There are other markers for oocyte reserve, but, according to Kutluk Oktay, MD, PhD, professor of obstetrics and gynecology and reproductive sciences and director of the laboratory of molecular reproduction and fertility preservation of Yale University School of Medicine, New Haven, Connecticut, and author of the study, AMH is most reliable. “It fluctuates less with menstrual cycle and it is produced directly from developing follicles and better represents the primordial follicle pool, which constitutes the ovarian reserve,” he told Cancer Therapy Advisor. There is no direct method to measure primordial follicles.
Patients were stratified according to BRCA status — never-tested according to the National Comprehensive Cancer Network Version 1.2018 criteria, BRCA-negative, or BRCA-positive. The geometric mean of age-adjusted postchemotherapy AMH levels was compared with levels obtained at baseline to determine ovarian recovery after chemotherapy.
Dr Oktay noted that “it may take up to 6 months or more for new follicles to grow from surviving primordial follicles after chemotherapy exposure.” As these developing follicles recover, they produce AMH again, he said. “However, if chemotherapy damaged primordial follicles, the new AMH levels would be lower than the baseline.”
Ovarian recovery was similarly greater among patients who did not undergo BRCA testing and those were tested negative at 3.7% and 5.2%, respectively, compared patients who were BRCA-positive at 1.6%. This translated to a significant approximate 33% decrease in ovarian recovery among women who were BRCA-positive compared with the other groups (2-group ANOVA, P = .034). The data were similar when women only treated with doxorubicin and cyclophosphamide with paclitaxel or docetaxel (P = .044).
Dr Oktay highlighted that, “our and others’ data now strongly suggest that women with BRCA mutations have lower ovarian reserve to begin with. Add to that the higher likelihood of ovarian reserve loss post-chemotherapy, and it is a double-whammy.” He also noted that women with BRCA mutations are “also facing ovarian removal to reduce cancer risks.”
These data therefore indicate that women with BRCA mutations “should be preferentially counseled about fertility preservation and encouraged to complete family building as soon as possible,” Dr Oktay said.
ASCO guidelines state that all patients should be counseled about the potential for infertility, and patients who are unsure or interested in preservation should be counseled about fertility preservation options.2 For women, there are several approaches that can be employed, including embryo cryopreservation, unfertilized oocyte cryopreservation, and, in the near future, ovarian tissue cryopreservation.
The results from this study also demonstrated “the importance of DNA repair in oocyte aging and beyond,” Dr Oktay said. “Targeting DNA repair mechanisms may be a future strategy for preventing BRCA-mediated cancers, as well as aging,” he said.
- Oktay KH, Bedoschi G, Goldfarb SB, et al. Impact of BRCA mutations on chemotherapy-induced loss of ovarian reserve: a prospective longitudinal study. Presented at: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, TX. Abstract PD6-06.
- Oktay K, Harvey BE, Partridge AH, et al. Fertility preservation in patients with cancer: ASCO Clinical Practice Guideline update. J Clin Oncol. 2018;36(19):1994-2001.