Dr. Hima Kandimalla Mount Hope Women’s Hospital Trinidad & Tobago 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 Globally 90 million suffering with 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 Implantation or Metastatic theory - Sampson, 1927 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 1. Alteration in the Endometrium 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 Endometrioma Pathology Contains blood, fluid & menstrual debris Brown to black color due to Hemosiderin

Endometriosis Microscopy Pathology 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 Stage I – Minimal Stage II – Mild – 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 Stage III – Moderate Stage IV – Severe – 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 Reproductive organs Symptoms Dysmenorrhoea Lower abdominal, pelvic & low back pain Menstrual irregularities Infertility

Endometriosis GIT Symptoms Cyclical rectal bleeding Tenesmus Dyschesia Diarrhea/ Cyclic constipation Image courtesy of Dr. Andrew Cook. Visit his site: Endometriosis

Endometriosis Urinary tract Symptoms Cyclical hematuria Cyclical dysuria Ureteric obstruction

Endometriosis Lungs Symptoms 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 Umbilicus & Surgical scars Symptoms Cyclical pain & swelling

Endometriosis Pelvic pain Infertility Dyspareunia Symptoms Dysmenorrhoea Pelvic pain Infertility Dyspareunia Menstrual irregularities Cyclical dysuria / hematuria Dyschesia Cyclic Rectal bleeding 60-80% 30-50% 30-40% 25-40% 10-20% 1-2% <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 infertility has not been established Incidence of endometriosis in general population of reproductive age : 2-10% - Barbieri et al, 1990 Incidence of endometriosis in infertile women: 20-40% 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 Laparoscopy Investigations ‘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 Serum CA 125 Investigations 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 I 19 II 40 III 77 IV 182 - Cheg YM et al, Obst Gyn, 2002

Endometriosis Ultrasound Investigations Sensitivity for focal endometrial implants is poor

Endometriosis Ultrasound Investigations For Endometriomas sensitivity 83% & specificity 98%

Endometriosis CT scan Investigations Endometriomas may appear solid, cystic or mixed Because of poor specificity & high radiation, CT has been replaced by MRI

Endometriosis MRI Investigations 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 Indications Hormonal Treatment 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 Causes anovulation by 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 much better in moderate & severe cases 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

Pelvic pain & suspected Endometriosis Empirical GnRH agonist + Treatment Pelvic pain & suspected Endometriosis Continue drug therapy NSAID or OCP Success Failure Empirical GnRH agonist + Estro & Prog add-back therapy Operative Laparoscopy Continue Drug therapy Failure Success GnRH agonist + Estro & Prog add-back therapy

Suspected endometriosis Treatment Infertility & Suspected endometriosis Operative Laparoscopy Assisted Reproduction Pregnancy Success Watchful waiting Failure

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