From the Guidelines
BEP chemotherapy can significantly impact fertility, particularly in men, with a 50-70% risk of temporary azoospermia and approximately 15-30% risk of permanent infertility, as reported in studies such as 1.
Impact on Fertility
The risk of infertility increases with higher cumulative doses of cisplatin, particularly exceeding 400 mg/m². For women, BEP can cause temporary or permanent ovarian damage, leading to premature ovarian insufficiency, with risk increasing with age, especially over 35.
Fertility Preservation Options
Fertility preservation options should be discussed before starting treatment. For men, sperm banking is recommended prior to beginning BEP, as seen in guidelines from 1 and 1. Women may consider oocyte or embryo cryopreservation, ovarian tissue freezing, or GnRH agonists during treatment.
Mechanism of Gonadotoxicity
BEP affects fertility because cisplatin and etoposide damage rapidly dividing cells, including sperm-producing cells and ovarian follicles, while bleomycin contributes to the overall gonadotoxic effect. The damage occurs through DNA crosslinking and oxidative stress mechanisms that particularly affect germ cells, as discussed in 1.
Key Considerations
- The NCCN Guidelines recommend discussing the risks of infertility due to cancer and its treatment with all patients at the time of diagnosis, before starting treatment, as stated in 1.
- Patients with good prognosis should receive three cycles of BEP or four cycles of EP if contra-indications against bleomycin exist, according to 1.
- Fertility preservation options should be considered for all patients undergoing BEP chemotherapy, especially those with a high risk of infertility, as highlighted in 1.
From the FDA Drug Label
The effects of bleomycin on fertility have not been studied. The FDA drug label does not answer the question.
From the Research
Impact of BEP Chemotherapy on Fertility
- The BEP chemotherapy regimen, which consists of bleomycin, etoposide, and cisplatin, has been shown to have adverse effects on spermatogenic function, posing a long-term reproductive health risk to cancer survivors and their progeny 2.
- Studies have demonstrated that BEP treatment can reduce testicular weights, impair spermatogenesis, and increase germ cell apoptosis in male rats 2, 3.
- However, despite these effects, male rats exposed to BEP treatment were still found to be fertile, although they experienced a decrease in litter size and an increase in preimplantation and postimplantation losses 2, 3.
- The effects of BEP treatment on fertility in humans are less clear, but one study found that patients who underwent fertility-sparing surgery and received BEP chemotherapy were able to recover their menstrual cycles and give birth to healthy children 4.
- Another study found that the BEP regimen was as safe as the paclitaxel/carboplatin regimen for preserving reproductive function in patients with malignant ovarian germ cell tumors 5.
Mechanisms of BEP Chemotherapy-Induced Fertility Impairment
- The exact mechanisms by which BEP chemotherapy impairs fertility are not fully understood, but it is thought that the drugs may induce DNA damage and telomere dysfunction in male germ cells 6.
- Telomeres, which are specialized structures at the ends of chromosomes, play an important role in maintaining genetic stability, and damage to telomeres may contribute to infertility and developmental defects in offspring 6.
- The effects of BEP chemotherapy on telomeres and DNA damage may be reversible, as one study found that germ cell apoptosis and postimplantation loss induced by BEP treatment were reversible in male rats 2.
Clinical Implications
- The findings of these studies have important implications for the clinical management of patients with testicular cancer and other cancers who are treated with BEP chemotherapy.
- Patients who are treated with BEP chemotherapy should be informed about the potential risks to their fertility and should be offered fertility preservation options, such as sperm banking, if possible.
- Further research is needed to fully understand the effects of BEP chemotherapy on fertility and to develop strategies to mitigate these effects and preserve reproductive function in cancer survivors.