Human Chorionic Gonadotropin: Does It Affect Human Endometrial Morphology In Vivo?

 

 Buy Article Permissions and Reprints

ABSTRACT

Human chorionic gonadotropin (hCG) is widely used as a surrogate to luteinizing hormone (LH) to trigger ovulation in controlled ovarian hyperstimulation (COH). Yet this molecule may exert direct effects on the endometrium. These effects, not mediated by ovarian hormones, are probably a consequence of stimulation of endometrial hCG/LH receptors. Because the half-life of hCG differs markedly from that of LH, possible pharmacological effects of hCG on the endometrium could alter endometrial receptivity in COH. Arguments supporting a clinical action of gonadotropins, and hCG in particular, on the endometrium abound. Notably, evidence has been reported of decidualization of stromal cells of the human endometrium in vitro as a result of exposure to gonadotropins, including hCG. The present article discusses, from a clinical standpoint, the main basis supporting the hypothesis that hCG administration as commonly used in infertility treatments may exert direct effects in vivo on endometrial histology and partake in endometrial transformations of the luteal phase. Preliminary results suggest that endometrial effects of hCG exist in vivo and should be taken into account when assessing the endometrial effects of hormones.

REFERENCES

• 1 Paulson R J, Sauer M V, Lobo R A. Embryo implantation after human in vitro fertilization: importance of endometrial receptivity.  Fertil Steril . 1990;  53 870-874
  PubMedGoogle Scholar
• 2 Check J H, Nowroozi K, Chase J, Nazari A, Braithwaite C. Comparison of pregnancy rates following in vitro fertilization-embryo transfer between the donors and the recipients in a donor oocyte program.  J Assist Reprod Genet . 1992;  9 248-250
  PubMedGoogle Scholar
• 3 Forman R, Fries N, Testart J, Belaisch-Allart J, Hazout A, Frydman R. Evidence for an adverse effect of elevated serum estradiol concentrations on embryo implantation.  Fertil Steril . 1988;  49 118-122
  PubMedGoogle Scholar
• 4 Gidley-Baird A A, O'Neill C, Sinosich M J, Porter R N, Pike I L, Saunders D M. Failure to implantation in human in vitro fertilization and embryo transfer patients: the effect of the altered progesterone/estrogen ratios in humans and mice.  Fertil Steril . 1986;  45 69-74
  PubMedGoogle Scholar
• 5 Fanchin R, de Ziegler D, Taieb J, Hazout A, Frydman R. Premature elevation of plasma progesterone alters pregnancy rates of in vitro fertilization and embryo transfer.  Fertil Steril . 1993;  59 1090-1094
  PubMedGoogle Scholar
• 6 Kolb B A, Paulson R J. The luteal phase of cycles utilizing controlled ovarian hyperstimulation and the possible impact of this hyperstimulation on embryo implantation.  Am J Obstet Gynecol . 1997;  176 1262-1267
  CrossrefPubMedGoogle Scholar
• 7 de Ziegler D, Fanchin R. Endometrial receptivity in controlled ovarian hyperstimulation (COH): the hormonal factor.  Ann N Y Acad Sci . 1994;  734 209-220
  PubMedGoogle Scholar
• 8 Rao C V. The beginning of a new era in reproductive biology and medicine: expression of low levels of functional luteinizing hormone/human chorionic gonadotropin receptors in nongonadal tissues.  J Physiol Pharmacol . 1996;  47 41-53
  PubMedGoogle Scholar
• 9 Reshef E, Lei Z M, Rao C V, Pridham D D, Chegini N, Luborsky J L. The presence of gonadotropin receptors in nonpregnant human uterus, human placenta, fetal membranes, and decidua.  J Clin Endocrinol Metab . 1990;  70 421-430
  PubMedGoogle Scholar
• 10 Lei Z M, Reshef E, Rao V. The expression of human chorionic gonadotropin/luteinizing hormone receptors in human endometrial and myometrial blood vessels.  J Clin Endocrinol Metab . 1992;  75 651-659
  CrossrefPubMedGoogle Scholar
• 11 Bernardini L, Moretti-Rojas I, Brush M, Rojas F J, Balmaceda J P. Status of hCG/LH receptor and G proteins in human endometrium during artificial cycles of hormone replacement therapy.  J Soc Gynecol Invest . 1995;  2 630-635
  CrossrefPubMedGoogle Scholar
• 12 Tang B, Gurpide E. Direct effect of gonadotropins on decidualization of human endometrial stroma cells.  J Steroid Biochem Mol Biol . 1993;  47 115-121
  CrossrefPubMedGoogle Scholar
• 13 Diczfalusy E, Harlin J. Clinical-pharmacological studies on human menopausal gonadotrophin.  Hum Reprod . 1988;  3 21-27
  PubMedGoogle Scholar
• 14 Noyes R W, Hertig A T, Rock J. Dating the endometrial biopsy.  Fertil Steril . 1950;  1 3-15
  PubMedGoogle Scholar
• 15 Han S W, Lei Z M, Rao C V. Up-regulation of cyclooxygenase-2 gene expression by chorionic gonadotropin during the differentiation of human endometrial stromal cells into decidua.  Endocrinology . 1996;  137 1791-1797
  CrossrefPubMedGoogle Scholar
• 16 Frank G R, Brar A K, Cedars M I, Handwerger S. Prostaglandin E2 enhances human endometrial stromal cell differentiation.  Endocrinology . 1994;  134 258-263
  CrossrefPubMedGoogle Scholar
• 17 Han S W, Lei Z M, Rao C V. Treatment of human endometrial stromal cells with chorionic gonadotropin promotes their morphological and functional differentiation into decidua.  Mol Cell Endocrinol . 1999;  25 7-16
  PubMedGoogle Scholar
• 18 Garcia J E, Acosta A A, Hsiu J G, Jones Jr W H. Advanced endometrial maturation after ovulation induction with human menopausal gonadotropin/human chorionic gonadotropin for in vitro fertilization.  Fertil Steril . 1984;  41 31-35
  PubMedGoogle Scholar
• 19 Rosenwaks Z. Donor eggs: their application in modern reproductive technologies.  Fertil Steril . 1987;  47 895-909
  PubMedGoogle Scholar
• 20 Steingold K, Stumpf P, Kreiner D, Liu H C, Navot D, Rosenwaks Z. Estradiol and progesterone replacement regimens for the induction of endometrial receptivity.  Fertil Steril . 1989;  52 756-760
  PubMedGoogle Scholar
• 21 Navot D, Anderson T L, Droesch K, Scott R T, Kreiner D, Rosenwaks Z. Hormonal manipulation of endometrial maturation.  J Clin Endocrinol Metab . 1989;  68 801-807
  PubMedGoogle Scholar
• 22 Fanchin R, de Ziegler D, Taieb J, Olivennes F, Castracane V D, Frydman R. Human chorionic gonadotropin administration fails to increase androgen levels in controlled ovarian hyperstimulation.  Fertil Steril . 2000;  73 275-279
  CrossrefPubMedGoogle Scholar
• 23 Fanchin R, Peltier E, Righini C, Olivennes F, de Ziegler D, Frydman R. Direct effects of hCG on the human endometrium. The 45th Annual Meeting of The Society for Gynecologic Investigation, Atlanta, 1998, abstract 288
  Google Scholar
• 24 Stewart E A, Sahakian M, Rhoades A, Van Voorhis J B, Nowak R A. Messenger ribonucleic acid for the gonadal luteinizing hormone/human chorionic gonadotropin receptor is not present in human endometrium.  Fertil Steril . 1999;  71 368-372
  CrossrefPubMedGoogle Scholar
• 25 Saal W, Heinz-Jürgen G, Hengst W, Happ J. Pharmacodynamics and pharmacokinetics after subcutaneous and intramuscular injection of human chorionic gonadotropin.  Fertil Steril . 1991;  56 225-229
  PubMedGoogle Scholar
• 26 Han S W, Lei Z M, Rao C V. Homologous down-regulation of luteinizing hormone/chorionic gonadotropin receptors by increasing the degradation of receptor transcripts in human uterine endometrial stromal cells.  Biol Reprod . 1998;  57 158-164
  PubMedGoogle Scholar
• 27 Lelaidier C, de Ziegler D, Gaetano J, Hazout A, Fernandez H, Frydman R. Controlled preparation of the endometrium with exogenous oestradiol and progesterone: a novel regimen not using a gonadotrophin-releasing hormone agonist.  Hum Reprod . 1992;  7 1353-1356
  PubMedGoogle Scholar
• 28 Li T C, Serle E, Warren M A, Cooke I D. Is endometrial development in the peri-implantation period influenced by high concentrations of luteinizing hormone in the follicular phase?.  Hum Reprod . 1993;  8 1021-1024
  PubMedGoogle Scholar
• 29 Imoedemhe D A, Sigue A B, Pacpaco E L, Olazo A B. Stimulation of endogenous surge of luteinizing hormone with gonadotropin-releasing hormone analog after ovarian stimulation for in vitro fertilization.  Fertil Steril . 1991;  55 328-332
  PubMedGoogle Scholar