gender equality, longevity and fulfilment. Ultimately fertility is the victim.
The gathering storm – the creation of an Infertility TrapWhile previous publications have looked at individual aspects of the issues shaping our population size, the reality is that many different factors are working together to drive human fertility into a cul-de-sac of its own making. From a social perspective many young people, particularly young, educated women, do not feel that life’s purpose necessarily involves the creation of a family. As fertility rates fall, this lack of interest in procreation will be reinforced by the economic pressures placed on a dwindling workforce to achieve the productivity needed to support the swelling ranks of elderly citizens. We shall not be able to turn to immigration to solve this problem because the fall in fertility rates is global and the barriers to international movement put up by COVID will persist for some time to come. Affluent societies are also characterized by lifestyles, diets and levels of environmental pollution that negatively impact reproductive health. These features, when coupled with the lack of selection pressure on high fertility in modern industrialized societies, and the ability of ART to encourage poor fertility genotypes to remain within the population, will combine to drive fertility down to historically low levels.
A potential crisis in human fertility is brewing. As societies become more affluent, they experience changes that have a dramatic impact on reproduction. As average family sizes fall, the selection pressure for high-fertility genes decreases; exacerbated by the IVF industry which allows infertility-linked genes to pass into the next generation. Male fertility rates are low, for many reasons including genetics and exposure to environmental toxins. So, a perfect storm of factors is contriving to drive fertility rates down at unprecedented rates. If we do not recognize the reality of our situation and react accordingly, an uncontrollable decline in population numbers is likely, which we'll be unable to reverse. This book will address, in a unique and multi-faceted way, how the consequences of modern life affects fertility, so that we can consider behavioural, social, medical and environmental changes which could reduce the severity of what is about to come.
Prologue- the pending collapse of human populationsA perfect storm of social, political, environmental and biological factors is conspiring to suppress the fertility of our species. In this book, we shall explore the fundamental nature of human population dynamics and the wide range of factors responsible for the change that is about to come. Societies touched by prosperity’s wand experience many advantages including good health, education, security and longevity. However, these gifts come at a cost. Prosperous societies experience high levels of environmental pollution, psychological stress, obesity, addiction and a focus on individual fulfilment that combine to generate extremely low levels of fertility. As societies accumulate wealth, they sow the seeds of their own demise. In the short term, our ‘superaged’ societies must be supported by a shrinking, overstretched workforce, that have neither the motivational energy nor the biological capacity to procreate. In the long term, the lack of selection pressure on fertility, combined with the exponential growth of the IVF industry, will serve to drive fertility rates down still further. Unless we recognise and respond to the factors suppressing human fertility, we shall not be able to control the predictable population collapse – and escape will be challenging.
How do we escape the trap?Many of the social, biological and environmental mechanisms that are driving down human fertility, are self-reinforcing. They operate to accelerate the rate of fertility loss, not stabilize it. Escape from this downward spiral will involve several initiatives that, working together, may provide a measure of control over the rate and depth of fertility decline. For example, we need a complete overhaul of sex education that recognizes the fragility of human fertility and is not so focused on the prevention of teenage pregnancies. We also need to raise the profile of reproductive toxicology so that we can secure better control over the release of potentially harmful compounds into the biosphere. There is a particular need to control male exposures to oestrogens and to counteract those elements of lifestyle, metabolism and the environment, responsible for creating oxidative stress in both the male and female reproductive tract. Accommodating the ART industry would be easier if we secured a deeper understanding of the causes of human infertility so that ART does not become the default therapy for every couple and, when it is used, that IVF is preferred over ICSI. Finally, we need to engineer new social structures wherein fertility is facilitated and encouraged.
Increasing evidence has demonstrated that obesity impairs female fertility and negatively affects human reproductive outcome following medically assisted reproduction (MAR) treatment. In the United States, 36.5% of women of reproductive age are obese. Obesity results not only in metabolic disorders including type II diabetes and cardiovascular disease, but might also be responsible for chronic inflammation and oxidative stress. Several studies have demonstrated that inflammation and reactive oxygen species (ROS) in the ovary modify steroidogenesis and might induce anovulation, as well as affecting oocyte meiotic maturation, leading to impaired oocyte quality and embryo developmental competence. Although the adverse effect of female obesity on human reproduction has been an object of debate in the past, there is growing evidence showing a link between female obesity and increased risk of infertility. However, further studies need to clarify some gaps in knowledge. We reviewed the recent evidence on the association between female obesity and infertility. In particular, we highlight the association between fat distribution and reproductive outcome, and how the inflammation and oxidative stress mechanisms might reduce ovarian function and oocyte quality. Finally, we evaluate the connection between female obesity and endometrial receptivity.
Soy is a key food in human nutrition. It is widely used in eastern traditional cuisine and it has recently diffused among self-conscious and vegetarian diets. The success of soy mainly depends on versatility and supposed healthy properties of soy foods and soy components. Meanwhile, the possible influence on endocrine system, in particular by isoflavones, raised concerns among some researchers. The present paper aims to conduct a review of available data on the effect of soy, soy foods and soy components on women's fertility and related outcomes. Eleven interventional studies, eleven observational studies and one meta-analysis have been selected from the results of queries. A weak, not clinically relevant effect has been highlighted on cycle length and hormonal status. However, a suggestive positive influence has been shown among women with fertility issues and during assisted reproductive technologies. Overall, soy and soy components consumption do not seem to perturb healthy women's fertility and can have a favourable effect among subjects seeking pregnancy. However, because of the paucity of studies exploring the impact of soy intake on women's fertility, as well as the limited population sample size, the frequently incomplete specimens’ collection to investigate all cycle phases and the insufficient characterisation of participants, the evidence is suggestive and it needs further in-depth research taking into account all these aspects.
A uterine septum is a congenital abnormality that has been associated with poor reproductive outcome that can be readily corrected by hysteroscopic surgery. For this debate article we argue that all women with a uterine septum should have hysteroscopic septal resection before undergoing any fertility treatment. A uterine septum is a congenital uterine anomaly arising from the failure of canalisation of the uterus during embryological development. Uterine septa are more prevalent in women with a history of pregnancy loss, but not infertility alone, and are associated with an increased risk of first and second trimester miscarriage and preterm birth [1,2]. Diagnosis is straightforward with three-dimensional ultrasound. Adequate assessment of uterine morphology requires concurrent imaging of the external and internal controls of the uterus. Three-dimensional ultrasound facilitates such views and is safer and more acceptable to women than surgical assessment with hysteroscopy and laparoscopy which are required to see the internal and external fundal contours.
Uterus transplantation involves a vascularised composite allograft for women with absolute uterine factor infertility, and is considered research. It requires a large medical and surgical multidisciplinary team, requires adequate psychological support and risks premature birth in the offspring. We compare it with the alternative of surrogacy, with the pros and cons regarding the prospective parents and offspring, the parental project collaborators, whether dead or live uterine donor or the gestating surrogate, and society at large. The possible aspects of cross-border reproductive care are also considered before concluding that it is still ‘a step too far’.
Mitochondrial (mt)DNA mutations can cause a broad range of severely debilitating or fatal disorders. There is no cure available and the only available treatments have purely symptomatic effects. Preventing mitochondrial disease transmission is therefore a major priority. Germline nuclear transfer (NT), such as maternal spindle (ST), pronuclear (PNT) or polar body (PBT) transfer, has been proposed as a possible strategy to prevent mother-to-child transmission of mtDNA mutations. This technology involves nuclear genome transfer from an oocyte or zygote carrying mtDNA mutations to an enucleated donor counterpart with healthy mtDNA. In addition, the technology has also been considered as a treatment option for certain infertility indications, such as women experiencing poor embryo development, with the expectation of improving in vitro treatment outcomes. Here, we provide an overview on recent developments in the field of NT, either with the aim to avoid mtDNA diseases or to overcome certain forms of female infertility.
Interactions between infertility and sexuality are numerous and complex. Recently more attention is being paid to the impact of infertility on the marital sexuality.
The aim of this study was to determine the effects of infertility on sexual functions.
A cross-sectional descriptive study, the obstetric gynecology department Basic demographic information was collected. Respondents were surveyed regarding sexual impact and perception of their infertility etiology.
Our patients had an average age of 33.2. The average number of years of infertility was 3.9 years.. The most common cause of female infertility was an ovulat disorder (36%), that of male infertility was sperm production defect. The confrontation with a diagnosis of infertility marks a difference in the way couples organize their sexual life. In our study, sexual problems after this diagnosis were experienced by 38% of women. Sexual dysfunction was detected as a pain problem (24%), a desire problem (10%), an arousal problem (4%), and an orgasm problem in 6% and. Faced with this situation, women felt guilty (46%), angry (72%) and anxious (82%). Infertility was perceived as the worst experience of life by 78% of our patients.
Infertility can interfere negatively in women sexuality. The investigation of sexual difficulties in infertility consultations must be systematic.
Infertile males experience considerable psychological distress, with feelings of inadequacy, marginalization, guilt and loss ofself-esteem.
Our study aims to investigate the impact of male infertility on men’s self-esteem and to study risk factorsfor low self-esteem.
We conducted a cross sectional, descriptive and analytical study, including 108 infertile men who presented to the laboratory of reproductive biology and the unit of assisted medical procreation of Military Hospital of Tunis between June and September 2019. For each patient, we collected sociodemographic and clinical data. We used Rosenberg scale to assess self-esteem.
The average age of participants was 36.8 years. Eleven patients had a history of varicocele (10.18%) and six of them sufferedfrom associated erectile dysfunction (5.55%). Infertility was primary in most of patients (77.8%) with an average duration of 3.32 years. 25% of patients had at least one previous failed assisted reproductive attempt. Spermogram abnormalities were found in 78.7% of patients. The mean score of Rosenberg scale was 30.68±4.35. Low self-esteem was associated with older age (p=0.006), lower educational level (p=0.019) and longer duration of infertility (p=0.022). Men who had children had better self-esteem (p=0.022). No associations were found between self-esteem and erectile dysfunction or previous failed assisted reproductive technique attempt.
Our results show that infertility reduces men’s self-esteem, especially of patients with lower educational level and longer duration of infertility. Physician dealing with infertility should be aware of these psychosocial aspects and offer help when needed.
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.
Endometriosis is a chronic oestrogen-dependent condition that affects 10% of women from puberty to menopause. It is characterised by the presence and proliferation of endometrial-like cells outside the uterine cavity, generally within the pelvis. Endometriosis can present as superficial or deep peritoneal lesions, ovarian endometrioma or deep rectovaginal disease. The two hallmark symptoms of endometriosis are pelvic pain and infertility resulting in poor quality of life. There is no correlation between the extent of the disease and severity of symptoms. The true prevalence of the condition is not known, as it requires a laparoscopy to confirm the diagnosis. It is found in up to 30% of women with infertility and in 45% of those with pelvic pain. While there are several theories of pathogenesis, an interplay of genetic, hormonal, environmental and immunological factors is implicated in the development of endometriosis in susceptible women. Symptoms are managed with a combination of hormonal treatment and laparoscopic ablation or excision of lesions for pain and usually assisted reproduction for infertility. Endometriosis is prone to recurrence after treatment, requiring multiple contacts with healthcare and repeat surgery. Management of endometriosis requires an individualised approach based on the woman’s age, predominant symptoms and priorities, which are subject to change over time.
Psychosocial support in fertility clinics or centres providing third-party reproduction has changed over time as reproductive techniques have developed; social norms, legal systems and counselling standards have evolved; and access to information expanded with the world wide web. Today patient support and infertility counselling involves supporting and assessing patients, donors, surrogates and their partners, and the parents and children at all stages of family building from initial decision-making about choices to later family life. Infertility counsellors also address support needs of staff providing fertility care. However, not all centres provide this range of services. The present chapter will review essential components of patient support in third-party reproduction provided by clinic staff and infertility counsellors, highlighting key features of good practice according to the Human Fertilisation & Embryology Code of Practice (2019, 9th edition).
The present study evaluated the effect of the aqueous extract from leaves of E. speciosa on some physiological and biochemical parameters of reproduction and the onset of puberty in pregnant mare serum gonadotropin (PMSG)-primed immature female rats. High pressure liquid chromatography (HPLC) was used to quantify the phenolic compounds in the methanol/methylene chloride (1:1) extract, the ethanolic and ethyl acetate fractions and the aqueous residue of E. speciosa. E. speciosa (0, 8, 32 or 64 mg/kg) were administered for 15 days to 24 non-PMSG-primed and 24 primed rats with 0.01 IU of PMSG. At the end of the treatment period, animal were sacrificed and their body, ovarian, uterine weight, ovarian protein or cholesterol level, as well as data on puberty onset were recorded. Of the 16 polyphenolic compounds quantitatively revealed in the extracts and fractions of E. speciosa after HPLC analysis, quercetin, rutin, apigenin and eugenol were the most abundant. Non-primed rats showed a significant increase (P < 0.05) in the uterine relative weight at the dose of 8 mg/kg when compared with the other treatments. The uterine proteins and the ovarian cholesterol (P < 0.05), respectively, showed a reduction at doses of 64 mg/kg and 32 mg/kg in non-primed rats. However in PMSG-primed rats, a significant decrease (P < 0.05) was observed in ovarian cholesterol at 64 mg/kg. In conclusion, E. speciosa potentializes the PMSG-inducing effect on folliculogenesis in PMSG-primed rats.
Although the association between stress and poor reproductive health is well established, this association has not been examined from a life course perspective. Using data from the National Longitudinal Survey of Youth 1997 cohort (N = 1652), we fit logistic regression models to test the association between stressful life events (SLEs) (e.g., death of a close relative, victim of a violent crime) during childhood, adolescence, and early adulthood and later experiences of infertility (inability to achieve pregnancy after 12 months of intercourse without contraception) reported by female respondents. Because reactions to SLEs may be moderated by different family life experiences, we stratified responses by maternal responsiveness (based on the Conger and Elder Parent-Youth Relationship scale) in adolescence. After adjusting for demographic and environmental factors, in comparison to respondents with one or zero SLEs, those with 3 SLEs and ≥ 4 SLEs had 1.68 (1.16, 2.42) and 1.88 (1.38, 2.57) times higher odds of infertility, respectively. Respondents with low maternal responsiveness had higher odds of infertility that increased in a dose–response manner. Among respondents with high maternal responsiveness, only those experiencing four or more SLEs had an elevated risk of infertility (aOR = 1.53; 1.05, 2.25). In this novel investigation, we demonstrate a temporal association between the experience of SLEs and self-reported infertility. This association varies by maternal responsiveness in adolescence, highlighting the importance of maternal behavior toward children in mitigating harms associated with stress over the life course.
An awareness of fertility and the factors affecting it is crucial to dealing with infertility, though little research has been conducted in the context of rural India. This study assessed Indian women’s perceived causes of, and strategies for coping with, infertility and the associations with levels of reproductive health knowledge in rural areas. Primary data were collected through mapping and listing in high infertility prevalence districts of West Bengal in 2014–15. A total of 159 women aged 20–49 years who had ever experienced infertility were interviewed. A Reproductive Health Knowledge Index (RHKI) was computed to indicate respondent’s level of reproductive health knowledge, and to show its association with perceived causes of infertility and coping with infertility. The highest mean RHKI score was observed among women in the lowest age group (RHKI=5.75, p<0.001), those with a higher level of education (RHKI=9.39, p<0.001) and those who had exposure to any media (RHKI=5.88, p<0.001). Women with a poor wealth index (RHKI=2.11, p<0.01) and those from Scheduled Caste, Scheduled Tribe and Other Backward Class communities (RHKI=4.20, p<0.05) had lower RHKI scores than richer women and those from General Caste communities. Women with a higher RHKI score were more likely to give biology (98.0%, p<0.001), old age (94.1%, p<0.01) and repeated abortions/accident/injury (92.2%, p<0.001) as reasons for infertility, whereas women with a low RHKI were more likely to give religious (73.2%, p<0.001) and old-age-related causes (75.0%, p<0.01) of infertility. Women with a high RHKI score were more likely to opt for modern allopathic treatments (RHKI=7.04, p<0.001), whereas those with a low RHKI score were more likely to seek treatment from religious and superstitious practitioners, use home remedies or receive no treatment at all (RHKI=1.66, p<0.001). Appropriate reproductive health knowledge is crucial if rural Indian women are to correctly assess their infertility problems and choose effective coping strategies.
Sulphur mustard (HD) is a lipophilic caustic alkylating vesicant (blister agent) that has mutagenic and carcinogenic effects. Among the studied perturbations are long-term genitourinary (GU) and fertility effects. Approximately 50,000 Iranian soldiers and civilians were exposed to HD during the Iraq-Iran war (1980-1989). This study questioned the wives of Iraq-Iran war veterans to determine the effects of male HD-exposure on pregnancy complications, adverse pregnancy outcomes, and secondary infertility.
A retrospective, survey-based cohort study was conducted of wives of Iranian military veterans that survived HD-associated injuries while serving in Ahvaz, Iran during the Iraq-Iran war (1980-1989), as compared to non-exposed veterans serving concomitantly. Patients were identified from a database of injured veterans maintained by the Foundation of Martyrs and Veterans Affairs (Iran) via a systematic random sampling method utilizing a random number table. Using a validated questionnaire, collected data included: demographics; type and severity of chemical injury; spouse’s obstetric history (pregnancy number, duration, complications, and outcomes before and after spouse’s chemical injury); and secondary infertility.
An increase in spontaneous abortion (P = .03), congenital anomalies (P < .0001), and secondary infertility (P = .003) were observed. These findings were greatest amongst those with HD injuries affecting >50% body surface area. No difference in stillbirth, premature birth, or low birth weight was observed.
Exposure to HD in combat may have long-lasting fertility effects on soldiers and their spouses, including spontaneous abortion, congenital anomalies, and secondary infertility. Further investigation is needed into the long-term effects of HD exposure as well as methods to better protect soldiers.
While intracytoplasmic sperm injection (ICSI) is the most significant advance in assisted reproductive technology (ART) for the alleviation of male factor subfertility, its use has become increasingly widespread and indiscriminate in ART clinics, extending well beyond the reasons for its necessary application. But ICSI is not “better” than IVF using any established outcome metric. Indeed, available evidence indicates that ICSI yields fewer embryos per treatment cycle, embryos which may have impaired developmental potential compared to IVF-derived embryos. This chapter investigates the basis for the over-use of ICSI, and identifies risks to which couples are exposed by the unjustified use of ICSI: a debate that has been raging for two decades, and is now also extending into considerations of “andrological ignorance”, how ICSI has effectively blocked scientific advances in andrology, and how obligate ICSI has effectively transferred the treatment burden for male factor infertility to the female partner, who is expected to undergo possibly unnecessary controlled ovarian hyperstimulation, oocyte retrieval and embryo transfer procedures.