title: Aromatase (CYP19) gene variants influence ovarian response to standard gonadotrophin stimulation.
abstract: OBJECTIVE
  The association of cytochrome P450 aromatase gene CYP19(TTTA)                            (                               n                            ) polymorphism with ovarian response to FSH stimulation was explored.
  
  
  METHODS
  Three hundred women undergoing medically assisted reproduction and 300 women with at least one spontaneous pregnancy participated in the study. CYP19(TTTA)                            (                               n                            ) polymorphism was genotyped, while serum hormones were determined. During oocyte retrieval, the follicular size, the follicle and oocyte numbers were recorded.
  
  
  RESULTS
  Six CYP19(TTTA)                            (                               n                            ) alleles with 7 to 12 repeats were revealed. Women homozygous for long CYP19(TTTA)                            (                               n                            ) alleles presented with lower serum FSH levels at the third day of the menstrual cycle (p < 0.001) and higher large follicle numbers (p < 0.01), compared to women homozygous for short CYP19(TTTA)                            (                               n                            ) alleles. The CYP19(TTTA)                            (                               7                            ) allele was associated with higher serum FSH levels (p < 0.003), with lower total follicle (p < 0.02) and large follicle numbers (p < 0.03), while CYP19(TTTA)                            (                               7                            ) allele-carriers presented more frequently with small follicles than CYP19(TTTA)                            (                               7                            ) allele-non carriers (p < 0.01).
  
  
  CONCLUSIONS
  CYP19 genetic variants were associated with ovarian reserve and response to standard gonadotrophin stimulation of women undergoing in vitro fertilization.
authors.affiliation: Genetics and IVF Unit, Department of Obstetrics and Gynecology, Medical School, Ioannina University, Ioannina, Greece.
authors.forename: Leandros A
authors.initials: LA
authors.lastname: Lazaros
authors.forename: Elissavet G
authors.initials: EG
authors.lastname: Hatzi
authors.forename: Nectaria V
authors.initials: NV
authors.lastname: Xita
authors.forename: Georgios V
authors.initials: GV
authors.lastname: Makrydimas
authors.forename: Apostolos I
authors.initials: AI
authors.lastname: Kaponis
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takenaka
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Kosmas
authors.forename: Nikolaos V
authors.initials: NV
authors.lastname: Sofikitis
authors.forename: Theodoros I
authors.initials: TI
authors.lastname: Stefos
authors.forename: Konstantinos A
authors.initials: KA
authors.lastname: Zikopoulos
authors.forename: Ioannis A
authors.initials: IA
authors.lastname: Georgiou
mesh_terms: D000328:Adult; D001141:Aromatase / Q000097:blood / Q000235:genetics*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005787:Gene Frequency; D056726:Genetic Association Studies; D006062:Gonadotropins / Q000008:administration & dosage*; D006720:Homozygote; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D018895:Microsatellite Repeats / Q000235:genetics*; D009865:Oocytes / Q000166:cytology; D006080:Ovarian Follicle / Q000166:cytology; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D011110:Polymorphism, Genetic; D027724:Reproductive Techniques, Assisted
chemical_list: D006062:Gonadotropins; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D001141:Aromatase
references.citation: Asian J Androl. 2011 Mar;13(2):292-7
references.pmid: 21217768
references.citation: J Clin Endocrinol Metab. 1991 Mar;72(3):560-6
references.pmid: 1825497
references.citation: Fertil Steril. 2007 Sep;88(3):539-46
references.pmid: 17559842
references.citation: J Steroid Biochem Mol Biol. 2009 Jul;115(3-5):115-25
references.pmid: 19500729
references.citation: Eur J Endocrinol. 2008 Jun;158(6):861-5
references.pmid: 18505907
references.citation: Mol Hum Reprod. 2004 Feb;10(2):77-83
references.pmid: 14742691
references.citation: Menopause. 2006 Nov-Dec;13(6):902-10
references.pmid: 16977255
references.citation: Reprod Biomed Online. 2009 May;18(5):651-7
references.pmid: 19549443
references.citation: J Pediatr Endocrinol Metab. 1998 Sep-Oct;11(5):657-64
references.pmid: 9829218
references.citation: Int J Cancer. 2000 Jul 15;87(2):204-10
references.pmid: 10861475
references.citation: J Clin Endocrinol Metab. 1998 Apr;83(4):1348-57
references.pmid: 9543166
references.citation: Endocr Rev. 1996 Apr;17(2):121-55
references.pmid: 8706629
references.citation: Fertil Steril. 1995 Jan;63(1):1-11
references.pmid: 7805895
references.citation: Endocr Rev. 1994 Jun;15(3):342-55
references.pmid: 8076586
references.citation: Biol Reprod. 2006 Aug;75(2):217-25
references.pmid: 16641147
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):94-101
references.pmid: 14744739
references.citation: J Clin Endocrinol Metab. 2003 Nov;88(11):5127-31
references.pmid: 14602738
references.citation: J Clin Endocrinol Metab. 1999 Aug;84(8):2951-6
references.pmid: 10443703
references.citation: J Clin Endocrinol Metab. 1999 Dec;84(12):4677-94
references.pmid: 10599737
references.citation: Endocrinology. 2000 Jul;141(7):2614-23
references.pmid: 10875266
references.citation: J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):93-9
references.pmid: 12650705
references.citation: Fertil Steril. 2003 Mar;79 Suppl 1:735-42
references.pmid: 12620485
references.citation: Fertil Steril. 2001 Feb;75(2):305-9
references.pmid: 11172831
references.citation: Obes Res. 2003 Apr;11(4):578-85
references.pmid: 12690088
references.citation: J Clin Endocrinol Metab. 1997 Jun;82(6):1739-45
references.pmid: 9177373
references.citation: J Clin Endocrinol Metab. 2007 Mar;92(3):825-33
references.pmid: 17192292
references.citation: Hum Reprod. 2006 Feb;21(2):443-6
references.pmid: 16199427
references.citation: Endocrine. 1999 Apr;10(2):113-21
references.pmid: 10451219
references.citation: J Clin Endocrinol Metab. 1995 Dec;80(12):3689-98
references.pmid: 8530621
references.citation: J Steroid Biochem Mol Biol. 2008 Apr;109(3-5):212-8
references.pmid: 18448329
references.citation: Cancer Lett. 2004 Apr 30;207(2):191-6
references.pmid: 15072828
references.citation: Fertil Steril. 2010 Jun;94(1):250-4
references.pmid: 19324338
references.citation: J Clin Endocrinol Metab. 1994 Jun;78(6):1287-92
references.pmid: 8200927
references.citation: Fertil Steril. 1999 Dec;72(6):961-9
references.pmid: 10593363
references.citation: J Hum Genet. 2010 Mar;55(3):189-93
references.pmid: 20186154
references.citation: Physiol Rev. 1980 Jan;60(1):51-89
references.pmid: 6243782
references.citation: J Clin Endocrinol Metab. 2007 Mar;92(3):982-90
references.pmid: 17164303
references.citation: Gynecol Endocrinol. 2011 Jan;27(1):27-32
references.pmid: 20540673