Endometriozis ve İVF. Dr.Engin Oral. Cerrahpaşa Tıp Fak. Kadın Hastalıkları ve Doğum A.B.D Reprodüktif Endokrinoloji BilimDalı

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1 Endometriozis ve İVF Dr.Engin Oral Cerrahpaşa Tıp Fak. Kadın Hastalıkları ve Doğum A.B.D Reprodüktif Endokrinoloji BilimDalı

2 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

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4 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

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7 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.

8 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 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.

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11 Endometriozis-Evreleme EVRE-1 (minimal= 1-5) EVRE-2 (hafif = 6-15) EVRE-3 (orta = 16-40) EVRE-4 (ağır = > 40)

12 Endometriosis Different types Three clinicopathological entities with a different origin Peritoneal endometriosis, Ovarian endometriosis Deep pelvic endometriosis (adenomyotic nodules)

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14 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

15 Diğer faktörler Yaş ve over rezervi İnfertilite süresi Erkek faktörü Tubal faktör Daha önce yapılmış tedaviler

16 Cumulative conception rates with untreated endometriosis related to disease grading, compared with normal conception rate N Minor Moderate Severe Kevin D. Jones, 2002

17 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?

18 Fertilisation rates Endometriosis and ICSI Bükülmez et al, 2001 Minguez et al, 1997

19 Endometriosis-ART (Meta-analysis) published studies (2377 vs 4383 cycles) Pregnancy rate OR 0.56 ( ) Decreased implantation and fertilization rates, decrease number of oocytes by about 50% Pregnancy rates in severe disease lower than mild disease OR 0.60 ( ) Kurt Barnhart, 2002

20 IVF Gebelik oranları Endometriozis/ Tubal faktör Endometriozis Tubal faktör Düzeltilmiş OR Gebelik oranı Fertilizasyon % İmplantasyon % ( ) ( ) ( ) Kurt Barnhart, 2002

21 Endometriozis / Evre sonuç ilişkisi Evre I-II Evre III-IV OR Gebelik oranı İmplantasyon % Oosit sayısı ( ) (düzeltilmiş) 0.21 ( ) (düzeltilmiş) 0.31 ( ) (düzeltilmiş) Kurt Barnhart, 2002

22 SART-2005

23 SART-2006

24 Should endometriomas be treated before IVF ICSI cycles? Edgardo Somigliana, 2006

25 Impact of ovarian endometrioma on oocytes and pregnancy outcome in in vitro fertilization oma endo Takahiro Suzuki, 2005

26 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: ( ), 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

27 The outcome of in vitro fertilization in advanced endometriosis with previous surgery: A casecontrolled study 56% of the patients were treated by laparotomy once and 25% twice. Mohamed A. Aboulghar, 2003

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31 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 ± ±5.2 <0.001 Loh et al. (1999) Cyst enucleation NS Donnez et al. (2001) Cyst wall vaporization ± ±3.0 NS Ho et al. (2002) Cyst enucleation ± ±1.5 <0.001 Somigliana et al. (2003) Cyst enucleation ± ±1.7 ( 3 cm) < ± ±1.4 (>3 cm) <0.001 Wong et al (2004) Cyst enucleation no 5.0± ±1.1 NS

32 Damage to ovarian reserve associated with laparoscopic excision of endometriomas: A quantitative rather than a qualitative injury N: 38 Guido Ragni, 2005

33 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

34 Endometrioma and Laparoscopy Surgery (+) N:147 Surgery (-) N:63 P Number of oocytes NS Fertilisation rate NS Implantatation rate NS PR NS Garcio-Velasco, 2004

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36 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

37 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 twopronucleated 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

38 Aspiration of ovarian endometriomas before intracytoplasmic sperm injection aspiration of endometriomas at the beginning nonaspirated endometriomas history of ovarian surgery for endometriomas tubal factor infertility N: 171 Recai Pabuccu, 2004

39 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

40 Endometrioma vs. Simple cyst

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42 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

43 Ibrahim Esinler, 2006

44 The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta-analysis Ioanna Tsoumpou, 2008

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46 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

47 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.

48 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 preoperative medical treatment Sachiko Matsuzaki1,2009

49 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

50 Endometrioma ve IVF 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. (Hastanın kaderini belirlemede ilk operasyon çok önemlidir.) GPP Önerisi (ESHRE- Endometriosis) 2005

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52 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

53 GnRH agonist and antagonist protocols for stage I II endometriosis and endometrioma in in vitro fertilization/ intracytoplasmic sperm injection cycles Recai Pabuccu, 2007

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56 GnRH agonist v/s no agonist before IVF (Clinical pregnancy rate per woman) Sallam et al, Cochrane Database Syst Rev 25;(1):CD004635, 2006

57 GnRH agonist v/s no agonist before IVF (Ongoing pregnancy rate per woman) Sallam et al, Cochrane Database Syst Rev 25;(1):CD004635, 2006

58 Endometrioma ve oosit toplanması Hacim artması Enfeksiyon, abse Akut abdomen Toksik etki Malignite

59 Is the dimension of ovarian endometriomas significantly modified by IVF ICSI cycles? n.48 Laura Benaglia, 2009

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61 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, %). 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

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63 Endometriozisle İlişkili İnfertilitede Hasta yaşı: >37 ART seçimi 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

64 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

65 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