Long term safety of controlled ovarian stimulation for fertility preservation prior to chemotherapy treatment in breast cancer patients

Moran Shapira; Tal Sella; Myriam Safrai; Evyatar Villain; Dror Lifshitz; Raoul Orvieto; Einav Gal-Yam; Dror Meirow

doi:10.1016/j.fertnstert.2024.10.014

Long term safety of controlled ovarian stimulation for fertility preservation prior to chemotherapy treatment in breast cancer patients

Fertil Steril. 2024 Oct 18:S0015-0282(24)02308-2. doi: 10.1016/j.fertnstert.2024.10.014. Online ahead of print.

Authors

Moran Shapira¹, Tal Sella², Myriam Safrai³, Evyatar Villain⁴, Dror Lifshitz⁵, Raoul Orvieto¹, Einav Gal-Yam⁶, Dror Meirow¹

Affiliations

¹ Fertility preservation center, Obstetric & Gynecology department, Sheba Medical center, Ramat Gan, Israel; IVF Institute, Obstetrics & Gynecology department, Sheba Medical center, Ramat Gan, Israel; Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv, Israel.
² Department of Oncology, Sheba medical center, Ramat Gan, Israel.
³ Fertility preservation center, Obstetric & Gynecology department, Sheba Medical center, Ramat Gan, Israel; IVF Institute, Obstetrics & Gynecology department, Sheba Medical center, Ramat Gan, Israel.
⁴ Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv, Israel.
⁵ IVF Institute, Obstetrics & Gynecology department, Sheba Medical center, Ramat Gan, Israel.
⁶ Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv, Israel; Department of Oncology, Sheba medical center, Ramat Gan, Israel.

PMID: 39427822
DOI: 10.1016/j.fertnstert.2024.10.014

Abstract

Objective: To evaluate the long-term safety of controlled ovarian stimulation for fertility preservation prior to breast cancer chemotherapy treatment DESIGN: Retrospective observational cohort SUBJECTS: 213 women aged 18-43 years with newly diagnosed stage I-III breast cancer treated with systemic chemotherapy during 2015-2019. Of those, 74 underwent controlled ovarian stimulation for fertility preservation recipients and 141 did not (controls).

Exposure: Controlled ovarian stimulation for fertility preservation MAIN OUTCOME MEASURES: Invasive disease-free survival, calculated from the time of surgery to the time of detection of breast cancer recurrence or death, whichever came first.

Results: At diagnosis, fertility preservation recipients were significantly younger than controls (32.7 vs 38.5 years), were less likely to be partnered (44.4% vs 90.1%) or parous (38.9% vs 95%) and were more likely to harbor a BRCA germline mutation (36.5% vs 14.2%). Disease characteristics and treatment modalities were comparable between groups, apart from tumor staging, with maximal tumor diameter being over 5 cm in 22.2% of fertility preservation recipients as opposed to 5.7% of controls (P<0.05). Mean follow-up was 60.9 and 65.4 months for fertility preservation recipients and controls, respectively. 5-year-invasive disease free survival was 80% for fertility preservation recipients and 86% for controls (p=0.20). In a multivariate analysis adjusted for statistically significant covariates, invasive disease free survival remained similar between the groups (Hazards Ratio (HR), 0.86, 95CI 0.4-1.87, p = 0.71). Invasive disease free survival rates were not statistically different in clinically relevant subgroups including patients receiving neoadjuvant chemotherapy (HR 1.57, CI 95 0.62-3.99, p=0.34), and those co-treated with tamoxifen during stimulation due to an ER-positive disease (HR 1.66, 95CI 0.67-3.49, p=0.23).

Conclusions: Fertility preservation with controlled ovarian stimulation for patients with breast cancer was not found to impair long-term oncologic outcomes, including in emerging clinically relevant subgroups.

Keywords: IVF; breast cancer; controlled ovarian stimulation; fertility preservation; neo-adjuvant chemotherapy; tamoxifen.