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Female Fertility: What Does the Future Hold?

25 October 2021
Appeared in BioNews 1118

The Progress Education Trust (PET) event 'Female Fertility: What Does the Future Hold?' was the latest in a series of online discussions providing informative debate on future approaches to reproductive matters. Sarah Norcross, director of PET, chaired the event. The four experts presenting each provided distinct expertise in scientific, preclinical and clinical research relating to female fertility.

The first speaker, Professor Siladitya Bhattacharya, head of the School of Medicine, Medical Sciences and Nutrition at the University of Aberdeen, began by presenting an alternative approach to fertility, 'active family planning.' He discussed the stark relationship between the length of time spent trying to conceive and success rates in natural conception, with the latter dropping from 84 percent in the first year to 14 percent among those still trying to conceive three years later.

The current definition of infertility encompasses the length of time spent trying to conceive, but does not acknowledge the negative impact of female age; as a result, the rate of unexplained infertility – making up one-third of infertility diagnoses – increases with female age. Instead of this dichotomisation of fertility, Professor Bhattacharya argued for a personalised prognosis-driven approach, allowing for ownership of reproductive decisions through recognition of the interacting factors impacting upon success rates. Most excitingly, he introduced the audience to an online tool which helps to predict chances of conception following a diagnosis of unexplained infertility.

The second speaker, Colin Duncan, professor of reproductive medicine and science at the University of Edinburgh, focused on the barriers to fertility treatment. His research investigates obesity in relation to polycystic ovary syndrome (PCOS), given its prevalence in the general population, where one in eight women is on the PCOS spectrum. Furthermore, in the two fattest countries in the world, the USA and Australia, more two-thirds of people with PCOS are obese.

Unfortunately, obesity can prevent women from getting the fertility treatment they need, even though women with PCOS gain weight more easily through no fault of their own. In PCOS, reduced insulin signalling in the brain can result in effective reduction in energy expenditure by 25 percent, leading to weight gain and difficulty in losing weight. On average, a woman with PCOS may have to eat four percent less or exercise 20 percent more than a woman without PCOS, simply in order to maintain the same weight.

Professor Duncan and his research team worked on sheep to determine why this happens. Sheep born following testosterone exposure in utero were prenatally programmed to have a condition very similar to PCOS, and in adulthood become obese, exhibiting the exact same energy expenditure reduction (25 percent) as women with PCOS. After eating, insulin signalling in the brain alerts nerve cells to trigger fat cells to burn energy. Professor Duncan and his team found that the PCOS-sheep had less insulin signalling in the brain, resulting in the burning of less fat.

This, Professor Duncan hypothesised, could be treated by raising levels of insulin in the brain. A large number of insulin receptors are found in the olfactory bulb in the nose, hence Professor Duncan's team explored the impact of nasal administration of insulin. They found that this led the PCOS-sheep to have an increase in insulin signalling, resulting in the burning of more calories. This early phase research is exciting, even though it may be years away from making a difference in human contexts.

Professor Richard Anderson, head of Obstetrics and Gynaecology at the University of Edinburgh, continued on this scientific and clinical approach to female fertility. In particular, he focused on the trend of decreasing female fertility over the past decade, which he attributed to younger women exercising control over their reproductive capabilities and older women holding on to this capability.

Professor Anderson's presentation highlighted the regulation and control of ovaries over the course of a women's life, discussing novel ways of enhancing fertility through awareness of the underpinning biochemical pathways. Referring to Professor Adèle Marston's work, presented at a previous PET event (see BioNews 1116), Professor Anderson discussed the identification of 200 genes implicated in controlling menopause and linked to DNA repair.

The final speaker, Dr Rita Vassena, scientific director of the Eugin Group, shifted the focus of the discussion away from the clinical approach to female fertility. Noting how fertility patients tend to be risk-averse, Dr Vassena discussed the rate of elective caesarean sections following IVF, as well as the rate of preterm births. Giving a societal perspective, and using data from Spain, her presentation revealed the precarity of the population.

With 90 percent of employment contracts temporary, the reality is that most young adults spend more than half their income on rent, and 90 percent of those under 30 live with their parents. Stratifying the data by gender also reveals a stark pay gap: having children creates a gap of 20 percent, due to labour force participation, work hours and pay rate. The take-home message from Dr Vassena's presentation was clear: the future of fertility treatment requires pushing society to recognise and address the structural barriers that militate against having children, whether naturally or via assisted conception.

After the presentations, an informative Q&A followed. Professor Bhattacharya's proposed approach to fertility aims to enhance reproductive autonomy, recognising the importance of ownership of reproductive decisions. The onus is placed on women to ensure they control their fertility, but as Dr Vassena demonstrated, women may not be in a position to do so. Professor Duncan's early phase research pointed to potential ways to protect, control and – where necessary – enhance female fertility.

Professor Anderson referred to a famous call for 'freedom from the tyranny of excessive fertility' by the late Professor Sir Dugald Baird, a pioneering Scottish obstetrician/gynaecologist who was as passionate in advocating for women's access to abortion as he was in advocating for women's access to fertility/maternity services. That we are now so preoccupied with addressing women's lack of fertility, rather than addressing an excess of fertility, demonstrates how much things have changed.

PET is grateful to the Scottish Government for supporting this event.

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