Usefulness and Safety of Hybrid Uterine Septal Dissection.

Numerous uterine malformations are associated with recurrent pregnancy loss (RPL) and infertility. Although an arcuate uterus is the most frequent uterine malformation, a septate uterus is the most common cause of RPL.[ 1 ] Various diagnostic techniques, such as magnetic resonance imaging (MRI), hysterosalpingography (HSG), and computed tomography, are commonly employed to ensure accurate diagnosis of congenital uterine anomalies in gynecology and obstetrics. More recently, three-dimensional (3D) ultrasound has emerged as a practical and highly accurate method for diagnosing uterine malformations, offering promising results in the field of gynecology and obstetrics.[ 2 ] The usefulness of uteroplasty for treating uterine malformations has also been demonstrated.[ 3 ] However, these studies did not use a nonoperated observation group as a control, making complete evaluation difficult. Two types of hysteroplasties are performed for a septate uterus: open hysteroplasty (Jones and Jones procedure) and hysteroscopic septal resection. To mitigate the risk of complications associated with open hysteroplasties, such as intra-abdominal adhesions, fallopian tube obstruction, prolonged hospital stay, and extended postoperative recovery time, hysteroscopic septal resection has emerged as the preferred procedure in current medical practice. However, the incision method, in which an incision is made at the center of the uterine septum to widen the lumen without removing the septum itself, is now widely used.[ 4 ] The incisional method is easier to perform and reduces the risk of uterine perforations. However, determining the extent of septal resection and the possibility of uterine perforation using hysteroscopic surgery alone has proven difficult. Potential complications of hysteroscopic surgery (transcervical resection [TCR]) include uterine perforation, water intoxication, intrauterine infection, and intrauterine adhesions. The American Association of Gynecologic Laparoscopists reported uterine perforation in 14 of 1000 hysteroscopic procedures.[ 5 ] Therefore, in recent years, transabdominal ultrasonography has been performed simultaneously with a hysteroscopic incision during resection to reduce the risk of uterine perforation, confirm the contour of the uterus, remove the septum, and evaluate the presence of other abnormalities.[ 6 ] Since 2017, we have treated patients with septate uterus and vaginal septum more safely and reliably with hybrid septal resection, which involves preoperative 3D ultrasound evaluation, intraoperative thin laparoscopy, and intraoperative fluoroscopy, rather than hysteroscopic only septal resection. Further, we have routinely inserted intrauterine devices (IUDs) into the open uterus and performed estrogen–progestin replacement treatment for 1–2 months to avoid intrauterine adhesion. In this study, we investigated the pregnancy method and postoperative complication, live birth, pregnancy, and miscarriage rates associated with treatment using this modified technique.

According to ASRM definitions, couples who were unable to achieve a successful pregnancy after ≥12 months of regular unprotected sex were classified as infertile. Moreover, those who experienced two or more miscarriages or stillbirths were classified as having RPL.[ 8 ] Based on these classifications, 9 (56%) patients were infertile, and 7 (43%) had RPL [ Table 1 ]. The mean operative time for patients diagnosed with a septate uterus was 77 ± 17.81 min (mean ± standard deviation), and the mean operative time for patients with vaginal septal complications was 97 ± 17.25 min (mean ± standard deviation). No postoperative complications were observed in any of the 16 (0%) patients. Second-look hysteroscopy showed normalized uterus and no adhesions. Of the 16 patients who underwent surgery, 15 were followed up for more than 1 year postoperatively. In addition, 12 and 3 patients were in the postoperative pregnancy and infertility groups, respectively. The postoperative pregnancy rate was 80.0% (12/15), and the live birth rate was 40.0% (6/15) per operation and 50% (6/12) per pregnancy. Of the postoperative pregnancies, five resulted in miscarriage, and two patients are currently pregnant [ Table 1 ]. Patient backgrounds and outcomes Chromosomal testing was conducted for three patients who experienced miscarriage, all of whom exhibited chromosomal abnormalities. The perinatal prognosis was as follows: mean week of gestation, 38 weeks 3 days (34 weeks and 3 days–40 weeks and 1 days); mean birth weight, 2979 g (2404–3935 g); cesarean section rate, 100% (6/6); and breech presentation rate, 16% (1/6). No cases of uterine rupture, heavy bleeding during delivery, or placenta previa were reported. The mean age at surgery for the seven patients in the infertility group was 34.0 ± 1.82 years (mean ± standard deviation) (31–36 years). In addition, one patient underwent preoperative in vitro fertilization and embryo transfer (IVF-ET). Postoperatively, three patients underwent ovarian stimulation or IVF-ET. The postoperative pregnancy rate was 100.0% (7/7), and the live birth rate was 71% (5/7). The miscarriage rate after postoperative pregnancy was 28.5% (2/7) [ Table 1 ]. Chromosome analysis was performed for two patients who experienced postoperative miscarriages, and in both cases, chromosomal abnormalities were detected. The live birth rate was 100% in patients without chromosomal abnormalities. The mean age at surgery for the nine patients in the infertility group was 33.1 ± 3.14 years (mean ± standard deviation) (29–36 years). Of these patients, one underwent preoperative IVF-ET. Postoperatively, all patients underwent ovarian stimulation or IVF-ET. The postoperative pregnancy rate was 55.5% (5/9), and the live birth rate was 20% (1/5). In addition, one of the patients was pregnant. The postoperative miscarriage rate was 60% (3/5) [ Table 1 ]. Of the three cases of postoperative miscarriages, chromosomal analysis was performed for 1 and revealed the presence of a chromosomal abnormality. Of the six patients in the infertility and RPL groups who delivered infants, 1 (16.0%) had a perinatal complication (impending preterm labor). None of the cases (0%) involved vaginal delivery, as six cases (100%) required cesarean section as the mode of delivery. The reasons for performing cesarean sections were as follows: two cases each due to previous cesarean section and arrested labor, and 1 case each due to breech presentation and nonreassuring fetal status. No cases of cesarean section were performed because of preexisting uterine surgery.

A previous study showed that the frequency of septate uterus in the general female population is 6.7%, compared with 16.7% in infertile women.[ 9 ] Several reports have addressed the frequency of miscarriages in women with septate uterus. Chan et al . reported that the incidence of early miscarriage in patients with septate uterus was 33.6%, which was higher than that in the general population.[ 1 ] The ASRM and congenital uterine malformation expert classifications are helpful in the diagnosis of this condition.[ 10 ] In this study, we used the ASRM classification of uterine morphology to diagnose septate uterus in all cases.[ 6 10 ] A previous study comparing 3D ultrasound with hysteroscopy and laparoscopy for the diagnosis of uterine morphology reported a high specificity of 92.3%, positive predictive value of 98%, and negative predictive value of 100%.[ 2 ] For this reason, we used 3D ultrasound tomography, which has the lowest patient burden, to diagnose suspected abnormalities in uterine morphology. This method avoids the high cost of preoperative MRI and radiation exposure from hysterosalpingograms. Resection of the septate uterus is associated with infertility and perinatal complications because the septum is less sensitive to steroid hormones.[ 11 ] The endometrium of the septum shows a lower number of vascular endothelial growth factor receptors and reduced sensitivity to steroid hormones in both blood vessels and the endometrium itself.[ 12 ] Furthermore, narrowing of the intrauterine volume and poor extensibility due to the septum are thought to be responsible.[ 12 13 ] The results of a randomized controlled trial examining improved pregnancy outcomes for septate uterus showed that hysteroscopic septal resection did not improve birth rates or other reproductive outcomes in women with septate uterus.[ 13 ] However, this is difficult to conclude based on the results of this trial alone; therefore, we believe that further research is needed to determine the effects of the septate uterus on improved pregnancy outcomes. In this study, with the exception of miscarriages due to obvious chromosomal abnormalities, an improvement in postoperative live birth and miscarriage rates was observed, especially in the RPL group. This was thought to be attributed to the improvement in pregnancy outcomes resulting from the widening of the lumen after the removal of the septum, which is a hard muscular tissue with low vascular distribution. The effectiveness of hysteroscopic septal resection for a septate uterus has been reported, with an excellent postoperative live birth rate of 50%–60% found by Nouri et al .[ 14 ] In another report, the preoperative miscarriage rate in 599 pregnancies in women with a septate uterus was 86.4%, whereas, in 366 postoperative pregnancies, the miscarriage rate decreased to 16.4%.[ 15 ] In our study, the miscarriage rate in the RPL group was 28%, and the postoperative live birth rate was 100% for cases without chromosomal abnormalities, indicating a significant reduction in the miscarriage rate. Chromosomal abnormalities have been found in the aborted villi of most patients with miscarriages. These data suggest that septal resection may be a factor contributing to infertility in patients with septate uterus and infertility and that the septum is a female factor in infertility that can be eliminated by surgical intervention. Two methods can be applied to resect the uterine septum: resection of the body septum only when a vaginal septum is involved or resection of the cervical septum. In the case of a complete septate uterus, which was included in this study in six cases, an important issue is whether or not the cervical septum should also be removed. Homer et al . reported only 1 case that included cervical incompetence of 43 cases of the complete septate uterus after the removal of the cervical septum also.[ 16 ] Therefore, we removed the cervical septum in addition to removing the vaginal septum. Two methods can be used for this procedure: the removal method, which involves the complete removal of the septum, and the incision method, which entails vertical division of the septum and widening of the lumen through a central incision at the tip of the septum without its complete removal. The incisional method, a simple surgical technique, is comparatively easier, reduces operative time, and minimizes intraoperative blood loss.[ 16 ] Moreover, by cutting and releasing the septum, a normal uterine cavity may be achieved. Therefore, we used the septal incision method during septal uterine surgery. Although the effect of the remaining septum on pregnancy is unknown, some reports have indicated that the prognosis is similar if the remaining septum is <1 cm from the uterine fundus, compared with that of complete resection,[ 17 ] and that the addition of complete resection in cases with a residual septum of 1 cm improved the pregnancy rate.[ 18 ] Reduction of the residual septum to 1 cm while paying sufficient attention to intraoperative complications is important. However, determining the thickness of residual septum intraoperatively using hysteroscopic surgery alone can be difficult, and uterine perforation must be prevented. Therefore, an objective and accurate intraoperative method to determine the residual septum thickness is essential. Intraoperative monitoring using transrectal ultrasonography or laparoscopy has also been used.[ 19 ] However, real-time ultrasound monitoring is often difficult when only ultrasound images are used because of the electromagnetic interference caused by high-frequency waves of electrocautery during surgical operations, air bubbles during electrocautery operations, and probe manipulation interfering with surgical operations. Therefore, the development of a method that allows easy and accurate intraoperative monitoring and evaluation is necessary. Furthermore, we used fluoroscopy (HSG), which is easy to perform and understand, and laparoscopy, which allows surgeons to evaluate the abdominal cavity to ensure sufficient incision and no thinning of the myometrium. In cases of infertility and failure to thrive, endometriosis, fallopian tube obstruction, adhesions, and other problems not detected by ultrasound alone may occur. By performing HSG and laparoscopic intraoperative monitoring, uterine morphology can be normalized, bilateral tubal spacing can be confirmed, and intraperitoneal monitoring and resection of adhesion around the fallopian tubes and tubal appendages can be performed. There is no consensus till today, between societies and trained infertility specialists, on weather diagnostic laparoscopy should be adopted or not as a mandatory step before reaching the diagnosis of unexplained infertility. However, numerous uterine malformations are associated with RPL and infertility,[ 20 ] and the rate of spontaneous pregnancy drastically declines with infertility duration of more than 3 years and in women over 30 years of age.[ 21 ] Moayeri et al . also concluded that laparoscopy followed by fertility management is cost-effective for the management of young couples with long-term infertility (>3 years) and unexplained infertility.[ 22 ] This surgical procedure may reduce the burden on the patient at the time of examination for infertility, especially in cases of RIF. Through septal incision and intraperitoneal observation, it may also reduce the time and cost of live births. As septal resection is predominantly performed in patients with infertility, preventing postoperative adhesion of the uterine lumen is also important. Various opinions exist regarding the prevention of postoperative luminal adhesions.[ 10 ] Septal resection is mainly performed in patients with infertility, and postoperative adhesion of the uterine lumen is an important issue. Although no gold standard has been established for the prevention of adhesions after hysteroscopic septal resection, several approaches have shown utility. These include hormonal therapies such as Kaufmann therapy, physical therapies such as intrauterine contraceptives and early postoperative second-look hysteroscopy.[ 23 ] In our hospital, we perform hysteroscopy during the early postoperative period after intrauterine contraceptive device placement and application of hormonal therapy to confirm the absence of adhesions. No adhesions were observed when this method was used to prevent adhesion, suggesting effective prevention. Although the effectiveness of hysteroscopic septal resection is unclear, the postoperative live birth rate is high based on literature reports and our data, and the procedure is unlikely to cause infertility. Hybrid uterine septal resection improves pregnancy and miscarriage rates by reliably removing the septum without intraoperative or postoperative complications. Furthermore, most patients treated for infertility are older, which can be attributed, in part, to factors such as the tendency of women to pursue careers and marry at later stages in life. Early introduction of surgery for the septate uterus may be necessary in the future, as it could help to reveal the causes of infertility. In this study, we report the usefulness of hybrid septal resection after long-term observation of patients who underwent hysteroscopic resection for an incompetent uterine septum. These results suggest that hybrid septal resection may be helpful in patients with infertility and without other infertility factors. Hysteroscopic septectomy may be the first choice of treatment for infertility with an incompetent septate uterus, as it allows vaginal delivery with few intraoperative complications. S.S. collected the data, performed the analysis, and wrote the manuscript with support from A.F. A.F. conceived and designed the analysis, contributed data or analysis tools, and corrected and adviced for this paper. A.Y. collected the data. H.S. corrected and adviced for this paper. All authors discussed the results and commented for the manuscript. All authors have read and agreed to the final version of the manuscript. All data generated or analyzed during this study are included in this published article. Nil. There are no conflicts of interest.

From January 1, 2017, to September 1, 2021, 16 patients with infertility and RPL, diagnosed with septate uterus and vaginal septum complications according to the American Society for Reproductive Medicine’s (ASRM) classification of uterine morphology,[ 7 ] underwent surgery. The treatment approach involved preoperative 3D ultrasound evaluation, combined intraoperative thin laparoscopy, and hybrid septal resection combined with intraoperative fluoroscopy. The mean age at surgery was 33.41 ± 2.55 years (mean ± standard deviation). Septate uterus was classified according to the ASRM guidelines,[ 7 ] resulting in the following breakdown: 11 cases of partial septate uterus, 2 cases of complete septate uterus with a septate cervix and longitudinal vaginal septum, 2 cases of complete septate uterus with a duplicate cervix and longitudinal vaginal septum, and 1 case of complete septate uterus with a duplicate cervix and an obstructed right hemivagina. Cervical dilatation was performed using Lamicel ® (Medtronic, Dublin, Ireland) from the previous day as pretreatment, and TCR was performed using TCRis ® (TCR in saline) (Olympus, Tokyo, Japan) under general anesthesia. A laparoscope with a 5-mm scope and 2-mm fine forceps (Endo Relief, Hope-Denshi, Chiba, Japan) was used for intraperitoneal observation and intraoperative monitoring in all patients. Surgery was performed during the proliferative phase of the menstrual cycle to avoid difficulty securing the operative field owing to endometrial thickening, and a continuous irrigation device was used with saline solution as the irrigation fluid. In cases of a complicated vaginal septum, we performed vaginal and cervical septal resections for the visible part using a Harmonic Scalpel ® (Johnson and Johnson Medical, Inc., New Jersey, USA), followed by hysteroscopic surgery. Hysteroscopic surgery was performed by first assessing the bilateral fallopian tube orifices to determine the length and width of the septum. Septal resection was subsequently performed using a TCRis ® cut, cutting the middle of the septum from the front toward the uterine fundus. Figure 1 shows a virtual line connecting the bilateral fallopian tube ostium. The incision was carefully extended to this specific virtual line, ensuring neither excess nor deficiency. The procedure was performed with continuous verification through a laparoscope [ Figure 2 ]. We further used hysterosalpingogram for intraoperative monitoring of a shape of intrauterine cavity to confirm the normalization of the cavity shape [ Figure 2 ]. The soft fallopian tube contrast and ventilation catheter ® (Soft Medical Co., Ltd, Tokyo, Japan) was filled with a water-soluble contrast medium (Isovist ® Bayer Co., Ltd, Leverkusen, Germany). Tubal passability and uterine cavity morphology were confirmed by injecting an aqueous contrast through the catheter and assessing using intraoperative fluoroscopy [ Figure 2 ]. This process enables real-time evaluation of the opening of the fallopian ostium without relying solely on hysteroscopy and laparoscopy. (a) A virtual line(blue area) connecting the bilateral fallopian tube ostium(blue arrow), (b) The incision is made without excess or deficiency up to this virtual line with confirmation under laparoscopy Transcervical resection (TCR) is performed using TCRis ® (TCR in saline) (Olympus) with intraoperative monitoring and observation of the abdominal cavity by laparoscopy with a 5-mm scope and 2-mm fine forceps (Endo Relief, hope-denshi) in all cases. (a) Monitoring and observation of the abdominal cavity by laparoscopy with a 5-mm scope and 2-mm fine forceps, (b) Hysterosalpingography is used for intraoperative monitoring of uterine morphology, (c) At the end of the procedure, the spacing is evaluated using a water-like contrast medium to determine the completion of the procedure At the end of the procedure, a water-soluble contrast medium was used to confirm the shape of the uterine cavity and re-evaluate the completion of the process. After surgery, an IUD (FD-1[P-70] [Fuji Latex, Tokyo, Japan]) was inserted to prevent adhesion, and hormone replacement therapy (conjugated estrogen 1.25 mg/day ×20 days, medroxyprogesterone 5.0 mg/day ×10 days) was administered for 1–2 postoperative cycles. After the completion of hormone therapy, the IUD was removed, and a second-look hysteroscopy was performed as an outpatient procedure [ Figure 3 ]. Pregnancy was permitted when no abnormalities were observed. In cases with insufficient endometrial repair, additional hormone replacement therapy was done. We believe that vaginal delivery is possible unless uterine perforation or thinning of the myometrium occurs. (a) Preoperative outpatient hysteroscopy and three-dimensional (3D) ultrasound, (b) Intraoperative hysteroscopy and immediate postoperative ultrasound and intrauterine device placement, (c) Postoperative outpatient hysteroscopy and 3D ultrasound Information on medical history, current medical status, infertility or infertility screening outcomes, and intraoperative and postoperative courses were collected. The primary endpoint was the incidence of adverse events, whereas the secondary endpoints were the pregnancy, miscarriage, and live birth rates. By examining these endpoints, we showed that our method reliably releases the septum and normalizes uterine morphology in patients with septate uterus. The procedure was performed safely, showing promising results in terms of increased pregnancy and reduced miscarriage rates. This study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethical Review Committee of Hyogo Medical University (Approval No. 3881; Approval date: 2/28/2023). The surgical procedure and the purpose of publication were explained to the patients and their husbands, and consent form was signed and collected from each patient.