ABSTRACT

Purpose

Vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) hysterectomy is an increasingly adopted and most minimally invasive approach for benign gynecological indications. However, considerable heterogeneity exists in clinical practice regarding patient selection, perioperative management, surgical technique, and outcome reporting. This guideline aims to provide evidence-based and expert consensus-supported national recommendations for vNOTES hysterectomy in benign gynecology, developed on behalf of the Pelvic Floor and Cosmetic Gynecology (PETKOZ) Association.

Methods

A systematic search of Medline/PubMed, Cochrane, EMBASE, and Google Scholar was conducted for articles published between January 2015 and March 2026, yielding 1960 records. Fifty-seven studies met inclusion criteria, comprising eight systematic reviews/meta-analyses, six randomized controlled trials, six prospective and 37 retrospective cohort studies. Evidence quality and recommendation strength were graded using the SIGN classification system. For clinical questions insufficiently addressed by the literature, a three-round Delphi consensus process was conducted among 22 expert surgeons, each with a minimum of 50 vNOTES cases; ≥70% agreement defined consensus.

Results

Compared with total laparoscopic hysterectomy, vNOTES hysterectomy was associated with significantly shorter operative time (evidence level: 1+), reduced early postoperative pain (1+), a modest reduction in hospital stay (1+), and faster postoperative recovery. Intraoperative and postoperative complication rates, conversion rates, and readmission rates were comparable to other minimally invasive approaches. Comprehensive recommendations covering contraindications, preoperative preparation, intraoperative technique, and postoperative care were established through both evidence synthesis and the Delphi process.

Conclusion

This national guideline supports vNOTES hysterectomy as a safe and feasible approach for benign gynecological disease when performed in appropriately selected patients at centers with relevant surgical expertise. While findings are reinforced by structured evidence appraisal and formal consensus methodology, a substantial proportion of the evidence base remains observational. Future randomized trials, standardized outcome reporting, and prospective health-economic analyses are essential for refining recommendations in subsequent guideline updates.

INTRODUCTION

Purpose and Scope

The purpose of this guideline is to provide advice to guide clinicians, based on the best available evidence, regarding the use of vaginal natural orifice transluminal endoscopic surgery (vNOTES) for non-malignant hysterectomy. This guideline reviews patient selection, perioperative assessment, surgical technique, and postoperative management. It aims to standardize practice, optimize surgical outcomes, and minimize complications for women undergoing hysterectomy for benign conditions.

This guideline excludes hysterectomy performed for suspected or confirmed malignancy, as the surgical approach and perioperative considerations differ significantly. Recommendations have been developed as a practical guide for gynecology surgeons, residents, and other healthcare professionals involved in the perioperative care of these patients. It is recognized that in individual cases, alternative approaches may be reasonable based on patient factors, surgical expertise, and available resources.

Population and Setting

Women undergoing hysterectomy for benign gynecological conditions, including fibroids, adenomyosis, abnormal uterine bleeding, or pelvic organ prolapse, in both hospital and outpatient surgical settings.

Interventions to be Studied

The guideline focuses on the application of vNOTES as a surgical approach for non-malignant hysterectomy, including preoperative assessment, intraoperative technique, and postoperative care, and compares its outcomes with conventional vaginal or laparoscopic hysterectomy where relevant evidence is available.

Background

vNOTES hysterectomy has emerged as a novel minimally invasive approach for the management of benign gynecological disease.^{1, 2} By integrating the advantages of conventional vaginal surgery with endoscopic visualization, this technique offers the potential to reduce surgical morbidity, enhance postoperative recovery, and improve patient-centered outcomes.³ However, despite its growing adoption, considerable heterogeneity remains in clinical practice, particularly with respect to patient selection, perioperative management, surgical technique, and outcome reporting, reflecting the lack of standardized, evidence-based guidance. The aim of this guideline is to critically appraise the available evidence and provide comprehensive recommendations on the use of vNOTES for hysterectomy in benign gynecology, encompassing patient selection, preoperative evaluation, intraoperative considerations, and postoperative care. The overarching objective is to support safe implementation, optimize surgical outcomes, and minimize procedure-related complications. Given the variability in surgical expertise, institutional infrastructure, and resource availability across different healthcare settings, this guideline integrates both evidence-based recommendations and consensus-derived expert opinion. Where appropriate, recommendations have been contextualized to enhance their applicability across diverse clinical environments. Key recommendations and clinical pathways are summarized in structured tables and figures to facilitate translation into routine practice.

METHODS

This guideline was developed in accordance with standard methodology for producing national guideline on behalf of the Guidelines Committee of the Pelvic Floor and Cosmetic Gynecology (PETKOZ) (https://petkoz.org) Association. A comprehensive search was conducted in MEDLINE/PubMed, the Cochrane Database of Systematic Reviews and the Cochrane Methodology Register, EMBASE, and Google Scholar for articles published between January 2015 and March 2026. The following search string was applied: (“vNOTES” or “vaginal natural orifice transluminal endoscopic surgery” or “transvaginal notes”) and (“hysterectomy”) and (“benign” or “non-malignant” or “leiomyoma” or “fibroids” or “adenomyosis” or “abnormal uterine bleeding” or “pelvic organ prolapse”). No language restrictions were applied. Studies were eligible for inclusion if they: (1) enrolled adult women undergoing hysterectomy for benign indications; (2) reported vNOTES as a surgical approach; (3) included at least one comparator arm (laparoscopic or vaginal hysterectomy); and (4) reported at least one of the pre-specified participants, intervention, comparison, and outcome (PICO) criteria. Exclusion criteria comprised: case reports with fewer than five patients; studies focused exclusively on malignant indications; conference abstracts without full-text availability; and studies with no extractable outcome data.

The systematic review was undertaken using a PICO approach, resulting in the formulation of five key research questions focusing on the application of vNOTES in benign gynecology (Supplementary Material 1). The review specifically addressed standardized preoperative preparation protocols, comprehensive perioperative care management, and the identification of clinical contraindications for the vaginal approach. Furthermore, the analysis investigated specific intraoperative techniques and surgical nuances, alongside an evaluation of postoperative care and recovery outcomes.

An Assessment of Quality of Evidence and Grading of Strength of Recommendations

In evaluating the quality of evidence and grading the strength of recommendations, this guideline adopted the classification system proposed by the Scottish Intercollegiate Guidelines Network (SIGN), as outlined in Table 1. Evidence levels were assigned based on study design and methodological rigour, ranging from 1++ [high-quality meta-analyses or randomized controlled trials (RCTs) with very low risk of bias]to 4 (expert opinion), with intermediate categories reflecting case-control and cohort studies of varying quality (2++, 2+, 2−) as well as non-analytical studies such as case reports and case series (level 3). Grades of recommendations were subsequently assigned according to the highest level of evidence directly applicable to each clinical question: Grade A denotes recommendations supported by at least one meta-analysis, systematic review, or RCT rated 1++, or a body of evidence rated 1+ with overall consistency; Grade B reflects evidence rated 2++ or extrapolated from level 1 studies; Grade C corresponds to evidence rated 2+ or extrapolated from 2++; and Grade D is reserved for evidence of level 3 or 4, or extrapolated from 2+. Where no formal evidence was available but a clinical practice point could be identified, a good practice point (✓) was designated, reflecting the consensus-based clinical experience of the guideline development group.

Creating Expert Consensus Stataments

For clinical questions that could not be adequately addressed by the available literature, a Delphi consensus process was conducted to formulate expert-based recommendations.^{4, 5}

A panel of specialists experienced in the vNOTES technique and affiliated with the PETKOZ association were invited to participate in a structured, iterative questionnaire focusing on five domains: contraindications, preoperative preparation, perioperative care, intraoperative surgical technique, and postoperative care. Eligible clinicians were identified from the PETKOZ association expert register and invited to participate if they had performed at least 50 vNOTES procedures; this threshold was applied to ensure that panel responses reflected meaningful procedural experience. The authors acknowledge that this inclusion criterion may limit generalizability to centres with less vNOTES experience, and this is noted as a limitation of the guideline. The 22 specialists participating in the Delphi panel were affiliated with a diverse range of healthcare institutions, including university hospitals, training and research hospitals, and private healthcare centers, thereby ensuring broad representation across different levels of clinical practice and healthcare delivery settings.

A three-round survey was conducted using a web-based platform (Google Forms), with each round administered via a unique, anonymized secure link. In each round, panellists were asked to rate their level of agreement with a series of proposed recommendation statements using a five-point Likert scale (1= strongly disagree; 2= disagree; 3= neutral; 4= agree; 5= strongly agree). Responses were collected anonymously, and the aggregated results from each round were fed back to participants before the subsequent round, allowing them to reassess their judgements in light of the group’s overall responses. Statements were classified into three categories based on the proportion of panellists scoring 4 or 5 (agree or strongly agree): (1) consensus achieved (≥70% agreement)-statements were accepted and incorporated as recommendations; (2) neutral zone (50-69% agreement)-statements were revised based on qualitative feedback from the group and re-presented in the following round; and (3) no consensus (<50% agreement)-statements were excluded from the subsequent round and not carried forward. Before the third round, a virtual meeting was held to review the outcomes of the earlier rounds, concentrating particularly on statements in the neutral zone that had not yet achieved consensus. The PETKOZ expert group initially drafted the final manuscript, which was subsequently reviewed and endorsed by all participating clinicians. Recommendations derived through this process are clearly identified throughout the guideline as consensus-based expert recommendations, distinct from those grounded in the formal evidence hierarchy, as shown in Table 2.

Quality and Risk of Bias Assessment

Two independent authors assessed the methodological quality of articles independently of each other. This encompassed an evaluation of potential bias related to participant selection, outcome measurement, and data reporting, as well as bias associated with study funding sources. Discrepancies in quality assessment were resolved through discussion between reviewers. In instances where consensus could not be achieved, adjudication was provided by a third independent researcher. Cohort or observational studies were analyzed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool.⁶ Studies judged to be at critical risk of bias under the ROBINS-I framework were excluded from the quantitative synthesis, as such studies are considered incapable of providing credible effect estimates. For randomized studies, the Cochrane risk-of-bias tool was used for randomized trials (RoB 2) which scores studies as having a high, low, or unclear risk of bias in five domains: selection, performance, detection, attrition, and reporting biases.⁷ Systematic reviews and meta-analyses were critically appraised using the AMSTAR 2 framework to verify methodological integrity.⁸ AMSTAR-2 acts as a 16-item framework for assessing the methodological quality and transparency of systematic reviews. It classifies evidence into four confidence levels: high (accurate and comprehensive), moderate (minor weaknesses only), low (contains a critical flaw), and critically low (multiple critical flaws). Ultimately, reviews with low or critically low ratings are considered unreliable for providing an accurate summary of the evidence.

The results of the risk-of-bias assessments directly informed the evidence grading process. Studies rated as critical risk of bias under ROBINS-I were excluded from the evidence synthesis and did not contribute to formal recommendations. Systematic reviews rated as critically low confidence by AMSTAR 2 were excluded from primary evidence grading; their findings are reported descriptively where contextually relevant but are not cited as the evidentiary basis for any formal recommendation. For RCTs, the RoB 2 assessment was used to differentiate between evidence level 1++ (low risk across all domains) and level 1+ (some concerns in one or more domains); in the context of surgical trials, the inherent inability to blind operating surgeons was a consistent source of “some concerns” in Domain 2 (deviation from intended interventions) and was acknowledged as a domain-specific but unavoidable limitation. The overall confidence in each body of evidence, as determined through these assessments, was the primary determinant of the SIGN evidence level assigned and, subsequently, the grade of the corresponding recommendation.

Ethical approval was not required for the development of this guideline, as it was based solely on a review of the literature and expert consensus.

RESULTS

A total of 1960 records were identified through database searching, of which 57 studies met the inclusion criteria and were incorporated into the final analysis (Figure 1). The included evidence comprised eight systematic reviews and meta-analyses,^{9, 11-17} six RCTs,^{10, 18-20} six prospective cohort studies,^21-25 and 37 retrospective cohort studies.^26-65

The methodological quality of the eight included systematic reviews was appraised using the AMSTAR 2 tool across 16 items and seven critical domains (Supplementary Material 2). Only one review⁹ achieved a “high” confidence rating with full adherence across all critical domains, while five reviews were rated “low”,^{11, 12, 14, 15} one “Low-to-Moderate”,¹⁶ and one “Critically Low”.¹³ At the item level, full compliance (100%) was achieved for PICO formulation, comprehensive search strategy, duplicate study selection and data extraction, risk-of-bias tool application, interpretation of findings, and conflict-of-interest disclosure. Conversely, publication bias assessment (Item 15), a critical domain, was adequately reported in only two reviews (25%), and funding source disclosure (Item 10) was addressed in a single review (12.5%). Overall, while most reviews satisfied core methodological criteria, persistent deficiencies in publication bias assessment and funding transparency substantially limit confidence in the available evidence.

The risk of bias of the six included RCTs was evaluated using RoB 2 across five domains (Supplementary Material 3). No study was rated as high risk in any domain. Five trials^{18, 19, 20, 65} raised some concerns primarily due to the inherent impossibility of blinding surgeons in surgical trials (D2) and unblinded outcome assessment for subjective endpoints (D4). Prekatsounaki et al.⁶⁵ was a pre-planned secondary analysis of the HALON and NOTABLE trials. Both parent trials employed sham abdominal incisions to blind participants and outcome assessors, resulting in low risk of bias for D1, D2, and D4. Some concerns were noted for D3 due to exclusion of sexually inactive women, and for D5 due to the post-hoc pooled design without a pre-specified combined analysis protocol. The HALON trial¹⁰ was the only study rated as low risk across all domains, owing to participant and assessor blinding achieved through sham abdominal incisions.

The methodological quality of the 37 included retrospective studies was assessed using ROBINS-I, with full domain-level results reported in Supplementary Material 4. Under ROBINS-I, studies were rated across seven domains including bias due to confounding, participant selection, classification of interventions, deviations from intended interventions, missing data, outcome measurement, and selection of the reported result, yielding an overall judgement of low, moderate, serious, or critical risk of bias. The predominant rating across the retrospective evidence base was moderate risk of bias (n=21), most commonly driven by residual confounding inherent to non-randomized designs and incomplete adjustment for baseline differences between surgical groups. Sixteen studies were judged to carry a serious risk of bias, primarily due to substantial selection bias, absence of propensity-score adjustment, or inadequate control of confounding variables. No study was rated as critical.

Operative Time

1. Recommendation (Grade A)

vNOTES hysterectomy is associated with a significantly shorter operative time compared with TLH and should be considered in centers with appropriate surgical expertise.

Evidence Level: 1+

Among all perioperative metrics evaluated in this guideline, operative time is the most consistently reported and arguably the most reproducible advantage of vNOTES over TLH. The Cochrane systematic review by Pickett et al.⁹ provides the highest level of evidence, incorporating an RCT¹⁰ that demonstrated a mean operative time reduction of 34 minutes in favor of vNOTES compared to TLH [95% confidence interval (CI) -45.54 to -22.46], representing a clinically meaningful decrease in operative duration. This finding has been corroborated by multiple meta-analyses comparing vNOTES with laparoscopic approaches,^11-15 and the network meta-analysis by Guan et al.¹⁶ ranked vNOTES as having a shorter operative time than TLH among minimally invasive techniques. Furthermore, a systematic review evaluating robotic vNOTES hysterectomy versus robotic-assisted laparoscopic hysterectomy (RALH) for benign gynecological disease similarly favored vNOTES in operative time.¹⁷

Three high-quality RCTs comparing vNOTES with conventional laparoscopy, LESS, and vaginal approaches consequently reported shorter operative times for vNOTES.^{10, 18, 19} In contrast, a single RCT comparing vNOTES with vaginal hysterectomy for benign indications found no difference in operative time.²⁰ Prospective cohort studies of moderate-level evidence generally favored vNOTES over TLH,^21-24 although Fang et al.²⁵ reported shorter operative times with TLH. Studies in special populations, including obese patients^26-28 and those with enlarged uteri,^29-31 also demonstrated reduced operative times with vNOTES.

Conflicting results were predominantly observed in retrospective studies, which were generally of lower quality. A total of 33 retrospective studies compared vNOTES with alternative surgical approaches for hysterectomy: 11 reported no significant differences,^32-41 17 demonstrated clear advantages for vNOTES,^41-57 and five favored conventional approaches, including vaginal hysterectomy,^58-60 TLH,⁶¹ and LESS.⁶² Collectively, these findings suggest a trend toward improved outcomes with vNOTES, although heterogeneity in study design and endpoints necessitates cautious interpretation.

Hospital Stay

1. Recommendation (Grade A)

vNOTES is associated with a modest reduction in length of hospital stay compared with TLH. Although the absolute decrease is small, this reduction may contribute to improved perioperative efficiency and facilitate early discharge, particularly when integrated within ERAS protocols.

Evidence Level: 1+

Hospital length of stay is an important indicator of patient recovery and a major contributor to healthcare expenditures. Evidence from the Cochrane review by Pickett et al.⁹ demonstrates that vNOTES is associated with a modest but statistically significant reduction in hospitalisation compared with TLH (mean difference -0.50 days; 95% CI 0.97 to -0.03). While the absolute decrease is small, it may lead to meaningful efficiency gains at the system level when implemented across a hysterectomy service, especially within ERAS protocols. These findings are supported by several systematic reviews^{11, 12, 15} and reinforced by the network meta-analysis of Guan et al.,¹⁶ which positions vNOTES favorably relative to TLH, LESS, and RALH techniques.

RCTs comparing vNOTES with other minimally invasive hysterectomy approaches have consistently reported hospital stay outcomes either in favor of vNOTES or showing no significant difference. Park et al.¹⁹ found no significant difference when comparing LESS and vNOTES hysterectomy, while Yıldız et al.²⁰ reported similar findings in a comparison between vaginal hysterectomy and vNOTES. In two RCTs evaluating hysterectomy combined with apical prolapse repair to prevent post-hysterectomy vaginal cuff descent, Lowenstein et al.¹⁸ reported a shorter operative time in favor of vNOTES, whereas Bacak et al.⁶³ found no significant difference between approaches.

The perioperative advantage of vNOTES has been consistently demonstrated in prospective cohort studies^{21, 22} and corroborated across multiple retrospective series from diverse surgical centers.^{26-30,33,35,37,39,40,42,45-49,51,54,56,57,60,61} Notably, this benefit appears to be preserved in technically challenging patient populations, including those with non-descended uteri,³⁰ individuals with a history of prior pelvic surgery,⁵⁴ patients with obesity,^26-28 and those presenting with markedly enlarged uteri.^29-31

Hemoglobin Decline

1. Recommendation (Grade C)

Patients should be counseled that perioperative hemoglobin (Hb) decline following vNOTES hysterectomy is generally comparable to other minimally invasive approaches; however, variability may occur depending on surgical technique, surgeon experience, and patient-specific factors.

Evidence level: 1-

Perioperative Hb decline is a surrogate for intraoperative blood loss and is relevant to the risk of transfusion and postoperative anemia. Unlike operative time and hospital stay, the evidence for this outcome is heterogeneous and difficult to interpret. The majority of systematic reviews and meta-analyses that have addressed Hb decline, including Housmans et al.,¹¹ Marchand et al.,¹² and Chaccour et al.,¹⁵ have reported no significant difference between vNOTES and laparoscopic comparators. This finding of equivalence is supported in an RCT comparing vNOTES and LESS, also moderate-level evidence with prospective series.^{23, 64} Retrospective cohort studies of low-level evidence^{25, 26, 32, 38, 45, 54, 56} demonstrated comparable reductions in Hb levels in vNOTES cases relative to other surgical approaches.

However, the literature demonstrates some heterogeneity in findings. Several prospective and retrospective comparative studies have reported a greater decline in Hb levels following vNOTES compared to TLH,^{21, 33, 47, 62} which may be attributable to technical factors related to vaginal cuff hemostasis, the surgical learning curve, or differences in patient selection.

Estimated Blood Loss

4. Recommendation (Grade B)

1- Estimated blood loss during vNOTES hysterectomy is comparable to other minimally invasive approaches, including laparoscopic and vaginal hysterectomy.

2- Hemostatic preparation and intraoperative management should follow standard protocols for minimally invasive hysterectomy, although consideration should be given to surgical expertise and patient-specific risk factors.

Evidence level: 1-

Intraoperative blood loss estimation serves as a more dynamic clinical indicator than postoperative Hb reduction, primarily because it provides a real-time assessment of surgical hemorrhage. This immediate feedback is essential for guiding timely intraoperative interventions and fluid management strategies.

Multiple systematic reviews have assessed this outcome. Housmans et al.¹¹ observed lower EBL with vNOTES compared to laparoscopic hysterectomy, a result further supported by Marchand et al.,¹⁷ who evaluated robotic vNOTES against other surgical approaches for benign gynecological conditions. Conversely, studies by Sarkar et al.,¹³ Marchand et al.^{12, 14} and Chaccour et al.¹⁵ found no significant differences in EBL between vNOTES and laparoscopic, vaginal, or LESS approaches. In the network meta-analysis by Guan et al.,¹⁶ which included the widest range of comparators, vNOTES was positioned intermediately: EBL was higher than with TLH or RALH, yet lower than with vaginal hysterectomy in the network comparisons.

Across the currently available RCTs, in a moderate-level RCT, Park et al.¹⁹ found no difference in EBL when comparing vNOTES with LESS hysterectomy, while Lowenstein et al.¹⁸ demonstrated higher EBL with conventional vaginal hysterectomy compared to vNOTES; notably, no RCT has demonstrated a statistically significant increase in EBL in favor of any comparator over vNOTES.

In six prospective cohort studies^21-25,64 with moderate-to-high level evidence, four reported no significant difference in EBL between vNOTES and other hysterectomy approaches, while two demonstrated higher EBL with vNOTES compared to TLH. In the prospective cohort by Fang et al.,²⁵ vNOTES had a median EBL of 100 mL versus 30 mL for TLH; the authors attributed this difference to lack of prior vNOTES experience at their center, suggesting a learning curve effect rather than an intrinsic disadvantage of the technique. Moreover, in the study of Takahashi et al.,²³ vNOTES demonstrated significantly higher EBL compared to TLH (150 mL vs 70 mL, p<0.001), despite similar Hb decline. The study included surgeons with varying experience levels; while EBL was higher, the authors did not explicitly attribute this to surgical experience, although it remains a possible contributing factor given the real-world multicenter setting and the inherent learning curve associated with vNOTES procedures.

The majority of moderate-low quality retrospective series report no clinically significant difference in EBL between vNOTES and its comparators.^{27,29,35-39,42,54,55,59,62}

Blood Transfusion

5. Recommendation (Grade B)

There is insufficient evidence to recommend a specific practice. Clinicians should follow standard hemostatic protocols, with no additional precautions required solely for the vNOTES approach.

Evidence level: 2+

Blood transfusion is a clinically meaningful outcome reflecting the hemorrhagic risk of surgical procedures. Evidence comes from systematic reviews with low to critically low AMSTAR ratings,^{12, 15} a moderate-strength RCT,¹⁹ and several prospective and retrospective cohort studies of low to moderate quality. Marchand et al.¹² conducted a systematic review and meta-analysis including both randomized and observational studies, suggesting vNOTES may be associated with lower transfusion rates compared to conventional approaches; however, the review was rated critically low by AMSTAR due to limitations in study selection and risk-of-bias assessment. Similarly, Chaccour et al.¹⁵ performed a low-quality systematic review and reported no significant differences in transfusion rates between vNOTES and laparoscopic hysterectomy. At the study level, the moderate-strength RCT,¹⁹ a prospective cohort study,²⁵ and multiple retrospective cohort studies^{26,27,30,32,34,35,40-43,47,50,56} consistently found no statistically significant difference in transfusion requirements.

Overall, these data suggest that vNOTES does not increase the risk of perioperative blood transfusion. However, the evidence is limited by the predominance of retrospective studies and the low methodological quality of available systematic reviews. The primary limitation of evidence in this outcome domain is due to the rarity of the event and the consequent lack of adequately powered studies. Most reviews and individual studies are not powered to detect meaningful differences in transfusion rates.

Postoperative Pain

6. Recommendation (Grade A)

1- Patients may experience lower early postoperative pain scores with vNOTES compared with laparoscopic hysterectomy.

2- vNOTES hysterectomy is associated with lower postoperative pain compared with laparoscopic hysterectomy and should be considered when selecting the surgical approach.

Evidence level: 1+

Two RCTs^{10, 18} and four meta-analyses^12-15 consistently demonstrate that vNOTES hysterectomy results in lower early postoperative pain scores compared with conventional laparoscopic hysterectomy. The network meta-analysis by Guan et al.¹⁶ ranked approaches as LESS-LAVH > LAVH > vNOTES > TLH > LESS-TLH > VH for pain outcomes.

Prospective cohort^{23, 24, 64} and retrospective analyses from multiple institutions^{27,28,30,31,33-35,37,38,40,42-48,53,56,60-62} demonstrate that vNOTES is associated with lower postoperative pain compared with laparoscopic hysterectomy, even when controlling for uterine size, body mass index (BMI), and prior surgery.

In the RCT by Park et al.,¹⁹ postoperative abdominal pain did not differ significantly between vNOTES and LESS hysterectomy, which may reflect the widespread use of patient-controlled analgesia (PCA) potentially masking subtle differences in visceral discomfort. Vaginal pain was marginally higher in the vNOTES group, likely related to additional suturing required for cuff closure and hemostasis. Despite this, pain scores at 16 and 24 hours remained low, with no need for additional analgesics. The use of vessel-sealing devices in vNOTES, as opposed to conventional suture ligation, is proposed to further mitigate postoperative pain relative to standard laparoscopic hysterectomy.

Postoperative Analgesic Usage

7. Recommendation (Grade B)

1- Perioperative analgesic protocols for vNOTES hysterectomy should be individualized, with consideration for potentially reduced systemic analgesic requirements compared to laparoscopic approaches.

2- Clinicians should consider minimizing opioid use in patients undergoing vNOTES hysterectomy, as postoperative analgesic needs are generally low and can often be managed with non-opioid regimens.

Evidence level: 1+

Reduction in postoperative analgesic consumption is a clinically relevant surrogate for pain and patient comfort, and has direct implications for opioid-sparing recovery protocols.

A review of the available literature suggests that the current evidence is broadly consistent with this hypothesis. When the data are synthesized, postoperative analgesic requirements appear largely comparable between vNOTES and other minimally invasive techniques; however, several studies demonstrate a tendency toward lower analgesic consumption in the vNOTES cohort. In particular, the RCT by Baekelandt et al.¹⁰ reported significantly reduced analgesic requirements following vNOTES compared with TLH. Similar findings were observed in the randomized studies by Lowenstein et al.,¹⁸ who documented decreased analgesic use in vNOTES for apical prolapse relative to the conventional vaginal approach, and by Yıldız et al.,²⁰ who likewise demonstrated lower analgesic demand in patients undergoing vNOTES compared with vaginal hysterectomy.

Among prospective cohort studies comparing vNOTES with TLH, Takahashi et al.²³ and Sarikaya et al.³³ both reported reduced postoperative analgesic consumption in the vNOTES group. Jiamset et al.⁵⁷ corroborated these findings in a retrospective interrupted time-series analysis at a single centre, and Matak et al.²⁶ similarly documented lower analgesic use following vNOTES in obese patients undergoing laparoscopic versus vNOTES hysterectomy. Yıldız et al.²⁴ additionally reported lower analgesia requirements alongside improved quality-of-life scores in the vNOTES cohort.

Conversely, a number of studies across differing methodological designs and comparator groups found no statistically significant difference in postoperative analgesic consumption.^{12, 27, 30, 32, 48, 49}

Taken together, the body of evidence does not support a definitive superiority of vNOTES over other minimally invasive hysterectomy approaches with respect to postoperative analgesic consumption.

Re-Admission

8. Recommendation (Grade B)

1- Women should be informed that the risk of unplanned re-admission following vNOTES hysterectomy is comparable to that of other minimally invasive approaches.

2- Standard postoperative discharge criteria and re-admission thresholds should be applied without modification based on surgical route.

Evidence level: 1+

Unplanned hospital readmission is a composite safety outcome reflecting the severity of postoperative complications, adequacy of discharge planning, and patient resilience, and is routinely used as a quality indicator in surgical care. Reported readmission rates following vNOTES hysterectomy, across eleven studies including two RCTs, one systematic review and meta-analysis, two prospective cohort studies, and six retrospective studies, demonstrate no statistically significant differences compared with other minimally invasive hysterectomy approaches. Both the systematic review by Housmans et al.¹¹ and the randomized trial by Baekelandt et al.¹⁰ reported equivalent readmission rates between vNOTES and laparoscopic hysterectomy. These findings are further supported by a randomized trial comparing vNOTES with vaginal hysterectomy²⁰ as well as by prospective²⁵ and retrospective cohort studies from multiple centers.^{22, 36, 38, 44, 46-48} No published study has identified a significantly increased risk of readmission with vNOTES compared with any surgical comparator.

Anal Exhaust Time (Time to First Flatus)

9. Recommendation (Grade C)

1- Clinicians may consider vNOTES hysterectomy as an approach potentially associated with earlier recovery of gastrointestinal function, reflected by shorter time to first flatus, compared to other minimally invasive approaches. However, it should not be used as a sole determinant of clinical decisions.

2- Patients undergoing vNOTES hysterectomy may experience an earlier return of bowel function compared with other minimally invasive approaches; however, the magnitude of this benefit remains uncertain and may vary between individuals.

Evidence level: 2+

Time to first flatus (anal exhaust time) is used as a proxy for gastrointestinal recovery following surgery and reflects avoidance of postoperative ileus. There are no systematic reviews or RCTs addressing this specific outcome; the evidence derives entirely from prospective cohort and retrospective studies.

In a prospective cohort study, Wu et al.²¹ performed multivariate regression analysis to identify independent predictors of time to first flatus, demonstrating that vNOTES was associated with a 2.528-hour reduction compared to LESS (β=-2.528; 95% CI: -6.61 to 1.56; p=0.224), although this difference did not reach statistical significance, indicating that the observed trend in favour of vNOTES warrants further evaluation in adequately powered studies. Additionally, Tang et al.,²² in a prospective cohort study, performed linear regression analysis to identify independent predictors of postoperative recovery outcomes, confirming that surgical approach was a significant determinant of time to first anal exhaust; the median time to first flatus was significantly shorter in the vNOTES group compared to the laparoscopic hysterectomy group (48.0 h vs. 69.0 h; p<0.001), and this earlier restoration of bowel function was further associated with a favourable effect on return to work. These results are further supported by evidence from retrospective cohort studies.^{39, 43, 47}

The limitation of this evidence base is the complete absence of RCT data addressing bowel recovery as a primary endpoint. Measurement methodology is also heterogeneous, time to first flatus is subject to patient recall bias and ward documentation variability. These caveats notwithstanding, the consistency of the directional signal across studies from different institutions and countries lends biological plausibility to the finding. Prospective randomised data are needed to confirm the clinical magnitude and duration of this advantage.

Mobilization/Return to Daily Activities

10. Recommendation (Grade C)

1- vNOTES hysterectomy is associated with earlier mobilization and faster return to daily activities compared with laparoscopic hysterectomy, and this potential recovery advantage may be a relevant factor when counselling patients regarding their surgical options.

2- vNOTES may be integrated into ERAS programmes incorporating early mobilization protocols

3- Clinicians may consider vNOTES hysterectomy in patients for whom rapid postoperative recovery is a clinical priority, including obese patients and those with large uteri.

Evidence level: 2+

Earlier return to functional independence is the clinical endpoint that most directly reflects the patient experience of recovery, and available moderate-low quality evidence consistently favours vNOTES hysterectomy in this regard.

Fang et al.,²⁵ in a prospective cohort study conducted in primary hospitals, reported significantly shorter time to ambulation in the vNOTES group. Tang et al.,²² in a prospective cohort study specifically designed to evaluate rapid recovery outcomes, demonstrated earlier mobilization and faster return to daily activities following vNOTES hysterectomy. Among retrospective studies in general populations, Sarikaya et al.³³ and Uluutku Bulutlar et al.⁴⁵ similarly reported faster postoperative recovery in favour of vNOTES.

In specific patient populations, Albayrak Denizli et al.²⁸ reported earlier return to daily activities following vNOTES hysterectomy in obese patients, and Kheirbek et al.²⁹ demonstrated a similar recovery advantage in patients with large uteri.

Evidence regarding this outcome is limited by the absence of prospective randomized data and systematic analyses. Retrospective studies are inherently susceptible to ascertainment bias, as functional recovery outcomes are frequently extracted from routine clinical records rather than assessed through standardized, validated instruments. Future studies should incorporate validated patient-reported outcome measures at predefined postoperative time points and should distinguish between in-hospital mobilization and community-level return to activities.

Postoperative Sexual Function

11. Recommendation (Grade B)

1- Women should be reassured that vNOTES hysterectomy does not adversely affect postoperative sexual function compared with laparoscopic hysterectomy.

2- Clinicians should inform women that vNOTES hysterectomy is not associated with deterioration of sexual function and can be performed without expected adverse effects on postoperative sexual health.

Evidence level: 1+

Post-hysterectomy sexual function constitutes a key patient-reported outcome and is commonly a central focus during preoperative counseling. From a theoretical standpoint, the vNOTES approach could differentially impact sexual health compared with conventional laparoscopy, primarily due to the requirement for transvaginal cuff closure involving direct suturing of the vaginal vault and its adjacent supportive structures. This technical aspect has raised concerns regarding potential anatomical and functional sequelae, including vaginal vault shortening or altered sensory perception, which could negatively influence long-term sexual function.

However, the available clinical evidence does not substantiate these concerns. Randomized data from Baekelandt et al.,¹⁰ and more importantly, pooled analyses of two RCTs by Prekatsounaki et al.,⁶⁵ demonstrate no statistically significant differences in postoperative sexual function between vNOTES and laparoscopic hysterectomy when assessed using validated psychometric tools. These findings are further supported by one prospective cohort²² and three retrospective cohort studies^{32, 49, 54} in which sexual quality of life was typically evaluated as a secondary endpoint, consistently demonstrating comparable outcomes between surgical approaches.

Intraoperative Complications

12. Recommendation (Grade A)

1- Clinicians should consider vNOTES hysterectomy as a safe alternative to conventional laparoscopic or vaginal hysterectomy for benign indications, as current evidence shows comparable intra-operative complication rates.

2- Women may be reassured that undergoing vNOTES does not appear to increase the risk of intra-operative complications compared with other minimally invasive approaches.

Evidence level: 1+

The current body of literature consistently demonstrates no significant difference in intra-operative complication rates between vNOTES and other minimally invasive hysterectomy techniques, including TLH, VH, and single-port approaches.

Most systematic reviews and meta-analyses^{11, 12, 14, 15} report no significant differences when vNOTES is compared with laparoscopic or vaginal hysterectomy, although their methodological quality is often limited. A network meta-analysis suggested a relative advantage for conventional approaches, such as TLH and VH, but this finding was not consistently supported by direct comparative studies.¹⁶

Evidence from RCTs and prospective cohort series supports these findings, comparing vNOTES with both laparoscopic and vaginal approaches^{10, 18, 20, 22, 24, 64} reported similar intra-operative complication rates, with no clear advantage for either technique.

This consistency is further reinforced by a large number of retrospective cohort studies,^{26,28,29,31,32,34-36,38,39,40,41,43-50,53,59,60,62} including diverse patient populations (e.g., obese patients, large uteri, prior pelvic surgery). Across these studies, intra-operative complications, such as bleeding, organ injury, vascular injury or bladder/bowel injury, were comparable between vNOTES and alternative surgical approaches, with no reproducible increase in risk associated with vNOTES.

Postoperative Complications

13. Recommendation (Grade A)

1- Clinicians should consider vNOTES hysterectomy as having a similar post-operative complication profile compared with conventional laparoscopic or vaginal hysterectomy for benign indications.

2- Clinicians should counsel women that vNOTES does not appear to increase the risk of major or minor post-operative complications, including bleeding, infection, or need for reoperation.

3- Women may be reassured that recovery and safety outcomes with vNOTES are comparable to other minimally invasive hysterectomy techniques.

Evidence level: 1+

The systematic review by Housmans et al.¹¹ showed no significant difference in postoperative complication rates between vNOTES and laparoscopic hysterectomy.¹¹ Few meta-analyses have suggested a lower complication rate with vNOTES compared to laparoscopy,^{9, 12} while others comparing vNOTES with vaginal hysterectomy and robotic-assisted vNOTES found no meaningful differences between techniques.^{14, 17} Chaccour et al.¹⁵ reported fewer postoperative complications with vNOTES compared to classic laparoscopic hysterectomy. The network meta-analysis by Guan et al.¹⁶ ranked approaches as LESS-LAVH > LAVH > vNOTES > TLH > LESSLH > LH > VH > RALH > LESS-TLH for postoperative events, placing vNOTES among the more favourable approaches.

Well-designed RCTs^{10, 19, 20, 63} and multiple prospective cohort studies reported comparable safety profiles.^22-25 Notably, Basol et al.³⁵ and Qian et al.⁶² reported fewer postoperative complications with vNOTES. Zhang et al.⁴⁷ also reported fewer complications with vNOTES.

The majority of prospective cohort and retrospective studies found no significant difference between vNOTES and comparator approaches.^{26,28,29,31,35-40,42,43,45,46,50,51,54,56,57,59,60}

Indwelling Urinary Catheterization

14. Recommendation (Grade D)

Urinary catheter removal should be planned by clinicians for the earliest clinically appropriate time point following vNOTES hysterectomy and should be incorporated into ERAS protocols. Routine prolonged catheterisation is not indicated following uncomplicated vNOTES.

Evidence level: 2-

No systematic review or RCT has addressed catheterization duration as a primary endpoint in the context of vNOTES hysterectomy; the available evidence is therefore derived exclusively from observational data.

The prospective cohort study by Fang et al.,²⁵ which carries the highest methodological weight among the available non-randomized evidence, demonstrated significantly shorter indwelling urinary catheterization time in the vNOTES group compared to conventional laparoscopic hysterectomy (31.1±17.3 hours vs 45.6±22.7 hours, p=0.012). Consistent results have been reported across multiple moderate- to low-quality retrospective cohort studies, which also show shorter catheterization duration with vNOTES relative to laparoscopic or single-port approaches.^{26, 37, 39, 42, 48} However, the absence of randomized data and variability in catheter removal protocols across institutions limit the strength of conclusions.

Conversion Rate

15. Recommendation (Grade B)

Clinicians should counsel patients that conversion rates with vNOTES hysterectomy are low and comparable to other minimally invasive approaches. The choice of surgical technique should therefore be based on patient factors, surgeon experience, and available expertise rather than concerns regarding conversion risk.

Evidence level: 1+

Conversion from the planned surgical approach to a different modality (laparotomy or laparoscopy) represents an important safety indicator reflecting the feasibility and safety of vNOTES at institutional and individual surgeon levels. Low conversion rates are essential for any surgical technique to be incorporated into mainstream practice with confidence.

Three recent systematic reviews and meta-analyses, including two low-quality and one critically low-quality AMSTAR-rated study, reported no significant differences in surgical outcomes between vNOTES and laparoscopic hysterectomy for benign gynecological indications.^{12, 14, 15}

In an RCT by Baekelandt et al.,¹⁰ no conversions from vNOTES to an alternative surgical approach were reported among 70 women undergoing hysterectomy. Similarly, two additional RCTs^{18, 19} comparing vNOTES with laparoendoscopic single-site hysterectomy and conventional vaginal surgery for apical prolapse  reported zero conversions in either group

Consistently, moderate-to-low-quality prospective and retrospective cohort studies indicate comparable conversion rates between vNOTES and other hysterectomy techniques,^{22,25,26,29,31,35,36,38,41,40,43,46,48-51,56-60,64} with none demonstrating a statistically significant increase in conversions for vNOTES in benign gynecological surgery.

The notable exception is in the comparison with LESS, where Wu et al.²¹ reported a higher conversion rate with vNOTES (4.29%); in all three converted cases, the indication was severe adhesion at the posterior fornix, which precluded safe transvaginal access and created an unacceptable risk of injury to adjacent pelvic organs, rather than representing a limitation intrinsic to the vNOTES approach itself.

Cost Analysis

16. Recommendation (Grade D)

Institutions considering the adoption of vNOTES should undertake a prospective local economic evaluation accounting for equipment procurement, training costs, operative time savings, and bed day reductions. Formal health technology assessment is recommended prior to national-level commissioning decisions.

Evidence level: 2+

No RCT has included cost-effectiveness analysis as a primary endpoint for vNOTES, and no systematic review has addressed this outcome as a primary objective. Available evidence is limited to institutional cost analyses and observational comparisons. Potential cost drivers include equipment procurement, training requirements, and learning curve duration.

The strongest available evidence comes from the RCT by Baekelandt et al.,¹⁰ in which direct healthcare costs were assessed using the total hospital bill, encompassing all expenses incurred up to six weeks postoperatively. Although mean total costs were lower in the vNOTES group compared with TLH (USD 3.599±914 vs. USD 4.103±1.348), corresponding to a mean difference of -504 USD (95% CI -1,044 to +36), this difference did not reach statistical significance.

However, the broader literature does not consistently support a cost advantage for vNOTES. While the highest-quality evidence suggests cost neutrality, lower-quality retrospective studies^{52, 60} report conflicting findings, with some indicating lower costs for LAVH compared with vNOTES.

Overall, the economic impact of vNOTES remains highly context-dependent and is influenced by institutional case volume, existing laparoscopic infrastructure, and reimbursement models. In the absence of formal health technology assessment or prospective cost-effectiveness analyses, current evidence does not allow definitive conclusions regarding cost superiority.

DISCUSSION

The present national guideline suggests that vNOTES hysterectomy is a feasible and safe, minimally invasive approach for benign gynecological indications when performed in appropriately selected women and in centres with relevant surgical expertise.^66-68 The most consistent benefits identified across the available literature were shorter operative time, reduced early postoperative pain, a modest but noticeable reduction in hospital stay, and faster postoperative recovery compared with conventional laparoscopic hysterectomy. Importantly, these advantages were not accompanied by a clear increase in intraoperative or postoperative morbidity, as complication, readmission, and conversion rates were generally comparable with those reported for other minimally invasive hysterectomy techniques.

The main strength of this guideline is that it combines a structured appraisal of the available evidence with a formal Delphi-based expert consensus process, thereby allowing clinically relevant recommendations to be formulated even in areas where direct comparative data remain limited. This is particularly important in the context of vNOTES hysterectomy, where rapid clinical adoption has outpaced the development of standardized guidance in several domains of perioperative care and surgical technique. In addition, the guideline addresses both comparative surgical outcomes and practical aspects of implementation that are directly relevant to routine clinical practice.

These findings should, however, be interpreted in light of important limitations. Although some recommendations were supported by RCTs and systematic reviews, a substantial proportion of the evidence base consisted of observational studies with moderate to serious risk of bias. Methodological heterogeneity was also considerable, particularly with respect to patient selection, surgeon experience, perioperative protocols, comparator groups, and outcome definitions. Furthermore, several clinically important questions could not be answered from the published literature alone and therefore required consensus-based recommendations. As with other evolving surgical techniques, learning-curve effects and institutional variation are also likely to have influenced reported outcomes.

Within the Turkish healthcare system, the economic impact of vNOTES is further influenced by the cost of disposable access platforms and instruments, which are procured through institutional tender systems and may vary between centers. Current Social Security Institution (SGK) reimbursement policies do not always specifically cover these vNOTES-specific disposable materials, potentially increasing institutional cost burden. In comparison, although laparoscopic surgery also relies on disposable instruments, these are more standardized and better integrated into existing reimbursement frameworks. It should be noted that vPORT™, a novel Turkish disposable access device developed by Biomicro Medikal (Istanbul, Turkiye), has recently emerged as a cost-effective and efficient port system for use in vNOTES procedures. Surgeons in Turkiye are reducing costs by reusing disposable ports, using the cost-effective Turkish-branded vPORT™, and finally, using glove ports in exchange for surgical discomfort.⁶⁹ Despite potentially higher upfront costs, shorter hospital stay, reduced recovery time and the absence of additional uterine manipulator and trocar costs may partially offset overall expenses, making the net economic effect of vNOTES largely dependent on institutional volume and local procurement conditions.

Taken together, the evidence makes a credible case for vNOTES hysterectomy as a meaningful addition to the surgical armamentarium for benign gynecological disease. To truly establish its place, however, the field needs larger more rigorous RCTs, more consistent reporting of perioperative and patient-reported outcomes, and prospective health-economic analyses, all of which will be essential for refining patient selection and informing future iterations of this guideline.

Study Limitations

Most of the guideline recommendations have low certainty of evidence and serious to moderate risk of bias, highlighting the need for higher quality data to aid in refining future recommendations. In addition, the expert panel was restricted to surgeons with experience of at least 50 vNOTES cases. While this criterion was applied to ensure adequate procedural expertise, it may limit the generalizability of the recommendations to centres with lower case volumes or surgeons earlier in their learning curve.

Recommendations for Future Research

Despite recent advances, there remain several unanswered questions and priorities for future research. These areas include the following: (1) Optimal anesthesia regimen specifically for vNOTES hysterectomy; (2) the role of strategies to reduce postoperative pain such as intraperitoneal irrigation or rectus sheath block; (3) predictors for conversion to laparoscopy; (4) the role of outpatient management of benign vNOTES hysterectomy; (5) optimal technique for prophylactic apical suspension following vNOTES hysterectomy; (6) optimal technique for transvaginal surgical drain following a vNOTES hysterectomy; (7) the effects of vNOTES training courses using hands-on models and their outcomes; and (8) outcomes for repeat vNOTES following a vNOTES hysterectomy or repeat vNOTES hysterectomy following another vNOTES procedure. Further studies and research in these priority areas are needed to improve the outcomes of the vNOTES technique for hysterectomy performed for benign conditions and to better define optimal management.

Plans for Updating

The topics listed above that were not covered in this guideline will be addressed in future guideline documents and expert practice opinion papers. Given the expectation of new national data results and RCTs, this guideline is planned to be updated within two years, following a literature review of newly published works on the first anniversary of its publication.