A 33-year-old woman, gravida 2 para 1, comes to the office due to a positive home urine pregnancy test. Her last menstrual period was 6 weeks ago, and pelvic ultrasonography confirms an intrauterine pregnancy. The patient has idiopathic pulmonary hypertension complicated by Eisenmenger syndrome. She is aware that pregnancy poses a major mortality risk to herself and the fetus due to the hemodynamic changes of gestation, labor, and delivery. The patient consents to pregnancy termination with a mifepristone and misoprostol regimen. Which of the following is the mechanism of action for mifepristone in this clinical situation?

Question

A 33-year-old woman, gravida 2 para 1, comes to the office due to a positive home urine pregnancy test.  Her last menstrual period was 6 weeks ago, and pelvic ultrasonography confirms an intrauterine pregnancy.  The patient has idiopathic pulmonary hypertension complicated by Eisenmenger syndrome.  She is aware that pregnancy poses a major mortality risk to herself and the fetus due to the hemodynamic changes of gestation, labor, and delivery.  The patient consents to pregnancy termination with a mifepristone and misoprostol regimen.  Which of the following is the mechanism of action for mifepristone in this clinical situation?

Quizplus · Accepted Answer

11ec160b_3c46_3d19_9249_236e29e77697_MD0001_00 In the second half of the menstrual cycle, progesterone stimulates the development of secretory endometrium to create an environment favorable for implantation. In the first 7 weeks of pregnancy, progesterone is secreted by the corpus luteum; thereafter, its production is assumed by the placenta. Mifepristone is a progesterone antagonist that binds progesterone receptors with greater affinity than the natural hormone. Progesterone receptor blockade results in apoptosis and necrosis of the uterine decidua and prevents further development of a first trimester pregnancy. When misoprostol is used with mifepristone, pregnancy termination success rate is increased. Misoprostol, a prostaglandin E1 analog (Choice F), causes cervical softening and uterine contractions leading to expulsion of the pregnancy. (Choices A and B) Nifedipine (calcium channel blocker) and indomethacin (cyclooxygenase inhibitor) are tocolytic drugs used to stop preterm labor. The decreased intracellular calcium from nifedipine blocks myosin kinase phosphorylation, which in turn leads to myometrial relaxation. Indomethacin stops prostaglandin synthesis, which decreases uterine contractility. (Choice C) Folic acid antagonists (eg, methotrexate) inhibit trophoblast division, therefore decreasing trophoblast survival, hindering implantation, and encouraging expulsion. Methotrexate is used for the treatment of ectopic pregnancy and for termination of intrauterine pregnancy in conjunction with misoprostol when mifepristone is not available. (Choice D) Oxytocin is a peptide hormone released by the posterior pituitary that stimulates uterine contractions. Myometrial oxytocin receptor concentration increases at term; therefore, oxytocin has limited effects on the uterus in early gestation and does not cause pregnancy termination. (Choice G) Tamoxifen is a selective estrogen receptor modulator and is used primarily to treat estrogen receptor-positive breast cancer by selective blockade of estrogen-positive cancer cells. Conversely, in the uterus, tamoxifen stimulates endometrial estrogen receptors and can cause endometrial hyperplasia and endometrial adenocarcinoma. Educational objective: Progesterone is necessary for implantation and maintenance of pregnancy. Mifepristone is a progesterone antagonist that is used with misoprostol (a prostaglandin-E1 agonist) to terminate a first-trimester pregnancy. __________ References: Practice bulletin no. 143: medical management of first-trimester abortion. (http://www.ncbi.nlm.nih.gov/pubmed/24553166) Biological mechanisms underlying the clinical effects of mifepristone (RU 486) on the endometrium. (http://www.ncbi.nlm.nih.gov/pubmed/11742418)

A 33-Year-Old Woman, Gravida 2 Para 1, Comes to the Office