Clinical and Experimental Reproductive Medicine

  • 제34권1호
  • /
  • Pages.33-39
  • /
  • 2007
  • /
  • 2233-8233(pISSN)
  • /
  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지

자궁강 내 인공수정을 위한 과배란유도 시 hCG 투여 일에 측정한 혈중 Vascular Endothelial Growth Factor의 임상적 의의

The Clinical Significance of Serum Vascular Endothelial Growth Factor Levels Measured at Ovulation Triggering Day In Intrauterine Insemination Cycles

  • 김현준 (건국대학교 의과대학 산부인과학교실) ;
  • 지병철 (분당서울대학교병원 산부인과) ;
  • 서창석 (분당서울대학교병원 산부인과) ;
  • 김석현 (서울대학교 의과대학 산부인과학교실) ;
  • 최영민 (서울대학교 의과대학 산부인과학교실) ;
  • 김정구 (서울대학교 의과대학 산부인과학교실) ;
  • 문신용 (서울대학교 의과대학 산부인과학교실)
  • Kim, Hyun-Jun (Department of Obstetrics and Gynecology, College of Medicine, Konkuk University) ;
  • Jee, Byung-Chul (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Suh, Chang-Suk (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Kim, Seok-Hyun (Department of Obstetrics and Gynecology, College of Medicine, Seoul National University) ;
  • Choi, Young-Min (Department of Obstetrics and Gynecology, College of Medicine, Seoul National University) ;
  • Kim, Jung-Gu (Department of Obstetrics and Gynecology, College of Medicine, Seoul National University) ;
  • Moon, Shin-Yong (Department of Obstetrics and Gynecology, College of Medicine, Seoul National University)
  • 발행 : 2007.03.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

목 적: 자궁강 내 인공수정을 위한 과배란유도 시 혈청 vascular endothelial growth factor (VEGF) 농도가 과배란유도의 결과를 반영할 수 있는지를 확인해 보고자 하였다. 연구방법: 과배란유도 후 자궁강 내 인공수정을 시행 받은 49 명의 불임여성을 대상으로 hCG 투여 일에 혈청을 얻어 VEGF-A 및 estradiol 농도를 측정하였다. 과배란유도는 clomiphene citrate (100 mg/d on day 3$\sim$7) 와 human menopausal gonadotropin (150 IU every other day starting on day 5) 병합요법을 이용하였다. hCG 투여 일에 17mm 이상의 성숙난포 수와 자궁내막 두께를 동시에 측정하였다. 결 과: 혈청 VEGF-A 농도는 성숙난포 수, estradiol 농도 및 자궁내막 두께와는 무관하였던 반면 성숙난포 수와 estradiol 농도는 양의 비례관계를 보였다. 혈청 VEGF-A 농도는 성숙난포 수가 2 개 이하인 저 반응 군과 6 개 이상인 고 반응 군에서 통계적으로 유의하지는 않지만 낮은 수치를 보였다. 결 론: 혈청 VEGF-A 농도는 자궁강 내 인공수정 시술 시 과배란유도의 결과와 무관한 것으로 사료되지만 저 반응 군과 고 반응 군에서 낮은 농도를 보이는 것으로 보아 이들을 대상으로 한 추가 연구가 필요할 것으로 판단된다.

Objective: The objective of this study was to investigate whether serum levels of vascular endothelial growth factor (VEGF) measured at ovulation triggering day reflect ovarian response in intrauterine insemination (IUI) cycles. Methods: Forty-nine fertile women who undergoing superovulation and IUI were included. Superovulation was performed using clomiphene citrate (100 mg/d on day 3$\sim$7) in combination with human menopausal gonadotropin (150 IU every other day starting on day 5). Serum samples were obtained on the day of hCG administration and the levels of VEGF-A and estradiol were measured. The numbers of mature follicle $\geq$17 mm in diameter were also counted. Results: Serum VEGF-A levels did not correlate with the numbers of mature follicle count nor serum estradiol levels. Serum estradiol level was positively associated with mature follicle count. Serum VEGF-A levels tended to be lower in women with mature follicle count less than three or women with more than five. Conclusion: Our results indicate that serum VEGF-A levels do not have an association with superovulation outcome in IUI cycles. However, a tendency of lower VEGF-A level in poor and high responder suggests that those with extreme response to superovulation may be related with abnormal angiogenesis. Further studies should be warranted in larger populations.

키워드

참고문헌

  1. Ferrara N, Houck K, Jakeman L, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of polypeptides. Endocr Rev 1992; 13: 18-32 https://doi.org/10.1210/edrv-13-1-18
  2. Geva E, Jaffe RB. Role of vascular endothelial growth factor in ovarian physiology and pathology. Fertil Steril 2000; 74: 429-38 https://doi.org/10.1016/S0015-0282(00)00670-1
  3. Quintana R, Kopcow L, Marconi G, Sueldo C, Speranza G, Baranao RI. Relationship of ovarian stimulation response with vascular endothelial growth factor and degree of granulosa cell apoptosis. Hum Reprod 2001; 16: 1814-8 https://doi.org/10.1093/humrep/16.9.1814
  4. Barroso G, Barrionuevo M, Rao P, Graham L, Danforth D, Huey S, Abuhamad A, Oehninger S. Vascular endothelial growth factor, nitric oxide, and leptin follicular fluid levels correlate negatively with embryo quality in IVF patients. Fertil Steril 1999; 72: 1024-6 https://doi.org/10.1016/S0015-0282(99)00442-2
  5. Benifla JL, Bringuier AF, Sifer C, Porcher R, Madelenat P, Feldmann G. Vascular endothelial growth factor, platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 in the follicular fluid of patients undergoing IVF. Hum Reprod 2001; 16: 1376-81 https://doi.org/10.1093/humrep/16.7.1376
  6. Moncayo HE, Penz-Koza A, Marth C, Gastl G, Herold M, Moncayo R. Vacular endothelial growh factor in serum and in the follicular fluid of patients undergoing hormonal stimulation for in-vitro fertilization. Hum Reprod 1998; 13: 3310-4 https://doi.org/10.1093/humrep/13.12.3310
  7. Barboni B, Turriani M, Galeati G, Spinaci M, Bacci ML, Forni M, Mattioli M. Vascular endothelial growth factor production in growing pig antral follicles. Biol Reprod 2000; 63: 858-64 https://doi.org/10.1095/biolreprod63.3.858
  8. Mttioli M, Barhoni B, Turriani M, Galeati G, Zannoni A, Castellani G, Berardinelli P, Scapolo PA. Follicle activation involves vascular endothelial growth factor production and increased blood vessel extension. Biol Reprod 2001; 65: 1014-9 https://doi.org/10.1095/biolreprod65.4.1014
  9. Lee A, Buny KA, Christenson LK, Patton PE, Stouffer RL. Vascular endothelial growth factor levels in serum and follicular fluid of patients undergoing in vitro fertilization. Fertil Steril 1997; 68: 305-11 https://doi.org/10.1016/S0015-0282(97)81520-8
  10. Friedman CI, Danforth DR, Herbosa-Encarnacion C, Arbogast L, Alak BM, Seifer DB. Follicular fluid vascular endothelial growth factor concentrations are elevated in women of advanced reproductive age undergoing ovulation induction. Fertil Steril 1997; 68: 607-12 https://doi.org/10.1016/S0015-0282(97)00278-1
  11. Friedman CI, Seifer DB, Kennard EA, Arbogast L, Alak B, Danforth DR. Elevated level of follicular fluid vascular endothelial growth factor is a marker of diminished pregnancy potential. Fertil Steril 1998; 70: 836-9 https://doi.org/10.1016/S0015-0282(98)00301-X
  12. Peter L, Vassili R, Silke L,Tanja W, Ernst S, Ludwig W. Cycle dependency of intrauterine vascular endothelial growth factor levels is correlated with decidualization and corpus luteum function. Fertil Steril 2003; 80: 1228-33
  13. Iijima K, Jiang JY, Shimizu T, Sasada H, Sato E. Acceleration of follicular development by administration of vascular endothelial growth factor in cycling female rats. J Reprod Dev 2005; 51: 161-8 https://doi.org/10.1262/jrd.51.161
  14. Kaczmarek MM, Schams D, Ziecik AJ. Role of vascular endothelial growth factor in ovarian physiology - an overview. Reprod Biol 2005; 5: 111-36
  15. Malamitsi-Puchner A, Sarandakou A, Baka S, Hasiakos D, Kouskouni E, Creatsas G. In vitro fertilization: angiogenic, proliferative, and apoptotic factors in the follicular fluid. Ann N Y Acad Sci 2003; 997: 124-8 https://doi.org/10.1196/annals.1290.043
  16. Laitinen M, Ristimaki A, Honkasalo M, et al. Differential hormonal regulation of vascular endothelial growth factors VEGF, VEGF-B, and VEGF-C messenger ribonucleic acid expression in the primate ovary. Endocrinology 1992; 131: 254-60 https://doi.org/10.1210/en.131.1.254
  17. Kim KH, Oh DS, Jeong JH, Shin BS, Joo BS, Lee KS. Follicular blood flow is a better predictor of the outcome of in vitro fertilization-embryo transfer than follicular fluid vascular endothelial growth factor and nitric oxide concentrations. Fertil Steril 2004; 82: 586-92 https://doi.org/10.1016/j.fertnstert.2004.02.120
  18. Dvorak HE Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 2002; 20: 4368-80 https://doi.org/10.1200/JCO.2002.10.088
  19. Ferrara N, Houck K, Jakeman L, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of polypeptides. Endocr Rev 1992; 13: 18-32 https://doi.org/10.1210/edrv-13-1-18
  20. Van Blerkom J. Intrafollicular influences on human oocyte developmental competence: perifollicular vascularity, oocyte metabolism and mitochondrial function. Hum Reprod 2000; 15 suppl 2: 173-88
  21. Ocal P, Aydin S, Cepni I, Idil S, Idil M, Uzun H, Benian A. Follicular fluid concentrations of vascular endothelial growth factor, inhibin A and inhibin B in IVF cycles: are they markers for ovarian response and pregnancy outcome? Eur J Obstet Gynecol Reprod Biol 2004; 115: 194-9 https://doi.org/10.1016/j.ejogrb.2004.01.034
  22. Dom C, Reinsberg J, Kupka M, van der Ven H, Schild RL. Leptin, VEGF, IGF-l, and IGFBP-3 concentrations in serum and follicular fluid of women undergoing in vitro fertilization. Arch Gynecol Obstet 2003; 268: 187-93 https://doi.org/10.1007/s00404-002-0366-8
  23. Carmeliet P, Ferreira V, Bereier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996; 380: 435-9 https://doi.org/10.1038/380435a0
  24. Ferrara N, Carver-Moore K, Chen H, et al. Heterozygous embryonic lethally induced by targeted inactivation of the VEGF gene. Nature 1996; 380: 439-42. https://doi.org/10.1038/380439a0