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Medical or surgical treatment before embryo transfer improves outcomes in women with abnormal endometrial BCL6 expression

  • Assisted Reproduction Technologies
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the effect of medical or surgical treatment prior to embryo transfer in women with elevated endometrial BCL6 expression and suspected endometriosis in a prospective, cohort study design at a university-associated infertility clinic.

Methods

All subjects had at least 1 year of unexplained infertility (UI) and each prospectively underwent endometrial biopsy and immunostaining for the oncogene BCL6, prior to embryo transfer during an assisted reproductive technology (ART) cycle. To be included, subjects had to have an abnormal BCL6 result, defined by elevated HSCORE ≥ 1.4. Women that were pre-treated with laparoscopy or medical suppression with GnRH agonist (depot leuprolide acetate; Lupron®, Abbvie, Inc., Chicago, IL) for 2 months were compared to a group that went untreated (controls). Endpoints included implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR), and as well as cycle characteristics. Miscarriage rate were also compared between treatment and control group.

Results

Women in each group had similar characteristics. Those treated by medical suppression and those undergoing laparoscopy for endometriosis had a significantly higher LBR, (5/10; 50%; 95%CI 23.7 to 76.3%) and (11/21; 52.4%; 95%CI 32.4 to 71.7), respectively, compared to controls (4/54; 7.4%; 95%CI 2.9 to 17.6). An absolute benefit of 44.2% (16/31; 95%CI 24.6 to 61.2) and a number need to treat of 3 for those that received treatment (medical suppression and laparoscopy), compared to no treatment. Miscarriages were significantly more common in the control group.

Conclusions

Women with suspected endometriosis and aberrant endometrial BCL6 expression have worse reproductive outcomes following embryo transfer, including a high miscarriage rate, poor IR, and low LBR and CPR compared to cycles pre-treated with medical and surgical management.

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References

  1. Tsuji I, Ami K, Miyazaki A, Hujinami N, Hoshiai H. Benefit of diagnostic laparoscopy for patients with unexplained infertility and normal hysterosalpingography findings. Tohoku J Exp Med. 2009;219:39–42.

    Article  PubMed  Google Scholar 

  2. Nakagawa K, Ohgi S, Horikawa T, Kojima R, Ito M, Saito H. Laparoscopy should be strongly considered for women with unexplained infertility. J Obstet Gynaecol Res. 2007;33:665–70.

    Article  PubMed  Google Scholar 

  3. Meuleman C, Vandenabeele B, Fieuws S, Spiessens C, Timmerman D, D’Hooghe T. High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil Steril. 2009;92:68–74.

    Article  PubMed  Google Scholar 

  4. Littman E, Giudice L, Lathi R, Berker B, Milki A, Nezhat C. Role of laparoscopic treatment of endometriosis in patients with failed in vitro fertilization cycles. Fertil Steril. 2005;84:1574–8.

    Article  PubMed  Google Scholar 

  5. Mohamed AMF, Chouliaras S, Jones CJP, Nardo LG. Live birth rate in fresh and frozen embryo transfer cycles in women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2011;156:177–80.

    Article  PubMed  Google Scholar 

  6. Prapas Y, Goudakou M, Matalliotakis I, Kalogeraki A, Matalliotaki C, Panagiotidis Y, et al. History of endometriosis may adversely affect the outcome in menopausal recipients of sibling oocytes. Reprod BioMed Online. 2012;25:543–8.

    Article  PubMed  Google Scholar 

  7. Díaz I, Navarro J, Blasco L, Simón C, Pellicer A, Remohí J. Impact of stage III-IV endometriosis on recipients of sibling oocytes: matched case-control study. Fertil Steril. 2000;74:31–4.

    Article  PubMed  Google Scholar 

  8. Zullo F, Spagnolo E, Saccone G, Acunzo M, Xodo S, Ceccaroni M, et al. Endometriosis and obstetrics complications: a systematic review and meta-analysis. Fertil Steril 2017;108:667–72.e5.

  9. National Summary Report [Internet] [cited 2017 Jul 21];Available from: https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?reportingYear=2014.

  10. D’Hooghe TM, Debrock S, Hill JA, Meuleman C. Endometriosis and subfertility: is the relationship resolved? Semin Reprod Med. 2003;21:243–54.

    Article  PubMed  Google Scholar 

  11. Senapati S, Sammel MD, Boudhar S, Morse CB, Barnhart KT. The impact of endometriosis on IVF: an evaluation using the society of assisted reproductive technologies (SART) database. Fertil Steril. 2014;102:e48–9.

    Article  Google Scholar 

  12. Harton GL, Munné S, Surrey M, Grifo J, Kaplan B, McCulloh DH, et al. Diminished effect of maternal age on implantation after preimplantation genetic diagnosis with array comparative genomic hybridization. Fertil Steril. 2013;100:1695–703.

    Article  CAS  PubMed  Google Scholar 

  13. Pallacks C, Hirchenhain J, Krüssel J-S, Fehm TN, Fehr D. Endometriosis doubles odds for miscarriage in patients undergoing IVF or ICSI. Eur J Obstet Gynecol Reprod Biol. 2017;213:33–8.

    Article  PubMed  Google Scholar 

  14. Almquist LD, Likes CE, Stone B, Brown KR, Savaris R, Forstein DA, et al. Endometrial BCL6 testing for the prediction of in vitro fertilization outcomes: a cohort study. Fertil Steril. 2017;108:1063–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Evans-Hoeker E, Lessey BA, Jeong JW, Savaris RF, Palomino WA, Yuan L, et al. Endometrial BCL6 overexpression in eutopic endometrium of women with endometriosis. Reprod Sci. 2016;23:1234–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yoo J-Y, Kim TH, Fazleabas AT, Palomino WA, Ahn SH, Tayade C, et al. KRAS activation and over-expression of SIRT1/BCL6 contributes to the pathogenesis of endometriosis and progesterone resistance. Sci Rep. 2017;7:6765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. 2010.

  18. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Fertil Steril. 1950;1:3–25.

    Article  Google Scholar 

  19. Budwit-Novotny DA, McCarty KS, Cox EB, Soper JT, Mutch DG, Creasman WT, et al. Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res. 1986;46:5419–25.

    CAS  PubMed  Google Scholar 

  20. Schoenfeld DA. Sample-size formula for the proportional-hazards regression model. Biometrics. 1983;39:499–503.

    Article  CAS  PubMed  Google Scholar 

  21. Kohl Schwartz AS, Wölfler MM, Mitter V, Rauchfuss M, Haeberlin F, Eberhard M, et al. Endometriosis, especially mild disease: a risk factor for miscarriages. Fertil Steril. 2017;108:806–14.e2.

    Article  PubMed  Google Scholar 

  22. Santulli P, Marcellin L, Menard S, Thubert T, Khoshnood B, Gayet V, et al. Increased rate of spontaneous miscarriages in endometriosis-affected women. Hum Reprod. 2016;31:1014–23.

    Article  PubMed  Google Scholar 

  23. Yang X, Huang R, Cai M, Liang X. Endometriosis has no negative impact on outcomes of in vitro fertilisation in women with poor ovarian response. BJOG. 2016;123 Suppl 3:76–81.

    Article  CAS  PubMed  Google Scholar 

  24. González-Comadran M, Schwarze JE, Zegers-Hochschild F, Souza M do CB, Carreras R, Checa MÁ. The impact of endometriosis on the outcome of assisted reproductive technology. Reprod Biol Endocrinol. 2017;15:8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Brosens J, Verhoeven H, Campo R, Gianaroli L, Gordts S, Hazekamp J, et al. High endometrial aromatase P450 mRNA expression is associated with poor IVF outcome. Hum Reprod. 2004;19:352–6.

    Article  CAS  PubMed  Google Scholar 

  26. Miller PB, Parnell BA, Bushnell G, Tallman N, Forstein DA, Higdon HL 3rd, et al. Endometrial receptivity defects during IVF cycles with and without letrozole. Hum Reprod. 2012;27:881–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fox C, Morin S, Jeong J-W, Scott RT Jr, Lessey BA. Local and systemic factors and implantation: what is the evidence? Fertil Steril 2016;105:873–884.

  28. Bulun SE, Cheng Y-H, Yin P, Imir G, Utsunomiya H, Attar E, et al. Progesterone resistance in endometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol. 2006;248:94–103.

    Article  CAS  PubMed  Google Scholar 

  29. Bulun SE. Endometriosis. N Engl J Med. 2009;360:268–79.

    Article  CAS  PubMed  Google Scholar 

  30. Lessey BA, Lebovic DI, Taylor RN. Eutopic endometrium in women with endometriosis: ground zero for the study of implantation defects. Semin Reprod Med. 2013;31:109–24.

    Article  PubMed  Google Scholar 

  31. Burney RO, Talbi S, Hamilton AE, Vo KC, Nyegaard M, Nezhat CR, et al. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007;148:3814–26.

    Article  CAS  PubMed  Google Scholar 

  32. Website [Internet] . [cited 2018 Apr 19]. Available from: National Summary Report [Internet][cited 2017 Jul 21];Available from: https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?reportingYear=2014.

  33. Feinberg EC, Levens ED, DeCherney AH. Infertility surgery is dead: only the obituary remains? Fertil Steril. 2008;89:232–6.

    Article  PubMed  Google Scholar 

  34. Yu LP, Liu N, Liu Y. Effect of luteal-phase gonadotropin-releasing hormone agonist administration on pregnancy outcome in IVF/ICSI cycles: a systematic review and meta-analysis. Zhonghua Fu Chan Ke Za Zhi. 2016;51:850–8.

    CAS  PubMed  Google Scholar 

  35. Siristatidis CS, Gibreel A, Basios G, Maheshwari A, Bhattacharya S. Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction. Cochrane Database Syst Rev 2015;CD006919.

  36. Lensen S, Sadler L, Farquhar C. Endometrial scratching for subfertility: everyone’s doing it. Hum Reprod. 2016;31:1241–4.

    Article  CAS  PubMed  Google Scholar 

  37. van Hoogenhuijze NE, Torrance HL, Mol F, Laven JSE, Scheenjes E, Traas MAF, et al. Endometrial scratching in women with implantation failure after a first IVF/ICSI cycle; does it lead to a higher live birth rate? The SCRaTCH study: a randomized controlled trial (NTR 5342). BMC Womens Health. 2017;17:47.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N Engl J Med. 2017;377:28–40.

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by NICHD/NIH R01 HD067721 Grant 99999.003035/2015-08 (BAL) and by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior: CAPES/PROAP (RFS).

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Correspondence to Bruce A. Lessey.

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The Institutional Review Board approval was obtained from the Committee for the Protection of Human Subjects (GHS #00013885).

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Likes, C.E., Cooper, L.J., Efird, J. et al. Medical or surgical treatment before embryo transfer improves outcomes in women with abnormal endometrial BCL6 expression. J Assist Reprod Genet 36, 483–490 (2019). https://doi.org/10.1007/s10815-018-1388-x

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  • DOI: https://doi.org/10.1007/s10815-018-1388-x

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