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Oncology and Fertility


The revelation of a cancer diagnosis in young individuals and teenagers marks a transformative moment for them and their loved ones. Despite significant progress in treatments leading to about an 80% five-year survival rate for childhood cancers, it remains the second most common cause of death (after accidents) in children between the ages of 5 and 14. Although pediatric cancer represents a significant cause of mortality in both children and adults, it is comparatively rare in terms of overall numbers.

Particular cancers that are more prevalent among women or individuals with ovaries during their reproductive years pose a higher risk of fertility issues. This group includes breast, uterine, cervical, ovarian, thyroid cancers, and blood cancers such as lymphomas. In women, these treatments can lead to damage to the ovaries, potentially resulting in genetically compromised oocytes (eggs), ovarian failure, premature menopause, or other reproductive complications. In men or individuals with testicles, cancers located in the pelvic region or those requiring chemotherapy have a more pronounced impact on fertility. This encompasses prostate, testicular, lymphomas, thyroid, and colon cancers. For men, treatment may also cause harm to the testes, affecting sperm production and testosterone levels.

With the advancement in cancer treatments and an increase in survivorship, the emphasis on fertility preservation for women, men, and children is growing. Fortunately, a variety of options are available to enhance future fertility prospects. It is crucial to seek consultation with reproductive endocrinologists as soon as cancer is diagnosed, ideally before starting chemotherapy or pelvic radiation.


Factors determining the impact on fertility include:

– Initial fertility status

– Age at the time of treatment

– Type and specifics of the cancer and its treatments

– Dosage and duration of the treatment

– Other individual health aspects


A female might be diagnosed with infertility if:

– The ovaries lack healthy eggs

– Necessary hormonal support for egg release is disrupted

– Tumors or other issues impact the functionality of the ovaries or uterus

– Damage to the reproductive system hinders egg release, fertilization, or implantation

– The uterus is unable to support the growth of a fertilized egg

– Conditions arise that prevent the full-term carriage of a fetus, leading to miscarriage


Globally, in the age group of 0–19 years across both genders, leukemia tops the chart with 80,491 cases in 2020, followed by brain/central nervous system (CNS) cancers (30,766 cases), non-Hodgkin lymphoma (25,100), kidney cancer, and Hodgkin’s lymphoma. The incidence rates are higher in males, yet the top three cancers remain consistent across both sexes. In terms of mortality worldwide for both genders, leukemia is the leading cause, succeeded by brain/CNS tumors, non-Hodgkin’s lymphoma, and cancers of the kidney and liver, with males experiencing higher death rates.

Estimations for 2021 indicate that 4.6% of all new cancer diagnoses will be in individuals aged 15–39 years, with a 5-year relative survival rate of 85%. This statistic is similar for children aged 0–14 years. Survivors of cancer, especially those who pass the 5-year mark, may continue to face risks of recurrence or progression of their initial cancer, along with a heightened chance of developing new malignancies, chronic illnesses, and physical impairments. Long-term and delayed effects necessitate ongoing monitoring for those who have survived cancer during childhood and adolescence.

Impact of Cancer on Fertility

A cancer diagnosis alone poses a risk for infertility. As a systemic illness, cancer can influence fertility through various pathways, even prior to treatment initiation. Infertility in cancer survivors may stem from damage to the hypothalamic-pituitary-gonadal axis and the reproductive tract organs.

The hypothalamic-pituitary-gonadal axis operates on a classic feedback mechanism. Central hypogonadism arises from harm to the hypothalamus or pituitary gland, often due to tumors or their treatments; primary hypogonadism is a result of damage to the ovaries or testicles from tumors or their treatments. The primary hormones stimulating the human testes, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), are produced by the pituitary gland and enter systemic circulation. These hormones’ secretion is triggered by the pulsatile release of gonadotropin-releasing hormone (GnRH) from hypothalamic neurons. GnRH travels to the gonadotroph cells of the anterior pituitary through a portal vascular system. Dysfunction at any point in this axis can suppress testosterone production, thereby hindering spermatogenesis. Females experience similar gonadal failure, leading to infertility due to failed hormonal production.

Testicular tumors may produce β-human chorionic gonadotropin (β-hCG) and α-fetoprotein (AFP), impacting the axis as elevated β-hCG levels correlate with poor semen quality and inhibit spermatogenesis through negative feedback.
Studies have identified leukemia and lymphoma as pre-treatment azoospermia risk factors. Cancer’s immune response can also impact fertility, as many cancers cause lymphocytic infiltration and elevate pro-inflammatory cytokines.
The disease’s systemic symptoms also affect reproductive capabilities, notably in cases of severe malnutrition and fever (common in Hodgkin’s lymphoma), leading to changes in sperm motility, morphology, and concentration.

Impact of Cancer Treatments on Reproductive Capabilities

The reproductive health of cancer survivors often deteriorates due to the gonadotoxic nature of many oncological treatments, which, while increasingly effective in managing the disease and prolonging life, can negatively affect fertility.

Gonadotoxic effects from cancer treatments can be direct, such as damage to or depletion of ovaries, or indirect, leading to hormonal deficiencies via the hypothalamic-pituitary-gonadal axis. They may also cause functional changes, such as uterine issues in women or ejaculatory and erectile difficulties in men. These impacts can be permanent, temporary, or delayed, especially in women experiencing premature ovarian failure.

Surgical Interventions

Fertility can be compromised by surgeries like orchiectomy, hysterectomy, or oophorectomy. In adolescent males, certain cancer surgeries can lead to lasting effects on fertility and sexual function. Testicular surgeries may impede sperm and hormone production or disrupt sperm transport. Men undergoing unilateral orchiectomy for testicular cancer often see a post-surgery decline in semen quality, though most recover. Surgeries like retroperitoneal lymph node dissection or prostatectomy can damage the autonomic nervous system, affecting emission and ejaculation and potentially leading to ejaculatory impairment.
Pelvic surgeries in men may harm nerves critical for erection and ejaculation, increasing risks of erectile dysfunction or obstructive azoospermia. Radical surgeries for non-testicular malignancies often result in ejaculatory and erectile dysfunction. Women undergoing oophorectomy or total hysterectomy face permanent fertility loss. Surgeries affecting the bladder, intestine, and rectum can hinder the ability to carry a pregnancy to term. Bone marrow and stem cell transplants involving high-dose chemotherapy/radiation can lead to ovarian damage and infertility.


This prevalent treatment targets the body’s active cells, including those in reproductive organs, potentially harming the ovaries or testicles and affecting the production of viable eggs or sperm. Fertility prospects post-treatment depend on chemotherapy type, duration, dose, and patient age. Alkylating agents, in particular, pose higher risks.
Chemotherapy-induced gonadotoxicity arises from targeting rapidly dividing cells. Its effects vary based on chemotherapy type, dosage, initial semen quality, and impact on the spermatogenic/menstrual cycle. Specific chemo drugs linked to female infertility risk include Busulfan, Carboplatin, Carmustine, and others. Higher doses and drug combinations can cause more severe fertility changes, especially when combined with abdominal or pelvic radiation.
In women, drugs like cyclophosphamide and procarbazine can diminish ovarian reserve, causing lesions in the ovarian stroma. In men, chemotherapy can damage the seminiferous epithelium and decrease testosterone levels by harming Leydig cells. Normal sperm count usually recovers within 12 weeks after therapy with non-alkylating agents. However, alkylating agents, which disrupt DNA function, can cause irreversible effects on spermatogenesis and a high risk of infertility.
Childhood cancer survivors exposed to alkylating agents face a higher likelihood of premature menopause. Those treated without these agents do not show a significant increase in premature menopause or subfertility. Chemotherapy may also result in growth hormone deficiency, hypothyroidism, or pubertal abnormalities, affecting fertility by impacting the nervous system or pelvic reproductive organs.
Platinum-based heavy metal treatments can suppress spermatogenesis temporarily or permanently, but recovery is more favorable over time. Antimetabolite therapy and vinca alkaloids have a lesser impact on male fertility. Advances in chemotherapy aim to minimize toxicity while maintaining effectiveness.

Chemo and Pregnancy

Factors affecting fertility risks in females include age, puberty and menopause status, and menstrual cycle recovery post-chemo. Young women treated before 35 have the best pregnancy chances post-treatment. However, having periods post-treatment doesn’t guarantee fertility, requiring fertility expert consultation.


This treatment, especially at high doses in the pelvic area, can impact fertility. Options like repositioning ovaries out of the radiation field can reduce damage risks. Radiation therapy’s impact varies with the dose, location, and patient age. Pelvic radiation can cause uterine fibrosis, impacting pregnancy outcomes, while ovarian radiation exposure can lead to menstrual irregularities and ovarian failure. Cranial radiation can disrupt pituitary function, affecting ovulation. Spinal irradiation increases miscarriage rates, with the highest reproductive loss risks in patients receiving brain and pelvic region treatments. Total body irradiation prior to stem cell transplantation classifies patients as high-risk for gonadotoxicity.

In men, radiotherapy can harm testicular function, affecting both germ and Leydig cells. Testicular tissue is highly radiosensitive, and even low doses can impair spermatogenesis.

Hormone Therapy

Hormonal therapies, primarily used in breast and prostate cancers, can be reversible in their effects on fertility. Tamoxifen in breast cancer treatment may cause temporary amenorrhea but is not typically linked to ovulation cessation. Hormone therapy in men, mainly for prostate cancer, often involves azoospermia.

Hormone Therapy

Immune checkpoint inhibitors (ICIs) can cause primary and secondary hypogonadism and impact sexual function. Hypophysitis and panhypopituitarism from ICIs can disrupt the pituitary gonadal axis, reducing sex hormones and fertility. Little is known about the fertility effects of targeted therapy and immunotherapy drugs, but drugs like Bevacizumab can lead to ovarian failure, and others carry high birth defect risks, necessitating contraceptive measures. Conception and pregnancy should be avoided during ICI treatment.

Emotional and Psychological Consequences

The journey through cancer diagnosis and treatment can bring about various forms of sexual dysfunction, often linked to testosterone deficiency. Testosterone plays a crucial role in regulating monoamine neurotransmitters that are pivotal in managing anxiety and depression. An increase in dopamine neurotransmitter release in the brain’s limbic system is a known effect of testosterone, potentially mitigating pleasure disorders induced by depression and countering the decrease in dopamine activity in reward-centric neural pathways. As testosterone levels drop, there is a corresponding decrease in these neurotransmitter levels, potentially leading to symptoms of depression.

Mental Health Disorders and Hormonal Alterations

Confronting a cancer diagnosis, particularly in younger patients, often leads to significant emotional turmoil. This distress arises from various sources: constant awareness of symptoms, worries about family and financial stability, the burden of navigating healthcare, altered self-image and body perception, and fears of cancer recurrence.

This psychological strain is closely linked to symptoms of depression and anxiety. Patients grappling with infertility as a consequence of cancer treatments are particularly susceptible to heightened emotional distress and the accompanying psychiatric disorders.

Furthermore, the stress and mental strain resulting from a cancer diagnosis and its treatment can lead to psychiatric conditions like anxiety and depression, which in turn may lower testosterone levels, thus feeding into a cycle of psychological and hormonal imbalance.


Understanding Fertility and Cancer Treatment is important. Key Questions to Ask are as follows:

  1. Is there a possibility that the proposed cancer treatment could lead to infertility, or affect my ability to conceive or sustain a pregnancy in the future?
  2. Are there alternative cancer treatment options available that have a reduced risk of impacting fertility?
  3. What fertility preservation methods would be most suitable for my situation?
  4. Can you inform me about the fertility preservation services offered at this medical facility or at an external fertility clinic?
  5. Could you recommend a specialist in reproductive endocrinology for a more detailed discussion about my fertility options?
  6. Considering the type of treatment I will undergo, is it necessary to use condoms to protect my partner or preserve fertility?
  7. Is it advisable to use birth control methods during or after my cancer treatment?
  8. What is the likelihood of my fertility being restored post-treatment, and how long could this recovery process take?

Fertility outcomes after treatment

If you still have your reproductive organs, you may be able to conceive after cancer treatment without medical assistance. However, about one in three women will experience one of the following physical issues. 

Acute Ovarian Failure

During treatment, and for some time afterwards, the ovaries often stop producing hormones because of the damage caused by the cancer treatment. This is known as acute or temporary ovarian failure. You will have occasional or no periods, and symptoms similar to menopause, before regular periods return.

If ovarian failure continues for several years, it is less likely that your ovaries will work normally again. 

Early Menopause

Menopause before the age of 40 is known as premature ovarian insufficiency (POI). This is when you stop having menstrual periods because egg numbers are very low. It may also be called early or premature menopause.

POI could occur immediately or many years after treatment, depending on your age, type of treatment and the dose of any drugs you received. If the ovaries are surgically removed or too many eggs are damaged during treatment, menopause is permanent.

While menopause means you won’t ovulate, it is still possible to carry a baby if you have a uterus and use stored eggs or donor eggs. A small number of women with POI (5–10%) have a chance of becoming pregnant naturally, because in some rare cases, a remaining egg may mature and be fertilised by a sperm.

Fertility Prospects Following Cancer Treatment

Post-cancer treatment, if your reproductive system remains intact, there’s a possibility of natural conception. Nonetheless, roughly one-third of women may face one of these physiological challenges :

Temporary Ovarian Failure

During and following cancer treatment, your ovaries might temporarily halt hormone production due to treatment-induced damage, a condition referred to as acute or temporary ovarian failure. During this phase, you might experience infrequent or absent menstrual cycles, alongside symptoms resembling menopause, until regular cycles resume.

If ovarian failure persists for an extended period, the likelihood of your ovaries resuming normal function diminishes.

Premature Ovarian Insufficiency (POI)

Experiencing menopause before 40 is termed premature ovarian insufficiency (POI), characterized by the cessation of menstrual periods due to a significant reduction in egg count. This condition, also known as early or premature menopause, can manifest immediately or several years post-treatment, influenced by factors such as your age, treatment type, and medication dosage. Permanent menopause occurs if ovaries are surgically removed or excessively damaged during treatment.

While menopause implies the absence of ovulation, pregnancy is still possible with a functional uterus, utilizing either stored or donor eggs. A minority of women with POI (5–10%) may conceive naturally, as occasionally, a remaining egg might mature and be fertilized.