Journal of Assisted Reproduction and Genetics最新文献

Purpose: To explore the impact of seasonal variations on the risks of hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) in women who undergo in vitro fertilization (IVF) treatment.

Methods: We retrospectively included a total of 21,469 women who achieved singleton delivery during their first cycles of IVF, the risks of HDP and GDM were compared in different seasonal groups according to the time of embryo transfer and the time of oocyte retrieval.

Results: After adjustment via multivariable logistic regression, women who underwent embryo transfer in spring with the expected date of confinement in winter had a higher risk of HDP (4.9% vs. 3.8%; adjusted odds ratio (aOR), 1.34; 95% confidence interval (CI), 1.09-1.64; P = 0.005) than those underwent embryo transfer in winter with the expected date of confinement in autumn. There were no seasonal variations in the risk of HDP according to the time of oocyte retrieval or in the risk of GDM regardless of the time of embryo transfer or the time of oocyte retrieval. After subgroup analysis, the seasonal variations in the risk of HDP remained in frozen embryo transfer (FET) cycles but not in fresh embryo transfer (FreET) cycles.

Conclusions: The risk of HDP was increased in women who underwent embryo transfer in spring compared to those who underwent embryo transfer in winter. The risk of HDP is more likely to be affected by the season at the time of embryo transfer in FET cycles compared to FreET cycles.

Aim: Assisted reproductive technology (ART) is an invaluable strategy for preventing the inheritance of genetic disorders and promoting the birth of healthy children. Nevertheless, the general public's limited understanding of genetics and low awareness of available services obstruct effective utilization of genetic counseling. Our analysis of a family affected by mitochondrial genetic disease aims to improve public understanding of genetic knowledge and the importance of genetic counseling.

Methods: We gathered comprehensive data on a family with mitochondrial disease and scrutinized the genetic sequencing and diagnostic procedures used to identify mitochondrial disease within the family.

Results: In a case involving a family with two daughters, both began to exhibit symptoms such as abnormal gait, myodystonia, and excessive fatigue at the age of 4. These symptoms were incorrectly assumed to be paternally inherited, as the mother believed the father had a mild intellectual disability. As a result, the family opted for ART, specifically in vitro fertilization (IVF) with donor sperm, without thorough genetic counseling or a conclusive diagnosis for the children. Despite these precautions, the son born from IVF presented with symptoms mirroring his sisters' at the age of 6, including typical MRI abnormal signals in the bilateral basal ganglia. Furthermore, the eldest daughter's naturally conceived child also started to show identical symptoms by the age of 3. Subsequent genetic testing revealed a homoplasmic pathogenic mutation in the MT-ND6 gene (m.14459G>A), confirming that the dystonia was maternally inherited, with the mother exhibiting an 89.2% heteroplasmic variation in the same gene.

Conclusions: This case study demonstrates the significant consequences of a lack of genetic knowledge and prevailing misconceptions when applying ART. It underscores the urgent need to bolster genetic literacy and emphasizes the vital importance of informed decision-making within genetic healthcare services.

Background: Non-obstructive azoospermia (NOA) is considered one of the most severe forms of male infertility. Despite the limited range of testicular phenotypes, NOA exhibits considerable genetic heterogeneity. The aim of this study was to uncover the etiopathogenesis of NOA and provide insights into the outcomes of testicular sperm extraction (TESE).

Material method: To elucidate the potential causes of testicular pathogenesis, a cohort of 61 patients was analyzed. The genetic etiology was assessed using our developed gene panel, based on genes with prior functional studies conducted specifically in the context of testicular characterization.

Results: Our analytical approach, built upon these findings, enabled us to explore the potential genetic causes of NOA and assess their relevance to TESE outcomes. A potential causal defect was identified in 14 genes across a total of 26 individuals (42%). Of these, three genes-MEIOB, TERB1, and USP26-had been previously described in men, while eight genes-SPO11, RBBP7, STS, RBMXL3, ZCCHC13, HUWE1, ESR1, and ABCD1-had been reported in prior studies. Additionally, three genes-CEP85, NAP1L3, and CENPI-had been previously described only in knockout (KO) phenotype studies, and this study represents the first identification of these genes in men.

Conclusion: Interestingly, the histological findings of meiotic arrest were strongly linked to genes involved in meiosis, reinforcing the clinical diagnosis of patients in this cohort. Additionally, our study underscores the importance of refining diagnostic strategies that focus on genes associated with testicular phenotypes, which could enhance the accuracy of TESE success predictions.

Purpose: Premature ovarian insufficiency (POI) and non-obstructive azoospermia (NOA) are the most severe forms of infertility. Pathogenic variants in a number of genes cause both disorders in siblings. One of them is STAG3, which encodes a meiosis-specific subunit of a cohesin complex. Here, we searched for genetic cause of oligoasthenoteratozoospermia (OAT) and POI within one family.

Methods: The proband was a 16-year-old girl with secondary amenorrhea. She was diagnosed with hypergonadotropic hypogonadism and streak ovaries. She had normal karyotype 46,XX and no premutation in FMR1 gene. Her 28-year-old brother was diagnosed with severe oligoasthenoteratozoospermia (OAT) syndrome. The aneuploidy rate in his sperm was assessed by FISH assay and appeared to be extremely high with only 5% of morphologically normal spermatozoa being haploid. He had normal karyotype 46,XY and no AZF microdeletions.

Results: Whole exome sequencing identified two likely pathogenic heterozygous truncating variants in STAG3 gene, prevously described p.Arg926Ter and novel p.Glu1184Ter. Sanger sequencing showed that both the patient and her brother were compound heterozygotes.

Conclusion: In this study, we suggest the association of the identified variants in STAG3 gene with OAT syndrome and POI and describe the third familial case of STAG3-related infertility.

Purpose: The study investigates patient perspectives on the use of Preimplantation Genetic Testing for Polygenic disease (PGT-P) to select embryos with lower risks for common polygenic diseases. Participant responses and attitudes were evaluated after receiving simulated embryo PRS generated from their personal genetic profile.

Methods: Couples seeking OB/GYN or Reproductive Endocrinology and Infertility (REI) care with an interest in genetic risks for common diseases in their prospective children participated. A tool provided PRS scores for 11 conditions, using parental DNA to simulate genetic risks for hypothetical embryos produced during IVF. Participants received counseling, reviewed results online, and completed a post-test survey. Feedback from 90 participants assessed understanding and attitudes toward PRS use in IVF.

Results: Participants were overall more supportive of screening embryos for childhood-onset diseases (80%) compared to adult-onset conditions (63%); however, among specific diseases, participants expressed the greatest interest in screening for adult-onset cognitive disorders (Schizophrenia, 86%, Alzheimer's disease, 82%). Participant-free responses noted the importance of personalized counseling and participants not of European ancestry expressed frustration with limited PRS applicability. Negative reactions to testing (nervousness or anxiety 5%, regret 2%) were explored.

Conclusions: The findings examine the receipt of simulated embryo PRS in a patient population in which support for using PRS during embryo prioritization is high. Positive patient interest was consistent with other US studies; as prior studies identify significant clinician discomfort, these results highlight the need for comprehensive genetic counseling and inclusive stakeholder input in shaping guidelines for PRS during IVF.

Purpose: Semen manipulation for assisted reproductive technology (ART) causes spermatozoa damage; thus, we investigated the potential of the novel therapeutic BGP-15 to preserve sperm quality during semen washing prior to insemination.

Methods: Donated human ejaculates (N = 40), with or without 10 µM BGP-15, were analyzed for sperm motility, DNA fragmentation, and oxidation. Seminal plasma was removed using different clinical sperm selection methods: simple wash, swim-up, or density gradient centrifugation (DGC), followed by assessment for sperm motility, mitochondrial ROS (mtROS), mitochondrial membrane potential (MMP), and DNA fragmentation and oxidation.

Results: Donated semen samples incubated with BGP-15 had increased sperm motility (+ 15%, p = 0.002) and reduced oxidative DNA damage levels (- 57%, p = 0.03). Samples processed by simple wash had the highest sperm count compared with DGC (+ 55%, p < 0.005) and swim-up (+ 21%, p < 0.0005). Swim-up showed increased vitality compared with DGC (+ 18%, p < 0.001) and simple wash (+ 27%, p < 0.0001), as well as the lowest DNA oxidation levels compared with simple wash - 40%, (p = 0.01) and DGC (- 76%, p < 0.0001). Swim-up also had the lowest mitochondrial membrane potential compared with simple wash and DGC (- 28%, p < 0.03). Comparison between untreated and BGP-15-treated groups for each sperm washing method showed that BGP-15 increased MMP in DGC sperm (+ 11%, p = 0.0006), and reduced DNA fragmentation in washed samples (- 22%, p = 0.03). Moreover, BGP-15 lowered DNA oxidation in all preparation methods: washed (- 48%, p = 0.002), swim-up (- 42%, p = 0.04), and DGC (- 29%, p < 0.0001).

Conclusions: The inclusion of BGP-15 during semen preparation can protect sperm quality and, in the future, may be used clinically to improve sperm selection methods.