Clinical UM Guideline


Subject: Cryopreservation of Oocytes or Ovarian Tissue
Guideline #: CG-MED-66 Publish Date:    10/17/2018
Status: Reviewed Last Review Date:    09/13/2018


This document addresses oocyte and ovarian tissue cryopreservation which are alternative techniques to embryo cryopreservation for individuals who are at risk of infertility due to gonadotoxic therapies such as chemotherapy or radiation therapy. 

Clinical Indications

Medically Necessary:

Cryopreservation of mature oocytes is considered medically necessary in post-pubertal individuals facing anticipated infertility resulting from chemotherapy or radiation therapy.

Not Medically Necessary:

Cryopreservation of oocytes is considered not medically necessary when the criteria above are not met.

Cryopreservation of ovarian tissue is considered not medically necessary as treatment for anticipated infertility.


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.

Mature oocytes




Cryopreservation, mature oocyte(s)


Storage (per year); oocyte(s)


Thawing of cryopreserved; oocytes, each aliquot



ICD-10 Diagnosis



All diagnoses

Immature oocytes, ovarian tissue




Storage, (per year); reproductive tissue, testicular/ovarian [specified as ovarian tissue]


Thawing of cryopreserved; reproductive tissue, testicular/ovarian [specified as ovarian tissue]


Cryopreservation; reproductive tissue, ovarian


Cryopreservation; immature oocyte(s)



ICD-10 Diagnosis



Note: cryopreservation of immature oocytes or ovarian tissue is considered Not Medically Necessary for all indications


All diagnoses

Discussion/General Information

Therapies to treat medical conditions, such as cancer, may compromise fertility for females.  The American Society of Clinical Oncologists (ASCO®) article Fertility and Cancer Treatment (2013) lists chemotherapy agents that are linked to fertility issues, including: cisplatin, alkylators, such as cyclophosphamide, chlorambucil, busulfan, procarbazine, carmustine, iomustine, mechlorethamine and melphalan.  Radiation therapy may also have potential side effects that may affect fertility, including total body irradiation, radiation of the abdomen, pelvis, ovaries and uterus.  ASCO encourages providers to have an individualized “Discussion of fertility preservation with all females of reproductive age (and with parents or guardians of children and adolescents) if infertility is a potential risk of therapy.”  This discussion is recommended “As early as possible in the treatment process so as to allow for the widest array of options for fertility preservation” (Loren, 2013).

Options to preserve fertility for females who may become infertile as a result of planned gonadotoxic treatments include cryopreservation of oocyte and ovarian tissue.  However, there are many factors such as age, cancer type, timing and the type of treatment regimen, etc., to consider.

In 2013, the Practice Committees for both American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) updated the guideline for cryopreservation of mature oocytes.  The guideline concluded that over the past decade, “Oocyte cryopreservation has improved dramatically, and preliminary data for safety are reassuring.  Therefore, this technique should no longer be considered experimental.”  ASRM and SART noted individuals receiving gonadotoxic therapies for cancer are at high risk for infertility, therefore, the option of oocyte cryopreservation with appropriate counseling is recommended. 

The Practice Committee for ASRM (2013) published a committee opinion on fertility preservation for individuals undergoing gonadotoxic therapy or gonadectomy which includes embryo and oocyte cryopreservation as “established modalities for fertility preservation.”

The American College of Obstetricians and Gynecologists (ACOG) Committee on Gynecologic Practice published an opinion on oocyte cryopreservation in 2014.  The committee endorsed the ASRM and SART guideline for cryopreservation of mature oocytes.  The ACOG committee also noted there is “not yet sufficient data to recommend oocyte cryopreservation for the sole purpose of circumventing reproductive aging in healthy women.”

The National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines for Adolescent and Young Adult Oncology (2018) include oophoropexy for females receiving radiation therapy.  For individuals where treatment can be delayed long enough for a cycle of oocyte stimulation, then embryo cryopreservation or ovarian tissue cryopreservation should be discussed.

Cryopreservation of Oocytes

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 may be easily damaged both in freezing and thawing.  Due to these factors, survival of cryopreserved oocytes after thawing may be impacted.  Vitrification is an improved technique to freeze the oocytes and reduce the negative effects of cryopreservation. 

Cobo (2011) performed a systematic review and meta-analysis of five eligible randomized controlled trials that compared oocyte vitrification with slow-freezing and fresh oocytes.  The studies involved 4282 vitrified oocytes, 3524 fresh oocytes, and 361 slow-frozen oocytes between 2005 and 2009.  The vitrification process resulted in a higher oocyte survival rate compared to the slow-frozen oocytes (odds ratio [OR] 2.46; 95% confidence interval [CI], 1.82–3.32).  The rate of fertilization and a higher rate of top-quality embryo were also observed with the oocytes that were preserved by vitrification.  The rates of ongoing pregnancy, top-quality embryo, embryo cleavage, and fertilization did not differ between the vitrification and the fresh oocyte groups.  The authors concluded vitrification is an “Efficient method to preserve oocytes, although more large controlled clinical trials are needed to strengthen this conclusion.”

The ASCO guideline (Loren, 2013) addressing fertility preservation for those with cancer was updated after a systematic review of published literature from 2006 through January 2013.  The guideline was modified after a review of the evidence: 

Present both embryo and oocyte cryopreservation as established fertility preservation methods.

Discuss the option of ovarian transposition (oophoropexy) when pelvic radiation therapy is performed as cancer treatment.

Inform patients of conservative gynecologic surgery and radiation therapy options.

Cryopreservation of unfertilized oocytes: Cryopreservation of unfertilized oocytes is an option, particularly for patients who do not have a male partner, do not wish to use donor sperm, or have religious or ethical objections to embryo freezing.

Oocyte cryopreservation should be performed in centers with the necessary expertise.  As of October 2012, the American Society for Reproductive Medicine no longer deems this procedure experimental.  More flexible ovarian stimulation protocols for oocyte collection are now available.  Timing of this procedure no longer depends on the menstrual cycle in most cases, and stimulation can be initiated with less delay compared with old protocols.  Thus, oocyte harvesting for the purpose of oocyte or embryo cryopreservation is now possible on a cycle day–independent schedule.

Similarly, the ASCO guidelines on Fertility Preservation in Patients with Cancer (Oktay, 2018) state that:

Cryopreservation of unfertilized oocytes is an option and may be especially well suited to women who do not have a male partner, do not wish to use donor sperm, or have religious or ethical objections to embryo freezing. Oocyte cryopreservation should be performed in centers with the necessary expertise. As of October 2012, the American Society for Reproductive Medicine no longer deems this procedure experimental.

Cil and colleagues (2013) reported data from a meta-analysis of 1805 individual patient data (IPD) involving 2265 oocyte cryopreservation freeze-thaw cycles.  The goal of the study was to analyze slow-freezing (SF) and vitrification methods of oocyte cryopreservation and determine the probability of live birth as a function of age, cryopreservation method and number of oocytes thawed, injected or embryos transferred.  The participants’ mean age at oocyte freezing was 33.8 ± 4.0 (range, 20-48) years for SF and 34.1 ± 4.7 (range, 20-51) years for VF.  The overall oocyte survival and fertilization rates for VF (85% and 79%) were significantly higher (P<0.001) compared to SF (65% and 74%).  The authors concluded the VF process has improved success rates compared to SF.

In a meta-analysis, Zhou and colleagues (2013) compared the proportion of intact primordial follicles in ovarian tissue cryopreserved with vitrification versus slow freezing.  The primary outcome was the proportion of intact primordial follicles.  The meta-analysis included a total of six studies.  The number of participants ranged from 3 to 20, and were between 20 to 43 years of age.  The number of morphologically intact follicles ranged from 14 to 2058, of which 6 to 724 were primordial.  The pooled OR demonstrated no significant difference in the proportion of intact primordial follicles after slow freezing or vitrification (OR=1.228, 95% confidence interval [CI]: 0.769-1.961, P=0.390).  Sensitivity analysis using the leave-one-out approach revealed no considerable changes in the direction and magnitude of the pooled estimates when individual studies were excluded one at a time, indicating good reliability of the analysis.  The authors concluded that slow freezing and vitrification produce comparable results with respect to intact primordial follicles for the cryopreservation of human ovarian tissue.

Cryopreservation of Ovarian Tissue

Cryopreservation of ovarian tissue with subsequent autologous or heterotopic transplantation has been researched as a technique to sustain the reproductive function of females who are faced with infertility resulting from procedures such as chemotherapy, radiation therapy or surgery that are frequently utilized to treat malignant diseases.  A variety of articles have focused on the technical feasibility of these options, and there are retrospective case reports of successful pregnancies using this technique.  However, in general, the technique is not standardized, and there is ongoing investigation of the following unresolved issues (Donnez, 2010; Imbert, 2014; Kim, 2001):

The ASRM Practice Committee updated a 2008 committee opinion on ovarian tissue cryopreservation.  Based on the established criteria of ASRM, “Ovarian tissue cryopreservation and transplantation is experimental.”  The committee also noted:

Ovarian tissue cryopreservation is an option for patients who require immediate gonadotoxic treatment and is the only option available for prepubertal girls...Ovarian tissue cryopreservation and subsequent transplant may be offered to carefully selected patients as an experimental protocol. 

In addition, the Practice Committee for ASRM (2013) published a committee opinion on fertility preservation for individuals undergoing gonadotoxic therapy or gonadectomy, noting ovarian tissue cryopreservation “should be viewed as investigational.” 

The 2018 ASCO guidelines on Fertility Preservation in Patients with Cancer (Oktay, 2018) provide the following information on ovarian tissue cryopreservation and transplantation:

Ovarian tissue cryopreservation for the purpose of future transplantation does not require ovarian stimulation and can be performed immediately. In addition, it does not require sexual maturity and, hence, may be the only method available in children. Finally, this method may also restore global ovarian function. However, it should be noted that further investigation is needed to confirm whether it is safe in patients with leukemias.

These guidelines also go on to provide the following qualifying statement:

As of the time of this publication, ovarian tissue cryopreservation remains experimental. However, emerging data may prompt reconsideration of this designation in the future (this technique is already considered nonexperimental in some countries, and its experimental status is undergoing evaluation in the United States).  

The NCCN Clinical Practice Guidelines for Adolescent and Young Adult Oncology (2018) provide the following guidance with regards to cryopreservation of ovarian tissue:

Ovarian tissue cryopreservation is a promising, but less well-studied strategy for female fertility preservation when there is insufficient time for oocyte or embryo cryopreservation and/or the patient is prepubertal. This technique does not require hormonal stimulation, so there is no long delay in initiation of treatment. While evidence supporting the effectiveness and safety of ovarian tissue cryopreservation is scarce, a few systematic review have supported its use for fertility preservation in cancer patients. This procedure would not be appropriate for some women with cancer when there is a potential for reintroduction of malignant cells that could occur with grafting. While ovarian tissue cryopreservation is still considered investigational at some institutions, it may be discussed as an option for fertility preservation, if available.

There are recruiting and ongoing clinical trials studying ovarian tissue cryopreservation as well as cryopreservation and use of immature oocytes.  However, to date, results from these studies have not been published.  Although there have been case reports of successful live births after cryopreservation, thawing, and implantation of ovarian tissue, there are still many unanswered questions about this technology.  Data from prospective, randomized, long-term studies are needed to determine the safety and efficacy of ovarian tissue cryopreservation as a method to preserve fertility.


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

Gonad: A reproductive cell-producing gland, such as an ovary.

Gonadotoxic: Having a deleterious effect on the gonads, such as chemotherapy or radiation therapy.

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.

Oophoropexy (ovarian transposition): A surgical procedure that involves moving the ovaries to another place in the body, away from where radiation therapy will be directed.

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.


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. Cil AP, Bang H, Oktay K. Age-specific probability of live birth with oocyte cryopreservation: an individual patient data meta-analysis. Fertil Steril. 2013; 100(2):492-499.e3.
  6. Cobo A, Diaz C. Clinical application of oocyte vitrification: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2011; 96(2):277-285.
  7. 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.
  8. Donnez J, Jadoul P, Squifflet J, et al. Ovarian tissue cryopreservation and transplantation in cancer patients. Best Practice & Research Clinical Obstetrics and Gynaecol. 2010; 24(1):87-100.
  9. 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.
  10. Goswami D, Conway GS. Premature ovarian failure. Horm Res. 2007; 68(4):196-202.
  11. Imbert R, Moffa F, Tsepelidis S, et al. Safety and usefulness of cryopreservation of ovarian tissue to preserve fertility: a 12-year retrospective analysis. Hum Reprod. 2014; 29(9):1931-1940.
  12. Isachenko E, Rahimi 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.
  13. Kim SS, Battaglia DE, Soules MR. The future of human ovarian cryopreservation and transplantation: fertility and beyond. Fertil Steril. 2001; 75(6):1049-1056.
  14. Kim S, Lee W, Chung M, et al. Long-term ovarian function and fertility after heterotopic autotransplantation of cryobanked human ovarian tissue: 8-year experience in cancer patients. Fertil Steril. 2009; 91(6):2349-2354.
  15. Manipalviratn S, Decherney A. Clinical application of human oocyte cryopreservation. Rev Recent Clin Trials. 2008; 3(2):104-110.
  16. Oktay K, Cil AP, Bang H. Efficiency of oocyte cryopreservation: a meta-analysis. Fertil Steril. 2006; 86(1):70-80.
  17. Roberts JE, Oktay K. Fertility preservation: a comprehensive approach to the young woman with cancer. J Natl Cancer Inst Monogr. 2005; (34):57-59.
  18. Schmidt KT, Rosendahl M, Ernst E, et al. Autotransplantation of cryopreserved ovarian tissue in 12 women with chemotherapy-induced premature ovarian failure: the Danish experience. Fertil Steril. 2011; 95(2):695-701.
  19. 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. 
  20. Zhou XH, Zhang D, Shi J, Wu YJ, et al. Comparison of vitrification and conventional slow freezing for cryopreservation of ovarian tissue with respect to the number of intact primordial follicles: A meta-analysis. Medicine (Baltimore). 2016; 95(39):e4095.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American College of Obstetricians and Gynecologists (ACOG). Committee on Gynecologic Practice. Oocyte cryopreservation. Committee Opinion No. 584. Obstet Gynecol. 2014; 123(1):221-222.
  2. American College of Obstetricians and Gynecologists (ACOG). Ovarian tissue and oocyte cryopreservation. ACOG Committee Opinion No. 405. Obstet Gynecol. 2008; 111(5):1255-1256.
  3. American Society for Reproductive Medicine (ASRM). Guidance for Providers Caring for Women and Men of Reproductive Age with Possible Zika Virus Exposure (Modified from CDC a,b,c,d, FDAe and WHOf  Published Guidance) Updated September 2017. Available at: Accessed on August 15, 2018.
  4. American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART). Mature oocyte cryopreservation: a guideline. Fertil Steril. 2013; 99(1):37-43.
  5. Ethics Committee of the American Society for Reproductive Medicine. Fertility preservation and reproduction in patients facing gonadotoxic therapies: an Ethics Committee opinion. Fertil Steril. 2018; 110(3):380-386.
  6. Loren AW, Mangu PB, Beck LN, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical guideline update. J Clin Oncol. 2013; 31(19):2500-2510.
  7. National Comprehensive Cancer Network (NCCN®) Clinical Practice Guidelines in Oncology. Adolescent and young adult (AYA) oncology. © 2018 National Comprehensive Cancer Network, Inc. V2.2018. October 11, 2017. For additional information: Accessed on August 15, 2018.
  8. Oktay K, Harvey BE, Loren AW. Fertility preservation in patients with cancer: ASCO Clinical Practice Guideline Update Summary. J Oncol Pract. 2018; 14(6):381-385.
  9. Practice Committee of American Society for Reproductive Medicine. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril. 2013; 100(5):1214-1223.
  10. Practice Committee of American Society for Reproductive Medicine. Ovarian tissue cryopreservation: a committee opinion. Fertil Steril. 2014; 101(5):1237-1243.
Websites for Additional Information
  1. American Society for Reproductive Medicine. Available at: Accessed on August 15, 2018.
  2. Centers for Disease Control and Prevention (CDC). Assisted reproductive technology. Last reviewed May 1, 2017. Available at: Accessed on August 15, 2018.

Cryopreservation of Oocytes or Ovarian Tissue

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Medical Policy & Technology Assessment Committee (MPTAC) review. Updated review sate, Rationale, References, Websites for Additional Information and History sections.



MPTAC review. Initial document development.



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