Clinical outcomes in women with endometrial polyps underwent conservative management.

OBJECTIVE: To evaluate the regression rate of endometrial polyps (EPs) in a cohort of asymmetric women after conservative follow-up. MATERIALS AND METHODS: In this retrospective cohort study, a total of 1006 women with asymptomatic EPs were treated with expectant management or hormonal drugs between June 1999 and May 2018. Four hundred forty-eight women (44.5%) were administered with hormonal medications and 558 women were managed expectantly (55.5%). Office hysteroscopy was performed to confirm the diagnosis and regression of EPs. Hormonal administration included oral contraceptives, progestin and cyclic estrogen/progestin regimen according to physicians' preferences. Clinical characteristics, including the patient's age, body mass index, parity, and type of conservative management were collected. RESULTS: The mean observation time was 14.1 ± 18.5 months (range, 1-162 months). The overall regression rate of EPs in this cohort was 33.5%, 24.6% occurred after medication and 8.9% after expectant management. Patient age (<50 years) (p < 0.001), follow-up period (p = 0.005) and hormonal drugs used (p < 0.001) were significantly associated with EP regression. Twenty-four (7.1%) of the 337 EP regression patients later developed recurrent disease. Follow-up period (p < 0.001) and hormonal drugs used (p = 0.032) were closely related to polyp recurrence after initial regression. Nevertheless, multivariate logistic regression analysis revealed that hormonal drugs used was significantly associated with the regression (p < 0.001) and recurrence (p = 0.016) of EPs. CONCLUSION: Women aged 50 or less are more suitable for conservative treatment for EPs. Hormonal drugs used could increase the incidence of EP regression.

Targeted next-generation sequencing for the detection of cancer-associated somatic mutations in adenomyosis.

Adenomyosis is a condition characterised by the invasion of endometrial tissues into the uterine myometrium, the molecular pathogenesis of which remains incompletely elucidated. Lesion profiling with next-generation sequencing (NGS) can lead to the identification of previously unanticipated causative genes and the detection of therapeutically actionable genetic changes. Using an NGS panel that included 275 cancer susceptibility genes, this study examined the occurrence and frequency of somatic mutations in adenomyotic tissue specimens collected from 17 women. Extracted DNA was enriched using targeted formalin-fixed paraffin-embedded tissue cores prior to the identification of lesion-specific variants. The results revealed that KRAS and AT-rich interactive domain 1A (ARID1A) were the two most frequently mutated genes (mutation frequencies: 24% and 12%, respectively). Notably, endometrial atypical hyperplasia did not involve adenomyotic areas. We also identified, for the first time, two potentially pathogenic mutations in the F-box/WD repeat-containing protein 7 (FBXW7) and cohesin subunit SA-2 (STAG2) genes. These findings indicate that mutations in the KRAS, ARID1A, FBXW7 and STAG2 genes may play a critical role in the pathogenesis of adenomyosis. Additional studies are needed to assess whether the utilisation of oncogenic driver mutations can inform the surveillance of patients with adenomyosis who had not undergone hysterectomy.Impact statementWhat is already known on this subject? Although somatic point mutations in the KRAS oncogene have been recently detected in adenomyosis, the molecular underpinnings of this condition remains incompletely elucidated. Lesion profiling with next-generation sequencing (NGS) can lead to the identification of previously unanticipated causative genes and the detection of therapeutically actionable genetic changes.What do the results of this study add? The results of NGS revealed that KRAS and AT-rich interactive domain 1A (ARID1A) were the two most frequently mutated genes (mutation frequencies: 24% and 12%, respectively). We also identified, for the first time, two potentially pathogenic mutations in the F-box/WD repeat-containing protein 7 (FBXW7) and cohesin subunit SA-2 (STAG2) genes.What are the implications of these findings for clinical practice and/or further research? The utilisation of oncogenic driver mutations has the potential to inform the surveillance of patients with adenomyosis who had not undergone hysterectomy.

Analysis of endometrial lavage microbiota reveals an increased relative abundance of the plastic-degrading bacteria Bacillus pseudofirmus and Stenotrophomonas rhizophila in women with endometrial cancer/endometrial hyperplasia.

The pathogenic influences of uterine bacteria on endometrial carcinogenesis remain unclear. The aim of this pilot study was to compare the microbiota composition of endometrial lavage samples obtained from women with either endometrial hyperplasia (EH) or endometrial cancer (EC) versus those with benign uterine conditions. We hypothesized that specific microbiota signatures would distinguish between the two groups, possibly leading to the identification of bacterial species associated with endometrial tumorigenesis. A total of 35 endometrial lavage specimens (EH, n = 18; EC, n = 7; metastatic EC, n = 2; benign endometrial lesions, n = 8) were collected from 32 women who had undergone office hysteroscopy. Microbiota composition was determined by sequencing the V3-V4 region of 16S rRNA genes and results were validated by real-time qPCR in 46 patients with EC/EH and 13 control women. Surprisingly, we found that Bacillus pseudofirmus and Stenotrophomonas rhizophila - two plastic-degrading bacterial species - were over-represented in endometrial lavage specimens collected from patients with EC/EH. Using computational analysis, we found that the functional profile of endometrial microbiota in EC/EH was associated with fatty acid and amino acid metabolism. In summary, our hypothesis-generating data indicate that the plastic-degrading bacteria Bacillus pseudofirmus and Stenotrophomonas rhizophila are over-represented within the endometrial lavage microbiota of women with EC/EH living in Taiwan. Whether this may be related to plastic pollution deserves further investigation.

Restoring tubal patency with laparoscopic tubocornual anastomosis.

OBJECTIVE: To assess the technical feasibility of laparoscopic tubocornual anastomosis (TCA) at restoring tubal patency in patients with proximal tubal occlusions. MATERIALS AND METHODS: A retrospective analysis of fourteen females with identified proximal tubal occlusions seeking to restore their tubal patency in a university-affiliated tertiary hospital between 2011 and 2018. Tubal patency within one year after the surgery was evaluated. RESULTS: The patients had a mean age of 34.0 ± 3.6 years old, median parity of 1 child, and mean BMI of 23.0 ± 5.2 kg/m2. Of the fourteen patients, two (14.3%) received bilateral TCA, eight (57.1%) received only unilateral TCA, and four (28.6%) received TCA on one side and tubal anastomosis on the other. The operative time was 126.4 ± 37.9min for unilateral procedure and 201.0 ± 1.4 min for bilateral anastomoses. Postoperative hysterosalpingogram (HSG) demonstrated a patency rate of 64.2% at the TCA sites. Two ectopic pregnancies were reported thereafter. CONCLUSION: This preliminary series demonstrates that laparoscopic TCA is technically feasible and provides promising results for patients with proximal tubal occlusions hoping to restore their tubal function in order to conceive naturally. A larger prospective series is mandatory to establish its significance and application in clinical practices. Notably, infertile patients without surgically correctable factors are not suitable for this procedure.

Uterine fibroid-like tumors: spectrum of MR imaging findings and their differential diagnosis.

Uterine leiomyoma, also known as uterine fibroid, is the most common gynecological tumor, affecting almost 80% of women at some point during their lives. In the same time, other fibroid-like tumors have similar clinical presentations and about 0.5% of resected tumors of which were presumed benign fibroids in the preoperative diagnosis revealed as malignant sarcomas in the final histopathological examination. Amid the emergence of nonsurgical or minimally invasive procedures for symptomatic benign uterine fibroids, such as uterine artery embolization, high-intensity-focused ultrasound, or laparoscopic myomectomy, the preoperative diagnosis of uterine tumors through imaging becomes all the more relevant. Preoperative tissue sampling is challenging because of the variable location of the myometrial mass; thus, the preoperative evaluation of size and location is increasingly performed through magnetic resonance imaging. Features in images might also be useful for examining the full spectrum of such growths, from benign fibroids to neoplasms of uncertain behavior and malignant sarcomas. Benign fibroids include usual-type leiomyomas, myomas with degeneration, and mitotically active leiomyomas. Neoplasms of uncertain behavior include smooth muscle tumors of uncertain malignant potential, leiomyomas with bizarre nuclei, and cellular leiomyomas. Malignant sarcomas comprise leiomyosarcomas, endometrial stromal sarcomas, adenosarcomas, and carcinosarcomas. The purpose of this article is to review the spectrum of MRI findings of uterine fibroid-like tumors, from benign variants, uncertain behavior to malignant sarcomas, and update the advanced imaging modalities, including diffusion-weighted imaging, positron emission tomography/computed tomography, combining texture analysis and radiomics, to tackle this important issue.

Massively parallel sequencing of endometrial lavage specimens for the detection of cancer-associated mutations in atypical and non-atypical endometrial hyperplasia.

Background: Endometrial hyperplasia (EH), particularly with atypia, is considered an antecedent of endometrial adenocarcinoma. In this study, we aimed to apply massively parallel sequencing of endometrial lavage specimens for the detection of cancer-associated mutations in atypical (AEH) and non-atypical endometrial hyperplasia (NEH). The identified alterations were compared with those detected in tissue samples. Materials and methods: Endometrial lavage specimens and parallel biopsy samples (n = 11 for AEH and n = 9 for NEH) were obtained from 18 women (9 with AEH and 9 with NEH) who received an office hysteroscopy for suspected endometrial lesions. All samples were tested for somatic mutations in hotspot regions of 72 cancer-associated genes by massively parallel sequencing. Results: On analyzing sequencing data, the presence of at least one cancer-associated gene mutation was identified in 72.7 and 44.4% of endometrial lavage specimens obtained from women with AEH and NEH, respectively (p = 0.362, 95% confidence interval = 0.72-3.70). The concordance rates between mutations identified in endometrial lavage specimens and endometrial biopsies were 54.5 and 0% from women with AEH and NEH, respectively (p = 0.014). A patient with NEH harbored mutations in endometrial lavage with the same mutations found in the tissue specimen at low allele frequency below detection cutoff, raising the suspicion of missed focal atypia. Conclusion: Endometrial hyperplasia is characterized by a high burden of cancer-associated mutations, particularly in the presence of atypia. Our study, albeit performed with a relatively small number of samples, indicates that their detection by massively parallel sequencing of endometrial lavage is feasible. Our findings may allow tailoring of endometrial biopsies to the individual risk of AEH; additionally, they can pave the way toward less invasive surveillance protocols in patients with known EH.

A feasibility analysis of the ArcBlate MR-guided high-intensity focused ultrasound system for the ablation of uterine fibroids.

PURPOSE: Uterine fibroids are benign gynecologic tumors and commonly occur in women by the age of 50. Women with symptomatic uterine fibroids generally receive surgical intervention, while they do not favor the invasive therapies. To evaluate the feasibility and safety of a novel magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) modality, ArcBlate, in the treatment of uterine fibroids. METHODS: Nine patients with uterine fibroids and one patient with adenomyosis were treated with ArcBlate MRgHIFU. Tumor size and quality of life were evaluated postoperatively at 1 and 3 months by magnetic resonance imaging (MRI) and the 36-Item Short Form Survey (SF-36), respectively. RESULTS: All patients completed the ArcBlate MRgHIFU procedure and there were no treatment-related adverse effects either during the procedure or during the 3 months of follow-up. Despite limiting the ablation volume to under 50% of the treated fibroid volume as a safety precaution, tumor volumes were markedly reduced in four patients by 15.78-58.87% at 3-month post-treatment. Moreover, SF-36 scale scores had improved at 3 months from baseline by 2-8 points in six patients, indicating relief of symptoms and improved quality of life. CONCLUSION: This study evidence demonstrates the safety and feasibility of ArcBlate MRgHIFU and suggests its potential for treating uterine fibroids.

Molecular evidence for a clonal relationship between synchronous uterine endometrioid carcinoma and ovarian clear cell carcinoma: a new example of "precursor escape"?

Synchronous endometrial and ovarian carcinomas (SEOCs) that share the same endometrioid histology are generally considered as the result of metastatic spread from one organ to another. However, SEOCs with different histologies are regarded as distinct primary lesions that arise independently from each other. This study was undertaken to compare the mutational landscape of SEOCs with different histologies to confirm or refute the hypothesis of an independent origin. Four patients with synchronous uterine endometrioid carcinoma (UEMC) and ovarian clear cell carcinoma (OCCC) were examined. UEMCs were accompanied by endometrial hyperplasia/endometrioid intraepithelial neoplasia, whereas endometriosis was evident in two cases. Paired UEMC and OCCC specimens were subjected to mutation analysis with massively parallel sequencing. Surprisingly, we found that 50% (2/4) of paired SEOCs with different histologies shared the same somatic mutations, some of which localized in cancer driver genes. Clonality analyses indicated that these tumors were clonally related to each other. Notably, 75% (3/4) of the study patients had Lynch syndrome. The cancer-specific survival figures of patients with synchronous UEMCs and OCCCs were more favorable than those observed in a historical cohort of patients with isolated stage 2/3 OCCCs. Taken together, we set forth a potential explanation that considers clonally related SEOCs as a result of "precursor escape" - whereby precursor cells of endometrial cancer spread beyond the uterus to reach the pelvis and eventually evolve into an OCCC under an increasing mutational burden. KEY MESSAGES: • SEOCs characterized by different histologies are rare. • All cases of SEOCs were accompanied by endometrial hyperplasia. • Fifty percent of SEOCs were clonally related to each other. • Shared mutations in cancer driver genes were evident among SEOCs. • Clonally related SEOCs may be a result of "precursor escape." • Lynch syndrome is highly prevalent in patients with UEMC and synchronous OCCC. • The prognosis of synchronous UEMC and OCCC was favorable.

Use of human fibrin glue (Tisseel) versus suture during transvaginal natural orifice ovarian cystectomy of benign and non-endometriotic ovarian tumor: a retrospective comparative study.

BACKGROUND: To evaluate the use of a human fibrin glue (Tisseel) for minor bleeding control and approximation of ovarian defect during transvaginal natural orifice ovarian cystectomy (TNOOC) of benign and non-endometriotic ovarian tumors. METHODS: A total of 125 women with benign and non-endometriotic ovarian tumors who underwent TNOOC between May 2011 and January 2020: 54 with the aid of Tisseel and 71 with traditional suture for hemostasis and approximation of ovarian defect. Surgical outcomes such as length of surgery, operative blood loss, postoperative pain score, and postoperative hospital stay were recorded. Before and immediately (10 days) and at 6 months after the procedure, serum anti-Müllerian hormone (AMH) levels were also determined. RESULTS: Complete hemostasis and approximation of ovarian defect were achieved in all cases. No significant difference was noted in the operating time, operative blood loss, postoperative pain scores after 12, 24 and 48 h, length of postoperative stay, and baseline AMH levels between the two groups. The operation did not have a negative effect on the immediate and 6-month postoperative AMH levels in the suture group. However, the decline in the AMH levels was significant immediately after surgery in the Tisseel group, nevertheless, no significant difference was noted in the AMH levels at 6 months (3.3 vs. 1.7 mg/mL; p = 0.042, adjusted p = 0.210). CONCLUSION: The use of Tisseel in TNOOC of benign and non-endometriotic ovarian tumors without suturing the ovarian tissue is clinically safe and feasible.

Role of human papillomavirus status after conization for high-grade cervical intraepithelial neoplasia.

Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.

Learning curve analysis of applying Seprafilm hyaluronic acid/carboxymethylcellulose membrane during laparoscopic hysterectomy.

This study was designed to evaluate the learning curve of applying Seprafilm (modified hyaluronic acid and carboxymethylcellulose; Genzyme, Cambridge, MA, USA) during laparoscopic hysterectomy or subtotal hysterectomy with or without adnexectomy. In this retrospective cohort study, 35 patients who underwent laparoscopic hysterectomy or subtotal hysterectomy with or without adnexectomy were enrolled. The Seprafilm was cut into 4 pieces, rolled up with a trimmed plastic sleeve and delivered through an incision wound made for the 5-mm ancillary trocar. The membrane was unrolled and placed on the rough surface after hysterectomy or subtotal hysterectomy with or without adnexectomy. The time from the insertion of the first piece of membrane into the abdominal cavity to the complete removal of the trimmed plastic sleeve was recorded. The median time for Seprafilm placement was 3 min. The learning curve was analyzed using the power-law method and suggested that 10 cases were required to achieve proficiency in the procedure. The presence of adnexectomy was significantly associated with the time required for Seprafilm placement (P < 0.001). Although Seprafilm placement is more complicated compared to the liquid and gel forms of anti-adhesion barriers, surgical proficiency seemed to be attained after 10 cases for an experienced surgeon.

Performing laparoscopic adenomyomectomy with the four-petal method.

OBJECTIVE: To demonstrate an innovative idea for a four-petal method for performing laparoscopic adenomyomectomy on a patient with focal-type adenomyosis. DESIGN: A step-by-step explanation of the technique with narrated video footage. SETTING: University hospital. PATIENT(S): A 38-year-old female with a 7 × 4 cm adenomyoma at the anterior uterine wall. INTERVENTION(S): Laparoscopic adenomyomectomy began with a cruciate incision to turn the adenomyoma into the shape of a blooming four-petal flower to fully expose the tumor and maximize the removal of adenomyotic tissue. During excision of the lesion, around a 1 cm thickness of the myometrium was preserved at the subendometrial region and around a 0.5 cm thickness of the serosa flap was also left in each "petal." Suture repair in the method introduced is different from closing the wound by approximation of myometrium to myometrium as in traditional myomectomy; instead, herein we repaired the adenomyomectomy wound by anchoring the serosal flap to the subendometrial tissue, with care taken to avoid dead space. MAIN OUTCOME MEASURE(S): Subjective clinical symptoms as well as serial ultrasonographic measurement of the uterine size, shape, and wall thickness. RESULT(S): The specimen removed was 92 g in weight. The symptoms have dramatically decreased since the procedure and dysmenorrhea improved from visual analog scale 8 to 1 postoperatively. Besides achieving satisfactory symptomatic relief, the ultrasonographic measurement of the myometrium was of adequate thickness (2.3 cm) after the operation and did not increase in a serial follow-up of 33 months. CONCLUSION(S): The four-petal method of adenomyomectomy with cruciate incision offers full exposure to the localized adenomyosis. It greatly facilitates a balance between the maximized resection of the lesions and tailored reserves of myometrium. Subsequent repair by anchoring the serosal flap to the subendometrial tissue ensures adequate thickness of the uterine wall after the operation.

Learning Curve Analysis of Transvaginal Natural Orifice Adnexal Surgery.

STUDY OBJECTIVE: This study was designed to evaluate the learning curve of transvaginal natural orifice surgery (NOS) for adnexal tumors based on the type of procedure (adnexectomy or cystectomy). DESIGN: Retrospective cohort study. SETTING: Tertiary-care university hospital. PATIENTS: One hundred thirty-six women with adnexal tumors. INTERVENTIONS: A series of 136 consecutive transvaginal NOS for adnexal tumor were performed between April 2011 and June 2016. Eighty-five patients (62.5%) had undergone cystectomy, and 51 patients (37.5%) had undergone adnexectomy. MEASUREMENTS AND MAIN RESULTS: The transvaginal NOS procedures included vaginal, endoscopic, single-port access techniques and were divided into 2 categories: adnexectomy and cystectomy. Operating time was electronically recorded and was defined as the time from the creation of a posterior colpotomy incision until the complete closure of the posterior colpotomy opening. The average operating time for the cystectomy and adnexectomy groups was 42.7 and 37.7 minutes, respectively (p = .015). The learning curve was analyzed using the cumulative summation method and showed that 36 cases were needed to achieve proficiency in transvaginal NOS for ovarian cystectomy. However, there was no significant cut-off point to determine the number of patients who had undergone adnexectomy. CONCLUSION: A well-trained gynecologic endoscopist can achieve surgical proficiency in transvaginal NOS cystectomy after 36 cases. It is suggested that the surgical transvaginal NOS procedure should begin with adnexectomy rather than with cystectomy to avoid initial technical challenges.

A Simple Technique for the Placement of Seprafilm, a Sodium Hyaluronate or Carboxymethylcellulose Absorbable Barrier, during Laparoscopic Myomectomy.

This report describes a simple technique using conventional instrumentation for the placement of Seprafilm, a sodium hyaluronate or carboxymethylcellulose absorbable barrier for adhesion prevention. A total of 378 women with uterine myomas undergoing laparoscopic myomectomies had 737 Seprafilm pieces placed. Seprafilm sheet was softened through exposure to room air for 5 minutes, cut into 4 pieces (length, 5-10 mm), rolled up alongside a plastic sheet cut from a camera drape cover, and gently placed at the right paracolic gutter. The Seprafilm pieces unfolded semiautomatically on release and were then placed on the uterus. The median time to apply per Seprafilm piece was 1 (range: 0.8-3.5) minute. We failed to place 16 pieces (16 of 737, 2.2%) in 11 patients. Virginal status, myoma weight, and the number of removed myomas were the risk factors of failed placement. Our technique for Seprafilm placement during laparoscopic myomectomy is simple and safe.

Office Hysteroscopy as a Valid Tool for Diagnosis of Genital Tract Lesions in Females with Intact Hymen.

BACKGROUND: To evaluate the feasibility and applicability of using office hysteroscopy in women with intact hymen. METHODS: We recruited 836 patients with intact hymen with different indications who underwent diagnostic hysteroscopy without anesthesia in an outpatient setting from 2007 to 2016 at Chang Gung Memorial Hospital at Linkou. RESULTS: Patients' mean age was 35 ± 10.6 years (range 3-69 years). Most patients (86.4%) with postmenopausal bleeding had intrauterine lesions, and they were especially at high risk (50%) for endometrial hyperplasia or malignancy. Five hundred thirty (63.3%) patients had histologic findings confirming concordance between hysteroscopic and histologic findings. Submucosal myoma had the highest concordance (96.3%), whereas endometrial hyperplasia had the lowest concordance (50%). Forty-eight patients (5.7%) had endometrial hyperplasia, and 35 patients (4.2%) had endometrial malignancy. Two patients who were thought to have nonspecific endometrial thickening actually had endometrial pathology. CONCLUSIONS: Hysteroscopy through vaginoscopic approach is feasible and well-tolerated in the patients with intact hymen. This outpatient procedure provides accurate evaluation of lesions of the genital tract and should be considered in patients without a history of intercourse.

Learning curve analysis of transvaginal natural orifice transluminal endoscopic hysterectomy.

BACKGROUND: No data are available to assess the learning curve for transvaginal natural orifice transluminal endoscopic hysterectomy for non-prolapsed uteri in benign gynecologic diseases. The lack of exposure to transvaginal natural orifice transluminal endoscopic hysterectomy during training, in addition to a poorly defined learning curve, further deters interested physicians from applying this technique to daily practice. The aim of this study was to evaluate the learning curve and perioperative outcome of transvaginal natural orifice transluminal endoscopic hysterectomy by an experienced endoscopist. METHODS: A total of 240 cases of transvaginal natural orifice transluminal endoscopic hysterectomies with or without adnexectomy for various benign gynecologic diseases were included. Demographic data and various perioperative parameters were reviewed from the prospectively collected database. Operative time was set as a surrogate marker for surgical competency. The learning curve was evaluated using the cumulative sum method. RESULTS: The overall mean operative time (OT) was 76.5 min ± 22.4. Four unique phases of the learning curve were derived using cumulative sum analysis: the mean OT of phase I (the initial learning curve of 20 cases) was 86.3 ± 23.7 min, phase II (acquisition of competence of 80 cases) was 71.0 ± 21.4 min, phase III (proficiency and plateau of 80 cases) was 76.0 ± 20.4 min, and phase IV (post-learning in which more challenging cases were managed) was 81.3 ± 23.6 min. No major complications were encountered. One case in phase III converted to laparoscopy due to difficulty in performing anterior colpotomy. CONCLUSION: Our data demonstrated four distinct phases of the learning curve of transvaginal natural orifice transluminal endoscopic hysterectomy. In a well-trained endoscopist, surgical competence in transvaginal natural orifice transluminal endoscopic hysterectomy can be reached after 20 cases.