Reccurent Pregnancy Loss
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Recurrent Pregnancy Loss
Dr.Neeko Inees Chiriyankandath
MB BS, MD (Jipmer), MRCOG
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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.
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Risk factors
How to investigate
How to manage
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Risk factorsEpidemiological factors
Antiphospholipid syndrome
Genetic factors
Anatomical factors
Endocrine factors
Immune factors
Infective agents
Inherited thrombophilic defects
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Can obesity cause
RPL….?
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Yes
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Management….?
Weight reduction
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Can these cause RPL…….?
Smoking
AlcoholCaffeine
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? Treatment is Quit
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Can it….?
Video display terminals…..?
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Can Antiphospholipid syndrome cause
RPL…..?
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Antiphospholipid syndrome is the most important treatable cause of recurrent
miscarriage.
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Antiphospholipid antibodies
Lupus anticoagulant
Anticardiolipin antibodies
Anti-B2 glycoprotein-I
antibodies
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What is APS?
Antiphospholipid syndrome refers to the
association between antiphospholipid
antibodies
and adverse pregnancy outcome
or vascular thrombosis
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Adverse pregnancy outcome
Three or more consecutive
miscarriages before 10 weeks of gestation
One or more morphologically
normal fetal losses after the 10th week of
gestation
One or more preterm births
before the 34th week of gestation
owing to placental disease.
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Mechanism of APS
Inhibition of trophoblastic function and
differentiation
Activation of complement
pathways at the maternal–fetal
interface resulting in a
local inflammatory
response
And, in later pregnancy,
thrombosis of the
uteroplacental vasculature.
Can be reversed by LMWH
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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%.
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How to investigate?
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2 tests 12 weeks apart
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How to manage APS with RPL?
Aspirin LMWH
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When to start?
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In the early pregnancy
Before trophoblastic
invasion
Till 34 weeks
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Adverse effects?
Thrombocytopaenia
OsteoporosisPregnancy complications
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Can endocrine
factors cause RPL?
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Controlled Diabetes mellitus?
Controlled Thyroid disease?
Euthyroid with Antithyroid antibodies?
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Can PCOD cause RPL?
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Yes
Hyperinsulinemia
Insulin ResistanceHyperandrogenaemia
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LH suppression improve the
result?
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Metformin?
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Can Genetic factors
cause RPL?
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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.
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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.
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How to diagnose?
Send the abortus for cytogenetic
analysis
If unbalanced translocations
Karyotyping of the parents
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Management?
IVF and Preimplantation
Genetic Diagnosis (PGD)
Natural conception
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Can Immune factors
cause RPL?
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HLA Incompatibility
Maternal blocking
antibodies
Natural Killer cells (NK)
Evidence is lacking
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Partner leucocytes infusion Immunoglobulin's
Steroids Stays abandoned
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Cytokines?
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Cytokines
T-helper-1 (Th-1) type, with production of the pro-
inflammatory cytokines interleukin 2, interferon and tumour necrosis factor alpha
(TNF )
T-helper-2 (Th-2) type, with production of the anti-inflammatory cytokines interleukins 4,6 and 10
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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.
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Can cytokines response be
manipulated?
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Progesterone is necessary for
successful implantation and the
maintenance of pregnancy.
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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
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Can Anatomic factors cause
RPL?
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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
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Investigations
TVS + / - 3D Hystero – Laparoscopy MRI
Serial TVS during
pregnancy for Cervical
length
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Management
Uterine surgeries
Cervical cerclage
Evidences are
conflicting
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Can thrombophilias cause RPL?
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Factor V Leiden mutation
protein C deficiency
Protein S deficiency
Antithrombin III deficiency
Hyperhomocysteinaemia
Prothrombin gene mutation
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Diagnosed by thrombophilias screen
They are at high risk of DVT / PTE LMWH
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Can Infective agents cause
RPL?
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Torch?
Evidence shows
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Bacterial Vaginosis?
Evidence is positive and might be prevented by clindamycin.
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How to approach RPL?
History Clinical examination
Investigations Treatment
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Investigations
TSH
HbA1C
Anti thyroid Antibody
Anatomy screen
APS screen
Vaginal swab
PCOD screen
Cytogenetic examination of abortus
Karyotyping
Thrombophilias screen
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Evidence based
Progesterone
Weight reduction
Aspirin + LMWH
Cerclage
Clindamycin
Thyroxin
IVF + PGD
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Eminence based
Spiramycin
Steroids
Immunoglobulin's
hCG
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Unexplained RPL
Repeated scanning
ReassuranceReinforcement
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Unexplained RPL
IVF + PGD
Aspirin + LMWH
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Surrogacy might be a good option
for all cases of RPL except genetic
factors…..?
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Thank you……