Effectiveness, Safety, and Patient Satisfaction of Laparoscopic Uterosacral Nerve Ablation in Terms of Pain Relief in Women with Chronic Pelvic Pain

Currently, there is no uniform international definition of chronic pelvic pain (CPP). In most guidelines, CPP is defined as pain that originates in the pelvis and lasts longer than 6 months.[ 1 2 3 4 ] It is not related to pregnancy and may be either constant or episodic but is not cyclic.[ 5 ] As the name suggests, the pain is limited to the lower abdomen, the anatomical pelvis of the woman.[ 6 ] The symptoms are often associated with negative cognitive, behavioral, sexual, and emotional consequences and suggestive of lower urinary tract, sexual, bowel, myofascial, or gynecologic dysfunction.[ 1 7 ] The consequences are high incidences of illness and a poor subjective quality of life.[ 8 9 10 11 ] The exact prevalence of CPP is not known. There is no single etiology which causes CPP. The causes are not uniquely gynecologic but also involve other organ systems such as the gastrointestinal, urogenital, muscular, or nerval system.[ 12 13 14 ] Gynecologically, endometriosis is the most common cause of CPP.[ 15 16 ] Besides conservative therapies such as nonsteroidal anti-inflammatory drugs, laparoscopy is common for the diagnosis and treatment of CPP.[ 17 ] However, in a reasonable amount of cases, no definite cause of CPP is found during laparoscopy.[ 9 ] Laparoscopic uterosacral nerve ablation (LUNA) describes a surgical procedure in which the afferent sensory nerve fibers of the so-called Lee-Frankenhauser nerve plexus are interrupted.[ 8 ] From the inferior mesenteric ganglion/inferior mesenteric plexus, the superior hypogastric plexus, the hypogastric nerves, and the inferior hypogastric plexus arise the sympathetic fibers for supplying the uterus/vagina and the bladder. The pelvic splanchnic nerves, as the sacral part of the parasympathetic system, originate from the sacral nerve roots and supply the uterus/vagina and the bladder.[ 18 ] The technique of vaginal transection of the uterosacral nerves was first described by Doyle in 1955.[ 19 ] There are numerous studies in which the therapy of LUNA has been tested for its effectiveness. Some of these show a positive effect of LUNA on pain perception in patients with primary or secondary dysmenorrhea.[ 20 21 ] In contrast, several randomized controlled studies show that patients with dysmenorrhea undergoing surgical therapy in terms of LUNA did not report significant pain relief.[ 8 21 22 23 24 ] Because of the lack of evidence, LUNA has not been recommended as a routine procedure. Through our study, we aim to improve the evidence for LUNA and shed light on the influence of LUNA in CPP patients without underlying endometriosis.

In this retrospective study, we included 13 women who underwent LUNA for chronic lower abdominal pain without underlying intraoperative pathological correlate. The general characteristics of the patients are shown in Table 1 . The average age of the study population was 25.8 years. All women were premenopausal. Two-third of the study participants had a higher education status. Regarding the occupations of the female patients, there were no discernible patterns. Most of the patients were of normal weight. 33.3% were light obese, and only one study participant had Grade I obesity. Almost half of all patients were healthy. The others had various previous diseases, but no conspicuously frequent disease could be identified. Structure of the study group BMI: Body mass index The results of the survey before and after surgery are presented in Tables 2 and 3 . Patients were asked if they felt controlled by the pain. Statistical significance was found when comparing pre- and postoperative status ( P = 0.0312) [ Figure 1 ]. Whereas before surgery there were nine patients who felt controlled by their pain, postoperative only three patients reported to be controlled by their pain. Patients were better able to deal with pain postoperatively and no longer felt unable to cope with it ( P = 0.0039) [ Figure 1 ]. Nine patients indicated preoperatively they could not deal with their pain. After the surgical procedure with LUNA, only two patients still reported being unable to cope with pain. Distress level decreased significantly after surgery ( P = 0.0156). Before treatment with LUNA, 11 out of 12 patients were desperate due to the pain. After surgery, only four patients stated that they were still in despair because of the pain. Eight patients indicated that they were hardly or no longer desperate. The results are shown in Figure 1 . Survey results - questionnaire before and after surgery Survey results - questionnaire before and after surgery Evaluation of pain during menstruation before and after surgery. All results were statistically significant The amount of painkillers taken was significantly higher before than after surgery, and the pain level was lower after surgery ( P = 0.0156 and P = 0.0312) [ Figure 2 ]. Seven patients stated that they frequently took painkillers before surgery. Postoperatively, only three patients did any longer. Four patients stated that they needed less painkillers. Evaluation of how often dysmenorrhea appeared a week before and after surgery. * P < 0.05 When we asked patients about the intensity of pain on the Numeric Rating Scale (NRS) before and after surgery, women indicated that after surgery the pain would be less intense ( P = 0.0041) [ Figure 3 ]. The NRS Pain Scale ranges from 1 to 10, with 1 being no pain and 10 being the most severe pain the patient could imagine. Before surgery, two patients, respectively, reported pain of 2 and 4 on the NRS. Four patients reported pain of 8 on the pain scale. Two patients, respectively, had pain of 7 or even 9 on the NRS. Overall, it was found that none of the patients had pain below 4 on the NRS Pain Scale (low pain level) before surgery. After the procedure, a total of 4 patients stated that they had pain of 1–3 on the NRS Pain Scale. Three of them even stated that they had pain of 1 on the pain scale. The reported pain reduction was statistically significant. Evaluation of pain associated with dysmenorrhea before and after surgery throughout the study population. * P < 0.05 Furthermore, questions were asked about social isolation, sexual activity, self-confidence, disgruntlement, and ability to work. The evaluation of these questions showed a positive trend in each case but was not statistically significant. Preoperatively, 3 out of 12 patients felt isolated due to their pain. Postoperatively, only one patient reported feeling socially isolated. This result was not significant but showed a slightly positive trend. Preoperatively, six patients avoided sexual activity while five patients stated that they did not avoid sexual contact due to the pain. Postoperatively, only two patients avoided sexual contact due to pain. The other four patients reported the pain to be compensated, so that they were able to have sexual intercourse. The questionnaire also specified whether a sexual intercourse was painful for the patients. Before treatment with LUNA, five patients reported pain during sexual intercourse. Only 3 out of 12 patients had no pain during sexual intercourse. Postoperatively, only three patients reported pain during sexual contact. Instead of three, there were eight patients postoperatively who no longer experienced pain during sex. Although the results were not statistically significant, they still show a positive trend. The survey did not reveal any major difference about the question whether the patients could participate in everyday work. Preoperatively, there were eight patients who were able to work regardless of the pain; postoperatively, there were nine patients for whom the pain did not affect their everyday work. Although the patients were able to work, eight patients stated that their performance at work was impaired by the pain preoperatively. Only four patients stated that their performance was not negatively affected due to pain. After treatment with LUNA, only a third of the patients stated that their performance at work was negatively affected by the pain. Patients were also asked about the pain frequency during the week. A third of the patients reported suffering from pain every day pretreatment. One patient reported suffering from pain at least once a week. Respectively, two patients had pain at least two and three times a week. Three patients had pain at least 5 out of 7 days. Postoperatively, two and four patients, respectively, only suffered from pain once or twice a week. Postoperatively, instead of four patients, there were now only two patients who suffered 7 days a week from pain.

In our retrospective study, we were able to show a decrease of pain frequency and pain insensitivity for women with CPP who underwent LUNA. Further prospective randomized, double-blind studies are needed to test if LUNA as a surgical technique is an appropriate treatment option for CPP. LS: Project development, Data management, Data analysis, Manuscript writing, JH: Manuscript editing, DF: Manuscript editing, EK: Manuscript editing, PH: Manuscript editing, LB: Project development, Data analysis, Manuscript editing. All authors read and approved the final manuscript. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. There are no conflicts of interest.

CPP is a common symptom in women, which often leads to severe symptoms reducing quality of life and absenteeism from work. The causes are variable. Pain from the uterus and ligamentous structures is transmitted to the parasympathetic ganglia through the Lee-Frankenhauser nerve plexus (sensory) and through the uterosacral ligaments.[ 25 ] It can be concluded that a disruption of the same leads to a decrease in pain transmission. With our retrospective study, we aimed to evaluate the effectiveness of the LUNA surgical technique as a treatment for CPP. Patients were retrospectively asked about their experience and satisfaction after LUNA surgery. We were able to show that LUNA had a significant improvement in terms of pain relief. Study participants reported suffering less frequently and less severely from CPP. This was also reflected in the decrease of painkillers’ consumption after surgery. These results go in line with findings in the literature.[ 20 21 ] Limitations of our study include the small patient population, the retrospective approach, and the nonblinding of patients and practitioners. The patients were selected according to strict criteria: the prerequisites were the presence of CPP, no intraoperative abnormalities, no previous diseases, and the consent of the patients to perform a LUNA in this case. This resulted in a small, selected sample size. Due to the promising results of this study, a large, randomized prospective study is planned to review this retrospective observational study. Another limiting factor is the placebo effect of laparoscopic interventions. Laparoscopy may have a placebo effect for up to 3–6 months.[ 26 27 ] In the literature, endometriosis surgery is associated with a 30% placebo response rate. This is independent on the severity of the disease.[ 28 29 ] Thus, there may also be a mechanism by which laparoscopy alone leads to a temporary improvement in pelvic pain symptoms. Based on a 30% placebo rate after laparoscopy, our study nevertheless shows a positive effect of LUNA therapy. Despite a small study population, we were able to demonstrate a significant reduction in pain and pain intensity. A controlled randomized trial by Johnson et al . demonstrated a significant benefit of LUNA in patients with dysmenorrhea without endometriosis.[ 8 ] In contrast, our patients were not randomized to endometriosis and nonendometriosis and the target group was CPP. Nevertheless, our results revealed a significant reduction in pain, too. Juang et al . could show that over half of the study patients felt satisfied with the results of treatment with LUNA. Performed by trained gynecologic laparoscopic surgeons, the surgery time was extended by only a few minutes.[ 30 ] In concordance with our study, they could show a reduction of pain in women with dysmenorrhea. In concomitance with Johnson et al .’s study, we were also able to show that LUNA as a surgical therapy for dysmenorrhea has very low risk. No major complications were recorded in our study.[ 8 ] Statistical significance can be particularly emphasized here, as this is a very small study population because in large case numbers, even small differences may become significant. Participation rate is the most important potential bias. In addition, retrospective study design is potentially associated with recall bias. The National Institute for Health and Clinical Excellence[ 31 ] has studied LUNA for CPP. There is some evidence supporting the effectiveness of performing LUNA in women with primary dysmenorrhea. This is contradicted by the 2005 guidelines of the European Society for Human Reproduction and Embryology. This concludes that there is no evidence that a LUNA is necessary.[ 32 ] Another guideline published by the Royal College of Obstetricians and Gynecologists states that there is no evidence of the effectiveness of the LUNA technique for endometriotic lesions.[ 33 ] The concept of the LUNA method is based on the anatomical fact that afferent nerves from the pelvic organs run through the uterosacral ligament. By interrupting these, a reduction in pain should occur. Daniels et al . are not convinced by this method after conducting a large randomized control trail. The authors assumed that the anatomical and physiological situation in CPP is more complicated than pain induction by the afferent nerves in the uterosacral ligament alone. LUNA could extinguish some of the nerve fibers, but the others would be densely interwoven with vessels or the uterus.[ 9 ] They reported no significant difference in noncyclic pain, dysmenorrhea, or dyspareunia on a Visual Analog Pain Scale after a medial follow-up of 69 months. Furthermore, in women with CPP, LUNA did not result in a statistically significant pain relief. The analgesic ladder developed by the World Health Organization recommends initial treatment of chronic pain with nonopioid medication.[ 34 ] Nonopioid medication is also commonly used in the treatment of CPP.[ 35 ] Another conservative approach to treat CPP is physiotherapy, which typically targets dysfunction of the pelvic floor, hip, back, and abdominal wall muscles. This refers to therapeutic interventions such as manual therapy, tissue mobilization, and biofeedback, but also other techniques such as acupressure and ultrasound therapy are recommended.[ 2 ] However, women affected by CPP who do not respond to nonpharmacological and conservative therapies have the option of surgical treatment for pain relief. These include procedures such as presacral neurectomy, adhesions dissolution, and LUNA. For the moment, there are limited data supporting a role for these surgeries in the treatment of CPP. During a presacral neurectomy, the hypogastric plexus is dissected in order to denervate the sensory communication between the pelvic organs and the abdominal wall. This is an effective way of treating refractory pelvic pain and thus alleviate the existing pain.[ 36 ] This surgical procedure should only be carried out by a surgeon experienced in the presacral space. A prospective randomized double-blind controlled trial compared combined presacral neurectomy and surgical treatment of endometriosis with laparoscopic treatment of endometriosis alone in women with dysmenorrhea. The authors reported improved pain control with the combined approach (12-month cure rate: 86% vs. 57%).[ 37 ] Other retrospective studies report success rates of 62%–73%, particularly in patients with CPP who did not respond to other treatments.[ 38 39 ] The two methods for reducing primary dysmenorrhoea were compared in a study by Chen et al. , in which the presacral neurectomy performed better than LUNA.[ 22 ] The National Institute for Health and Clinical Excellence states that there are no significant differences in short-term pain relief between LUNA and laparoscopic presacral neurectomy.[ 31 ] A meta-analysis reported a few complications. two case reports described five cases of uterine prolapse after LUNA, two of them had already given birth to children, three were nulliparous.[ 30 40 41 ] Overall, this is a very small number of complicating events. Major complications such as urinary urgency, constipation, and postoperative bleeding were more common with presacral neurectomy than with LUNA.[ 42 ] In terms of effectiveness on improving health-related quality of life, psychiatric profile, and sexual satisfaction, the study by Johnson et al . showed that women with CPP without endometriosis experienced a significant reduction in dysmenorrhea after 12 months if they had undergone LUNA therapy. In contrast, the authors found that there was no significant difference in nonmenstrual pelvic pain, deep dyspareunia, or dyschezia in women without endometriosis who underwent LUNA compared to women without LUNA. Thus, the authors concluded that LUNA is effective for dysmenorrhea, but only when endometriosis is not present.[ 8 ] However, this did not apply to those women who were diagnosed with endometriosis. An Italian randomized controlled trial by Vercellini et al . included 180 patients who underwent surgical laparoscopy as first-line treatment for symptomatic Stage I to IV endometriosis. These women were randomized into two study arms: surgical laparoscopy with resection of the uterosacral ligament or conservative surgery alone. Primary endpoint was the rate of women with moderate-to-severe dysmenorrhea 1 year after surgery. The authors concluded that additional resection of the uterosacral ligament during laparoscopic surgery for endometriosis did not lead to a reduction in the frequency and severity of recurring dysmenorrhea.[ 23 ] El-Din Shawki found a significant difference in dyspareunia, but not in primary and secondary dysmenorrhea. Two groups that underwent diagnostic laparoscopy and LUNA were compared.[ 7 ] Certainly, there is a need to discuss how LUNA should be performed in detail, i.e., how much the sacrouterine ligament should be incised after coagulation. Not only due to the small study population, our retrospective study suggests that further large, randomized trials are needed to establish the LUNA surgical technique as a treatment option for CPP and dysmenorrhea. Furthermore, long-term outcome of LUNA should be investigated in further studies.

This is an analytical semi-longitudinal observational study. All women who underwent LUNA within the last 3 years with an inconspicuous intraoperative site were included. The cohort was determined using the codes of surgery and routines 5–694 and a physician letter search using the terms: “LUNA” and “laparoscopic uterosacral nerve ablation.” The data were provided by the Enterprise Clinical Research Data Warehouse (ECRDW). ECRDW is a multidisciplinary platform for research-relevant issues. The data stock of this ECRDW consists of consolidated, high-quality data from heterogeneous systems. Exclusion criteria were language barriers, which did not allow participation to take part in the questionnaire. Between January 2018 and December 2020, medical data were collected for research purpose from patients undergoing LUNA with an inconspicuous intraoperative site during laparoscopy. We identified 13 patients who agreed to participate in the study and underwent LUNA because of CPP without a pathological correlate intraoperatively. After information and written consent was given, medical data were collected retrospectively. The women participated in a postsurgery questionnaire. The questions addressed effectiveness, outcome, and satisfaction after LUNA. The primary endpoint of this study was to provide an overview of the effectiveness, safety, and patient satisfaction of laparoscopic uterosacral nerve ablation. Preparation of the patient under general anesthesia according to standard for a laparoscopy with appropriate positioning and attachment of the head supports for Trendelenburg position. Creation of a pneumoperitoneum using a Veress needle and entering with the 10 mm trocar at umbilical level was done to visualize the anatomy in the pelvis. Insertion of at least two 5 mm trocars followed. We visualized the ureter in their retropelvic course before identification of the uterosacral ligaments on the left and right sides. The ablation was performed close to the uterus at least 1 cm posterolaterally on each side. The ablation of the uterosacral ligaments on both sides by bipolar electrodiathermy using a Kelly bipolar coagulation forceps was performed. Final separation of the ligaments after coagulation using a Metzenbaum scissors was done. Finally, we checked for blood dryness. By performing the ablation, the sensory nerve fibers leaving the uterus, which are located in the uterosacral ligaments, were cut. The surgical report was written by the surgeon himself immediately after the surgery. This study was approved by the local ethics committee and conducted according to the principles of the Declaration of Helsinki (approval number: 9684_BO_K_2021). Informed consent was waived by the ethics committee due to the use of retrospective and de-identified data. However, patients who completed the questionnaire part were required to give written informed consent. The data were assembled in a databank and were analyzed using Microsoft Excel 2021 (version 16.56; Microsoft Corp., Redmond, WA, USA). Statistical analyses were performed using GraphPad Prism 9 software (GraphPad Software Inc., 225 Franklin Street. Fl. 26 Boston, MA 02110) and IBM SPSS Statistics 28 (IBM SPSS Software Version 28.0. Armonk, NY: IBM Corp). Shapiro–Wilk normality test was used to test for normal distribution of epidemiological data. Unpaired t -test and Mann–Whitney U -test were used as appropriate.