MITOCHONDRIAL SUPPORT OF EMBRYOS FROM WOMEN OF ADVANCED MATERNAL AGE DURING ART

Abstract

The supplementation of MitoTempo and mitoquinol (MTQ) in mouse embryo culture results in better quality blastocysts by supporting mitochondrial function. Women of advanced maternal age have reduced oocyte quality due in part to dysfunctional mitochondria. The aim of this study was to determine the effect of supplementation of mitochondrially targeted antioxidants (MTQ) during human embryo culture for women of advanced maternal age (≥35 yr). Prospective clinical trial with sibling embryos. MATERIALS AND METHODS:: After oocyte retrieval, cumulus oocyte complexes (COC) were denuded of cumulus cells. Mature oocytes (MII) were fertilized by ICSI and randomly allocated into sequential culture medium, 2/3 to control and 1/3 to medium with MTQ. Zygotes were moved into second step medium on day 3 and cultured for 5-7 days, at which time good quality blastocysts were biopsied for PGT-A and vitrified. MTQ was present throughout the culture period. A total of 11 patients with advanced maternal age (AMA) (average age 39.4 yr, range 35-46) were included in this study. Post ICSI, 143 presumptive zygotes were placed in control medium and 66 in medium supplemented with MTQ. Normal fertilization, determined by presence of 2 pronuclei (2PN), was 83% in control and 91% in MTQ (p=0.11). There were no differences between control and MTQ treatment in D5 (control, 18%; MTQ, 20%) or total (control, 48%; MTQ, 45%) good quality blastocyst (≥grade 3BB) development (per 2PN), or total blastocyst development (control, 63%; MTQ, 62%). There was also no difference in the percentage of euploid blastocysts (control, 33%; MTQ, 30). To date, four euploid blastocysts from the control treatment and one from the MTQ treatment have been transferred individually to a total of 5 patients, all resulting in ongoing pregnancies with fetal heart beat. In this preliminary study, we did not note any improvement in good quality or euploid blastocyst development due to inclusion of MTQ in the culture media. Both treatments resulted in an equal percentage of transferrable euploid embryos per oocyte injected with sperm. One embryo has been transferred after MTQ treatment, resulting in a healthy ongoing pregnancy. These data suggest that MTQ treatment of human embryos in culture is safe, although at this point it does not appear to be effective in increasing blastocyst development for women of AMA. However, further research is required to determine if there are any positive effects of MTQ treatment on implantation and/or pregnancy loss that are not yet evident from this initial trial.