‘Seeing is believing’: arguing for diagnostic laparoscopy as a diagnostic test for endometriosis

(Jarrell & Arendt-Nielsen 2018). This does not mean that the procedure was in vain. A negative result informs the patient that they do not have endometriosis: an incurable, progressive disease which can cause chronic pain and infertility. In addition, a negative result expedites the additional investigation required to reach a non- endometriosis diagnosis. These alternative diagnoses include pelvic floor dysfunction, allodynia, vaginismus This work is licensed under a Creative Commons Attribution 4.0 International License. https://doi.org/10.1530/RAF-21-0117 https://raf.bioscientifica.com © 2022 The authors Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/07/2026 10:48:14PM via Open Access. This work is licensed under a Creative Commons Attribution 4.0 International License. http://creativecommons.org/licenses/by/4.0/ C253:3 and gut-related pain such as irritable bowel syndrome and interstitial cystitis for example. Referral to gastroenterology, urogynaecology, pain management specialists and pelvic floor physiotherapy can likewise be expedited, and the focus can shift to these new lines of enquiry. It must be stressed that this renewed campaign to accurately diagnose is essential and must be coordinated by the gynaecologist. Failure to do so can lead to delayed diagnosis, feelings of abandonment and the incorrect labelling of the patient as having illness anxiety disorder. In the context of such a failure, the negative diagnostic laparoscopy is ironically reframed as an undesired result because the patient remains without a justifiable explanation for their symptoms. Argument 4: diagnostic laparoscopy remains the best method to rule out endometriosis Ultrasound and MRI can be used to diagnose (i.e. rule in) endometriosis. Biomarkers, patient history and response to medical therapies can increase the suspicion of endometriosis. Whether on their own or in combination, none of these tools has replaced diagnostic laparoscopy, which is still considered the gold standard for diagnosis (NICE 2017 , RANZCOG 2021 ). Several studies have examined the diagnostic accuracy of imaging. A Cochrane review of 49 studies and 4807 participants concluded that MRI and ultrasound were equivalent; however, neither had sufficient diagnostic accuracy to replace surgery for the diagnosis of overall pelvic endometriosis ( Nisenblat et  al. 2016). Imaging has higher diagnostic accuracy for deep than for superficial endometriosis. Using laparoscopy as the gold standard, the sensitivity and specificity for ultrasound detection of deep endometriosis were 79 and 94%, respectively. However, this is an evolving area and new techniques for diagnosing superficial endometriosis are being reported. A recent pilot study with 42 participants demonstrated a significant improvement in diagnostic accuracy for superficial endometriosis, when a specialized technique was employed ( Leonardi et  al. 2020 b). When excluding those with more advanced forms of endometriosis, the diagnostic performance was as follows: sensitivity 77.7%, specificity 100.0%, positive predictive value 100.0% and negative predictive value 33.3%. In general, high PPV infers that disease identified on imaging is sufficient for diagnostic purposes. This is relevant as any subsequent laparoscopic procedure should be planned and consented accordingly. Conversely, a low NPV infers that the absence of disease on imaging does not rule it out, and diagnostic laparoscopy is still required for diagnosis. The anatomical location of deep endometriosis is a key variable when considering its diagnostic accuracy. A series of three meta-analyses demonstrate this ( Gerges et  al. 2021 a,b,c). Rectosigmoid disease has the highest sensitivity, followed by uterosacral ligament, vaginal, rectovaginal septum and then bladder deep endometriosis. The sensitivities are 86–89, 60–81, 52–64, 57 and 55%. Where a range is quoted, a difference between transvaginal sonography (TVS) and MRI was detected. MRI was superior for uterosacral and vaginal disease, while TVS was superior for rectosigmoid disease. Across all locations and modalities, specificity was excellent, ranging from 95 to 100%. Another similar systematic review specifically examined deep endometriosis. Again, MRI and ultrasound performed equally well; however, accuracy depended on location. Again, rectosigmoid disease had the highest sensitivity at 85% for both modalities (Guerriero et al. 2018). While imaging is improving our diagnostic rate of endometriosis pre-operatively, historically and still in settings where advanced imaging techniques are available, most abnormalities that are discovered at laparoscopy are not identified in pre-operative workup at all. In a cohort of 48 women with chronic pelvic pain, 98% had pathology that was not identified during pre-operative history, examination or imaging ( Brichant et  al. 2018). Another cohort of 120 women was admitted to the hospital under the care of the gynaecology team with an uncertain diagnosis after 4 weeks. Despite the assistance of imaging, more than half of these cases had new diagnoses following a diagnostic laparoscopy ( Nar et  al. 2014 ). Likewise, a cohort of 100 women who underwent laparoscopy by a gynaecologist for acute abdomen found that 44% had an incorrect pre-operative diagnosis ( Cohen et  al. 2001 ). Therefore, there is good evidence to support the assertion that diagnostic laparoscopy plays a very important part in the diagnosis, not just of endometriosis but of other pain presentations in gynaecology more broadly. Just as imaging should not replace laparoscopy, nor should laparoscopy replace imaging. The Ultrasound- Based Endometriosis Staging System (UBESS) has been temporally and externally validated to accurately predict the surgical complexity level encountered at laparoscopy (Menakaya et  al. 2016, Tompsett et  al. 2019, Espada et  al. 2021). Ultrasound, therefore, has a vital role to play in pre-operative triage, in making sure an appropriately skilled surgeon is performing the laparoscopy, and the patient has been adequately consented and prepared for This work is licensed under a Creative Commons Attribution 4.0 International License. https://doi.org/10.1530/RAF-21-0117 https://raf.bioscientifica.com © 2022 The authors Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/07/2026 10:48:14PM via Open Access. This work is licensed under a Creative Commons Attribution 4.0 International License. http://creativecommons.org/licenses/by/4.0/ J Mak et al. C263:3 the anticipated pathology. Indeed, it is important that the surgeon performing the laparoscopy has the ability to ‘see and treat’ disease with the highest level of surgical complexity and to adequately survey the pelvis and abdomen. Expertise is required as lesions can be subtle, occult or atypical. A cohort of 61 women who had been referred to a specialist centre after a negative diagnostic laparoscopy underwent repeat laparoscopy. A quarter of these women were found to have occult posterior compartment endometriosis that was previously not identified ( Griffiths et  al. 2007 ). This study may simply highlight the operator-dependent diagnostic nature of diagnostic laparoscopy, which is shared among all diagnostic tests (Pascoal et al. 2022). The diagnostic accuracy of UBESS increases as the severity of the disease increases, with the highest level of accuracy found with deep endometriosis ( Nisenblat et  al. 2016 ). By happy coincidence, this corresponds to the potential for a diagnostic laparoscopy to miss the deep disease. Goncalves and colleagues have shown that for vaginal and rectosigmoid endometriosis, diagnostic laparoscopy had lower sensitivity and specificity than TVS (Goncalves et al. 2021). This highlights the potential for a diagnostic laparoscopy and imaging to complement one another. While further research is needed, laparoscopy may not be the gold standard when it comes to diagnosing endometriosis in some locations. Endometriosis is already notorious for delayed diagnosis;therefore, a false negative diagnostic laparoscopy compounds what is already a harrowing patient journey. The recent European Society of Human Reproduction and Embryology (ESHRE) 2022 endometriosis guidelines recommend that empirical (pharmacological) treatment can be considered in place of diagnostic laparoscopy (ESHRE 2022 a). This is significant divergence from antecedent guidelines. It should be noted that there is no clear empirical evidence for this statement, and supporting citations consist of three opinion pieces ( ESHRE 2022 b). The accompanying review report reveals an apparent risk of bias, whereby the main proponents of empirical therapy are the pharmaceutical company representatives who contributed to the document. In addition, of the 15 independent reviewers, 9 list pharmaceutical company funding in their disclosures ( ESHRE 2022 c). Response to empirical therapy should not be considered diagnostic. Just as laparoscopy is not mandatory in all cases of endometriosis, empirical treatment does not replace diagnosis or exclude laparoscopy for diagnosis or treatment. Care should be individualized and the informed choice of the patient should be supported. Argument 5: diagnostic laparoscopy is valuable for the infertile patient Endometriosis is a double-edged disease. Alongside pain, infertility is also an important implication. Whether excision of endometriosis improves fertility outcomes is still highly debated (Gordts 2021, Leonardi 2021) and that debate should not be confused with the value of diagnosis. What is not controversial is the fact that endometriosis has a very strong association with infertility. In women undergoing laparoscopy for unexplained infertility, 60% are found to have endometriosis, making it a high-yield diagnostic tool (Pantou et al. 2019). A retrospective cohort study of 1322 women using self-reported outcomes found that one-third of women undergoing assisted reproductive technologies (ART) had a diagnosis of endometriosis. It also identified an interesting difference between women who were diagnosed with endometriosis before vs after commencing ART. Women who were diagnosed after commencing ART required more in vitro fertilization cycles and were less likely to report a birth than women who were diagnosed with endometriosis before commencing ART (Moss et al. 2021). Whether endometriosis is identified or not, diagnostic laparoscopy provides valuable information for the infertile couple.

For the sufferer of chronic pelvic pain or the infertile couple, diagnostic laparoscopy provides the answers that are desperately sought. Whether endometriosis is diagnosed or not and whether treatment is triggered or not are irrelevant to this debate. The reality is laparoscopy is safe and is irreplaceable. We have argued that diagnostic laparoscopy plays a critical role in diagnosing endometriosis, but the surgeon should never fly blind. Pre-operative assessment with history-taking, physical examination and imaging provides an important triage and clinical decision-making role. While the benefits of a positive laparoscopy are obvious, the importance of a negative laparoscopy is often an undervalued key step in redirecting investigations and treatment. Despite advances in diagnostic imaging for endometriosis, the data demonstrate the disease cannot be ruled out until the pelvis and abdomen are directly visualized, with biopsies taken of abnormal areas. Diagnostic laparoscopy is not yet antiquated. While it should not be considered mandatory, it remains the gold standard for diagnosis and an important gateway to treatment. This work is licensed under a Creative Commons Attribution 4.0 International License. https://doi.org/10.1530/RAF-21-0117 https://raf.bioscientifica.com © 2022 The authors Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/07/2026 10:48:14PM via Open Access. This work is licensed under a Creative Commons Attribution 4.0 International License. http://creativecommons.org/licenses/by/4.0/ C273:3 Declaration of interest The authors declare that they are both gynaecology surgeons and sonologists: distinctiona that carry mutually exclusive risks of bias in this debate. J M has no funding or sponsorship to report. M L reports grants from OZWAC, Endometriosis Australia, AbbVie, CanSAGE, MRFF, HHS; honoraria for lectures/writing from GE Healthcare, Bayer, AbbVie, TerSera, consulting fees from Imagendo, outside the submitted work. G C reports grants from Endometriosis Australia and MRFF; honoraria for lectures from G E Healthcare and Imperial College London. Mathew Leonardi is an Associate Editor of Reproduction and Fertility. Mathew Leonardi was not involved in the review or editorial process for this paper, on which he is listed as an author. Funding This work did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. Author contribution statement All listed authors contributed to the conceptualization, writing and editing of this piece.

Abbott J, Hawe J, Hunter D, Holmes M, Finn P & Garry R 2004 Laparoscopic excision of endometriosis: a randomized, placebo- controlled trial. Fertility and Sterility 82 878–884. (https://doi. org/10.1016/j.fertnstert.2004.03.046) Agarwal SK, Chapron C, Giudice LC, Laufer MR, Leyland N, Missmer SA, Singh SS & T aylor HS 2019 Clinical diagnosis of endometriosis: a call to action. American Journal of Obstetrics and Gynecology 220 354.e1–354.e12. (https://doi.org/10.1016/j. ajog.2018.12.039) Ahmad G, Baker J, Finnerty J, Phillips K & Watson A 2019 Laparoscopic entry techniques. Cochrane Database of Systematic Reviews 1 CD006583. (https://doi.org/10.1002/14651858.CD006583. pub5) Bajaj P , Bajaj P , Madsen H & arendt-Nielsen L 2003 Endometriosis is associated with central sensitization: a psychophysical controlled study. Journal of Pain 4 372–380. (https://doi.org/10.1016/s1526- 5900(03)00720-x) Brichant G, Denef M, T ebache L, Poismans G, Pinzauti S, Dechenne V & Nisolle M 2018 Chronic pelvic pain and the role of exploratory laparoscopy as diagnostic and therapeutic tool: a retrospective observational study. Gynecological Surgery 15 1. (https:// doi.org/10.1 186/s10397-018-1045-5) Chapron C, Querleu D, Bruhat MA, Madelenat P , Fernandez H, Pierre F & Dubuisson JB 1998 Surgical complications of diagnostic and operative gynaecological laparoscopy: a series of 29,966 cases. Human Reproduction 13 867–872. (https://doi.org/10.1093/ humrep/13.4.867) Cohen SB, Weisz B, Seidman DS, Mashiach S, Lidor AL & Goldenberg M 2001 Accuracy of the preoperative diagnosis in 100 emergency laparoscopies performed due to acute abdomen in nonpregnant women. Journal of the American Association of Gynecologic Laparoscopists 8 92–94. (https://doi.org/10.1016/s1074-3804(05)60555-5) Cromeens MG, Carey ET, Robinson WR, Knafl K & Thoyre S 2021 Timing, delays and pathways to diagnosis of endometriosis: a scoping review protocol. BMJ Open 11 e049390. (https://doi.org/10.1 136/ bmjopen-2021-049390) ESHRE 2022a ESHRE Guideline on Endometriosis. European Society of Human Reproduction and Embryology. ESHRE 2022b ESHRE Guideline on Endometriosis – Annex 7 – Literature Report. European Society of Human Reproduction and Embryology. ESHRE 2022c Review Report – ESHRE Endometriosis Guideline. European Society of Human Reproduction and Embryology. Espada M, Leonardi M, aas-Eng K, Lu C, Reyftmann L, T etstall E, Slusarczyk B, Ludlow J, Hudelist G, Reid S, et al. 2021 A multicenter international temporal and external validation study of the ultrasound-based endometriosis staging system. Journal of Minimally Invasive Gynecology 28 57–62. (https://doi.org/10.1016/j. jmig.2020.04.009) Gerges B, Li W, Leonardi M, Mol BW & Condous G 2021a Meta- analysis and systematic review to determine the optimal imaging modality for the detection of bladder deep endometriosis. European Journal of Obstetrics, Gynecology, and Reproductive Biology 261 124–133. (https://doi.org/10.1016/j.ejogrb.2021.04.030) Gerges B, Li W, Leonardi M, Mol BW & Condous G 2021b Meta- analysis and systematic review to determine the optimal imaging modality for the detection of uterosacral ligaments/torus uterinus, rectovaginal septum and vaginal deep endometriosis. Human Reproduction Open 2021 hoab041. (https://doi.org/10.1093/hropen/ hoab041) Gerges B, Li W, Leonardi M, Mol BW & Condous G 2021c Optimal imaging modality for detection of rectosigmoid deep endometriosis: systematic review and meta-analysis. Ultrasound in Obstetrics and Gynecology 58 190–200. (https://doi.org/10.1002/uog.23148) Goncalves MO, siufi neto J, Andres MP , Siufi D, De Mattos LA & Abrao MS 2021 Systematic evaluation of endometriosis by transvaginal ultrasound can accurately replace diagnostic laparoscopy, mainly for deep and ovarian endometriosis. Human Reproduction 36 1492–1500. (https://doi.org/10.1093/humrep/ deab085) Gordts S 2021 Infertile patients with endometriosis benefit from surgery. In 50 Big Debates in Reproductive Medicine. Eds R Homburg, AH Balen & RF Casper. Cambridge: Cambridge University Press. Griffiths AN, Koutsouridou RN & Penketh RJ 2007 Rectovaginal endometriosis – a frequently missed diagnosis. Journal of Obstetrics and Gynaecology 27 605–607. (https://doi.org/10.1080/01443610701497660) Guerriero S, Saba L, Pascual MA, Ajossa S, Rodriguez I, Mais V & Alcazar JL 2018 Transvaginal ultrasound vs magnetic resonance imaging for diagnosing deep infiltrating endometriosis: systematic review and meta-analysis. Ultrasound in Obstetrics and Gynecology 51 586–595. (https://doi.org/10.1002/uog.18961) Jarrell J & Arendt-Nielsen L 2018 Negative laparoscopy unveiled. Journal of Endometriosis and Pelvic Pain Disorders 10 18–21. (https://doi. org/10.1 177 /2284026517749478) Lamvu G, Antunez-Flores O, Orady M & Schneider B 2020 Path to diagnosis and women’s perspectives on the impact of endometriosis pain. Journal of Endometriosis and Pelvic Pain Disorders 12 16–25. (https://doi.org/10.1 177 /2284026520903214) Leonardi M 2021 Infertile patients with endometriosis benefit from surgery. In 50 Big Debates in Reproductive Medicine. Eds R Homburg, AH Balen & RF Casper. Cambridge: Cambridge University Press. Leonardi M, Singh SS, Murji A, Satkunaratnam A, Atri M, Reid S & Condous G 2018 Deep endometriosis: a diagnostic dilemma with significant surgical consequences. Journal of Obstetrics and Gynaecology Canada 40 1 198–1203. (https://doi.org/10.1016/j.jogc.2018.05.041) Leonardi M, Gibbons T, Armour M, Wang R, Glanville E, Hodgson R, Cave AE, Ong J, T ong YYF, Jacobson TZ, et al. 2020a When to do surgery and when not to do surgery for endometriosis: a systematic review and meta-analysis. Journal of Minimally Invasive Gynecology 27 390.e3–407.e3. (https://doi. org/10.1016/j.jmig.2019.10.014) This work is licensed under a Creative Commons Attribution 4.0 International License. https://doi.org/10.1530/RAF-21-0117 https://raf.bioscientifica.com © 2022 The authors Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/07/2026 10:48:14PM via Open Access. This work is licensed under a Creative Commons Attribution 4.0 International License. http://creativecommons.org/licenses/by/4.0/ J Mak et al. C283:3 Leonardi M, Robledo KP , Espada M, V anza K & Condous G 2020b SonoPODography: a new diagnostic technique for visualizing superficial endometriosis. European Journal of Obstetrics, Gynecology, and Reproductive Biology 254 124–131. (https://doi.org/10.1016/j. ejogrb.2020.08.051) Mancini M, Righetto M, dal moro F & Zattoni F 2020 Incidence and treatment of incarcerated trocar-site hernias after robotic surgery: presentation of three cases. Journal of Endourology Case Reports 6 271–274. (https://doi.org/10.1089/cren.2020.01 10) Menakaya U, Reid S, Lu C, Gerges B, Infante F & Condous G 2016 Performance of ultrasound-based endometriosis staging system (UBESS) for predicting level of complexity of laparoscopic surgery for endometriosis. Ultrasound in Obstetrics and Gynecology 48 786–795. (https://doi.org/10.1002/uog.15858) Moss KM, Doust J, Homer H, Rowlands IJ, Hockey R & Mishra GD 2021 Delayed diagnosis of endometriosis disadvantages women in ART: a retrospective population linked data study. Human Reproduction 36 3074–3082. (https://doi.org/10.1093/humrep/deab216) Nar AS, Bawa A, Mishra A & Mittal A 2014 Role of diagnostic laparoscopy in chronic abdominal conditions with uncertain diagnosis. Nigerian Journal of Surgery 20 75–78. (https://doi. org/10.4103/1 1 17-6806.137301) NICE 2017 Endometriosis: Diagnosis and Management (NG73). London, UK: National Institute for Health and Care Excellence. Nisenblat V, Bossuyt PM, Farquhar C, Johnson N & Hull ML 2016 Imaging modalities for the non-invasive diagnosis of endometriosis. Cochrane Database of Systematic Reviews 2 CD009591. (https://doi. org/10.1002/14651858.CD009591.pub2) Pantou A, Simopoulou M, Sfakianoudis K, Giannelou P , Rapani A, Maziotis E, Grigoriadis S, Tsioulou P , Syrkos S, Souretis K, et al. 2019 The role of laparoscopic investigation in enabling natural conception and avoiding in vitro fertilization overuse for infertile patients of unidentified aetiology and recurrent implantation failure following in vitro fertilization. Journal of Clinical Medicine 8 548. (https://doi.org/10.3390/jcm8040548) Pascoal E, Wessels JM, Aas-Eng MK, Abrao MS, Condous G, Jurkovic D, Espada M, Exacoustos C, Ferrero S, Guerriero S, et al. 2022 Strengths and limitations of diagnostic tools for endometriosis and relevance in diagnostic test accuracy research. Ultrasound in Obstetrics and Gynecology In press. (https://doi. org/10.1002/uog.24892) RANZCOG 2021 Australian Clinical Practice Guideline for the Diagnosis and Treatment of Endometriosis. Melbourne, Australia: RANZCOG Research Foundation. Roman H, chanavaz-Lacheray I, Ballester M, Bendifallah S, T ouleimat S, T uech JJ, Farella M & Merlot B 2018 High postoperative fertility rate following surgical management of colorectal endometriosis. Human Reproduction 33 1669–1676. (https:// doi.org/10.1093/humrep/dey146) Sao CH, chan-Tiopianco M, Chung KC, Chen YJ, Horng HC, Lee WL & Wang PH 2019 Pain after laparoscopic surgery: focus on shoulder-tip pain after gynecological laparoscopic surgery. Journal of the Chinese Medical Association 82 819–826. (https://doi.org/10.1097 / JCMA.0000000000000190) Stratton P & Berkley KJ 201 1 Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Human Reproduction Update 17 327–346. (https://doi.org/10.1093/humupd/ dmq050) Sutton CJ, Ewen SP , Whitelaw N & Haines P 1994 Prospective, randomized, double-blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal, mild, and moderate endometriosis. Fertility and Sterility 62 696–700. (https://doi. org/10.1016/s0015-0282(16)56990-8) T ompsett J, Leonardi M, Gerges B, Lu C, Reid S, Espada M & Condous G 2019 Ultrasound-based endometriosis staging system: validation study to predict complexity of laparoscopic surgery. Journal of Minimally Invasive Gynecology 26 477–483. (https://doi.org/10.1016/j. jmig.2018.05.022) Warren DK, Nickel KB, Wallace AE, Mines D, Tian F, Symons WJ, Fraser VJ & Olsen MA 2017 Risk factors for surgical site infection after cholecystectomy. Open Forum Infectious Diseases 4 ofx036. (https://doi.org/10.1093/ofid/ofx036) Received in final form 1 May 2022 Accepted 10 June 2022 Accepted Manuscript published online 10 June 2022 This work is licensed under a Creative Commons Attribution 4.0 International License. https://doi.org/10.1530/RAF-21-0117 https://raf.bioscientifica.com © 2022 The authors Published by Bioscientifica Ltd Downloaded from Bioscientifica.com at 06/07/2026 10:48:14PM via Open Access. This work is licensed under a Creative Commons Attribution 4.0 International License. http://creativecommons.org/licenses/by/4.0/