Background: As in other domains of medicine, high-throughput sequencing methods have led to the identification of an ever-increasing number of gene variants in the fields of both male and female infertility. The increasing number of recently identified genes allows an accurate diagnosis for previously idiopathic cases of female infertility and more appropriate patient care. However, robust evidence of the gene-disease relationships (GDR) allowing the proper translation to clinical application is still missing in many cases.

Objective And Rationale: An evidence-based curation of currently identified genes involved in female infertility and differences in sex development (DSD) would significantly improve both diagnostic performance and genetic research. We therefore performed a systematic review to summarize current knowledge and assess the available GDR.

Search Methods: PRISMA guidelines were applied to curate all available information from PubMed and Web of Science on genetics of human female infertility and DSD leading to infertility, from 1 January 1988 to 1 November 2021. The reviewed pathologies include non-syndromic as well as syndromic female infertility, and endocrine and reproductive system disorders. The evidence that an identified phenotype is caused by pathogenic variants in a specific gene was assessed according to a standardized scoring system. A final score (no evidence, limited, moderate, strong, or definitive) was assigned to every GDR.

Outcomes: A total of 45 271 publications were identified and screened for inclusion of which 1078 were selected for gene and variant extraction. We have identified 395 genes and validated 466 GDRs covering all reported monogenic causes of female infertility and DSD. Furthermore, we present a genetic diagnostic flowchart including 105 genes with at least moderate evidence for female infertility and suggest recommendations for future research. The study did not take into account associated genetic risk factor(s) or oligogenic/polygenic causes of female infertility.

Wider Implications: We have comprehensively reviewed the existing research on the genetics of female infertility and DSD, which will enable the development of diagnostic panels using validated genes. Whole genome analysis is shifting from predominantly research to clinical application, increasing its diagnostic potential. These new diagnostic possibilities will not only decrease the number of idiopathic cases but will also render genetic counselling more effective for infertile patients and their families.

Download full-text PDF

Source
http://dx.doi.org/10.1093/humupd/dmac044DOI Listing

Publication Analysis

Top Keywords

female infertility
36
infertility dsd
12
female
10
infertility
10
systematic review
8
gene-disease relationships
8
human female
8
infertility differences
8
differences sex
8
sex development
8

Similar Publications

Background: Previous studies on the impact of mitochondrial DNA (mtDNA) copy number on female infertility were limited and inconsistent.

Methods: The causal relationship between mtDNA copy number and female infertility was evaluated using a bidirectional 2-sample Mendelian randomization (MR) method. Inverse variance weighted (IVW) method was applied for principal analysis, and MR-Egger, weighted median, simple mode, weighted mode method for secondary analyses.

View Article and Find Full Text PDF

Background: Chronic salpingitis is one of the most common causes of female infertility. Luteal support is a critical step for embryo transfer. Here, we evaluated the effects of two luteal support regimens, intramuscular progesterone (IMP) and progesterone vaginal gel (VAG), on the pregnancy outcomes in patients with chronic salpingitis undergoing vitrified-warmed embryo transfer.

View Article and Find Full Text PDF

Pharmacognostic Standardization, Morphometric Analysis, and Multivariate Analysis of Croton lobatus L. and Croton zambesicus Mull. Arg.

Microsc Res Tech

December 2024

Phytomedicine, Molecular Toxicology, and Computational Biochemistry Research Laboratory (PMTCB-RL), Department of Biochemistry, Bowen University, Iwo, Nigeria.

Croton lobatus L. and Croton zambesicus Mull. Arg.

View Article and Find Full Text PDF

Diagnostic and therapeutic hysteroscopy in Ethiopia: a retrospective study on practice and outcomes.

BMC Womens Health

December 2024

Department of Obstetrics and Gynecology, School of Medicine, Debre Markos University, Debre Markos, Amhara Region, Ethiopia.

Background: Hysteroscopy is considered the standard for evaluating the uterine cavity. Limited data exists regarding hysteroscopy in Ethiopia. Therefore, the objective of the study was to describe the diagnostic and operative hysteroscopic procedures at St.

View Article and Find Full Text PDF

Background: Primary ovarian insufficiency (POI) is a critical cause of infertility and is increasingly recognized as a complex metabolic disorder. Dietary factors may influence the risk of POI, but causal relationships remain unclear.

Methods: We conducted an MR study using genetic instrumental variables for 83 dietary preferences from the UK Biobank, with the Inverse Variance Weighted method as the primary analysis.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!