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The occurrence of cancer during pregnancy is observed in 1 in 1000 pregnancies and is expected to increase given the trend of delaying childbearing. While breast cancer is the most common, the incidence of other cancers, such as cervical, ovarian, and lung cancers as well as hemopathies and melanomas, is also increasing. Thus, cancer occurrence in pregnant women raises questions of management during pregnancy and, especially, assessment of the treatment benefit–risk ratio to ensure optimal management for the mother while ensuring the safety of the fetus. Chemotherapy remains a cornerstone of cancer management. If the use of anticancer agents appears possible during pregnancy, while avoiding the first trimester, the extent of placental transfer of different anticancer agents varies considerably thereafter. Furthermore, the significant physiological pharmacokinetic variations observed in pregnant women may have an impact on the placental transfer of anticancer agents. Given the complexity of predicting placental transfer of anticancer agents, preclinical studies are therefore mandatory. The aim of this review was to provide updated data on in vivo and ex vivo transplacental transfer of anticancer agents used in the management of the most common pregnancy-associated cancers to better manage these highly complex cases.

Whereas the initially strategy for the genetic analysis of male infertility was based on a candidate gene approach, the development of next-generation sequencing technologies (such as whole-exome sequencing (WES)) provides an opportunity to analyze many genes in a single procedure. In order to recommend WES or whole-genome sequencing (WGS) after genetic counselling, an objective evaluation of the current genetic screening strategy for male infertility is required, even if, at present, we have to take into consideration the complexity of such a procedure, not discussed in this commentary.

Objective: The effect of lockdowns during the coronavirus (COVID-19) pandemic on pregnancy outcomes remains uncertain. We aimed to evaluate the association between the COVID-19-related lockdown and pregnancy outcomes in maternity hospitals in France. Study design: This was a retrospective cohort study from six tertiary referral hospitals in different regions of France. Three 55-day periods were compared: Pre-lockdown from 22 January 2020, lockdown from 17 March 2020, and post-lockdown from 11 May 2020 to 4 July 2020. We included all women who delivered singleton or multiple pregnancies, who delivered at ≥24 weeks of gestation and with birthweights ≥500 g. We documented gestational ages at the delivery of liveborn and stillborn infants (‘stillbirths’). These were categorized as having a very low birthweight (VLBW, <1500 g), or a low birthweight (LBW, <2500 g). Adjustments were made for place of birth, maternal age, parity and diabetes, and hypertensive disorders, as well as for multiple pregnancies. Results: In total, 11,929 women delivered in the six selected centers. This figure is constituted of 4093, 3829, and 4007 deliveries in the pre-lockdown, peri-lockdown, and post-lockdown periods, respectively. There were no differences in pregnancy outcomes between these three periods. Overall, birth rates <27+6 weeks, between weeks 28+0 and 31+6, and between 32+0 and weeks 36+6 were 1.0%, 1.9%, and 4.4%, respectively. After adjustment, these rates were stable between periods 1 and 2 (adjusted odds ratio, aOR 0.90; 95% confidence interval, CI 0.69–1.19) and between periods 2 and 3 (aOR 1.04; 95% CI 0.80–1.36). Although more VLBW neonates were born during lockdown (3.5% vs. 2.6%, p = 0.03), this difference did not persist after adjustment (aOR 0.84, CI 95% 0.64–1.10). The LBW rates were similar during the three periods at 12.5% overall. The stillbirth rate was unaffected by the lockdown. Conclusion: The pregnancy outcomes (preterm birth, LBW, VLBW, and stillbirth rates) were not modified by the COVID-19 lockdown in our cohort study in France. Considering the discrepancies in results and methodological issues in previous published studies, there is not sufficient evidence to conclude that such lockdowns have any impact on perinatal outcomes.

Endometriosis is a common chronic gynaecological disease causing various symptoms, such as infertility and chronic pain. The gold standard for its diagnosis is still laparoscopy and the biopsy of endometriotic lesions. Here, we aimed to compare the eutopic endometrium from women with or without endometriosis to identify proteins that may be considered as potential biomarker candidates. Eutopic endometrium was collected from patients with endometriosis (n = 4) and women without endometriosis (n = 5) during a laparoscopy surgery during the mid-secretory phase of their menstrual cycle. Total proteins from tissues were extracted and digested before LC-MS-MS analysis. Among the 5301 proteins identified, 543 were differentially expressed and enriched in two specific KEGG pathways: focal adhesion and PI3K/AKT signaling. Integration of our data with a large-scale proteomics dataset allowed us to highlight 11 proteins that share the same trend of dysregulation in eutopic endometrium, regardless of the phase of the menstrual cycle. Our results constitute the first step towards the identification of potential promising endometrial diagnostic biomarkers. They provide new insights into the mechanisms underlying endometriosis and its etiology. Our results await further confirmation on a larger sample cohort.

Introduction: Sexual function of patients with endometriosis should be assessed by patient-reported outcome measures (PROMs) that present high reliability and validity. The objective was to study the PROMs used to assess sexual function for patients with endometriosis to improve their selection for research and clinical practice. Material and methods: We performed a systematic literature review from January 2000 to September 2023. All studies including women with confirmed endometriosis and assessing sexual quality of life or sexual function or sexual distress were retrieved. Different properties of PROMs used for sexual dysfunction were assessed according to the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) recommendations. Properties evaluated were: structural validity, internal consistency, cross-cultural validity, reliability, measurement error, criterion validity, construct validity, and responsiveness. This literature review was registered on Prospero as 2018 CRD42018102278. Results: Seventy-four articles with evaluation of sexual function were included. Of the 25 PROMs assessing sexual function, the Female Sexual Function Index (FSFI) was the most frequently used (34/74 [45.9%] items), followed by the Female Sexual Distress Scale (9/74 [12.2%] items) and the Sexual Activity Questionnaire (SAQ) (8/74 [10.8%] items). The most commonly used measurement properties were “hypothesis testing” and “responsiveness”. The PROMs with a high level of evidence for these two measurement properties were the FSFI, the SAQ, the Short Sexual Functioning Scale, the Sexual Satisfaction Scale for Women, Sexual Quality of Life-Female, the Brief Profile of Female Sexual Function, and the Sexual Health Outcomes in Women Questionnaire. The FSFI questionnaire appeared to be more relevant for evaluating medical treatment, and the SAQ for evaluating surgical treatment. Only one instrument was specific to endometriosis (the Subjective Impact of Dyspareunia Inventory. Conclusions: In this systematic literature review of sexual function assessment questionnaires in endometriosis, the FSFI and the SAQ questionnaires emerged as having the best measurement properties according to the COSMIN criteria. The FSFI questionnaire appears to be suited for evaluating medical treatment, and the SAQ for surgical treatment. The SIDI is the only specific questionnaire, but its responsiveness remains to be defined.

The objectives of the present study were to determine whether obesity impacts human decidualization and the endometrial control of trophoblast invasion (both of which are required for embryo implantation) and evaluate the potential involvement of endometrial extracellular vesicles (EVs) in the regulation of these physiological processes. Using primary human cell cultures, we first demonstrated that obesity is associated with significantly lower in vitro decidualization of endometrial stromal cells (ESCs). We then showed that a trophoblastic cell line's invasive ability was greater in the presence of conditioned media from cultures of ESCs from obese women. The results of functional assays indicated that supplementation of the culture medium with EVs from nonobese women can rescue (at least in part) the defect in in vitro decidualization described in ESCs from obese women. Furthermore, exposure to endometrial EVs from obese women (vs. nonobese women) was associated with significantly greater invasive activity by HTR‐8/SVneo cells. Using mass‐spectrometry‐based quantitative proteomics, we found that EVs isolated from uterine supernatants of biopsies from obese women (vs. nonobese women) presented a molecular signature focused on cell remodelling and angiogenesis. The proteomics analysis revealed two differentially expressed proteins (fibronectin and angiotensin‐converting enzyme) that might be involved specifically in the rescue of the decidualization capacity in ESCs from obese women; both of these proteins are abundantly present in endometrial EVs from nonobese women, and both are involved in the decidualization process. In conclusion, our results provided new insights into the endometrial EVs’ pivotal role in the poor uterine receptivity observed in obese women.

Semen analysis is the cornerstone of male fertility evaluation with WHO guidelines providing the basis for procedural standardization and reference values worldwide. The first WHO manual was published in 1980, and five editions have been subsequently released over the last four decades. The 6th Edition was published in July 2021. In this review, we identify the key changes of this 6th Edition. Additionally, we evaluate the utility of this 6th Edition in clinical practice using SWOT (strengths, weaknesses, opportunities, and threats) analysis. This new Edition has made the analysis of basic semen parameters more robust, taking into account the criticisms and grey areas of the previous editions. The tests assessing sperm DNA fragmentation and seminal oxidative stress are well-described. The main novelty is that this latest edition abandons the notion of reference thresholds, suggesting instead to replace them with “decision limits”. While this seems attractive, no decision limits are proposed for either basic semen parameters, or for extended or advanced parameters. This critical review of the 6th Edition of the WHO laboratory manual combined with a SWOT analysis summarizes the changes and novelties present in this new Edition and provides an in-depth analysis that could help its global use in the coming years.

This study aimed to identify the risk factors for placenta accreta spectrum (PAS) in women who had at least one previous cesarean delivery and a placenta previa or low-lying. The PACCRETA prospective population-based study took place in 12 regional perinatal networks from 2013 through 2015. All women with one or more prior cesareans and a placenta previa or low lying were included. Placenta accreta spectrum (PAS) was diagnosed at delivery according to standardized clinical and histological criteria. Of the 520,114 deliveries, 396 fulfilled inclusion criteria; 108 were classified with PAS at delivery. Combining the number of prior cesareans and the placental location yielded a rate ranging from 5% for one prior cesarean combined with a posterior low-lying placenta to 63% for three or more prior cesareans combined with placenta previa. The factors independently associated with PAS disorders were BMI ≥ 30, previous uterine surgery, previous postpartum hemorrhage, a higher number of prior cesareans, and a placenta previa. Finally, in this high-risk population, the rate of PAS disorders varies greatly, not only with the number of prior cesareans but also with the exact placental location and some of the women's individual characteristics. Risk stratification is thus possible in this population.

Oxidative stress (OS) due to an imbalance between reactive oxygen species (ROS) and antioxidants has been established as an important factor that can negatively affect the outcomes of assisted reproductive techniques (ARTs). Excess ROS exert their pathological effects through damage to cellular lipids, organelles, and DNA, alteration of enzymatic function, and apoptosis. ROS can be produced intracellularly, from immature sperm, oocytes, and embryos. Additionally, several external factors may induce high ROS production in the ART setup, including atmospheric oxygen, CO2 incubators, consumables, visible light, temperature, humidity, volatile organic compounds, and culture media additives. Pathological amounts of ROS can also be generated during the cryopreservation-thawing process of gametes or embryos. Generally, these factors can act at any stage during ART, from gamete preparation to embryo development, till the blastocyst stage. In this review, we discuss the in vitro conditions and environmental factors responsible for the induction of OS in an ART setting. In addition, we describe the effects of OS on gametes and embryos. Furthermore, we highlight strategies to ameliorate the impact of OS during the whole human embryo culture period, from gametes to blastocyst stage.

BackgroundDespite the availability of whole exome (WES) and genome sequencing (WGS), chromosomal microarray (CMA) remains the first-line diagnostic test in most rare disorders diagnostic workup, looking for copy number variations (CNVs), with a diagnostic yield of 10%–20%. The question of the equivalence of CMA and WES in CNV calling is an organisational and economic question, especially when ordering a WGS after a negative CMA and/or WES.MethodsThis study measures the equivalence between CMA and GATK4 exome sequencing depth of coverage method in detecting coding CNVs on a retrospective cohort of 615 unrelated individuals. A prospective detection of WES-CNV on a cohort of 2418 unrelated individuals, including the 615 individuals from the validation cohort, was performed.ResultsOn the retrospective validation cohort, every CNV detectable by the method (ie, a CNV with at least one exon not in a dark zone) was accurately called (64/64 events). In the prospective cohort, 32 diagnoses were performed among the 2418 individuals with CNVs ranging from 704 bp to aneuploidy. An incidental finding was reported. The overall increase in diagnostic yield was of 1.7%, varying from 1.2% in individuals with multiple congenital anomalies to 1.9% in individuals with chronic kidney failure.ConclusionCombining single-nucleotide variant (SNV) and CNV detection increases the suitability of exome sequencing as a first-tier diagnostic test for suspected rare Mendelian disorders. Before considering the prescription of a WGS after a negative WES, a careful reanalysis with updated CNV calling and SNV annotation should be considered.