Reproductive Medicine and Biology最新文献

Purpose: Fetal cells in maternal blood are a pure source of fetal genomic DNA for noninvasive prenatal testing (NIPT), if successfully isolated. We assessed whether single-cell genome and transcriptome sequencing (G&T-seq) can be applied to efficiently isolate fetal nucleated red blood cells (fNRBCs) suitable for genetic testing.

Methods: Using umbilical cord blood as a model, we isolated 165 single NRBC candidates from four samples and 12 single lymphocytes as controls from one sample. G&T-seq was used to estimate the maturation stage of each NRBC candidate from the transcriptome data, and genomic integrity was assessed using shallow whole-genome sequencing (WGS) data.

Results: Multi-dimensional scaling (MDS) of the transcriptome data revealed that five NRBC candidates clustered separately, classifying them as primitive NRBCs. Two of these cells showed high yields of WGS libraries and high mapping rates comparable to control lymphocytes, suggesting an intact nuclear genome.

Conclusions: G&T-seq effectively identified primitive NRBCs with high-quality DNA among candidate cells dominated by mature RBCs. Single-cell multi-omics technology may advance the development of fNRBC-based NIPT.

This commentary addresses Kuwabara et al.'s study on biochemical pregnancy loss (BPL) in recurrent pregnancy loss (RPL) patients following euploid embryo transfers. While their methodology minimizes embryonic bias and strengthens maternal factor assessment, concerns regarding statistical interpretation and potential ascertainment bias limit generalizability. Nonetheless, this study raises important questions regarding the incorporation of BPL into RPL diagnostic frameworks.

Background: Mitochondria play a critical role in cellular bioenergetics and signaling, with particular importance in the context of reproductive biology. This review summarizes their role in reproduction and explores current and emerging mitochondrial therapies for fertility treatment.

Methods: A comprehensive literature search using terms like mitochondria, infertility, reproduction, gametes, mitochondrial replacement, and mitochondrial transplantation identified relevant studies on mitochondria's role in gametogenesis, fertilization, and early embryonic development in relevant databases. Selected publications were reviewed and summarized to present current and future mitochondrial therapies for fertility.

Main findings: Mitochondrial dynamics and functions are critical for meeting the energy requirements of essential reproductive processes, including gametogenesis, fertilization, and early embryonic development. Dysregulation of mitochondrial function has been associated with a range of reproductive disorders, such as infertility, recurrent pregnancy loss, and maternally inherited mitochondrial diseases. Emerging therapeutic strategies, such as mitochondrial replacement therapy, antioxidant supplementation, and mitochondrial transplantation, offer promising avenues for overcoming these challenges and improving reproductive outcomes.

Conclusions: Utilizing mitochondrial-based therapies represents a promising and innovative approach in the advancement of fertility treatments. Ongoing research and clinical development in this area hold significant potential to enhance reproductive outcomes and improve the quality of life for individuals and couples facing fertility challenges.

Background: In in vitro fertilization (IVF), transferring frozen-thawed blastocysts is a widely adopted practice. This meta-analysis aims to evaluate the reproductive outcomes of transferring blastocysts derived from frozen-thawed cleavage embryos (FT-CDB group) compared to direct frozen-thawed blastocyst (DFB group) transfers.

Methods: We searched the following electronic databases for relevant studies: PubMed/MEDLINE, EMBASE, Scopus, and Web of Science. Studies were included if they compared the clinical and neonatal outcomes of IVF patients receiving either FT-CDB or DFB transfer with vitrification method. The protocol for this review has been registered in PROSPERO.

Results: A total of seven studies (2057 patients) were included in the analysis. Participants in the FT-CDB group demonstrated significantly higher odds of achieving clinical pregnancy (OR 1.24, 95% CI 1.03-1.49, p = 0.022, I ² = 27%), and live birth (OR 1.31, 95% CI 1.08-1.60, p = 0.007, I ² = 0%) compared to the DFB group. No significant differences were observed in the birth weights of infants between the groups (MD -87.05 g, 95% CI -293.77 to 119.67, p = 0.41, I ² = 83%).

Conclusion: Transferring blastocysts derived from frozen-thawed cleavage embryos is associated with higher odds of clinical pregnancy and live birth compared to frozen-thawed blastocyst transfers.

Trial registration: PROSPERO number: CRD42024591620.

Background: This systematic review aimed to evaluate whether specific single nucleotide polymorphisms (SNPs) in miRNAs are associated with recurrent implantation failure (RIF).

Methods: A comprehensive literature search was conducted across PubMed-MEDLINE, Web of Science, Scopus, and the Excerpta Medica DataBASE.

Results: The Newcastle-Ottawa Scale (NOS) yielded an intermediate to high quality, with one study rated with 6 stars, and the remaining four with 7 stars. RIF risk-related genotypes included miR-196a, miR-449b, miR-34a, miR-146aCG+GG-miR-196a2CC, miR-149TT-miR-196a2CC, miR-196a2CC-miR-499AA, miR-608GC-miR-938CC, miR-27aAG-miR-423CC/miR-604AG/GG and miR-34aC>A AA-miR-130aG>A GG. Protective combinations included miR-1302-3, miR-631II-miR-1302-3CT, and miR-938CC-miR-1302-3CT. Protective allele combinations G-T-T-A, C-T, T-T-G, T-T and G-C-A-G, G-A-G, A-G-G were less frequent in RIF cases, whereas A-T-C, T-C-C-T, T-C-T, A-C-G-A, A-A-G-G, G-A-A-A, A-A-C-A and G-G-A haplotypes were more commonly associated with increased risk. Notably, miR-608 GC+CC, miR-1302-3 CC, miR-27a AG+GG, miR-423 CA+AA, miR-604 AG+GG, miR-222 GT+TT, and miR-34a GA+AA were associated with altered coagulation parameters. Additionally, miR-222 correlated with decreased creatinine levels, the G>T mutation with elevated follicle-stimulating hormone (FSH), miR-34aC>A AA genotype with reduced thyroid-stimulating hormone (TSH) levels, and CA+AA with increased blood urea nitrogen (BUN) levels.

Conclusions: This systematic review highlights that specific miRNA SNPs and haplotype combinations are significantly associated with either increased susceptibility to or protection against RIF.

Purpose: To evaluate the clinical relevance of biochemical pregnancy loss (BPL) in recurrent pregnancy loss (RPL) patients, using data from preimplantation genetic testing for aneuploidy (PGT-A) to minimize embryonic factors.

Methods: This retrospective cohort study included 52 PGT-A cycles (48 patients) with single euploid embryo transfers between April 2020 and December 2022. Patients were stratified into three groups: Group A (ART failure without RPL, 18 cycles/17 patients), Group B (RPL following ART pregnancies, 12 cycles/10 patients), and Group C (RPL following natural pregnancies, 22 cycles/21 patients). This classification aimed to assess maternal factors contributing to BPL across different clinical backgrounds. The incidence of BPL, clinical pregnancy rate, and predictive performance of ART outcomes were analyzed, with and without BPL included, using ROC curve analysis.

Results: Biochemical pregnancy loss occurred in 0% (A), 25.0% (B), and 37.5% (C) of patients (p = 0.037). Incorporating BPL into miscarriage history significantly improved ART outcome prediction (AUC 0.871 vs. 0.759).

Conclusion: Biochemical pregnancy loss after euploid embryo transfer likely reflects maternal or endometrial pathology. Incorporating BPL into the diagnostic criteria for RPL may enhance clinical assessment and personalized care.

Background: In vitro-matured oocytes play an increasingly vital role in livestock production and fertility treatments. However, oocytes grown in vitro are not yet practical for widespread use. So far, only mouse oocytes have achieved full developmental competence granted in vitro from the early growth stage.

Methods: This review provides an overview of established culture methods and conditions, analyzing their effects. When evaluating studies, outcomes specifically related to in vitro-grown (IVG) oocytes rather than the follicle were prioritized.

Main findings: Neonatal mouse first-wave oocytes show a hypothesized linear volume increase, and IVG mouse oocytes have followed a similar developmental timeline across multiple studies. In other species, a proportion of bovine oocytes from early antral follicles achieved full size during 2-week cultures, with some producing viable offspring, confirming developmental competence. Preantral follicle culture systems are typically designed to address specific research parameters, such as developmental competence assessment. Preimplantation embryogenesis has been reported in several species, including humans.

Conclusion: For species with oocytes ≥ 125 μm in diameter, normal growth can be achieved during the final 2 weeks of growth as shown in bovines. However, developing culture systems that can maintain follicle viability for the preceding 4-5 weeks remains a critical challenge.

Background: With the trend of delayed childbearing, the incidence of poor ovarian response (POR) with diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI) has increased. Effective treatments for ovarian function restoration are limited. Platelet-rich plasma (PRP), an autologous regenerative therapy, shows potential for improving ovarian function; however, its mechanisms of action and optimal treatment protocols remain unclear.

Methods: A literature review was conducted using PubMed and Google Scholar, covering studies published from January 2021 to March 2025, focusing on preclinical and clinical studies evaluating the effects of PRP on ovarian function.

Main findings: Preclinical studies indicate that PRP promotes primordial follicle activation and growth. It also enhances oocyte quality by promoting angiogenesis, exerting anti-inflammatory and antioxidative effects, and modulating the extracellular matrix. Clinically, PRP may increase the number of retrieved oocytes and improve certain ovarian reserve markers, but its impact on oocyte quality and pregnancy rates remains inconclusive. The optimal dosage and treatment duration also require further investigation.

Conclusions: PRP holds promise in reproductive medicine, but additional research is required to evaluate long-term effects, optimize treatment protocols, and standardize preparation methods.

Purpose: Glucose plays a critical role in early embryonic development, influencing metabolic dynamics and developmental competence in a sex-specific manner. This study investigates the complex interplay between glucose availability, developmental competence, and sex-specific outcomes in preimplantation mouse embryos.

Methods: Mouse embryos were cultured in a modified KSOM medium with varying glucose concentrations (0-20 mM), monitored via time-lapse microscopy, and analyzed for developmental competence, sex determination by PCR, and X-linked metabolic gene expression. Stage-specific glucose addition/removal experiments and PDHA1 immunofluorescence staining were performed to assess temporal glucose dependency and sex-specific metabolic patterns.

Results: Glucose is essential during the morula-to-blastocyst transition. Analysis of developmental dynamics showed that glucose concentration affected the variability in developmental rates, particularly at the four-cell and eight-cell stages. Interestingly, sex ratio skewing was observed, with male embryos dominating the early developmental groups regardless of glucose levels. Expression analysis of X-linked metabolic genes revealed stage-specific patterns, with PDHA1 exhibiting the highest activity at the eight-cell stage.

Conclusions: Glucose availability accelerated embryonic development and created sex-specific patterns of developmental timing, with male embryos exhibiting faster progression rates, which might be associated with differential X-linked PDHA1 metabolic gene expression during early mouse embryogenesis.

Case: Ovarian transposition (OT) is performed to preserve ovarian function in patients undergoing pelvic or abdominal radiotherapy. Although complications, such as ovarian torsion and cyst formation, have been reported, ovulation-related peritoneal irritation requiring surgical intervention after pediatric OT has not been documented. In this case, a 12-year-old girl who underwent bilateral OT at the age of 6 years during treatment for recurrent rhabdomyosarcoma presented with severe pain in the right lower quadrant. Owing to prior pelvic radiotherapy, the assessment of menstrual history was unreliable. Considering the young age of the patient and the absence of a definitive diagnosis, hormonal therapy, such as low-dose estrogen-progestin therapy, was withheld. Conservative management with analgesics was initiated; however, the pain persisted and progressively worsened.

Outcome: Emergent laparoscopic OT release was performed for diagnostic and therapeutic purposes, owing to the severity of pain. Intraoperative findings revealed corpus luteum in the retracted right ovary. Postoperatively, the patient's symptoms resolved immediately without recurrence.

Conclusion: Ovulation-induced peritoneal irritation should be recognized as a potential postoperative complication following childhood OT. In adolescent patients with a history of pediatric OT and pelvic radiotherapy, ovulation-related complications should be carefully considered during the differential diagnosis of acute abdominal pain.