Freezing all embryos in IVF with transfer in a later non-stimulated cycle may improve outcome
There is growing interest in a "freeze-all" embryo policy in IVF. Such an approach, which cryopreserves all embryos generated in a stimulated IVF cycle for later transfer in a non-stimulated natural cycle, would avoid any of the adverse effects which ovarian stimulation might have on endometrial receptivity during the treatment cycle. Ovarian stimulation has been shown to have adverse effects on endometrial receptivity and the risk of ovarian hyperstimulation syndrome (OHSS) is also increased when embryo transfer is performed in the stimulated cycle.
Freezing all embryos for later transfer might therefore improve implantation and pregnancy rates and increase the safety of IVF. Presently, the highest success rates in reproductive medicine are seen in the recipients of donor eggs. These are women who have not had ovarian stimulation - their endometrial tissue has not been exposed to high hormone levels, and they are not at risk of OHSS.
However, while the theory of a freeze-all policy seems attractive - and the technique has been commonly employed as a safety measure when OHSS is a threat - no robust systematic studies have indicated whether the cryopreservation of all viable embryos with later frozen embryo transfer (FET) is associated with better outcomes than fresh embryo transfers.
Now, the first meta-analysis on this subject indicates that the chance of a clinical pregnancy is around 30% higher when all embryos are frozen for later transfer than with fresh embryo transfer. The results were presented today at the annual meeting of ESHRE (European Society of Human Reproduction and Embryology) by Professor Miguel Angel Checa from the Hospital Universitari del Mar in Barcelona, Spain.
The study was a systematic review of the entire literature, which provided a pool of 64 relevant studies - with three randomised trials - performed before December 2011. The current review was based on information from 633 IVF/ICSI cycles in which 316 were randomised to fresh embryo transfer and 317 to FET. Results showed - based on a relative risk calculation - that the probability of a clinical pregnancy is significantly higher from freeze-all cycles than in fresh embryo transfers (a relative risk of 1.31, which was statistically significant). The miscarriage rates did not show significantly differences between the two groups.
"The pooled data demonstrates that embryo cryopreservation and subsequent FET may improve the outcome of assisted reproduction treatment," said Professor Checa. The study recorded an ongoing pregnancy rate of 38% in fresh transfer cycles, and 50% in the FET cycles.
Professor Checa also explained why FET in a later non-stimulated cycle might improve IVF results. He noted that the multiple eggs generated by ovarian stimulation will increase release of the hormone estradiol from the ovary, which affects the receptivity of endometrial tissue. In addition, some recent studies have shown that ovarian stimulation causes changes to the endometrial DNA pattern, which are not evident in the normal receptive endometrium.
Professor Checa added that the results of his study were "preliminary", but statistically robust. However, with other groups known to be performing similar studies, he urged patience until their results were known. "We are quite confident with our results," he said. "But in our view we should wait until the end of the year for results from other studies to confirm our data and recommend a change in IVF policy."
He added that, with improvements in the technologies of embryo cryopreservation (through vitrification), the evolution of freeze-thawed embryos in IVF is now comparable to that of fresh embryos. A freeze-all approach may thus extend that success even further - and with a greater degree of safety. "When we freeze all of the embryos, we completely avoid the risk of OHSS," said Professor Checa. "So freezing all the embryos we collect would avoid the biggest complication that exists in assisted reproduction."
Fresh embryo transfer versus frozen-thawed embryo transfer in assisted reproduction technique cycles: a systematic review and meta-analysis