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October 2017 VOL 8, NO 10

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Fertility Preservation

Reproductive Considerations in Younger Cancer Survivors

In younger women who are cancer survivors, pregnancy planning and fertility preservation are important options. Speakers at the recent 2017 Annual Meeting of the Multinational Association of Supportive Care in Cancer addressed these issues from a supportive care perspective.

Cancer is relatively rare in childhood and young adults and affects about 20 of every 100,000 women. The 5-year survival rate is 80%. This age group develops a wide range of cancers that vary by age. The goal of cancer therapy in younger people is curative, but treatment can affect long-term reproductive health, including pubertal development, hormonal production and regulation, fertility, and sexual function.

Pregnancy Planning in Adolescents and Young Adults

“Addressing pregnancy planning needs for adolescents and young adults entails tailoring based on cancer diagnosis and treatment regimen. Early pregnancy planning improves outcomes for mothers and babies,” said Aletha Y. Akers, MD, MPH, Children’s Hospital of Philadelphia, PA.

Factors that affect reproductive health include age at diagnosis, primary cancer diagnosis and site, and cancer treatment (dosing, duration, and intensity).

Pregnancy planning is an important element of care for all women, including cancer survivors. Preconception care and counseling have many benefits, including reducing the risk of low birth weight and other adverse outcomes. Preconception care is recommended at least once prior to conception for all women planning to conceive. This advice is relevant for all women, not just cancer survivors, Dr Akers said.

Preconception planning encompasses optimizing current medical conditions; discussions about medication management; addressing behavioral issues that include diet, nutrition, weight, exercise, and substance use (tobacco, alcohol, and drug use). Discussions should include advice on environmental risks and psychosocial factors that can affect pregnancy and having a child (family support, financial stability, unemployment, and work-related hazards).

Survivors of childhood cancers have a 20% reduction in fertility. For young cancer survivors, the recommendation is to complete childbearing before the age of 30 years to reduce the risk of poor pregnancy outcomes that may result from damage to ovaries from chemotherapy or radiation.

Contraception

Hormonal contraceptives are used not only for prevention of pregnancy, but also for management of the menstrual cycle and chronic disease. Hormonal contraception can improve several gynecologic conditions, including menstrual disorders, endometriosis, ovarian cysts, and a variety of benign breast diseases. Hormonal contraception improves dermatologic conditions, including seborrhea, acne, hirsutism, and alopecia, and reduces asthma symptoms as well.

“To select the right patient for hormonal contraception, we need to know the patient’s menstrual history and sexual history,” Dr Akers explained. “The proportion of adolescents who have had sex increases rapidly with age. There is no difference between young women undergoing cancer treatment compared with matched age controls, with a few exceptions.”

The mean age of initiation of sexual intercourse is 17 years. The rate of unintended pregnancies is highest in younger women, with almost 90% occurring between the ages of 15 and 17 years. These younger women need contraception, she said.

Contraceptive choices are well known to healthcare providers and include barrier methods (diaphragm, condoms), intrauterine devices (IUDs), birth control pills, and longer-acting injectable contraception.

“The data are limited on IUD use in women who have undergone immunosuppression during cancer. The WHO [World Health Organization] and CDC [Centers for Disease Control and Prevention] say IUDs are safe in young women with other immunocompromised states, and family planning experts endorse their use,” Dr Akers noted.

Oncofertility

The pros and cons of options available for fertility preservation among young female cancer patients were described by Mindy Christianson, MD, Director of Fertility Preservation at Johns Hopkins University School of Medicine, Baltimore, MD.

Fertility preservation entails saving or protecting eggs, sperm, and other reproductive tissue to have biological children. Dr Christianson confined her remarks to females, who have a set number of eggs.

“Early referral for fertility preservation is key for females facing gonadotoxic treatment, either chemotherapy or radiation therapy,” she said.

Chemotherapy can have devastating effects on the follicles and the ovary and reduce the supply of eggs. The effects of chemotherapy depend on the patient’s age, drug, and dose. Cyclophosphamide and alkylating agents are the most potent inducers of ovarian failure.

“Radiation is even more damaging to ovarian tissue than chemotherapy. The damage is dose- and age-dependent,” she said.

Options for Fertility Preservation

Embryo cryopreservation is widely established and safe. Patients undergo controlled ovarian hyperstimulation, oocyte retrieval, fertilization, and then cryopreservation. Embryos are thawed and transferred to the patient. This procedure has a better than 40% success rate for pregnancy, depending on the patient’s age and the time when eggs were harvested; it requires 2 to 4 weeks.

Candidates for embryo cryopreservation include females with a partner or who are willing to use donor sperm. However, it is not suitable for children or minors.

Freezing eggs (oocyte cryopreservation) is more technically challenging than embryo cryopreservation, she said. Although it was considered experimental in the past, it is now an established technique for fertility preservation. This technique also requires ovarian hyperstimulation and egg retrieval. Candidates include postmenarcheal patients and those for whom cancer treatment can be delayed for 2 to 4 weeks. This is not a suitable technique for prepubertal females or when a treatment delay is not advisable.

“More than 1000 babies have been born from frozen eggs, but there is no central registry. One study looked at 936 babies born from frozen eggs and found no increased risk of congenital anomalies,” Dr Christianson told listeners.

Ovarian tissue cryopreservation, another potential option, enables storage of significant numbers of primordial follicles and is currently done at about 100 centers worldwide, with approximately 80 live births to date. This procedure is considered experimental, but it is the only option available for fertility preservation for prepubertal girls or patients who cannot delay treatment.

“This is a young technology that will be developed for the future,” she noted.

Letrozole for Hyperstimulation

Breast cancers are in a special category, because there is a window of opportunity for fertility preservation 2 to 4 weeks after surgery.

“There is concern that ovarian hyperstimulation is risky for breast cancer patients (both hormone-positive and hormone-negative) because of the need for high estrogen levels. Because of these concerns, we and others have been using letrozole off-label for ovarian stimulation. One study found no increased risk of recurrence with this protocol at 4 years compared with patients who declined assistive reproduction technology,” Dr Christianson said.

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