Options for Preservation of Fertility in Women
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《新英格兰医药杂志》
To the Editor: In a review article on preservation of fertility in women, Lobo (July 7 issue)1 states that multidrug chemotherapy leads to amenorrhea in 25 to 50 percent of patients with cancer under 20 years of age and in 80 to 90 percent of those over 25 years of age. More specific data are available for women receiving adjuvant chemotherapy for early-stage breast cancer,2 and the risk of menopause onset in this group is highly dependent on age. Less than 5 percent of women under 30 years of age, almost 40 percent of 40-year-old women, and 80 percent of 45-year-old women enter menopause during the first year after starting chemotherapy. Because fertility is a chief concern among young women with breast cancer,3 it is important that they be given age-specific and treatment-specific information so that they may make informed decisions about adjuvant chemotherapy. Many of these women will readily accept a low risk of early menopause to receive the benefits of adjuvant chemotherapy. Although these short-term data are somewhat reassuring, further research is needed to examine longer-term fertility and pregnancy rates after adjuvant chemotherapy in this group of young women.
Pamela J. Goodwin, M.D.
University of Toronto
Toronto, ON M5G 1X5, Canada
References
Lobo RA. Potential options for preservation of fertility in women. N Engl J Med 2005;353:64-73.
Goodwin PJ, Ennis M, Pritchard KI, Trudeau M, Hood N. Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol 1999;17:2365-2370.
Partridge AH, Gelber S, Peppercorn J, et al. Web-based survey of fertility issues in young women with breast cancer. J Clin Oncol 2004;22:4174-4183.
To the Editor: We have developed an algorithmic approach to fertility preservation in patients with cancer.1 Lobo refers to our work to indicate that the transplanted ovarian tissue may not function for more than three years. The patients we described were more than 30 years of age. Ovarian function should be sustained for longer periods of time in younger women and children. Lobo argues that heterotopic transplantation may not be ideal. In our study,2 much of the inefficiency was due to the timing of egg collection and the process of developing new tools for oocyte retrieval. Thus, no conclusion can yet be made as to whether or not a heterotopic site is inferior to an orthotopic site. Resumption of function in the recipient ovary after intraovarian transplantation cannot be ruled out. The heterotopic approach may provide conclusive evidence of fertility after ovarian transplantation. Finally, in patients with breast cancer, the use of tamoxifen and letrozole followed by cryopreservation of embryos is an option.3,4 By combining letrozole and gonadotropins, efficiency similar to that of standard protocols can be achieved, without increasing the rates of cancer recurrence.
Kutluk H. Oktay, M.D.
Weill Medical College of Cornell University
New York, NY 10021
kuo9001@med.cornell.edu
References
Sonmezer M, Oktay K. Fertility preservation in female patients. Hum Reprod Update 2004;10:251-266.
Oktay K, Buyuk E, Veeck L, et al. Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. Lancet 2004;363:837-840.
Oktay K, Buyuk E, Davis O, Yermakova I, Veeck L, Rosenwaks Z. Fertility preservation in breast cancer patients: IVF and embryo cryopreservation after ovarian stimulation with tamoxifen. Hum Reprod 2003;18:90-95.
Oktay K, Buyuk E, Libertella N, Akar M, Rosenwaks Z. Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J Clin Oncol 2005;23:4347-4353.
The author replies: Goodwin cites age-specific data for amenorrhea in women undergoing adjuvant chemotherapy for early breast cancer. She stresses the importance of age at treatment as well as the type of treatment. These are the most important variables and are addressed in my review article. The data reported by Goodwin et al.1 provide information on women with early-stage breast cancer over a one-year follow-up period. It should be remembered that amenorrhea alone does not always signify menopause. There is great variability in the onset of amenorrhea soon after chemotherapy, with some women having some resumption in menstrual function after an episode of amenorrhea. The more important question for future fertility is the risk of early menopause several years down the line. This risk is increased substantially as is the risk of diminished ovarian reserve when fertility is desired in the last years before menopause.
Oktay stresses the importance of age and notes that heterotopic transplantation may or may not be less advantageous than orthotopic transplantation. There is no disagreement with these points, and I agree that more data are needed on the issue of the best site for ovarian transplantation. Oktay also suggests that the use of tamoxifen or letrozole with gonadotropins in patients with breast cancer is beneficial for stimulation before embryo cryopreservation. I state in my review that use of these agents alone is less efficient if gonadotropins are not added. However, although the use of more "gentle" stimulation with gonadotropins (150 IU daily) helps to improve the yield of embryos generated — from one or two to three, four, or five — estrogen levels are definitely increased, particularly with the use of tamoxifen, and average 1182 pg per milliliter.2 Small, short-term studies are not able to determine whether this increase in estrogen carries any absolute increased risk. As I point out, probably the safest approach is the aspiration of immature oocytes without stimulation, followed by in vitro maturation. However, the reported success with this technique may not be extrapolated to all centers offering such treatment.
Rogerio A. Lobo, M.D.
Columbia University College of Physicians and Surgeons
New York, NY 10032
ral35@columbia.edu
Pamela J. Goodwin, M.D.
University of Toronto
Toronto, ON M5G 1X5, Canada
References
Lobo RA. Potential options for preservation of fertility in women. N Engl J Med 2005;353:64-73.
Goodwin PJ, Ennis M, Pritchard KI, Trudeau M, Hood N. Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol 1999;17:2365-2370.
Partridge AH, Gelber S, Peppercorn J, et al. Web-based survey of fertility issues in young women with breast cancer. J Clin Oncol 2004;22:4174-4183.
To the Editor: We have developed an algorithmic approach to fertility preservation in patients with cancer.1 Lobo refers to our work to indicate that the transplanted ovarian tissue may not function for more than three years. The patients we described were more than 30 years of age. Ovarian function should be sustained for longer periods of time in younger women and children. Lobo argues that heterotopic transplantation may not be ideal. In our study,2 much of the inefficiency was due to the timing of egg collection and the process of developing new tools for oocyte retrieval. Thus, no conclusion can yet be made as to whether or not a heterotopic site is inferior to an orthotopic site. Resumption of function in the recipient ovary after intraovarian transplantation cannot be ruled out. The heterotopic approach may provide conclusive evidence of fertility after ovarian transplantation. Finally, in patients with breast cancer, the use of tamoxifen and letrozole followed by cryopreservation of embryos is an option.3,4 By combining letrozole and gonadotropins, efficiency similar to that of standard protocols can be achieved, without increasing the rates of cancer recurrence.
Kutluk H. Oktay, M.D.
Weill Medical College of Cornell University
New York, NY 10021
kuo9001@med.cornell.edu
References
Sonmezer M, Oktay K. Fertility preservation in female patients. Hum Reprod Update 2004;10:251-266.
Oktay K, Buyuk E, Veeck L, et al. Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. Lancet 2004;363:837-840.
Oktay K, Buyuk E, Davis O, Yermakova I, Veeck L, Rosenwaks Z. Fertility preservation in breast cancer patients: IVF and embryo cryopreservation after ovarian stimulation with tamoxifen. Hum Reprod 2003;18:90-95.
Oktay K, Buyuk E, Libertella N, Akar M, Rosenwaks Z. Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J Clin Oncol 2005;23:4347-4353.
The author replies: Goodwin cites age-specific data for amenorrhea in women undergoing adjuvant chemotherapy for early breast cancer. She stresses the importance of age at treatment as well as the type of treatment. These are the most important variables and are addressed in my review article. The data reported by Goodwin et al.1 provide information on women with early-stage breast cancer over a one-year follow-up period. It should be remembered that amenorrhea alone does not always signify menopause. There is great variability in the onset of amenorrhea soon after chemotherapy, with some women having some resumption in menstrual function after an episode of amenorrhea. The more important question for future fertility is the risk of early menopause several years down the line. This risk is increased substantially as is the risk of diminished ovarian reserve when fertility is desired in the last years before menopause.
Oktay stresses the importance of age and notes that heterotopic transplantation may or may not be less advantageous than orthotopic transplantation. There is no disagreement with these points, and I agree that more data are needed on the issue of the best site for ovarian transplantation. Oktay also suggests that the use of tamoxifen or letrozole with gonadotropins in patients with breast cancer is beneficial for stimulation before embryo cryopreservation. I state in my review that use of these agents alone is less efficient if gonadotropins are not added. However, although the use of more "gentle" stimulation with gonadotropins (150 IU daily) helps to improve the yield of embryos generated — from one or two to three, four, or five — estrogen levels are definitely increased, particularly with the use of tamoxifen, and average 1182 pg per milliliter.2 Small, short-term studies are not able to determine whether this increase in estrogen carries any absolute increased risk. As I point out, probably the safest approach is the aspiration of immature oocytes without stimulation, followed by in vitro maturation. However, the reported success with this technique may not be extrapolated to all centers offering such treatment.
Rogerio A. Lobo, M.D.
Columbia University College of Physicians and Surgeons
New York, NY 10032
ral35@columbia.edu