Time-lapse microscopy, an 'add-on' in some jurisdictions, is given an ‘amber’ evaluation by the HFEA as a result of ‘conflicting evidence’ of benefit.
Published 13 December 2021
ESHRE took part in the annual meeting of the UK’s Progress Educational Trust, publisher of the internationally read BioNews (www.bionews.org.uk). The ESHRE-sponsored and presented session was one of four on the meeting’s theme of regulation in fertility.
The question of add-ons in the treatment of infertility continues to trouble clinics and regulators, said Anja Pinborg, a former Executive Committee member of ESHRE, in the opening presentation of this ESHRE session. She reaffirmed ESHRE’s endorsement of the HFEA’s statement on the responsible use of add-ons and a clinic’s obligation to inform patients of evidence for use and cost.(1) That evidence is ‘usually missing or unreliable’, she said, and most add-ons will incur additional cost.
The HFEA’s own list of add-ons has proved somewhat controversial, not just in its definition of an add-on, but also the glaring absence of any ‘green-for-go’ treatments in its traffic-light evaluation system. The list includes such commonly studied initiatives as assisted hatching and endometrial scratching (both red) but still fails to find supportive evidence for elective freeze-all, time-lapse imaging or PGT-A. Indeed, on the latter initiative, there were questions from the floor of this online meeting wondering why trophectoderm biopsy for PGT-A was still proscribed by the HFEA. Indeed, Pinborg herself conceded that some approaches – even if not an add-on, such as elective freeze-all - may yet turn out to be effective in improving LBRs.
Hopes are that the evidence for an even longer list of add-ons will be addressed in a forthcoming guideline now in development with ESHRE. With four diagnostic procedures, 11 laboratory interventions, three ‘selective’ treatments, and 15 initiatives of clinical management, the ESHRE guidance ‘will be a huge task and will take some time’, said Pinborg. Among the laboratory interventions evaluated will be in vitro activation of dormant follicles, tests for sperm DNA damage, phosphodiesterase inhibitors for sperm motility, enriched media, IMSI and PICSI, and, as ever, PGT-A.
Clinical initiatives will include platelet-rich plasma, dual stimulation with freeze-all, intrauterine culture, immunological treatments, antioxidants, uterine receptivity arrays, and, again as ever, endometrial scratching.
Pinborg stressed that the evidence must come first, but she was also sensitive to the balance necessary between innovation and routine treatment. And to this end she reiterated the principles of the HFEA/ESHRE statement – that patients must be made aware of the evidence base for any add-on offered, and that its use may be of ‘an experimental nature’. However, she reiterated several well worn caveats: that an emphasis on only evidence-based treatments should not limit research or inhibit new initiatives, especially when randomised trials in reproductive medicine are becoming increasingly expensive to run and are often past their sell-by date before the results are published.
As expected, there was broad consensus on Pinborg’s (and ESHRE’s) position on add-ons, but there seems little agreement on the question of anonymity in gamete donation, even in the neighbouring jurisdictions of Europe. Heidi Mertes, co-ordinator of ESHRE’s SIG Ethics & Law, detailed three systems in Europe: anonymous donation only, as in Spain, Italy, Poland, Greece; a mixed system, as in Germany, Sweden, Belgium, Denmark; and no anonymous donation whatsoever, as in UK, Netherlands, Portugal, France. However, although there seems a regulatory trend towards accepting identity disclosure, Mertes dubbed her talk the ‘enduring appeal of anonymity’ and offered strong ethical claims and counter-claims for both positions.
The arguments for abandoning donor anonymity are largely based on the offspring’s rights to know one’s genetic origins, a right enshrined in two articles of the UN’s Convention on the Rights of the Child. In addition, added Mertes, allowing identity disclosure will help protect the principle of harm avoidance, both psychological and physical (in allowing disclosure of any history of genetic illness, for example), and underline basic values of honesty and openness. And of course, overshadowing all such arguments lies the real-life near-impossibility of protecting donor anonymity from the DNA databanks of genealogy revelation services.
Mertes reiterated the arguments in favour of donor anonymity, notably the donor’s own privacy rights and a doubt over the ‘basic rights’ of the offspring to know (a right or mere curiosity?). Moreover, there seem many possible ways in which an individual or family might still be ‘harmed’ by identity disclosure.
These are arguments, she said, which will not be resolved any day soon, but may be helped towards a resolution by setting up registers for donors and donor-conceived people where those who wish to find each other may do so more easily, where information about hereditary health risks is more accessible, and where the one agreed principle in gamete donation is preserved, that donors are not parents.
1. See https://www.eshre.eu/Europe/Position-statements/Treatment-addons
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