# Spectrum and Clinical Reproductive Significance of Cytogenetic Abnormalities in Infertility and Recurrent Early Pregnancy Loss: A Five-Year Retrospective Study of 10,285 Cases

## TL;DR

This study analyzed 10,285 cases and found that chromosomal abnormalities are common in infertility and recurrent pregnancy loss, with variants and structural rearrangements being the most frequent.

## Contribution

The study provides a comprehensive five-year retrospective analysis of cytogenetic abnormalities in reproductive disorders across a large cohort.

## Key findings

- Chromosomal variants were the most frequent abnormalities, found in 52.4% of abnormal cases.
- Structural rearrangements like translocations and inversions were common, affecting both autosomes and sex chromosomes.
- Numerical abnormalities such as Klinefelter syndrome and isochromosome X were less frequent but clinically significant.

## Abstract

Introduction

Cytogenetic abnormalities are a major genetic cause of infertility and recurrent early pregnancy loss (REPL), conditions that affect a substantial proportion of couples of reproductive age. Both numerical and structural chromosomal abnormalities can impair gametogenesis, fertilization, implantation, or embryonic development. This study aimed to evaluate the frequency, spectrum, and clinical relevance of chromosomal abnormalities in individuals referred for infertility, single miscarriage, or recurrent pregnancy loss (RPL).

Materials and methods

This large retrospective cytogenetic study analyzed 10,285 individuals referred for infertility, single miscarriage, or recurrent pregnancy loss over a five-year period. Conventional G-banded karyotyping was performed in accordance with International System for Human Cytogenomic Nomenclature (ISCN) 2025 guidelines. Chromosomal abnormalities were classified as numerical or structural, with variants further categorized by specific chromosome involvement. Data on sex distribution and abnormality patterns were summarized to identify trends and clinically significant associations.

Results

Among the 10,285 individuals evaluated, cytogenetic abnormalities were identified in 980 cases, representing 9.5% of the study population. The cohort demonstrated a largely balanced sex distribution, with 46,XX karyotypes observed in 5,380 cases (52.3%) and 46,XY karyotypes in 4,857 cases (47.2%). Analysis of abnormal karyotypes revealed that chromosomal variants were the most frequent finding, accounting for 514 cases (52.4%), followed by variant inversions in 94 cases (9.6%). Structural chromosomal rearrangements were commonly observed and included reciprocal translocations in 120 cases (12.2%) and Robertsonian translocations in 33 cases (3.4%), involving multiple autosomes and sex chromosomes. Sex chromosome abnormalities comprised a notable subset, with Klinefelter syndrome identified in 53 cases (5.4%), Y-chromosome inversions in 36 cases (3.7%), mosaic karyotypes in 38 cases (3.9%), isochromosome X in 18 cases (1.8%), and additional X chromosomes in 12 cases (1.2%). Other abnormalities such as derivative chromosomes (24 cases, 2.4%), deletions (13 cases, 1.3%), autosomal inversions (14 cases, 1.4%), marker chromosomes (3 cases, 0.3%), and rare duplications or insertions (one case each, 0.1%) were observed less frequently, highlighting the broad spectrum of cytogenetic abnormalities associated with infertility and recurrent pregnancy loss.

Conclusion

This study demonstrates that chromosomal variants and structural rearrangements constitute the majority of cytogenetic abnormalities in individuals with infertility or recurrent pregnancy loss. Although clinically significant numerical and complex structural abnormalities were less frequent, they confer substantial reproductive risk through mechanisms affecting gametogenesis, chromosomal segregation, and embryonic viability.