Table 4.

Pragmatic clinical approach and unsolved questions on checkpoint inhibitors, fertility, and sexuality

Adverse event	Clinical approaches	Unsolved questions
Primary hypogonadism	•Discuss the possibility of infertility linked with the treatment and the strategies of fertility preservation (e.g. cryopreservation)	•Frequency •Duration after discontinuation of immunotherapy •Alteration of sex hormones levels (e.g. testosterone, estradiol) •Impact on fertility, pregnancy, and complicated pregnancy •Impact on libido and sexual life
Secondary hypogonadism	•Discuss the possibility of hypopituitarism-induced infertility linked with the treatment and the strategies of fertility restoration (e.g. hormonal therapy if clinically safe)	•Frequency of secondary hypogonadism •Frequency of isolated secondary hypogonadism •Impact on fertility, pregnancy, and complicated pregnancy •Impact on libido and sexual life
Pregnancy	•Strongly suggest avoiding pregnancy during treatment using at least one contraceptive methods •In case of pregnant woman, discuss the current evidence and risks of concurrent immunotherapy administration. Discuss the possibility of treatment discontinuation in case of long-term complete response •If therapy will be administered during pregnancy, after delivery, follow-up the child for development abnormalities, autoimmune diseases •Strongly suggest a minimum time from the end of therapy and the beginning of a pregnancy (3 months for ipilimumab and durvalumab, 4 months for pembrolizumab, and 5 months for nivolumab and atezolizumab)	•Trimester-specific toxicity •Frequency of miscarriage, stillbirth, premature delivery •Frequency of fetal malformation, fetal autoimmune disease •Frequency of complicated pregnancy
Libido and sexual life	•Discuss the theoretical possibility of reduced libido and impaired sexual life •Consider hormone replacement therapy in case of deficiencies and if clinically indicated	•Frequency •Duration after discontinuation of immunotherapy •Type of disturbance •Impact on procreation •Impact on quality of life