Grafting Cryopreserved Ovarian Tissue
Some survivors presenting with POI who previously cryopreserved ovarian
tissue may consider ovarian tissue grafting. There is extreme hesitance
to graft tissue in patients who were treated for leukemia and some
lymphomas, due to concern for reintroducing cancer cells that may have
been harbored in the ovary. In patients for whom grafting is considered
safe, sites that can be used include the remaining contralateral ovary,
pelvic side wall, abdominal wall, and other peripheral locations with
adequate blood flow and accessibility for subsequent follicle aspiration
if required.(45) Restoration of fertility with ovarian tissue harvested
from post pubertal patients and grafting is no longer considered
experimental as there have been over 140 births reported.(46) There has
been one live birth from ovarian tissue harvested from a prepubertal
girl, and another birth from tissue harvested in a peripubertal girl
prior to menarche.(47) There are limited but reassuring data on follow
up studies of thawed and engrafted ovarian tissue, in regards to safety,
hormonal function, and restoration of fertility.(48–51) Ovarian
endocrine function usually resumes two to five months after surgery and
duration of function depends on many factors including the age of the
patient at the time of retrieval, tissue volume, and follicle
density.(52–54) Unfortunately, even with demonstrated restoration of
endocrine function, pregnancy may not ensue after grafting, either from
spontaneous conception or assisted by in vitro fertilization, and
procurement of good quality embryos can be difficult. Current data
suggest an approximately 25-30% chance of live birth where ovarian
tissue was cryopreserved in adulthood.(48,49)
For those patients in whom risk exists for malignant cell transmission
from grafting, various strategies including in vitro maturation,
use of an “artificial” ovary, and xenotransplantation are currently
being explored in multiple centers.(55,56) Testing of ovarian tissue
using appropriate histological, immunological and molecular modalities
is essential prior to transplantation, but does not provide total
reassurance.(57) International registries with robust follow-up are
needed to advance this field of fertility preservation safely and
effectively.
Pregnancy Risks in Female AYA Survivors
Pre-conception consultation with a Maternal-Fetal Medicine specialist is
recommended for female cancer survivors at risk of end-organ damage from
cancer treatment. Survivors who received anthracycline chemotherapy or
chest radiation are at increased risk for cardiomyopathy, thus closer
monitoring of cardiac function before and during pregnancy may be
warranted in higher risk patients.(58) Additionally, women who received
abdominal radiation, nephrectomy, hematopoietic cell transplantation,
ifosfamide, or platinum containing compounds are at risk for renal
insufficiency,(11) and pregnancy associated hypertension, eclampsia, or
pre-eclampsia may be exacerbated by pre-existing kidney disease.
Women who received radiation to the uterus also have increased pregnancy
risks,(59,60) as radiation induced injury may not allow the uterus to
accommodate the necessary growth that occurs during pregnancy. A large
study of offspring of women who received uterine radiation doses of more
than 5 Gy were more likely to be small for gestational age (birth weight
<10 percentile for gestational age; 18.2% v 7.8%).(60)
Survivors treated with abdominal radiotherapy may also be at higher risk
for preterm delivery, low birth weight, and peripartum
hemorrhage.(61,62) Typically uterine and ovarian doses of radiotherapy
are highly correlated,(10) and thus patients who received substantial
doses of radiation to the uterus would also be less likely to have
preserved ovarian function and natural fertility due to high ovarian
doses. However, in the present age of oocyte or ovarian tissue
cryopreservation, oophoropexy prior to radiotherapy, and oocyte/embryo
donation, there may be a greater likelihood of these women attempting
and achieving pregnancy. Donor uterine transplantation is also an active
area of research that may benefit these survivors in the future.(63)
Data on pregnancy risks, including hypertensive diseases of pregnancy,
gestational diabetes, maternal anemia, preterm birth, low birth weight,
and peripartum hemorrhage, in otherwise healthy AYA cancer survivors who
did not receive abdominopelvic radiation are limited, with mixed
results. Importantly, studies examining risks of congenital anomalies or
genetic abnormalities in the offspring of female AYA cancer survivors
have shown no increase risk compared to that of the general
population.(64)