Review
Paul C. Lin, M.D., Seattle Reproductive Medicine

In this observational study, the authors assessed a unique high-frequency protocol of misoprostol administration consisting of 400-µg administered intravaginally every four hours for a maximum of three days. Pregnancy failure was diagnosed in the 108 women based on the following criteria:

1. presence of an intrauterine gestational sac containing an embryonic pole of 5-14 mm in length, without cardiac activity on transvaginal ultrasonography 

2. presence of an irregular intrauterine gestational sac with a mean sac diameter of >17 mm, but absence of an embryonic pole; 

3. presence of a yolk sac, but abnormally increasing circulating human chorionic gonadotropin concentrations (<50 percent increase over a 48-hour period). 

These criteria, while subject to debate, are considered widely to be reliable in confirming the diagnosis of pregnancy failure. Stricter criteria of pregnancy failure, e.g., a fetal pole >1 cm, a gestational sac > 2 cm and an hCG rise of < 50 percent over two consecutive two-day periods, might have decreased the possibility of treating normal pregnancies with misoprostol. Nevertheless, for the purposes of this study, these inclusion criteria were appropriate clinically. Successful treatment was defined as an hCG level < 50 IU/L and an endometrial stripe < 15 mm at < 7 days after treatment, whichever occurred first. Failed treatment was defined as no clinical evidence of miscarriage after 7 days. Sixty-eight percent of patients were treated successfully after 24 hours, 83 percent were successfully treated after 48 hours and 90 percent after 72 hours. Ten percent required a surgical intervention. Side effects affected 44 percent of subjects and were minimal, with 24 percent having nausea, 15 percent experiencing vomiting, 7 percent reporting headache and 4 percent with diarrhea. Eighty-two percent of subjects were “very satisfied” with the clinical results. No control group of expectant management was available to assess the efficacy of the misoprostol protocol in a truly scientific manner, but the numbers are impressive and warrant further investigation. A randomized controlled study should be performed before this protocol is recommended for widespread clinical application.

Comments 
Daniel B. Williams, M.D., Cincinnati, OH

This article demonstrates another non-surgical option in addition to expectant management to manage these patients. The success rates achieved with this particular regimen of medical treatment are very encouraging. Controlled trials compared to expectant management should be performed to validate these findings. 

You may also want to visit Highlights from Fertility and Sterility taken from the ASRM medical journal and ASRM Journal Highlights to read summaries of current articles from other medical journals in the field of reproductive medicine. 

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