Reproductive Function and Outcomes in Female Survivors of Childhood, Adolescent, and Young Adult Cancer: A Review

Abstract

Some survivors of childhood, adolescent, and young adult cancer are at increased risk of gonadal dysfunction and adverse pregnancy outcomes. We reviewed currently available literature that evaluated reproductive function and pregnancy outcomes of female cancer survivors diagnosed before the age of 25 years. High-dose alkylating agent chemotherapy and abdominal/pelvic radiotherapy adversely affect gonadal function in a dose-related fashion, with older age at exposure conferring greater risk as a result of the age-related decline in ovarian reserve. Gonadal injury clinically manifests as ovarian hormone insufficiency (delayed or arrested puberty, premature ovarian insufficiency, or premature menopause) and infertility. The effect of molecular-targeted agents on ovarian function has not been established. For female cancer survivors who maintain fertility, overall pregnancy (relative risk, 0.67 to 0.81) and live birth rates (hazard ratio, 0.79 to 0.82) are lower than those in the general public. Pregnancy in cancer survivors also may be associated with risks to both the mother and the fetus related to miscarriage; preterm birth; and, rarely, cardiomyopathy. Women at risk for these complications require preconception assessment and counseling from both obstetricians and oncology providers. The risk for inherited genetic disease in offspring conceived after cancer treatment exposure is not increased. The optimization of reproductive outcomes and minimization of risks of pregnancy complications in survivors requires informed, risk-based assessment and monitoring.

Hypogonadism in Children with a Previous History of Cancer: Endocrine Management and Follow-Up

“…In this cohort, adolescent men with cancer had lower HR for a first live birth than men surviving childhood cancer (HR 0.56 vs. 0.70). For women surviving childhood cancer, the opposite was found, with a lower HR than when compared to women diagnosed with cancer in adolescence (HR 0.47 vs. 0.89) [6, 62]. This study clearly showed that there are large differences in HR for first live birth between groups of cancer survivors with different diagnoses.…”

“…Also more preterm births have been reported in female CCS, which may be due to the condition of the uterus after radiation exposure or lack of sex steroids [6]. …”

“…However, the value of AMH in predicting early menopause in CCS remains uncertain [19] and a very low AMH does not exclude spontaneous pregnancy in young CCS up to 25 years of age. For these reasons, AMH has currently not been recommended as a screening tool for POI [6]. Of note, AMH levels seem to be influenced not only by treatment but also by the general disease state [20].…”

“…Premature ovarian insufficiency (POI) is a clinical condition that develops under the age of 40 years and is characterized by the absence of menstrual cycles for ≥4 months and 2 sequential elevated FSH levels in the postmenopausal range [6]. In males, primary gonadal failure is defined as decreased androgen concentrations in combination with elevated LH and FSH levels or failure to develop signs of puberty by age 14 or no change in pubertal stage for at least 6 months at the age at which progression would be expected in combination with elevated levels of LH and FSH [7].…”

The development of ovarian tissue cryopreservation in Edinburgh: Translation from a rodent model through validation in a large mammal and then into clinical practice

“…These advances follow on from developments in pediatric, adolescent and young adult oncology, which now achieves very high rates of survival; as a result, in those fields there has been the development of a focus on the late effects of cancer and its treatment. 3 Although fertility preservation is most commonly used for individuals with an oncological diagnosis, it is of course appropriate for those facing other fertility compromising therapies, such as rheumatological conditions treated by cytotoxic agents. It is also being explored in some other causes of premature ovarian failure including Turner syndrome, and there is a rapidly growing interest in fertility preservation for transgender individuals.…”