Reproductive Medicine and Biology最新文献

Purpose: To evaluate the role of optimizing the maternal microbiome in improving pregnancy outcomes, focusing on preconception and early gestation, and to propose practical diagnostic and preventive strategies, particularly in low- and middle-income countries (LMIC).

Methods: A comprehensive review of peer-reviewed literature was conducted, analyzing the impact of vaginal, endometrial, gastrointestinal, urinary, and oral microbiomes on fertility and pregnancy. Key factors included microbial dysbiosis, sexually transmitted infections (STIs), and lifestyle interventions. Diagnostic approaches (cultures, gene sequencing) and preventive measures (nutrition, probiotics, vaccinations) were assessed for efficacy in optimizing the microbiome.

Results: An optimized microbiome, particularly with Lactobacillus crispatus dominance, enhances fertility and reduces pregnancy complications like miscarriage, preterm birth, and congenital infections. Dysbiosis, linked to obesity, antibiotic overuse, and poor nutrition, increases STI susceptibility and pregnancy risks. Preconception screening and targeted treatments (e.g., antibiotics for STIs, probiotics) improve outcomes. Nutritional interventions, including Mediterranean diets and supplements, support microbial health. LMIC face challenges due to limited access to care and nutrition, exacerbating adverse outcomes to be addressed.

Conclusions: Preconception microbiome optimization through diagnostics, lifestyle changes, and targeted therapies significantly improves pregnancy outcomes. Simple, cost-effective measures are critical also in LMIC to prevent and reduce maternal and fetal morbidity and mortality.

Purpose: Density gradient centrifugation (DGC) enriches motile sperm but may increase sperm DNA fragmentation (SDF), whereas microfluidic sperm sorting devices, such as ZyMōt and CA0, enable centrifugation-free selection with lower SDF. Direct comparisons are limited, and their relative clinical efficacy remains unclear. We compared sperm parameters and SDF after DGC, ZyMōt, and CA0 to evaluate sperm selection performance and assessed the clinical utility of ZyMōt and CA0 based on intracytoplasmic sperm injection (ICSI) outcomes.

Methods: Seventeen semen samples were aliquoted into three groups and processed using DGC, ZyMōt, or CA0. Sperm parameters and SDF were evaluated before and after selection. ICSI was performed using ZyMōt or CA0-selected sperm, inseminating 108 oocytes with ZyMōt and 64 with CA0, followed by the comparative analysis of embryo development.

Results: ZyMōt-selected sperm exhibited higher motility, average path velocity, and amplitude of lateral head displacement than DGC (p < 0.01); CA0-selected sperm showed higher linearity and wobble. ZyMōt achieved higher rates of fertilization, blastocyst formation, and good-quality blastocysts, and a lower percentage of poor-quality cleavage-stage embryos than CA0 (all p < 0.05).

Conclusions: ZyMōt demonstrated superior sperm quality compared with DGC and CA0, and favorable ICSI outcomes further support its potential clinical applicability.

Trial registration: The study (H2023-230) was registered in the Japan Registry of Clinical Trials (jRCT) Clinical Trials Registry in Japan (jRCT1040230045).

Purpose: This study examined whether the incidence of retained products of conception (RPOC) differs between hormone replacement cycles (HRC) and natural ovulation cycles (NC) in frozen-thawed embryo transfer (FET) pregnancies.

Methods: We retrospectively analyzed 425 clinical pregnancies following FET at a single center from 2017 to 2021. Pregnancies were classified as HRC (n = 204) or NC (n = 221). The primary outcome was RPOC incidence, diagnosed by ultrasound, Doppler, and histopathology when available. Management approaches and perinatal outcomes were descriptively assessed. Exact tests and Firth's penalized logistic regression were applied given the small number of events.

Results: RPOC occurred in 14/425 pregnancies (3.3%), with 11/204 (5.4%) in HRC and 3/221 (1.4%) in NC. The Cochran-Mantel-Haenszel odds ratio was 4.47 (95% confidence interval [CI] 1.29-16.39), and the adjusted Firth odds ratio was 3.92 (95% CI 1.18-12.96). Among RPOC cases, 5 were managed conservatively, 8 required uterine evacuation, and 1 required uterine artery embolization; histopathological confirmation was obtained in 7 cases. No significant associations were observed with embryo-transfer-related procedures.

Conclusion: HRC was associated with a higher RPOC incidence than NC. These exploratory findings suggest potential protocol-related differences in placental separation and warrant validation in larger, prospective multicenter studies.

Purpose: To study incidence, clinical risk factors, and pregnancy outcomes of trophectoderm- and inner cell mass-poor-quality blastocysts in single blastocyst transfer cycles.

Design: A retrospective cohort study included patients who underwent their first single blastocyst transfer cycle. A multivariate log-binomial regression model with COPY methods was performed.

Results: The incidence of having no transferable high-quality blastocysts was 33.8% (15 685/46 433). Maternal age, BMI, infertility duration, cycle number, embryo developmental stage, and transfer strategies are independent risk factors that affect the quality of blastocysts (p < 0.05). After adjusting for 11 confounding factors, the CPR and LBR significantly decreased across the groups in the order of high-grade blastocysts, low TE grade, and low ICM grade. Late-term miscarriage, preterm birth, singleton live birth, low birth weight of singleton, and birth weight of singleton were not statistically different between three groups. Low TE grade blastocysts exhibited significantly higher rates of small gestational sacs compared to high-grade blastocysts, while low ICM grade blastocysts were associated with a significantly higher incidence of small yolk sacs compared to both high-grade blastocysts and those with low TE grade.

Conclusions: Differential impacts of blastocyst component quality on early embryonic development.

Purpose: To determine the prevalence and clinical significance of arcuate uterus among infertile women using three-dimensional transvaginal ultrasound (3D-TVUS).

Methods: This retrospective cohort included 327 women evaluated for infertility between January 2021 and May 2025. Arcuate uterus was defined as fundal indentation < 10 mm and angle ≥ 90°. The primary outcome was live birth, with subgroup analysis in assisted reproductive technology (ART) cases. Logistic regression was used to assess independent associations.

Results: Arcuate uterus was found in 19% (62/327) of infertile women and was more frequent in unexplained infertility than in explained cases (32% vs. 14%; cOR 2.82, 95% CI 1.59-5.00, p = 0.001). Live birth rates did not differ significantly between arcuate and normal uterus, overall (17% vs. 14%; aOR 1.3, 95% CI 0.2-5.9) or in ART (65% vs. 63%; aOR 1.1, 95% CI 0.5-2.4). Reproducibility was excellent (κ = 0.94).

Conclusions: Arcuate uterus was relatively common, especially in unexplained infertility, but did not independently affect live birth. 3D-TVUS assessment may help identify subgroups within unexplained infertility, warranting validation in multicenter studies.

Purpose: In mouse embryos derived from round spermatid injection (ROSI), low developmental potential due to abnormal histone modification is improved by histone deacetylase (HDAC) inhibitors. However, some studies suggest that the use of such inhibitors leads to the birth of hypomorphic offspring. We examined the genetic risk of Scriptaid on mouse ROSI embryos over two generations.

Methods: Oocytes were penetrated by spermatids treated with Scriptaid (250 nM 10 min) and transferred to host mothers. After the offspring were born and matured, some first-generation males and females were mated to obtain second-generation offspring. One-cell ROSI embryos treated with Scriptaid (250 nM 16 h) underwent the same process.

Results: Scriptaid reduced H3K9me3 residues in the spermatid nuclei and in the male pronuclei of ROSI embryos, resulting in increased blastocyst formation and live birth rates compared with the untreated group. All offspring exposed to Scriptaid had normal body weight and external appearance and subsequently grew as well as the IVF offspring. Additionally, all second-generation offspring were also healthy.

Conclusion: Scriptaid improved the developmental potential of ROSI embryos, and no clear teratogenic effect was observed in the live offspring, suggesting that Scriptaid is safer than Trichostatin-A, which has been reported to induce hypomorphic offspring in ROSI.

Background: Lipid droplets (LDs) are organelles consisting of a central core of neutral lipids covered by a single layer of phospholipids and are found in most eukaryotic cells. It has long been known that mammalian oocytes accumulate different amounts of LDs between animals; however, it is largely unknown why LD content varies from animal to animal and its physiological role remains unclear. Reflecting the growing interest in LDs in mammalian oocyte and early embryos, several comprehensive reviews have appeared in the last few years, but none have reviewed methods for visualizing and analyzing LDs stored in oocytes or fertilized eggs.

Methods: We outline experimental methods for visualizing LDs in mammalian oocytes and early embryos. We also describe a method for LD degradation by fertilization-induced autophagy and a centrifugation-based method for the removal of LDs from ovulated metaphase II (MII) oocytes in mice.

Main findings: This review outlines the advantages and disadvantages of some of the typical methods for observing and analyzing LDs in oocytes and fertilized embryos.

Conclusion: Our review provides useful information not only to basic researchers interested in LDs in mammalian oocytes and fertilized embryos, including humans, but also to embryologists and medical doctors.

Purpose: Conization for high-grade cervical intraepithelial neoplasia (CIN2-3) often harms obstetric outcomes. Photodynamic therapy (PDT) with talaporfin sodium provides a cervix-sparing alternative with short photosensitivity. We investigated the efficacy and safety of talaporfin-PDT for CIN2-3.

Methods: We conducted a prospective, multicenter, single-arm phase II trial (jRCT2041190087) in women ≥ 20 years with biopsy-proven CIN2-3. Patients received talaporfin sodium (40 mg/m²) and 664-nm laser irradiation. Efficacy was evaluated by cytology/histology from weeks 12 to 24; the primary endpoint was complete response (CR) versus an 85% threshold. Safety, HPV status, cervical length, and reproductive outcomes were monitored.

Results: Of 88 enrolled, 79 were treated and 77 (CIN2 = 7; CIN3 = 70; median age 32 years; 93.5% desiring future pregnancy) were evaluable. CR was achieved in all 77 (100%; lower 95% CI: 96.2%), including 95.8% in CIN3. High-risk HPV clearance occurred in 82.4%. One recurrence (1.3%) was observed. No serious adverse events occurred; four grade ≥ 3 events resolved. Cervical length was preserved. Eleven pregnancies occurred, yielding eight full-term deliveries.

Conclusions: Talaporfin-PDT showed excellent efficacy, safety, and fertility preservation in CIN2-3, supporting its potential as a non-excisional alternative.

Trial registration: This study was registered in the Japan Registry of Clinical Trials (jRCT) under the identifier jRCT2041190087.

Purpose: Maternal age-related fertility decline is considered to be directly attributed to either embryonic or endometrial factors. Aneuploidy, as the dominant defect in aging embryos, has long diverted attention away from the effects of endometrial senescence. By analyzing the outcomes of euploid blastocyst transfers verified through preimplantation genetic testing for aneuploidy (PGT-A), we aimed to corroborate impaired endometrial receptivity among older women and determine whether the aging uterus also contributes to pregnancy maintenance.

Methods: This is a single-center, real-world retrospective cohort study recruiting subfertile couples intended for PGT-A. We assessed the comprehensive correlations between maternal age and clinical outcomes, including clinical pregnancy and clinical miscarriage that represent distinct stages of pregnancy, as well as biochemical pregnancy, live birth, and maternal and neonatal events.

Results: A total of 1816 subfertile couples intended for PGT-A were initially recruited, among whom 1376 obtained euploid blastocysts, leading to 2035 serial single frozen-thawed transfers. Baseline endometrial receptivity exhibited age-dependent impairment, as partially indicated by a reduction in thickness (9.409 ± 2.413 mm to 8.893 ± 2.286 mm; p = 0.0113) and unfavorable alterations in pattern (p < 0.0001). Based on the endometrial age at transfer, 256, 782, 477, 361, and 159 cycles were conducted in women aged < 30, 30-34, 35-37, 38-40, and over 40 years, respectively. Univariable analyses did not identify any discernible trend in the indicators of pregnancy progression across different age groups, independent of aneuploidy. Multivariable analyses, adjusting for embryonic and endometrial confounders, revealed that women over 35 years of age faced higher risks of poor pregnancy initiation (implantation), as evidenced by lower odds of biochemical pregnancy (0.8198 [0.6814-0.9864]) and clinical pregnancy (0.8258 [0.6851-0.9954]). Nevertheless, no such correlation was found during pregnancy maintenance, according to current findings regarding live birth and clinical miscarriage.

Conclusions: PGT-A, serving as an autologous model to control embryonic quality and study endometrial factors, seems feasible, although nonchromosomal and procedure-related factors may require further distinguishment. Advanced maternal age (AMA) is related to decreased receptivity, and endometrial aging is an independent determinant of euploid implantation. This message offers insights for profound research and appropriate counseling on AMA conditions.

Purpose: The present study examined the relationship between Anti-Mullerian hormone (AMH) concentrations in follicular fluid (FF) and AMH gene expression levels in granulosa cells (GCs) and the embryological outcomes of retrieved oocytes.

Methods: Patients who underwent intracytoplasmic sperm injection (ICSI) treatment at our hospital were included. A total of 270 FF samples from 20 patients were used to evaluate AMH concentrations. A total of 140 GCs obtained during oocyte denudation for ICSI were used to assess AMH mRNA expression. The relationships between FF AMH concentrations or GC AMH mRNA expression levels and the maturity of the oocytes obtained, as well as fertilization and blastocyst arrival, were investigated.

Results: FF AMH concentrations and GC AMH mRNA expression levels markedly varied among follicles. There was no correlation in the degree of variation in FF AMH concentration and GC AMH mRNA expression. Serum AMH concentrations correlated with mean FF AMH concentrations (r ² = 0.78, p < 0.05), whereas no correlation was observed between follicular size and the FF AMH concentration. FF AMH concentrations were significantly lower in fertilized oocytes than in unfertilized oocytes, whereas GC AMH mRNA expression levels did not correlate with clinical outcomes.

Conclusion: The FF AMH concentrations may be associated with oocyte fertilization capacity.