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Table 1 The 8 recommendations drafted by the expert panel

From: Reproductive issues in carriers of germline pathogenic variants in the BRCA1/2 genes: an expert meeting

Recommendations
1) In healthy BRCA mutation carriers, the impact of pregnancy and breastfeeding remains controversial. Women should be encouraged to complete childbearing at early age and discuss thorough breast follow-up during pregnancy and breastfeeding if they decide to maintain their breasts. In BRCA-mutated breast cancer patients, subsequent pregnancy following adequate treatment and follow-up does not seem to increase the risk of breast cancer recurrence and should not be discouraged.
2) A potential negative impact of BRCA pathogenic variants on women ovarian reserve and reproductive potential cannot be excluded and should be discussed; however, no strong conclusions can be drawn from existing data. Healthy carriers should be advised to not delay pregnancy beyond 35 years.
3) A potential negative impact of BRCA pathogenic variants on women ovarian reserve and reproductive potential including a diminished response to ovarian stimulation in breast cancer patients cannot be excluded and should be discussed during the oncofertility counseling; however, no strong conclusions can be drawn from existing data.
4) The available limited evidence does not demonstrate an increased risk of chemotherapy-induced POI in BRCA carriers but the overall risk remains significant for all patients and fertility preservation should be discussed with all women diagnosed at reproductive age. No data exist on the gonadotoxicity of newer treatment options in these patients.
5) Temporary ovarian suppression obtained by administering GnRHa during (neo-)adjuvant chemotherapy should be offered to all patients with cancer who wish to preserve ovarian function, including BRCA carriers diagnosed years before the recommended age of risk-reducing surgery. Most of the available efficacy data exist in women with breast cancer not carrying BRCA pathogenic variants. GnRHa use during chemotherapy does not replace established fertility preservation methods.
6) Despite the lack of exhaustive data, oocyte and embryo cryopreservation following COS can be considered a safe option that should be proposed both to BRCA-healthy carriers and patients with cancer interested in fertility preservation, whenever feasible. The use of letrozole to suppress supra-physiologic estrogens can be used safely without a reduction in the number or quality of oocytes.
7) Ovarian tissue cryopreservation should not be in principle recommended for known BRCA pathogenic variant carriers because of the potential ovarian cancer risk associated with the transplantation of ovarian tissue. However, in selected cases and motivated patients diagnosed several years before the recommended age of RRSO, ovarian tissue cryopreservation may be considered with caution when other possibilities are not feasible, but special considerations also for the transplantation procedure are needed. IVM is considered a promising but still experimental strategy in this setting.
8) Carriers of BRCA pathogenic variants interested in avoiding the transmission of their mutation to the offspring have to be informed about the possibility to undergo PGT-M. A thorough and balanced genetic and fertility counseling should be offered to all interested carriers, underlying pros and cons of the procedure.