title: Aging and the environment affect gamete and embryo potential: can we intervene?
abstract: Optimal maturation of the oocyte depends on its environment and determines embryo competence, because the embryonic genome is not active until the cleavage stage and new mitochondria are not produced until blastulation. Adverse environmental factors include aging, andropause, oxidative stress, obesity, smoking, alcohol, and psychologic stress, whereas androgen supplementation, a prudent diet, exercise, nutritional supplements, and psychologic interventions have beneficial effects. Mitochondrial function and energy production deteriorate with age, adversely affecting ovarian reserve, chromosome segregation, and embryo competence. In aging mice, the mitochondrial cofactor coenzyme Q10 reverses most of these changes. Early human experience has been encouraging, although only a small study using a shorter duration of intervention compared with the murine model has been carried out. Mitochondrial metabolic stress can result in an abnormal compensatory increase in mitochondrial DNA, which can be assessed in biopsied blastomeres of trophectoderm as a predictive biomarker of implantation failure. Psychologic stress may reduce oocyte competence by shifting blood flow away from the ovary as part of the classic "fight or flight" physiologic response, and methods to reduce stress or the body's reaction to stress improve pregnancy success. Enhancing oocyte competence is a key intervention that promises to reduce the number of euploid embryos failing to produce viable deliveries.
authors.affiliation: Reproductive Partners San Diego and Division of Reproductive Endocrinology and Infertility, University of California, San Diego, California. Electronic address: drmeldrum@gmail.com.
authors.forename: David R
authors.initials: DR
authors.lastname: Meldrum
authors.affiliation: Division of Reproductive Sciences, University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; TCART Fertility Partners, Toronto, Ontario, Canada.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Casper
authors.affiliation: Igenomix, Parc Cientific Valencia University, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Diez-Juan
authors.affiliation: Fundación Instituto Valenciano de Infertilidad, Department of Obstetrics and Gynecology, School of Medicine, Valencia University, Valencia, Spain; Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simon
authors.affiliation: Domar Center for Mind/Body Health, Boston IVF, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Alice D
authors.initials: AD
authors.lastname: Domar
authors.affiliation: Department of Obstetrics and Gynecology, Hopital Foch de Suresnes, Suresnes, France.
authors.forename: Rene
authors.initials: R
authors.lastname: Frydman
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D001755:Blastocyst / Q000378:metabolism / Q000473:pathology*; D004272:DNA, Mitochondrial / Q000378:metabolism; D004624:Embryo Transfer; D004734:Energy Metabolism; D004777:Environment; D005260:Female; D005298:Fertility; D005307:Fertilization in Vitro; D007246:Infertility / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D008019:Life Style; D008297:Male; D000068097:Maternal Health; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D054315:Oocyte Retrieval; D009865:Oocytes / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects; D012307:Risk Factors; D040242:Risk Reduction Behavior; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology*; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000150:complications; D016896:Treatment Outcome
chemical_list: D004272:DNA, Mitochondrial
keywords: Aging; coenzyme Q10; lifestyle; mitochondrial DNA; oocyte quality