Miscarriages after Natural Conception & IVF: Comparative Study of Genetic Analysis of Products of Conception

Abstract

Assisted reproductive technologies (ART), including in vitro fertilization (IVF), are modern medical technologies widely used in developed countries. A frequent complication of pregnancy resulting from ART is miscarriage. The leading cause of miscarriage, both sporadic and recurrent, is chromosomal abnormalities (CA) of the embryo. To compare the frequency and structure of chromosomal abnormalities (CA) of the embryo during miscarriages after IVF and natural conception. Retrospective cohort comparative study. The study, conducted in 2018-2022, included 1,000 products of conception (POCs) samples from patients with miscarriage. The study participants were divided into 2 groups depending on the origin of pregnancy: group 1 – women whose pregnancy occurred naturally (n = 862), group 2 – women whose pregnancy occurred as a result of in vitro fertilization (IVF) (n = 138). Miscarriage was confirmed by ultrasound performed at 6-10 weeks of pregnancy. A genetic study of POCs was carried out using chromosomal microarray analysis (CMA). In total, CA was detected in 580 samples (58%), and a normal molecular karyotype was determined in 420 (42%). CAs in abortive material during pregnancy loss are detected with a frequency of 59.05% in cases of natural conception and with a frequency of 51.05% in pregnancies resulting from IVF (p = 0.093). There were no statistically significant differences in the frequency and structure of CA in the study groups. Autosomal trisomies were most often detected. In our study, among all autosomal trisomies, the most common were trisomy 16, trisomy 22 and trisomy 15. Among the sex chromosome abnormalities, monosomy X was most often detected - in total, it was determined in 66 (6.6%) samples, which significantly exceeds the frequency of monosomy X among live births. Only in 0.2-0.3% of cases, when the embryo has monosomy X, pregnancy progresses and ends in a live birth. Copy number variations (CNVs) were often detected - a total of 52 (5.2%) samples with different CNVs, respectively 46 (5.3%) and 6 (4.3%) in groups 1 and 2. Detection of such abnormality is critically important, as it can be the result of carriage of a balanced CAs in one of the parents, which significantly increases the risk of miscarriage in the future. In pregnancies resulting from IVF, mosaicism in abortive material was more common, but the differences were not statistically significant. In group 1, mosaicism was detected in 66 (7.6%) cases and in group 2 - 13 (9.4%) cases. The IVF procedure does not increase the risk of CA in the embryo but also does not significantly reduce it. Considering the high frequency of CA in miscarriage, persons referred for IVF and with a history of idiopathic recurrent pregnancy loss should be informed about the possibility of PGT.