Recurrent Pregnancy Loss An Overview

1. Recurrent Pregnancy LossAn Overview Dr Uma.T Department of Obstetrics and Gynecology SAT Hospital,Government Medical College Trivandrum

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

4. 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

5. Incidence • 1% of all pregnancies. • 10 -15 % clinically recognized pregnancy  end in miscarriage ( RCOG )

6. Live birth 25% Clinical pregnancy 2% 12-15% 12 – 15 % Miscarriage Early pregnancy loss 30% Preclinical loss 30% Failure of implantation 30 %

7. 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

8. CAUSES 1.Endocrinological disorders 2 Infections 3.Environmental factors 4.Smoking 5.Maternal systemic diseases

9. Maternal origin 90-95%Paternal origin 5-10%GENETIC CAUSES

10. When to start investigating? no specific number or criteria that justifies evaluation for RPL or defines the scope of investigation Usually ……. ≥ 3 pregnancy losses

11. Investigate after 2 losses if ●Female partner > 35 yrs ●Infertility ●Foetal heart activity observed in any of the pregnancy losses ●Normal karyotype of conceptus

12. Risk of subsequent pregnancy loss 24 % …. After 2 clinically recognized losses 30 % …. After 3 40 – 50 % …. After 4

13. ETIOLOGY ? Only 2 undisputed causes ●Parental chromosomal abnormality ●APLA < 10 – 15 % of RPL

14. Other causes……. • Anatomic congenital acquired

15. Endocrine causes Thyroid ? LPD Diabetes Mellitus e

16. Other causes……. • Inherited thrombophilias • Infections ? Bacterial vaginosis • Environmental exposure Smoking / Alcohol / Caffeine

17. WHEN….? • APLA any trimester (T2,3> T1) • Parental chromosomal abnormality I trimester • Uterine anomalies II …. I …. Septate uterus

18. Endocrine I or late Inherited thrombophilias III Infections Late II / III Environmental toxins I/ late

19. EVALUATION….. • Age • Trimester • h/o DM, thyroid dysfuntion, SLE & other connective tissue disorder, h/o thrombotic episodes • Family history – DM, thrombosis

20. 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)

21. 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

22. peripheral blood karyotyping performed. Abnormal - Geneticist PGD – translocation carriers Disadvantage – IVF pregnancy success lower * without treatment > 50% live birth

23. Balanced Translocation carrier 14;21

24. Karyotype (Husband)

25. 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

26. Karyotype important Abnormal Normal Further evaluation • ●Aneuploidy • (reassure) • Unbalanced translocation • ( balanced translocation in parent)

27. APLA 15 % of women with RPL

28. Diagnostic Criteria • International Thrombosis society (2006) • One clinical & one lab criteria Clinical criteria • Vascular thrombosis • Pregnancy morbidity

29. Sapporo criteria 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 CRITERIA aCL assay - aCAIgG >20GPL units aCAIgM >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

30. 1.Vascular thrombosis arterial venous small vessel

31. 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.

32. 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

33. Without treatment…. chance of a live pregnancy only 10% • Treatment…. Aspirin & Heparin

34. Aspirin – 75-85 mg/day preconceptionally • Heparin – 5000 – 10,000 U s/c bd unfractionated heparin begin at the first indication of pregnancy

35. Monitor platelet count • No increased risk of osteoporosis

36. Low molecular weight heparin equally beneficial • Once daily administration Enoxaparine (clexane) – 1mg/kg Dalteparine (fragmin )- 100U/kg

37. Stop aspirin by 34 weeks Planned delivery stop unfractionated heparin 6 hrs before delivery LMW Heparin – 12hrs

38. Post natal thromboprophylaxis Reintroduce following delivery Unfractionated – 6 hrs LMW Heparin - 12 hrs

39. Aspirin + Heparin …. 70 % live birth rate • Aspirin alone …. 40 % only

40. INHERITED THROMBOPHILIAS Activated protein C Resist( Factor V Leiden gene mutation ) Deficiency of protein C/S Deficiency of antithrombin III Hyperhomocysteinemia PT gene mutation

41. established causes of systemic thrombosis • Pregnancy – data scarce due to low prevelance Thrombophilia screen

42. Treatment of women with Inherited/acquired thrombophilias Unfractionated / LMW Heparin Therapeutic / Prophylactic dose Monitor aPTT

43. Therapeutic dose- 10,000-15,000 every 8 – 12 hrs aPTT – 1.5-2.5 LMW Heparin Enoxaparin 40-80 mg s/c bd or dalteparin 5000 – 10,000 U s/c bd

44. Prophylactic dose Unfractionated Heparin 5000 bd (I) 7500 bd (II) 10000 bd (III) LMW Heparin Enoxaparin – 40 mg s/c od dalteparin - 5000 U s/c od

45. Anatomic factors • Usually late miscarriages ( II TM ) due to associated cervical weakness • I TM also As in septate uterus In intrauterine volume / Poor vascularity

46. ROLE OF HSG • Questionable • Patient discomfort • Invasive • Risk of pelvic infection • Radiation exposure • Not more sensitive than pelvic USS

47. PELVIC USS • Investigation of choice & should be used to assess uterine anatomy and morphology in a woman with RPL

48. Role of encerclage? • QUESTIONABLE ! Definite history – should be done suspicion – monitor with serial USS

49. Hysteroscopic septal resection Septate uterus with RPL Didelphis / Bicornuate no correction Asherman Syndrome hysteroscopic lysis

50. Uterine leiomyomas * submucous * large intramural - remove only if compressing cavity