Casson10 in 2000 was the first to suggest that exogenous androgens could possibly improve fertility in older women or those with DOR/POI. It was not until Gleicher and Barad’s group in 200511 and subsequently Shulman12, Mamas and Mamas13, 14 and many others around the world , published similar papers, did this concept gain acceptance, to the state now that over 30% of world wide IVF centers use exogenous androgens in patients of any age with DOR/POI. “When too old15” to get pregnant with one’s own eggs have opened an avenue of treatment that up to now recommended using donor eggs.
Bentov in his early publications on the use of mitochondrial nutrients in mice, opened another avenue for improving cell biology16-18. We have been very impressed with the concomitant use of DHEA with CoQ10 in our patients aged 35 to 40yrs age undergoing COH/IUI with a LBR/IUI cycle of 8.1( DHEA alone ) versus 14.3 (DHEA + CoQ10) in 241 cycles in 114 patients presented at CFAS Victoria 2013. We had a twin pregnancy rate/IUI of 2.7 and 4.8% confirming the DOR/POI status of these patients who satisfied the Bologna criteria19. Note the consistent 2/1 ratio of FSH to LH on day 3 of cycle, on average for all patients20. We expected to see the same dramatic improvement in our IVF subset with DOR/POI.
The addition of CoQ10 to DHEA in women with DOR/POI undergoing IVF treatment did not seem to have a beneficial effect over DHEA alone. However, administration of DHEA or DHEA + CoQ10 results in an acceptable LBR/ET in this poor prognosis group of patients in comparison with world-wide statistics.
1. Elizur, S.E., et al., Factors predicting IVF treatment outcome: a multivariate analysis of 5310 cycles. Reprod Biomed Online, 2005. 10(5): p. 645-9.
2. Freour, T., et al., IVF conversion to IUI in poor responders: an observational study. Arch Gynecol Obstet, 2010. 282(4): p. 445-9.
3. Levi, A.J., et al., Reproductive outcome in patients with diminished ovarian reserve. Fertil Steril, 2001. 76(4): p. 666-9
4. Klipstein, S., et al., One last chance for pregnancy: a review of 2,705 in vitro fertilization cycles initiated in women age 40 years and above. Fertil Steril, 2005. 84(2): p. 435-45.
5. Lawlor, D.A. and S.M. Nelson, Effect of age on decisions about the numbers of embryos to transfer in assisted conception: a prospective study. Lancet, 2012. 379(9815): p. 521-7.
6. Malizia, B.A., M.R. Hacker, and A.S. Penzias, Cumulative live-birth rates after in vitro fertilization. N Engl J Med, 2009. 360(3): p. 236-43.
7. Nelson, S.M. and D.A. Lawlor, Predicting live birth, preterm delivery, and low birth weight in infants born from in vitro fertilisation: a prospective study of 144,018 treatment cycles. PLoS Med, 2011. 8(1): p. e1000386.
8. Olivius, K., et al., Cumulative probability of live birth after three in vitro fertilization/intracytoplasmic sperm injection cycles. Fertil Steril, 2002. 77(3): p. 505-10.
9. Smith, J.F., et al., Fertility treatments and outcomes among couples seeking fertility care: data from a prospective fertility cohort in the United States. Fertil Steril, 2011. 95(1): p. 79-84.
10. Casson, P.R., et al., Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Human Reproduction, 2000. 15(10): p. 2129-32.
11. Barad, D.H. and N. Gleicher, Increased oocyte production after treatment with dehydroepiandrosterone. Fertility & Sterility, 2005. 84(3): p. 756.
12. 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.
13. Mamas, L. and E. Mamas, Premature ovarian failure and dehydroepiandrosterone. Fertil Steril, 2009. 91(2): p. 644-6.
14. Mamas, L. and E. Mamas, Dehydroepiandrosterone supplementation in assisted reproduction: rationale and results. Curr Opin Obstet Gynecol, 2009. 21(4): p. 306-8.
15. 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.
16. 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.
17. Bentov, Y., et al., The contribution of mitochondrial function to reproductive aging. J Assist Reprod Genet, 2011. 28(9): p. 773-83.
18. Bentov, Y. and R.F. Casper, The aging oocyte--can mitochondrial function be improved? Fertil Steril, 2013. 99(1): p. 18-22.
19. 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.
20. Muasher, S.J., et al., The value of basal and/or stimulated serum gonadotropin levels in prediction of stimulation response and in vitro fertilization outcome. Fertil Steril, 1988. 50(2): p. 298-307.
ACKNOWLEDMENTS: We thank Ferring Canada for the unrestricted grant for this study.
Special thanks to Dr. Zohreh Nazemian for helping with statistical analyses.