[Evaluation of embryotoxicity of misoprostol using the whole embryo culture assay]. / Evaluación de la embriotoxicidad de misoprostol utilizando el ensayo cultivo de embriones postimplantación.

BACKGROUND: Approximately 15% of misoprostol-induced-abortions may not be successful, leading to in utero exposure to the drug and to the induction of a series of defects including central nervous system, limb and visceral defects. A common proposal is that the drug causes disruption of the fetal vasculature leading to embryonic or fetal hypoxia. AIM: To evaluate the teratogenicity of misoprostol using the rat post-implantation embryo culture. MATERIAL AND METHODS: Rat embryos were collected at the beginning of organogenesis and cultured in rat serum containing misoprostol at concentrations of 200, 2,000 or 20,000 pg/ml. Functionality, morphology and morphometry parameters were evaluated. RESULTS: Misoprostol induced a dose-dependent embryotoxic effect causing a decrease in embryo viability and function (poor vascular development and survival) and morphometry (alterations in branchial arches, heart and cephalic portions of the neural tube, among others). CONCLUSIONS: All the manifestations observed are indicative of the ability of misoprostol to directly induce developmental retardation and alterations.

Evaluación de la embriotoxicidad de misoprostol utilizando el ensayo cultivo de embriones postimplantación / Evaluation of embryotoxicity of misoprostol using the whole embryo culture assay

Background: Approximately 15 percent of misoprostol-induced-abortions may not be successful, leading to in utero exposure to the drug and to the induction of a series of defects including central nervous system, limb and visceral defects. A commonproposal is that the drug causes disruption of the fetal vasculature leading to embryonic or fetal hypoxia. Aim: To evaluate the teratogenicity of misoprostol using the rat post-implantation embryo culture. Material and Methods: Rat embryos were collected at the beginning of organogenesis and cultured in rat serum containing misoprostol at concentrations of 200, 2,000 or 20,000 pg/ml. Functionality, morphology and morphometry parameters were evaluated. Results: Misoprostol induced a dose-dependent embryotoxic effect causing a decrease in embryo viability and function (poor vascular development and survival) and morphometry (alterations in branchial arches, heart and cephalic portions of the neural tube, among others). Conclusions: All the manifestations observed are indicative of the ability of misoprostol to directly induce developmental retardation and alterations.

Aborto provocado: redução da frequência e gravidade das complicações. Consequência do uso de misoprostol / Artificial abortion: is reduction in the frequency and severity of complications a result of the use of misoprostol

OBJECTIVES: to ascertain the frequency and severity of complications resulting from artificial abortions and their possible association with the use of misoprostol. METHODS: a cross-sectional study was carried out. For ten months, a checklist (of World Health Organization criteria) was applied to all 543 women admitted to hospital for abortion at two hospitals in the city of Campinas, in the State of São Paulo, Brazil. Those classified as having a possibly, pro-bably or certainly artificial abortion were asked to fill in the questionnaire. RESULTS: of all the women admitted to hospital, 259 (48 percent) were classified as possibly, probably or certainly having an induced abortion and these filled in the questionnaire; 25 women stated that they had induced the abortion and, of these, nine mentioned the use of misoprostol. Infections and hemorrhaging were complications in 10 percent and 13 percent of the 259 women. Those who used misoprostol had fewer complications than those who used other methods, although this difference was not statistically significant, perhaps for reason of the low frequency for complications. CONCLUSIONS: the data show a reduction in the frequency and severity of complications arising from abortion, although it is not possible to point to the use of misoprosol as being responsible for this.

OBJETIVOS: verificar a frequência e a gravidade das complicações por abortos provocados e suas possíveis associações com o uso de misoprostol. MÉTODOS: estudo de corte transversal. Durante dez meses aplicou-se uma lista de verificação (critérios da World Health Organization) a todas as 543 mulheres internadas por aborto em dois hospitais na cidade de Campinas, São Paulo. Àquelas classificadas como aborto possível, provável ou certamente provocado foi aplicado também um questionário. RESULTADOS: dentre todas as mulheres internadas, 259 (48 por cento) foram classificadas como aborto possível, provável ou certamente induzido e responderam ao questionário; 25 mulheres declararam a indução do aborto e, destas, nove referiram uso de misoprostol. Complicações infecciosas e hemorrágicas ocorreram respectivamente em 10 por cento e 13 por cento das 259 mulheres. As que usaram misoprostol se complicaram menos que as que usaram outros métodos, porém essa diferença não foi estatisticamente significativa, talvez pela baixa freqüência de complicações. CONCLUSÕES: os dados mostram redução da freqüência e da gravidade das complicações do aborto, mas não permitem avaliar o papel do misoprostol.

Moebius syndrome and holoprosencephaly following exposure to misoprostol.

Moebius syndrome is a rare disease characterized by congenital facial paralysis and abducens palsy. Involvement of other cranial nerves, orofacial dysmorphism, and limb abnormalities are frequently associated. Reported here is the case of a 10-month-old child born with Moebius syndrome and presenting with holoprosencephaly, following exposure in utero to misoprostol. To our knowledge, this is the first published case report describing this association. The etiologic hypotheses of Moebius syndrome are also discussed.

Embryotoxic effects of misoprostol in the mouse.

Misoprostol (MSP) is a synthetic prostaglandin E1 methyl analogue indicated for the prevention of gastric ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Because of its abortifacient properties, MSP has been extensively misused for abortion induction in Brazil. Since abortion induction with MSP very often fails and pregnancy continues to term, there has been increasing concern regarding the potential teratogenicity of this PGE1 analogue in humans. The objective of the present study was to evaluate the embryotoxicity of MSP in mice. A single dose of MSP (20 or 30 mg/kg body weight) was administered to Han:NMRI mice (ca 60 days old) by gavage on day 10 of pregnancy. The number of treated mice was as follows: control, 19; MSP 20 mg/kg, 10; MSP 30 mg/kg, 28. Cesarean sections were performed on day 18 of pregnancy and the number of resorptions and implantation sites were recorded. Fetuses were weighed, examined for external malformations, fixed, cleared and stained with Alizarin Red S for skeleton evaluation. No evidence of embryotoxicity was found at the lower dose tested. A slight and reversible deficit in pregnancy weight gain (day 10-11: control, 1.3 +/- 0.3 g; MSP 20 mg/kg, -0.9 +/- 0.9 g; MSP 30 mg/kg, -1.7 +/- 0.6 g) was the only sign of maternal toxicity noted in both groups of mice treated with misoprostol.(ABSTRACT TRUNCATED AT 250 WORDS)

Embryotoxic effects of misoprostol in the mouse

Misoprostol (MSP) is a synthetic prostaglandin E1 methyl analogue indicated for the prevention of gastric ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Because of its abortifacient properties, MSP has been extensively missused for abortion induction in Brazil. Since abortion induction with MSP very often fails and pregnancy continues to term, there has been increasing concern regarding the potential teratogenicity of this PGE1 analogue in humans. The objective of the present study was to evaluate the embryotoxicity of MSP in mice. A single dose of MSP(20 or 30 mg/kg body weight) was administered to Han:NMRI mice (ca 60 days old) by gavage on day 10 of pregnancy. The number of treated mice was as follows: control, 19; MSP 20 mg/kg, 10; MSP 30 mg/kg, 28. Cesarean sections were performed on day 18 of pregnancy and the number of resorptions and implantation sites were recorded. Fetuses were weighed, examined for external malformations, fixed, cleared and stained with Alizarin Red S for skeleton evaluation. No evidence of embryotoxicity was found at the lower dose tested. A slight and reversible deficit in pregnancy weight gain ...