Spontaneous Abortion, Recurrent Miscarriage

Recurrent miscarriage is perhaps the most difficult medical event that some couples must deal with. It is especially stressful and traumatic, if the couple conceived using advanced reproductive technologies (IVF). There is a profound sense of loss coupled with the emotional and financial stresses that often accompany these therapies.

Studies reveal that the risk of miscarriage is approximately 15-25% for all pregnancies. Unfortunately, if a woman has one miscarriage her chance of another increases with each successive pregnancy. If a patient has had two miscarriages, the chance for a third increases to 40%.

Pregnancy loss of fertilized eggs, prior to missed menses, may account for up to 40% of pregnancy loss in natural or IVF cycles. It is therefore important to understand the causes of miscarriage and the treatments for recurrent pregnancy loss and IVF failure.

Causes of Recurrent Miscarriage

Miscarriages can be caused by chromosomal abnormalities, metabolic problems like diabetes, immunologic factors, hormonal problems, and diseases of the uterus. A thorough workup is needed to rule out all of the potential causes of miscarriage.

Genetic

Chromosomal, or genetic, abnormalities are a major cause of miscarriages. DNA, contained on the chromosomes, provides the blueprint for all body characteristics and functions. Aneuploidy is a condition where there are "more or less" than the normal diploid (pair) number of chromosomes.

A common aneuploidy is Down's syndrome, also known as Trisomy 21, where there are three copies of chromosome 21. If these children survive to birth, there will be some degree of mental retardation. Monosomy is the lack of "one of a pair" of chromosomes and is usually fatal. The incidence of genetic abnormalities and miscarriage increases with female age.

Another type of genetic abnormality is known as a translocation. This is where the genetic material of one chromosome "switches places" with genetic material on another chromosome. The translocation is contained in one of the partner’s genome (genetic makeup).

Assisted reproductive technologies offer a means to screen for many genetic problems and may be recommended for certain patients with recurrent pregnancy loss. This includes older patients who have an increased incidence of genetically abnormal eggs.

The Washington Center for Reproductive Medicine has a very successful preimplantation genetic diagnosis program (PGD). In a PGD cycle, embryos are produced by in vitro fertilization and then examined for specific chromosome abnormalities. Embryos identified as carrying abnormalities are not transferred back to the uterus.

Immune System

Antiphospholipid antibody production can also increase the risk of miscarriage. Phospholipid molecules are normal and required elements of all cell membranes. Dr. Kustin can screen for many of these disorders using the latest tests and technologies.

Metabolic Disorders

Metabolic disorders, such as diabetes or thyroid disorders, account for approximately 15% of miscarriages. These conditions can be diagnosed with the appropriate laboratory tests and treated with fertility medications.

Another potential endocrine "disorder" is the "luteal phase defect". This is when the corpus luteum (initially) and the placenta (later) do not produce enough progesterone. Progesterone is essential to support the growth and development of the endometrium (lining of the uterus), which supplies the fetus with nutrients. A luteal phase defect can often be treated with the administration of progesterone by injection or other means.

Reproductive Tract Defects

Uterine factors account for approximately 10% of miscarriages. The lining of the uterus must be able to accept and support the developing embryo. It must be free of obstructions, such as fibroid tumors, polyps, adhesions (Asherman’s Syndrome), or scar tissue, and be normally developed from birth. Many of these conditions can be corrected with surgery.

Hormonal Issues

The lining of the uterus and its blood supply are hormonally mediated; therefore, subtle hormonal aberrations in estrogen, progesterone, and thyroid hormone may be responsible for the development of a milieu that is not compatible with the development of an ongoing pregnancy.

Diabetes and pre-diabetes, as well as other illnesses, can contribute to pregnancy loss.

Immunologic

Immunologic mechanisms may play a very important role in failed IVF attempts or recurrent pregnancy loss.  This is a new and emerging science with several important facets.

1. Cytokines- may cause inflammation that hinders implantation.
2. Natural killer cells are circulating immune cells that may also hinder implantation.
3. Antiphospholipid and anticardiolipin antibodies may impair the blood supply to a pregnancy and may be associated with failed IVF or recurrent pregnancy loss.
4. Genetic causes of altered blood clotting may inhibit the establishment, or continuation, of a pregnancy because the fetus is malnourished. These include Leiden Factor, and methylenetetrahydrafolate reductase ( MTHFR), which also includes abnormalities in folic acid metabolism, the precursor to DNA.

Immunological testing includes the following: 

1. Antiphospholipid antibody testing
2. Antinuclear antibody
3. AntiDNA antibody
4. Natural killer cell assay
5. Other testing:
   a) Lupus anticoagulant
   b) Factor 5 Von Leiden
   c) Hyperhomocysteinemia (MTHFR)
   

DNA abnormalities in the sperm may cause the conception of an abnormal embryo that may result in a failed IVF or pregnancy loss.  See our pages male infertility.                        

Diagnosis

There are many tests available for couples with recurrent pregnancy loss. First, a thorough medical history should be taken, including a gynecological examination.  Infections such as Mycoplasma, and other bacterial infections, should be excluded. 

a) The uterine cavity should be evaluated by a hysterosonogram, where saline is instilled into the uterine cavity and ultrasound evaluation performed.  A hysterosalpingogram, where dye is injected into the uterus and x-rays are obtained, may be indicated.

In some cases, the uterine cavity is evaluated by hysteroscopy with the insertion of a telescope, under general anesthesia.  Adhesions, fibroids, and polyps can be removed during this procedure.

The lining of the uterus can be sampled via an endometrial biopsy and its receptivity to an embryo correlated with blood hormonal tests, including tests of ovarian reserve performed on day 3 of the cycle. These hormones include FSH, estradiol, and inhibin.  Women whose ovaries show signs of diminished ovarian reserve are most more likely to produce an embryo that has chromosomal abnormalities and hence predispose the pregnancy to miscarriage.

b) Chromosomal testing may be carried out on the partners, the sperm or pregnancy tissue that may be available after miscarriage, or curettage of the uterine cavity.

Conclusions

Failed IVF and recurrent pregnancy loss are emotionally devastating but may not necessarily signify the loss of a couple's dream to achieve parenthood.  Over the years, we have successfully treated many disappointed couples who had failed treatments at other centers. We offer a comprehensive evaluation followed by straightforward analysis of the issues and options. Once the underlying problems are identified they are treated appropriately.

Treatment options include:

• Surgery to correct uterine factors
• Hormonal treatments
• Anticoagulant therapy with aspirin and or heparin to increase the blood supply to the fetus
• Correction of folic acid issues with vitamins
• Infusion of IVIG to treat elevated circulation natural killer cells, or other antibodies directed against the embryo