Journal of Assisted Reproduction and Genetics最新文献

Purpose: To characterize the opinions of patients undergoing infertility treatment on the use of artificial intelligence (AI) in their care.

Methods: Patients planning or undergoing in vitro fertilization (IVF) or frozen embryo transfers were invited to complete an anonymous electronic survey from April to June 2024. The survey collected demographics, technological affinity, general perception of AI, and its applications to fertility care. Patient-reported trust of AI compared to a physician for fertility care (e.g. gamete selection, gonadotropin doing, and stimulation length) were analyzed. Descriptive statistics were calculated, and subgroup analyses by age, occupation, and parity were performed. Chi-squared tests were used to compare categorical variables.

Results: A total of 200 patients completed the survey and were primarily female (n = 193/200) and of reproductive age (mean 37 years). Patients were well educated with high technological affinity. Respondents were familiar with AI (93%) and generally supported its use in medicine (55%), but fewer trusted AI-informed reproductive care (46%). More patients disagreed (37%) that AI should be used to determine gonadotropin dose or stimulation length compared to embryo selection (26.5%; p = 0.01). In the setting of disagreement between physician and AI recommendation, patients preferred the physician-based recommendation in all treatment-related decisions. However, a larger proportion favored AI recommendations for gamete (22%) and embryo (14.5%) selection, compared to gonadotropin dosing (6.5%) or stimulation length (7.0%). Most would not be willing to pay more for AI-informed fertility care.

Conclusions: In this highly educated infertile population familiar with AI, patients still prefer physician-based recommendations compared with AI.

Objective: Preclinical evidence has demonstrated that gut microbiota composition can influence steroid hormone biosynthesis and spermatogenesis. This study aims to investigate the association of seminal microbiota and testicular steroidogenesis.

Patients and methods: One hundred adult eugonadal men were consecutively enrolled. The seminal concentration of Lactobacilli, anaerobic and facultative bacteria, as well as serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and total testosterone (TT) were evaluated. Unadjusted and adjusted multi-regression models were built to evaluate the relationship between seminal Lactobacilli, anaerobic and facultative bacteria, and Lactobacilli/total bacteria ratio, and serum LH, FSH, and TT. The concentrations of seminal Lactobacilli, anaerobic, and facultative bacteria predictive of serum TT values in the lowest quartile (< 3.8 ng/mL) were calculated.

Results: TT levels were weakly and positively correlated with seminal Lactobacillus concentration (r = 0.33; p = 0.001), with seminal Lactobacilli/total bacteria ratio (r = 0.89; p < 0.001), and negatively with anaerobic and facultative bacteria (r = - 0.69; p < 0.001). Opposite correlations were found for gonadotropin concentrations. These data persisted after adjustment for confounding factors. Seminal concentration of Lactobacilli ≤ 0.1 × 10⁶/mL (AUC 0.917, 95% CI: 0.845 to 0.963), of anaerobic and facultative bacteria > 2 × 10⁴/mL (AUC 0.924, 95% CI: 0.853 to 0.967), or a Lactobacilli/total bacteria ratio ≤ 90% (AUC 0.910, 95% CI: 0.837 to 0.958) were found to predict serum TT level < 3.8 ng/mL with a sensitivity of 92.0% and a specificity of 88.0%.

Conclusion: A relationship between the composition of the seminal microbiota and testicular steroidogenesis seems to exist. The mechanisms underlying this association are still unknown.

Purpose: To develop a predictive model for estimating the total dose of gonadotropins and the number mature oocytes in planned oocyte cryopreservation cycles.

Methods: In this retrospective study, oocyte cryopreservation cycles recorded in the Society for Assisted Reproductive Technology Clinic Outcome Reporting System Database from 2013 to 2018 were analyzed. Bivariate copula additive models for location, scale, and shape were performed to create a predictive model for estimating total dose of gonadotropins and number of mature oocytes.

Results: A total of 15,806 oocyte cryopreservation cycles between 2013 and 2018 were included in the analysis. The average age of participants was 35.4 years, the mean duration of stimulation was 11.8 days, and the average number of mature oocytes retrieved was 11.8. The treatment dose increased with age, FSH levels, BMI ≥ 35 kg/m², smoking, and history of diminished ovarian reserve, while it decreased with increasing AMH, ovulatory disorder, and BMI < 25 kg/m². The number of mature oocytes retrieved was positively correlated with AMH and negatively correlated with age, FSH levels, Asian race, and diminished ovarian reserve. With a maximum gonadotropin dosage of 450 IU per day for 12 ± 3 days of stimulation and a tolerance level of six mature oocytes, the predictive model achieved 70% accuracy. An interactive version of the equation was created as an online tool.

Conclusions: We developed a predictive model to estimate the total treatment dosage and the number of mature oocytes. This calculator, utilizing objective patient variables, can assist in patient counseling prior to planned oocyte cryopreservation cycles.

Purpose: Studies have shown mixed findings regarding the impact of stress on the success of fertility treatments. To the best of our knowledge, stress in the context of the workplace has not been investigated to date in relation to the success of fertility treatments. This research investigates the impact of work-related stress and emotional exhaustion experienced by both partners on in vitro fertilization (IVF) treatment outcomes.

Methods: We conducted a cross-sectional study that included 44 heterosexual couples (N = 88) in which both partners filled out the research questionnaire. The couples were recruited in a hospital IVF unit in the center of Israel.

Results: Women's job-related stress and emotional exhaustion lowered their chances of achieving pregnancy when undergoing IVF treatments. Moreover, when partners' emotional exhaustion was relatively low, the job-related stress of women did not affect pregnancy outcomes.

Conclusion: This is the first study to explore whether job-related stressors of both partners may have an impact on success rates of IVF treatments. We propose some practical implications as to how to eradicate their negative impact on IVF outcomes.

Purpose: This study identified novel variants of the FSIP2 and SPEF2 genes in multiple morphological abnormalities of the sperm flagella (MMAF) patients and to investigate the potential effect of variations on male infertility and assisted reproductive outcomes.

Methods: Whole-exome sequencing was performed in 106 Chinese MMAF patients. The discovered variants were evaluated in silico and confirmed by Sanger sequencing. A mini-gene assay and immunofluorescence staining were used to determine the effects on mRNA and protein. Assisted reproductive technology (ART) based on intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) was used for MMAF patients carrying novel variants.

Results: Biallelic variants in FSIP2 or SPEF2 involving nineteen novel variations were found in eleven MMAF patients. These variations included fourteen missense variants, two nonsense variants, two frameshift variants, and a splicing variant. The FSIP2 protein was markedly reduced or mislocalized to the spermatozoa head. Two novel missense variants of SPEF2 reduced cell diameter. Eleven MMAF couples had 12 ICSI cycles and 2 IVF cycles. The 2PN fertilization rate, good-quality embryos rate, and clinical pregnancy rate were 80.1% (133/166), 74.4% (99/133), and 45.7% (16/35). Four of them have seven babies born.

Conclusion: Our work revealed that missense variations of FSIP2 or SPEF2 might cause a milder spermatozoa damage. The infertility caused by FSIP2 and SPEF2 variants can be mitigated through ICSI or even IVF. The results of this study presented signs of the correlation of phenotype/genotype for the FSIP2 and SPEF2, which might provide a reference for clinical genetic and fertility consultation.

Purpose: This study is to evaluate duration of oocyte cryostorage and association with thaw survival, fertilization, blastulation, ploidy rates, and pregnancy outcomes in patients seeking fertility preservation.

Methods: Retrospective cohort study to evaluate clinical outcomes in patients who underwent fertility preservation from 2011 to 2023 via oocyte vitrification for non-oncologic indications. Primary outcome was thaw survival rate. Secondary outcomes included rates of fertilization, blastulation and embryo ploidy, as well asn pregnancy outcomes. Demographic, controlled ovarian stimulation, and laboratory data were collected for each patient. Analyses were conducted using Kruskal-Wallis, Fisher's exact test, or Chi-squared test, as appropriate. A multivariate logistic regression analysis was utilized, and adjusted odds ratios with 95% confidence intervals were calculated using Group A as the reference group.

Results: A total of 5995 oocytes met inclusion criteria. These were divided into quartiles based on duration of cryostorage. Group A included oocytes in cryostorage for 0-2 years; Group B, 3-5 years; and Group C, 6-11 years. Significant differences were found when comparing thaw survival (p < 0.0001), fertilization (p = 0.0009), and blastulation rates (p = 0.0002) among groups; however, no significant differences were seen after multivariate GEE regression analysis. No significant differences were seen in rates of euploidy (p = 0.70), live birth (p = 0.81), and clinical pregnancy (p = 0.58) among groups. After analyzing years in cryostorage as a continuous variable and controlling for confounders, duration of cryostorage was not related to odds of thaw, fertilization, blastulation, euploid rates, or pregnancy outcomes.

Conclusion: Length of time in cryostorage is not associated with compromised rates of oocyte thaw survival, fertilization, blastulation, ploidy, or pregnancy outcomes.

Purpose: Preimplantation aneuploidy in humans is one of the primary causes of implantation failure and embryo miscarriage. This study was conducted to gain insight into gene expression changes that may result from aneuploidy in blastocysts through RNA-Seq analysis.

Methods: The surplus embryos of preimplantation genetic testing for aneuploidy (PGT-A) candidate couples with normal karyotype and maternal age < 38 were collected following identical ovarian stimulation protocol. The embryos were selected based on trophectoderm biopsy and array comparative genomic hybridization in three groups: normal group, small chromosomes aneuploidy group (SCA), including single aneuploidy for small chromosomes 16, 20, 21, 22, and other chromosomes aneuploidy group (OCA), including single aneuploidy for other chromosomes.

Results: Principal component analysis revealed overall differentiation of transcriptome of the groups, confirming embryo classification. The Gene Ontology indicated that transcription, ubiquitination, autophagy, and DNA repair pathways were upregulated in aneuploid embryos. The overexpression of five genes, UBE2E2 and VPS4A, BUB1B, CDCA8, and COX14 was confirmed by quantitative real-time PCR. Additionally, overexpression was observed in translation and protein synthesis pathways in aneuploid embryos. Mitochondrial pathway upregulation was notable in both SCA and OCA groups, while the apoptosis pathway was overexpressed only in the OCA group. Only cellular lipid synthesis pathway differed between SCA and OCA, the two aneuploid groups.

Conclusions: This study highlights the impact of aneuploidy on the gene expression in blastocysts independent of aneuploidy type and paves the way for understanding the molecular mechanisms underlying the generation of aneuploidy.

A couple presenting with more than 3 years' history of infertility and three miscarriages was tested for serum homocysteine levels and for the two principal MTHFR SNPs: 677C < T and 1298A < C, as per our general policy for patients with infertility of long duration. The woman was found to be wild type for both MTHFR SNPs with a serum homocysteine 10.5 µM, slightly higher than our accepted normal value of 8.5 µM. The man was found to be a carrier of a triple mutation for 677C < T and 1298 A < C, with an elevated homocysteine level of 19 µM. Since high doses of folic acid (FA) exacerbate perturbations in the DNA methylome, the husband was treated with 5-methyl tetrahydrofolate together with nutritional support of the one-carbon cycle (OCC). After 3 months of treatment, the couple conceived, and the woman delivered a healthy female baby. Three years later, she again conceived and delivered a second healthy female baby. Our treatment can restore fertility in males affected by a triple SNP mutation in the MTHFR gene; this confirms that Hcy and MTHFR SNP testing should not be overlooked in patients affected by long duration of infertility/repeat miscarriages.

Purpose: To investigate the genotype-phenotype correlations of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and their impact on male reproductive tract development in a cohort of Chinese patients with congenital absence of the vas deferens (CAVD).

Methods: A total of 121 Chinese CAVD patients underwent genetic testing for CFTR and ADGRG2 mutations, semen analysis, scrotal and transrectal ultrasound examinations, and reproductive hormone measurements. The genotype-phenotype correlations were analyzed, focusing on the impact of CFTR variants on the presence or absence of the epididymis, vas deferens, seminal vesicles, and other related structures.

Results: CFTR mutations were identified in 72.7% (88/121) of CAVD patients, with the IVS9-5 T variant being the most prevalent (54.5%, 66/121). Six novel CFTR variants (CFTR: L218Ffs*15, V1007Ffs*40, V938M, A566V, S605P, H949P) were identified in Chinese men. Patients with CFTR homozygous IVS9-5 T variants had a significantly lower rate of epididymal absence compared to those with one 5 T and one non-5 T variant or two non-5 T variants (p = 0.016). Notably, patients carrying at least one non-5 T variant were associated with an 8.17-fold increased risk of epididymal partial absence compared to those having the homozygous 5 T mutation (95% confidence interval 1.52-59.58, p = 0.009).

Conclusion: This study provides novel insights into the genotype-phenotype correlations of CFTR variants in Chinese CAVD patients, highlighting the differential impact of 5 T and non-5 T variants on male reproductive tract development. These findings provide additional information that may be helpful for genetic counseling, clinical management, and the development of personalized diagnostic and therapeutic strategies for CAVD patients.

Purpose: The objective of this study was to investigate the correlation between the pronuclear/cytoplasmic (PN/C) ratio and the number of chromosomes in mouse zygotes to understand the implications of pronuclear size regulation in early embryonic development.

Methods: A combination of enucleation and aggregated chromosomes/chromatin (AC) transfer was utilized to create oocytes with varying numbers of chromosomes. Time-lapse imaging and immunofluorescence staining were employed to analyze pronuclear dynamics and chromosomal configurations.

Results: Higher chromosome numbers correspond to a larger PN/C ratio. Oocytes with a higher number of chromosomes exhibited larger pronuclei.

Conclusion: The study underscores the complexity of pronuclear size regulation and its correlation with the number of chromosomes. The findings suggest potential applications in ART, where assessing the PN/C ratio could serve as a biomarker for zygote quality and aneuploidy.