Uterine Inflammatory Characteristics

Background As the rate of caesarean section continues to increase, concern regarding the association between delivery by caesarean section and long-term maternal morbidity has been growing . In the past decade, several articles have described a defect that can be seen on ultrasound at the site of the caesarean delivery scar, known as a 'niche' . A 'niche' describes the presence of a hypoechoic area within the myometrium of the lower uterine segment, reflecting a discontinuation of the myometrium at the site of a previous cesarean delivery. An incompletely healed scar is a long-term complication of cesarean delivery and is associated with symptoms such as postmenstrual spotting, dysmenorrhoea, chronic pelvic pain dyspareunia and subfertility. Furthermore, it can increase rates of complications during gynaecological procedures and it is associated with higher complication rate in subsequent pregnancy including: risk of rupture and morbidly adherent placenta.

Lately, a surgical resection of the abnormal myometrial area has been proposed mainly for symptomatic women, or for women that are planning future pregnancy. Different techniques have been used including hysteroscopy, laparoscopy and vaginal repair. Consideration of the surgical approach is usually determined by the patient's plans for fertility and by niche thickness. For women who do not desire pregnancy and whose niche thickness is >3 mm, a hysteroscopic approach is considered. Patients who desire future fertility, especially those with <3 mm of myometrium at the niche site, is usually recommended laparoscopic resection.

Data regarding fertility following niche repair is limited. It has been reported that a niche can reduce the chances of embryo implantation and may lead to spontaneous miscarriages if the implantation is close to or in the niche. One possible theory refers to inflammatory process at the area of the niche that harms the endometrial environment. Additional theories address the mechanical changes influencing the myometrium and the discontinuation of the endometrium at the site of the niche. Gurol Urganci et al. reported in a meta-analysis including 16 studies, that caesarean delivery reduces the probability of subsequent pregnancy by 10% [relative risk (RR) 0.91; 95% 0.87-0.95] on average, compared with a previous vaginal delivery, however, none of the studies included in the meta-analysis evaluated the relation between subsequent fertility and the presence of a niche. So far there is no definite proof for niche as a cause of infertility. Should this be supported by randomized controlled trials, it would be grounds for providing treatment that will expectedly lead to beneficial effects on reproductive outcomes. This yet needs to be proven in.

Due to the aforementioned, the aim of our study is to compare the inflammatory characteristics of women with cesarean uterine scar to those without.

Material and Methods This is a prospective study including all women visiting hysteroscopy ambulatory clinics for diagnostic hysteroscopy . All women meeting inclusion criteria will sign informed consent prior to the hysteroscopy after given explanation by one of the research team. During hysteroscopy 5 cc of the flushed water, that usually is drilled into a collecting bin that is thrown away, will be collect threw a small outlet port using a syringe connected to the outlet port of the hysteroscope. Women with normal diagnostic hysteroscopy will be included in the study. Those with low segment cesarean deliver scar will comprise the study arm and will be compared to women with no uterine scar (controls). Samples will be send to the IVF laboratory for analyzing inflammatory characteristics. Date regarding demographics, obstetrical and gynecological history will be collected from women's medical records. Primary outcome is defined as the level of inflammatory cytokines as a composite outcome

Inclusion criteria

• Fertility age 18-45
• No abnormal finding during hysteroscopy

Exclusion criteria

• Women with other uterine scars (following myomectomy, T/J scar)