Fertility and melanoma

Patient Guide

If you are thinking of starting or expanding your family anytime during, or after your melanoma diagnosis or treatment, you may have questions on the potential effects to your fertility. We’ve put together some key advice and information to help you below.

Please note that, here, we are referring to fertility as the following depending on your gender:
Sperm count, sperm quality (motility, morphology and DNA integrity); ability to father children.
Egg viability, ovarian reserve, uterine (womb) integrity, ability to conceive and give birth to healthy children.

Speak to your medical team as early as possible in your melanoma journey

It is important to inform your medical team of your wish to have children as early as possible in your diagnosis, so they can make personalised recommendations for you. This will help you make informed decisions on your fertility. Don’t assume your doctor or nurse will ask you about fertility concerns.

What could affect your fertility?

Many cancer therapies including immunotherapies, targeted therapies, chemotherapy, and radiotherapy all have the potential to impact your fertility whilst you are receiving them and afterwards. This is because it can sometimes take a while for the treatment to completely leave your body, or the normal function of your body to return. Sometimes, in certain situations, these effects can be permanent. These effects vary by the individual drug and type of therapy.

Another important aspect of cancer care and treatment is medical scans and imaging. In general, certain types of imaging are not recommended if you are pregnant, as the ionising radiation they use can cause harm to an unborn baby.

Since the treatment you receive will vary dependent on the stage of your melanoma, we have highlighted the risks by stage below, as well as some specific things you may wish to discuss with your treating medical team.

NB: There is a whole scientific research area known as ‘oncofertility’ that focusses on preserving patient fertility during and after cancer treatment.

Fertility advice according to melanoma stage

Localised melanoma (Stage 0 – 1)

If you have melanoma, at an early stage that has not spread and can be removed completely by surgery (either stage 0, melanoma in situ) or stage 1, localized melanoma), this is unlikely to affect your fertility. Whilst some research studies indicate that pregnancy rates amongst those recovering from cancer are often lower than control populations (people unaffected by cancer), this does not apply to those who have had early stage melanoma. This is likely due to the fact the treatment is minor surgery, with no treatments that affect the body as a whole.

Stage 2 melanoma

At Stage 2, the melanoma has not spread beyond the original site, but there is a risk it may do so in the future. If you are diagnosed with a stage 2 melanoma, you may require a procedure called a sentinel lymph node biopsy (SNLB) to determine whether the melanoma has spread to nearby lymph nodes.

>Read more about sentinel lymph node biopsy here.

The blue dyes and radioactive tracers typically used for SNLB, are very unlikely to impact your fertility (as they are very low dose). However, they are not recommended for use in pregnancy. Whilst some reports suggest these agents have minimal effects on your baby, this has not been studied in large numbers of pregnant women. If your medical team recommend a SLNB, it is worth discussing the timing of this, and whether it is safe to wait until you have delivered.

Stage 3 melanoma

If you are diagnosed with stage 3 melanoma (with a positive SNLB and spread to lymph nodes) you may be offered treatments, including immunotherapy and targeted therapies, with the aim of reducing the risk of your melanoma returning. These treatments will continue for up to a year. Your medical team will discuss these risks with you when you meet them. We discuss these treatments individually below.

Immunotherapy

Immunotherapy (immune checkpoint inhibitors) uses your own immune system to attack cancer cells, but while this effect can help treat your melanoma, it has the potential to have adverse effects elsewhere in your body. This includes your reproductive system.

There are several ways that immunotherapy could affect your fertility. These include hormonal changes, immune-system related changes and direct changes to your reproductive organs. They could also potentially harm an unborn child. There is also a risk that immunotherapy could directly affect egg production (oogenesis) and sperm production (spermatogenesis). At present, we have limited knowledge on the exact effects in people, as this has not been studied directly. There have been some animal studies, which have shown mixed results. These animal studies often use much higher doses of drug than those used in human treatment, so should be interpreted with caution.

The drug manufacturer of pembrolizumab (an immune checkpoint inhibitor) suggests you avoid becoming pregnant or fathering a child while receiving treatment and for at least 4 months after receiving your final dose.

Targeted therapies

Dabrafenib and trametinib are targeted treatments that are usually used together in some people with melanoma. There is some evidence that these treatments can affect fertility and this includes potential disruption to hormonal cycles in women; and sperm count and sperm motility in men. Animal studies suggest that these drugs can reduce sperm production and quality, and in addition, egg production in the ovaries during treatment. All treatments given to people are categorised based on the risk they present to fertility and dabrafenib and trametinib are classified as;

“Category C: Risk not ruled out: animal studies have shown an adverse effect on male or female reproductive organs AND there are no adequate and well-controlled studies in humans of reproductive potential”. Once again, patients are recommended not to get pregnant or father a child whilst taking these treatments, and within 4-6 months of stopping them.

Fertility Preservation

It is becoming increasingly common for patients to be offered risk-reducing treatment for stage 3 melanoma for patients of child-bearing age (male and female), but this is not considered standard practice, so may not be offered automatically.

Important conversations to have with the medical team about fertility preservation:

  • You can talk to your doctor or nurse about the effects of your particular treatment (note there may not be any, or they may be inconclusive)
  • You can discuss an effective contraception plan, if becoming pregnant is not advised before you start a particular treatment
  • Another important consideration is asking about accessing a fertility clinic for options like sperm, egg or embryo freezing if timings are critical. For example, you may have a family history of early menopause, and want to ensure that you have the best chances possible of conceiving after your treatment if you have to delay having a child
  • Discussing assisted reproductive technologies like IVF and options for using egg or sperm donors may also be useful

Stage 4 Melanoma

In stage 4 melanoma, your melanoma has spread to other parts of your body, so treatment is offered in an effort to control your melanoma. You may be offered treatments similar to those given to patients with stage 3 melanoma including targeted treatments or immunotherapy. Sometimes you might also be offered radiotherapy (discussed further below). Patients with active stage 4 melanoma are advised not to conceive or father a child during treatment, both because of the effects of the treatments and because of the serious nature of stage 4 melanoma. Patients diagnosed with stage 4 melanoma are not routinely offered fertility preservation as it is often important for treatment to start quickly, and fertility treatment could delay this.

Due to advances in treatments, increasing numbers of people diagnosed with stage 4 melanoma are surviving with no evidence of active melanoma. If this applies to you, and you wish to start or expand your family, discuss the openly with your medical team who can guide you regarding the timing of this, and how best to monitor you during your pregnancy.

Radiotherapy

In some cases, radiotherapy can be given to treat your melanoma. Fertility issues, either permanent or temporary can result, depending on the amount of radiation the reproductive organs (testes and ovaries) are exposed to.

Fertility and Melanoma: Useful resources

Women’s fertility and chemotherapy – Cancer Research UK
https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/chemotherapy/fertility/women

Men’s fertility and chemotherapy – Cancer Research UK
https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/chemotherapy/fertility/women

Ways to preserve your fertility – Cancer Research UK
https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/chemotherapy/fertility/women/ways-to-keep-fertility?

How cancer and cancer treatments can affect fertility in females. American Cancer Society
https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/fertility-and-sexual-side-effects/fertility-and-women-with-cancer/how-cancer-treatments-affect-fertility.html

How cancer and cancer treatments can affect fertility in males. American Cancer Society.
https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/fertility-and-sexual-side-effects/fertility-and-men-with-cancer/how-cancer-treatments-affect-fertility.html

Relevant References:

American Academy of Dermatology. “Melanoma And Pregnancy: What Every Woman Needs To Know About The Risks, Prognosis.” ScienceDaily. ScienceDaily, 12 May 2009. www.sciencedaily.com/releases/2009/05/090504210204.htm

Duma N, Lambertini M. It Is Time to Talk About Fertility and Immunotherapy. Oncologist. 2020;25(4):277-278. doi:10.1634/theoncologist.2019-0837

Ghezzi M, Garolla A, Magagna S, Šabovich I, Berretta M, Foresta C, De Toni L. Fertility Outcomes and Sperm-DNA Parameters in Metastatic Melanoma Survivors Receiving Vemurafenib or Dabrafenib Therapy: Case Report. Front Oncol. 2020 Mar 5;10:232. doi: 10.3389/fonc.2020.00232. PMID: 32211316; PMCID: PMC7066495.

Gori, Alessia; Salvini, Camilla; Fabroni, Caterina; Lo Scocco, Giovanni Is the mitotic rate of 1/mm2 the correct cutoff point for performing sentinel lymph node biopsy in pregnant patients with thin melanoma?, Melanoma Research: October 2013 – Volume 23 – Issue 5 – p 420-421 doi: 10.1097/CMR.0b013e3283644a2d

Lambertini, M., Del Mastro, L., Pescio, M.C. et al. Cancer and fertility preservation: international recommendations from an expert meeting. BMC Med 14, 1 (2016). https://doi.org/10.1186/s12916-015-0545-7

Stensheim H, Cvancarova M, Møller B, Fosså SD. Pregnancy after adolescent and adult cancer: a population-based matched cohort study. Int J Cancer J Int Cancer. 2011;129(5):1225–36.

Walter JR, Xu S, Paller AS, Choi JN, Woodruff TK. Oncofertility considerations in adolescents and young adults given a diagnosis of melanoma: Fertility risk of Food and Drug Administration-approved systemic therapies. J Am Acad Dermatol. 2016;75(3):528-534. doi:10.1016/j.jaad.2016.04.031