7 Sep 2012
INTRODUCTION: Since our first use of exogenous androgens in early 2006 for patients with age related poor ovarian response (POR) or patients of any age with diminished ovarian reserve (DOR)¹ we have extensive data in over 1865 cycles in women treated with natural cycles, oral aromatase inhibitors (AI) , COH with IUI or IVF. From this large group we here report our analysis of the results in our first 401 cycles using COH+ IUI in varying age groups.
METHODS: These 401 cycles were all from patients who had failed to get pregnant on DHEA alone, DHEA with oral AI and were not candidates for IVF yet. We divided the age groups into: group 1: women <35yrs (N=45); group 2: women 35-39 yrs (N=148); group 3: women 40-42 completed yrs (N=107); and group 4: women 43-48 yrs (N=99).
RESULTS: Group 1, 45 cycles of COH-IUI, pregnancy rate per cycle started (PR/cycle) 8.5%, cancellation rate 4.3%, loss rate 25%, PR/completed cycle 8.9% and take home baby rate per cycle (THBR/cycle) 6.67%.
Group 2, 148 cycles of COH-IUI, PR/cycle 14.9%, none-cancelled, loss rate 36.4% included 2 ectopic pregnancies and one chemical pregnancy and THBR/cycle of 9.46%.
Group 3, 107 cycles of COH-IUI, PR/cycle 13.1%, none-cancelled, loss rate 35.7% and THBR/cycle 8.4%.
Group 4, 99 cycles of COH-IUI, PR/cycle 2.02%, cancellation rate of 3%, loss rate 50% , PR/completed cycle 2.08% and THBR 1%.
CONCLUSION: 33% of all IVF centers worldwide now use androgen supplementation¹. We used the commonly accepted definition of “poor responders“². Our PR/IUI cycle completed in group 2 is 15% with a THBR of 9.5% compares well with Merveils data³ of a 3 cycle cumulative PR of 38.5% in women under 30 yrs of age who are not in this prognostically poor group of DOR patients. He had a PR of 12.5% cumulative for 3 cycles over age 40. Of special note is the poor outcome in our group 1 raising the issue of a different pathophysiology in the young DOR patients, ranging from FMR1 premutations to other gene specific abnormalities⁴ on the autosomes.
Najihara⁵ showed that androgen induced changes in human myometrial stromal cells increases implantation. DOR/POF up to now has been mainly thought of as an X chromosomal problem⁶-10. It is now known that aside from FMR1 premutations, changes in BMP15, POF1B, GDF9, FIGLA, FOXO1a, NOBOX, and microduplications and microdeletions on chromosomes # 1, 2, 3, 4, 6, 7, 8, 9, 11, and 16 may have a role in DOR/POF.
From our stats it is evident that the best performing group is from 35-39 yrs of age, followed by the 40-42, but >43 yrs the results are very poor. We will be looking forward to seeing more results from other centers with DOR, POF patients who undergo aggressive COH with IUI before proceeding to IVF or Donor egg programs.
1: Poor responders; survey of 196 IVF centers; www.ivf-world-wide.com.
2: Ferraretti et al. ESHRE consensus of “poor responders” Bologna criteria. Human Reprod. 2011, 26(7); p1616-24.
3: Merviel et al. Fertil Steril. 93, 1; p79-88.
4: Geno McGuire Megan et al. Fertil Steril. 2011, 5; p1595-1599.
5: Najihara T et al. Effect of androgens on Human endometrial stromal cells, acting through FOXO1 and SOD2. Fertil Steril. 2012. 97; p185-91.
6: Toniolo D. Semin Reprod Med. 2007
7: Bione S et al. DACH2 and POF1B. Human Reprod. 2004, 19; p2759-66.
8: Rizzolio F et al. Human Reprod. 2006, 21; p1477-84.
9: Rossetti F et al. Eur. J. Human Genetics. 2004, 12; p829-34
10: Toniolo D . Semin Reprod Med. 2007 25. p264-71.