Abstract
The article under discussion suggests the use of ovarian transplantation to treat or prevent peri-menopausal symptoms [1]. There currently exists a sizable amount of literature on ovarian transplantation in mice and sheep. Over the last 5 years, there have been several case reports of either autologous or homologous human ovarian transplantation. It has been reported that frozen, thawed transplants of ovarian tissue to the pelvic sidewalls have also resulted in ovulation. Early reports have demonstrated that transplantation could result in ovarian function, menses and ovulation. Oktay and colleagues described two patients who had an autologous ovarian transplantation to their forearm [2]. The first patient was aged 35 years and had stage III squamous cell carcinoma of the cervix. Fresh transplants in the patient's forearm resulted in hormonal levels in the fertile range. Ovulation could be induced with exogenous gonadotropins.
In the second case, bilateral ovariectomy was performed in a 37-year-old woman with benign ovarian cysts. The patient also had fresh forearm transplants of ovarian cortical tissue. These transplants produced ovulation locally and at a normal level, which resulted in monthly menstrual cycles.
In 2004, seven rhesus monkeys had their ovaries removed laparoscopically and cut into small pieces. They were immediately transplanted into either the arm or the abdomen. Follicles were collected after human chorionic gonadotropin injection and fertilized by intracytoplasmic sperm injection (ICSI). Two embryos were transferred, resulting in a live birth after ovarian tissue transplantation [3].
In 2002, Poirot demonstrated the feasibility of human ovarian tissue transplantation [4]. This was suggested to be an appropriate procedure in young girls or women before chemotherapy that would cause ovarian failure. The suggested age was less than 24 years, but the best results were obtained in very young women or girls, since their ovaries had the densest oocyte concentration.
Silver and colleagues described ovarian transplantation from one 24-year-old identical twin, who had already had three children, to her sister who had developed premature ovarian failure at the age of 14 years and had been amenorrheic and without ovarian function for a decade [5]. Two cycles of egg donation had previously been unsuccessful. An ovary was removed from the donor twin and the streak ovary of the recipient was denuded. The cortical tissue was attached onto this denuded remnant. Normal ovulation resulted and a pregnancy occurred 2 months later. The cortical tissue of the recipient was found to have no follicles. Thus, it is clear that the grafting procedure did not compromise ovarian function, since pregnancy was able to occur after what appeared to be normal hormonal ovulation.
In the case initially abstracted, the recipient was aged 46 years. This is clearly beyond the age where in vitro fertilization is successful. Hormone levels of gonadotropins were never in a range consistent with normal fertile ovulation. Hence, while there was ovarian function, it was not normal. This is likely since there was some procedural oocyte loss in this older woman with an already low endogenous ovarian concentration of oocytes. The authors suggested that this procedure might be appropriate for hormonal replacement, but it is unlikely that this is a reasonable approach in an older woman, since the ovaries of older women are likely to have limited and abnormal function. However, this may be an appropriate procedure in very young women who have had ovarian freezing before chemotherapy, since it might allow normal hormonal function and the possibility of oocyte harvest for future pregnancy.
Reviewer's perspective
There is a clear need for the preservation of hormonal secretion and fertility in women who lose their ovaries for medical reasons. Currently, there are multiple methods to deal with this problem. One approach to fertility preservation is to freeze embryos. A woman may not want to have an unknown donor and may not be at a stage in her life where she has a partner whom she would like to father her child. Freezing embryos may be appropriate even if the woman then undergoes hysterectomy, since it is possible for the frozen embryos to be transplanted into a surrogate recipient. Oocyte freezing is another possibility, with later ICSI for fertility. However, the current methodology suggests that this is a procedure with a low likelihood of success. Obviously, egg donation may be used if the woman has no endogenous ovarian function, but a functioning uterus.
Certainly, young girls or women whose ovaries will be rendered nonfunctional by either pelvic radiotherapy or chemotherapy, who may have had removal of ovarian tissue for benign disease, or who have an autoimmune disease that may compromise ovarian function, may be candidates for ovarian cortical transplantation. Even in the absence of a desire for fertility, ovarian cortical transplantation may have advantages in that it may produce the most normal hormone replacement and produce other ovarian products, such as androgens.
There are many potential problems with ovarian cortical transplantation. The safety of this procedure is not clearly established. The lengths of time that the ovaries will function have yet to be defined. If the ovarian cortical tissue is removed in the presence of a malignancy, it is possible that malignant cells may be carried over with the autologous transplant. However, autologous transplantation may be a promising procedure to produce a pregnancy in an appropriately screened individual. When used in a young girl who is a cancer survivor, autologous transplantation may be able to produce a more normal puberty and, later, fertility. Therefore, the future holds significant promise to help these individuals.