Freeze–All Strategy In High-Responding Patients
In recent years there has been increased use of the GnRH agonist as the final trigger to complete oocyte (egg) maturation in IVF treatment cycles. The GnRH trigger shot practically eliminates the development of ovarian hyperstimulation syndrome (OHSS), a potentially life threatening complication of stimulation of the ovaries for IVF. While the use of the GnRH trigger has proven quite effective in preventing OHSS, it has not been without drawbacks. The traditional method for completing the maturation of oocytes has been through the administration of human chorionic gonadotropin (hCG). In addition to completing the maturation of eggs, hCG also has a favorable effect on the developing uterine lining. When the GnRH agonist trigger shot is used to complete oocyte maturation, the beneficial effect on the uterine lining is lost, and the uterine lining breaks down very early unless aggressive hormonal supplementation is given. Currently, when a GnRH agonist trigger is used, the uterine lining is vigorously supported through the use of supplemental progesterone and estrogen.
Some have suggested that freezing all of the embryos is the best strategy in situations where a GnRH agonist trigger has been used to complete egg maturation, rather than risk poor endometrial preparation.
A recent study (2017) published in Reproductive BioMedicine Online, (Vlaisavljevic, V), looked at a group of high responder patients who were at risk for the development of ovarian hyperstimulation syndrome and therefore received GnRH agonist triggers. Patients in the study had all of their embryos frozen at the blastocyst stage, and then underwent frozen embryo transfers until they became pregnant or had transferred all of their embryos. The investigators evaluated the cumulative live birth rate for each patient completing the study.
Since some of the patients with frozen embryos did not return for frozen embryo transfers, in one calculation the authors assumed that had they returned for embryo transfers, they would have had the same chance of achieving a live birth as those who did complete the study. Applying this assumption, the cumulative live birth rate for patients in this study was 76.6%. The calculations assumed that the patients had six frozen embryo transfers. If only the patients who completed their participation in the study are included, the cumulative live birth rate over a maximum of 6 cycles of frozen embryo transfers was 65.9%. The highest live birth rates were achieved in the first two frozen transfer cycles, (42.2% and 34.5% respectively).
None of the patients in this study developed ovarian hyperstimulation syndrome. Approximately 60% of the women in the study achieved a live birth within the first three frozen embryo transfers.
This paper adds further support for the concept of using the GnRH agonist as the preferred trigger shot in women at risk for ovarian hyperstimulation syndrome. Acceptable cumulative live birth rates were achieved in this study using the GnRH agonist in patients who were known to be “high responders”, and who were therefore at risk for ovarian hyperstimulation syndrome. No cases of severe OHSS occurred in this study.
The study also supports the concept of “freeze all” in high responder patients who receive a GnRH agonist. Using a “freeze all” approach resulted in respectable cumulative live birth rates among a group of patients expected to at risk for reduced success rates due to hormonal effects on endometrial development and/or possible adverse effects of high responder status on egg quality.
This paper does not address the question of whether a “freeze-all” approach would have similar success rates across a group of patients who were not high responders.
Although this paper did not include patients who used preimplantation genetic screening (PGS), it is likely that this technique would have shortened the number of months needed to achieve pregnancy for some patients, but would not have changed the cumulative pregnancy rate in patients who completed the study.