Impact of lead follicle size in clomiphene citrate-only minimal stimulation in-vitro fertilization (IVF) cycles

OBJECTIVE: To evaluate the effect of aromatase inhibitor (letrozole) cotreatment for patients with severe poor ovarian response: matched comparison of previous (w/o) and current (w/) cycles in the same patients. DESIGN: Retrospective cohort analysis. MATERIALS AND METHODS: From January 2012 to February 2014, Letrozole/GnRH-antagonist treated 77 patients were analyzed. Inclusion criteria: severe poor responder, at least two of the following three feature must be present were included; 1) R40 yrs, 2) no. of previous collected oocytes; %3, 3) level of AMH; <1.1ng/ml. Matched comparison of previous (treated with GnRH antagonist) and current (co-treated with Letrozole (5.0mg/day)/GnRH antagonist) cycles in the same patients was performed. Estradiol level on the day of HCG injection, the number of total and mature oocytes collected and the clinical pregnancy outcome were evaluated between two groups. RESULTS:Mean level of AMHwas 0.7 0.7 (ng/ml) and mean no. of previous cycle was 4.7 3.9. No. of collected oocytes and mature oocytes were significantly increased in letrozole co-treatment cycles (1.6 1.9 vs. 2.6 2.2, p<0.005 and 0.8 1.1 vs. 1.3 1.4, p<0.01). Retrieval failure rates (29.9%, 23/77 vs. 9.1%, 7/77, p<0.0001) were reduced in letrozole co-treatment cycles. However, there were no differences in the maturation rate (45.7%, 58/ 127 vs. 48.5%, 99/204 p1⁄40.6123), fertilization rate (85.8%, 97/113, vs. 79.9%, 143/179 p1⁄40.1953) and top quality embryo rate (76.3%, 45/59 vs. 76.8%, 53/69 p1⁄40.9426). Cycles with all embryos cryopreserved were 23.4% and 29.9% respectively. Clinical pregnancy and implantation rate were higher in letrozole co-treatment cycles but were not significantly different (19.2%, 5/26 vs. 27.6%, 8/29, p1⁄40.3367 and 8.5%, 5/59 vs. 14.1%, 9/64, 0.3296). Especially, estradiol levels and endometrium thickness on day of HCG administration were significantly low in letrozole treated patients (629.2 514.5 pg/ml vs. 312.9 328.8 pg/ml, p<0.005 and 8.5 1.7 mm vs. 7.7 1.8 mm, p<0.05). Ongoing pregnancy rate (0.0%, 0/26 vs. 20.7%, 6/ 29, p<0.05) were significantly higher in letrozole co-treatment cycle. CONCLUSION: The aromatase inhibitor, letrozole blocks estrogen synthesis and increases intraovarian androgen level. Although the use of letrozole presented the low levels of estradiol and endometrium thickness, the patients who received letrozole co-treatment showed a significant higher number of collected oocytes and higher ongoing pregnancy rate. The present study suggests that adding of aromatase inhibitor is a suitable protocol for patients with severe poor response.