- 學位論文
抗穆勒氏管荷爾蒙及介白素基因多型性與試管嬰兒療程結果之間的關聯性
Correlation of single nucleotide polymorphisms in anti-Müllerian hormone and interleukin genes with the outcomes of in vitro fertilization cycles
摘要
影響試管嬰兒(IVF)療程懷孕率與活產率的因素:包括取卵的數量，胚胎著床與流產。一些研究已經證明了取得更多的卵，可以增加累積懷孕率與活產率，而取卵的數量又與卵巢儲備量有關，目前抗穆勒氏管荷爾蒙(AMH)是可以用來預測卵巢濾泡數量的ㄧ種最敏感的生物指標。而胚胎著床與流產則涉及眾多因子，其中參與異常免疫反應的介白素 (IL)值得研究。單點核苷酸多型性(SNPs)，是最常見的基因多型性之一，當我們能預知個體中某些重要的 SNPs 時，也許我們就可以推論出此個體可能造成何種情況的缺陷。我們的研究目的在探討AMH，AMH II型受體（AMHRII）與 IL SNPs 跟試管嬰兒療程預後的關聯性。在這項前瞻性研究中，有635名接受IVF的女性其AMH 146 T> G，AMHRII -482 A> G和AMHRII IVS1 +149 T> A變異進行了基因分型。另外有1015名接受IVF的女性，探討了5種IL基因中6種SNPs對IVF結果的影響：IL-1α（rs1800587 C / T），IL-3（rs40401 C / T），IL-6（rs1800795 C / G），IL-15（rs3806798 A / T），IL-18（rs187238 C / G）和IL-18（rs1946518 G / T）。從所有參與者的血中提取DNA，並通過實時聚合酶鏈反應對SNP進行基因分型。結果發現AMH 146 T> G G / G基因型有較低的臨床妊娠率；與TT基因型女性相比，具有AMH 146 T> G GG基因型的女性其臨床妊娠的可能性是一半，至於AMHRII基因多型性則與IVF臨床妊娠無顯著差異。另外，IL-3 CC基因型的不孕婦女，其流產率高於CT + TT基因型。我們的研究結果表明，AMH 146 T> G似乎是一種能夠預測IVF妊娠結果的生物標誌物，而且IL-3 rs40401多型性與IVF患者流產風險增加有關。進一步的研究應該集中在這些關聯的機制和包含其他種族群體，以確認這項研究的結果。
並列摘要
Factors affecting the pregnancy rates and live birth rates of IVF include the numbers of pick-up oocytes, embryo implantation and abortion. Some studies have shown that getting more oocytes can increase the cumulative pregnancy rate and live birth rate. The number of oocytes is related to the ovarian reserve. Currently, the anti-Müllerian hormone (AMH) is the most sensitive biological indicator that can be used to predict the amount of ovarian follicles. Embryo implantation and abortion involve many mechanisms and factors. The interleukin (IL) system involved in abnormal immune response and is worthy of study in implantation failure and abortion. Single nucleotide polymorphisms (SNPs) are one of the most common gene polymorphisms. When we can predict some important SNPs in an individual, we may be able to deduce the flaws that may arise in this individual. The aim of this study was to investigate the effects of SNPs in the AMH, AMH type II receptor (AMHRII) and IL genes on in vitro fertilization (IVF) outcomes. In this prospective cohort study, we genotyped the AMH 146 T > G, AMHRII −482 A > G and AMHRII IVS1 +149 T > A variants in 635 women undergoing their first IVF. Another prospective cohort analysis was performed from 1015 female patients undergoing fresh IVF cycles. The effects of the following six SNPs in five IL genes on IVF outcomes were explored: IL-1α (rs1800587 C/T), IL-3 (rs40401 C/T), IL-6 (rs1800795 C/G), IL-15 (rs3806798 A/T), IL-18 (rs187238 C/G) and IL-18 (rs1946518 G/T). DNA was extracted from the peripheral blood of all participants, and the SNPs were genotyped by real-time polymerase chain reaction. The results revealed that the AMH 146 T > G G/G genotype in women was associated with a lower clinical pregnancy rate. Women with the AMH 146 T > G GG genotype were half as likely to have a clinical pregnancy compared with women with TT genotypes. No significant difference was found between AMHRII polymorphisms and clinical pregnancy outcomes of IVF. Infertile women with IL-3 homozygous major genotype had a higher abortion rate than those with heterozygous and homozygous minor genotype. Our results show that AMH 146 T > G seems to be a susceptibility biomarker capable of predicting IVF pregnancy outcomes and the IL-3 rs40401 polymorphism is associated with increased risk of abortion of IVF patients. Further studies should focus on the mechanism of these associations and the inclusion of other ethnic populations to confirm the findings of this study.