Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy

Ettore Cicinelli; Maria Matteo; Raffaele Tinelli; Achiropita Lepera; Raffaello Alfonso; Ugo Indraccolo; Sonia Marrocchella; Pantaleo Greco; Leonardo Resta

doi:10.1093/humrep/deu292

Infections and the Reproductive Microbiome Chronic Endometritis

Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy

Cicinelli E, Matteo M, Tinelli R, Lepera A, Alfonso R, Indraccolo U, Marrocchella S, Greco P, Resta L

Published February 2015 Human reproduction (Oxford, England), 30(2), 323-30

DOI 10.1093/humrep/deu292 PMID 25385744

RRM Academy Synopsis

Chronic endometritis in 66.0% of women with repeated implantation failure

A retrospective study of 106 women with repeated unexplained implantation failure found that 66.0% had chronic endometritis, a long-lasting inflammation of the uterine lining. After antibiotics, women whose condition cleared had a significantly higher live birth rate at the next IVF attempt. Live birth followed in about 61 of 100 attempts when it cleared and about 13 when it persisted.

Key Findings

Of 106 women, 70 (66.0%) had chronic endometritis diagnosed at hysteroscopy. Histology confirmed it in 61 (57.5%) and cultures in 48 (45.0%).
Cultures most often grew common bacteria and mycoplasma, which the authors link with chronic endometritis.
Among the 61 women with both hysteroscopic and histologic findings, chronic endometritis resolved after antibiotics in 46 (75.4%, Group 1). Signs remained in 15 (24.6%, Group 2).
The next IVF attempt gave a clinical pregnancy rate of 65.2% in Group 1 and 33.0% in Group 2 (P = 0.039).
Live birth rates were 60.8% in Group 1 and 13.3% in Group 2 (P = 0.02).

Interpretation

This synopsis rests on the published abstract alone. The abstract describes a retrospective review of cases from January 2009 through June 2012, in which the two groups were formed by response to treatment, without randomization. The authors list possible biases related to retrospective studies, preferential referral of patients with chronic endometritis and a limited number of cases as limitations. They state that a prospective randomized trial is needed to confirm the findings. The abstract also reports a further IVF attempt within 6 months after treatment and compares only the two groups that received antibiotics.

RRM Context

Repeated implantation failure is often labeled unexplained. Among these women, about two thirds had chronic endometritis found at hysteroscopy. RRM holds that unexplained infertility is undiagnosed, and the uterine tests named the problem. Antibiotics treat the condition itself, while IVF goes ahead without learning why implantation fails.

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

Abstract

Study Question

What is the prevalence of chronic endometritis (CE) in women with repeated unexplained implantation failure (RIF) at IVF, and how does antibiotic treatment affect the reproductive outcome?

Summary Answer

Chronic endometritis, associated with infection with common bacteria or mycoplasma, is common in women complaining of RIF and antibiotic treatment significantly improves the reproductive outcome at a subsequent IVF cycle.

What Is Known Already

We have reported that CE is a frequent finding in women with repeated pregnancy loss and a significantly higher rate of successful pregnancies was achieved after adequate antibiotic treatment. Moreover, CE was identified in 30.3% of patients with repeated implantation failure at IVF and women diagnosed with CE had lower implantation rates (11.5%) after IVF cycles. In contrast, other authors reported that the clinical implication of CE should be considered minimal and that the reproductive outcome at IVF/ICSI cycles was not negatively affected by CE.

Study Design, Size, Duration

A retrospective study was performed from January 2009 through June 2012 on 106 women with unexplained infertility and a history of RIF.

Participants/Materials, Setting, Methods

All patients underwent hysteroscopy and endometrial sampling for histology and microbiological investigations. Women diagnosed with CE underwent antibiotic treatment and the effect of treatment was confirmed by hysteroscopy with biopsy. Within 6 months after treatment all women had a further IVF attempt. The IVF outcomes were compared in women without signs of CE (Group 1) and persistent CE (Group 2) after antibiotic treatment. Clinical pregnancy rate (PR), and live birth rate (LBR) were compared at post-treatment IVF attempt.

Main Results and the Role of Chance

Seventy (66.0%) women were diagnosed with CE at hysteroscopy. In 61 (57.5%) CE was confirmed by histology and 48 (45.0%) by cultures. Common bacteria and mycoplasma were the most prevalent agents. In 46 (75.4%) out of 61 women, with diagnosis of CE at hysteroscopy and histology, examinations were normal after appropriate antibiotic treatment control (Group 1) while in 15 (24.6%) cases signs of CE were still present (Group 2). At IVF attempt after treatment, a significantly higher PR and LBR was reported in women from Group 1 compared with women from Group 2 (65.2 versus 33.0% P = 0.039; 60.8 versus 13.3%, P = 0.02, respectively).

Limitations, Reasons for Caution

Possible biases related to retrospective studies and to preferential referral of patients with CE, and limited number of cases.

Wider Implications of the Findings

A prospective randomized clinical trial is needed to confirm our findings but in women with RIF a hysteroscopic evaluation of the uterine cavity to exclude CE should be considered and appropriate antibiotic treatment should be given before submitting the patient to a further IVF attempt.

Read the guide

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

Chronic endometritis is a persistent, low-grade inflammation of the uterine lining diagnosed by CD138 endometrial biopsy. It is frequently missed in recurrent miscarriage and implantation failure workups, and it is treatable with antibiotic therapy.

18 min read

Topics

Infections and the Reproductive Microbiome › Chronic Endometritis › Endometritis and Reproductive Outcomes · Infertility › Uterine Factor › Endometrial Receptivity · Diagnostics › Microbiome and Infection Testing › Culture and Infection Testing

Ettore Cicinelli, Maria Matteo, Raffaele Tinelli, Achiropita Lepera, Raffaello Alfonso, Ugo Indraccolo, Sonia Marrocchella, Pantaleo Greco, Leonardo Resta

E Cicinelli, M Matteo, R Tinelli, A Lepera, R Alfonso, U Indraccolo, S Marrocchella, P Greco, L Resta

PMID 25385744 25385744 DOI 10.1093/humrep/deu292 10.1093/humrep/deu292 Cicinelli et al. 2015, Cicinelli 2015

Keywords

IVF/ICSI outcome, antibiotic treatment, chronic endometritis, hysteroscopy, repeated implantation failure

Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy

Chronic endometritis in 66.0% of women with repeated implantation failure

Key Findings

Interpretation

RRM Context

Abstract

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Topics

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