Implantation: Clinical evidence for a detrimental effect on uterine receptivity of high serum oestradiol concentrations in high and normal responder patients

Abstract

This study was undertaken to investigate an empirical observation that 'high responder patients have poorer in-vitro fertilization (IVF) outcome than normal responder patients'. The aim of our study was to analyse the effect of high serum oestradiol and progesterone concentrations at the day of human chorionic gonadotrophin (HCG) administration on endometrial receptivity and oocyte-embryo quality in high and normal responder patients. The IVF patients were divided into two groups: 59 high responder patients who voluntarily donated some of their oocytes, and a control group consisting of 105 normal responder patients. Both groups were compared in terms of the number and quality of oocytes retrieved, embryos transferred, fertilization, implantation and gestation rates, serum oestradiol and progesterone concentrations and the oestradiol:progesterone ratio on the day of HCG injection. To ascertain oocyte-embryo quality, a second control group of 96 women undergoing oocyte donation (receiving oocytes from high responder patients) was considered. To assess the impact of steroid concentrations on endometrial receptivity, high responder patients were divided into two subgroups according to oestradiol concentration, above or below the minimal oestradiol and progesterone concentrations (mean--SD) in this group. The normal responder patients were divided into two subgroups according to oestradiol concentration, above or below the maximal oestradiol and progesterone concentrations (mean+SD) in this group. To assess further the relevance of oestradiol concentration on endometrial receptivity, patients were divided into different subgroups according to increasing oestradiol concentration, regardless of whether they were high or normal responders. High responder patients had significantly decreased implantation and pregnancy rates per cycle compared with normal responder patients (33.3 versus 16.3 and 11.1 versus 5.4% respectively; P < 0.05). The results of 108 embryo transfers in 91 recipients who received oocytes from the high responder group showed normal embryo quality. Implantation rates and pregnancies per cycle were significantly lower in high responder patients with serum oestradiol concentrations > 1700 pg/ml compared with those having oestradiol concentrations < or = 1700 pg/ml, as well as in normal responder patients with serum oestradiol concentrations > 2200 pg/ml compared with those having oestradiol concentrations < or = 2200 pg/ml. Considering all the patients together, significant decreases in pregnancy and implantation rates were observed when oestradiol concentrations were > 2500 pg/ml compared with patients having lower oestradiol concentrations. Our clinical results demonstrate that high serum oestradiol concentrations on the day of HCG injection in high and normal responder patients, regardless of the number of oocytes retrieved and the serum progesterone concentration, are detrimental to uterine receptivity without affecting embryo quality.