Masaryk University Schol of Medicine and Brno University Hospital Department of Obstetrics and Gynecology Head: Prof. Pavel Ventruba, DrSc.,MBA General Medicine Obstetrics and Gynecology Seminary 2017 – 2018 – Autumn Semester Endometriosis Endometriosis Seminars in Gynecology and Obstetrics General medicine School year 2015-2016 Logo Gynekologicko - porodnická klinika FN Brno a Masarykovy univerzity Přednosta: prof. MUDr. P. Ventruba, DrSc., MBA logo_mu Definition šEndometriosis is a disease in which endometrial glands and stroma implant and grow in areas outside the uterus š šMost commonly implants are found in the pelvis š šLesions may occur at distant sites: pleural cavity, liver, kidney, gluteal muscles, bladder, etc Features of Endometriosis šPrevalence 2-50% of women; 21-47% of infertility cases š šExposure to ovarian hormones appears to be essential š šNo known racial or socioeconomic predilection š šSevere disease may occur in families Is Endometriosis Increasing? š1965-1984, endometriosis rose from 10 to 19% as primary indication for hysterectomy š šSimultaneously, a trend of more conservative therapies was occurring, which suggests a true increase in the incidence š šTheories include delay of childbearing, less use of OCs, and exposure to environmental toxins such as dioxin Etiologies of Endometriosis šSampson's theory: Retrograde menses and peritoneal implantation šMost women retrograde menstruate š šMeyer's theory: Coelomic metaplasia š Low incidence of pleural disease š šHalban's theory: Hematogenous or lymphatic spread to distant tissues šDoes not explain gravity dependent disease sites š šImmunogenic defect š š Localisation 1UPRAV Sakrouterinní vaz 63 % Ovaria 56 % Cavum Douglasi 25 % Měchýř 20 % Samps. cysty 20 % Lig. latum 8 % Střevo 6 % Normal pelvic organs as seen by laparascopy. Normal Pelvic Structures Endometriosis endo_gen_typical2 Endometriosis endo_deep_atyp1 Endometriosis endo_deep_atyp1 Endometriosis endo_deep_atyp2 figure3 figure3 figure3 figure3 Stage I (Minimal) Stage II (Mild) Stage III (Moderate) Stage IV (Severe) Classification of Endometriosis 4* 9 114 29 * Revised AFS Score Klasifikace endometriózy Koninncky PR, Martin DC: Deep endometriosis,Fertil. Steril1992;58:924-928 Clinical Presentation šPelvic pain š šInfertility šPelvic mass Klasifikace endometriózy – B & B skóre Dysmenorrea Dyspareunia Pánevní bolest Pánevní citlivost Indurace Chybí Mírná Středně Silná Nevstahuje se Chybí Mírná Středně silná Silná Nevstahuje se Chybí Mírná Středně silná Silná Chybí Mírná Středně silná Silná Chybí Mírná Středně silná Silná 0 Bez diskomfortu 1 Mírná ztráta pracovní efektivity 2 Část dne zůstává v posteli, občasná absence v práci 3 Jeden a více dní v posteli, pracovní neschopnost 4 Amenorrhoea 0 Bez obtíží nebo bolestí 1 Tolerovaný diskomfort 2 Bolestivá soulož až přerušení soulože 3 Vyhýbání se souloži pro bolest 4 Sexuálně neaktivní, nebo preferuje neodpovídat 0 Bez diskomfortu 1 Občasný pánevní diskomfort 2 Patrný diskomfort pro větší část cyklu 3 Vyžaduje silní analgetika, perzistující počas cyklu 0 Bez citlivosti 1 Minimální citlivost při palpaci 2 Výrazná citlivost při palpaci 3 Nemožnost palpovat vzhledem k citlivosti 0 Bez indurace 1 Děloha volně mobilní, indurace v cul-de-sac 2 Zbytnělé a zatvrdlé adnexa a cul-de-sac, omezená hybnost 3 Nodulární adnexa a cul-de-sac, děloha imobilní (frozen) Biberoglu & Behrman Scale (1981) Pelvic Pain šFrequency š Cyclic: Variable length prior to and after menses š Acyclic: constant and unrelenting š šAssociated activities š May include dyspareunia, dysuria, or dyspepsia š šOther sites of pain š Muscle regions š Distant tissues Infertility šModerate to severe disease š š Adhesions š š Distortion of normal anatomy š š Prevent sperm-egg interaction š š šMinimal to mild disease š š Mild infertility š š Mechanism(s) unknown š Physical Findings šTender nodules along the uterosacral ligaments or in the cul-de-sac, especially just before menses š šPain or induration without nodules commonly in the cul-de-sac or rectovaginal septum š šUterine or adnexal fixation, or an adnexal mass š Diagnosis of Endometriosis šDirect visualization of implants š Laparoscopically š Conscious pain mapping š šImaging of endometriomas š MR appears to be best (3 mm implants) š Ultrasound helpful in office setting š šBiochemical markers š Lack specificity š Endometriosis endo_typ_atyp3 Endometriosis endo_typ_atyp3 endo_typ_atyp2 Endometriosis endo_typ_atyp3 endo_typ_atyp5 Ultrasound of Endometrioma 2277ultrasound MR of Endometrioma Click to see larger picture Endometrioma Ovarian_Endometrioma Treatment of Endometriosis š šManagement of pain š Surgery š Medical therapy š šTreatment of infertility š Surgery š Ovulation induction š Assisted reproductive technology š Management of Pain š šSurgical treatment š š Ablation of endometrial implants š š Lysis of adhesions š š Ablation of uterosacral nerves š Resection of endometriomas š šCombined surgical and medical treatment š Endometriosis Endometriosis over bladder Removal of Endometriosis Endometriosis over bladder being excised Dissection of an Endometrioma endo_endometrioma_1 endo_endometrioma_2 endo_endometrioma_4 endo_endometrioma_5 Tube Ovary Incision Removal Result Treatment of Pain šMedical management š (ovarian suppression, removal of š estrogen) š š Oral contraceptives, progestin, danazol š š GnRH agonist with add-back š š Alternating GnRH agonist and OCs š Aromatase inhibitors š š Medical Treatment Ovary Estrogen Endometriosis Tissue Medical Treatment Ovary Estrogen Endometriosis Tissue Oral contraceptives Danazol GnRH agonists Progestin Role of Estrogen in Endometriosis Estrogen Role of Estrogen in Endometriosis Estrogen Cell growth Role of Estrogen in Endometriosis Aromatase Estrogen Cell growth Role of Estrogen in Endometriosis Aromatase Estrogen Cell growth PGE2 Cytokines Aromatase In Endometriosis šAromatase is key for the biosynthesis of estrogen š šIn patients aromatase expression is higher in endometriosis tissue than in normal endometrium š šIn endometriosis tissue aromatase activity is stimulated by prostaglandin š šEstrogen synthesized by endometriotic tissue stimulates growth of lesions Role of Estrogen in Endometriosis Aromatase Estrogen Cell growth PGE2 Cytokines Aromatase Inhibitors • Letrozole • Exemestane • Anastrozole Role of Estrogen in Endometriosis Aromatase Estrogen Cell growth PGE2 Cytokines Aromatase Inhibitors • Letrozole • Exemestane • Anastrozole • Danazol Treatment of Infertility šRemoval of disease š Surgery improve conception rates at all stages š šOvulation induction š Gonadotropins with ovarian suppression š Insemination with either clomiphene or FSH š šMedical suppression of ovarian function š No benefit š šAssisted reproductive technology š