Patient age the determinant of success in elective fertility preservation for women - and men

Published 07 January 2021

A well attended online Campus meeting in December heard that outcome from elective oocyte cryopreservation depends on the number of MII oocytes retrieved, and that varies with age. Older age also brings more neonatal risks for mother and baby.

A Campus meeting in December provided a major evaluation of the latest data and social trends in elective fertility preservation, with highlights including the consequences of postponing parenthood, the optimum oocyte number for vitrification, and whether men should also freeze their gametes.

Age was a theme throughout. The consensus from presenters was that most women who choose to preserve their fertility believe they’re stopping their biological clock and gaining an insurance policy for conception at a later date, but outcomes will depend on how old they are at the time of freezing their eggs.

Emphasising that a younger age means a better chance of success, Javier Domingo, from IVIRMA in Las Palmas, detailed evidence that age 36 was the threshold for ‘better and worse outcomes’ such as oocyte number, survival and clinical results. Findings from his IVI group have shown the cumulative live birth rate for elective fertility preservation in younger women (<35 years) is more than double that for older patients (>35), and at least 8-10 metaphase II oocytes are necessary to achieve reasonable success.(1) Overall, he reported, 10 to 15 oocytes would give younger women (<35) a 40-70% chance of having a baby compared with 25-40% for older patients (>36) - and 55.5 oocytes needed per live birth in those aged 40 and above compared with 15 for 35-year-olds and younger.(2) Domingo stressed that patients ‘must be clearly informed’ of their chances of success before freezing.

Marian Knight, professor of maternal health at the UK’s National Perinatal Epidemiology Unit, noted that later-in-life pregnancies come with increased risks for both mother and baby - premature birth, pre-eclampsia, and stillbirth (>age 40 = 60% risk) - with her findings showing independent associations for complications in women of very advanced age (>48) (eg, gestational diabetes and intensive care admission).(3) While maternal mortality rates remain low overall, research shows, deaths are highest in older and very young women (<20=2.47 per 1000 births; >40=2.32). ART, co-morbidity and multiple pregnancies could be factors, said Knight, but exactly why older women and their babies die has yet to be fully analysed by comprehensive studies.(4)

Cardiovascular disease remains the number one cause of maternal death (<2 per 100,000 pregnancies) and cases documented have featured older women with high-risk heart conditions whose pregnancies were unplanned, a fact underlining the need for counselling of patients, said Knight. In addition, she suggested cardiac assessments prior to ART and making women aware of any red flag symptoms such as breathlessness so they can make informed choices.

Do the questions around older parenting just affect women and, if not, should men be encouraged to freeze sperm? Himself an ‘older father’, Herman Tournaye analysed the arguments and data, including a recent study suggesting that paternal age has increased over the past few decades from the late 20s to early 30s, a trend sharing the same drivers as found in women (economic, work and social).

Men may produce more than 500 billion sperm cells in a lifetime, but of what quality in older fathers and with what consequences for their offspring? Tournaye noted that Lionel Penrose’s ‘copy error’ hypothesis - that advanced age results in greater DNA replication failures - still stands today, with male reproductive ageing also attributed to neuroendocrine changes. Studies also suggest the risk of mental disorders appears to increase in children of older fathers, said Tournaye. However, he pointed out that the impact of age on exocrine function varies among men, with no longitudinal cohort studies to explain why, while non-controlled retrospective studies feature many confounding factors such as obesity.

So fertility services are faced with a ‘greying’ patient population where older women partnered with older men seek treatment despite their reproductive risks.(5) On this basis, suggested Tournaye, ART outcomes could benefit from social sperm freezing. Arguments against this, however, include the fact that frozen sperm can only be used with medically assisted treatments, storage is expensive (unless men resort to home-freezing kits), and as yet not enough is known about the long-term effects of DNA fragmentation.

The clear message from this popular Campus meeting is that freezing for women presents a quite clear question: if they delay, they risk losing their chance of motherhood. But for men it’s still a grey area with more research needed into the consequences of putting fatherhood on hold.

1 Cobo A, García-Velasco J, Coello A, et al. Oocyte vitrification as an efficient option for elective fertility preservation. Fertil Steril 2016; 105: 755-764. doi:10.1016/j.fertnstert.2015.11.027
2 Cobo A, García-Velasco J, Coello A, t al. Six years' experience in ovum donation using vitrified oocytes: report of cumulative outcomes, impact of storage time, and development of a predictive model for oocyte survival rate. Fert Steril 2015; 104: 1426-1434. https://www.fertstert.org/article/S0015-0282(15)01866-X/pdf
3 Fitzpatrick K, Tuffnell D, Kurinczuk J, Knight M. Pregnancy at very advanced maternal age: a UK population‐based cohort study. BJOG 2016; 124: 1097-1106. doi:10.1111/1471-0528.14269
4 MBRRACE-UK Perinatal Mortality Surveillance Report UK Perinatal Deaths for Births from January to December 2018. https://www.npeu.ox.ac.uk/mbrrace-uk#mbrrace-uk-perinatal-mortality-surveillance-report-uk-perinatal-deaths-for-births-from-january-to-december-2018
5 Gleicher N, Kushnir V, Weghofer A, Barad D. The “graying” of infertility services: an impending revolution nobody is ready for. Reprod Biol Endocrinol 2014; doi:10.1186/1477-7827-12-63

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