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CAMPUS: EGG DONATION

Biological or donor parenthood in the treatment of infertility

Genetic continuity or the greater chance of ART success? Campus meeting explores the questions raised by third-party gamete donation.

Published 12 December 2019

A Campus meeting in November reviewed the arguments for and against donor conception, and the sometimes difficult ethical arguments raised by the prospect of a donor-conceived child. About the latter, opinion now seems universally in favour of early disclosure of biological origins.

At the heart of a wide-ranging Campus meeting on the relevance of genetic inheritance in plotting the outcome of fertility treatment was a simple everyday conundrum: if birth rate from ART in autologous cycles declines with age, why do so many women of advancing maternal age ignore the evidence of egg donation and persist in trying with their own eggs? Where does the balance between genes and treatment success lie, asked Jackson Kirkman-Brown, co-ordinator of the SIG Andrology, in introducing this interesting meeting.(1)

Defining 'success' as a single healthy birth delivered at term, ESHRE's senior research specialist Nathalie Vermeulen presented indisputable evidence (from SART and ESHRE registries) that success rates decline terminally with age; by contrast, LBR with donor eggs at 35 years and over is almost 30%, and continues at this steady rate to age 40 and beyond, while the rate with non-donor eggs declines to below 5%. Although this considerably improved outcome in women over 35 should be balanced by an added risk of maternal hypertension during pregnancy, such risk rates do little to explain the continuing attraction of autologous cycles.

Is it simply that patients are not adequately informed? Consultant Meena Choudhary from Newcastle, UK, was quite categorical about what patients should be told: that the risk of birth defects increases with rising female age; IVF treatment cannot reverse the effect of ageing; the chance of having a healthy baby becomes much lower as mothers age; and PGT‐A will not increase the chance of live birth. Moreover, de novo mutations are more common with paternal than maternal ageing (although paternal age on its own does not affect the chance of success), and, as with PGT-A, there is no robust evidence to suggest that DNA fragmentation testing will improve results. And echoing Nathalie Vermeulen, Choudhary reaffirmed that egg donation 'surpasses' the effect of female age in live birth rate (while sperm donors up to age 45 have not been shown
to reduce that chance in older women).

This Campus meeting was jointly organised by the SIGs Andrology and Psychology & Counselling and it was clear from many presentations that psychological factors - what Mariana Martins of the latter SIG described as 'concerns' - explain the value of genetic parenthood for many couples, especially those faced with the option of third-party donation. However, said Martins, many of the concerns associated with third-party donation, or more accurately the wish for a fully genetically related child, are the result of misconceptions about the importance of genetics. For example, disposition to a range of psychological traits cited by Martins - from depression to hyperactivity - can be clearly attributed to experience and the environment. There is also strong evidence that, while heritability of personality traits decreases over the life-span, environmental influence increases. Martins also suggested, particularly with reference to poor prognosis patients, that, in assuming option one is always IVF with your own genes and gametes, years may actually pass by before option two (donor gametes) is even considered. 'We may unintentionally be delaying a live birth, or even promoting dropout,' said Martins, 'so leaving patients with an unfulfilled child wish.'

However, Kirkman-Brown named disclosure to the future child about their origin of conception as 'probably the most studied and controversial subject' governing decisions about donor treatment. Despite the 'harms' associated with secrecy and non-disclosure, fewer than half the parents of 10-year and older children reported disclosure to them in one 2016 study. Petra Thorn, a former co-ordinator of the SIG Psychology & Counselling, listed several commonly cited reservations about third-party donation, including 'abnormal' family composition, the possibility of stigmatisation, the contrast between 'social' and biological parenthood, and of course disclosure and access to information. These, said Thorn, were important concerns for many couples, which makes counselling at the earliest stage - and certainly before any treatment begins - imperative. 'We must ensure that both partners fully support the type of treatment,' she insisted, 'and avoid any risk of ambivalences during pregnancy.' This might be achieved through exploring the new family boundaries implied by donation, disclosure, the role of the donor, and legal implications. Moreover, said Thorn, all the evidence suggests that, if children are informed of their conception early with the opportunity to access their
biological origins, if parents feel comfortable with the idea of third-party conception and if donors are well informed and prepared for offspring to contact them, the children, parents and donors will do well.

Direct-to-consumer DNA testing
Near the surface of this presentation was a view shared by all speakers at this meeting, that donor children should be informed of their origins at an early stage. 'No-one should go into treatment with a view that they will not tell their children,' said Marilyn Crawshaw from the University of York, UK, after describing the implications of direct-to-consumer DNA testing. As Focus on Reproduction has already reported, the huge DNA databanks now assembled by genealogy discovery companies have already rendered donor anonymity an unsustainably impossible concept. Our report a few months ago noted DNA samples in storage of around 30 million people, with traceability going back three or four generations. However, this burgeoning increase, said Crawshaw, is likely to reach 100 million samples by 2021, with countless internet-based forums and support groups for donor-conceived individuals, their donors and their parents. 'Everything will change,' said Crawshaw. Or has changed already? Indeed, 37% of donor-conceived children in one recent study said they found out about their origins from results of a commercial DNA test (against 51% from their parents when a child or adult).

The shift in attitude towards donor anonymity - and reflected in more relaxed attitudes to fertility treatment in single and lesbian women with donor sperm - was already evident in so many jurisdictions switching their policies from anonymity to formal information release mechanisms. Even France, which has long protected the anonymity of sperm donors in its CECOS system, will with new legislation switch to an identity release system.

Of course, for those discovering unexpected information about their biological origins, the consequences can be devastating. Citing one parent quoted in BioNews, Crawshaw reported: 'More support is needed, urgently, as the tidal wave of unanticipated disclosure is only beginning. The future for social justice in donor conception leads towards openness and support, not bans and anonymity.’ And where will that 'support' come from? From the fertility clinics, the ancestry industry, the state?

The vulnerability of donor-conceived people to such surprises has prompted calls for greater openness and inclusivity, argued Eric Blyth, a veteran researcher in gamete donation and families. He too saw a shift in the narrative - from an exclusively medical perspective (treatment for infertility/childlessness) to a broader family‐building paradigm, reflected in more widespread disclosure legislation, greater use of sperm donation treating singles and lesbians, in increasing number of jurisdictions, and in direct-to-consumer genetic testing. And he too looked to the 'family-building' approach to donor conception as the way forward in accommodating a child's genetic heritage and integrating donor relationships within existing family ties.

1. Much of the content of this Campus meeting has now been summarised. See when published: Kirkman-Brown J, Martins MV. 'Genes versus children': If the goal is parenthood, are we using the optimal approach? Hum Reprod 2019; doi:10.1093/humrep/dez256.