F&S reviews最新文献

Approximately 15% of couples in the US are affected by infertility, with male factor infertility acting as the sole or contributing factor in 20% and 40% of cases, respectively. Of the numerous potential causes of male infertility, varicocele is the most common and correctable. Although there are several hypotheses for the mechanism by which varicocele may cause symptoms such as infertility, pain, or hypogonadism, many patients with varicocele remain asymptomatic, and it remains unclear why only a subset of men with varicocele develop symptomatic pathology. Biomarkers are measurable indicators of disease presence or progression and have been proposed for use in the diagnosis and management of men with various reproductive conditions, including varicocele. This study examines a range of markers, including proteins, ribonucleic acid, deoxyribonucleic acid, and metabolites. Proteins implicated in heat shock reactions, oxidative stress, and mitochondrial function, including heat shock protein family A member 2, apolipoprotein A2, and TOM22, have been investigated within the context of varicocele when compared with their expression in healthy men. Additionally, potential biomarkers associated with sperm motility and spermatogenesis, such as serpin family A member 5 and adenosine triphosphate synthase delta domain protein, have been identified with studies showing improvement in concentrations post varicocelectomy. The pursuit of noninvasive biomarkers has gained significance for predicting improvement in fertility and assessing responses to varicocelectomy, offering opportunities for early intervention, minimizing unnecessary surgeries, and optimizing patient outcomes. This review consolidates current knowledge, underscores existing gaps, and outlines future research directions refining diagnostic and therapeutic strategies for varicocele-related infertility.

Research into menstrual fluid (MF), also referred to as menstrual blood or effluent in the literature, and its potential as a diagnostic tool has been largely overlooked. The current understanding of the endometrium has been principally derived from invasive techniques, such as endometrial biopsies, yet endometrial tissue is cyclically shed in MF. Menstrual fluid has a composition that distinctly reflects the endometrial environment and provides an easily accessible source of endometrial constituents that can be collected relatively noninvasively using a menstrual cup. Menstrual fluid offers a renewable and inexpensive option that has the potential to replace more invasive and uncomfortable methods of collecting endometrial samples. Menstrual health can provide invaluable insight into the endometrial environment and the development of endometrial disorders. Menstrual fluid has been recently utilized to research the pathogenesis of endometriosis, chronic endometritis, and unexplained infertility; however, some logistical challenges in the recruitment of participants, collection, and processing of MF samples require optimization. This review detailed what we currently know about the composition of MF and the recent advances in MF research, as well as future directions. Menstrual fluid provides a unique window into the endometrium, and further research could help uncover the pathogenesis of endometrial disorders and have exciting prospects as a diagnostic tool.

Objective

To pool all available data from literature and compare the differences in cell percentages and cytotoxicity of peripheral blood, peritoneal fluid, and uterine natural killer (NK) cells (pNK, pfNK, uNK) between individuals with endometriosis and those without. In addition, we examined the differences in NK cells between early and advanced stages of endometriosis.

Evidence review

International databases such as PubMed, Web of Science, Scopus, Google Scholar, and EMBASE through OVID were searched. Meta-analysis was conducted according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol) and PICO (Population, Intervention, Comparison, and Outcome) frame. STATA 17 was used to analyze the data. T² and I² Statistics were calculated to check heterogeneity. Meta-analysis was performed to compare the percentage and cytotoxic activity of NK cells between different groups. A random effect model was used to pool all the available data. Subgroup and sensitivity analysis were used to identify the source of heterogeneity.

Results

We included 29 case control and 2 cross-sectional studies across 13 countries that met our inclusion criteria. There was no significant difference in the percentage of pNK cells (mean difference [MD] 1.94, 95% confidence interval [CI] −0.52, 4.39; I² 94.52%; total of 915 women), and pfNK cells (MD 2.12, 95% CI −5.26, 9.5; I² 96.59%; total 397 women) between women with endometriosis and controls. However, the percentage of uNK cells (MD 3.91, 95% CI 1.63, 6.19; I² 0%; a total of 149 women) was significantly higher in women with endometriosis compared with controls. The study also found that the cytotoxic activity of pNK cells (MD −8.01, 95% CI −13, −3.02; I² 40.27%; total of 187 women), pfNK cells (MD −9.94, 95% C: −13.53, −6.34; I² 0%; total 110 women), and uNK cells (MD −12.1, 95% CI −17.95, −6.27; I² 16.75%; total 104 women) were significantly lower in women with endometriosis compared with the control group. Similarly, the pooled mean lytic unit of pNK cell cytotoxicity in women with endometriosis (MD −2.77, 95% CI −3.91, −1.63; I² 0%; total of 74 women) was significantly lower than controls. However, there was no significant difference in the NK cell cytotoxicity between the early and advanced stages of endometriosis.

Conclusion

The consistent reduction of NK cell cytotoxicity across different samples (peripheral blood, peritoneal fluid, and endometrial tissue) may provide insights into the pathogenesis of endometriosis. Establishing standardized references for the cytotoxicity of uNK, pfNK, and pNK cells, as well as the percentage of uNK cells, is a prerequisite to determining their potential values in clinical diagnosis and treatments.

Chronic endometritis (CE) is a challenging clinical diagnosis that is often encountered in patients with conditions impacting fertility. Evaluation for CE is somewhat controversial, largely because of a lack of consensus regarding appropriate screening methods and benefits of treatment. Testing is relatively invasive, requiring direct endometrial sampling with histologic evaluation for the presence of plasma cells, a key feature of CE. However, other testing methods have been proposed, including, more recently, microbiome testing. Moreover, defined histologic criteria are currently lacking with significant variability in practice patterns regarding diagnosis. We seek to comprehensively review the literature and examine what is known regarding the pathophysiology, histologic findings, clinical presentation, and treatment of CE. We further examine the association of CE and its implications for patients with conditions impacting fertility, including infertility, recurrent pregnancy loss, recurrent implantation failure, and endometriosis. On the basis of the evidence, we aim to better define when to initiate evaluation for CE and to determine indications for treatment. We also provide a clinical algorithm for CE screening and management.

Objective

To assess the initial human chorionic gonadotropin (hCG) value as a predictor of live birth (LB) after in vitro fertilization (IVF) therapy.

Evidence Review

A systematic search of PubMed, Embase, and Google Scholar results between January 1, 1985, and January 20, 2022, was conducted. Studies that reported hCG levels for adult females who underwent IVF treatment and had a positive serum pregnancy test were included. Studies must have measured serum hCG levels before 10 weeks gestational age and calculated cutoff hCG level values for predicting pregnancy outcome from receiver operating characteristic (ROC) curves. Exclusion criteria included spontaneous pregnancies, intrauterine insemination, gamete intrafallopian transfer, and ovulation induction cycles. The outcome assessed was pregnancies resulting in LB. Study quality and risk of bias were assessed via the Newcastle–Ottawa Scale and the QUADAS-2 tool.

Result(s)

A total of 1,510 abstracts were screened, and 157 full texts were reviewed. Twenty-six retrospective cohort studies were selected, which included 34,220 IVF cycles with positive hCG values. Gestational age on the day of hCG level measurement ranged from 23–33 days, with days 28 and 31 as the most frequently occurring days. Day 28 hCG cutoff values for predicting LB ranged from 49.2–108.0 IU/L, with sensitivities ranging from 71.5%–93.7%. Day 31 hCG cutoff values ranged from 145.00–411.45 IU/L, with sensitivities ranging from 61.2%–96.1%. Summary ROC curves generated from bivariate analyses of sensitivity and specificity showed areas under the curves of 0.845 and 0.718 for days 28 and 31, respectively. Summary ROC curves of day 31 hCG values after fresh and frozen-thawed embryo transfers showed areas under the curve of 0.701 and 0.889, respectively.

Conclusion(s)

Day 28 hCG cutoff values may provide more reliable predictions for LB compared with day 31. On day 28, an hCG level of 49.2 IU/L would identify 93.7% of the patients who will go on to have a LB, and an hCG level of 108 IU/L would identify 71.5%. However, significant study heterogeneity complicates the quality of estimated hCG levels, sensitivity, and specificity comparisons.

Objective

To assess the current literature evaluating the epigenetics of endometriosis in humans.

Evidence Review

A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines within PubMed, EBSCOhost, Cochrane Library, Embase, Scopus, and Web of Science Core Collection. A comprehensive search strategy was developed by a data informationist. Observational and interventional studies assessing epigenetics in humans published in English up to January 15, 2023, were included. Two reviewers independently screened studies evaluating the role of epigenetics in endometriosis. The risk of bias was assessed using Cochrane RoB 2.0 tool and the Newcastle-Ottawa scale. Extracted data were analyzed descriptively.

Results

We identified 18,639 studies, of which 57 were included, comprising 1,623 patients with endometriosis and 1,243 controls. Among the 57 studies included, 50 (88%) were case-control studies, and 7 (12%) were cross-sectional. Fifty-nine percent of the studies were Asian, 25% were from America, 14% were European, and 2% were from Africa. Acetylation and methylation were the two main key histone modifications that were centered in this review. Accordingly, we classified the studies as those focusing on genome-wide methylation and those on histone acetylation. Several studies identified an association between endometriosis and hypermethylated genes, including the PGR-B, SF-1, and RASSF1A. The genes HOXA10, COX-2, IL-12B, and GATA6 were found to be hypomethylated in endometriotic tissue by several studies. In regard to histone modification, multiple studies reported that the acetylation levels of histones H3 and H4 affect multiple genes associated with endometriosis. In addition, HDAC2 was found to be elevated in patients with endometriosis in two studies.

Conclusion

Several studies reported a significant difference between specific genes’ methylation levels in endometrial biopsies and normal tissue, which suggests that DNA methylation may play an important role in the modulation of the genotype in endometriotic tissue. Acetylation and methylation are the two key histone modifications leading to differential gene expression in endometriotic tissues. The alterations in gene expression reported by the 57 studies can have direct implications on cell cycle growth, cell cycle arrest, and apoptosis and, therefore, might play a key role in the pathogenesis of endometriosis. This review offers insight into the fact that histone modifications need further research to evaluate their role as potential biomarkers and treatment targets for endometriosis. Although several key similarities were reported, there were some disagreements among the results, which might be attributable to the heterogeneity between studies. Further research with a more robust standardization is needed to validate the epigenetic