Gonadotropin Releasing Hormone agonist (GnRHa) during chemotherapy and post-cancer childbirths - a Nationwide population-based cohort study of 24,922 women diagnosed with cancer in Sweden

Background Worldwide, an increasing number of women with cancer are receiving Gonadotropin Releasing Hormone agonist (GnRHa) co -treatment during chemotherapy aiming at ovarian protection. There is divergence among guidelines, and some have recommended GnRHa co -treatment for women with breast cancer, however, the effect of GnRHa on future fertility is uncertain. Methods In this population -based cohort study we included all women diagnosed with cancer at ages 15-45 between July 2005 and March 2017 in Sweden, identified in the Swedish Cancer Register. Exposure to GnRHa co -treatment was captured using the Prescribed Drug Register. Post -cancer childbirth, extracted from the Medical Birth Register, was the main outcome. Secondary outcomes included childbirths achieved through natural conception (NC), infertility diagnosis and cancer mortality. For each outcome, adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were estimated using delayed -entry Cox models, stratified by age and cancer site. Findings Among 24,922 women diagnosed with cancer, 1.5% had GnRHa co -treatment. Breast cancer diagnoses were found in 80.2% of GnRHa exposed women and the GnRHa exposure was not associated with higher rates of childbirth (aHR 1.23, 95% CI 0.80-1.89), or NC childbirth (aHR 1.02, 95% CI 0.62-1.67), whereas the rate of infertility was significantly higher (aHR 2.42, 95% CI 1.44-4.08). In women with lymphoma and other cancers, GnRHa exposure was not associated with higher rates of childbirth, NC childbirth or infertility. GnRHa exposure was not associated with higher cancer mortality for any cancer type. Interpretation We did not find evidence of improved or maintained fertility, estimated as childbirth rates post -cancer, in women who received GnRHa during cancer treatment. Copyright (c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).