Infertility Education - Recurrent Pregnancy Loss

Recurrent pregnancy loss is a disease distinct from infertility, defined by two or more failed pregnancies. When the cause is unknown, each pregnancy loss merits careful review to determine whether specific evaluation may be appropriate. After three or more losses, a thorough evaluation is warranted. Although approximately 25% of all recognized pregnancies result in miscarriage, less than 5% of women will experience two consecutive miscarriages, and only 1% experience three or more. Couples who experience recurrent pregnancy loss may benefit from a medical evaluation and psychological support.

Causes of Recurrent Miscarriage

Genetic/Chromosomal Causes

A chromosome analysis performed from the parents’ blood identifies an inherited genetic cause in less than 5% of couples. Translocation (when part of one chromosome is attached to another chromosome) is the most common inherited chromosome abnormality. Although a parent who carries a translocation is frequently normal, their embryo may receive too much or too little genetic material. When this occurs, a miscarriage usually follows. Couples with translocations or other specific chromosome defects may benefit from pre-implantation genetic diagnosis in conjunction with in vitro fertilization.

In contrast to the uncommon finding of an inherited genetic cause, many early miscarriages are due to the random (by chance) occurrence of a chromosomal abnormality in the embryo. In fact, 60% or more of early miscarriages may be caused by a random chromosomal abnormality, usually a missing or duplicated chromosome.

Age

The chance of a miscarriage increases as a woman ages. After age 40, more than one-third of all pregnancies end in miscarriage. Most of these embryos have an abnormal number of chromosomes.

Hormonal Abnormalities

Progesterone, a hormone produced by the ovary after ovulation, is necessary for a healthy pregnancy. Persistently low progesterone levels after ovulation, often called ‘luteal phase deficiency’, may cause repeated miscarriages. Treatments include ovulation induction, progesterone supplementation or injections of human chorionic gonadotropin (hCG). There is some evidence to support the effectiveness of these treatments, however their overall benefits are difficult to quantify.Thyroid dysfunction and/or the presence of thyroid antibodies have been associated with recurrent pregnancy loss. Abnormal production of the hormone prolactin can also disrupt normal ovulation and has been linked with miscarriage.

Metabolic Abnormalities

Poorly controlled diabetes increases the risk of miscarriage. Women with diabetes improve pregnancy outcomes if blood sugars are controlled before conception. Women who have insulin resistance, such as obese women and many who have polycystic ovarian syndrome (PCOS), also have higher rates of miscarriage. There is still not enough evidence to know if medications that improve insulin sensitivity lower miscarriage risks in women with PCOS.

Uterine Abnormalities

Distortion of the uterine cavity may be found in approximately 10% to 15% of women with recurrent pregnancy losses. Diagnostic screening tests include hysterosalpingogram, sonohysterography, ultrasound, or hysteroscopy. Congenital uterine abnormalities include a double uterus, uterine septum, and a uterus in which only one side has formed. Asherman’s syndrome (scar tissue in the uterine cavity), uterine fibroids, and uterine polyps are abnormalities that may also cause recurrent miscarriages. Often these conditions can be surgically corrected.

Antiphospholipid Syndrome

Blood tests for anticardiolipin antibodies, lupus anticoagulant, and B2-glycoprotein 1 antibodies may identify women with antiphospholipid syndrome, a cause for 3% to 15% of recurrent miscarriages. In women who have high levels of antiphospholipid antibodies, pregnancy outcomes can be improved by the use of aspirin and heparin.

Thrombophilias

Inherited disorders that raise a woman's risk of serious blood clots (thrombosis) may also increase the risk of miscarriage as well as fetal death in the second half of pregnancy. While there is no clear consensus that testing or treatment for these disorders can significantly reduce miscarriages in the first trimester, some evidence demonstrates improvement in outcomes using low-dose aspirin or heparin in patients with specific thrombotic risks or unexplained recurrent pregnancy loss.

Male factor

Some evidence suggests that abnormal integrity (intactness) of sperm DNA may affect embryo development and possibly increase miscarriage risk. However, these data are still very preliminary, and it is not known how often sperm defects contribute to recurrent miscarriage. Currently, testing for sperm DNA integrity is not recommended, as there is no evidence of benefit following treatment in men who had abnormal testing.

Unexplained

No explanation is found in 50% to 75% of couples with recurrent pregnancy losses.

Tests and Treatments with No Benefit

Tests with no proven benefit for recurrent miscarriage include cultures for bacteria or viruses, tests for insulin resistance, antinuclear antibodies, maternal antipaternal antibodies, antibodies to infectious agents, and embryotoxic factors.

Treatments with no proven benefit include leukocyte (white blood cell) immunization and intravenous immunoglobulin (IVIG) therapy.

Conclusion

A couple may be comforted to know that the next pregnancy is successful in 60% to 70% of those with unexplained recurrent pregnancy losses. A healthy lifestyle and folic acid supplementation is recommended before attempting another pregnancy. Smoking cessation, reduced alcohol and caffeine consumption, moderate exercise, and weight control may all be of benefit.
Counseling may provide comfort and help cope with the grief, anger, isolation, fear, and helplessness that many individuals experience after repeated miscarriages.

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