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研究生: 邱立嫻
Chiu, Li-Hsien
論文名稱: 助孕科技對於多胞胎、早產、低出生體重及胎兒小於妊娠年齡影響之年代趨勢
Secular trends in the effects of assisted reproductive technology on multiple births, preterm birth, low birth weight , and small for gestational age.
指導教授: 余聰
Yu, Tsung
學位類別: 碩士
Master
系所名稱: 醫學院 - 公共衛生學系
Department of Public Health
論文出版年: 2024
畢業學年度: 112
語文別: 中文
論文頁數: 71
中文關鍵詞: 人工生殖輔助生殖技術人工生殖法多胞胎早產低出生體重胎兒小於妊娠年齡人群歸因危險度直接標準化時間序列分析
外文關鍵詞: Assisted reproduction, Assisted reproductive technology, Assisted Reproduction Act, Multiple births, Premature birth, Low birth weight, Small for gestational age (SGA), Population attributable risk, Age direct standardization, Time series analysis
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  • 背景與目的: 近年來,台灣的生育率不斷下滑,整體晚婚晚育的風氣,使得不孕症的盛行率逐漸上升。目前主要藉由人工生殖技術來解決不孕的問題,然而,進行人工輔助生殖技術時,為了提高懷孕成功的機率,醫生常常會植入多個胚胎,因此會使雙胞胎或多胞胎的機率提高,也因子宮內的空間有限,當缺乏空間和營養時,可能會使子宮提早收縮,進而導致新生兒早產、低出生體重(LBW)和胎兒小於妊娠年齡(SGA)的情形,加上在進行人工生殖時的胚胎操作與環境因素容易導致基因變異,也較易產生較高早產、低出生體重及SGA的風險。因此為有效避免多胞胎的發生及降低新生兒不良健康風險,我國也於2007年施行之《人工生殖法》中第16條第5項訂定每次不得植入超過5個以上胚胎之規定。基於此背景,本研究目的除了要探討台灣人工生殖與自然受孕的多胞胎、早產、低出生體重及SGA比率與可歸因風險(PAR)的年代趨勢變化外,也希望透過母親生育年齡因素的校正去做更深入的比較分析,另外,本研究也將分析人工生殖法施行前後對多胞胎、早產、低出生體重(LBW)和SGA隨時間變化所產生的趨勢影響。

    方法:將出生通報檔與人工生殖資料庫藉由ID來進行串聯分析,並標記出各年度是屬於人工生殖的生產結果,研究對象為2001年至2020年出生的活產胎兒。20年間,共計4,016,530例活產分娩,其中有71,000人(1.77%)接受了輔助生殖技術。本研究計算了2001年至2020年期間使用及不使用輔助生殖技術的受術者中,每年每1000例分娩中有多少多胞胎和周產期結果的比率,並且計算人群歸因危險度(PAR),分析我國年代趨勢變化,並利用中斷時間序列分析來評估人工生殖法介入前後的效果。

    結果:輔助生殖使用率在2001年為0.57%,2020年來到了4.03%,並且在2009年開始明顯有急遽上升的情形。母親年齡也有明顯的老化,因此數據皆進行了直接年齡標準化的校正。在比率的部分未使用輔助生殖組多數呈現上升趨勢(僅有多胞胎呈現微幅下降),使用輔助生殖組則皆呈現下降的趨勢,在人工生殖法通過後更呈現顯著的下降,多胞胎為(每年-10.63,p<0.001)、早產(每年-6.74, p = 0.003)、低出生體重(每年-9.38,p<0.001)以及SGA(每年-4.48, p = 0.001),也觀察到介入後SGA立即的顯著下降(-53.45, p = 0.005)。然而,PAR在介入前後均維持上升,但SGA的PAR在介入後(每年+0.06,p=0.032)的成長趨勢明顯低於介入前(每年+0.16,p<0.001)。

    結論: 在未使用輔助生殖技術的台灣人口中,早產、低出生體重和SGA的發生率實際上都呈現上升的趨勢,推測原因是危險因子皆隨時間呈現平行增加或嬰兒死亡率下降導致有健康問題的胎兒存活率上升。在2007年施行《人工生殖法》後,多胞胎率、早產率、低出生體重率和SGA率隨之下降,尤其SGA在介入後產生立即明顯的下降,也顯示人工生殖法的施行有助於降低多胞胎及周產期不良結果。然而,由於使用輔助生殖技術的受術者逐年增多,在人群歸因危險度(PAR)的部分仍維持上升趨勢,其中多胞胎人群歸因危險度(PAR)更高達48%,,這也表明目前台灣的輔助生殖技術是產生多胞胎的主要因素之一。

    The purpose of this study is to explore the secular trends in the rates and attributable risks (PAR) of multiple births, preterm birth, low birth weight (LBW), and small for gestational age (SGA) between assisted reproduction and natural conception in Taiwan, with adjustments for maternal age to provide a more in-depth comparative analysis. Additionally, this study examines the trend effects of multiple births, preterm birth, LBW, and SGA before and after the implementation of the Assisted Reproduction Act over time. The study analyzed the Birth Registration Database and the Artificial Reproduction Database, focusing on live births from 2001 to 2020. A total of 4,016,530 live births were recorded, of which 71,000 (1.77%) involved assisted reproductive technology. Results indicate that the proportion of deliveries involving assisted reproductive technology increased from 0.57% in 2001 to 4.03% in 2020, with a sharp increase observed since 2009. Additionally, there was significant aging in maternal age. In terms of rates, the majority of those who did not use assisted reproduction showed an upward trend (with only multiple births showing a slight decrease), while those who used assisted reproduction showed a downward trend. After the implementation of the Assisted Reproduction Act, significant reductions in rates were observed through interrupted time series analysis, particularly an immediate decrease for SGA. However, while the PAR continued to rise before and after the intervention, the increasing trend of SGA post-intervention was significantly lower than that pre-intervention.

    摘要 I 致謝 VII 目錄 VIII 圖目錄 X 表目錄 XI 第一章、緒論 1 第一節、研究背景 1 第二節、知識缺口 3 第三節、研究目的 3 第二章、文獻回顧 4 第一節、人工生殖之介紹及台灣人工生殖之情形 4 第二節、人工生殖與多胞胎的相關性 5 第三節、人工生殖與早產、低體重、胎兒小於妊娠年齡新生兒的相關性 6 第四節、胎數別(移植胚胎數)對早產、低體重、胎兒小於妊娠年齡新生兒的影響 7 第五節、冷凍與新鮮胚胎的結果差異 8 第六節、台灣人工生殖法的變革 9 第三章、研究設計 10 第一節 、資料來源與研究對象 10 第二節 、資料分析與處理 11 第三節 、研究設計與研究架構 13 第四章、研究結果 15 第一節、研究之描述性統計 15 第二節、使用及不使用輔助生殖技術之分娩的各產婦年齡組分布及變化趨勢 15 第三節、未使用輔助生殖技術者之相關結果 15 第四節、使用輔助生殖技術者之相關分析結果 16 第五節、人群歸因危險度(PAR)相關分析結果 17 第六節、台灣各年度人工生殖使用情形與多胞胎、早產、低出生體重及SGA發生比率 18 第五章、討論 21 第一節、主要研究發現 21 第二節、研究貢獻與限制 22 第三節、結論與建議 23 第六章、參考文獻 25 圖與表 30

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