Uterine wound healing after caesarean section: A systematic review

Abstract

The rate of caesarean section (CS) is increasing worldwide. Defects in uterine healing have a major gynaecological and obstetric impact (uterine rupture, caesarean scar defect, caesarean scar pregnancy, placenta accreta spectrum). The complex process of cellular uterine healing after surgery, and specifically after CS, remains poorly understood in contrast to skin wound healing. This literature review on uterine wound healing was mainly based on histological observations, particularly after CS. The primary objective of the review was to examine the effects of CS on uterine tissue at the cellular level, based on histological observations. The secondary objectives were to describe the biomechanical characteristics and the therapies used to improve scar tissue after CS. This review was performed using PRISMA criteria, and PubMed was the data source. The study included all clinical and animal model studies with CS and histological analysis of the uterine scar area (macroscopic, microscopic, immunohistochemical and biomechanical). Twenty studies were included: 10 human and 10 animal models. In total, 533 female humans and 511 female animals were included. Review articles, meeting abstracts, case series, case reports, and abstracts without access to full-text were excluded. The search was limited to studies published in English. No correlation was found between cutaneous and uterine healing. The histology of uterine scars is characterized by disorganized smooth muscle, fibrosis with collagen fibres and fewer endometrial glands. As for skin healing, the initial inflammation phase and mediation of some growth factors (particularly connective tissue growth factor, vascular endothelial growth factor, platelet-derived growth factor, tumour necrosis factor α and tumour necrosis factor β) seem to be essential. This initial phase has an impact on the subsequent phases of proliferation and maturation. Collagen appears to play a key role in the initial granulation tissue to replace the loss of substance. Subsequent maturation of the scar tissue is essential, with a decrease in collagen and smooth muscle restoration. Unlike skin, the glandular structure of uterine tissue could be responsible for the relatively high incidence of healing defects. Uterine scar defects after CS are characterized by an atrophic disorganized endometrium with atypia and a fibroblastic highly collagenic stromal reaction. Concerning immunohistochemistry, one study found a decrease in tumour necrosis factor β in uterine scar defects. No correlation was found between biomechanical characteristics (particularly uterine strength) and the presence of a collagenous scar after CS. Based on the findings of this review, an illustration of current understanding about uterine healing is provided. There is currently no validated prevention of caesarean scar defects. Various treatments to improve uterine healing after CS have been tested, and appeared to have good efficacy in animal studies: alpha lipoic acid, growth factors, collagen scaffolds and mesenchymal stem cells. Further prospective studies are needed.

Keywords: Caesarean scar defect; Caesarean section; Fibrosis; Healing defect; Uterine healing.