联合应用dI-15-甲基PGF_(2α)与RU486抗早孕的临床研究

本文报道80例早孕≤49天,用不同剂量dl-15-甲基PGF_(2α)(以下简称PG)与不同剂量RU486配伍,分成三组,进行抗早孕比较,结果三组成功率达100%,完全流产率94.87%。三组完全流产率无显著差异。组ⅢRU486 25mg,每日2次,2天总量100mg,第三天加PG 0.5mg 肌注,完全流产率95%,大大减少PG 用量,明显减轻了副反应,为三组首选抗早孕配伍。为目前国内外报道抗早孕的RU486最小剂量。     

联合应用dl—15—甲基PGF2α与RU486抗早孕的临床研究

本文报道80例早孕≤49天，用不同剂量dl-15-甲基PGF2α（以下简称PG）与不同剂量RU486配伍，分成三组，进行抗早孕比较，结果三组成功率达100％，完全流产总量94．87％。三级流产率无显著差异。组ⅢRU48625mg，每日2次，2天总量100mg，第三天加PG0．5mg肌注，完全流产率95％，大大减少PG用量，明显减轻了副反应，为三组首选抗早孕配伍。为目前国内外报道抗早孕的TU486最小剂量。     

三种不同剂量RU486合并ONO802终止早孕的临床研究

本研究比较了不同剂量RU486合并ONO802用于终止早孕(停经天数≤56d)的临床有效性及其副反应。从1989年5月至1991年1月,我们共接纳了99例对象(分三组,每组33例)。各组对象分别服用200mg、400mg 或600mg 的RU486,在第三天早晨阴道给药ONO802 1mg。三组治疗结果相似,其完全流产率分别为94%、100%和100%,无明显统计学差异。在200mg 组有2例(6%)为不全流产并由于流血较多施行了刮宫术,其中1例输血200ml。三纽均来继续妊娠。除轻微腹痛外,三组均无明显副反应。ONO802阴道给药后,各组胚囊排出时间为3.5h、3.2h 和3.2h,其间亦无统计学差异。但终止妊娠后阴道流血时间200mg组明显短于400mg 组和600mg 组,分别为11.5d、14.0d 和16.1d,有显著差异(P<0.01)。本文提示RU486合并ONO802用于终止早孕时,200mg 的RU486就可能足够了。     

孕妇及非孕妇口服不同剂量RU 486后的药物动力学研究

非孕妇(n=9)及早孕妇(n=36)口服不同剂量RU 486后,以HPLC测定服药后RU486及其代谢产物RU 42633、RU 42848和RU 42698的血浆浓度,结果显示不论妊娠与否,药物的吸收及代谢都很迅速;服药后20 min 即可测得血浆中的RU 486及其代谢产物;母药达峰时间Tmax 均为1～2h,其峰浓度Cmax 对数与剂量对数之间呈显著正相关。服相同剂量后,非孕组药-时曲线水平及药时曲线下面积AUC 大于早孕组,但两组间并无显著性差异(P>0.05)。无论非孕组及早孕组,口服25 mg、100 mg 和200 mg后,RU 486代谢符合二室开放模型,口服400 mg 和600mg 后则呈非线性动力学过程。     

药流与负压吸宫法的效果和可接受性研究

研究的目的:比较RU486/Cytotec药物和负压吸宫术两种流产方法的效果,以及医学的和个人的可接受性.对象为通过咨询,介绍两种流产方法后,让对象自愿选择而组成.年龄在20～34岁.药物组100例,闭经35～42天,第1天口服RU486 600mg,第3天服Cytotec(PGE1)0.4mg,第17、43天回医院随访.手术组100例,闭经≤56天,负压吸宫术后第14、43天回医院随访.结果:完全流产率药物组为89%,手术组为100%.对象选择这两种流产方法的主要原因:药物组94%的人认为痛苦少,手术组的55%认为手术快、节省时间,而且手术同时可取出或放置宫内节育器(占45%).结论:RU486/Cytotec药物流产和负压吸宫术在各自适合的人群中都具有高度的可接受性.两种方法各具优缺点,不能相互取代,二者相辅相成,取长补短,将使终止妊娠的措施更为安全     

正常早孕与流产患者蜕膜局部PRL、P、E_2水平及其受体mRNA表达水平的比较

目的:比较正常组与流产组蜕膜PRL、P、E_2及其受体mRNA水平的差异,探讨其在早孕维持中的作用。方法:收集18例正常早孕人流与12例保胎失败刮宫患者的蜕膜组织,应用放免法测定蜕膜匀浆PRL、P、E_2水平,并行RT-PCR方法检测了相应激素受体(PRLR、PR、ER)mRNA表达的差异。结果:正常早孕组蜕膜匀浆PRL、P水平显著高于流产组(P<0.05),PRLR、PRmRNA表达正常早孕组亦显著高于流产组(P<0.05和0.01)。结论:蜕膜局部正常水平的PRL、P及其受体mRNA的正常表达对妊娠的维持起着重要的作用。     

RU486抗早孕蜕膜血管形态计量学研究

目的:研究RU486抗早孕子宫出血时间长的机理。方法:应用MIPS图象分析系统,测定RU486药物流产(药流)者的蜕膜及负压吸引人工流产者的蜕膜血管总截面积及血管密度。结果:RU486药物流产后蜕膜血管总截面积及血管密度均明显小于人工流产组者,差异有显著性(P<0.05)。结论:药流者子宫出血时间长可能与RU486、米索前列醇二者合用影响人蜕膜血供有关。     

米非司酮影响早孕滋养细胞的信号传导和凋亡的机制研究

目的　探讨米非司酮 (RU486 )在早孕滋养细胞信号传导及其凋亡中的影响。方法　 2 19例服用RU486早孕药物流产者 ,对其有效组 30例 ,失败组 2 3例 ,人流组对照 16例 ,以免疫组化法分别标记孕激素受体(PR)、雌激素受体 (ER)、表皮生长因子受体 (EGFR)、酪氨酸蛋白激酶C(αPKC)、分裂激活蛋白激酶 (MEK - 1)、细胞转化分裂介质 (raf- 1)和抗凋亡蛋白 (Bcl- 2 )。三组均计数凋亡指数 (AI)。有效组与失败组各 5例观察透射电镜下凋亡改变。结果　有效组PKC、raf- 1、MEK - 1、Bcl- 2的表达有明显抑制 (P <0 0 5 ) ;AI为 0 19%。失败组信号传导受抑主要为PR、ER和EGFR(P <0 0 1) ,AI为 0 11%。结论　RU486抑制早孕滋养细胞PKC信号通路及raf- 1瀑布激酶链和分裂激活蛋白 ,抑制增生分裂分化并诱导凋亡发生 ;而失败组可能在PR、ER和EGFR信号传导初始阶段发生受体介质功能紊乱和抑制     

米非司酮配伍前列腺素抗早孕效果影响因素的探讨

目的:探讨国产米非司酮配伍前列腺素抗早孕效果的影响因素。方法:将500例分为两组,一组用米非司酮25mg,每日2次,连服3d,第4天上午阴道塞卡前列腺素栓(15-甲基PGF_(2a)酸)1mg(简称卡前列素栓组)。另一组米非司酮的用法及剂量与前一组同,第4天上午口服米索前列醇0.6mg(简称米索组)。结果:米索组完全流产率为93.2%,明显高于卡前列素栓组的88.4%(P<0.05)。米索组的流产效果受服药者年龄、既往人工流产次数、用药前胚囊平均直径与血β-hCG水平的影响较卡前列素栓组小。结论:米非司酮配伍米索前列醇是方便、有效、副作用小的抗早孕方法。用药后2w测定β-hCG值结合B超检查可用于监测药物流产效果,有实用价值。     

dl-15-甲基前列腺素 F~(2α)合并丙酸睾丸酮抗早孕新方案的临床研究

本文介绍1984年1月至1985年7月期间应用改良Corey 氏新路线合成的dl-15-甲基PGF_(α2)(简称PG)合并丙酸睾丸酮(简称丙睾)简化的新方案抗早孕956例的结果,并对其中资料较完整的507例进行分析讨论。随机分为海绵组及栓剂组两组。在用PG 前3天每天肌注丙睾100mg,共300mg,第4天于阴道后穹窿置含dl-15-甲基PGF_(2α)5mg 海绵一块或栓剂一枚,观察6小时或12小时,若不见绒毛球排出,则肌注PG2mg。两组成功率均达92%以上,完全流产率为72.72%～92.11%。6小时疗程组疗程短,可在门诊应用,12小时疗程组成功率有增高趋势,特别是海绵组中55.36%,栓剂组中26.32%仅需一次阴道给药就发生了流产,不需再肌注PG。新方案抗早孕的方法简便、安全、高效,不影响正常月经恢复及生育功能,对近期有剖宫产史、流产刮宫史、有子宫畸形、子宫过度倾屈或哺乳期妊娠者,尤为适用。     

Termination of early pregnancy with RU 486 (mifepristone) in combination with a prostaglandin analogue (sulprostone)

The antiprogestin RU 486 (mifepristone) has been shown to induce abortion when administered in early pregnancy, but the rate of incomplete abortion is high, around 40%. As blockage of the progesterone receptor increases the myometrial sensitivity to prostaglandins, a combination of RU 486 and a prostaglandin E2-analogue was tested for termination of pregnancy. One hundred and sixteen women, with a gestational length of less than 49 days from the first day of the last menstrual period, were treated with a daily dose of 50 or 100 mg RU 486 for 3 to 6 days, complemented with an intramuscular dose of 0.25 mg sulprostone (16-phenoxy-PGE2-sulfonylamide) on the last day of RU 486 treatment. The results confirmed that a reduction of treatment duration to 3 days is just as effective for inducing abortion (91% complete abortion) as a 4-6-day treatment regimen (95% complete abortion). Six patients had an incomplete abortion and in one the pregnancy continued unaffected. Side effects included intense uterine pain after the prostaglandin administration (16%), vomiting associated with the antiprogestin intake (9%) and after the prostaglandin administration (9%). One woman needed emergency curettage due to heavy bleeding. Six percent of the treated patients had a decrease in hemoglobin exceeding 20 g/l during the first week but no patient needed blood transfusion. No serious side effects were recorded.     

米非司酮对早孕妇女内分泌的影响

共征集２４名停经≤４９ｄ、要求中止妊娠的健康妇女，分４组，各组依次口服米非司酮５０ｍｇ（组Ⅰ）、５０ｍｇＱ１２ｈ×６（组Ⅱ）、２００ｍｇ（组Ⅲ）和６００ｍｇ（组Ⅳ），首次服药后７２ｈ行人流术（组Ⅰ）或阴道内放置卡前列甲酯栓（ＰＧ０５）１ｍｇ（组Ⅱ～Ⅳ）。结果显示各组之间临床效果及临床经过差异均无统计学意义（Ｐ＞０．０５）。血清β－ｈＣＧ、Ｅ２Ｐ变化趋势亦基本一致。β－ｈＣＧ在用药前２４ｈ内上升５０％～１００％（Ｐ＜０．０１），服药后至孕囊排出前仍呈上升趋势，口服首剂米非司酮后，各组Ｅ２水平亦持续高于服药前，而Ｐ水平则缓慢下降。妊娠中止后，上述三种激素急剧下降。服药期间，各组ＰＲＬ和皮质醇明显上升，孕囊排出后前者下降缓慢，而后者下降迅速，ＡＣＴＨ、Ｔ３、Ｔ４和ＴＳＨ变化均无统计学意义。本研究结果表明来非司酮（５０ｍｇＱ１２ｈ×６，２００ｍｇ和６００ｍｇ）抗早孕时无明显量效关系；其主要作用部位似不在卵巢和绒毛；但对垂体一肾上腺轴有一定影响，尤其是大剂量时；对垂体一甲状腺轴影响不明显；ＰＲＬ水平变化似为药物直接作用所致，其临床意义尚待进一步研究。     

Clinical trial of pregnancy terminations in 353 patients where amenorrhea was present for less than 49 days by 600 mg of RU 486 (administered orally) and 500 mg of sulprostone (Nalador) administered intramuscularly

354 women seeking abortions were treated at a hospital in Paris between February-September 1988 with 600 mg of RU 486 taken orally in 1 dose and an injection of 500 mg sulprostone 48 hours later. The women all had amenorrhea of less than 49 days. 1/3 were 18-25 years old, 1/2 were 25-35, and 16% were over 35. 206 were nulliparas. 110 were married and the rest were separated, widowed, divorced, or single. Sulprostone was injected early in the morning in the hospital and the women were discharged after expulsion of the products of conception, which occurred usually 2 1/2 to 3 1/2 hours later. If expulsion did not occur, the woman returned in 3 days for a sonogram to confirm uterine vacuity. 13 of the 354 women had RU 486 only. 2 refused the sulprostone and underwent aspiration and 11 experienced spontaneous expulsions in the 48 hours following RU 486 administration. 338 of the women had spontaneous expulsions. 2 pregnancies were terminated but not expelled and aspiration was required. 285 of the women expelled in the hospital within 4 hours of sulprostone administration and the other 55 did so at home 6 or more hours later. RU 486 was very well tolerated. Secondary effects were more common with sulprostone but generally subsided within 3 hours. 70 patients required treatment for uterine pain after sulprostone administration. 150 complained of nausea but only 6 required treatment. 5 women required aspiration of curettage for hemorrhage but none required transfusion. In 3 cases the hemorrhages were due to histologically proven retention. 1 patient developed endometritis 3 days after expulsion and another, who had a history of extrauterine pregnancy, developed salpingitis 15 days after expulsion. Both patients were treated with antibiotics. The method appears to be safe and effective. Its major disadvantages are that it prolongs the amount of time required for abortion and it frequently causes pelvic pain. The responsibility of the patient is also increased.     

二种单剂量RU486合并ONO802终止57～63天妊娠的随机双盲法比较研究

本研究共接纳停经５７～６３ｄ的健康早孕妇女１００例，按随机双盲法分为二组，分别口服ＲＵ４８６２００ｍｇ和６００ｍｇ，４８ｈ后加用阴道栓剂ＯＮＯ８０２１ｍｇ。完全流产率分别为９６．０％和９４．０％；两组各有上例继续妊娠，２００ｍｇ组有１例不全流产，而６００ｍｇ组有２例，两组间无明显差异。２００ｍｇ组一例不全流产者输血２００ｍｌ。用药后副反应都较轻微，无需特殊处理。两组阴道流血量、流血持续时间及转经天数相似。实验结果表明：６００ｍｇ及２００ｍｇ单剂量ＲＵ４８６合并１ｍｇＯＮＯ８０２对终止停经５７～６３ｄ的早孕是有效的；２００ｍｇ单剂量ＲＵ４８６可达到６００ｍｇ同样的效果。     

Early pregnancy termination: a comparison between vacuum aspiration and medical abortion using prostaglandin (16,16 dimethyl-trans-delta 2-PGE1 methyl ester) or the antiprogestogen RU 486

Three different regimens for termination of early pregnancy by medical means were compared to vacuum aspiration. Women seeking therapeutic abortion of pregnancy (less than or equal to 56 days amenorrhoea) were allocated to one of four treatment groups: (1) vacuum aspiration (n = 28); (2) 1 mg vaginal pessary of a prostaglandin analogue (gemeprost) every 3 h for up to 5 pessaries (n = 30); (3) the antigestogen (RU 486--mefipristone) 150 mg per day for 4 days by mouth (n = 20); (4) RU 486 in the same dose as group 3 together with 1 mg gemeprost on day 3 (n = 19). Complete abortion occurred more often in women treated with vacuum aspiration (96%), gemeprost alone (97%) and RU 486 plus gemeprost (95%) than in those treated with RU 486 alone (60%). In women receiving up to five gemeprost pessaries alone vomiting occurred in 7 (23%) and diarrhoea in 10 (33%); 16 (53%) required parenteral opiates for relief of pain. Side-effects and analgesic requirements were much reduced in the women who received RU 486 alone or in combination with a single gemeprost pessary. There was no difference in the number of days of vaginal bleeding after abortion between the four groups although there was wide individual variation (mean 10 days, range 1-34). These results confirm that medical induction of abortion in early pregnancy with prostaglandin vaginal pessaries is as effective as vacuum aspiration and that the dose can be reduced five-fold without loss of efficacy when used in combination with RU 486.     

Early pregnancy termination: a comparison between vacuum aspiration and medical abortion using prostaglandin (16,16 dimethyl-trans-Delta;2-PGE, methyl ester) or the antiprogestogen RU 486

Summary. Three different regimens for termination of early pregnancy by medical means were compared to vacuum aspiration. Women seeking therapeutic abortion of pregnancy (56 days amenorrhoea) were allocated to one of four treatment groups: (1) vacuum aspiration (n = 28); (2) 1 mg vaginal pessary of a prostaglandin analogue (gemeprost) every 3 h for up to 5 pessaries ( n =30); (3) the antigestogen (RU 486 mefipristone) 150 mg per day for 4 days by mouth ( n =20); (4) RU 486 in the same dose as group 3 together with 1 mg gemeprost on day 3 (n = 19). Complete abortion occurred more often in women treated with vacuum aspiration (96%), gemeprost alone (97%) and RU 486 plus gemeprost (95%) than in those treated with RU 486 alone (60%). In women receiving up to five gemeprost pessaries alone vomiting occurred in 7 (23 %) and diarrhoea in 10 (33%); 16 (53%) required parenteral opiates for relief of pain. Side-effects and analgesic requirements were much reduced in the women who received RU 486 alone or in combination with a single gemeprost pessary. There was no difference in the number of days of vaginal bleeding after abortion between the four groups although there was wide individual variation (mean 10 days, range 1–34). These results confirm that medical induction of abortion in early pregnancy with prostaglandin vaginal pessaries is as effective as vacuum aspiration and that the dose can be reduced five-fold without loss of efficacy when used in combination with RU 486.     

Interruption of early pregnancy by an anti-progestational compound, RU 486

RU 38-486 (17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)-17 alpha-(1-propynyl)estra-4,9-dien-3-one), an antiprogestational compound, was given to 33 women seeking termination of pregnancy. The patients were divided into two groups, 24 patients in group I with amenorrhoea up to 7 6/7 wk = 55 days, and 9 patients in group II with 8-10 wk amenorrhoea. The patients received 200 mg orally per day for 4 days. The start, duration and amount of bleeding were determined for 14 days. beta-HCG, plasma progesterone, estradiol and cortisol were determined at day 0 and day 7. All patients started to bleed during treatment. The frequency of complete abortion was 79% (19 out of 24 patients) in group I. In group II 33% (3 out of 9 patients) had a complete abortion. Most of the patients experienced only minor side-effects in terms of mild uterine pain and bleeding as in a spontaneous abortion. However, 2 patients in group II with 8 and 9 2/7 wk amenorrhoea suffered from heavy bleeding, requiring blood transfusion and curettage. In the patients with complete abortion, beta-HCG, estradiol and progesterone decreased significantly within 1 week. Cortisol concentrations remained within the normal range at day 0 and day 7. Treatment with RU 486 provides an acceptable method of early abortion, especially in women who refuse operative treatment and prefer a 'spontaneous abortion'. In 22 women RU 486 was administered from day 24 to day 27 of the menstrual cycle as a late 'morning-after pill' in the same dosage. All women except one started to bleed before day 28 and observed a normal menstrual period. One woman stayed amenorrhoeic for 2 months; she was not pregnant but apparently had an anovulatory cycle with a low progesterone level.     

Mifepristone (RU486) alone or in combination with a prostaglandin analogue for termination of early pregnancy: a review

The availability of a medical mode of termination of early pregnancy by the administration of RU486, an antiprogesterone alone, or in combination with one of the PG analogues significantly reduces the maternal morbidity and mortality associated with the classical surgical abortion. RU486 given alone in early pregnancy induces complete abortion in 60% to 85% of cases, and when combined with prostaglandin analogues, gemeprost or sulprostone, reaches a success rate of 95% to 99%. RU486 may also be of potential value in the medical treatment of ectopic pregnancy. Its use as a postcoital contraception is suggested, but further research is required to determine whether RU486 can be used on a once-a-month basis for contraception.