Over three decades ago researchers observed a high rate of premature ovarian failure associated with poly-endocrine autoimmune disease and suggested that there might be an autoimmune disease of the ovary. At about the same time IVF workers observed auto-antibodies to eggs in the ovary in women with infertility and also suggested there might be an autoimmune disease of the ovary. Since that time, the concept of ovarian autoimmune disease has become more widely recognized but significant advances in our understanding are only just beginning to occur.
Such antibodies would bind to important functional sites in the ovary and granulosa cells and impair the normal response. The anti-ovarian antibodies were found fairly recently, and their complete function is not well known yet. It is believed that these antibodies cause disturbances that are a cause of ovarian failure/non-ovulation or poor ovulation. They are believed also to be a cause of less-than-expected response to various medications to stimulate proper ovarian function, and possibly even formation of less-than-excellent and normal eggs. The treatment of this condition is more or less experimental. Very infrequently, this condition can be helped through in vitro fertilization and if everything else fails an egg donation from a fertile donor is the evidence based-medicine’s answer to this disorder. When such a pregnancy is properly supported by administration of exogenous hormones – progesterone and sometimes even estrogen – it has an excellent chance to lead to normal delivery.
Ovarian autoimmune disease is principally associated with Premature Ovarian Failure (POF) and with unexplained infertility. It is possible that autoimmune unexplained infertility is an early stage of autoimmune POF but this remains to be demonstrated conclusively. POF is the onset of menopause before age 40 and occurs in one to two percent, or about one to two million women. Like natural menopause around age 50, premature menopause is identified by cessation of menstrual cycles for one year, accompanied by elevated follicle stimulating hormone (FSH) and reduced estradiol levels in blood . While some cases of POF have a genetic cause (such as Turner syndrome), or are due to chemotherapy, recent studies suggest that about half the cases of premature menopause are due to an autoimmune attack on ovarian follicles and the eggs (oocytes).
There is still a lack of information on the specific features of autoimmune POF. Some women with POF may have a family history of POF but most do not. However, women with POF have a higher risk for other autoimmune endocrine diseases, such as thyroid disease, Addison disease, type 1 diabetes, and autoimmune poly-glandular syndromes.
Women with infertility and ovarian auto-antibodies tend to have lower than expected estradiol responses to gonadotropin hormone stimulation (i.e. poor responders) and lower pregnancy rates following infertility treatment. Poor responders with ovarian antibodies were younger than poor responders without ovarian antibodies. This suggests that although some poor responses are associated with early stages of the menopause progression and reduced number of functional follicles, others are associated with an autoimmune process.
Ovarian autoimmunity is identified by the presence of anti-ovarian antibodies. There are several different types of tests and consequently different names for these antibodies. Antibodies specifically to eggs and to the zona pellucida (an area surrounding the eggs), or to ovarian cells have been described (9). Some women have antibodies to both ovarian cells and to eggs and others have only one of these antibodies. Ovarian autoimmunity is not identified by traditional tests for ovarian function, such as elevated pituitary follicle stimulating hormone in POF. Although the cause may differ, the symptoms of autoimmune and non-autoimmune POF are the same as in a normal menopause, including hot flashes, dry vaginal tissues, painful sex, infertility, bone loss, and an increased risk of cardiovascular disease. Likewise, autoimmune infertility can only be distinguished from non-autoimmune infertility by specific antibody tests.
As with other endocrine disorders, POF is treated by replacing the lost hormone, in this case hormone replacement therapy (HRT) with estrogen and progesterone to protect the heart, bones, genital and urinary tract tissues, and the nervous system. However, if a woman with infertility or POF wants to become pregnant, treatment with hormones that stimulate ovarian follicles to grow and produce eggs can be tried. If hormone stimulation alone does not result in a pregnancy, women may be treated by more aggressive methods such as in vitro fertilization (IVF). There have been reports of success in combination with low dose immunosuppression. However, success rates are relatively low and there are concerns about the side effects of immunosuppressant therapy. We, at Rotunda do not believe in Immunosuppression with steroids. This sort of approach has not been helpful or useful for any patients in our experience. In some rare cases of POF, follicular function may spontaneously resume, and a pregnancy can occur.
The next significant advance in characterizing ovarian autoimmune disease will be identification of the specific ovarian proteins recognized by the auto antibodies. Once we have tests that detect specific auto-antigens, we will be moving closer to some evidence-based medicine answers. This will permit development of tests based on use of specific antigens, which will improve clinical diagnosis. An understanding of how these proteins become targets of an autoimmune attack would be a significant step toward designing therapies for reversing the effects of this disorder.
As of now, the only known treatment which gives results for this disorder is Donor Egg IVF.
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