Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
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Comparison of Expression of Endometrial Prolactin in Infertile Women with Luteal Phase Defect According to Clomiphene Citrate Administration

황체기 결함이 있는 불임환자에서 클로미펜 투여 여부에 따른 자궁내막 내의 Prolactin의 발현 양상의 비교 연구

  • Goh, Seung-Hee (Department of Obstetrics and Gynecology, School of Medicine, Inje University) ;
  • Hwang, Jung-Hye (Department of Obstetrics & Gynecology, School of Medicine, Hanyang University) ;
  • Sim, Ey-Sub (Department of Obstetrics and Gynecology, School of Medicine, Inje University) ;
  • Koh, Jae-Whoan (Department of Obstetrics and Gynecology, School of Medicine, Inje University) ;
  • Kim, Yong-Bong (Department of Obstetrics and Gynecology, School of Medicine, Inje University) ;
  • Jang, Se-Jin (Department of Pathology, School of Medicine, Hanyang University)
  • 고승희 (인제대학교 의과대학 산부인과학교실) ;
  • 황정혜 (한양대학교 의과대학 산부인과학교실) ;
  • 심의섭 (인제대학교 의과대학 산부인과학교실) ;
  • 고재환 (인제대학교 의과대학 산부인과학교실) ;
  • 김용봉 (인제대학교 의과대학 산부인과학교실) ;
  • 장세진 (한양대학교 의과대학 병리학교실)
  • Published : 2003.03.30
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Abstract

Objective : Clomiphene citrate is one of the most commonly used drugs in the treatment of infertility, but the pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to its antiestrogenic effect on the endometrium. Endometrial prolactin is considered to be a marker and an inducer of predecidualization that is characteristic of secretory endometrium. The purpose of this study was to evaluate the association of clomiphene citrate and unsatisfactory endometrial differentiation to secretory endometrium by examining the endometrial expression of prolactin in clomiphene citratetreated infertile women with luteal phase defect. Methods : The endometrial samples from infertile women with luteal phase defect (n=27) were examined. Five cases during secretory phase and six cases during proliferative phase were obtained by biopsy. Sixteen cases were obtained by biopsy during secretory phase after clomiphene citrate treatment. By immunohistochemical staining for prolactin, all obtained endometrial tissues were examined. The differences in the endometrial expression of prolactin were evaluated between proliferative phase and secretory phase, and between clomiphene citrate treated group and no treatment group during secretory phase. Results: The staining of endometrial prolactin was significantly more intense in the glandular epithelial cells and stromal cells in the secretory endometrium than in the proliferative endometrium. The glandular expression of prolactin in the secretory endometrium was not significantly different between the clomiphene citrate-treated group and no treatment group (p=0.719), but the staining of prolactin in the stromal cells was significantly less intense in the clomiphene citrate-treated group than no treatment group (p=0.019). Conclusion: In this investigation, we demonstrated that the endometrial stromal expression of prolactin in the secretory phase was significantly lower in the clomiphene citrate-treated group campared with no treatment group in infertile women with luteal phase defect. And our finding suggests that clomiphene citrate may have an adverse effect on the endometrial predecidualization in infertile women.

Keywords

References

  1. Blankstein J. Use of clomiphene citrate for ovulation induction. In Collins RL, editor Ovulation Induction. New York: Springer, 1991: p.62-8
  2. Fritz MA, Holmes RT, Keenan EJ. Effect of clomiphene citrate treatment on endometrial estrogen and progesterone receptor induction in women. Am J Obstet Gynecol 1991; 165: 177-85 https://doi.org/10.1016/0002-9378(91)90247-O
  3. Adashi EY. Ovulation induction: clomiphene citrate. In: Adashi EY, Rock JA, Rosenwaks Z, editors. Reproductive endocrinoligy, surgery and technology. Philadelphia: Lippincott-Raven Publishers, 1996: p. 1182-206
  4. Nelson LM, Hershlag A, Kurl RS, Hall JL, Stillman RJ. Clomiphene citrate directly impairs endometrial receptivity in the mouse. Fertil Steril 1990; 53: 727-31 https://doi.org/10.1016/S0015-0282(16)53472-4
  5. Li TC, Warren MA, Murphy C, Sargeant S, Cooke ID. A prospective, randomised, corss-over study comparing the effects of clomiphene citrate and cyclofenil on endometrial morphology in the luteal phase of normal fertile women. Br J Obstet Gynaecol 1992; 99: 1008-13 https://doi.org/10.1111/j.1471-0528.1992.tb13708.x
  6. Gelety TJ, Buyalos RP. The effect of clomiphene citrate and menopausal gonadotropins on cervical mucus in ovulatory cycles. Fertil Steril 1993; 60: 471-6 https://doi.org/10.1016/S0015-0282(16)56163-9
  7. Fazlebas AT, Yeko TR, Connelly KM. Effect of clomiphene citrate on the synthesis and release of the human b-lactoglobulin homolgue, pregnancy associated endometrial a2-globulin, by the uterine endometrium. Num Reprod 1991; 6: 783-90
  8. Yeko TR, Nicosia SM, Maroulis GB. Histology of mid-luteal corpus luteum an endometrium from clomiphene citrate-induced cycles. Fertil Steril 1992; 57: 28-32 https://doi.org/10.1016/S0015-0282(16)54771-2
  9. Bonhoff A, Naether O, Johanisson E, Bohnet HG. Morphometric characteristics of endometrial biopsies after different types of ovarian stimulation for infertility treatment. Fertil Steril 1993; 59: 560-6 https://doi.org/10.1016/S0015-0282(16)55800-2
  10. Massai MR, de Ziegler D, Lesobre V. Clomiphene citrate affects cervical mucus and endometrial morphology independently of the changes in plasma hormonal levels induced by multiple recruitment. Fertil Steril 1993; 59: 1179-86 https://doi.org/10.1016/S0015-0282(16)55973-1
  11. Miller RT, Hapke MR, Greene GL. Immunohistochemical assay for estrogen receptor with monoclonal antibody D753P in routine processed formaldehyde-fixed breast tissue. Cancer 1993; 71: 3541-6 https://doi.org/10.1002/1097-0142(19930601)71:11<3541::AID-CNCR2820711113>3.0.CO;2-X
  12. Carpenter SE. Implantation. In: Wallach EE, Zacur HA, editors. Reproductive medicine and surgery. St. Louis (MO): Mosby, 1995: p.158-65
  13. Dimitriadis E, Salamonsen LA, Robb L. Expression of interleukin-11 during the human censtrual cycle: coincidence with stromal cell decidualization an drelationship to leukaemia inhibitory factor and prolactin. Mol Hum Reprod 2000; 6: 907-14 https://doi.org/10.1093/molehr/6.10.907
  14. Braverman MB, Bagni A, de Ziegler D, Den T, Gurpide E. Isolation of prolacin producing cells from first and second trimester decidua. J Clin Endocrinol Metab 1984; 58: 521-5 https://doi.org/10.1210/jcem-58-3-521
  15. Tang B, Gurpide E. Direct effect of gonadotropins on decidualization of human endometrial stroma cells. J Steroid Biochem Mol Biol 1993; 47: 115-21 https://doi.org/10.1016/0960-0760(93)90064-4
  16. Tabanelli S, Tang B, Gurpide E. In vitro decidualization of human endometrial stromal cells. J Steroid Biochem Mol Biol 1992; 42: 337-44 https://doi.org/10.1016/0960-0760(92)90137-8
  17. Benedetto MT, Tabanelli S, Gurpide E. Estrone sulfate sulfatase activity is increased during in vitro decidualization of stromal cells from human endometrium. J Clin Endocrinol Metab 1990; 70: 342-5 https://doi.org/10.1210/jcem-70-2-342
  18. Zhu HH, Huang JR, Mazella J, Rosenberg M, Tseng L. Differential effects of progestin and relaxin on the synthesis and secretion of immunoreactive prolactin in long term culture of human endometrial stromal cells. J Clin Endocrinol Metab 1990; 71: 889-99 https://doi.org/10.1210/jcem-71-4-889
  19. Tseng L, Gao J-G, Chen R, Zhu HH, Mazella J, Powell DR. Effect of progestin, antiprogestin, and relaxin on the accumulation of prolactin and insulinlike growth factor-binding protein-1 messenger ribonucleic acid in human endometrial stromal cells. Biol Reprod 1992; 47: 441-50 https://doi.org/10.1095/biolreprod47.3.441
  20. Kofinas AD, Rose JC, Meis PJ. Changes in cyclic adenosine monophosphate-phosphodiesterase activity in pregnant and non-pregnant human myometrium. J Am J Obstet Gynecol 1987; 157: 733-8 https://doi.org/10.1016/S0002-9378(87)80040-6
  21. Shapiro DJ, Blume JE, Nielsen DA. Regulation of messenger RNA stability in eukaryotic cells. Bio-Essays 1987; 6: 221-6
  22. Baez M, Sargan DR, Elbrecht A, Kulomaa MA, Zaruchi-Schulz T, Tsai MJ, O'Malley BW. Steroid hormone regulation of gene encoding the chicken heat shok protein Hsp 108. J Biol Chem 1987; 262: 6582-8
  23. Tang B, Guller S, Gurpide E. Cyclic adenosine 3', 5'-monophosphate induces prolactin expression in stromal cells isolated from human proliferative endometrium. Endocrinology 1993; 133: 197-203
  24. Richards RG, Brar AK, Frank GR, Hartman SM, Jikihara H. Fibroblast cells from term decidua closely resemble endometrial stromal cells: induction of prolactin and insulin-like growth factor binding protein-1 expression. Biol Reprod 1995; 52:609-15 https://doi.org/10.1095/biolreprod52.3.609
  25. Yong EL, Baird DT, Hillier SG. Transduction of gonadotropin effects on human granulosa cells by cyclic AMP: on molecule, two messages. In: Sjoberg NO, Hamberger L, Janso PO, Owman C, Coelin GH, Bennink HJT, editor. Local Regulation of Ovarian Fucntion. Parthenon: Lancs, 1992: p.123-7
  26. Frank GR, Brar A, Cedars M, Handwerger S. Prostaglandin E2 dramatically enhances endometrial stromal cell differentiation. 75th Annual Meeting of The Endocrine Society, Las Vegas NV, 1993: p.350 (Abstract 1197)
  27. Bonhoff AJ, Naether OGJ, Johannisson E. Effects of clomiphene citrate stimulation on endometrial structure in infertile women. Jum Reprod 1996; 11:844-9
  28. Nakamura Y, Ono M, Yoshida Y, Sugino N, Ueda K, Kato H. Effects of clomiphene citrate on the endometrial thickenss and echogenic pattern of the endometrium. Fertil Steril 1997; 67: 256-60 https://doi.org/10.1016/S0015-0282(97)81907-3
  29. Grunfeld L. Physiology of the menstrual cycle. Ultrasonography in reproductive medicine. Infertil Reprod Med CLin North Am 1991; 2: 637-97
  30. Johannisson E, Parker RA, Landgren B-M, Diczfalusy E. Morphometric analysis of the human endometrium in relation to peripheral hormone levels. Fertil Steril 1982; 38: 564-71 https://doi.org/10.1016/S0015-0282(16)46636-7
  31. Hirama Y, Ochiai K. Estrogen and progesterone receptors of the out-of-phase endometrium in female infertile patients. Fertil Steril 1995; 63: 984-8 https://doi.org/10.1016/S0015-0282(16)57534-7