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  • Cited by 13
Publisher:
Cambridge University Press
Online publication date:
February 2014
Print publication year:
2009
Online ISBN:
9781107784734

Book description

Reproductive ageing affects both individuals and wider society, and obstetricians and gynaecologists are witness to the impact of reproductive ageing and to some of the fears and misapprehensions of the general public. This book raises awareness of societal trends and their implications. The wider importance of the subject to the whole of society is emphasized by contributions from outside the world of obstetrics and gynaecology, both within and outside medicine. The 56th RCOG Study Group brought together a range of experts to examine reproductive ageing. This book presents the findings of the Study Group, with sections covering:background to ageing and demographicsbasic science of reproductive ageingpregnancy: the ageing mother and medical needsthe outcomes: children and mothersfuture fertility insurance: screening, cryopreservation or egg donors?sex beyond and after fertilityfertility treatment: science and reality - the NHS and the marketthe future: dreams and waking up.

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Contents


Page 1 of 2


  • 1 - Ageing: what is it and why does it happen?
    pp 3-14
  • View abstract

    Summary

    Demographers encapsulate the rate of population ageing by estimating the years taken for a doubling from 7% to 14% of the number of people aged 65 years or over as a proportion of the total population. The stages of the lifespan of mammals can be distinguished as: fertilisation and birth, infancy to sexual maturity and adult reproductive life through to death, which may include a distinct post-reproductive phase. The molecular changes that are commonly regarded as ageing do not begin at a defined stage but seem to develop gradually. At the molecular level, it is clear that damage to all cellular components accumulates with increasing age. According to the disposable soma theory, evolution has favoured strategies that devote energy and resources to enable the soma to attain reproductive fitness with the germ line safe from damage. Non-adaptive strategies have been suggested based on the disposable soma theory.
  • 2 - Culture and reproductive ageing
    pp 15-26
  • View abstract

    Summary

    There have been several cultural, anthropologically based studies on reproductive ageing since the 1990s. The starting section of this chapter sets out what an ethnographic perspective entails and its significance in understanding reproductive ageing. The subsequent sections discuss the kinds of variation that exist within populations thought to be culturally similar and some of the challenges that the cultural perspectives present to current dominant thinking on reproductive ageing. The association of reproductive ageing with each childbearing and birth, as in the Gambian example, underscores a key anthropological understanding of the relationship between biology and culture: it can be non-linear and culture can influence biological ageing, bringing it forward or delaying it. Policies should encourage a gender- and sexuality-based perspective on ageing that recognises that the experiences of fertility, infertility and reproductive ageing are products of the unequal relations between the sexes.
  • 3 - Ageing
    pp 27-32
  • View abstract

    Summary

    This chapter presents a discussion between experts on ageing. Data from women who have late menopause suggest they have better health fitness afterwards. That is, they live longer and appear to be healthier. On the topic of association between longevity and late age at childbirth, Jane Preston says that women did not have more children within their extended fertile period so they were not becoming more fecund during that time. Everything about ageing that we understand from animal models, and human populations, suggests that the menopause has not evolved as a result of some killer gene. Ageing is seen as a non-adaptive process by which repair mechanisms and other mechanisms just fail to be supportive at a sufficient level to keep us going a bit longer. All ageing theories are non-adaptive and ageing is a by-product of what has gone on earlier.
  • 4 - What has happened to reproduction in the 20th century?
    pp 33-40
  • View abstract

    Summary

    The total fertility rate (TFR) is the average number of children a woman would have if she experienced the age-specific fertility rates for a particular year throughout her childbearing life. The peak ages for abortion are in the 20-24 and 16-19 year age groups. Conception statistics include both terminations of pregnancy by legal abortion and maternities in which one or more live births or stillbirths occur. Later generations had fewer children on average by their mid-20s, but higher rates in the future at older ages may mean their completed fertility rates are at a similar level to earlier cohorts. There has been a continued reduction in the age at which sexual intercourse first took place together with an increase in the proportion of young people who had sexual intercourse before the age of consent. In 2006/07, the youngest women were the least likely to be using contraception.
  • 5 - Trends in fertility: what does the 20th century tell us about the 21st?
    pp 41-58
    • By Stijn Hoorens, RAND Europe, 37 Square de Meeus, B-1000 Brussels, Belgium
  • View abstract

    Summary

    This chapter focuses on one of the factors driving population change: fertility. Firstly, current trends in fertility are outlined, followed by a brief discussion of the various indicators used to measure fertility. Secondly, the determinants and drivers of fertility are explored, after which several implications of these drivers for the future are examined. Finally, the chapter concludes with some speculative remarks on possible future trends in fertility and their potential impact. Contraception has provided couples, and women in particular, with the freedom to choose when not to have children, and the mass introduction of the oral contraceptive pill had an unprecedented demographic and societal impact in the 20th century. The impact of a second reproductive revolution in the 21st century may be of similar magnitude. As low fertility, population ageing and migration are currently at the top of European political agendas, governments will continue to be challenged by demographic developments.
  • 6 - Demographics
    pp 59-62
  • View abstract

    Summary

    This chapter presents a discussion between experts on demographics. They discuss the effect of the prolonged one-child-per-couple policy in China and its economic consequences. Cohort graphs reveal that in the past overseas-born mothers were a very heterogeneous group. Particularly the mothers from India and Pakistan somewhat tended to have births younger and (b) have more births. But what we are seeing now is fewer new births coming in through those mothers. We now have mothers from the accessioncountries who tend to have similar, or lower, fertility, albeit at slightly younger ages than UK-born mothers. Regarding migration and fertility studies, the massive decline in fertility was unanticipated. The sustained low levels of fertility in Europe were unanticipated.
  • 7 - Is ovarian ageing inexorable?
    pp 65-74
  • View abstract

    Summary

    The total number of oocytes (follicles) declines continuously after birth such that, by the time of menarche, only a quarter of a million follicles remains, or even fewer in girls prone to premature ovarian failure. In this chapter, attention has been drawn to ovarian ageing as an inexorable process, which has sometimes been simplistically compared to an hourglass. It focuses on the factors regulating the primordial-to-primary follicle growth transition. The number of follicles established at birth and the subsequent rate of loss determines the time of follicle depletion and hence menopause. The mechanism of the primordial-to-primary follicle transition has been evolutionarily conserved, as expected with a process that crucially affects fertility and the reproductive lifespan. The number of oocytes in the ovary is fixed early in life and not renewable in adulthood but a contrary view came to the fore, namely that oocytes are continually replaced from germline stem cells.
  • 8 - The science of ovarian ageing: how might knowledge be translated into practice?
    pp 75-88
  • View abstract

    Summary

    All ovarian follicles are doomed to degenerate through atresia unless they receive adequate trophic support from specific growth-differentiation factors or gonadotrophins at critical stages in their development. Throughout folliculogenesis, granulosa cells strongly express transforming growth factor-beta (TGFβ) superfamily genes encoding homo- or heterodimeric proteins that orchestrate the entire process of oogenesis at autocrine and paracrine levels. It is clearly established that ovarian ageing is heritable in women. The development-related changes in TGF�uperfamily gene expression throughout folliculogenesis create an efflux of potential biomarkers in blood or urine that can be measured to reflect follicle number and stage of maturity. Such assays potentially provide a rational basis for the endocrine diagnosis of ovarian sufficiency, in combination with conventional markers of ovarian status (follicle-stimulating hormone and estradiol) and ultrasonographic measurements of follicle size and number. Unquestionably, human homologues of the numerous mouse genes that regulate ovarian ageing operate in women.
  • 9 - Basic science: eggs and ovaries
    pp 89-94
  • View abstract

    Summary

    This chapter presents a discussion between experts on eggs and ovaries. There is no genetic condition in humans which seems to be associated with a long-time rescue of primordial follicles. Sixty seems to be pretty close to the limit, maybe very exceptionally beyond that. Eggs or ovarian tissue can be frozen. The central role that signalling pathway plays in cell growth throughout the body is indisputable, which actually limits what we might be able achieve in an oocyte. But there are molecules that suppress the destruction of FOXO. An aspect is some fascinating data in mice suggest that nutrition has a major impact on the rate at which oocytes are lost from the ovary. Certainly, reproductive lifespan and functional lifespan of the ovary can be prolonged by calorie restriction. Real clock genes operate in oocytes that intrinsically regulate the rate at which the follicles start to grow and become atretic.
  • 10 - Male reproductive ageing
    pp 95-104
  • View abstract

    Summary

    Age-related changes in sperm output develop gradually without any evidence of sudden onset. Female fecundity starts to decline after 30 years of age and is greatly reduced after age 40 years. The effect of male age on fecundity remains controversial and few studies show a similar trend in men. The effect of ageing of the male partner on the risk for miscarriage has been studied extensively, although many studies are retrospective, span long observational periods and fail to control properly for maternal age effects, or have small sample sizes. The Royal College of Obstetricians and Gynaecologists (RCOG) recommends the British Andrology Society guideline of limiting the age of sperm donors to 40 years. Paternal ageing does not affect the risk of miscarriage, and increased paternal age on its own is not an indication for prenatal diagnosis since the absolute risk for genetic anomalies in offspring is low.
  • 11 - The science of the ageing uterus and placenta
    pp 105-116
  • View abstract

    Summary

    The scientific study of ageing of the uterus and placenta is clinically relevant because of the associations between advanced maternal age and outcome of pregnancy. This chapter includes some clinical observations to demonstrate parallels between the scientific observations and the clinical outcomes that are thought to be related. The subject is addressed in terms of the ageing myometrium, decidua and placenta. The chapter discusses two biological mechanisms that are thought to be important in ageing, namely telomere length and failure of autophagy. Gosden et al. examined nonpregnant human myometrium obtained at the time of hysterectomy and demonstrated the presence of cytoplasmic lipofuscin inclusions in uterine smooth muscle cells from older women. A combination of biological epidemiology and smooth muscle studies indicates a mechanistic basis for the effect of ageing on performance during labour, namely that prolonged prepregnancy stimulation of the uterus by estrogens and progestogens may adversely affect its function.
  • 12 - Basic science: sperm and placenta
    pp 117-122
  • View abstract

    Summary

    This chapter presents a discussion between experts on the basic science of sperm and placenta. They speculate whether the cervix might be similarly affected as the uterus. Gordon smith states that cervical tissue is obviously much harder to get, and it is relatively straightforward to obtain lower uterine segment at caesarean section. Dimitrios Nikolaou states that the cephalopelvic disproportion is important, but not as important as intrauterine growth restriction or stillbirth. There are data about pre-eclampsia and eclampsia which show increased risks at the extremes of age. The effectiveness of sperm is controlled by fibroblast growth factor, and by knocking out the receptor, the likelihood of the sperm fertilising the egg is increased. Herman Tournaye states that the endocrine function is going down with ageing, and it is called andropause but without sudden stop as in menopause. The terminology used is late-onset hypogonadism and is a natural phenomenon.
  • 13 - The effect of age on obstetric (maternal and fetal) outcomes
    pp 125-140
  • View abstract

    Summary

    The risk of fetal loss according to maternal age at conception follows a J-shaped curve, with a steep increase after the age of 35 years. Older mothers are more likely to be nulliparous. Even without consideration of maternal age, multiple pregnancies have increased rates of obstetric complications such as pre-eclampsia. Porreco attempted to address the specific effect of ovum donation on pregnancy outcome in older mothers while also considering plurality. Stillbirths affect one in 200 pregnancies. In a population where 1091 of 10737 women were aged 35 years or over, the need for oxytocin and the incidence of prolonged labour, instrumental delivery, intrapartum caesarean section and intrapartum caesarean section because of dystocia all increased with increasing maternal age. Obstetricians and gynaecologists should advocate for policies that enable women to reproduce safely without personal cost to their education, careers, identity or their own or their offspring's health.
  • 14 - The older mother and medical disorders of pregnancy
    pp 141-162
  • View abstract

    Summary

    The implications for ageing pregnant women are a greater likelihood of a high-risk pregnancy and, for local NHS providers, a need for increased resources with improved care pathways in primary and secondary care and more specialists who are trained to look after medical diseases in pregnancy. This chapter covers the effect of age on the occurrence of systemic medical disorders that have an impact on pregnancy, such as hypertension, obesity, diabetes, ischaemic heart disease and cancer. The UK government has recently focused on bringing maternity care into the community. Women contemplating delaying pregnancy should be informed of the health consequences of this and advised that completion of childbearing in their 20s will greatly reduce their obstetric and medical risks. A growing number of women are requesting assisted reproductive technologies (ART) to conceive in their 40s and 50s.
  • 15 - The ageing mother and medical needs
    pp 163-170
  • View abstract

    Summary

    This chapter presents a discussion between fertility experts on ageing mother and medical needs. Framing the age for pregnancy is an individual's problem and women should have children in their 20s. The first pregnancy increases the risks of pre-eclampsia. No woman should be bullied into a pregnancy when, or if, she does not want to. However, it is recommended that women should be counselled that it is better to have children in your 20s. The graphs show that fertility falls with age, and miscarriages and complications increase with age on the J-shaped curves available in family clinics. Family planning used to be about planning families - now it's merely about contraception. Gordon points out that the real numbers of maternal mortality are very small. That is only because obstetricians work fantastically hard to keep them low. For every woman who dies, at least a hundred others go to intensive care, and several thousands will have a severe morbidity of childbirth such as a hospital admission, complication, induction or caesarean section.
  • 16 - What is known about children born to older parents?
    pp 173-182
  • View abstract

    Summary

    Conception, pregnancy and childbirth in older mothers involve increased physical risks to both the mother and the offspring. After the age of 31 years, the probability of conception falls rapidly and older women take longer to conceive and are more likely to require reproductive assistance. Older mothers felt a lack of preparation for the material needs of the baby and a tendency to put aside thoughts of being a mother but younger infertile women were more likely to have irrational idealistic cognitions about pregnancy and parenthood. Maternal age is likely to be associated with different domains of parenting and parenting outcomes. The three distinct parenting theories are: the intuitive parenting theory, linear relationship of age to parenting, and Rossi's timing of events model. Older couples are likely to have been in a longer term partnership, on average 3-5 years longer, than younger couples, creating an altered parenting context.
  • 17 - Consequences of changes in reproductive patterns on later health in women: a life course approach
    pp 183-192
    • By Gita Mishra, University College Medical School, Rachel Cooper, University College Medical School Department of Epidemiology and Public Health
  • View abstract

    Summary

    Reproductive health, from menarche to menopause, is not only understood as integral to women's overall health and wellbeing but is increasingly recognised as a sentinel of chronic disease in later life. The changing patterns of reproductive function are explained with regard to trends in child bearing. The difficulty in conceiving naturally for those women who delay childbearing may have also contributed to the increased use of assisted reproductive technologies (ART) such as in vitro fertilisation. The rise in popularity of these treatments over the past two decades reflects both the increasing demand for fertility treatments but also their wider acceptability and availability. To predict future trends in chronic disease for women based on their changing patterns of reproductive characteristics, the risk factors linked to reproductive health and health in later life to be considered are: obesity, hormone therapy use, and other risk factors such as social inequalities.
  • 18 - The outcomes: children and mothers
    pp 193-198
  • View abstract

    Summary

    This chapter presents a a discussion on children and mothers. The observed distribution of age of onset of menopause is a mixture of two distributions; one distribution is normal with an early age of menopause around 40, and other one is normal with a mean age around 50. If the mother had a very early age menopause, the person is more likely to be in the earlier distribution. There is a third group of women that had hysterectomy. A series of competitive risks analyses and work is performed on hysterectomy because these women already have high risk of cardiovascular disease. There is no relationship between the age of menarche and menopause. Women think that if they started their periods early, they will finish early. The stigma is with the child rather than on the parents themselves. When the children go to school the parents were being mistaken for grandparents.
  • 19 - Screening for early ovarian ageing
    pp 201-210
  • View abstract

    Summary

    A number of tests have been used to predict ovarian ageing/poor ovarian reserve. Despite the large number of tests in current use, an ideal test has yet to be developed. The most comprehensive systematic review for tests of ovarian reserve concluded that an in vitro fertilisation (IVF) cycle itself may be a more reliable predictor of ovarian response to stimulation than any of the existing tests. The predictive value of four of the most commonly used tests are: basal serum follicle-stimulating hormone, antral follicle count (AFC), serum inhibin B and serum antimillerian hormone (AMH). Internationally, a number of fertility prediction tests have been marketed, and the tests have been mainly developed within an IVF setting, using data on outcomes of ovarian stimulation. Serum AMH concentration and AFC tests can predict oocyte yield but not oocyte quality or pregnancy.
  • 20 - Egg freezing: the reality and practicality
    pp 211-226
  • View abstract

    Summary

    Cryopreservation protocols for isolated oocytes and complex ovarian tissues can be broadly classified as equilibrium freezing (slow-freezing protocols) or rapid freezing (vitrification protocols). Oocyte cryopreservation requires that the gametes tolerate three non-physiological conditions: exposure to molar concentrations of cryoprotective agents (CPAs); cooling to subzero temperatures and removal of or conversion of almost all of the liquid cell water into the solid state. Penetrating CPAs, such as glycerol, dimethyl sulphoxide (DMSO), ethylene glycol (EG) and 1,2-propanediol (PrOH), are all membrane-soluble and can pass into cells. Non-penetrating CPAs include sucrose, glucose, trehalose and polymers such as hydroxyethyl starch and polyvinyl pyrrolidone. The rate at which cells are cooled is fundamental to the success of cryopreservation. Consequently, at the time of writing, mature metaphase II (MII) oocyte cryopreservation remains a potential solution rather than a practical remedy for infertile women.

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