Recurrent Pregnancy Loss & Miscarriage

Recurrent pregnancy loss – also known as recurrent miscarriages – is by definition three confirmed uterine pregnancies that are lost prior to 20 weeks.

The two common terms for this stage is chemical pregnancy and clinical pregnancy. A chemical pregnancy is one in which the pregnancy hormone test is positive but an ultrasound does not confirm the pregnancy in the uterus. These pregnancies cannot be located and are often treated as an ectopic pregnancy.

A clinical pregnancy is visible in the uterus by ultrasound but does not progress normally and may require a surgical or medical procedure to remove it. In general, 15 percent of all pregnancies between four and 20 weeks will undergo clinically recognized spontaneous miscarriage.

The true loss rate is close to 50 percent due to unrecognized losses from two to four weeks after conception. After three or more consecutive losses there is a 40 percent chance for a fourth loss.

It’s important to keep in mind that the chance for a successful live birth after three losses is close to 60 percent, and if a woman has at least one previous normal pregnancy the chance increases to 70 percent.

Even though the percentage rate is in favor of a good pregnancy, the psychological impact on the woman and couple can be significant. Therefore, our choice is to begin a recurrent pregnancy loss evaluation after two losses to help avoid a third if possible.

Normal statistics

Reproductive loss from conception to a clinically recognizable pregnancy is approximately 50 percent. This is due to the fertilized egg failing to divide and grow normally.

Between implantation and six weeks, 30 percent are lost and by 12 weeks gestation a total of 80 percent of recognized and unrecognized pregnancies due not progress to a normal pregnancy. We can identify a cause in 40 percent of cases. The other 60 percent could be a result of failure to divide and implant normally.

Maternal age plays a major role in recurrent pregnancy loss. As a woman gets older the eggs do not divide normally and pregnancy loss rate increases from 12 percent, for those younger than 20 years old, to 26 percent by age 40.

After the detection of a live embryo in a young woman the loss rate decreases to 3 to 5 percent, however in a woman older than 40 the risk is 23 percent. We understand the impact this has on a woman and couple; therefore we initiate a full evaluation after two losses.

Genetic factors

Recurrent pregnancy loss due to chromosomal abnormalities affects approximately 3 – 8 percent of gestations. The most frequent is a balanced chromosomal rearrangement or translocation.

Chromosomal translocations and inversions are the relocation of a segment of genes from one chromosome to another or the rearrangement of genes on the same chromosome. In these situations the parents with this condition are normal because they have all the normal chromosomal complement (46 chromosomes with two sex chromosomes).

The embryo itself gets half of its genetic material from both the egg and sperm. Depending on whether the embryo gets the switched chromosomes would determine if the embryo is affected. You may end up missing a portion of a chromosome or an extra chromosomal which could result in a pregnancy which could result in a miscarriage, a normal offspring carrying the same chromosomal anomaly as the parents, or a genetically normal baby.

Depending on the genetic anomaly would determine the possibility for a normal offspring. If a genetic condition is discovered, you will be referred to a geneticist to discuss the implications to yourself and for our future reproductive health.

To detect genetic problems, a blood test on both partners evaluates cells for the normal amount and the correct order of genetic material. This testing requires approximately two to three weeks before results are available. Insurance coverage is variable and you should call your company prior to getting the test.

Environmental factors

In a woman’s social life and work place, environmental exposures could affect the outcome of a pregnancy. Some anesthetic agents as well as tetrachoroethylene, used in dry cleaning, have been associated with miscarriages. If proper precautions are used including a mask respirator, and specialized clothing then the exposure is minimal and should not cause a problem.

Additionally, several reports have shown a strong association between smoking and pregnancy losses. The risk increases with the number of cigarettes smoked per day.

Exposure to Aspartame (an artificial sweetener found in a variety of beverages), heavy caffeine and alcohol intake have all been associated with pregnancy loss too, but scientists have not defined the exact amount. Therefore, we advocate limiting the intake of these beverages while trying to conceive and avoid these during pregnancy.

Endocrine problems

An endocrine problem is found in 15 percent of recurrent miscarriers. Any hormonal imbalance that affects ovulation could impair normal uterine lining development, and ultimately implantation.

Thyroid disease or pituitary dysfunctions are the most common findings associated with an endocrine cause for recurrent pregnancy losses. Studies have shown that women with an elevated LH (lutinizing hormone) level, as with polycystic ovary syndrome or PCOS, may be at increased risk of miscarriage. This is due to an increased amount of a male hormone, androgens, that adversely affects the uterine lining.

A controversial area is the topic of a luteal phase defect. It is suggested that this is caused by an insufficient production of progesterone secretion by the ovary after ovulation.

This may be due to under-development of the appropriate cells during the first part of the cycle. As the egg develops prior to ovulation, the two cells surrounding the follicle which contains the egg have to mature.

If this fails to occur the cells will not be able to produce the appropriate amount of progesterone to help maintain the pregnancy. This condition can be diagnosed by either a blood progesterone level, performed in the middle of the luteal phase, which is after ovulation, or by performing an endometrial biopsy prior to menstruation.

An abnormal result can be treated with supplemental progesterone, but the studies regarding this treatment have not been convincing. While the evidence suggests that luteal phase defect results from poor follicular development in the first half of the menstrual cycle we attempt to enhance egg development by using fertility medication.

Age related pregnancy loss is associated with poor egg quality. The best available technique for assessing the quality of a woman’s eggs is measuring what’s known as ovarian reserve. This is performed by measuring an FSH (Follicle Stimulating Hormone) and Estradiol (E2) level on the second, third, or fourth day of the menstrual cycle.

In some cases a clomiphene challenge test is performed in women over the age of 38, a solitary ovary, or a prior poor response with fertility medications. This test is conducted by obtaining an estradiol and FSH level on the second, third or fourth day of the menstrual cycle and on day 10 or 11 after taking clomiphene citrate for five days.

The FSH and E2 results will determine if aggressive therapy is indicated and how successful we will be at attaining a pregnancy using a woman’s own eggs.

Anatomical causes

Uterine anomalies are found in 12 to 15 percent of woman with pregnancy losses. These abnormalities include fibroid tumors, derived from the muscle wall of the uterus, or polyps, overgrowth of the uterine lining, and may result in miscarriage.

Congenital uterine malformations such as a uterine septum are associated with a 60 percent pregnancy loss rate. Surgical correction by operative hysteroscopy has been reported to provide an 80 percent delivery rate.

Incompetent cervix is a condition in which the cervix opens prior to 20 weeks gestation without detectable contractions. In these women, the use of cervical cerclage, suture placed in the cervix, at the end of the first trimester may reduce the risk of a pregnancy loss.

Uterine Anomaly Percent Risk for a Pregnancy Loss
Septate 60 percent
Unicornuate 35 percent
Bicornuate 33 percent
Didelphic 29 percent
DES exposure 28 percent

Infectious causes

Cervical infections have been reported to be associated with pregnancy loss. These studies are based on anecdotal reports. Recently, studies have failed to support the causes and affect relationship.

The cultures normally performed are chlamydia trachomatis, gonorrhea, ureaplasma urealyticum, and mycoplasma hominis. There is no association with chlamydia or gonorrhea and based on poorly designed studies we treat ureaplasma and mycoplasma with vibramycin.

Thrombophilia

Abnormalities in blood clotting function resulting from chromosomally anomalies are also a potential cause of pregnancy losses. Factor V Leiden, Prothrombin gene mutation, Antithrombin III, plasminogen activator inhibitor-1 (PAI-1), and the methlytetrahydrofolate reductase mutation (MTHFR) are genetically determined factors that may increase the risk of miscarriage.

Thrombophilia is the tendency for increased blood clotting which may be treated with a baby aspirin, heparin anticoagulant injections, and/or increased amount of folic acid to have a good outcome.

Immunologic factor

Blood clots in the small placental blood vessels may be due to antibodies to phospholipids (antiphospholipid antibodies) which are located in the walls of blood vessels and on the platelets.

These antibodies attach to the wall of the blood vessel and attract clotting factors that can impede blood flow. The result is placental insufficiency and possible miscarriage. The antibodies tested for are lupus anticoagulant and anticardiolipin.

Treatment with aspirin and / or heparin anticoagulant injections are not guaranteed but can improve studies have reported success rates approaching 85 percent for most women.

The most controversial cause for pregnancy losses is allogenic immunity. We know that when an organ is transplanted the body tries to reject the foreign object. This is due to an intact immune system responding normally.

In pregnancy, the embryo is genetically different from the mother but yet over nine months is not rejected. To date we have no absolute answers. There are many theories and the results are conflict.

One theory proposes that the body makes blocking antibodies which hide pregnancy from the immune system. A defect in this process may result in a pregnancy loss.

Immunotherapy has been suggested as a possible treatment for this condition. Treatment with IVIG (intravenous immunoglobin) infusion or Embrel is quite expensive and is still considered experimental. Studies have not been conclusive and therefore any treatment performed should be in a research center under institutional approved guidelines.

Treatment options

If any of the above tests should suggest an underlying problem, then treatment is directed in one or more of several directions: genetic counseling, removal of polyps or fibroids, hormonal correction, anticoagulation.

If all of the tests are normal then the diagnosis is recurrent miscarriage of unknown cause. Repetitive losses are frustrating and can cause depression as well as family discord.

One often overlooked factor of tremendous importance is the psychological impact. Along with medical treatment, we encourage counseling to help with coping.