Recurrent Pregnancy Loss


A miscarriage is an involuntary loss of a pregnancy prior to 20 weeks gestation. It is estimated that 15% of all clinically recognized pregnancies end in miscarriage. This is distinguished from recurrent pregnancy loss (RPL) which is defined as two or more miscarriages. Physicians differ in their judgment to begin a full work up after two miscarriages.

Certain factors which favor an earlier work up are:

  1. History of no prior live birth
  2. Fetal cardiac activity was seen sonographically prior to the loss
  3. Woman is 35 years of age or older
  4. Long time to conception between miscarriages

Recurrent pregnancy loss can be further divided into early (12 weeks or less) and late (between 12 weeks and 20 weeks).

Late losses are more likely to be the result of a problem with the mother. Examples include an abnormal shape of the uterus, uterine fibroids or cervical incompetence (weakness of the cervix).

The work up for Recurrent Pregnancy Loss is divided into the following categories:

Genetic causes:

The chromosomes of each parent are analyzed with a test called a karyotype. A translocation is when part of one chromosome has broken off and attached to another chromosome. A parent that has a balanced translocation has not lost any of their genetic material and is likely normal. When that parent makes a gamete (egg or sperm) however, it can lead to an unbalanced embryo and thus increase the risk for a miscarriage. Those patients are referred to a genetics counselor who can provide them with a detailed analysis of their future risk for miscarriage. In vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD) can be used to screen embryos for the translocation or other specific chromosome defects. As a woman ages, her risk for miscarriage will increase especially after the age of 35. More mistakes are made in the formation of her mature egg which leads to an unbalanced (or aneuploid) embryo. 

Anatomic causes:

When a women’s uterine cavity is distorted, her chance for miscarriage is increased. She can be born with an abnormally shaped uterus (congenital cause). Examples include a double uterus, a uterine septum or a uterus in which only one half developed. Other problems can develop over time such as the presence of uterine fibroids. The location of the fibroids and their size are the most important factors in determining their contribution to miscarriages. Scar tissue may develop within the uterine cavity (intrauterine adhesions) as a result of multiple medical procedures (i.e. D&Cs or terminations of pregnancy) or surgeries (i.e. C-sections, myomectomies) or from infections (i.e. tuberculosis). Diagnostic evaluation for these conditions includes transvaginal sonogram and office hysteroscopy or hysterosalpingogram (HSG). Many of these anatomic causes can be treated surgically.

Endocrine causes:

An evaluation of certain endocrine labs is warranted in the setting of RPL. Thyroid disease, especially hypothyroidism (an underactive thyroid gland), is known to increase the risk for miscarriage. A TSH (thyroid stimulating hormone) level is the best initial test. Thyroid hormone replacement is easily accomplished. A luteal phase defect is thought to occur when a woman has ovulated but is producing inadequate amounts of progesterone which leads to a uterine lining that is immature for a potential embryo. Sometimes endometrial biopsies are used to document the maturation of the uterine lining. A less invasive approach is to use ovulation induction medications to promote higher progesterone production from the ovary. Vaginal progesterone supplements are also an option. Elevated prolactin levels (hyperprolactinemia) may also contribute to an ovulatory dysfunction with subsequent poor progesterone production. This condition may be heralded by inappropriate milk production from the breasts, increased headaches or visual changes. Depending on the level of the prolactin, brain imaging may be needed to search for a brain tumor (prolactinoma). Uncontrolled sugar levels in diabetic women are known to increase their miscarriage risk. Long-term sugar control can be tested with the Hemoglobin A1c test. 

Immunologic causes:

Even though a fetus is not genetically identical to its mother, most pregnancies are not harmed by a mother’s immune system response to the fetus. There are shifts which occur in the immune system of the mother to accommodate for this new genetic creation. There are pathologic immune disorders which upset this balance and endanger the pregnancy. An autoimmune disorder occurs when the body’s immune response is directed against the patient herself. Autoimmune disorders that are associated with recurrent pregnancy loss include systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). For women with SLE it is important that they work with their rheumatologist prior to conception to be certain the disease is well controlled. APS has both clinical and laboratory hallmarks. The laboratory testing includes lupus anticoagulant (LAC) and anti-cardiolipin antibodies (ACA). Treatment for APS involves a combination of low-dose aspirin (81mg per day) and heparin (either unfractionated or low-molecular-weight) injections. Thrombophilias (tendencies towards clotting) may also be inherited. The most common of these are the Factor V Leiden mutations, a prothrombin gene mutation and mutations in a gene involved in the metabolism of folic acid. Therapy will depend on the specific disorder found. 


Despite all known testing, about 50% of couples will remain without a specific diagnosis. This can be a frustrating situation for the couple. Psychological support (counselors, support groups, church groups) can help the couple through this difficult time. The couple should be encouraged by the fact that most women with this diagnosis will eventually have a successful term pregnancy.

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