CSP is a rare ectopic pregnancy that occurs at the site of a lower uterine segment scar leftover from an earlier cesarean delivery. With the progress of diagnosis, there has been an increase in the incidence of CSP globally in recent years. The worldwide incidence of recurrent CSP reported in the literature is about 14.3%15.6%[18,19]. The cause of recurrent CSP is likely to be multifactorial. Risk factors that have been suggested for the occurrence of CSP include cesarean delivery history, thin lower uterine segment, gestational sac bulging into the uterovesical fold, and early termination (56 days) of the first cesarean scar pregnancy . However, only a few studies reported the incidence and risk factors of recurrent CSP, and most of them include only a small sample. The present study included 1000 CSP patients who were followed up with for 66±19.54 months, and the risk factors of recurrent CSP were evaluated using multivariate statistical analysis. The incidence rate of recurrent CSP is 8.6%, and the risk factors of recurrent CSP were history of ectopic pregnancy (OR=26.565) and prior abortions (OR=1.480), and the incidence of RCSP in patients >35-years-old was lower than that in patients <35-years-old (6.4% vs. 9.8%, P=0.031). The current study investigated risk factors for recurrent CSP and demonstrated several risk factors.
Previous studies suggested that the incidence of recurrent CSP is not related to patient age[6,20-22]. Conversely, the current study showed that the incidence of recurrent CSP in patients >35-years-old was significantly lower than that in patients <35-years-old (P=0.031, OR=0.437) at only 6.4%. This finding may be related to the idea that the fertility ability and desire of patients >35years-old are declined compared to their younger counterparts.
This research showed that abortion was an independent risk factor for recurrent CSP. The incidence of recurrent CSP was positively correlated with the number of previous induced abortions (P=0.013, OR=1.48). The majority of the studies also speculated that the incidence of CSP is related to inflammation and injury. Jauniaux et al.  reported that CSP might be related to unsafe abortion. Prada et al. suggested that the occurrence of CSP is clearly related to a history of uterine surgery and the abnormal implantation of embryos. Lumbiganon et al.  found that 35% of the abortion tissues contained uterine myometrium, and thus, it was hypothesized that most abortion curettage would result in the loss of endometrium. With an increasing number of abortions, the resultant larger area of endometrial and myometrial disruption or scarring could constitute a predisposing factor in abnormal pregnancy implantation. Trophoblast adherence or invasion is enhanced when scant decidualization of the lower uterine segment is impaired by a previous myometrial disruption. The underlying mechanism explicates that scar implantation is the invasion of the myometrium through a microscopic tract that develops from the trauma of early uterine surgery, such as curettage, cesarean section, and myomectomy. Moreover, an unsuitable intrauterine environment for embryo implantation makes the gestational sac more likely to implant at the scar site again.
The present study showed that a woman with a previous ectopic pregnancy was likely to have recurrent CSP (P<0.001, OR=26.565). Currently, none of the studies have reported the correlation between ectopic pregnancy and CSP. Qian et al.  reported the incidence of RCSP in patients with previous ectopic pregnancy was higher than that in patients without previous ectopic pregnancy (4.76% vs. 2.38%), albeit not significantly. The main risk factor for ectopic pregnancy is a pelvic infectious disease, which is primarily caused by ascending infections. We speculated that patients with a previous history of an ectopic pregnancy might often have endometritis, which could lead to an unfavorable uterine environment for the implantation of embryos.
The present study found that the incidence of RCSP in CSP patients with more than two cesarean section times was higher than that in patients with only one cesarean section history (13.26% versus 6.92%, P=0.073), albeit not significantly (P=0.073). Qian et al. reported that a woman with a thin lower uterine segment putatively showed RCSP. The direct cause of CSP is the existence of uterine diverticulum in the cesarean section incision, which is the local defect of the uterine wall incision or poor scar healing after cesarean section. These findings support the following hypothesis: Endometrial and myometrial disruption or scarring could be predisposing factors in abnormal pregnancy implantation. Trophoblast adherence or invasion is enhanced when scant decidualization of the lower uterine segment was impaired by a previous myometrial disruption. Typically, the uterine diverticulum caused by multiple cesarean sections was large.
Because of the limited number of reports with a large number of cases, there are no guidelines for the management of CSP or RCSP. Treatments vary from expectant management, medical management, local treatment, and surgical approach. In any event, early treatment will provide the best results, and most are combined treatments . The present study revealed that there was no statistical difference in the incidence of recurrent CSP among different surgical groups. However, Nagi et al.  reported that the management of CSP is correlated with the recurrence rate of CSP. Also, laparotomy and the repair of a uterine defect might be successful in preventing recurrent CSP. However, the patient experienced recurrence even after surgical reconstruction of the cesarean scar, suggesting that no treatment can guarantee 100% safety of a subsequent pregnancy. Surgical treatment and uterine repair could be complicated by poor scar healing and postoperative adhesions, which might affect the patient's fertility. Maheux-Lacroix et al. analyzed a large number of studies and found that scar excision and repair were not helpful in reducing recurrent CSP occurrence.
The current study did not reveal any association between recurrent CSP and the duration of amenorrhea, the interval between CS and CSP, preoperative and postoperative hCG levels, the maximum diameter of the CSP gestational sac, the thickness of the lower uterine segment revealed by ultrasonography, gravidity history, parity history, vaginal bleeding, lower abdominal pain, number of cesarean sections, CSP classification, blood flow signals of CSP lesions, ultrasonic heartbeat, treatment technique used for the first-time CSP, or amount of bleeding. Since this is a retrospective study, some factors have not been included, and the follow-up time is relatively limited. A prolonged follow-up duration would detect additional risk factors and the correlation could be clarified.
Although recurrent CSP is rare, maintaining a high index of clinical suspicion is essential. The harm of recurrence is substantial, including uncontrolled hemorrhage and uterine rupture. Recurrent CSP does not have specific symptoms and could easily be diagnosed incorrectly. Appropriate diagnostic methods, optimal treatment(s), and possible risk factors of recurrent CSP are not well-known and have not been optimized. A previous history of ectopic pregnancy and abortion is suggested as independent risk factors for recurrent CSP. The current findings regarding these and the other potential risk factors explored might aid in the prevention and early diagnosis of recurrent CSP and could be used to counsel patients at risk of recurrent CSP. Future high-quality, multicenter, large sample, randomized controlled trials are required to substantiate the current findings.