Archives of Gynecology and Obstetrics

, Volume 300, Issue 6, pp 1773–1783 | Cite as

Changes and correlations of anti-Müllerian hormone and stem-cell factors in different ovarian reserve patients during GnRH-antagonist protocol and the effects on controlled ovarian hyperstimulation outcomes

  • Xiao-Hui Liu
  • Xiao-Hua WuEmail author
  • Shuai Yang
Gynecologic Endocrinology and Reproductive Medicine



To explore the changes and correlations of anti-Müllerian hormone (AMH) and stem-cell factors (SCF) in different ovarian reserve patients during controlled ovarian hyperstimulation (COH) and the effects on COH outcomes.


Serum at six different timepoints during GnRH-antagonist protocol and follicular fluid (FF) on oocyte retrieval day of 52 patients with polycystic ovary syndrome (PCOS), 61 patients with normal ovarian reserve (NOR) and 42 patients with diminished ovarian reserve (DOR) were collected. AMH and SCF were assessed using enzyme-linked immunosorbent assay.


During COH, AMH in the PCOS group was the highest, but SCF did the opposite, and serum AMH gradually decreased, while SCF inversely increased. In the PCOS group, SCF on the first and fourth days of gonadotropin (Gn) administration was negative with Gn dosage (r = − 0.362, P < 0.05; r = − 0.344, P < 0.05). In the NOR group, the basal AMH was also negative with Gn dosage (r = − 0.297, P < 0.05) and positive with COH outcomes (number of retrieved oocytes, MII oocytes, and 2PN fertilization) as well as serum SCF after Gn administration. In the DOR group, both AMH and SCF were significantly associated with COH outcomes. Serum AMH in the DOR group after Gn administration and FF AMH showed a negative correlation with SCF.


Serum AMH decreased, while SCF increased during COH. AMH and SCF are effective for Gn time and dosage adjustment and predicting COH outcomes for NOR and DOR patients. In addition, serum AMH in DOR patients after Gn administration and FF AMH has a negative effect on SCF.


AMH SCF Follicular fluid PCOS DOR 



Thanks all the staff, nurses, and physicians at the Reproductive Medicine Center for their support in this study. The authors declared no potential conflicts of the research, authorship, or publication of this article.

Author contribution

XHL project development, sample and data collection, and manuscript writing. XHW project development and writing review. SY data collection


This study was supported by the Graduate Student’s Research and Innovation Fund of Heibei Province Department of Education in China (CXZZBS2018082) and the 2013 Chinese People’s Liberation Army Logistics Research Project (BBJ13C001).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Jeppesen JV, Anderson RA, Kelsey TW et al (2013) Which follicles make the most anti-Mullerian hormone in humans? Evidence for an abrupt decline in AMH production at the time of follicle selection. Mol Hum Reprod 19:519–527. CrossRefPubMedGoogle Scholar
  2. 2.
    Josso N (2019) Anti-Müllerian hormone: a look back and ahead. Reproduction. CrossRefPubMedGoogle Scholar
  3. 3.
    Sermondade N, Sonigo C, Sifer C et al (2019) Serum antimüllerian hormone is associat -ed with the number of oocytes matured in vitro and with primordial follicle density in candidates for fertility preservation. Fertil Steril 111:357–362. CrossRefPubMedGoogle Scholar
  4. 4.
    Kwee J, Schats R, Mcdonnell J et al (2008) Evaluation of anti-Müllerian hormone as a test for the prediction of ovarian reserve. Fertil Steril 90:740–743. CrossRefGoogle Scholar
  5. 5.
    Kunt C, Ozaksit G, Keskin Kurt R et al (2011) Anti-Mullerian hormone is a better marker than inhibin B, follicle stimulating hormone, estradiol or antral follicle count in predicting the outcome of in vitro fertilization. Arch Gynecol Obstet 283:1415–1421. CrossRefPubMedGoogle Scholar
  6. 6.
    Baker VL, Gracia C, Glassner MJ et al (2018) Multicenter evaluation of the access AMH antimullerian hormone assay for the prediction of antral follicle count and poor ovarian response to controlled ovarian stimulation. Fertil Steril 31:506–513CrossRefGoogle Scholar
  7. 7.
    Xu J, Bishop CV, Lawson MS et al (2016) Anti-Müllerian hormone promotes pre- antral follicle growth, but inhibits antral follicle maturation and dominant follicle selection in primates. Hum Reprod 31:1522–1530. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Zhang T, Deng L, Xiong Q (2018) Anti-Müllerian hormone inhibits proliferation and induces apoptosis in epithelial ovarian cancer cells by regulating the cell cycle and decreasing the secretion of stem cell factor. Oncol Lett 16:3260–3266. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Zhang X, Zhang H, Gao Q et al (2015) Sohlh2 inhibits the apoptosis of mouse primordial follicle oocytes via C-kit/PI3 K/Akt/Foxo3a signalling pathway. Reprod Biomed Online 30:514–521. CrossRefPubMedGoogle Scholar
  10. 10.
    Jeong W, Jung S, Bazer F et al (2017) Stem cell factor-induced AKT cell signaling pathway: effects on porcine trophectoderm and uterine luminal epithelial cells. Gen Comp Endocrinol 250:113–121. CrossRefPubMedGoogle Scholar
  11. 11.
    Tuck AR, Mottershead DG, Fernandes HA et al (2015) Mouse GDF-9 decreases KITL gene expression in human granulosa cells. Endocrine 48:686–695. CrossRefPubMedGoogle Scholar
  12. 12.
    Gizzo S, Quaranta M, Andrisani A (2016) Serum stem cell factor assay in elderly poor responder patients undergoing IVF: a new biomarker to customize follicle aspiration cycle by cycle. Reprod Sci 23:61–68. CrossRefPubMedGoogle Scholar
  13. 13.
    Cela V, Obino MER, Alberga Y et al (2018) Ovarian response to controlled ovarian stimulation in women with different polycystic ovary syndrome phenotypes. Gynecol Endocrinol 34:518–523. CrossRefPubMedGoogle Scholar
  14. 14.
    Morin SJ, Patounakis G, Juneau CR, Neal SA, Scott RT Jr, Seli E (2018) Diminished ovarian reserve and poor response to stimulation in patients < 38 years old: a quantitative but not qualitative reduction in performance. Hum Reprod. CrossRefPubMedGoogle Scholar
  15. 15.
    Tan J, Zou Y, Wu XW et al (2017) Increased SCF in follicular fluid and granulosa cells positively correlates with oocyte maturation, fertilization, and embryo quality in humans. Reprod Sci 24:1544–1550. CrossRefPubMedGoogle Scholar
  16. 16.
    The Rotterdam ESHRE/ASRM (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41–47. CrossRefGoogle Scholar
  17. 17.
    Cohen J, Chabbert-Buffet N, Darai E (2015) Diminished ovarian reserve, premature ovarian failure, poor ovarian responder aplea for universal definitions. J Assist Reprod Genet 32:1709–1712. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tan J, Wen XY, Su Q (2016) Reduced expression of SCF in serum and follicle from patients with polycystic ovary syndrome. Eur Rev Med Pharmacol Sci 20:5049–5057PubMedGoogle Scholar
  19. 19.
    Gorsic LK, Dapas M, Legro RS et al (2019) Functional genetic variation in the anti-müllerian hormone pathway in women with polycystic ovary syndrome. J Clin Endocrinol Metab. CrossRefPubMedGoogle Scholar
  20. 20.
    Dewailly D, Robin G, Peigne M et al (2016) Interactions between androgens, FSH, anti-Müllerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary. Hum Reprod Update 22:709–724. CrossRefPubMedGoogle Scholar
  21. 21.
    Liu XY, Yang YJ, Tang CL et al (2019) Elevation of antimüllerian hormone in women with polycystic ovary syndrome undergoing assisted reproduction: effect of insulin. Fertil Steril 111:157–167. CrossRefPubMedGoogle Scholar
  22. 22.
    Guedikian AA, Lee AY, Grogan TR et al (2018) Reproductive and metabolic determinants of granulosa cell dysfunction in normal-weight women with polycystic ovary syndrome. Fertil Steril 109:508–515CrossRefGoogle Scholar
  23. 23.
    Salmassi A, Zorn S, Mettler L et al (2011) Circulating concentration of stem cell factor in serum of stimulated IVF patients. Reprod Biomed Online 22:140–147. CrossRefPubMedGoogle Scholar
  24. 24.
    Li Y, Nie M, Liu Y et al (2015) The dynamic changes of anti-Mullerian hormone and inhibin B during controlled ovarian hyperstimulation in decreased ovarian reserve women and the effect on clinical outcome. Gynecol Endocrinol 31(450–4):53. CrossRefGoogle Scholar
  25. 25.
    Liberty G, Ben-Chetrit A, Margalioth EJ et al (2010) Does estrogen directly modulate anti-müllerian hormone secretion in women? Fertil Steril 94:2253–2256. CrossRefPubMedGoogle Scholar
  26. 26.
    Urrutia M, Grinspon RP, Rey RA et al (2019) Comparing the role of anti-Müllerian hormone as a marker of FSH action in male and female fertility. Expert Rev Endocrinol Metab 4:203–214. CrossRefGoogle Scholar
  27. 27.
    Devillers M, Petit F, Cluzet V et al (2018) FSH inhibits AMH to support ovarian estradiol synthesis in infantile mice. J Endocrinol. CrossRefGoogle Scholar
  28. 28.
    Zhang Y, Wang SF, Zheng JD et al (2016) Effects of testosterone on the expression levels of AMH, VEGF and HIF-1α in mouse granulosa cells. Exp Ther Med 12:883–888. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Fang Y, Lu X, Liu L et al (2016) Vascular endothelial growth factor induces anti-Müllerian hormone receptor 2 overexpression in ovarian granulosa cells of in vitro fertilization/intracytoplasmic sperm injection patients. Mol Med Rep 13:5157–5162. CrossRefPubMedGoogle Scholar
  30. 30.
    Bi LY, Zhao DA, Yang DS et al (2015) Effects of autologous SCF- and G-CSF-mobilized bone marrow stem cells on hypoxia-inducible factor-1 in rats with ischemia-reperfusion renal injury. Genet Mol Res 27:4102–4112. CrossRefGoogle Scholar
  31. 31.
    Shayya RF, Rosencrantz MA, Chuan SS et al (2014) Decreased inhibin B responses following recombinant human chorionic gonadotropin administration in normal women and women with polycystic ovary syndrome. Fertil Steril 101:275–279. CrossRefPubMedGoogle Scholar
  32. 32.
    Lee JR, Kim SH, Jee BC, Kim SM et al (2010) Anti-Mullerian hormone dynamics during contro -lled ovarian hyperstimulation and optimal timing of measurement for outcome prediction. Hum Reprod 25:2597–2604. CrossRefPubMedGoogle Scholar
  33. 33.
    Vembu R, Reddy NS (2017) Serum AMH level to predict the hyper response in women with PCOS and non-PCOS undergoing controlled ovarian stimulation in art. J Hum Reprod Sci 10:91–94. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Friis PJ, Løkkegaard E, Andersen LF et al (2019) A randomized controlled trial of AMH-based individualized FSH dosing in a GnRH antagonist protocol for IVF. Hum Reprod Open 27:1–11. CrossRefGoogle Scholar
  35. 35.
    Stracquadanio M, Ciotta L, Palumbo MA et al (2018) Relationship between serum anti- Mullerian hormone and intrafollicular AMH levels in PCOS women. Gynecol Endocrinol 34:223–228. CrossRefPubMedGoogle Scholar
  36. 36.
    Parrott JA, Skinner MK (1999) Kite-ligand/stem cell factor induces primordial follicle development and initiates folliculogeness. Endocrinology 140:4262–4271. CrossRefPubMedGoogle Scholar
  37. 37.
    Thuwanut P, Comizzoli P, Wildt DE et al (2017) Stem cell factor promotes in vitro ovarian follicle development in the domestic cat by upregulating c-kit mRNA expression and stimulating the phosphatidylinositol 3-kinase/AKT pathway. Reprod Fertil Dev 29:1356–1368. CrossRefPubMedGoogle Scholar
  38. 38.
    Sneed ML, Uhler ML, Grotjan HE et al (2008) Body mass index: impact on IVF success appears age-related. Hum Reprod 23:1835–1839. CrossRefPubMedGoogle Scholar
  39. 39.
    Baker VL, Gracia C, Glassner MJ et al (2018) Multicenter evaluation of the Access AMH antimüllerian hormone assay for the prediction of antral follicle count and poor ovarian response to controlled ovarian stimulation. Fertil Steril 110:506–513. CrossRefPubMedGoogle Scholar
  40. 40.
    Hu R, Wang FM, Yu L et al (2014) Antimeullerian hormone regulates stem cell factor expression in human granulosa cells. Fertil Steril 102:1742–1750. CrossRefPubMedGoogle Scholar
  41. 41.
    Zhang JF, Yu CM, Yan LL et al (2018) Effect of anti-mullerian hormone on stem cell factor in serum, follicular fluid and ovarian granular cells of polycystic ovarian syndrome patients. Eur Rev Med Pharmacol Sci 22:7877–7882. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Hebei Medical UniversityShijiazhuangPeople’s Republic of China
  2. 2.Reproductive Medicine CenterShijiazhuang Obstetrics and Gynecology HospitalShijiazhuangPeople’s Republic of China
  3. 3.Nanxishan HospitalGuilinPeople’s Republic of China

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