Effect of Low-dose Aspirin on Implantation and Pregnancy Rates in Patients Undergoing Frozen-thawed Embryo Transfer

동결보존 배아 이식에서 저 용량 아스피린 투여가 임신율과 착상율에 미치는 영향에 관한 연구

  • Kim, Min Ji (Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Hyun Jung (Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Yu, Young (Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Seo, Back Kyung (Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Cha, Sun Hwa (Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Hae Suk (Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Song, In Ok (Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Byun, Hye Kyung (Laboratory of Reproductive Biology and Infertility, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Koong, Mi Kyoung (Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Kang, Inn Soo (Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Yang, Kwang Moon (Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine)
  • 김민지 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 이현정 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 유영 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 서백경 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 차선화 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 김해숙 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 송인옥 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 변혜경 (성균관대학교 의과대학 삼성제일병원 생식내분비 및 불임연구실) ;
  • 궁미경 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 강인수 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 양광문 (성균관대학교 의과대학 삼성제일병원 산부인과)
  • Published : 2005.09.30

Abstract

Objective: Low-dose aspirin have been proposed to improving endometrial receptivity and pregnancy rate in COH-IVF by increasing endometrial perfusion. However, the effect of low-dose aspirin in COH-IVF could be negligible because there have been large quantity of other important factors responsible for changing endometrial perfusion accompanied by COH procedure. In contrast, in frozen-thawed embryo transfer cycles which were not accompanied by COH procedure, the effects of low-dose aspirin in endometrial blood flow seems to be more certain than in COH-IVF cycles. In this study, we analyzed the effect of low-dose aspirin treatment on implantation and pregnancy rates in patients undergoing frozen-thawed embryo transfer Methods: From January 2003 to December 2003, total 264 cycles from 264 patients who attended infertility clinic at Samsung Cheil Hospital were enrolled in this study. All cases included in this study, embryos were frozen and thawed at the pronuclear stage and three days after incubation, at least 2 or more good quality embryos were transferred into uterus. In study group, low dose aspirin (100 mg/day) was administrated from the first or second date of menstrual day to 9 days after embryo transfer. On the other hand, control group did not take any medicine except estradiol valerate for endometrial priming. Several variables including implantation and pregnancy rates were compared in both groups. After then, each groups were stratified by endometrial thickness checked at embryo transfer (ET) day such as (28 mm versus <8 mm) and same variables above described were compared between study and control groups. Results: The mean age, infertility duration, endometrial thickness at embryo transfer day and mean number of transferred embryo were not significantly different in both groups. Also, implantation rates (study group: 15.8%, control group: 20.5%) and pregnancy rate (study group: 45.1%, control group: 43.5%) were not significantly different between two groups. (p>0.05) After we analyzed same variables stratified by endometrial thickness checked at embryo transfer day, we could not found any significant difference between study and control groups. Conclusions: Low-dose aspirin treatment seems to have no advantage of improving implantation and pregnancy rates in patients undergoing frozen-thawed embryo transfer.

Keywords

References

  1. Steer CV, Campbell S, Tan SL, Crayford T, Mills C, Mason BA, et al. The use of transvaginal color flow imaging after in vitro fertilization to identify optimum uterine conditions before embryo transfer. Fertil Steril 1992; 57: 372-6
  2. Favre R, Bettahar K, Grange G, Ohl J, Arbogast E, Moreau L, Dellbach P. Predictive value of transvaginal uterine Doppler assessment in an in vitro fertilization program. Ultrasound Obstet Gynecol 1993; 3: 350-3 https://doi.org/10.1046/j.1469-0705.1993.03050350.x
  3. Serafini P, Batzofin J, Nelson J, Olive D. Sonographic uterine predictors of pregnancy in women underlying ovulation induction for assisted reproductive treatments. Fertil Steril 1994; 62: 815-22
  4. Coulam CB, Stem JJ, Soenken DM, Britten S, Bustilo M. Comparisonof pulsatility indices on the day of oocyte retrivel and embryo transfer. Hum Reprod 1995; 10:82-4 https://doi.org/10.1093/humrep/10.1.82
  5. Cacciatore B, Simberg N, Fusaro P, Tiitinen A. Transvaginal Doppler study of uterine artery blood flow in in vitro fertilization-embryo transfer cycles. Fertil Setril 1996; 66: 130-4
  6. Zaidi J, Kyei-Mensah A, Pittrof R, Campbell S, Shaker A, Tan SL. Assessment of uterine artery blood flow on the day of human chorionic gonadotropin administration by transvaginal color Doppler ultrasound in an in vitro fertilization program. Fertil Steril 1996; 65: 377-81
  7. Battaglia C, Artini PG, Giulini S, Salvatory M, Maxia N, Petraglia F, et al. Color Doppler changes and thromboxane production after ovarian stimulation with gonadotrophine-relcasing hormone agonist. Hum Reprod 1997; 11: 2477-82
  8. Yang JH, Wu MY, Chen CD, Jiang MC, Ho HN, Yang YS. Association of endometrial blood flow as determined by a modified color Doppler technique with subsequent outcome oh in-vitro fertilization. Hum Reprod 1999; 14: 1606-10 https://doi.org/10.1093/humrep/14.6.1606
  9. Raine-Fenning NJ, Camptobell BK, Kendall NR, Clewes JS, Johnson IR. Endometrial subendometrial perfusion are impaired in women with unexplained subfertility. Hum Reprod 2004; 19: 2605-14 https://doi.org/10.1093/humrep/deh459
  10. Gonen Y, Casper RF. Prediction of implantation by the sonographic appearance oh the endometrium during controlled ovarian stimulation for in vitro fertilization. J. in Vitro Fertil. Embryo Transfer 1990; 7: 146-52 https://doi.org/10.1007/BF01135678
  11. Sher G, Herbert C, Maassarani G, Jacobs MH. Assessment of the late proliferative phase endometrium by ultrasonography in patients undergoing in-vitro fertilization and embryo transfer. Hum Reprod 1991; 6: 232-7
  12. Lorenze RL, Boehlig B, Vedelhoven WM, Weber PC. Superior antiplatelet action of alternative day pulsed dosing versus split dose administration of aspirin. Am J Cardiol 1989; 64: 1185-8 https://doi.org/10.1016/0002-9149(89)90875-8
  13. Smith JB, Willis AL. Aspirin selectively inhibits prostaglandin production in human platelets. Nsture (New Biol) 1971; 231: 235-7
  14. Patrignani P, Filabozzi P. Selective cumulative inhibition of platelet thromboxane production by lowdose aspirin in healthy subjects. J Clin Invest 1982; 69: 1366-72 https://doi.org/10.1172/JCI110576
  15. Moncada S, Vane JR. Arachidonic acid metabolites and the interactions between platelets and blood vessel walls. N Eng J Med 1979; 300: 1142-7 https://doi.org/10.1056/NEJM197905173002006
  16. Wada I, Hsu CC, Wiliams G, Macnamee MC, Brinsden PR. The benefits of low-dose aspirin therapy in women with impaired uterine perfusion during assised conception. Hum Reprod 1994; 9: 1954-7
  17. Weckstein LN, Jacobson A, Galen D, Hampton K, Hammel J. Low-dose aspirin for oocyte donation recipients with a thin endometrium: prospective, randomized study. Fertil Steril 1997; 68: 927-30 https://doi.org/10.1016/S0015-0282(97)00330-0
  18. Rubistein M, Marazzi A, Polak de Fried E. Lowdose aspirin treatment improves ovarian responsiveness, uterine and ovarian blood flow velocity, implantation, and pregnancy rates in patients undergoing in vitro fertilization: a prospective, ramdomized, doble-blind placebo-controlled assay. Fertil Steril 1999; 71: 825-9 https://doi.org/10.1016/S0015-0282(99)00088-6
  19. Waldenstrom U, Hellberg D, Nilsson S. Low-dose aspirin in a short regimen as standard treatment in in vitro fertilization: a randomized, prospective study. Fertil Steril 2004; 81: 1560-4 https://doi.org/10.1016/j.fertnstert.2004.02.082
  20. Check JH, Dietterich C, Lurie D, Nazari A, Chuong J.A match study to determine whether low-dose aspirin without heparin improves pregnancy rates following frozen embryo transfer and/or affects endometrial sonographic parameters. J Assist Reprod Genet 1998; 15: 579-82 https://doi.org/10.1023/A:1020373009043
  21. Urman B, Mercan R, Alatas C, Balaban B, Isiklar A, Nuhoglu A. Low dose aspirin dose not increase implantation rates in patients undergoing intracytoplasmic sperm injection: a prospective ramdomized study. J Assist Reprod Genet 2000; 17: 586-90 https://doi.org/10.1023/A:1026491426423
  22. Lok IH, Yip SK, Cheung LP, Leung PHY, Haines CJ. Adjuvant low-dose aspirin therapy in poor response undergoing in vitro fertilization: a prospective, randomized, double-blind, placebo-controlled trial. Fertil Steril 2004; 81: 556-61 https://doi.org/10.1016/j.fertnstert.2003.07.033
  23. Kupesic S, Kurjak A. Uterine and ovarian perfusion during the periovulatory period assessed by transvaginal color Doppler. Fertil Steril 1993; 60: 439-43