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Recurrent Pregnancy Loss An Overview
Dr Uma.T Department 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. % clinically recognized pregnancy end in miscarriage ( RCOG )
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Live birth 12-15% 30% 25% Clinical pregnancy 2% 12 – 15 % Miscarriage
Early pregnancy loss 30% Preclinical loss 30% Failure of implantation 30 %
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RISK DECREASES AS DURATION OF PREGNANCY INCREASES
RISK FACTORS Number of miscarriage Increasing maternal & paternal 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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CAUSES 1.Endocrinological disorders 2 Infections
GENETIC FACTORS-5% ANATOMICAL FACTORS-15% IMMUNOLOGICAL-30% 1.Endocrinological disorders 2 Infections 3.Environmental factors 4.Smoking 5.Maternal systemic diseases
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Maternal origin 90-95% Paternal origin 5-10% GENETIC CAUSES
NUMERICAL(90%) Autosomal trisomy-50% Monosomy-25% Polyploidy % Sex chromosome polysomy - rare STRUCTURAL Translocation-5% Inversions Mosaicism
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When to start investigating?
no specific number or criteria that 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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Risk of subsequent pregnancy loss
24 % …. After 2 clinically recognized losses 30 % …. After 3 40 – 50 % …. After 4
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ETIOLOGY ? Only 2 undisputed causes ●Parental chromosomal abnormality ●APLA < 10 – 15 % of RPL
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Other causes……. Anatomic congenital acquired
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Endocrine causes Thyroid ? LPD Diabetes Mellitus e
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Inherited thrombophilias Infections ? Bacterial vaginosis
Other causes……. Inherited thrombophilias Infections ? Bacterial vaginosis Environmental exposure Smoking / Alcohol / Caffeine
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WHEN….? APLA any trimester (T2,3> T1)
Parental chromosomal abnormality I trimester Uterine anomalies II …. I …. Septate uterus
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Endocrine I or late Inherited thrombophilias III Infections Late II / III Environmental toxins I/ late
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EVALUATION….. Age Trimester
h/o DM, thyroid dysfuntion, SLE & other connective tissue disorder, h/o thrombotic episodes Family history – DM, thrombosis
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GENETIC FACTORS 50 – 70 % spontaneous miscarriages
numerical chromosomal abn MC - Trisomy Most end in miscarriages except – 21, 18, 13 22%, 5%,3% First trimester losses Trisomic miscarriage does not increase the risk of subsequent miscarriage ( Random events)
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Structural genetic defects
3 – 5 % couples with RPL Most common- Balanced reciprocal or Robertsonian more 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 – IVF pregnancy success lower * without treatment > 50% live birth
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Balanced Translocation carrier 14;21
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Karyotype (Husband)
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Karyotyping of abortus?
2 schools of thought 1. Unnecessary & expensive luxury 2. Important to differentiate b/w those who need further evaluation from those who do not
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Karyotype important Abnormal Normal Further evaluation ●Aneuploidy
(reassure) Unbalanced translocation ( balanced translocation in parent)
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APLA 15 % of women with RPL
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International Thrombosis society (2006)
Diagnostic Criteria International Thrombosis society (2006) One clinical & one lab criteria Clinical criteria Vascular thrombosis Pregnancy morbidity
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Sapporo criteria CLINICAL CRITERIA LABORATORY 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 CRITERIA aCL assay aCA IgG >20GPL units aCA IgM >15MPL units low positive 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 arterial venous small 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 Lupus anticoagulant (LA)..APTT
Anticardiolipin antibody IgG & / IgM > 40 GPL or MPL or > 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 bd unfractionated heparin begin 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 delivery LMW Heparin – 12hrs
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Post natal thromboprophylaxis
Reintroduce following delivery Unfractionated – 6 hrs LMW Heparin hrs
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Aspirin + Heparin …. 70 % live birth rate
Aspirin alone …. 40 % only
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INHERITED THROMBOPHILIAS
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 – LMW Heparin Enoxaparin mg s/c bd or dalteparin 5000 – 10,000 U s/c bd
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Prophylactic dose Unfractionated Heparin 5000 bd (I) 7500 bd (II) 10000 bd (III) LMW Heparin Enoxaparin – 40 mg s/c od dalteparin U s/c od
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Anatomic factors In intrauterine volume / Poor vascularity
Usually late miscarriages ( II TM ) due to associated cervical weakness I TM also As in septate uterus In intrauterine volume / Poor vascularity
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ROLE OF HSG Questionable Patient discomfort Invasive
Risk of pelvic infection Radiation exposure Not more sensitive than pelvic USS
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PELVIC USS Investigation of choice & should be used to assess uterine anatomy and morphology in a woman with RPL
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Role of encerclage? QUESTIONABLE ! Definite history – should be done
suspicion – monitor with serial USS
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Hysteroscopic septal resection
Septate uterus with RPL Didelphis / Bicornuate no correction Asherman Syndrome hysteroscopic lysis
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Uterine leiomyomas * submucous * large intramural - remove only if
compressing cavity
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ENDOCRINE CAUSES 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 supplementation
Insufficient evidence in RPL Preterm labour IVF pregnancies
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Vaginal Vs. Intramuscular Progesterone - Results of a Recent Study
Vaginal and intramuscular progesterone have comparable outcomes This similarity may weigh in favor of vaginal route due to relative patient comfort Fertil Steril Feb;93(2):
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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
? Role of immunotherapy Paternal cell immunisation 3rd party donor leucocyte Trophoblast membranes IVIg Not recommended Does not improve the live birth rate
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TORCH screening To be abandoned
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Bacterial vaginosis I 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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ENVIRONMENTAL FACTORS
Smoking Alcohol Caffeine
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UNEXPLAINED RPL ? 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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Tender loving care What these women need ??? Psychological support
& reassurance Tender loving care
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Thank you……..
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