Reproductive Medicine and Biology最新文献

Purpose: To evaluate the applicability of overseas-approved dosage of relugolix combination tablets (relugolix 40 mg, estradiol [E2] 1 mg, and norethisterone acetate 0.5 mg) in healthy premenopausal Japanese women.

Methods: A randomized, double-blind phase I/II study was conducted to compare the pharmacokinetics, pharmacodynamics, and safety of repeated once-daily administration of relugolix combination tablets and relugolix (40 mg) for 6 weeks.

Results: There were 26 participants in each treatment group. The mean maximum concentration and area under the concentration-time curve from time zero to 24 h ratios for relugolix (relugolix combination tablet group/relugolix group) were both approximately 0.7-0.9. The mean E2 level ranged from 20 to 50 pg/mL. There was no notable difference in luteinizing hormone or follicle-stimulating hormone levels between the two groups. There was less change from baseline in type I collagen C-terminal telopeptide concentration and a lower cumulative incidence of hot flashes in the relugolix combination tablet group compared with the relugolix group, but more participants experienced uterine bleeding (mostly spotting or light bleeding). There were no new safety concerns and relugolix combination tablets were well tolerated.

Conclusion: Relugolix combination tablets have favorable safety and efficacy profiles, potentially making them suitable for long-term use in Japanese patients.

Trial registration: The trial registration number is JapicRCT2071230042.

Purpose: This study investigated the cryoprotective and antioxidant effects of lavender hydroalcoholic extract-loaded solid lipid nanoparticle (LHE-SLN) during handling, freezing, and thawing of NMRI mouse sperm.

Methods: LHE-SLNs were synthesized using the self-assembly method. After evaluating their physicochemical characteristics, NMRI mouse sperm were exposed to four concentrations (1.5, 3, 4.5 and 10 μg/mL) of LHE-SLN in handling, freezing and post-thaw incubation. After each step, sperm viability, motility and DNA fragmentation were assessed. The activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as the levels of nitric oxide (NO), were measured. The gene expression of Sod1, Sod2, Gpx, Cat, Bax, Bcl2, and Casp3 was analyzed using quantitative real-time PCR (qRT-PCR).

Results: The nanoparticles were spherical, with an average size of 235.8 ± 11.06 nm and a zeta potential of -21.7 ± 5.35 mV. All experiments showed increased cell viability and motility, reduced DNA fragmentation, and elevated NO levels. The activity of SOD, CAT, and GPX was significantly enhanced. Additionally, antioxidant genes were upregulated, while pro-apoptotic genes were downregulated.

Conclusion: These findings suggest that LHE-SLNs, particularly at 1.5 μg/mL, can effectively reduce oxidative stress, potentially enhancing sperm preservation outcomes through sustained delivery of antioxidants.

Purpose: The selection of high-quality spermatozoa affects embryo quality and, consequently, the success rates of clinical outcomes. This study aimed to evaluate the efficacy of a cumulus cell-based sperm selection method for identifying high-quality spermatozoa and to determine whether this process enhances ICSI clinical outcomes.

Methods: A total of 88 ICSI cycles were analyzed, generating 640 embryos, 331 in the control group and 309 in the study group. Standard density gradient centrifugation was applied in the control group, while the study group underwent an additional selection step using cumulus cell columns (CCC) in microcapillary pipettes. Embryo development was monitored through time-lapse imaging up to the blastocyst stage, and clinical outcomes were also recorded.

Results: Results demonstrated a significant reduction in sperm DNA fragmentation following CCC selection (37.08% vs. 23.36%, p = 0.0001). Embryos derived from CCC-selected sperm exhibited accelerated developmental kinetics and fewer cleavage abnormalities. Clinical outcomes were markedly enhanced in the study group, with higher implantation (58% vs. 28.4%), chemical pregnancy (81.8% vs. 50%), clinical pregnancy (77.3% vs. 25%), and live birth rates (72.7% vs. 25%) compared with controls (all p = 0.001).

Conclusions: The Use of cumulus cell-based sperm selection improves embryo quality and reproductive outcomes.

Purpose: The optimal GnRH agonist (GnRHa) dosing for ovulation triggering remains controversial, particularly regarding oocyte competence versus OHSS mitigation. Here, we analyzed the repeated dose of GnRHa as a trigger of ovulation on intracytoplasmic sperm injection (ICSI) results.

Methods: This single-blinded randomized clinical trial was conducted on 362 ICSI candidates who met the inclusion criteria. The subjects underwent the antagonist protocol and based on the received trigger, were divided into two groups: single dose (group A) and repeated dose (group B) of GnRHa. Demographic and clinical data were collected and analyzed using SPSS-24.

Results: Repeated dosing of GnRH increased M2 oocyte numbers yield by 22.84% ± 6.92% (95% CI: 9.23-25.38, p = 0.001). Also, the maturity rate (p = 0.001), the number of pronuclear embryos (p = 0.001), and the number of good and excellent quality embryos (p = 0.004) were higher in group B. Empty follicle syndrome was presented in no cases. Despite the high ovarian response, no OHSS cases were reported (mean oocytes> 17 ± 8). There was no significant difference regarding premature ovulation, use of Cabergoline, chemical and clinical pregnancy, miscarriage, and live birth rates between the 2 study groups.

Conclusion: It seems that the administration of the second dose of GnRHa 12 h after the first dose leads to better oocyte maturation and higher quality embryos.

Trail registration: IRCT20081007001306N11; https://irct.behdasht.gov.ir/trial/60387.

Purpose: This study evaluated the effects of double-layer interrupted sutures (DIS) and double-layer continuous sutures (DCS) on uterine blood flow and residual myometrial thickness (RMT) in cynomolgus monkeys after cesarean section (CS).

Methods: In DIS (n = 8) and DCS (n = 8) groups, uterine blood flow was assessed at 6 months post-CS using MRI by Ktrans. RMT was measured by T2-weighted magnetic resonance imaging (MRI) at 6 months. Laparoscopic evaluations were performed at 2 and 6 months.

Results: At 6 months, Ktrans was significantly higher in the DIS group 6. RMT at the suture site did not differ significantly between groups. Adhesions were observed in three DIS and two DCS animals. Nonadhesive DIS animals had significantly higher Ktrans and greater RMT at 6 months compared with adhesive DIS animals. Nonadhesive DIS exhibited significantly higher Ktrans and greater RMT at 6 months than nonadhesive DCS.

Conclusion: While overall differences were limited, exploratory findings indicate that DIS demonstrated superior uterine blood flow compared with DCS. Nonadhesive DIS animals exhibited greater RMT than adhesive DIS animals, suggesting a potential benefit of adhesion prevention.

Objective: To develop and validate a predictive model for live birth following single vitrified-warmed blastocyst transfer (SVBT) by integrating early pregnancy ultrasound radiomics with clinical parameters.

Methods: This retrospective cohort study analyzed 925 SVBT cycles (2019-2022). Patients were randomly divided into a training set (n = 740) and a testing set (n = 185). Radiomics features were extracted from gestational sac and embryonic structures at 4 weeks post-transfer. Machine learning (ML) models were trained using Least Absolute Shrinkage and Selection Operator (LASSO) regression and validated with receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA). Model performance was compared among clinical, radiomics, and combined clinical-radiomics models.

Results: The combined clinical-radiomics model demonstrated the highest predictive performance (AUC = 0.806, training; 0.718, testing), outperforming the radiomics-only model (AUC = 0.786, training; 0.708, testing) and the clinical-only model (AUC = 0.673, training; 0.579, testing). DCA confirmed superior clinical utility, and calibration curves indicated excellent agreement between predicted and observed outcomes.

Conclusion: Integrating ultrasound radiomics with clinical features significantly improves the prediction of live birth following SVBT. This model provides a novel, objective tool for personalized reproductive decision-making, improving embryo transfer strategies and patient counseling in assisted reproductive technology (ART).

Purpose: To investigate how two methods for managing early miscarriage after frozen embryo transfer (FET) cycles impact live birth rates and other reproductive and perinatal outcomes in subsequent FET cycles without preimplantation genetic testing for aneuploidy (PGT-A).

Methods: This retrospective cohort study of women undergoing FET cycles (January 2016-December 2022) in our department who experienced early miscarriage diagnosed by transvaginal ultrasound examined the impact of medical versus surgical evacuation on subsequent live birth rates (LBR).

Results: Analysis of 1685 women revealed no significant differences in implantation, miscarriage, preterm birth, obstetric complications, or neonatal disease rates between groups. However, the surgical management group had lower positive pregnancy test, clinical pregnancy, and live birth rates, and higher cesarean rates. While adjustments for confounders eliminated the significance of differences in positive pregnancy tests and clinical pregnancies, lower live birth rates (aOR 0.80, 95% CI: 0.65-0.99) and higher cesarean rates (aOR 1.84, 95% CI: 1.19-2.84) persisted. The surgical group also showed significantly reduced endometrial thickness in subsequent cycles.

Conclusion: Subsequent FET cycles after surgical miscarriage evacuation show lower live birth rates and thinner endometrial lining than those following medical evacuation; surgical evacuation also correlates with increased cesarean section rates in non-PGT-A FET cycles.

Tran et al. synthesized seven studies (n = 2,057) comparing frozen-thawed cleavage embryos cultured to blastocyst then transferred (FT-CDB) with direct frozen-thawed blastocyst transfer (DFB) in vitrification cycles. They found higher odds of clinical pregnancy and live birth with FT-CDB and no difference in neonatal birth weight. We discuss implications for laboratories weighing thaw-and-extend versus direct blastocyst transfer, emphasizing estimands per oocyte retrieval/intention-to-treat, workflow metrics, and laboratory-level covariates. Context from randomized controlled trials (RCTs) and systematic reviews suggests cumulative live birth may converge, highlighting the need for target-trial emulation and transparent reporting to inform clinical decision-making and guideline development.

Background: Oxidative stress (OS) is a critical factor in male infertility, where excessive reactive oxygen species (ROS) impair sperm quality and DNA integrity. Although physiological ROS levels support sperm maturation, imbalance can trigger oxidative or reductive stress (RS), both harmful to fertility. Thus, empirical antioxidant therapy without confirmed OS may be unwarranted and risk overtreatment.

Methods: We searched PubMed for original and review articles on OS, RS, antioxidants, redox imbalance, and male infertility, emphasizing mechanisms, diagnostics, therapeutic outcomes, and epigenetic implications.

Main findings: Although antioxidants may improve semen parameters, their effect on pregnancy and live birth rates remains inconclusive. Conventional diagnostics often overlook redox imbalance, leading to empirical antioxidant use. A precision redox approach-guided by oxidative profiling to assess redox balance-offers a more effective strategy. Although multiple tools have been proposed to assess redox status, identifying a clinically robust and reliable assay remains challenging. Emerging evidence shows that redox imbalance alters nuclear and mitochondrial epigenetics, potentially affecting embryo development and transgenerational health.

Conclusion: Managing male infertility should prioritize restoring redox balance rather than eliminating ROS. Future studies should prioritize standardized diagnostics, individualized antioxidant therapy, and a deeper understanding of how redox imbalance affects sperm epigenetics and offspring outcomes.

Background: Müllerian duct anomalies (MDAs) are developmental malformations of the female genital tract that present as a series of abnormalities within the reproductive tracts of females. The etiology of MDAs is complex and heterogeneous, especially genetic factors.

Methods: We conducted a comprehensive literature search in PubMed to identify relevant research articles and reviews. The search primarily targeted English-language publications from January 1978 to June 2025. Key search terms included Müllerian duct anomalies, Müllerian duct development, candidate gene, genetic, epigenetic, whole-exome sequencing, DNA methylation, chromosome, and related keywords.

Results: This review provides a comprehensive overview of the genetic factors and mechanisms underlying human Müllerian duct development. It systematically examines the genetic mutations and other mechanisms contributing to Müllerian duct anomalies (MDAs), including candidate genes and epigenetic abnormalities. Furthermore, the review summarizes recent advances in MDAs research and the digenic mode of inheritance.

Conclusion: We summarized the current genetic status of MDAs and discussed the research progress of relevant candidate genes in recent years in detail, and reviewed the reasons hindering progress in the field of MDAs.