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Interceed and Estrogen Reduce Uterine Adhesions and Fibrosis and Improve Endometrial Receptivity in a Rabbit Model of Intrauterine Adhesions

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Abstract

Intrauterine adhesions (IUA) remain a major cause of infertility. Interceed, a regenerated cellulose adhesion barrier, is used to prevent adhesions in abdominal cavity. This study aimed to determine whether Interceed could reduce adhesions and tissue fibrosis and improve endometrial receptivity (ER) in rabbit. Rabbits were randomized into 6 groups:sham Operation, Interceed control, IUA model, Interceed therapy, estrogen therapy, and combination therapy. Four rabbits per group were euthanized to evaluate adhesion severity on the day before intervention and day 7, 14, and 28 after intervention. Number of endometrial glands and degree of endometrial fibrosis acted as markers for adhesion severity. Pseudopregnancy was induced in the remainder, and 8 rabbits per group were killed for assessing ER on days 6, 7, and 8 of pseudopregnancy by avß3 integrin and pinopode. We found that Interceed or estrogen therapy led to significant improvement in the adhesion severity on day 28 after intervention, respectively, compared to IUA model group (all P <.05). However, after combination therapy, such improvement achieved comparable to sham Operation group as early as day 14 after intervention (glands, P =.711, fibrosis, P =. 154). Among the IUA modeis treated, ER was highest after combination therapy on day 7 of pseudopregnancy, similar to sham Operation group (integrin, P =.352, pinopode, P =.154). In conclusion, Interceed and estrogen reduce adhesions and tissue fibrosis and improve ER in a rabbit model and may be novel therapeutic approaches for infertility resulting from IUA.

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References

  1. Yu D, Wong YM, Cheong Y, Xia E, Li TC. Asherman Syndrome-one Century later. Fertil Steril. 2008;89(4):759–779.

    Article  PubMed  Google Scholar 

  2. AAGL Advancing Minimally Invasive Gynecology Worldwide. AAGL practice report:practice guidelines for management of intrauterine synechiae. J Minim Invasive Gynecol. 2010;17(1):1–7.

    Article  Google Scholar 

  3. Johary J, Xue M, Zhu X, Xu D, Velu PP. Efficacy of estrogen therapy in patients with intrauterine adhesions:systematic review. J Minim Invasive Gynecol. 2014;21(1):44–54.

    Article  PubMed  Google Scholar 

  4. Capella-Allouc S, Morsad F, Rongieres-Bertrand C, Taylor S, Fernandez H. Hysteroscopic treatment of severe Asherman’s Syndrome and subsequent fertility. Hum Reprod. 1999;14(5):1230–1233.

    Article  CAS  PubMed  Google Scholar 

  5. Valle RF, Sciarra JJ. Intrauterine adhesions:hysteroscopic diag-nosis, Classification, treatment, and reproductive outcome. Am J Obstet Gynecol. 1988;158(6pt 1):1459–1470.

    Article  CAS  PubMed  Google Scholar 

  6. Fernandez H, Al-Najjar F, Chauveaud-Lambling A, Frydman R, Gervaise A. Fertility after treatment of Asherman’s Syndrome stage 3 and 4. J Minim Invasive Gynecol. 2006;13(5):398–402.

    Article  PubMed  Google Scholar 

  7. AOrhue AA, Aziken ME, Igbefoh JO. A comparison of two adjunctive treatments for intrauterine adhesions following lysis. Int J Gynaecol Obstet. 2003;82(1):49–56.

    Article  Google Scholar 

  8. Pabuccu R, Onalan G, Kaya C, et al.. Efficiency and pregnancy outcome of serial intrauterine device-guided hysteroscopic adhe-siolysis of intrauterine synechiae. Fertil Steril. 2008;90(5):1973–1977.

    Article  PubMed  Google Scholar 

  9. Myers EM, Hurst BS. Comprehensive management of severe Asherman Syndrome and amenorrhea. Fertil Steril. 2012;97(1):160–164.

    Article  PubMed  Google Scholar 

  10. Lin X, Wei M, Li TC, et al.. A comparison of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of adhesion reformation following hysteroscopic sur-gery for Asherman Syndrome:a cohort study. Eur J Obstet Gynecol Reprod Boil. 2013;170(2):512–516.

    Article  CAS  Google Scholar 

  11. Acunzo G, Guida M, Pellicano M, et al.. Effectiveness of auto-cross-linked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic adhesiolysis:a prospective, rando-mized, controlled study. Hum Reprod. 2003;18(9):1918–1921.

    Article  CAS  PubMed  Google Scholar 

  12. Amer MI, Abd-El-Maeboud KH. Amnion graft following hysteroscopic lysis of intrauterine adhesions. J Obstet Gynaecol Res. 2006;32(6):559–566.

    Article  PubMed  Google Scholar 

  13. Amer MI, Abd-El-Maeboud KH, Abdelfatah I, Salama FA, Abdallah AS. Human amnion as a temporary biologic barrier after hysteroscopic lysis of severe intrauterine adhesions:pilot study. J Minim Invasive Gynecol. 2010;17(5):605–611.

    Article  PubMed  Google Scholar 

  14. Makker A, Singh MM. Endometrial receptivity: clinical assessment in relation to fertility, infertility, and antifertility. Med Res Rev. 2006;26(6):699–746.

    Article  CAS  PubMed  Google Scholar 

  15. Simon C, Moreno C, Remohi J, Pellicer A. Cytokines and embryo implantation. J Reprod Immunol. 1998;39(1-2):117–131.

    Article  CAS  PubMed  Google Scholar 

  16. Ledee-Bataille N, Lapree-Delage G, Taupin JL, Dubanchet S, Frydman R, Chaouat G. Concentration of leukaemia inhibitory factor (LIF) in uterine flushing fluid is highly predictive of embryo implantation. Hum Reprod. 2002;17(1):213–218.

    Article  CAS  PubMed  Google Scholar 

  17. Schlaff WD, Hurst BS. Preoperative Sonographie measurement of endometrial pattern predicts outcome of surgical repair in patients with severe Asherman’s Syndrome. Fertil Steril. 1995;63(2):410–413.

    Article  CAS  PubMed  Google Scholar 

  18. Malhotra N, Bahadur A, Kalaivani M, Mittal S. Changes in endometrial reeeptivity in women with Asherman’s Syndrome under-going hysteroscopic adhesiolysis. Arch Gynecol Obstet. 2012; 286(2):525–530.

    Article  PubMed  Google Scholar 

  19. Chen Y, Chang Y, Yao S. Role of angiogenesis in endometrial repair of patients with severe intrauterine adhesion. Int J Clin Exp Pathol. 2013;6(7):1343–1350.

    PubMed  PubMed Central  Google Scholar 

  20. Dinarvand P, Hashemi SM, Seyedjafari E, et al.. Function of poly (lactic-co-glycolic aeid) nanofiber in reduetion of adhesion bands. J Surg Res. 2012;172(1):e1–e9.

    Article  CAS  PubMed  Google Scholar 

  21. Ahmad G, O’Flynn H, Hindocha A, Watson A. Barrier agents for adhesion prevention after gynaecological surgery. Cochrane Database Syst Rev. 2015;4:cd000475.

    Google Scholar 

  22. Jackson ND, Rosenblatt PL. Use of intereced absorbable adhesion barrier for vaginoplasty. Obstet Gynecol. 1994;84(6):1048–1050.

    CAS  PubMed  Google Scholar 

  23. Motoyama S, Laoag-Fernandez JB, Mochizuki S, Yamabe S, Maruo T. Vaginoplasty with Intereeed absorbable adhesion barrier for complete squamous epithelialization in vaginal agenesis. Am J Obstet Gynecol. 2003;188(5):1260–1264.

    Article  PubMed  Google Scholar 

  24. Kajikawa MM, Järmy-Di Bella ZI, Focchi GR, Dornelas J, Giräo MJ, Sartori MG. Role of estrogen receptor alpha on vaginal epithelialization of patients with Mayer-Rokitansky-Kuster-Hauser Syndrome submitted to neovaginoplasty using oxidized regenerated cellulose. Int Urogynecol J. 2012;23(4):467–472.

    Article  PubMed  Google Scholar 

  25. Lee J, Bae Y. The use of absorbable interecedâ pouch with double- layer skin closure for partial defect of breast. Breast J. 2014; 20(4):414–419.

    Article  PubMed  Google Scholar 

  26. Lee J, Lee S, Jung Y, Bae Y. Use of an absorbable adhesion barrier for reconstruetion of partial mastectomy defects in the upper quadrant of large ptotic breasts. Surg Oncol. 2015;24(2):123–127.

    Article  PubMed  Google Scholar 

  27. Park KS, Lee KE, Ku do H, et al.. Antiadhesive effect and safety of oxidized regenerated cellulose after thyroidectomy:a prospective, randomized controlled study. J Korean Surg Soc. 2013;84(6):321–329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Marshburn PB, Meek JM, Gruber HE, Gordon BE, Norton JH, Hurst BS. Preoperative leuprolide acetate combined with Intereeed* optimally reduces uterine adhesions and fibrosis in a rabbit model. Fertil Steril. 2004;81(1):194–197.

    Article  CAS  PubMed  Google Scholar 

  29. Liu F, Zhu ZJ, Li P, He YL. Creation of a female rabbit model for intrauterine adhesions using mechanical and infectious injury. J SurgRes. 2013;183(1):296–303.

    Google Scholar 

  30. Tan G, Guo W, Zhang B, Xiang X, Chen W, Yang J. Temporary reduetion and slow recovery of integrin αvß3 in endometrium after uterine arterial embolization. Eur J Obstet Gynecol Reprod Biol. 2012;160(1):66–70.

    Article  CAS  PubMed  Google Scholar 

  31. Yu N, Yan W, Wang Y, Yin T, Guo Y, Yang J. Effect of Zhuyun reeipe on endometrial pinopode expression in mice with embryo-nic implantation dysfunetion and Ovulation Stimulation. Exp Ther Med. 2015;9(2):488–492.

    Article  PubMed  Google Scholar 

  32. Chen C, Yan Q, Liu K, et al.. Endometrial reeeptivity markers in mice stimulated with raloxifene versus clomiphene citrate and natural cycles. Reprod Sci. 2016;23(6):748–755.

    Article  CAS  PubMed  Google Scholar 

  33. Casals G, Ordi J, Creus M, et al.. Endometrial pinopode and α v ß 3 Integrin expression is not impaired in infertile patients with endometriosis. Hum Reprod. 2012;27(3):805–813.

    Article  CAS  PubMed  Google Scholar 

  34. von Grothusen C, Lalitkumar S, Boggavarapu NR, Gemzell-Danielsson K, Lalitkumar PG. Recent advances in understanding endometrial receptivity:molecular basis and clinical applications. Am J Reprod Immunol. 2014;72(2):148–157.

    Article  Google Scholar 

  35. Illera MJ, Lorenzo PL, Gui YT, Beyler SA, Apparao KB, Lessey BA. A role for alphavbeta3 integrin during implantation in the rabbit model. Biol Reprod. 2003;68(3):766–771.

    Article  CAS  PubMed  Google Scholar 

  36. Bildirici I, Bukulmez O, Ensari A, Yarali H, Gurgan T. A prospective evaluation of the effect of salpingectomy on endometrial reeeptivity in cases of women with communicating hydrosalpinges. Hum Reprod. 2001;16(11):2422–2426.

    Article  CAS  PubMed  Google Scholar 

  37. Zhong Y, Li J, Wu H, et al.. Surgical treatment for hydrosalpinx increases the expression of integrin a v ß 3 in the endometrium during the implantation window. Exp Ther Med. 2012;4(3):415–418.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lessey BA, Damjanovich L, Coutifaris C, Castelbaum A, Albelda SM, Buck CA. Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle. J Clin Invest. 1992;90(1):188–195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Yuanli He MD.

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Cai, H., Li, H. & He, Y. Interceed and Estrogen Reduce Uterine Adhesions and Fibrosis and Improve Endometrial Receptivity in a Rabbit Model of Intrauterine Adhesions. Reprod. Sci. 23, 1208–1216 (2016). https://doi.org/10.1177/1933719116632923

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