ENDOMETRIOSIS Dr. Nayan Sarkar MD(JIPMER), DNB Assistant Professor, Department of Obst. And Gynae Learning objectives----Define endometriosis Evaluate a case of endometriosis Understand the importance of diagnosis, management of such a case How to manage a case of endometriosis Definition Presence of endometrium-like glands and stroma outside the uterus Adenomyosis = Invasion of the myometrium by endometrial tissue Prevalence Not precisely known—2-5% 20-40% of women in infertile couple vs. 5% of fertile women. But also found in 6-43% of women undergoing laparoscopic sterilization. 52% of teenagers with CPP Syndrome. Up to 80% women with CPP What you might see.. Endometriomas May reach up to 15-20cm “Chocolate cysts” Pathogenesis Direct implantation of endometrial cells – by means of retrograde menstruation Vascular and lymphatic dissemination of endometrial cells Coelomic metaplasia of multipotential cells in the peritoneal cavity Composite Immune factors Retrograde menstruation happens in nearly everyone – so why do some women get endometriosis?? Macrophages are found in higher concentration in the peritoneal fluid of women with endometriosis They secrete growth factors and cytokines Familial association Relative Risk to siblings 2.3 overall Relative Risk to sibs if severe endometriosis 15 Risk factors Single/ nulliparous Early menarche Non oral contraception Non smoker shorter cycle/longer duration of flow Dysplastic naevus syndrome, melanoma symptoms Severe dysmenorrohoea (90%) Chronic Pelvic Pain (70%) Deep dyspareunia (75%) infertility (55%) Presentation Pelvic pain - Most common** Dysmenorrhea Deep thrust dyspareunia Infertility – May be only complaint Abnormal bleeding Cyclical hematochezia or hematuria Endometriosis pain Psycho-physical treatmentsaccupuncture, massage, relaxation, Exercise Anti-oestrogen drugs. Laparoscopy/open surgery Infertility May be caused by distortion of the pelvic anatomy Severe adhesions may impair egg release, block sperm entry into fallopian tube, or inhibit ovum pickup May be other mechanisms as well – anovulation, immune dysfunction, corpus luteum insufficiency, embryo or sperm toxicity of peritoneal fluid… Infertility mechanisms Adhesions distorsion Increased PGs Defective folliculoge nisis LUFFS Altered Cytokines tubal motil Fertilizatio hyperprola n failure ctinaemia Chronic salpingitis Impaired oocyte pick up Cell mediated gamete inj Activated Increased macrophag prev. ABs Sperm Early spon Luteal phagocyto abortion phase sed deficency Where can’t it go? Most common – Ovaries (60%), pelvic peritoneum, ant and post cul-de-sacs, uterosacral ligaments, tubes, pelvic lymph nodes Infrequent – Recto sigmoid (10-15%), other GI sites (5%), vagina Rare – Umbilicus, episiotomy or surgical scars, kidney, lungs, arms, legs, nasal mucosa, brain Differential Diagnosis Pain - Chronic PID, Adhesions, GI dysfunction, Interstitial cystitis Dyspareunia – Chronic PID, Ovarian cysts, Symptomatic uterine retroversion AUB – Anovulation, Hypothyroidism, Hyperprolactinemia Premenstrual spotting – Luteal phase defect, Polyps, Cervical lesions Acute pain – Ecoptic, PID, Torsion, Ruptured corpus luteum Evaluation H&P Transvaginal U/S MRI – Helpful in detecting rectal involvement Colonoscopy and barium enema if GI bleeding present Diagnostic laparoscopy Conscious pain mapping hpe Definitive diagnosis can only be made with tissue bx Will see endometrial glands, stroma, and hemosiderin-laden macrophages American Society of Reproductive Medicine Classification Stage 1 (min) – 1-5 Stage II (mild) – 6-15 Stage III (mod) – 16-40 Stage IV (severe) – >40 treatment Is treatment always required? Who needs treatment? Does any treatment really work? Does treatment in young women prevent infertility and progression? Difficult to answer Endometriosis progress in most cases of moderate and severe disease. Spontaneous regression can occur in up to 58% of milder cases. Natural history is still uncharted to a large extent. However---Medical treatment and surgery fail to arrest disease in up to a third. Combinations of treatments have also failed to control disease for indefinite periods when followed up. Pregnancy has a variable effect on endometriosis—persistence, regression and progression. And also------Endometriosis may occur in the early menopause, usually in association with HRT. Laparoscopic ablation of visible endometriotic lesion in infertile women is associated with significantly increased fertility rates. There is no data regarding early intervention wrt prevention. Treatment Expectant Medical – Good for patient’s with symptoms who desire pregnancy in the future Surgery – Conservative or extirpative **There is no cure** Medications Analgesics (NSAIDs) OCPs Progestins – Provera, Depo Provera Danazol (17 alpha-ethinyl testosterone derivative) GnRH agonists (Lupron) Treatment of pain NSAIDS: all significantly better than placebo, studies vary which one is best Naproxen >mefanemic acid>aspirin Naproxen=ibuprofen Naproxen only drug with significant SEs treatment of menstrual pain Treatment level of evidence Simple analgesics Herbal remedies alcohol Antidepressants/ anxiolytics OCPs NSAIDS 1 1 2 2 1 3 OCPs OCPs cause a decidual reaction in the functioning endometriotic tissue Usually use low-dose OCPs continuously for 6-9 months Contraindications – Smoker >35, hx of thromboembolic disease Progestins Can use oral or depot medroxyprogesterone acetate Progestins suppress gonadotropin release and in turn ovarian steroidogenesis There may be a prolonged interval to resumption of ovulation with Depo so it should not be used in women who desire fertility in the near future Danazol Derivative of synthetic steroid 17α-ethinyl testosterone – has progestagenic and androgenic effects Suppresses LH and FSH mid cycle surges so the ovary no longer produces estrogen Symptomatic relief in 80% of pts with recurrence in 5-20% after discontinuing therapy Side effects – weight gain, acne, hirsutism, oily skin, decrease in breast size GnRH agonist Desensitizes the pituitary and impairs release of LH and FSH and therefore estrogen production Less androgenic side effects than Danazol Aromatase inhibitors Aromatase catalyzes the conversion of testosterone to estradiol Being evaluated for use in refractory cases of endometriosis Letrozole for 6 months has showed promising results in studies Limitations of drug therapy Only shrinks some types of endometriosis which are oestrogen sensitive i.e. red and blister appearance not brown, black and white. Shrinkage not complete– usually leaves micro disease. Results for infertility treatment no better than no treatment. Does not deal with adhesions. Conservative surgery Typically in patients who would like to retain their fertility Goal is to destroy all visible implants and adhesions 87% of patients report improvement in pain following ablation High recurrence rates Extirpative surgery TAH, BSO, and removal of implants If all ovarian tissue is removed, it is unlikely residual disease will be stimulated May leave ovarian tissue in younger patients but they may require further surgery Pregnancy rates after laparoscopy Without surgery After surgery Minimal/Mil d 37.4% Moderate/ Severe 3.1% 51.7% 41.3% META-ANALYSIS MIN/MILD ENDOMETRIOSIS PREG RATE NO TREAT 44% DRUG THERAPY SURGERY IVF n 235 FOLLOWUP 0.5-3 41% 418 1- 5 65% 912 1-6 20 257 Assesment Best method to diagnose endometriosis MRI USG Laparoscopy PAP Smear Advanced endomeriosis may contribute to sub fertility by Distorting tubal anatomy Causing apareunia Creating a hostile peritoneal environment Affecting sperm transport Facts about endometriosis Disease severity is and indicator of the amount of pain experienced by the patient F 65% of the patients have ovarian involvement Commonly presented with superficial dyspareunia Is easily diagnosed by clinical examination in an outpatient setting Concerning endometrioma Less than 3 cm cyst may be managed effectively medically Cyst aspiration by usg guidance is associated with high recurrence rate Ovulation induction with follitropin requires higher doses to yield similar result Excision of the cyst with thermal injury to its base is the treatment of choice Consisting ART in woman with advanced stage endometriosis Ovulation induction alone is a valid option IVF-ET is a recognized first line of treatment Success rates are similar to those women with tubal disease Medical therapy prior to ART increases success Concerning conservative surgery for advanced stage disease in woman with subfertility Pregnancy rate following laparotomy are significantly higher than following laparoscopy Excision of endometriotic deposits in the POD improves fecundity Recurrence is uncommon It has little effect on quality of life measures Concerning medical treatment for advanced stage of endometriosis and infertility GNRH agonists are the treatment of choice for the suppression of symptoms Pregnancy rates following discontinuation of medical therapy are similar to those following surgery Ovarian suppression following surgery improves subsequent pregnancy rates