OVARIAN CRYOPRESERVATION AND TRANSPLANTATION: An Emerging Tool for Fertility Preservation By Kutluk Oktay, M.D.

Body: 

In the US alone, hundreds of thousands of women and children are subjected to medical treatment which result in infertility and premature ovarian failure. Among the many treatments that cause infertility and premature ovarian failure are:

1) Chemotherapy: Women and children are given chemotherapy for not only cancer but other conditions such as treatment of lupus nephritis, rheumatoid arthritis, sickle cell anemia etc. A common chemotherapy agent cyclophosphamide causes significant damage to ovarian follicles and result in infertility.

2) Radiation treatment: Pelvic and whole body radiation is also used in the treatment of thousands of cancer and non-cancer patients and when ovaries are in the vicinity of the radiation area, fertility is compromised

3) Tens of thousands of women undergo ovary removal procedures for benign diseases such as endometriosis and ovarian cysts.

4) Thousands of women undergo ovary removal preventively when there is family history of ovarian cancer and/or when BRCA gene is detected.

 

What are the techniques to preserve fertility?

When there is enough time and no medical hurdle to perform ovarian stimulation, and if the patient has a partner, embryo freezing can be performed to preserve fertility. In single patients, even though the success rates are much lower than that of embryo freezing, oocyte freezing is also possible. Even in breast cancer patients, tamoxifen or letrozole (an aromatase inhibitor) can be used to stimulate ovaries for the purpose of embryo or oocyte freezing. Unfortunately children, and many adult patients who have to start their sterilizing treatments within a short time will not have sufficient time to undergo ovarian stimulation. Ovarian tissue freezing was developed for those patients who cannot utilize more established assisted reproduction techniques to preserve fertility.

 

How is ovarian tissue frozen?

This procedure does not require ovarian stimulation and can be done anytime during the cycle. Typically, one ovary is removed with a simple laparoscopic technique within an hour, and the patient is discharged home the same day. The mantle of the ovary, which contains all the immature eggs called primordial follicles is separated from the connective tissue of the ovary and cut into dime size pieces. These pieces were then mixed with antifreeze substances and then frozen with a computerized machine very slowly. Tissue pieces are then stored in liquid nitrogen as long as needed without any significant compromise.

 

How is ovarian tissue transplanted?

Ovarian tissue can be transplanted either back to its origin in patient’s pelvis or it can be placed underneath the patient’s skin either in the forearm or lower abdomen. The latter technique is developed because:

1) In some cancer patients it may not be completely safe to put back ovarian tissue inside the body; It can be done under local anesthesia with less inconvenience , discomfort, and cost to the patient

2) Tissue can be tracked more practically

3) Not all of the tissue pieces are needed to implanted at once; since this is a procedure with local anesthesia, tissue strips can be inserted in repetitive procedures as the prior ones run out of its egg reserve.

Both techniques resulted in reversal of menopause in several patients. However, up until now only with placement under the skin that in vitro fertilization and embryo development was possible. Quest for achieving the first pregnancy after ovarian transplant is continuing in several centers around the world.

 

Are there any risks associated with ovarian transplant?

The biggest theoretical risk is the possibility of the transplanted ovarian tissue harboring cancer cells. For most cancers of children and young women however, this risk is negligible. In all cases of ovarian transplant however, samples of tissue are tested for presence of cancer cells prior to transplant. Because ovarian transplantation is a very recent experimental technique, a record of long term success and safety has not yet been established in patients. However, animal studies showed successful pregnancies without an increase in birth defects.

 

Conclusions:

Ovarian cryopreservation and transplantation are currently used to preserve fertility in women who run the risk of infertility and premature ovarian failure due to medical treatments. Even though pregnancies occurred in animal studies and embryos developed in patients after ovarian transplantation, first pregnancies are anticipated in patients within the recent future. At the present time, this experimental technique is recommended for elective purposes, such as postponement of childbearing.

 

References

Oktay K, Buyuk E, Veeck L et al. Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004 Mar 13;363 (9412): 837-40.

Sonmezer M and Oktay K. Fertility preservation in female patients.
Hum Reprod Update. 2004 May-Jun;10(3):251-66.

Oktay K and Buyuk E. Fertility preservation in women undergoing cancer treatment.
Lancet. 2004 May 29;363(9423):1830. Oktay et al, JAMA

Oktay K and Karlikaya G. Ovarian function after transplantation of frozen, banked autologous ovarian tissue.
N Engl J Med. 2000 Jun 22;342(25):1919.

Oktay K, Buyuk E, Davis O et al. Fertility preservation in breast cancer patients: IVF and embryo cryopreservation after ovarian stimulation with tamoxifen.
Hum Reprod. 2003 Jan;18(1):90-5.

Kutluk Oktay, M.D. 
Phone: 212-746-1762
Email: kuo9001@med.cornell.edu
 

 

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