Endometriozis ve İVF

Dr.Engin OralCerrahpaşa Tıp Fak.

Kadın Hastalıkları ve Doğum A.B.DReprodüktif Endokrinoloji BilimDalı

ŞG 37 y, 3yıldır pr infertilite

Sol overde 6 cm end’oma+ male faktör(3mil/ml+%10+%37)FSH:10

Op vs ART anlatıldı. Hasta önce ART’yi tercih etti.

Nisan’08 Hybrid px; 300IU FSH+ 2 amp HMG step down, 11 gün stimülasyon, 7 oosit 5 MII 5x 2pn, 2. gün 5 ET ( grade 1)

Sonuç(+) tekil gebelik, 38 GH SCA, 2850 gr, E

EÇ 29y, 5 yıldır pr infertilite

Dismenore+, dyspareni+, kr pelvik ağrı+Kasım’05de L/S, Evre IV end’zis; Adezyolizis ve sağ overden5 cm end’oma ekstirpasyonu.

Şubat’06 Antg px 3 MII 3x2pn, 2. gün 3 ET sonuç(-)Mayıs’06 Antg px 5 MII, 2. gün 2 ET Sonuç(-)

Temmuz’06 da her iki overde loküller halinde 3-4 cm boyutunda multipl end’oma odakları izleniyor. Geri kalan over rezervi grade 2

2 ay depo GnRH analog tx

- Eylül’06 da mikrodoz px, 15 oosit, 15 MII,7x 2pn 3.gün 4 ET sonuç negatif

-Ocak ‘07 de Antg px ( 2 ay GnRH analog tx yi takiben)12 oosit, 12 MII 9x2pn 3. Gün 4ET sonuç(+)

33. Haftada dikor-diamn ikiz gebelik , Pl.previa , 2095gr kız/ 1885 gr kız bebek SCA ile doğurdu.

SG,31y, 4 yıldır sekonder infertilite

İlk gebelik 8 yıl önce varikosel cerrahisinin ardından spontan gerçekleşmiş.Spermiogram;2,6 ml 5,5mil/ml,%0+%9

TVUSG de sağ over grade 2 ,sol overde 3,5 cm end’oma, sağ overde 16 mm end’oma, gerikalan over rezervi grade1-2

2 ay depo GnRH analog tx

Antg px, 250 FSH+ 2amp HMG, 12 gün stimülasyon, 14 oosit, 12 MII 11x 2pn, 3 gün 3 ET(grade1)27 haftalık dikor-diamn ikiz gebelik devam ediyor.

Endometriozis-Evreleme

EVRE-1 (minimal= 1-5) EVRE-2 (hafif = 6-15)

EVRE-3 (orta = 16-40) EVRE-4 (ağır = > 40)

Endometriosis

Different types

Three clinicopathological entities with a different

origin.------------

• Peritoneal endometriosis,

• Ovarian endometriosis

• Deep pelvic endometriosis (adenomyotic

nodules)

Sorular

• Endometriozis IVF sonuclarina etkili mi

• Endometrioma varlığı fertiliteyi etkiliyor mu

• Ivf oncesi endometrioma cerrahisi ivf sonuçları etkiliyor mu

• Başarısız IVF sonrası cerrahi faydalı mı• IVF oncesi depo GnRHa faydalı mı• Endometrioma varlığında ovum toplanmasında risk var mı• Tekrarlayan endometriomanın yönetim (Cerrahi vs. ivf)

• Hangi protokol

• Ne zaman IVF

Diğer faktörler

• Yaş ve over rezervi

• İnfertilite süresi• Erkek faktörü• Tubal faktör• Daha önce yapılmış tedaviler

Cumulative conception rates with untreated

endometriosis related to disease grading, compared

with normal conception rate

Kevin D. Jones, 2002

N

Minor

Moderate Severe

What is the impact of endometriosis on the

results of ART?

1. Number of oocytes ?

2. Oocyte quality ?

3. Fertilisation ?

4. Implantation ?

5. Miscarriage rates ?

Endometriosis and ICSI

Fertilisation rates

Bükülmez et al, 2001Minguez et al, 1997

Endometriosis-ART

(Meta-analysis)

• 1983-1999

• 22 published studies (2377 vs 4383 cycles)

• Pregnancy rate OR 0.56 (0.44-0.70)

• Decreased implantation and fertilization rates, decrease number of oocytes by about 50%

• Pregnancy rates in severe disease lower than mild disease OR 0.60 (0.42-0.87)

Kurt Barnhart, 2002

IVF Gebelik oranları Endometriozis/ Tubal faktör

Endometriozis Tubal faktör Düzeltilmiş OR

Gebelik oranı25.38 27.71 0.56 (0.44–0.70)

Fertilizasyon %59.50 66.09 0.81 (0.79–0.83)

İmplantasyon %12.72 18.08 0.86(0.85–0.88)

Kurt Barnhart, 2002

Endometriozis / Evre sonuç ilişkisi

Evre I-II Evre III-IV OR

Gebelik oranı21.12 13.84

0.64 (0.35–1.17)

(düzeltilmiş)İmplantasyon %

11.31 10.230.21 (0.15–0.32)

(düzeltilmiş)Oosit sayısı

8.19 6.700.31 (0.24–0.39) (düzeltilmiş)

Kurt Barnhart, 2002

SART-2005

SART-2006

Should endometriomas be treated

before IVF–ICSI cycles?

Edgardo Somigliana, 2006

Impact of ovarian endometrioma on oocytes and

pregnancy outcome in in vitro fertilization

Takahiro Suzuki, 2005

oma endo

Impact of ovarian endometrioma on assisted reproduction

outcomes.

• Metaanalysis

• The odds for clinical pregnancy were not affected significantlyin patients with ovarian endometrioma compared withcontrols, with an overall odds ratio of 1.07 from three studies[95% CI: (0.63-1.81), P = 0.79].

• Decreased ovarian responsiveness to ovarian stimulation in patients with ovarian endometrioma may be due to a reduced number of follicles in these patients compared with controls (P = 0.002).

Gupta S, 2006

The outcome of in vitro fertilization in advanced

endometriosis with previous surgery: A case-

controlled study

Mohamed A. Aboulghar, 2003

56% of the patients were treated

by laparotomy once and 25% twice.

%53

Studies comparing the number of follicles in the operated

and in the contralateral non-operated ovary during IVF

Reference Surgical

technique

No. of

cycles

Control

ovary

Operated

ovary

P

Nargund et al. (1996) Not reported 90 8.9±5.1 6.3±5.2 <0.001

Loh et al. (1999) Cyst enucleation 12 3.6 4.6 NS

Donnez et al. (2001) Cyst wall

vaporization

87 6.6±3.5 5.2±3.0 NS

Ho et al. (2002) Cyst enucleation 38 3.3±2.1 1.9±1.5 <0.001

Somigliana et al. (2003)

Wong et al (2004)

Cyst enucleation

Cyst enucleation

46

no

4.2±2.0

4.4±2.7

5.0±0.8

2.1±1.7 (≤3 cm)1.9±1.4 (>3 cm)

6.3±1.1

<0.003

<0.001

NS

Damage to ovarian reserve associated with

laparoscopic excision of endometriomas: A

quantitative rather than a qualitative injury

Guido Ragni, 2005

N: 38

Embryo quality before and after surgical

treatment of endometriosis in infertile patients

Stage I 40%

Stage II 17%

Stage III 13%

Stage IV 30% Lora K. Shahine, 2009

Endometrioma and Laparoscopy

Garcio-Velasco, 2004

Surgery (+)

N:147

Surgery (-)

N:63

P

Number of oocytes 10.8 11.8 NS

Fertilisation rate 76.5 69.9 NS

Implantatation rate 12.8 14.1 NS

PR 25.4 22.7 NS

Effect of endometrioma cystectomy on IVF outcome: a

prospective randomized study.

• prospectively randomized

• group I (49 patients) - ovarian surgery before ICSI

• group II (50 patients) -ICSI cycle directly

• Group 1- lower oocyte number

• There was no difference in terms of fertilization (86% in

group I and 88% in group II), implantation (16.5% in

group I and 18.5% in group II) pregnancy rates (34% in

group I and 38% group II).

Demirol A, 2006

Outcome of in vitro fertilization/intracytoplasmic sperm

injection after laparoscopic cystectomy for endometriomas.

• Retrospektif analysis

• unilateral (n = 34)

• bilateral (n = 23) laparoscopic cystectomy

• control group (n= 99 ) tubal factor infertility

• The mean number of oocytes, metaphase II oocytes, and two-

pronucleated oocytes were significantly lower in the bilateral

cystectomy group

• fertilization rate, the mean number of embryos transferred, the

mean number of grade 1 embryos transferred, the clinical

PR/ET, implantation rate, were comparable among the three

groups.

• Laparoscopic endometrioma cystectomy does reduce the

ovarian reserve. However, diminished ovarian reserve does

not translate into impaired pregnancy outcome.Esinler İ, 2006

Aspiration of ovarian endometriomas

before intracytoplasmic sperm injection

Recai Pabuccu, 2004

aspiration of endometriomas at the beginning

nonaspirated endometriomas

history of ovarian surgery for endometriomas

tubal factor infertility N: 171

ICSI uygulaması öncesi Ovaryan endometrioma aspirasyonu

• Endometrioma varsa (Tubal faktör hst.a göre ) daha az Metafaz II oosit

• KOH öncesi endo aspirasyonu– Gonadotropin miktarını azaltmaz

– M II oosit sayısını– İmplantasyon oranlarını artırmaz– Gebelik oranlarını

• 1-6 cm endometriomaların rezeksiyonu IVF’e fayda sağlamaz

Recai Pabuccu, 2004

Endometrioma vs. Simple cyst

IVF-ICSI outcome in women operated on for bilateral

endometriomas.

• 68 cases (bilat. cystectomy)- 136 controls

• the number of follicles (P = 0.006), oocytes retrieved

(P = 0.024) and embryos obtained (P = 0.024) were significantly lower.

• The clinical pregnancy rate per started cycle in cases and controls was 7% and 19% (P = 0.037)

• CONCLUSIONS: IVF outcome is significantly impaired in women operated on for bilateral ovarian endometriomas.

Edgardo Somigliana1, 2008

Ibrahim Esinler, 2006

The effect of surgical treatment for endometrioma on

in vitro fertilization outcomes: a systematic review

and meta-analysis

Ioanna Tsoumpou, 2008

Management of endometriomas in women requiring IVF:

to touch or not to touch.

proceeding directly to IVF to reduce

time to pregnancy, to avoid potential

surgical complications and to limit

patient costs.

Garcia-Velasco JA., 2008

IVF Planlanan Endometriomalı Hastalarda Endometriomanın Çıkarılıp Çıkarılmamasında Kararı

Etkileyen Kriterler

Cerrahi Bekleme

Geçirilmiş endometriosis op yok ≥ 1

Ovarian rezerv intakt azalmış

Ağrı var yok

monolat.- bilateral monolateral bilateral

USG de malignite şüphesi var yok

Büyüme hızı hızlı stabil

Garcia-Velasco JA and Somigliana E: Hum Reprod 1(1):1-6,2009.

Analysis of risk factors for the removal

of normal ovarian tissue during laparoscopic

cystectomy for ovarian endometriosis

• A total of 121 patients who had histologically confirmed ovarian

endometriosis and 56 control patients who had other histologically

confirmed benign cysts were included

• Normal ovarian tissue adjacent to the cyst wall was detected in 71

patients (58.7%) with endometriosis, whereas normal ovarian tissue

was removed from only three patients (5.4%) with other benign cysts.

• A significant factor that was independently associated with the

removal of normal ovarian tissue with ovarian endometriosis was pre-

operative medical treatment

Sachiko Matsuzaki1,2009

Postsurgical ovarian failure after laparoscopic

excision of bilateral endometriomas

• Objective: This study was undertaken to determine the frequency of

postsurgical ovarian failure in patients undergoing laparoscopic

excision of bilateral endometriomas.

• Study design: Patients who had been operated on for bilateral ovarian

endometriosis between January 1995 and December 2003 and who

were younger than 40 years at the time of surgery were contacted by

telephone and interviewed.

• Results: Atotal of 126 patients were recruited. Mean age of patients at

the time of surgery was 30.4 years. Postsurgical ovarian failure was

documented in 3 cases, corresponding to a rate of 2.4% (95% CI 0.5%-

6.8%). In all cases, this complication occurred immediately after

surgery.

• Conclusion: Patients who had been operated on for bilateral

endometriomas have a low but definite risk of premature ovarian failure occurring immediately after surgery.

Mauro Busacca, 2006

Endometrioma ve IVF

GPP Önerisi (ESHRE- Endometriosis) 2005

Hastaya cerrahi öncesi overfonksiyonlarında azalma olabileceği ve hatta bazen over kaybının olabileceği konusunda bilgi ve danışmanlık verilmelidir.

Eğer hastaya daha önce bir ovaryan cerrahi yapılmışsa, karar bir kez daha gözden geçirilmelidir. (Hastanın kaderini belirlemede ilk operasyon çok önemlidir.)

Cerrahi Tedavi

Clinical condition Recommendation

ESHRE 2005 ASRM 2006 RCOG 2006

Minimal-Mild

(Stage I-II)

Limited Benefit:

Surgery recommended

Small benefit: Surgery

recommended

Demonstrated benefit:

surgery recommended

Moderate-Severe

(Stage III-IV)

Possible but unproven

benefit: surgery

recommended

Possible benefit:

surgery recommended

Possible benefit:

surgery recommended

Postoperative Adj

Treatment

No benefit: Not

recommended

No benefit: Not

recommended

No benefit: Not

recommended

Surgery before IVF Recommended if

endometrioma > 4 cm

Doubtful benefit: no

recommended

Recommended if

endometrioma > 4 cm

Recurrent

endometriosis

No recommendation Second-line surgery

not recommended

No recommendation

Vercellini et al., Human Reproduction 2009

GnRH agonist and antagonist protocols for stage I–II

endometriosis and endometrioma in in vitro fertilization/

intracytoplasmic sperm injection cycles

Recai Pabuccu, 2007

GnRH agonist v/s no agonist before IVF(Clinical pregnancy rate per woman)

Sallam et al, Cochrane Database Syst Rev 25;(1):CD004635, 2006

GnRH agonist v/s no agonist before IVF(Ongoing pregnancy rate per woman)

Sallam et al, Cochrane Database Syst Rev 25;(1):CD004635, 2006

Endometrioma ve oosit

toplanması• Hacim artması• Enfeksiyon, abse

• Akut abdomen

• Toksik etki

• Malignite

Is the dimension of ovarian endometriomas

significantly modified by IVF–ICSI cycles ?

Laura Benaglia, 2009

n.48

Endometrioma and oocyte retrieval–induced pelvic

abscess: a clinical concern or an exceptional

complication

• The authors evaluated the risk of developing a pelvic

abscess in a series of 214 in vitro fertilization cycles that

were performed in women with endometriomas. This

complication was never recorded, indicating that its risk is

very low (0.0; 95% confidence interval, 0.0–1.7%).

• Literature

– nine cases were described. Prophylactic antibiotics have been

administered in at least eight cases. The endometrioma was

punctured at the time of oocyte retrieval in at least six cases.

Laura Benaglia, 2008

Endometriozisle İlişkili İnfertilitede ART seçimi

Hasta yaşı: >37

Önceki tedaviler: 3-4 KOH/IUI denemesi

İleri evre endometriozis

Male faktör , tubal infertilite eşlik ediyorsa Optimal olmayan cerrahi

Kötü over rezervi

Uzun süreli infertilite > 5 yıl

İn vitro fertilizasyon

Sorular ve cevaplar

• Endometriozis IVF sonuclarina etkili mi

– Etkili değil (ileri evre ?)

• Endometrioma varlığı fertiliteyi etkiliyor mu

– değiştirmiyor

• Ivf oncesi endometrioma cerrahisi ivf sonuçları etkiliyor mu

– Değiştirmiyor (azalmış over rezervi ?)

• Başarısız IVF sonrası cerrahi faydalı mı– Bazı olgularda

Sorular ve cevaplar

• IVF oncesi depo GnRHa faydalı mı– Etkili gibi ama daha çok çalışmaya gerek var

• Endometrioma varlığında ovum toplanmasında risk var mı– yok

• Tekrarlayan endometriomanın yönetim (Cerrahi vs. ivf)

– ivf

• Hangi protokol

– Fark yok

• Ne zaman IVF

– Olguya göre değişir