Melanoma survivorship in reproductive-age women is increasing due to the advent of effective therapies in the curative setting. However, while the impact on fertility and ovarian function of chemotherapy agents is well known, there is still a lack of consistent data regarding novel the Mitogen-activated protein kinase (MAP) kinase pathway inhibitors and immune-checkpoint inhibitors (ICIs) used in melanoma.

A recent study showed that a single course of anti-PD-1 (PD, Programmed cell death protein 1) or anti-CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4) reduced both the number and quality of oocytes in mice through an immune-mediated mechanism. In particular, primordial follicle damage cannot be restored, leading to relevant clinical implications.

The study aims to help to determine the impact of MAP kinase pathway inhibitors and ICIs on reproductive outcomes, and whether clinicians should discuss (and in what terms) fertility preservation techniques in reproductive-age women receiving ICIs and MAP kinase pathway inhibitors in the adjuvant setting.

Inclusion Criteria:

1. Stage II, III, IV completely resected melanoma
2. Female sex
3. Under 40 years of age
4. Not previously treated with chemotherapy and/or radiotherapy
5. Being able to give written informed consent.

Exclusion Criteria:

1. Unresectable melanoma
2. Predisposing conditions for infertility
3. Early menopause or family history of early ovarian failure (idiopathic, < 45 years)
4. Previous bilateral ovariectomy or other ovarian surgery
5. Personal history of autoimmune diseases, endocrine disorders (except for hypothyroidism)
6. Personal history of severe mental disorders associated with infertility (e.g., nervous anorexia) and/or requiring treatments that could impair fertility
7. Inability to give written informed consent.

Reproductive-age female patients with completely resected stage II, III, IV melanoma, irrespective of BRAF mutational status, with no previous history of chemo, radiation therapy and/or ovarian surgery.