COMMENTARY

Ovarian Tissue Cryopreservation: An Option for Patients Undergoing Cancer Therapy

Peter Kovacs, MD, PhD

Disclosures

September 04, 2014

Ovarian Tissue Cryopreservation: A Committee Opinion

The Practice Committee of the American Society for Reproductive Medicine
Fertil Steril. 2014;101:1237-1243

Background

Cancer is the second leading cause of death in the 0-19 and 20-39 years age groups and the leading cause of death in those 40-59 years of age.[1] According to a 2013 report, over 800,000 new cancer cases were expected that year in the United States, and about one third of them were expected to result in death.[1]

Treatment typically involves radical surgery, chemotherapy, and radiation therapy. Chemo- and radiation therapy are often associated with gonadotoxic effects, including severely reduced ovarian function or even gonadal failure.

Cancer therapy, however, has improved significantly; in certain cases, surgery has become less radical, and medical treatments with less toxic side-effect profiles have been developed. Because of more specific treatments, efficacy has improved and survival rates have increased.

The improved survival of children and young adults with cancer leaves many of these patients with the desire to start a family. Therefore, the fertility needs of these patients have to be addressed prior to initiating cancer treatment.

A committee of the American Society for Reproductive Medicine has reviewed the current status of ovarian tissue cryopreservation and its role in the management of patients with cancer.

The Study

The review emphasizes that ovarian tissue cryopreservation is still an experimental procedure. It can be considered for patients who require immediate gonadotoxic therapy, for those with hormone-sensitive malignancies whereby the use of stimulation is not an option, for elective cryopreservation in cases of autoimmune disease, for prepubertal girls, and for those with an increased risk for premature ovarian failure due to genetic causes.

Ovarian tissue (or whole ovary) can be obtained during laparoscopy or laparotomy. Slow-freezing and vitrification technology are available; both methods have been shown to be effective.

Cortical tissue can be transferred back to the original anatomic site (orthotopic autotransplantation, onto the medullary portion of the remaining ovary or into the ovarian fossa) or to a distant location (heterotopic autotransplantation; forearm, abdominal wall). Orthotopic autotransplantation has been shown to result in ovarian activity (hormone synthesis, follicular growth), and pregnancies have been reported. In the case of pregnancy, however, the activation of the native ovary cannot be ruled out, and therefore the origin of the oocyte (native ovary or transplanted tissue) cannot be confirmed. Activity of heterotopically transplanted ovarian tissue has also been reported, although pregnancy has not yet been achieved this way.

Ischemia and resulting follicular atresia have been seen with ovarian tissue transplantation. Concern over ischemia decreases when a fresh, whole ovary with a proper vascular pedicle is transplanted. Successful frozen-thawed whole-ovary transplantation has not yet been reported.

Another concern is the transmission of cancer cells via transplantation. Detection rate of cancer cells depends on the method used (lower with immunohistochemistry, higher with PCR). The risk is highest with bloodborne cancers and cancers that typically metastasize to the ovary, while risk is less likely with cancers that typically do not metastasize to the ovary.

The committee concluded that ovarian tissue cryopreservation is an experimental option that can be offered to carefully selected patients with the diagnosis of malignant disease.

Viewpoint

Certain types of cancers are typically diagnosed in women of reproductive age or even in childhood. Current cancer therapies often result in gonadal failure or severely reduced ovarian function. As a result of cancer treatment, those who survive are affected by the lack of hormone production and the inability to conceive. Hormone replacement can be used to manage hypoestrogenism.

There are several options to choose from to manage fertility needs. Embryo cryopreservation is an established method.[2,3] It can be offered to those with regular ovarian cycles who are either in a stable relationship or accept the use of donated sperm. Embryos can be created with eggs obtained in a natural cycle (when stimulation is contraindicated) or following stimulation. Because of the need for stimulation, this option requires time and may not be an alternative when immediate cancer treatment is needed. It cannot be offered to prepubertal girls, either.

Oocyte cryopreservation is an alternative to those not yet in a stable relationship.[4,5] Similar to embryo cryopreservation, it also can be carried out during a natural cycle or following stimulation. Immature oocytes can be collected without stimulation and cryopreserved. Immature eggs need to mature in vitro before being fertilized later on. Oocyte cryopreservation is now an accepted method of fertility cryopreservation.

The isolation of immature oocytes from ovarian tissue with subsequent maturation, cryopreservation, and fertilization is another potential alternative.

It is important that patients are counseled about the full impact of cancer therapy. Their fertility needs and the available options must be discussed and require a multidisciplinary approach.

Abstract

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