난소의 기능이 저하된 불임 환자에서 연령 및 기저 혈중 FSH 수치가 체외수정시술의 예후에 미치는 영향에 관한 연구

Age or Basal Serum FSH Levels; Which One is Better for Prediction of IVF Outcomes in Patients with Decreased Ovarian Reserve?

  • 유영 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 김민지 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 조연진 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 연명진 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 안영선 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 차선화 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 김혜옥 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 박찬우 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 김진영 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 송인옥 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 궁미경 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 강인수 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 전종영 (관동대학교 의과대학 제일법원 산부인과학교실) ;
  • 양광문 (관동대학교 의과대학 제일법원 산부인과학교실)
  • Yu, Young (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Kim, Min-Ji (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Cho, Yeon-Jean (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Yeon, Myeong-Jin (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Ahn, Young-Sun (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Cha, Sun-Hwa (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Kim, Hye-Ok (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Park, Chan-Woo (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Kim, Jin-Young (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Song, In-Ok (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Koong, Mi-Kyoung (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Kang, Inn-Soo (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Jun, Jong-Young (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Yang, Kwang-Moon (Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Kwandong University, College of Medicine)
  • 발행 : 2007.09.30

초록

목 적: 본 연구의 목적은 난소기능이 저하된 불임 환자에서 체외수정시술 시 그 결과의 예측인자로서 환자의 연령과 혈중 FSH 수치의 중요성 및 그 임상적인 의미를 알아보고자 하였다. 연구방법: 2000년 1월부터 2004년 12월까지 본원 불임센터에서 체외수정시술을 시행받은 환자 중 이전 체외수정시술주기에서 획득된 난자 수가 5개 이하이며 FSH 농도가 15 mIU/ml 이상 25 mIU/ml 이하로 그 연령이 42세 이하인 난소기능이 저하된 불임 환자 85명의 85 체외수정시술 주기를 연구대상으로 하였다. 남성요인의 불임이나 착상 전 유전진단인 경우는 제외시켰다. 과배란유도의 방법은 단기요법 (flare-up protocol)을 사용한 경우로 제한하였다. 결 과: 대상군을 환자의 나이에 따라 분류하여 분석하였을 때 환자의 연령이 낮은 군 (age < 35, n=35)에서 고령환자 군 (age $\geq$ 35, n=50)에 비해 통계적으로 의미 있게 높은 착상률 (19.0% versus 4.0%, p<0.05)과 높은 지속임신율(100% versus 14.3%, p<0.05)을 보였으며, 연구대상 군을 기저 혈중 FSH농도에 의해 두 군으로 비교하였을 때 낮은 기저 혈중 FSH를 가진 군 (basal serum FSH < 20 mIU/ml, n=58)에서 기저혈중 FSH가 높았던 군 (basal serum FSH $geq$ 20 mIU/ml, n=27)에 비해 획득된 난자 숫자는 통계적으로 의미 있게 높은 반면 (4.6$\pm$0.7 versus 2.2$\pm$0.5, p<0.05)주기 취소율은 의미 있게 낮은 (19.0% versus 55.6%, p<0.05) 결과를 보였다. 결 론: 난소반응이 저하된 불임 환자의 체외수정시술 시 그 예후에 관련된 인자로서 환자의 연령은 해당 주기의 임신성공 및 임신 지속여부에 대한 예후를 예측할 수 있는 인자로서 의미가 있는 반면 기저 혈중 FSH농도는 해당 주기에서의 난소의 반응에 대한 예측인자로써 활용이 가능 할 것으로 사료된다.

Objectives: The purpose of this study is to investigate the clinical significance of age and basal serum FSH in predicting the outcomes of in vitro fertilization (IVF) in patients with poor-ovarian response. Methods: From January 2000 to December 2004, 85 second IVF cycles of 85 poor-ovarian response patients under the age of 42 with a back-ground of the first IVF cycles at our infertility center and 5 or less oocytes were retrieved and their basal serum FSH levels of 15$\sim$25 mIU/ml were enrolled in this study. Exclusion criteria were patients with a male factor for the etiology of infertility and undergoing genetic diagnosis of embryo such as PGD. Flare-up protocol was used for ovarian stimulation in all cases. Results: When we stratified the study groups by patient's age, the younger age group (age<35, n=35) showed significantly higher implantation rate (19.0% versus 4.0%, p<0.05) and higher ongoing pregnancy rate (100% versus 14.3%, p<0.05) than the older age group (age$\geq$35, n=50). And then, when we stratified the study populations by basal serum FSH level, the lower FSH group (basal serum FSH<20 mIU/ml, n=58) showed significantly higher number of retrieved oocytes (4.6$\pm$0.7 versus 2.2$\pm$0.5, p<0.05) and lower cancellation rate (19.0% versus 55.6%, p<0.05) than higher FSH group (basal serum FSH$\geq$20 mIU/ml, n=27). Conclusions: In conclusion, it was suggested that the patient's age could predict the IVF outcomes in respect to its potency of pregnancy and ongoing pregnancy. Serum basal FSH levels could predict more accurately the ovarian response of cycle, but not clinical outcomes.

키워드

참고문헌

  1. Keay SD, Liversedge NH, Mathur RS, Jenkins JM. Assisted conception following poor oUArian response to gonadotropin stimulation. British Joumal of Obstetrics and Gynecology 1997; 104: 521-7 https://doi.org/10.1111/j.1471-0528.1997.tb11525.x
  2. Tarlatzis BC, Zepiridis L, Grimbizis G, Bontis J. Clinical management of low oUArian response to stimulation for IVF: a systemic review. Hum Reprod Update 2003; 9: 61-76 https://doi.org/10.1093/humupd/dmg007
  3. Fasouliotis SJ, Simon A, Laufer N. EUAluation and treatment of low responders assisted reproductive technology: a challenge to meet. J Assist Reprod Genet 2000; 17: 357-73 https://doi.org/10.1023/A:1009465324197
  4. Cameron IT, O'Shea FC, Rolland JM, Hughes EG, de Krester DM, Healey DL. Occult ovarian failure: a syndrome of infertility, regular menses and elevated follicle-stimulating hormone concentrations. J Clin Endocrinol Metab 1988; 67: 1190-4 https://doi.org/10.1210/jcem-67-6-1190
  5. Frattarelli JL, Peterson E. Effect of androgen levels on in vitro fertilization cycles. Fertil Steril 2004; 81: 1713-4 https://doi.org/10.1016/j.fertnstert.2003.11.032
  6. Stone BA, Marrs RP. Ovarian responses to menopausal gonadotrophins in groups of patients with differing basal growth hormone levels. Fertil Steril 1992; 58: 32-6 https://doi.org/10.1016/S0015-0282(16)55133-4
  7. Keay SD, Liversedge NH, Akande VA, Mathur RS, Jenkins JM. Serum insulin-like growth fucter I concentrations following pituitary desensitization do not predict the ovarian response to gonadotrophin stimulation prior to IVF. Hum Reprod 2003; 18: 1797-801
  8. Seifer DB, MacLaughlin DT, Christian BP, Feng B, Shelden RM. Early follicular serum mullerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles. Fertil Steril 2002; 77: 468-71 https://doi.org/10.1016/S0015-0282(01)03201-0
  9. Seifer DB, Larnbert-Messerlian G, Hogan JW, Gardiner AC, Blazar AS, Berk CA. Day 3 serum inhibin-B is predictive of assisted reproductive technologies outcome. Fertil Steril 1997; 67: 110-4 https://doi.org/10.1016/S0015-0282(97)81865-1
  10. Thomas C, Nuojua-Huttunen S, Martikainen F. Pretreatment transvaginal ultrasound examination predicts ovarian responsiveness to gonadotrophins in in-vitro fertilization. Hum Reprod 1997; 12: 220-3 https://doi.org/10.1093/humrep/12.2.220
  11. Lass A, Skull J, Mc Veigh E, Margara R, Winston RM. Measurement of ovarian volume by transvaginal sonography before ovulation induction with human menopausal gonodrophin for in-vitro fertilization can predict poor response. Hum Reprod 1997; 12: 294-7 https://doi.org/10.1093/humrep/12.2.294
  12. Akande VA, Fleming CF, Hunt LP, Keay SD, Jenkins JM. Biological versus chronological aging of oocytes, distinguishable by raised FSH levels in relation to the success of IVF treatment. Hum Reprod 2002; 17: 2003-8 https://doi.org/10.1093/humrep/17.8.2003
  13. Scott RT, Hofmann GE, Oehninger S, Muasher SJ. Intercycle UAriability of day 3 follicle-stimulating hormone levels and its effect on stimulation quality in in-vitro fertilization. Fertil SteriI 1990; 54: 297-302 https://doi.org/10.1016/S0015-0282(16)53707-8
  14. Karande V, Jones G, Veeck L, Mausher S. High dose FSH stimulation at the onset of the menstrual ctcle dose not improve IVF outcome of low reponder patients. Fertil Steril 1990; 53: 486-90 https://doi.org/10.1016/S0015-0282(16)53345-7
  15. Cameron IT, O'shea FC, Rolland JM, Hughues EG, deKrester DM, Healy DL. Occult ovarian failure: a syndrome of infertility, regular menses, and elevated FSH concentrations. J Clin Endocrinol Metab 1988; 67: 1190-4 https://doi.org/10.1210/jcem-67-6-1190
  16. Scott RT, Hofmann GE. Prognostic assessment of ovarian reserve. FertiI Steril 1995; 63: 1-11 https://doi.org/10.1016/S0015-0282(16)57287-2
  17. Sharif K, Afnan M. The IVF league tables: time for a reality check. Hum Reprod 2003; 18: 483-5 https://doi.org/10.1093/humrep/deg134
  18. Lass A, Gerrard A, Abusheikha N, Akagbosu F, Brinsden P. IVF performance of women who have fluctuating early follicular FSH levels. J Assist Reprod Genet 2000; 17: 566-73 https://doi.org/10.1023/A:1026485830540
  19. Bancis LF, Huijs AM, den Ouden CT, Broekmans FJ, Looman CW, Blankenstein MA, et aI. Basal follicle-stimulating hormone levels are of limited Value in predicting ongoing pregnancy rates in vitro fertilization. Fertil Steril 2000; 73: 552-7 https://doi.org/10.1016/S0015-0282(99)00552-X
  20. Richardson SJ, Senikas V, Nelson JF. Follicular depletion during the menopausal transition: evidence for accelerated loss and ultimate exhaustion. J Clin Endocrinol Metab 1987; 65: 1231-7 https://doi.org/10.1210/jcem-65-6-1231
  21. Wallach EE. Pitfalls in evaluating ovarian reserve. FertiI Steril 1995; 63: 12-4 https://doi.org/10.1016/S0015-0282(16)57288-4
  22. Chuang C, Chen C, Chao K, Chen S, Ho H, Yang Y. Age is a better predictor of pregnancy potential than basal folliclestimulating hormone levels in women undergoing in vitro fertilization. Fertil Steril 2003; 79: 63-8 https://doi.org/10.1016/S0015-0282(02)04562-4