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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

  • Reproductive Endocrinology: Original Article
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Abstract

Patients with primary ovarian insufficiency (POI) occasionally present with follicle growth; however, accurately predicting cycles accompanied by follicle growth is challenging. Early-stage follicles produce serum anti-Müllerian hormone (AMH), a useful marker of ovarian reserve. Therefore, serum AMH levels indicate growth of small follicles (which are difficult to detect ultrasonographically) and may predict follicle growth in patients with POI. Using an ultrasensitive enzyme-linked immunosorbent assay (ELISA) kit, we observed very low serum AMH levels in patients with POI. We further evaluated follicle growth in each patient during each cycle to determine the usefulness of measuring serum AMH levels as a predictor of follicle growth in patients with POI who receive hormone replacement therapy (HRT). We investigated 19 patients with POI in whom we analyzed 91 cycles; 14 cycles showed positive and 77 cycles showed negative results on serum AMH testing. The rate of cycles showing follicle growth in AMH-positive cycles was higher than that in AMH-negative cycles (64.3% vs. 6.5%, p = 0.0001). The median serum AMH level (7.7 pg/mL [25th and 75th percentiles 4.6 pg/mL and 22.3 pg/mL, respectively]) in AMH-positive cycles 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 follicle-stimulating hormone (< 10 mIU/mL). These results indicate that a very low level of serum AMH detected using picoAMH assays is a useful predictor of follicle growth in patients with POI receiving HRT.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Yukiyo Kasahara, Satoko Osuka, Natsuki Nakanishi, Tomohiko Murase, Tomoko Nakamura, Maki Goto, Tomomi Kotani & Fumitaka Kikkawa

  2. Department of Maternal and Perinatal Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Satoko Osuka & Tomomi Kotani

  3. Bell Research Center for Reproductive Health and Cancer, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan

    Bayasula

  4. Department of Obstetrics and Gynecology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan

    Akira Iwase

Authors
  1. Yukiyo Kasahara
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  2. Satoko Osuka
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  3. Bayasula
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  4. Natsuki Nakanishi
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  5. Tomohiko Murase
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  6. Tomoko Nakamura
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  7. Maki Goto
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  8. Tomomi Kotani
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  9. Akira Iwase
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  10. Fumitaka Kikkawa
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Contributions

YK performed the data analysis and the writing of the manuscript. SO analyzed and interpreted the data. Bayasula measured serum levels using the picoAMH assays. Data were collected and analyzed by TM, NN, and TN. Interpretation of the data was done by MG, TK, AI, and FK. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Satoko Osuka.

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Conflict of Interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethics Approval

The study was approved by the ethical committee of Nagoya University Hospital (approval reference number 422), registered as a clinical trial (UMIN000029464) on April 4, 2018. All procedures were performed according to the Declaration of Helsinki regarding human experimentation.

Statement of Informed Consent

Informed consent was obtained from all patients prior to enrollment.

Code Availability

Prism software (Prism 8; GraphPad Software, San Diego, CA USA) and EZR software (Version 1.40; Saitama Medical Center, Jichi Medical University, Saitama, Japan), the latter of which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria).

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Kasahara, Y., Osuka, S., Bayasula et al. 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. Reprod. Sci. 28, 31–36 (2021). https://doi.org/10.1007/s43032-020-00278-4

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  • DOI: https://doi.org/10.1007/s43032-020-00278-4

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