Oocyte and ovarian tissue cryopreservation is a technique that is being researched as an alternative to embryo cryopreservation for women with a malignancy who would become infertile due to chemotherapy, radiation therapy or surgery. 

Investigational and Not Medically Necessary:

Cryopreservation of ovarian tissue or oocytes is considered investigational and not medically necessary as treatment for anticipated infertility.

Cryopreservation of Ovarian Tissue
Cryopreservation of ovarian tissue with subsequent auto- or heterotopic transplant has been researched as a technique to sustain the reproductive function of females who are faced with sterilizing procedures, such as chemotherapy, radiation therapy or surgery that are frequently due to malignant diseases. A variety of articles have focused on the technical feasibility of such an option, and there are a few individual case reports of successful pregnancies using this technique. However, in general, the technique is not standardized, has been investigated more thoroughly in animal models and has not been widely applied to humans. Kim (2001) identifies the following unresolved issues:

• Optimization and standardization of a freeze-thaw method;
• Metabolic injury;
• Ischemia-reperfusion injury (i.e., after autotransplant);
• The optimal graft site;
• The quality of oocytes matured in a graft;
• The efficacy of frozen-thaw grafts for fertility restoration and hormonal function;
• Safety issues, particularly regarding the risk of reseeding residual cancer cells within a graft.

Cryopreservation of Oocytes
Unlike cryopreservation of ovarian tissue, cryopreservation of oocytes is less commonly performed in the setting of malignancy due to the time constraints inherent in ovarian stimulation. The mature oocyte is very fragile due to its large size, high water content and chromosomal arrangement. For example, the mature oocyte is arrested in meiosis, and as such the chromosomes are lined up in a meiotic spindle. This spindle apparatus is easily damaged both in freezing and thawing. Due to these factors, there is a poor survival of cryopreserved oocytes after thawing. Survival after thawing may also be associated with sublethal damage, which may further impact on the quality of the subsequent embryo. While several individual cases of successful pregnancies have been reported, the technique for cryopreservation and thawing of oocytes has not been standardized. 

In 2004, the Practic Committees for both American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) addressed cryopreservation of ovarian tissue and oocytes in the following practice guideline:

Given the uncertain and unestablished state of this procedure, it is essential that cryopreservation of ovarian tissue be offered only as part of an IRB-approved protocol with full disclosure of risks and uncertainty of benefits to the patient. Later efforts to thaw and transplant the removed ovarian tissue should also be subject to IRB review until the safety and efficacy of transplantation or other use of the tissue have been established.

…we believe that the success rate is still too low to justify routine offering of oocyte cryopreservation as an established procedure to female cancer patients. Programs may, however, offer it experimentally as part of an IRB-approved protocol with full disclosure of risks and uncertainty of benefits to the participant. Marketing of oocyte cryopreservation is not yet justified due to the investigational status of egg freezing and uncertainty about its safety and efficacy.

Note: IRB is an abbreviation for Institutional Review Board.

In 2008, the ASRM and SART further stated:

Although currently investigational, ovarian tissue cryopreservation and oocyte cryopreservation hold promise for future female fertility preservation, particularly following aggressive chemotherapy and/or radiotherapy treatment protocols.

The American Society of Clinical Oncologists (ASCO, 2006), addressing fertility preservation for those with cancer state: 

Sperm and embryo cryopreservation are considered standard practice and are widely available; other available fertility preservation methods should be considered investigational and be performed in centers with the necessary expertise.

There are recruiting and ongoing clinical trials studying oocyte cryopreservation. However, to date, results from these studies have not been published.

While cryopreservation of sperm and embryos are established techniques in the treatment of infertility, cryopreservation of oocytes, ovarian tissue segments or the entire ovary has been more problematic. Due to the high water content and fragility of their chromosomal arrangement, mature oocytes encounter problems with the freezing and thawing components of cryopreservation. These problems may impact the subsequent embryos. Ovarian tissue cryopreservation is a technique that addresses the fertility potential for those with prepubertal cancer or adults with cancer who do not have the luxury of the time required to undergo ovarian stimulation as part of an in vitro fertilization procedure followed by embryo cryopreservation. The cryopreserved ovarian tissue can either be autografted back into the host at a later date, or primordial follicles can be extracted from the ovarian tissue and then allowed to mature in vitro. In contrast to the limited number of mature oocytes that can be harvested after ovarian stimulation, ovarian tissue typically contains an abundant number of primordial follicles.

Oocyte and ovarian tissue cryopreservation may become an option for females when their fertility has been compromised due to cancer treatment. Oocyte and ovarian tissue cryopreservation may allow her to bear genetic offspring by banking oocytes or ovarian tissue, should she survive, but be infertile. At present, cryopreservation of oocytes or ovarian tissue is being studied in clinical trials, as the safety and possibilities for fertility preservation in humans are not yet proven. Techniques for cryopreservation, such as vitrification, are being investigated and may reduce cellular damage during the freeze-thaw procedure. Potential ethical issues need to be addressed by the medical community.

Cryopreservation: The process of preserving and storing living systems in a viable condition at low temperatures for future use.

Institutional review board (IRB): An institutional review board is a group that has been formally designated to approve, monitor and review biomedical and behavioral research involving humans with the aim to protect the rights and welfare of the subjects. The Food and Drug Administration and the Office of Protection from Research Risks (part of the National Institutes of Health) set the guidelines and regulations governing human subject research and IRBs.

Oocyte: The egg cell produced in the ovaries; also called the ovum or gamete.

Ovarian: Having to do with the ovaries, the female reproductive glands in which the ova (eggs) are formed. The ovaries are located in the pelvis, one on each side of the uterus.

Vitrification: Ultra-rapid freezing process resulting in a glass-like solid that is free of any crystal formation.

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. 

When services are Investigational and Not Medically Necessary:

Peer Reviewed Publications:

1. Agarwal A, Said TM. Implications of systemic malignancies on human fertility. Reprod Biomed Online. 2004; 9(6):673-679.
2. Bagchi A, Woods EJ, Critser JK. Cryopreservation and vitrification: recent advances in fertility preservation technologies. Expert Rev Med Devices. 2008; 5(3):359-370.
3. Barritt J, Luna M, Duke M, et al. Report of four donor-recipient oocyte cryopreservation cycles resulting in high pregnancy and implantation rates. Fertil Steril. 2007; 87(1):189.e13-17. 
4. Beerendonk CC, Braat DD. Present and future options for the preservation of fertility in female adolescents with cancer. Endocr Dev. 2005; 8:166-175.
5. Demeestere I, Simon P, Emiliani S, et al. Options to preserve fertility before oncological treatment: cryopreservation of ovarian tissue and its clinical application. Acta Clin Belg. 2006; 61(5):259-263.
6. Feigin E, Abir R, Fisch B, et al. Laparoscopic ovarian tissue preservation in young patients at risk for ovarian failure as a result of chemotherapy/irradiation for primary malignancy. J. Pediatr. Surg. 2007; 42(5):862-864.
7. Goswami D, Conway GS. Premature ovarian failure. Horm Res. 2007; 68(4): 196-202.
8. Isachenko1 E, Rahimi1 G, Isachenko V, Nawroth F. In-vitro maturation of germinal-vesicle oocytes and cryopreservation in metaphase I/II: a possible additional option to preserve fertility during ovarian tissue cryopreservation. Reprod Biomed Online. 2004; 8(5):553–557.
9. Kim SS, Battaglia DE, Soules MR. The future of human ovarian cryopreservation and transplantation: fertility and beyond. Fertil Steril. 2001; 75(6):1049-1056.
10. Manipalviratn S, Decherney A. Clinical application of human oocyte cryopreservation. Rev Recent Clin Trials. 2008; 3(2):104-110.
11. Oktay K, Cil AP, Bang H. Efficiency of oocyte cryopreservation: a meta-analysis. Fertil Steril. 2006; 86(1):70-80.
12. Roberts JE, Oktay K. Fertility preservation: a comprehensive approach to the young woman with cancer. J Natl Cancer Inst Monogr. 2005; (34):57-59.
13. Varghese AC, du Plessis SS, Falcone T, Agarwal A. Cryopreservation/transplantation of ovarian tissue and in vitro maturation of follicles and oocytes: challenges for fertility preservation. Reprod Biol Endocrinol. 2008; 6:47. 

Government Agency, Medical Society, and Other Authoritative Publications:

1. American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART). Ovarian tissue and oocyte cyropreservation. 2008. Available at: http://www.asrm.org/uploadedFiles/ASRM_Content/News_and_Publications/Practice_Guidelines/Committee_Opinions/Ovarian_tissue_and_oocyte(1).pdf. Accessed on May 26, 2011.
2. American Society of Clinical Oncologists. Recommendations on Fertility Preservation in Cancer Patients. Available at: http://jco.ascopubs.org/content/24/18/2917.full.pdf+html. Accessed on June 20, 2011.
3. Centers for Disease Control and Prevention (CDC). Assisted Reproductive Technology. 2009. Available at: http://www.cdc.gov/art/index.htm. Accessed on May 26, 2011.

1. American Society for Reproductive Medicine. Available at: http://www.asrm.org/detail.aspx?id=75. Accessed May 26, 2011.

Cryopreservation of Oocytes or Ovarian Tissue