Transcript 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
Arch Gynecol Obstet (2010) 282:235–239, PCOS and pregnancy outcome
PCOS’da KLİNİK GÖRÜNÜM
• OLİGO/ANOVÜLASYON
• HİPERANDROJENEMİ
+/• PCO
• İNFERTİLİTE
• OBESİTE
• İNSÜLİN R, %40
Clinical manifestations of PCOS in adults UpToDate.com
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)
ERKEN GEBELİK KAYIPLARI
ETYOLOJİ
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KROMOZOMAL ANOMALİ
KONGENİTAL ANOMALİ
TRAVMA
UTERİN ANOMALİ
ENFEKSİYON
ENDOKRİNOPATİ; PCOS
TROMBOFİLİ
İMMÜNOLOJİK
ÇEVRESEL
AÇIKLANAMAYAN
(Spontaneous abortion, UpToDate.com)
TEKRARLAYAN GEBELİK KAYIPLARI
RİSK FAKTÖRLERİ ve ETYOLOJİ
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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)
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),
Arch Gynecol Obstet (2010) 282:235–239, PCOS and pregnancy outcome
Pregnancy complications in PCOS
Best Practice & Research Clinical Endocrinology & Metabolism Vol. 20, No. 2, 2006
The pathogenesis of infertility and early
pregnancy loss in polycystic ovary
syndrome
Best Practice & Research Clinical Obstetrics and Gynaecology Vol. 18, No. 5, 2004
How common is PCOS in recurrent miscarriage?
Vol 19. No 4. 2009 572-576 Reproductive BioMedicine Online
PCOS – ETYOPATOGENEZ
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HİPOTALAMUS/HİPOFİZ,
STEROİDOGENEZ,
OVERYAN HİPERANDROJENİZM, 2/3
ADRENAL HİPERANDROJENİZM, 1/3
İNTRİNSİK FAKT. & STEROİDOGENEZ,
EXTRİNSİK FAKT. & STEROİDOGENEZ,
İNSÜLİN R
Definition, pathogenesis, and etiology of PCOS UpToDate.com
PCOS – EPL & ETYOPATOGENEZ
• LH,
• HİPERANDROJENEMİ,
• HİPERİNSÜLİNEMİ
PROGESTERON,
HİPERHOMOSİSTEİNEMİ,
GLUKODELİN, AZALMA
IGFBP-2, AZALMA
PAI AKTİVİTESİ, ARTIŞ
• BMI
• ENDOTELYAL DİSFONKSİYON
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HİPOFİZ
OVER
ENDOMETRİUM
EPL
Arch Gynecol Obstet (2010) 282:235–239, PCOS and pregnancy outcome
• PI, DİASTOLİK ÇENTİK
(Uterine blood flow in pregnant patients with PCOS: relationships with clinical outcomes.
BJOG (2010) 117(6))
LH HİPERSEKRESYONU (%40)
• FOLİKÜLER FAZ
• ESTROJEN, İNSÜLİN
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OOSİT MATÜRASYONU, OOGENEZİS
FOLİKÜLOGENEZİS
LH YÜKSEK
LH NORMAL
OVÜLASYON
FERTİLİZASYON
%67 GEBE
%88 GEBE
%65 ABORT
%12 ABORT
İMPLANTASYON
EMBRYO SURVİVAL
Oİ YANIT ve ABORT RİSKİ (CC)
Best Practice & Research Clinical Obstetrics and Gynaecology Vol. 18, No. 5, 2004
HİPERANDROJENEMİ
• LH
• İNSÜLİN R
• OBESİTE
EGF-R, ARTIŞI
HOXA-10, AZALIŞI
ENDOTELYAL DİSFOKSİYON
• SHBG
• HİPOFİZ
• OVER
• ENDOMETRİUM
Best Practice & Research Clinical Obstetrics and Gynaecology Vol. 18, No. 5, 2004
HİPERİNSÜLİNEMİ
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LH
BMI
SHBG
HİPERANDROJENEMİ
PAI-1, ARTIŞ
• HİPOFİZ
• OVER
• ENDOMETRİUM: GLİKODELİN, IGFBP-1,
ENDOTELİN-1
Best Practice & Research Clinical Obstetrics and Gynaecology Vol. 18, No. 5, 2004
Extra- and intra-ovarian factors in PCOS:
impact on oocyte maturation and embryo
developmental competence
BOOGENEZİS
FOLİKÜLOGENEZİS
OVÜLASYON
FERTİLİZASYON
İMPLANTASYON
EMRYOGENEZİS
Human Reproduction Update, Vol.17, No.1 pp. 17–33, 2011
The Pathophysiology of Miscarriage in Women with
Polycystic Ovary Syndrome. Review and Proposed
Hypothesis of Mechanisms Involved
HORMONES 2004, 3(4):221-227
PCOS
METFORMİN TDV’si
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İNSÜLİN
PAI-1
VASKÜLARİZASYON
ENDOTELİN-1
GLİKODELİN
LH/ANDROJEN
BMI
Pregnancy complications in PCOS Best Practice & Research Clinical
Endocrinology & Metabolism Vol. 20, No. 2, 2006
PCOS – EPL - METFORMİN
• %41.9 & %8.8, METFORMİN +/(Effects of metformin on early pregnancy loss in the PCOS. J Clin
Endocrinol (2002) Metab 87(2))
• %49.5 & %12.5, ‘OBES + PCOS’
(Continuation of metformin reduces early pregnancy loss in obese
Pakistani women with PCOS. Gynecol Obstet Invest (2009) 69(3))
• %35, RİSK ARTIŞI +
(Pregnancies following use of metformin for ovulation induction in
patients with PCOS. Fertil Steril (2002) 77(4))
• EPL RİSKİNE ETKİSİ YOK
(Effect of preconceptional metformin on abortion risk in PCOS: a
systematic review and meta-analysis of randomized controlled
trials. Fertil Steril (2009) 92(5))
PCOS
METFORMİN TDV’si
Pregnancy outcomes among women with PCOS treated with
metformin. Human Reproduction 2002; 17
PCOS
CC/Gn TDV’si
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SPONTAN ABORT RİSKİ, %25
OBESİTE
EM’da ANTİ-ESTROJEN
LH ARTIŞI
• DÜŞÜK DOZ FSH protokol,
• KONVANSİYONEL Gn
CC
Gn
Pregnancy complications in PCOS Best Practice & Research Clinical
Endocrinology & Metabolism Vol. 20, No. 2, 2006
PCOS & GnRH agonist TDV’si
• LH YÜKSEK + PCOS; LH NORMAL +
MEKANİK İNFERT.
GnRH agonist reduces the miscarriage rate for pregnancies
achieved in women with PCOS. Fertililty and Sterility 1993;
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• hMG +/- GnRH agonist; %17.6/%39
IVF-ET for the treatment of infertility associated with PCOS.
Fertility and Sterility 1993; 60
PCOS & GnRH agonist TDV’si
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FEED-BACK
UZUN SÜRE
Gn DOZU
FOLİKÜL SAYISI
ÇOĞUL GEBELİK
OHSS
SİKLUS İPTALİ
LH YÜKSEK
Gn İLE GEBELİK YOK
1 < ABORT
Pregnancy complications in PCOS Best Practice &
Research Clinical Endocrinology & Metabolism Vol. 20,
No. 2, 2006
Pregnancy outcome in women with PCOS comparing the
effects of laparoscopic ovarian drilling and clomiphene
citrate stimulation in women pre-treated with
metformin: a retrospective study
Reproductive Biology and Endocrinology 2010, 8:45
PCOS & DİET
Weight loss results in significant improvement in reproductive outcome for all
forms of fertility treatment. Human Reproduction (Oxford, England) 1998; 13
A reappraisal of the role of PCOS in
recurrent miscarriage
• PCO MORFOLOJİ
• LH
• ANDROJEN
• HİPERİNSÜLİNEMİ
• OBESİTE
ANOVULATUAR
CC (%14-25)
Gn; low-dose step-up,
GnRH agonist + FSH
HMG; EM’al reseptivite
OVER DRİLLİNG (%1115)
• METFORMİN, EM’al
reseptivite
• DİET
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Vol 17 No 1. 2008 ¡51-161 Reproductive BioMedicine Online
PCOS and pregnancy outcome: red herring or
red flag?
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İNFERTİL KADIN; %15
PCO MORFOLOJİ: %15-32
SUBGRUP + PREDİSPOZAN FAKTÖRLER
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HİPERİNSÜLİNEMİ, İNSÜLİN R, %30-70
POLİGENİK PREDİSPOZİSYON
OBESİTE
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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.
Polycystic ovary syndrome and pregnancy outcome: red herring or red flag?
BJOG. 2007 Aug;114(8):922-32. Review.
PCOS and the risk of spontaneous abortion following ART treatment
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BACKGROUND: This study aims to determine the effect of PCOS status on the
risk of spontaneous abortion with adjustment for body mass and several other
confounding factors in a large cohort of pregnant infertile women. METHODS:
The patients (n = 1018) were treated in a tertiary infertility centre. Their PCOS
status was determined by standard criteria and their BMI had been taken less
than 1 year before the pregnancy. Student's t-test or χ2 test were used to test
the difference between the PCOS and non-PCOS groups while a multivariate
logistical regression model was used to assess the effect of PCOS, BMI and
other confounding factors. RESULTS: Overall, the incidence of PCOS was 37% in
this cohort. The overall incidence of spontaneous abortion in the study
population was 21%. Univariate analysis showed that women with PCOS had a
significantly greater risk of spontaneous abortion compared with non-PCOS
women (25 versus 18%, P < 0.01). However, using multivariate logistic regression
analysis this effect was reduced to a non-significant level [odds ratio (OR) = 1.10,
95% confidence interval (CI) 0.85–1.36] after adjusting for obesity and
patients/treatment combination factor, and to nil after adjusting for all
confounding factors considered in this study (OR = 0.98, 95% CI 0.75–1.28).
CONCLUSION: The results of this study suggest that the higher risk of
spontaneous abortion observed in women with PCOS is likely to be due to their
high prevalence of obesity and the type of treatment they receive.
Human Reproduction Volume 16, Issue 12, 2001
Prevalence of PCO in women with self-reported symptoms of
oligomenorrhoea and/or hirsutism: Northern Finland Birth
Cohort 1966 Study
Human Reproduction Vol.19, No.5 pp. 1083±1088, 2004
The adverse effects of obesity
on conception and implantation
Reproduction (2010) 140 347–364
The adverse effects of obesity on conception and implantation
Reproduction (2010) 140 347–364
The adverse effects of obesity
on conception and implantation
Reproduction (2010) 140 347–364
PCOS & SPONTAN ABORT PREVALANSI
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YAŞ
PARİTE
GEBE KALMA SÜRESİ
OBSTETRİK ÖYKÜ
EK FAKTÖR
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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
Pregnancy complications in PCOS Best Practice & Research Clinical Endocrinology &
Metabolism Vol. 20, No. 2, 2006
Sustained fertility from 22 to 41 years
of age in women with PCOS
Human Reproduction, Vol.26, No.9 pp. 2499–2504, 2011
The pathogenesis of infertility and early
pregnancy loss in polycystic ovary syndrome
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Gn SEKRESYONU
İNSÜLİN SEKRESYONU
PARAKRİN FONKSİYON BOZUKLUĞU
FOLİKÜLOGENEZİS
STEROİDOGENEZİS
OVER DİSFONKSİYONU
• LH
• HİPERANDROJENEMİ
• HİPERİNSÜLİNEMİ
EPL (HİPOFİZ, OVER, ENDOMETRİUM)
• PAI AKTİVİTESİ
• ENDOTELYAL DİSFONKSİYON
• BMI
Best Practice & Research Clinical Obstetrics and Gynaecology Vol. 18, No. 5, 2004