Evidence
Girls who undergo therapy for urogenital RMS are at significant risk for future infertility and ovarian insufficiency resulting in premature menopause. Identification of, and subsequent interventions to prevent the complications of premature menopause (osteoporosis, cardiovascular disorders, and impaired psycho-social well-being) are important.27
In a large study of survivors of childhood cancer, 38% of survivors reported having or desiring a pregnancy compared to 62% of siblings.28 Patients and families are interested in being informed about their risk of infertility and discussing fertility preservation options, even when the risk of infertility is relatively modest.29 Higher doses of alkylating agents, which form the backbone of chemotherapy regimens for RMS, have been consistently associated with reduced germ cell function and fertility rates.30 Furthermore, other components of the multimodal therapy for FGU-RMS can likewise negatively impact future fertility, including pelvic radiation with EBRT or BT, as well as surgical resection of genitourinary organs. In females, a CED of 4-8 g/m2was associated with greater than a 2.5x relative risk of premature menopause, and a CED >8 g/m2 with a greater than 4x relative risk.31 However in a long-term study of over 10,000 survivors of childhood cancer, only CED doses in the highest quartile (>9,639 mg/m2) versus no exposure was associated with reduced pregnancy rates.28 Therefore, while the doses of alkylating agents given to most children with urogenital RMS impart some risk of future infertility and ovarian insufficiency, further efforts are required to delineate this risk and inform decisions about when to offer fertility preservation procedures.
Oocyte harvest is a non-experimental option available for post-pubertal girls. Random start ovarian stimulation protocols, which no longer require timing with the menstrual cycle, can be performed with minimal delay in treatment initiation.29 Laparoscopic OTC is an investigational option for both pre- and post-pubertal girls. Total or partial oophorectomy allows for preservation of ovarian cortical strips for future reimplantation with potential restoration of fertility and hormone function.32
While the potential benefit of OTC for girls with RMS of the genitourinary tract is generally driven by the dose of alkylating agent chemotherapy, consideration must also be given to the fertility impact from radiation. The radiation dose to the ovary has a significant effect on future fertility, with one study showing a decrement in the relative chance of pregnancy of 0.18 with doses >10 Gy.30 The RT doses for RMS, generally ranging from 27-60 Gy regardless of modality, exceed the doses accepted to cause sterilization; 20.3 Gy in infants, 18.4 Gy at age 10 years, and 16.5 Gy at age 20 years.33 Depending on their location relative to the tumor and position in the radiation field, the anticipated RT dose to the ovaries should be calculated to assess this risk. Ovarian transposition has an important role for girls receiving pelvic radiation with EBRT or BT. Patients undergoing EBRT require transposition of the ovary to the paracolic gutters with the division of the ligamentous attachments.34 In some cases, relocation back to the pelvis after therapy completion is required. Temporary transposition for the 3-10 days of treatment for girls receiving brachytherapy can be achieved without division of the ligamentous attachments.6 However, in patients who received pelvic RT for Hodgkin’s lymphoma, ovarian transposition did not seem to modify the risk of ovarian insufficiency and further studies are required to assess the long-term benefit of transposition.35