The early luteal hormonal profile in IVF patients triggered with hCG.

Abstract

What is the early luteal phase hormonal profile in patients undergoing ovarian stimulation for IVF/ICSI followed by hCG trigger and a freeze-all strategy without luteal phase support? The peak concentration of progesterone occurred 4days after oocyte pick-up (OPU + 4), with an average 35% fall from OPU + 4 to OPU + 6, and progesterone levels before and 12h after hCG administration predicted levels during the early luteal phase. The luteal phase during IVF differs from that during normal cycles, particularly with respect to the serum progesterone level profile. This can cause asynchrony between the embryo and the endometrium, potentially resulting in implantation failure and poor reproductive outcomes. This prospective study included 161 women with normal ovarian reserve receiving GnRH antagonist co-treatment during ovarian stimulation with FSH who were followed up to 6days after OPU in a single IVF cycle. Women aged 18-42years undergoing IVF with ovarian stimulation using FSH were included. Ovulation was triggered with recombinant hCG 250μg. Hormone levels were determined from blood samples taken on the day of trigger, before hCG, at 12, 24 and 36h after hCG and at 1, 2, 3, 4, 5 and 6days after OPU. The primary endpoint was early luteal phase serum concentrations of progesterone, LH, estradiol and hCG. One outlier with a pre-hCG serum progesterone level of 11.42ng/mL was excluded, so all analyses included 160 subjects. Progesterone levels began to increase 1day after OPU, peaked 4days after OPU (114ng/mL), then declined from OPU + 5 onwards. Peak progesterone levels were at OPU + 4, OPU + 5 or OPU + 6 in 38.8, 29.4 and 13.8% of patients, respectively. Approximately two-thirds of patients had a fall in serum progesterone from OPU + 4 to OPU + 6. Pre-hCG progesterone levels correlated significantly with those at 24h after hCG (r2= 0.28; P< 0.001), which in turn correlated significantly with progesterone at OPU + 4 (r2= 0.32; P< 0.001). LH peaked (4.4IU/L) 12h after hCG trigger, persisting for 24h but was barely elevated compared with physiological levels. Serum estradiol peaked twice: at 24h post-trigger and at OPU + 4. Highest hCG levels (130mIU/mL) occurred at 24h post-injection. The best correlations between the number of follicles ≥11mm and serum progesterone level were seen at 24 and 36h after hCG and OPU + 1. The influence of different profiles of serum progesterone on reproductive outcomes could not be determined because a freeze-all strategy was used in all patients. In addition, data were not available to relate serum hormone level findings with endometrial histology or endometrial receptivity analysis to clearly identify the relationship between serum hormones and the window of implantation. Detailed information about early luteal phase hormone levels could be used to optimize and individualize luteal phase support to improve reproductive outcomes. This study was funded by My Duc Hospital, Ho Chi Minh City, Vietnam. All authors state that they have no conflicts of interest to disclose. NCT02798146; NCT03174691.