Correlation between oocyte morphology and the embryo aneuploidy rate in IVF cycles

Abstract

Aneuploidy is the main genetic cause of miscarriages and congenital birth defects following both natural conception and in vitro fertilization (IVF). The oocyte aneuploidy rate varies over a wide range, but there is a close correlation between advancing maternal age and the increasing aneuploidy rate. Controlled ovarian stimulation additionally complicates this problem because it leads to the maturation of oocytes that would naturally undergo apoptosis. A large proportion of oocytes recovered from exogenous gonadotropin-stimulated cycles exhibit different morphological abnormalities (dysmorphisms). The purpose of the study was to evaluate the aneuploidy rates of chromosomes 13, 18, 21, X and Y in embryos from patients with different oocyte morphotypes. Materials and methods: This prospective study included 84 patients treated with IVF at a single academic center. The patients were divided into the following groups: group 1 consisted of women with cytoplasmic dysmorphisms (n = 28), group 2 consisted of women with extracytoplasmic dysmorphisms (n = 28), and group 3 consisted of women with morphologically normal oocytes (n = 28). One blastomere from each embryo was analyzed for aneuploidies of chromosomes 13, 18, 21, X, and Y results. In total we sampled 368 embryos on day 3 (98 from group 1, 126 from group 2 and 144 from group 3). In group 1, there were 67 aneuploid embryos (68.4%); in group 2, there were 49 aneuploid embryos (38.9%); and in group 3, there were 45 (31.3%) (p < 0.0001). To identify the factors that influenced the appearance of aneuploidy in the embryo, we compared the groups with euploid (group A, n = 161) and aneuploid embryos (group B, n = 207). The aneuploidy rate was related to some of the female baseline characteristics, specifically, body mass index (BMI) and the basal AMH level. The women in group B were more likely to have histories of chlamydia infection. The summary dose of gonadotropins was higher in group B. Sperm quality (from the fertile or subfertile males) did not influence the embryo aneuploidy rate. The adjusted odds ratio (OR) for an aneuploid embryo in cases of cytoplasmic dysmorphisms was 3.6 (95% CI = 1.8; 7.2) after adjusting for the confounders. The adjusted OR for an aneuploid embryo in cases of extracytoplasmic dysmorphisms was 1.3 (95% CI = 0.7; 2.1) after considering the confounders. The highest percentage of aneuploid embryos occurred in the subgroup of oocytes with vacuoles (100%) followed by the oocytes with dark cytoplasm (73.1%), centrally located granular cytoplasm (66.7%) and SERc (65.2%) (Table 1). The most frequent type of aneuploidy was chromosomal polysomy. The prevalence of all of the types of polysomies was much higher in the group of women with cytoplasmic dysmorphisms. Discussion: Aneuploidies of the gametes are not only the limiting factors for human fertility but are also for the medical treatment of infertility. Morphological assessments of oocytes are the most common method for evaluating oocyte quality in routine practice. Oocyte dysmorphisms are correlated with impaired embryo quality and thus poor clinical outcomes, which may be related to high aneuploidy rates in oocytes with dysmorphisms. We recommend that woman with oocyte dysmorphisms, especially a centrally located granular cytoplasm, SERc and a dark cytoplasm, be subjected to additional genetic counseling to improve the effectiveness of IVF cycles and reduce the risk of giving birth to children with congenital defects.