Progressive decline of residual follicle pool after clinical diagnosis of autoimmune ovarian insufficiency

Abstract

In approximately 5-8% patients with primary ovarian insufficiency (POI), the disease is caused by an autoimmune process made evident by the appearance of autoantibodies against steroidogenic enzymes (SCA-POI). Anti-müllerian hormone (AMH) is the best marker of the residual follicular pool. To evaluate the rate of loss of the residual follicle pool in women with SCA-POI after clinical diagnosis. One hundred and thirty-two women with POI were tested for 21-hydroxylase autoantibodies, 17α-hydroxylase autoantibodies and P450scc autoantibodies, and 35 patients with SCA-POI were identified. AMH was analysed at the time of the first visit in all women with POI, and in follow-up, serum samples were taken 1-3years after in 11 women with SCA-POI and detectable AMH. 12/35 (35%) women with SCA-POI had AMH levels within the normal range at the time of first sampling, as compared to 6/97 (6%) with idiopathic POI (P<0·001). 11/17 (65%) women with SCA-POI with <6years disease duration had normal serum AMH concentration. A progressive decline in AMH concentration was observed at longitudinal follow-up in all 11 AMH-positive women with SCA-POI, at an estimated average rate of 1·6μg/l AMH/year (corresponding to an average 57% of preserved follicle pool/previous year) (R(2) =0·219, P=0·028). After 6years of disease duration, only 1/18 (6%) women with SCA-POI had detectable levels of AMH, similar to women with idiopathic POI (5/78, 6%). Most women with SCA-POI present at clinical diagnosis with a preserved follicle pool that is progressively lost within a few years.