Creinin M D, Stewart-Akers A M, DeLoia J A
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Hospital, Pennsylvania, USA.
Am J Obstet Gynecol. 1998 Sep;179(3 Pt 1):604-9. doi: 10.1016/s0002-9378(98)70052-3.
Our purpose was to determine whether methotrexate affects the trophoblast or corpus luteum when administered for abortion.
A randomized controlled trial was performed in women requesting an abortion up to 49 days' gestation. Twenty patients were treated with intramuscular methotrexate 50 mg/m2 (10 women) or 60 mg/m2 (10 women). Serum beta-human chorionic gonadotropin, progesterone, and 17-hydroxyprogesterone levels were determined at baseline and then serially after methotrexate administration for the first 24 hours, then every 24 hours for 7 days. On the seventh day misoprostol 800 microg was administered vaginally.
Serum beta-human chorionic gonadotropin increased at a lower rate than occurs in normal pregnancy. Progesterone levels averaged 56.9 +/- 19.8 nmol/L at baseline and 45.5 +/- 20.5 nmol/L (P = .01) 1 week after methotrexate. Progesterone decreased in 16 women over the 7 days and increased in the other 4; these latter women all aborted after a single dose of misoprostol. Levels of 17-hydroxyprogesterone plateaued during the first day after methotrexate administration; both progesterone and 17-hydroxyprogesterone declined simultaneously between the third and fourth day after methotrexate.
Methotrexate most likely primarily affects trophoblast production of human chorionic gonadotropin, as evidenced by a blunting of the expected increase in serum beta-human chorionic gonadotropin resulting in less support for the production of progesterone by the corpus luteum. However, changes in progesterone levels after methotrexate administration were inconsistent and are unlikely to represent the ultimate effect of methotrexate in abortion. The less-than-normal increase in serum beta-human chorionic gonadotropin levels after methotrexate administration is most likely a result of disruption of cytotrophoblast syncytialization. This disruption may be the true effect of methotrexate in destabilizing the implantation site of an early pregnancy.
我们的目的是确定甲氨蝶呤用于流产时是否会影响滋养层细胞或黄体。
对妊娠49天内要求流产的女性进行了一项随机对照试验。20例患者接受肌肉注射甲氨蝶呤治疗，剂量为50mg/m²（10例女性）或60mg/m²（10例女性）。在基线时测定血清β-人绒毛膜促性腺激素、孕酮和17-羟孕酮水平，然后在甲氨蝶呤给药后的头24小时内连续测定，之后每24小时测定一次，共7天。在第7天经阴道给予米索前列醇800μg。
血清β-人绒毛膜促性腺激素的升高速率低于正常妊娠。基线时孕酮水平平均为56.9±19.8nmol/L，甲氨蝶呤给药1周后为45.5±20.5nmol/L（P = 0.01）。7天内16例女性的孕酮水平下降，另外4例升高；后4例女性在单次服用米索前列醇后均流产。甲氨蝶呤给药后第1天17-羟孕酮水平达到平稳；甲氨蝶呤给药后第3天和第4天之间，孕酮和17-羟孕酮同时下降。
甲氨蝶呤很可能主要影响滋养层细胞产生人绒毛膜促性腺激素，血清β-人绒毛膜促性腺激素预期升高的减弱证明了这一点，这导致黄体产生孕酮的支持减少。然而，甲氨蝶呤给药后孕酮水平的变化并不一致，不太可能代表甲氨蝶呤在流产中的最终作用。甲氨蝶呤给药后血清β-人绒毛膜促性腺激素水平低于正常的升高很可能是细胞滋养层细胞合体化受到破坏的结果。这种破坏可能是甲氨蝶呤使早期妊娠着床部位不稳定的真正作用。
