Skip to main content
SpringerLink
Log in

Clomiphene Citrate co-treatment with low dose urinary FSH versus urinary FSH for clomiphene resistant PCOS: randomized controlled trial

  • Assisted Reproduction Technologies
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

An Erratum to this article was published on 01 March 2014

Abstract

Purpose

The aim of this study was to examine the effect of clomiphene citrate [CC] co-administration during the use of exogenous low-dose urinary FSH [uFSH] for induction of ovulation in CC-resistant infertile PCOS women.

Methods

In a randomised controlled setting, 174 CC-resistant infertile PCOS women were randomized into two parallel groups; Group I received CC 100 mg/day for 5 days plus uFSH 37.5 IU/day while group II received only uFSH 37.5 IU /day. Subsequent increments of uFSH by 37.5 IU/day were made according to response. Primary outcome was ovulation rate. Secondary outcomes were clinical pregnancy rates, number of follicles, endometrial thickness, and gonadotropins consumption.

Results

Our results have demonstrated that group I compared to group II had significantly higher ovulation rate per intention to treat [ITT] [72.4 % vs. 34.2 %, p < 0.001]. Clinical pregnancy and live birth rates were comparable between the two groups. Group I consumed significantly lower total FSH dose and needed significantly shorter stimulation duration compared to group II.

Conclusion

CC co-administered during low dose HP uFSH versus uFSH for CC-resistant PCOS yields significantly higher ovulation rate and less consumption of FSH.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. The Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS). Hum Reprod. 2012;27:14–24.

    Article  Google Scholar 

  2. Gianaroli L, Racowsky C, Geraedts J, Cedars M, Makrigiannakis A, Roger L. Best practices of ASRM and ESHRE: a journey through reproductive medicine. Hum Reprod. 2012;27:3365–79.

    Article  CAS  PubMed  Google Scholar 

  3. Balen A. Strategies for ovulation induction in the management of anovulatory polycystic ovary syndrome. In: Azziz R, editor. The polycystic ovary syndrome: Current concepts on pathogenesis and clinical care. Springer Science, Business Media, LLC; 2007. p. 99–112.

  4. Eijkemans J, Habbema D, Fauser C. Characteristics of the best prognostic evidence: an example on prediction of outcome after clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. Semin Reprod Med. 2003;1:39–47.

    Google Scholar 

  5. Palomba S, Fallo A, Zullo F. Management strategies for ovulation induction in women with PCOS and known clomiphene citrate resistance. Curr Opin Obstet Gynecol. 2009;21:465–73.

    Article  PubMed  Google Scholar 

  6. White M, Polson W, Kiddy D, Sagle P, Watson H, Gilling-Smith C, et al. Induction of ovulation with low-dose gonadotropins in polycystic ovary syndrome: an analysis of 109 pregnancies in 225 women. J Clin Endocrinol Metab. 1996;81:3821–4.

    CAS  PubMed  Google Scholar 

  7. Balasch J, Fabregues F, Creus M, Casamitjana R, Puerto B, Vanrell A. Recombinant human follicle-stimulating hormone for ovulation induction in polycystic ovary syndrome: a prospective, randomized trial of two starting doses in a chronic low-dose step-up protocol. J Assist Reprod Genet. 2000;17:561–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Homburg R, Hendriks L, König E, Anderson A, Balen H, Brincat M, et al. Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study. Hum Reprod. 2012;27:468–73.

    Article  CAS  PubMed  Google Scholar 

  9. Dickey P, Olar T, Taylor N, Curole N, Rye H. Sequential clomiphene citrate and human menopausal gonadotrophin for ovulation induction: comparison to clomiphene citrate alone and human menopausal gonadotrophin alone. Hum Reprod. 1993;8:56–9.

    CAS  PubMed  Google Scholar 

  10. Bedaiwy M, Forman R, Mousa A, Al Inany H, Casper F. Cost-effectiveness of aromatase inhibitor co-treatment for controlled ovarian stimulation. Hum Reprod. 2006;22:2838–44.

    Article  Google Scholar 

  11. The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19:41–7.

    Article  Google Scholar 

  12. Fritz A, Speroff L. In: Frtiz MA, Speroff L, editors. Induction of ovulation in clinical gynecologic endocrinology and infertility. 8th ed. Philadelphia USA: Lippicott Williams; 2011. p. 1293–300.

    Google Scholar 

  13. World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction. 4th ed. Cambridge, UK: Cambridge University Press; 1999.

    Google Scholar 

  14. Trinder P. Determination of blood glucose using an oxidase-peroxidase system with a non-carcinogenic chromagen. J Clin Pathol. 1969;22:158–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Wahlefeld W. Triglyceride: determination after enzymatic hydrolysis. In: Bergmeyer HU, editor. Methods of Enzymatic Analysis. 2 Englishth ed. New York and London: Verlag Chemie Weinhiem and Academic press, Inc; 2000. p. 1831.

    Google Scholar 

  16. Assmann G, Schriewer H, Schmitz G, Hagele O. Quantification of high-density-lipoprotien cholesterol by precipitation with phosphotungestic acid/MgCl2. Clin Chem. 1983;29:2026–30.

    CAS  PubMed  Google Scholar 

  17. Friedwald T, Levy I, Fredrickson S. Estimation of the concentration of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.

    Google Scholar 

  18. Matthews R, Hosker P, Turner C. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  CAS  PubMed  Google Scholar 

  19. Mc Cann D, Kirkish L. Immunoassay. 1985;8:234–6.

    CAS  Google Scholar 

  20. Liberopoulos N, Mikhailidis P, Elisaf S. Diagnosis and management of the metabolic syndrome in obesity. Obes Rev. 2005;6:283–96.

    Google Scholar 

  21. Moran L, Teede H. Metabolic features of the reproductive phenotypes of polycystic ovary syndrome. Hum Reprod Update. 2009;15:477–88.

    Article  CAS  PubMed  Google Scholar 

  22. Homburg R. Clomiphene citrate—end of an era? A mini-review. Hum Reprod. 2005;20:2043–51.

    Article  CAS  PubMed  Google Scholar 

  23. Imani B, Eijkemans J, te Velde R, Habbema D, Fauser C. Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab. 1998;83:2361–5.

    CAS  PubMed  Google Scholar 

  24. Hamilton-Fairley D, Kiddy D, Watson H, Paterson C, Franks S. Association of moderate obesity with a poor pregnancy outcome in women with polycystic ovary syndrome treated with low dose gonadotrophin. Br J Obstet Gynaecol. 1992;99:128–31.

    Article  CAS  PubMed  Google Scholar 

  25. Yarali H, Basaran M, Yigit N, Bukulmez O, Bildirici I. Gonadotropin treatment using the low-dose step-up protocol in patients with clomiphene citrate [CC] resistant polycystic ovary syndrome (PCOS): factors affecting outcome. Fertil Steril. 2001;76:S207–20.

    Article  Google Scholar 

  26. Orviet R, Homburg R. Chronic ultra-low dose follicle-stimulating hormone regimen for patients with polycystic ovary syndrome: one click, one follicle, one pregnancy. Fertil Steril. 2009;S1:1533–5.

    Article  Google Scholar 

  27. Dale O, Tanbo T, Haug E, Åbyholm T. The impact of insulin resistance on the outcome of ovulation induction with low-dose follicle stimulating hormone in women with polycystic ovary syndrome. Hum Reprod. 1998;13:567–70.

    Article  CAS  PubMed  Google Scholar 

  28. Wely V, Bayram N, van der Veen F, Bossuyt M. Predicting ongoing pregnancy following ovulation induction with recombinant FSH in women with polycystic ovary syndrome. Hum Reprod. 2005;20:1827–32.

    Article  PubMed  Google Scholar 

  29. Andersen N, Balen H, Platteau P, Pettersson G, Arce C. Prestimulation parameters predicting live birth in anovulatory WHO Group II patients undergoing ovulation induction with gonadotrophins. Hum Reprod. 2010;25:1988–95.

    Article  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the efforts of Ms Nessma, Mr Salah in endocrinology laboratory for their role in serum sample processing and storage. Also we thank the nursing staff and centre secretary for their efforts in patient cycle filing throughout the trial.

Declaration of interest

The authors report no declarations of interest.

Author information

Authors and Affiliations

  1. Mansoura Integrated Fertility Center, Mansoura, Egypt

    Mohamad E. Ghanem, Laila A. Elboghdady, Mohamad Hassan, Adel S. Helal & Ibrahiem Bahlol

  2. Department of Obestetrics & Gynecology, Mansoura Faculty of Medicine, Mansoura, Egypt

    Mohamad E. Ghanem, Laila A. Elboghdady, Mohamad Hassan, Adel S. Helal, Ahmed Gibreel, Ibrahiem Bahlol & Yaser Mesbah

  3. Department of Biochemistry, Faculty of Pharmacy, Damanhur University, Damanhur, Egypt

    Maha Houssen

  4. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt

    Mohamed E. Shaker

Authors
  1. Mohamad E. Ghanem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laila A. Elboghdady
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohamad Hassan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adel S. Helal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ahmed Gibreel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maha Houssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohamed E. Shaker
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ibrahiem Bahlol
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yaser Mesbah
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahmed Gibreel.

Additional information

Contributors

MG was the principal investigator, designed the trial, wrote the protocol, managed the trial, recruited participants, interpreted the data and results, and wrote the first draft of the paper. LA advised on the study design and data analysis and helped to draft the paper. AG helped in the design and performing the statistical analysis, interpreted the data and results, and helped to draft the paper. MH and MES performed the biochemical assays. MH, AH and IB and YM recruited patients and entered data.

Trial registration number

ClinicalTrials.gov Identifier: NCT01212263

Capsule Clomiphene citrate and uFSH versus uFSH alone in clomiphene –resistant PCOS patients.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ghanem, M.E., Elboghdady, L.A., Hassan, M. et al. Clomiphene Citrate co-treatment with low dose urinary FSH versus urinary FSH for clomiphene resistant PCOS: randomized controlled trial. J Assist Reprod Genet 30, 1477–1485 (2013). https://doi.org/10.1007/s10815-013-0090-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-013-0090-2

Keywords

Search

Navigation