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)