Our results unveil that impaired autophagy is a novel pathophysiological mechanism involved in human POI.

Our objective was to determine whether psychological factors have an influence on the outcome of the fertilization step of in vitro fertilization (IVF) trials. The design was a prospective cohort study. We studied 48 women and 32 of their spouses. Each subject was assessed psychologically on the day before oocyte retrieval (OR) with the Child Project Questionnaire (CPQ) and the Ways of Coping Checklist. In addition, the State-Trait Anxiety Inventory was filled in by subjects 2 days before OR, and the State form was completed again for 6 additional days. The outcome measure was the success of the fertilization step. Logistic regression analysis was used to test the influence of psychological factors while taking into account the effect of medical and sociodemographic variables. The following variables were found to be statistically significant predictors of fertilization: normal sperm; tubal lesions or occlusion; women's factor II of the CPQ, i.e. Perception of Marital Harmony in the Project to Conceive a Child. We conclude that, even when the influence of biomedical variables is taken into account, the women's Perception of Marital Harmony in the Project to Conceive a Child, is a statistically significant predictor of the success of the fertilization step of IVF.

Context Primary ovarian insufficiency (POI) is a frequently occurring disorder affecting approximately 1% of women under 40 years of age. POI, which is characterized by the premature depletion of ovarian follicles and elevated plasma levels of follicle-stimulating hormone, leads to infertility. Although various etiological factors have been described, including chromosomal abnormalities and gene mutations, most cases remain idiopathic. Objective To identify and to functionally validate new sequence variants in 2 genes that play a key role in mammalian ovarian function, BMPR1A and BMPR1B (encoding for bone morphogenic protein receptor), leading to POI. Methods The impact on bone morphogenic protein (BMP) signaling of BMPR1A and BMPR1B variants, previously identified by whole-exome sequencing on 69 women affected by isolated POI, was established by different in vitro functional experiments. Results We demonstrate that the BMPR1A-p.Arg442His and BMPR1B-p.Phe272Leu variants are correctly expressed and located but lead to an impairment of downstream BMP signaling. Conclusion In accordance with infertility observed in mice lacking Bmpr1a in the ovaries and in Bmpr1b-/- mice, our results unveil, for the first time, a link between BMPR1A and BMPR1B variants and the origin of POI. We show that BMP signaling impairment through specific BMPR1A and BMPR1B variants is a novel pathophysiological mechanism involved in human POI. We consider that BMPR1A and BMPR1B variants constitute genetic biomarkers of the origin of POI and have clinical utility.