Why Do Euploid Embryos Fail to Implant? The Role of CD138 and Chronic Endometritis

Jennifer K Blakemore Jennifer K Blakemore,Brooke Hodes-Wertz Brooke Hodes-Wertz,James A Grifo James A Grifo,Alexis K Masbou Alexis K Masbou,M Elizabeth Fino M Elizabeth Fino,David L Keefe David L Keefe

doi:10.18314/cogo.v3i1.1867

Jennifer K Blakemore Jennifer K Blakemore, Brooke Hodes-Wertz Brooke Hodes-Wertz + Show 4 more

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https://doi.org/10.18314/cogo.v3i1.1867

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Abstract

The objective of this prospective cohort study was to investigate the relationship between chronic endometritis (CE) and its treatment on pregnancy outcomes in patients undergoing frozen embryo transfers (FETs) from in vitro fertilization (IVF) with preimplantation genetic testing (PGT) who had previously failed ≥ 1 euploid FET. The diagnosis of CE was made using CD138 as a marker. This study occurred at a single, high volume academic based fertility center. 305 patients were included with a history of ≥ 1 failed euploid transfers. 59 patients underwent endometrial biopsies (EMB) prior to subsequent FET (Tested), 246 patients did not undergo EMB prior to subsequent transfer (Untested). Patients in the Tested group had an EMB prior to subsequent FET, whereas the patients in the Untested group did not have an EMB prior to next FET. Patients tested and found positive for CE were treated with antibiotics and underwent test-of-cure (TOC) EMBs prior to next FET to assess for adequate treatment. Patients without CE on EMB proceeded to next FET without antibiotic treatment. Main outcome measures included positive Beta-hCG (βhCG) on cycle day 28, implantation rate (IR), and subsequent ongoing pregnancy/live birth rates (OPR/LBR). Our results showed that 51% of patients (30/59) were diagnosed with CE and treated with antibiotics (Tested, CE treated); negative TOC biopsies were obtained prior to next FET. 49% of patients (29/59) tested negative for CE (Tested, No CE) and were not treated prior to next FET. Tested patients without CE (CE treated and No CE) had significantly higher incidences of positive βhCG, IR and OPR/LBR than patients who were not tested. Those who were biopsied and treated for CE had significantly higher OPR/LBR compared to patients who were biopsied and negative for CE (80% vs. 55%). We conclude that CE is common, with a prevalence of 51% in patients who have failed euploid FETs. Testing for CE may provide a benefit to patients, assuring higher incidences for positive βhCG, implantation, and subsequent ongoing/live births. CE is a treatable condition warranting investigation in patients with poor pregnancy outcomes.

Highlights

Why do patients fail to become pregnant after the transfer of chromosomally-normal embryos? Certainly undetected genetic variation in the embryo is one component; the endometrium represents a major contributing factor and an area of potential improvement for in vitro fertilization (IVF) pregnancy outcomes.Chronic endometritis (CE), one such consideration, is a pathologic inflammation of the endometrium marked by the presence of plasma cells
It appears that certain higher risk populations like recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) groups may have a higher prevalence of CE, upwards of 42.9% and 57%, respectively [1,2,3,4,5,6,7,8]
59 patients had endometrial biopsy (EMB) (Tested) prior to undergoing the subsequent frozen embryo transfers (FETs) and 246 patients proceeded directly to the FET without having an EMB (Untested). 51% (30/59) of patients who underwent EMB tested positive for CE as evidenced by CD138 staining and were treated with antibiotics (Tested, CE Treated); negative TOC biopsies were obtained after completing antibiotics and prior to proceeding to the FET. 11/30 (37%) patients required additional antibiotic treatment to adequately treat CE, which was confirmed with negative TOC biopsies following the second round of antibiotics. 49% (29/59) of patients tested negative for CE (Tested, No CE)

Summary

Introduction

Chronic endometritis (CE), one such consideration, is a pathologic inflammation of the endometrium marked by the presence of plasma cells. Prevalence is poorly understood as endometritis is not routinely screened for in all IVF or gynecologic settings, and most patients with the diagnosis are asymptomatic. It appears that certain higher risk populations like recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) groups may have a higher prevalence of CE, upwards of 42.9% and 57%, respectively [1,2,3,4,5,6,7,8].

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