Evaluating the link between chromosomal abnormalities and diminished ovarian reserve, mode of conception, and history of prior miscarriages in cases of early missed abortion using CNV-seq

Objective: This study was developed as a retrospective analysis of the rates of embryonic chromosomal abnormalities in cases of missed miscarriages during early pregnancy, with a focus on identifying associated factors as a means of clarifying the genetic basis for missed miscarriages and how this pregnancy outcome relates to a variety of clinical and demographic characteristics. Methods : The present study enrolled 1490 patients who had been diagnosed with missed miscarriage and underwent CNV-seq testing at the Jiangxi Maternal and Child Health Hospital from January 2020 through December 2022. Medical records were accessed to obtain clinical data pertaining to these miscarriage cases, and the results of chromosomal abnormality testing were analyzed. Results: Chromosomal abnormalities were detected in 63.76% of all missed miscarriages, and included instances of autosomal trisomy (68.38%), triploidy/polyploidy (11.68%), 45XO (10.84%), CNVs (8.84%), double/multiple trisomy (4.32%), sex chromosome trisomy/polyploidy (0.32%), and complex abnormalities (2.95%). An examination of the relationship between these chromosomal abnormalities and clinical characteristics revealed that chromosomal abnormality incidence rates were significantly related to maternal age, mode of conception, AMH levels, and the presence or absence of an embryonic/fetal heartbeat. Advanced maternal age, mode of conception, and lower AMH levels were associated with a greater risk of embryonic chromosomal abnormalities. Specifically, the rates of autosomal trisomy gradually rose with maternal age (P<0.05), whereas 45XO, CNVs, and triploidy/polyploidy detection rates declined with age (P<0.05). Declining ovarian reserve function was associated with higher rates of karyotypic abnormalities (P<0.05). Higher rates of karyotypic abnormalities were also evident in the natural conception (NC) group, as were rates of CNVs and trisomy/polyploidy (P < 0.01), whereas higher rates of autosomal trisomy were detected in the assisted reproductive technology (ART) group. No relationship between a history of spontaneous miscarriages and the incidence of embryonic chromosomal abnormalities was detected. Conclusion: Embryonic chromosomal abnormalities are the leading cause of early missed miscarriages. The present results indicate that advanced maternal age, declining ovarian reserve function, and mode of conception can all increase the risk of these chromosomal abnormalities. Age and the presence of a fetal/embryonic heartbeat may be related to the incidence of different types of chromosomal abnormalities, while a history of prior missed miscarriages is not related to the odds of embryonic chromosomal abnormalities.