Modified Flare/GnRH antagonist protocol versus GnRH antagonist protocol in oocyte cryopreservation cycles

Abstract Study question Is there an advantage for modified flare/ GnRH antagonist protocol in comparison to antagonist protocol in oocyte cryopreservation cycles? Summary answer Modified flare/ GnRH antagonist protocol is at least as good as antagonist protocol in oocyte cryopreservation cycles, potentially improving maturity rate in subgroup of patients. What is known already Ultrashort flare GnRH agonist (GnRHa)/GnRH -antagonist protocol offer benefits of stimulatory effect of repeated microdose flare on endogenous FSH and the advantages of GnRH antagonist suppression, including the option to use GnRHa ovulation trigger to avoid ovarian hyperstimulation syndrome. GnRHa ovulation trigger has been associated with suboptimal response that refers to lesser than expected oocyte yield. Our research group previously demonstrated the value of GnRHa follicular challenge test (FACT) in prediction of suboptimal response assessed by post ovulation trigger LH levels and as a dynamic ovarian reserve test (not published yet). Study design, size, duration A retrospective, age- matched, cohort study that included all non-medical oocyte cryopreservation cycles from October 2020 to December 2021. The study group included 110 women that received modified flare/ GnRH antagonist protocol and were matched with 110 women that received antagonist protocol. Participants/materials, setting, methods Women in the modified flare/ GnRH antagonist protocol were administered GnRHa (Decapeptyl 0.2 mg) on day 2 to menstrual cycle followed by flexible antagonist protocol. They were compared to age matched women that received flexible antagonist protocol. In both study groups GnRHa final ovulation trigger was administered. Main results and the role of chance Among 110 women that underwent non-medical fertility preservation with modified Flare/GnRH antagonist protocol, in comparison to 110 women that received antagonist protocol, a reduced dosage of gonadotropins was consumed with more oocytes retrieved (14.63 vs. 13.86) and more mature oocytes cryopreserved (11.32 vs. 10.14), but differences were not significantly different. In a subgroup with more than 6 oocytes retrieved significantly more mature oocytes were cryopreserved in women that received modified flare/antagonist protocol (14.03± 0.90 vs. 11.63± 0.71, p = 0.03) in comparison to women that received antagonist protocol. Limitations, reasons for caution Limitations of our study are its retrospective nature and lack of information on the oocyte’s fertilization competence and pregnancy outcomes. Wider implications of the findings Future studies will further explore the advantages of this protocol in terms of higher oocytes maturity rate, intra cycle prediction of ovarian response and suboptimal response to GnRHa triggering. Trial registration number not applicable