infertility next generation sequencing

IMPORTANCE: The safety of exogenous gonadotropin treatment, based on its effect on embryos and pregnancy outcomes, remains inconclusive. OBJECTIVE: To evaluate the associations of different doses and durations of gonadotropins with embryonic genetic status and pregnancy outcomes after euploid embryo transfer in couples with infertility. DESIGN, SETTING, AND PARTICIPANTS: This study was a post hoc analysis of a multicenter randomized clinical trial (RCT) conducted at 14 reproductive centers throughout China from July 2017 to June 2018 that evaluated the cumulative live birth rate with or without preimplantation genetic testing for aneuploidy (PGT-A) among couples with infertility and good prognosis...

PURPOSE: Unpredictable genetic modifications and chromosomal aberrations following CRISPR/Cas9 administration hamper the efficacy of germline editing. Repair events triggered by double-strand DNA breaks (DSBs) besides non-homologous end joining and repair template-driven homology-directed repair have been insufficiently investigated in mouse. In this work, we are the first to investigate the precise repair mechanisms triggered by parental-specific DSB induction in mouse for paternal mutational correction in the context of an infertility-related mutation...

Background Infertility remains a significant global challenge, and recurrent implantation failure (RIF) poses a considerable concern in assisted reproductive technology. Understanding the factors contributing to implantation failure is essential for developing accurate diagnostic tools and treatment strategies. Endometrial receptivity (ER) during the window of implantation is crucial for successful embryo implantation in in vitro fertilization (IVF) procedures. Molecular-based endometrial receptivity analysis and next-generation sequencing provide insights into ER, but there is a lack of research on these in the Indian population, particularly in patients with RIF...

Silver-Russell syndrome (SRS) is a heterogeneous disorder characterized by intrauterine and postnatal growth retardation. HMGA2 variants are a rare cause of SRS and its functional role in human linear growth is unclear. Patients with suspected SRS negative for 11p15LOM/mUPD7 underwent whole-exome and/or targeted-genome sequencing. Mutant HMGA2 protein expression and nuclear localization were assessed. Two Hmga2-knockin mouse models were generated. Five clinical SRS patients harbored HMGA2 variants with differing functional impacts: 2 stop-gain nonsense variants (c...

OBJECTIVE: This review provides a comprehensive overview of the existing research on the seminal microbiome and its association with male infertility, while also highlighting areas that warrant further investigation. METHODS: A narrative review was conducted, encompassing all relevant studies published between 1980-2023 on the male reproductive tract microbiome in humans. This review considered studies utilizing culture-based, polymerase chain reaction (PCR)-based, and next-generation sequencing (NGS)-based methodologies to analyze the microbiome...

PURPOSE: To identify germline mutations related to azoospermia etiology and reproductive potential of surgically retrieved spermatozoa, and to investigate the feasibility of predicting seminiferous tubule function of nonobstructive azoospermic men by transcriptomic profiling of ejaculates. MATERIALS AND METHODS: Sperm specimens were obtained from 30 men (38.4 ± 6 years) undergoing epididymal sperm aspiration for obstructive azoospermia (OA, n = 19) acquired by vasectomy, or testicular biopsy for nonobstructive azoospermia (NOA, n = 11)...

OBJECTIVE: Analysis of cell free DNA in spent culture media has been identified as a non-invasive alternative to trophectoderm biopsy for PGT-A. However, the clinical value has not been well studied. We performed a pilot study with the primary interest of estimating the positive predictive value of copy number variations to predict nonviable or aneuploid embryos and investigate the false positive risk. DESIGN: Diagnostic/prognostic accuracy study. SUBJECTS: Patients aged 35 and younger with an indication for IVF-ICSI and elective single frozen embryo transfer at a single, private IVF centre...

OBJECTIVE: To explore the taxonomic and predicted functional relationship between the urine microbiome and alterations of semen analysis (SA) parameters. DESIGN: Cross-sectional study. SETTING: Academic medical center. SUBJECTS: Men presenting for fertility evaluation or men presenting for vasectomy consultation with proven biological paternity were recruited and stratified based on alterations, or lack thereof, in SA parameters...

CONTEXT: Little is known about the microbial composition of stallion semen. AIMS: To describe the microbiota detected in equine semen of healthy miniature pony stallions. METHODS: Semen specimens were collected using a Missouri artificial vagina at a single time point. PacBio (Pacific Biosciences) genomic DNA sequencing of the 16S rRNA gene was performed on these specimens, following which next-generation microbiome bioinformatics platform QIIME2 was used to process fastq files and analyse the amplicon data...

Endometriosis is an inflammatory condition affecting approximately 10% of the female-born population. Despite its prevalence, the lack of noninvasive biomarkers has contributed to an established global diagnostic delay. The intricate pathophysiology of this enigmatic disease may leave signatures in the blood, which, when detected, can be used as noninvasive biomarkers. This review provides an update on how investigators are utilizing the established disease pathways and innovative methodologies, including genome-wide association studies, next-generation sequencing, and machine learning, to unravel the clues left in the blood to develop blood biomarkers...

The dynamic interplay between the immunome and microbiome in reproductive health is a complex and rapidly advancing research field, holding tremendously vast possibilities for the development of reproductive medicine. This immunome-microbiome relationship influences the innate and adaptive immune responses, thereby affecting the onset and progression of reproductive disorders. However, the mechanisms governing these interactions remain elusive and require innovative approaches to gather more understanding. This comprehensive review examines the current knowledge on reproductive microbiomes across various parts of female reproductive tract, with special consideration of bidirectional interactions between microbiomes and the immune system...

Mean sperm counts are declining at an accelerated rate and infertility is increasingly becoming a public health concern. It is now understood that human semen, previously considered to be sterile, harbours its own specific microbiome. Via activated leucocytes and the generation of reactive oxygen species, bacteria have the capability of evoking an immune response which may lead to sperm damage. Men with infertility have higher rates of both reactive oxygen species and sperm DNA damage. Due to the lack of sensitivity of routine culture and PCR-based methods, next-generation sequencing technology is being employed to characterise the seminal microbiome...

BACKGROUND: Infection and inflammation of the genital tract are major potentially treatable factors contributing to male infertility. The profile of small non-coding RNA (sncRNAs) in spermatozoa can be altered by environmental exposures and inflammatory conditions. OBJECTIVES: Experimental autoimmune epididymo-orchitis (EAEO) is a well-established model of autoimmune-induced chronic testicular and epididymal inflammation. This model investigates the effect of chronic inflammation on sperm sncRNA profiles and offspring phenotypes...

This retrospective cohort study aimed to assess the effect of chromosomal reciprocal translocation on meiotic segregation products of non-translocation chromosomes. A total of 744 reciprocal translocation carriers and 875 non-carriers were included in this study. A total of 6,832 blastocysts were biopsied and tested by next-generation sequencing. Blastocysts from the carrier group were classified into five subgroups according to the theoretical segregation pattern of quadrivalent structure. For carrier patients, normal meiotic segregation products of the non-translocation chromosome were classified after excluding the segregation modes of the quadrivalent structure...

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common autosomal dominant genetic diseases. Whole exome sequencing (WES) is a routine tool for diagnostic confirmation of genetic diseases, and it is usually performed to confirm the clinical diagnosis in ADPKD. Reciprocal translocation is the most common chromosomal structural abnormalities and most of its carriers have normal phenotypes until they are encountered infertility problems in adulthood. However, for the polycystic kidney disease caused by abnormal chromosome structure, WES is difficult to achieve the purpose of gene diagnosis...

Advanced reproductive technologies are utilized to identify the genetic mutations that lead to spermatogenic impairment, and allow informed genetic counseling to patients to prevent the transmission of genetic defects to offspring. The purpose of this study was to identify potential single nucleotide polymorphisms (SNPs) associated with male infertility. Genetic variants that may cause infertility are identified by combining the targeted next-generation sequencing (NGS) panel and whole exome sequencing (WES)...

BACKGROUND: Sex determining region Y box transcription factor 2 (SOX2) mutations lead to bilateral anophthalmia with autosomal dominant human inheritance. SOX2 mutations could result in severe ocular phenotypes usually associated with variable systemic defects. Most patients described with SOX2 anophthalmia syndrome possessed de novo mutations in this gene. CASE PRESENTATION: In this case report, we describe 2 brothers with mental retardation and bilateral anophthalmia caused due to SOX2 germline mosaicism in unaffected parents...

OBJECTIVES: The objective of the study was to describe phenotype-genotype correlation in selected cases with infertility and emphasise the importance of genetic testing as useful tool for proper treatment decision making MATERIAL AND METHODS: Genetic tests were performed in four patients as a part of diagnostic procedure by Sanger sequencing or targeted next generation sequencing (NGS gene panel). RESULTS: We found the genetic causes of hypogonadotropic hypogonadism in 3 males and female with infertility...

BACKGROUND: Expanded genetic screening before conception or during prenatal care can provide a more comprehensive evaluation of heritable fetal diseases. This study aimed to provide a large cohort to evaluate the significance of expanded carrier screening and to consolidate the role of expanded genetic screening in prenatal care. METHODS: This multicentre, retrospective cohort study was conducted between 31 December 2019 and 21 July 2022. A screening panel containing 302 genes and next-generation sequencing were used for the evaluation...

PURPOSE: Kallmann syndrome is a rare disease characterized by delayed puberty, infertility and anosmia. We report the clinical and genetic characteristics of three patients with Kallmann syndrome who presented with Klinefelter syndrome and defined this neglected combined form of hypogonadism as mixed hypogonadism. METHODS: Clinical data and examinations were obtained, including laboratory examination and magnetic resonance imagination (MRI) of the olfactory structures...