Update on Infertility Research in Taiwan 林永明 國立成功大學醫學系泌尿學科

Transcription

1 Update on Infertility Research in Taiwan 林永明 國立成功大學醫學系泌尿學科

2 民 65.07

3 目前國內研究男性不孕症機搆 台大醫院泌尿部 台北榮總泌尿科 三軍總醫院泌尿科 林口長庚醫院泌尿科 北醫附設泌尿科 輔仁大學 成大醫院泌尿部 / 婦產部 中研院生醫所 台北市聯合醫院仁愛院區

4 資料收集方式 男性不孕症研究小組成員 國內其他非泌尿科研究室研究男性不孕症 NCBI 網站搜尋近 10 年論文 ISI Web of Knowledge: impact factor and times cited 發表論文主題分類 統計分析

5 四大類論文數比例 ( 共 80 篇 ) [ 類別名稱 ] [ 百分比 ] [ 類別名稱 ] [ 百分比 ] [ 類別名稱 ] [ 百分比 ] [ 類別名稱 ] [ 百分比 ] Endocrine Clinical Genetic Procedure Total paper number Average impact factor

6 Genetic study category and impact factor Topic No. paper Average Impact factor Y chromosome Septin CFTR DAZ CDC25AB Genetic screening DAZL FGF Lrwd Histone USP MPF GTPase-activating BOULE TEX HIBADH Total paper number 47 Average impact factor 3.648

7 Topic Genetic study times cited No. paper Times cited Y chromosome Septin 7 52 CFTR 5 74 DAZ 4 81 CDC25AB 4 24 Genetic screening 3 48 DAZL 3 29 FGF Lrwd1 1 6 Histone 1 2 USP MPF 1 13 GTPase-activating 1 1 BOULE 1 19 TEX HIBADH 1 0 Total times cited Average times cited

8 Y chromosome related studies A simplified gene-specific screen for Y chromosome deletions in infertile men. (Fertil Steril 2007) Transcriptional levels of four Y chromosome-linked AZF genes in azoospermic men and their association with successful sperm retrieval. (Urology 2004) Uniform deletion junctions of complete AZFc deletion in Taiwanese infertile Men. (Asian J Androl 2006) Isochromosome of Yp in a man with Sertoli-cell-only syndrome. (Fertil Steril 2005)

9 Y chromosome related studies Partial duplication at AZFc on the Y chromosome is a risk factor for impaired spermatogenesis. (Hum mut 2007) Testicular biopsy specimen was poorly correlated with the different deletion areas of the Y chromosome. (Asian J Androl 2004) A two-step protocol for the detection of rearrangements at the AZFc region on the human Y chromosome. (Mol Hum Reprod 2006) Evolution of the DAZ gene and the AZFc region on primate Y chromosomes (BMC Evol 2008)

10 Septin related studies Mutant in Septin 12 results in misshapen nuclei, disorganized mitochondria, and broken acrosomes of sperm, indicating indicate that Septin12 expression levels are critical for mammalian spermiogenesis. (Am J Pathol. 2009) SEPT12-microtubule complexes are required for sperm head and tail formation. (Int J Mol Sci. 2013) SEPT12 mutations (two missense SEPT12 mutations, c.266c>t/p.thr89met and c.589g>a/p.asp197asn) cause male infertility with defective sperm annulus. (Hum Mutat 2012) SEPTIN12 genetic variants confer susceptibility to teratozoospermia. (PLoS One. 2012)

11 CFTR related studies The overall frequency of CFTR mutant alleles in Taiwanese CBAVD males was 26 out of 72 (36%). The mutation spectrum of CFTR in CBAVD patients does not overlap with the Caucasian CFTR mutation spectrum. Unlike Caucasian patients, the CFTR mutations cannot account for the majority of Taiwanese CBAVD. (Hum Reprod 2004, 2005) IVS8-5T linked to either 12 or 13 TG repeats exhibits a high prevalence among CBAVD patients. (Clin Genet 2009) Gene copy number variations in Asian patients with congenital bilateral absence of the vas deferens. (Hum Reprod 2009) CFTR mutation analysis of a Caucasian father with CBAVD, a Taiwanese mother, and twins resulting from ICSI procedure (J Formos Med Assoc 2008)

12 Clinical analysis category and impact factor Topic No. paper Average Impact factor Varicocele Testicular volume Oxidative stress Klinefelter's syndrome Microlithiasis ,XX male Maturation arrest CAVD Total paper number Average impact factor

13 Clinical analysis times cited Topic No. paper Times cited Varicocele Testicular volume 2 16 Oxidative stress 1 23 Klinefelter's syndrome 1 30 Microlithiasis ,XX male 1 0 Maturation arrest 1 4 CAVD 1 0 Total times cited Average times cited

14 Varicocele related studies Predictive factors of successful varicocelectomy in infertile patients were high testicular volume, low serum concentration of FSH and high number of ligated veins. (Urol Int 2011) Risk factors (greater PRF and scrotal temperature) for progressive deterioration of semen quality in patients with varicocele. (Urology 2012) Attenuation of oxidative stress after varicocelectomy in subfertile patients with varicocele. (J Urol 2008) 8-OHdG in leukocyte DNA and in sperm DNA, and 4977 bp deletion of mtdna in sperm might be useful markers for the assessment of oxidative stress. (J Urol 2004)

15 Varicocele related studies The prevalence of varicocele was higher in patients with a lower BMI (J Chin Med Assoc 2010 X 2; Int J Androl 2008) Modified subinguinal varicocelectomy for painful varicocele and varicocele-associated infertility. (J Chin Med Assoc 2004) High inguinal loupe-assisted varicocelectomy for subfertile men with varicococeles. (Arch Androl 2006)

16 Endocrine study - category and impact factor Topic No. paper Average Impact factor GnRH Hyperprolactinemia Estorgen receptor Androgen receptor Hormone profile Total paper number Average impact factor

17 Endocrine study times cited Topic No. paper Times cited Total times cited Average Times cited GnRH 3 84 Hyperprolactinemia 3 8 Estrogen receptor 2 20 Androgen receptor 1 49 Hormone profile

18 GnRH related studies Although hypothalamus and pituitary are the principal source and target sites for GnRH, several reports have recently suggested extra-hypothalamic GnRH and GnRH receptors in various reproductive tissues such as ovaries, placenta, endometrium, oviducts, testes, prostrate, and mammary glands. (Anim Reprod Sci. 2005) GnRH directly stimulated murine Leydig cell steroidogenesis by activating 3b-HSD enzyme expression. (Asian J Androl. 2008) Increased testicular GnRH transcripts, steroidogenic enzyme transcripts, and ITT levels are associated with spermatogenic failure in infertile men. Testicular GnRH is involved in the regulation of human spermatogenesis and steroidogenesis. (Fertil Steril. 2008)

19 Hyperprolactinemia related studies Hyperprolactinemia-induced hypogonadism involves a mechanism of prolactin-originated, macrophage-mediated inhibitory regulation of testosterone release by Leydig cells. (J Cell Biochem. 2003) The suppression of hcg-induced T release associated with hyperprl is through a TNF-α-mediated mechanism to suppress the Leydig cells. (J Sex Med. 2012) Anti-TNF-α Ab has a potential therapeutic application on hyperprl-induced hypogonadism or suppression of hcginduced T release. (J Sex Med. 2012)

20 Procedure analysis category and impact factor Topic No. paper Average Impact factor Vasovasostomy Cryopreservation Electroejaculation ART analysis Total paper number Average impact factor

21 Procedure analysis times cited Topic No. paper Times cited Vasovasostomy 2 9 Cryopreservation 1 5 Electroejaculation 1 17 ART analysis 1 0 Total times cited Average times cited

22 Procedure related studies There was no significant difference in the patency and paternity rates between loupe-assisted and microsurgical modified one layer vasovasostomy. (BJU Int. 2005) The low rates of sperm cryostorage for fertility preservation in cancer patients (75 patients in 10 years) suggest that there is a need for greater emphasis of this option for male oncology. (J Formos Med Assoc. 2006) Electroejaculation and systematic ART are highly efficient for achieving pregnancy with the spouses of men with SCI (with cumulative successful pregnancy rate per couple of 80%). The neurologic deficit and electroejaculation did not affect the outcome of ICSI. (Arch Phys Med Rehabil. 2003)

23 Most frequent studies Topic No. paper Average Impact factor Y chromosome Varicocele Septin CFTR DAZ

24 Papers published in 30 journals Journal Impact factor (2012) No. paper published Hum Reprod Fertil Steril Urology Asian J Androl Int J Androl Arch. Andrology J Chin Med Assoc J Formos Med Assoc Am J Pathol J Androl J Urol Hum Mutation

25 Papers published in 30 journals (cont.) Journal Impact factor (2012) No. paper published J Clin Endocr Metab Mol. Endocrinol Mol. Hum. Reprod J Sex Med BMC Evol Clin Genet Genomics J Cell Biochem BJU Int Arch Phys Med Rehab Sex Dev Reprod Bio Endocrin

26 Impact factor distribution Impact factor No. paper IF <1 8 1 IF < IF < IF < IF <5 15 IF 5 3 Average IF: 3.077

27 Impact factor > 5 Post-transcriptional regulation of CDC25A by BOLL is a conserved fertility mechanism essential for human spermatogenesis J Clin Endocrinol Metab Partial duplication at AZFc on the Y chromosome is a risk factor for impaired spermatogenesis in Han Chinese in Taiwan Hum Mut SEPT12 mutations cause male infertility with defective sperm annulus Hum Mut

28 結論 國內研究男性不孕症機構過去 10 年來發表至少 80 篇 SCI 論文 最常研究的類別為基因相關研究, 最常研究的主題為 Y chromosome Varicocele 與 Gene related 平均 Impact factor 為 3.077, 平均被引用次數為 11.2 次, 共被引用 892 次 論文最常發表於 Human Reproduction (10 篇 ) 及 Fertility Sterility (10 篇 ) 台灣男性不孕症之研究有相當的深度與廣度, 過去 10 年來, 成果非常豐碩