Published Research > E.A.J. Ryan, S. Blanco Mejia, E.A. Claessens. Improving fertility in patients with diminished ovarian reserve undergoing controlled ovarian hyperstimulation with intra uterine insemination. Meeting of the Canadian Fertility and Andrology Society, Vancouver, Canada. September 2013.

27 Sep 2013

INTRODUCTION: Women with diminished ovarian reserve (DOR) or premature ovarian insufficiency (POI) have a poor fertility prognosis1-7. Dehydroepiandrosterone (DHEA) and Coenzyme-Q10 (CoQ10) have been found to improve pregnancy rate and to decrease pregnancy loss rate. The aim of the study was to analyze the difference in pregnancy rates in women 35-39 years old with DOR/POI treated with DHEA or DHEA+CoQ10 undergoing COH with intra uterine insemination (IUI).

METHODS: We conducted a historical and prospective cohort study. We included women between 35-39 years old who had a diagnosis of DOR/POI as per the Bologna criteria, who had not got pregnant either spontaneously or with aromatase inhibitors. COH/IUI cycles were performed using day 3 agonist flare protocol, a dose of 75 to 450 IU FSH per day and 10.000 IU of HCG was given once the lead follicle was 1.8-2.2 cm. Patients were taking either DHEA alone, or DHEA+CoQ10 for an average of 3 months before the treatment cycle. Pregnancy rate per IUI (PR/IUI) and pregnancy loss rate (PLR) per IUI (PLR/IUI) excluded chemical pregnancies. Live birth rate (LBR) per intra-uterine insemination (LBR/IUI) was the main outcome. 
RESULTS: We included 114 women (81 on DHEA alone and 33 on DHEA+CoQ10) that underwent a total of 241 COH/IUI cycles (Average 2.1 cycles per patient). There was no statistical difference for LBR/IUI, PR/IUI or PLR (Table 1). 
CONCLUSION: The addition of CoQ10 to DHEA does not seem to add a statistically significant beneficial effect in women with DOR/POI undergoing COH/IUI treatment. A definite trend to a higher LBR/IUI is noted in the DHEA+ CoQ10 group and will require  larger full scale studies to prove statistical significance.
The mainstay for achieving a pregnancy for almost 50 yrs was COH/IUI8. The problem is, the pregnancy rate, and especially the multiple pregnancy rates with its attendant high cost to Global health care, were so varied from study to study that concerns are being raised about the use of COH/IUI at al.9-11. Very few of the published studies to date have been done on documented patients with DOR/POI and on the costs of IUI cycles versus IVF7, 12-14 and when one should switch from a planned COH/IUI cycle to IVF15, 16 or vice-versa. Our results here show a good LBR /cycle in this worst scenario type of patient and yet a very low multiple pregnancy rate confirming our underlying diagnosis of DOR/POI in our study group. An ideal study would be an RCT based on strict definition of DOR/POI as per Bologna criteria with a sample size of approx  160 patients in each arm of the study,17. This planned ideal study seems unlikely now,  due to the widespread evidence especially from IVF results18 worldwide, with over 30% of IVF centers now using exogenous Androgens to  improved embryo numbers and  quality and reduce pregnancy loss rates19. The work of Bentov et al.20, 21  has opened the door further to “micromanipulation “ of intracellular biology for the betterment of oocyte function in older women who already have DOR/POI. The future looks much better for older women who want a pregnancy without resorting to a donor egg solution22.


  1. Belaisch-Allart, J., J.M. Mayenga, and M. Plachot, [Intra-uterine insemination]. Contracept Fertil Sex, 1999. 27(9): p. 614-9.
  2. Levi, A.J., et al., Reproductive outcome in patients with diminished ovarian reserve. Fertil Steril, 2001. 76(4): p. 666-9.
  3. Williams, R.S., et al., A randomized, multicenter study comparing the efficacy of recombinant FSH vs recombinant FSH with Ganirelix during superovulation/IUI therapy. Am J Obstet Gynecol, 2004. 191(2): p. 648-51; discussion 651-3.
  4. Tomlinson, M.J., et al., Prognostic indicators for intrauterine insemination (IUI): statistical model for IUI success. Hum Reprod, 1996. 11(9): p. 1892-6.
  5. Stone, B.A., et al., Determinants of the outcome of intrauterine insemination: analysis of outcomes of 9963 consecutive cycles. Am J Obstet Gynecol, 1999. 180(6 Pt 1): p. 1522-34.
  6. Hughes, E.G., Stimulated intra-uterine insemination is not a natural choice for the treatment of unexplained subfertility. 'Effective treatment' or 'not a natural choice'? Hum Reprod, 2003. 18(5): p. 912-4.
  7. Goverde, A.J., et al., Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost-effectiveness analysis. Lancet, 2000. 355(9197): p. 13-8.
  8. Custers, I.M., et al., Intrauterine insemination: how many cycles should we perform? Hum Reprod, 2008. 23(4): p. 885-8.
  9. Reindollar, R.H. and M.B. Goldman, Gonadotropin therapy: a 20th century relic. Fertil Steril, 2012. 97(4): p. 813-8.
  10. Nuojua-Huttunen, S., et al., Intrauterine insemination treatment in subfertility: an analysis of factors affecting outcome. Hum Reprod, 1999. 14(3): p. 698-703.
  11. Merviel, P., et al., Predictive factors for pregnancy after intrauterine insemination (IUI): an analysis of 1038 cycles and a review of the literature. Fertil Steril, 2010. 93(1): p. 79-88.
  12. Guzick, D.S., et al., Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network. N Engl J Med, 1999. 340(3): p. 177-83.
  13. Iberico, G., et al., Analysis of factors influencing pregnancy rates in homologous intrauterine insemination. Fertil Steril, 2004. 81(5): p. 1308-13.
  14. Lashen, H., et al., Poor responders to ovulation induction: is proceeding to in-vitro fertilization worthwhile? Hum Reprod, 1999. 14(4): p. 964-9.
  15. Nicopoullos, J.D.M. and H. Abdalla, Poor response cycles: when should we cancel? Comparison of outcome between egg collection, intrauterine insemination conversion, and follow-up cycles after abandonment. Fertility and sterility, 2011. 95(1): p. 68-71.
  16. Norian, J.M., et al., Conversion from assisted reproductive technology to intrauterine insemination in low responders: is it advantageous? Fertil Steril, 2010. 94(6): p. 2073-7.
  17. Ferraretti, A.P., et al., ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod, 2011. 26(7): p. 1616-24.
  18. Wiser, A., et al., 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(10): p. 2496-500.
  19. Gleicher, N., A. Weghofer, and D.H. Barad, The role of androgens in follicle maturation and ovulation induction: friend or foe of infertility treatment? Reproductive Biology & Endocrinology, 2011. 9: p. 116.
  20. Bentov, Y. and R.F. Casper, The aging oocyte--can mitochondrial function be improved? Fertil Steril, 2013. 99(1): p. 18-22.
  21. Bentov, Y., et al., The use of mitochondrial nutrients to improve the outcome of infertility treatment in older patients. Fertil Steril, 2010. 93(1): p. 272-5.
  22. Gleicher, N., A. Weghofer, and D. Barad, Too old for IVF: are we discriminating against older women? J Assist Reprod Genet, 2007. 24(12): p. 639-44.