Recurrent Pregnancy Loss
Post (After)-Implantation
What is post-implantation pregnancy loss?
Post-implantation pregnancy losses are manifest
as early or late pregnancy losses Early pregnancy
losses are losses of embryos during the first
trimester of pregnancy and have been termed
miscarriages. Although many advances in reproductive
medicine have been made during the past 25 years,
miscarriages remain the most common complication of
pregnancy. While most miscarriages are sporadic and
not repetitive, there is a subset of couples that
suffer recurrent miscarriage. While the risk of
miscarriage increases with maternal age, overall 15%
of pregnancies miscarry. Approximately 13% of all
recognized first pregnancies are lost. The risk of a
second consecutive miscarriage is only slightly
increased to 17%. However the risk of miscarriage
after two consecutive pregnancy losses rises to 35
to 40% and continues to rise with each subsequent
miscarriage. As many as 5% of all couples conceiving
experience two consecutive miscarriages and 2% have
three or more losses. Late pregnancy losses are
losses of fetuses after the first trimester of
pregnancy. Late pregnancy losses occur far less
frequently than early pregnancy losses and comprise
only 1% of pregnancies. Late pregnancy losses are
usually associated with incompetent cervix,
premature rupture of membranes, preterm labor,
intrauterine growth retardation or placental
abruption.
What are the causes of recurrent post-implantation
pregnancy loss?
Historically, the cause of recurrent
post-implantation pregnancy loss was unknown in most
couples. More recently, however, much progress has
been made in understanding the mechanisms involved.
Just as with pre-implantation and peri-implantation
pregnancy loss, two major reasons for repeat
post-implantation pregnancy loss exist. One is that
there is something wrong with the pregnancy itself,
such as a chromosomal abnormality that
prohibits the pregnancy from implanting or growing
properly. The other reason is a problem within in
environment in which the pregnancy grows that does
not allow an otherwise normal embryo to implant or
grow properly. Problems within the uterine
environment or lining of the uterus have been
classified as anatomic, hormonal and immunologic.
Problems with the Pregnancy - Problems
with the pregnancy are usually characterized by the
presence of an abnormal chromosome of the conceptus.
Chromosomal abnormalities occur in about 50%
of all products of conception from first trimester
miscarriages, 5% of late pregnancy losses and 0.5%
of live births. When products of conception from
over 200 miscarriages of women with repeat pregnancy
loss were tested with chromosomal analysis, 55% were
abnormal. Of interest, only 35% of women
experiencing recurrent pregnancy loss after a live
birth were chromosomally abnormal. Some pregnancy
losses associated with abnormal chromosomes such as
an extra chromosome (trisomy) have been reported to
have a high risk of a repeating. However, if such
“accidents” explained all of recurrent miscarriage,
the probability of three or more miscarriages in a
row resulting from “accidents” would account for 5%
or less of the observed incidence of losses.
Biochemical or clinical abortion occurs in 30%-40%
of women who achieve pregnancy after IVF and ET.
Statistically, greater than 80% of transfers of
three preimplantation embryos should include at
least one normal karyotypic preimplantation embryo.
Furthermore, it has been estimated that 75% of
karyotypically normal preimplantation embryos fail
to implant. Therefore, while chromosomal
abnormalities play a major role in earlier pregnancy
losses, other causes account for most late pregnancy
losses as well as around half of miscarriages and
occult losses.
A number of studies have reported observations
suggesting the existence of paternal (sperm derived)
effect on human embryo quality and pregnancy outcome
that are not reflected as a chromosomal abnormality.
Damaged sperm DNA can have a negative impact on
fetal development and present clinically as occult
or early clinical miscarriage. The Sperm DNA
Integrity assay (SDIa) serves as a tool for
measuring important properties of sperm chromatin
integrity.
Problems with the Uterine Environment -
Problems within the environment in which the embryo
implants and fetus grows have been classified as
anatomic, hormonal and immunologic. While
anatomic and hormonal abnormalities have been
associated with pre-implantation pregnancy losses,
there roles in post-implantation pregnancy loss have
been controversial. The mechanism of the losses in
post-implantation pregnancy failures seems to
involve clotting off the small placental vessels so
that the pregnancy “withers on the vine”. Clotting
of these vessels can be caused by:
- proteins or cytokines that are produced
by immunologic cells within the lining of the
uterus or
- by antiphospholipid antibodies produced
by circulating immune B cells or
- by a genetic predisposition contributed by
thrombophilia genes.
Cytokines
Miscarriages can be caused by cytokines or
proteins secreted by cells within the uterus. The
activity of these cytokines has been characterized
as pro-inflammatory and anti-inflammatory. While
initial exposure to pro-inflammatory cytokines is
necessary to stimulate invasion of the blastocyst
and formation of new blood vessels at the time of
implantation, prolonged exposure of pro-inflammatory
cytokines to the pregnancy is detrimental. Thus, for
pregnancy to be successful a change in balance of
secretion of cytokines from pro-inflammatory to
anti-inflammatory cytokines must occur. Three major
types of immune cells within the lining of the
uterus contribute to the pro-inflammatory and
anti-inflammatory responses: T cells, NK cells and
macrophages. Macrophages and NK cells infiltrate
implantation sites destined to miscarry. Both of
these cells are sources of pro-inflammatory
cytokines that can activate production of the
prothrombinase, fgl2. Fgl2 leads to deposition of
fibrin (a clotting factor) and activation of another
white blood cell called polymorphonuclear leukocytes
(PMN) that can destroy the vascular supply to the
placenta. Blood supply to the embryo is compromised
and the pregnancy essentially withers on the vine.
Increased expression of fgl2 has been shown
association with miscarriage of chromosomally normal
embryos as contrasted with chromosomally abnormal
embryos.
Antiphospholipid Antibodies
Antiphospholipid antibodies (APA) have been shown
to be associated with pregnancy loss (both early and
late). The action of APA on the blood vessel cells
results in blood clotting within the vessels and
thus blood supply to the pregnancy is impaired.
While testing for anticardiolipins (cardiolipins are
a kind of phospholipid) is standard in some
infertility clinics, this test alone cannot identify
the presence of all underlying autoimmune processes
that causes recurrent pregnancy loss. A panel of
tests for antibodies to six additional phospholipids
is recommended to determine the presence of APA.
Testing positive for one or more kind of
antiphospholipid antibodies indicates the woman has
the immune response that can causes recurrent
pregnancy loss. Of the antiphospholipid antibodies
tested, antiphosphoserine, choline, glycerol,
inositol and ethanolamine have been shown to target
the preimplantation embryo; antiphosphoserine and
ethanolamine to target placental cells; and
antiphosphoserine, ethanolamine and cardiolipin to
target blood vessel cells.
Because some circumstances can cause false
positives for these tests, it is important to
determine persistent positive levels by repeating
the tests in six to eight weeks.
The live birth rate for a patient with untreated
APA ranges from 11 percent to 20 percent.
Individuals with recurrent pregnancy loss and/or
implantation failure, venous or arterial,
thrombosis, thrombocytopenia, elevated APTT or a
circulating lupus-like anticoagulant are among those
at risk for development of APA. Also at risk may be
women experiencing infertility associated with
endometriosis, premature ovarian failure, multiple
failed in-vitro fertilization, and unexplained
infertility. With treatment, the live birth rate for
women with APA increases to 70 to 80 percent.
Thrombophilia Panel
Thrombophilia or blood clotting can be both
acquired or inherited. The most common cause of
acquired thrombophilia is antiphospholipid
antibodies. Inherited thrombophilias can result from
gene mutations involved in coagulation. A number of
genes involved in blood clotting have been shown to
be associated with abnormal clotting and a history
of thrombosis. Deficiencies of antithrombin III,
protein S or C are usually associated with a
previous history of blood clots or thromboses. Other
gene mutations or “changes” are not associated with
such a high risk of blood clots, but are associated
with recurrent pregnancy loss. These include Factor
V von Leiden, Factor II Prothrombin, Fibrinogen,
Factor XIII), fibrinolysis (PAI-1) and thrombosis
(Human Platelet Antigen-1, Methylenetetrahydrofolate
reductase gene mutations. All of these mutations
have been associated more with second and third
trimester loss than first trimester loss. However,
it appears the more mutations you have, the higher
the risk for early pregnancy loss. In one study,
about 8 percent of women with a history of recurrent
miscarriage had combined thrombophilic defects
compared with 1 percent of controls.
How can we determine the cause of recurrent peri-implantation pregnancy losses?
There are a number of tests mentioned in the
above description of the cause of recurrent
post-implantation pregnancy loss that are available
to diagnose post-implantation pregnancy failure.
These are listed below in alphabetical order.
- Activated Reproductive Immunophenotype
- The Activated Reproductive Immunophenotype
measures not only the percentage of circulating
lymphocytes as the Reproductive Immunophenotype
does, but also activated NK and T cells. Women
experiencing implantation failure after IVF/ET
have significantly higher expression of NK cell
activation marker of CD69+ and of T cell
activation marker of HLA-DR.
- Antinuclear Antibodies - The presence
of ANA indicates there may be an underlying
autoimmune process that affects the clotting off
of the placenta and can lead to early pregnancy
loss.
- Antiphospholipid Antibodies -
Antiphospholipid antibodies have a direct action
on the blood vessel to cause clotting.
- Antithyroid Antibodies - Women with
thyroid antibodies face double the risk of
miscarriage as women without them. Increased
levels of thyroglobulin and thyroid microsomal
(thyroid peroxidase) autoantibodies show a
relationship in an increased miscarriage rate, and
as many as 31 percent of women experiencing RSA
are positive for one or both antibodies. Chances
of a loss in the first trimester of pregnancy
increase to 20 percent, and there is also an
increased risk of post-partum thyroid dysfunction.
- Embryotoxicity Assay - The
embryotoxicity assay (ETA) is looking measures
substances in blood that kill embryos. Embryotoxic
factors have been identified in as many as 60
percent of women with recurrent, unexplained
miscarriage, and also reported among women
endometriosis-associated infertility.
- HLA G Testing - The major
histocompatability complex (MHC), well known for
its role in the regulation of cell-cell
interaction in the immune response, also
influences reproductive success. The MHC affects a
variety of reproductive parameters including
spontaneous abortion, protection of fetus from
attack by the maternal immune system and
regulation of preimplantation embryo growth and
survival. One gene in the MHC has that has had
special attention with respect to reproduction is
the class I gene HLA-G because it is important in
establishing immunotolerance of the pregnancy.
Mutations in the HLA gene could interfere with
this vital process, resulting in pregnancy loss.
- Immunoglobulin Panel -
Hypogammaglobulinemia of IgA needs to be further
evaluated to rule out IgA antibodies before
treatment with intravenous immunoglobulin is
considered.
- Inhibin B - Inhibin-B serum
concentration provides a new measure of ovarian
reserve and, as such, can predict risk for
chromsosomal abnormalies among eggs.
- Lupus-like Anticoagulant - About four
percent of women with recurrent miscarriage test
positive for lupus-like anticoagulant, and nine
percent of individuals diagnosed with SLE have a
positive lupus anticoagulant test, or activated
partial thromboplastin time (APTT). APTT is an
adequate screening test for lupus-like
anticoagulant antibodies, but there is a high
incidence of false positives. Women who have a
positive APTT should also have more specific
tests, such as Kaolin clotting time, Russel viper
venom assay and the platelet neutralization assay
a to confirm the presence of lupus anticoagulant
antibody activity. And, since some women do not
test positive until they are pregnant or have
suffered a pregnancy loss, repeat testing during
early pregnancy is highly recommended when there
is a history of recurrent post0implantation
pregnancy loss.
- Natural Killer Activity - Natural
Killer cell activity or activation assay (NKa)
measures the killing activity (cytotoxicity)
within each cell. Increased killing activity is
associated with implantation failure and pregnancy
loss. A value of greater than 105 killing with a
target to effector ratio of 1:50 is considered
abnormal. The NKa also measures the ability of
IVIg to suppress the killing activity. Patients
with high NK cell activity that suppress with IVIg
in the NKa will respond very well to intravenous
immunoglobulin (IVIg) therapy. In fact, the live
birth rate with preconception IVIg is more than 80
percent, compared to 20 percent without treatment.
- Reproductive Immunophenotype - White
blood cells that belong to the innate or primitive
immune system kill anything perceived as foreign .
Some types of NK cells produce a substance called
tumor necrosis factor (TNF), which might be
described as your body's version of chemotherapy,
and is toxic to a developing fetus. Patients who
have high levels of these cells are at risk for
implantation failure and miscarriage. The
proportion of NK cells is determined by a
reproductive immunophenotype (RIP) test, which
looks for cells that have the CD56+ marker. An NK
(CD56+) cell range above 12 percent is abnormal.
- Sperm DNA Integrity Assay - Results of
recent research indicate that sperm influences not
only rates of fertilization of eggs but also
subsequent embryo development. The markers of
sperm quality used to predict pregnancy outcome
are not the parameters included in the standard
semen analysis (sperm concentration, motility or
morphology) but rather the results of the Sperm
DNA Integrity assay, which measures the amount of
sperm DNA that is fragmented. A sperm DNA
fragmentation index of greater than 30% is
associated with poor fertility potential.
- Thrombophilia Panel - Thrombophilia is
defined as a predisposition for thrombosis.
Increased thrombosis can result from defects in
coagulation, fibrinolysis, platelet aggregation
and endothelial damage. About 40% of patients with
thrombosis are inherited. Inherited thrombophilias
have been associated with early and late recurrent
pregnancy loss. Obstetrical complications such as
intrauterine growth retardation, placental
abruption as well as preeclampsia have also been
related to abnormal placental vasculature. Genetic
thrombophilia are suspected to account for about
30% of these obstetrical complications. Poor
pregnancy outcomes are associated with maternal
thrombophilia but may also be associated with
fetal thrombophilia by inheritance of maternal and
paternal thrombophilic genes. Because hemostasis
involves not only blood clotting but also
dissolution of the clot once formed and damage to
the blood vessel wall, the Thrombophilia Panel
contains gene muations for 10 genes involved in
all aspects of normal hemostasis, not just the
usual 3 performed in commericial laboratories.
- Y Chromosome Microdeletion Assay Related to
Recurrent Pregnancy Loss (MYC/RPL) - While Y
chromosome deletions were initially reported to be
associated with infertility due to low or no sperm
counts, more recent research has shown a site in
the proximal AZFc region of the Y chromosome to be
microdeleted among men whose partners experienced
recurrent pregnancy loss. The four sites analyzed
for deletions are DYS262, DYS220, DYF85S1,
DYF86F1.
How can we treat recurrent post-implantation
pregnancy loss?
Effective treatment depends on the cause of the
pregnancy loss. If the cause of the pregnancy loss
is a problem within the embryo itself, elimination
of the problem involves treatments including donor
egg, donor sperm or IVF with preimplantation genetic
diagnosis (PGD). If, however, the cause is related
to activated immune cells and their cytokines,
treatments include: Intravenous Immunoglobulin (IVIg),
Intralipid, and Phosphodiesterase Inhibitors. If
either acquired or inherited thrombophilia is
causing clotting of the placental vessel and
subsequent pregnancy loss, then heparin and aspirin
is the treatment of choice. If the blood clotting is
the result of an immune process, then steroids
and/or IVIg can be used.
1. Intravenous Immunoglobulin (IVIg)
IVIg has been used to treat pre-implantation,
peri-implantation and post-implantation recurrent
pregnancy loss associated with elevated levels of
antiphospholipid antibodies, antithyroid antibodies,
circulating NK cells and NK cell killing activity
and embryotoxins. It has also been used for
treatment of unexplained recurrent pregnancy loss.
The mechanisms by which IVIg works include:
- IVIg provides antibodies to antibodies (anti-idiotypic
antibodies)
- IVIg suppresses B cells production of
autoantibodies
- IVIg enhances regulatory T cell activity
- IVIg suppresses NK cell killing activity
Originally, IVIg therapy was used to treat women
who had not been successful in pregnancies
previously treated with aspirin and prednisone or
heparin. The rationale for the use of IVIG in the
original studies was the suppression of the lupus
anticoagulant in a woman being treated for severe
thrombocytopenia. IVIg was often given with
prednisone or heparin plus aspirin. The estimated
success rate of 71% for women at very high risk for
failure with a history of previous treatment
failures suggested IVIg treatment was effective.
More recently, IVIg therapy alone has been used to
successfully treat women with antiphospholipid
antibodies as well as women who become refractory to
conventional autoimmune treatment with heparin or
prednisone and aspirin.
Proinflammatory cytokines at the maternal-fetal
surface can cause clotting of the placental vessels
and subsequent pregnancy loss. One source of these
cytokines is the NK cell. Biopsies of the lining of
the uterus from women experiencing repeat pregnancy
loss reveal an increase in activated NK cells.
Peripheral blood NK cells are also elevated in women
with repeat pregnancy loss compared with women
without a history of pregnancy loss. Measurement of
NK cells in peripheral blood of women with a history
of recurrent miscarriage and a repeated failing
pregnancy has shown a significant elevation
associated with loss of a normal karyotypic
pregnancy and a normal level associated with loss of
embryos that are karyotypically abnormal.
Furthermore, increased NK activity in the blood of
nonpregnant women is predictive of recurrence of
pregnancy loss. Suppressor T cells with are required
for protection against NK cytokine-dependent
pregnancy loss. IVIg has been shown to decrease NK
killing activity and enhance Suppressor T cell
activity. Both of these events are necessary for
pregnancy to be successful. IVIg has been used to
successfully treat women with elevated circulating
levels of NK cells, NK cell killing activity and
embryotoxins with live birth rates between 70% and
80%.
IVIg has also been used to treat women with
unexplained repeat pregnancy loss. Four randomized,
controlled trials of IVIg for treatment of repeat
pregnancy loss have been published. A European-based
study showed a positive trend but did not achieve
statistical significance due to too few patients for
adequate statistical power given the magnitude of
the effect. However, a US-based trial did show a
significant benefit, the difference in live birth
rates being 62% among women receiving IVIg and 33%
among women receiving placebo. The greater magnitude
of effect in the US-based study than the
European-based trial could have arisen from the use
of a different study design. Patients began IVIg
treatment before conception in the US-based trial,
but after implantation in the European-based trial.
By waiting until 5-8 weeks of pregnancy to begin
treatment, women with NK cell-related pathology
occurring earlier would have been excluded and those
pregnancies destined to succeed would be included,
providing an opportunity for selection bias. Indeed,
a negative correlation with delay in treatment was
significant in this study. A third trial treated
only women who had a previous live birth, a group
that showed no significant benefit of treatment
using leukocyte immunization, but significant
benefit from IVIg. The fourth Canadian-based trial
had too few patients for adequate statistical power
to give significant results but did show a trend
toward benefit in women with a history of previous
live birth followed by recurrent miscarriage. When
the results of all of these trials were combined in
a meta-analysis the conclusion showed IVIg to be
effective treatment for repeat pregnancy loss. None
of the studies took into account the pregnancies
lost as a result of chromosomal abnormalities except
the US-based trial. Approximately 60% of the
pregnancies lost in the clinical trial would be
expected to have chromosomal abnormalities that
would not be corrected by IVIg.
The usual dosage of IVIg for treatment of repeat
post-implantation pregnancy loss is 25 grams but
successful pregnancies have been reported using
dosages from 20 to 60 grams. The half-life in
circulation is 28 days so infusions are usually
given every 28days. Depending on the obstetric
history, IVIg is continued every 28 days until the
end of the first trimester (women with a history of
first trimester pregnancy losses) or until 28-32
weeks gestation (women with a history of late
pregnancy losses). Pregnancies are monitored with
immunologic blood tests and treatment can be
modified based on the results of the blood tests.
Side effects of treatment with IVIg include
nausea, vomiting, headaches, chills, chest pain,
difficulty breathing—all comfort side effects which
usually occur during the infusion of IVIg and are
related to the rate of infusion. If these side
effects occur, the rate of the infusion of IVIg is
slowed. Other side effects that have been reported
much less frequently are migraine-type headaches and
sore or stiff neck occurring from one to four days
after the infusion. Last, but not least, while IVIg
is a purified protein particulate that is
reconstituted in fluid and infused in veins, the
protein is extracted from human plasma. Therefore,
it runs the same theoretic risks for transmittable
disease as other blood products. However, IVIg has
been available on the American market under FDA and
CDC surveillance since 1981, with no reported
instance of HIV transmission. There were reports of
cases of hepatitis C after IVIg treatment reported
in 1992 and the first part of 1993 for which some
manufactures changed the method of extraction and
added a detergent solubilization step. Thus the
theoretic risk at this time is an unknown risk of
transmission of presently unidentified infectious
particles. Because of the rigorous screening it must
undergo, the cost of IVIg is high. The high cost of
IVIg therapy can be a deterrent to treatment for
some individuals.
2. Intralipid
Evidence from both animal and human studies
suggest that intralipid administered intravenously
may enhance implantation and maintenance of
pregnancy. Intralipid is a 20% intravenous fat
emulsion used routinely as a source of fat and
calories for patients requiring parental nutrition.
It is composed of 10% soybean oil, 1.2% egg yolk
phospholipids, 2.25% gylcerine and water. Intralipid
stimulated the immune system to remove “danger
signals” that can lead to pregnancy loss. The appeal
of Intralipid lies in the fact that it is relatively
inexpensive and is not a blood product. Its likely
benefit to IVF patients with immunologic dysfunction
is under evaluation.
3. Aspirin
Low-dose aspirin (80mg or 1 baby aspirin) alone
has used for treatment of recurrent
post-implantation pregnancy losses. Among women with
increased resistance of blood flow through their
uterine arteries who were treated with aspirin for a
minimum of two weeks, the pregnancy rate was
increased from 17% to 47% after IVF/ET and the
miscarriage rate decreased from 60% to 15%. As a
prostaglandin inhibitor, aspirin would be expected
to increase blood flow to the ovary prior to
implantation, to the endometrium during implantation
and to prevent clotting of the placental vessels
following implantation. However, in studies of women
experiencing recurrent post-implantation pregnancy
loss/miscarriage associated with antiphospholipid
antibodies, results of clinical trials have shown
aspirin alone to be half as effective as other
treatments including heparin and steroids. In two
studies women receiving aspirin alone or heparin
plus aspirin for treatment of repeat pregnancy loss
associated with antiphospholipid antibodies, heparin
plus aspirin provided a significantly better outcome
that aspirin alone (live birth rate of 80% vs 44%).
A rationale for the use of low-dose aspirin
therapy during pregnancy for women with
antiphospholipid antibodies is to decrease blood
clots from forming in the placental vessels. The
mechanisms by which aspirin prevents blood clots are
through its antiprostaglandin and antiprostacyclin
effects and inhibition of platelet adhesiveness and
aggregation.
4. Heparin
Heparin has also been used in conjunction with
aspirin to prevent blood clotting. The rational for
using heparin is that it is a blood thinner and
inhibits clot formation by a different pathway that
the aspirin. While the effectiveness of heparin and
aspirin for treatment of women with elevated
circulating antiphospholipid antibodies and a
history of recurrent miscarriage is well accepted,
the use of heparin with or without aspirin to
enhance implantation rates has been controversial.
Most clinical trials of women with elevated
antiphospholipid antibodies and a history of
implantation failure undergoing IVF/ET show no
enhancement of implantation rates with heparin and
aspirin compared with no treatment. This observation
is not surprising since the action of heparin is on
the cells lining the blood vessels and pre- and peri-
implantation pregnancy loss occurs before placental
blood vessels appear. The combination of both
heparin and aspirin given to women experiencing
repeat pregnancy loss who had antiphospholipid
antibodies are associated with a live birth rate of
80% compared with a live birth rate of 44% in women
receiving aspirin alone. Live birth rates with
heparin, aspirin and a steroid called prednisone are
74%. Thus no enhancement of live birth rates are
noticed when prednisone is added to heparin and
aspirin therapy for treatment of recurrent
miscarriage.
Heparin is usually administered at a dose of
5,000-10,000 units subcutaneous twice a day along
with aspirin 80mg each day. In women with a
circulating lupus-like anticoagulant, more heparin
may be required. The side effects of heparin therapy
include bleeding, decreased platelet count and
osteoporosis or thinning of the bones. Calcium
supplementation (two tablets of Tums a day) is
recommended while taking heparin. Low molecular
weight heparins such as Lovenox and Fragmin have
also been used to treat recurrent pregnancy loss
associated with thrombophilias, either acquired or
inherited.
5. Steroids
Historically, repeat pregnancy loss associated
with antiphospholipid antibodies was treated with
combinations of prednisone and aspirin. The
rationale for prednisone therapy is suppression of
autoantibodies such as antiphospholipid and
antinuclear antibodies. A study comparing live birth
rates in women treated with heparin and aspirin with
prednisone and aspirin showed 75% live births in
both groups. However, both maternal complications
and preterm delivery with premature rupture of
membranes and toxemia of pregnancy were
significantly higher in pregnant women treated with
prednisone and aspirin compared with heparin and
aspirin. Other side effects of steroid medication
include fluid retention, weight gain, and mood
changes. Therefore, the current recommendation for
“first attempt” treatment for repeat pregnancy loss
associated with antiphospholipid antibodies is
heparin and aspirin.
6. Host Uterus
If the cause of the recurrent pregnancy loss
resides within the uterine environment and if that
cause cannot be corrected, then a host uterus may be
a final solution for treatment. A host uterus is a
uterus donated by a woma n other than the patient.
In this situation, embryos are generated using the
egg of the patient and sperm of her husband through
in vitro fertilization (IVF). The embryos thus
generated are transferred into the uterus of the
host. The intention is that the host will achieve
pregnancy with the patients’ embryos, carry the
pregnancy to term and, upon delivery, return the
babies to the genetic parents.
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