A drop-in serum progesterone from day-3 to day-5 of fresh blastocyst transfer, using HCG-trigger and standard luteal support is associated with lower ongoing pregnancy rates

In fresh embryo transfer cycles, significant inter-personal variation occurs in serum progesterone (P4) levels during the luteal phase. There is paucity of data exploring the possible impact of luteal phase serum P4 levels on reproductive outcomes. We aimed to investigate the effect of early/mid-luteal serum P4 levels on ongoing pregnancy rate (OPR) in fresh blastocyst transfer cycles employing rhCG trigger and standard luteal phase support (LPS). Using a prospective cohort study design, 126 patients were included in the analysis. A GnRH agonist (n=31) or GnRH antagonist (n=95) protocol was used for ovarian stimulation and rhCG was employed for trigger. 90 mg of vaginal progesterone gel once daily was used for LPS. Serum P4 levels were measured on five occasions; on the day of ovulation trigger, OPU, OPU+3, OPU+5 and OPU+14 day. The primary outcome was ongoing pregnancy (OP), as defined by pregnancy ≥12 weeks of gestational age. While mean P4 levels on the day of trigger, OPU, and OPU+3 were comparable among patients with (n=57) or without (n=69) OP, a significantly higher P4 levels on OPU+5 day (104.4±35.1 vs 84.8±34.8 ng/ml, p<0.001) was seen in patients with OP. A drop in P4 level from OPU+3 to OPU+5 day (negative-ΔP4) was seen in ≈1/3 of patients, and was associated with a significantly lower OPR when compared with positive-ΔP4 counterparts (31.1% vs 53.1%, p=0.03). For negative-ΔP4 patients, the magnitude of negative-ΔP4 was a significant predictor of OP. Body mass index and FSH consumption for OS were significant predictors of negative-ΔP4. When logistic regression analysis was performed, only ΔP4 was noted to be an independent predictor of OP. Two measurements of serum P4 levels may delineate those patients with a drop in P4 levels and associated with 2.5-fold lower OPRs. Rescuing these IVF cycles with additional P4 supplementation or adopting a blastocyst freeze-all policy should be tested in future randomized controlled trials. Keywords: IVF, hCG trigger, luteal phase, progesterone, ongoing pregnancy