Initially produced in Europe in 1958, metformin is still one of the most widely prescribed drugs to treat type II diabetes and other comorbidities associated with insulin resistance. Metformin has been shown to improve fertility outcomes in females with insulin resistance associated with polycystic ovary syndrome (PCOS) and in obese males with reduced fertility. Metformin treatment reinstates menstrual cyclicity, decreases the incidence of cesareans, and limits the number of premature births. Notably, metformin reduces steroid levels in conditions associated with hyperandrogenism (e.g., PCOS and precocious puberty) in females and improves fertility of adult men with metabolic syndrome through increased testosterone production. While the therapeutical use of metformin is considered to be safe, in the last 10 years some epidemiological studies have described phenotypic differences after prenatal exposure to metformin. The goals of this review are to briefly summarize the current knowledge on metformin focusing on its effects on the female and male reproductive organs, safety concerns, including the potential for modulating fetal imprinting via epigenetics.

Rat aortic smooth muscle cells were isolated and maintained in primary culture. After 2-3 days, cells recovered their contractile phenotype and could be induced to contract in response to vasopressin and angiotensin II. Vasopressin- and angiotensin-specific binding sites were detected on these cells, using tritiated Lys8-vasopressin, Asn1-Val5-angiotensin II, and Sarc1-Ile8-angiotensin II. Vasopressin binding sites had Kd values of 30 and 12 nM for Lys8-and Arg8-vasopressin, respectively, and a maximal binding capacity of 25,000 sites/cell. They displayed several of the expected characteristics of vasopressin receptors involved in the vasopressor response in vivo. A highly significant correlation was found between the relative agonistic or antagonistic vasopressor potencies of a series of vasopressin structural analogues and their relative abilities to inhibit [3H]vasopressin binding to aortic smooth muscle cells. Specific binding sites for Asn1-Val5-angiotensin II and Sarc1-Ile8-angiotensin II had the following characteristics: Kd = 2.3 and 1.3 nM, respectively; maximal capacity: 50,000 sites/cell. Vasopressin and angiotensin did not modify the intracellular cyclic AMP content of aortic smooth muscle cells.

Purpose Management and outcomes of pregnant women with coronavirus disease 2019 (COVID-19) admitted to intensive care unit (ICU) remain to be investigated. Methods A retrospective multicenter study conducted in 32 ICUs in France, Belgium and Switzerland. Maternal management as well as maternal and neonatal outcomes were reported. Results Among the 187 pregnant women with COVID-19 (33 ± 6 years old and 28 ± 7 weeks’ gestation), 76 (41%) were obese, 12 (6%) had diabetes mellitus and 66 (35%) had pregnancy-related complications. Standard oxygenation, high-flow nasal oxygen therapy (HFNO) and non-invasive ventilation (NIV) were used as the only oxygenation technique in 41 (22%), 55 (29%) and 18 (10%) patients, respectively, and 73 (39%) were intubated. Overall, 72 (39%) patients required several oxygenation techniques and 15 (8%) required venovenous extracorporeal membrane oxygenation. Corticosteroids and tocilizumab were administered in 157 (84%) and 25 (13%) patients, respectively. Awake prone positioning or prone positioning was performed in 49 (26%) patients. In multivariate analysis, risk factors for intubation were obesity (cause-specific hazard ratio (CSH) 2.00, 95% CI (1.05–3.80), p = 0.03), term of pregnancy (CSH 1.07, 95% CI (1.02–1.10), per + 1 week gestation, p = 0.01), extent of computed tomography (CT) scan abnormalities > 50% (CSH 2.69, 95% CI (1.30–5.60), p < 0.01) and NIV use (CSH 2.06, 95% CI (1.09–3.90), p = 0.03). Delivery was required during ICU stay in 70 (37%) patients, mainly due to maternal respiratory worsening, and improved the driving pressure and oxygenation. Maternal and fetal/neonatal mortality rates were 1% and 4%, respectively. The rate of maternal and/or neonatal complications increased with the invasiveness of maternal respiratory support. Conclusion In ICU, corticosteroids, tocilizumab and prone positioning were used in few pregnant women with COVID-19. Over a third of patients were intubated and delivery improved the driving pressure. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-022-06833-8.

From C. elegans to mammals (including humans), nutrition and energy metabolism significantly influence reproduction. At the cellular level, some detectors of energy status indicate whether energy reserves are abundant (obesity), or poor (diet restriction). One of these detectors is AMPK (5′ AMP-activated protein kinase), a protein kinase activated by ATP deficiency but also by several natural substances such as polyphenols or synthetic molecules like metformin, used in the treatment of insulin resistance. AMPK is expressed in muscle and liver, but also in the ovary and testis. This review focuses on the main effects of AMPK identified in gonadal cells. We describe the role of AMPK in gonadal steroidogenesis, in proliferation and survival of somatic gonadal cells and in the maturation of oocytes or spermatozoa. We discuss also the role of AMPK in germ and somatic cell interactions within the cumulus-oocyte complex and in the blood testis barrier. Finally, the interface in the gonad between AMPK and modification of metabolism is reported and discussion about the role of AMPK on fertility, in regards to the treatment of infertility associated with insulin resistance (male obesity, polycystic ovary syndrome).