Skip to main content

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 Sciences volume 28, pages 31–36 (2021)Cite this article

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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig 1

References

  1. Nelson LM. Primary ovarian insufficiency. N Engl J Med. 2009;360(6):606–14.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet. 2010;376(9744):911–21.

    PubMed  Article  Google Scholar 

  3. Nelson LM, Anasti JN, Kimzey LM, Defensor RA, Lipetz KJ, White BJ, et al. Development of luteinized graafian follicles in patients with karyotypically normal spontaneous premature ovarian failure. J Clin Endocrinol Metab. 1994;79(5):1470–5.

    CAS  PubMed  Google Scholar 

  4. Miyazaki K, Miki F, Uchida S, Masuda H, Uchida H, Maruyama T. Serum estradiol level during withdrawal bleeding as a predictive factor for intermittent ovarian function in women with primary ovarian insufficiency. Endocr J. 2015;62(1):93–9.

    CAS  PubMed  Article  Google Scholar 

  5. Surrey ES, Cedars MI. The effect of gonadotropin suppression on the induction of ovulation in premature ovarian failure patients. Fertil Steril. 1989;52(1):36–41.

    CAS  PubMed  Article  Google Scholar 

  6. Tartagni M, Cicinelli E, De Pergola G, De Salvia MA, Lavopa C, Loverro G. Effects of pretreatment with estrogens on ovarian stimulation with gonadotropins in women with premature ovarian failure: a randomized, placebo-controlled trial. Fertil Steril. 2007;87(4):858–61.

    CAS  PubMed  Article  Google Scholar 

  7. Broer SL, Broekmans FJM, Laven JSE, Fauser BCJM. Anti-Müllerian hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update. 2014;20(5):688–701.

    CAS  PubMed  Article  Google Scholar 

  8. Iwase A, Osuka S, Goto M, Murase T, Nakamura T, Takikawa S, et al. Clinical application of serum anti-Müllerian hormone as an ovarian reserve marker: a review of recent studies. J Obstet Gynaecol Res. 2018;44(6):998–1006.

    PubMed  Article  Google Scholar 

  9. Visser JA, Schipper I, Laven JSE, Themmen APN. Anti-Müllerian hormone: an ovarian reserve marker in primary ovarian insufficiency. Nat Rev Endocrinol. 2012;8(6):331–41.

    CAS  PubMed  Article  Google Scholar 

  10. Iwase A, Nakamura T, Kato N, Goto M, Takikawa S, Kondo M, et al. Anti-Müllerian hormone levels after laparoscopic cystectomy for endometriomas as a possible predictor for pregnancy in infertility treatments. Gynecol Endocrinol. 2016;32(4):293–7.

    CAS  PubMed  Article  Google Scholar 

  11. Iwase A, Nakamura T, Osuka S, Takikawa S, Goto M, Kikkawa F. Anti-Müllerian hormone as a marker of ovarian reserve: what have we learned, and what should we know? Reprod Med Biol. 2016;15(3):127–36.

    CAS  PubMed  Article  Google Scholar 

  12. Saito A, Iwase A, Nakamura T, Osuka S, Bayasula, Murase T, et al. Involvement of mesosalpinx in endometrioma is a possible risk factor for decrease of ovarian reserve after cystectomy: a retrospective cohort study. Reprod Biol Endocrinol. 2016;14(1):72.

    PubMed  PubMed Central  Article  Google Scholar 

  13. Iwase A, Osuka S, Nakamura T, Kato N, Takikawa S, Goto M, et al. Usefulness of the ultrasensitive anti-Müllerian hormone assay for predicting true ovarian reserve. Reprod Sci. 2016;23(6):756–60.

    CAS  PubMed  Article  Google Scholar 

  14. Su HI, Sammel MD, Homer MV, Bui K, Haunschild C, Stanczyk FZ. Comparability of anti-Müllerian hormone levels among commercially available immunoassays. Fertil Steril. 2014;101(6):1766–72.e1.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. Check JH, Nowroozi K, Chase JS, Nazari A, Shapse D, Vaze M. Ovulation induction and pregnancies in 100 consecutive women with hypergonadotropic amenorrhea. Fertil Steril. 1990;53(5):811–6.

    CAS  PubMed  Article  Google Scholar 

  17. Li HWR, Wong BPC, Ip WK, Yeung WSB, Ho PC, Ng EHY. Comparative evaluation of three new commercial immunoassays for anti-Müllerian hormone measurement. Hum Reprod. 2016;31(12):2796–802.

    CAS  PubMed  Article  Google Scholar 

  18. Streuli I, Fraisse T, Pillet C, Ibecheole V, Bischof P, de Ziegler D. Serum anti-Müllerian hormone levels remain stable throughout the menstrual cycle and after oral or vaginal administration of synthetic sex steroids. Fertil Steril. 2008;90(2):395–400.

    CAS  PubMed  Article  Google Scholar 

  19. Li HWR, Wong CYG, Yeung WSB, Ho PC, Ng EHY. Serum anti-Müllerian hormone level is not altered in women using hormonal contraceptives. Contraception. 2011;83(6):582–5.

    CAS  PubMed  Article  Google Scholar 

  20. Burks HR, Ross L, Opper N, Paulson E, Stanczyk FZ, Chung K. Can highly sensitive antimüllerian hormone testing predict failed response to ovarian stimulation? Fertil Steril. 2015;104(3):643–8.

    CAS  PubMed  Article  Google Scholar 

  21. Reijnders IF, Nelen WLDM, Inthout J, Van Herwaarden AE, Braat DDM, Fleischer K. The value of anti-Müllerian hormone in low and extremely low ovarian reserve in relation to live birth after in vitro fertilization. Eur J Obstet Gynecol Reprod Biol. 2016;200:45–50.

    CAS  PubMed  Article  Google Scholar 

  22. FDA news release: FDA permits marketing of a diagnostic test to aid in the determination of menopausal status. 24 Oct 2018. https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-diagnostic-test-aid-determination-menopausal-status. Accessed 15 Jan 2020.

Download references

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Satoko Osuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bayasula
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Natsuki Nakanishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tomohiko Murase
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomoko Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maki Goto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tomomi Kotani
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Akira Iwase
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fumitaka Kikkawa
    View author publications

    You can also search for this author in PubMed Google Scholar

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.

Ethics declarations

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).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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

Keywords

  • Primary ovarian insufficiency
  • Anti-Müllerian hormone
  • picoAMH
  • Ultrasensitive assay
  • Follicle growth