Journal of Assisted Reproduction and Genetics最新文献

Purpose: To evaluate whether a micronutrients supplement combined with probiotics improves oocyte retrieval outcomes in normoresponder women undergoing controlled ovarian hyperstimulation for oocyte donation.

Methods: A multicenter, prospective, randomized, double-blind, controlled clinical trial was conducted between July 2022 and July 2024 with 196 normoresponder oocyte donors at three fertility centers in Spain. Participants received either study supplement or a placebo for at least 30 days before and during controlled ovarian hyperstimulation.

Results: The intention-to-treat analysis showed a significant increase in the total number of follicles (28.01 ± 10.4 vs. 24.7 ± 7.1; p = 0.0314) and follicles ≥ 16 mm (19.3 ± 8.6 vs. 15.8 ± 6.1; p = 0.0065) in the study group compared to the placebo group. Regarding the quality of MII oocytes, the mean number of good-quality oocytes showed no differences between groups (17.0 ± 7.7 (84.1%) vs. 15.4 ± 8.2 (81.4%); p = 0.2187). The per-protocol analysis (participants who completed the study and adhered fully to the supplement regimen, n = 79) revealed significantly higher total oocytes retrieved (27.7 ± 10.4 vs. 21.2 ± 7.9; p = 0.0045), MII oocytes (22.5 ± 8.89 vs. 17.3 ± 7.25; p = 0.0092), and good-quality MII oocytes (18.97 ± 7.7 vs. 13.42 ± 6.5; p = 0.0019) in the study group.

Conclusions: Probiotic micronutrients supplementation improved follicular development and oocyte yield, in normoresponder oocyte donors, especially when administered according to the recommended protocol. These findings suggest potential benefits for oocyte donation programs; however, further research is needed to establish definitive recommendations. The study protocol was registered at ClinicalTrials.gov (TRN: NCT05473039) on June 27, 2022.

Purpose: Recurrent spontaneous abortion (RSA) involves complex pathophysiology, making it difficult to develop effective treatments and causing significant health and economic burdens. This study evaluated miR-363-5p as a potential biomarker for RSA and explored its role in disease progression to provide insights for clinical management.

Methods: A total of 68 serum samples from RSA patients and 97 from healthy pregnant controls were analyzed to determine miR-363-5p expression and its clinical significance. The EVT cell line HTR-8/SVneo was used for in vitro experiments. Cell proliferation was assessed using CCK-8 assays, while Transwell assays evaluated migration and invasion. qRT-PCR detected miR-363-5p and S100A1 expression levels. Dual-luciferase reporter assays confirmed the interaction between miR-363-5p and S100A1.

Results: miR-363-5p expression was significantly lower in RSA patients than in healthy pregnant controls. ROC analysis indicated its high diagnostic potential for RSA. In vitro experiments showed that miR-363-5p promoted HTR-8/SVneo cell proliferation, migration, and invasion while inhibiting apoptosis. S100A1 was identified as a direct target of miR-363-5p in RSA. miR-363-5p regulates EVT cell functions by suppressing S100A1 expression.

Conclusions: Serum miR-363-5p downregulation may serve as a diagnostic biomarker for RSA. miR-363-5p likely affects pregnancy outcomes in RSA by targeting S100A1 to regulate EVT cell functions. These findings suggest that miR-363-5p has potential for both diagnosing and treating RSA.

Background: Balanced reciprocal translocations and Robertsonian translocations represent two of the most prevalent structural chromosomal rearrangements and may lead to reproductive challenges, including recurrent spontaneous abortion (RSA). The co-occurrence of both translocation types in a single individual constitutes an exceptionally rare cytogenetic finding with significant clinical implications.

Case presentation: We present a 36-year-old female with a history of RSA who was found to harbor a compound chromosomal rearrangement consisting of a balanced reciprocal translocation t(2;5)(q33;p13.3) and a Robertsonian translocation der(13;15)(q10;q10). High-resolution karyotyping confirmed the identical rearrangement pattern in the proband's daughter. The patient underwent intracytoplasmic sperm injection with preimplantation genetic testing for structural rearrangements (PGT-SR). Among seven blastocysts biopsied, only one euploid embryo with normal karyotype was identified and subsequently transferred in a natural cycle, resulting in a successful singleton pregnancy with normal prenatal cytogenetic findings.

Discussion and conclusion: This case highlights the critical role of accurate cytogenetic diagnosis and the application of PGT-SR in improving reproductive outcomes in patients with complex chromosome rearrangement. It also underscores the importance of chromosomal karyotyping in detecting complex chromosomal rearrangements-not only for individuals with RSA but also for their family members. Individualized reproductive planning and genetic counseling remain pivotal for managing such challenging cases.

Purpose: To explore the molecular mechanisms underlying male reproductive defects in Down syndrome (DS) by analyzing the transcriptomic characteristics of testis tissue in the DS mouse model.

Methods: In this study, we used Dp(16)1Yey/ + (hereafter called Dp16) mice as a DS model. The morphological features were assessed by H&E staining, PAS staining, and transmission electron microscopy in the testicular and epididymal tissues of Dp16 and normal mice. Sperm were diluted for microscopic observation. Sperm count, motility, abnormal sperm proportion, and parameters like VAP, VSL, and VCL were evaluated. Mitochondrial membrane potential was assessed with the JC-1 fluorescent probe using flow cytometry. In addition, to evaluate the reproductive ability of male Dp16 mice, adult male Dp16 mice and female WT mice were caged in a 1:1 ratio, and IVF was performed. Further RNA-seq sequencing was performed on Dp16 mice testis tissue and compared with normal mice.

Results: We found that they also exhibited similar phenomena as individuals with DS, such as decreased sperm count and abnormal morphology. RNA-seq sequencing was performed to compare the testis tissues of Dp16 mice with normal mice. The results showed that there were many differentially expressed genes in Dp16 mouse testis, involving signaling pathways related to spermatogenesis, testis development, and hormone synthesis. In addition, many genes in Dp16 mouse testis were associated with non-obstructive azoospermia and Klinefelter syndrome, suggesting that these diseases may have common pathogenic genes.

Conclusions: This study systematically revealed the transcriptomic characteristics of DS model mouse testis tissue, uncovering key genes and pathways involved in male fertility defects. The findings provide clues to understanding how chromosomal abnormalities affect fertility and a scientific basis for developing new strategies for treating DS.

The mammalian spermatozoon neck is a unique structure that functions during spermatid differentiation and spermatozoa swimming, and its contents are critical for post-fertilization embryogenesis. Mutations in proteins localizing to the neck connecting piece (the modified pericentriolar material) result in acephalic spermatozoa. In contrast, mutations in proteins localizing to the centriole often produce abnormal tail morphology. Acephalic spermatozoa can be categorized based on the exact location of the neck breakpoint. Here, we classify 24 proteins known to cause acephaly in human and mice spermatozoa into five different acephalic types, depending on where the breakpoint occurs. We also discuss other proteins found in the spermatozoon neck, which may result in spermatozoa acephaly. The relationship between the exact location of the neck's break and intracytoplasmic sperm injection (ICSI) outcomes is explored in the context of the spermatozoon centrosome's role. We conclude that to understand this relationship, future research should investigate DNA, phospholipase C zeta, and centriole functionality, in addition to the location of the acephalic breakpoint in the patient's sperm.

Purpose: To identify novel pathogenic genes and variants responsible for oocyte degeneration and death.

Methods: Whole-exome sequencing was conducted in 78 individuals with primary infertility characterized with oocyte degeneration and death, followed by Sanger sequencing of candidate variants. Pathogenicity of identified COX15 variants was characterized through morphological assessment, AlphaFold3-based structural modeling and functional validation including Western blotting and immunofluorescence.

Results: We identified a compound-heterozygous COX15 variants and a homozygous COX15 variant in two affected individuals with oocyte degeneration. The variants c.C664T [p.R222C] was a previously reported recurrent pathogenic variant. The clinical records showed that majority of oocytes retrieved from affected individuals were immature and degenerated. Structural modeling assay showed that all the COX15 variants affected the binding pocket with heme o. The compound-heterozygous COX15 variants c.C905T [p.P302L] and c.C664T [p.R222C] in family 1 significantly decreased COX15 protein level in HeLa cells. While the homozygous variant c.C647T [p.P216L] decreased the COX1 protein level in oocytes from family 2 (II-1), implying the disruption of respiratory complex IV (COXIV) assembly.

Conclusions: Our study identified two novel variants in COX15, and functional analysis confirmed the pathogenicity of the variants. Our findings expand the mutational spectrum of COX15 and making it a potential genetic diagnostic marker for those suffering from female infertility causing by oocyte degeneration.

Purpose: To evaluate whether reduced oxygen tension (5% O₂) during embryo culture is associated with differences in neonatal outcomes compared with atmospheric oxygen (20% O₂) in fresh IVF/ICSI singleton births.

Methods: We conducted a retrospective cohort study at Peking University Third Hospital (2015-2022), including 13,831 singleton live births after fresh cleavage-stage transfers. Neonates conceived under 5% O₂ (n = 3192) were compared with 20% O₂ (n = 10,639). Primary outcomes were gestational age, birthweight, and gestational age and sex-adjusted Z-scores; secondary outcomes included small-for-gestational-age (SGA), large-for-gestational-age (LGA), and macrosomia. Multivariable regression adjusted for maternal/paternal age, body mass index (BMI), infertility type, stimulation protocol, gonadotropin dose, fertilization method, endometrial thickness, number of embryos transferred, and culture medium. Birthweight-related outcomes were further adjusted for gestational age and sex.

Results: Compared with 20% O₂, 5% O₂ was associated with longer gestation (β = 0.073 weeks; P = 0.009), lower birthweight (β =  - 44.6 g; P < 0.001), and lower Z-scores (β =  - 0.105; P < 0.001). SGA risk increased (OR = 1.26; P = 0.030), while LGA (OR = 0.80; P < 0.001) and macrosomia (OR = 0.81; P = 0.006) decreased; preterm birth did not differ.

Conclusions: Reduced oxygen tension during embryo culture was associated with lower neonatal birthweight and a reduced incidence of LGA or macrosomic infants, indicating a favorable effect on neonatal outcomes. Prospective multicenter and mechanistic studies are warranted to confirm these findings and refine oxygen management in Assisted reproductive technologies (ART).

Purpose: To determine the effectiveness of an educational intervention in improving health insurance literacy and utilization of in vitro fertilization insurance benefits.

Methods: Randomized controlled trial, with 217 participants randomized in a 2:1 fashion to receive either an educational intervention or university-provided information sheet. Participants were 18 to 50 years, intending to conceive within a year, eligible for employee-offered health insurance coverage. The primary outcome was health insurance literacy. Secondary outcomes included comparing health insurance plans, plan selection, in vitro fertilization service utilization, benefit utilization, out-of-pocket costs, and acceptability, appropriateness, and feasibility of the intervention materials. Semi-structured interviews evaluated participant experiences with intervention materials, plan selection, benefit utilization, in vitro fertilization services, and out-of-pocket costs.

Results: Both groups reported low confidence using their health insurance (intervention: 1.00 [SD = 0.90], usual care: 0.74 [SD = 0.76], β = 0.26, 95% CI - 0.09, 0.62) and moderately high confidence being proactive when using their health insurance (intervention: 2.26 [SD = 0.86], usual care: 2.47 [SD = 0.58], β =  - 0.20, 95% CI - 0.52, 0.11). Utilization of in vitro fertilization services was similar between groups (intervention: 40% [10/25], usual care: 45% [9/20]; p = 0.35). Use of insurance for these services did not differ between groups (intervention: 36% [9/25], usual care: 40% [8/20]; p = 0.78), and both groups experienced moderate out-of-pocket costs. Qualitative data revealed challenges in benefit utilization in both groups.

Conclusions: Despite the educational intervention not improving health insurance literacy or in vitro fertilization benefit utilization, our findings suggest that being able to navigate health insurance benefits is essential for effective utilization of in vitro fertilization services.

Trial registration number: NTC05663645.

Purpose: To investigate the impact of different frozen embryo transfer regimens on maternal thyroid function during early pregnancy and subsequent thyroid function in the newborns.

Methods: A secondary analysis of a randomized controlled trial including women aged 18-40 years with a body mass index ≤ 35 kg/m² undergoing frozen embryo transfer at Copenhagen University Hospital - Herlev (April 2021-May 2024). Ovulatory participants were randomized to modified natural or programmed cycle, and anovulatory participants to gonadotrophin-stimulated or programmed cycle. Maternal thyroid-stimulating hormone, free thyroxine, total thyroxine, and total triiodothyronine were measured. Neonatal thyroid-stimulating hormone was evaluated through the neonatal screening program.

Results: In total, 251 cycles were analyzed: 94 modified natural and 99 programmed in the ovulatory group, and 29 gonadotrophin-stimulated and 29 programmed in the anovulatory group. Total triiodothyronine and thyroxine levels were significantly higher in programmed cycles during endometrial preparation and early pregnancy. Free thyroxine was elevated at gestational age 4 + 2 in programmed vs. modified natural cycles, but not compared to gonadotrophin-stimulated cycles. Thyroid-stimulating hormone levels were comparable at all time points. Neonatal thyroid-stimulating hormone did not differ between groups.

Conclusions: Although significantly higher maternal levels of total triiodothyronine, thyroxine, and free thyroxine were observed in programmed cycle, both maternal and neonatal thyroid-stimulating hormone levels were unaffected. These findings provide reassuring evidence for the endocrine health of women conceiving through programmed cycle and their newborns. The trial was prospectively registered in EudraCT with identification no. 2020-001218-39, registration date: 17 November 2020. Date of first patient's enrollment: 20 April 2021.

Purpose: To assess gender-based differences in career trajectories among reproductive endocrinology and infertility (REI) physicians in the United States, focusing on leadership, research productivity, and professional involvement.

Methods: This was a cross-sectional comparative study of demographic, professional, and research metrics stratified by gender. Practicing REI physicians were identified through the ASRM directory. Physician gender was evaluated as a variable influencing career outcomes. Main outcome measures included practice setting, geographic distribution, research productivity (h-index, publications, citations), academic leadership, journal editorial board, and society board positions. Mann-Whitney U and Chi-square tests were performed.

Results: Among 767 REI physicians, 55% were male and 45% female. Slightly more females worked in academic settings (33.3% vs. 25.1%), while more males were in private practice (70.4% vs. 66.7%). Leadership representation was comparable between genders. Female physicians had marginally greater representation on editorial (7.8% vs. 7.1%) and society boards (5.8% vs. 4.3%). Males, however, had significantly higher research productivity (mean h-index: 16.44 vs. 10.94; publications: 52.53 vs. 26.72; citations: 2216.69 vs. 1155.28; all p < 0.001).

Conclusion: Despite near parity in leadership representation, gender disparities persist in research productivity among REI physicians. These discrepancies may reflect systemic inequities in academic support, promotion criteria, and institutional culture. Structural barriers such as inequitable research resources, gendered service loads, and family-building or domestic responsibilities may further constrain women's ability to engage in sustained scholarly productivity and advancement. Future efforts can prioritize inclusive data practices, equitable promotion policies, and targeted interventions to support diversity within reproductive medicine.