{"paper_id":"56395f43-bcd9-42d1-ae69-2cb5faad047b","body_text":"The ENZIAN Classification: A comprehensive \nframework for Understanding Deep \nEndometriosis\nDr Medhavi Sharma, Dr Ashish Varma*, Dr Munjal Pandya\nAbstract\nThe ENZIAN classification system offers a comprehensive framework for assessing endometriosis, taking \ninto account various factors beyond traditional staging systems. Developed as an alternative to the ASRM \nclassification, ENZIAN categorizes endometriosis into five stages (P1 to P5) based on a multifactorial \nassessment that includes symptoms, anatomical location, and depth of infiltration. This classification \nemphasizes a symptom-based approach, incorporating patient-reported symptoms to guide treatment \ndecisions effectively. ENZIAN provides a detailed anatomical assessment, considering the involvement \nof different pelvic structures and organs, facilitating surgical planning and personalized treatment \nstrategies. By enhancing clinical management with a nuanced understanding of the disease’s severity and \ncomplexity, ENZIAN classification aims to improve treatment outcomes and patient satisfaction in the \nmanagement of endometriosis.\nCrimson Publishers\nWings to the Research Review Article\n*Corresponding authors:  Dr. Ashish \nVarma, MS (Obstetrics & Gynecology) \nSubmission: \n  March 10, 2025\nPublished: \n  May 06, 2025\nVolume 5 - Issue 3\nHow to cite this article:  Dr Medhavi \nSharma, Dr Ashish Varma*, Dr Munjal \nPandya. The ENZIAN Classification: \nA comprehensive framework for \nUnderstanding Deep Endometriosis . \nInvest Gynecol Res Women’s Health. 5(3). \nIGRWH. 000614. 2025.\nDOI: 10.31031/IGRWH.2025.05.000614\nCopyright@  Ashish Varma, This article is \ndistributed under the terms of the Creative \nCommons Attribution 4.0 International \nLicense, which permits unrestricted use \nand redistribution provided that the \noriginal author and source are credited.\nISSN: 2577-2015\nInvestigations in Gynecology Research & Womens Health 469\nIntroduction\nEndometriosis is a chronic gynaecological disorder characterized by the presence of \nendometrial-like tissue outside the uterus, often causing pelvic pain and infertility [1]. \nAccurate classification of endometriosis is crucial for effective management and treatment. \nThe ENZIAN classification system, developed by the World Endometriosis Society in 2020, \noffers a comprehensive approach to categorizing endometriosis based on its extent, nature, \nand zygosity. This chapter aims to provide an in- depth understanding of the ENZIAN \nclassification and its clinical implications [2]. The 2021 revision of the classification, under \nthe Scientific Endometriosis Foundation (SEF), was the result of a rigorous multi-round expert \nconsensus involving gynecologists, sonographers, and radiologists with extensive experience \nin the diagnosis and treatment of endometriosis [3].\nHistorical Context of Endometriosis Classification\nHistorically, endometriosis classification systems have evolved from descriptive to more \nstructured approaches. The American Society for Reproductive Medicine (ASRM) classification, \nintroduced in 1973, was based primarily on anatomical staging. However, limitations in \npredicting symptom severity and treatment outcomes prompted the development of more \nnuanced classification systems like the ENZIAN.\nIntroduction to the ENZIAN Classification\nThe ENZIAN classification system encompasses three main components:\nA. E (Extent of Endometriosis): Defines the anatomical distribution and severity of \nendometriotic lesions.\nB. N (Nature of Endometriosis): Describes the morphological characteristics and histological \nfeatures of endometriotic lesions.\nC. Z (Zygosity of Endometriosis): Indicates the presence or absence of bilateral involvement \nof the ovaries and/or fallopian tubes.\n\n470\nInvest Gynecol Res Women’s Health       Copyright ©  Ashish Varma\nIGRWH.000614. 5(3).2025\nClinical Application of the ENZIAN Classification\nThe ENZIAN classification system serves as a valuable \ntool for guiding clinical decision-making in the management \nof endometriosis. By accurately stratifying patients based on \ndisease severity and biological characteristics, clinicians can \ntailor treatment strategies to individual needs. Furthermore, the \nENZIAN classification facilitates communication among healthcare \nproviders and enhances prognostic accuracy [4]. It is endorsed \nby major societies including European Society for Gynecological \nEndoscopy, European Society of Human Reproduction and \nEmbryology, and World Endometriosis Society [3].\nThe Enzian classification\nThe Enzian classification is for Deep Endometriosis using three \ncompartments:\nA: Vagina, Recto Vaginal Space (RVS)\nB: Utero Sacral Ligaments (USL) / cardinal ligaments/pelvic \nsidewall and\nC: Rectum\nF: Far locations such as the urinary bladder (FB), the Ureters \n(FU), and other extra-genital lesions (FO), Intestinal locations \n(sigmoid colon, small bowel; FI)\nP: Peritoneum (P)\nO: Ovary (O)\nT: Adhesions, involving the tubo-ovarian unit (T), and, tubal \npatency can also be assessed and noted\nA. Individual compartments or organ involvement are identified \nwith capital letters (P , O, T , A, B, C, F). The extent of endometriosis \nis represented by the numbers 1, 2 and 3 in compartments P , \nO, T , A, B, and C.\nB. Each compartment is graded 1 (<1cm), 2 (1–3cm), or 3 (>3cm).\nC. Paired organs (Ovary, Tube, USL, Parametrium, Ureter): the \nseverity is arranged separately after the letter (left / right).\nD. Missing / invisible ovary or tube are described with suffix (m, \nmissing; x, unknown).\nE. The individual anatomical locations and their annotation are \nannotated in a bracket, i.e. (r) or (l)\nF. The classification is applicable via all diagnostic modalities: \nTransvaginal Sonography (TVS), MRI, or surgery-annotated \nwith prefixes (u), (m), and (s) (Figure 1).\nFigure 1: Enzian (Classification of Endometriosis).\n\n471\nInvest Gynecol Res Women’s Health\n      Copyright ©  Ashish Varma\nIGRWH.000614. 5(3).2025\nDeep Endometriosis (DE)\nAll lesions exhibiting sub peritoneal infiltration of >5mm is \nclassified as per the DE definition.\nThe description takes into account the different extent of the \ndisease in terms of size, site, and different organ involvement.\nThe Enzian classification comprises three levels, represented \nby the compartments:\nA. Compartment A (craniocaudal axis)\nB. Compartment B (mediolateral axis) and\nC. Compartment C (ventro-dorsal axis)\nUterine and other extragenital locations (F) are also described:\nAdenomyosis (FA); Bladder involvement (FB); Extrinsic and/or \nIntrinsic ureteric involvement with signs of obstruction (FU); Bowel \ndisease (FI) cranial to the rectosigmoid junction (>16cm from the \nanal verge), Upper sigmoid, Transverse colon, Cecum, Appendix, \nSmall bowel; and other locations (FO) such as the abdominal wall, \ndiaphragm, and nerve.\nCompartment A (vagina, rectovaginal space):\nRuns in the craniocaudal direction and assesses the posterior \nvaginal fornix and involvement of the RVS.\na. The maximal diameter (cm) of the lesion is measured in the \nsagittal(midline) section.\nb. In cases of combined involvement of the vagina and RVS, the \nmaximal diameter of the whole (vagina and RVS) lesion will be \nmeasured in the sagittal (midline) plane.\nc. The description is as follows: A1 = <1cm, A2 = 1–3cm, A3 = \n>3cm. (On TVS)\nCompartment B (USL, cardinal ligaments, and pelvic \nsidewall)\nThis compartment represents the mediolateral axis, which also \nslightly extends dorso-laterally. Hereby, the participation of the \nparametrial area and USL are taken into account. Measurement \nthen follows according to the shape of the anatomical structures. \nThe right and left sides will be recorded separately. Endometriotic \nlesions causing intrinsic or extrinsic involvement of the ureters \nwith hydro ureteric changes or hydronephrosis will be classified as \nlesions in compartment FU (ureteral endometriosis).\nThe description is as follows:\nB1 = <1cm maximal diameter, \nB2 = 1–3cm,\nB3 = >3cm.\nAnnotation of the left (l) and right (r) side is separated by a \nslash (/).\nIn diagnosis by TVS, the probe is inserted in the posterior \nvaginal fornix and the cervix is visualized defining the mid-sagittal \nplane by visualization of the cervical canal. Visualization of the \nUSL is achieved via horizontal movement of the TVS probe by 20 \ndegrees (cervical insertion of the USL) laterally. Rotation of the \nprobe maybe necessary because the USL or cardinal ligament are \nnot parallel to the sagittal axis of the uterus.\nCompartment C (rectum) runs in the ventrodorsal direction \nand issued to assess the length of the lesion in the anterior wall \nof the rectum. Lesions located up to 16cm from the anal verge will \nbe assigned to compartment C. If the lesion is located higher than \n16 cm, it will be classified as a lesion in Enzian compartment FI. \nSeverity grade is determined by the maximal diameter of the lesion \nmeasured in the sagittal section along the axis of the rectum as \nfollows: C1 = <1cm maximal diameter, C2 = 1-3cm, C3 = >3cm. In \ncase of both rectal and sigmoidal DE, both anatomical sites (C and \nFI) have to be coded.\nPeritoneum (P)\nThe classification of peritoneal endometriosis takes into \naccount all superficial (sub peritoneal invasion <5mm) peritoneal \nfoci located in the pelvis and abdomen above the pelvic rim, that are \nnot considered Deep endometriosis. (Noted during surgery)\nThe diameter of a virtual circle is calculated, in which all \nendometrial foci can be included.\nP1 = <3cm (sum of all lesions);\nP2 = 3–7cm (sum of all lesions),\nP3 = >7cm (sum of all lesions).\nOvary (O)\nAll endometriomas and infiltrating ovarian surface foci (≥5 mm) \nare considered as ovarian endometriosis. In the case of multilocular \nendometriomas, the sum of the maximal diameter of all lesions is \nseparately calculated for each side. (Can be noted during surgery \nand during Ultrasound TVS)\nO1 = <3cm (sum of all endometriomas);\nO2 = 3–7cm (sum of all endometriomas);\nO3 = >7cm (sum of all endometriomas).\nAnnotation of the left (l) and right (r) side is separated by a \nslash (/);\nm = missing organ (ovary),\nx = not visualized or unknown.\nTubo-ovarian condition\nThe evaluation of the tubo-ovarian condition, specifically the \npresence of possible adhesions affecting the mobility of the ovaries \nand tubes, as well as tubal patency, is described as follows:\n\n472\nInvest Gynecol Res Women’s Health       Copyright ©  Ashish Varma\nIGRWH.000614. 5(3).2025\nT1 = adhesions between the ovary and pelvic sidewall +/− \ntubo-ovarian adhesions;\nT2 = T1 plus adhesions to the uterus or isolated adhesions \nbetween the adnexa and uterus;\nT3 = T2 plus adhesions to the USL and/or bowel or isolated \nadhesions between the adnexa and the USL and/or bowel.\nOptionally, tubal patency can be annotated with “+” (patent) \nor “−” not patent. Annotation of the left (l) and right (r) side is \nseparated by a slash (/);\nm = missing tube,\nx = tube not visualized or unknown (only for surgical \nevaluation).\nTubal patency can optionally be assessed using TVS \n(hysterosalpingo contrast sonography)\nImaging and Surgical Considerations\nTVS is a key diagnostic tool. For compartment A, lesions are \nmeasured in the mid-sagittal plane. For B, probe rotation of 20–90° \nhelps visualize USLs. For C, measurements are taken along the \nrectal axis, with lesions >16cm classified under FI. Tubo-ovarian \nadhesions are evaluated using the sliding sign and tubal patency can \nbe assessed with hysterosalpingo contrast sonography (HyCoSy)\nCoding of the Enzian classification\nIndividual compartments are written with capital letters in an \norder: #Enzian P_, O_/_, T _/_, A _, B_/_, C _, F\na) The individual stages (numbers) according to the specification \nare written directly after the letter: number 0 is used in case of \nno involvement.\nb) There is a comma between each individual compartment.\nc) Paired organs (e.g.: ovary, tube) are annotated according to the \nside.\nd) A slash separates left and right (/). In the case of paired organs, \nboth sides are annotated, even if only one side is affected.\nThis code should be used independently of the imaging modality \n(TVS, MRI) and type of surgery.\nA prefix can be used optionally in brackets following the word \n#Enzian (ie #Enzian(s) P1, …) in order to depict the modality of \nevaluation of the disease when using the #Enzian:\n#Enzian (u) assessment by ultrasound #Enzian (m) assessment \nby MRI #Enzian (s) assessment by surgery\nIf the surgical #Enzian (s) classification of a particular \ncompartment (ie in case of severe obliteration of the pouch of \nDouglas or hidden extraperitoneal lesions) cannot be completed at \nsurgery, the “x” suffix should be used after the compartment code.\nValidation and Reliability of ENZIAN Classification\nSeveral studies have validated the ENZIAN classification \nsystem, demonstrating its reliability and predictive value in clinical \npractice. These studies have highlighted the system’s ability to \ncorrelate with symptom severity, surgical outcomes, and disease \nrecurrence. Additionally, the ENZIAN classification has shown good \ninterobserver agreement among expert endometriosis specialists, \nsupporting its widespread adoption in clinical settings.\nChallenges and Limitations\nDespite its merits, the ENZIAN classification system has some \nlimitations. Variability in lesion morphology and histopathological \ninterpretation may pose challenges to accurate classification. \nAdditionally, the complexity of the ENZIAN system may require \nspecialized training for healthcare providers to ensure consistent \napplication. Further research is needed to address these challenges \nand refine the ENZIAN classification for improved clinical utility.\nEndometriosis Fertility Index (EFI)\nThe EFI system was developed to predict pregnancy rates in \npatients with surgically confirmed endometriosis. Proposed by \nAdamson & Pasta [5], the EFI system considers historical factors \nsuch as age, duration of infertility, and previous pregnancies. \nSuccessful pregnancy requires proper functioning of the fallopian \ntube, fimbria, and ovary. The functional score assesses the ability of \nthe embryo to implant in the uterus, the uterus’s capacity to support \nearly embryo development, and the fallopian tubes’ efficiency in \npicking up the ovum.\nScore is calculated by evaluating the function of the ovary, \nfallopian tube, and fimbria on each side, then summing the lowest \nscores from the left and right. Surgeons determine functional \nscores, which range from 0 to 4: 0 for absent or nonfunctional, 1 \nfor severe dysfunction, 2 for moderate dysfunction, 3 for mild \ndysfunction, and 4 for normal function. In addition to the least \nfunctional score, other surgical factors like the rASRM total score \nand the endometriosis lesion score of rASRM are included (Figure \n2).\n\n473\nInvest Gynecol Res Women’s Health\n      Copyright ©  Ashish Varma\nIGRWH.000614. 5(3).2025\nFigure 2: Endometriosis Fertility Index (EFI) Surgery form.\nThe EFI score, ranging from 0 to 10, is derived by summing \nhistorical and surgical scores, with 10 indicating the best prognosis \nand 0 the worst. The EFI system is advantageous for predicting \npregnancy outcomes, outperforming the rASRM classification. \nAccording to Zeng et al [6]., the pregnancy rates for rASRM stages \nI, II, III, and IV were 53.6%, 36.0%, 51.7%, and 41.7%, respectively, \nwith no statistically significant difference (p= 0.246). However, the \nEFI score showed statistically significant pregnancy rates: 8.3% for \nscores 0 to 3, 41.2% for scores 4 to 7, and 60.9% for scores 8 to 10 \n(p< 0.001) [6]. Similarly, Wang et al. [7] found that IVF outcomes \nwere better for patients with an EFI score of 6 or higher compared \nto those with a score of 5 or lower.\nHowever, the EFI system has some drawbacks. It does not \ncorrelate with pain, and the least functional score can vary \nsubjectively between surgeons, leading to inconsistent total scores. \nNo studies have yet assessed the interobserver reliability and \ninterobserver reproducibility of the EFI system. Additionally, the \nEFI score is more complex to use than the rASRM classification and \nENZIAN score due to the need to calculate and sum scores from \nvarious categories.\nFuture Directions\nThe ENZIAN classification represents a significant advancement \nin the field of endometriosis classification, but ongoing research is \n\n474\nInvest Gynecol Res Women’s Health       Copyright ©  Ashish Varma\nIGRWH.000614. 5(3).2025\nessential to enhance its efficacy and relevance. Future directions \ninclude integrating molecular markers and imaging modalities \ninto the classification system to provide a more comprehensive \nunderstanding of endometriosis pathophysiology. Additionally, \nlarge-scale prospective studies are needed to validate the ENZIAN \nclassification across diverse patient populations and healthcare \nsettings.\nConclusion\nThe ENZIAN classification of endometriosis offers a \ncomprehensive framework for characterizing the extent, nature, \nand zygosity of the disease. By providing detailed insights into \ndisease severity and biological behaviour, the ENZIAN classification \nfacilitates personalized treatment approaches and improves clinical \noutcomes for patients with endometriosis. Continued research \nand collaboration are essential to refine and validate the ENZIAN \nclassification for optimal patient care.\nKey Points\nA. Multifactorial assessment: ENZIAN considers various factors \nbeyond the traditional ASRM staging, such as symptoms, \nanatomical location, and depth of infiltration.\nB. Five stages: It categorizes endometriosis into five stages (P1 \nto P5), with each stage reflecting the severity and complexity \nof the disease.\nC. Symptom-based classification : ENZIAN emphasizes \nsymptomatology, incorporating patient-reported symptoms \ninto the classification to guide treatment decisions.\nD. Detailed anatomical assessment: It provides a more detailed \nanatomical assessment, considering the involvement of \ndifferent pelvic structures and organs.\nE. Surgical planning: The classification aids in surgical planning \nby providing a comprehensive evaluation of the extent and \nseverity of endometriosis, helping surgeons determine the \nmost appropriate approach.\nF. Tailored treatment : Allows for a more personalized and \ntailored approach to treatment, considering both the severity \nof the disease and the patient’s symptoms and preferences.\nG. Improved clinical management : ENZIAN classification \nenhances clinical management by providing a more nuanced \nunderstanding of endometriosis, leading to improved \ntreatment outcomes and patient satisfaction.\nReferences\n1. Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T , et al. \n(2014) ESHRE guideline: management of women with endometriosis. \nHum Reprod 29: 400-412.\n2. Tuttlies F, Keckstein J, Ulrich U, Possover M, Schweppe KW, et al. (2005) \nENZIAN- score, a classification of deep infiltrating endometriosis. \nZentralbl Gynakol 127(5): 275-281.\n3. Keckstein J, Saridogan E, Ulrich UA, Sillem M, Oppelt P , et al. (2021) The \n#Enzian classification: A comprehensive non- invasive and surgical \ndescription system for endometriosis. Acta Obstet Gynecol Scand \n100(7): 1165-1175.\n4. Di Paola V, Manfredi R, Castelli F, Negrelli R, Mehrabi S, et al. (2015) \nDetection and localization of deep endometriosis by means of MRI and \ncorrelation with the ENZIAN score. Eur J Radiol 84(4): 568-574.\n5. Adamson GD, Pasta DJ (2010) Endometriosis fertility index: The new, \nvalidated endometriosis staging system. Fertil Steril 94(5): 1609-1615.\n6. Zeng C, Xu JN, Zhou Y, Zhou YF, Zhu SN, et al. (2014) Reproductive \nperformance after surgery for endometriosis: Predictive value of the \nrevised American Fertility Society classification and the endometriosis \nfertility index. Gynecol Obstet Invest 77(3):180-185.\n7. Wang W, Li R, Fang T , Huang L, Ouyang N, et al. (2013) Endometriosis \nfertility index score maybe more accurate for predicting the outcomes \nof in vitro fertilisation than r-AFS classification in women with \nendometriosis. Reprod Biol Endocrinol 11: 112.","source_license":"CC0","license_restricted":false}