Overview of Care Before Gonadotoxic Therapy

Introduction:

Chemotherapy, radiation, and surgical resection are examples of gonadotoxic treatments used to treat disease, gender affirmation surgery, malignancy, or medical disorders that can permanently impair reproductive function. Surgical interventions for diseases such as cancer or medical disorders can significantly impair reproductive function. Ovulation and the menstrual cycle are the key aspects of the female reproductive system. Women have regular monthly menstrual periods during their reproductive years because they ovulate regularly each month. Eggs mature inside fluid-filled spheres called "follicles." Just before the onset of every menstrual cycle, when a woman is experiencing her period, a hormone produced in the pituitary gland (follicle-stimulating hormone (FSH)), situated in the brain, stimulates a group of follicles to grow more rapidly on both sides of the ovaries. At the same time, male fertility is not determined by semen or sperm traits alone. Fertility is not solely dependent on semen quality; hormonal, genetic, and immunological factors also play key roles.

What Are the Agents Affecting Fertility?

Gonadotoxic is related mostly to the agents used in treating cancer. Regimens, including chemotherapy and radiotherapy, can cause adverse effects on gonadal function relative to dose-related. Gonadotoxic therapies target rapidly dividing cells but can also damage reproductive tissues, affecting fertility in both men and women.

• Chemotherapy: Chemotherapy protocols have the potential for gonadal toxicity as per the American Society of Clinical Oncology (ASCO) recommendations on fertility preservation. Among chemotherapeutic drugs, the alkylating agents, particularly Procarbazine and Cyclophosphamide, appear to cause the most elevated hazard in a dose-related mode, with the highest doses inducing a significant probability of permanent amenorrhea. However, amenorrhea induced by chemotherapy treatment may be temporary, and menstruation may return after several months post-treatment. The gonadotoxic effect of chemotherapy is influenced by the patient's age, type of chemotherapy, dosage, and the number of cycles employed.
• Radiotherapy: Gonadal injury caused by field radiation of the total body, mainly the abdominal or pelvic region, disrupts the hypothalamic-pituitary axis function, provoking ovarian failure or direct damage to the uterus. Oocytes are especially sensitive to radiation, with an estimated dose of less than 2 grays (units used to measure radiation) needed to destroy 50 percent of primordial follicles. The magnitude of the adverse effect is related to dose, fractionation schedule, and age at the time of treatment, which increases the risk of miscarriage, premature delivery, low birth weight, maternal bleeding, and damage to structures and vessels in the pelvis and abdomen.

What Are the Procedures for Women to Preserve Fertility Before Cancer Treatment?

Women who are close to undergoing malignant tumor treatment have various options regarding fertility preservation.

• Embryo Cryopreservation: This process requires additional egg harvesting, fertilization, and freezing for them to be ready to transfer later. Studies suggest that embryos can survive the freezing and thawing process up to 90 percent of the time. Advances in freezing techniques have allowed embryos to survive better, thus offering a sure alternative to women who want to preserve their fertility.
• Egg Freezing or Oocyte Cryopreservation: In this technique, the eggs are removed and frozen before being fertilized. Human eggs freeze less successfully than human embryos. New freezing protocols have greatly improved results for egg freezing.
• Radiation Shielding: The best method to prevent radiation-induced damage is using small lead shields positioned over the ovaries to diminish radiation exposure.
• Ovarian Transposition or Oophoropexy: The procedure involves surgically repositioning the ovaries in the pelvis to save them from radiation when delivered to the pelvic area. Thus, because of scatter radiation, ovaries cannot be protected completely, as the ovaries are radiosensitive, and scatter radiation can lead to damage. Still, this method has a relatively high chance of ovaries being protected. With the help of a lead shield, the ovaries are protected. After completing all radiation sessions, the ovaries are repositioned.
• Surgical Removal of the Cervix: To handle early-stage cervical cancer, a large triangular-shaped cervix, including the cancerous area, is withdrawn, called cervical conization. The rest of the remaining cervix and the uterus are conserved. Alternatively, a radical trachelectomy is called a partial or total removal of the cervix and the connective tissues following the uterus and cervix.
• Proactive fertility preservation can ensure better decisions about the reproductive future before undergoing potentially harmful gonadotoxic treatments.

What Are the Procedures for Men to Preserve Fertility Before Cancer Treatment?

The following methods can be used for men desiring to preserve their fertility before undergoing cancer treatment.

• Sperm Cryopreservation: The best and safest procedure involves freezing and storing sperm at a sperm bank or fertility clinic for later use. Advances in cryopreservation allow long-term storage without deterioration in sperm quality, enabling men to father children even years after undergoing gonadotoxic therapies.
• Radiation Shielding: Small lead shields are used to position over the testicles to diminish the amount of radiation exposure received.

What Can Parents Do to Preserve the Fertility of a Cancer Child?

Issues of fertility should be discussed with children who are treated for cancer when they are of the appropriate age to understand. For children facing gonadotoxic treatments, fertility preservation discussions should involve both the child and the parents as soon as the child is old enough to understand. The parent's and the child's consent might be required before a procedure can be accomplished. If the child has begun puberty, options include oocyte or sperm cryopreservation. Females who have cancer treatment before puberty have an option for ovarian tissue cryopreservation. In this procedure, ovarian tissue is surgically extracted, frozen, and later thawed and reimplanted after tumor radiation. Whereas for preserving fertility in boys undergoing cancer treatment before puberty, testicular tissue is surgically removed and frozen.

Does Fertility Preservation Interfere With Successful Cancer Therapy or Increase the Recurrence Risk?

No evidence suggests that current fertility preservation methods can directly affect the success of cancer treatments. There is no strong evidence suggesting that fertility preservation interferes with the success of cancer therapies. Regardless, one may compromise the treatment success if one delays surgery or chemotherapy to seek fertility preservation. There seems to be no advanced chance of cancer recurrence associated with most fertility conservation methods. Regardless, there is a possibility that during the reimplantation of frozen tissue, tumor cells could be reintroduced depending on the type and stage of cancer. Hormone-sensitive cancers should be handled with caution to avoid the risk of propagating cancer cells when fertility preservation techniques such as tissue reimplantation are considered. Therefore, in such cases, expert advice should be sought to produce optimal results.

Conclusion:

Prevention is better than cure or treatment. However, diagnosing and treating the disease or disorder as soon as possible is always equally important. Malignant tumor treatments mostly involve chemotherapy and radiation that can induce adverse effects. From pre-treatment consultation and advanced technologies like cryopreservation and protective shielding, among others, patients can guarantee a reproductive future without sacrificing much of the consequences in treating their cancers. Radiation can cause deterministic (which causes damage related to superficial areas like mucositis, where inflammation of the oral mucous membrane) and stochastic effects (which cause deoxyribonucleic acid (DNA) alteration, which can induce the mutation or secondary radiation-induced cancer, mainly leukemias) on the body. Gonads are the radiosensitive organs or systems of the body that require protection and preservation. However, any delay in cancer treatment due to gonadotoxicity can be fatal for an individual. Thus, early intervention, careful planning, and personalized approaches are key to maximizing fertility preservation success. It is better to contact the experts for a better method with a great outcome.