COMMENTARY

Chronic Endometritis: A Factor in IVF Failure?

Peter Kovacs, MD, PhD

Disclosures

October 24, 2018

Effect of Chronic Endometritis on IVF Success

In vitro fertilization (IVF) success rates are far from perfect.[1] Our knowledge about the process of implantation is incomplete. For example, which factors aid implantation, and which impede success? Chronic endometritis has been identified as one of the pathologies associated with repetitive implantation failure. A recent systematic review evaluated the impact of chronic endometritis on IVF success.[2]

Meta-analysis Findings

The results of five studies (a total of 796 patients) evaluating the association between chronic endometritis and repetitive implantation failure (two or more failed IVF cycles) were included in this meta-analysis. In all studies, follicular phase endometrial biopsies were obtained and hematoxylin-eosin staining showing plasma cells or immunohistochemistry were used to confirm chronic endometritis. Doxycycline, ciprofloxacin, and metronidazole were offered to treat the condition. Comparisons were made, with the following findings:

  • No impact of chronic endometritis on clinical outcome was shown when treated chronic endometritis (no test of cure was performed, however) vs untreated chronic endometritis were compared based on the result of a single study

  • Clinical outcomes significantly improved after cured (test of cure performed) chronic endometritis when compared with persistent chronic endometritis. The live-birth-rate odds ratio was 6.81 (95% confidence interval, 2.08-22.24)

  • The clinical outcomes were similar after cured chronic endometritis compared with nonchronic endometritis cases. The live birth rate, clinical pregnancy rate, and implantation rate were not significantly different

The review authors concluded that treatment of chronic endometritis results in superior clinical outcomes after IVF when compared with persistent disease. Cure, however, should be confirmed by a repeat biopsy. These findings are based on data obtained from retrospective and prospective observational studies but not randomized controlled trials; therefore, the authors call for future clinical trials on this topic.

Viewpoint

Successful implantation requires a healthy, euploid embryo, a receptive endometrium, and proper synchronization. Among assisted reproductive technologies, IVF offers the highest chance to achieve a pregnancy. Yet IVF success rates are far from perfect.[1] Even a single failed cycle can be stressful, but repetitive implantation failure is frustrating for both patients and providers. Diagnosing and treating a potentially curable condition such as endometritis can turn failure into success.

Chronic endometritis is a pathological condition caused by microbial infection. Most infections are ascending, but can also spread via the bloodstream or the lymphatic system. The uterine cavity is not sterile. Its microbial composition is similar to that of the lower genital tract but it is less dominated by lactobacilli (30% vs 99% found in the vagina/ cervix).

Bacteria (Escherichia coli, Enterococcus, Mycoplasma, Klebsiella, Pseudomonas, Gardnerella, etc) as well as yeast may be responsible for chronic endometritis. They can overgrow when the otherwise dominant lactobacilli are reduced.

Chronic endometritis may alter the inflammatory process responsible for implantation, may induce abnormal endometrial histologic changes, and could result in alterations in the gene expression profile. Endometrial buildup is typically reduced, leading to suboptimal endometrial thickness.[3]

Figure. Histology of chronic endometritis with hematoxylin and eosin stain showing characteristic plasma cells and scattered neutrophils. Image from Wikipedia.

It seems, based on this and other systematic reviews, that oral antibiotics (doxycycline, clindamycin, ciprofloxacin, metronidazole, etc) are effective in treating chronic endometritis. A repeat biopsy should confirm cure, because pregnancy outcomes only improve in cured cases.

The biopsy itself can also have a positive impact on implantation if done in the cycle preceding the transfer.[4] Therefore, if a biopsy is needed as part of the workup, it should be planned right before the transfer cycle to benefit from its potential positive effect on implantation, even if the histology turns out to be negative.

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