Mutations in the BRCA1 and BRCA2 genes place female carriers at an increased risk for breast and ovarian cancers, and there is evidence now that this genetic status may be associated with reduced ovarian reserve.
In a review published in Future Oncology, a group of French researchers assessed fertility issues as well other concerns—such as fertility preservation (FP)—in women who are BRCA-mutation carriers.
Michael Grynberg, MD, PhD, from the Department of Reproductive Medicine & Fertility Preservation at the Hôpital Antoine Béclère in Clamart, France, and colleagues concluded that oocyte cryopreservation should be systematically considered in this specific group of patients, in healthy carriers, and before gonadotoxic treatments.
Young women who are BRCA mutation carriers often face difficult family planning decisions. Cancer treatments frequently result in gonadal toxicity, which may lead to infertility. In an effort to reduce the risk of breast and ovarian cancer for women with BRCA1-mutation, the current recommendation is prophylactic bilateral salpingo-oophorectomy between the ages of 25 and 40.
The risk for loss of fertility and premature ovarian failure depends primarily on the chemotherapy regimen used, as well as the age and baseline ovarian reserve of the patient. Before starting chemotherapy, follicular ovarian status should be evaluated.
The authors noted one study that investigated the risk of chemotherapy-induced amenorrhea in BRCA mutation carriers. Overall, no difference was reported between 1426 BRCA carriers and 100 noncarriers.
Some studies implied that BRCA mutations might directly affect ovarian function. The authors suggested that a relationship between BRCA mutation and early menopause might be the result of a reduced ovarian reserve inherent to the genetic status.
In studies that evaluated fertility outcomes, most failed to find significant differences between BRCA mutation carriers and noncarriers.
Two studies that analyzed ovarian response to stimulation in BRCA mutation carriers yielded mixed results.
Various techniques for FP are available. The most established and reliable method is oocyte and embryo cryopreservation after controlled ovarian hyperstimulation. Data regarding efficacy and safety of oocyte cryopreservation in breast cancer patients are scarce, and even more limited in patients with BRCA mutations.
Fertility treatments are not associated with an increased risk of breast or gynecologic cancers, even in healthy BRCA mutation carriers; however, the authors noted that additional studies are needed to evaluate efficacy and safety to properly counsel patients with the mutations.
Although ovarian tissue cryopreservation (OTC) is still considered experimental, it is the only strategy that allows for preservation of both fertility and endocrine ovarian function. Freezing fragments of ovarian cortex preserves a large number of eggs and gives the chance for multiple future pregnancies. Unfortunately, it is not possible to make recommendations to women with BRCA mutations, as only one live birth has been reported in a breast cancer patient with a BRCA2 mutation.
Recent evidence has shown that pregnancy in breast cancer survivors can be safe; however, there is no specific information regarding pregnancy in breast cancer survivors with BRCA mutations.
Finally, women carrying the BRCA mutation are faced with a decision to conceive naturally with a 50% risk of transmitting the mutated gene, or undergo assisted reproductive technologies such as in vitro fertilization and preimplantation genetic diagnosis (PGD). Given that the BRCA mutation is not lethal, but only plays a role in the risk certain cancers, counseling and psychosocial evaluation are important to assist a woman with her decision.
“BRCA mutations place women at increased risk of infertility, most often as a result of anticancer treatments,” the authors wrote. “Therefore, oocyte cryopreservation should now be systematically considered in this specific group of patients, before gonadotoxic treatments, but also in healthy carriers. Indeed, FP offers a new option for limiting the difficult resort to egg donation or adoption, while keeping the possibility of avoiding the risk of transmission of BRCA-mutations throughout PGD.”
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