BRCA carriers have similar reproductive potential at baseline to noncarriers: comparisons in cancer and cancer-free cohorts undergoing fertility preservation

Abstract

Seven-hundred and ninety-five oocyte cryopreservation patients, comprising BRCA carriers with and without malignancy (n ¼ 57) and BRCA noncarriers (n ¼ 738). Intervention(s): Fertility preservation with oocyte cryopreservation. Main Outcome Measure(s): Antral follicle count (AFC), antim€ ullerian hormone (AMH) concentration, day-3 follicle-stimulating hormone (FSH) level, number of harvested oocytes, and number of mature/cryopreserved oocytes. Result(s): In the cancer cohort we compared BRCA-positive breast cancer (n ¼ 38) with BRCA-negative breast cancer (n ¼ 53) and with non-breast-cancer malignancies (n ¼ 85). In the cancer-free cohort we compared BRCA carriers (n ¼ 19) with women undergoing elective egg freezing (n ¼ 600). We also compared the BRCA1 (n ¼ 31) versus the BRCA2 carriers (n ¼ 18). The patients' mean ages were 32.4 AE 3.6 years and 35.5 AE 4.3 years in the BRCA carrier and noncarrier cohorts, respectively. BRCA status was associated with a higher day-3 FSH level in the cancer cohort, but we found no changes in the other outcomes compared with the BRCAnegative cancer groups. BRCA carriers without cancer exhibited a higher AFC and number of mature oocytes compared with the patients undergoing planned egg freezing. Overall (cancer and cancer-free cohorts), the BRCA carriers had an increased AFC (15.5 AE 4.6 vs. 12.6 AE 5.7) and number of mature/cryopreserved oocytes (14.0 AE 7.9 vs. 10.4 AE 6.9) compared with the BRCA noncarriers but had no differences in other outcomes. Conclusion(s): BRCA carriers with and without malignancy exhibit comparable ovarian reserve and responses to ovarian stimulation compared with women with BRCA-negative cancers and cancer-free controls. (Fertil Steril Ò 2019;111:363-71. Ó2018 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

Adjusting for age: is it enough to just say you did it?

“…A potential reason for the discordant conclusion with other published data is the confounder of age in the study by Gunnala et al (1). Tables 2 and 3 in their study show a large difference in mean age between the BRCA carrier and BRCA noncarrier groups.…”

“…In conclusion, just because the possibility exists that a study's results may be due to inappropriate adjustment of a significant confounder does not mean that is necessarily the case. In the study by Gunnala et al (1), an equally valid argument can be made to support the findings of the study in an analogous manner as the hypothetical example above. Since age is such an important confounder in many studies of reproductive medicine, our proposal is to make it incumbent on the study authors to provide enough evidence that the confounder of age was handled appropriately.…”

“…The study by Gunnala et al (1) examined an important and controversial question in the literature regarding the fertility potential of BRCA mutation carriers. As pointed out by the authors, determining whether or not carriers of the BRCA mutation have less reproductive potential when viewed from the standpoint of fertility preservation is important for counseling these patients because of their shortened reproductive window.…”

“…The controversy in the literature surrounding the BRCA mutations as they relate to fertility has been previously reviewed along with the proposed mechanisms that cause reduced fertility potential in these patients (2). Gunnala et al (1) have added to the body of literature on this topic by performing a large retrospective cohort study of patients undergoing fertility preservation at their institution. The cohort was split by BRCA carrier status for analysis to answer the question of reproductive potential.…”

“…In this study, reproductive potential was assessed by ovarian reserve testing and number of mature cryopreserved oocytes. Gunnala et al (1) found that BRCA carrier status conferred a statistically significant increase favoring BRCA carriers in the number of mature cryopreserved oocytes and antral follicle count. This is contrary to most published studies on the topic, which either show no difference or fertility outcomes favoring BRCA noncarriers (2).…”