Endometriozis ve İVF

Endometriozis ve İVF

Dr.Engin Oral

Cerrahpaşa Tıp Fak.

Kadın Hastalıkları ve Doğum A.B.D Reprodüktif 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 grade 1-2

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, 2001

Minguez 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 oranı

25.38 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 oranı

21.12 13.84 0.64 (0.35–1.17)

(düzeltilmiş) İmplantasyon %

11.31 10.23 0.21 (0.15–0.32)

(düzeltilmiş) Oosit sayısı

8.19 6.70 0.31 (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 significantly in patients with ovarian endometrioma compared with

controls, 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)

Hastaya cerrahi öncesi over

fonksiyonlarında 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

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