A global survey published in CA: A Cancer Journal for Clinicians estimates that 19.3 million new cases of cancer were diagnosed in 2020. Of particular note for reproductive specialists is that this includes an estimated 2.3 million new cases of female breast cancer, over 600,000 cases of cervical cancer and over 74,000 cases of testicular cancer.
Cancer patients of reproductive age may already know whether they want to build a family; they may even be planning it. Others only consider future children for the first time when they receive their cancer diagnosis. In any situation, the emerging field of oncofertility can bridge the gap between cancer patients and fertility specialists.
Oncofertility vs. Fertility Preservation
Fertility preservation is often considered an elective procedure and refers to any surgical or nonsurgical option to preserve a patient's ability to have biological children in the future. The topic can come up in preparation for cancer treatment — planning for fertility after cervical cancer, for example — but it may be entirely unrelated to cancer, such as a transgender patient preserving sperm or oocytes prior to undergoing hormone replacement therapy or gender affirmation surgery.
Oncofertility is an interdisciplinary field at the intersection of oncology and reproductive medicine that expands fertility options specifically for cancer survivors. It involves cancer specialists, reproductive endocrinologists, embryologists, social workers and other healthcare practitioners, each playing a specific role based on their area of expertise.
Impact of Cancer Treatments on Fertility
Many cancer treatments affect fertility for patients of all genders. Reproductive endocrinologists should discuss the possibility of future infertility for any patient undergoing chemotherapy, radiation treatment or cancer surgery. If the patient is a minor, a guardian must be part of the conversation.
Factors that play into how fertility may be impacted include:
- Age
- Type of cancer
- Proposed treatment plan, including dose and duration
- Amount of time that has passed since completing treatment
- Baseline infertility workup results
- Other health factors
The specific treatment will determine if and how fertility may be affected.
Chemotherapy
Chemotherapy causes premature ovarian insufficiency by preventing the ovaries from producing estrogen and releasing oocytes. The remaining oocytes will likely not be as healthy as they were prior to chemotherapy. People of advanced reproductive age are at the most risk of reduced fertility. These effects may be temporary or permanent.
Chemotherapy may also damage sperm-forming germ cells in adolescents and sperm in adults, especially when using alkylating drugs. Since bone marrow and stem cell transplants require high levels of chemotherapy and radiation, these procedures may also damage sperm, germ cells or ovaries.
Radiation Therapy
Aside from radiation directly to the ovaries or prostate, the reproductive organs are at the most risk when radiating the abdomen, pelvis or spine. Additionally, the pituitary gland may be harmed when radiating the brain. This can affect fertility by disrupting the production of hormones such as estrogen and testosterone.
Surgery
The location and size of the tumor determine if and how much fertility may be impacted by cancer surgeries. In some cases, surgery for cancer of the bladder, colon or rectum may affect the reproductive organs as well as nearby lymph nodes and nerves.
Oncofertility Encompasses Many Options
Depending on the urgency of treatment, cancer patients often have multiple options for preserving their fertility. For those who have a uterus and ovaries, oocyte cryopreservation is a common fertility preservation option. Since this procedure entails four to six weeks of ovarian stimulation before oocytes can be removed, it may not be an option for patients who need immediate cancer treatment. For cancer patients with testes, semen cryopreservation or testicular sperm extraction (for patients unable to produce a semen sample) are a similar but more expeditious option.
For patients who have not yet gone through puberty or produced mature oocytes, ovarian tissue cryopreservation or testicular tissue cryopreservation may be viable. This procedure removes part or all of an ovary or testicle. The ovarian tissue is frozen for later use and surgically reintroduced when the patient is ready to conceive while testicular tissue is later simply thawed to retrieve sperm. One major advantage of this option is its speed.
Oncofertility also includes alternatives to surgical fertility preservation options. In ovarian or testicular shielding, a protective lead cover is placed over the reproductive organs during radiation therapy to shield them from scatter radiation.
Since oncofertility remains an emerging field, many of the fertility preservation tactics it involves are very new or still considered experimental. In vitro activation is one emerging option for patients of advanced reproductive age or who have a low ovarian reserve. As described by research published in Frontiers in Endocrinology, this procedure involves extracting ovarian tissue and fragmenting it into cubes. Combined with in vitro incubation with Akt (AK strain transforming) stimulators, this leads to Hippo signaling disruption and promotes follicle growth. Primordial follicles rarely activate spontaneously in patients with primary ovarian insufficiency; this procedure does it for them.
An emerging nonsurgical option is gonadotropin-releasing hormone agonist treatment. This experimental treatment either causes the ovaries to stop producing estrogen and progesterone or suppresses the hypothalamic-pituitary-gonadal axis during chemotherapy in an effort to protect the layer of cells covering the testicle.
Actions for Healthcare Providers
After being diagnosed, patients will understandably have many questions. They may also be overwhelmed and not know what to ask. Physicians should prepare in advance to lead the conversation.
When discussing a patient's recommended treatment plan, be candid about any increased risk of infertility it may pose. Outline the chance of fertility returning in the future and how long it might take, including the possibility of becoming pregnant or carrying to term. It may be appropriate to refer a patient to a reproductive endocrinologist, pediatric gynecologist or another specialist who can help with the patient's age- and gender-specific fertility needs.
For more information, the Oncofertility Consortium offers an online decision-making tool to help healthcare providers navigate the options available to patients, including adolescents.
