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ObjectiveWe sought to determine whether the early luteal serum progesterone (P4) level predicts the success of IVF treatment with oral dydrogesterone for luteal support.MethodThis retrospective monocentric cohort study included 242 women who underwent IVF treatment with fresh embryo transfer (ET) between July 2017 and June 2018. The population was unselected, and women were treated according to our unit's usual stimulation protocols. For the luteal phase support (LPS), all women were supplemented with a 10 mg three-times-daily dose of oral dydrogesterone beginning on the day of oocyte pick-up (OPU). Blood sampling was performed on the day of ET (Day 2-3 after OPU) to determine the early luteal serum progesterone level.ResultsROC curve analysis allowed us to determine two thresholds for the prediction of live birth using the early P4 level. Women who had early luteal P4 levels greater than 252 nmol/l had a significantly higher live birth rate (27.1%) than women with early luteal P4 between 115 and 252 nmol/l (17.2%) and women with early luteal P4 below 115 nmol/l (6.0%; p = 0.011). After a multiple regression analysis, an early luteal P4 level greater than 252 nmol/l was still associated with a higher chance of a live birth than a P4 between 115 and 252 nmol/l (OR = 0.40 [0.18-0.91]; p = 0.028) or a P4 below 115 nmol/l (OR = 0.10 [0.01-0.52]; p = 0.006).ConclusionsOur study suggests a positive association between early P4 levels and reproductive outcomes in IVF using oral dydrogesterone for luteal support. The inconsistencies between our results and those of other studies suggest that extrapolation is impractical. Further larger prospective cohort studies should be conducted to determine reliable thresholds that could be used to personalize luteal phase support.

Preterm birth is associated with altered angiogenesis and with increased risk of cardiovascular dysfunction and hypertension at adulthood. We previously demonstrated that in preterm newborns circulating cord blood endothelial progenitor cells (ECFC), responsible for angio/vasculogenesis, are reduced in number and display altered angiogenic properties. Altered angiogenic function was associated with a decreased expression of pro-angiogenic genes, among which the AMOT gene which is a strong positive regulator of angiogenesis. Such dysregulation may be related to epigenetic factors. In this study we analyse the methylation profiling of the AMOT gene during development, through a comparative analysis of the cord blood ECFC of preterm newborns and their term counterpart.We used both cloning-sequencing and pyrosequencing experiments to perform a comparative analysis of the DNA methylation profile of the promoter CpG island of AMOT gene in the cord blood ECFC of 16 preterm newborns (28-35 weeks gestational age-GA) and 15 term newborns (>37 weeks GA).Twenty nine clones (obtained from 2 term newborns) and forty clones (obtained from 3 preterm newborns) were sequenced. The AMOT gene methylation rate was significantly higher in preterm compared to term newborns (4.5% versus 2.5% respectively: χ2 = 3.84; P = 1.8 10-02). Bisulfite pyrosequencing identified four CpG dinucleotides with significantly higher methylation levels in preterm newborns. This CpG-targeted methylation significantly decreased with increasing gestational age.These findings highlight importance of pro-angiogenic AMOT gene methylation in ECFC, suggesting that epigenetic mechanisms may control the regulation of angiogenesis during development. Therefore they pave the way to specific short term and long term complications of preterm birth by altered angiogenesis.

A low-protein diet applied during pregnancy in the rat results in intrauterine growth restricted (IUGR) fetuses. In humans, IUGR is associated with increased perinatal morbidity, higher incidence of neuro-developmental defects and increased risk of adult metabolic anomalies, such as diabetes and cardiovascular disease. Development and function of many organs are affected by environmental conditions such as those inducing fetal and early postnatal growth restriction. This phenomenon, termed "fetal programming" has been studied unconnectedly in some organs, but very few studies (if any) have investigated at the same time several organs, on a more comparative basis. However, it is quite probable that IUGR affects differentially most organ systems, with possible persistent changes in gene expression. In this study we address transcriptional alterations induced by IUGR in a multi-organ perspective, by systematic analysis of 20-days rat fetuses. We show that (1) expressional alterations are apparently stronger in organs functioning late in foetal or postnatal life than in organs that are functioning early (2) hierarchical classification of the deregulations put together kidney and placenta in one cluster, liver, lungs and heart in another; (3) the epigenetic machinery is set up especially in the placenta, while its alterations are rather mild in other organs; (4) the genes appear deregulated in chromosome clusters; (5) the altered expression cascades varies from organ to organ, with noticeably a very significant modification of the complement and coagulation cascades in the kidney; (6) we found a significant increase in TF binding site for HNF4 proteins specifically for liver genes that are down-regulated in IUGR, suggesting that this decrease is achieved through the action of HNF transcription factors, that are themselves transcriptionnally induced in the liver by IUGR (x 1.84 fold). Altogether, our study suggests that a combination of tissue-specific mechanisms contributes to bring about tissue-driven modifications of gene cascades. The question of these cascades being activated to adapt the organ to harsh environmental condition, or as an endpoint consequence is still raised.