Impact of repeated ovarian hyperstimulation on the reproductive function.

One of six couples (17.5 % of the adult population) worldwide is affected by infertility during their lifetime. This number represents a substantial increase in the prevalence of this gynecological condition over the last decade. Ovulatory dysfunction and anovulation are the main causes of female infertility. Timed intercourse, intrauterine insemination, and assisted reproductive technology (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), are the most common interventions for infertile couples. Ovulation induction protocols for IVF/ICSI routinely use supraphysiological doses of gonadotropins to stimulate many preovulatory follicles. Animal and human studies suggested that ovarian hyperstimulation, alone or repeatedly, for ART cycles can induce changes in the immune response and increase the oxidative stress (OS) in the ovarian microenvironment. The consequences of repeated ovarian hyperstimulation on the human ovary remain poorly understood, particularly in relation to the effects of ovarian stimulation on the immune system and the potential for ovarian stimulation to cause OS. Animal studies have observed that repeated cycles of ovarian hyperstimulation can accelerate ovarian aging. Changes in ovarian hormone levels, accelerated loss of ovarian reserve, disorders in ovarian ultrastructure, ovarian senescence, and decreased reproductive performance represent possible long-term effects of repeated ovarian hyperstimulation. The short and long-term impact of the combination of antioxidant agents in ovarian hyperstimulation protocols in women undergoing ART must urgently be better understood. The recent increase in the number of ART and fertility preservation cycles may accelerate ovarian aging in these women, promoting consequences beyond the reproductive function and including health deterioration.

Repeated ovarian hyperstimulation promotes depression-like behavior in female mice.

Controlled ovarian hyperstimulation (COH) is a common step for treating infertile couples undergoing assisted reproductive technologies and in female fertility preservation cycles. In some cases, undergoing multiple COHs is required for couples to conceive. Behavioral changes such as anxiety and depression can be caused by ovulation-inducing drugs. Sex steroids play a role in locomotor activity, behavioral changes, and nociception, specifically during fluctuations and sudden drops in estrogen levels. This study evaluated the effect of repeated ovarian hyperstimulation (ROH) on weight, locomotor activity, anxiety-like and depression-like behavior, and nociception in female mice. The animals were divided into two groups: control (placebo; Control) and treated (ROH; Treatment). Ovulation was induced once weekly for 10 consecutive weeks. Locomotor activity (open field test), anxiety-like behavior (elevated plus maze, hole board, and marble burying tests), depression-like behavior (splash and forced swim tests), and nociception (hot plate and Von Frey tests) were evaluated before and after ROH. Statistical analysis was conducted using two-way analysis of variance to evaluate the effects of ROH, age of mice, and their interaction. The results suggested that ROH contributed to weight gain, increased locomotor activity, and induced depression-like behavior in female mice. Furthermore, the age of the mouse contributed to weight gain, increased locomotor activity, and induced anxiety-like and depression-like behavior in female mice. ROH could change the behavior of female mice, particularly inducing depression-like behavior. Further studies are required to evaluate various COH protocols, specifically with drugs that prevent fluctuations and drastic drops in estrogen levels, such as aromatase inhibitors.

Obesity and recurrent miscarriage: The interconnections between adipose tissue and the immune system.

Currently, obesity is considered a global public health problem. It is the main risk factor for noncommunicable diseases and reproductive complications, such as recurrent miscarriage (RM). RM affects approximately 1% of couples of reproductive age, and recent studies suggest that its prevalence is increasing. Immunological abnormalities may be responsible for a significant number of cases of unexplained RM. Obesity is recognized as a chronic low-grade inflammatory condition. The accumulation of fat in obese adipose tissue promotes changes in the local and systemic immune response. Adipokines, exosomes, micro-RNAs, lipids, and other factors released or secreted by adipose tissue are responsible for the interconnection between obesity and the immune system. Obesity-induced dysregulation of the innate and acquired immune response is also involved in the immunopathology of pregnancy loss in patients with unexplained RM. Therefore, understanding the communication pathways between maternal adipose tissue and the immune response in women living with obesity and RM is an important objective. Thus, diagnostic tools and new immunomodulatory therapies may be proposed for the management of patients with concurrent obesity and RM.