Fertility preservation in women harboring deleterious BRCA mutations: ready for prime time?

Abstract

Fertility issues have become critical in the management and counseling of BRCA mutation carriers. In this setting four points deserve consideration. (1) Women in general lose their ability to conceive at a mean age of 41 years, thus the suggested policy of prophylactic bilateral salpingo-oophorectomy at age 40 for BRCA mutation carriers does not affect the chances of natural pregnancy. Conversely, if the procedure is chosen at 35 years old, oocyte cryopreservation prior to surgery should be considered. (2) Some evidence suggests that ovarian reserve may actually be partly reduced in BRCA mutations carriers and that the mutation may affect ovarian responsiveness to stimulation. However, these findings are still controversial. (3) Breast cancer is not rare before the age of 40 and fertility preservation after diagnosis can be requested in a significant proportion of BRCA mutation carriers. Thus, a policy of oocyte cryopreservation in young healthy carriers deserves consideration. The procedure could be considered at a young age and in an elective setting, when ovarian stimulation may yield more oocytes of better quality. (4) Preimplantation genetic diagnosis (PGD) could be considered in BRCA mutations carriers, particularly when good quality oocytes have been stored at a young age. Based on the current knowledge, a univocal approach cannot be recommended; in depth patient counseling is warranted.

Impact of BRCA1 and BRCA2 mutations on ovarian reserve and fertility preservation outcomes in young women with breast cancer

“…Oocytes cryopreservation is a feasible option that should be suggested to these patients, especially considering the frequent recommendation of a prophylactic bilateral salpingooophorectomy at the age of 40 for both BRCA1 and 2 women [36].…”

Ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy in cancer patients: From biological evidence to clinical application

“…Therefore, subsequent ovarian function suppression as part of adjuvant endocrine therapy should be considered for patients with estrogen receptor-positive breast cancer who received temporary ovarian suppression with GnRHa during chemotherapy. Notably, so far, there is the lack of data on the efficacy of using temporary ovarian suppression with GnRHa during chemotherapy in breast cancer patients with hereditary cancer syndromes such as those carrying deleterious germline BRCA mutations [92,93]. Some evidence suggests that baseline ovarian reserve of BRCA-mutated breast cancer patients can be partly reduced with subsequent potential higher risk of chemotherapy-induced POI [94].…”

Fertility in female cancer survivors: a systematic review and meta-analysis

“…A documented fertility discussion should include assessing women's desire for future fertility, the potential effect of each treatment regimen on future fertility and, possibly, an exploration of options for fertility preservation (McCray et al, 2016). In this setting, fertility preservation procedures become urgent, even if there is generally enough time to set up an ovarian stimulation cycle before starting the planned treatment (Peccatori et al, 2018). The recent development of random start and repetitive stimulation protocols, e.g.…”

“…Ovarian tissue freezing and transplantation is an alternative option (De Vos et al, 2014), although the success of this approach is predominantly inherent to ovarian reserve at cancer diagnosis. Moreover, the carcinological risk of ovarian tissue transplantation in women with breast cancer remains an unresolved issue (Peccatori et al, 2018).…”