Why do euploid embryos fail to implant: the role of CD-138 and chronic endometritis

Abstract

To investigate the relationship between CE and its treatment on pregnancy outcomes in patients undergoing FETs from in vitro fertilization (IVF) with pre-implantation genetic testing (PGT) who had previously failed ≥1 euploid FET. Retrospective cohort study. Inclusion criteria: single, euploid FET cycles, patients failing ≥1 single FET (autologous/donor recipient IVF-PGT cycles) between 2012-2017 at a university-based fertility center. Results for repeat FETs were compared between treatment groups. Patients meeting inclusion criteria were grouped as CE negative (having a post-FET endometrial biopsy (EMB) and were either treated for CE or not treated because no CE was found) vs patients who did not undergo EMB (Untested). EMBs were obtained by Pipelle® and stained for CD-138 to rule out CE. Pts were excluded from Untested if they had uterine procedures <2 months before the next transfer. Outcomes from the subsequent FETs were analyzed: positive βhCG on cycle day 28, implantation (IR), ongoing pregnancy/live birth (OPR/LBR) rates. Chi-squared was used for analysis. 305 cycles met inclusion criteria; 59 patients had EMBs (Tested) prior to next FET, 246 patients proceeded to next FET without EMB (Untested). 51% of patients (30/59) were diagnosed with CE and treated with antibiotics (CE treated); negative test-of-cure biopsies were obtained prior to next FET. 49% of patients (29/59) tested negative for CE (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, implantation and ongoing live birth than patients who were not tested (See Table, A vs B). Untested patients were presumed to have an incidence of CE comparable to Tested patients. 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%). CE is common, with a prevalence of 51% in patients who have failed FETs. Testing for CE provides a clear benefit to patients, assuring higher incidences for positive βhCG, implantation, and ongoing & live births. It is unclear whether the benefit was derived from assurance of no CE or from the effect of the endometrial scratch during EMBs. This determination will require further investigation. CE is a treatable condition warranting investigation in patients with poor pregnancy outcomes.Tabled 1Pregnancy outcomes according to testing and CE statusOutcome/GroupsPositive βhCGIROPR/LBRA) Untested70% (171/246)54% (132/246)42% (104/246)B) Tested86% (51/59)71% (42/59)68% (40/59)B1) CE Treated93% (28/30)80% (24/30)80% (24/30)B2) No CE79% (23/29)62% (18/29)55% (16/29)Significancea, ba, ba, b, ca A vs B1 vs B2 p<0.05, b A vs B p<0.05, c B1 vs B2 p<0.05. Open table in a new tab