ENDOMETRIOSISENDOMETRIOSIS

AYMAN SHEHATAAYMAN SHEHATADepartment of Obstetrics and Gynecology Department of Obstetrics and Gynecology

TANTA UNIVERSITYTANTA UNIVERSITY

Endometriosis Endometriosis

Definition: Definition:

Presence of active functioning endometrial implants Presence of active functioning endometrial implants

outside its normal place i.e uterine cavityoutside its normal place i.e uterine cavity

Histology: Histology:

Endometrial Glands with Stroma +/- Inflammatory Endometrial Glands with Stroma +/- Inflammatory

ReactionReaction

SitesSites

AA(( Extra uterine (external) endometriosisExtra uterine (external) endometriosis it means ectopic endometriumit means ectopic endometrium Pelvic:Pelvic:

CommonlyCommonly » Ovaries (75%)Ovaries (75%) - Uterosacral ligaments - Uterosacral ligaments» Pelvic peritoneum (DP) - Recto‑vaginal septumPelvic peritoneum (DP) - Recto‑vaginal septum

Less commonlyLess commonly -- Rectum, urinary bladderRectum, urinary bladder- Cervix, vagina & tubes- Cervix, vagina & tubes

Extra pelvicExtra pelvic:: Skin, lungs, stomach, eyes, nose, ears, Skin, lungs, stomach, eyes, nose, ears, umbilicusumbilicus

BB(( Uterine (internal) adenomyosisUterine (internal) adenomyosis:: in Myometriumin Myometrium

IncidenceIncidence

Incidence: 0.6-10%Incidence: 0.6-10%

*30-50% of infertility*30-50% of infertility

*52% of chronic pelvic pain*52% of chronic pelvic pain

* Age : 10 - 50 years* Age : 10 - 50 years

Etiology: Etiology: Predisposing FactorsPredisposing Factors

HyperestrogenismHyperestrogenism

aa)) Fibroid & metropathia hemorrhagica. Fibroid & metropathia hemorrhagica.

b)b) Delayed marriage, infertility, nullipara Delayed marriage, infertility, nullipara

c)c) estrogen secreting tumors of the ovary as granulosa & theca cell tumors estrogen secreting tumors of the ovary as granulosa & theca cell tumors

d) d) prolonged estrogen therapy.prolonged estrogen therapy.

Uterine manipulation just before or during menses( IUD, Uterine manipulation just before or during menses( IUD, D&C ,HSG,Intercourse) D&C ,HSG,Intercourse)

Interruption of menstual flowInterruption of menstual flow

*Outflow obstruction (impeforate hymen, vag.septum, Cx.stenosis (impeforate hymen, vag.septum, Cx.stenosis or atrsia)or atrsia)

* Use of tampoons during menses Enviromental pollutionsEnviromental pollutions

Etiology: TheoriesEtiology: Theories

Sampson: “Retrograde Menstruation”Sampson: “Retrograde Menstruation”

Celomic MetaplasiaCelomic Metaplasia( irritating factors transform ( irritating factors transform

derivatives of celom into endometrium)derivatives of celom into endometrium)

Combined regurge / metaplasiaCombined regurge / metaplasia

Hematologic / Lymphatic SpreadHematologic / Lymphatic Spread

Diverticular theoryDiverticular theory (uterine cont. leads to (uterine cont. leads to

dipping of endo. Into myomert.)dipping of endo. Into myomert.)

EtiologyEtiology

Genetic FactorsGenetic Factors (run in families)(run in families)

Immune FactorsImmune Factors (weak (weak immunity leave endomertial immunity leave endomertial fragments in pelvis to grow)fragments in pelvis to grow)

Iatrogenic direct Iatrogenic direct implantation(implantation( at CS scar and at CS scar and Episiotomy scar )Episiotomy scar )

Hormonal theoryHormonal theory

TThe initial genesis of endometriosis based on the he initial genesis of endometriosis based on the presence of hormones, mainly oestrogen.presence of hormones, mainly oestrogen.

Pregnancy causes atrophy of endometriosis through Pregnancy causes atrophy of endometriosis through high progesterone level. high progesterone level.

Regression also follows oophorectomy and irradiation. Regression also follows oophorectomy and irradiation. Endometriosis is rarely seen before puberty and it Endometriosis is rarely seen before puberty and it

regresses after menopause. regresses after menopause. Hormones with antioestrogenic activity also suppress Hormones with antioestrogenic activity also suppress

endometriosis and are used therapeutically.endometriosis and are used therapeutically.

No Single Theory Explains All Cases of Endometriosis

PathologyPathology

SitesSites……….ovaries, pelvic peritonium ……….ovaries, pelvic peritonium Gross picture:Gross picture: Lesions are variable in size ,depth and color Lesions are variable in size ,depth and color

**superficial lesions: multiple,brown or purple(powder burn)

* Fibrosed lesions: (blueberry spots)

* Chocolate cyst: large ,single, filled with dark brown semi fluid

Micoscopic picture:Micoscopic picture: Endometrial Glands with Stroma +/- Inflammatory reactionEndometrial Glands with Stroma +/- Inflammatory reaction

Clinical picture Clinical picture

Clinical picture Clinical picture

Patient characters: age ,parity, family history, age ,parity, family history, associated conditionsassociated conditions

Symptoms: AsymptomaticAsymptomatic Chronic Pelvic Pain.(chemical peritonitis, stretch of perit., PG)Chronic Pelvic Pain.(chemical peritonitis, stretch of perit., PG) Dysmenorrhea (cong., spasmo., ascending)Dysmenorrhea (cong., spasmo., ascending) Deep Dyspareunia (RVF, implants in DP)Deep Dyspareunia (RVF, implants in DP) Low Back Pain (uterosacral lesions) Low Back Pain (uterosacral lesions) Abnormal Uterine Bleeding (menorrhagia, polymenorrhea)Abnormal Uterine Bleeding (menorrhagia, polymenorrhea) Infertility( adhesions, dyspareunia, tubal motility affection)Infertility( adhesions, dyspareunia, tubal motility affection) Pelvic Mass (Endometrioma)Pelvic Mass (Endometrioma) Misc: Tenesmus, Hematuria,, Hemoptysis, epistaxisMisc: Tenesmus, Hematuria,, Hemoptysis, epistaxis Acute abdomenAcute abdomen

Infertility:Infertility: 30-40% of cases 30-40% of cases

Tubal factorTubal factor Autoimmune Autoimmune mechanismmechanism

Uterine, Uterine, vaginal factorvaginal factor

Ovarian Ovarian factorfactor

Peritubal Peritubal AdhesionsAdhesions

Activated Activated macrophagemacrophage

DyspareuniaDyspareunia

RVF uterusRVF uterus

Anovulation Anovulation due to pelvic due to pelvic congestioncongestion

Altered tubal Altered tubal motility motility (PGs)(PGs)

Sperm Sperm phagocytosisphagocytosis

Implantation Implantation failurefailure

Luteal phase Luteal phase deficiencydeficiency

Impaired Impaired oocyte pick oocyte pick upup

Fertilization Fertilization failurefailure

Increased Increased PGs pelvicPGs pelvic

congestioncongestion

LUFSLUFS

SignsSigns

General ex.General ex.:: pallor, ill health Abdominal ex.:Abdominal ex.:• Pelvi-abdominal swelling• Acute abdomen Vaginal ex:Vaginal ex:• Pelvic tenderness• Fixed, retroverted uterus• Tender uterosacral ligaments or • Enlarged ovaries

Diagnosis Diagnosis

Laparoscopy (“Gold Standard)Laparoscopy (“Gold Standard) LaparotomyLaparotomy Inconclusive: CA-125, Pelvic Exam, Inconclusive: CA-125, Pelvic Exam,

History, Imaging StudiesHistory, Imaging Studies Biopsy histopathology examinationBiopsy histopathology examination Beta-3 protein expression in Beta-3 protein expression in

endometrium endometrium day19-20(absent in day19-20(absent in endometriosis) endometriosis)

Endometriosis

Endometriosis

Endometriosis

DENSE ADHESIONSDENSE ADHESIONS

Ultrasonic diagnosisUltrasonic diagnosis

Sonographic FeaturesSonographic Features : :

Endometritic cysts ,fine homogeneous, uniform, Endometritic cysts ,fine homogeneous, uniform,

granular echoes, anechoic, single or multiple, granular echoes, anechoic, single or multiple,

unilateral or bilateralunilateral or bilateral

On Doppler: no vascularity within the massOn Doppler: no vascularity within the mass

Chocolate cystChocolate cyst

MRIMRI UltrasoundUltrasound

Chocolate cystChocolate cyst

Classification / StagingClassification / Staging

Several Proposed SchemesSeveral Proposed Schemes Revised AFS System: Most Often UsedRevised AFS System: Most Often Used Ranges from Stage I (Minimal) to Stage IV Ranges from Stage I (Minimal) to Stage IV

(Severe)(Severe) Staging Involves Location and Depth of Staging Involves Location and Depth of

Disease, Extent of AdhesionsDisease, Extent of Adhesions

AFS scoring (1985)AFS scoring (1985)Stage1 (1-5), II (6-15), III (16-40), IV (> 40)Stage1 (1-5), II (6-15), III (16-40), IV (> 40)

Treatment: Overall ApproachTreatment: Overall Approach

Recognize Goals: Recognize Goals:

–– Pain ManagementPain Management

–– Preservation / Restoration of FertilityPreservation / Restoration of Fertility Discuss with Patient:Discuss with Patient:

–– Disease may be Chronic and Not CurableDisease may be Chronic and Not Curable

–– Optimal Treatment Unproven or Optimal Treatment Unproven or Nonexistent Nonexistent

Age.Age.

Symptoms.Symptoms.

Stage.Stage.

InfertilityInfertility

TREATMENTTREATMENT CONSIDERATIONCONSIDERATION

Treatment of EndometriosisTreatment of Endometriosis

Management of painManagement of pain– Surgery Surgery

– Medical therapyMedical therapy

Treatment of infertilityTreatment of infertility– SurgerySurgery– Ovulation inductionOvulation induction– Assisted reproductive technologyAssisted reproductive technology

Treatment of PainTreatment of Pain

Medical managementMedical management

– Oral contraceptives, progesterone, Oral contraceptives, progesterone, danazoldanazol

– GnRH agonist with add-backGnRH agonist with add-back

– Aromatase inhibitors - letrozoleAromatase inhibitors - letrozole

– NSAIDNSAID

Management of PainManagement of Pain

Surgical treatment Surgical treatment

– Ablation of endometrial implantsAblation of endometrial implants

– Lysis of adhesions Lysis of adhesions

– Ablation of uterosacral nerves Ablation of uterosacral nerves

– Resection of endometriomasResection of endometriomas

Combined surgical and medical Combined surgical and medical treatmenttreatment

CHOICES OF MEDICAL CHOICES OF MEDICAL THERAPYTHERAPY

Drug group Example Side effects

1 Progestogens Medroxyprogesterone

Duphaston

Norculot

Mood swing

Nausea

bloatedness

2 Danazol

(synthetic androgen)

Danocrine Hoarseness

Hirsuitism, acne

3 Oral contraceptives Any OCPs Weight gain, bloatedness

4 GnRH analogue Zoladex (Goserelin)

Lucrin

Vasomotor symptoms/ osteoporosis

Continuous OCPsContinuous OCPs

COCPs act by ovarian suppression COCPs act by ovarian suppression leading to leading to Pseudopregnancy statePseudopregnancy state

? Minimizes Retrograde Menstruation? Minimizes Retrograde Menstruation Choose OCPs with Least Estrogenic Choose OCPs with Least Estrogenic

Effects, Maximal Androgenic / Progestin Effects, Maximal Androgenic / Progestin Effects (Marvelon)Effects (Marvelon)

ProgestinsProgestins

All progestational agents act by decidualization All progestational agents act by decidualization and atrophy of the endometrium.and atrophy of the endometrium.

MPA 10-30 mg/dayMPA 10-30 mg/day DP 150 mg Semi-MonthlyDP 150 mg Semi-Monthly The LNG-IUS(Mirena)The LNG-IUS(Mirena) GestrinoneGestrinone Dienogest (Visanne) 2 mg/dayDienogest (Visanne) 2 mg/day Side-Effects: AUB, Mood Swings, Weight Gain, Side-Effects: AUB, Mood Swings, Weight Gain,

AmenorrheaAmenorrhea

DanazolDanazol

Weak AndrogenWeak Androgen Suppresses LH / FSHSuppresses LH / FSH Causes Endometrial Regression, AtrophyCauses Endometrial Regression, Atrophy ExpensiveExpensive The recommended dose is 600-800 mg/dThe recommended dose is 600-800 mg/d

Side-Effects: Weight Gain, Side-Effects: Weight Gain, Masculinization, Occ. Permanent Vocal Masculinization, Occ. Permanent Vocal ChangesChanges

GnRH-aGnRH-a

Initially Stimulate FSH / LH ReleaseInitially Stimulate FSH / LH Release Down-Regulates GnRH Down-Regulates GnRH

Receptors–”Pseudomenopause”Receptors–”Pseudomenopause” Goserelin, Triptorelin, Buserelin, Naserelin, Goserelin, Triptorelin, Buserelin, Naserelin,

and leuprolide acetate and leuprolide acetate are the commonly are the commonly used agonists.used agonists.

ExpensiveExpensive Use Limited by Hypoestrogenic EffectsUse Limited by Hypoestrogenic Effects May be Combined with Add-Back therapyMay be Combined with Add-Back therapy

Medical treatmentMedical treatment

Interferons:Interferons:

combination with GnRH have resulted in higher cumulative combination with GnRH have resulted in higher cumulative

pregnancy rates and monthly fecundity ratespregnancy rates and monthly fecundity rates

SERMs:SERMs:

Selective antiestrogenic activity on the endometrium, Selective antiestrogenic activity on the endometrium,

agonist activity on bones and lipoproteinsagonist activity on bones and lipoproteins eg: Tamoxifeneg: Tamoxifen

Indications:Indications:

Mild Endometriosis associated with infertilityMild Endometriosis associated with infertility

Endometrioma >4 cm in diameterEndometrioma >4 cm in diameter

Endometriosis of rectovaginal septum or rectal Endometriosis of rectovaginal septum or rectal

wallwall

Failed Medical therapyFailed Medical therapy

Intolerable side effects of medical therapyIntolerable side effects of medical therapy

SURGICAL MANAGEMENTSURGICAL MANAGEMENT

Surgical treatmentSurgical treatment

Surgical care can be classified as: Surgical care can be classified as: ConservativeConservative when reproductive when reproductive potential is retainedpotential is retainedSemiconservativeSemiconservative when reproductive when reproductive ability is eliminated but ovarian function ability is eliminated but ovarian function is retainedis retainedRadicalRadical when the uterus and ovaries when the uterus and ovaries are removed. are removed.

Surgical Treatment Surgical Treatment (Laparoscopy / Laparotomy)(Laparoscopy / Laparotomy)

Excision / FulgerationExcision / Fulgeration Resection of EndometriomaResection of Endometrioma Lysis of Adhesions, Cul-de-sac ReconstructionLysis of Adhesions, Cul-de-sac Reconstruction Uterosacral Nerve AblationUterosacral Nerve Ablation Presacral NeurectomyPresacral Neurectomy Hysterectomy +/- BSOHysterectomy +/- BSO

EndometriomaEndometrioma