CLINICAL ARTICLE Effect of cesarean delivery on the endometrium Jara Ben-Nagi a, ⁎, Amy Walker b , Davor Jurkovic a , Joseph Yazbek a , John D. Aplin b a Early Pregnancy and Gynaecology Assessment Unit, King's College Hospital, London, UK b Maternal and Fetal Health Research Group, University of Manchester, St Mary's Hospital, Manchester, UK abstract article info Article history: Received 16 December 2008 Received in revised form 27 January 2009 Accepted 20 February 2009 Keywords: Cesarean scar Endometrium Implantation factors Objective: To compare endometrial tissue samples from cesarean scar (CS) sites and from the posterior uterine wall to better understand the pathophysiology of implantation into a CS. Methods: Endometrial samples were taken from both a CS site and the posterior wall in premenopausal women with CSs, and from the posterior wall in premenopausal women who had spontaneous vaginal deliveries (SVDs) only. Results: In the secretory phase, there were significantly fewer leukocytes at CS sites than in the endometrium of women who had SVDs only (P b 0.05). Significant differences in leukocytic infiltration and cell proliferation between the proliferative and secretory phases were only found in women who had SVDs only (P b 0.05). Conclusion: Leukocyte recruitment to the endometrium during the secretory phase may be affected by the presence of a CS. © 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction Implantation into a deficient uterine cesarean scar (CS) has increased in frequency and is associated with a high risk of pregnancy loss and serious complications [1]. The placenta invades the myome- trium in most cases of scar implantation, resulting in placenta accreta or percreta [1,2]. Removing such a placenta surgically typically leads to severe hemorrhage, and hysterectomy is often necessary to achieve hemostasis. Implantation within the normal endometrium is a precisely timed process leading to placentation, which allows for oxygen and nutrient transfer between fetal and maternal circulations. The reasons for abnormal placentation are poorly understood, and so is the patho- physiology of implantation into a previous CS. In particular, in women with a deficient CS, it is not clear whether implantation is more probable in the CS than at any other place in the endometrium. An aberrant regulation of early developmental events may result in insufficient or excessive invasion of maternal tissues, compromising both maternal and fetal health. Factors responsible for regulating the extent of invasion are poorly understood, however. It has been postulated that abnormalities within the uterine luminal epithelium or in the expression of mucin 1 (MUC1) may play a part in abnormal implantation [3]. Decidualization of the uterine stroma begins in the mid-secretory phase and is sustained if a pregnancy occurs. Immune cells, including macrophages and uterine natural killer cells, colonize the decidua and have been implicated in the control of trophoblast invasion. Moreover, extravillous trophoblasts target and remodel spiral arteries to increase blood flow, and since the normal uterine vascular bed has specific receptivity for these invading cells, alterations in vascular properties are likely to be important in pregnancy pathology. Various hypotheses have been proposed to explain why the embryo can implant within a cesarean scar. Some explanations are that it enters the myometrium through a microscopic opening in the scar, or that the decidua may not completely cover the scar site, or that there is a complete absence of decidua basalis over the scar [4–6]. The aim of this study was 3-fold: (1) to characterize the CS endometrium using histologic, histochemical, and immunohistochemical methods; (2) by assessing epithelial MUC1 expression, to evaluate the hypothesis that luminal epithelial cells have less antiadhesive activity at scar sites than in the normal endometrium; and (3) to assess stromal composition using markers for leukocyte infiltration (CD45), vascularization (CD34), and cell proliferation (Ki67). 2. Materials and methods We recruited women undergoing elective gynecologic procedures during which endometrial samples were taken. The inclusion criteria were age between 18 and 45 years and a history of spontaneous vaginal delivery (SVD) and/or cesarean delivery. Exclusion criteria were the use of any form of hormonal contraception or hormonal treatment, or the evidence of endometrial polyps, submucous fibroids, or any other endometrial abnormality on ultrasound. The study was approved by the Ethics Committee of King's College Hospital, London, UK. Under continuous abdominal ultrasound guidance, Hegar dilators up to size 7 were introduced through the cervical canal to the internal os, followed by a 7.5-mm Sims uterine curette (Downs Surgical, Sheffield, UK). Cesarean scars were identified from the internal os International Journal of Gynecology and Obstetrics 106 (2009) 30–34 ⁎ Corresponding author. Early Pregnancy and Gynaecology Assessment Unit, King's College Hospital, Denmark Hill, London SE5 8RX, UK. E-mail address: jbennagi@gmail.com (J. Ben-Nagi). 0020-7292/$ – see front matter © 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2009.02.019 Contents lists available at ScienceDirect International Journal of Gynecology and Obstetrics journal homepage: www.elsevier.com/locate/ijgo