{"paper_id":"14761088-c878-4491-9118-018b1df99a74","body_text":"Cesarean scar defects, called \"isthmocele\" or \"niche,\" were first described by Poidevin in 1961 \n 1 \n . During ultrasonography, a wedge-shaped anatomical defect in the uterine wall is observed as a hypoechoic area in the lower uterine segment at the site of the uterine cesarean incision \n 2 \n . The incidence of isthmocele diagnosed by transvaginal ultrasonography (TVUSG) is between 24 and 70%, and the rate increases from 56 to 84% with the use of sonohysterography \n 2 – 4 \n . The incidence of isthmocele increases with the increasing number of cesarean section (CS).\nIsthmocele patients can be asymptomatic or may experience gynecological symptoms such as abnormal uterine bleeding (AUB), chronic pelvicpain, dyspareunia, secondary infertility, or obstetric complications \n 2 , 4 – 6 \n . The diagnostic criteria and a set protocol for the treatment of isthmocele are still missing from the guidelines. Conservative medical treatment with combined estrogen and progesterone therapy can be used for bleeding disorders, while hysteroscopy and laparoscopy, in combination, can be applied for surgical repair of the niche area \n 7 \n . In the literature, the large size of isthmocele is associated with symptoms such as postmenstrual spotting (PMS), intermenstrual spotting (IMS), dysmenorrhea, and chronic pelvic pain (PP) \n 6 , 8 \n . In the surgical treatment of isthmocele, hysteroscopic repair is recommended as the first choice if the residual myometrium thickness is at least 2.5–3 mm 9 .\nGenerally, studies in the literature compare surgical or medical treatment modalities and their pre- and postoperative results. In the present study, the relationship between preoperative ultrasound niche measurements and the presence and regression of symptoms in patients who underwent hysteroscopic metroplasty due to symptomatic isthmocele was evaluated.\n\nThis retrospective study was conducted at the Reproductive Endocrinology and Infertility Clinic, and patient data were extracted from the medical records. All consecutive patients who underwent hysteroscopic repair surgery for symptomatic isthmocele between May 2017 and January 2022 and met the inclusion criteria were included in the study. The study assessed the correlation between preoperative niche dimensions and postoperative symptom resolution in a cohort of patients diagnosed with symptomatic isthmocele. The study received approval from the local ethics committee (date: January 01, 2022 number: 01), and as a hospital policy, written signed consent was obtained from all patients for the anonymous use of medical data.\nPatients of reproductive age (18–45 years) who had undergone at least one cesarean delivery and presented with complaints of intermenstrual bleeding or pelvic pain, in whom a cesarean niche (isthmocele) was identified via two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasonography (TVUSG) or hysterosalpingography (HSG), and who subsequently underwent hysteroscopic surgical repair due to this condition were included in the study (TVUSG;  Figure 1a , HSG;  Figure 1b ).\nThe inclusion criteria were having a uterine niche at the cesarean scar site with AUB described as spotting or bleeding at the end of menstruation for more than 2 days (PMS), and/or intermittent or continuous chronic PP that persisted for 6 months or longer, independent of the menstrual cycle and sexual intercourse, after exclusion of endometriosis and adenomyosis. Furthermore, cases of secondary infertility were recorded in couples, even when standard infertility test results were within normal limits.\nExclusion criteria included peri- or postmenopausal status regardless of age (follicle-stimulating hormone [FSH] >15 IU/mL), suspected or confirmed pregnancy, a history of irregular menstrual cycles before CS, and known genital malignancy. Additionally, patients with concomitant uterine polyps, leiomyomas, or endometrial hyperplasia; endocrine disorders such as diabetes mellitus or thyroid dysfunction; and other conditions that may cause PP, such as endometriosis and adenomyosis detected by TVUSG, were also excluded. Furthermore, the study did not include patients who had undergone laparotomy and/or concomitant laparoscopy.\nIn the literature, there are various RMT cutoff values, such as 3 mm, 2.5 mm, and 3.5 mm, due to risks such as uterine perforation and bladder injury associated with hysteroscopic isthmocele surgical repair \n 10 – 12 \n . In our study, since we only evaluated patients who underwent hysteroscopy, patients with an RMT of 3 mm or less were excluded from the study in accordance with our clinical algorithm \n 9 \n .\nAll the patients were evaluated by the same team via TVUSG (Samsung H570A, 5–6 MHz) during the early follicular phase after routine gynecological examination. Ultrasonographic measurements of residual myometrial thickness (RMT), the depth of the wedge-shaped niche (ND), and the width of the niche (NW) ( Figure 2 ) at the site of the previous CS scar were obtained by TVUSG without performing saline infusion sonography or sonohysterography.\nAll patients evaluated underwent hysteroscopy under regional (spinal) anesthesia. After adequate distension of the cavity was provided with 1.5% glycine, at an intrauterine pressure of 150 mmHg, the isthmocele site was resected by using monopolar energy with a loop resectoscope (Karl Storz, Germany). No medical treatment was administered routinely in the postoperative period.\nAll patients were followed up for 1 year. Ultrasonographic measurements were not routinely repeated because the patients were living in other cities, and they came to the hospital for surgery only. Although postoperative follow-up of the patients was conducted via phone, patients’ symptoms and reproductive outcomes were recorded on follow-up forms.\nThe primary outcome of the study was the evaluation of symptom improvement after the surgery in patients with different isthmocele dimensions. Two symptoms were evaluated: spotting/bleeding and PP. For a study specifically addressing PP improvement, in the power analysis conducted with G-Power 3.0.0.1 software, when a 5% margin of error, 95% power, and a standard effect size of 1 were set, a minimum of eight patients are determined to be required \n 13 \n .\nStatistical analyses were performed using IBM SPSS 26.0 software (IBM Corporation, released 2019; IBM SPSS Statistics for Windows, Version 26.0; Armonk, NY, USA). The normality of the distribution of continuous data was checked by using the Kolmogorov-Smirnov test. Descriptive statistics were presented as mean±standard deviation or median (minimum–maximum). Categorical variables were presented as numbers and percentages. The independent samples t-test was used to analyze differences in normally distributed data. Data without a normal distribution were analyzed using the Mann-Whitney U test. A p<0.05 was considered statistically significant.\n\nA total of 29 patients who met the inclusion criteria were included, with a mean age of 33.0±4.19 years. Among them, 10 patients (34.5%) had accompanying complaints of secondary infertility, with a median duration of 19.80±7.51 months. More than half of the patients (57.5%, n=19) had only one previous CS.\nWhen the patients’ complaints were evaluated, PMS was the most common complaint, with an incidence of 72.4% (21 out of 29), while PP+PMS was the second most common complaint, occurring in 27.6% (8 out of 29) of the patients ( Table 1 ). When comparing the symptoms between obstetrical history parameters, no significant differences were found ( Table 2 ). When the relationship between niche size and symptoms was evaluated, patients with both PMS and PP symptoms had thinner RMTs. However, no significant difference was found between symptoms and other measurements (ND and NW;  Table 2 ).\nND: niche depth; NW: width of the niche; PMS: postmenstrual spotting; PP: pelvic pain; RMT: residual myometrial thickness; SD: standard deviation. The data are presented as mean±SD or median (min–max). A t-test was applied for parametric values, and the Mann-Whitney U test was applied for nonparametric values.\nND: niche depth; NW: width of the niche; PMS: postmenstrual spotting; PP: pelvic pain; RMT: residual myometrial thickness. The data are presented as mean±SD or median (min–max). A t-test was applied for parametric values, and the Mann-Whitney U test was applied for nonparametric values.\np<0.05 was considered statistically significant.\nAfter hysteroscopic surgery, complete remission was achieved in 75.8% (22 out of 29) of the patients with PMS+PP symptoms. Among these patients, 79.3% (23 out of 29) experienced remission of PMS symptoms, while only 17.24% (5 out of 29) experienced remission of PP symptoms. In patients for whom remission was not achieved, the RMT was significantly lower in both the PMS+PP group and the PMS-only group (6.57±1.90, p=0.002, and 6.50±2.07, p=0.005, respectively,  Table 3 ). Pregnancy was not achieved during the postoperative follow-up period in secondary infertility patients.\nThe data are presented as mean±SD or median (min–max). A t-test was applied for parametric values, the Mann-Whitney U test was applied for nonparametric values, and a p<0.05 indicates statistical significance.\nM*: measurements; ND: niche depth; NW: width of the niche; PMS: postmenstrual spotting; PP: pelvic pain; RMT: residual myometrial thickness.\n\nIsthmocele repair surgery has gained importance because of the increase in CS rate in recent years. Patients may present with AUB symptoms such as PMS, IMS, menometrorrhagia, PP, unexplained secondary infertility, or a combination of these symptoms. In this study, complete regression of symptoms was observed in 75.8% (22 out of 29) of the patients with PMS+PP symptoms and in 79.3% of the patients with PMS symptoms. The RMT was lower in the PMS+PP group than in the PMS group.\nPreoperative diagnosis of the isthmocele via sonohysterography is preferred, especially in patients with a myometrial wall thickness <2.5 mm. 3D TVUSG is becoming more widely used because it might lead to a better evaluation of the niche and its distance from the myometrial and serosal surfaces of the uterus than TVUSG \n 14 \n . When magnetic resonance imaging (MRI) and TVUSG were compared, there was no statistically significant difference despite the high positive predictive value of MRI \n 15 \n . In the present study, all the patients were evaluated with TVUSG, and niche measurements were carried out.\nThinner RMT can be interpreted as the presence of a deeper isthmocele that leads to increased blood collection inside the pouch. Blood collection in the pouch is explained to cause an inflammatory response \n 8 , 16 \n  and the release of inflammatory cytokines that affect the nerve fibers around the lesion. In a prospective study comparing pre- and postoperative symptoms in patients with isthmocele, AUB disappeared in 87.5% of patients within the first month, and in the second month after the operation, 96.8% of the patients achieved full recovery. Additionally, PP resolved 1 month after surgery in all patients \n 17 \n . In another study, after hysteroscopic surgery, the complaints of IMS and PP symptoms resolved in 80% of patients, while 13% had no improvement and 7% had some degree of improvement \n 18 \n . The high success rate achieved in resolving PMS (79.3%) aligns with broader findings on AUB management, where surgical correction of structural defects often leads to significant symptom improvement \n 6 \n . However, the persistence of PP in some patients suggests multifactorial etiologies beyond niche dimensions. In the present study, PMS was treated in 79.3% of women, and a total cure was observed in 75.8% of women with all the symptoms. The RMTs were thinner in these two groups, but the other dimensions (ND and NW) were not significantly different.\nThe hysteroscopic approach is the most widely used method as observed in published studies for the correction of isthmocele with adequate myometrial thickness at the isthmocele site, as well as for biopsy in cases of recurrent failure in infertile patients. Generally, hysteroscopy is a safe and successful diagnostic technique \n 19 \n . As it is a safe and effective surgical method, it can be repeated in certain cases. When hysteroscopic surgical resection was performed repeatedly for patients with ongoing symptoms, IMS complaints regressed, while no adverse effects on reproductive outcomes were observed \n 20 \n . No repeated hysteroscopy was performed in the patient groups in the present study.\nA prospective cohort study evaluating the effectiveness of hysteroscopic resection of a uterine cesarean niche used bleeding symptoms and MRI measurements, reporting at least a 3-day reduction in abnormal bleeding. In contrast, our study showed improvement not only in bleeding but also in PP symptoms \n 21 \n .\nCasadio et al. conducted a single-center, observational, prospective, cohort study involving 32 patients and reported a significant change in the mean visual analog scale (VAS) score for dyspareunia (-5.84; p<0.001), dysmenorrhea (-8.94; p<0.001), PP (-2.94; p<0.001), and AUB rates after channel-like (360°) hysteroscopic resection of the isthmocele (91 vs. 3%; p<0.001) \n 13 \n . In our study, dysmenorrhea and dyspareunia were not evaluated, and the success rate for PMS was 79.3%, with a total cure rate of 75.8%.\nThe present study demonstrated that ultrasonographic measurements of isthmocele size are useful in predicting symptom improvement after hysteroscopic surgery. Its findings may help guide patient selection for hysteroscopic surgery in clinical practice.\nThe major strength of this study is that it is the first research to report the association between isthmocele symptoms, surgical success, and ultrasound niche dimension measurements. However, there are also limitations to the study. One of the limitations is its retrospective design. The pre- and postoperative ultrasound measurements of niche sizes were obtained retrospectively from the participants’ medical records, which could introduce potential bias. Another limitation of the study is the small sample size. Prospective studies with larger patient populations are needed to support our results. Future prospective studies should incorporate standardized AUB classifications to better correlate niche anatomy with specific bleeding patterns \n 6 \n .\n\nThe results of this study demonstrated that preoperative ultrasound isthmocele measurements could be a potential predictor of hysteroscopic surgery outcomes. In our study population, the mean RMT measurement was thicker in women with improved PMS symptoms after hysteroscopic surgery. However, there was no relationship between isthmocele measurements and PP symptoms. These findings may assist clinicians in selecting appropriate patients for hysteroscopic isthmocele surgery.","source_license":"CC-BY-4.0","license_restricted":false}