Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study

Abstract

Is there a relationship between serum progesterone (P) and endometrial volume on the day of embryo transfer (ET) with ongoing pregnancy rate (OPR) in artificial endometrium preparation cycles? Patients with serum P < 9.2 ng/ml on the day of ET had a significantly lower OPR but endometrial volume was not related with OPR. A window of optimal serum P levels during the embryo implantation period has been described in artificial endometrium preparation cycles. A very low endometrial volume is related to poor reproductive outcome. Prospective cohort study with 244 patients who underwent ET in an oocyte donation cycle after an artificial endometrial preparation cycle with estradiol valerate and vaginal micronized progesterone (400 mg/12 h). The study period went from 22 February 2016 to 25 October 2016 (8 months). Sample size was calculated to detect a 20% difference in OPR (35–55%) between two groups according to serum P levels in a two-sided test (80% statistical power, 95% confidence interval (CI)). Patients undergoing their first/second oocyte donation cycle, aged 2, triple layer endometrium >6.5 mm and 1–2 good quality transferred blastocysts. A private infertility centre. Serum P determination and 3D ultrasound of uterine cavity were performed on the day of ET. Endometrial volume measurements were taken using a virtual organ computer-aided analysis (VOCAL™) system. The primary endpoint was OPR beyond pregnancy week 12. About 211 of the 244 recruited patients fulfilled all the inclusion/exclusion criteria. Mean serum P on the day of embryo transfer was 12.7 ± 5.4 ng/ml (Centiles 25, 9.2; 50, 11.8; 75,15.8). OPRs according to serum P quartiles were: Q1: 32.7%; Q2: 49.1%; Q3: 58.5%; Q4: 50.9%. The OPR of Q1 was significantly lower than Q2–Q4: 32.7% versus 52.8%; P = 0.016; RR (95% CI): 0.62 (0.41–0.94). The mean endometrial volume was 3.4 ± 1.9 ml. Serum P on the day of ET did not correlate with endometrial volume. A logistic regression analysis, adjusted for all the potential confounders, showed that OPR significantly lowered between women with serum P < 9.2 ng/ml versus ≥9.2 ng/ml (OR: 0.297; 95%CI: 0.113–0.779); P = 0.013. The ROC curve showed a significant predictive value of serum P levels on the day of ET for OPR, with an AUC (95%CI) = 0.59 (0.51–0.67). Only the women with normal uterine cavity, appropriate endometrial thickness and good quality blastocysts transfer were included. Extrapolation to an unselected population or to other routes and/or doses of administering P needs to be validated. The role of endometrial volume could not be fully defined as very few patients presented a very low volume. The present study suggests a minimum threshold of serum P values on the day of ET that needs to be reached in artificial endometrial preparation cycles to optimize outcome. No upper threshold could be defined. None. NCT02696694