Oocyte cryopreservation: Recent progress, future expectations

Key Points

Oocytes are probably the most complex of human cells and their numbers are genetically determined. Oocyte numbers are believed to peak around 24 weeks of intrauterine life and progressively decrease to between 500,000 and 1 million at birth,^1,2 although there is no universal agreement about that. Throughout a woman's reproductive life, her oocytes are progressively depleted and their quality simultaneously begins to deteriorate. Oocyte cryopreservation may be one of the most innovative methods for safeguarding against age-related degenerative changes and extending fertility opportunities.

Oocyte cryopreservation can theoretically suspend the biologic clock. Most studies aimed at perfecting the technology have been carried out in Italy in response to laws enacted in 2004 banning embryo freezing.³ Since then, many Italian in vitro fertilization (IVF) centers have learned how to perform oocyte cryopreservation, improved on the process, and now offer the technique.

A very large body of knowledge about oocyte freezing was amassed in the 5-year period between passage of the law and May 2009, when most of the restrictions were removed by the Italian Constitutional Court.⁴

Risk of premature ovarian failure. This condition can result from ovarian diseases such as cysts, benign tumors, and recurrent or large endometriomas that require ovary removal, and when chemotherapy or radiation therapy is used to treat cancer or other systemic diseases. Patients diagnosed with Turner syndrome (mosaic) are also candidates for oocyte freezing because their reproductive life span is often reduced. With improvements in cancer treatment protocols, more patients are experiencing long-term survival.

Chemotherapy and total-body irradiation in preparation for bone marrow transplantation are associated with significant gonadal toxicity. The most common cancers in women of reproductive age are lymphomas (both Hodgkin and non-Hodgkin), leukemias, and breast cancer. Because the level of gonadotoxic risk of chemotherapy cannot be assessed with certainty, fertility preservation options-including oocyte cryopreservation-should always be considered in this setting.

Breast cancer is the most frequently diagnosed malignancy in women, with 25% of cases occurring before menopause and 7% diagnosed in women younger than age 40. More than 90% of all breast cancers are local or regional at diagnosis, and the 5-year survival rate is 98% for women with local disease and 84% for those with regional disease.⁵

Because breast tumors are hormone sensitive in about 60% of patients, conventional gonadotrophin-stimulated IVF treatment has been modified to mitigate the increase in estradiol levels associated with chemotherapy protocols involving aromatase inhibitors.^5,6 Short-term follow-up on use of these modified regimens in a small cohort of patients with both estrogen receptor-positive and -negative tumors found comparable disease-free and survival rates compared with women who were not undergoing fertility preservation procedures.⁶

Methods for maintaining fertility are important to the lives of reproductive-aged women who are battling malignancy, and they are an integral component of improving post-treatment quality of life. For a long time, embryo cryopreservation was the only option offered to cancer survivors but was underused because it requires sperm. Creation and storage of embryos are associated with a number of ethical, religious, and social issues, particularly in the face of malignancy. For women who are unmarried or not in stable relationships, oocyte cryopreservation is the best alternative to preserve future fertility.

In the setting of conditions that predispose to ovarian failure, including autoimmune disease, severe endometriosis, and genetic or familial conditions such as Fragile X, chromosomal imbalances, and structural defects such as translocations or deletions, oocyte preservation should be considered part of a multidisciplinary approach. In women at risk of premature ovarian failure, however, data are limited regarding its success.