Perspectives on results from cryopreservation/thawing cycles

Le résumé fourni par la source

Sir, We read with interest the paper by Groenewoud et al. (2016), recently published in Human Reproduction. The authors performed an ambitious multi-centre trial aimed at evaluating whether the artificial cycle is inferior, or equal to, the modified natural cycle for cryopreserved-thawed embryo transfer. The trial is a huge undertaking and is performed according to high academic standards. However, we were surprised to see that the authors report very low success rates from cryopreservation/thawing cycles. According to the most recent European Infertility Monitoring (EIM) report (Kupka et al., 2016), deliveries per thawing cycle on a national level are reported to lie between 10.0 and 25.4%. Thus, the results reported in the paper are below the lowest national levels reported in the EIM. Additionally, the artificial cycle, which according to the paper is not inferior to the modified natural cycle, showed live birth rates at 8.8% per cycle. In any single clinic, this would lead to immediate analysis of results and procedures; immediate cessation of activities would be recommended until the reason for the low delivery rate had been identified. When results in a clinical programme are sub-optimal, immediate action must be considered. In a large multi-centre study, the situation may perhaps be considered to be more complex. Feedback on clinical results is slow and any corrective action may be difficult to achieve. At the time of publication however, any such problems should be addressed. Additionally, we infer from the data that the rate of miscarriage (not explicitly reported in the paper) seems alarmingly high. The overall rate of pregnancy loss in the study is 38.5% according to the paper as 66 of the clinical pregnancies did not lead to a live birth. This is, in our opinion, another indication of a severe problem in the cryopreservation/thawing programme. Optimal cryopreservation methods give low rates of miscarriage and much higher pregnancy rates can be expected in a successful cryopreservation/thawing programme (Edgar and Gook, 2012; Ahlström et al., 2013). Here also, a comment is motivated. The methods reported in the paper also give rise to some questions that need clarification: The modified Natural Cycle includes an hCG trigger. Was the actual time of ovulation monitored by LH test in urine? Did the hCG trigger affect the time of transfer relative to “true” natural cycle replacements? The authors did not elect to give luteal phase support in the natural cycle even though they refer to a publication showing this to be beneficial (Bjuresten et al., 2011). How many days of progesterone support preceded transfer in the artificial thawing cycles? Maintaining good results in cryopreservation/thawing cycles is not easy to achieve. It requires team work and optimal methods and procedures. Conclusions drawn from data where the applied methods are not optimal must, of course, be interpreted with caution. The present study is performed according to the high academic standards, however, it seems that the data need further discussion and analysis.

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