Miscarriage / RPL Flashcards
How common is RPL?
What is RPL?
3 or more consecutive miscarriages
1% of couples
What are the epidemiological risk factors for pregnancy loss?
AMA - decline in number and oocyte quality rate 20-24 year old 11% 30 15% 40 50% >45 90% Paternal age matters too
Previous miscarriages
risk of a pregnancy loss after 3 consecutive is 40%
General factors obesity caffeine intake more then 5 ETOH drinks per week smoking
Why is testing for antiphospholipid syndrome important?
most important treatable risk factor likelihood of a pregnancy without treatment if APLS <10% Occurs in 15% of woman with RPL (vs 2% baseline population) fits obs criteria
What are the anti phospholipid antibodies
To diagnose antiphospholipid syndrome it is mandatory that the woman has two positive tests at least 12
weeks apart for either lupus anticoagulant or anticardiolipin antibodies of immunoglobulin G and/or
immunoglobulin M class present in a medium or high titre over 40 g/l or ml/l,or above the 99th percentile).
What are the pregnancy outcomes that count for APLS dx?
3 or more consecutive miscarriages before 10 weeks
One or more morphologically normal fetal loss after the 10th week of gestation
one or more PTB before 34th week owing to placental disease
What is the mechanism that APLS results in pregnancy morbidity
Inhibition of trophoblast function and differentiation
activation of complement pathways at the maternal fetal interface resulting in local inflammatory response
Thrombosis of the uteroplacental vasculature
These are reserved by heparin
what genetic factors do you need to test for in RPL
In approximately 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
Although carriers of a balanced translocation are usually phenotypically normal,their pregnancies are at
increased risk of miscarriage and may result in a live birth with multiple congenital malformation and/or
mental disability secondary to an unbalanced chromosomal arrangement. The risk of miscarriage is
influenced by the size and the genetic content of the rearranged chromosomal segment
are Embryonic chromosomal abnormalities a factor in RPL?
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. However,it is important to note that as the number of miscarriages
increases,the risk of euploid pregnancy loss increases
Anatomical factors
What factors contribute to loss when?
difficult to know the exact impact
large variability in trials
There does seem to be a correlation in T2 loss
with uterine abnormalities - as resulting cx weakness
Septate uteri increase the risk of T1 loss
What is the classic presentation of T2 cx incompetence
Painless cx dilatation
PPROM
Endocrine factors
What tests for woman with RPL?
T2DM and thyoid disease increase the risk of RPL
if UNtreated
What is the effect of PCOS on early pregnancy?
Increased miscarriage
unsure mechanism
Elevated androgen index appears to be a prognostic factor for a subsequent miscarriage in woman with recurrent miscarriage
Should we do a TORCH screen for RPL?
nope
Does BV have an affect on miscarriage?
The presence of bacterial vaginosis in the first trimester of pregnancy has been reported as a risk factor
for second-trimester miscarriage and preterm delivery,
63,64 but the evidence for an association with firsttrimester miscarriage is inconsistent.
65,66 A randomised placebo-controlled trial
67 reported that treatment
of bacterial vaginosis early in the second trimester with oral clindamycin significantly reduces the
incidence of second-trimester miscarriage and preterm birth in the general population.There are no
published data to assess the role of antibiotic therapy in women with a previous second-trimester
miscarriage.
should we test for thrombophilias? if so which ones?
Women with second-trimester miscarriage should be screened for inherited
thrombophilias including factor V Leiden, factor II (prothrombin) gene mutation and
protein S.
What can cause + antiphospholipids?
transient positivity secondary to infections,
suboptimal sample collection and preparation
lack of standardisation of laboratory tests for their detection
Should every one who has RPL have a karyotype?
Parental peripheral blood karyotype of both parents should be performed in RPL if testing of the products reports an unbalanced structural chromosomal abnormality
If a balanced translocation is detected, what are the options for pregnancy?>
VF and pre implantation diagnosis - pregnancy rate 30%
A Dutch study38 reported that couples with balanced translocations have a low risk (0.8%) of
pregnancies with an unbalanced karyotype surviving into the second trimester and that their
chance of having a healthy child is 83%
(higher pregnancy rate with spont attempt)
How to prevent RPL if + APLS
Low dose aspirin and heparin to prevent further miscarriage
Complications of heparin in pregnancy?
Heparin can,however,be associated with maternal complications including bleeding,hypersensitivity reactions,heparin-induced thrombocytopenia and,when used long term,osteopenia and
vertebral fractures.Two prospective studies82,83 have shown that the loss of bone mineral density
at the lumbar spine associated with low-dose long-term heparin therapy is similar to that which
occurs physiologically during normal pregnancy.
What are the risks of APLS in pregnancy ?
Pregnancies associated with antiphospholipid antibodies treated with aspirin and heparin
remain at high risk of complications during all three trimesters.Although aspirin plus heparin
treatment substantially improves the live birth rate of women with recurrent miscarriage
associated with antiphospholipid antibodies, these pregnancies remain at high risk of complications during all three trimesters, including repeated miscarriage, pre-eclampsia, fetal growth
restriction and preterm birth;
85,86 this necessitates careful antenatal surveillance.
N
So should we resect the uterine septums to help with miscarriage rates?
No RCT on this
Open resection seem like a bad idea due to adhesions, and uterine rupture.
hysteroscopic probably ok
Progesterone for recurrent miscarriage
PROMISE trial says to progesterone for RPL
How do we treat woman with a positive screen for thrombophilias with RPL
There is insufficient evidence to evaluate the effect of heparin in pregnancy to
prevent a miscarriage in women with recurrent first-trimester miscarriage associated
with inherited thrombophilia.
Heparin therapy during pregnancy may improve the live birth rate of women with
second-trimester miscarriage associated with inherited thrombophilias.
