ENDOMETRIOMA: How it occurs?

21/01/2016
ALCOOLISATION DES ENDOMETRIOMES
ETHANOL SCLEROTHERAPY (EST)
Diplôme d’endoscopie en Gynécologie
Janvier 2015
Dr Anne Sophie GREMEAU, Pr Jean‐Luc POULY, Dr DEJOU BOUILLET lydie, Pr CANIS, Dr COMPAN Clara, Dr CHAUFFFOUR Candice. OVARIAN ENDOMETRIOMA (OE): How it occurs? 3 theories
– HUGHESTON (1957)/ BROSENS (1994)
The OE have their origin in superficial peritoneal implants of ovarian fossas. An accumulation of cyclic micro‐
haemorrhages is responsible for the accumulation of blood
and debris with progressive invagination al inside the ovary.
– NISOLLE ET DONNEZ (1996)
OE are due to an invagination of the mesothelium to the surface of the ovaries followed by coeliomic metaplasia of the invaginated tissue. This explains the OE having no contact with the fossa and OE multilocular formation
– JAIN 1999 et VERCELLINI (2009)
Colonization of functional ovarian cyst by endometriosis
implants.
Medulla
Internal layer
Cortex and follicules
Chocolate fluid
ENDOMETRIOMA: How it occurs?
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ENDOMETRIOMA And FERTILITY:
Current Trends
•
Negative impact of endometriosis on fertility: if> 2‐3 cm
–
Shubert B et al, Human reprod, 2005: histological evaluation of ovarian cortex surrounding the EO shows a –
Benaglia et al 2009: The physiological mechanisms leading to ovulation are deranged in ovaries with OE.
direct negative effect of the cyst on the on the follicular adjacent capital
•
Improving spontaneous conception rates after surgery: VERCELLINI et al, 2009
But cystectomy can also be deleterious to ovarian reserve
• Cystectomy negative effect on fertility:
– Alteration of ovarian Reserve (decrease in l’AMH level, poor response to COH)
– Especially if second surgeries, multiple or large endometriomas.
MORE OVER NO NEGATIVE IMPACT OF EO ON IVF RESULTS
No cyctectomy if ART required
Laparoscopic excision of OE
Recognizable ovarian tissue adjacent
to OC wall
Oma cyst wall:
no follicule
OMAs
14/26 (54%)
Non OMAs
1/16 (6%)
Serous
Oma cyst wall:
Scanty primordial follicule
< 0.005
0/7 (0%)
Dermoid
1/6 (17%)
Mucinous
0/3 (0%)
Muzii et al., Fertil Steril (2002)
Oma cyst wall:
Two primordial follicule
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OE SURGERY and AMH
Streuli et al, Human Reprod 2012
In women with endometriosus AMH levels are decreased only in those with previous endometrioma surgery
Raffi et al., JCEM (2012)
Negatif impact of excision of OE
on ovarian reserve
But new study VIGNALI 2015
showing that AMH level increase
One year after cystectomy
Medulla
Cortex et follicules
Paroi du kyste
The crucial question with the use
of the surgical treatment of OE
THE CLEAVAGE PLANE
Liquide chocolat
Cystectomy: YES but, GOOD WRONG
2 MAJORS RISK for THE FERTILITY
‐A part of normal cortex is removed in 59% of the cases vs 5 % for other cyst.
‐Risk of ovarian devascularization due to intensive coagulation for hemostasis.
No negative impact of endometrioma on IVF results
To treat or not to treat?
2 SITUATIONS: NO ART or ART REQUIRED
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Sociétés Savantes (1)….
•
2006
L’endométriose peut être responsable d’une hypofertilité, la chirurgie première est possible avec un délai de 6 à 12 mois derrière pour obtenir une grossesse spontanée
•
–
La ponction écho‐guidée n’est pas le traitement de première intention
–
Le drainage percoelioscopique n’est pas recommandé car il conduit à une récidive immédiate
–
KIP coelio si > 3cm (infertilité, douleur ou masse annexielle)
–
Traitement médical en préopératoire non recommandé.
Les endométriomes n’ont pas d’impact sur les résultats de l’AMP
–
. Ne pas interrompre une FIV si découverte d’un EO en cours de traitement
–
Pour les EO < 6cm, ni le traitement chirurgical, ni la ponction des EO ne sont recommandés avant la FIV.
Sociétés Savantes (2)….
•
2012
Laparoscopic cystectomy for OE greater than 4 cm improved fertility compared to cyst drainage and coagulation which is associated with a high risk of recurrence.
•
A possible adverse consequence is the loss of viable ovarian cortex.
•
After the first infertility operation, additional surgery has only rarely increased fecundability, and these patients may be better servec by using ART.
•
Ovarian endometrioma and IVF
–
For women who are found to have an asymptomatic OE ans who are planning to undergo IVF there is
insufficient evidence to suggest that removal of the endometrioma will improve IVF success rate.
–
But if the OE is large > 4cm, surgery should be considered to confirm the diagnosis histollogically, to improve
–
The patient should be made aware that extensive ovarian surgery could compromise ovarian function and access to follicle during OCR, and possibly to improve ovarian response.
diminish the response to ovarian stimulation.
Sociétés Savantes (3)….
•
2014
Surgery for infertility and pain.
–
Cyctectomy instead of drainage and coagulation or laser vaporization: less pain (Hart 2011), less
recurrence rate (Carmona et al 2011) In women with OE receiving surgery for infertility or pain, –
Excision of the endometrioma capsule increases the spontaneous post operative pregnancy rate when
compared with drainage and electrocoagulation of the OE wall
–
The GDG recommand that clinicians counselled women with OE regarding the risks of reduced ovarian
–
THE DECISION TO PROCEED SURGERY SHOULD BE CONSIDERED CAREFULLY IF THE WOMAN HAS function after surgery and the possible loss of the ovary.
HAD PREVIOUS SURGERY.
•
Endometrioma and ART
–
Several studies have evaluated the usefullness of cystectomy prior to ART to improve reproductive outcome in women with OE, but there is limited consistency in the interpretation of the results.
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Les sociétés savantes conclusions
OPERER LES ENDOMETRIOMES SI DOULEURS, HYPOFERTILITE sans autres causes ASSOCIEES
PREFERER LA KYSTECTOMIE LAPAROSCOPIQUE
EXCLURE LE DRAINAGE DE L’ENDOMETRIOME
4CM
3CM
3CM
ART AND ENDOMETRIOMA
No surgery if endometrioma
< 6cm
Surgery possible if
4cm but risque of ovarian
failure
No recommandation
NOTHING ABOUT ENDOMETRIOMA RECURRENCE
And MULTIPLES ENDOMETRIOMA
OE TREATMENTS: Goals and Methods
•
GOALS OF ENDOMETRIOMA TREATMENT
–
–
–
–
–
–
•
To permit a spontaneous pregnancy if there is no others causes of infertility
To remove the internal layer of the cyst
As much as possible to limit the risk of recurrence
Without destroying the surounding tissue and mainly the oocytes Without impairing the ovarian vascularization
Without missing an hypothetical cancer AVAILABLE TREATMENT
–
–
–
Medical treatment : not for infertility
Cystectomy: still the gold standard
Destruction of the internal layer of the cyst
•
•
Laser or plasma jet vaporization
Sclerotherapy
KYSTECTOMIE: Gold standard
Revue COCHRANE HART 2011
Comparaison of cystectomy versus excision
Less recurrence of endometrioma
Less requirement for further surgery
Less requirement of pelvic pain
Most subsequent spontaneous conception
BUT TWO MAJOR RISKS
‐Risk of removed normal ovarian cortex
‐Risk of ovarian devascularization due to
intensive coagulation for hemostasis.
ALTERNATIVES METHODS
‐ Ablative surgery: CO2, plasmajet
‐ Ethanol sclerotherapy
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Endometrioma: The optimal strategy
Surgery: EXCISIONAL or ABLATIVE
‐To Remove endometrioma, check the pelvis (tube adhesion), and to dicrease recurrence rate. (Hart 2011)
‐To get a specimen
‐To expect a natural pregnancy : 40 % deliveries (Hart 2011)
‐Knowledge of the surgeons (Matzuzaki 2009)
No Surgery ‐Low ovarian reserve : AFC and AMH (Somigliani 2012)
‐Multiple endometriomas (busacca 2009: IOP x2,4)
‐Recurrence of endometrioma (Streuli 2012, ferrero 2015)
‐Another pemanent indication of IVF (ASRM, ESHRE)
PLACE OF ETHANOL SCLEROTHERAPY
OE and IVF: The optimal strategy
•
What is proven •
–
No impact of endometrioma on IVF results (Benaglia 2013)
–
No benefits to remove the endometrioma before Ivf
PLACE OF ETHANOL
SCLEROTHERAPY
But –
Pains –
Less matures oocytes obtained (Yazbeck 2006, Busacca 2009)
–
Difficulty for ovum pick‐up
–
Risk of ovarian abscess (Padila 1997, Younis 1993)
IVF must be the option When endometrioma < 3 cm ‐
Direct IVF without OE treatment
When endometrioma > 3 cm or multiple or recurrence
‐
Ultralong protocole + sclerotherapy
ETHANOL SCLEROTHERAPY
•
ADVANTAGES:
–
Simple, fast
–
Cheep
–
Efficient on pain –
Recurrence rate <15 % –
Can be repeated
–
No histological sample
–
No evidence of alteration
of the ovarian reserve
Garcia Tejedor 2015 EJOG
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History
•
Initial
development
in
pulmonary
tuberculosis and in the treatment of
malignant pleural oncology. Then in
various types of cysts (thyroid, heart,
liver, kidney ..)
•
The simple echo‐guided aspiration has
been promoted first, but the high rate of
recurrence
restricted
its
application
(Giorlandino 1993, Chan 2003) and those
of other sclerotic agents (Chang 1997)
•
It was in Japan that has developed in the
ethanol sclerotherapy of endometriomas,
which led to a clear reduction of the
recurrence rate (Okagaki et al, 1999,
Noma and Yoshida 2001, Koide and Al
2002)
•
Investigate and test the efficacity
of Ethanol sclerotherapy for recurrent endometrioma before
COH in infertile patients.
– Cases: n=31 patients with positive histological diagnosis at previous
surgery, recurrent OE between 2 and 6 cm.
– Controls n=26, patients with an history of moderate to severe
endometriosis including one conventional laparoscopic
cystectomy for recurrent OE.
YAZBECK 2009: Endometrioma EST
Recurrence rate = 12.9%
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3 groups
‐Cystectomy
‐EST
‐Abstention
Same results in term of
Livebirth rate per cycle in the 3 groups
But place for EST
If huge endometrioma
And place to abstention
If small endometrioma
How we do?
•
In the AMP unit, we offer ethanol sclerotherapy for women requiring ART when:
– Previous surgery of endometriosis and recurrence of OE > 3cm
– Bilateral endometrioma
– Huge endometrioma if ART is indicated for another indication (MRI necessary)
– In extensive stage IV endometriosis with endometrioma when infertility is the main symptom (no or moderate pain)
– Abstention is offered if small recurrent endometrioma.
•
Sclerotherapy was done during ultra long GNRH agonist suppression protocol
– Just before the second injection
– US control of cysts was done before the controlled ovarian stimulation
Before IVF: Ethanol Sclerotherapy
during ultralong agonist protocols
GNRH ANALOGUE
DEPOT GNRH ANALOGUE
DEPOT GNRH ANALOGUE
DEPOT FSH‐HMG 30 DAYS 30 DAYS 20 DAYS CONTROL
Before COH SCLEROTHERAPY 8
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TECHNIQUE: Materiel
‐ Paracervical block and Sedation
‐ US with Endovaginal probe
‐ Transvaginal Needle 17 or 18G
‐ Nacl and Ethanol
EST: TECHNIQUE
•
‐Outpatient, oral sedation
•
‐Vagina sterilized with povidone iodine
•
‐Transvaginal US guidance and 18 gauge 30 cm single lumen needle
•
‐Cyst aspirated and Flushed with normal saline. Aspirate send for pathological review
•
‐Injection of pure sterile ethanol in an amount equal To 60% of the aspirated volume
•
‐Ethanol was lef 10min n the cyst and removed in case of important quantity (more than
30cc) and left in situ in case of small quantity (<30cc)
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Our Experience: 2010‐2013
PARAMETRES
n=27
Age
FSH (J3)
32,02 (27‐41)
8,5 (2,1‐11,8)
INDICATIONS
‐Endometriomes recidivants apres KIP
‐Endometrioses de stade IV avec mauvais pronostic chirurgical
16 (55,2%)
13 (44.8%)
NOMBRES DE KYSTES
‐ Patientes avec 1 Kyste
‐ Patientes avec 2 kystes
‐ Patientes > 3 kystes
‐ Endometriomes bilatéraux
57
14 (48.3%)
10 (34.5%)
5 (17.2%)
16 (59,3%)
CARACTERISTIQUES DES KYSTES
‐Diametre (mm)
‐Volume aspiré (ml)
‐Volume d’ethanol injecté (ml)
‐% volume/alcool
42,5 (10‐90)
50,7 (5‐170)
31,9 (2‐150)
63%
RESULTATS AMPS
‐ Protocoles ultralong
‐ Grossesses débutantes par cycles
‐ Grossesses evolutives
21
11 (35,5%)
7 (22,5%)
AMP Results after EST
2010‐2015
CASES n=40
Sclerotherapy
CONTROLS n=411 p
Endometriosis
Age moyen
32,03
34,28
Nombres de ponctions
‐ Blanches
‐ déprogrammées
51
2 (3.70%)
3 (5.70%)
685
11 (1.52%)
40 (5.52%)
Résultats ponction
‐Nombre ovocytes matures
taux de fecondation FIV
taux de fecondation ICSI
‐Nombre d’Embryons obtenus
‐Nombre d’embryons transférés
‐moyenne d’emb congelés
4.92 (251)
69.7%
75,58%
3.53 (180)
1.31 (59)
0.76 (39)
7.63 (5225)
61.34%
65.67%
4.74 (3250)
1.46 (872)
1.11 (762)
0.001
Grossesses cliniques
‐FCS
‐GEU
‐FCT et ITG
Accouchement attendus
15 (29.41%)
2 (13,33%)
1 (6.67%)
0 (0%)
12 (21,57%)
208 (30.36%)
45 (21.63)
6 (2.88%)
5 (2.40%)
152 (19.27%)
ns (0.9)
ns
ns
ns
ns (0.3)
ns (0.4)
ns (0.9)
0.001
LIVEBIRTH after EST
p
GROSSESSES
Sclerotherapy
n= 40 patients
GROSSESSES
All Endometriosis
n=425
Nb de grossesse
Accouchements faits
15
11 (27.5%)
208
132 (31.05%)
ns
TYPE DE GROSSESSE
‐Singletons
‐Jumeaux
‐Triplets
11 (100%)
0
0
116 (87,9%)
15 (11,3%)
1 (0,6%)
ns
ns
ns
A TERME >37SA
‐<32SA
‐32 à 37SA
CESARIENNES
8 (72%)
1
2
6 (54.55%)
112 (75%)
4
16
48 (36.36%)
ns
ENFANTS nombre
‐Terme moyen
‐poids moyen
11
35+7SA
2965 grammes
149
36+5SA
2868 grammes
ns
ns
ns
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COMPLICATIONS after EST (1)
•
PELVIC ABCESS (Younis 1997, J Assist Reprod
genetic)
– Prevention with strict aspesie and the use of sterile
equipment.
– Unsystematic Antibiotic prophylaxis unsystematic
(OH = bacteriostatic) unless history of pelvic
infection
•
ADHERENCES POST EST
– OKAGAKI R et al 1999, Human Reprod Oxf England; Severe and unusual discoveries adhesions around the ovaries during laparoscopy post EST (peritoneal
diffusion of ethanol?)
– MUZZI et al 2002: Same adhesions after simple EO punctures
COMPLICATIONS after EST (2)
•
DO NOT KNOW A MALIGNANT HISTOLOGY –
•
0.7% estimated risk of malignant disease in women with endometriosis of reproductive age (Nishida et al 2000)
–
Endometriosis disease often known before EST: Histology on previous surgery
–
Ultrasound imaging or MRI has excellent sensitivity specificity for benin or malignant ovarian tumor.
PERFORATIONS INTESTINALES, ALCOOLISATION SYSTEMIQUE
–
Perforations: non relevée après EST d’endometriome dans la littérature. Précautions d’injection de l’ethanol.
–
Alcoolisation systemique (Tei et al 1996, Masui)
•
Risque faible, lié a une diffusion sanguine de l’ethanol. Mais précaution systématique, surveillance 6h post ponction et test d’alcoolémie au moindre doute
AUTRES DONNEES SUR la SCLEROTHERAPIE
•
HSIEH and al, fertil steril 2009: Ethanol left in situ
– Group 1: n=78: 10 minutes sclerotherapy
– Group 2: n=30 Ethanol left in situ
– Same AFC and pain score in two groups, less recurrence in group 2 (13,3% vs 32,1%, p<0.005)
•
ZHANG and al, AJOG 2014: sclerotherapy of hydrosalpinx prior IVF
– US sclerotherapy on women with hydrosalpinx could improve the outcomes of IVF by improving the blood flow of uterine arcuate artery. No adverse effect on perinatal outcomes
was seen
•
FURMAN et al, 2007 Ulstrasound Obstet gynecol: case report
– Alcohol sclerotherapy for successful treatment of Focal adenomyosis
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EST and Fertility PRESERVATION
•
EST can offer a preservation of mature oocyte by vitrification for patient with severe
endometriosis, before of potentiel important surgery with risk for their ovarian reserve.
•
EST makes oocyte pick up easier ans could increase the number of mature oocyte obtained.
Long GNRH AGONIST
SUPPRESSION
ETHANOL
SCLERO
THERAPY
OVOCYTE
RETRIEVAL And VITRIFICATION
CONTROLLED
OVARIAN
STIMULATION
EXTENSIVE
SURGERY
Conclusion 1: OE and ART
Therpeutic options before an ART
SURGERY
EST
ABSTENTION
NO
YES
YES
LOW
Hystory of endometriosis
surgery
Ovarian reserve
NORMAL
LOW
Pain
YES
YES/NO
NO
Bilateral OE
NO
YES
YES
>6CM
>3CM
<3 CM
NO
YES
YES
Growth
FAST
STABLE
STABLE
Histological doubt
YES
NO
NO
Size
Recurrence os OE
Conclusion 2: EO without ART
•
GOLD STANDARD = CYSTECTOMY.
– Hormonal suppression if no pregnancy desire
– 6 to 12 months for spontaneous conception
•
EST CAN BE OFFERED – In fertility preservation before an extensive surgery (stade IV avec OE bilat)
– Recurrence of pain
– Recurrences of endometrioma with multiples previous
surgery
– Complex abdominal surgical history
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•
•
No more than one surgery
• Cystectomy +++
• Laser or plasma jet : expensive but valuable technologies
Sclerotherapy : multiple endometriomas and recurrence mainly
before IVF Symptômes
Désir de grossesse Iconographie
RCP
Radiologue
Chirurgiens
Médecin PMA
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