Impact of obstetric and surgical factors on isthmocele development: insights from a prospective cohort study.

This study demonstrated that a retroverted uterus is an independent risk factor for isthmocele development. The results highlight that surgical technique and inter-pregnancy interval are modifiable factors for reducing isthmocele formation after the first cesarean section.

A total of 262 women who fulfilled the inclusion criteria were recruited in the study. Among them, 50 women (19.1%) were diagnosed with isthmocele based on transvaginal ultrasound performed six months postpartum. The mean age of the participants was 25.91 ± 5.13 years, ranging from 15 to 46 years, with no significant difference between the isthmocele and non-isthmocele groups. ( P  = 0.79) The mean gestational age at delivery was significantly higher in the isthmocele group (39.24 ± 0.89 weeks vs. 38.53 ± 1.65 weeks, p  = 0.004). Parity was lower in women with isthmocele (1.76 ± 0.84 vs. 2.04 ± 1.05, p  = 0.08). Other demographic and clinical characteristics are summarized in Table  1 . Table 1 Baseline characteristics of participants Characteristic Total ( n  = 262) Isthmocele Group ( n  = 50) Non-Isthmocele Group ( n  = 212) P value Age (years), mean ± SD 25.91 ± 5.13 25.74 ± 4.47 25.95 ± 5.27 0.79 Gestational age (weeks), mean ± SD 38.66 ± 1.56 39.24 ± 0.89 38.53 ± 1.65 0.004 Parity, mean ± SD 1.99 ± 1.02 1.76 ± 0.84 2.04 ± 1.05 0.08 BMI, mean ± SD 27.97 ± 4.57 27.78 ± 4.15 28.01 ± 4.67 0.75 Hypertension, n (%) 125 (47.7) 17 (34) 108 (50.9) 0.03 Gestational diabetes, n (%) 40 (15.3) 7 (14) 33 (15.6) 0.78 Smoking, n (%) 26 (10) 1 (2) 25 (11.8) 0.04 Data are presented as mean ± standard deviation (SD) or number (percentage).  P values are derived from independent t tests or chi-square tests Baseline characteristics of participants Data are presented as mean ± standard deviation (SD) or number (percentage).  P values are derived from independent t tests or chi-square tests The prevalence of hypertension was significantly lower in the isthmocele group (34% vs. 50.9%, p  = 0.03). The prevalence of diabetes was similar between groups (14% vs. 15.6%, p  = 0.75). Only 2% of women with isthmocele were smokers compared to 11.8% in the non-isthmocele group ( p  = 0.04). As shown in Table  2 , women with isthmocele had a higher prevalence of prior curettage (22% vs. 12.3%, p  = 0.07). Emergency cesarean rates were similar between groups (90% isthmocele vs. 82.1% non-isthmocele, p  = 0.17). No significant differences in cervical dilation (2.62 ± 1.52 cm vs. 3.08 ± 1.91 cm, p  = 0.11) or effacement (3.38 ± 1.02 vs. 3.11 ± 1.13, p  = 0.12) were observed. Women with isthmocele had a longer duration of labor (5.16 ± 0.62 h vs. 4.26 ± 1.36 h, p  < 0.001). The time between deliveries was significantly shorter in the isthmocele group (4.58 ± 1.32 years vs. 5.22 ± 0.93 years, p  = 0.01). The incidence of endometritis was markedly higher in the isthmocele group (10% vs. 2.4%, p  < 0.001). The lock repair technique was significantly higher in the isthmocele group compared to the non-isthmocele group (20% vs. 7.1%, p  = 0.005). Additionally, uterine retroversion showed a significantly higher prevalence in women with isthmocele (28% vs. 11.3%) ( p  = 0.003). The findings indicated no significant association between chorioamnionitis or labor induction with oxytocin and the presence of an isthmocele. (Table  2 ). Table 2 Obstetrics and surgical factors associated with isthmocele Factor Total Isthmocele (n = 50) No Isthmocele (n = 212) P-value Emergency cesarean, n (%) 219 (83.6%) 45 (90) 174 (82.1) 0.17 History of curettage, n (%) 37 (14.1) 11 (22%) 26 (12.3%) 0.07 Inter-delivery interval (year), mean ± SD 4.69 ± 1.28 4.58 ± 1.32 5.22 ± 0.93 0.01 Labor duration (hours), mean ± SD 4.43 ± 1.30 5.16 ± 0.62 4.26 ± 1.36  < 0.001 Uterine position, n (%)  Anteversion 224 (85.5) 36 (72) 188 (88.7) 0.003  Retroversion 38 (14.5) 14 (28) 24 (11.3) Cervical dilation(cm), mean ± SD 2.99 ± 1.85 2.62 ± 1.52 3.08 ± 1.91 0.11 Effacement of cervix, mean ± SD 3.16 ± 1.12 3.38 ± 1.02 3.11 ± 1.13 0.12 Chorioamnionitis, n (%) 65 (24.9) 10 (20.4) 55 (25.9) 0.42 Induction with oxytocin, n (%) 230 (87.8) 40 (80) 190 (89.6) 0.06 Endometritis, n (%) 10 (3.8) 5 (10) 5 (2.4) 0.01 Lock repair technique, n (%) 25 (9.5) 10 (20) 15 (7.1) 0.005 Significant differences ( p  <  0.05 ) are highlighted in bold Obstetrics and surgical factors associated with isthmocele Significant differences ( p  <  0.05 ) are highlighted in bold As presented in Table  3 , in the univariate logistic regression analysis, longer gestational age (OR = 1.68, 95% CI 1.22, 2.35), a history of endometritis (OR = 4.60, 95% CI 1.27, 6.55), locking repair (OR = 3.28, 95% CI 1.38, 7.83), and retroverted uterus (OR = 3.05, 95% CI 1.44, 6.44) were associated with increased odds of developing isthmocele after cesarean section. Table 3 Univariate and multivariable logistic regression for isthmocele risk factor Variable Univariate OR (95% CI) P value Multivariable OR (95%CI) P value Gestational age 1.68 (1.22, 2.35) 0.002 1.71 (1.19, 2.45) 0.004 Endometritis 4.60 (1.27, 6.55) 0.02 4.43 (0.94, 8.78) 0.06 Inter-delivery interval 0.74 (0.52, 1.04) 0.08 0.65 (0.44, 0.97) 0.04 Previous uterine curettage 2.01 (0.92, 4.43) 0.08 1.03 (0.41, 2.59) 0.95 Locking uterine closure 3.28 (1.38, 7.83) 0.007 2.13 (0.80, 5.65) 0.13 Uterine position 3.05 (1.44, 6.44) 0.004 2.82 (1.25, 6.35) 0.01 BMI 0.98 (0.92, 1.06) 0.75 – – Odds ratios (OR) with 95% confidence intervals (CI) are reported Univariate and multivariable logistic regression for isthmocele risk factor Odds ratios (OR) with 95% confidence intervals (CI) are reported In the multivariable logistic regression model, which includes variables with p  < 0.1 from the univariate analysis, only gestational age (OR = 1.71, 95% CI 1.19, 2.45) and retroverted uterine position (OR = 2.82, 95% CI 1.25, 6.35) remained significantly associated with increased odds of isthmocele. Conversely, the inter-delivery interval was inversely associated with the outcome (OR = 0.65, 95% CI 0.44, 0.97), indicating that each additional year between deliveries reduced the odds of developing an isthmocele by approximately 35%. According to the data presented in Table  4 , among the 50 patients identified with isthmocele, 58% were classified as having CS scar dehiscence and 42% as having non-dehiscence. Some factors, such as gestational diabetes (17.2 vs. 9.5), smoking (3.4 vs. 0), retroverted uterus (34.5 vs. 19), and locking repair technique (27.6 vs. 9.5), were higher in the CS scar dehiscence group compared to the non-dehiscence group, but this difference was not statistically significant (Table  5 ). Table 4 Classification of isthmocele largeness ( n  = 50) in relation to morphological parameters and associated explanatory factors Variables Non-large isthmocele, N  = 38 (76%) Large isthmocele, N  = 12 (24%) P value Gestational age (weeks), mean ± SD 39.18 ± 0.73 39.42 ± 1.31 0.43 Parity, mean ± SD 1.82 ± 0.89 1.58 ± 0.67 0.41 BMI, mean ± SD 27.74 ± 4.50 27.92 ± 2.91 0.89 Hypertension, n (%) 12 (31.6) 5 (41.7) 0.52 Gestational diabetes, n (%) 7 (18.4) 0 0.17 * Smoking, n (%) 0 1 (8.3) 0.24 * History of curettage, n (%) 6 (15.8) 5 (41.7) 0.06 Inter-delivery interval (year), mean ± SD 5.29 ± 0.90 5 ± 1.09 0.52 Uterine position, n (%)  Anteversion 29 (76.3) 7 (58.3) 0.22  Retroversion 9 (23.7) 5 (41.7) Endometritis, n (%) 3 (7.9) 2 (16.7) 0.37 Locking repair technique, n (%) 8 (21.1) 2 (16.7) 0.74 Depth (mm), mean ± SD 2.74 ± 0.89 2.50 ± 0.67 0.42 Width (mm), mean ± SD 2.13 ± 0.47 2.50 ± 0.52 0.03 Residual myometrial thickness (mm), mean ± SD 3.29 ± 0.51 1.92 ± 0.28  < 0.001 * P value from Fisher's exact test, other p values for Chi-square test or independent t test Table 5 Classification of isthmocele according to Depth/RMT ratio ( n  = 50) in relation to morphological parameters and associated explanatory factors Variables Non-dehiscence, N  = 21 (42%) Dehiscence, N  = 29 (58%) P value Gestational age (weeks), mean ± SD 39.43 ± 0.81 39.10 ± 0.93 0.21 Parity, mean ± SD 2 ± 0.71 1.59 ± 0.91 0.08 BMI, mean ± SD 28.48 ± 4.97 27.28 ± 3.43 0.31 Hypertension, n (%) 8 (38.1) 9 (31) 0.60 Gestational diabetes, n (%) 2 (9.5) 5(17.2) 0.68 Smoking, n (%) 0 1 (3.4) 0.98 * History of curettage, n (%) 6 (28.6) 5 (17.2) 0.34 Inter-delivery interval (year), mean ± SD 5.38 ± 0.72 5 ± 1.18 0.31 Uterine position, n (%)  Anteversion 17 (81) 19 (65.5) 0.23  Retroversion 4 (19) 10 (34.5) Endometritis, n (%) 3 (14.3) 2 (6.9) 0.64 Locking repair technique, n (%) 2 (9.5) 8 (27.6) 0.16 Depth (mm), mean ± SD 2.05 ± 0.22 3.14 ± 0.83  < 0.001 Width (mm), mean ± SD 2.33 ± 0.66 2.24 ± 0.35 0.73 Residual myometrial thickness (mm), mean ± SD 3.48 ± 0.60 2.59 ± 0.63  < 0.001 Classification of isthmocele largeness ( n  = 50) in relation to morphological parameters and associated explanatory factors Inter-delivery interval (year), mean ± SD Residual myometrial thickness (mm), mean ± SD * P value from Fisher's exact test, other p values for Chi-square test or independent t test Classification of isthmocele according to Depth/RMT ratio ( n  = 50) in relation to morphological parameters and associated explanatory factors Inter-delivery interval (year), mean ± SD Residual myometrial thickness (mm), mean ± SD

This prospective cohort study was conducted at Arash Women’s Hospital, a tertiary referral center in Tehran, Iran, from 2021 to 2024. Women aged 14–50 years who underwent their first cesarean section at Arash Women’s Hospital during the study period were eligible for inclusion. Inclusion criteria consisted of a primary cesarean section performed at the study center, an age range of 14–50 years, and the provision of written informed consent. Women were excluded if they had a history of previous cesarean section(s), prior uterine surgery such as myomectomy, repeated uterine curettage, congenital uterine anomalies, or an age below 14 or above 50 years. This study was approved by the Institutional Review Board of Arash Women’s Hospital (Ethics ID: IR.TUMS.MEDICINE.REC.1402.408). Written informed consent was obtained from all participants before enrollment, and all procedures adhered to institutional and national ethical standards. Data were collected at the time of cesarean sections using standardized forms by trained staff based on electronic medical records and patient interviews. The demographic and clinical data included the following: age, parity, cigarette smoking, and underlying medical conditions, including diabetes or hypertension. Obstetric and intraoperative variables recorded were gestational age at delivery, indications for cesarean section (whether the procedure was elective or emergency), labor status at the time of surgery, uterine closure technique (locking or unlocking suture), position of uterus (anteverted or retroverted), the presence of chorioamnionitis, and whether labor had been induced using oxytocin. Postoperative data regarding any uterine infections, including endometritis, were recorded. The diagnosis of endometritis was established through patient interview and verification of hospital readmission records, based on standard clinical criteria requiring antibiotic treatment. Hypertension was defined as a documented diagnosis of chronic hypertension or gestational hypertension that required antihypertensive medication. Gestational diabetes mellitus (GDM) was defined using standard institutional criteria based on a 75-g oral glucose tolerance test and included both diet-controlled and medication-requiring GDM [ 19 ]. All cesarean sections were performed using a standardized technique. The uterine incision was closed in two layers using a continuous suture. The first layer (either locking or unlocking) included the endometrial layer, and inner myometrium, and the second layer involved outer myometrium and the serosal layer (unlocking suture) over the first. The suture material used for uterine closure was 1–0 Vicryl for all patients. Six months after the cesarean section, all participants underwent a transvaginal ultrasound performed by an experienced radiologist who was blinded to the clinical data. The cesarean scar site was evaluated for the presence of an isthmocele, which was defined as a hypoechoic, triangular niche located in the anterior wall of the uterus, with a minimum depth of 2 mm at the site of the CS scar. Niche characteristics, including depth, width, and residual myometrial thickness, were measured and documented. We classified isthmoceles according to the risk of dehiscence. A Depth to Residual Myometrial Thickness (D/RMT) ratio ≥ 0.785, as described by Pomorski et al., was used to define isthmocele with sonographic features of dehiscence. A ratio < 0.785 was defined as 'isthmocele without dehiscence [ 20 ]. The primary outcome of the study was the presence of an isthmocele on transvaginal ultrasound performed six months postpartum. The sample size had been estimated based on a Type I error rate of 5% and a statistical power of 80%. An expected isthmocele prevalence of 20%, based on Antila-Langsjo et al. [ 21 ]. This calculation indicated that a minimum of 260 participants were required. Participants were then recruited using a convenience sampling method. Kolmogorov–Smirnov test was used to assess the normality of continuous variables. Continuous variables are presented as mean ± standard deviation (SD), and categorical variables are reported as frequencies and percentages. Differences in continuous variables between the two groups were analyzed using the independent t test, or Mann–Whitney U test when distributions were non-normal. Categorical variables were compared using Chi-square test. Univariate logistic regression was performed to identify factors associated with isthmocele development. Variables with p  < 0.1 in the univariable analysis were included in the multivariable logistic regression model. Statistical analysis was conducted using SPSS software, version 20 (IBM Corp, Armonk, NY, USA). A two-sided p  < 0.05 was considered statistically significant.

In this prospective cohort study, we investigated the risk factors associated with isthmocele formation in 262 women following their first cesarean section. The sonographic prevalence of isthmocele was found to be 19.1%. This is consistent with the wide range (19–60%) reported in previous studies, reflecting differences in diagnostic methods and population characteristics[ 11 , 12 , 22 ]. The main findings of our multivariable analysis reveal that advanced gestational age at delivery and a retroverted uterine position are independent risk factors for isthmocele formation, while a longer inter-delivery interval shows a protective effect. Our results, which identified advanced gestational age as a significant and independent factor, are consistent with the findings reported by Fakhr et al. [ 3 ]. This is also in line with the pathophysiological hypothesis that prolonged uterine distension near term impairs the healing capacity and structural integrity of the lower uterine segment incision [ 16 ]. Carrying to term or beyond, increases myometrial thinning and tension, which can interfere with proper wound edge alignment, decrease the local blood flow, and ultimately lead to defective scar healing [ 15 ]. While the timing of delivery is often determined by obstetric indications and is not modifiable, identifying this association is vital for risk stratification and postoperative counseling [ 3 ]. A novel and important finding from our study is that a retroverted uterine position represents an independent predictor for the presence of isthmocele. Our analysis, which controlled for other variables, found that a retroverted uterus was associated with a nearly three-fold increase in odds (OR = 2.82). This finding is corroborated by other studies that have also identified a retroverted uterine position as a significant risk factor for isthmocele formation [ 16 , 23 – 26 ]. The retroverted position may anatomically place the cesarean scar in a more dependent location of the pelvis. This could expose the healing incision to different mechanical stresses, interfere with the postoperative drainage, or cause impaired blood supply, which could be harmful to the healing process [ 25 ]. While previous literature has suggested a possible link, our study provides stronger evidence through a multivariable model, emphasizing an anatomical factor that needs more biomechanical and clinical study. The results of our study align with existing research that highlights a shorter inter-delivery interval as one of the significant risk factors for the development of isthmocele [ 15 ]. Our results indicate that a longer inter-delivery interval offers protection: for each additional year between deliveries, the risk of developing isthmocele decreased by about 35%. This supports the idea that not enough healing time between pregnancies hampers proper scar remodeling. A longer interval allows for better tissue repair and restoration of strength at the cesarean scar site. This signifies the importance of counseling about proper spacing between pregnancies as one of the factors to decrease the risk of isthmocele. The results of our study contradict those of Lonardo Pinto et al., who reported that a longer inter-delivery interval is associated with the development of isthmocele [ 27 ]. In the univariate analysis, both the locking suture technique and a history of postpartum endometritis emerged as being strongly associated with isthmocele. Our findings regarding locked sutures are in accordance with some previous studies [ 28 – 30 ]. The finding regarding locked sutures is particularly important for surgical practice. While this technique is often used to ensure hemostasis, it may compromise microvascular perfusion at the wound edges, leading to localized ischemia and impaired healing. Although it did not retain independent significance in the final multivariable model, potentially due to confounding or sample size limitations, its potent univariate association and clinical relevance cannot be ignored. Similarly, the association between endometritis and isthmocele formation observed in our study corroborates existing literature[ 13 , 21 ]. Endometritis is known to interfere with physiological healing through incessant inflammatory and microbiological invasion damage that weakens scar integrity, as reported in detail previously [ 13 ]. Our findings highlight post-surgical infection control plays an important role in the proper healing of a cesarean scar. The limitations of our study include the single-center design and the lack of long-term clinical follow-up. Future studies should investigate symptom development, fertility outcomes, and the impact of specific surgical modifications (for example, double-layer closure or suture material) on isthmocele prevention. Standardized ultrasound criteria for the diagnosis of isthmocele are also needed to enhance the comparability of results between studies. Although our study confirmed advanced gestational age at delivery as an independent risk factor for isthmocele, this risk factor is often determined by obstetric indications and cannot be easily modified in clinical practice. Patients delivering at a later gestational age, mainly those with other risk factors, may benefit from closer postoperative monitoring and counseling regarding potential long-term complications of isthmocele. It is important to acknowledge that our study was designed to identify anatomical defects using transvaginal ultrasonography and did not contain a systematic assessment of long-term clinical symptoms associated with isthmocele, such as post-menstrual spotting, pelvic pain, or secondary infertility. Therefore, we cannot establish any direct correlation between the finding of a sonographic niche and symptomatic disease in our study. Future studies with long-term clinical follow-up will be required to determine which anatomical defects progress to become clinically significant and require intervention. Data regarding potential confounding factors, including alcohol consumption, recreational drug use, and specific medication histories were not collected, and their impact on scar healing remains unexplored.

Advanced gestational age at delivery and a retroverted uterine position are identified as independent risk factors for the formation of an isthmocele after a primary cesarean section, whereas longer inter-delivery intervals were found to be protective. Although not reaching independence in the final model, the strong association of the locking suture technique with overall and particularly severe isthmoceles requires serious consideration in surgical practice. These findings indicate that counseling regarding optimal spacing between pregnancies and heightened attention to surgical technique can potentially reduce the risk of this common complication. Future studies should focus on studies utilizing standardized ultrasound criteria and larger prospective studies that correlate sonographic findings with long-term clinical symptoms.

Cesarean section (CS) is one of the most performed surgical procedures in the world, with a rising trend over the last few years [ 1 , 2 ]. The increase in the rates of cesarean sections has led to greater awareness of the long-term complications related to CS, including the formation of isthmocele, also termed as cesarean scar defect (CSD) [ 1 ]. Isthmocele is defined as any discontinuity or niche in the myometrium at the uterine incision site, visible through imaging methods such as transvaginal ultrasound [ 3 ]. The exact cause remains unknown; however, impaired scar healing, inadequate vascularization, and suboptimal tissue repair all contribute to its occurrence and continuation [ 4 , 5 ]. An isthmocele is defined as a myometrial defect with a depth of at least 2 mm [ 6 ]. A large Isthmocele is defined as an incision of a depth of at least 50 or 80% of the anterior myometrium, or the remaining myometrial thickness ≤ 2.2 mm when evaluated by transvaginal ultrasound and ≤ 2.5 mm when evaluated by sonohysterography [ 4 ]. Although many women with isthmocele remain asymptomatic, clinical symptoms manifest in some of them and include post-menstrual spotting, prolonged bleeding, intermittent spotting, midcycle intrauterine fluid accumulation, cesarean scar ectopic pregnancy, chronic pelvic pain, dysmenorrhea, dyspareunia, and secondary infertility [ 3 , 7 , 8 ]. Furthermore, isthmocele has been linked with significant morbidities during subsequent pregnancies, such as placenta accreta spectrum disorders and uterine rupture, carrying considerable risks for maternal hemorrhage and mortality [ 1 , 9 , 10 ]. The prevalence of isthmocele has been reported to vary widely, influenced by diagnostic methods and the studied populations, ranging from 19% to over 60% [ 11 , 12 ]. Several risk factors have been suggested, including advanced maternal age, higher body mass index, hypertension, diabetes, and surgical factors, such as labor status at the time of CS, cervical dilation, number of previous CSs, inter-delivery interval, and uterine closure technique [ 3 , 13 ]. Some of these studies report that CS performed during active labor or with advanced dilation of the cervix increases the risk of isthmocele, possibly resulting from incisions through cervical tissue, which generally has a poorer healing capacity [ 1 – 3 , 14 , 15 ]. Additionally, short intervals between pregnancies can impair uterine healing and increase the likelihood of scar defects [ 2 , 3 , 13 , 16 ]. Several studies have investigated the potential role of uterine position (retroverted uterus)[ 4 , 17 ], genetic factors such as connective tissue disorders, and the presence of endometriosis as additional risk factors [ 7 ]. Surgical factors, including single vs double-layer uterine closure and locking vs unlocking suture techniques, may also affect scar quality, though evidence is inconclusive [ 1 , 2 , 18 ]. Although several studies have investigated risk factors for isthmocele, many of these included women with multiple cesarean sections, which is itself a strong confounding factor. Moreover, the effect of a retroverted uterus, as a possible important anatomical risk factor, remains unknown in prospective studies. Therefore, this prospective cohort study aimed to identify important obstetric and surgical predictors of isthmocele formation specifically in a defined group of women undergoing their first cesarean section. By focusing on this primary population and evaluating under-investigated factors, such as uterine position, this study seeks to provide insights for the primary prevention of this common complication. This study aimed to identify significant predictors of isthmocele in women after their first cesarean section at Arash Women’s Hospital, Iran.