The Role of Inflammatory Pathways in Implantation Failure: Chronic Endometritis and Hydrosalpinges

Abstract The process of implantation is highly complex and involves a delicate interplay between the embryo and the appropriate maternal environment. The failure to implant is thought to be due to maternal factors or embryonic factors. Inflammation can be a part of the normal physiologic process during implantation; however, there are also pathologic entities that adversely affect uterine receptivity. This review will focus on chronic endometritis and hydrosalpinges as two specific inflammatory processes that contribute to implantation failure. For both chronic endometritis and hydrosalpinges, we will review the diagnosis, pathophysiology, and effect on implantation following treatment. The existing literature conclusively demonstrates that hydrosalpinges should be addressed by either laparoscopic salpingectomy or proximal tubal occlusion prior to in vitro fertilization. The picture for chronic endometritis is less clear since the diagnosis and treatment of chronic endometritis are not standardized, and there are no available randomized controlled trials on this topic. Future studies may target gene expression arrays as a method for further elucidating the role of inflammatory markers in normal and abnormal implantation processes.

[1]  E. Cicinelli,et al.  Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. , 2015, Human reproduction.

[2]  H. Duan,et al.  Salpingectomy and Proximal Tubal Occlusion for Hydrosalpinx Prior to In Vitro Fertilization: A Meta-analysis of Randomized Controlled Trials , 2015, Obstetrical & gynecological survey.

[3]  Terumi Hayashi,et al.  Comprehensive Endometrial Immunoglobulin Subclass Analysis in Infertile Women Suffering from Repeated Implantation Failure with or without Chronic Endometritis , 2014, American journal of reproductive immunology.

[4]  E. Odacı,et al.  Endometrial injury may increase the clinical pregnancy rate in normoresponders undergoing long agonist protocol ICSI cycles with single embryo transfer. , 2014, European journal of obstetrics, gynecology, and reproductive biology.

[5]  T. Gurgan,et al.  Recurrent implantation failure: definition and management. , 2014, Reproductive biomedicine online.

[6]  J. Qiao,et al.  The hysteroscopy and histological diagnosis and treatment value of chronic endometritis in recurrent implantation failure patients , 2014, Archives of Gynecology and Obstetrics.

[7]  B. Prieto,et al.  Hysteroscopic hydrosalpinx occlusion with Essure device in IVF patients when salpingectomy or laparoscopy is contraindicated. , 2013, European journal of obstetrics, gynecology, and reproductive biology.

[8]  T. Hamatani,et al.  Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity , 2013, Reproductive Biology and Endocrinology.

[9]  E. Cicinelli,et al.  Altered Transcriptional Regulation of Cytokines, Growth Factors, and Apoptotic Proteins in the Endometrium of Infertile Women with Chronic Endometritis , 2013, American journal of reproductive immunology.

[10]  L. Nardo,et al.  Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis. , 2012, Reproductive biomedicine online.

[11]  Wenming Xu,et al.  NF kappaB expression increases and CFTR and MUC1 expression decreases in the endometrium of infertile patients with hydrosalpinx: a comparative study , 2012, Reproductive Biology and Endocrinology.

[12]  P. Casali,et al.  Immunoglobulin class-switch DNA recombination: induction, targeting and beyond , 2012, Nature Reviews Immunology.

[13]  E. Jungheim,et al.  How members of the Society for Reproductive Endocrinology and Infertility and Society of Reproductive Surgeons evaluate, define, and manage hydrosalpinges. , 2012, Fertility and sterility.

[14]  P. Devroey,et al.  The impact of chronic endometritis on reproductive outcome. , 2011, Fertility and sterility.

[15]  G. Mor,et al.  Local injury of the endometrium induces an inflammatory response that promotes successful implantation. , 2010, Fertility and sterility.

[16]  K. Kitaya,et al.  Aberrant expression of selectin E, CXCL1, and CXCL13 in chronic endometritis , 2010, Modern Pathology.

[17]  L. Engmann,et al.  Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. , 2010, Fertility and sterility.

[18]  N. Gupta,et al.  Does local endometrial injury in the nontransfer cycle improve the IVF-ET outcome in the subsequent cycle in patients with previous unsuccessful IVF? A randomized controlled pilot study , 2010, Journal of human reproductive sciences.

[19]  M. Karimzadeh,et al.  Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilisation/intra cytoplasmic sperm injection: A randomised clinical trial , 2009, The Australian & New Zealand journal of obstetrics & gynaecology.

[20]  Rong Li,et al.  Local injury to the endometrium: its effect on implantation , 2009, Current opinion in obstetrics & gynecology.

[21]  N. Kanakas,et al.  The Role of Matrix Metalloproteinases in the Pathogenesis of Endometriosis , 2009, Reproductive Sciences.

[22]  E. Cicinelli,et al.  ORIGINAL ARTICLE: Abnormal Pattern of Lymphocyte Subpopulations in the Endometrium of Infertile Women with Chronic Endometritis , 2009, American journal of reproductive immunology.

[23]  P. Devroey,et al.  In vitro fertilization pregnancy in a patient with proven chronic endometritis. , 2009, Fertility and sterility.

[24]  C. Heijnen,et al.  Embryonic implantation: cytokines, adhesion molecules, and immune cells in establishing an implantation environment , 2008, Journal of leukocyte biology.

[25]  Rong Li,et al.  Local injury to the endometrium in controlled ovarian hyperstimulation cycles improves implantation rates. , 2008, Fertility and sterility.

[26]  A. Coomarasamy,et al.  Ultrasound-guided hydrosalpinx aspiration during oocyte collection improves pregnancy outcome in IVF: a randomized controlled trial. , 2008, Human reproduction.

[27]  E. Cicinelli,et al.  Chronic endometritis: correlation among hysteroscopic, histologic, and bacteriologic findings in a prospective trial with 2190 consecutive office hysteroscopies. , 2008, Fertility and sterility.

[28]  H. Shapiro,et al.  Essure treatment of hydrosalpinges. , 2007, Fertility and sterility.

[29]  J. Rinehart.  Recurrent implantation failure: definition , 2007, Journal of Assisted Reproduction and Genetics.

[30]  A. Raziel,et al.  Favorable influence of local injury to the endometrium in intracytoplasmic sperm injection patients with high-order implantation failure. , 2007, Fertility and sterility.

[31]  D. Botsis,et al.  Proximal tubal occlusion and salpingectomy result in similar improvement in in vitro fertilization outcome in patients with hydrosalpinx. , 2006, Fertility and sterility.

[32]  J. Hanna,et al.  Decidual NK cells regulate key developmental processes at the human fetal-maternal interface , 2006, Nature Medicine.

[33]  Hai-yan Lin,et al.  Effects of E-cadherin on mouse embryo implantation and expression of matrix metalloproteinase-2 and -9. , 2006, Biochemical and biophysical research communications.

[34]  P. Ho,et al.  Comparison of endometrial and subendometrial blood flows among patients with and without hydrosalpinx shown on scanning during in vitro fertilization treatment. , 2006, Fertility and sterility.

[35]  V. Wells,et al.  Presence of hydrosalpinx correlated to endometrial inflammatory response in vivo. , 2002, Fertility and sterility.

[36]  Salpingectomy for hydrosalpinx prior to in vitro fertilization. , 2006, Fertility and sterility.

[37]  U. Kayisli,et al.  Removal of hydrosalpinges increases endometrial leukaemia inhibitory factor (LIF) expression at the time of the implantation window. , 2005, Human reproduction.

[38]  U. Kämmerer.  Antigen-presenting cells in the decidua. , 2005, Chemical immunology and allergy.

[39]  R. Stones,et al.  Proximal occlusion of hydrosalpinx by hysteroscopic placement of microinsert before in vitro fertilization-embryo transfer. , 2004, Fertility and sterility.

[40]  G. Serour,et al.  Fluid accumulation of the uterine cavity before embryo transfer: A possible hindrance for implantation , 1991, Journal of in Vitro Fertilization and Embryo Transfer.

[41]  M. Robinson,et al.  ESHRE PGD Consortium 'Best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS)'. , 2005, Human reproduction.

[42]  B. Innes,et al.  Immunohistochemical characterization of endometrial leucocytes in endometritis , 2004, Histopathology.

[43]  R. Romero,et al.  Can endometrial infection/inflammation explain implantation failure, spontaneous abortion, and preterm birth after in vitro fertilization? , 2004, Fertility and sterility.

[44]  Dutch-speaking Brussels.  ESHRE PGD Consortium 'Best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS)' , 2004 .

[45]  Salpingectomy for hydrosalpinx prior to in vitro fertilization. , 2004, Fertility and sterility.

[46]  L. Kornman,et al.  Analysis of intra-uterine cytokine concentration and matrix-metalloproteinase activity in women with recurrent failed embryo transfer. , 2003, Human reproduction.

[47]  E. Bambirra,et al.  Detection of chronic endometritis by diagnostic hysteroscopy in asymptomatic infertile patients. , 2001, Gynecologic and Obstetric Investigation.

[48]  L. Salamonsen,et al.  Leukocyte networks and human endometrial remodelling. , 2002, Journal of reproductive immunology.

[49]  K. Barnhart,et al.  Reliability of clinicians versus radiologists for detecting abnormalities on hysterosalpingogram films. , 2002, Fertility and sterility.

[50]  A. Ensari,et al.  A prospective evaluation of the effect of salpingectomy on endometrial receptivity in cases of women with communicating hydrosalpinges. , 2001, Human reproduction.

[51]  S. Ghaskadbi,et al.  Reproductive toxicity of piperine in Swiss albino mice. , 2000, Planta medica.

[52]  U. Waldenström,et al.  Hydrosalpinx and IVF outcome: a prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF. , 1999, Human reproduction.

[53]  F. Goffinet,et al.  Pregnancy rates after in-vitro fertilization in cases of tubal infertility with and without hydrosalpinx: a meta-analysis of published comparative studies. , 1999, Human reproduction.

[54]  M. Bloechle.  What is a hydrosalpinx? A plea for the use of a proper terminology in scientific discussion. , 1999, Human reproduction.

[55]  A. Arıcı,et al.  Adverse effects of hydrosalpinx on pregnancy rates after in vitro fertilization-embryo transfer. , 1998, Fertility and sterility.

[56]  B. Lessey.  Endometrial integrins and the establishment of uterine receptivity. , 1998, Human reproduction.

[57]  J. Daurès,et al.  Does previous salpingectomy improve implantation and pregnancy rates in patients with severe tubal factor infertility who are undergoing in vitro fertilization? A pilot prospective randomized study. , 1998, Fertility and sterility.

[58]  R. Schats,et al.  Only hydrosalpinges visible on ultrasound are associated with reduced implantation and pregnancy rates after in-vitro fertilization. , 1998, Human reproduction.

[59]  J. Williams,et al.  Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx? , 1997, Human reproduction.

[60]  J. Harris,et al.  Hydrosalpinges adversely affect markers of endometrial receptivity. , 1997, Human reproduction.

[61]  M. Bloechle,et al.  Recurrence of hydrosalpinges after transvaginal aspiration of tubal fluid in an IVF cycle with development of a serometra. , 1997, Human reproduction.

[62]  T. Mukherjee,et al.  Hydrosalpinx fluid has embryotoxic effects on murine embryogenesis: a case for prophylactic salpingectomy. , 1996, Fertility and sterility.

[63]  D. Anderson,et al.  T-helper 1-type immunity to trophoblast in women with recurrent spontaneous abortion. , 1995, JAMA.

[64]  D. Charnock-Jones,et al.  Leukaemia inhibitory factor mRNA concentration peaks in human endometrium at the time of implantation and the blastocyst contains mRNA for the receptor at this time. , 1994, Journal of reproduction and fertility.

[65]  T. Inoue,et al.  Expression of leukemia inhibitory factor in human endometrium and placenta. , 1994, Biology of reproduction.

[66]  T. Inoue,et al.  Tumour necrosis factor alpha inhibits in-vitro decidualization of human endometrial stromal cells. , 1994, Human reproduction.

[67]  Christos Coutifaris,et al.  Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle. , 1992, The Journal of clinical investigation.

[68]  K. Imai,et al.  Interleukin-1 inhibits in vitro decidualization of human endometrial stromal cells. , 1991, The Journal of clinical endocrinology and metabolism.

[69]  J. Edwards,et al.  Endometrial lymphoid tissue: an immunohistological study. , 1985, Journal of clinical pathology.

[70]  S. Greenwood,et al.  Chronic Endometritis: Morphologic and Clinical Observations , 1981, Obstetrics and gynecology.