Diagnosis and Treatment of Recurrent Pregnancy Loss

DIAGNOSIS
The basic diagnostic testing for recurrent pregnancy loss includes:

Evaluation of parental chromosomes ("karyotype"). This test is performed by analyzing a blood sample obtained from each parent. Please see Genetic Causes of RPL
Cervical cultures, which are performed on the woman to rule out the presence of an infection. Please see Infectious Causes of RPL
Hysterosalpingogram (HSG), which is an X Ray in which dye is injected through the vagina into the uterus to evaluate the shape and contour of the uterine cavity. Please see Anatomic Causes of RPL
A blood test for lupus anticoagulant (aPTTT as well as a confirmatory test) and a blood test for anticardiolipin antibodies. Please see Hematologic or Immunologic Causes of RPL

Other tests, such as testing for insulin resistance, lupus, anti-thyroid antibodies, or endo-toxins have been determined by the American Society for Reproductive Medicine to be of no proven benefit.
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TREATMENT
The treatment of anatomic defects consists of surgical correction. In the case of uterine fibroids, endometrial polyps, intrauterine adhesions, or a uterine septum, this can usually be performed on an outpatient basis by passing a telescope through the vagina into the uterus (hysteroscopy). As discussed above, the unicornuate uterus and bicornuate uterus are not corrected, as studies show that pregnancy rates do not improve following surgical correction.
Treatment of genetic abnormalities may include the use of either donor oocytes or donor sperm, in order to replace the gametes of the affected parent when one of the parents has a genetic abnormality that would likely be passed on to the child.

Infections are treated with the appropriate antibiotics.
The treatment for hematologic causes usually includes baby aspirin. For those cases that are more severe, additional anticoagulation with heparin or Lovenox may be recommended.

Hormonal disorders are treated with progesterone, bromocriptine, or thyroid hormone to correct the actual hormonal deficiency.

Treatment for the largest category of patients, those with an unknown cause for their miscarriages, consists of empiric therapy with either in vitro fertilization with pre-implantation genetic screening (PGS) of the embryos, or the use of donor gametes. PGS is a technique in which a single cell can be removed from an embryo and then tested genetically to evaluate its chromosomes. Until recently, the technology to test all 24 chromosomes (numbers 1-22 plus X and Y) has not been clinically available. Therefore our laboratories tested only the 9 chromosomes that are most commonly abnormal. Thanks to significant advances in technology, we are now able to test not only all embryonic chromosomes, but we can also frequently determine, when an embryo is chromosomally abnormal, whether the abnormality came from the egg or from the sperm. The accuracy of this new technology exceeds 95%, allowing our physicians and embryologists to select the embryo(s) for transfer that are thought to be chromosomally normal, significantly lessening the risk of a chromosomally abnormal pregnancy that would more than likely miscarry.

Lifestyle alterations may also benefit many couples with recurrent pregnancy loss. Without question, all couples attempting to conceive should completely eliminate the use of nicotine – regardless of the source. All women should take folic acid supplementation. They should also reduce their caffeine and alcohol intake, although the exact levels of caffeine and alcohol that are appropriate remain somewhat controversial. Moderate exercise (less than four hours of cardiovascular exercise per week) is also recommended, as are weight and diet control.
Treatments with no proven benefit include the use of Viagra©, immunization with paternal leukocytes, and/or treatment with intravenous immunoglobulin.
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PROGNOSIS
The following table illustrates the likelihood of a successful pregnancy based on maternal age and the number of prior pregnancy losses.

	NUMBER	OF PRIOR	LOSSES
PATIENT AGE	2	3	4	5
20	92	90	88	85
25	89	86	82	79
30	84	87	76	71
35	77	73	68	62
40	69	64	58	52
45	60	54	48	42

Brigham S, Conlon C, Farquharson R., Human Reproduction 1999; 14:2868
As shown in this table, the likelihood of a successful pregnancy remains very high, even when a patient has already had up to five prior miscarriages. As one can see, a 30-year-old woman who has had five previous miscarriages still has a 71% likelihood that her next pregnancy will be healthy.

In summary, there are many causes of recurrent pregnancy loss. The evaluation of this condition frequently leads to a definitive diagnosis, and effective treatments are available. Even patients in whom no diagnosis can be determined have an overwhelming likelihood of eventually having a successful pregnancy.