Recurrent Miscarriage: Causes, Evaluation, and Treatment

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Medscape General Medicine. 1998;1(3) 

In This Article

Endocrine Abnormalities

Luteal Phase Defect

There is a long history of attempts to implicate progesterone deficiency as a cause of spontaneous abortion. Endometrial biopsy and/or serum progesterone concentrations have been time-honored assessments of luteal phase ovarian function. When buildup of the endometrium during the preovulatory, or luteal, phase of the menstrual cycle lags by more than 2 days, a pathologic entity termed an inadequate corpus luteum is said by some to be present. The manifestation of this hormone-deficient state might be infertility or spontaneous abortion. It is impossible to know whether the bleeding associated with a threatened abortion occurs because the progesterone level is low or whether the hormone concentration is low because the pregnancy is not normal. Although it is not unreasonable to continue to make assessments of progesterone production or action, simple treatments with exogenous progesterone in the form of suppositories, injections, or micronized oral agents are unlikely to salvage many pregnancies.

The weight of evidence suggests that most abnormalities of luteal function originate in the follicular phase of the cycle. Thus, well-documented, persistently low levels of progesterone in the luteal phase of the cycle are likely to be the consequence of abnormal folliculogenesis. This condition is more likely to be improved by low doses of clomiphene citrate in the early follicular phase of the cycle than by postovulatory administration of progesterone. A search for subtle ovulatory dysfunction, such as that related to hyperprolactinemia, should be conducted, and treatment should be administered accordingly.

Abnormal corpus luteum function may be due to a number of pathogenic factors: (1) aberrant follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion early in the cycle; (2) a miscue in the timing (too early or too late) of the midcycle LH surge; or (3) insufficient estrogen production to allow normal progesterone action at the level of the endometrium. None of these conditions would be improved by postovulatory progesterone administration.[43]

LH Hypersecretion

Perhaps a more impressive endocrine-related explanation for recurrent spontaneous abortion is the prospective study by Regan and colleagues.[44] This study indicates that midfollicular (cycle day 8) LH hypersecretion (random serum LH of 10 mIU/mL or greater) is associated with a marked increase in the incidence of spontaneous abortion. Those findings, which have since been confirmed by others, suggest that hypersecretion of LH is associated with subfertility and early pregnancy failure. To date, however, prepregnancy treatments to suppress elevated serum concentrations of LH with GnRH agonists have not improved pregnancy outcome when compared with expectant management/supportive care during early pregnancy.[45]