Threatened abortion, hormone therapy and malformed embryos

Abstract

Causal relations between maternal genital bleeding, supportive hormone therapy and external malformations of the embryos were investigated with special reference to the critical period of organogenesis. This was done using morphological and obstetrical data obtained by Nishimura and his associates from 667 undamaged embryos derived from induced abortions whose mothers had genital bleeding in early pregnancy. In addition, data from 90 embryos with polydactyly and 38 with limb reductions in the Nishimura collection were used for case history studies. Evidence was presented to demonstrate that, for major malformations such as CNS anomalies, cleft lip, polydactyly and limb reductions, maternal genital bleeding was not a cause but a consequence of the conception of an abnormal embryo. No indication was revealed that exogenous female hormones currently used in Japan for preventing miscarraiges could produce major malformations recognizable at the embryonic stage, including limb reductions, nor salvage the severely malformed embryos. This does not however mean to exclude the possible relationship of progestogens/estrogens intake during early pregnancy with an increased incidence at birth of certain internal and/or external malformations. It was suggested that most, if not all, of the minor anomalies observed at certain embryonic stages are kinds of normal variants without any functional impairment of embryonic development.

PIP: This paper explored, using induced abortuses both alive and dead in utero in a Nishimura consecutive series, the causal relationships among maternal genital bleeding, supportive hormone therapy, and congenital anomalies, with special reference to the critical organogenesis period. Data from 667 undamaged embryos from induced abortions whose mothers had had early genital bleeding and from 90 embryos with polydactyly and 38 with limb reductions were studied. The following conclusions were drawn from examining this series and the damaged abortuses' case histories: 1) Major malformations such as central nervous system anomalies, cleft lip, polydactyle, and limb reductions were not caused by maternal genital bleeding but that the bleeding was a consequence of conceiving an abnormal embryo. 2) No indication was found that exogenous hormones, especially those used in Japan for preventing miscarriages, induced major malformations at the embryonic stage, including limb reductions, nor that they could salvage embryos already severely malformed. 3) Most of the minor anomalies seen at embryonic stages are suggested to be normal variants without any functional impairment of embryonic development. 4) Though this retrospective investigation could not link estrogens used to prevent miscarriages with major malformations, the authors do not rule out the possibility that progestogen/estrogen intake during early pregnancy may be related to increased incidence at birth of internal anomalies such as cardiac anomalies and esophageal atresia, or external malformations manifested at the fetal or neonatal stage.