Poseidon Grup 1 ve 2 Hastalarda GnRH-antagonist, GnRH-agonist ve “Progestin Primed” Ovaryan Stimulasyon (PPOS) Protokollerinin Canlı Doğum Oranı Üzerine Etkilerinin Retrospektif Olarak Karşılaştırılması

Abstract

Tez, R., Comparison of the Live Birth Rates (LBRs) between GnRH-antagonist, GnRH-agonist and Progestin Primed Ovarian Stimulation (PPOS) Protocols in patients with POSEIDON Group-1&2, Hacettepe University Faculty of Medicine, Thesis in Obstetrics and Gynecology, Ankara 2022 We aimed to determine the effect GnRH-antagonist, GnRH-agonist and PPOS protocols on LBR in patients with POSEIDON group-1&2. A total of 1327 consecutive couples undergoing their first ICSI cycle at tertiary academic center during January 2014-July 2021 were included. Patients meeting POSEIDON group-1 (<35 years-old, anti-mullerian hormone (AMH) level 1,2 ng/ml or antral follicle count (AFC) 5 and number of oocytes retrived after OS <10, n =643), POSEIDON group-2 (35 years-old, AMH level 1,2 ng/ml or AFC 5 and number of oocytes retrived after OS <10, n =344) or normo-responder (number of oocytes retrived after OS is between 10-15, n =340) criteria were included to study. Primary outcome measure was LBR and secondary outcome measure was follicle oocyte index (FOI). Gonadotropin starting dose was adjusted according to patient's age, BMI and ovarian reserve markers. For pituitary suppression, GnRH-antagonist, long GnRH-agonist or PPOS were used. While either fresh or frozen-warmed ET was performed in GnRH-antagonist and GnRH-agonist cycles, only frozen-warmed ET was performed in PPOS cycle. The female age was significantly older (30 vs 37,5 vs 30; p<0,001), AFC (14 vs 10 vs18; p<0,001) and AMH (2,6 vs 1,9 vs 3,8 ng/ml; p<0,001) were significantly lower in POSEIDON group-2 patients compared to POSEIDON group-1 and normo-responders. BMI (24,5 vs 24,6 vs 23,8; p=0,02) was significantly lower in normoresponders compared to POSEIDON group-1 and 2 patients. Dose of total gonadotropin used was significantly higher (2250 vs 2700 vs 1988 IU; p<0,001) in POSEIDON group-1 and 2 patients compared to normoresponders. As expected, cycle cancellation rates were significantly higher in POSEIDON group patients compared to normoresponders (13,8% vs 20,9% vs 7,1% p<0,001), while live birth rates per transfer were significantly lower (31,8% vs 22,3% vs 36,2%; p=0,001). When logistic regression analysis was performed to determine independent factors affecting unexpected hypo-response in POSEIDON group 1 and 2 patients; female age (OR= 1,05, 95% CI 1,02–1,08; p=0,001), AFC (OR=1,03, 95% CI 1,02– 1,05; p<0,001) and BMI (OR= 1,06, 95% CI 1,03– 1,10; p<0,001) were found to be independent predictors of unexpected hypo-response. Whereas pituitary suppression protocol (OR= 1, 95% CI 0,5–1,88, p=0,57) and gonadotropin type (OR= 0,65, 95% CI 0,4–1,04; p=0,07) were not found to be independent predictors of unexpected hypo-response. On the other hand, FOI was found to be significantly higher with GnRH-agonist cycles compared to GnRH-antagonist and progestin primed cycles. This difference reached a statistical significance in favor of the agonist in POSEIDON group-1 and normoresponder patients. Regression analysis was performed to determine the independent predictors of live birth rate. In POSEIDON group-1 patients, only day of ET (OR= 1,626, 95% CI 1,041–2,534; p=0,03) was found to be a significant predictor of live birth rate. When the same analysis was performed for POSEIDON group-2 patients, female age (OR=0,83 95% CI 0,71–0,97; p=0,02), BMI (OR= 0,8 95% CI 0,66–0,97, p=0,02), antral follicle count (OR=1,05 95% CI 1,01– 1,11; p=0,046), treatmant year (OR= 0,8 95% CI 0,66– 0,97; p=0,02), and number of embryos transferred (OR= 2,47 95% CI 1,09– 5,57; p=0,03) were found to be significant predictors of live birth rate. The pituitary suppression protocol was not an independent predictor of live birth rate in patients with unexpected hypo-response. For patients with unexpected hypo-response, diagnosed as POSEIDON Group 1&2, LBR is comparable among the GnRH-antagonist, GnRH-agonist and PPOS protocols, either can be preffered for treatment. Considering the higher FOI rate of GnRH-agonist protocols in younger patient groups such as POSEIDON group-1, GnRH-agonist protocols may have positive effects on cumulavite delivery rate therefore may be preferred in some special young patients with a history of asynchronous follicular development in their previous OS cycles, although higher doses of gonadotropins may be required. Further randomized controlled trials are warranted. Key Words: Poor ovarian response, pituitary supression, live birth rate, POSEIDON classification