Uterine immune profiling for increasing live birth rate: A one-to-one matched cohort study

J Reprod Immunol. 2017 Feb:119:23-30. doi: 10.1016/j.jri.2016.11.007. Epub 2016 Nov 24.

Abstract

Background: Embryo implantation remains the main limiting factor in IVF/ICSI program. Endometrial immune remodeling events begin before implantation and are a vital process for pregnancy, preparing future maternal immune tolerance and regulating the placentation process.

Methods: Between 2012 and 2014, 193 patients (analyzed group) enrolled in our IVF program benefitted of an endometrial immune profiling to determine if their uterus was immunologically ready to accept an embryo and, if not, the specific immune mechanisms involved. Subsequently, they had an effective embryo transfer (ET) with personalization of their treatments if an immune deregulation has been diagnosed. Each analyzed patient was paired to the closest patient included in the IVF program according to biological criteria (age, number of mature oocytes, stage and number of transferred embryo), which had no endometrial immune profiling (193 patients, non-analyzed group).

Finding: 78% of analyzed patients had a uterine immune dysregulation and therefore care personalization. Their corresponding live birth rate (LBR) was twice higher than observed in the matched control group with conventional cares (30.5% versus 16.6%, OR: 2.2 [1.27-3.83] p=0.004) with a simultaneous drastic reduction of miscarriages per initiated pregnancy (17.9% versus 43.2%, OR: 0.29 [0.12-0.71], p=0.005). 22% of analyzed patients had no dysregulation. They did not differ from their matched controls for LBR and miscarriages.

Conclusion: Uterine immune profiling enables an integrated approach of infertility that includes endometrial immunity as a key factor in planning personalized IVF/ICSI treatments. Personalization of treatment according to the woman's uterine immune balance produced a very significantly higher LBR.

Keywords: Embryo implantation; Endometrium; IVF/ICSI; Repeated implantation failures; Uterine receptivity.

MeSH terms

  • Abortion, Spontaneous / diagnosis
  • Abortion, Spontaneous / therapy*
  • Adult
  • CD56 Antigen / metabolism
  • Cohort Studies
  • Cytokine TWEAK / genetics
  • Cytokine TWEAK / metabolism
  • Embryo Implantation
  • Endometrium / immunology*
  • Female
  • Fertilization in Vitro*
  • Humans
  • Interleukin-15 / genetics
  • Interleukin-15 / metabolism
  • Interleukin-18 / genetics
  • Interleukin-18 / metabolism
  • Killer Cells, Natural / immunology*
  • Pregnancy
  • Pregnancy Rate
  • Retrospective Studies
  • TWEAK Receptor / genetics
  • TWEAK Receptor / metabolism
  • Treatment Outcome

Substances

  • CD56 Antigen
  • Cytokine TWEAK
  • Interleukin-15
  • Interleukin-18
  • TNFRSF12A protein, human
  • TNFSF12 protein, human
  • TWEAK Receptor