Age-Old Question: Exploring Fertility and Ageing

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26 October 2020 - by Annabel Slater
'Age and fertility – a topic that never gets old.' So said Sarah Norcross - director of the Progress Educational Trust (PET), the charity which publishes BioNews - excusing herself for the pun as she chaired the latest PET event 'Age-Old Question: Exploring Fertility and Ageing'.

The Office of National Statistics still shows the age of conception for men and women is rising. What are the consequences, and what is the understanding of experts and the general public?

The first speaker was Richard Anderson, professor of clinical reproductive science at the University of Edinburgh, who discussed female ageing and fertility at a clinical level. Women create all their eggs before they're born, in the form of immature egg follicles. Throughout their life, even before puberty, the numbers of these follicles decline.

Nonetheless, older women are having babies more than ever, with numbers of mothers in their late 30s having tripled since 1980. Yet the chance of miscarriage increases dramatically with age. According to data from the Human Fertilisation and Embryology Authority (HFEA), the occurrence of live birth following in vitro fertilisation (IVF) is over 30 percent for a woman under 35, and as low as 3-4 percent for a woman in her 40s.

What can be done? Science offers a few options, which Professor Anderson outlined: freeze your eggs, freeze part of your ovary, or use another younger woman's eggs. The first option, egg freezing, continues to increase in popularity and is an area of great research interest. Yet a Spanish study found that out of 5289 women who froze their eggs, only 12.1 percent went on to use them. Data also suggest that only one egg out of 20-25 collected will result in a baby.

Evidence suggests that the reasons women opt for elective egg freezing are due to partner choice, wish for financial stability, and their housing situation, instead of the 'glossy, slightly trite' adverts about egg freezing circulating in the US and probably soon in the UK. Professor Anderson said what is needed is an evidence-based, unbiased information source such as Michelle Peate's Decision Aid. It's essential that women, and men, should recognise the likelihood of success of egg freezing and the associated costs and risks.

Next to speak was Evelyn Telfer, professor of reproductive biology at the University of Edinburgh, and lead researcher at the lab which first created a mature human egg entirely outside the human body (see BioNews 937).

Professor Telfer spoke of a technique for storing pieces of ovary which contain primordial follicles. These immature follicles can be cultured to produce mature eggs, at about a 30 percent success rate – one possible approach to in vitro gametogenesis (IVG). This process is known as a 'multi-step culture system', and has been used to examine the effect of age, chemotherapy, and the role of signalling pathways.

But the big question is whether ovaries have the capacity to make new eggs. Are there germline stem cells in the adult human ovary? This question was answered in 2012 in a Nature Medicine publication showing that this cell type could indeed be isolated from the adult human ovary (see BioNews 646). Professor Telfer's lab has since reported that under the right conditions, such stem cells may be able to form new eggs (see BioNews 872).

Professor Telfer and her team are now investigating eggs produced by IVG, to find how similar they are to conventional eggs. Extensive further research will be needed before any clinical applications are developed.

Christopher Barratt, professor of reproductive medicine at the University of Dundee, delivered a talk focused on male fertility. Ageing somatic tissue can be disguised somewhat – consider those middle-aged celebrities who seem to have looked young for decades. Yet reproductive tissue changes with age, and the effects are visible in studies.

Is the age of first-time fathers increasing? Yes. In Australia in 1976, the average age of new fathers was 27.5 years old. Now, it is 33.5 years.

Is older reproductive age significant? Yes. Studies show that older men have lower odds of conception – a drop of 50 percent for men aged 35-39, compared to under 25-year-olds (see BioNews 974). Older men have increased semen abnormalities, incur a higher risk of premature birth and low birth weight, and other endocrine influences influencing their reproductive success, such as lower libido.

Furthermore, older fathers are also linked to higher rates of autism and schizophrenia in children. An observational study of four centuries of data in four different populations also indicates that children of older fathers have lower reproductive success and reduced longevity.

What can we do? Educate people, advised Professor Barratt, as knowledge about age and male fertility is very poor. According to Professor Barratt, even university science students don't tend to know how age impacts male fertility.

Dr Vasanti Jadva, principal research associate at the University of Cambridge's Centre for Family Research, addressed the psychological impact of older reproductive age on both parents and their children. Studies concerning older parent and child psychology are mixed, she reported. The findings are further confounded by different definitions for older parenthood, a lack of studies examining impact on later childhood, and how large cohort studies can't always identify mechanisms to explain the differences. Older women facing stressful fertility problems may also experience poorer mental health.

Judging by the studies that do exist, children do not appear to be adversely affected by having older parents. If anything, it is the parents themselves who may be adversely affected - some studies of older mothers reported lower social support, worse relationships with their partners, and more parental stress.

Another study indicated that older mothers are more likely to use donor eggs. They may also report regret in not having more children. Dr Jadva concluded that more studies are needed to investigate aspects of older parenthood.

It was time for questions. Professor Barratt was asked if men should be freezing their gametes to avoid age-related issues, as women do. Not likely on a global scale, he said, since sperm freezing is quite costly.

Asked about the production of eggs from ovarian stem cells, Professor Telfer recalled her initial reluctance to believe that she and her colleagues had achieved this. Their achievement continues to rock the scientific community, and is still controversial (see BioNews 1038). The adult stem cells that do exist in the ovarian tissue are not there to make new eggs normally. Professor Telfer stressed that while research using animal models is ongoing, research using human cells is still at an early stage.

What current steps and systems exist to raise awareness about age and fertility? Professor Barrett said it was 'blatantly obvious' that society overall does not understand its reproductive capacity. An unfair burden is placed on women, and that better education needs to implemented, beginning with young people. Dr Jadva agreed that many people don't understand that fertility declines with age, and that fertility studies tend to focus on people who have already started facing difficulties.

An audience member commented that the challenges discussed during the event were not just issues for science and medicine, but for policymakers and society more broadly, and were challenges that faced women and men alike.