More Encouraging Research On “Freeze-All”!
More Encouraging Research On “Freeze-All”!
There have long been concerns that high hormone levels generated through controlled ovarian hyperstimulation used for IVF may adversely affect the receptivity of the endometrium. However, it is only in the past two years that studies have focused on implantation and ongoing pregnancy rates when all embryos are frozen, then transferred to the uterus in a future natural or minimally controlled cycle. This approach avoids transferring any embryos when hormone levels may be high from stimulation and endometrial receptivity low.
STUDY DESCRIPTION
A paper published in the May 2015 issue of Fertility and Sterility from “Origin, Center for Reproductive Medicine” in Rio de Janeiro, compares the ongoing pregnancy rates in patients undergoing “freeze-all”, with those who had fresh embryo transfers. The study was unique in that in order to be in the study patients undergoing fresh embryo transfer had to have progesterone levels of <1.5 on the day of trigger shot administration. This is significant because most clinics recognize that progesterone elevation at the time of trigger shot (human menopausal gonadotropins) is detrimental to implantation success, and withhold fresh embryo transfer when this condition exists. These patients would be considered as “freeze all” candidates in most clinics. Since this study excluded those patients with progesterone elevation at the time of trigger administration, the control group (those having fresh embryo transfer) would have had no identifiable reason for implantation failure, and would be quite comparable to the “freeze-all” group.
In this study 179 patients had all of their embryos frozen (freeze-all group) and 351 patients were in the fresh embryo transfer group.
RESULTS
Freeze All Group Fresh Embryo Transfer Group
Implantation Rate 26.5% 19.5%
Clinical Pregnancy Rate 46.4% 35.9%
Ongoing Pregnancy Rate 39.7% 31.1%
The results of this study clearly suggest that the freeze-all group had significantly better IVF results compared to the “fresh embryo transfer” group. Since implantation failure currently represents the greatest obstacle to IVF success, it would be advantageous to improve the implantation environment by any means possible. At present the main measurable indicators of endometrial receptivity are progesterone (with rising progesterone prior to egg retrieval suggesting poor endometrial receptivity) and endometrial thickness (less than 7mm suggesting poorer outcomes). Freezing all embryos allows us to abandon the highly stimulated endometrium in the fresh cycle in favor of the more normally developed lining that can be achieved in either the natural cycle or a minimally stimulated cycle. We have observed more striking improvements in ongoing pregnancy rates in our practice using a freeze-all policy. One reason for this difference may be that patients in our study with progesterone elevation prior to hCG were included in the freeze all group. Since these patients are known to have reduced endometrial receptivity, and they were excluded in the Rio de Janeiro study reviewed here, the improved ongoing pregnancy rate we have observed in the freeze-all group would be expected. Additionally, we have a blastocyst program, while the Rio de Janeiro group transferred day 3 (cleavage stage) embryos. By culturing to blastocyst, we presumably have done more to select the best embryo(s) for transfer.
This study was prospective, but not randomized. Additional randomized controlled studies are needed to confirm these findings. The application of any successful freeze-all program will likely be dependent on having excellent freeze/thaw embryo survival as well as successful blastocyst culturing capabilities.
