Oocyte–cumulus cell interaction is essential for oocyte maturation and competence. The bidirectional crosstalk network mediated by gap junctions is fundamental for the metabolic cooperation between these cells. As cumulus cells exhibit a more glycolytic phenotype, they can provide metabolic substrates that the oocyte can use to produce ATP via oxidative phosphorylation. The impairment of mitochondrial activity plays a crucial role in ovarian aging and, thus, in fertility, determining the success or failure of assisted reproductive techniques. This review aims to deepen the knowledge about the electro-metabolic coupling of the cumulus–oocyte complex and to hypothesize a putative role of potassium channel modulators in order to improve fertility, promote intracellular Ca2+ influx, and increase the mitochondrial biogenesis and resulting ATP levels in cumulus cells.
Uterine aging is the process of the senescence of uterine tissue, observed in all middle-aged mammals. Since the aging-related changes in the uterus are associated with infertility and poor pregnancy outcomes, with a lack of studies discussing uterine aging, authors reviewed uterine aging and its consequences on reproduction. MEDLINE, Scopus, and PubMed searches during the years 1990–2023 were performed using a combination of keywords and terms on such topics. According to the author’s evaluation, articles were identified, selected, and included in this narrative review. The aging process has an unfavorable impact on the uterus of mammals. There are different and selected molecular pathways related to uterine aging in humans and animals. Uterine aging impairs the function of the uterine myometrium, neurofibers of the human uterus, and human endometrium. These biological pathways modulate oxidative stress, anti-inflammatory response, inflammation, mitochondrial function, DNA damage repair, etc. All these dysregulations have a role in poorer reproductive performance and pregnancy outcomes in older mammals. The most recent data suggest that uterine aging is accompanied by genetic, epigenetic, metabolic, and immunological changes. Uterine aging has a negative impact on the reproductive performance in mammalian species, but it could be potentially modulated by pharmacological agents, such as quercetin and dasatinib.
Background: The purpose of this narrative review is to describe the mechanisms that are responsible for the development of infertility and PCOS, with a focus on the role of obesity, insulin sensitivity and treatment with metformin and GLP-1s. Methods: The relevant publications were identified after systematic queries of the following sources: PubMed, Google Scholar, Web of Science, and publishers’ databases, complemented by a cross-check of the reference lists. We used a combination of the search terms “polycystic ovary syndrome”, “obesity” and “insulin resistance” with “metformin”, “exenatide”, “liraglutide”, “semaglutide”, “orlistat” and terms relevant to the topic of each paragraph (e.g., “pathophysiology”, “metabolism”, “infertility”, “treatment”). Results: All articles describing the mechanisms responsible for the development of infertility and PCOS, with a focus on the role of obesity, insulin sensitivity and treatment with metformin and GLP-1s, were considered for this review. Conclusions: The existing research on GLP-1 receptor agonists (GLP-1RAs) has not conclusively established a specific therapeutic use for these drugs. Additionally, the efficacy of the newer generation of GLP-1RAs, particularly in terms of dosage and duration of exposure, warrants more extensive research. Understanding the optimal dosing and treatment duration could significantly enhance the therapeutic use of GLP-1RAs in managing PCOS and its associated conditions.
Background: Hysteroscopy currently represents the gold standard for the diagnosis and treatment of intrauterine pathologies. Recent technological progress has enabled the integration of diagnostic and operative time, leading to the “see and treat” approach. Diode laser technology is emerging as one of the most innovative and intriguing techniques in this context. Methods: A comprehensive search of the literature was carried out on the main databases. Only original studies reporting the treatment of intrauterine pathologies using diode laser were deemed eligible for inclusion in this systematic review (PROSPERO ID: CRD42023485452). Results: Eight studies were included in the qualitative analysis for a total of 474 patients undergoing laser hysteroscopic surgery. Eighty-three patients had female genital tract abnormalities, 63 had submucosal leiomyomas, 327 had endometrial polyps, and one patient had a scar pregnancy. Except for leiomyomas, whose technique already included two surgical times at the beginning, only seven patients required a second surgical step. Cumulative rates of intraoperative and postoperative complications of 2.7% and 0.6%, respectively, were reported. Conclusions: Diode laser through “see and treat” hysteroscopy appears to be a safe and effective method. However, additional studies with larger sample sizes and improved designs are needed to consolidate the evidence currently available in the literature.
Background: The incidence of pregnant women with uterine fibroids is increasing. As they are reactive to hormonal stimuli, in some cases, uterine fibroids tend to grow during pregnancy and potentially generate symptoms with different levels of severity, causing maternal–fetal complications. In very select cases, when other treatment strategies fail to manage symptoms and there is a substantial risk of adverse pregnancy outcomes, a surgical approach during pregnancy may be considered. Methods: From 2016 to 2021, the data from 28 pregnant women with symptomatic uterine fibroids who underwent laparotomic myomectomy during pregnancy were prospectively collected, and operative and maternal–fetal outcomes were analyzed (ClinicalTrial ID: NCT06009562). Results: The procedure was carried out between 14 and 16 weeks of pregnancy. Four (14.3%) patients had intraoperative complications (miscarriages) and nine (32.1%) had postoperative complications (threatened preterm birth). Overall, 24 (85.7%) women delivered at full term (mean: 38.2 gestational weeks), more than half (n = 13; 54.2%) by vaginal delivery, with normal fetal weights and 1 and 5 min Apgar scores. Conclusions: Laparotomic myomectomy during pregnancy can be considered in selected cases for uterine fibroids with severe symptoms when other treatment options have failed and there is high risk of adverse maternal–fetal outcomes.