The Effect of Concomitant Co Enzyme Q10 Use on Pregnancy Outcome of IVF

The objective of this study is to evaluate the efficacy of CoQ10 administration with respect to its effect on the rate of aneuploidy of oocytes and cumulative live birth rate.

Study Design This is a prospective randomized placebo controlled study. Study participants will undergo up to 3 cycles as part of this protocol. All clinical assessments will be conducted at the participating infertility clinics.

The study will be organized on an outpatient basis at the Toronto Centre for Advanced Reproductive Technology (TCART). The study will involve 54 women aged 35-43 years undergoing IVF treatment. All women will collect 2 mL of saliva in a 5 mL polyethylene tube for baseline measurement of coQ10 activity by arNOX assay (described below).

Study participants will be randomly assigned to either placebo or COQ10 capsules, (AOR - Advanced Orthomolecular Research Inc. 19 St NE Calgary, Alberta, NHPD registration codes 135307). Study participants will take 600 mg of CoQ10 orally once a day with breakfast or identical placebo capsules for 2 months prior to an IVF cycle and up to 3 cycles if pregnancy does not occur. On cycle day 3, subjects will start the ovarian stimulation for in vitro fertilization while continuing the consumption of the supplements. The controlled ovarian stimulation (COH) will consist of the microdose GnRH agonist flare protocol, which is the clinic's standard protocol for older women. COH will be done using recombinant FSH (Puregon; Schering-Plough Inc.,Mississauga, ON, Canada) or human menopausal gonadotropins (Menopur, Ferring Inc, Oakville, ON, Canada) 150 units twice daily S.C. and Buserelin Acetate ( Superfact, Sanofi-Aventis Canada Inc, Laval, Quebec) 0.05 mg subcutaneously B.I.D, and will continue until the day prior to 10,000 units human chorionic gonadotropin (hCG) (Pregnyl, Organon). The dosage will not be changed and must be maintained for the duration of the study. Both drugs will continue daily until follicular development is considered adequate (at least 3 follicles >17 mm, and the E2 level is acceptable for the number of follicles present) at which time the hCG will be injected to trigger final follicular maturation. Oocyte retrieval will be done 36 hours later by vaginal ultrasound guided needle aspiration and with the use of local anesthesia and mild sedation. At the time of retrieval, subjects will collect 2 mL of saliva, in addition, 2 mL of follicular fluid will be collected from the first follicle aspirated from each ovary for determination of coQ10 activity by arNOX assay. AS it is not possible to measure CoQ10 levels in a single cells (e.g. oocytes), FF represents direct cellular environment that can reflect the metabolical profile of this cell. After retrieval, the oocytes will be fertilized with ICSI in order not to contaminate the maternal DNA during polar body biopsy sample with sperm DNA. On the following day, all the oocytes with 2 pronuclei will undergo a biopsy of one or both polar bodies.

Polar body biopsy The oocyte is then inseminated using the intracytoplasmic sperm injection (ICSI) technique and is kept in culture in an incubator. In order to biopsy the polar body, the oocyte is held by the holding pipette with the polar body at the 11-12 o'clock position. An opening is made in the zona pellucida and a polished glass needle is introduced into the perivitelline space and the polar body is carefully removed.