Integrating oncofertility: Contraceptive guidance in chronic lymphocytic leukemia

Abstract Background: Chronic lymphocytic leukemia (CLL) is a hematological malignancy that causes uncontrolled growth of white blood cells. It predominantly affects older adults with a median age at diagnosis of 70 years, however 9% of patients are diagnosed before age of 45. Therefore, women with child-bearing potential face several challenges, not only with the complications of the disease and its treatment, but also with contraception, fertility and pregnancy-planning. Many CLL therapies can compromise ovarian reserve and are teratogenic, and some also increase thrombosis risk. These factors highlight the need for personalized contraceptive counseling in this population. Methods: A thorough literature search of major databases including PubMed, Google Scholar, WHO databases was conducted for English-language publications up to April 2025 using keywords such as “CLL,” “contraception,” “fertility preservation,” “targeted therapy,” and “immunotherapy”. Priority was given to clinical guidelines, randomized trials, and large observational studies relevant to contraceptive use in CLL. No formal inclusion/exclusion criteria were used as the study was a narrative review. Results: Women with CLL undergoing contemporary treatments face significantly increased thrombosis risks, requiring careful contraceptive selection. BTK inhibitors (e.g ibrutinib) increase thrombotic risk through platelet dysfunction and coagulopathy and may reduce the efficacy of estrogen-containing contraceptives through CYP3A4 induction. Similarly, BCL-2 inhibitors (e.g venetoclax) increase thrombotic risk, particularly when combined with other platelet-function impairing agents, warranting cautious use of estrogen-based contraceptives. Therefore, non-hormonal or progestin-only options are considered safer options. Furthermore, conventional chemotherapy (e.g fludarabine, cyclophosphamide) and some target therapies (e.g idelalisib) also present high thrombosis risk and hepatotoxicity, potentially impairing hormonal contraceptive metabolism. Hence, non-hormonal contraception such as copper IUD and barrier methods are preferrable options to mitigate the risk of thrombosis. On the other hand, immunotherapy agents (e.g rituximab) demonstrate variable thrombosis risks, especially when used in combination therapies. Although immunotherapies do not directly reduce hormonal contraceptive efficacy, their immunosuppressive effects necessitate caution with invasive contraceptive methods as it may predispose the patients to infections. Therefore, non-invasive barrier methods or non-hormonal IUDs are preferred. It can be noted that across all treatment classes, estrogen-containing contraceptives are discouraged due to increased thrombotic risks and pharmacokinetic interactions. Therefore, non-hormonal contraceptives (copper IUDs, barrier methods) are preferred for their minimal thrombosis risk and lack of drug interactions. Progestin-only contraceptives (mini-pill, implants, hormonal IUDs) also offer safe and effective alternatives with low thrombotic risk. Regular monitoring of platelet counts, liver function, and hematologic parameters is crucial to ensure contraceptive safety and efficacy. Conclusion: Contraception in women with chronic lymphocytic leukemia (CLL) presents complex challenges requiring individualized care. As many CLL treatments have gonadotoxic and teratogenic properties, it is imperative to have early discussion of fertility preservation prior to treatment initiation. Selecting the appropriate contraceptive method involves careful consideration of patient age, treatment regimen, fertility goals, and overall well-being. While hormonal contraceptives are effective, they may pose risks in women receiving targeted therapy, immunotherapy or chemotherapy. Non-hormonal alternatives and progestin-only contraceptives provide safer options for women with compromised immune systems. As novel CLL therapies continue to emerge, effective contraception management remains a critical aspect of comprehensive patient-centered care, necessitating close collaboration between healthcare providers and patients to align contraceptive choices with individual health and reproductive objectives.