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Recurrent Pregnancy Loss

We are familiar with the pain and disappointment that accompanies miscarriage. Our fertility specialists are highly trained to deal with the medical causes of miscarriage and can often help couples carry their baby to term.

The following information is provided as a summary of conditions that may cause recurrent pregnancy loss and medical testing that will be performed in evaluation.  We have also provided information on conditions that you may have heard of from the lay press but are not recognized causes of recurrent pregnancy loss.  This information will, in some cases, draw the important distinction of whether a condition is recognized as a possible cause of an occasional pregnancy loss versus recurrent pregnancy loss.  In other words, some pregnancy losses may have an identifiable cause - such as an infection - but there is no evidence that the condition will persist to cause future pregnancy losses.

UTERINE ABNORMALITIES:

Congenital or acquired abnormalities of the uterus may cause recurrent pregnancy loss.  A hysterosalpingogram (HSG) will be performed to evaluate the uterus in this regard.  Conditions that may be diagnosed include:  uterine anomalies (abnormalities in the formation of the uterus) - septate uterus or bicornuate uterus; intrauterine adhesions; uterine myomas (fibroids); in utero diethylstilbestrol (DES) exposure.  The management of some uterine abnormalities which cause recurrent pregnancy loss is surgical.  Septate uteri, intrauterine adhesions and some uterine fibroids may be treated by hysteroscopy (endoscopic surgery) as an outpatient procedure.  Surgery for large uterine fibroids requires a major operation.  Other abnormalities may not be amenable to surgical treatment.  The prognosis for subsequent normal pregnancy after surgical treatment of most conditions listed above is excellent.

CHROMOSOME IMBALANCE:

Abnormalities of maternal or paternal chromosomes may cause recurrent pregnancy loss.  It is possible for men or women to be physically normal in every way but carry a chromosomal abnormality that will affect the risk of early pregnancy loss.  The incidence of chromosome abnormalities in couples with at least two spontaneous miscarriages is approximately 5%.  A simple (but expensive) blood test may be performed to determine maternal and paternal chromosome make up and diagnose this condition.  The test involves culturing cells obtained from a blood sample and takes several weeks to complete.  Occasionally, the cells fail to grow and the test must be repeated.

A common and untreatable cause of early pregnancy loss is a "spontaneous" chromosome imbalance in the early embryo.  In this situation, the chromosomes of the sperm and the egg are normal however a problem develops during the early process of egg fertilization leading to a chromosome make-up in the early embryo that is not compatible with life -e.g. too many chromosomes or too few chromosomes.  Of all early pregnancy losses, approximately half are due to this type of genetic abnormality.  This is not a cause of recurrent pregnancy loss but rather should be anticipated as occurring occasionally during the reproductive years as a percentage of all pregnancies.   There is no treatment for this natural spontaneous event.  Couples who experience an early pregnancy loss due to this type of genetic error will be expected to have a normal chance to carry a subsequent pregnancy to full term.  The risk of this type of pregnancy loss increases with increasing maternal age. 

AUTOIMMUNITY:

Several diseases are caused by apparent confusion within the body's normal mechanisms that respond to disease.  Normally, the human body makes antibodies against infection or any foreign tissue (as in rejection of organ transplants).  In some disease states, the body becomes confused and apparently makes antibodies against its own normal tissue.  Some of these disease states are associated with recurrent pregnancy loss.

 ANTIPHOSPHOLIPID ANTIBODY SYNDROME (APA): 

Recent information suggests that high levels of either anti-cardiolipin antibodies or the ‘lupus’ anticoagulant antibody may be linked to early pregnancy loss.  Some women with normal reproductive histories have low levels of these antibodies.  The reason for early pregnancy loss due to APA is unclear.  There are several theories - the most widely accepted explanation links the presence of these antibodies to damage of the small blood vessels which link the mother to the fetus resulting in inadequate blood flow to the baby.  There are several medical studies suggesting that treatment with heparin, lovenox and/or aspirin improves the successful pregnancy rate when APA is proven to exist in women experiencing recurrent pregnancy loss.  It should be emphasized that pregnancy loss may occur in spite of treatment.  In addition, there are risks associated with treatment - an effect on the pregnancy or fetus due to the medications.  The overall "state of the art" related to APA-linked pregnancy loss supports the treatment of these conditions as noted above.  Testing for APA will be part of your evaluation. 

OTHER AUTOIMMUNE DISEASES:

Several other maternal autoimmune diseases may cause early pregnancy loss: rheumatoid arthritis; systemic scleroderma; polymyositis; polyarteritis nodosa, mixed connective tissue disease.   The link between these rarer autoimmune diseases and recurrent pregnancy loss is not clear.  The state of the art of recurrent pregnancy loss work ups at this time does not include screening tests for these diseases. 

BLOOD CLOTTING DISORDERS: 

Some mild forms of blood clotting disorders can cause recurrent early pregnancy losses (and/or problems with later stages of pregnancy) even if the mother does not have a known problem with blood clotting herself.  As a cause for recurrent pregnancy loss these particular disorders are relatively rare.  A screening test for these disorders, some of which can be inherited and some of which are sporadic, is part of your evaluation.

DIABETES:

Poorly controlled diabetes mellitus has been linked to early pregnancy loss.  Although it is very unlikely that unrecognized diabetes causes recurrent pregnancy loss, screening for diabetes will be performed by a blood test.

THYROID DISEASE:

Thyroid dysfunction may be a cause of early pregnancy loss - either under-activity (hypothyroidism) or over-activity (hyperthyroidism).  Thyroid disease is a very rare cause of recurrent miscarriage.  Your thyroid function will be tested.

ENVIRONMENTAL CAUSES OF PREGNANCY LOSS:

Several environmental factors may increase the risk of early pregnancy loss.  The use of alcohol or cigarettes has been associated with a higher than normal incidence of spontaneous pregnancy loss. Most women who smoke or drink alcohol carry pregnancies successfully and therefore there may be an unusual susceptibility on the part of some pregnancies or mothers. There is also likely to be a dose related effect.  In other words, excessive smoking or alcohol consumption, in some women (it is not possible to identify which women) may cause early pregnancy loss.

Many chemicals have been implicated in early pregnancy loss.  Women with occupational exposure to anesthetic gases, lead, or mercury may suffer increased pregnancy loss.  The wives of men exposed to vinyl chloride, chloroprene, or DBCP have also suffered an increased rate of early pregnancy loss. 

Maternal exercise is often a matter of concern.  There is no substantial evidence that strenuous maternal exercise causes pregnancy loss.  Even so, "taking it easy" or even bed rest are often recommended in cases of threatened miscarriage.  These measures may or may not help.

LUTEAL PHASE DEFECT (INADEQUATE PROGESTERONE PRODUCTION): 

This problem is the most common erroneous diagnosis of infertility and pregnancy loss.  Luteal phase defect is an extremely rare disorder.  After ovulation, the ovaries produce the hormone progesterone.  This hormone prepares the endometrium (the uterine lining) for arrival of the early embryo and affects changes that promote implantation and therefore pregnancy.  After pregnancy is established, the ovaries continue to produce progesterone.  Progesterone from the ovaries is important through the first 6-8 weeks of pregnancy.  If the amount of progesterone produced by the ovaries is inadequate, infertility or pregnancy loss may result.

Testing for luteal phase defect (LPD) is unfortunately quite difficult.  A timed blood test for progesterone is performed five to nine days after ovulation can be suggestive of a luteal phase defect but as the hormone progesterone is secreted in a pulsatile manner, a single progesterone test cannot diagnose or exclude LPD. Clinical history including a short number of days between ovulation and onset of menses can also be suggestive but again is not diagnostic.  There is no advantage to perform multiple blood tests, and endometrial biopsy for uterine dating has been proven to be useless.  Luteal phase defect may be treated by clomiphene citrate (an oral medication) or by progesterone vaginal suppositories or pills (see separate information sheets on both of these therapies). 

GENERAL PROGNOSIS FOR PREGNANCY SUCCESS:

Lastly, in terms of general prognosis, two of the largest studies that have investigated the problem of recurrent pregnancy loss have shown that women experiencing even 3 or 4 early spontaneous pregnancy losses with no known cause and no medical intervention have a fairly high chance of having a normal term delivery with their next pregnancy.  The table below shows various data on the chance of subsequent pregnancy loss.

Age Pregnancy History Chance next pregnancy will be term/normal
<35 3-4 miscarriages, (+) previous live birth 70%
<35 3-4 miscarriages, (-) previous live birth 60%
35-40 3-4 miscarriages, regardless of previous history 60%
>40 >2 miscarriages, regardless of previous history 50%

CONDITIONS THAT MAY CAUSE PREGNANCY LOSS THAT IS NOT RECURRENT: INFECTIONS:  BACTERIAL and VIRAL

CYTOMEGALOVIRUS (CMV)

CMV infection may affect live born infants of term pregnancies.  Whether this virus causes early pregnancy loss or recurrent pregnancy loss is not clear.  Half or more of adult females have been exposed to CMV.  After initial exposure, the virus enters a latent (or quiet) stage and may or may not affect the woman or her offspring.  Women with an active CMV infection or reactivation of a previous infection may deliver infants that are in some way affected.  CMV infection may be responsible for some early pregnancy losses - this is probably very rare.  There is no clear information that CMV infection is responsible for recurrent pregnancy loss.  There is no treatment for this viral disease. 

RUBELLA VIRUS:

Rubella (German measles) when acquired during the first trimester of pregnancy may cause early pregnancy loss or fetal developmental abnormalities.  This happens if the initial maternal infection occurs during early pregnancy.  After the initial infection, reinfection is not possible (or is extremely rare) and therefore, rubella is not a cause of recurrent pregnancy loss. 

HERPES SIMPLEX VIRUS (HSV):

HSV is a sexually transmitted virus that may affect babies born to mothers with an initial (or primary) infection.  Babies affected by HSV may suffer serious or fatal complications.  Women who contract an initial HSV infection during early pregnancy may have an increased risk of early pregnancy loss.  There is no recognized link between HSV infection and recurrent pregnancy loss.  Although reactivation of maternal herpes lesions may occur, this type of infection is not thought to cause recurrent pregnancy loss.