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Endometriosis Dr. Hima Kandimalla Mount Hope Women’s Hospital Trinidad & Tobago Endometriosis Presence of endometrial glands & stroma outside the endometrial cavity and uterine musculature Endometriosis Epidemiology • Globally 90 million suffering with Endometriosis • Prevalence: 3-10% of reproductive age group & 25-35% of infertile women • Peak incidence: 30-45 yrs of age • Prevalence is similar in all races Endometriosis sites Endometriosis Pathogenesis Implantation or Metastatic theory - Sampson, 1927 Retrograde menstruation • More common in young girls with genital outflow obstruction • Physiological phenomenon – Halme et al, AJOG, 1984 Endometriosis • Retrograde menstruation ? Contributing factors 1. Alteration in the Endometrium 2. Altered Immune response 3. Favorable Peritoneal environment • Mechanical – Endometriotic foci in surgical scars • Lymphatic or Hematogenous – Extragenital locations Endometriosis Metaplasia theory – Meyer, 1919 Metaplastic changes in coelomic membrane towards endometrial like tissue following prolonged irritation or Oestrogen stimulation Endometriosis Genetic, Immunological & environmental factors • 7 times more common in 1°relatives – Halme et al, 1986 & Sampson et al 1980 • More common in Monozygotic twins than in Dizygotic twins – Simpson et al, 1984 • Decreased cellular immunity to endometriotic tissue - Dmowski et al, 1981 • ? Dioxins – Endometriosis association, 1993 Endometriosis Mechanical Endocrine Immunological Genetic Implantation Metaplasia Endometrial implant Progression & invasion Lymphatic & Blood spread Adapted & Modified from – R.W. Shaw, Gynecology Endometriosis Pathology • Puckered black lesions • White scarring • Red polyps • Clear blebs White plaques & Clear vesicles Blue-black lesions Newly formed blood vessels Endometriosis Pathology Endometrioma • Contains blood, fluid & menstrual debris • Brown to black color due to Hemosiderin Endometriosis Pathology Microscopy • Endometrial glands & stroma • Often contain fibrous tissue, blood & cysts Endometriosis Stromal endometriosis • Implants contain only stromal component without glandular part • Not hormonal dependent • Locally malignant Endometriosis Staging – American society of Reproductive Medicine, 1996 Stage I – Minimal Isolated superficial implants, No adhesions Stage II – Mild More superficial implants (<5cm), No significant adhesions Endometriosis Staging – American society of Reproductive Medicine, 1996 Stage III – Moderate Multiple superficial & invasive implants, Peritubal & Periovarian adhesions may be present Stage IV – Severe Multiple implants, Ovarian endometriomas, Many dense adhesions Endometriosis Staging – American society of Reproductive Medicine, 1996 • Staging is designed to predict the likelihood of future fertility • There is no correlation between the stage of disease & the degree of pain or the prognosis with treatment Endometriosis Diagnosis • Often misdiagnosed • The average time to diagnosis is 9.28 years – Endometriosis association study, 1998 • Delay in diagnosis: - Progression of symptoms - Infertility till complete reproductive failure Endometriosis Symptoms Reproductive organs • Dysmenorrhoea • Lower abdominal, pelvic & low back pain • Menstrual irregularities • Infertility Endometriosis Symptoms GIT • Cyclical rectal bleeding • Tenesmus • Dyschesia • Diarrhea/ Cyclic constipation • Image courtesy of Dr. Andrew Cook. Visit his site: Endometriosis Endometriosis Symptoms Urinary tract • Cyclical hematuria • Cyclical dysuria • Ureteric obstruction Endometriosis Symptoms Lungs • Cyclical hemoptysis • Blood stained Pleural effusions • Catamenial Pneumothorax Haemothorax & ascites associated with endometriosis. - Charran D, Roopnarinesingh S. Department of Obstetrics and Gynaecology, U.W.I., Trinidad. West Indian Med J. 1993 Mar;42(1):40-1. Endometriosis Symptoms Umbilicus & Surgical scars • Cyclical pain & swelling Endometriosis Symptoms • Dysmenorrhoea 60-80% • Pelvic pain 30-50% • Infertility 30-40% • Dyspareunia 25-40% • Menstrual irregularities 10-20% • Cyclical dysuria / hematuria 1-2% • Dyschesia 1-2% • Cyclic Rectal bleeding <1% Endometriosis Signs • Pelvic tenderness. • Fixed retroverted uterus. • Nodularity of the Douglas pouch and uterosacral ligaments. • Ovaries may be enlarged and tender . Ovarian cyst may be detected. Endometriosis Infertility • Clear association with 40 infertility has not been 35 established 30 • Incidence of endometriosis in 25 general population of 20 reproductive age : 2-10% 15 - Barbieri et al, 1990 10 • Incidence of endometriosis in 5 infertile women: 20-40% 0 Normal Infertile - Mahmood et al, 1990 Endometriosis Infertility In early stages: • Activated macrophages in peritoneal fluid • PG, IL-1, TNF & proteases in peritoneal fluid • levels of anti-endometrial antibodies • Luteal phase dysfunction • Abnormal follicle growth • Multiple premature LH surges • LUF syndrome Endometriosis Infertility In advanced stages: • Pelvic adhesions impairs ova release, blocks sperm entry into the peritoneal cavity & inhibits tubal pickup of the oocyte Endometriosis Risk of cancer • Ovarian Clear cell & Endometrial cell carcinomas • Breast cancer, Melanoma & NHL - Endometriosis Association study, 1998 Endometriosis Differential diagnosis • Pelvic infection • Uterine Myomas • Ovarian malignant tumors with metastatic deposits in the pouch of Douglas • Acute abdomen • Rectal carcinoma Endometriosis Investigations Laparoscopy ‘Gold standard’ diagnostic test for endometriosis It permits a “see & treat” approach, although its effectiveness may be limited by the nature of the disease and the surgeon's skill Endometriosis Investigations I 19 Serum CA 125 II 40 III 77 IV 182 - Cheg YM et al, Obst Gyn, 2002 • Sensitivity 28% & specificity 90% - Mol BW et al, Fertil Steril, 1998 • Not useful for screening, because of poor sensitivity • Can be used to identify a sub-group of women who are likely to benefit from early laparoscopy & to follow the progress of disease after establishing the diagnosis Endometriosis Investigations Ultrasound Sensitivity for focal endometrial implants is poor Endometriosis Investigations Ultrasound For Endometriomas sensitivity 83% & specificity 98% Endometriosis Investigations CT scan • Endometriomas may appear solid, cystic or mixed • Because of poor specificity & high radiation, CT has been replaced by MRI Endometriosis Investigations MRI • Role is limited in visualizing small endometriotic implants and adhesions • More useful for lesions in extraperitoneal locations & the contents of pelvic mass • More frequently used in staging & treatment response monitoring Endometriosis Treatment Consider • Age • Symptoms • Stage • Infertility Endometriosis Treatment Rationale • Recognize Goals: – Pain Management – Preservation / Restoration of Fertility • Discuss with Patient: – Disease may be Chronic and Not Curable – Optimal Treatment Unproven or Nonexistent Endometriosis Lines of management • Expectant • Medical • Hormonal • Surgical Endometriosis Expectant management • Young , asymptomatic infertile patient with mild endometriosis. • If pregnancy does not achieved within 12 - 18 months of observation, hormonal or surgical treatment is indicated . Endometriosis Medical Treatment Symptomatic pts with minimal or mild lesions • NSAIDs • Opioids. Endometriosis Hormonal Treatment Produces pseudo pregnancy or pseudo menopause • Danazol • Progestins • Gestrinone • Combined oestrogen-progestogen Pills • GnRH agonists. Endometriosis Hormonal Treatment Indications • Small & superficial lesions • Recurrence after conservative surgery • Preoperative for 6-12 wks to decrease size • Postoperative for residual lesions • When surgery is contraindicated or refused by the patient. Enometriosis in Rectovaginal septum & laparotomy scars doesn’t respond to Hormonal therapy Endometriosis Danazol • Isoxazole derivative of 17 – alpha ethinyl testosterone • Causes anovulation by • Attenuating the mid cycle surge of LH • Inhibiting multiple enzymes in steroidogenic pathway • Testosterone levels • Dose: 400 – 800 mg/ day for 6 months • Adverse effects: Androgenic effects, effects on serum lipids, Bone mineral density & Liver damage Endometriosis Progestational drugs • Causes endometrial decidualization & atrophy • Medroxyprogesterone (Provera) is commonly used • Dose: 20-30 mg/ day for 6 -9 months • Adverse effects: Abnormal uterine bleeding, nausea, breast tenderness, fluid retention & depression Endometriosis Gestrinone (Ethylnorgestrienone) • Antiprogestational steroid causes estrogen & progesterone receptors • Dose: 5-10 mg/ wk - dly or twice a wk or 3 times a wk, for 6-9 months • Adverse effects: deepening of voice, hirsuitism & Clitorial hypertrophy Endometriosis Combined pills • Well tolerated & can be continued for long term • 1 pill/ day either continuously or cyclically • Continuous regimen is superior in patients with dysmenorrhea • Adverse effects: weight gain, abnormal bleeding & HTN Endometriosis GnRH agonists • FSH & LH & results in endometrial atrophy & amenorrhea • Intranasally or SC or IM with a frequency of twice dly to once in 3 months up to 3 - 6 months • Adverse effects: transient vaginal bleeding, hot flushes, vaginal dryness, libido, breast tenderness, insomnia, depression, irritability, fatigue, headache, osteoporosis, elasticity of skin • GnRH agonists + Add-back therapy (estrogens & progestogen) – less side-effects but with same efficacy, can be continued beyond 6 months Endometriosis Hormonal Treatment The choice between the COCPs, Progestogens, Danazol & GnRH agonists depends principally upon their side-effect profiles because they relieve pain associated with endometriosis equally well - Clinical Green Top Guidelines, 2000 Endometriosis Surgical management • Conservative – Excision, Cauterization & Evaporation • Surgeries for pain - Uterosacral Nerve Ablation (LUNA), Presacral Neurectomy • Radical surgeries - Hysterectomy +/- BSO • Surgeries for Endometrioma – Cystectomy, Drainage & coagulation, Fenestration Endometriosis Surgical management Laparotomy Vs Laparoscopy • Efficacy is same • Laparoscopy – less cost & shorter recovery time even in women with advanced endometriosis Endometriosis Laparoscopic management 1. Excision 2. Vaporization 3. Fulguration & Desiccation 4. Cystectomy for endomterioma 5. Drainage & Coagulation for endometrioma 6. Fenestration for endometrioma • No RCTs available to compare these procedures • Cystectomy offer better results than drainage & coagulation for Endometrioma • If no cyst wall is present, Fenestration followed by GnRH agonists may prove beneficial Endometriosis Laparoscopic management Surgical management • outcome was poorest in minimal endometriosis • much better in moderate & severe cases - Sutton CJ et al, Fertil Steril 1994 Endometriosis Combination of Hormonal & Surgical • Postoperative Danazol & Medroxyprogesterone for 6 months lowered the pain scores significantly – Telimaa S et al, Gynecol Endo, 1987 • Postoperative GnRH agonist for 6 months lowered the recurrence rates but with no change in pain scores – Parazzini F et al, AJOG, 1994 • Sufficient data is not available to conclude that hormonal & surgical combination is associated with significant benefits. The possible benefits should be weighed in the context of the adverse effects & costs of these therapies - Cochrane review, May 2004 Endometriosis Infertility Management • No role for medical therapy with hormonal drugs • Laparoscopic ablation of minimal – mild endometriosis may improve fertility rates - Cochrane review, 2004 Endometriosis IUI • The presence of endometriosis does not generally impair the results of IUI • Ovarian hyperstimulation using Gonadotrophins with IUI is better than no treatment or IUI alone - Nulsen Jc et al, Obst Gyn, 1993 & - Tummon IS et al, Fertil Steril, 1997 Endometriosis Treatment Pelvic pain & suspected Endometriosis Continue drug therapy Success NSAID or OCP Failure Continue Empirical GnRH agonist + Operative Success Failure Drug therapy Estro & Prog Laparoscopy add-back therapy GnRH agonist + Estro & Prog add-back therapy Endometriosis Treatment Infertility & Suspected endometriosis Operative Laparoscopy Assisted Pregnancy Success Watchful waiting Failure Reproduction Endometriosis Conclusion • Endometriosis is a mystery tour as it requires decision making at every stage by the physician and the patient. • Endometriosis still stand as one of the most- investigated disorders in gynecology. So is one of the highest priorities for research. Thank you
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