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PCOS ve ABORTUS

PCOS ve ABORTUS. Dr. Teksin Çırpan Ege Üniversitesi Kadın Hastalıkları ve Doğum Anabilim Dalı, İzmir 08.10.2011. PCOS. İNSİDANS: %5-10 OLİGO/AMENORE, HİPERANDROJENEMİ, SONOGRAFİ ( Hum Reprod 19(1):41–47 ) ANOVÜLASYON +NORMO- Gntropik : %70 OBES: %50 İNSÜLİN R: %25-70 SUB-GRUP: 4

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PCOS ve ABORTUS

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  1. PCOS ve ABORTUS Dr. Teksin Çırpan Ege Üniversitesi Kadın Hastalıkları ve Doğum Anabilim Dalı, İzmir 08.10.2011

  2. PCOS • İNSİDANS: %5-10 • OLİGO/AMENORE, HİPERANDROJENEMİ, SONOGRAFİ (Hum Reprod 19(1):41–47 ) • ANOVÜLASYON +NORMO-Gntropik: %70 • OBES: %50 • İNSÜLİN R: %25-70 • SUB-GRUP: 4 ArchGynecolObstet (2010) 282:235–239, PCOS andpregnancyoutcome

  3. PCOS’da KLİNİK GÖRÜNÜM • OLİGO/ANOVÜLASYON • HİPERANDROJENEMİ +/- • PCO • İNFERTİLİTE • OBESİTE • İNSÜLİN R, %40 Clinical manifestations of PCOSin adults UpToDate.com

  4. ERKEN GEBELİK KAYIPLARI • EN SIK KOMPLİKASYON • KLİNİK İNSİDANS, %8-20, (+%13-26) • REKÜRRENS RİSKİ: %5, %20, %28, %43 • RİSK FAKTÖRLERİ: YAŞ, ÖYKÜ, SİGARA, ALKOL, KOKAİN, NSAI, ATEŞ, KAFEİN, OVÜLASYON/İMPLANTASYON, GEBE KALMA SÜRESİ, FOLAT, BMI (Spontaneous abortion, UpToDate.com)

  5. ERKEN GEBELİK KAYIPLARIETYOLOJİ • KROMOZOMAL ANOMALİ • KONGENİTAL ANOMALİ • TRAVMA • UTERİN ANOMALİ • ENFEKSİYON • ENDOKRİNOPATİ; PCOS • TROMBOFİLİ • İMMÜNOLOJİK • ÇEVRESEL • AÇIKLANAMAYAN (Spontaneous abortion, UpToDate.com)

  6. TEKRARLAYAN GEBELİK KAYIPLARIRİSK FAKTÖRLERİ ve ETYOLOJİ • ÖYKÜ; YAŞ, PARİTE, GEBELİK HFT. • UTERİN FAKTÖR • İMMÜNOLOJİK • ENDOKRİNOPATİ; PCOS • GENETİK • TROMBOFİLİ, FİBRİNOLİTİK SİSTEM • ÇEVRESEL FAKTÖRLER, STRES • MADDE KULLANIMI, ERKEK FAKTÖR, ENFEKSİYON, AZALMIŞ OVER REZERVİ, CELIAC HST (RPL, UpToDate.com)

  7. PCOS – ERKEN GEBELİK KAYIPLARI • KESİN KANIT ? • EGK: %33 (Hum Reprod 15(3):612–615) • INTRA-UTERİN PRO-İNFLAMTUAR YANIT, • BMİ/OBESİTE (PCOS), • İNSÜLİN R (PCOS), ArchGynecolObstet (2010) 282:235–239, PCOS andpregnancyoutcome

  8. Pregnancycomplications in PCOS Best Practice & ResearchClinicalEndocrinology & MetabolismVol. 20, No. 2, 2006

  9. The pathogenesis of infertility and earlypregnancy loss in polycystic ovary syndrome Best Practice & Research Clinical Obstetrics and GynaecologyVol. 18, No. 5, 2004

  10. Howcommon is PCOS in recurrentmiscarriage? Vol 19. No 4. 2009 572-576 ReproductiveBioMedicine Online

  11. PCOS – ETYOPATOGENEZ • HİPOTALAMUS/HİPOFİZ, • STEROİDOGENEZ, • OVERYAN HİPERANDROJENİZM, 2/3 • ADRENAL HİPERANDROJENİZM, 1/3 • İNTRİNSİK FAKT. & STEROİDOGENEZ, • EXTRİNSİK FAKT. & STEROİDOGENEZ, • İNSÜLİN R Definition, pathogenesis, and etiology of PCOSUpToDate.com

  12. PCOS – EPL & ETYOPATOGENEZ • LH, • HİPERANDROJENEMİ, • HİPERİNSÜLİNEMİ • PROGESTERON, HİPOFİZ • HİPERHOMOSİSTEİNEMİ, OVER • GLUKODELİN, AZALMA ENDOMETRİUM • IGFBP-2, AZALMA • PAI AKTİVİTESİ, ARTIŞ • BMI EPL • ENDOTELYAL DİSFONKSİYON ArchGynecolObstet (2010) 282:235–239, PCOS andpregnancyoutcome • PI, DİASTOLİK ÇENTİK (Uterinebloodflowin pregnantpatientswith PCOS: relationshipswithclinicaloutcomes. BJOG (2010) 117(6))

  13. LH HİPERSEKRESYONU (%40) • FOLİKÜLER FAZ • ESTROJEN, İNSÜLİN • OOSİT MATÜRASYONU, OOGENEZİS • FOLİKÜLOGENEZİS • OVÜLASYON • FERTİLİZASYON • İMPLANTASYON • EMBRYO SURVİVAL • Oİ YANIT ve ABORT RİSKİ (CC) Best Practice & Research Clinical Obstetrics and GynaecologyVol. 18, No. 5, 2004 LH YÜKSEK %67 GEBE %65 ABORT LH NORMAL %88 GEBE %12 ABORT

  14. HİPERANDROJENEMİ • LH • İNSÜLİN R EGF-R, ARTIŞI • OBESİTE HOXA-10, AZALIŞI ENDOTELYAL DİSFOKSİYON • SHBG • HİPOFİZ • OVER • ENDOMETRİUM Best Practice & Research Clinical Obstetrics and GynaecologyVol. 18, No. 5, 2004

  15. HİPERİNSÜLİNEMİ • LH • BMI • SHBG • HİPERANDROJENEMİ • PAI-1, ARTIŞ • HİPOFİZ • OVER • ENDOMETRİUM: GLİKODELİN, IGFBP-1, ENDOTELİN-1 Best Practice & Research Clinical Obstetrics and GynaecologyVol. 18, No. 5, 2004

  16. Extra- andintra-ovarianfactors in PCOS: impact on oocytematurationandembryodevelopmentalcompetence BOOGENEZİS FOLİKÜLOGENEZİS OVÜLASYON FERTİLİZASYON İMPLANTASYON EMRYOGENEZİS Human Reproduction Update, Vol.17, No.1 pp. 17–33, 2011

  17. ThePathophysiology of Miscarriage in WomenwithPolycysticOvarySyndrome. ReviewandProposedHypothesis of MechanismsInvolved HORMONES 2004, 3(4):221-227

  18. PCOSMETFORMİN TDV’si • İNSÜLİN • PAI-1 • VASKÜLARİZASYON • ENDOTELİN-1 • GLİKODELİN • LH/ANDROJEN • BMI Pregnancycomplications in PCOS Best Practice & ResearchClinicalEndocrinology & MetabolismVol. 20, No. 2, 2006

  19. PCOS – EPL - METFORMİN • %41.9 & %8.8, METFORMİN +/- (Effectsof metforminon earlypregnancyloss in thePCOS. J ClinEndocrinol (2002) Metab87(2)) • %49.5 & %12.5, ‘OBES + PCOS’ (Continuation of metforminreducesearlypregnancyloss in obesePakistaniwomenwithPCOS. GynecolObstetInvest (2009) 69(3)) • %35, RİSK ARTIŞI + (Pregnanciesfollowinguseof metforminforovulationinduction in patientswith PCOS. Fertil Steril (2002) 77(4)) • EPL RİSKİNE ETKİSİ YOK (Effect of preconceptionalmetformin on abortion risk in PCOS: a systematicreviewand meta-analysis of randomizedcontrolledtrials. Fertil Steril (2009) 92(5))

  20. PCOSMETFORMİN TDV’si Pregnancyoutcomesamongwomenwith PCOS treatedwithmetformin. HumanReproduction 2002; 17

  21. PCOSCC/GnTDV’si • SPONTAN ABORT RİSKİ, %25 • OBESİTE • EM’da ANTİ-ESTROJEN • LH ARTIŞI • DÜŞÜK DOZ FSH protokol, Gn • KONVANSİYONEL Gn Pregnancycomplications in PCOS BestPractice & ResearchClinicalEndocrinology & MetabolismVol. 20, No. 2, 2006 CC

  22. PCOS & GnRHagonistTDV’si • LH YÜKSEK + PCOS; LH NORMAL + MEKANİK İNFERT. GnRHagonistreducesthemiscarriagerate forpregnanciesachieved in womenwith PCOS. FertililtyandSterility 1993; 59 • hMG +/- GnRHagonist; %17.6/%39 IVF-ETforthetreatment of infertilityassociatedwith PCOS. FertilityandSterility 1993; 60

  23. PCOS & GnRHagonistTDV’si • FEED-BACK • UZUN SÜRE • Gn DOZU • FOLİKÜL SAYISI • ÇOĞUL GEBELİK • OHSS • SİKLUS İPTALİ Pregnancycomplications in PCOS Best Practice & ResearchClinicalEndocrinology & MetabolismVol. 20, No. 2, 2006 LH YÜKSEK Gn İLE GEBELİK YOK 1 < ABORT

  24. Pregnancyoutcome in womenwith PCOS comparingtheeffects of laparoscopicovariandrillingandclomiphenecitratestimulation in womenpre-treatedwithmetformin: a retrospectivestudy Reproductive Biology and Endocrinology 2010, 8:45

  25. PCOS & DİET Weightlossresults in significantimprovement in reproductiveoutcomeforallforms of fertilitytreatment. HumanReproduction (Oxford, England) 1998; 13

  26. A reappraisal of the role of PCOS in recurrentmiscarriage • PCO MORFOLOJİ • LH • ANDROJEN • HİPERİNSÜLİNEMİ • OBESİTE • ANOVULATUAR • CC (%14-25) • Gn; low-dose step-up, • GnRHagonist + FSH • HMG; EM’alreseptivite • OVER DRİLLİNG (%11-15) • METFORMİN, EM’alreseptivite • DİET Vol 17 No 1. 2008 ¡51-161 ReproductiveBioMedicine Online

  27. PCOS andpregnancyoutcome: redherringorredflag? • İNFERTİL KADIN; %15 • PCO MORFOLOJİ: %15-32 • SUBGRUP + PREDİSPOZAN FAKTÖRLER • HİPERİNSÜLİNEMİ, İNSÜLİN R, %30-70 • POLİGENİK PREDİSPOZİSYON • OBESİTE • EPL, 1/3 • LH (FOLİKÜLER FAZ) • ANORMAL PROGESTERON ÜRETİMİ • PAI-1 , ARTIŞ • HİPERANDROJENEMİ • GLİKODELİN, AZALMA • IGFBP-2, AZALMA; EM’al IGF-1, AZALMA • HİPERHOMOSİSTEİNEMİ (İNSÜLİN R) • EM’al PRO-İNFLAMATUVAR HADİSE (İNSÜLİN R) • GnRH/METFORMİN & ART/EPL BJOG. 2007 Aug;114(8):922-32. Review.

  28. Polycysticovarysyndromeandpregnancyoutcome: redherringorredflag? BJOG. 2007 Aug;114(8):922-32. Review.

  29. PCOS andthe risk of spontaneousabortionfollowingART treatment • BACKGROUND: Thisstudyaimstodeterminetheeffect of PCOS status on the risk of spontaneousabortionwithadjustmentfor body massandseveralotherconfoundingfactors in a largecohort of pregnantinfertilewomen. METHODS: Thepatients (n = 1018) weretreated in a tertiaryinfertilitycentre. Their PCOS statuswasdeterminedbystandardcriteriaandtheir BMI had beentakenlessthan 1 yearbeforethepregnancy. Student'st-test or χ2 test wereusedto test thedifferencebetweenthe PCOS andnon-PCOS groupswhile a multivariatelogisticalregression model wasusedtoassesstheeffect of PCOS, BMI andotherconfoundingfactors. RESULTS: Overall, theincidence of PCOSwas37% in thiscohort. Theoverallincidence of spontaneousabortionin thestudypopulationwas21%. UnivariateanalysisshowedthatwomenwithPCOS had a significantlygreater risk of spontaneousabortioncomparedwithnon-PCOSwomen (25 versus 18%, P < 0.01). However, usingmultivariatelogisticregressionanalysisthiseffectwasreducedto a non-significantlevel[oddsratio (OR) = 1.10, 95% confidenceinterval (CI) 0.85–1.36] afteradjustingforobesityandpatients/treatmentcombinationfactor, andtonilafteradjustingforallconfoundingfactorsconsidered in thisstudy (OR = 0.98, 95% CI 0.75–1.28). CONCLUSION: Theresults of thisstudysuggestthatthehigher risk of spontaneousabortionobserved in womenwith PCOS is likelyto be duetotheirhighprevalence of obesityandthetype of treatmenttheyreceive. Human Reproduction Volume 16, Issue 12, 2001

  30. Prevalence of PCO in womenwith self-reportedsymptoms of oligomenorrhoeaand/orhirsutism: NorthernFinlandBirthCohort 1966 Study HumanReproductionVol.19, No.5 pp. 1083±1088, 2004

  31. Theadverseeffects of obesity on conceptionandimplantation Reproduction (2010) 140 347–364

  32. Theadverseeffects of obesity on conceptionandimplantation Reproduction (2010) 140 347–364

  33. Theadverseeffects of obesity on conceptionandimplantation Reproduction (2010) 140 347–364

  34. PCOS & SPONTAN ABORT PREVALANSI • YAŞ • PARİTE • GEBE KALMA SÜRESİ • OBSTETRİK ÖYKÜ • EK FAKTÖR • SPONTAN / OI-ART / İLAÇ • PCOS’da SPNT ABORT PREVALANSI ? • SENSİTİF TESTLER • PCOS & OBESİTE & İNSÜLİN R (BAĞIMSIZ FAKTÖR MÜ ?) • SUBGRUP YATKINLIĞI • TANI KRİTERLERİ (NIH-ROTERDAM) • ÇOĞUL GEBELİK Pregnancycomplications in PCOS Best Practice & ResearchClinicalEndocrinology & MetabolismVol. 20, No. 2, 2006

  35. Sustainedfertilityfrom22 to 41 yearsof age in womenwith PCOS HumanReproduction, Vol.26, No.9 pp. 2499–2504, 2011

  36. The pathogenesis of infertility and earlypregnancy loss in polycystic ovary syndrome • Gn SEKRESYONU • İNSÜLİN SEKRESYONU • PARAKRİN FONKSİYON BOZUKLUĞU • FOLİKÜLOGENEZİS • STEROİDOGENEZİS OVER DİSFONKSİYONU • LH • HİPERANDROJENEMİ EPL (HİPOFİZ, OVER, ENDOMETRİUM) • HİPERİNSÜLİNEMİ • PAI AKTİVİTESİ • ENDOTELYAL DİSFONKSİYON • BMI Best Practice & Research Clinical Obstetrics and GynaecologyVol. 18, No. 5, 2004

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