Reproductive Medicine and Biology最新文献

Purpose: This study aimed to identify factors influencing the accuracy and effectiveness of non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) and develop clinical integration workflows to provide alternative embryo assessment and improve pregnancy outcomes.

Methods: A two-phase study analyzed 341 blastocysts and spent culture medium (SCM) from 90 IVF patients. Phase 1 assessed niPGT-A accuracy by comparing SCM/trophectoderm (TE) with whole blastocysts (100 frozen embryos). Phase 2 examined concordance, assisted hatching, and culture-duration effects, focusing on outcomes after frozen embryo transfer using 241 fresh embryos. Nineteen euploid-TE/euploid-SCM and 14 euploid-TE/aneuploid-SCM blastocysts were transferred, and a meta-analysis was conducted using data from 163 euploid embryos across four studies.

Results: The optimized niPGT-A workflow achieved a superior PPV of 92.1% and accuracy of 91.3%, outperforming conventional PGT-A. Ploidy and sex concordances were 76.5% and 98.9% among 183 fresh embryos. Assisted hatching improved amplification rates, while culture duration/ploidy did not impact concordance. Meta-analysis showed SCM-guided embryo transfer significantly improved pregnancy outcomes, compared to TE biopsy.

Conclusion: This optimized niPGT-A procedure provides a highly accurate chromosomal assessment, seamlessly integrates with IVF workflows. It supports informed embryo transfer decisions, improves outcomes, reduces embryo damage risk, and limits invasive procedures, enhancing clinical management in reproductive medicine.

Purpose: Recurrent spontaneous abortion (RSA) is an abnormal phenomenon that severely affects women's quality of life. Inhibiting Th17 cell differentiation can alleviate RSA. This research explored the mechanism by which BRD4 Inhibitor (BETi) suppressed the differentiation of Th17 cells to mitigate RSA.

Methods: PBMCs and Naive CD4⁺ T cells were induced to differentiate into Th17 and Treg cells. An abortion-prone pregnancy mouse model was constructed by intraperitoneal injection of lipopolysaccharide. The Th17/Treg ratio was determined by flow cytometry. The association between STAT3 and IL-17A promoter was investigated by ChIP and dual luciferase assays. Co-IP and yeast two-hybrid assays were used to determine BRD4 binding to STAT3. The markers of Th17/Treg cell differentiation and lipid synthesis were checked by ELISA, IHC, RT-qPCR, and Western blot.

Results: The Th17/Treg ratio and the expression levels of BRD4, STAT3, and IL-17A were elevated, while STAT5b expression was down-regulated in RSA patients. BETi or STAT3 knockdown decreased the differentiation of Th17 cells and lipid synthesis. BRD4 inhibition impaired STAT3-mediated IL-17A transcription. BETi inhibited embryo absorption in mice.

Conclusions: BETi inhibits the differentiation of Th17 cells in RSA by reducing the STAT3-mediated IL-17A expression.

Purpose: Endometrial receptivity is a critical determinant of successful embryo implantation and is intricately linked to the pathophysiology of infertility. This study aimed to elucidate the role of exosomal miR-203a-3p in regulating endometrial receptivity, thereby providing insights into potential therapeutic strategies for infertility treatment.

Methods: Transcriptomic profiling of exosomes was performed to identify factors associated with endometrial receptivity. miR-203a-3p, exhibiting high expression levels in exosomes, was selected for further investigation. Human endometrial tissues from different menstrual phases and patient groups were analyzed for miR-203a-3p expression. Functional studies using miR-203a-3p mimics and engineered exosomes were conducted in non-receptive AN3-CA cells.

Results: During the secretory phase, miR-203a-3p expression was markedly higher in the endometria of fertile women than in those of infertile women. Overexpression of miR-203a-3p, which directly targeted Snail family transcriptional repressor (SNAI1), resulted in increased E-cadherin expression and enhanced spheroid attachment in non-receptive AN3-CA cells. Consistently, delivery of miR-203a-3p mimics via engineered exosomes increased E-cadherin expression by suppressing SNAI1 and enhanced spheroid adhesion in AN3-CA cells.

Conclusions: Our data highlight the importance of the miR-203a-3p/SNAI1/E-cadherin axis in governing endometrial receptivity. Exosome-mediated delivery of miR-203a-3p mimics may represent a promising therapeutic strategy for improving embryo implantation and treating infertility.

Purpose: This study investigated the therapeutic effects of Chitosan/Alginate-loaded Astragalus hamosus extract (Chn/Al-AH) on the expression of miRNA-222 and ESR1 genes, inflammatory cytokines, lipid profile, and reproductive hormones in a rat model of polycystic ovary syndrome (PCOS) induced by estradiol valerate (EV).

Methods: Twenty-five female Wistar rats, weighing an average of 180 g, were divided into control and PCOS groups. The PCOS model was induced by a single intramuscular injection of EV (4 mg/kg). After 28 days of PCOS induction, the rats were orally administered Chitosan/Alginate-loaded AH at 5, 10, and 15 mg/kg. Following 4 weeks of treatment, histological and biochemical parameters, pro-inflammatory cytokines, body weight, and the expression of miRNA-222 and ESR1 genes were evaluated.

Results: EV-induced PCOS rats showed increased body weight, dyslipidemia, elevated inflammatory cytokines, disrupted sex hormone levels, upregulation of miRNA-222, and decreased ESR1 expression. Treatment with Chn/Al-AH significantly ameliorated these alterations by improving metabolic and endocrine profiles, reducing miRNA-222 expression, enhancing follicular development, decreasing cystic follicles, and promoting corpus luteum formation.

Conclusions: Chn/Al-AH demonstrates therapeutic potential in mitigating hormonal, inflammatory, and genetic disruptions associated with PCOS in rats.

Background: We appreciate the commentary by Satapathy, Mehta, and Sah on our study examining biochemical pregnancy loss (BPL) in recurrent pregnancy loss (RPL) following euploid embryo transfer. Their remarks on statistical interpretation, ascertainment bias, and sample size overlap coincide with limitations already acknowledged in our article.

Methods: Our analysis was exploratory in nature and not powered for definitive conclusions. We acknowledge the need for larger prospective studies using standardized biochemical monitoring and advanced statistical approaches.

Results: The commentary highlights methodological considerations that align with our stated limitations. Despite these, our findings indicate that BPL may provide clinically relevant information beyond conventional pregnancy outcomes.

Conclusion: Against the backdrop of divergent international definitions regarding whether biochemically recognized losses should count toward RPL, our findings support multicenter investigations to clarify the prognostic and therapeutic implications of including BPL and to inform harmonized definitions and clinical practice.

Purpose: To compare the efficacy of migration-gravity sedimentation (MGS) and density gradient centrifugation (DGC) for sperm preparation in intracytoplasmic sperm injection (ICSI) cycles, focusing on sperm DNA fragmentation (SDF) and ICSI outcomes.

Methods: In this prospective study, 32 patients who underwent ICSI using sibling oocytes were enrolled. Half of the oocytes were fertilized with DGC-prepared sperm and the other half with MGS-prepared sperm. Semen parameters were assessed using computer-assisted sperm analysis (CASA), and SDF levels were measured using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay before and after sperm preparation. Fertilization, blastocyst development, and clinical pregnancy rates were compared between the two groups.

Results: MGS significantly reduced SDF levels compared to raw semen and DGC. CASA demonstrated enhanced motility, straightness, and linearity with MGS, although curvilinear velocity, average path velocity, and amplitude of lateral head displacement were lower. Fertilization and clinical outcomes, including blastocyst formation and pregnancy rates, were comparable between the groups.

Conclusion: MGS is a simple, centrifuge-free, and low-cost sperm preparation technique that effectively reduces sperm DNA fragmentation and achieves ICSI outcomes similar to those of DGC. These findings indicate that MGS may be a viable alternative to assisted reproductive technology, specifically in patients without male-factor infertility.

Trial registration: This study was registered in the University Hospital Medical Information Network (UMIN000043585).

Purpose: To investigate the histopathological association between chronic endometritis (CE) and adenomyosis, focusing on basal endometrial alterations and the potential involvement of tissue injury and repair (TIAR) mechanisms.

Methods: This retrospective case-control study included 146 propensity score-matched hysterectomy specimens (73 adenomyosis, 73 controls). CE was diagnosed via CD38 immunohistochemical staining, identifying ≥ 5 plasma cells per high-power field. Basal endometrial thickness was measured digitally at the endo-myometrial junction. Basal endometrial loss was defined as the absence of the basal layer in at least two of three regions.

Results: CE was significantly more frequent in the adenomyosis group (23.3%) than in controls (9.6%; p = 0.028). Basal endometrial loss, observed in 23.3% of cases, was strongly associated with CE (47% vs. 7.1%; p < 0.001). In patients with measurable thickness, a 0.15 mm cutoff predicted CE with AUC 0.888 (sensitivity 83.3%, specificity 86.9%). In multivariate analysis, basal endometrial loss was an independent risk factor for CE (adjusted OR 10.45, 95% CI 4.12-26.51; p < 0.001).

Conclusions: CE is significantly associated with adenomyosis. Basal endometrial loss may mediate this relationship through TIAR-related mechanisms, suggesting CE as a potential therapeutic target in adenomyosis.

Purpose: Preimplantation genetic testing for monogenic disorders (PGT-M) offers BRCA variant carriers the option of preventing hereditary cancer transmission. We investigated the awareness and attitudes toward PGT-M among patients with breast cancer who underwent fertility preservation.

Methods: A questionnaire-based survey was administered to 264 patients with breast cancer who were eligible for oocyte or embryo cryopreservation at in vitro fertilization clinics between October 2024 and March 2025. A total of 161 valid responses were analyzed. The survey assessed BRCA testing status, PGT-M awareness, willingness to undergo PGT-M, and opinions on future availability.

Results: The uptake rate of BRCA1/2 testing was 53.4%; 14% of the respondents were variant carriers. Only 16.8% had prior awareness of PGT-M, and 47.8% expressed a willingness to use PGT-M if available. Among BRCA-variant carriers, 3.3% reported that they would consider PGT-M, and 75% believed it should be made available upon request. Overall, 68.3% supported information sharing between oncology and fertility providers.

Conclusion: These findings highlight the importance of expanding reproductive options and patient awareness of PGT-M in the care of patients with hereditary cancer. Discussions should focus on how best to provide accurate information and enable informed reproductive choices for those at genetic risk.

Purpose: This study evaluated the feasibility of single-nucleotide polymorphism (SNP) genotyping using dried blood spot (DBS) samples stored under various conditions, based on the genotyping success rate and concordance with whole blood results. It also examined associations between selected SNPs and endometriosis risk in Japanese women.

Methods: DBS samples from 41 cohort participants and 28 hospital patients were used to assess genotyping feasibility. Five endometriosis-associated SNPs-rs10965235, rs12700667, rs12024204, rs16826658, and rs801112-were genotyped in 37 cases and 144 controls. Genotype distributions were evaluated for Hardy-Weinberg equilibrium (HWE) using Pearson's χ ² test or, when appropriate, Fisher's exact test, with a significance threshold of p < 0.05. Fisher's exact test was used for association analysis.

Results: SNP genotyping for rs12700667 showed 100% success and complete concordance between DBS and whole blood samples under all storage conditions. Four of five SNPs met HWE, while rs10965235 significantly deviated from it (p = 0.0225). The CC genotype of rs10965235 was potentially associated with lower endometriosis risk (odds ratio: 0.19), although this was not statistically significant after correction.

Conclusions: DBS is a robust DNA source for SNP genotyping under various conditions and suitable for mail-based epidemiological studies. Population-specific validation is essential when applying GWAS findings.

Purpose: Compare reproductive outcomes between patients with subtle distal fallopian tube abnormalities (SDFTA) and unexplained infertility (UI) undergoing in vitro fertilization (IVF), exploring influencing factors.

Methods: This retrospective study analyzed 447 women undergoing their first IVF cycle after laparoscopic evaluation for UI between January 2019 and December 2021. Based on laparoscopic findings, 162 women were classified into the SDFTA group and 285 into the UI group. Propensity score matching (PSM) created 160 matched pairs. The primary outcome was the cumulative live birth rate (CLBR) over 24 months.

Results: The CLBR per oocyte retrieval cycle, biochemical pregnancy rate, clinical pregnancy rate, live birth rate per transfer, and preterm birth rate were comparable between the two groups (p > 0.05). However, the SDFTA group had a significantly lower early miscarriage rate (8.3% vs. 16.1%, p = 0.036) but a higher ectopic pregnancy rate (5.8% vs. 1.3%, p = 0.033). Independent predictors of CLBR were age at retrieval, the number of oocytes retrieved, and the number of IVF cycles.

Conclusions: In conclusion, despite an increased risk of ectopic pregnancy, patients with SDFTA undergoing IVF exhibit favorable cumulative reproductive outcomes.