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Fertility Preservation
Ovarian Tissue Transplantation as an Option for Fertility Preservation
J Ryan Martin
1
and Pasquale Patrizio
2
1. Fellow, Reproductive Endocrinology and Infertility;
2. Professor of Obstetrics and Gynecology, and Director, Yale Fertility Centre, Yale University School of Medicine
Abstract
Over the last two decades, cancer treatment modalities have significantly improved to the point at which many patients are cancer
survivors. Currently, there are several options for fertility preservation in young females with cancer, including cryopreservation of oocytes
or embryos and cryopreservation of ovarian tissue (either as a cortical strip or, as recently reported, as whole ovaries). As the ovarian
cortex has abundant quantities of primordial and primary follicles, cryopreservation of the ovarian cortex has been a successful strategy
for fertility preservation. The transplantation of whole ovaries has been successfully accomplished in animal models, but is still considered
experimental in humans. Research and continued development in cryoprotectants and surgical techniques will allow for enhancement of
vascularisation of transplanted tissues to minimise post-transfusion ischaemia, which is critical for the viability of ovarian tissue and
therefore improved reproductive success.
Keywords
Fertility preservation, ovarian cryopreservation, cortical strips, paediatric oncology, ovarian tissue transplantation
Disclosure: The authors have no conflicts of interest to declare.
Received: 21 November 2008 Accepted: 31 March 2009
Correspondence: Pasquale Patrizio, Yale Fertility Center, Yale University School of Medicine, 150 Sargent Drive, New Haven, CT 06511, US. E: Pasquale.Patrizio@Yale.edu
Over the last two decades, cancer treatment modalities have also requires a few weeks to stimulate the ovaries. In addition,
significantly improved to the point at which many patients are there are other options to preserve fertility such as the combination
cancer survivors. As quality of life after cancer is an important of ovarian transposition out of the radiation field with ovarian
paradigm, the possibility of preserving fertility is of paramount cryopreservation as a potential treatment to optimise fertility
concern to these patients. According to data from the Surveillance, preservation
11
and the harvesting of immature oocytes from cortical
Epidemiology, and End Results (SEER) programme of the National strips and allowing maturation in vitro. In this article, we will discuss
Cancer Institute (NCI), the five-year survival rates for all childhood the option of preserving fertility by banking ovarian tissue.
cancers combined increased significantly from 58.1% between
1975 and 1977 to 79.6% between 1996 and 2003.
1
These Cryopreservation of Ovarian Tissue
improvements are likely due to cumulative improvements in Ovarian tissue cryopreservation and transplantation is not a new
surgical techniques, early diagnosis techniques, chemotherapy, idea; in fact, it was initially investigated in animals in the 1950s, but
radiotherapy and supportive care. Although radiation therapy has been studied in humans only over the last 10 years.
12,13
Early
and chemotherapeutic agents are effective treatments, they are studies demonstrated viable follicles following freeze–thaw cycles
known to be gonadotoxic and can cause premature ovarian failure from both whole ovaries and ovarian tissue.
14–16
The two main
and infertility.
2,3
It is well established that radiotherapy and approaches to ovarian tissue cryopreservation are cortical strip and
chemotherapeutic agents, especially alkylating agents, have been whole-ovary cryopreservation.
shown to increase the risk of ovarian failure.
4–10
The cortex of the ovary contains primordial follicles with oocytes
Currently, there are several options for fertility preservation in that are arrested in prophase of meiosis 1 and are metabolically
young females with cancer, including cryopreservation of oocytes quiescent and undifferentiated.
17,18
It has been suggested that the
or embryos and cryopreservation of ovarian tissue (either as a low content of water, the relatively high surface-to-volume ratio
cortical strip or, as recently reported, as whole ovaries). The gold and low metabolic rate and the absence of the zona pellucida make
standard proven method for banking reproductive success is to primordial follicles less susceptible to cryodamage.
4
As the ovarian
freeze embryos; however, most cancers require immediate cortex has abundant quantities of primordial and primary follicles,
chemotherapeutic or radiation treatment. As standard stimulation cryopreservation of the ovarian cortex has been a successful
of the ovaries takes at least two weeks, embryo (or oocyte) freezing strategy for fertility preservation.
19,20
The cortex is then surgically
is generally not a viable option for most oncological patients. The removed via laparoscopy or laparotomy and cut into thin 1–3mm
technique of oocyte cryopreservation has greatly improved over strips that allow for the proper penetration of cryoprotectants.
21
the last few years and is another option for select patients, but this Once the tissue is cryopreserved, patients can opt for re-
40 © TOUCH BRIEFINGS 2009
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