Hormones, cytokines and fetal anomalies in habitual abortion.
Recurrent miscarriage may be due to an inherently abnormal embryo (e.g. chromosomal aberrations), or maternal factors (e.g. uterine anomalies or antiphospholipid antibodies). However, there may be another mechanism; fetuses may have anomalies induced by toxic maternal factors. Early ultrasound scanning has revealed structural anomalies in karyotypically normal embryos in pregnancies that have terminated in first-trimester missed abortion. The serum of recurrently miscarrying women is toxic to blastocysts, embryos and fetuses. Teratogens such as cyclophosphamide or toxins such as lipopolysaccharide cause fetal demise by excessive apoptosis. Excessive apoptosis may be mediated by tumor necrosis factor-alpha and other cytokines. Both immunomodulation and hormonal support (progesterone or human chorionic gonadotropin supplements) have been used to improve the live birth rate in recurrently aborting women. Each may modulate the balance between Th1 and Th2 cytokines. Th2 cytokines are thought to benefit the developing embryo by enhancing placental growth and function, and possibly by preventing inappropriate apoptosis. Although neither hormonal support nor immunopotentiation have proved to be beneficial, no trial has limited itself to pregnancies that are karyotypically normal. This review assesses fetal structural anomalies in humans and laboratory animals as causes of pregnancy loss, the role of cytokines in those anomalies and the role of immunomodulation and hormones in modifying these effects.
Carp
H
H
Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Aviv, Israel.
Torchinsky
A
A
Fein
A
A
Toder
V
V
D000026:Abortion, Habitual / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D006063:Chorionic Gonadotropin / Q000008:administration & dosage; D000013:Congenital Abnormalities; D016207:Cytokines / Q000502:physiology*; D005260:Female; D006728:Hormones / Q000502:physiology*; D006801:Humans; D011247:Pregnancy; D011374:Progesterone / Q000008:administration & dosage; D016216:Ultrasonography, Prenatal
D006063:Chorionic Gonadotropin; D016207:Cytokines; D006728:Hormones; D011374:Progesterone