- 學位論文
比較在進行黃體素輔助排卵刺激療程中，卵巢高反應者單獨使用促性腺激素釋放激素破卵與雙重破卵對於臨床結果的影響
Comparison of GnRH agonist alone trigger versus dual trigger for final oocyte maturation in high responders undergoing progestin-primed ovarian stimulation protocol
摘要
研究背景： 在試管嬰兒治療中，患者可分為三個亞群，分別是卵巢正常反應者、弱反應者和高反應者。根據目前的文獻證據，對於卵巢正常反應者來說，使用雙重破卵（GnRH agonist加上hCG）進行最終卵子細胞的成熟，可以改善生殖臨床結果。而對於卵巢弱反應者來說，雙重破卵有可能會改善臨床結果。然而，關於卵巢高反應者方面，雙重破卵的效果目前證據不足。對於卵巢高反應者來說，僅使用GnRH agonist進行破卵，然後進行全胚胎冷凍週期，可以將OHSS（卵巢過度刺激症候群）的風險降至最低。然而，有關僅使用GnRH aognist破卵的擔憂在於，對於少數患者而言，可能無法產生足夠的內生性LH和FSH，從而減少卵子細胞的成熟，降低取卵數量，最終影響懷孕結果。 目標與理由： 本研究旨在探討在卵巢高反應者進行黃體素輔助排卵刺激療程中（PPOS），使用雙重破卵的效果。該雙重破卵的組成由GnRH agonist（Lupro 2mg）和低劑量人絨毛膜促性腺激素（1000IU hCG）組成，用於最終卵子細胞成熟。研究結果主要在觀察這種雙重破卵對於卵巢高反應者的生殖臨床結果是否有所改善，同時觀察雙重破卵對於卵巢高反應者所產生的OHSS風險。 研究方法： 這是一項回溯性性研究。我們的假設是，在試管嬰兒冷凍周期中，對於卵巢高反應者，使用GnRH agonist加上低劑量hCG（1000 IU）作為卵巢排卵觸發的方式將是安全且有效的。這將有助於獲得更多成熟卵子細胞和優質胚胎。我們的納入標準如下：年齡<40歲，採集的卵子細胞數 >10個，並且採用全部胚胎冷凍策。排除標準如下：採集的卵子細胞數 >30個，卵子捐贈，PGT-A週期，先前經歷過卵巢手術，先天性子宮畸形，子宮內膜病變和曾有過全身系統性及病史。對照組為使用PPOS療程，最終卵子細胞成熟的破卵方式為僅使用GnRH agonist的患者。研究組為使用PPOS療程，最終卵子細胞成熟的破卵方式為hCG 1000IU + GnRHagonist的患者。 研究結果： 主要結果是成熟卵子（MII卵子）率。研究組的MII卵子率為90.4±13.0%，明顯高於對照組的85.5±16.5%，p<0.05。次要結果包括良好胚胎率、著床率、臨床懷孕率和活產率，在這些指標上研究組和對照組之間無顯著差異。對照組有一例OHSS病例，而研究組則有六例OHSS病例。 結論： 根據我們的研究結果，在PPOS療程中，雙重破卵可以比單獨使用GnRH agonist破卵產生更高的MII卵子率。然而，在臨床懷孕率和活產率方面並沒有顯示出明顯差異。此外，在實驗組共有六名患者患有中度至重度的OHSS。這個研究結果對於那些進行選擇性卵子冷凍的患者，雙重破卵可能會在可接受的OHSS風險下提高MII卵子率。然而對於那些接受試管嬰兒療程，並採用全部胚胎冷凍策略的患者，相比僅使用GnRH agonist破卵，雙重破卵並未顯示出其優勢。
並列摘要
Background/What is known already There are three subgroups of patients in IVF/ICSI treatment, which is normal responders, poor responders and high responders. According to the current evidence, dual trigger (GnRH agonist plus hCG) for final oocyte maturation in normal responders could improve reproductive clinical outcomes. Besides, some growing evidence suggest dual trigger may improve clinical outcomes in poor responders. However, there is insufficient evidence regarding the effect of dual trigger in high responders. In high responders undergoing IVF/ICSI treatment, GnRH agonist alone trigger and subsequent freeze-all cycle could minimize the OHSS risk. However, there are concerns about GnRH agonist trigger alone may fail to produce sufficient LH and FSH activity in a small subset of patients and resulting in reduced oocyte recovery, maturation and ultimately affecting pregnancy outcomes. Objective and rationale The present study was aimed to explore the effect of using a “dual trigger” consisting of low dose human chorionic gonadotropin (1000IU hCG) plus GnRH agonist (Lupro 2mg) for final oocyte maturation could improve the reproductive clinical outcomes for high responder patients undergoing progestin-primed ovarian stimulation (PPOS) protocol, and observe the OHSS risk of dual trigger in high responders. Study Design This is a retrospective study. We hypothesize that GnRH agonist + low dose hCG (1000 IU) would be a safe and efficacious ovulation trigger in subgroup of high responders undergoing IVF/ICSI freeze-all cycle. And more MII oocytes and good quality embryo could be obtained. Our inclusion criteria were as followed: age <40 y/o, oocyte pick up number>10#, all freeze-all cycle. Exclusion criteria were as followed: oocyte pick up number >30#, oocyte donation, PGT-A cycle, previous ovarian surgery, congenital uterine anomaly, endometrial lesion, and previous systemic medical history. The control group were patients using PPOS protocol witch GnRH agonist alone trigger for final oocyte maturation. The study group were patients using PPOS protocol with hcg 1000IU + GnRH agonist trigger for final oocyte maturation. Results Primary endpoint is MII oocyte rate. The MII oocyte rate in study group is significantly higher than in control group, 90.4±13.0% vs 85.5±16.5%, p<0.05. The secondary endpoints include good embryo rate, implantation rate, clinical pregnancy rate and live birth rate are no significant different. There was one OHSS case in the control group where there were six patients of OHSS cases in the study group. Conclusion According to our findings, the dual trigger could induce more MII rate than GnRH agonist trigger alone in PPOS protocol. However, no differences in the clinical pregnancy rate and live birth rate. Besides, there were six patients suffering from moderate to severe OHSS. For those receiving elective oocyte freezing, dual trigger may increase the MII oocyte rate with acceptable OHSS risk. For those receiving IVF/ICSI with freeze-all strategy, dual trigger didn’t show its advantage compared to the GnRH agonist trigger alone.