ENDOMETRIOSIS

Dr. dr. Nusratuddin A., SpOG(K), MARS

DIVISI FERTILITAS DAN

ENDOKRINOLOGI REPRODUKSI (FER)
BAGIAN OBGIN FK UNHAS
 TUJUAN PEMBELAJARAN
Mahasiswa mengetahui:
-Definisi endometriosis
-Klasifikasi endometriosis
-Etiologi/Patogenesis endometriosis
-Gambaran klinik endometriosis
-Diagnosis endometriosis
-Penanganan endometriosis
 PENDAHULUAN
ENDOMETRIOSIS:
• The disease of theory
Koninckx/Barlow/Kennedy, Gynecol Obstet Invest 1999;47(suppl 1):3–10

• The great imitator Woodward, P. J. Journal de Radiologie, 2005;86(10), 1205.

• The silence invader Perloe M, Christie LG. 1986. Endometriosis :

Conquering The Silent Invader. New York Rawson

• The missed disease

Engemise, S., Gordon, C., & Konje, J. C. (2010). Endometriosis. BMJ, 340(jun23 2),
c2168–c2168.

• The puzzle disease

Ballweg M.L. (1995) The Puzzle of Endometriosis. In: Nezhat C.R., Berger G.S., Nezhat F.R., Buttram
V.C., Nezhat C.H. (eds) Endometriosis. Springer, New York, NY
 DEFINISI
• Endometriosis : penyakit ginekologis kronis
dengan adanya jaringan menyerupai
endometrium di luar uterus dan berkaitan
dengan nyeri panggul dan infertilitas

• Jaringan endometrium ektopik lebih sering

ada di pelvik, namun juga bisa : ovarium,
tuba fallopi, sigmoid, kolon, dan appendiks

Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed.
LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER
 EPIDEMIOLOGI
“Prevalensi sesungguhnya tidak diketahui pasti”

• Secara umum  endometriosis perempuan usia

reproduktif  10%

• Endometriosis asimtomatik  1–7% perempuan yang

melakukan sterilisasi elektif
• 60% perempuan usia reproduktif dengan nyeri panggul
• 50–60% perempuan dewasa atau remaja dengan nyeri
panggul dan/atau infertilitas

Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed.
LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER
 PATOGENESIS
Etiologi : Tidak pasti (disease of theory)
Beberapa teori diusulkan :
• Menstruasi RETOGRAD (Teori Sampson)
• Penyebaran LIMFATIK
• Penyebaran HEMATOGEN
• Penyebaran IATROGENIK/LANGSUNG
• Sisa sel EMBRIONIK
• Metaplasia SELOMIK
• Teori INDUKSI
• Teori INVAGINASI
 PATOGENESIS
Etiologi : Tidak pasti (disease of theory)
Beberapa teori diusulkan :
• Teori HORMONAL
• Teori IMUNOLOGI
• Teori LINGKUNGAN
• Teori GENETIK
 PATOGENESIS
• Teori Sampson  “the most well-accepted
theory”

jaringan endometrium selama menstruasi

mengalir dan keluar dari tuba fallopi ke kavitas
peritoneal kemudian diikuti oleh implantasi dan
pertumbuhan di tempat lain di rongga panggul

Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed.
LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER
 Endometriosis
•Backward flow of menstrual fluid
into the pelvic region instead of
out the vagina
•Endometrial cells attach to
ovaries or elsewhere in uterus
•All women are thought to have
some degree of retrograde
menstruation

Obstructions of the lower genital

tract which might cause menstrual
back up, such as vaginal or uterine
infections  higher rates of
endometriosis (Mastro, 1996)
 PATOGENESIS
• Yang mendukung teori Sampson dan implantasi
1. Endometriosis lebih prevalen pada perempuan dengan anomali
Mullerian dibandingkan dengan malformasi yang tidak mengobstruksi aliran
keluar darah menstruasi  80% perempuan dengan stenosis servikal dan
endometrium fungsional, terjadi endometriosis
2. Sel endometrium viable dari cairan peritoneum selama haid dapat
ditumbuhkan dalam kultur sel dan dapat melekat dan prenetrasi di
permukaan mesotelial peritoneum
3. Insiden endometriosis meningkat pada perempuan dengan menarche lebih
awal dan/atau siklus menstruasi pendek
4. Endometriosis diobservasi lebih banyak pada bagian pelvik : ovarium,
kavum douglas dan retzi, ligament uterosakral, uterus posterior dan
posterior ligament latum
5. Endometriosis eksperimental dapat diinduksi pada tikus atau primate
setelah tindakan induksi menstruasi peritoneal operatif

Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed.
LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER
Yen & Jaffe’s. 2018. REPRODUCTIVE ENDOCRINOLOGY PHYSIOLOGY,
PATHOPHYSIOLOGY, AND CLINICAL MANAGEMENT 8th ed. Elsevier.
 Teori Regurgitasi dan
Implantasi Sampson

Sampson JA. AmJOG 1927;14:422-26

Nisolle M, Donnez J. Fertil Steril 1997;68:585-96
Etiopatogenesis
Teori Mayor : Metastasis dan Metaplasia

Retrograde menstruation
(a), lymphatic spread (b),
hematogenous spread (c),
and coelomic metaplasia
(d)
“Induction of
undifferentiated
mesenchyma by
unidentified endometrial
substances is also
theorized. “
Teori Sampson tentang Menstruasi Retrograde

Th 1921. Sampson, pelimbahan darah haid

kerongga pelvik

70-90 % Pelimbahan ke rongga pelvik

(Halme. Obstet Gynecol 1984)

79% Sel endometrium yang masih hidup

(Blumenkranz MJ. Obstet Gynecol 1981)

3-10% menderita endometriosis

 ENDOMETRIOSIS
Genetic, immunological & environmental factors
• 7 times more common in 1°relatives
– Halme et al, 1986 & Sampson et al 1980
• An altered immune response to the displaced
endometrial tissue  Diminished cell-mediated
immunity with decreased T-cell and natural killer
cell responsiveness - Dmowski et al,
1981
• Dioxinsimplying further dysfunction of the
immune system – Endometriosis association, 1993
 PATOGENESIS
• Teori penyebaran hematogen :
Jaringan endometriosis berasal jaringan
endometrium yang memasuki pembuluh
darah kemudian menyebar beberapa
tempat ditubuh
 PATOGENESIS
• Teori penyebaran limfogen :
Endometriosis berasal jaringan endometrium
yang memasuki limfe dari uterus saat
menstruasi kemudian menyebar ke bagian
pelvik lain.
 PATOGENESIS
Teori Metastasis imfatik dan vaskuler (Halban)

Endometriosis disebarkan dan berkembang melalui limfatik dan vaskuler

 PATOGENESIS
• Diseminasi iatrogenik :
penyebaran langsung jaringan
endometrium dapat terjadi saat operasi,
misalnya endometriosis yang terjadi pada
tempat insisi seksio sesar, histerektomi
dan episiotomi
 CAESAREAN SCARS
ENDOMETRIOSIS
Hoffman, BL., et al. 2016. Williams Gynecology 3 rd ed. Elsevier.
 PATOGENESIS
• Sisa sel embrionik :
Sel-sel dari paramesonefros (Muller) mungkin
terdapat disuatu tempat didalam tubuh dan
memberikan respon terhadap hormon ovarium
sehingga mengaktifkan sisa-sisa sel ini
membentuk endometrium ditempat lain.
 PATOGENESIS
• Metaplasia selomik  Fergusson and
colleagues th 1960

endometriosis berasal dari perubahan

metaplastik di sel mesotelial yang berasal dari
epitel coelomic (di periteonum dan pleura)

Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed.
LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER
 Metaplasia Theory
Meyer, 1919

• The endometrium and the

peritoneum are derivatives of
the same coelomic wall
epithelium
• Metaplastic changes in coelomic
membrane towards endometrial
like tissue/type glands following
prolonged irritation or Estrogen
stimulation

(Witz CA. Clin Obstet Gynecol. 1999)

 PATOGENESIS
Teori Induksi

Fokus endometriosis peritoneal disebabkan oleh karena iritan spesifik di konten

kista yang menstimulasi endothelium peritoneal menjadi metaplasia dengan
pembentukan jaringan endometrium yang tipikal baik secara struktur maupun
fungsi
Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed.
LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER
 PATOGENESIS

Teori Invaginasi

Kista endometriosis berasal dari invaginasi

epitel ovarium yang kemudian mengalami
metaplasia
Pembentukan Endometrioma

Implan endometrial pada permukaan ovarium dilapisi

adhesi. Invaginasi dari korteks ovarium terjadi pada
stadium dini yang merupakan kunci pembentukan
endometrioma
 TEORI Bone marrow–derived
stem cells (BMDSCs)
• Stem cell yang beredar berasal dari
sumsum tulang yang diferensiasi menjadi
jaringan endometrium di berbagai lokasi
• Hal ini menjelaskan bagaimana
endometrium ektopik dapat muncul di luar
pelvis, seperti : paru dan SSP

Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed.
LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER
 PATOLOGI
Secara histologi endometriosis td:
• Kelenjar
• Stroma
• Kelenjar/stroma
• Dengan/tanpa hemosiderin
• Makrofag
 ENDOMETRIOSIS
Pathology
• Puckered black
lesions
• White scarring
• Red polyps
• Clear blebs

White Opacification  inactive Lesion

Red-Flame Like Lesion  active Lesion
PERITONEAL ENDOMETRIOSIS
White Opacification  inactive Lesion
Red-Flame Like Lesion  active Lesion

Burney, R. O., & Giudice, L. C. (2012). Pathogenesis and

pathophysiology of endometriosis. Fertility and Sterility, 98(3), 511–
519.
Susunan mirip endometrium yang menampilkan
perubahan klinis seperti endometrium
normal kavum uteri yang dapat tumbuh
di hampir semua bagian tubuh

Elemen kelenjar
Stroma
Hemosiderin
Makrofaga mengandung
hemosiderin
Yen & Jaffe’s. 2018. REPRODUCTIVE ENDOCRINOLOGY
PHYSIOLOGY, PATHOPHYSIOLOGY, AND CLINICAL
MANAGEMENT 8th ed. Elsevier.
 LOKASI
• Ovarium
• Peritoneum, lig.sakrouterina, kav.douglasi,
ddg blkg uterus, tuba fallopi, plika v.Ut,
lig.rot.
• Serviks,vagina,VU.
• Umbilikus
• Paru,mata,perkardium, otak.
LOKASI ENDOMETRIOSIS
 LOKASI
• Endometriosis interna (adenomiosis)

• Endometriosis pelvik (endometriosis sejati)

• Endometriosis ekstra-genital
“three different entities”
ADENOMIOSIS

Yen & Jaffe’s. 2018. REPRODUCTIVE ENDOCRINOLOGY PHYSIOLOGY,

PATHOPHYSIOLOGY, AND CLINICAL MANAGEMENT 8th ed. Elsevier.
NORMAL
 CUL DE SAC

Yen & Jaffe’s. 2018. REPRODUCTIVE ENDOCRINOLOGY PHYSIOLOGY,

PATHOPHYSIOLOGY, AND CLINICAL MANAGEMENT 8th ed. Elsevier.
UTEROSACRAL LIGAMENT
UTEROSACRAL LIGAMENT
 SIDE WALL

Light micrograph of peritoneal endometriotic implant

shows endometrial glandular epithelium (arrow) and
surrounding stroma.
The peritoneum in this woman with endometriosis is
studded with reddish, irregularly shaped implants.
OVARIUM

Yen & Jaffe’s. 2018. REPRODUCTIVE ENDOCRINOLOGY PHYSIOLOGY,

PATHOPHYSIOLOGY, AND CLINICAL MANAGEMENT 8th ed. Elsevier.
CHOCOLATE CYSTS
ENDOMETRIOSIS ON/IN THE OVARY
 forms a dark, chocolate cystic mass
Hoffman, BL., et al. 2016. Williams Gynecology 3 rd ed. Elsevier.
Yen & Jaffe’s. 2018. REPRODUCTIVE ENDOCRINOLOGY PHYSIOLOGY,
PATHOPHYSIOLOGY, AND CLINICAL MANAGEMENT 8th ed. Elsevier.
BOWEL
 BLADDER

Transabdominal sagittal pelvic ultrasonography

showing a heterogeneous endometriotic nodule
protruding from the posterior wall of the bladder
into the vesical lumen.
 Endometriosis
Extra-genital endometriosis

ENDOMETRIOSIS UMBILIKALIS

Endometriotic lesion of the

diaphragm
ENDOMETRIOSIS UMBILIKALIS

H-4 (2 Des. 03) H-8 (6 Des. 03) H-15 (13 Des. 03) H-22 (20 Des. 03)

H-1 (24 Des. 03) H-2 (25 Des. 03) H-3 (26 Des. 03) H-9 (1 Jan. 04)

H-7 post eksisi (19 H-11/H-25 post eksisi (6

Eksisi (12 Jan. 04) Eksisi (12 Jan. 04) Jan. 04) Peb. 04)
 GEJALA / TANDA
• End ovarium : jarang bergejala
• End peritoneum : nyeri perut terutama bag
bawah saat haid (dismenore)
• End vagina / kav. douglasi : dispareunia
• End usus : nyeri BAB dan hematemesis
• End vesika : disuri + hematuri
• End paru : hemaptoe
• End otak : nyeri kepala hebat
• Infertilitas
Endometriosis…TANTANGAN
1.Patogenesis : belum seluruhnya
terungkap
2.Klinis : amat beragam
3.Diagnosis : tidak selalu mudah
4.Penanganan : tidak ada cara tunggal
5.Pencegahan : belum ada

58
59
 DIAGNOSIS
• ANAMNESIS (t/u: dismenore+infertilitas)
• PEM FISIS
VT/RT : didapatkan nodul disertai nyeri pd
lig sakro uterina/kav. douglasi
• USG : bisa kista atau adenomiosis
• LAPAROSKOPI : bercak endometriosis dan kista
endometriosis (endometrioma)
• CT Scan
• MRI
 ANAMNESIS
Derajat endometriosis tidak berkorelasi
dengan jumlah dan beratnya gejala 
perempuan dengan stadium lanjut dapat
memiliki gejala ringan atau tidak
bergejala (nyeri)
Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed.
LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER
 PEMERIKSAAN FISIK
“Pemeriksaan Fisik memiliki
sensistivitas, spesifisitas dan nilai preditif
yang buruk dan tidak dapat dipakai
untuk mengeksklusi diagnosis
Endometriosis”
Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed.
LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER

These endometriotic lesions (dark lesions)

infiltrate the vaginal mucosa and are visible on
speculum examination of the posterior vaginal
fornix.

Lateral displacement of
the cervix, which can be
documented by visual
examination of the
cervix on speculum
examination or by
digital examination

Yen & Jaffe’s. 2018. REPRODUCTIVE ENDOCRINOLOGY PHYSIOLOGY,

PATHOPHYSIOLOGY, AND CLINICAL MANAGEMENT 8th ed. Elsevier.
 ENDOMETRIOSIS
Pemeriksaan
Ultrasound (TVUS)
“Sensitivity for focal
endometrial implants is poor”
“TVUS dapat mendeteksi
endometrioma, namun tidak dapat
menunjukkan adhesi pelvik atau focus
peritoneal superfisial endometriosis”

Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed.
LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER
Transvaginal ultrasound image of the right adnexa
showing an endometrioma of the right ovary. The
homogeneous echo pattern of the cyst contents (ie,
"ground-glass" appearance) is characteristic of an
endometrioma (short arrow).
 ENDOMETRIOSIS
Pemeriksaan
Ultrasound (TVUS)
Jika ditemukan Endometriomas
sensitivitas 90% &
specifisitas hampir 100%

Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed.
LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER

Yen & Jaffe’s. 2018. REPRODUCTIVE ENDOCRINOLOGY PHYSIOLOGY,

PATHOPHYSIOLOGY, AND CLINICAL MANAGEMENT 8th ed. Elsevier.
 ENDOMETRIOSIS
Pemeriksaan
CT scan
• Endometriomas  solid,
kistik atau mixed
“Because of poor specificity
& high radiation, CT has
been replaced by MRI”
Axial CT scan of the pelvis in a 29-year-old woman
demonstrates a well-circumscribed, low attenuation
mass (arrow) in the left pelvis immediately posterior to
the uterus. This mass was found to be an endometrioma
of the left ovary at surgery.
Computed tomogram (CT) of the chest showing
opacities in the right lower lobe (arrow) in a young
woman with chest pain during menstruation (panel
A). The opacities have completely resolved two
weeks later after menstruation (panel B), illustrating
the importance of obtaining imaging when patients
with suspected thoracic endometriosis are
symptomatic peri-menstruation.
 ENDOMETRIOSIS
Pemeriksaan
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 Fritz, MA & Sperof, L. 2019. Clinical Gynecologic
Endocrinology and Infertility 9th ed. LIPPINCOTT
WILLIAMS & WILKINS, a WOLTERS KLUWER

Hoffman, BL., et al. 2016. Williams Gynecology 3 rd ed. Elsevier.

Yen & Jaffe’s. 2018. REPRODUCTIVE ENDOCRINOLOGY PHYSIOLOGY,
PATHOPHYSIOLOGY, AND CLINICAL MANAGEMENT 8th ed. Elsevier.
 ENDOMETRIOSIS
Pemeriksaan
Laparoscopy
‘Gold standard’ diagnostic
test for endometriosis
“see & treat” approach,
Tergantung kemampuan
operator

Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed.
LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER
Yen & Jaffe’s. 2018. REPRODUCTIVE ENDOCRINOLOGY PHYSIOLOGY,
PATHOPHYSIOLOGY, AND CLINICAL MANAGEMENT 8th ed. Elsevier.
Hoffman, BL., et al. 2016. Williams Gynecology 3 rd ed. Elsevier.
Yen & Jaffe’s. 2018. REPRODUCTIVE ENDOCRINOLOGY PHYSIOLOGY,
PATHOPHYSIOLOGY, AND CLINICAL MANAGEMENT 8th ed. Elsevier.
 ENDOMETRIOSIS
• ACOSTA
• EEC (Endoscopic Endomet
Classification)

• AFS (American
Fertility Society)
- Minimal (AFS I)
- Ringan (AFS II)
- Sedang (AFS III)
- Berat (AFS IV)
Fritz, MA & Sperof, L. 2019. Clinical Gynecologic
Endocrinology and Infertility 9th ed. LIPPINCOTT
WILLIAMS & WILKINS, a WOLTERS KLUWER
 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
Revised AFS 1985
• Stage I (minimal)  1 – 5

• Stage II (mild)  6 – 15

• Stage III (moderate)  16 –

40

• Stage IV (severe)  > 40.

Stadium I/II
Stadium III
Stadium IV
Sebelum terapi Sesudah terapi
 EFI SURGERY FORM

Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed. LIPPINCOTT WILLIAMS & WILKINS,
a WOLTERS KLUWER
 Faktor Resiko
• Single/nulliparous
• Early menarche
• Non oral contraception
• Shorter cycle/longer duration of flow
• Inferility
• Stenosis of cervix
PENANGANAN ENDOMETRIOSIS
Penanganan terdiri dari :
• Medikamentosa
• Operatif
• Medikamentosa + Operatif
Penanganan Medikamentosa 6-12 bulan td:
• Pil kombinasi
• DMPA (Injeksi)
• MPA (Tablet)
• Danazol
• Leprolide
• Gosarelin
 NSAID dan HORMONAL

Yen & Jaffe’s. 2018. REPRODUCTIVE ENDOCRINOLOGY PHYSIOLOGY,

PATHOPHYSIOLOGY, AND CLINICAL MANAGEMENT 8th ed. Elsevier.
Hoffman, BL., et al. 2016. Williams Gynecology 3rd ed. Elsevier.
PENANGANAN ENDOMETRIOSIS
Penanganan Bedah td :
Konservatif dengan:
• Elektrokauter
• Reseksi
• Ablasi

Definitif dengan:
• HT+SOB PROGNOSIS?
 PENANGANAN ENDOMETRIOSIS
Pilihan penanganan tergantung :
• Ringan/berat endometriosis (klasifikasi)
• Aktif/non aktif endometriosis
• Ada anak/tidak ada anak
• Tingkat rekurensi
• Usia

Yen & Jaffe’s. 2018.

REPRODUCTIVE
ENDOCRINOLOGY PHYSIOLOGY,
PATHOPHYSIOLOGY, AND
CLINICAL MANAGEMENT 8th ed.
Elsevier.
Hoffman, BL., et al. 2016. Williams Gynecology 3rd ed. Elsevier.
Fritz, MA & Sperof, L. 2019. Clinical Gynecologic Endocrinology and Infertility 9th ed. LIPPINCOTT WILLIAMS & WILKINS,
a WOLTERS KLUWER
 ENDOMETRIOSIS
Hormonal
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.
“Endometriosis in rectovaginal septum & laparotomy
scars doesn’t respond to hormonal therapy”
 ENDOMETRIOSIS
Hormonal

“Produces pseudo pregnancy or pseudo

menopause”
• Danazol
• Progestins
• Gestrinone
• Combined oestrogen-progestogen Pills
• GnRH agonists
Kondisi endometriosis Pengobatan

Minimal/ringan non aktif Kauter+simptomatik

Minimal/ringan aktif Kauter+MPA/Danazol

Sedang/berat non aktif Segera kauter/kistektomi

Sedang/berat aktif GnRH+Operatif

ENDOMETRIOSIS & FERTILITAS

Endometriosis menyebabkan infertilitas:

• Oklusi tuba
• Distorsi anatomik organ pelvik  adhesi
• Menghslk zat toksik  prostanoid, sitokin
dan growth factors: mengganggu motilitas
sperma, interaksi sperma-sel telur,
transportasi embrio