Prevention of endometrial apoptosis: randomized prospective comparison of human chorionic gonadotropin versus progesterone treatment in the luteal phase

J Clin Endocrinol Metab. 2005 Apr;90(4):2351-6. doi: 10.1210/jc.2004-2130. Epub 2005 Jan 25.

Abstract

To study control of apoptosis in human endometrium, we examined late luteal-phase endometrial biopsies obtained in the late luteal phase for evidence of apoptosis and compared the effects of exogenous human chorionic gonadotropin (hCG) and progesterone on this process. Using a controlled, prospective, and randomized study design, 12 healthy, fertile, reproductive-age women (ages 20-34 yr) with regular menstrual cycles (range, 26-32 d) were recruited. Each underwent an endometrial biopsy 12 d after a urinary LH surge in a control and treatment cycle. After biopsy in a natural cycle, subjects were randomized to receive luteal doses of either 200 mg intravaginal progesterone (d 18-27) or a single im injection of 10,000 IU of hCG (d 19) followed by repeat endometrial biopsy and collection of serum on d 26. Apoptosis was assessed by DNA laddering, localizing apoptotic bodies using immunofluorescent labeling of DNA fragments (the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method), and immunohistochemical assessment of apoptosis markers bcl-2, bcl-x, and bax. Serum progesterone levels were compared between treatment groups. Evidence of apoptosis in control cycles was significantly reduced in endometrium after both luteal-phase treatments. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling results demonstrated significantly less apoptosis in the hCG treatment group compared with controls. Immunostaining for bcl-2 was higher in hCG- and progesterone-treated cycles, whereas bax expression was decreased and bcl-x immunostaining was not different between treatments. Serum progesterone levels were highest in the hCG-treated group, although statistical significance was not reached (P = 0.08). These results demonstrate that signs of apoptosis, already apparent by d 26 of the menstrual cycle can be reduced with either hCG or progesterone treatment. The clinical utility of these findings includes a rational use of luteal-phase support for treatment of women with infertility and/or recurrent pregnancy loss.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Apoptosis / drug effects*
  • Chorionic Gonadotropin / pharmacology*
  • DNA Fragmentation
  • Endometrium / drug effects*
  • Endometrium / pathology
  • Female
  • Humans
  • In Situ Nick-End Labeling
  • Luteal Phase
  • Progesterone / blood
  • Progesterone / pharmacology*
  • Prospective Studies
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • bcl-2-Associated X Protein
  • bcl-X Protein

Substances

  • BAX protein, human
  • BCL2L1 protein, human
  • Chorionic Gonadotropin
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Progesterone