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Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding and infertility and are frequent manifestations of polycystic ovary syndrome (PCOS). There are many potential causes and contributors to ovulatory dysfunction that challenge clinicians, trainees, educators, and those who perform basic, translational, clinical and epidemiological research. Similarly, therapeutic approaches to ovulatory dysfunction potentially involve a spectrum of lifestyle, psychological, medical and procedural interventions. Collaborative research, effective education and consistent clinical care remain challenged by the absence of a consensus comprehensive system for classification of these disorders. The existing and complex system, attributed to the World Health Organization (WHO), was developed more than three decades ago and did not consider more than 30 years of research into these disorders in addition to technical advances in imaging and endocrinology. This article describes the development of a new classification of ovulatory disorders performed under the aegis of the International Federation of Gynecology and Obstetrics (FIGO) and conducted using a rigorously applied Delphi process. The stakeholder organizations and individuals who participated in this process comprised specialty journals, experts at large, national, specialty obstetrical and gynecological societies, and informed lay representatives. After two face-to-face meetings and five Delphi rounds, the result is a three-level multi-tiered system. The system is applied after a preliminary assessment identifies the presence of an ovulatory disorder. The primary level of the system is based on an anatomic model (Hypothalamus, Pituitary, Ovary) that is completed with a separate category for PCOS. This core component of the system is easily remembered using the acronym HyPO-P. Each anatomic category is stratified in the second layer of the system to provide granularity for investigators, clinicians and trainees using the 'GAIN-FIT-PIE' mnemonic (Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and Vascular; Physiological, Idiopathic, Endocrine). The tertiary level allows for specific diagnostic entities. It is anticipated that, if widely adopted, this system will facilitate education, clinical care and the design and interpretation of research in a fashion that better informs progress in this field. Integral to the deployment of this system is a periodic process of reevaluation and appropriate revision, reflecting an improved understanding of this collection of disorders.

Selective serotonin reuptake inhibitors (SSRIs), including citalopram, are widely used antidepressants during pregnancy. However, the effects of prenatal exposure to citalopram on neurodevelopment remain poorly understood. We aimed to investigate the impact of citalopram exposure on early neuronal differentiation of human embryonic stem cells using a multi-omics approach. Citalopram induced time- and dose-dependent effects on gene expression and DNA methylation of genes involved in neurodevelopmental processes or linked to depression, such as BDNF, GDF11, CCL2, STC1, DDIT4 and GAD2. Single-cell RNA-sequencing analysis revealed distinct clusters of stem cells, neuronal progenitors and neuroblasts, where exposure to citalopram subtly influenced progenitor subtypes. Pseudotemporal analysis showed enhanced neuronal differentiation. Our findings suggest that citalopram exposure during early neuronal differentiation influences gene expression patterns associated with neurodevelopment and depression, providing insights into its potential neurodevelopmental impact and highlighting the importance of further research to understand the long-term consequences of prenatal SSRI exposure. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What changes occur in the endometrium during aging, and do they impact fertility? SUMMARY ANSWER Both the transcriptome and cellular composition of endometrial samples from women of advanced maternal age (AMA) are significantly different from that of samples from young women, suggesting specific changes in epithelial cells that may affect endometrial receptivity. WHAT IS KNOWN ALREADY Aging is associated with the accumulation of senescent cells in aging tissues. Reproductive aging is mostly attributed to the decline in ovarian reserve and oocyte quality, whereas the endometrium is a unique complex tissue that is monthly renewed under hormonal regulation. Several clinical studies have reported lower implantation and pregnancy rates in oocyte recipients of AMA during IVF. Molecular studies have indicated the presence of specific mutations within the epithelial cells of AMA endometrium, along with altered gene expression of bulk endometrial tissue. STUDY DESIGN, SIZE, DURATION Endometrial transcriptome profiling was performed for 44 women undergoing HRT during the assessment of endometrial receptivity before IVF. Patients younger than 28 years were considered as the young maternal age (YMA) group (age 23–27 years) and women older than 45 years were considered as the AMA group (age 47–50 years). Endometrial biopsies were obtained on Day 5 of progesterone treatment and RNA was extracted. All endometrial samples were evaluated as being receptive based on the expression of 68 common endometrial receptivity markers. Endometrial samples from another 24 women classified into four age groups (YMA, intermediate age group 1 (IMA1, age 29–35), intermediate age group 2 (IMA2, age 36–44), and AMA) were obtained in the mid-secretory stage of a natural cycle (NC) and used for validation studies across the reproductive lifespan. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 24 HRT samples (12 YMA and 12 AMA) were subject to RNA sequencing (RNA-seq) and differential gene expression analysis, 20 samples (10 YMA and 10 AMA) were used for qPCR validation, and 24 NC samples (6 YMA, 6 IMA1, 6 IMA2 and 6AMA) were used for RNA-seq validation of AMA genes across the woman's reproductive lifespan. Immunohistochemistry (IHC) was used to confirm some expression changes at the protein level. Computational deconvolution using six endometrial cell type-specific transcriptomic profiles was conducted to compare the cellular composition between the groups. MAIN RESULTS AND THE ROLE OF CHANCE Comparisons between YMA and AMA samples identified a lower proportion of receptive endometria in the AMA group (P  = 0.007). Gene expression profiling identified 491 differentially expressed age-sensitive genes (P adj < 0.05) that revealed the effects of age on endometrial epithelial growth and receptivity, likely contributing to decreased reproductive performance. Our results indicate that changes in the expression of the cellular senescence marker p16INK4a and genes associated with metabolism, inflammation, and hormone response are involved in endometrial aging. Importantly, we demonstrate that the proportion of multi-ciliated cells, as discovered based on RNA-seq data deconvolution and tissue IHC results, is affected by endometrial aging, and propose a putative onset of age-related changes. Furthermore, we propose that aging has an impact on the transcriptomic profile of endometrial tissue in the context of endometrial receptivity. LARGE SCALE DATA The raw sequencing data reported in this article are deposited at the Gene Expression Omnibus under accession code GSE236128. LIMITATIONS, REASONS FOR CAUTION This retrospective study identified changes in the endometrium of patients undergoing hormonal replacement and validated these changes using samples obtained during a NC. However, future studies must clarify the importance of these findings on the clinical outcomes of assisted reproduction. WIDER IMPLICATIONS OF THE FINDINGS The findings reported in this study have important implications for devising future strategies aimed at improving fertility management in women of advanced reproductive age. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by the Estonian Research Council (grant no. PRG1076), Horizon 2020 innovation grant (ERIN, grant no. EU952516), Enterprise Estonia (grant no. EU48695), MSCA-RISE-2020 project TRENDO (grant no. 101008193), EU 874867 project HUTER, the Horizon Europe NESTOR grant (grant no. 101120075) of the European Commission, the EVA specialty program (grant no. KP111513) of the Maastricht University Medical Center (MUMC+), MICIU/AEI/10.13039/501100011033 and FEDER, EU projects Endo-Map (grant no. PID2021-12728OB-100), ROSY (grant no. CNS2022-135999), and the National Science Fund of Bulgaria (grant no. KII-06 H31/2). The authors declare no competing interests. [ABSTRACT FROM AUTHOR]

Introduction: Available data on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and pregnancy outcomes mostly refer to women contracting the infection during advanced pregnancy or close to delivery. There is limited information on the association between SARS‐CoV‐2 infection in early pregnancy and outcomes thereof. Material and methods: We aimed to systematically review the maternal, fetal and neonatal outcomes following SARS‐CoV‐2 infection in early pregnancy, defined as <20 weeks of gestation (PROSPERO Registration 2020 CRD42020177673). Searches were carried out in PubMed, Medline, EMBASE, and Scopus databases from January 2020 until April 2023 and the WHO database of publications on coronavirus disease 2019 (COVID‐19) from December 2019 to April 2023. Cohort and case–control studies on COVID‐19 occurring in early pregnancy that reported data on maternal, fetal, and neonatal outcomes were included. Case reports and studies reporting only exposure to SARS‐CoV‐2 or not stratifying outcomes based on gestational age were excluded. Data were extracted in duplicate. Meta‐analyses were conducted when appropriate, using R meta (R version 4.0.5). Results: A total of 18 studies, 12 retrospective and six prospective, were included in this review, reporting on 10 147 SARS‐CoV‐2‐positive women infected in early pregnancy, 9533 neonates, and 180 882 SARS‐CoV‐2 negative women. The studies had low to moderate risk of bias according to the Newcastle–Ottawa quality assessment Scale. The studies showed significant clinical and methodological heterogeneity. A meta‐analysis could be performed only on the outcome miscarriage rate, with a pooled random effect odds ratio of 1.44 (95% confidence interval 0.96–2.18), showing no statistical difference in miscarriage in SARS‐CoV‐2‐infected women. Individual studies reported increased incidences of stillbirth, low birthweight and preterm birth among neonates born to mothers affected by COVID‐19 in early pregnancy; however, these results were not consistent among all studies. Conclusions: In this comprehensive systematic review of available evidence, we identified no statistically significant adverse association between SARS‐CoV‐2 infection in early pregnancy (before 20 weeks of gestation) and fetal, neonatal, or maternal outcomes. However, a 44% increase in miscarriage rate is concerning and further studies of larger sample size are needed to confirm or refute our findings. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the impact of maternal SARS‐CoV‐2 infection at the time of admission for delivery on labor process and outcomes of vaginal birth. Material and methods: A cohort study was carried out at the Obstetrics Department of Anhui Provincial Hospital, China, where universal reverse transcriptase polymerase chain reaction (RT‐PCR) testing for SARS‐CoV‐2 infection was introduced for all women admitted for labor and delivery from December 1–31, 2022. Women were divided into positive and negative groups based on the test result. All women having a singleton vaginal birth were included in final analysis. The effect of SARS‐CoV‐2 positivity on labor process and outcomes of vaginal birth was estimated by regression analyses. Results: Among a total of 360 women included, 87 had a positive SARS‐CoV‐2 test and 273 a negative test. Women in the positive group had an increased likelihood of having longer labor (median 9.3 vs 8.3 hours; sB [log‐transformed] 0.19; 95% confidence interval [CI] 0.09–0.28), episiotomy (39.1% vs 23.8%; adjusted odds ratio [aOR] 2.31; 95% CI 1.27–4.21), grade III meconium‐stained amniotic fluid (19.5% vs 7.0%; aOR 2.52; 95% CI 1.15–5.54) and postpartum hospital stay exceeding 37 hours (58.6% vs 46.5%; aOR 1.71; 95% CI 1.00–2.91). They had reduced rates exclusive breastfeeding (26.7% vs 39%; aOR 0.21; 95% CI 0.09–0.46) as well as mixed feeding (46.5% vs 52.2%; aOR 0.28; 95% CI 0.13–0.60) at 1 week postpartum. No significant differences were observed in other aspects of labor process and birth outcomes, including the uptake of labor analgesia, postpartum hemorrhage (>500 mL) or neonatal outcomes. Conclusions: A positive maternal SARS‐CoV‐2 test in labor among women having vaginal birth was associated with a slightly longer duration of labor, increased likelihood of episiotomy, increased incidence of grade III meconium‐stained amniotic fluid, a longer postpartum hospital stay and a lower rate of breastfeeding 1 week postpartum. However, it did not have an adverse impact on other birth outcomes. [ABSTRACT FROM AUTHOR]

The article discusses the challenges and opportunities presented by the integration of artificial intelligence (AI) and machine learning (ML) in scientific publishing. The main challenge is how to authenticate the validity and quality of research, as AI/ML tools can produce counterfeit reports. Different journals have varying opinions on the use of AI/ML, with some rejecting any output produced with AI/ML assistance and others allowing it. Guidelines have been suggested to transparently report and acknowledge the use of AI/ML techniques in article preparation. The article emphasizes the need for intelligent oversight, transparency, and fairness in integrating AI in the editorial workflow. The authors conclude that a collaborative effort is needed to harness AI/ML techniques for the benefit of patients. [Extracted from the article]

To systematically identify and critically assess the quality of clinical practice guidelines (CPGs) on management fetal growth restriction (FGR). Medline, Embase, Google Scholar, Scopus and ISI Web of Science databases were searched to identify all relevant CPGs on FGR. Diagnostic criteria of FGR, recommended growth charts, recommendation for detailed anatomical assessment and invasive testing, frequency of fetal growth scans, fetal monitoring, hospital admission, drugs administrations, timing at delivery, induction of labor, postnatal assessment and placental histopathological were assessed. Quality assessment was evaluated by AGREE II tool. Twelve CPGs were included. Twenty-five percent (3/12) of CPS adopted the recently published Delphi consensus, 58.3% (7/12) an estimated fetal weight (EFW)/abdominal circumference (AC) EFW/AC <10th percentile, 8.3% (1/12) an EFW/AC <5th percentile while one CPG defined FGR as an arrest of growth or a shift in its rate measured longitudinally. Fifty percent (6/12) of CPGs recommended the use of customized growth charts to assess fetal growth. Regarding the frequency of Doppler assessment, in case of absent or reversed end-diastolic flow in the umbilical artery 8.3% (1/12) CPGs recommended assessment every 24–48, 16.7% (2/12) every 48–72 h, 1 CPG generically recommended assessment 1–2 times per week, while 25 (3/12) did not specifically report the frequency of assessment. Only 3 CPGs reported recommendation on the type of Induction of Labor to adopt. The AGREE II standardized domain scores for the first overall assessment (OA1) had a mean of 50%. There is significant heterogeneity in the management of pregnancies complicated by FGR in published CPGs. [ABSTRACT FROM AUTHOR]

Problem: Vaginal bleeding during early pregnancy is estimated to occur in 20% of all pregnancies and it is often difficult to predict who will ultimately miscarry. The role of immune cells in early pregnancy loss is poorly understood. Method of Study: In this prospective cohort study, 28 pregnant women presenting with first‐trimester vaginal bleeding donated vaginal blood, peripheral venous blood, and saliva during their initial emergency room visit, and at a follow‐up. The composition, frequency, and phenotype of immune cells in the vaginal blood were determined using flow cytometry. The proteome of serum and saliva was analyzed with OLINK proximity extension assay and correlated to vaginal immune cell phenotype and outcome of pregnancy. The course and outcome of pregnancies were followed and recorded. Results: Vaginal blood contained all main immune cell lineages including B cells, NK cells, T cells, and monocytes/macrophages. Notably, vaginal blood immune cells expressed tissue residency markers including CD49a. Women who subsequently miscarried had a higher frequency of vaginal blood CD49a+ NK cells compared to those who did not miscarry, and this correlated with serum levels of granzyme A and H, as well as CSF1, CAIX, and TWEAK. Women in the miscarriage group also had a higher frequency of peripheral blood T cells expressing CD49a. Conclusions: Our study provides novel insight into human reproductive immunology in relation to miscarriage. Tissue‐resident NK cells in vaginal blood alone or in combination with serological biomarkers hold potential as prognostic factors in the prediction of pregnancy outcome in women with early pregnancy bleedings. [ABSTRACT FROM AUTHOR]