Ovarian stimulation using human chorionic gonadotrophin impairs blastocyst implantation and decidualization by altering ovarian hormone levels and downstream signaling in mice

Abstract

Ovarian stimulation induced by follicle-stimulating hormone and human chorionic gonadotrophin (hCG) is commonly used in assisted reproductive technology to increase embryo production. However, recent clinical and animal studies have shown that ovarian stimulation disrupts endometrial function and embryo development and adversely affects pregnancy outcomes. How ovarian stimulation impairs pregnancy establishment and the precise mechanisms by which this stimulation reduces the chances of conception remain unclear. In this study, we first demonstrated that ovarian stimulation using hCG alone impairs implantation, decidualization and fetal development of mice by generating abnormal ovarian hormone levels. We also showed that ovarian hormone levels were altered because of changes in the levels of the enzymes involved in their synthesis in the follicles and corpora lutea. Furthermore, we determined that anomalous ovarian hormone secretion induced by ovarian stimulation alters the spatiotemporal expression of progesterone receptors and their downstream genes, especially in the uterine epithelium. Epithelial estrogenic signaling and cell proliferation were promoted on the day of implantation in stimulated mice and these changes led to the failure of uterine transition from the prereceptive to the receptive state. Collectively, our findings indicate that ovarian stimulation using hCG induces an imbalance in steroid hormone secretion, which causes a failure of the development of uterine receptivity and subsequent implantation and decidualization by altering the expression of steroid receptors and their downstream signaling associated with embryo implantation.

Genome‐wide association study reveals novel variants for growth and egg traits in Dongxiang blue‐shelled and White Leghorn chickens

“…), and previous studies have revealed that steroid hormones are associated with luteinizing hormone and follicle‐stimulating hormone and play key roles in ovarian stimulation and embryo development (Andersen & Ezcurra ; Ezoe et al . ). Although the function of DGKQ is undefined in chickens, it may interact with the sex steroid hormone system to affect egg production traits.…”

Nausea and vomiting of pregnancy - What's new?

“…In terms of the mechanism behind the role of estrogen and progesterone in NVP, it has been reported that stimulation with hCG increase serum concentrations of progesterone and estrogen in a mouse model (Ezoe et al, 2014). Progesterone and estrogen can alter gastric rhythms in non-pregnant women increasing gastric intestinal transit time and slowing gastric emptying which may lead to increased nausea and vomiting (Bruce et al, 1978; Lee et al, 2011; Milenov et al, 1973; Walsh et al, 1996).…”

Preparation of endometrium for frozen embryo replacement cycles: a systematic review and meta-analysis

“…In regularly cycling women, it has been hypothesized that ovarian stimulation with either oral agents or exogenous gonadotropins (Gns) may improve certain defects in the follicular and subsequent luteal phase, resulting in a better endometrial preparation for embryo implantation [17,18]. However, it has also been claimed that ovarian stimulation may lead to decreased endometrial receptivity [3,19,20].…”