Clinical trial NCT02119117: Aneuploidy Rates in Advanced Maternal Age Patients Supplemented With Coenzyme Q10 (CoQ10) Versus Those That Are Not: a Pilot Study
Official title: Blastocyst Aneuploidy Rates From Advanced Maternal Age Patients Supplemented With Coenzyme Q10 (CoQ10) Versus Those That Are Not: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mitochondrial DNA
Aneuploidy
Keywords: mtDNA
aneuploidy
IVF
blastocyst
COQ10
Lead sponsor: Reproductive Endocrinology Associates of Charlotte
Sponsor class: OTHER
First posted: 2014-04-21
Enrollment: 21
Sex: FEMALE
Minimum age (years): 36
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Pregnancy rates for women over 35 years old are significantly lower when compared to younger women. One of the causes for this decrease is believed to be chromosomal aneuploidy. Chromosomal aneuploidy is a natural phenomena and occurs in women of every age and has been implicated in spontaneous miscarriages, and preimplantation embryo wastage (Hassold and Hunt, 2001).

As maternal age increases, so too does the incidence of chromosomal aneuploidy. Embryo quality from older patients undergoing IVF tends to be reduced and associated with higher rates of chromosomal abnormalities when compared to good quality embryos (Munne et al., 1995).

Chromosomal aneuploidy derives from the improper segregation of chromosomes during preimplantation development. The process of segregation, or mitosis, includes synthesis of the complete genome, equal division of chromosomes to opposite poles by the spindle apparatus, and separation of the two cells by cytokinesis, yielding two chromosomally identical cells. The entire process of cellular and genetic replication requires energy in the form of adenosine tri phosphate (ATP). ATP is mainly produced in mitochondria in the process known as the electron transport chain (ETC). There are many important molecules required for ATP production, CoQ10 can act as the appropriate carrier of electrons through the ETC. When a deficiency in CoQ10 is present, ATP production is decreased resulting in aneuploidy (Bentov et al., 2013). Similarly, research has shown that chromosome alignment and spindle formation are affected by mtDNA copy number (Ge et al., 2012). It has also been shown that the transfer of ooplasm from young, healthy oocyte donors into oocytes of women with repeated embryonic failure has result in children with subsequent mitochondrial heteroplasmy (Cohen et al., 1998).

CoQ10 concentrations have been shown to decrease as age increases (Bentov et al., 2011). Consequently, the decrease in CoQ10 concentrations seen in older women may cause an increase in chromosomal aneuploidy in subsequent embryos (Bentov et al., 2013). In this pilot study, we test the hypothesis that the supplementation of CoQ10 prior to an IVF cycle can increase mitochondrial DNA activity and possibly decrease chromosomal aneuploidy in AMA patients.

Detailed description: Brief Summary

Eligibility criteria: Inclusion Criteria:

1. 36-42 years old
2. Must present with an AMH level ≤2.0 ng/mL
3. 1st cycle of IVF treatment
4. Antral follicle count \>5 and \<20

Exclusion Criteria:

1. BMI \>39
2. Active smoker
3. Blood serum baseline level of CoQ10 ≥2.20 µg/mL
4. Prior use of CoQ10
5. Type II diabetes mellitus

Primary outcomes:
measure: Embryo mitochondrial DNA (mtDNA)
timeFrame: mtDNA levels will be assesed from day 5 or day 6 blastocysts
Secondary outcomes:
measure: preimplantation chromosomal aneuploidy
timeFrame: aneuploidy rates will be measured utilizing SNP array from day 5 and day 6 blastocysts
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: REACh
state: North Carolina
Study officials:
affiliation: Reproductive Endocrinology Associates of Charlotte
name: Jack L Crain, MD
role: PRINCIPAL_INVESTIGATOR
References: