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