Download - Dr Uma.T Department of Obstetrics and Gynecology SAT Hospital,Government Medical College Trivandrum
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Dr Uma.TDepartment of Obstetrics and Gynecology SAT Hospital,Government Medical College Trivandrum
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Recurrent miscarriages
≥ 3 consecutive losses before 20 weeks of gestation or less than 500 gms.
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•Primary recurrent pregnancy loss" refers to couples that have never had a live birth,
•while "secondary RPL" refers to those who have had repetitive losses following a successful pregnancy
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Incidence • 1% of all pregnancies. • 10 -15 % clinically recognized
pregnancy end in miscarriage( RCOG )
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12-15%2%
30%Preclinical loss
Clinical pregnancy
Failure of implantation
Early pregnancy loss
Miscarriage
Live birth
30 %
30%
12 – 15 %
25%
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RISK FACTORSNumber of miscarriage Increasing maternal & Number of miscarriage Increasing maternal &
paternal agepaternal age 15% after 1 loss 24% after 2 losses 30% after 3 losses 40% after 4 losses.
RISK DECREASES AS DURATION OF PREGNANCY
INCREASES
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1.Endocrinological disorders2 Infections3.Environmental factors4.Smoking5.Maternal systemic diseases
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When to start investigating?no specific number or criteriathat justifies evaluation for
RPL or defines the scope of
investigation Usually ……. ≥ 3 pregnancy losses
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Investigate after 2 losses if ●Female partner > 35 yrs
●Infertility●Foetal heart activity
observed in any of the pregnancy losses
●Normal karyotype of conceptus
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24 % …. After 2 clinically recognized losses
30 % …. After 3
40 – 50 % …. After 4
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Only 2 undisputed causes
●Parental chromosomal abnormality
●APLA
< 10 – 15 % of RPL
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Anatomiccongenitalacquired
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Thyroid ? LPD
Diabetes Mellituse
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Inherited thrombophilias
Infections ? Bacterial vaginosis
Environmental exposureSmoking / Alcohol / Caffeine
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APLA any trimester (T2,3> T1)
Parental chromosomal abnormalityI trimester
Uterine anomaliesII ….I …. Septate uterus
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EndocrineI or late
Inherited thrombophiliasIII
InfectionsLate II / III
Environmental toxinsI/ late
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Age Trimester h/o DM, thyroid dysfuntion, SLE & other
connective tissue disorder, h/o thrombotic episodes
Family history – DM, thrombosis
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50 – 70 % spontaneous miscarriagesnumerical chromosomal abn
MC - Trisomy Most end in miscarriages except –
21, 18, 1322%, 5%,3%
First trimester losses
Trisomic miscarriage does not increase the risk of subsequent miscarriage ( Random events)
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Structural genetic defects3 – 5 % couples with RPL
Most common-Balanced reciprocal or
Robertsonianmore frequent in female partner
> 50% live birth rate Homologous – all pregnancies affected
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peripheral blood karyotyping performed.
Abnormal - Geneticist PGD – translocation carriers
Disadvantage – IVFpregnancy success lower
* without treatment > 50% live birth
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2 schools of thought
1. Unnecessary & expensive luxury
2. Important to differentiateb/w those who need further evaluation from those who do not
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Karyotype important
Normal
Further evaluation
Abnormal
●Aneuploidy(reassure) •Unbalanced translocation( balanced translocation in parent)
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15 % of women with RPL
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International Thrombosis society (2006)
One clinical & one lab criteria
Clinical criteria1. Vascular thrombosis2. Pregnancy morbidity
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CLINICAL CRITERIA
Thrombosis, one or more confirmed episodes of venous, arterial, or small vessels disease
One or more unexplained fetal deaths after ten weeks of pregnancy.
Premature birth -pre eclampsia or placental insufficiency occurring before 34 weeks
Three or more unexplained consecutive spontaneous abortions less than 10 weeks.
LABORATORY CRITERIAaCL assay - aCA IgG >20GPL units aCA IgM >15MPL units 15 -20 low positive 20 - 40 moderate positive > 40 u/ml high positive.LA – KCT, aPTT, dilute Russel viper venom time. 2 positive tests at 6 weeks apart
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1.Vascular thrombosis
arterialvenoussmall
vessel
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2.Pregnancy morbidity●≥1unexplained deaths of a morpholgically normal fetus at or beyond 10 weeks of gest with normal fetal morphology- USS/direct exam≥ 1 premature births of a morphologically normal neonate before 34 weeks of gestation- eclampsia or preeclampsia/ features of placental insufficiency
≥ 3 unexplained consecutive spontaneous abortions before 10 weeks of gestation with maternal anatomic or hormonal abnormalities & paternal & maternal chromosomal causes to be excluded.
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Laboratory criteria
1. Lupus anticoagulant (LA)..APTT2. Anticardiolipin antibody
IgG & / IgM > 40 GPL or MPLor > 99th percentile
3. Anti beta 2 glycoprotein antibody of IgG or IgM > 99th percentile
12 weeks apart
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Without treatment….chance of a live pregnancy only
10%
Treatment….Aspirin & Heparin
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Aspirin – 75-85 mg/day
preconceptionally
Heparin –5000 – 10,000 U s/c bdunfractionated heparinbegin at the first indication of pregnancy
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Monitor platelet count
No increased risk of osteoporosis
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Low molecular weight heparin equally beneficial
Once daily administration Enoxaparine (clexane) – 1mg/kg
Dalteparine (fragmin )- 100U/kg
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Stop aspirin by 34 weeks Planned delivery
stop unfractionated heparin 6 hrs before deliveryLMW Heparin – 12hrs
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Post natal thromboprophylaxisReintroduce following delivery
Unfractionated – 6 hrs LMW Heparin - 12 hrs
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Aspirin + Heparin …. 70 % live birth rate
Aspirin alone …. 40 % only
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Activated protein C Resist( Factor V Leiden gene mutation )
Deficiency of protein C/S Deficiency of antithrombin III Hyperhomocysteinemia PT gene mutation
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established causes of systemic thrombosis
Pregnancy – data scarce due to low prevelance
Thrombophilia screen
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Treatment of women with Inherited/acquired thrombophilias
Unfractionated / LMW Heparin
Therapeutic / Prophylactic dose
Monitor aPTT
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Therapeutic dose-10,000-15,000 every 8 – 12 hrs
aPTT – 1.5-2.5LMW Heparin
Enoxaparin 40-80 mg s/c bdor
dalteparin 5000 – 10,000 U s/c bd
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Prophylactic doseUnfractionated Heparin
5000 bd (I)7500 bd (II)10000 bd (III)
LMW HeparinEnoxaparin – 40 mg s/c oddalteparin - 5000 U s/c od
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Usually late miscarriages ( II TM )due to associated cervical weakness
I TM also As in septate uterusIn intrauterine volume / Poor vascularity
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Questionable
Patient discomfort Invasive Risk of pelvic infection Radiation exposure Not more sensitive than
pelvic USS
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Investigation of choice & should be used to assess uterine
anatomy and morphology in a woman with RPL
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QUESTIONABLE !
Definite history – should be done
suspicion – monitor with serial USS
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Hysteroscopic septal resectionSeptate uterus with RPL
Didelphis / Bicornuate no correction
Asherman Syndromehysteroscopic lysis
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Uterine leiomyomas
* submucous * large intramural - remove only if
compressing cavity
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Well controlled DM and thyroid is not a risk factor for RPL
Routine screening for occult thyroid and DM ?
Uninformative(RCOG)
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Progesterone supplementationInsufficient evidence in RPL
Preterm labourIVF pregnancies
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Vaginal and intramuscular progesterone have comparable outcomes
This similarity may weigh in favor of vaginal route due to relative patient comfort
Fertil Steril. 2010 Feb;93(2):554-69.53
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? hCG failed to show any benefit
not given
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PCOS … role for prepregnancy LH suppression?
NO role as it does not improve the live birth rate
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Prolactin levels?Insufficient evidence
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Paternal cell immunisation 3rd party donor leucocyte Trophoblast membranes IVIg
Not recommendedDoes not improve the
live birth rate
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To be abandoned
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Bacterial vaginosisI TM loss- evidence inconsistent
For women with a previous history of preterm birth- detection & treatment of bacterial vaginosis………. Prevents further preterm birth
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Smoking
Alcohol
Caffeine
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? Role for empirical Heparin , Aspirin
Resisted (RCOG)
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In unexplained pregnancy loss , the woman should be reassured that with supportive care alone, the chance for a successful pregnancy outcome is 75%
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What these women need ???
Psychological support & reassurance
Tender loving care
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Thank you……..