【作者】 庄亚玲；

【导师】 黄丽丽；

【作者基本信息】 浙江大学 ， 妇产科学， 2003， 硕士

【摘要】 人工流产作为避孕失败的补救措施已有悠久的历史，但手术流产是一种侵入性的方法使妇女的身心健康受到一定的影响。由于米非司酮与米索前列醇配伍终止早孕的方法可以达到90％以上的完全流产率，同时该方法具有方便、自然、痛苦少和更有利于保护个人隐私的优点，已越来越受到广大妇女的接受，尤其是未婚女性的喜爱。药物流产为广大人工流产的妇女提供了另一种选择，但药物流产后子宫出血时间长的问题仍未得到解决，影响了它的安全性和可接受性。 国内对药物流产后子宫出血时间长的问题，研究较多。有研究发现米非司酮药物流产后，血供丰富的蜕膜组织中蜕膜细胞能分泌大量层粘连蛋白(LM，Laminin)和纤维粘连蛋白(FN，Fibronectins)，使蜕膜组织紧密固着于内膜组织并干扰内膜组织(尤其血管)的生长发育，从而导致了蜕膜的残留和子宫内膜修复不良。另有对药物流产后妇女绒毛、蜕膜组织中纤溶系统进行研究发现组织型纤溶酶原激活剂(t-PA)活性增加，而其抑制剂(PAI)活性降低；对药物流产妇女进行研究发现，服药后血中t-PA含量明显升高而血清凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)和纤维蛋白原无改变，凝血功能未受到影响，认为纤溶系统亢进可能是出血时间长的原因之一。也有研究证实米非司酮抗早孕使蜕膜中的ER、PR明显下降。但至今药物流产后子宫出血时间长的机理，仍未明了。 浙江大学硕士学位论文 国内外研究均证实米非司酮对卵巢功能有影响。卵泡期妇女服用米非司酮 后，引起卵巢卵泡发育受抑制及延迟排卵。在卵泡早期，米非司酮暂时性抑制 卵泡发育，在服药期间雌激素分泌下降，而排卵不受影响，FSH、h分泌不受 影响。认为在卵泡早期米非司酮是直接作用于卵巢水平。在卵泡中、晚期，随 服用剂量增大，米非司酮能使原已出现的优势卵泡萎缩，发育中断，雌激素分 泌下降并维持于低水平，而在停药后出现新的卵泡发育；或优势卵泡受到一定 程度的抑制，停药后卵泡恢复正常生长，研究认为在卵泡中晚期由于米非司酮 抑制了 FSH、h的分泌，故必然影响卵泡的发育。低剂量时门）甚至可 不抑制卵泡生长而只抑制排卵。更低剂量时①．lmgld）对卵泡生长、排卵均不 抑制。由于剂量减小，米非司酮对卵泡发育的抑制作用减弱，因此停药后卵泡 发育恢复也快，排卵被延迟的时间也缩短，但在卵泡发育不受抑制情况下，米 非司酮仍可使排卵延迟2－5天。其原因可能米非司酮抑制了排卵前卵泡孕酮的分 泌及在下丘脑、垂体中桔抗了孕酮的正反馈效应而延迟了LH峰的出现。米非司 酮可使黄体期妇女的卵巢黄体功能受抑制，主要发生在黄体中晚期，对早期黄 体功能无明显影响。服用较大剂量时，米非司酮能诱导黄体提前溶解，雌激素 和孕激素分泌迅速下降，黄体期缩短：剂量较小时，米非司酮可逆行性抑制黄 体功能，雌激素和孕激素分泌轻微下降后即恢复，黄体期稍延长或不变。因而 米非司酮影响黄体功能与用药剂量及黄体的不同阶段有关。但有学者研究认为 在黄体晚期，米非司酮在经前自然孕激素撤退时给药并不影响黄体期的长短或 激素水平。子宫内膜的生理和病理变化与卵巢功能息息相关，由此我们提出了 这样一个假设：药物流产后是否存在卵巢功能抑制，影响了子宫内膜的功能， 而引起出血时间延长。 对米非司酮抗早孕后的生殖激素变化，WHO对使用两种不同剂量的米非司 酮合并前列腺素药物流产后妇女进行研究，用放射免疫法测定了流产4天内、 第8天、第15天和第43天时的激素水平变化。在服药后至孕囊排出前EZ水平 持续高于服药前，而P水平缓慢下降。孕囊排出后EZ和P则急剧下降，EZ和 P的变化趋势基本一致。国内贺昌海研究了流产8天内、第15天和第43天时 二 浙江大学硕士学位论文一 的激素水平变化，结果与 W41O的类似。目前未见药流 10天后激素水平连续测 定的相关报道。 本课题对米非司酮配伍米索前列醇终止早孕后妇女的血生殖激素水平进行 研究，以进一步探讨药物流产后子宫出血时间长的机理。 材料与方法 本研究根据研究对象的纳入标准选择了605例正常健康生育年龄妇女， 其中药流后出血正常组 199例，药流后出血时间长组 196例，手术流产组 ZIO 例。分另于流产后第10－11天、第12－13天、第14－15天、第16－17天、第18－19 天、第20－ZI天、第22－23天抽静脉血，取血清，用放射免疫法（RIA）测定女 性生殖激素，包括EZ、P、FSH和LH。采用电化学发光免疫分析法测定HCG。 所有数据用 SPSS刀 for indows软件包处理。资料用 5土 SE表示。 结果 3组妇女的年龄、月经周期和经期经统计学检验无显著性差异0＞0刀5）?更多还原

【Abstract】 Induced abortion has a long history as a remedial measurement of contraceptive failure. Surgical abortion which is an invasive procedure impairs women’s health. For more than ten years medical abortion has been used in our country. The complete abortion rate of termination of early pregnancy by mifepristerone and misoprostol is above 90%. The advantages of medical abortion are convenience, natural, less pain and greater privacy. It is an alternative method for women who needed abortion. But uterine prolonged bleeding after medical abortion is still unsolved, which influences its security and receptivity.Many studies on the problem of uterine prolonged bleeding after medical abortion have been done. Some suggested that decidual cells produced a great deal of laminins(LM) and fibronectins ( FN) after termination of early pregnancy by mifepristerone and misoprostol, laminins(LM) and fibronectins ( FN) made decidual tissue stick to the endometrium closely, which had an influence on repair of endometrium. It was assumed that fibrinolysis system hyperfunction and significantdecreasing of ER and PR expression in decidual tissues correlated with uterine prolonged bleeding after abortion.The effect of mifepristerone on ovarian function has been proved. In follicular phase of menstrual cycle, mifepristerone inhibited development of follicle and delayed ovulation. In early follicular phase of menstrual cycle, mifepristerone temporarily inhibited the follicular development, estradiol secretion decreased during treatment. Serum FSH, LH levels had no changes. In mid- and late follicular phase of menstrual cycle, with the doses increasing, previous dominant follicle was atrophied, estradiol secretion decreased and maintained at a low level. Once stopping administration of mifepristerone, new follicle began to develop; or dominiant follicle was inhibited to some extent, the dominant follicle recovered to grow after treatment,. With low doses of mifepristerone (1mg/day), it did not inhibit the follicle growth, but inhibited ovulation. when follicular growth was not inhibited, mifepristerone still delayed ovulation for two-five days. The reason was that it inhibited the progesterone secretion before ovulation or delayed the LH surge which resulted from mifepristerone resisting the positive feedback of progesterone in hypothalamus and pituitary levels. In this phase, serum FSH, LH levels decreased. Mifepristerone had influences on luteal function of ovary in luteal phase of menstrual cycle, especially in mid- and late luteal phase. In early luteal phase, mifepristerone did not affect luteal function or length of the cycle. With high doses given, mifepristerone can induce luteolysis in advance, so estradiol and progesterone secretion decreased rapidly and luteal phase of cycle was shorter. When low dose given, mifepristerone can inhibit luteal function of cycle reversibly, estradiol and progesterone secretion recovered after decreased slightly, slight lengthening or no change of luteal phase. So the effect of mifepristerone on the luteal function of cycle is associated with its doses and various stages during menstrual cycle. Physiology and pathology of uterine endometrium is closely correlated with ovarian function. So we presumed thatinhibition of ovarian function after medical abortion influenced the repair of uterine endometrium and results in uterine prolonged bleeding.WHO studied reproductive hormone profiles after pregnancy termination with mifepristerone of two different doses. Serum estradiol and progesterone levels on 1st 4 days ,eighth .fifteenth, and forty-third after abortion were assayed by RIA. Serum estradiol levels increased during the 1st 48 hours after the start of treatment, and their concentrations were still higher than pretreatment values on day 4. In contrast ,the levels of serum progesterone started to decline immediately and were significantly lower on day 4 than on day 1. After prostaglandin, the concentrations of all two hormones rapidly decreased to nonpregnant values. He CH et al assa更多还原