Aubény E, Peyron R, Turpin C L, Renault M, Targosz V, Silvestre L, Ulmann A, Baulieu E E
Centre d'Orthogénie de l'Hôpital Broussais, Paris, France.
Int J Fertil Menopausal Stud. 1995;40 Suppl 2:85-91.
The efficacy and tolerability of mifepristone in combination with misoprostol for termination of early pregnancy (up to 49 days of amenorrhea) are established. We studied the efficacy and tolerability of this combination therapy for termination of pregnancy in women up to 63 days of amenorrhea. We also examined the effect of an additional dose of misoprostol in cases of nonexpulsion within 3 hours after the first dose. The multicenter trial included 1,108 women, mean age 27.9 +/- 6.2 years. The mean duration of pregnancy was 51.7 +/- 9.2 days. On day 1, the women received an oral dose of mifepristone, 600 mg. On day 3, they received an oral dose of misoprostol, 400 micrograms, and were monitored for up to 3 hours. If they did not expel the conceptus within 3 hours, an additional dose of 200 micrograms of misoprostol was given and they were monitored for 2 more hours. From days 10 to 18, the women were followed up with clinical examination, human chorionic gonadotropin measurement, or ultrasound examination. Overall, the procedure was successful in 92.9% of women. Efficacy decreased with the duration of pregnancy, especially after 56 days of amenorrhea. Up to 42 days of amenorrhea, the success rate was 97.6%; between days 42 and 49, 94.8%; between days 50 and 56, 93.4%; between days 57 and 63, 86.8%; and after day 63, 83.3%. The most common side effects were moderate uterine cramps (80.5%) and gastrointestinal (GI) symptoms (34.9%), especially vomiting (18.3%) and diarrhea (10.5%). GI symptoms were generally mild. A second dose of misoprostol was given to 61.6% of the women. In a subgroup analysis, we assessed the efficacy of 600 mg of mifepristone plus 400 or 600 micrograms of misoprostol (one or two doses) in women with up to 49 days of amenorrhea and compared it with the efficacy in women who received mifepristone plus only 400 micrograms (one dose) of misoprostol in a previous study. The overall rate of success (termination of pregnancy) was 95.5% in the current study compared with 95.4% in the previous study. The additional dose of misoprostol did not significantly increase the overall rate of success, but did increase the rate of termination within the monitoring period (69.7% versus 64.9% (and within 72 hours after administration of mifepristone (92.7% versus 90.4%). We have confirmed that the combination of mifepristone and misoprostol was effective, safe, and well tolerated for termination of pregnancies at 49 or fewer days of amenorrhea. The efficacy decreased slightly between 49 and 56 days, and then decreased significantly between 56 and 63 days. For maximal safety and tolerability, we recommend this method only for women with 49 or fewer days of amenorrhea. A second dose of misoprostol did not improve overall efficacy, but did increase the rate of early termination.
米非司酮与米索前列醇联合用于终止早期妊娠（闭经49天内）的有效性和耐受性已得到证实。我们研究了这种联合疗法用于终止闭经63天内女性妊娠的有效性和耐受性。我们还研究了在首剂后3小时内未排出妊娠物的情况下额外一剂米索前列醇的效果。这项多中心试验纳入了1108名女性，平均年龄27.9±6.2岁。平均妊娠时长为51.7±9.2天。第1天，女性口服600毫克米非司酮。第3天，她们口服400微克米索前列醇，并接受长达3小时的监测。如果她们在3小时内未排出妊娠物，则给予额外一剂200微克米索前列醇，并再监测2小时。在第10至18天，对女性进行临床检查、检测人绒毛膜促性腺激素或超声检查进行随访。总体而言，该程序在92.9%的女性中成功。有效性随妊娠时长而降低，尤其是在闭经56天后。闭经42天内，成功率为97.6%；42至49天之间，为94.8%；50至56天之间，为93.4%；57至63天之间，为86.8%；63天后，为83.3%。最常见的副作用是中度子宫痉挛（80.5%）和胃肠道（GI）症状（34.9%），尤其是呕吐（18.3%）和腹泻（10.5%）。胃肠道症状一般较轻。61.6%的女性给予了第二剂米索前列醇。在亚组分析中，我们评估了600毫克米非司酮加400或600微克米索前列醇（一剂或两剂）用于闭经49天内女性的有效性，并将其与先前一项研究中接受米非司酮加仅400微克（一剂）米索前列醇的女性的有效性进行比较。本研究中总体成功（终止妊娠）率为95.5%，而先前研究中为95.4%。额外一剂米索前列醇并未显著提高总体成功率，但确实提高了监测期内的终止率（69.7%对64.9%）以及米非司酮给药后72小时内的终止率（92.7%对90.4%）。我们已证实，米非司酮与米索前列醇联合用于终止闭经49天或更短时间的妊娠是有效、安全且耐受性良好的。有效性在49至56天之间略有下降，然后在56至63天之间显著下降。为实现最大安全性和耐受性，我们建议仅将此方法用于闭经49天或更短时间的女性。第二剂米索前列醇并未提高总体有效性，但确实提高了早期终止率。
