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Efficacy of oxytocin antagonist infusion in improving in vitro fertilization outcomes on the day of embryo transfer: A meta-analysis

  • Kim, Seul Ki (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Han, E-Jung (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Kim, Sun Mie (Seoul National University Hospital Healthcare System Gangnam Center) ;
  • Lee, Jung Ryeol (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Jee, Byung Chul (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital) ;
  • Suh, Chang Suk (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Kim, Seok Hyun (Department of Obstetrics and Gynecology, Seoul National University College of Medicine)
  • Received : 2016.07.20
  • Accepted : 2016.09.23
  • Published : 2016.12.31

Abstract

Objective: Uterine contraction induced by the embryo transfer (ET) process has an adverse effect on embryo implantation. The aim of this study was to determine the effect of oxytocin antagonist supplementation on the day of ET on in vitro fertilization outcomes via a meta-analysis. Methods: We performed a meta-analysis of randomized controlled trials (RCTs). Four online databases (Embase, Medline, PubMed, and Cochrane Library) were searched through May 2015 for RCTs that investigated oxytocin antagonist supplementation on the day of ET. Studies were selected according to predefined inclusion criteria and meta-analyzed using RevMan 5.3. Only RCTs were included in this study. The main outcome measures were the clinical pregnancy rate, the implantation rate, and the miscarriage rate. Results: A total of 123 studies were reviewed and assessed for eligibility. Three RCTs, which included 1,020 patients, met the selection criteria. The implantation rate was significantly better in patients who underwent oxytocin antagonist infusion (19.8%) than in the control group (11.3%) (n = 681; odds ratio [OR], 1.92; 95% confidence interval [CI], 1.25-2.96). No significant difference was found between the two groups in the clinical pregnancy rate (n = 1,020; OR, 1.57; 95% CI, 0.92-2.67) or the miscarriage rate (n = 456; OR, 0.76; 95% CI, 0.44-1.33). Conclusion: The results of this meta-analysis of the currently available literature suggest that the administration of an oxytocin antagonist on the day of ET improves the implantation rate but not the clinical pregnancy rate or miscarriage rate. Additional, large-scale, prospective, randomized studies are necessary to confirm these findings.

Keywords

References

  1. Richter ON, Kubler K, Schmolling J, Kupka M, Reinsberg J, Ulrich U, et al. Oxytocin receptor gene expression of estrogen-stimulated human myometrium in extracorporeally perfused non-pregnant uteri. Mol Hum Reprod 2004;10:339-46. https://doi.org/10.1093/molehr/gah039
  2. Liedman R, Hansson SR, Howe D, Igidbashian S, McLeod A, Russell RJ, et al. Reproductive hormones in plasma over the menstrual cycle in primary dysmenorrhea compared with healthy subjects. Gynecol Endocrinol 2008;24:508-13. https://doi.org/10.1080/09513590802306218
  3. Fanchin R, Righini C, Olivennes F, Taylor S, de Ziegler D, Frydman R. Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Hum Reprod 1998;13:1968-74. https://doi.org/10.1093/humrep/13.7.1968
  4. Mansour RT, Aboulghar MA, Serour GI, Amin YM. Dummy embryo transfer using methylene blue dye. Hum Reprod 1994;9:1257-9. https://doi.org/10.1093/oxfordjournals.humrep.a138690
  5. Menezo Y, Anker D, Salat-Baroux J. Conception and realization of artificial dyed embryos for training in in vitro fertilization and embryo transfer (IVF and ET). Acta Eur Fertil 1985;16:55-8.
  6. Poindexter AN 3rd, Thompson DJ, Gibbons WE, Findley WE, Dodson MG, Young RL. Residual embryos in failed embryo transfer. Fertil Steril 1986;46:262-7. https://doi.org/10.1016/S0015-0282(16)49523-3
  7. Lesny P, Killick SR, Tetlow RL, Robinson J, Maguiness SD. Embryo transfer: can we learn anything new from the observation of junctional zone contractions? Hum Reprod 1998;13:1540-6. https://doi.org/10.1093/humrep/13.6.1540
  8. Frydman R. Impact of embryo transfer techniques on implantation rates. J Gynecol Obstet Biol Reprod (Paris) 2004;33:S36-9. https://doi.org/10.1016/S0368-2315(04)96403-4
  9. Fanchin R, Righini C, de Ziegler D, Olivennes F, Ledee N, Frydman R. Effects of vaginal progesterone administration on uterine contractility at the time of embryo transfer. Fertil Steril 2001;75:1136-40. https://doi.org/10.1016/S0015-0282(01)01787-3
  10. Pinheiro OL, Cavagna M, Baruffi RL, Mauri AL, Petersen C, Franco JG Jr. Administration of beta2-adrenergic agonists during the peri-implantation period does not improve implantation or pregnancy rates in intracytoplasmic sperm injection (ICSI) cycles. J Assist Reprod Genet 2003;20:513-6. https://doi.org/10.1023/B:JARG.0000013652.17193.38
  11. Moon HS, Park SH, Lee JO, Kim KS, Joo BS. Treatment with piroxicam before embryo transfer increases the pregnancy rate after in vitro fertilization and embryo transfer. Fertil Steril 2004;82:816-20. https://doi.org/10.1016/j.fertnstert.2004.02.140
  12. European Atosiban Study Group. The oxytocin antagonist atosiban versus the beta-agonist terbutaline in the treatment of preterm labor: a randomized, double-blind, controlled study. Acta Obstet Gynecol Scand 2001;80:413-22.
  13. Husslein P, Cabero Roura L, Dudenhausen JW, Helmer H, Frydman R, Rizzo N, et al. Atosiban versus usual care for the management of preterm labor. J Perinat Med 2007;35:305-13.
  14. Pierzynski P, Gajda B, Smorag Z, Rasmussen AD, Kuczynski W. Effect of atosiban on rabbit embryo development and human sperm motility. Fertil Steril 2007;87:1147-52. https://doi.org/10.1016/j.fertnstert.2006.08.089
  15. Ahn JW, Kim CH, Kim SR, Jeon GH, Kim SH, Chae HD, et al. Effects of administration of oxytocin antagonist on implantation and pregnancy rates in patients with repeated failure of IVF/ICSI treatment. Korean J Reprod Med 2009;36:275-81.
  16. Ng EH, Li RH, Chen L, Lan VT, Tuong HM, Quan S. A randomized double blind comparison of atosiban in patients undergoing IVF treatment. Hum Reprod 2014;29:2687-94. https://doi.org/10.1093/humrep/deu263
  17. Chou PY, Wu MH, Pan HA, Hung KH, Chang FM. Use of an oxytocin antagonist in in vitro fertilization-embryo transfer for women with repeated implantation failure: a retrospective study. Taiwan J Obstet Gynecol 2011;50:136-40. https://doi.org/10.1016/j.tjog.2011.04.003
  18. Lan VT, Khang VN, Nhu GH, Tuong HM. Atosiban improves implantation and pregnancy rates in patients with repeated implantation failure. Reprod Biomed Online 2012;25:254-60. https://doi.org/10.1016/j.rbmo.2012.05.014
  19. Liang YL, Kuo TC, Hung KH, Chen TH, Wu MH. Oxytocin antagonist for repeated implantation failure and delay of delivery. Taiwan J Obstet Gynecol 2009;48:314-6. https://doi.org/10.1016/S1028-4559(09)60314-4
  20. Pierzynski P, Reinheimer TM, Kuczynski W. Oxytocin antagonists may improve infertility treatment. Fertil Steril 2007;88:213.e19-22.
  21. Decleer W, Osmanagaoglu K, Devroey P. The role of oxytocin antagonists in repeated implantation-failure. Facts Views Vis Obgyn 2012;4:227-9.
  22. Kalmantis K, Loutradis D, Lymperopoulos E, Beretsos P, Bletsa R, Antsaklis A. Three dimensional power Doppler evaluation of human endometrium after administration of oxytocine receptor antagonist (OTRa) in an IVF program. Arch Gynecol Obstet 2012;285:265-70. https://doi.org/10.1007/s00404-011-2019-2
  23. Song XR, Zhao XH, Bai XH, Lu YH, Zhang HJ, Wang YX, et al. Application of oxytocin antagonists in thaw embryo transfer. Zhonghua Fu Chan Ke Za Zhi 2013;48:667-70.
  24. Moraloglu O, Tonguc E, Var T, Zeyrek T, Batioglu S. Treatment with oxytocin antagonists before embryo transfer may increase implantation rates after IVF. Reprod Biomed Online 2010;21:338-43. https://doi.org/10.1016/j.rbmo.2010.04.009
  25. Visnova H, Pierson RA, Mrazek M, Garcia-Velasco JA, Blockeel C, Arce JC. Effects of barusiban, a selective oxytocin antagonist, on uterine contractility in the luteal phase after controlled ovarian stimulation. Fertil Steril 2012;98:S183.
  26. Visnova H, Coroleu B, Piro M, Blockeel C, Mrazek M, Arce JC. Barusiban and atosiban for reduction of uterine contractions on day of embryo transfer do not alter the endocrine profile at time of implantation. Hum Reprod 2009;24(suppl 1):i180.
  27. Blockeel C, Pierson R, Popovic-Todorovic B, Visnova H, Garcia-Velasco JA, Mrazek M, et al. Effects of barusiban and atosiban on frequency of uterine contractions in the luteal phase after stimulation: a randomised placebocontrolled trial. Hum Reprod 2009;24 (suppl 1):i26. https://doi.org/10.1093/humrep/dep716
  28. Pierzynski P. Oxytocin and vasopressin V(1A) receptors as new therapeutic targets in assisted reproduction. Reprod Biomed Online 2011;22:9-16. https://doi.org/10.1016/j.rbmo.2010.09.015
  29. Vayssiere C. Special management for threatened preterm delivery in multiple pregnancies. J Gynecol Obstet Biol Reprod (Paris) 2002;31(7 Suppl):5S114-23.
  30. Fanchin R, Ayoubi JM. Uterine dynamics: impact on the human reproduction process. Reprod Biomed Online 2009;18 Suppl 2:57-62. https://doi.org/10.1016/S1472-6483(10)60450-6
  31. Lesny P, Killick SR. The junctional zone of the uterus and its contractions. BJOG 2004;111:1182-9. https://doi.org/10.1111/j.1471-0528.2004.00350.x
  32. Chibbar R, Wong S, Miller FD, Mitchell BF. Estrogen stimulates oxytocin gene expression in human chorio-decidua. J Clin Endocrinol Metab 1995;80:567-72.
  33. Giussani DA, Jenkins SL, Mecenas CA, Winter JA, Barbera M, Honnebier OM, et al. The oxytocin antagonist atosiban prevents androstenedione-induced myometrial contractions in the chronically instrumented, pregnant rhesus monkey. Endocrinology 1996;137:3302-7. https://doi.org/10.1210/endo.137.8.8754755
  34. de Heus R, Mulder EJ, Derks JB, Visser GH. Acute tocolysis for uterine activity reduction in term labor: a review. Obstet Gynecol Surv 2008;63:383-8. https://doi.org/10.1097/OGX.0b013e31816ff75b
  35. European Medicines Agency. Tractocile (atosiban): European public assessment report revision 12. London: European Medicines Agency; 2009.

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