CME given at Aluva on 17th February, 2012

1. Recurrent Pregnancy
Loss

2. Miscarriage is defined as the spontaneous loss of pregnancy
before the fetus reaches viability (24 weeks)
Recurrent miscarriage, defined as the loss of three or
more ( ≥ 3) consecutive pregnancies.
Affects 1% of couples trying to conceive.

4. Risk factors
Epidemiological factors
Antiphospholipid syndrome
Genetic factors
Anatomical factors
Endocrine factors
Immune factors
Infective agents
Inherited thrombophilic defects

8. Can these
cause RPL…….?
Smoking
Caffeine Alcohol

10. Can it….?

14. Antiphospholipid
antibodies
Lupus
anticoagulant
Anti-B2
Anticardiolipin
glycoprotein-I
antibodies
antibodies

15. Antiphospholipid
syndrome refers to the
association between
antiphospholipid
antibodies
and adverse
or vascular
pregnancy
thrombosis
outcome

16. Adverse pregnancy
outcome
Three or more
consecutive
miscarriages before
10 weeks of gestation
One or more One or more
preterm births morphologically
before the 34th normal fetal
week of gestation losses after the
owing to 10th week of
placental disease. gestation

17. Mechanism of
APS
Activation of
complement
And, in later
pathways at
Inhibition of pregnancy,
the maternal– Can be
trophoblastic thrombosis of
fetal interface reversed by
function and the
resulting in a LMWH
differentiation uteroplacental
local
vasculature.
inflammatory
response

18. Antiphospholipid antibodies are present in
15% of women with recurrent miscarriage.
By comparison, the prevalence of
antiphospholipid antibodies in women with a
low-risk obstetric history is less than 2%.
In women with recurrent miscarriage associated
with antiphospholipid antibodies, the live birth
rate in pregnancies with no pharmacological
intervention has been reported to be as low as
10%.

21. How to manage APS with RPL?

23. Before
In the early
trophoblastic
pregnancy
invasion
Till 34 weeks

24. Adverse effects?
Thrombocytopaenia
Pregnancy
Osteoporosis
complications

26. Controlled Diabetes mellitus?
Controlled Thyroid disease?
Euthyroid with Antithyroid
antibodies?

28. Yes
Hyperinsulinemia
Hyperandrogenaemia Insulin Resistance

30. Metformin?

32. In couples with recurrent miscarriage,
chromosomal abnormalities of the embryo
account for 30–57% of further miscarriages.
The risk of miscarriage resulting from
chromosomal abnormalities of the embryo
increases with advancing maternal age.

33. 2–5% of couples with recurrent miscarriage, one of
the partners carries a balanced structural
chromosomal anomaly most commonly a balanced
reciprocal or Robertsonian translocation.

34. How to
diagnose?

35. Management?

38. Partner
leucocytes Immunoglobulin's
infusion
Steroids Stays abandoned

40. Cytokines
T-helper-1 (Th-1) type, with
production of the pro- T-helper-2 (Th-2) type, with
inflammatory cytokines production of the anti-
interleukin 2, interferon and inflammatory cytokines
tumour necrosis factor alpha (TNF interleukins 4,6 and 10
)

41. Normal pregnancy might be the result of a
predominantly Th-2 cytokine response, whereas
women with recurrent miscarriage have a bias
towards mounting aTh-1 cytokine response.

43. Progesterone is
necessary for
successful
implantation and the
maintenance of
pregnancy.

44. This benefit of progesterone could be explained
by its immmunomodulatory actions in inducing a
pregnancy-protective shift from pro-inflammatory
Th-1 cytokine responses to a more favourable
anti-inflammatory Th-2 cytokine response

46. The reported prevalence of uterine anomalies in recurrent
miscarriage populations ranges between 1.8% and 37.6%.
The prevalence of uterine malformations appears to be
higher in women with second-trimester miscarriages
compared with women who suffer first-trimester
miscarriages, but this may be related to the cervical
weakness that is frequently associated with uterine
malformation

47. Investigations
Serial TVS
during
Hystero –
TVS + / - 3D MRI pregnancy
Laparoscopy
for Cervical
length

50. Factor V Leiden mutation
protein C deficiency
Protein S deficiency
Antithrombin III deficiency
Hyperhomocysteinaemia
Prothrombin gene
mutation

52. Can Infective
agents cause
RPL?

56. Investigations
TSH
HbA1C
Anti thyroid Antibody
Anatomy screen
APS screen
Vaginal swab
PCOD screen
Cytogenetic examination of abortus
Karyotyping
Thrombophilias screen

57. Evidence based
Progesterone
Weight reduction
Aspirin + LMWH
Cerclage
Clindamycin
Thyroxin
IVF + PGD

58. Eminence based
Spiramycin
Steroids
Immunoglobulin's
hCG

59. Unexplained
RPL
Repeated
scanning
Reinforcement Reassurance

60. Unexplained
RPL