Elevated serum progesterone at end of stimulation with recombinant FSH, but not with highly purified menotropin, is associated with poor outcome in GnRH antagonist cycles

Abstract

To investigate the impact on treatment outcome of elevated progesterone at end of stimulation in a GnRH antagonist cycle. Retrospective investigation of an RCT. Data from 749 patients undergoing COS in a GnRH antagonist cycle with highly purified menotropin (HP-hMG, MENOPUR, Ferring Pharmaceuticals) or rFSH (FOLLISTIM, Merck) using 150 IU for the first five days and adjusted individually thereafter [MEGASET; ClinicalTrials.gov NCT00884221]. Blood was drawn on stimulation day 1, day 6 and at end of stimulation, and analysed centrally. Ongoing pregnancy rate (OPR) (10-11 weeks after single blastocyst transfer) and clinical profiles were compared according to serum progesterone at end of stimulation using 4 nmol/L as cut-off. Progesterone > 4 nmol/L at end of stimulation was similarly frequent with HP-hMG (16%) and rFSH (14%). The OPR in the progesterone > 4 nmol/L and ≤ 4 nmol/L groups was 16% and 29% for rFSH (P<0.05) and 29% and 30% for HP-hMG, respectively. For patients with transfer, the OPR was 21% and 33% with rFSH, and 35% and 35% with HP-hMG, respectively. In both treatment groups, patients with progesterone > 4 nmol/L at end of stimulation had significantly (P<0.001) higher progesterone and testosterone on day 1, higher progesterone and LH on day 6, and higher estradiol, progesterone, estradiol/progesterone ratio, testosterone and SHBG at the end of stimulation as well as more oocytes retrieved. Those in the rFSH group also had significantly (P<0.001) lower FSH on day 1, higher inhibin B on day 6 and higher FSH on day 6 and at end of stimulation. There were no major differences in endometrial profile or blastocyst quality. Elevated progesterone at the end of stimulation in a GnRH antagonist cycle is associated with follicular steroidogenesis and higher ovarian response irrespective of type of gonadotropin used, but only with a significantly lower ongoing pregnancy rate when stimulated with rFSH and not with HP-hMG.