The Impact Of High Serum Progesterone Concentration Prior To Oocyte Retrieval On The Expression Of Adhesion Molecular Of Endometrium In Peri-implantation Period In Women Undergoing IVF Treatment

BackgroundOur previous study(including consecutive 5828 ovarian stimulation cycles for IVFF/ICSI treatment carried out in the Reproductive Center, Sir Run Run Shaw Hospital, Medical School of Zhe Jiang University between January 2011 and May 2013) confirmed that not only elevated progesterone on the day of hCG administration, but also elevated progesterone on the day after hCG adminstration could adversely affect the pregnancy outcomes. It was interesting to note that elevated progesterone prior to oocyte retrieval significantly increased the number of non-pregnant cycles, but not the number of miscarriage cycles. It was therefore reasonable to suppose that the adverse impact of high progesterone on the endometrium occurred at a rather early stage. Therefore we consider high progesterone concentration on the day or/and after hCG administration may impair the receptivity of endometrium through the expression of adhesion molecules. Different type cells of endometrium may react to progesterone differently, research of the impact of high serum progesterone concentration prior to oocyte retrieval on the expression of adhesion makers of the endometrial lumenal epithelial compartment peri-implantation period may fill the blank of this field.AimHigh progesterone level prior to oocyte retrieval has been reported to adversely affect endometrial receptivity, resulting in reduced implantation rate. The exact molecular mechanism by which high progesterone level prior to oocyte retrieval affect endometrial development is still unclear. We were particularly interested in the impact of high progesterone on the adhesion molecules expression on luminal epithelium of the endometrium in the peri-implantation period (seven days after hCG administration) in women undergoing IVF treatment.MethodsThe overall 40 endometrial specimens examined in this study were archived from a previous single-center, prospective cohort study carried out in our unit—between June 2013 and December 2014.All subjects included in the study were advised not to proceed with fresh embryo transfer in the treatment cycle but to have embryos frozen for replacement in a subsequent cycle, according to our establish clinical protocol to avoid ovarian hyperstimulation syndrome, either because there were more than 15 oocytes retrieved or because the progesterone level on the day of hCG administration was elevated to(?) 1.5 ng/ml. Overall 40 women included in our study did not proceed to have fresh embryo transfer. In all the study cycles, luteal support continued until the day of endometrium biopsy, and consisted of intramuscular progesterone in oil at 40 mg/day for 1 day, starting from the night of oocyte retrieval and then at 60 mg/day for 2 days and then at 80 mg/day for 3 days.A total of 40 endometrial samples were collected using a Pipelle sampler (Prodimed, France) seven days after hCG administration (hCG+7) from the uterine fundus. Expression of OPN, MUC16,and integrins aVb3 was determined by immunohistochemistry.All the specimens were assessed by two independent observes, experienced in the use of dating criteria of h-score to evaluate expression of adhesion molecules. The observers were blinded to the clinical details of the specimens.All subjects had 2 consecutive blood tests for estrogen and progesterone.According to a consecutive series of 5828 samples routinely collected from patients undergoing ovarian stimulation treatments for IVF from 2011-2013 in our hospital, the 90% percentile was used as the cut-off to define high progesterone level, which was 1.7 ng/ml on the day of hCG administration and 9.5 ng/ml on the day after hCG administration.The results of h-score were further compared between groups of subjects with normal or high progesterone.Results1. The expression of OPN of the luminal epithelial endometrium was slightly higher in women with high progesterone, however, no statistic differences (3.44 ± 0.58 & 3.42 ± 0.6, P>0.05)2. The expression of ανβ3 was slightly higher in women with high progesterone on both days, however, no statistic differences (2.73 ± 1.35 & 2.47 ± 1.33, P>0.05)3.The expression of MUC16 was significantly higher in women with high progesterone compared to those subjects with normal progesterone (3.54 ± 0.77 days & 2.51 ± 1.19, P<0.001)ConclusionElevated progesterone prior to oocyte retrieval could possible enhance the anti-adhesion function of luminal epithelial endometrium by increasing the expression of MUC16.