GnRH Antagonist Use in IVF and ICSI Cycles Decreases Implantation and Clinical Pregnancy Rates Without Affecting Embryo Quality and Blastulation

Abstract

We aimed to compare the outcome of ovarian stimulation protocols using GnRH antagonist to those incorporating GnRH agonist in IVF or ICSI, non-donor fresh blastocyst transfer cycles. Retrospective comparison of GnRH antagonist IVF or ICSI cycles to GnRH agonist cycles from a university-affiliated private ART program. Cycles were included only if they resulted in blastocyst transfer. A total of 750 IVF and 1288 ICSI, fresh non-donor blastocyst transfer cycles were included. Patients on GnRH agonists received daily leuprolide acetate injections using either long luteal phase or flare protocols. Patients on GnRH antagonist received cetrorelix acetate 3 mg administered 4 days before the start of FSH stimulation for synchronization of the antral follicle cohort and a repeat dose was given when a lead follicular diameter of 13-14 mm was reached. Embryo Progression Index (EPI) was calculated from the area under the curve of numerical conversion of the available embryo progression data by trapezoidal integration. Gardner/Schoolcraft blastocyst grades were converted into numerical Blastocyst Quality Scores (BQS). Mean EPI for day 3 and day 5/6 for all blastocysts and mean BQS of developed and transferred embryos were used as separate variables to serve as measures of embryo progression and blastulation. IVF and ICSI cycles were analyzed separately. The comparisons were made by independent t- and chi-square tests where appropriate. The significant predictors of clinical pregnancy were analyzed by logistic regression. Cycle outcomes were summarized in the following table (Table 1.). Cycles with GnRH antagonists had reduced implantation and clinical pregnancy rates although the embryo progression and blastulation parameters were comparable in IVF cycles and were superior in ICSI cycles which employed GnRH antagonists. Evaluation of first treatment cycles did not change these findings. Logistic regression models further supported the negative impact of GnRH antagonist on clinical pregnancy in both IVF and ICSI cycles. Tabled 1 Non-donor IVF or ICSI cycles with fresh blastocyst transfer using GnRH antagonist result in lower implantation and clinical pregnancy rates as compared with GnRH agonist cycles, although the embryo progression and blastulation scores are comparable or superior in GnRH antagonist cycles. These findings suggest potential adverse effects of GnRH antagonist on endometrial receptivity which justifies further investigation.