1. Recurrent Pregnancy Loss An 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.
% clinically recognized pregnancy  end in miscarriage
( RCOG )

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

7. 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

8. 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

9. 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

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. Inherited thrombophilias Infections ? Bacterial vaginosis
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. International Thrombosis society (2006)
Diagnostic Criteria
International Thrombosis society (2006)
One clinical & one lab criteria
Clinical criteria
Vascular thrombosis
Pregnancy morbidity

29. 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

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 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 –
LMW Heparin
Enoxaparin 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 U s/c od

45. 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

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

51. ENDOCRINE CAUSES
Well controlled DM and thyroid is not a risk factor for RPL
Routine screening for occult thyroid and DM ?
Uninformative
(RCOG)

52. Progesterone supplementation
Insufficient evidence in RPL
Preterm labour
IVF pregnancies

53. 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):

54. ? hCG
failed to show any benefit
not given

55. … PCOS … role for prepregnancy LH suppression?
NO role as it does not improve the live birth rate

56. Prolactin levels?
Insufficient evidence

57. 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

58. TORCH screening
To be abandoned

59. 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

60. ENVIRONMENTAL FACTORS
Smoking
Alcohol
Caffeine

61. UNEXPLAINED RPL
? Role for empirical Heparin , Aspirin Resisted (RCOG)

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

63. Tender loving care What these women need ??? Psychological support
& reassurance
Tender loving care

64. Thank you……..