The role of trophoblast dysfunction in the aetiology of miscarriage

Objective To investigate the endocrine changes associated with spontaneous miscarriage after fetal heart activity has been demonstrated. Design Prospective study during the first trimester of pregnancy comparing the circulating levels of human chorionic gonadotrophin (hCG), Schwangerschaft protein 1 (SP-1), pregnancy-associated plasma protein A (PAPP-A), oestradiol (E2), and progesterone (P), and fetal growth (crown-rump length [CRL] and gestational sac volume [GSV]) in women who miscarried after the identification of fetal heart activity with those of normal singleton and twin pregnancies achieved following in vitro fertilisation (IVF) and embryo transfer (ET). Setting The Assisted Conception Unit of King's College Hospital, London. Subjects Nine women who miscarried after demonstration of fetal heart activity, 52 normal singleton and 22 normal twin pregnancies. Interventions Weekly blood tests and ultrasound assessments of CRL and GSV. Results Four fetuses (all singleton) died between 9 and 12 weeks gestation (Group 1), and seven (three singleton and two twin) died between 16 and 20 weeks gestation (Group 2). In Group 1, both fetal growth and placental function, as assessed by serial measurements of CRL and GSV, and of serum levels of PAPP-A, SP-1 and hCG respectively, were reduced before fetal death. In Group 2, while fetal growth was maintained in all but one case, placental function was reduced in 4 of 5 women. Conclusion These findings suggest that there may be a relationship between trophoblast dysfunction and some forms of miscarriage. Furthermore, the pattern of the reduction in the circulating levels of the placental proteins in later miscarriages suggests that the function of specific cell types may be impaired.