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Endometrial receptivity profile in patients with premature progesterone elevation on the day of HCG administration.

ABSTRACT: The impact of a premature elevation of serum progesterone level, the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure, on human endometrial receptivity is still debated. In the present study, we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles. Then, specific biomarkers of endometrial receptivity in these two groups of patients were tested. Endometrial biopsies were performed on oocyte retrieval day and on day 3 of embryo transfer, respectively, for each patient. Samples were analysed using DNA microarrays and qRT-PCR. The endometrial gene expression shift from the prereceptive to the receptive stage was altered in patients with high serum progesterone level (>1.5 ng/mL) on hCG day, suggesting accelerated endometrial maturation during the periovulation period. This was confirmed by the functional annotation of the differentially expressed genes as it showed downregulation of cell cycle-related genes. Conversely, the profile of endometrial receptivity was comparable in both groups. Premature progesterone rise alters the endometrial gene expression shift between the prereceptive and the receptive stage but does not affect endometrial receptivity.

SUBMITTER: Haouzi D

PROVIDER: S-EPMC4022194 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Endometrial receptivity profile in patients with premature progesterone elevation on the day of HCG administration.

Haouzi Delphine D Bissonnette Laurence L Gala Anna A Assou Said S Entezami Frida F Perrochia Hélène H Dechaud Hervé H Hugues Jean-Noel JN Hamamah Samir S

BioMed research international 20140428

The impact of a premature elevation of serum progesterone level, the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure, on human endometrial receptivity is still debated. In the present study, we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles. Then ...[more]

PMID: 24877150

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Project description:Study questionIs there an association of progesterone (P4) on the day of trigger with live birth in autologous ART transfer cycles on day 5 versus day 6?Summary answerP4 had a greater negative effect on live birth in day 6 fresh transfers compared to day 5 fresh transfers.What is known alreadyPremature P4 elevation is associated with lower live birth rates in fresh autologous ART cycles, likely due to worsened endometrial-embryo asynchrony. Few studies have evaluated whether the effect of an elevated P4 on the day of trigger is different on live birth rates with a day 5 compared to a day 6 embryo transfer.Study design size, durationThis was a retrospective cohort study with autologous IVF cycles with fresh embryo transfers on day 5 and day 6 from 2011 to 2014. A total of 4120 day 5 and 230 day 6 fresh autologous embryo transfers were included. The primary outcome was live birth, defined as a live born baby at 24 weeks gestation or later.Participants/materials, setting, methodsPatients from a large private ART practice were included. Analysis was performed with generalized estimating equations (GEE) modeling and receiver operating characteristic (ROC) curves.Main results and the role of chanceDay 6 transfers were less likely to have good quality embryos (73% versus 83%, P < 0.001) but the cohorts had similar rates of blastocyst stage transfer (92% versus 91%, P = 0.92). Live birth was less likely in fresh day 6 versus day 5 embryo transfers (34% versus 46%, P = 0.01) even when controlling for embryo confounders. In adjusted GEE models, the effect of P4 as a continuous variable on live birth was more pronounced on day 6 (P < 0.001). Similarly, the effect of P4 > 1.5 ng/ml on day of trigger was more pronounced on day 6 than day 5 (P < 0.001). Day 6 live birth rates were 8% lower than day 5 when P4 was in the normal range (P = 0.04), but became 17% lower when P4 was > 1.5 ng/ml (P < 0.01). ROC curves for P4 predicting live birth demonstrated a greater AUC in day 6 transfers (AUC 0.59, 95% CI 0.51-0.66) than day 5 (AUC 0.54, 95% CI 0.52-0.55). Interaction testing of P4 × day of embryo transfer was highly significant (P < 0.001), further suggesting that the effect of P4 was more pronounced on day 6 embryo transfer. In fresh oocyte retrieval cycles with elevated P4, a subsequent 760 frozen-thaw transfers did not demonstrate a difference between embryos that were frozen after blastulation on day 5 versus 6.Limitations reasons for cautionLimitations include the retrospective design and the inability to control for certain confounding variables, such as thaw survival rates between day 5 and day 6 blastocysts. Also, the data set lacks the known ploidy status of the embryos and the progesterone assay is not currently optimized to discriminate between patients with a P4 of 1.5 versus 1.8 ng/ml.Wider implications of the findingsThis study suggests further endometrial-embryo asynchrony when a slow growing embryo is combined with an advanced endometrium, ultimately leading to decreased live births. This suggests that premature elevated P4 may be a factor in the lower live birth rates in day 6 fresh embryo transfers. Further studies are needed to evaluate if a frozen embryo transfer cycle can ameliorate the effect of elevated P4 on the day of trigger among these slower growing embryos that reach blastocyst staging on day 6.Study funding/competing interestsNo external funding was received for this study. There are no conflicts of interest to declare.Trial registration numberNot applicable.

Project description:BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disorder with the disorders of estrogen(E2) and progesterone(P) secretion. The purpose of this study was to evaluate the association between the progesterone level or progesterone/estradiol(P/E2) ratio on human chorionic gonadotropin (hCG) trigger day and the outcome of in vitro fertilization in PCOS patients and explore the value of progesterone and P/E2 ratio for predicting the clinical pregnancy.MethodsThe clinical data of 1254 PCOS patients who satisfied the inclusion criteria were retrospectively analyzed, including baseline characteristics such as age, body mass index, basal sex hormone levels, et al., as well as ovarian stimulation data and clinic outcome.ResultsThe number of follicles larger than 14 mm in diameter (P < 0.001) and retrieved oocytes (P < 0.001) was greater in the high progesterone group (progesterone ≥ 0.92 ng/mL). In the high P/E2 group(P/E2 ratio ≥ 0.3), the number of follicles larger than 14 mm in diameter (P < 0.001) and retrieved oocytes (P < 0.001), as well as the rate of high-quality embryos (P = 0.040) were significantly decreased. In ultralong GnRH agonist protocol, the implantation rate(P < 0.001), hCG positive rate (P < 0.001), clinical pregnancy rate (P < 0.001) and live birth rate (P < 0.001) were all significantly higher than long GnRH agonist protocol and GnRH antagonist protocol. The clinical pregnancy rate of high progesterone group was significantly lower than that of low progesterone group in ultralong GnRH agonist (P = 0.008). The progesterone level could be used as an indicator to predict the positive clinical pregnancy (long GnRH agonist: P = 0.001; ultralong GnRH agonist: P < 0.001) except in cycles using GnRH antagonist (P = 0.169). In the ultralong GnRH agonist, the value of progesterone level in the prediction of clinical pregnancy was significantly higher than that of the P/E2 ratio (P = 0.021).ConclusionsIn PCOS patients, the progesterone level is associated with clinical pregnancy rate while P/E2 ratio is not. In subgroup analysis using three different COS protocols, a significant association between progesterone level and clinical pregnancy rate can be observed in the long GnRH agonist protocol and ultralong GnRH agonist protocol. The progesterone level is significantly better than the P/E2 ratio in predicting the pregnancy outcome of PCOS patients, especially in ultralong GnRH agonist cycles.

Dataset Information

Endometrial receptivity profile in patients with premature progesterone elevation on the day of HCG administration.

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Endometrial receptivity profile in patients with premature progesterone elevation on the day of HCG administration.

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