Abstract
ObjectiveTo characterize the ovarian reserve indicators for premature ovarian insufficiency (POI) at different disease stages and with various etiologies.MethodsAccording to different FSH levels and menstrual conditions, patients with normal ovarian reserve (NOR with 5 IU/L<FSH<10 IU/L, n=987), precursor stage of POI (pre-POI with 10 IU/L<FSH ≤ 25 IU/L, n=410), early POI (25 IU/L<FSH ≤ 40 IU/L n=147), and premature ovarian failure (POF with FSH>40 IU/L, n=454) were retrospectively screened and their records were abstracted from Reproductive Hospital Affiliated to Shandong University between 2014 and 2019. Based on the known etiologies, POI patients were subdivided into genetic, iatrogenic, autoimmune and idiopathic subsets according to the known etiologies. The phenotypic features were compared within different subgroups, and the predictive value of ovarian reserve markers was analyzed.ResultsThe ovarian reserve indicators consecutively deteriorated with the progress of ovarian insufficiency, indicated as an increase of FSH and LH but decrease of AMH, inhibin B, AFC, E2 and T (P<0.01). Most of them changed significantly from NOR to pre-POI while remained relatively stable at a low level or even undetectable at early POI and POF stage. AMH showed the highest predictive value for pre-POI (AUC 0.932, 95% CI 0.918-0.945) and POI (AUC 0.944, 95% CI 0.933-0.954), and the combination of AMH and AFC was highly promising for early prediction. Additionally, significant differences existed in AMH, inhibin B and AFC among women with different etiologies of POI (P<0.05), and the genetic POI presented the worst hormone status.ConclusionsOur study indicated a high heterogeneity of POI in both endocrine hormones and etiological phenotypes. The quantitative changes and cutoff values of AMH and AFC could provide new insights in the prediction and early diagnosis of POI.
Highlights
Premature ovarian insufficiency (POI) is a common reproductive endocrine disorder defined by the cessation of ovarian function before the age of 40
The records of 1998 women aged before 40 years old were retrospectively abstracted, including 987 women with NOR, 410 pre-POI, 147 early POI and 454 Premature ovarian failure (POF)
The age at diagnosis significantly varied among pre-POI, early POI and POF groups (32.38 ± 4.07 y vs. 30.22 ± 3.72 y vs. 29.55 ± 4.19 y, P
Summary
Premature ovarian insufficiency (POI) is a common reproductive endocrine disorder defined by the cessation of ovarian function before the age of 40. Ovarian insufficiency is a continuum of impaired ovarian function or ovarian aging rather than a specific dichotomous state. This condition can be transient or progressive, and usually results in eventual premature menopause [2, 3]. According to different FSH levels, fecundity, and menstrual status, POI has been subdivided into three consecutive but progressive stages: occult, biochemical, and overt ovarian insufficiency [3]. Premature ovarian failure (POF) is considered as the end stage of POI with FSH>40 IU/L. The evidence-based progression of POI is still lacking
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