Endometrial preparation for the transfer of frozen/thawed embryos

Published 05 July 2022

Studies suggest a greater risk of pre-eclampsia and other hypertensive disorders of pregnancy in artificial cycles prepared with hormone therapy. Is that risk related to an absence of corpus luteum?

We’re in the midst of a freezing mania, said Nikolaos Polyzos from Dexeus University Hospital in Barcelona. ‘Vitrification changed the way we’re thinking,’ he told an invited session here in Milan. His theme was endometrial preparation for FET, which since the freeze-all trials of a few years ago – and the emergence of a possible pre-eclampsia risk in cycles artificially prepared with hormone replacement therapy - has become a hot topic. So how should we transfer our frozen embryos, he asked.

There are three types of endometrial preparation, he explained, each with their own pros and cons. Thus, while transfer in a natural cycle avoids medication and maintains the presence of a corpus luteum, the downside implies difficulty in planning and defining the LH surge, as well as multiple visits for the patient.

Transfer in a modified natural cycle will address some of those negatives (better treatment planning, fewer patient visits) but no corpus luteum to support the pregnancy. And in the fully artificial cycle there is complete control over treatment times, few clinic visits for the patient – and an endometrium suitably prepared for implantation, but still no corpus luteum.

So why should the corpus luteum – or its absence – be so important? Polyzos described it as ‘a transient ovarian gland’ which maintains pregnancy, releasing progesterone, estradiol and vasoactive compounds such as the vasodilator relaxin. And it’s the effect of relaxin, or its absence, which may explain the adverse obstetric events seen in FET pregnancies – mainly hypertensive disorders – associated with the type of endometrial preparation.

The latest reports suggest that an artificial transfer cycle roughly doubles the risk of such disorders found in a natural cycle transfer (or in a spontaneous pregnancy), but, asked Polyzos, how does that relative risk translate to a ‘real risk’. His own calculations, based on data from a 2021 study, suggest that an artificial transfer cycle would increase the risk of pre-eclampsia by around four cases in every hundred pregnancies. Is that a clinically relevant risk, he asked? Or should be avoid any risk and go back to FET transfers in the natural cycle?

Poluyzos had no strong answers. All three approaches – natural and modified natural cycle and artificial – are all ‘valid options’ to prepare the transfer of frozen-thawed embryos, each with several advantages and disadvantages. But he did emphasise that the corpus luteum appears to ‘play a special role’ not only in maintaining early pregnancy but also in maintaining vascular health. The question remains if the risk of pre-eclampsia is clinically relevant, and, as ever, only further data will resolve those questions.

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