Study question: Which factors related to patient, treatment or disease are associated with ovarian function recovery after chemotherapy in premenopausal women with breast cancer?
Summary answer: Younger age and GnRH agonist (GnRHa) administration during chemotherapy were significantly associated with menses recovery, but this recovery was less likely in patients exposed to taxanes.
What is already known: To date, published meta-analyses have only assessed GnRHa administration as a possible factor for ovarian function recovery, and their results were conflicting. Current guidelines present distinct recommendations regarding the use of GnRHa for fertility preservation (FP) in women with breast cancer.
Study design, size, duration: A systematic review and meta-analysis of published studies in the English, Portuguese, French or Spanish languages (1990-2015), ongoing trials or completed trials (1990-2015) and conference proceedings (2000-2015) were performed.
Participants/materials, setting, methods: We searched the MEDLINE, Embase, LILACS, Scielo, Toxline and DART databases, online trial registries and conference proceedings. Studies were eligible if they included premenopausal women with early breast cancer treated with chemotherapy, reported ovarian function recovery data and identified factor(s) associated with recovery. Two authors independently screened the studies, extracted data and assessed the risk of bias. An odds ratio (OR) was estimated from the number of recovery events. A meta-analysis was conducted using a random-effects model.
Main results and the role of chance: Fifteen articles were included. Five different factors were analysed: younger age and baseline levels of anti-Müllerian hormone (patient-related factors), co-administration of GnRHa, addition of taxanes to anthracycline-based chemotherapy and addition of endocrine therapy to chemotherapy (treatment-related factors). Menses recovery was the most used marker. Younger age (≤40 years) and exposure to GnRHa were positively associated with menses recovery (OR 6.07 and 2.03, respectively) but exposure to taxanes adversely affected recovery (OR 0.49). Significant heterogeneity among studies was found.
Limitations, reasons for caution: A general limitation of the included studies is the use of menses as the main recovery marker. Regarding GnRHa, the substantial heterogeneity and conflicting results limit the interpretation of our results. Studies that use additional markers and have a longer follow-up are needed.
Wider implications of the findings: The decision for using chemotherapy regimens with taxanes must take into account their potential adverse effects on female fertility. Considering the conflicting results regarding GnRHa agonist use, other fertility preservation strategies should also be considered.
Study funding/competing interests: No external funding was received. There are no conflicts of interest to declare.
Prospero registration number: This review was registered at PROSPERO (CRD42015013494).
Keywords: GnRH agonists, chemotherapy; antineoplastic agents; breast cancer; fertility; fertility preservation; ovarian function; recovery factors.
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