Chronic Endometritis in Infertile Women: Impact of Untreated Disease, Plasma Cell  Count and Antibiotic Therapy on IVF Outcome-A Systematic Review and  Meta-Analysis

Vitagliano A; Laganà AS; Cicinelli R; Santarsiero CM; Buzzaccarini G; Chiantera V; Cicinelli E; Marinaccio M; de Ziegler D

doi:10.3390/diagnostics12092250

Infections and the Reproductive Microbiome Chronic Endometritis

Chronic Endometritis in Infertile Women: Impact of Untreated Disease, Plasma Cell Count and Antibiotic Therapy on IVF Outcome-A Systematic Review and Meta-Analysis

Vitagliano A, Laganà AS, Cicinelli R, Santarsiero CM, Buzzaccarini G, Chiantera V, Cicinelli E, Marinaccio M, de Ziegler D

Published September 18, 2022 Diagnostics (Basel, Switzerland), 12(9), 2250

DOI 10.3390/diagnostics12092250 PMID 36140651 PMC PMC9498271

RRM Academy Synopsis

Chronic endometritis is linked to lower IVF pregnancy rates

Chronic endometritis was linked to lower pregnancy and live birth rates after IVF. This meta-analysis pooled ten observational studies of 4145 infertile women having IVF. Women with cured endometritis had similar outcomes to women without it in three studies. Two studies found no difference for mild disease.

Key Findings

In eight studies, women without chronic endometritis had higher ongoing pregnancy or live birth rates (odds ratio 1.97, 95% CI 1.11–3.48) and clinical pregnancy rates (odds ratio 2.28, 95% CI 1.34–3.86).
Compared with untreated or persistent disease, cured endometritis had higher ongoing pregnancy or live birth (odds ratio 5.33, 95% CI 2.41–11.79) and clinical pregnancy (odds ratio 3.64, 95% CI 1.89–7.04) rates.
Across 609 patients in three studies, women with cured endometritis and women without it showed no significant difference in ongoing pregnancy or live birth, clinical pregnancy or miscarriage rates.
In two studies, severe endometritis had lower ongoing pregnancy or live birth (odds ratio 0.43, 95% CI 0.25–0.74) and clinical pregnancy (odds ratio 0.40, 95% CI 0.24–0.68) than mild endometritis.
Two studies found no significant difference in any outcome between mild endometritis and no endometritis. The pooled comparison of women with and without endometritis found no significant difference in miscarriage rate.

Interpretation

The review pooled ten observational studies: four prospective, five retrospective and one cross-sectional. The findings describe associations in women having IVF. The comparison of women with and without endometritis showed high heterogeneity between studies. The authors rate the evidence on severity as low quality, and it rests on two studies. They graded severity by plasma cell counts in a biopsy of the womb lining. Some studies enrolled women up to age 44 without adjusting for embryo chromosome changes. The authors write that the number of patients and events is insufficient for a definitive conclusion on miscarriage. Women with recurrent miscarriage were excluded.

RRM Context

Chronic endometritis is an inflammation of the womb lining that antibiotics can resolve. The authors tie it to an abnormal microbiome in the lining. They cite reports of prevalence often above 30% in infertility, recurrent pregnancy loss and repeated IVF failure. Restorative reproductive medicine puts evaluation before treatment. A diagnosable lining condition belongs among the causes that evaluation looks for. IVF proceeds without establishing why conception fails.

Our editorial summary of this paper, not the article's abstract.

Abstract

This systematic review and meta-analysis aims to evaluate the impact of chronic endometritis (CE) and its therapy on in vitro fertilization (IVF) outcome. Additionally, we aim to investigate whether various degrees of CE severity may exert a different effect on IVF outcome. Ongoing-pregnancy rate/live-birth-rate (OPR/LBR), clinical-pregnancy rate (CPR), and miscarriage rate (MR) were calculated. A total number of 4145 patients (from ten studies) were included. Women with CE had lower OPR/LBR (OR 1.97, p = 0.02) and CPR (OR 2.28, p = 0.002) compared to those without CE. CE cure increased OPR/LBR (OR 5.33, p < 0.0001) and CPR (OR 3.64, p = 0.0001). IVF outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR and MR: p = ns). Women with severe CE had lower OPR/LBR (OR 0.43, p = 0.003) and CPR (OR 0.40, p = 0.0007) compared to those mild CE. Mild CE showed no influence on the IVF outcome as compared to women without CE (OPR/LBR, CPR and MR: p = ns). Based on this data analysis, CE significantly reduces OPR/LBR and CPR in women undergoing IVF. Importantly, CE resolution after antibiotic therapy may improves IVF outcome, leading to similar OPR/LBR and CPR as compared to unaffected patients. The negative effects of CE on IVF outcome may be restricted to severe disease, whereas mild CE may have no influence on IVF success.

Read the guide

Chronic Endometritis: The Missed Diagnosis Behind Recurrent Miscarriage and Failed Implantation

Topics

Infections and the Reproductive Microbiome › Chronic Endometritis › Endometritis and Reproductive Outcomes · Assisted Reproduction › Outcomes and Effectiveness › Outcomes by Diagnosis · General Gynecology › Infections › Pelvic Inflammatory Disease

Dominique De Ziegler, Rossana Cicinelli, Vito Chiantera, Giovanni Buzzaccarini, Ettore Cicinelli, Antonio Simone Laganà, Marco Marinaccio, Carla Mariaflavia Santarsiero, Amerigo Vitagliano

D Ziegler, R Cicinelli, V Chiantera, G Buzzaccarini, E Cicinelli, A Laganà, M Marinaccio, C Santarsiero, A Vitagliano

PMID 36140651 36140651 DOI 10.3390/diagnostics12092250 10.3390/diagnostics12092250 Vitagliano et al. 2022, Vitagliano 2022