Recurrent implantation failure and elective oocyte freezing: hot topics open 2021 meeting

Filippo Ubaldi presented persuasive evidence in favour of dual stimulation for predicted poor responders in IVF

Published 16 April 2021

Almost 2000 members of ESHRE and ASRM (as well as many non-members) were registered for this seventh joint meeting of the two societies - indeed more attending virtually than had ever attended live.

Despite the change of access, the menu of presentations for this Best of ASRM & ESHRE meeting was designed as ever, with a mix of debates, back-to-back reviews and cutting-edge lectures to explore emerging themes which are still without hard conclusions. Among those explored on the first day were recurrent implantation failure and whether treatment was indicated, and elective oocyte cryopreservation.

RIF: to treat or wait?
This was billed as a debate and it was revealing that 94% of the online audience before any presentations voted in favour of treatment – thus a strong opinion that RIF was attributed to pathology and thus treatable. However, by the close of arguments and answers to a stream of audience questions, that voting divide had shifted measurably - to only 65% in favour of treatment, and an indication of how open the RIF question remains.

For Zev Williams, from Columbia University Fertility Center in New York, truly idiopathic RIF was a rare condition, as illustrated in a recent large retrospective study which found that only 5% of IVF patients with euploid embryos were unable to achieve pregnancy after three consecutive SETs.(1) The results, said the authors of the study, raised the question of whether there is a truly ‘recalcitrant’ group of IVF patients unable to sustain implantation, or if there is indeed some enigmatic endometrial factor requiring specific evaluation and treatment. Those explaining factors, said Williams, could be uterine, endocrine, embryonic or sperm-related.

Taking a more pragmatic view but without addressing any ‘debate’, Bettina Toth, who is presently co-ordinator of ESHRE’s SIG Implantation and Early Pregnancy, reported a high recognition that RIF does indeed exist, but with varied definitions according to a recent survey published from the SIG.(2) Nevertheless, the survey (with more than 1000 clinicians and embryologists responding) found that some two-thirds took lifestyle factors into account, mainly drugs, smoking and BMI. The highest consensus on diagnostic investigations was for anatomical malformations, endometrial thickness and endometriosis.

However, Williams found little strong evidence in favour of correcting uterine disorders ahead of IVF (other than submucous fibroids), with similarly little evidence in favour of PGT-A, immunological treatments, endometrial receptivity assays, or sperm DNA fragmentation tests. His conclusion, like that of Toth, was a call for international guidelines on the definition, diagnosis and treatment of RIF, not least to avoid the risk of ‘useless and sometimes risky and/or costly adds-ons’. The session thus ended less as a debate on a motion but more as a concerted call for consensus and better designed studies to provide the evidence.

Elective oocyte cryopreservation
Although not billed as a ‘debate’, a back-to-back session on elective egg freezing did provide opposing views, no doubt a hazy reflection of self/insurance-funded treatment in the USA and the more state-organised structures in Europe. The question before the speakers was whether elective egg freezing was ‘emancipatory’ or ‘exploitative’, but again, no hard conclusions were drawn.

Belgian bioethicist Guido Pennings thought neither, but a consequence of a gender gap which is itself a consequence of women’s emancipation. But elective egg freezing, insisted Pennings, will not lead to further emancipation but will only reflect it. However, he did predict that the ‘male deficit’ will increase in the future and many well educated women will find themselves without a suitable partner. ‘They will have to choose,’ said Pennings. ‘Single motherhood or another life plan.’

His co-speaker in this back-to-back session, New York gynecologist Nicole Noyes, was the cheerleader of elective egg freezing, listing its emancipatory features (enhanced reproductive autonomy, buying time ‘to move up the work ladder’ and make family plans, and allowing later age pregnancy) and warning against its exploitative potential (always keep respect for autonomy, beware commoditisation). However, Noyes did conclude by saying that oocyte cryopreservation is ‘here to stay’, and there can be no doubt of that, especially in fertility sectors driven by private commercial clinics. Registry data from the USA or UK show rapidly escalating levels of uptake, and a confidence among clinics to vitrify oocytes for banking without fear of spindle damage or loss of viability. Results analysis so far, said Noyes, suggest that women aged 25-34 will need eight MII oocytes for one euploid embryo, and 14 MIIs to achieve one live birth, with MII requirements increasing with age beyond 35 years.

1. Pirtea P, De Ziegler D, Tai X, et al. Rate of true recurrent implantation failure is low: results of three successive frozen euploid single embryo transfers, Fertil Steril 2021; 115: 45–53.
2. Cimadomo D, Craciunus L, Vermeulen N, et al. Definition, diagnostic and therapeutic options in recurrent implantation failure: an international survey of clinicians and embryologists. Hum Reprod 2021; 36: 305-317.

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