Endometriosis Endometriosis A 21A 21stst century enigma century enigma

Dr. Parul Sehgal Dr. Parul Sehgal Infertility & ART Specialist Infertility & ART Specialist Maharaja Agrasen Infertility & ART Center Maharaja Agrasen Infertility & ART Center

Maharaja Agarsen Hospital, Maharaja Agarsen Hospital,

Punjabi Bagh, New Delhi-110026Punjabi Bagh, New Delhi-110026

Struggle with endometriosisStruggle with endometriosis

It is a painful debilitating diseaseIt is a painful debilitating disease World over incidence is 20%-25%World over incidence is 20%-25% IN NORTH INDIA-20% & SOUTH INDIA- 25%IN NORTH INDIA-20% & SOUTH INDIA- 25% 1 in 15 women of reproductive age1 in 15 women of reproductive age Major symptoms are Pain & infertilityMajor symptoms are Pain & infertility

WHY AN ENIGMA ?WHY AN ENIGMA ?

Cyclical pain during menstruationCyclical pain during menstruation Pain during & after urinationPain during & after urination Pain during & after bowel movementsPain during & after bowel movements Pain during & after intercoursePain during & after intercourse Pelvic pain unrelated to mensesPelvic pain unrelated to menses Heavy prolonged menstrual flowHeavy prolonged menstrual flow InfertilityInfertility

Endo metriosisEndo metriosisinside inside uterus uterus

Presence of Presence of ectopic depositsectopic deposits of of endometrial tissue( glands and stroma) endometrial tissue( glands and stroma) outsideoutside the uterus the uterus

ovarian hormonesovarian hormones

cyclical bleeding in the depositscyclical bleeding in the deposits

Bening disease that spreads like cancerBening disease that spreads like cancer

Reproductive tractReproductive tract Urinary tactUrinary tact GITGIT Surgical scar/umbilicusSurgical scar/umbilicus LungsLungs

Reasons for ectopic locationsReasons for ectopic locations

There are multiple theoriesThere are multiple theories Most cases are explained by Metastatic theory Most cases are explained by Metastatic theory

i.e. Metastasis of endometrial tissues to ectopic i.e. Metastasis of endometrial tissues to ectopic locationslocations

Dissemination byDissemination by regurgitation through tubesregurgitation through tubes diaphragmatic defects/ lymphatics to exrapleural diaphragmatic defects/ lymphatics to exrapleural

sites or extrapelvic sitessites or extrapelvic sites Intraoperative implantationIntraoperative implantation Haematogenous disseminationHaematogenous dissemination

Observation in support of metastatic theoryObservation in support of metastatic theory

More common in women with early menarcheMore common in women with early menarche heavy & long flowheavy & long flow

frequent cyclesfrequent cycles

Commenest site closest to tubal ostiaCommenest site closest to tubal ostia

Distribution mostly gravity dependent Distribution mostly gravity dependent Follow surgery on uterus / curettage Follow surgery on uterus / curettage immediately afterimmediately after delivery delivery

Metaplastic theoryMetaplastic theory Coelomic epithelium endometrial tis Coelomic epithelium endometrial tis ex: Endometriosis inTurners ex: Endometriosis inTurners

Induction theory Peritoneal cells EndometrialInduction theory Peritoneal cells Endometrial Infection hypothesis - Shigella or shigella like organismInfection hypothesis - Shigella or shigella like organism Genetic predispositionGenetic predisposition Hormonal-estrogensHormonal-estrogens

Immune factors - impaired immunity , cytokinesImmune factors - impaired immunity , cytokines

How to make diagnosisHow to make diagnosis

Clinical examination may reveal a tender nodule Clinical examination may reveal a tender nodule

First line of Invesigation – USGFirst line of Invesigation – USG 83% sensitivity, 98% specificity for 83% sensitivity, 98% specificity for

Ovarian endometrioma. Ovarian endometrioma. Not so sensitive for focal endometrial implantNot so sensitive for focal endometrial implant MRI-deep lesions in retroperitoneum or those MRI-deep lesions in retroperitoneum or those

burried under adhesions, endometrial deposits in burried under adhesions, endometrial deposits in rectovaginal septum, uterine ligament, bowel.rectovaginal septum, uterine ligament, bowel.

Gold standard in diagnosis-Gold standard in diagnosis-LAPAROSCOPYLAPAROSCOPY

Ideal practice is to record the findings on video.Ideal practice is to record the findings on video. Histology – confirms the diagnosisHistology – confirms the diagnosis Cyst >3cm histological confirmationCyst >3cm histological confirmation by excision is recommended.by excision is recommended. Ovarian endometriosis is mostly accompanied Ovarian endometriosis is mostly accompanied

by pelvic or intestinal lesions as well.by pelvic or intestinal lesions as well.

DILEMMASDILEMMAS

WHAT ARE WE TREATINGWHAT ARE WE TREATING

diseasedisease InfertilityInfertility

PainPain

Medical treatment –Medical treatment –

How effective?How effective?

Surgical treatment –Surgical treatment –

Is it too aggressive?Is it too aggressive?

Medical managementMedical management

Pain reliefPain relief

NSAIDNSAID

Mefenemic acidMefenemic acid

lesions lesions

oc pillsoc pills

progestogensprogestogens

danazol danazol

GnRH agonist GnRH agonist

InfertilityInfertilityMedical therapies have not much role Medical therapies have not much role suppressive treatment delays fertilitysuppressive treatment delays fertility

Oral contraceptiveOral contraceptive

For Pt who currently does not desire For Pt who currently does not desire fertilityfertility

Endometriosis may remain activeEndometriosis may remain active

ProgestinsProgestins1. Causes initial decidualisation1. Causes initial decidualisation

atrophyatrophy2.Oppose growth promoting effect of E2 2.Oppose growth promoting effect of E2

receptorsreceptors3.In high doses inhibit gonadotropin 3.In high doses inhibit gonadotropin

secretion and ovarian hormone production secretion and ovarian hormone production inducing an ammenorrhic stateinducing an ammenorrhic state

Side effects: Wt gain, headache, fluid Side effects: Wt gain, headache, fluid retention, depressionretention, depression

DanazolDanazolInhibit steroidogenic enzymes Inhibit steroidogenic enzymes

dec dec pit gonadotropic secretion pit gonadotropic secretion

endometriotic endometriotic sex hormone binding levels sex hormone binding levels

implants implants Increase testosterone levelsIncrease testosterone levels side effects Wt gain, hot flushes , side effects Wt gain, hot flushes ,

moodchanges, dec breast sizemoodchanges, dec breast size dec HDL , increased liver dec HDL , increased liver

enzymesenzymes

Gonadotropin releasing hormone agonistGonadotropin releasing hormone agonist

Create hypoestrogenic environment with Create hypoestrogenic environment with menopause like statemenopause like state

Endometriosis undergoes atrophyEndometriosis undergoes atrophy Impovement of symptomsImpovement of symptomsNasal sprays or injectionsNasal sprays or injectionsSide effects- vaginal dryness, hot flushes, Side effects- vaginal dryness, hot flushes,

insomnia, libido changes,fatigue, headacheinsomnia, libido changes,fatigue, headache dec in bone densityupto 6 % in 6 month has dec in bone densityupto 6 % in 6 month has

been reportedbeen reported

Add back therapyAdd back therapy

MPAMPA Transdermal 17 beta estradiol Transdermal 17 beta estradiol Cojugated equine estrogen with MPACojugated equine estrogen with MPA Tibolone-progestogenic activity in endometriumTibolone-progestogenic activity in endometrium estrogenic activity in vaginaestrogenic activity in vagina

DrugsDrugs

Medroprogesterone acetate 50 mg daily improves Medroprogesterone acetate 50 mg daily improves symptoms in 80%symptoms in 80%

Norethindrone acetate 5mg daily for6 monthsNorethindrone acetate 5mg daily for6 months Magestrol acetate 40 mg dailyMagestrol acetate 40 mg daily

Danazol 400-800 mg daily for 6 Danazol 400-800 mg daily for 6 monthsmonths

GnRH agonistGnRH agonist Naferelin 800mcg nasal sprayNaferelin 800mcg nasal spray Goserelin 3.6 mg monthly injGoserelin 3.6 mg monthly inj Leuprolide 3.75 mg monthly injLeuprolide 3.75 mg monthly inj Goserelin 3.6 mg monthlyGoserelin 3.6 mg monthly Luprondepot 22.5 mg Luprondepot 22.5 mg

Levonorgesterol –IUDLevonorgesterol –IUD Aromatase inhibitor –LetrazoleAromatase inhibitor –Letrazole MifepristoneMifepristone

Facts of Medical therapyFacts of Medical therapy

Medical management can often manage pain Medical management can often manage pain Reduction in size of lesionReduction in size of lesion Medical therapy can not eradicate the lesionsMedical therapy can not eradicate the lesions Medical therapy cannot br used during the Medical therapy cannot br used during the

treatment of infertility.treatment of infertility. Recurrence rate of diseasea & its symptoms are Recurrence rate of diseasea & its symptoms are

high with medical therapyhigh with medical therapy Medical Tt when combined with surgical Ttgive Medical Tt when combined with surgical Ttgive

best results.best results.

ACOG RecommendationACOG Recommendation

GnRha treatment for 3 monthsGnRha treatment for 3 months Danazol for 6 months for pain reliefDanazol for 6 months for pain relief Add back therapy with progestins or Add back therapy with progestins or

estrogen progestin combination to reduce estrogen progestin combination to reduce bone loss if GnRha continued.bone loss if GnRha continued.

Adolescent endometriosisAdolescent endometriosis

More conservative medical approach is More conservative medical approach is neededneeded

Avoid aggressive surgical treatmentAvoid aggressive surgical treatment

Mild to moderate endometriosisMild to moderate endometriosis

Laparoscopic fulguration is not compulsoryLaparoscopic fulguration is not compulsory

Progestins like dydrogestone can be given Progestins like dydrogestone can be given and iui can be done in patients of and iui can be done in patients of infertility.infertility.

Moderate endometriosisModerate endometriosis

Symptomatic > 4 cm cystSymptomatic > 4 cm cyst Laparoscopic excision Laparoscopic excision

Always confirm the diagnosis histologicallyAlways confirm the diagnosis histologically

Advatages: It reduces the risk of infectionAdvatages: It reduces the risk of infection adhesions,adhesions, prevent progression of diseaseprevent progression of disease Improve ovarian responseImprove ovarian response

Young Patient with severe Young Patient with severe endometriosisendometriosis

Laparoscopy may be combined at the same Laparoscopy may be combined at the same sitting with 1.removal(excision) or sitting with 1.removal(excision) or destruction(ablation) of destruction(ablation) of

endometriotic tissue, endometriotic tissue, 2.division of adhesions 2.division of adhesions

3. restoring normal pelvic anatomy as far as 3. restoring normal pelvic anatomy as far as possible.possible.

4. Care to preserve normal ovarian tissue4. Care to preserve normal ovarian tissue 5. Not to damage tubes during surgery.5. Not to damage tubes during surgery. 6. Tubal flushing improves pregnancy rates6. Tubal flushing improves pregnancy rates guides about tubal statusguides about tubal status 7. Good surgical technique & meticulous 7. Good surgical technique & meticulous

haemostasis adhesion haemostasis adhesion

Endometriosis is detrimental for Endometriosis is detrimental for fertilityfertility

Damage healthy ovarian tissueDamage healthy ovarian tissue affects oocyte qualityaffects oocyte quality affects embryo qualityaffects embryo quality dec implantation ratedec implantation rate

Best chances of conceptionBest chances of conceptionimmediately after surgeryimmediately after surgery

Tubal status intact Tubes are intact Tubal status intact Tubes are intact damageddamaged

IUIIUI

Failed IVFFailed IVF

Symptoms are debilitatingSymptoms are debilitating Pt is never pain freePt is never pain free Presurgery counselling is neededPresurgery counselling is needed Many pts may have had previous surgeries alsoMany pts may have had previous surgeries also OPTIONSOPTIONS 1. Preoperative GnRHa( Leuprolide etc) to 1. Preoperative GnRHa( Leuprolide etc) to

reduce the lesions f/b LAPAROSCOPYreduce the lesions f/b LAPAROSCOPY Oophorectomy with/without hysterectomyOophorectomy with/without hysterectomy

Severe EndometriosisSevere Endometriosis

With advanced diseaseWith advanced disease--dense dense adhesions, infiltrating deposits to pelvic adhesions, infiltrating deposits to pelvic

colon & uretercolon & ureter

Risk of injury to adjacent organsRisk of injury to adjacent organs Chance of conversion of laparoscopy to Chance of conversion of laparoscopy to

laparotomy(39% laparotomy(39% redwine DBredwine DB))

RecurrenceRecurrence

- - After laparoscopic resection is 6-30%After laparoscopic resection is 6-30%- After GnRh agonist 53%- 74%After GnRh agonist 53%- 74%- More with medical therapy & conservative TtMore with medical therapy & conservative Tt For prevention of recurrenceFor prevention of recurrence- Technique of hysterectomy –First surgery has the - Technique of hysterectomy –First surgery has the

best chance to give maximum results and best chance to give maximum results and prevent recurrence.prevent recurrence.

- Peritoneal involvement (>3cm)plus all visible and - Peritoneal involvement (>3cm)plus all visible and palpable implantsahould be removedpalpable implantsahould be removed

-Risk with estrogen replacement therapy-Risk with estrogen replacement therapy

NEWER DEVELOPMENTSNEWER DEVELOPMENTS

Biomarker studies role of micro RNA expressionBiomarker studies role of micro RNA expression

Nerve bundles densities are found greater in Nerve bundles densities are found greater in women with endometriosiswomen with endometriosis

Oxidative stress to ovarian cortex surroundingOxidative stress to ovarian cortex surrounding endometriotic cyst ( endometriotic cyst ( fertil steril 2009,oct9fertil steril 2009,oct9))

THANK YOUTHANK YOU