Recurrent miscarriage

20149,13

(5) 20-24 (5) 500g(7,2)

10-20% (6)25-50%51

5

3 (5) (1) 76

10

90%12-14 , 2-5%8.5148.514 (6)

12~15% (5,6,7)

50% (30~60%) (5,6,7)

ART13%

0.5~2% (1,2,5,6,8)

2004-2011

Chart1

18.640.65

12.93.80.27

13.34.20.45

12.46.50.16

13.24.50.25

13.53.70.22

13.63.40.32

12.34.20.36

13.70.35

%

%

%

Sheet1

%%%

200418.63.60.65

200512.940.27

200613.33.80.45

200712.44.20.16

200813.26.50.25

200913.54.50.22

201013.63.70.32

201112.33.40.36

13.74.20.35

25-57% 4-8% 6-7% 3-5% (9),15% (5)(7)

about 50%

90%

50%30%3%

75% FISH (fluorescence in situ hybridization), CGH (comparative genomic hybridization), (7)

90%103X (5)7% of 3 (5)

41.6% (25%-57%) (4)

7

85% (200/233)

35.7 % (4)

17-18% (5,7)

Anencephaly, encephalocele, spina bifida, syndactyly, pseudo-syndactyly, polydactyly, cleft hand and cleft lip. (4)

90% (56-60%FISHCGH75%17-18%

Tow studies including 30 and 43 patients with an aneuploid abortion, only 10% and 19% had a subsequent aneuploid abortion, respectively (4)

15% (4)50-70% (6)

2-4% (6) 4%-8% (57) 3-10% (4)60%40%26

50-70% (5)

697

39 (4)69%

karyotypecasesproportion%174310265133513X25

Sugiura-ogasawara: 32%Carp et al: 44%Goddijin et al: 70%

: 47.5% with mean of 3.7 previous miscarriage (4)

45

71074

%4075 (

71074

%

2% (7), 7-8% (6)

6-7% (7) or 10-15% (6) 1.8-37.6% (5)

80-90% (7)

malformationMiscarriage rate%managementSeptate 65septoplastyUnicornuate50expectantBicornuate30-40expectantDidelphys40expectantAdhesion40-80ashesiolysis

80%, 5%, 15% (7)

, 50% (6), 50-90% , 7-23% (7)

, 3-5%, (7) 15% (5)

1/3-3/4107

90% (5)

(57)

annexin V

thrombembolism

aPL

310110134 (5)

anticardiolipin antibodies IgG /the lupus anticoagulant (6)

Aspirin, intravenous immunoglobulin, heparin

RM and APSaspirin75-85mg/d,heparin5000-10000bid)

70-80% VS 20-40%

5-6

50% (6)

V leiden prothrombin,8%

2-3 (6)

(5)

Interferon r

Th1

IL122,TNF

Th115-20%3%, Th1 cell

IL4

Th2

IL10,4,56

Human Reproduction Update, Vol.20, No.3 pp. 429438, 2014NKcNKc

NKc %NKC %NK

NKc IVF

NKc %NKcNKc

-

-

HLA

PRL, LPD, PCOS

PCOS36-56%PCOS 6

6

6

(5)

8 (5)

(5)

Environment (The association between miscarriage and ionizing radiation, organic solvents , alcohol, mercury and lead is confirmed

An association to caffeine, hyperthermia and cigarette smoking is suspected (2)

BMI, (TSH,LPD,PRL blood sugar level) (LA, aCL) (2,5,6) (2,5,6), (2,5,6)D3FSH, D3AFC (5)

NK cells

(factor V leiden, prothrombin 20210 mutation)

(5)

1. (5)

86% of 33% (2)

2. 2

Th1 Th2

Th1

Th2

NK

ABs

Th2 (PIBF)ABs

-P-

3. PCOS

(5)

4. 2aspirin

aspiringastroschisis2-3 (5)

5. (5), Th1 cytokine interferon gamma 54%,-70%. (5)

6. , -TNFa ,

Anti TNFa ,

(5)

7. 77% 37%

(7studies, 470 women)(6)

(5)

70%63%

7p300 71081

Hum Reprod 2010,125:2203

8.

37IVF26%75% (5)

50-65%

IVF+PGS38%

PGS (5)

Evidence level for given intervention of RM (5)

Level of evidencereferencesIntervention of benefitAspirin, heparin for antiphospholipid syndromeb99Psychological support146-148Metformin for insulin resistance153Heparin for thrombophilic defects160Intervention of no benefitprogesterone150Intravenous immunoglobulin/glucocorticosteroidsa93,161Aspirin for unexplained RMa155,156Embryo aneuploidy screeninga165

///A1aRCTSR1bRCT1cB2aSR2bRCT

risk

Risk is still less than 40% after 4 previous losses, not higher then 50% even with 6 or more (7)

Women who had at least one live born infantPrior miscarriagesRisk of miscarriage in next pregnancy012124226332426653Women who have not had at least one live born infant2 or more40-45%

25-30% 70% 16-27202856

30-45%40-45%130% 7

Thanks A Lot

references1.Duckit K, Qureshi A, recurrent miscarriage. Clin Evid(online)2008,14:1409

2. Jauniaux E, et al ,Evidence-based guidelines fro the investigation and medical treatment of recurrent miscarriage. Human reproduction 21:2216-2222,2006

3. Szekeres- Bartho J, Progesterone therapy for recurrent miscarriage. Human reproduction update 14:27-35, 2008

4. howard JA, recurrent miscarriage: genetic factors and assessment of the embryo, IMAJ 10;229-231,2008

5.Rai R, Regan L, recurrent miscarriage lancet 368:601-11,2006

6. Porter TF, et al, Evidence-based care of recurrent miscarriage. Best practice & research clinical Obstetrics and Gynecology,19:85-101 2005

7. recurrent early pregnancy loss in clinical gynecological endocrinology and infertility 7th ed 1069

8. Laird SMet alA review of immune cells and molecules in women with recurrent miscarriage. Human Reproduction update 9:163-174,20039090591219100305100604100619140913140909

10-12

10 6

*The key to this embryo-protective immuno-modulation and embryo survival is Progesterone Induced Blocking Factor, or PIBF. PIBF-PIBF is produced by CD56+ cells at the foe to-maternal interface.PIBF-CD56+PIBF induces asymmetric, blocking antibodies. This is due to a mannose residue on one of the Fab arms of the antibody.PIBF cause a Th2 dominancePIBF reduces NK cell activity by stabilizing the membranes of the NK/LAK cells which inhibits the release of perforin granules into a cell.In this way, PIBF ensures embryo-protective immuno-modulation. (Note: V1 are a histochemically well described cell population. PBMC stands for Peripheral Blood Mononuclear Cells)

PIBFFabPIBFTh2PIBFNKNK/LAK PIBF(: V1. PBMC )

*