Combining luteal estradiol patch and GnRH antagonist suppression with co-flare and microdose flare stimulation for IVF in poor responders

Abstract

OBJECTIVE: Luteal administration of estradiol (E2) patch and GnRH antagonist (Ant) is effective in preventing follicular recruitment in the preceding luteal phase. The objective is to compare the efficacy of combining E2 patch/Ant pretreatment with 3 commonly applied poor responder IVF protocols: Co-flare (CF), microdose lupron (MDL), and Ant. DESIGN: Retrospective analysis. MATERIALS AND METHODS: Patients who underwent the 3 protocols from 1/2004-10/2009 were included. All patients applied 0.1mg E2 patch every alternate day, starting 10 days post-LH surge. On 2nd dy of E2 patch, patients started Ant for 3 days. CF protocol entailed administering 1mg leuprolide acetate (LA) from cycle day (CD) 2 to 4 and decreasing to 0.5mg on CD5. High dose gonadotropins (FSH/HMG) started on CD3. MDL protocol involved starting 80ug MDL on CD2 followed by FSH/HMG administration on CD4. Ant protocol involved starting FSH/HMG on CD2. Ant was started when leading follicle reached 13mm or E2 measured 300pg/ml. HCG was given when 2 follicles attained 17 mm. Retrieval occurred 35 hours later. The main outcome measures were: no-start rate, days of stimulation, and cancellation and clinical pregnancy rates. Statistical analyses included χ2 test and Mann-Whitney test. P<0.05 was deemed statistically significant. RESULTS: 89 CF, 56 MDL, and 2125 Ant cycles were identified. The baseline characteristics were comparable. The no-start rates were low in all 3 groups. Compared to E2/Ant/Ant group, the E2/Ant/MDL group had a significantly higher cancellation rate (36.4% vs. 18.3%), required more days of stimulation (12.6 ± 2.1 vs. 10.8 ± 2.2) and higher dose of FSH/HMG (6534.1 ± 1517.6IU vs. 5754.9 ± 1459.8IU). The clinical pregnancy rates per cycle started were comparable in 3 groups (16.3% vs. 20.0% vs. 22.7% respectively). CONCLUSION: Combinations of luteal E2 patch/Ant pretreatment with CF and MDL protocols yielded similar clinical pregnancy rates compared to E2 patch/Ant/Ant protocol and represent viable treatment options for poor responders.