Skip to main content
Log in

Antiestrogenic effect of clomiphene citrate in a multiple follicular stimulation protocol

  • Special Contributions
  • Published:
Journal of in Vitro Fertilization and Embryo Transfer Aims and scope Submit manuscript

Abstract

End-organ antiestrogenic effects of clomiphene citrate (CC) have been demonstrated in the female reproductive tract at the levels of the ovary, cervix, and endometrium. However, it has not been established whether this effect is manifested during concomitant human menopausal gonadotropin (hMG) administration, as occurs in hMG/ CC stimulations of multiple follicular development. To assess this question a review was made of serum estradiol (E2) and cervical mucus in 47 hMG and 56 hMG/CC stimulations on days-2,-1,0, and+1 relative to the day of hCG administration. E2 levels (pg/ml) were significantly lower in the hMG as compared to the hMG/CC group. However, comparing the hMG and hMG/CC groups, cervical mucus scores were significantly higher in the former. Furthermore, an analysis of covariance demonstrated that the cervical mucus scores on each day were significantly lower in the hMG/CC group (P<0.001). Thus, in hMG/CC stimulations for in vitro fertilization (IVF), despite the concomitant administration of pharmacologic doses of hMG, CC exerts an antiestrogenic effect on at least one end organ, cervical mucus production. Potentially, this antiestrogenic effect in IVF stimulations would be exerted at other female reproductive tract sites including the endometrium; however, its clinical significance, if any, is unclear.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Vargyas JM, Marrs RP, Kletzky OA, Mishell DR Jr: Correlation of ultrasonic measurement of ovarian follicle size and serum estradiol levels in ovulatory patients following clomiphene citrate for in vitro fertilization. Am J Obstet Gynecol 1982;144:569–573

    PubMed  Google Scholar 

  2. Quigley MM, Maklad NF, Wolf DP: Comparison of two clomiphene citrate dosage regimens for follicular recruitment in an in vitro fertilization program. Fertil Steril 1983;40:178–182

    PubMed  Google Scholar 

  3. Marrs RP, Vargyas JM, Gibbons WE, Saito H, Mishell DR Jr: A modified technique of human in vitro fertilization and embryo transfer. Am J Obstet Gynecol 1983;147:318–322

    PubMed  Google Scholar 

  4. Edwards RG, Fishel SB, Cohen J, Fehilly CB, Purdy JM, Slater JM, Steptoe PC, Webster JM: Factors influencing the success of in vitro fertilization for alleviating human infertility. J Vitro Fert Embryo Transfer 1984;1:3–23

    Google Scholar 

  5. Sher G, Knutzen V, Stratton CJ, Montakhab MM, Allenson SG, Mayville J, Rubenstein JA, Glass MJ, Bilach SM: The development of a successful non-university-based ambulatory in vitro fertilization/embryo transfer program. Phase I. Fertil Steril 1984;41:511–518.

    Google Scholar 

  6. Diamond MP, Wentz AC, Herbert CM, Pittaway DE, Maxson WS, Daniell JF: One ovary or two: Differences in ovulation induction, estradiol levels, and follicular development in a program for in vitro fertilization. Fertil Steril 1984;41:524–529

    PubMed  Google Scholar 

  7. Marrs RP, Vargyas JM, Shangold GM, Yee B: The effect of time of initiation of clomiphene citrate on multiple follicle development for human in vitro fertilization and embryo replacement procedures. Fertil Steril 1984;41:682–685

    PubMed  Google Scholar 

  8. Quigley MM, Berkowitz AS, Gilbert SA, Wolf DP: Clomiphene citrate in an in vitro fertilization program: Hormonal comparisons between 50 and 150 mg daily dosages. Fertil Steril 1984;41:809–815

    PubMed  Google Scholar 

  9. Lopata A: Concepts in human in vitro fertilization and embryo transfer. Fertil Steril 1983;40:289–301

    PubMed  Google Scholar 

  10. Trounson A, Wood C: In vitro fertilization results, 1979–1982 at Monash University, Queen Victoria, and Epworth Medical Centres. J Vitro Fert Embryo Transfer 1984;1:42–47

    Google Scholar 

  11. Kerin JF, Warnes GM, Quinn P, Kirby C, Jeffrey R, Malthews CD, Seamark RF, Texler K, Antonas B, Cox LW: In vitro fetilization and embryo transfer program, Department of Obstetrics and Gynecology, University of Adelaide at the Queen Elizabeth Hospital, Woodville, South Australia. J Vitro Fert Embryo Transfer 1984;1:63–71

    Google Scholar 

  12. Quigley MM, Schmidt CL, Beauchamp PJ, Pace-Owens S, Berkowitz AS, Wolf DP: Enhanced follicular recruitment in an in vitro fertilization program: Clomiphene alone versus a clomiphene/human menopausal gonadotropin combination. Fertil Steril 1984;42:25–33

    PubMed  Google Scholar 

  13. Vargyas JM, Moreute C, Shangold G, Marrs RP: The effect of different methods of ovarian stimulation for human in vitro fertilization and embryo transfer. Fertil Steril 1984; 42:745–749

    PubMed  Google Scholar 

  14. Cohen JJ, Debache C, Pigeau F, Mandelbaum J, Plachut M, de Brux J: Sequential use of clomiphene citrate, human menopausal gonadotropin, and human chorionic gonadotropin in human in vitro fertilization. II. Study of luteal phase adequacy following aspiration of the pre-ovulatory follicles. Fertil Steril 1984;42:360–365

    PubMed  Google Scholar 

  15. Laufer N, Pratt BM, DeCherney AH, Naffolin F, Merino M, Markert CL: The in vivo and in vitro effects of clomiphene citrate on ovulation, fertilization, and development of cultured mouse oocytes. Am J Obstet Gynecol 1983;147:633–639

    PubMed  Google Scholar 

  16. Nakano R, Nakayama T, Iwao M: Inhibition of ovarian follicle growth by a chemical anti-estrogen. Horm Res 1982;16:230–236

    PubMed  Google Scholar 

  17. Marut EL, Hodgen GD: Anti-estrogen action of high-dose clomiphene in primates: Pituitary augmentation but with ovarian attenuation. Fertil Steril 1982;38:100–104

    PubMed  Google Scholar 

  18. Lamb BJ, Guderian AM: Clinical effects of clomiphene on anovulation. Obstet Gynecol 1966;28:505–512

    PubMed  Google Scholar 

  19. Maxson WS, Pittaway DE, Herbert CM, Garner CH, Wentz AC: Antiestrogenic effect of clomiphene citrate: Correlation with serum estradiol concentrations. Fertil Steril 1984; 42:356–359

    PubMed  Google Scholar 

  20. Lamb BJ, Colliflower WW, Williams JW: Endometrial bistology and conception rates after clomiphene citrate. Obstet Gynecol 1972;39:389–396

    PubMed  Google Scholar 

  21. Garcia J, Jones GS, Wentz AC: The use of clomiphene citrate. Fertil Steril 1977;28:707–717

    PubMed  Google Scholar 

  22. Yen SSC, Vla P, Ryan KJ: Effect of clomiphene citrate in polycystic ovary syndrome: Relationship between serum gonadotropin and corpus luteum function. J Clin Endocrinol Metab 1970;31:7–13

    PubMed  Google Scholar 

  23. Dalasch J, Vanrell JA, Duran M, Gonzalez-Merlo J: Luteal phase evaluation after clomiphene-chorionic gonadotropin induced ovulation. Int J Fertil 1983;28:104–109

    PubMed  Google Scholar 

  24. Wentz AC, Torbit CH, Daniell JF, Fleischer AC, Garner CH, Pittaway DE, Christianson CD, Repp JE, Maxson WS Combined screening laparoscopy and timed follicular aspiration for human in vitro fertilization. Fertil Steril 1983;39:270–276

    PubMed  Google Scholar 

  25. Diamond MP, Wentz AC, Vaughn WK, Webster BW, Herbert CM, Osteen KG, Maxson WS: Outcome of successive cycles of ovulation induction in the same individual. Fertil Steril 1985;43:369–372

    PubMed  Google Scholar 

  26. Jones GS, Demoraes Ruehsen M, Johanson A, Raiti J, Blizzard RM: Elucidation of normal ovarian physiology by exogenous gonadotrophin stimulation following steroid pituitary suppression. Fertil Steril 1969;20:14–34

    PubMed  Google Scholar 

  27. Grant A, Robertson S: An evaluation of monitor tests for the induction of ovulation. Aust NZ J Obstet Gynecol 1970;10:172–174

    Google Scholar 

  28. Moghissi KS, Syner FN, Borin B: A composite picture of the menstrual cycle. Am J Obstet Gynecol 1972;114:405–418

    PubMed  Google Scholar 

  29. Schenker JG, Weinstein D: Ovarian hyperstimulation syndrome: A current survey. Fertil Steril 1978;30:255–268

    PubMed  Google Scholar 

  30. Schwartz M, Jewelewicz R: The use of gonadotropins for induction of ovulation. Fertil Steril 1981;35:3–12

    PubMed  Google Scholar 

  31. Marrs RP, March CM, Mishell DR Jr: A comparison of clinical and laboratory methods in monitoring human menopausal gonadotropin therapy. Fertil Steril 1980;34:542–547

    PubMed  Google Scholar 

  32. Garcia JE, Jones GS, Acosta AA, Wright G Jr: Human menopausal gonadotropin/human chorionic gonadotropin follicular maturation for oocyte aspiration: Phase 1, 1981. Fertil Steril 1983;39:167–173

    PubMed  Google Scholar 

  33. Garcia JE, Jones GS, Acosta AA Wright G Jr: Human menopausal gonadotropin/human chorionic gonadotropin follicular maturation for oocyte aspiration: Phase II, 1981. Fertil Steril 1983;39:174–179

    PubMed  Google Scholar 

  34. Sundstrom P, Nilsson O, Liedholm P: Scanning electron microscopy of human preimplantation endometrium in normal and clomiphene/human chorionic gonadotropin stimulated cycles. Fertil Steril 1983;40:642–647

    PubMed  Google Scholar 

  35. Huppert LC: Induction of ovulation with clomiphene citrate. Fertil Steril 1979;31:1–7

    PubMed  Google Scholar 

  36. Jones HW Jr, Jones GS, Andrews MC, Acosta A, Bundren C, Garcia J, Sandow B, Veeck L, Wilkes C, Witmyer J, Wortham JE, Wright G: The brogram for in vitro fertilization at Norfolk. Fertil Steril 1982;38:14–21

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Diamond, M.P., Maxson, W.S., Vaughn, W.K. et al. Antiestrogenic effect of clomiphene citrate in a multiple follicular stimulation protocol. J Assist Reprod Genet 3, 106–109 (1986). https://doi.org/10.1007/BF01139355

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01139355

Key Words

Navigation