To the Editor: Successful human ovarian transplantation wasfirst reported with the use of a cortical-tissue grafting techniquein monozygotic twins who were discordant for premature ovarianfailure.1 Subsequently, six additional cases have been reported,which have resulted in a return of ovulation in all patients,with spontaneous conception and delivery of six healthy infants,with one from tissue that had been frozen.2 The concept of ovariancortical grafting is based on the fact that all follicles containingeggs are located in the outer 1 mm of the ovary, which can besutured to the recipient's medulla just like a full-thicknessskin graft. However, a limitation of this technique is thatthe graft generally loses two thirds of its follicles from ischemiaduring revascularization, which reduces its life span.3 Thepatients we have described previously became menopausal after3 years, although pregnancy then occurred again after graftingof frozen ovarian tissue. Data from studies in animals suggestthat microvascular whole-ovary transplantation could avoid thisproblem.4
A pair of 38-year-old monozygotic twins requested ovary transplantation.One of the sisters had two children and normal ovarian function,whereas the other had undergone premature menopause at the ageof 15 years, with amenorrhea for 23 years and a follicle-stimulatinghormone (FSH) level of 81 mIU per milliliter.
After the procedure was approved by the review board at ourinstitution and written informed consent was obtained from thepatients, we laparoscopically removed one ovary from the fertilesister by dividing the infundibulopelvic ligament at its basefor maximum length. The ovary was then prepared for microvasculartransplantation in the recipient. With the use of minilaparotomy,the donor's ovarian veins (3.0 mm in diameter) were anastomosedto the recipient's ovarian veins with 9-0 nylon sutures, andthe donor's ovarian arteries (0.5 mm in diameter) were anastomosedto the recipient's ovarian arteries with 10-0 nylon interruptedsutures (Figure 1). Normal-appearing blood flow was immediatelyobserved through the ovarian vessels of the transplanted ovaryafter an ischemic period of 100 minutes.
Figure 1. Whole-Ovary Transplantation between Monozygotic Twins.
Panel A shows various structures in the ovarian vasculature that are key during transplantation of an ovary. In Panel B, the donor's ovarian artery (0.5 mm in diameter) is prepared for transplantation. The donor's ovarian artery and ovarian vein are then anastomosed to the recipient's ovarian artery and vein, as shown in Panels C and D, respectively.
The recipient's first menstruation in 22 years occurred on day101 after transplantation; by day 158, the FSH level had droppedto 7.4 U per liter. Ultrasonography revealed continuing normalblood flow to the transplanted ovary and normal follicular development.The patient had 11 regular menstrual cycles until, by day 427after transplantation, the level of beta human chorionic gonadotropinwas 174 mIU per milliliter. The results of ultrasonography performedat 7, 10, and 12 weeks for prenatal evaluation were normal.A healthy baby girl was born November 11 at 40 weeks, with anApgar score of 9/10; the baby weighed 7 lb 15 oz and was 21.25in. in length. Both mother and baby are doing well.
Although technically more challenging than ovarian corticalgrafting, whole-ovary microvascular transplantation may resultin a longer duration of graft function, although this aspectrequires further study. The delay of 101 days until the firstmenstruation is consistent with the projected time course offollicular growth in humans, since it takes 3 months for eggsin small preantral follicles to reach sufficient maturity toenter the menstrual and ovulatory cycles.5 This case demonstratesthe potential for using whole-ovary transplantation betweenmonozygotic twins who are discordant for premature ovarian failure,in order to restore fertility in the affected twin.
Sherman J. Silber, M.D. St. Luke's Hospital St. Louis, MO 63017 silber{at}infertile.com
Gedis Grudzinskas, M.D. London Bridge Fertility, Gynaecology,and Genetics Centre London SE1 9RY, United Kingdom
Roger G. Gosden, Ph.D. Weill Medical College of Cornell University New York, NY 10021
References
Silber SJ, Lenahan KM, Levine DJ, et al. Ovarian transplantation between monozygotic twins discordant for premature ovarian failure. N Engl J Med 2005;353:58-63. [Free Full Text]
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Wang X, Chen H, Yin H, Kim SS, Tan SL, Gosden RG. Fertility after intact ovary transplantation. Nature 2002;415:385-385.
Gougeon A. Dynamics of follicular growth in the human: a model from preliminary results. Hum Reprod 1986;1:81-87. [Free Full Text]
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