輸卵管切除術對於年輕不孕症患者卵巢反應之影響

Abstract

輸卵管因素造成的不孕症所佔的比例約為所有因素綜合之30~40%，主要原因為骨盆腔感染造成的輸卵管炎、子宮內膜異位症或外科手術造成的沾黏阻塞及水腫，亦可間接造成子宮外孕。而過去文獻於1998年Zeyneloglu.等人表示，預防性將水腫的輸卵管切除可提高試管嬰兒成功率以及降低流產率。體外胚胎活體的實驗也證明水腫的輸卵管會影響子宮內膜胚胎著床的機轉。 然而，將輸卵管切除後是否對於卵巢功能及之後進入取卵療程的結果有影響，過去則一直有爭議。由於影響卵巢的因素主要有年紀、卵巢手術、子宮內膜異位症、多囊性卵巢等因素，2020年由Chen.等人發表於journal of ovarian research的研究探討女性年齡35 至39歲顯示基礎濾泡數(AFC)可能因為輸卵管手術而下降，但缺乏較年輕不孕症族群的比較以及其他衡量卵巢功能之指標比較。因此本研究欲探討35歲以下的不孕症患者其先前曾接受過輸卵管手術後，對其取卵數目之影響。2003年於Human reproduction 雜誌表示子宮外孕病人的輸卵管切除對於卵巢的大小及供應血流有顯著影響，而2015-2017年四篇 meta-analysis皆認為手術不會對卵巢有影響，但是研究異質性高，主要針對輸卵管水腫病人，而且術後長期追蹤結果未明。因此於新光醫院收集2012-2019年間的輸卵管因素的不孕試管病人，為降低年齡對於卵巢功能本身之影響。研究對象為年紀35歲以下接受取卵手術者，以曾接受輸卵管手術與否分組，並控制Age、BMI、卵巢功能指標(AMH 及AFC)、使用排卵刺激藥物劑量及刺激天數，來探討其經陰道取卵手術的結果(取卵數目)差異。 本研究為病例回溯性研究，病例及對照研究，病例資料取得以健保資料手術代碼(腹腔鏡輸卵管等附屬器切除術、子宮外孕手術以及經陰道取卵手術)委由新光醫院資訊部人員查詢，先取得病歷號資料並交由本案主持人，由主持人借閱紙本病歷，並篩選，經確定收案後即去除識別化資料(如病歷號、姓名)，之後依阿拉伯數字編碼分為研究組及對照組，過程中再將已去識別化的資料交由本案統計分析人員分析。本計畫最後收案對象以2012年1月1日至2019年12月31日，期間接受取卵手術時，35歲以下之不孕症病人，一共113人，且過去有接受過輸卵管切除術者為實驗組(54人)，其中包含輸卵管外孕及水腫。而對照組為相同年紀配對之男性不孕及不明原因不孕症之患者(59人)。我們主要比較其進入刺激排卵療程之結果。如總取卵數目、總排卵針劑量及刺激天數。 本研究以無母數分析方法，比較有無接受輸卵管手術的兩組，其術後第一次取卵手術之取卵數目、排卵針使用劑量、刺激天數。並校正BMI、day 3 FSH值、術前AMH及AFC等因子。再由線性回歸分析找出顯著影響取卵數目之因子，如AMH及AFC。再參考過去文獻以及對照本實驗之族群決定所選因子之臨界值(cut-off value)。然後依臨界值進一步做次群組分析(sub-group analysis)。 本研究納入於接受取卵手術時年齡為35歲以下之不孕症患者，實驗組包含曾接受輸卵管切除術的不孕病人54位，而輸卵管切除術的適應症有輸卵管外孕26位以及輸卵管水腫28位。對照組則包含男性因素及不明原因之不孕症一共56位；若曾接受過卵巢手術、患有子宮內膜異位症或多囊性卵巢者則排除於此研究。 結論及討論 : 在35歲以下較為年輕的不孕症患者，因輸卵管問題造成的不孕，不論是先前子宮外孕或是輸卵管水腫的原因，在經過輸卵管手術切除後，與輸卵管正常的不孕症族群相比，其試管療程的取卵數目顯著下降；而其中取卵前的卵巢功能指標次佳者如AFC <12 或是AMH <4 ng/mL者，則取卵數顯著下降。因此在有接受過輸卵管手術的年輕不孕症患者，若非有絕佳的卵巢功能指標則可考慮積極地使用刺激排卵試管嬰兒療程。本研究亦嘗試討論手術間隔、輸卵管切除的側性對於卵巢反應的影響，但由於樣本數較少故無一致性的結論。

Study Objective: The impairment of the ovarian response in in vitro fertilization (IVF) cycles after salpingectomy remains controversial. Therefore, we investigated whether a history of salpingectomy affects the number of oocytes retrieved in young women undergoing IVF in comparison with the number in women without the underlying tubal disease. We also considered the factors affecting the ovarian response as separate groups, such as indications of salpingectomy, laterality of salpingectomy, and the time interval between tubal surgery and oocyte retrieval. Design: Retrospective Case-control study (Canadian Task Force Classification II-2) Setting: A tertiary hospital–affiliated fertility center. Patients: We recruited patients under the age of 35 from 2012 to 2019, which received salpingectomies and entered IVF treatment afterward. Only Fifty-four women aged <35 years with a history of salpingectomy and 59 age-matched women without tubal disease. Interventions: Laparoscopic salpingectomy, Gonadotropin-releasing hormone antagonist protocol for controlled ovarian stimulation and transvaginal oocyte retrieval. Measurements and Main Results:The antral follicle count (AFC), anti-Müllerian hormone (AMH) levels, and the number of retrieved oocytes were significantly lower in women with prior salpingectomy than in women without tubal disease. Day-3 follicle-stimulating hormone (FSH) levels, total gonadotropin dosage, and stimulation days did not significantly differ between the groups. The indications of salpingectomy (i.e., hydrosalpinx and ectopic pregnancy) did not differ significantly in terms of ovarian response or reserve among women with salpingectomy history. A history of salpingectomy and other factors related to ovarian response in IVF, such as age, AMH, AFC, day-3 FSH, and total gonadotropin dose, were significantly correlated with the number of oocytes retrieved by univariate regression analysis. In the multivariate-adjusted model after controlling all the above-mentioned variables, only AFC and AMH levels continued to exhibit significant associations with the number of retrieved oocytes. In a subgroup analysis, the negative impact of prior salpingectomy on the number of retrieved oocytes was especially significant in women with suboptimal ovarian reserves (defined as AMH < 4 ng/mL), regardless of the indication of salpingectomy or whether salpingectomy was bilateral or unilateral. Conclusion:A negative effect on the number of retrieved oocytes in the subsequent IVF cycle after salpingectomy is more likely in women aged <35 years with suboptimal ovarian reserve. Nevertheless, postsurgical AMH and AFC levels still possess a more direct predictive value on ovarian response than the history of salpingectomy.