Preimplantation genetic testing for mitochondrial DNA mutation: ovarian response to stimulation, outcomes and follow-up

Abstract

Research question: How do carriers of pathogenic mitochondrial DNA (mtDNA) respond to ovarian stimulation?

Design: A single-centre, retrospective study conducted between January 2006 and July 2021 in France. Ovarian reserve markers and ovarian stimulation cycle outcomes were compared for couples undergoing preimplantation genetic testing (PGT) for maternally inherited mtDNA disease (n = 18) (mtDNA-PGT group) with a matched-control group of patients undergoing PGT for male indications (n = 96). The PGT outcomes for the mtDNA-PGT group and the follow-up of these patients in case of unsuccessful PGT was also reported.

Results: For carriers of pathogenic mtDNA, parameters of ovarian response to FSH and ovarian stimulation cycle outcomes were not different from those of matched-control ovarian stimulation cycles. The carriers of pathogenic mtDNA needed a longer ovarian stimulation and higher dose of gonadotrophins. Three patients (16.7%) obtained a live birth after the PGT process, and eight patients (44.4%) achieved parenthood through alternative methods: oocyte donation (n = 4), natural conception with prenatal diagnosis (n = 2) and adoption (n = 2).

Conclusion: To the best of our knowledge, this is the first study of women carrying a mtDNA variant who have undergone a PGT for monogenic (single gene defects) procedure. It is one of the possible options to obtain a healthy baby without observing an impairment in ovarian response to stimulation.

Keywords: PGT; medical counselling; mitochondria; ovarian stimulation; pregnancy.