Chromosomal abnormalities in couples with recurrent pregnancy loss: a 16-year cross-sectional study of 4030 cases from Turkey.

Abstract

Background: Chromosomal abnormalities are a significant cause of miscarriages. Carriers of balanced chromosome rearrangement are often at risk of recurrent pregnancy loss (RPL), as they are more likely to produce gametes with unbalanced chromosome rearrangements.

Objective: This study evaluated the chromosomal abnormalities detected in couples with history of primary recurrent pregnancy loss.

Design: Retrospective, cross-sectional study.

Setting: Single center, tertiary healthcare center in Turkey.

Patients and methods: This study reviewed conventional cytogenetic/molecular cytogenetic analysis data of 4030 patients (2015 couples) who visited the clinic from 2008-2024.

Main outcome measures: Chromosomal abnormalities in patients diagnosed with primary recurrent pregnancy loss and genetic testing results of spontaneously achieved pregnancies in 16 patients with a balanced chromosomal rearrangement.

Sample size: 4030 individuals (2015 couples).

Results: Majority of couples had a history of two spontaneous miscarriages (59.4%), followed by couples with 3 miscarriages (28.1%), 4 miscarriages (7.5%), and 5 or more miscarriages (4.91%). Chromosomal abnormality was detected in 133 (3.3%) cases. Among the revealed abnormalities, 130 (97.7%) were structural chromosome anomalies, while only 3 (2.3%) numerical chromosome anomalies were observed, including sex chromosome aneuploidy in 2 cases and mosaic karyotype in one case. Among the detected 130 structural chromosome abnormalities, reciprocal translocations (86 cases, 66.2%) were most frequently observed, followed by Robertsonian translocations in 26 cases (20.0%), inversion in 11 cases (8.5%), marker chromosome in 5 cases (3.8%), and derivative chromosomes in 2 cases (1.5%). Products of conception (conceptus materials) were analyzed from 16 spontaneously conceived pregnancies in individuals identified as carriers of chromosomal rearrangements. Although reciprocal translocations involving acrocentric chromosomes are typically expected to result in 3:1 meiotic segregation, adjacent-1 segregation was observed in two female individuals carrying the translocation t(9;15)(p22;q23). This finding is likely due to the limited genetic content of the translocated segments. Additionally, a novel complex three-way translocation, t(5;7;13)(p12;p12;p11), was identified for the first time.

Conclusion: Cytogenetic and molecular analyses are crucial components in the etiological investigations of couples with RPL.

Limitations: Retrospective design.