| 摘要: | 根據世界衛生組織定義，不孕症是一對擁有正常性生活且沒有採避孕措施的夫婦，12個月內仍然無法自然懷孕者稱之。臺灣男性不孕症比例約是10-15%。本研究分為三個部分，分別是男性不孕症於全民健康保險研究資料庫分析、探討血液賀爾蒙檢測值與精子品質之相關性、研究鈣離子通道相關基因多型性與精子特徵之關聯性。
本研究使用國際疾病統計分類第九修訂版代碼（ICD-9）做為納入族群之依循，分析西元1997至2010年國人男性不孕症於健保資料庫記載之盛行率及年發生率，並探討男性不孕症於不同都市化程度分群狀態及伴隨共病症之比例。結果顯示，男性不孕症盛行率自西元1997年到2001年逐年增加。於2003年後，男性不孕症之盛行率落在0.24~0.32 %、每年新發生率維持在0.15~0.20 %。在子族群分析，男性不孕症就診紀錄以都市化程度為分群一、年收入大於25,001元、年齡落於30~39歲相對比例為高。五分之一男性不孕症者伴隨有焦慮症，9.5%患有糖尿病，6.6%有甲狀腺功能異常之診斷。
在2013至2014年間，本研究於萬芳醫院婦產科收案共計70位男性，採取受檢者之血液執行賀爾蒙檢測及去氧核醣核酸（DNA）萃取，亦進行精液分析。結果顯示，年齡與精液濃度、精子活動力、嚴格精蟲型態學均呈現負相關；年齡與黃體化激素、濾泡刺激素、性荷爾蒙結合球蛋白呈現正相關。本研究族群之四碘甲狀腺素、游離四碘甲狀腺素與精液濃度呈現正相關（p值分別為0.040、0.034）。
本研究第三部分係以TaqMan技術探討鈣離子通道相關基因TRPC3、TRPV5、STIM1、Orai1、TRPC4及ITPKC上標籤單一核苷酸基因多型性與精子活動力、精液濃度、精蟲型態的關連性。結果顯示，STIM1、Orai1、TRPC、ITPKC上各有單一核苷酸多型性與精子活動力相關；TRPC3、STIM1、Orai1上有單一核苷酸多型性基因與精液濃度相關；TRPV5、Orai1、ITPKC上各有單一核苷酸多型性基因與精蟲型態相關。當中Orai1_5位點與精子活動力、精液濃度、精蟲型態三者均有顯著相關性。
致使男性不孕症發生的原因相當複雜，本研究結果顯示，特定的血液賀爾蒙及鈣離子通道相關單一核苷酸多型性基因未來有做為生物標記以預測精子品質的可能性。受限於收案人數，仍需擴大收案人數以得到更具可信度之推論。
According to World Health Organization, infertility is defined as a couple failures to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. Infertility rate in Taiwan ranged from 10 % to 15 %. Three parts of studies related to male infertility were conducted in this research. (1) Analysis for male infertility in Taiwan through National Health Insurance Research Database (NHIRD). (2) To find associations between serum hormone levels and sperm qualities. (3) To find out whether there are associations between calcium channel-related genetic polymorphisms and sperm qualities.
For database analysis, we searched the NHIRD from 1997 to 2010 and further constructed the relationships between male infertility (MI) with both urbanization level and different comorbidities. Study population was retrieved by using International Classification of Diseases, Ninth Revision set (ICD-9). The prevalence rate of MI increased steadily between 1997 and 2001. After year 2003, the prevalence rate ranged from 0.24 % to 0.32 %. Yearly new occurrence rate remain between 0.15 % and 0.20 % from then on. For subgroup analysis, infertile males living in townships stratified as urbanization level 1, with monthly income more than 25,001 and aging within 30~39 have relatively higher percentage of MI diagnosis. One-fifth of MI population accompanied with anxiety, 9.5% of which had diabetes mellitus, and 6.6% had been diagnosed of thyroid gland disorders.
In our study, 70 participants from WanFang Hospital with varied sperm qualities were recruited during the period from 2013 to 2014. Both biochemical data and deoxyribonucleic acid (DNA) samples were collected. Semen analysis was performed as well. In our study population, age was inversely related to sperm motility, concentration and strict morphology, thus positively related to luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin. Serum hormone level T4 and fT4 have positive correlation with sperm concentration. (p= 0.040 and 0.034 respectively)
The third part of our research was to identify the associations between sperm qualities and tagging single nucleotide polymorphisms (SNPs) in calcium channel-related genes by using TaqMan genotyping assay. In our study population, STIM1, Orai1, TRPC4 and ITPKC were observed to have associations with sperm motility. SNP(s) in TRPC3, STIM1, Orai1 were associated with sperm concentration. SNP(s) in TRPV5, Orai1 and ITPKC were found to have relationships with sperm morphology. Furthermore, Orai1_5 was observed to have significant association with sperm motility, concentration and sperm strict morphology.
In summary, despite the complexity of the pathology to cause male infertility, certain serum hormones and single nucleotide polymorphisms among calcium channel-related genes may be potential biomarkers to predict sperm qualities. Larger sample size is needed to confirm the results before making further conclusion and implementing to clinical practice. |
