This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oktay, K. Search for Related Content PubMed Articles by Oktay, K.

Evidence for Limiting Ovarian Tissue Harvesting for the Purpose of Transplantation to Women Younger than 40 Years of Age^b

Cornell Institute for Reproductive Medicine, Weill Medical College of Cornell University, New York, New York 10021

To the editor:

Callejo et al. (1) recently reported on four cases of autologous heterotopic ovarian transplantation of fresh (n = 3) and frozen-thawed (n = 1) ovarian tissue. Ovarian tissue was removed from women with the age range of 46–49 yr during total abdominal hysterectomy and bilateral oophorectomy performed because of leiomyomas. In two women who received fresh grafts in the arm, estrogen production occurred for 2–4 months. In one woman who received frozen-thawed implants in the rectus abdominus muscle, ovarian function lasted for 5–6 months as demonstrated by follicle development and estrogen production. In one patient, where preimplant histological analysis did not show any primordial follicles, ovarian function did not recover. Authors concluded that ovarian function could be restored after fresh and frozen heterotopic ovarian transplantation, albeit for only a short reproductive life span. We have previously performed three ovarian transplantation procedures, one to an orthotopic location using frozen-thawed tissue in a 32-yr-old woman (2, 3), and two to the forearm (ages 35 and 37 yr) with fresh tissue (4, 5). All three had ovarian function, lasting up to 2 yr as demonstrated by ovarian follicle development and luteinization, and in one patient, spontaneous ovulation. It has been shown that there are approximately 25,000 primordial follicles left at the age of 37 yr (6), and this number is less than a few thousand per ovary (and in many cases less than a few hundred) in the age range of 46–49 yr. Because of the high rate of follicle losses exceeding 50% during the revascularization process (7), Callejo et al. (1) probably transplanted not more than a few hundred of primordial follicles with the few strips that they grafted to each patient (8). Therefore, their study should be interpreted differently. Because of the dwindling numbers of primordial follicles after age 37, we have limited ovarian cryopreservation for the purpose of transplantation to patients younger than age 40. The fact that a low number of primordial follicles resulted in several months of ovarian function in the Callejo et al. study (1) is encouraging for these patients. We recommend cryopreservation of a whole ovarian cortex, because of the losses associated with revascularization. Transplantation of larger amounts of tissue from patients younger than 40 yr of age is likely to result in longer periods of ovarian function. In the long-term follow-up of the 37-yr-old patient in which we transplanted ovarian tissue to the forearm, endocrine function lasted at least 2 yr, and we were able to retrieve oocytes percutaneously. Patients who had their ovarian tissue cryopreserved at earlier ages may have even longer ovarian function and may even be able to conceive. In the two patients who received transplants to the forearm, menopausal symptoms also disappeared, and the patients indicated that they felt better with their endogenous hormones than with the hormone replacement. Although this is not sufficient evidence that ovarian transplantation can replace hormone replacement, it suggests that relief of menopausal symptoms may be an added benefit to the preservation of fertility in some patients. Considering that more than 50,000 reproductive age women are exposed to sterilizing chemotherapy and radiotherapy annually in the U.S. alone (9) and thousands lose their ovarian function due to gynecologic surgery, larger trials of ovarian cryopreservation and transplantation are strongly justified.

Footnotes

^b Address all correspondence to: Kutluk Oktay, M.D., Cornell Institute for Reproductive Medicine, Weill Medical College of Cornell University, 505 East 70th Street, Suite HT-300, New York, New York 10021. E-mail: .

Received November 29, 2001.

References

1. Callejo J, Salvador C, Miralles A, Vilaseca S, Lailla JM, Balasch J 2001 Long-term ovarian function evaluation after autografting by implantation with fresh and frozen-thawed human ovarian tissue. J Clin Endocrinol Metab 86:4489–4494[Abstract/Free Full Text]
2. Oktay K, Karlikaya G 2000 Ovarian function after transplantation of frozen, banked autologous ovarian tissue. N Engl J Med 342:1919[Free Full Text]
3. Oktay K, Aydin BA, Karlikaya G 2001 A technique for laparoscopic transplantation of frozen-banked ovarian tissue. Fertil Steril 75:1212–1216[CrossRef][Medline]
4. Oktay K, Aydin BA, Economos K, Rucinski J, Kan MT, Veeck L, Rosenwaks Z 2000 Restoration of ovarian function after autologous transplantation of ovarian tissue in the forearm. Fertil Steril 74(Suppl 3):S79
5. Oktay K, Economos K, Kan M, Rucinski J, Veeck L, Rosenwaks Z 2001 Endocrine function and oocyte retrieval after autologous transplantation of ovarian cortical strips to the forearm. JAMA 286:1490–1493[Abstract/Free Full Text]
6. Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF 1992 Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod 7:1342–1346[Abstract/Free Full Text]
7. Baird DT, Webb R, Campbell BK, Harkness LM, Gosden RG 1999 Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at -196 C. Endocrinology 140:462–471[Abstract/Free Full Text]
8. Oktay K, Nugent D, Newton H, Salha O, Chatterjee P, Gosden RG 1997 Isolation and characterization of primordial follicles from fresh and cryopreserved human ovarian tissue. Fertil Steril 67:481–486[CrossRef][Medline]
9. American Cancer Society 2001 Cancer facts and figures 2001. Atlanta: American Cancer Society

This article has been cited by other articles:

				S. J. Lee, L. R. Schover, A. H. Partridge, P. Patrizio, W. H. Wallace, K. Hagerty, L. N. Beck, L. V. Brennan, and K. Oktay American Society of Clinical Oncology Recommendations on Fertility Preservation in Cancer Patients J. Clin. Oncol., June 20, 2006; 24(18): 2917 - 2931. [Abstract] [Full Text] [PDF]

				A. Revel and J. Schenker Ovarian tissue banking for cancer patients: is ovarian cortex cryopreservation presently justified? Hum. Reprod., January 1, 2004; 19(1): 14 - 19. [Abstract] [Full Text] [PDF]

				T. B. Twickler, M. J. M. Cramer, G. M. Dallinga-Thie, M. J. Chapman, D. W. Erkelens, and H. P. F. Koppeschaar Adult-Onset Growth Hormone Deficiency: Relation of Postprandial Dyslipidemia to Premature Atherosclerosis J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2479 - 2488. [Full Text] [PDF]

This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oktay, K. Search for Related Content PubMed Articles by Oktay, K.