Marjan Firoozeh Corresponding Author
- Infertility Treatment Ward, Shariati Hospital, Faculty of Medicine, Tehran University of Medical Sciences & Health Services University, Tehran, Iran
Leili Safdarian
- Infertility Treatment Ward, Shariati Hospital, Faculty of Medicine, Tehran University of Medical Sciences & Health Services University, Tehran, Iran

Received: 7/1/2005 Accepted: 7/1/2005 - Publisher : Avicenna Research Institute

Related Articles


Other Format



Introduction: From half a century ago, exogenic gonadotropins have been used by different methods for ovulation induction in the treatment of ovulatory problems and in ART. According to the extensive use of step-down and fixed-dose regimens of hMG in ovulation induction and in view of the fact that previous studies have not provided similar results, are expensive and have some complications, this study was performed to compare the aspects of the two methods that follows: hMG dosage, the need for increasing the dosage during therapy, endometrial thickness, pattern of endometrium and pregnancy rates. Materials and Methods: In this historical cohort study, 245 cycles of each regimen used in infertile patients who had been admitted to Shariati Hospital in Tehran during 2003-2004, were reviewed. All patients were under 35 and had not volunteered for zygote donation and were not suffering from PCOS or hypothalamic amenorrhea too. After the pituitary gland suppression by long-term GnRH agonist protocol, employing the step- down regimen, the initial dose of hMG, 2-4 ampoules (150 IU each), was administered and then in several stages the dosage was lowered, about 0.5 ampoule every 2-3 days based on sonographic findings. In the fixed dose regimen, 2-4 ampoules of hMG were administered without any decrease throughout the cycle. After injection of hCG, the resultant oocytes were used in ZIFT. The data were analyzed by SPSS software, using t-test, 2and Fishers exact test. Differences were considered significant at 5% level (p-value0.05). Results: In the two mentioned regimens, the mean number of oocytes which were retrieved, grades of zygotes, endometrial thickness and pregnancy rates didn't have significant statistical differences. There were significantly more triple lines and less echogenic patterns of endometrium in step- down regimen (p-value=0.001). The mean number of used hMG ampoules in step- down regimen was significantly lower than the fixed- dose (26.4 versus 32.2 respectively, p-value= 0.000) as the need for increasing the dosage during treatment was_42 cycles (17.1%) versus 99 cycles (40.4%) respectively; p-value=0.000. Conclusion: According to significant differences in pregnancy rates and outcomes between the two regimens, the step- down regimen, by administering less hMG, seems to be better but further investigations by including patients suffering from PCOS, hypothalamic amenorrhea, etc in the study are needed to generalize these results.

Keywords: Ovulation induction, Human menopausal genadotropin, Fixed-dose regimen, Step-down regimen, Infertility, ZIFT, Assisted Reproductive Techniques

To cite this article:


  1. Speroff L., Glass R.H., Kase N.G. Female infertility. Clinical Gynecologic Endocrinology and Infertility. 6th Edition. Maryland USA, Wolters kluwer Company. 1999;pp:1013-1019.
  2. Speroff L., Glass R.H., Kase N.G. Induction of ovula-tion, Mitchell Ch. Clinical Gynecologic Endocrinolory and Infertility.6th Edition. Maryland USA, Wolters klu-wer Company.1999;pp:1097-1115.
  3. Nugent D., Vandekerckhove P., Hughes E., Amot M., Lilford R. Gonadotrpin therapy for ovulation induction in subfertility associated with PCOs. Cochrane data-base of systemic reviews.2002;(4):CD000410. Review.
  4. Daya S. Updated metaanalysis of recombinant FSH versus urinary FSH for ovarian stimulation in assisted reproduction. Fertil Steril.2002;77:645.
  5. Sagle M.H.F., Kiddy D.S., Franks S. A comparative randomized study of low dose human menopausal go-nadotropin and follicle stimulating hormone in women with PCOs. Fertil Steril.1991;55:56-60.
  6. Aboulghar M.A., Mansour R.T., Serour G.I., Amin Y. M., Fattar M.A., et al. Recombinant FSH in treatment of patients with history of sever OHSS. Fertil Steril. 1996;66:757-60.
  7. Nugent D., Hughes E., Arnot M., Lilford R. Gonado- tropin therapy for ovulation induction in subfertility associated with PCOs. Hum Reprod.2002; 17:3305-9.
  8. Balash J. Inducing follicular development in anovula-tory patients and normally ovulating women: Current concepts and the role of recombinant gonadotropins. Assisted Reproductive Techniques. London.2001;pp: 67-83.
  9. Imani B., Faessen G.H., Bouchard P., Giudice L.C., Faufer B.T. Prediction of the individual FSH threshold for gonadotropin induction of ovulation in normo-gonadotropic anovulatory infertility. Fertil Steril.2002; 77:83-90.
  10. Hugues J.N., Avril C., Bulwa S., Cedrins D.U.I., Herve F. Sequential step up and step down dose regi-men, an alternative method for ovulation induction with FSH in PCOs. Hum. Reprod.1996;11:2581-2584.
  11. Diedrich K., Felberaum R. New approaches to ovarian stimulation. Hum Reprod.1998;13:2900(S3).
  12. Hugues J.N. Step protocols. Contracept Fertil Sex. 1998;26(4):307-11. Review.
  13. Evert J.P., Van Santbrink A.M., Fauser B.C.J.M. Uri-nary FSH for normogonadotropic clomiphen resistant anovulatory infertility: Prospective Randomized Com-parison between low dose step up and step down dose regimens. J Clin Endocrinol Metab. 1997;82(11):3597-3602.
  14. Christin S., Hugues J.N. A comparative randomized multicentric study comparing the step up versus step down protocole in PCOs. Hum Reprod.2003;18(8): 1626-1631.
  15. Henk J., Ishay D., Raphael R., Shevach F., Eliezer Sh., et al.A randomized double blind clinical trial using fixed dailydoses 100 or 200 IU of recombinant FSH in ICSI cycles. Hum Reprod.2001;16(6):1104-1109.
  16. Henk J., Svend L., Mikkelsen A.L. Talia E.G., David L. A prospective randomized double blind clinical trial to study the efficacy and efficiency of a fixed dose of r. FSH in women undergoing ovarian stimulation. Hum Reprod.1999;14(3):622-625.
  17. Nakamura Y., Takasaki A., Sugino N., Tamura H., Takiguchi S. et al. Studies on the effects of initial in-jection doses of follicle stimulating hormone on the pregnancy and the ovarian hyperstimulation syndrome incidence in PCOs patients. Reprod Med Biol.2003; 2(2):63.
  18. Ehimen P., Sharhan M., Grudzinskas J. A comparison of a step up protocole with high fixed dose gonado-tropin administration in obese patients with PCOs. MEFS Journal.2003;7(3):356-360.
  19. Andoh K., Mizunuma H., Liu XI., Kanigo T., Yamada K. et al. A comparative of fixed dose, step down and low dose step up regimens of HMG for patients with PCOs. Fertil Steril.1998;70(5):840-6.
  20. Lolis D.E., Tsolas O., Messinis I.E. The FSH thre-shold level for follicle maturation in superovulated cycles. Fertil Steril.1995;63:1272-7.
  21. Van Santbrink E.J.P., Hop W.C., Van Dessel T.J.H.M., Dejong F.H., Fauser B.C.J.M. Decremental FSH and dominant follicle development during the normal menstrual cycle. Fertil Steril.1995;64:37-43.
  22. El Tabbakh M.N. Ovulation in invitro fertilization. Fertil Steril.2001;73(6):1012-16.


Home | About Us | Current Issue | Past Issues | Submit a Manuscript | Instructions for Authors | Subscribe | Search | Contact Us

"Journal of Reproduction & Infertility" is owned, published, and managed by Avicenna Research Institute .
Creative Commons License

This work is licensed under a Creative Commons Attribution –NonCommercial 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

Journal of Reproductoin and Infertility (JRI) is a member of COMMITTEE ON PUBLICATION ETHICS . Verify here .

©2024 - eISSN : 2251-676X, ISSN : 2228-5482, For any comments and questions please contact us.