ENDOMETRIOSIS

Dr. Nayan Sarkar MD(JIPMER), DNBAssistant Professor, Department of Obst. And Gynae

Learning objectives-----

Define endometriosisEvaluate a case of endometriosisUnderstand the importance of diagnosis, management of such a caseHow to manage a case of endometriosis

DefinitionPresence of endometrium-like glands and stroma outside the uterusAdenomyosis = 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 menstruationVascular and lymphatic dissemination of endometrial cellsCoelomic metaplasia of multipotential cells in the peritoneal cavityComposite

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 endometriosisThey 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/ nulliparousEarly menarcheNon oral contraceptionNon smoker shorter cycle/longer duration of flowDysplastic 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 treatments-accupuncture, massage, relaxation, ExerciseAnti-oestrogen drugs.Laparoscopy/open surgery

Infertility

May be caused by distortion of the pelvic anatomySevere 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

Cell mediated gamete inj

Defective folliculogenisis

Chronic salpingitis

Activated macrophag

Increased prev. ABs

LUFFS

Altered tubal motil

Cytokines Fertilization failure

hyperprolactinaemia

Impaired oocyte pick up

Sperm phagocytosed

Early spon abortion

Luteal phase 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&PTransvaginal U/SMRI – Helpful in detecting rectal involvementColonoscopy and barium enema if GI bleeding presentDiagnostic laparoscopyConscious pain mapping

hpe

Definitive diagnosis can only be made with tissue bx

Will see endometrial glands, stroma, and hemosiderin-laden macrophages

American Society of ReproductiveMedicine Classification

Stage 1 (min)– 1-5Stage II (mild) – 6-15Stage III (mod) – 16-40Stage 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

ExpectantMedical – Good for patient’s with symptoms who desire pregnancy in the futureSurgery – Conservative or extirpative

**There is no cure**

Medications

Analgesics (NSAIDs)OCPsProgestins – Provera, Depo ProveraDanazol (17 alpha-ethinyl testosterone derivative)GnRH agonists (Lupron)

Treatment of pain

NSAIDS: all significantly better than placebo, studies vary which one is bestNaproxen >mefanemic acid>aspirinNaproxen=ibuprofenNaproxen only drug with significant SEs

treatment of menstrual painTreatment level of evidence

Simple analgesics 1Herbal remedies 1 alcohol 2Antidepressants/ anxiolytics 2OCPs 1NSAIDS 3

OCPs

OCPs cause a decidual reaction in the functioning endometriotic tissueUsually use low-dose OCPs continuously for 6-9 monthsContraindications – Smoker >35, hx of thromboembolic disease

Progestins

Can use oral or depot medroxyprogesterone acetateProgestins suppress gonadotropin release and in turn ovarian steroidogenesisThere 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 effectsSuppresses LH and FSH mid cycle surges so the ovary no longer produces estrogenSymptomatic relief in 80% of pts with recurrence in 5-20% after discontinuing therapySide 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 productionLess androgenic side effects than Danazol

Aromatase inhibitors

Aromatase catalyzes the conversion of testosterone to estradiolBeing evaluated for use in refractory cases of endometriosisLetrozole 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 fertilityGoal is to destroy all visible implants and adhesions87% of patients report improvement in pain following ablationHigh recurrence rates

Extirpative surgery

TAH, BSO, and removal of implantsIf all ovarian tissue is removed, it is unlikely residual disease will be stimulatedMay leave ovarian tissue in younger patients but they may require further surgery

Pregnancy rates after laparoscopy

Minimal/Mild

Moderate/Severe

Without surgery

37.4% 3.1%

After surgery

51.7% 41.3%

META-ANALYSIS MIN/MILD ENDOMETRIOSIS

PREG RATE

n FOLLOW-UP

NO TREAT

44% 235 0.5-3

DRUG THERAPY

41% 418 1- 5

SURGERY 65% 912 1 - 6

IVF 20 257

Assesment

Best method to diagnose endometriosis

MRIUSGLaparoscopyPAP Smear

Advanced endomeriosis may contribute to sub fertility by

Distorting tubal anatomyCausing apareuniaCreating a hostile peritoneal environmentAffecting sperm transport

Facts about endometriosis

Disease severity is and indicator of the amount of pain experienced by the patient F65% of the patients have ovarian involvementCommonly presented with superficial dyspareuniaIs easily diagnosed by clinical examination in an outpatient setting

Concerning endometrioma

Less than 3 cm cyst may be managed effectively medicallyCyst aspiration by usg guidance is associated with high recurrence rateOvulation induction with follitropin requires higher doses to yield similar resultExcision 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 optionIVF-ET is a recognized first line of treatmentSuccess rates are similar to those women with tubal diseaseMedical 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 laparoscopyExcision of endometriotic deposits in the POD improves fecundityRecurrence is uncommonIt 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 symptomsPregnancy rates following discontinuation of medical therapy are similar to those following surgeryOvarian suppression following surgery improves subsequent pregnancy rates