Many female patients present with malignant and non-malignant conditions whose treatment causes infertility. Women who are diagnosed with neoplastic diseases before or during their reproductive years and undergo ootoxic therapies, those who undergo an oophorectomy due to non-malignant disorders, those of reproductive age at risk for premature menopause associated with genetic disorders, and those who have undergone conditioning regimens for bone marrow transplantation may experience partial or total loss of their fertility. Fortunately, in recent decades, medical science has witnessed dramatic improvements in chemo- and radiotherapy for neoplastic diseases together with noteworthy advances in fertility preservation techniques. Such advances have allowed more and more women who survive malignant and non-malignant illnesses to focus on improving their post-treatment quality of life, including the restoration of their fertility and the possibility of childbearing. Ovarian tissue cryopreservation and transplantation, though still experimental, hold out real promise for these women.
Here, I will conduct a teleological analysis of selected ethical issues from three clinical cases of women who experienced the reactivation of ovarian function and a live birth as a result of ovarian tissue transplantation (OTT). In case #1, a woman who experienced ovarian failure after cancer therapy for non-Hodgkins lymphoma subsequently conceived by means of IVF following a frozen-thawed ovarian autograft. In case #2, an infertile monozygotic twin conceived spontaneously as a result of a fresh ovarian graft from her fertile identical twin, and, in case #3, a woman who experienced ovarian failure after cancer therapy for stage IV Hodgkins lymphoma conceived spontaneously through autotransplantation of frozen-thawed ovarian tissue. Lastly, I will assess the ethics of case #4 in which a healthy woman has stored her ovarian tissue to prolong her reproductive life.
Part One-Ovarian Tissue Transplantation: What's Involved?
A. Collection and Cryopreservation of the Ovarian Tissue
Because of the ootoxic nature of chemo- and radiation therapies, the goal is to harvest ovarian tissue before the woman undergoes these therapeutic regimens. Theoretically, there are three ways of cryopreserving ovarian tissue: as fragments of ovarian cortex, 16 as a whole ovary with or without its vascular pedicle, or as isolated follicles. 17 In current practice, however, OT cryopreservation (and transplantation) is almost exclusively limited to avascular fragments of the ovarian cortex. 18 Most primordial follicles are contained in the outer layer of the ovarian cortex and, fortunately, are less susceptible to cryoinjury than more mature occytes. In the collection process via laparoscopy or laparotomy, then, surgeons remove the millimeter-thick outer shell of the ovary, cut the cortex into strips around 1-3 mm in thickness and up to 1 cm2 in total area, and allow the cryoprotectants to thoroughly penetrate the tissue. Each of these strips potentially contains thousands of primordial follicles capable of developing into mature oocytes or egg cells when thawed and transplanted.19 A slow-cooling technique was originally used to freeze the excised ovarian tissue. More recently, however, vitrification-a fastcooling method of cryopreservation-has proven effective in reducing cryoinjury due to formation of ice crystals.20
Before being frozen, however, each cortical strip must be examined both for the presence of primordial follicles and the absence of malignant cells. One of the primary risk factors of cryopreserving ovarian tissue from cancer survivors and, a fort/on, a critical ethical issue for those researchers who are experts in OTT and responsible for its ongoing refinement, is that of re-implanting malignant cells through the graft. For this reason, then, research clinicians insist that, prior to any cryopreservation of ovarian tissue, strict IRB oversight of OTT21 must require thorough examination of ovarian graft tissue to verify the absence of neoplastic cells. …