Recurrent Miscarriage Epidemiologymmm

Recurrent miscarriage: epidemiology
By Liji Thomas, MD
Recurrent pregnancy loss (RPL) has various definitions, but most
specialists would define it as the loss of 3 or more clinically confirmed
pregnancies. This criterion has been fixed on the basis of
epidemiological studies.
Credit: Piotr Adamowicz/ Shutterstock.com
RPL itself is subdivided into primary and secondary types, depending on
whether the woman has never carried a successful pregnancy or has had one
successful pregnancy succeeded by consecutive miscarriages. It is seen to
affect about 1 in 100 women of reproductive age, but the reported incidence
varies between 0.4 to 3%. Of this 1%, about a third is attributable to chance
alone.
According to the Practice Committee of the American Society for Reproductive
Medicine, RPL is diagnosed as two or more miscarriages, and the risk
increases after each loss. The true incidence is harder to find because of the
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impact of age, definition of pregnancy loss (biochemical versus clinical
pregnancy).
Causes and classification
Identified causes consisted chiefly of anomalies of the uterus, chromosomal
defects, and endocrine defects, including polycystic ovarian syndrome. In
more than 50% no reason was detected.
Other studies show that it is possible that much RPL is the product of chance,
but a small percentage is actually associated with definite pathology. This has
led to another type of classification for unexplained RPL, namely:
Type I
This refers to unexplained RPL occurring purely by chance and with a good
pregnancy outcome to be expected in future.
These women are usually older. Women who are between 40–44 are a
hundred times at risk of RPL (13.3%) due to chance alone, in comparison
with those aged 20–24 years (0.13%). The miscarriages involve mostly or
only biochemical (very early) pregnancies (when the pregnancy test is
positive, but no clinical confirmation of pregnancy was achieved before the
miscarriage).
Biochemical pregnancy loss is very common, occurring in 6 of 10 early
pregnancies in the general population. About one in five women can,
therefore, have three or more biochemical pregnancy losses just by chance.
In these cases, the karyotypes of aborted fetuses are likely to be abnormal in
at least half the cases, and three losses are likely.
Type II
This refers to unexplained RPL associated with an unidentified but existing
pathology and which has therefore a worse expected prognosis.
Such women are typically below 30 years. They have had four or more
miscarriages with normal karyotypes. The fetal heartbeat, which normally
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miscarriages with normal karyotypes. The fetal heartbeat, which normally
signifies a very low risk of miscarriage, was detected prior to the loss.
Diagnostic difficulties
Defining the criteria for RPL is important because biochemical pregnancies are
often lost unlike clinical pregnancies. Additionally, women with a history of
previous miscarriage are likely to be monitored more closely so that
pregnancy is detected in the biochemical stage itself, unlike other pregnant
women who are diagnosed only after clinical pregnancy begins.
For instance, a woman with two or more previous losses would have serum
betaHCG levels measured quite early, enabling even biochemical pregnancies
to be identified and their loss to be detected. This causes a higher rate of
pregnancy loss to be calculated in this subpopulation, compared with women
in the general population, in whom a miscarriage is identified only after a
clinical pregnancy is first confirmed.
Thus, the reported incidence of spontaneous abortions can vary significantly,
depending on the population being studied, whether of an infertile group
under fertility treatment or of the general female population of reproductive
age. In fact, women undergoing in vitro fertilization have been found to have
18% pregnancy loss compared with the almost 8% found in women with RPL.
Epidemiologic variables
Age
The risk of RPL varies from about 11% 11% in the age group between 20 and
24, to over 50% in women between the ages of 40 and 44 years.
Previous miscarriage
The risk of having a miscarriage is between 17% and 25% after 2 consecutive
abortions, but between 25% and 46% after 3.
Thrombophilia
One common identified cause of RPL is a thrombophilia, which is also
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One common identified cause of RPL is a thrombophilia, which is also
associated with preterm births, pregnancyinduced hypertension and
eclampsia, antiphospholipid syndromes (APS), intrauterine growth restriction
and placental insufficiency.
The most common mutations behind heritable thrombophilias are those of
factor V Leiden (FVL) and prothrombin gene (G20210A). FVL causes the risk
of thrombosis to increase by 510 times even in carriers (with one normal and
one defective gene), and 80 times in homozygotes (both genes carry the
same defect).
The discrepancy in carriers results from the interaction between the small
increase in absolute risk and the effects of additional risk factors such as
pregnancyassociated hypercoagulable states, which results in serious
thrombosis. On the other hand, the G20210A mutation does occur in 14% of
the general population in the US, especially among those who originally came
from the south of Europe.
Women with this mutation have 3 times the average risk of venous clots, as
well as higher odds for heart attacks and strokes, compared to those who do
not carry the mutation.
Research shows the risk of RPL is increased by 2 times in women with either
G20210A or FVL mutations. The interesting fact is that these inherited
thrombophilias are far more likely to cause sporadic miscarriages than to
result in RPL.
Most carriers fail to show any clinical signs of hypercoagulability, and may
have one or no pregnancy losses with one or more successful pregnancies.
Thus, most carriers are probably missed due to lack of testing in women who
have carried at least one fetus to term and had a live delivery.
Antiphospholipid syndrome
APS occurs in only 2% of healthy pregnancies, but in a fifth of women who
have unexplained RPL, but a third of women with systemic lupus
erythematosus.
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Uterine anomalies
These are found in 3% of women overall, but in 27% of women with RPL. The
rate of miscarriage in women with a bicornuate uterus is 47%, in uterine
septa it is 26%, but with a unicornuate uterus it is 17%.
Single gene mutations
Several mutations such as G6PD deficiency or phenylketonuria can cause a
higher risk of miscarriage.
Endocrine disorders
When diabetes is poorly controlled, the risk of sporadic miscarriage increases
because of several mechanisms. However, the actual increase in the risk of
RPL is not significant, according to several studies.
The same is true for deficient thyroid function. Some of the confusion may be
because disruptive thyroid antibodies are not always associated with overt
abnormality in thyroid hormone levels, but may still undermine normal
thyroid function as well as be associated with other autoimmune states, and
lead to miscarriage. High prolactin levels independent of thyroid disease may
also be associated with miscarriage.
Anovulation
Pregnancies in a woman with a history of anovulation, such as polycystic
ovarian syndrome, are more prone to miscarry because of the abnormal
hormonal environment which may lead to an unfavorable endometrium for
proper implantation and growth of early pregnancy.
Smoking, drinking and drug abuse
While each of these is associated with sporadic abortions, RPL as a direct
result of any of these is not established.
Luteal phase defects
The lack of specific diagnostic tests and evidence for the efficacy of treatment
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The lack of specific diagnostic tests and evidence for the efficacy of treatment
of supposed luteal phase defects has led to controversy over the actual
existence or importance of this factor. Luteal phase support is possible with
appropriate administration of estrogen and progesterone.
Others
Alloimmune factors and environmental causes such as chemical exposure
through tap water are also linked to RPL but evidence is weak.
Outcomes
One study showed that of 1214 pregnancies, those with RPL were generally
older but had the same number of deliveries as the general population.
However, these women were typically at higher risk of having bad pregnancy
outcomes, such as:
Increased history of antepartum hemorrhage (bleeding before delivery),
either in the patient or her family
Increased chance that the personal or family history was positive for
fetal anomalies
Increased number of stillborn babies
Increased newborn deaths
Reviewed by Afsaneh Khetrapal Bsc (Hons)
Sources
1. jamanetwork.com/journals/jamainternalmedicine/fullarticle/216789
2. https://www.ncbi.nlm.nih.gov/pubmed/16866793
4. academic.oup.com/humrep/articlelookup/doi/10.1093/humrep/des102
10. https://www.medscape.com/viewarticle/722321
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Further Reading
Early Signs of Pregnancy
Pregnancy: 08 weeks
Pregnancy: 9 12 weeks
More...
Further Reading
Recurrent miscarriage: causes
Last Updated: Jan 25, 2018
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