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Essam R Othman,1,2 Ayman Al-Hendy,3 Radwa Mostafa,1 Cornelis B Lambalk,2 Velja Mijatovic2 1OB-GYN Department, Assiut University, Assiut, 71515, Egypt; 2Academic Endometriosis Center, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; 3Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL, 60637, USACorrespondence: Essam R Othman, Department of Obstetrics and Gynecology, Assiut University, Assiut, Egypt, Email essamothman@aun.edu.egAbstract: Current medical treatment options for endometriosis associated pains are inadequate. Evidence on effects of nonsteroidal anti-inflammatory drugs is scarce. Around one third of patients are not responsive to oral contraceptives or progestins due to progesterone resistance. Gonadotropin-releasing hormone (GnRH) agonists can only be used for a short duration because of associated side effects. Oral GnRH antagonists, including elagolix, relugolix, and linzagolix allow oral administration, induce dose dependent reduction of estradiol levels, do not cause initial flare up of endometriosis symptoms, and allow the fast return of ovarian function and menstruation after discontinuation. Elagolix at a low dose of 150 mg once daily, or the higher dose of 200 mg twice daily, significantly increased the proportion of women achieving clinically meaningful decline of dysmenorrhea, noncyclic pelvic pain, and dyspareunia. Relugolix at an oral dose of 40 mg/day results in improvement in different forms of endometriosis related pelvic pain, with an efficacy and side effect profile similar to that of GnRH agonists. Adding 1 mg of estradiol and 0.5 mg of norethindrone to 40 mg of relugolix (relugolix combination therapy) allows extension of treatment to 24 weeks with maintained efficacy and an improved side effect profile. Linzagolix, in a dose of 75 mg/day, can be used alone to treat endometriosis associated pain. For severe pelvic pain and dyspareunia, linzagolix can be used in a high dose of 200 mg/day with hormonal add-back therapy to preserve bone health.Plain Language Summary: Oral gonadotropin-releasing hormone (GnRH) antagonists, including elagolix, relugolix, and linzagolix, represent a new addition in the armamentarium against endometriosis associated pain. They are given orally, do not cause an initial flare-up of disease symptoms, allow a return of menses quickly after their withdrawal and produce a balance between ability to relieve endometriosis associated pain and side effects profile. The addition of hormonal agents like estradiol 1 mg and norethindrone acetate 0.5 mg to relugolix (relugolix combination therapy) allowed longer use of the medication for relief of endometriosis associated pain while reducing side effects like bone mineral density loss and hot flushes.Keywords: endometriosis, pain, elagolix, relugolix, linzagolix, estradiol, norethindrone

Matthanja Bieze,1,2,* Annelotte Pauline van Haaps,3,4,* Leonardo Kapural,5 Sean Li,6 Kris Ferguson,7 Ralph de Vries,8 Michael E Schatman,9,10 Velja Mijatovic,3,4 Jan Willem Kallewaard1,11 1Department of Anesthesiology and Pain Management, Amsterdam UMC Location University of Amsterdam, Amsterdam, the Netherlands; 2Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; 3Department of Reproductive Medicine, Amsterdam University Medical Center location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; 4Amsterdam Reproduction and Development, Amsterdam University Medical Centers, Amsterdam, the Netherlands; 5Carolina’s Pain Institute and Center for Clinical Research, Winston Salem, North Carolina, USA; 6National Spine and Pain Centers, Shrewsbury, New Jersey, USA; 7Aspirus Langlade Hospital Pain Clinic, Antigo, Wisconsin, USA; 8Medical Library, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; 9Department of Anesthesiology, Perioperative Care & Pain Medicine, NYU Grossman School of Medicine, New York, New York, USA; 10Department of Population Health – Division of Medical Ethics, NYU Grossman School of Medicine, New York, New York, USA; 11Department of Anesthesiology and Pain Management, Rijnstate Ziekenhuis, Arnhem, the Netherlands*These authors contributed equally to this workCorrespondence: Jan Willem Kallewaard, Department of Anaesthesiology and Pain Management, Amsterdam UMC location University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands, Email j.w.kallewaard@amsterdamumc.nlAim: Visceral pain, characterized by pain that is diffuse and challenging to localize, occurs frequently and is difficult to treat. In cases where the pain becomes intractable despite optimal medical management, it can affect patients’ Quality of Life (QoL). Spinal Cord Stimulation (SCS) has emerged as a potential solution for intractable visceral pain.Purpose: In this narrative review, we collected all evidence regarding the efficacy of SCS for visceral pain across various underlying conditions.Methods: A comprehensive literature search was conducted in PubMed, Embase, and Web of Science in which articles published from October 1st, 1963 up to March 7th, 2023 were identified.Results: Seventy articles were included in this review of which most were retrospective cohort studies, case series and case reports. The studies, often with a small number of participants, reported on SCS for chronic pancreatitis, anorectal pain and bowel disorders, gynaecological diagnoses, visceral pelvic pain, urological disorders and finally general visceral pain. They found positive effects on pain and/or symptom relief, opioid consumption, anxiety and depression and QoL. Complications occurred frequently but were often minor and reversible.Conclusion: Better screening and selection criteria need to be established to optimally evaluate eligible patients who might benefit from SCS. A positive outcome of a sympathetic nerve block appears to be a potential indicator of SCS effectiveness. Additionally, women receiving SCS for endometriosis had a better outcome compared to other indications. Finally, SCS could also relief functional symptoms such as voiding problems and gastroparesis. Complications could often be resolved with revision surgery. Since SCS is expensive and not always covered by standard health insurance, the incorporation of cost-analyses is recommended. In order to establish a comprehensive treatment plan, including selection criteria for SCS, rigorous prospective, possibly randomized and controlled studies that are diagnosis-oriented, with substantial follow-up and adequate sample sizes, are needed.Keywords: neuromodulation, SCS, spinal cord stimulation, visceral pain, chronic pelvic pain, chronic pain

STUDY QUESTION What is the influence of dietary interventions, namely the low fermentable oligo-, di-, mono-saccharides, and polyols (Low FODMAP) diet and endometriosis diet, on endometriosis-related pain and quality of life (QoL) compared to a control group? SUMMARY ANSWER After adhering to a dietary intervention for 6 months, women with endometriosis reported less pain and an improved QoL compared to baseline whereas, compared to the control group, they reported less bloating and a better QoL in 3 of 11 domains. WHAT IS KNOWN ALREADY Standard endometriosis treatment can be insufficient or may be accompanied by unacceptable side effects. This has resulted in an increasing interest in self-management strategies, including the appliance of the Low FODMAP diet and the endometriosis diet (an experience-based avoidance diet, developed by women with endometriosis). The Low FODMAP diet has previously been found effective in reducing endometriosis-related pain symptoms, whereas only limited studies are available on the efficacy of the endometriosis diet. A survey study recently found the endometriosis diet effective in improving QoL but currently no guidelines on use of the diet exist. STUDY DESIGN, SIZE, DURATION A prospective one-center pilot study was performed between April 2021 and December 2022. Participants could choose between adherence to a diet—the Low FODMAP diet or endometriosis diet—or no diet (control group). Women adhering to a diet received extensive guidance from a dietician in training. The follow-up period was 6 months for all three groups. For all outcomes, women adhering to the diets were compared to their baseline situation and to the control group. PARTICIPANTS/MATERIALS, SETTING, METHODS We included women diagnosed with endometriosis (surgically and/or by radiologic imaging) who reported pain scores ≥3 cm on the visual analogue score (0–10 cm) for dysmenorrhea, deep dyspareunia, and/or chronic pelvic pain. The primary endpoint focused on pain reduction for all pain symptoms, including dysuria, bloating, and tiredness. Secondary endpoints, assessed via questionnaires, focused on QoL, gastro-intestinal health, and diet adherence. MAIN RESULTS AND THE ROLE OF CHANCE A total of 62 participants were included in the low FODMAP diet (n = 22), endometriosis diet (n = 21), and control group (n = 19). Compared to their baseline pain scores, participants adhering to a diet reported less pain in four of six symptoms (range P  < 0.001 to P  = 0.012) and better scores in 6 of 11 QoL domains (range P  < 0.001 to P  = 0.023) after 6 months. Compared to the control group, analyzed longitudinally over the 6-month follow-up period, participants applying a diet reported significant less bloating (P  = 0.049), and better scores in 3 of 11 QoL domains (range P  = 0.002 to P  = 0.035). LIMITATIONS, REASONS FOR CAUTION No sample size was calculated since efficacy data were lacking in the literature. In order to optimize dietary adherence, randomization was not applied, possibly resulting in selection bias. WIDER IMPLICATIONS OF THE FINDINGS Our study suggests that women could benefit from adherence to a dietary intervention, since we found lower pain scores and better QoL after 6 months. However, caution is implied since this is a pilot study, no sample size was calculated, and data on long-term effects (>6 months) are lacking. The results of this pilot study underline the importance of further research and the drawing up of guidelines. STUDY FUNDING/COMPETING INTEREST(S) A.v.H. reports receiving a travel grant from Merck outside the scope of this study. J.W. S.V. J.T. and B.D.B. have no conflicts of interest to report. A.d.V. reports having received KP-register points for internship guidance of J.W. performing paid consultations with endometriosis patients outside the study and receiving reimbursements for educational lectures at the local hospital (Albert Schweitzer Ziekenhuis, Dordrecht, the Netherlands). A.S. reports having received expenses for travel and hotel costs as an invited speaker from ESHRE. This was outside the scope of this study. M.v.W. reports that she is a Co-Ed of Cochrane Gynecology and Fertility. V.M. reports receiving travel and speaker's fees from Guerbet and research grants from Guerbet, Merck and Ferring. The department of reproductive medicine (V.M.) of the Amsterdam UMC, location VUmc, has received several research and educational grants from Guerbet, Merck and Ferring not related to the submitted work. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

This article is a response to comments made by Dr. Bashir regarding a study on the effects of dietary interventions on pain and quality of life in women with endometriosis. The authors acknowledge that they did not investigate or exclude other self-management strategies such as CBD oil, yoga, and relaxation exercises, but their main focus was on dietary interventions. They found that yoga was inferior to dietary interventions for managing endometriosis symptoms. The study participants reported minimal use of yoga, Pilates, and CBD oil, so these factors were not included in the article. The authors also address concerns about the accuracy of participants' food diaries and suggest a balanced approach that includes both digital and non-digital tools for dietary interventions. They agree with Dr. Bashir's suggestion to involve the service industry in addressing barriers to dietary adherence. [Extracted from the article]

This article presents a systematic review and diagnostic test accuracy meta-analysis on the use of hysterosalpingography (HSG) and outpatient transvaginal hydrolaparoscopy (THL) for the diagnosis of tubal occlusion. The study included 9 studies on HSG and 3 studies on THL, assessing their sensitivity and specificity for double-sided and at least one-sided tubal occlusion. The results showed that THL is an accurate test for diagnosing tubal occlusion, while HSG is less sensitive but specific. The article provides valuable information for individuals researching infertility and tubal occlusion. [Extracted from the article]

This article presents a systematic review and diagnostic accuracy test meta-analysis on the use of sono-hysterosalpingography (sono-HSG) for the diagnosis of tubal occlusion. The study included 9 studies and found that sono-HSG is an accurate test for diagnosing tubal occlusion. The use of color Doppler was associated with higher specificity. The article provides valuable information for researchers and healthcare professionals working in the field of infertility and reproductive health. [Extracted from the article]