A Significant Reduction in Clinical Ovarian Function and Spontaneous Pregnancy Rates in Cancer Survivors Treated by Gonadotoxicity High Risk Protocol – Conclusion from Long Term (20 Years) Follow-Up

Introduction: Young cancer patient are counseled before treatment about the gonadotoxic effects of chemotherapy. Long term fertility outcomes according to treatment gonadotoxicity risk is the basis for consulting patients enabling informed consent. It is imperative that fertility preservation options, including ovarian tissue cryopreservation (OTC), performed for more than 20 years, are explained.

Aim: To compare reproductive outcomes of patients who underwent OTC in accordance with chemotherapy regimen and malignancy.

Materials and Methods: A retrospective cohort study comprised of 231 patients referred for oncological fertility preservation at Hadassah Medical center between 1997 and 2017. Long term follow up on clinical ovarian function, reproductive outcomes and preserved ovarian tissue usage were collected using a questionnaire. Patients were divided into groups according to malignancy. Results were additionally reported by 3 groups (low, moderate and high risk) according to gonadotoxic potential of chemotherapy. This was defined by the regimen being used, the cumulative dose of chemotherapy administered and radiation therapy extent.

Results: Long term reproductive follow up and data regarding chemotherapy regimen were available for 92 patients. Clinical ovarian function and spontaneous pregnancy rates were significantly reduced in the high risk compared with the low risk gonadotoxicity regimen (30.4% vs. 88.0% and 28.6% vs. 64.7%, respectively; p=0.001 and p=0.05). A trend towards higher autotransplantation rates was observed in the high-risk group (3/14 vs. 1/17, NS).

Conclusions: Clinical ovarian function and spontaneous pregnancy rates are reduced in correlation to gonadotoxicity risk. This data allows precursory custom fertility consult for cancer survivors when reaching reproductive age.