Journal of Assisted Reproduction and Genetics最新文献

Objective: To investigate the distribution of ABO blood groups among infertile couples in Southern China (Ganzhou region) and to explore the association between blood types and male reproductive parameters.

Methods: This single-center retrospective study analyzed data from 696 infertile couples who sought treatment at a tertiary reproductive medicine center in Southern China between 2016 and 2024. ABO blood group distributions in infertile men and women were compared with those of a large-scale reference population from Southern China (n ≈ 14.41 million). Chi-square tests, Cramér's V effect size, and the observed-to-expected ratio (O/E) were used to evaluate associations between couple blood type combinations and semen parameters, including sperm concentration, total sperm count, progressive motility, and normal morphology.

Results: Blood group O was significantly overrepresented in infertile men (39.51% vs. 34.21%, P = 0.008) and women (41.67% vs. 34.19%, P < 0.001), whereas blood group AB was underrepresented (men: 6.18% vs. 8.91%, P = 0.008; women: 6.47% vs. 8.91%, P = 0.008). The O/O couple blood type combination showed a significantly higher prevalence among infertile couples (16.81% vs. 11.70%, O/E = 1.44, P < 0.001), while combinations involving A/B and B/AB occurred less frequently (O/E = 0.57-0.78, P < 0.05). Male blood type was associated with sperm normal morphology (O < A < B < AB, P = 0.02), but not with sperm concentration or progressive motility.

Conclusion: Blood group O-particularly the O/O couple combination-may be associated with an increased risk of infertility, whereas combinations involving B or AB blood groups may confer a potential protective effect. The ABO blood group type may influence male fertility, partly through its association with sperm morphology. These findings provide region-specific evidence and underscore the need for large-scale, multi-center studies to further validate the observed associations.

The higher incidence of ovarian aging has led to a significant decline in the female fertility rate, raising social concerns about women's health. In recent years, the rapid development of RNA cross-linked proteomics technology has identified the role of RNA-binding proteins (RBPs) in ovarian aging. Ovarian aging disrupts the hypothalamic-pituitary-ovarian axis, resulting in aberrant hormone secretion, irregular menstrual cycles, oocyte apoptosis, and abnormal embryonic development. Given this, we have compiled the role of RNA-binding proteins in ovarian aging and further explored how different ovarian RBPs promote apoptosis and serve as therapeutic targets. We aim to analyze the effects of RNA-binding proteins on ovarian function to provide more explicit ideas for delaying ovarian aging and treating ovarian diseases.

Purpose: To investigate the impact of serum luteinizing hormone (LH) levels on the day of human chorionic gonadotropin (hCG) trigger on cumulative live birth in women undergoing in vitro fertilization (IVF) cycles.

Methods: This was a secondary analysis of a multicenter randomized controlled trial (NCT03118141). A total of 1212 infertile women undergoing their first IVF cycle with a good prognosis for live birth were included. Participants were stratified into three groups according to tertiles of serum LH levels on the hCG trigger day (hLH): low-hLH (< 1.28 IU/L), medium-hLH (1.28-3.26 IU/L), and high-hLH (> 3.26 IU/L). Logistic regression and restricted cubic spline models were used to evaluate associations, adjusting for maternal age, body mass index, and baseline hormones.

Results: Compared to the medium-hLH group, the low-hLH group exhibited significantly lower cumulative clinical pregnancy and live birth rates, along with a higher biochemical pregnancy loss rate (P < 0.05). The high-hLH group demonstrated a reduced cumulative live birth rate, while other pregnancy outcomes were comparable to the medium-hLH group. A restricted cubic spline analysis revealed a significant nonlinear, inverted U-shaped relationship between serum hLH levels and cumulative live birth rates, with the optimal threshold around 1.95 IU/L. Stratified analysis indicated that the impact of hLH levels was more pronounced in women undergoing GnRH antagonist protocols.

Conclusions: Serum hLH levels exhibit a nonlinear association with cumulative live birth rates in IVF cycles, highlighting 1.95 IU/L as a potential threshold. Individualized adjustment of hLH levels may improve pregnancy outcomes, especially in GnRH antagonist protocols.

The assessment of oocyte and blastocyst quality plays a pivotal role in reproductive biology, directly influencing the success of assisted reproductive technologies (ART) in both humans and farm animals. In livestock, technologies such as Ovum Pick-Up and In Vitro Embryo Production (OPU-IVEP) have revolutionized genetic improvement strategies by enabling the production of a higher number of genetically superior offspring from elite females. However, the manual evaluation of oocytes and embryos remains subjective, time-consuming, and susceptible to human error. Recent advances in Artificial Intelligence (AI), particularly in computer vision and deep learning, have opened new avenues for automating the assessment process. AI models such as convolutional neural networks (CNNs) have demonstrated high accuracy in classifying oocyte and embryo quality, providing standardized, rapid, and reproducible evaluations. This review focuses on the applications of artificial intelligence in bovine oocyte and blastocyst grading, highlighting its potential to improve assessment accuracy, support OPU-IVEP programs, and enhance reproductive efficiency.

Purpose: PGT utilizing SNP-based linkage analysis for monogenic defects associated with microdeletions/duplications has been the standard method for preventing disease inheritance. However, its high cost and time consumption limit its accessibility. This study introduces a novel platform, the GenoLab M DX gene sequencer, designed to leverage next-generation sequencing (NGS) technology, aiming to reduce costs and increase sequencing efficiency in preimplantation genetic testing (PGT) for microdeletions/duplications.

Methods: Couples with microdeletion/duplication syndromes were recruited, and GenoLab was employed to detect copy number variations (CNVs) under 4 Mb in their abnormal blastocysts, developmentally arrested embryos, and peripheral blood, assessing the diagnostic validity of GenoLab.

Results: Blastocysts and arrested embryos from eight couples were thawed and sequenced using GenoLab. Of 69 affected blastocyst samples, 49 (71.0%) exhibited submicroscopic abnormalities, with 94% concordance to prior biopsy findings. Among 15 arrested embryo samples, 6 (40%) showed submicroscopic abnormalities, while 3 (20%) were mosaic. Additionally, 138 developmentally arrested embryos, peripheral blood, and 1 abortive tissue were analyzed, achieving diagnostic accuracy exceeding 90%. Clinically, two couples with microdeletions/duplications had embryos successfully transferred, resulting in the birth of two healthy children.

Conclusions: The GenoLab M DX sequencer is a reliable, rapid (< 2 weeks), and cost-effective platform suitable for CNV analysis in monogenic diseases. It offers an innovative solution for cases involving de novo pathogenic variants or when family DNA samples are unavailable, representing a significant advancement in assisted reproduction.

Purpose: Sixty-five percent of US workers get their health insurance from self-insured employers who are exempt from state insurance coverage mandates. We evaluated if self-insured employers in states with in vitro fertilization coverage mandates offer insurance coverage for in vitro fertilization and other fertility treatments, and if so, we evaluated the details of that coverage.

Methods: We qualitatively analyzed 165 health plan documents from 2019 to 2021 from 45 self-insured employers in seven states with in vitro fertilization coverage mandates (Arkansas, Connecticut, Illinois, Maryland, Massachusetts, New Jersey, New York).

Results: A minority (41%) of self-insured employers in states with in vitro fertilization coverage mandates cover in vitro fertilization. Most health plans impose lifetime limits on in vitro fertilization use, with those limits split almost evenly between dollar-based and cycle-based limits. Finally, health plans in our sample from the finance and insurance, manufacturing, and educational services industries, and from non-union employers, had more comprehensive coverage for infertility testing and treatments.

Conclusion: While state in vitro fertilization coverage mandates are important policy initiatives to improve access to in vitro fertilization, our findings suggest that state mandates are insufficient to expand access to all patients since a minority of self-insured employers in our sample covered in vitro fertilization. In addition, it is insufficient to label a health plan as simply "covering" or "not covering" in vitro fertilization; instead, the details of that coverage matter since the "coverage" may not be sufficient for the patient to afford even one in vitro fertilization attempt.

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.

Purpose: The purpose of this study was to identify genes in the placenta of monosomy X embryos whose methylation abnormalities may be associated with embryonic death.

Methods: Methylation levels were assessed via reduced representation bisulfite sequencing of the chorionic villi of embryos from 8 spontaneous abortions during the first trimester of pregnancy with the 45,X karyotype and 7 embryos from medical abortions with the 46,XX and 46,XY karyotypes. The methylation levels of several identified differentially methylated genes were analyzed in 22 embryos from spontaneous abortions with monosomy X compared with 11 embryos from medical abortions using targeted bisulfite massive parallel sequencing.

Results: Compared with embryos with 46,XX and 46,XY karyotypes, respectively, differentially methylated CpG sites in embryos with monosomy X were located in 831 and 254 differentially methylated genes (DMGs). However, only 74 DMGs were unique for 45,X embryos after subtraction of the DMG of spontaneously aborted embryos with a normal karyotype (n = 4). Compared with embryos of both sexes, 48 genes in embryos with monosomy X were differentially methylated, 21 of which are important in normal placental and embryonic development and whose dysregulation is linked to preeclampsia and embryonic death. Targeted analysis confirmed that the ALCAM gene is hypermethylated and that the BDH1 gene is hypomethylated in embryos with monosomy X.

Conclusion: Aberrant methylation of genes involved in placentation, proliferation, and cell differentiation has been detected in spontaneously aborted embryos with monosomy X. These disorders may be associated with the high lethality of embryos with monosomy X.

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.

Purpose: Fatty acid-supplemented warming solutions have been shown to improve blastocyst development and pregnancy outcomes after single vitrified-warmed cleavage stage embryo transfers. However, the effects of fatty acids, phospholipids, and L-carnitine on oocyte mitochondrial function and blastocyst development remain unexplored. This study aimed to evaluate whether supplementing both vitrification and warming solutions with these compounds enhance oocyte mitochondrial function and embryo development.

Methods: Preclinical study conducted with a C57Bl/6 J mouse strain. The study included five experimental groups. The control group comprised fresh oocytes not subjected to vitrification. The vitrification groups consisted of oocytes vitrified in Tvitri-4 medium supplemented with L-carnitine (T4/LC), L-carnitine and fatty acids (T4/FA), or L-carnitine, fatty acids, and phosphatidylcholine (T4/PC). Total cell number in the trophectoderm and inner cell mass (ICM) was analyzed by differentially labeling the nuclei with polynucleotide-specific fluorochromes. Oocyte mitochondrial activity was assessed by mitochondrial membrane potential (ΔΨm), intracellular oxidant levels, and oxidative metabolism. ΔΨm and the levels of oxidant species were evaluated using JC-1 and carboxy-H2DCFDA, respectively, while redox state was measured by the FAD/NAD(P)H autofluorescence ratio.

Results: The ICM cell number did not differ between fresh and oocytes vitrified and warmed with L-carnitine and lipids (Tvitri-4/fatty acids and Tvitri-4/phosphatidylcholine) (p > 0.05). Additionally, oleic and linoleic acids with L-carnitine preserved mitochondrial membrane potential and reduced oxidative stress by lowering oxidant levels.

Conclusion: Adding lipids to the vitrification and warming solutions can modulate mitochondrial membrane potential and the production of oxidant species in mouse oocytes.