Dr Uma.TDepartment of Obstetrics and Gynecology SAT Hospital,Government Medical College Trivandrum

Recurrent miscarriages

≥ 3 consecutive losses before 20 weeks of gestation or less than 500 gms.

•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

Incidence • 1% of all pregnancies. • 10 -15 % clinically recognized

pregnancy end in miscarriage( RCOG )

12-15%2%

30%Preclinical loss

Clinical pregnancy

Failure of implantation

Early pregnancy loss

Miscarriage

Live birth

30 %

30%

12 – 15 %

25%

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

1.Endocrinological disorders2 Infections3.Environmental factors4.Smoking5.Maternal systemic diseases

When to start investigating?no specific number or criteriathat justifies evaluation for

RPL or defines the scope of

investigation Usually ……. ≥ 3 pregnancy losses

Investigate after 2 losses if ●Female partner > 35 yrs

●Infertility●Foetal heart activity

observed in any of the pregnancy losses

●Normal karyotype of conceptus

24 % …. After 2 clinically recognized losses

30 % …. After 3

40 – 50 % …. After 4

Only 2 undisputed causes

●Parental chromosomal abnormality

●APLA

< 10 – 15 % of RPL

Anatomiccongenitalacquired

Thyroid ? LPD

Diabetes Mellituse

Inherited thrombophilias

Infections ? Bacterial vaginosis

Environmental exposureSmoking / Alcohol / Caffeine

APLA any trimester (T2,3> T1)

Parental chromosomal abnormalityI trimester

Uterine anomaliesII ….I …. Septate uterus

EndocrineI or late

Inherited thrombophiliasIII

InfectionsLate II / III

Environmental toxinsI/ late

Age Trimester h/o DM, thyroid dysfuntion, SLE & other

connective tissue disorder, h/o thrombotic episodes

Family history – DM, thrombosis

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)

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

peripheral blood karyotyping performed.

Abnormal - Geneticist PGD – translocation carriers

Disadvantage – IVFpregnancy success lower

* without treatment > 50% live birth

2 schools of thought

1. Unnecessary & expensive luxury

2. Important to differentiateb/w those who need further evaluation from those who do not

Karyotype important

Normal

Further evaluation

Abnormal

●Aneuploidy(reassure) •Unbalanced translocation( balanced translocation in parent)

15 % of women with RPL

International Thrombosis society (2006)

One clinical & one lab criteria

Clinical criteria1. Vascular thrombosis2. Pregnancy morbidity

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

1.Vascular thrombosis

arterialvenoussmall

vessel

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.

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

Without treatment….chance of a live pregnancy only

10%

Treatment….Aspirin & Heparin

Aspirin – 75-85 mg/day

preconceptionally

Heparin –5000 – 10,000 U s/c bdunfractionated heparinbegin at the first indication of pregnancy

Monitor platelet count

No increased risk of osteoporosis

Low molecular weight heparin equally beneficial

Once daily administration Enoxaparine (clexane) – 1mg/kg

Dalteparine (fragmin )- 100U/kg

Stop aspirin by 34 weeks Planned delivery

stop unfractionated heparin 6 hrs before deliveryLMW Heparin – 12hrs

Post natal thromboprophylaxisReintroduce following delivery

Unfractionated – 6 hrs LMW Heparin - 12 hrs

Aspirin + Heparin …. 70 % live birth rate

Aspirin alone …. 40 % only

Activated protein C Resist( Factor V Leiden gene mutation )

Deficiency of protein C/S Deficiency of antithrombin III Hyperhomocysteinemia PT gene mutation

established causes of systemic thrombosis

Pregnancy – data scarce due to low prevelance

Thrombophilia screen

Treatment of women with Inherited/acquired thrombophilias

Unfractionated / LMW Heparin

Therapeutic / Prophylactic dose

Monitor aPTT

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

Prophylactic doseUnfractionated Heparin

5000 bd (I)7500 bd (II)10000 bd (III)

LMW HeparinEnoxaparin – 40 mg s/c oddalteparin - 5000 U s/c od

Usually late miscarriages ( II TM )due to associated cervical weakness

I TM also As in septate uterusIn intrauterine volume / Poor vascularity

Questionable

Patient discomfort Invasive Risk of pelvic infection Radiation exposure Not more sensitive than

pelvic USS

Investigation of choice & should be used to assess uterine

anatomy and morphology in a woman with RPL

QUESTIONABLE !

Definite history – should be done

suspicion – monitor with serial USS

Hysteroscopic septal resectionSeptate uterus with RPL

Didelphis / Bicornuate no correction

Asherman Syndromehysteroscopic lysis

Uterine leiomyomas

* submucous * large intramural - remove only if

compressing cavity

Well controlled DM and thyroid is not a risk factor for RPL

Routine screening for occult thyroid and DM ?

Uninformative(RCOG)

Progesterone supplementationInsufficient evidence in RPL

Preterm labourIVF pregnancies

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

? hCG failed to show any benefit

not given

PCOS … role for prepregnancy LH suppression?

NO role as it does not improve the live birth rate

Prolactin levels?Insufficient evidence

Paternal cell immunisation 3rd party donor leucocyte Trophoblast membranes IVIg

Not recommendedDoes not improve the

live birth rate

To be abandoned

Bacterial vaginosisI TM loss- evidence inconsistent

For women with a previous history of preterm birth- detection & treatment of bacterial vaginosis………. Prevents further preterm birth

Smoking

Alcohol

Caffeine

? Role for empirical Heparin , Aspirin

Resisted (RCOG)

In unexplained pregnancy loss , the woman should be reassured that with supportive care alone, the chance for a successful pregnancy outcome is 75%

What these women need ???

Psychological support & reassurance

Tender loving care

Thank you……..