Skip to main content

Adjunctive Treatments in ART

  • Chapter
  • First Online:
In Vitro Fertilization
  • 2212 Accesses

Abstract

A variety of approaches have been proposed to enhance ovarian response or implantation in the assistive reproductive technologies of which many have offered routinely in the absence of adequate evidence supporting their use. In this chapter, we investigate four commonly employed adjunctive treatments and critically assess both the logic behind and evidence supporting their use. (1) Growth hormone has been evaluated in a variety of randomized clinical trials as adjunctive therapy for controlled ovarian hyperstimulation regimes. Its use does not appear to be beneficial for the average patient, but there is suggestive evidence that ovarian response and live birth rates may be improved in a subset of prior poor responders. However, the ideal dose or duration has not been determined. (2) DHEA has only been evaluated in a small prospective published randomized trial which demonstrated enhanced pregnancy rates and embryo quality in poor responders who had failed IVF. Case control studies do not consistently confirm enhanced IVF pregnancy rates, although ovarian response may be improved. The appropriate dose and duration of therapy has not been defined. (3) The addition of low dose aspirin had been shown in earlier meta-analyses to slightly increase IVF pregnancy rates. However, recent randomized clinical trials demonstrate no benefit when administered routinely prior to IVF. Nevertheless, it is possible that administration to a subset of patients with antiphospholipid antibody syndrome, recurrent pregnancy loss, or history of prior failed cycles, may be of some benefit, although confirmatory data is lacking. (4) Analysis of results from trials on the effect of acupuncture and IVF cycle outcome is confounded by variables including variations in technique, patient populations, timing, and control groups. An overview of randomized control trials shows no clearly defined benefit of acupuncture on IVF pregnancy and delivery rates, although the ideal study has not been performed. If there is a benefit of this approach, it may be when performed the day of embryo transfer. In conclusion, it is critical that adjunctive therapies be critically evaluated in appropriately designed randomized trials before they are generally accepted and introduced into widespread use.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Surrey E, Schoolcraft W. Evaluating strategies for improving ovarian response of the poor responder undergoing assisted reproductive technologies. Fertil Steril. 2000;73:667–76.

    Article  PubMed  CAS  Google Scholar 

  2. Hull K, Harvey S. Growth hormone: roles in female reproduction. J Endocrinol. 2001;168:1–23.

    Article  PubMed  CAS  Google Scholar 

  3. Adashi E, Resnick C, Hernandez E, Hurwitz A, Roberts C, Leroth D, et al. Insulin-like growth factor as an intraovarian regulator: basic and clinical implications. Ann N Y Acad Sci. 1992;626:161–8.

    Article  Google Scholar 

  4. Mason H, Martikainen H, Beard R, Anyaolou U, Fraiks S. Direct gonadotropin effect of growth hormone on oestradiol production by human granulosa cells on-vitro. J Endocrinol. 1990;126:1–4.

    Article  Google Scholar 

  5. European and Australian Multicenter Study. Cotreatment with growth hormone and gonadotropin for ovulation induction in hypogonadotropic patients: a prospective, randomized, placebo-controlled, dose-response study. Fertil Steril. 1995;64:917–23.

    Google Scholar 

  6. Harper K, Proctor M, Hughes E. Growth hormone for in vitro fertilization. Cochrane Database Syst Rev. 2003(3);CD000099.

    Google Scholar 

  7. Kucuk T, Kozinoglu H, Kaba A. Growth hormone co-treatment within a GnRH agonist long protocol in patients with poor ovarian response: a prospective randomized clinical trial. J Assist Reprod Genet. 2008;25:123–7.

    Article  PubMed  Google Scholar 

  8. Tesarik J, Hazout A, Mendoza C. Improvement of delivery and live birth rates after ICSI in women aged >40 years by ovarian co-stimulation with growth hormone. Hum Reprod. 2005;20:2536–41.

    Article  PubMed  Google Scholar 

  9. Kolibianakis E, Venetis C, Diedrich K, Tarlatzis B, Griesinger G. Addition of growth hormone to gonadotropins in ovarian stimulation of poor responders treated by in-vitro fertilization: a systematic review and meta-analysis. Hum Reprod Update. 2009;15:613–22.

    Article  PubMed  CAS  Google Scholar 

  10. Frattarelli J, Peterson E. Effect of androgen levels on in vitro fertilization cycles. Fertil Steril. 2004;81: 1713–4.

    Article  PubMed  Google Scholar 

  11. Haning Jr R, Hackett R, Flood C, Loughlin J, Zhao Q, Longcope C. Plasma dehydroepiandrosterone sulfate serves as a prehormone for 48% of follicular fluid testosterone during treatment with menotropins. J Clin Endocrinol Metab. 1993;76:1301–7.

    Article  PubMed  CAS  Google Scholar 

  12. Casson P, Santoro N, Elkind-Hirsch K, Carson S, Hornsby P, Abraham G, et al. Postmenopausal dehydroepiandrosterone administration increases free insulin-like growth factor-I and decreases high density lipoprotein: a six-month trial. Fertil Steril. 1998;70:107–10.

    Article  PubMed  CAS  Google Scholar 

  13. Weil S, Vendola K, Zhou J, Adesanya O, Wang J, Okafor J, et al. Androgen receptor gene expression in the primate ovary: cellular localization, regulation and functional correlations. J Clin Endocrinol Metab. 1998;83:2470–8.

    Article  Google Scholar 

  14. Barad D, Brill H, Gleicher N. Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function. J Assist Reprod Genet. 2007;24:629–34.

    Article  PubMed  Google Scholar 

  15. Wiser A, Gonen O, Ghetler Y, Shavit T, Berkovitz A, Shulman A. Addition of dehydroepiandrosterone (DHEA) for poor responder patients before and during IVF treatment improves the pregnancy rate: A randomized prospective study. Hum Reprod. 2010;25:2496–500.

    Article  PubMed  CAS  Google Scholar 

  16. Ozturk O, Greaves M, Templeton A. Aspirin dilemma: remodeling the hypothesis from a fertility perspective. Hum Reprod. 2002;17:1146–8.

    Article  PubMed  CAS  Google Scholar 

  17. Catella-Lawson F. Vascular biology of thrombosis: platelet vessel wall interactions and aspirin effects. Neurology. 2001;57(5 Suppl 2):5–7.

    Article  Google Scholar 

  18. Rubinstein M, Marazzi A, Polak de Fried E. Low-dose aspirin treatment improves ovarian responsiveness, uterine and ovarian blood flow velocity, implantation and pregnancy rates in patients undergoing in vitro fertilization: a prospective randomized, double-blind placebo-controlled assay. Fertil Steril. 1999;71:825–9.

    Article  PubMed  CAS  Google Scholar 

  19. Khairy M, Banerjee K, El-Toukhy T, Coomarasamy A, Khalaf Y. Aspirin in women undergoing in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril. 2007;88:822–31.

    Article  PubMed  Google Scholar 

  20. Dirckx K, Cabri P, Merien A, Galajdova L, Gerris J, Dhont M, et al. Does low-dose aspirin improve pregnancy rate in IVF/ICSI? A randomized double-blind placebo controlled trial. Hum Reprod. 2009;24:856–60.

    Article  PubMed  CAS  Google Scholar 

  21. Haapsamo M, Martikainen H, Räsänen J. Low-dose aspirin and uterine haemodynamics on the day of embryo transfer in women undergoing IVF/ICSI: a randomized, placebo-controlled, double-blind study. Hum Reprod. 2009;24:861–6.

    Article  PubMed  CAS  Google Scholar 

  22. Lambers M, Hoozemans D, Schats R, Homburg R, Lambalk C, Hompes P. Low-dose aspirin in non-tubal IVF patients with previous failed conception: a prospective randomized double-blind placebo-controlled trial. Fertil Steril. 2009;92:923–9.

    Article  PubMed  CAS  Google Scholar 

  23. Ruopp M, Collins T, Whitcomb B, Schisterman E. Evidence of absence or absence of evidence? A reanalysis of the effects low-dose aspirin in in vitro fertilization. Fertil Steril. 2008;90:71–6.

    Article  PubMed  CAS  Google Scholar 

  24. Ng Y, So W, Gao J, Wong Y, Ho P. The role of acupuncture in the management of subfertility. Fertil Steril. 2008;90:1–13.

    Article  PubMed  Google Scholar 

  25. Dieterle S, Ying G, Hatzmann W, Neurer A. Effect of acupuncture on the outcome of in vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study. Fertil Steril. 2006;85:1347–51.

    Article  PubMed  Google Scholar 

  26. Paulus W, Zhang M, Strehler E, El-Danasouri I, Sterzik K. Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproductive therapy. Fertil Steril. 2002;77:721–4.

    Article  PubMed  Google Scholar 

  27. Domar A, Meshay I, Kelliher J, Alper M, Powers R. The impact of acupuncture on in vitro fertilization outcome. Fertil Steril. 2009;91:723–6.

    Article  PubMed  Google Scholar 

  28. Smith C, Coyle M, Norman R. Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer. Fertil Steril. 2006;85:1352–8.

    Article  PubMed  Google Scholar 

  29. So E, Ng E, Wong Y, Lau E, Yeung W, Ho P. A randomized double blind comparison of real and placebo acupuncture in IVF treatment. Hum Reprod. 2009; 24:341–8.

    Article  PubMed  Google Scholar 

  30. Andersen D, Lossl K, Andersen A, Fürbringer J, Bach H, Simonsen J, et al. Acupuncture on the day of embryo transfer: a randomized controlled trial of 635 patients. Reprod Biomed Online. 2010;21:366–72.

    Article  PubMed  Google Scholar 

  31. Zhang R, Feng X-J, Guan Q, Cui W, Zheng Y, Sun W, et al. Increase of success rate for women undergoing embryo transfer by transcutaneous electrical acupoint stimulation: a prospective randomized placebo-controlled study. Fertil Steril. 2011;96:912–6.

    Article  PubMed  Google Scholar 

  32. Manheimer E, Zhang G, Udoff L, Haramati A, Langenberg P, Berman B, et al. Effects of acupuncture on rates of pregnancy and live birth among women undergoing in vitro fertilization: a systematic review and meta-analysis. BMJ. 2008;336:545–9.

    Article  PubMed  Google Scholar 

  33. El-Toukhy T, Sunkara S, Khairy M, Dyer R, Khalaf Y, Coomarasamy A. A systematic review and meta-analysis of acupuncture in in vitro fertilisation. BJOG. 2008;115:1203–13.

    Article  PubMed  CAS  Google Scholar 

  34. Cheong Y, Nardo L, Rutherford T, Ledger W. Acupuncture and herbal medicine in in vitro fertilization: a review of the evidence for clinical practice. Hum Fertil. 2010;13:3–12.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eric Surrey M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media New York

About this chapter

Cite this chapter

Surrey, E. (2012). Adjunctive Treatments in ART. In: Ginsburg, E., Racowsky, C. (eds) In Vitro Fertilization. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9848-4_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-9848-4_12

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-9847-7

  • Online ISBN: 978-1-4419-9848-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics