Fertility preservation in women with BRCA1/2‑related cancers: contemporary strategies, international recommendations, and a multidisciplinary approach

Inherited mutations in the BRCA1/BRCA2 genes significantly increase the risk of breast and ovarian cancer in women of reproductive age, posing a clinical and socioeconomic challenge due to loss of fertility during cancer treatment and preventive interventions. The expansion of genetic testing programs is shifting the focus to proactive management of reproductive potential, requiring the integration of oncology, reproductive medicine, and medical genetics. The novelty of this review lies in its comprehensive synthesis of data on the impact of treatment and prevention of BRCA-associated cancer on fertility and a critical assessment of the effectiveness of fertility preservation strategies.

Purpose of the study. To summarize and analyze current advances, clinical guidelines, and unresolved issues related to preserving reproductive function in women carrying BRCA1/BRCA2 mutations.

Materials and methods. A systematic search of PubMed/MEDLINE, Embase, the Cochrane Library, and Web of Science was performed, along with an analysis of international guidelines (ESHRE (European Society of Human Reproduction and Embryology), ASCO (American Society of Clinical Oncology), ASRM (American Society for Reproductive Medicine), NCCN (National Comprehensive Cancer Network), ESMO (European Society for Medical Oncology)). Keywords: “BRCA1,” “BRCA2,” “fertility preservation,” “oocyte cryopreservation,” “embryo cryopreservation,” “ovarian tissue cryopreservation,” “PGT-M,” “PARP inhibitors,” and “chemotherapy gonadotoxicity.”, in the period of 2005–2025. Studies with incomplete data, duplicates, reviews of low methodological quality, and case series with fewer than 10 observations were excluded. Priority was given to meta-analyses, RCTs, large cohorts, and consensus reports.

Results. The included studies included cancer patients before and after treatment, BRCA carriers with and without prophylactic strategies, and IVF/ICSI cohorts with cryopreservation. Alkylating agents and taxanes have been shown to increase the risk of premature ovarian failure, while GnRH agonists partially reduce the risk of ovarian toxicity. The efficacy of oocyte and embryo cryopreservation in BRCA-positive women is comparable to the population-­based efficacy with optimized stimulation (GnRH antagonists, letrozole-­containing protocols). Ovarian tissue cryopreservation is applicable in urgently needed patients but requires oncoprotective assessment. PGT-M ensures the selection of mutation-free embryos. Multidisciplinary pathways improve the timelines of referrals and the completion rate of fertility preservation programs.

Conclusion. Early identification of BRCA-positive women and the integration of a gynecologic oncologist, reproductive specialist, and geneticist enable personalized strategy selection: gamete/embryo cryopreservation, ovarian tissue, pharmacoprotection, and PGT-M. Standardized stimulation protocols and therapy timing, long-term safety and fertility data, and economic access models are needed. Improvements in biotechnology and patient pathways improve reproductive outcomes and quality of life.

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