Lessons learned from bovine subclinical endometritis: a systematic review exploring its potential relevance to chronic endometritis in women

Abstract

Chronic endometritis (CE) in humans is asymptomatic inflammation of the endometrium, associated with poor reproductive outcomes. Similarly, asymptomatic endometrial inflammation in cows, termed subclinical endometritis (SCE), is associated with adverse reproductive outcomes. While the pathophysiology and treatment options for CE in humans remain poorly defined, the well-known financial implications of SCE in dairy cows have attracted intensive research. We performed a systematic review to determine potential areas of interest in human CE research, by analysing emergent themes that arose in studies of SCE in cows. A literature search for studies of subclinical endometritis in cows published between 1990 and November 2021 was performed across Embase, Medline, Scopus and CINAHL. Studies of symptomatic or clinical endometritis were excluded. A thematic analysis across two broad themes was explored: i) diagnostic methods of SCE and ii) pathophysiology of SCE. In total, 51 bovine studies were included. Twelve studies reported on diagnostic methodology. The primary emergent theme was the use of cytology for the diagnosis of SCE. Cytological analysis has a lower sensitivity than histopathology but is less invasive and more specific than alternative techniques such as ultrasound, vaginoscopy or metabolic markers. The subthemes related to pathophysiology were identified as the type of endometritis, metabolic stress, artificial insemination, infective causes and altered cellular pathways. Despite the lack of symptoms, cellular pathways of inflammation including NF-κB, MAPK and inflammasomes were found to be activated. The key themes related to the diagnosis and pathophysiology of SCE in cows identified in this systematic review highlight potential areas for future research into human CE. Lay summary Long-term or chronic endometritis (CE) is a condition associated with inflammation in the womb lining. People with CE commonly experience recurrent miscarriages and subfertility. The cause of CE is poorly understood, and as such there are no specific treatments. Comparatively, a form of CE (i.e. subclinical endometritis (SCE)) has been extensively researched in dairy cows due to its financial impact. A systematic review of cow studies was carried out and key themes around cause and diagnosis of SCE in cows were identified and analysed. In total, 44 studies were included. Six main themes around the way SCE is diagnosed were found, and examining cells (i.e. cytology) was found to be more sensitive and practical than other techniques. Six themes were also found for causes of SCE, notably difficult delivery, metabolic stress and infection. This study shows potential areas for future research into human SCE and provides insight into the causes of disease within humans.