Comparison of IVF Outcomes in Patients with Endometriosis According to Severity

자궁내막증이 있는 불임 여성에서 중등도에 따른 체외 수정의 결과 비교

  • Kim, Hye Ok (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital, Sungkyunkwan University School of Medicine) ;
  • Kang, Inn Soo (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital, Sungkyunkwan University School of Medicine)
  • 김혜옥 (성균관대학교 의과대학 제일병원 산부인과) ;
  • 강인수 (성균관대학교 의과대학 제일병원 산부인과)
  • Published : 2006.12.31

Abstract

Objective: To evaluate the impact of endometriosis on IVF-ET cycles and to compare IVF outcomes between stage I/II and stage III/IV endometriosis. Methods: We analyzed 697 patients (1,199 cycles) with endometriosis (stage I-II:638 cycles, stage III-IV: 561 cycles) and 325 pts (459 cycles) with tubal factor as controls between January 1994 and April 2004. Pts with endometriosis were diagnosed by laparoscopy and medical and surgical treatment were done in 353 cycles (55.3%) and 466 cycles (83.1%) of stage I-ll/stage III-IV endometriosis. Cycles with age>35 years or FSH>20 miU/mL or severe male factor infertility were excluded. Results: The number of retrieved oocytes ($9.97{\pm}7.2$ vs. $13.4{\pm}7.9$ (p<0.0001 )), total number of embryos ($6.5{\pm}4.8$ vs. $9.1{\pm}5.6$ (p<0.0001)), and good quality embryos ($2.43{\pm}1.6$ vs. $2.74{\pm}1.7$ (p=0.013)) significantly decreased in stage III-IV endometriosis than in control. But pregnancy rate of stage III-IV endometriosis was comparable with control (35.7% vs. 36.8%). Fertilization rate and number of total embryos were lower in stage I-II endometriosis than in control ($64.8{\pm}22.9$ vs. $70.8{\pm}20.8$ (p<0.0001), $7.6{\pm}5.0$ vs. $9.1{\pm}5.6$ (p<0.0001)). In patients with medical and surgical treatment of endometriosis, pregnancy rate and live birth rate was significantly lower in stage I-II than in stage III-IV endometriosis (29.2 vs. 36.2 (%), p=0.045, 23.9 vs. 31.5 (%), p=0.043). There was no difference in the mean age, but the duration of infertility was significantly longer ($56.5{\pm}26.3$ vs. $46.9{\pm}25.8$ (mon), p<0.0001) and fertilization rate was lower ($64.7{\pm}23.3$ vs. $70.5{\pm}22.7$ (%), p=0.001) in stage I-II than stage III-IV endometriosis. Conclusion: We suggest that IVF should be considered earlier in patients with minimal to mild endometriosis because of significantly decreased fertilization rates.

목 적: 자궁내막증이 체외 수정에 미치는 영향에 대하여 알아보고, 자궁내막증의 체외 수정 결과의 차이에 대해 살펴보고자 하였다. 연구방법: 1994년부터 2004년까지 제일병원 아이소망센타에서 자궁내막증으로 체외 수정을 시술 받은 697명의 환자 (총 1,199주기)를 후향적으로 연구하였다. 경증의 자궁내막증은 638주기, 중증의 자궁내막증은 561주기였으며, 난관 요인을 가진 325명 (459주기)를 대조군으로 하였다. 제외 기준으로는 여성의 나이가 35세 이상, basal FSH level이 20 mIU/ml 이상인 경우, 심각한 남성 요인의 경우를 제외하였다. 결 과: 중증의 자궁내막증은 난관 요인 보다 획득된 난자의 수 ($9.97{\pm}7.2$ vs. $13.4{\pm}7.9$ (p<0.0001)), 총 배아 수 ($6.5{\pm}4.8$ vs. $9.1{\pm}5.6$ (p<0.0001)), 양질의 배아 수 ($2.43{\pm}1.6$ vs. $2.74{\pm}1.7$ (p=0.013))가 통계적으로 유의하게 낮았다. 하지만, 중증의 자궁내막증의 임신율은 난관 요인과 유사하였다 (35.7 vs. 36.8 (%)). 경증의 자궁내막증은 중증의 자궁내막증과 난관 요인보다 불임 기간이 길었으며 ($55.4{\pm}25.7$ vs. $47.6{\pm}25.6$ vs. $44.4{\pm}30.9$ (개월) p<0.0001)), 수정률이 의미 있게 낮았으나 ($64.8{\pm}22.9$ vs. $69.9{\pm}22.5$ vs.$70.8{\pm}20.8$ (%) (p<0.0001)), 임신율에 유의한 차이는 없었다 (31.1 vs. 35.7 vs. 36.8 (%)). 또한, 체외 수성 이전에 치료 받은 병력이 있던 경증과 중증의 자궁내막증 (363주기 vs. 470주기)은 경증의 자궁내막증에서 중증의 자궁내막증보다 불임 기간이 길고 ($56.5{\pm}26.3$ vs. $46.9{\pm}25.8$ (개월), p<0.0001), 수정률이 낮았으며 ($64.7{\pm}23.3$ vs. $70.5{\pm}22.7$ (%), p=0.001), 임신율과 태아 생존율이 통계적으로 유의하게 낮았다 (29.2 vs. 36.2 (%), p=0.045, 23.9 vs. 31.5 (%), p=0.043). 결 론: 체외 수정 시 이전에 치료를 받았던 경증의 자궁내막증은 중증의 자궁내막증보다 임신율과 태아 생존율이 낮았고, 이는 현저한 수정률 감소와 긴 불임 기간이 관련이 있다고 생각된다. 따라서, 장기간의 불임 기간을 가진 경증의 자궁내막증을 가진 불임 여성은 체외 수정을 좀 더 일찍 고려해 볼 수 있겠다.

Keywords

References

  1. ASRM. Practice Committee Report; A Committee Opinion: endometriosis infertility. Fertil Steril 2004; 81: 1441-6 https://doi.org/10.1016/j.fertnstert.2004.01.019
  2. Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am 1997; 24: 235-8 https://doi.org/10.1016/S0889-8545(05)70302-8
  3. Smith S, Pfiefer SM, Collins J. Diagnosis and management of female infertility. JAMA 2003; 290: 17
  4. Barnhart KT, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in-vitro fertilization. Fertil Steril 2002; 77: 1148-55 https://doi.org/10.1016/S0015-0282(02)03112-6
  5. Koniwckx PR. Is mild endometriosis as disease- Is mild endometriosis a condition occurring intermittently in all women- Hum Reprod 1994; 9: 2702-5
  6. Moen HM. Is mild endometriosis a disease? Why do women develop endometriosis and why is it diagnosed? Hum Reprod 1995; 10: 8-11 https://doi.org/10.1093/humrep/10.1.8
  7. Gleicher N, Barad D. Unexplained infertility: Does it really exist- Hum Reprod 2006; 21(8): 1951-5 https://doi.org/10.1093/humrep/del135
  8. Brosens I. Endometriosis and the outcome of in vitro fertilization. Fertil Steril 2004; 81: 1198-200 https://doi.org/10.1016/j.fertnstert.2003.09.071
  9. Olivennes F. Results of IVF in women with endometriosis. J Gynecol Obstet Biol Reprod 2003; 32: S45-47
  10. Olivennes F, Feldberg D, Liu H-C, Cohen J, Moy F, Rosenwaks Z. Endometriosis: a stage by stage analysis-the role of in vitro fertilization. Fertil Steril 1995; 64: 555-62
  11. Bergendal A, Naffah S, Nagy C, Bergqvist A, Sjoblom P, HiIIensjo T. Outcome of IVF in patients with endometriosis in comparison with tubal-factor infertility. J Assist Reprod Genet 1998; 15: 530-4 https://doi.org/10.1023/A:1022526002421
  12. Kuivasaari P, Hippelainen M, Anttila M, Heinonen S. Effect of endometriosis on IVF/ICSI outcome: stage III/IV endometriosis worsens cumulative pregnancy and live-born rates. Hum Reprod 2005; 20(11): 3130 -5 https://doi.org/10.1093/humrep/dei176
  13. Veeck L. The morphological assessment of human oocytes and early conception. In: Keel BA, Webster BW, editors. Handbook of the laboratory diagnosis and treatment of infertility. Boca Raton: CRC Press, 1990; p.353
  14. Azem F, Lessing JB, Geva E, Shahar A, Lerner-Geva L, Yovel I, et al. Patients with stages III and IV endometriosis have a poorer outcome on in vitro fertilization-embryo transfer than patients with tubal infertility. Fertil Steril 1999; 72: 1107-9 https://doi.org/10.1016/S0015-0282(99)00392-1
  15. Garrido N, Navarro J, Remohi J, Simon C, Pellicer A. follicular hormonal environment and embryo quality in women with endometriosis. Hum Reprod Update 2000; 6: 67-74 https://doi.org/10.1093/humupd/6.1.67
  16. Vernon MW, Beard JS, Graves K, Wilson EA. Classification of endometriotic implants by morphological appearance and capacity to synthesize prostaglandin F. Fertil Steril 1986; 46: 801-6 https://doi.org/10.1016/S0015-0282(16)49814-6
  17. Redwine DB. Age related evolution in colour appearances of endometriosis. Fertil Steril 1987; 48: 1062-3 https://doi.org/10.1016/S0015-0282(16)59611-3
  18. Cahill DJ, Wardle PG, Maile LA, Harlow CR, Hull MG. Ovarian dysfunction in endometriosis-associated and unexplained infertility. J Assist Reprod Genet 1997; 14: 554-7 https://doi.org/10.1023/A:1022568331845
  19. Hull MGR, Willians JA, Ray B, McLaughlin EA, Akande VA, Ford We. The contribution of subtle oocyte or sperm dysfunction affecting fertilization in endometriosis-associated or unexplained infertility: a controlled comparison with tubal infertility and use of donor spermatozoa. Hum Reprod 1998; 13: 1825-30 https://doi.org/10.1093/humrep/13.7.1825
  20. Minguez Y, Rubio C, Bernal A, Gaitan P, Remohi J, Simon C, et al. The impact of endometriosis in couples undergoing intracytoplasmic sperm injection because of male infertility. Hum Reprod 1997; 12: 2282-5 https://doi.org/10.1093/humrep/12.10.2282
  21. Simon C, Gutierrez A, Vidal A, del los Santos MJ, Tarin JJ, Remohi J. Outcome of patients with endometriosis in assisted reproduction results from invitro fertilization and oocyte donation. Hum Reprod 1994; 9: 725-9 https://doi.org/10.1093/oxfordjournals.humrep.a138578
  22. Cahill DJ, Hull MG. Pituitary-ovarian dysfunction and endometriosis. Hum Reprod Update 2000; 6: 56 -66 https://doi.org/10.1093/humupd/6.1.56
  23. Harlow CR, Cahill DJ, Maile LA, Talbot WM, Mears J, Wardle PG, et al. Reduced preovulatory granulosa cell steroidogenesis in women with endometriosis. J Clin Endocrinol Metab 1996; 81: 426-9 https://doi.org/10.1210/jc.81.1.426
  24. Ronnberg L, Kaupilla A, Rajaniemi H. Luteinizing hormone receptor disorder in endometriosis. Fertil Steril 1984; 42: 64-8 https://doi.org/10.1016/S0015-0282(16)47959-8
  25. Surrey ES, Schoolcraft WB. Does surgical management of endometriosis within 6 months of an in vitro fertilization-embryo transfer cycle improve outcome- J Assist Reprod Genet 2003; 20: 365-70 https://doi.org/10.1023/A:1025429027610
  26. Garcia-Velasco JA, Mahutte NG, Corona J. Removal of endometriomas before in vitro fertilization does not improve fertility outcomes: a matched, casecontrol study. Fertil Steril 2004; 81: 1194-7 https://doi.org/10.1016/j.fertnstert.2003.04.006
  27. Marcoux S, Maheux R, Berube S. Laparoscopic surgery in infertile women with minimal to mild endometriosis. Canadian Collaborative Group on Endometriosis. N Eng J Med 1997 Jul 24; 337(4): 217-22 https://doi.org/10.1056/NEJM199707243370401
  28. Werbrouck E, Spiessens C, Meuleman C, D'Hooghe T. No difference in cycle pregnancy rate and in cumulative live birth rate between women with surgically treated minimal-mild endometriosis and women with unexplained infertility after controlled ovarian hyperstimulation (COR) and intrauterine insemination (IUI). Fertil Steril 2006; 86: 566-71 https://doi.org/10.1016/j.fertnstert.2006.01.044
  29. De Hondt A, Meuleman C, Tomassetti C, Peeraer K, D'Hooghe. Endometriosis and assisted reproduction: the role for reproductive surgery- Curr Opin Obstet Gynecol 2006; 18: 374-9 https://doi.org/10.1097/01.gco.0000233929.27145.f3