Journal of Assisted Reproduction and Genetics最新文献

Purpose: To identify treatment-related factors influencing low oocyte maturation rates in standard ovarian stimulation (OS) cycles and patients' candidates for clinical studies on rescue-IVM.

Methods: Retrospective study including retrievals with ≥ 1 cumulus-oocyte-complex (COC; years: 2008-2022). The weighted-mean immaturityrate (19%) was defined in the whole dataset (N = 16,155). Variables associated with immaturity rates and warning limit (defined as weighted average + 2SD) were appraised among first retrievals with ≥ 5 COCs (N = 7962). Of the patients undergoing a first oocyte pick-up, 667 completed three retrieval cycles, enabling evaluation of the true prevalence of patients exceeding the immaturity rate warning threshold over multiple cycles.

Results: Factors influencing immaturity rate included OS duration, trigger type (GnRH-agonist versus urinary-hCG), ovulation trigger to oocytes' denudation interval and ratio COC to follicle > 14 mm at ovulation trigger. In first retrievals with ≥ 5 COCs, the immaturity rate warning limit was 51%, occurring in 3.6% of initial retrievals, 3.8% of second retrievals, and 2.1% of third retrievals. In three consecutive retrievals, the conservative prevalence of patients exceeding this threshold once, twice, and three times was 4.4%, 0.3%, and 0.03%, respectively. Assuming all patients would have conducted three retrievals, these rates were estimated as 7.8%, 1.5%, and 0.3%. In the 667 patients who conducted three retrievals, observed rates were 7.6%, 0.9%, and 0.4%, confirming the reliability of the estimates.

Conclusions: Ovarian stimulation and laboratory factors impact oocyte maturation rate. An oocyte immaturity rate exceeding 51%, in patients retrieving ≥ 5 oocytes, may represent a strong inclusion criterion for future clinical studies on rescue-IVM.

Objective: To evaluate the impact of a history of gestational trophoblastic disease on pregnancy outcomes in in vitro fertilization-embryo transfer procedures(IVF-ET) and to utilize logistic regression to analyze potential risk factors influencing re-pregnancy outcomes among women with GTD histories undergoing IVF-ET.

Methods: This retrospective cohort study collected data from patients with a history of GTD who underwent IVF-ET at the hospital from January 2018 to January 2023. The study group comprised 27 women with a history of GTD. A control group of 54 women, matched at a 1:2 ratio, without a GTD history, was selected from those who underwent IVF-ET during the same period at the same hospital. Statistical analyses were employed to compare baseline characteristics, embryological parameters, and pregnancy outcomes between the two groups.

Results: The study group exhibited significantly lower endometrial thickness (EMT) during the mid-luteal phase of the natural menstrual cycle, reduced EMT on the day of embryo transfer (ET), and a decreased blastocyst formation rate compared to the control group (p < 0.05). Furthermore, the study group had a higher number of uterine curettages prior to transfer, an increased rate of discarded embryos, and higher total sperm motility (PR + NP) in their spouses (p < 0.05). Logistic regression analysis revealed that a history of GTD does not significantly affect pregnancy outcomes post-IVF-ET.

Conclusion(s): A history of GTD does not significantly influence pregnancy outcomes following IVF-ET. Therefore, patients with a GTD history and their physicians can approach the IVF-ET process with less anxiety and adopt a more positive and rational outlook.

Purpose: To investigate whether targeting the ER-mitochondria axis can improve embryonic development in a post-ovulatory aging (POA) model by evaluating organelle-specific modulation.

Methods: Fresh oocytes were collected immediately after ovulation, and post-ovulatory aged oocytes were obtained using a mouse model. Fresh oocytes were treated with thapsigargin (an ER stress inducer) or CCCP (a mitochondrial inhibitor), and ER stress (GRP78 fluorescence) and mitochondrial superoxide status (MitoSOX™ fluorescence) were assessed. Aged oocytes were treated with salubrinal (an ER stress modulator), 5-aminolevulinic acid (5-ALA, a mitochondrial modulator), or both. Embryonic development was evaluated via blastocyst formation and cell death rates.

Results: In fresh oocytes, CCCP increased GRP78 fluorescence, and thapsigargin increased MitoSOX fluorescence, consistent with bidirectional ER-mitochondria stress propagation. In POA oocytes, salubrinal reduced GRP78 fluorescence but not MitoSOX, whereas 5-ALA reduced MitoSOX fluorescence but not GRP78; the combined treatment showed no additive effects on either proxy marker. Despite the lack of additivity at the marker level, blastocyst formation increased and apoptosis decreased in all treatment groups, with no additional benefit of combined treatment compared with single agents.

Conclusions: In this POA model, ER-mitochondria coupling detected in freshly ovulated oocytes appeared attenuated. While our single-marker readouts (GRP78 and MitoSOX) are limited proxies, independent targeting of either organelle modestly improved blastocyst formation. These data support a hypothesis-generating framework for future studies in maternal aging models. Results were obtained under 20% O₂ culture and may be conservative relative to physiologic (5%) O₂ conditions.

Purpose: To investigate how different forms of chromosomal imbalance affect human embryo morphokinetics, using a dataset of PGT-A tested embryos and a robust statistical framework that accounts for patient- and cycle-level variability.

Methods: This retrospective cohort study included 1303 embryos from 525 ICSI-PGT-A cycles from a single centre. Embryos were categorized by aneuploidy type as euploid, single, double, or complex (≥ 3) and further subtyped by chromosomal configuration. Developmental timings were extracted from time-lapse monitoring and compared using linear mixed-effects models with random intercepts for patient and treatment cycle. Estimated marginal means and pairwise contrasts were calculated for each morphokinetic parameter (tPB2 to tEB) and key developmental intervals (tSC → tB, tM → tEB).

Results: Morphokinetic behavior varied according to chromosomal load and aneuploidy type. Single aneuploidies, particularly monosomies, showed a biphasic delay pattern, with subtle slowing during early cleavage (tPNf-t2) and more pronounced divergence during blastulation (tSB-tEB). Double aneuploidies demonstrated partial early compensation followed by late-stage deceleration, suggesting non-additive or adaptive effects. Complex aneuploidies, and especially complex mosaic embryos, exhibited global and cumulative delays across nearly all stages, reflecting a progressive loss of developmental synchrony with increasing genomic imbalance.

Conclusion: These findings support a dosage-dependent model of developmental disruption, in which the severity and timing of morphokinetic delay correlate with aneuploidy complexity in a stage-specific and non-linear manner. While not diagnostic on their own, time-lapse imaging may contribute to ploidy risk assessment and help identify embryos that could benefit from biopsy and further evaluation through PGT-A, particularly when integrated with clinical, biomarker, and genomic information.

Purpose: Does fertility preservation (FP) through oocyte cryopreservation provide realistic reproductive opportunities for diminished ovarian reserve (DOR)? Literature suggests cumulative live birth rates of 30-45% with 8-10 oocytes under 35 years old. Insufficient data exist to define whether DOR patients should be offered FP systematically.

Methods: This retrospective single-center study analyzed data from 304 women undergoing oocyte cryopreservation (January 2016-December 2024). Patients were stratified into cohort 1 (Anti-Müllerian hormone-AMH-≤ 0.5 ng/mL, n = 49) and cohort 2 (AMH > 0.5 ng/mL, n = 255). Primary outcomes included retrieved oocytes (RO) and vitrified oocytes (VO). Secondary outcome examined DuoStim results. Statistical analysis included correlation assessments, ANCOVA, and multiple linear regression.

Results: DOR patients achieved lower oocyte yields compared to cohort 2 (RO: 3.1 ± 2.3 vs. 9.0 ± 6.5; VO: 2.3 ± 1.9 vs. 7.4 ± 5.1; p < 0.001), despite higher gonadotropin doses. AMH strongly correlated with RO (ρ = 0.636, p < 0.001) and VO (ρ = 0.624, p < 0.001). Linear regression confirmed AMH (B = 1.151, p < 0.001) and age (B =  - 0.139, p = 0.002) as significant predictors of VO. In DuoStim subgroup, DOR patients achieved 3.3 ± 2.1 total VO compared to 6.9 ± 3.3 in cohort 2 (p = 0.001).

Conclusion: DOR patients achieve oocyte yields substantially below thresholds associated with reasonable live birth rates, raising concerns regarding FP efficacy. These findings highlight the need for personalized counseling that considers individual patient characteristics and provides evidence-based, realistic expectations for FP. A revision of current AMH thresholds may improve patient selection and cost-effectiveness of FP programs. Younger DOR patients may benefit from oocyte cryopreservation for FP, emphasizing the importance of age stratification.

Purpose: The purpose of this study is to assess whether discontinuing routine serum hormone testing following gonadotropin-releasing hormone (GnRH) agonist trigger affects the incidence of empty follicle syndrome (EFS) and embryological outcomes in controlled ovarian stimulation (COS) cycles.

Methods: This retrospective cohort study analyzed 3834 COS cycles at a single fertility center from May 2020 to May 2024. Cycles were grouped based on post-trigger testing: 1964 with routine serum hormone measurement and 1870 without. The primary outcome was EFS, defined as failure to retrieve oocytes despite adequate follicular development. Secondary outcomes included the number of oocytes retrieved, mature oocytes, fertilization rates, and utilizable embryos.

Results: The incidence of EFS did not significantly differ between groups (0.87% with testing vs. 1.07% without; p = 0.06). In GnRH agonist-triggered cycles, the incidence was 0.74% with testing and 0.96% without (p = 0.53). After adjusting for age, trigger medication type, and estradiol level, there was no significant difference in the odds of EFS (adjusted OR 1.26; 95% CI, 0.63 to 2.53; p = 0.52). Secondary outcomes showed statistically significant improvements in the group without testing: oocytes retrieved (mean 12.6 vs. 12.0; p = 0.03), mature oocytes (mean 7.3 vs. 6.4; p < 0.01), and embryos suitable for clinical use (mean 4.0 vs. 3.6; p < 0.01). Fertilization rates were similar between groups.

Conclusion: The discontinuation of routine hormone testing following the GnRH agonist trigger did not increase the incidence of EFS and was associated with comparable embryological outcomes. These findings suggest that routine testing may be unnecessary in most cases, supporting a selective approach, potentially reducing clinical burden and cost without compromising patient care.

Purpose: Idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are rare reproductive disorders with known genetic heterogeneity. Using exome sequencing, our group previously reported the prevalence of pathogenic and likely pathogenic (P/LP) variants in genes causing IHH/KS as the primary endpoint of our study. Here, we investigate the frequency of secondary findings (SF) to determine whether individuals with IHH/KS harbor an increased burden of P/LP variants in medically actionable genes (MAGs) defined by the American College of Medical Genetics and Genomics (ACMG).

Methods: We analyzed exome sequencing data from 156 individuals with clinically confirmed IHH/KS. Variants were filtered for P/LP classification using ACMG guidelines across all 84 MAGs in ACMG SF v3.3. Sanger sequencing was used for orthogonal confirmation. The prevalence of MAG variants was compared to external control datasets from the U.K. Biobank (UKB, ~ 50,000 genomes) and the NIH eMERGE Network (~ 21,000 genomes), both based on the ACMG SF v2.0 59-gene list.

Results: Among 370,000 variants, 2 individuals (1.3%) carried validated P/LP variants in two distinct MAGs: SCN5A and MYBPC3. Genes 60-84, the additional 25 genes on the ACMG SF v3.3 list, yielded no additional variants. The prevalence of MAG variants in IHH/KS (1.3%) was not significantly different from UKB (2.0%) or eMERGE (2.5%) (OR vs. UKB: OR 0.64; 95% CI, 0.16-2.61; P = 0.57).

Conclusions: The frequency of P/LP variants in MAGs among IHH/KS patients is comparable to the general population, suggesting that MAG variants are not common in IHH/KS in contrast to some other types of infertility.

Purpose: Sperm DNA damage is linked to male infertility and poor reproductive outcome. Single-stranded DNA (ssDNA) damage in sperm is the most common type of damage yet is not specifically targeted by the commonly used DNA damage assays. This study aimed to quantitatively detect sperm ssDNA damage using a novel, direct method.

Methods: The sperm repair-assisted damage detection (SRADD) assay is a single-molecule technique that uses specific repair enzymes to excise damaged segments and incorporates fluorescently labeled nucleotides, enabling visualization and quantification of the damage. We assessed ssDNA damage in sperm donors following induced damage using varying concentrations of H₂O₂. The assay was evaluated for sensitivity, repeatability, and reproducibility. SRADD results were compared with the direct TUNEL assay and the indirect sperm chromatin dispersion (SCD) assay.

Results: SRADD demonstrated high inter-slide reproducibility (ICC = 0.95). Sensitivity was confirmed by quantifying induced damage in a dose-dependent manner (0.5, 1, 1.5 mM of H₂O₂), demonstrating mean damage ratios of 1.06, 2.16, and 4.83 relative to control, respectively. Baseline damage levels exhibited strong positive correlation with increased induced damage (r = 0.91, p < 0.001). Analysis of healthy sperm donors (n = 59) revealed that 8.5% of men with normal sperm parameters presented with high ssDNA damage levels. SRADD had a moderate correlation with SCD assay and no correlation with conventional semen parameters and TUNEL assay.

Conclusion: The SRADD assay quantifies sperm ssDNA with high sensitivity and can process dozens of samples simultaneously, making it valuable for andrology and toxicology research and potentially useful in clinical settings such as sperm banks and male-infertility assessment.

Trial registration: (6573-19-SMV).

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.