The relationship between H19 and parameters of ovarian reserve

Reprod Biol Endocrinol. 2020 May 13;18(1):46. doi: 10.1186/s12958-020-00578-z.


Context: The H19 long noncoding RNA (lncRNA) belongs to a highly conserved, imprinted gene cluster involved in embryonic development and growth control. We previously described a novel mechanism whereby the Anti-mullerian hormone (Amh) appears to be regulated by H19. However, the relationship between circulating H19 and markers of ovarian reserve including AMH not been investigated.

Objective: To determine whether H19 expression is altered in women with decreased ovarian reserve.

Design: Experimental study.

Setting: Yale School of Medicine (New Haven, USA) and Gazi University School of Medicine (Ankara, Turkey).

Patients or other participants: A total of 141 women undergoing infertility evaluation and treatment.

Intervention: Collection of discarded blood samples and cumulus cells at the time of baseline infertility evaluation and transvaginal oocyte retrieval, respectively.

Main outcome measure: Serum and cumulus cell H19 expression.

Results: Women with diminished ovarian reserve (as determined by AMH) had significantly lower serum H19 expression levels as compared to controls (p < 0.01). Serum H19 was moderately positively correlated with serum AMH. H19 expression was increased 3.7-fold in cumulus cells of IVF patients who demonstrated a high response to gonadotropins, compared to low responders (p < 0.05).

Conclusion: In this study, we show that downregulation of H19 in serum and cumulus cells is closely associated with decreased ovarian reserve, as measured by decreased AMH levels and reduced oocyte yield at oocyte retrieval. Further study with expanded sample sizes is necessary to determine whether H19 may be of use as a novel biomarker for diminished ovarian reserve.

Keywords: AMH; H19; Noncoding RNA; Ovarian reserve; ncRNA.

MeSH terms

  • Adult
  • Anti-Mullerian Hormone / blood
  • Biomarkers / analysis
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cell Count
  • Cumulus Cells / metabolism*
  • Drug Resistance / genetics
  • Female
  • Fertility Agents, Female / therapeutic use
  • Gene Expression
  • Humans
  • Infertility, Female / diagnosis
  • Infertility, Female / genetics
  • Infertility, Female / metabolism*
  • Infertility, Female / pathology
  • Oocyte Retrieval
  • Oocytes / pathology
  • Ovarian Reserve / physiology*
  • Ovulation Induction
  • RNA, Long Noncoding / analysis
  • RNA, Long Noncoding / blood*
  • RNA, Long Noncoding / metabolism*
  • Retrospective Studies
  • Treatment Outcome


  • Biomarkers
  • Fertility Agents, Female
  • H19 long non-coding RNA
  • RNA, Long Noncoding
  • Anti-Mullerian Hormone