Controlled Ovarian Stimulation Contributes to the Incidence of de Novo Chromosomal Abnormalities in Cleavage-Stage Embryos

Abstract

Background

Studies on the effects of ovarian stimulation on the embryo aneuploidy rate have shown conflicting results.

Objectives

To investigate whether parameters of controlled ovarian stimulation (COS) are associated with the incidence of de novo chromosomal abnormalities in cleavage-stage embryos undergoing preimplantation genetic testing (PGT).

Methods

This retrospective study examined data from biopsies of cleavage-stage embryos with one blastomere from the Women’s Hospital at Zhejiang University School of Medicine. De novo chromosomal abnormalities were classified as: de novo chromosomal segmental abnormalities (DCSAs) or de novo whole chromosomal abnormalities (DWCAs). A multivariable logistic regression model was used to identify factors that may affect the genomic stability of embryos. Further stratification analysis was performed to explore the impact of these factors on DCSAs and DWCAs.

Results

A total of 1,994 cleavage-stage biopsied embryos were included in the analysis. The number of DWCAs but not DCSAs increased significantly with maternal age. The incidence of de novo chromosomal abnormalities was similar between different COS protocols. Longer stimulation duration was associated with a considerably higher DWCA rate (p = 0.003). The DCSA rate increased with higher gonadotropin dosages. Furthermore, cotreatment with growth hormone (GH) supplementation was associated with a significantly lower incidence of DWCAs (p = 0.006).

Conclusion

Ovarian stimulation parameters are related to the incidence of de novo chromosomal abnormalities in preimplantation embryos. GH supplementation had a beneficial effect in decreasing aneuploidy, and higher gonadotropin doses may be related to mitotic errors.