Very low levels of serum anti- Müllerian hormone as a possible marker for follicle growth in patients with primary ovarian insufficiency under hormone replacement therapy

Background: Patients with primary ovarian insufficiency (POI) occasionally present with follicle growth; however, it is difficult to predict exactly which cycles will show follicle growth. Serum anti-Müllerian hormone (AMH), a useful marker for ovarian reserve, is produced in early-stage follicles. Therefore, AMH levels should reflect the presence of small follicles, which are difficult to detect using ultrasonography, and may be useful as a marker for predicting follicle growth in patients with POI. Methods: Using an ultrasensitive enzyme-linked immunosorbent assay (ELISA) kit, we found very low serum AMH levels in patients with POI. We assessed the follicle growth of each patient during each cycle to clarify the usefulness of measuring serum AMH levels for predicting follicle growth in patients with POI under hormone replacement therapy (HRT). Results: A total of 91 cycles of 19 patients with POI were analyzed in this study. Five patients presented with positive serum AMH levels during the observational periods, and all five experienced follicle growth. Only two of the 14 patients with negative serum AMH levels had follicle growth. Serum AMH and follicle-stimulating hormone (FSH) levels in cycles with follicle growth were significantly higher than in cycles without follicle growth. The median serum AMH level (2.77 pg/mL; 25th, 75th percentiles: 0.0, 9.64) in cycles with follicle growth was lower than the lower limit of detection of conventional AMH ELISA kits. The positive predictive value of positive serum AMH levels for follicle growth was higher than that of FSH (< 10 mIU/mL).Conclusions: Measurement of very low levels of serum AMH using picoAMH assays is useful for prediction of follicle growth in patients with POI under HRT conditions. Trial registration: UMIN-CTR UMIN000029464. Retrospectively registered on April 4, 2018. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000033550