Background Little is known about the pathophysiology underlying the increased risk for impaired reproductive outcomes in women with a septate uterus. Objectives We explored the available evidence on the pathophysiology of the septate uterus in an attempt to find a biological basis for these effects. Search strategy We performed a systematic literature search in OVID MEDLINE and OVID EMBASE from inception to January 2018. Selection criteria We selected studies that investigated the pathophysiology of the septate uterus. Case reports or reviews without original data were excluded. Data collection and analysis Two reviewers independently evaluated potentially eligible papers. Main results Thirty‐eight studies were included for analysis. The overall findings were that the intrauterine septum consists of endometrium and myometrium similar to the uterine wall. All five imaging studies that evaluated vascularity found that most of the intrauterine septa were vascularised. Histological studies found that the intrauterine septum consisted of myometrium and was covered by endometrium (n = 9). The endometrium covering the septum showed differences in histological composition in four studies and in gene expression in three studies compared with the normal uterine wall. Conclusions We found no clear biological basis for the impaired reproductive outcomes in women with a septate uterus. Either the gross anatomy of the septum itself or differences in histology or gene expression of the septum could account for the increased risk of reproductive waste observed after implantation in the septum. Tweetable abstract In women with a septate uterus differences in histology or gene expression could account for impaired reproductive outcome.
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