(380) The Effect of Contemporary Oncologic Agents on Fertility Outcomes: A Review of the Literature
Authors: Mallory C , Lorduy S , Staley L , Ligon J , Halpern J , Potts S , Campbell K 
Published: February 2024

Abstract

Introduction
There is a growing number of referrals to urologists for oncofertility inquiries and concerns. Contemporary oncologic agents and their effect on fertility outcomes remain poorly understood. No study to date has evaluated the most common chemotherapeutic, immunologic, and targeted therapies seen by urologists and assessed their respective impacts on fertility.

Objective
We evaluated the effect of common contemporary chemotherapy, immunotherapy, and targeted therapy regimens on fertility outcomes.

Methods
We performed a single institutional review of all oncologic drugs taken by patients in the hematology/oncology clinic over the past five years (April, 2018- April, 2023). Agents were defined as contemporary if approval was received by the Food and Drug Administration 2006 or later. A review of the literature was conducted using PubMed to evaluate the effects on fertility for each drug. The MESH terms included agents [common name] OR [brand name] AND [sperm] OR [fertility] OR [infertility] OR [pregnancy] OR [birth] OR [reproductive] OR [reproduction] OR [ovarian] OR [testicular]. Search results for each agent were classified as “fertility impacted” or “fertility not impacted”. Studies were excluded if the primary aim or. secondary aim included fertility outcomes as a direct impact of chemotherapy, immunotherapy, or target therapy.

Results
We identified 75 patients who were treated with 28 unique contemporary oncologic agents. At least half of these agents demonstrated fertility inquiries in multiple patients referred. Agents with consultation &gt;5 occasions included brentuximab (9), pembroluzimab (8), blinotumomab (8), pazopanib (6), and nivolumab (6). A total of 2,629 studies resulted from our search of which 56 studies met inclusion criteria determined by two independently blinded reviewers. Impact on fertility was defined as impaired spermatogenesis, reduced total sperm count/function, hypogonadism, impaired folliculogenesis or decreased ovarian reserve/function. Eight studies were conducted on animal models. Thirty-two studies reported an impact on fertility. Agents mostly commonly demonstrating fertility concerns included Melphalan (14), Ipilimumab (4), Pembrolizumab (3), Olaparib (2), and Trametinib (2). The most common drug classes affecting fertility outcomes included alkylating agents and immune checkpoint inhibitors. The majority of agents had only one study assessing fertility outcomes. At least a third of agents had literature to both support and oppose their impact on fertility.

Conclusions
Contemporary oncologic agents demonstrate significant variability in their impact on fertility. There is limited consensus on fertility outcomes amongst common oncologic agents referred to urologists for fertility workup. Evidence supporting negative fertility impacts is more commonly demonstrated among alkylating agents and immune checkpoint inhibitors. However, the available literature regarding the fertility impact of contemporary oncologic agents is limited and varied, reinforcing the need for provider familiarity and future research.

Disclosure
No.