Significantly Lower Pregnancy Rates in the Presence of Progesterone Elevation in Patients Treated with GnRH Antagonists and Gonadotrophins: A Systematic Review and Meta-Analysis

The current meta-analysis aimed to answer the following research question: is progesterone elevation on the day of hCG administration associated with the probability of clinical pregnancy in women undergoing ovarian stimulation for IVF using GnRH antagonists? A literature search in MEDLINE, EMBASE and CENTRAL electronic databases followed by extensive hand-searching from two independent reviewers was performed to identify relevant studies. Eventually five eligible studies (n=585 patients) were identified. No significant differences were present between patients with and those without progesterone elevation regarding female age, duration of stimulation and total dose of gonadotrophins required. However, patients with progesterone elevation were characterized by higher serum estradiol levels on the day of hCG administration (+956 pg/ml, 95% +248 to +1664, random effects model, p=0.008) and more COCs retrieved (+2.9, 95% CI +1.5 to +4.4, fixed effects model, p<0.001). Progesterone elevation on the day of hCG administration was associated with a significantly decreased probability of clinical pregnancy per cycle (-9%, 95% CI -17 to -2, fixed model effects, p&equals0.02). In conclusion, in patients treated with GnRH antagonists and gonadotrophins, progesterone elevation on the day of hCG administration is significantly associated with a lower probability of clinical pregnancy.