Reproductive Sciences最新文献

Background: POI is a multifactorial disease due to lack of estrogen resulting in symptoms such as insomnia, osteoporosis, and voiding disorders. For most women, fertility is affected. Autoimmune diseases are chronic diseases caused by disorders of immune regulation that often harm the ovaries. Recent epidemiological studies have reported a correlation between autoimmune diseases (AIDs) and premature ovarian insufficiency (POI). This study aims to explore the causal relationship between AIDs and POI using bidirectional two-sample Mendelian randomization (MR). The data regarded AIDs from the Genome-wide association studies (GWAS) Catalog and the IEU Open GWAS project. POI was obtained from the FinnGen Study. All data were extracted from European populations. We used bidirectional MR with inverse variance weighting (IVW) as the primary study method, supplemented by weighted median and MR Egger validation analyses. Our original data has been uploaded to Figshare, number and distribution of the DOI (DOI: 10.6084 / m9 Figshare. 25,525,585). Figshare is an open-access data storage and sharing platform designed to make it easy for researchers to store, manage, and share their research data, code, and other academic achievements. Our study showed that the liability to Systemic lupus erythematosus (SLE) and Myasthenia gravis (MG) affect POI risk. The reverse MR analysis supported the effect of POI on Crohn's disease (CD). The result of the IVW method was supported by the sensitivity MR analysis. The IVW results showed that the odds ratio (OR) value of SLE was 1.13 and MG was 0.83. In the reverse MR, the OR value of CD was 1.22. We used MR methods to look into the causal association between 13 different kinds of AIDs and POI. Our study took a novel approach to traditional observational studies by adhering to the MR principle, which states that gamete formation depends on random assortment independent of external variables and that genetic variations precede outcomes, reducing the risk of reverse causality. The study found a correlation between SLE, MG, CD, and POI. Patients with SLE should have their ovarian function checked regularly, while those with POI should be aware of the possibility of CD and pay attention to their CD screening. MG, as a protective factor, can reduce the risk of POI.

Uterine myomas can cause infertility. Studies are attempting to determine the indications for myomectomy. However, the multiplicity and localization of myomas complicate this issue. We aimed to develop a visualization tool to aid patients with infertility in their decision-making for myomectomy. We included 191 women with uterine myoma attending an outpatient infertility clinic, of whom 124 patients underwent myomectomy. Of these, 65 (52.4%) patients became pregnant within 17.6 months after surgery, and 54 (83.1%) of them had a live birth. A logistic regression model predicting the pregnancy rate (area under the curve, 0.82; 95% confidence interval, 0.74-0.89; validation value, 74.6%) was generated using the leave-one-out cross-validation method. This model incorporated five factors: age, maximum level of infertility intervention following myomectomy, presence of submucosal myoma, maximum diameter of the myoma, and type of myomas (multiple or single). We successfully visualized the degree of involvement of each factor in the pregnancy rate by developing a nomogram based on this model. We expanded the data from the preoperative magnetic resonance images and applied machine learning using a convolutional neural network. The classification accuracy was 71.4% for sensitivity and 77.7% for specificity. Heatmap images, generated using gradient-weighted class activation mapping to show the classification results of this model, could distinguish between myomas that required enucleation and those that did not. Although a larger sample size is needed to further validate our findings, this innovative pilot study demonstrates the potential of machine learning to refine assessment criteria and improve patient decision-making.

Recurrent spontaneous abortions (RSA) is defined as a loss of two or more consecutive clinically recognized pregnancies before the 20th week of gestation. In RSA, several causative maternal factors are known, but still, 50% of the cases remain unexplained. Evidence suggests that paternal factors are also equally important. Epigenetic phenomenon such as genomic imprinting and regulation of gene expression by miRNAs plays an important role in embryonic and placental development. Two large miRNA clusters, C14MC (Chromosome 14 microRNA cluster) and C19MC (Chromosome 19 microRNA cluster) are imprinted and expressed in the placenta during pregnancy and are known to regulate functionally important processes such as the trophoblast proliferation, adhesion, and migration. Hence, we studied the DNA methylation at the Differentially Methylated Regions (DMRs) of these clusters in spermatozoa and chorionic villi by pyrosequencing. In Spermatozoa, few Cytosine followed by Guanosine (CpG) sites at DMRs of C14MC and C19MC showed significant hypermethylation. In Chorionic villi, CpG sites showed significant hypomethylation in the RSA group as compared to control group. Semen parameters like sperm concentration, sperm motility, morphology, and chromatin compaction were comparable in control and RSA groups. The study suggests aberrant DNA methylation in spermatozoa and chorionic villi at DMRs of both miRNA coding clusters to be associated with RSA.

This study aimed to elucidate the effect of hatching status on in vitro fertilization (IVF) outcomes in frozen-thawed blastocyst transfer cycles. Frozen-thawed embryo transfer (FET) cycles performed at a single fertility center between 2016 and 2021 were retrospectively assessed. Analyses were restricted to 6,821 frozen-thawed blastocyst transfers in women aged 24-47 years. For optimal comparability, double embryo transfer (ET) cycles consisting of one hatching and one hatched blastocyst were excluded. The implantation and pregnancy rates were evaluated and compared between the hatching and hatched blastocyst transfer groups based on patients' age (<38 vs. ≥38 years), blastocyst grade (good vs. bad grade), and the number of transferred embryos (single ET vs. double ET). Hatched blastocyst transfer was associated with higher implantation and clinical pregnancy rates in the single ET group (15.7% and 15.6%, respectively; p<0.001). The transfer of two hatched blastocysts had higher implantation and clinical pregnancy rates compared to the transfer of two hatching blastocysts (19.5% and 20.4%, respectively; p<0.001) in the double ET group. In the hatched blastocyst transfer group, the clinical pregnancy and implantation rates were higher, regardless of each woman's age and embryo quality. The IVF treatment outcomes were improved when the blastocysts were hatched during FET cycles. Hence, hatched blastocyst transfer in FET cycles could be considered a superior method in IVF practice.

This study aimed to determine whether the use of vaginal Endometrin plus intramuscular progesterone on every third day (VIM) in programmed frozen embryo transfer (FET) is associated with lower pregnancy and live birth rates compared to daily intramuscular progesterone (IM). FET data from a single program were collected between November 2018 and December 2021. A total of 903 FETs were analyzed, including 504 FETs in the IM group, and 399 FETs in the VIM group. Inclusion criteria were women undergoing FETs with either 50 mg daily IM progesterone only (control) or 200 mg Endometrin twice daily plus 50 mg IM progesterone on every third day, with the transfer of a single day 5 or 6 frozen embryo. There were no significant differences in patient age at time of FETs, BMI, endometrial thickness, blastocyst quality, or infertility diagnosis between the groups. The VIM had significantly lower positive hCG and clinical pregnancy rates compared to the IM (60.2% vs 72.0% and 40.6% vs 56.7%, respectively, P = 0.0002 and P < 0.0001). The live birth rate was 36.1% in the VIM, compared to 49.4% in the IM (P < 0.0001). These findings also remained significant when excluding FETs with donor egg (35.9% vs 50.1%, P < 0.0001). This study demonstrated that VIM in FET cycles yields significantly lower pregnancy and live birth rates compared to IM along. IM progesterone alone may be preferable to combined Endometrin and IM progesterone in patients undergoing programmed frozen embryo transfers.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in premenopausal women. This investigation was to elucidate the underlying mechanism of endoplasmic reticulum stress (ERS) activation in granulosa cells, which has been implicated in the etiology of PCOS. Differentially expressed genes (DEGs) between PCOS and control groups were integrated with ERS gene lists from databases to identify DE-ERS genes, and functional analyses were performed. Univariate regression analysis and the LASSO method were used to select diagnostic factors, followed by establishing a DE-ERS gene-based diagnostic model. A nomogram model was further generated to predict the risk of PCOS. The correlation between ERS gene expression and immune cell proportion was assessed. A total of 14 DE-ERS genes associated with "protein processing in endoplasmic reticulum", "ferroptosis", and "glycerophospholipid metabolism" were selected as PCOS-related factors. An eight-DE-ERS genes-based diagnostic model was developed and displayed satisfactory performance in the training (Area under curve (AUC) = 0.983) and validation datasets (AUC = 0.802). High risk of PCOS can be accurately predicted, which might contribute to clinical decision-making. Moreover, EDEM1 expression was significantly positively correlated with naive B cell infiltration, while PDIA6 was negatively correlated with neutrophil proportion (P < 0.001). We identified eight novel molecules and developed an ERS gene-based diagnostic model in PCOS, which might provide novel insight for finding biomarkers and treatment methods.

Preeclampsia (PE) is one of the serious complications of pregnancy, and the management of PE remains an important problem for obstetricians. This study aims to identify the characteristics and trends of published articles on PE management through bibliometric analysis. We searched the Web of Science database for articles related to PE management from 2000 to 2022. Metadata was obtained, including the titles, publication dates, authors, institutions, countries, and keywords of all articles, and then network visualization and burst keyword analysis were performed using Citespace and VOSviewer software. A total of 5190 articles were included in the analysis. The number of publications in the field of PE management has steadily increased over the years, and a visual analysis of collaborative networks of authors, institutions, and countries revealed that the United States, United Kingdom, Australia, and Canada have contributed the most to the field and formed extensive collaborations. The Journal of maternal-fetal & neonatal medicine has the most publications in this field, and the Journal of Obstetrics and gynecology has not only more publications but also 64.75 citations per article. The keywords mainly focused on prevention, diagnosis, risk factors, and outcome of PE. In addition, hypertensive disorders of pregnancy and fetal growth restriction have received a lot of attention in this field in recent years. We analyzed the partnerships in the field of PE management through bibliometrics and showed trends and developments in the field. The available results suggest that PE management will continue to be a focus of attention for obstetricians and researchers.

The advancement of next-generation sequencing has spurred the growing adoption of whole-exome sequencing (WES) for genetic screening. Preimplantation genetic testing for monogenic disorders (PGT-M) can effectively prevent the transmission of pathogenic variants. However, interpreting vast data volumes and ensuring precise genetic counseling, especially with variants of uncertain significance (VUS), remains challenging. In this study, we investigated a family with recurrent fetal malformations detected by prenatal ultrasound. WES identified compound heterozygous POMT1 variants, c.1052 + 1G > A and c.1483G > A in the proband; the latter was initially categorized as a VUS. Then our bioinformatics analysis revealed that c.1483G > A variant was located in a highly conserved domain essential for POMT1's enzymatic activity, potentially altering the protein's 3D structure. In vitro studies using HEK293T cells showed that the variant led to aberrant POMT1 mRNA and protein accumulation, impaired cell viability, and abnormal protein localization in the cytoplasm, indicating disruption of normal glycosylation processes. Combining bioinformatics analysis with in vitro experiments, we reclassified the c.1483G > A variant as likely pathogenic. Subsequently, the couple opted for PGT-M, culminating in the birth of a healthy child. Our findings underscore the pivotal role of genetic testing in recurrent fetal malformations and expand the spectrum of POMT1 variants. The successful reclassification of the variant by integrating in vitro experiments with bioinformatics provides substantial evidence for clinicians implementing PGT-M, offering a feasible strategy for counseling with VUS detected by WES.

Uterine leiomyomas are common noncancerous hormonally-dependent neoplasms comprised of uterine smooth-muscle cells and fibroblasts. Despite their significant impact on morbidity, effective non-hormonal medical treatments are lacking. In vitro studies have identified the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway as a promising target in leiomyoma cells. Our objective was to evaluate the efficacy of AZD1480, a JAK 1/2 inhibitor, in treating uterine leiomyomas using a patient-derived xenograft murine model. Ovariectomized immunodeficient mice received an estrogen and progesterone pellet and were subsequently implanted with human leiomyoma tissue surgically resected from premenopausal women not on hormonal medication. Mice were divided into treatment (n = 6) and vehicle control (n = 6) groups receiving either 50 mg/kg of AZD1480 or vehicle via oral gavage for 5 days/week for 28 days. Our results demonstrate a significant AZD1480-mediated reduction in both xenograft volume (59.5% vs. 0.3%; treated vs. control, p < .0001) and weight (56.0% vs. 31.2%; p = 0.03) compared to controls. Moreover, xenografts from the treated group exhibited a significant decrease in cell density(p = 0.01). Levels of pSTAT3-positive cells (4.1% vs. 10.3%), Ki67-positive cells (4.1% vs. 6.5%), and fibrillar collagen (19.8% vs. 29.5%) declined but did not reach statistical significance, whereas AZD1480 treatment significantly reduced blood vessel formation in the xenografts (20.1 vs 45.6 per FOV; p = 0.01). These findings suggest JAK inhibition as a potential treatment for uterine leiomyomas by targeting angiogenesis. However, further studies are warranted to explore alternative JAK inhibitors, examine downstream effects, optimize dosing, and establish clinical efficacy and safety.

Pomegranate (Punica granatum) is a widely cultivated fruit historically recognized for its health benefits and is regarded as a nutritional powerhouse. Pomegranate has a unique composition of bioactive compounds including hydrolysable tannins, anthocyanins, and other polyphenolic components. Of those, punicalagin and its subsequent metabolites are the most extensively studied, demonstrating antioxidant, anti-inflammatory, anti-cancer, and anti-nociceptive activity. The compounds possess promising therapeutic potential for many diseases, including conditions affecting the female reproductive system. This scoping review examines the pharmacodynamics of pomegranate's bioactive compounds and synthesizes the current literature concerning the role in benign gynecological disorders. Pomegranate extract decreased testosterone levels, levels of oxidative stress and inflammation biomarkers in women with polycystic ovary syndrome, erstwhile favorably impacting some cardiovascular risk factors in women. Pomegranate supplementation improved menopause specific health-related quality of life in women. In a pre-clinical murine model following ovariectomy, improved bone formation and reduced vaginal atrophy were associated with pomegranate treatment. Existing data suggests that additional research on the beneficial antioxidant, anti-inflammatory, anti-proliferative, and anti-nociceptive effects of pomegranate extracts for benign gynecologic conditions is warranted.