Corifollitropin alfa在不同不孕症族群中的效能：一項系統性回顧和統合分析

中文摘要研究目的：在試管嬰兒治療中，誘導排卵療程是關鍵步驟之一。 如何能夠獲得較多成熟卵子與治療成功率至關重要。目前，大部分的療程需要每天施打藥物，許多夫妻更是需要經過多次療程才能成功懷孕。 打針次數常常造成病人極大的心理壓力。Corifollitropin alfa(CFA)是一種透過基因重組的技術所製成的長效型排卵針，可在一劑藥效下維持7天誘導濾泡發育。這樣的設計可以減少病人針劑施打的次數和醫院往返的次數。然而，關於CFA能否取代傳統的重組卵泡刺激激素(recombinant follicle stimulating hormone;rFSH)目前仍有爭議。 臨床上尚缺乏對低與高反應族群的統合分析研究。2019年的一項統合分析發現，在卵巢反應正常族群中，CFA和重組卵泡刺激激素的比較，在最重要的取卵數會有多取得一顆成熟卵子的優勢，但懷孕率上沒有顯著差異。本次研究旨在探討CFA在不同子群中，尤其是低反應族群，的效果和安全性，進一步比較其與重組卵泡刺激激素的差異。研究方法及資料：此研究是一項關於CFA在試管嬰兒治療中的應用做系統性回顧和統合分析。我們分析了從2008年至2020年間發表的10篇臨床隨機對照試驗。這些試驗比較了CFA與重組卵泡刺激激素在不同試管嬰兒療程中的療效和安全性。研究結果：主要結果方面，我們發現CFA組與重組卵泡刺激激素組的持續懷孕率沒有顯著差異（風險比 0.93; 95% 信賴區間, 0.81-1.06, P=0.27），且CFA在正常反應者中有取得較多卵子、成熟卵子(MII)和胚胎的優勢。(卵子數 (平均差異=1.01[95% 信賴區間,0.3-1.72], P=0.006), 成熟卵子數(平均差異=1.17 [95% 信賴區間, 0.42-1.92], P=0.002), 胚胎數(平均差異=0.55 [95% 信賴區間,0.1-1.0], P=0.02)。 然而，在低反應者中，這些優勢並不明顯。在安全性方面，CFA組與重組卵泡刺激激素組之間的卵巢過度刺激症候群發生率沒有顯著差異。綜合來看，本研究提供了對CFA在試管嬰兒治療中的應用提供了實證支持，對於臨床醫師在選擇治療方案和提供患者咨詢時具有指導意義。然而，仍需要進一步研究來探討CFA在不同反應者群體，特別是高反應著中的效果和安全性，以及其在成本效益方面的影響。結論與建議：本系統性回顧和統合分析的結果顯示，在拮抗劑療程使用CFA與傳統的重組卵泡刺激激素相比，在卵巢正常反應著中，懷孕率並沒有顯著差異，但有取得較多卵子、成熟卵子和胚胎的優勢。這表明CFA可能在此族群可作為一種替代重組卵泡刺激激素用於試管嬰兒治療的排卵誘導劑。低反應者使用CFA，則沒有觀察到取卵數目及胚胎數的優勢，但與重組卵泡刺激激素比較，在持續懷孕率及活產率也沒有發現有劣勢。然而，對於高反應族群的效果尚臨床隨機試驗的研究來探討統合分析。關鍵詞: Corifollitropin alfa, Elonva, IVF, GnRH antagonist, poor responder

AbstractOvarian stimulation is a critical step in in vitro fertilization (IVF) treatment and achieving a higher number of mature oocytes is essential for the success rate of the treatment. Most ovarian stimulation protocols require daily injections, and many couples undergo more than one cycle before achieving pregnancy. This may lead to significant psychological stress. Corifollitropin alfa (CFA) is a long-acting follicle-stimulating hormone developed through genetic recombination and is capable of maintaining follicular development for seven days with a single injection. This reduces the number of injections and hospital visits for patients.However, there is still controversy regarding whether CFA can replace traditional recombinant follicle-stimulating hormone (rFSH). There is a lack of comprehensive analysis of CFA's effectiveness and safety in low and high responder groups. A 2019 meta-analysis found that in normal ovarian responders, CFA had an advantage of yielding one more mature oocyte compared to rFSH, but there was no significant difference in pregnancy rates. Our study aims to investigate the effectiveness and safety of CFA in different subgroups, especially low responders, and to compare it with rFSH.Methods:This study is a systematic review and meta-analysis of the application of CFA in IVF treatment. We analyzed ten randomized controlled trials published between 2008 and 2020. These trials compared the efficacy and safety of CFA with rFSH in various IVF protocols.Results:The primary outcomes showed no significant difference in ongoing pregnancy rates between the CFA and rFSH groups (risk ratio 0.93; 95% confidence interval, 0.81-1.06, P=0.27). However, in normal responders, CFA had advantages in the number of oocytes retrieved, mature oocytes (MII), and embryos (oocytes: mean difference=1.01 [95% confidence interval, 0.3-1.72], P=0.006; mature oocytes: mean difference=1.17 [95% confidence interval, 0.42-1.92], P=0.002; embryos: mean difference=0.55 [95% confidence interval, 0.1-1.0], P=0.02). These advantages were not significant in low responders. Regarding safety, there was no significant difference in the incidence of ovarian hyperstimulation syndrome between the CFA and rFSH groups.Overall, this study provides more concrete evidence for the application of CFA in normal and low responders, offering guidance for clinicians in choosing treatment protocols and advising patients. Further research is needed to explore the effects and safety of CFA in high responders. Conclusion:The results of this systematic review and meta-analysis indicate that using CFA in GnRH antagonist protocols compared to traditional rFSH in normal ovarian responders does not significantly differ in pregnancy rates. In addition, it has the advantages in obtaining more oocytes, mature oocytes, and embryos. This suggests that CFA may be a viable alternative to rFSH for ovarian stimulation in IVF treatment for this population. For low responders, CFA did not show advantages in the number of oocytes retrieved or embryos but was not inferior to rFSH in ongoing pregnancy and live birth rates. However, the effects in high responders still require further investigation through clinical trials and meta-analyses.Keywords: Corifollitropin alfa, Ovarian stimulation, poor response, normal response, ongoing pregnancy, IVF