Recurrent Spontaneous Pregnancy Loss

Recurrent spontaneous abortion (RSA) or miscarriage is a common, although emotionally devastating, clinical problem affecting approximately 1 in 500 reproductive age couples. RSA has been defined as three or more clinically detected pregnancy losses prior to the 20th gestational week. Currently, an evaluation for RSA is recommended following two consecutive pregnancy losses.

Human reproduction is known to be an inefficient process with at least 15%-20% of clinically recognizable pregnancies ending in miscarriage. Studies measuring pregnancy hormone levels prior to the missed menses suggest that upwards of 30%-50% of all conceptions end prior to the second trimester. Chromosomal or genetic abnormalities in the fetus are the most common cause of pregnancy losses accounting for up to 70% of first trimester losses. Once a couple has experienced one pregnancy loss, the chance for a second loss is 24%. After two miscarriages, the risk for a third loss increases to 30%, after a third miscarriage the risk for a fourth loss is 35%, and the risk is 40% to lose a pregnancy after the fourth miscarriage. However, couples who have had a prior live birth with subsequent spontaneous miscarriage have a risk for a repeated miscarriage of less than 30%, regardless of the number of previous losses.

Causes of Recurrent Spontaneous Pregnancy Loss

The causes for RSA can be determined in approximately half of the couples evaluated. Chromosomal, anatomic, hormonal, environmental, immunologic and infectious problems may account for up to 60% of RSA. For the remaining 40% of couples, the cause for their recurrent pregnancy loss remains unexplained.

Genetic Factors

Chromosomal abnormalities in the fetus account for 60%-70% of spontaneous pregnancy losses and approximately 25% of RSA. Advancing maternal age correlates with an increased incidence of genetic abnormalities in the fetus. In approximately 3%-5% of couples who have experienced repeated pregnancy loss, one of the prospective parents has an abnormal arrangement of their chromosomes. Even when an individual has chromosomal rearrangement, the couple still has at least a 50% chance of delivering a normal baby.

Anatomic Factors

Uterine abnormalities including fibroids, scar tissue within the uterus, certain cervical problems and congenital uterine malformations account for 10%-15% of RSA. The most common uterine anomaly associated with RSA is a septate uterus. A septum is a band of tissue inside the uterus which usually disappears before a female is born. If the uterine septum of a female does not regress by her birth and if later in her reproductive years an embryo implants on that septum, the blood supply will often be inadequate to sustain fetal growth which may result in a pregnancy loss. Removal of the septum results in a successful pregnancy outcome for at least 80% of couples experiencing RSA.

Hormonal Factors

Inadequate development of the lining of the uterus (endometrium) may lead to poor attachment (implantation) of the embryo resulting in pregnancy loss. Deficient ovarian hormone production (estrogen and progesterone) or inadequate response of the uterine lining to the hormones produced may result in a uterine environment unfavorable for maintaining a pregnancy.

Environmental Factors

Tobacco and alcohol use by pregnant women have been associated with increased spontaneous abortion rates. Women who smoke more than one-half pack of cigarettes daily have a 1.7 times greater risk for miscarriage compared to non smokers. Consumption of 1 once of alcohol per week doubles the risk of pregnancy loss. Caffeine use has also been associated in some preliminary studies with an increased risk of miscarriage. The role of environmental pollutants and occupational toxins in RSA is uncertain although high levels of carbon tetrachloride, benzene and ionizing radiation have been associated with pregnancy loss.

Immunologic Factors

Although many questions exist and theories abound regarding the role of the immune system in causing RSA, only 3%-5% of women experiencing pregnancy losses during the first trimester will be found to have an immunologic cause. The presence of certain antibodies (antiphospholipid and anticardiolipin antibodies) in women’s blood has been associated with repeated pregnancy loss. The mechanism for spontaneous abortion is believed to be due to thrombosis or blood clot formation between the placenta and uterine surface resulting in insufficient blood flow to the fetus. The possibility of maternal-paternal incompatibility or rejection has not been supported by research studies.

Infectious Factors

The role of infection causing RSA remains unproven. Although a correlation between a bacterial vaginal infection caused by mycoplasma and pregnancy loss was reported previously, follow up studies have failed to confirm this earlier finding.

Evaluation And Treatment

Couples experiencing more than two consecutive pregnancy losses should seek an evaluation with a physician having interest and specialized training in this area of reproductive endocrinology. Following a complete examination, several tests may be recommended.

Blood testing for chromosomal analysis (karyotype) should be performed on both partners. Although treatments are not available to correct a chromosomal rearrangement, genetic counseling can better determine the couple’s risk for further pregnancy losses. A chromosome test on pre-embryos (fertilized eggs) derived from In Vitro Fertilization called preimplantation genetic diagnosis (PGD) may allow for selection of chromosomally normal pre-embryos to be implanted into the woman’s uterus. Chromosomal analysis of the tissue from the miscarriage should be obtained following a second pregnancy loss to further clarify a possible cause of the failed pregnancy.

Measurement of thyroid hormone and prolactin levels in the blood may detect a hormonal cause for pregnancy loss. Progesterone is a key hormone involved in implantation and the maintenance of the early pregnancy. An inappropriate progesterone effect on the uterine/endometrial lining will result in a luteal phase defect (LPD). LPD can be diagnosed by obtaining a sample of the endometrial lining 1-3 days prior to the anticipated onset of menses or 11-13 days after a luteinizing surge (LH surge - indicating ovulation). If a LPD is confirmed, treatment options include progesterone supplementation which is started 3 days after ovulation and continued until the end of the eighth week of pregnancy, or clomiphene citrate which is used during the early part of the cycle prior to ovulation.

eBlood tests are available to detect the presence of antibodies associated with pregnancy loss. The presence of anticardiolipin antibodies and antiphospholipid antibodies determined by abnormalities in blood assays have been associated with blood clotting disorders and RSA. Several treatment regimens have been utilized for women diagnosed with “antiphospholipid syndrome”. Low dose aspirin (approximately 80 mg daily) and heparin therapy have been utilized with excellent success rates.

Prognosis

Prognosis for successful pregnancy outcome in couples experiencing RSA is determined by the specific cause. Correction of a uterine abnormality results in an 80%-85% successful pregnancy rate. Similarly, up to 90% of women found to have a luteal phase defect will have a healthy child after initiating hormone treatment. Live birth rates of 75% have been reported for women with antiphospholipid syndrome receiving aspirin and heparin. When a cause for RSA can not be determined, close clinical monitoring and counseling are critical. Successful pregnancy outcomes as high as 85% have been reported in women with a history of RSA who receive frequent feedback and emotional support during the first trimester of pregnancy. RSA is an emotionally devastating disorder. Evaluation and determination of a treatment course can significantly enhance a couple’s chances of having a successful pregnancy outcome. We would be happy to discuss these issues related to RSA with you.