Stimulation and aneuploidy: Why are milder stimulation protocols better?

There is an ever-increasing trend in assisted reproductive techniques to reduce the intensity of ovarian stimulation for in vitro fertilization (IVF) and to restrict the number of embryos that are transferred into the uterine cavity. Recent findings suggest that the magnitude of ovarian stimulation affects the proportion of euploid embryos. Ovarian stimulation regimens for IVF seem to have a deleterious effect on oocyte quality and embryo aneuploidy in a dose-dependent manner. We are moving to a global era of single embryo transfers and now it becomes more important than ever before to ensure that this single embryo has the highest implantation potential. Strategies are being adopted to improve the accuracy for selecting euploid, viable embryos for transfer. One such strategy involves further refinement of morphological criteria associated with improved viability by considering, for example, pronuclei disposition, nucleolar organization, and identification of the fast-cleaving embryos, with only mononucleate blastomeres and trying to correlate morphokinetics with cytogenetics. Another strategy employs preimplantation genetic diagnosis whereby a biopsied blastomere is tested for ploidy using next-generation sequencing. Even in older patients, lower oocyte yields may represent a more appropriate response to ovarian stimulation, allowing the most competent follicles and oocytes to develop and thereby reducing the occurrence of embryo aneuploidy. IVF Lite plus ACCUVIT by repeated mild stimulation cycles with subsequent vitrification of blastocysts, combined with preimplantation genetic screening, is a promising new approach for poor responders as well as women of advanced maternal age.