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Endometriosis is an estrogen-dependent chronic inflammatory condition that affects women in their reproductive period causing infertility and pelvic pain. The disease, especially at the ovarian site has been shown to have a detrimental impact on ovarian physiology. Indeed, sonographic and histologic data tend to support the idea that ovarian follicles of endometriosis patients are decreased in number and more atretic. Moreover, the local intrafollicular environment of patients affected is characterized by alterations of the granulosa cell compartment including reduced P450 aromatase expression and increased intracellular reactive oxygen species generation. However, no comprehensive evaluation of the literature addressing the effect of endometriosis on oocyte quality from both a clinical and a biological perspective has so far been conducted. Based on this systematic review of the literature, oocytes retrieved from women affected by endometriosis are more likely to fail in vitro maturation and to show altered morphology and lower cytoplasmic mitochondrial content compared to women with other causes of infertility. Results from meta-analyses addressing IVF outcomes in women affected would indicate that a reduction in the number of mature oocytes retrieved is associated with endometriosis while a reduction in fertilization rates is more likely to be associated with minimal/mild rather than with moderate/severe disease. However, evidence in this field is still far to be conclusive, especially with regards to the effects of different stages of the disease and to the impact of patients’ previous medical/surgical treatment(s).

Pathogenesis of endometriosis is still unclear and a role of both innate and adaptive immune system has been postulated. Some recent findings have revealed an increased risk to have concomitant autoimmune disease in women with endometriosis, but no study so far has investigated whether this association could affect endometriosis severity and stage. We retrospectively reviewed medical patients’ notes of women with a confirmed diagnosis of endometriosis who referred to our endometriosis outpatient clinic between January 2015 and December 2019. Cases (endometriosis and an autoimmune disease) were matched in a 1:3 ratio by age and study period with controls (endometriosis without history of autoimmunity). At univariate logistic analysis, concomitant autoimmunity (OR 2.63, 95% CI 1.64–4.21, p < 0.001) and the number of laparoscopic procedures performed (OR 2.81, 95% CI 1.45–5.43, p = 0 . 002) emerged as factors significantly associated with the likelihood of stage IV endometriosis. In the multivariate logistic regression model, concomitant autoimmunity remained a significant predictor of stage IV endometriosis (OR 2.54, 95% CI 1.57–4.10, p = 0.004), whereas the association between the number of laparoscopic procedures performed and stage IV endometriosis was found to be of borderline-significance (OR 2.70, 95% 1.37–5.30, p = 0.050). Our findings suggest that endometriosis is more severe in patients who are also affected by autoimmune disturbances after controlling for relevant confounders.

To review the current evidence on the risk of gestational diabetes mellitus (GDM) in women with endometriosis, taking into account relevant confounders such as the higher frequency of Assisted Reproductive Technologies (ART) conceptions. Database searches on PubMed, Medline, Embase and Scopus through June 2022, using combinations of relevant keywords. A total of 18 studies, involving N = 4,600,885 women, were included. The overall risk of GDM in endometriosis patients was significantly higher than in controls (OR, 1.23; 95% CI 1.07–1.51). This significant association persisted in natural pregnancies (OR, 1.08; 95% CI 1.04–1.12) but not in pregnancies conceived through ART (OR, 0.93;95% CI 0.70–1.24). Based on the limited number of studies that examined this association in relation to endometriosis phenotype, an increased risk was found in more severe stages (OR, 3.20; 95% CI 1.20–8.54) but independently from localization of the lesions. Endometriosis increases the risk of GDM, with a possible progressive effect in more advanced stages of the disease. Although the effect magnitude may be limited in some subgroups, this finding has a clinically relevant impact due to both the strong biological plausibility and to the relatively high incidence of both endometriosis and GDM.

Communication between embryo and maternal endometrium occurs during a specific time frame in which implantation is possible. Here we demonstrate for the first time that conditioned media from non-manipulated human embryos cultured in vitro for 3 days or up to the blastocyst stage contain extracellular vesicles (EVs) with a diameter of 50 to 200 nm and bearing the traditional microvesicle and exosome marker proteins CD63, CD9 and ALIX. The embryonic origin of these EVs has been confirmed by the presence of stemness gene transcripts and their enrichment in the non-classical HLA-G protein. NANOG and POU5F1 transcripts were shown to be contained in vesicles deriving from embryos at different stages of development. In line with a higher detection rate of the HLA-G protein in blastocysts compared to cleavage stage embryos, a significantly higher amount of HLA-G was found in vesicles accumulated in spent media from day 3 to day 5 of development compared to those isolated from the earlier stage. Uptake of dye-labeled embryo-derived EVs by human primary endometrial epithelial and stromal cells was also demonstrated with a fluorescence intensity signal significantly higher for cells treated with vesicles derived from blastocysts. Based on these findings, EV exchange may be suggested as an emerging way of communication at the maternal-fetal interface.

SARS-CoV-2 infection poses a significant risk increase for adverse pregnancy outcomes both from maternal and fetal sides. A recent publication in BMC Pregnancy and Childbirth presented a machine learning algorithm to predict this risk. This commentary will discuss potential implications and applications of this study for future global health policies.

This review examines the factors that affect the decision-making process of parental couples evaluating prenatal screening and diagnostic tests. A systematic search was performed using PubMed and PsycInfo databases. The 46 included studies had to: investigate the decision-making process about prenatal testing; focus on tests detecting trisomy 21, 18, 13, and abnormalities of sex chromosomes; be published in English peer-reviewed journals. The decision-making process seems composed of different levels: an individual level with demographic, clinical, and psychological aspects; a contextual level related to the technical features of the test and the information received; a relational level involving family and society.

Extracellular vesicles (EVs) derived from different parts of the male reproductive tract can be internalized by human spermatozoa affecting their maturation and regulating their functions. Here we demonstrate that EVs derived from the female tract can be uptaken by sperm and affect their competence. Primary endometrial cells release EVs with a diameter between 50 and 350 nm and bear the standard vesicle and exosome marker proteins CD63, CD9, TSG101 and ALIX. The uptake of dye-labelled endometrial cell-derived EVs by spermatozoa, quantified as fluorescence intensity, was significantly higher when EVs were derived from cells in the proliferative phase. Vital, motile fluorescent sperm could be appreciated after a 48-hour co-incubation with endometrial cells previously labelled with the Vybrant™ DiO dye. EV internalization by sperm was blocked at 4 °C and by incubation with filipin, suggesting an energy-dependent process probably attributable to the lipid-raft domain mediated-endocytosis. Sperm ability to undergo capacitation and acrosome reaction was stimulated by endometrial cell-derived EVs as manifested by the increased protein tyrosine phosphorylation and evident reactivity when stimulated with a calcium ionophore. Based on these findings, EVs exchange may be suggested as an emerging way through which female reproductive tract cells can interact with the passing spermatozoa.

The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight heparin (LMWH) has gained increasing relevance for its therapeutic potential. On this regard, the aim of this systematic review and meta-analysis is to analyze the efficacy of low molecular weight heparin (LMWH) from the beginning of pregnancy in terms of live birth rates (LBR) in U-RPL. Registered randomized controlled trials (RCTs) were included. We stratified findings based on relevant clinical factors including number of previous miscarriages, treatment type and control type. Intervention or exposure was defined as the administration of LMWH alone or in combination with low-dose aspirin (LDA). A total of 6 studies involving 1016 patients were included. The meta-analysis results showed that LMWH used in the treatment of U-RPL was not associated with an increase in LBR with a pooled OR of 1.01, a medium heterogeneity (26.42%) and no publication bias. Results of other sub-analyses according to country, treatment type, and control type showed no significant effect of LMWH on LBR in all subgroups, with a high heterogeneity. The results highlight a non-significant effect of LMWH in U-RPL on LBR based on moderate quality evidence. Registration number: PROSPERO: ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326433 ).

Extracellular vesicles (EVs) have been proven to have a crucial role in intercellular communication and have attracted significant attention in the physiology of reproduction because of their multiple functions in physiological processes essential for reproduction including gametogenesis, fertilization and embryo-endometrial cross-talk. Although EVs from the male reproductive tract have been extensively studied for their role in sperm maturation, research on female reproductive tract-derived EVs in humans is still emerging and supported by only a few studies to date. In vitro study was performed using spermatozoa from normozoospermic men and EVs isolated from follicular fluid (FF-EVs), cervicovaginal fluid collected 2 and 7 days after the LH surge (CVF-EVs LH + 2 and LH + 7, respectively) and spent medium of decidualized (dESCs-EVs) and non-decidualized (eESCs-EVs) endometrial stromal cells from healthy women of reproductive age. The principal outcome measures comprise the percentage of viable, progressively motile, and capacitated spermatozoa after treatment with FF-EVs, CVF-EVs LH + 2 and LH + 7, dESCs-EVs, and eESCs-EVs. Spermatozoa are able to capture EVs derived from all the considered tracts of the female reproductive system, with slightly varying efficiencies, albeit comparable in most cases. Incubating sperm cells with any of these EVs does not have any detrimental effect on sperm vitality, increases the percentage of spermatozoa displaying progressive motility and the percentage of acrosome-reacted spermatozoa. EVs produced and released in various regions of the female reproductive system likely contribute to spermatozoa maturation during their transit, promoting both capacitation and motility.

The maturation of the auditory-language brain network begins before birth, driven by gene-environment interactions. We investigated the association between familial and environmental factors and the foetal development of this network, as well as the predictive value of this association for postnatal language outcomes. Using prenatal resting-state fMRI, we examined 25 foetuses to identify functional connectivity within the auditory-language network. Postnatal language was assessed longitudinally between 1 and 3 years using the Bayley-III scale. Familial risk for language disorders and prenatal speech exposure were quantified using a newly developed questionnaire. First, hierarchical clustering on foetal functional connectivity confirmed that an auditory-language network can be identified in the foetal brain. In this network, foetuses with higher speech exposure exhibited increased connectivity between left-hemisphere regions and decreased connectivity between homologous right-hemisphere regions. Higher familial risk was linked to reduced connectivity within the left language network. Regression analyses revealed that prenatal functional connectivity between insula, caudate nucleus, and rolandic operculum significantly predicted postnatal language. These findings underscore the critical role of genetic and environmental influences in functionally shaping the foetal auditory-language network, with lasting impacts on early language development. By integrating prenatal brain connectivity, familial risk, and speech exposure, this study provides new insights into prenatal language neurodevelopment, highlighting its importance for future language capabilities.