Dr. Karine Matevossian, a fellow in reproductive endocrinology and infertility at Women & Infants Hospital, was part of a research team from the hospital that recently published a study looking into how BRCA1 and BRCA2 affect a patient’s ovarian aging and to assist those considering preserving their fertility and having children.
PBN: What are BRCA1 and BRCA2? According to the study, how do they affect a patient’s reproductive potential?
MATEVOSSIAN: BRCA1 and 2 are the genes most commonly affected in hereditary breast and ovarian cancer. Our study found that BRCA1 patients have both a lower ovarian reserve and increased markers of ovarian aging. BRCA2 patients have normal ovarian reserve but have increased markers of ovarian aging. For both BRCA1 and 2 carriers, the reproductive lifespan may be shorter than unaffected patients.
PBN: Given these findings, what other questions related to BRCA1, 2 and reproductive health are you hoping to study further?
MATEVOSSIAN: We hope to look at a subset of BRCA patients who had been previously diagnosed with infertility and determine how this population differs from fertile BRCA patients.
PBN: What are the best steps patients with BRCA1 or BRCA2 can take to help their reproductive health?
MATEVOSSIAN: Patients should discuss family planning and fertility preservation timing with their physician. They can consider freezing their eggs or embryos if deferring childbearing.
PBN: How has the research into reproductive potential evolved recently?
MATEVOSSIAN: There have been several studies looking at BRCA carriers and their anti-mullerian hormone levels. AMH is a surrogate marker of ovarian reserve. These studies have had inconsistent findings. However, a meta-analysis was published recently and found that BRCA1 carriers have lower AMH levels compared to controls, but there was no difference between BRCA2 carriers and controls.
PBN: The study found BRCA1 carriers have lower ovarian reserve, but BRCA2 carriers do not. Can you explain why and what this means for patients with BRCA1 or BRCA2?
MATEVOSSIAN: Both BRCA1 and 2 are involved in DNA repair pathways. Malfunctions in this pathway lead to the accumulation of damaged DNA and certain proteins that change the morphology of the ovary and translate to decreased oocytes.
BRCA1 plays a larger, more essential role in the DNA repair pathway and thus we hypothesize that dysfunction in that gene has a greater effect on a patient’s ovarian reserve. Clinically, this means that if a patient were to get ovarian reserve testing, BRCA1 patients will likely have lower values compared to other patients their age.
BRCA2 patients will likely have results comparable to others their age. However, our study shows that they have increased DNA damage, which cannot be measured by current lab tests and imaging. Thus, patients and their physicians should not be falsely reassured by ovarian reserve testing in BRCA2 carriers.
BRCA1 and 2 carriers should not delay childbearing or oocyte/embryo cryopreservation because they have a shorter reproductive lifespan.
Katie Castellani is a PBN staff writer. You may contact her at Castellani@PBN.com.
