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

Anne Mayeur; Emmanuelle Benaloun; Jonas Benguigui; Constance Duperier; Laetitia Hesters; Kalliopi Chatzovoulou; Sophie Monnot; Michael Grynberg; Julie Steffann; Nelly Frydman; Charlotte Sonigo

doi:10.1016/j.rbmo.2023.02.010

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

Reprod Biomed Online. 2023 Jul;47(1):61-69. doi: 10.1016/j.rbmo.2023.02.010. Epub 2023 Feb 28.

Authors

Affiliations

¹ Service de Biologie de la Reproduction- CECOS, Hôpital Antoine Béclère, AP-HP, Université Paris Saclay, cedex, F-92140 Clamart, France.; Université Paris-Sud, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France.. Electronic address: [email protected].
² Service de Biologie de la Reproduction- CECOS, Hôpital Antoine Béclère, AP-HP, Université Paris Saclay, cedex, F-92140 Clamart, France.
³ Service de Médecine de la reproduction et Préservation de la Fertilité, Assistance Publique Hôpitaux de Paris, Hôpital Antoine Béclère, Clamart 92140, France.
⁴ Université de Paris, Institut Imagine, INSERM UMR1163, Paris, France.
⁵ Université de Paris, Imagine INSERM UMR1163 et Service de Médecine Génomique des Maladies rares, Groupe Hospitalier Necker-Enfants Malades, AP-HP, Paris, France.
⁶ Université Paris-Sud, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France.; Service de Médecine de la reproduction et Préservation de la Fertilité, Assistance Publique Hôpitaux de Paris, Hôpital Antoine Béclère, Clamart 92140, France.
⁷ Université de Paris, Institut Imagine, INSERM UMR1163, Paris, France.; Université de Paris, Imagine INSERM UMR1163 et Service de Médecine Génomique des Maladies rares, Groupe Hospitalier Necker-Enfants Malades, AP-HP, Paris, France.
⁸ Service de Biologie de la Reproduction- CECOS, Hôpital Antoine Béclère, AP-HP, Université Paris Saclay, cedex, F-92140 Clamart, France.; Université Paris-Sud, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France.
⁹ Université Paris-Sud, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France.; Service de Médecine de la reproduction et Préservation de la Fertilité, Assistance Publique Hôpitaux de Paris, Hôpital Antoine Béclère, Clamart 92140, France.; Inserm U1185, Faculté de médecine Paris Sud, France.

PMID: 37202317
DOI: 10.1016/j.rbmo.2023.02.010

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.

MeSH terms

Aneuploidy
DNA, Mitochondrial / genetics
Female
Fertilization in Vitro*
Follow-Up Studies
Genetic Testing / methods
Humans
Male
Mutation
Pregnancy
Preimplantation Diagnosis* / methods
Retrospective Studies

Substances

DNA, Mitochondrial