05 Causes and Technical Information
Description
This article is from the Miscarriage FAQ, by Laura Brooks brook006@mc.duke.edu with numerous contributions by others.
05 Causes and Technical Information
**The following is from an actual M.D. on the net, but he did not give
permission to use his name**:
First let me express my condolences at your loss. It makes no difference
what the gestational age is, there is still the loss of a pregnancy, and
this will result in grief and the need to work that through. Trying to find
out 'why' is part of the grief work.
Let me reassure you that your experience is VERY common. I see similar
cases every month in my practice. The problem is that experience with the
vaginal probe ultrasound is very limited, and to extrapolate the presence
of fetal cardiac activity on vaginal probe ultrasound to previous
reassuring statistics about discenment of cardiac activity by abdominal
ultrasound (doppler) or earlier auditory auscultation (stethescope) are not
valid. Most spontaneous abs occur prior to the 12th week, and a very short
time ago, cardiac activity was not discernable prior to the 12th week with
any degree of regularity, so the common statement was "Once we hear the
fetal heart we don't worry about miscarriage."
But now we are using a more sensitive technology and this trueism will not
hold up.
So I can only encourage you to work thru the loss of this one, and have
confidence that you will conceive again with success. And another bit of
advice is to wait at least 4 months before trying again. We have good
studies that indicate the risk of repeated SAB is much greater in the first
three months after a previous miscarriage.
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> I would like to find out more about what the chromosomal test actually
> involves, and what they might be able to find out from it.
They will count the chromosomes to see if there is the right number (46).
They will look to see if the chromosomes are complete, with no missing
parts. They will look to see if part of one chromosome has broken off and
rejoined another chromosome. They will look for any kind of abnormality
they can find. Chromosomes in eggs and sperm are at a somewhat higher risk
for getting things screwed up because they undergo a process called
"crossing over" where, for instance, chromosome 1 from your father and
chromosome 1 from your mother may swap equivalent parts, leading to a new
combination of genes on the resultant chromosome 1's. This is good for the
species, but when things don't go quite right, it's bad for the individual
that will inherit those chromosomes. Most of the time when this happens,
the conceptus or zygote is completely incapable of normal development, and
either never implants or dies within a few days of doing so, and you never
know about it. But some limp along until some critical gene that has been
damaged is needed, and then they die in a first trimester miscarriage.
Because the chromosomes can be seen with an ordinary microscope, any large
rearrangements or duplications/omissions can be easily detected, and the
cause for the miscarriage known.
> Also I would like to talk to other people who've had tests run on
> themselves and/or their spouses. I would also like to hear from people
> who's progesterone levels were too low to support a pregnancy (my OBGYN
> doesn't think it was that but hasn't ruled it out - I keep wondering about
> it because it happened to my sister-in-law).
It would be helpful to know when your miscarriages occured. Through most of
the first trimester, progesterone is produced by the corpus luteum---the
"scar" left behind when the egg popped out of the ovary. It produces
progesterone because it detects chorionic gonadotropin (HCG) in your blood.
The HCG is produced by the part of the embryo that later becomes the
placenta---the trophoblast, in scientist-speak. For the first 10 or 11
weeks, a progesterone insufficiency would be due to either the trophoblast
not producing enough HCG, or the corpus luteum not responding with enough
progesterone. For instance, my mother miscarried all three times between 8
and 11 weeks, and never had any morning sickness with any of those
pregnancies, but she did get it when she had her four children. My personal
opinion of this is that the first 3 embryos were not producing enough HCG
to sustain the pregnancy for whatever reason, since the first trimester
nausea is often correlated with HCG levels. It's difficult to use morning
sickness as an indicator though, because women vary enormously in their
sensitivity to it. Some women can have raging levels, and have no morning
sickness, and some will still be vomiting from the low maintenance levels
in the 2nd and 3rd trimesters. Anyhow, getting back to established fact,
HCG levels in a normal pregnancy rise dramatically until about 2 months
(this does vary though), and then begins to drop off as the corpus luteum
ages and becomes incapable of producing hormones anymore. The placenta by
this time has become mature enough and large enough to produce its own
progesterone, and it ramps up production as the corpus luteum is winding
down. If these two events are not quite in sync, you can experience a
slight dip in progesterone levels, and since rising progesterone levels
(absolute level doesn't matter, it is the rate of change of levels, which
is why progesterone levels continue to rise throughout pregnancy) keep the
uterus relaxed, contractions that expel the fetus can result, just like at
birth. Rates of miscarriage decline the further along in pregnancy you get,
except that there is a slight spike right at the end of the first
trimester, when this switcheroo maneuver is underway.
> And finally, I would appreciate hearing from anyone with any information
> about women developing antibodies to their fetuses, and how common (or
> rare) this is. And basically, just anyone else who has anything to tell me
> at all that might be helpful.
It's very rare. It's not precisely known why all pregnant women don't
develop antibodies to their fetuses, since they are, after all, foreign
tissue. The theory is that the placental interaction between the cells
derived from the baby (placenta) and the mother's cells in the uterine wall
induces the fetus to produce an enzyme that damps the immune response at
the interface. Theoretically, certain "markers" are used to determine where
the immune response is supposed to be dampened, and the cells do a little
comparison between themselves and their neighbors on these markers and if
they are different, then they produce the enzyme. The difficulty (again,
theoretically) is when the father coincidentally has the same set of
markers as the mother, then the fetus' cells look just like the mother's
cells when the comparison is done, and no enzyme is produced. The mother's
immune system could care less about these markers, however, and the other
differences between mother and fetus trigger an immune reaction and
antibodies are produced. Again, this is all theory, nobody knows what the
markers are even if they exist, but what is known is that a woman who
consistently has an immune reaction against fetuses fathered by one man
will be able to carry a fetus fathered by another man (say by artificial
insemination) to term quite nicely. The man will also be quite capable of
having children with another woman.
Your practitioner probably did a blood test that included a white cell
count, and possibly other measures of immune system function. If you are
rejecting the fetuses, you may experience similar symptoms to an immune
reaction to just about anything else---a fever, feeling sick (not
necessarily nausea, but the same feelings you get whenver you're battling
the flu, a cold, or other infection---being very tired, loss of appetite or
a ravenous appetite, etc.), and the evidence of your immune system fighting
an invader may show up on your blood test. But it also may not unless it is
being explicitly looked for---if some of the theoretical enzyme is being
produced because at least one of the markers is different, then the immune
response may be weak enough not to show any symptoms, but still strong
enough to kill the fetus.
I hope this hasn't been too dry and technical for you, and I hope it's been
helpful. Myself, I cling to the example of my mother, who had so much
heartbreak and then was rewarded with four wonderful kids (if I may say so
myself :).
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Ok, so, if we're going to try to look for an answer to why these
miscarriages occured, we'll consider the facts. On a gestational age basis,
the first embryo died somewhere around 5 weeks old (LMP is approx. 2 weeks
longer than gestational age). At this age, the embryo is about 1 centimeter
or 4 tenths of an inch long. The second embryo died at about 6 weeks old,
and is a little over half an inch long at this age. Important to note is
that the embryos died well in advance of being expelled. If there were a
hormonal problem, the embryos would have been alive and well, but the
uterus would have expelled them anyway. Usually (though not always) in
cases of the mother's immune system attacking the fetus, the placenta
suffers the most damage, because it is the part directly connected to her.
Bleeding from the damaged placenta almost always precedes such a
miscarriage. So this is unlikely to be the cause.
When the embryo just up and dies like this, it is usually because something
has gone wrong (either chromosomally or developmentally), and the embryo is
simply incapable of continuing on. It's pretty amazing that development
ever goes totally right. The first weeks are an incredibly fast and furious
process of cells dividing, migrating, bending, making seams, all having to
be highly orchestrated to happen at just the right time. If something
doesn't happen quite right, the embryo may die or be born with profound
defects later on.
However, it's quite unusual to have 2 miscarriages in a row with this
cause. There's about a 1 in 20 or 25 chance of this happening in any given
pregnancy, and to have it happen twice is like drawing a ball from each of
two bags of 25 numbered balls and having both balls be number 25. It's a
very low chance, but somebody has to be the unlucky one, I suppose.
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[I sent eMail to someone on the net whom I knew from earlier postings to be
a geneticist, asking him about the chromosomal test - his answer:]
I am really sorry to hear about this situation with you and I hope that my
notes can expand your information base so you can ask better questions to
your doctor. To begin with, I would double-check my statements with your
doctor/genetic counselor in regards to the SPECIFICS of your INDIVIDUAL
case. When a miscarriage occurs, a cell tissue is taken for this test and
grows for a period of several days which can vary according to cell type:
blood, bone marrow, amniotic fluid. This is called "growing a culture"
which will take a number of days. For example, I am learning the procedure
this week and last Friday, I took my own blood and let it grow until
Tuesday. On tuesday, I activated the cells to grow at the same rate by
adding certain chemicals. After that I blew up the Red Blood cells and
removed the waste to leave behind only the White Blood Cells. This is done
because Reds do not contain any DNA while White do. Thursday, I will take
this purified blood sample and fix it onto a slide where I can analyze it.
By using a microscope with a computer screen, I cut apart the chromosomes
and sort them according to type. This results in creating my 'karyotype'
which I will print out & in the case of other people return this data to
their doctor.
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