Katz, Z., Lancet, M., Skornik, J., Chemke, J., Mogilner, B. M., & Klinberg, M. (1985). Teratogenicity of progestogens given during the first trimester of pregnancy. Obstetrics and gynecology, 65(6), 775-780.
Katz Z, Lancet M, Skornik J, Chemke J, Mogilner BM, Klinberg M. Teratogenicity of progestogens given during the first trimester of pregnancy. Obstet Gynecol. 1985;65(6):775-780.
Katz, Z., et al. "Teratogenicity of progestogens given during the first trimester of pregnancy." Obstetrics and gynecology, vol. 65, no. 6, 1985, pp. 775-780.
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Possible teratogenic effects of exogenous progestational agents given during early pregnancy were investigated by a controlled historic prospective study of 2754 infants born to mothers who had bled during the first trimester of pregnancy. The study group consisted of 1608 newborns whose mothers had been treated with progestogens (mostly medroxyprogesterone acetate) beginning in the first trimester. The control group comprised 1146 infants of untreated mothers. All newborns were subjected to thorough examination during the first days of life, with special attention to detection of various malformations classified according to the different anatomic systems. No significant difference was found between the treated and the control groups with respect to malformations in any of the systems examined. The overall rate of malformations was 120 per 1000 in the study group and 123.9 per 1000 in the control group. Major malformations occurred at rates of 63.4 and 71.5 per 1000, respectively. The study thus fails to demonstrate an increase in teratogenicity after administration of gestagens during the first trimester of pregnancy.
Eighty pregnant women at high risk of giving birth prematurely were divided randomly into two groups. Treatment with either 17 alpha-hydroxyprogesterone caproate, 250 mg by intramuscular injection once a week, or a placebo was given in a double-blind fashion. Imminent premature labor occurred in 29.0% of the treated group and in 59.4% of the control group (p less than 0.025). The rate of premature deliveries was also significantly lower in the treated group (16.1%) than in the control group (37.82%) (p less than 0.05). There were no cases of perinatal death or fetal malformations in either group. The mean birth weight of all infants of the treated group was significantly higher than in those of the control group (3111.9 +/- 905 gm versus 2680 +/- 813.4 gm, p less than 0.05). The results support treatment with progesterone caproate for the prevention of premature labor.
The results of combined ritodrine and indomethacine treatment (RI) in premature labor contractions were compared with ritodrine alone (R). One hundred and twenty patients with threatened premature labor in weeks 26-34 were studied. Sixty RI women received 100 mg ritodrine in infusion followed by 60 mg daily orally until 35 weeks and indomethacine 200 mg on the first day of treatment only. The R group included 60 women with identical tocolysis indices, age of pregnancy and anamnestic parameters who received ritodrine only. The mean prolongation index (PI) was 18.2 in the RI group, against 11.5 in the R patients (P less than 0.05). The mean prolongation of pregnancy was 5.6 weeks in the first and 3.6 in the control group (P less than 0.05). Birthweight and Apgar scores were similar in the two groups. In order to examine the possible early closure of the ductus arteriosus due to the indomethacin therapy, echocardiograms were done on all newborn in the RI group: the pre-ejection period and right ventricular ejection time ratio was 0.19-0.26 after delivery and 0.17-0.22 1 month later, which excludes pulmonary diastolic hypertension due to premature closure of the duct. The combined RI treatment is more effective that R alone and does not give rise to any complications in the mother or the fetus.
Medroxyprogesterone acetate (MPA; Provera) was given orally to 449 women from the 5th to 7th week of pregnancy until at least the 18th week. Data are recorded from two treatment groups (recurrent abortion and threatened abortion) and are compared to a matched series. A total of 1,016 pregnancies are included in the study, and all patients were recruited from a subfertile population conceiving from a range of infertility treatments. Early pregnancy wastage was high throughout the groups and was significantly elevated (43%; P less than .001) in those women who had vaginal bleeding in early pregnancy. The study focuses on the question of potential teratogenicity of progestagens administered in the first trimester. There were 15/366 (4.1%) infants with congenital abnormalities in the MPA-treated group and 15/428 in the untreated group (3.5%). The difference was not significant, and MPA is considered to have no embryopathic risk, nor is it likely to retain an abnormal fetus that might otherwise abort. It appears that MPA is a safe drug to use in pregnancy although the question of efficacy has not been addressed in this report. Considering other recent negative epidemiologic studies with regard to teratogenicity, we add to the conclusion that MPA cannot be demonstrated to have a measurable teratogenic risk and certainly does not present a risk for congenital heart disease and limb reduction defects.
Pregnant mice were treated with a single subcutaneous injection of either cyproterone acetate (CA) or medroxyprogesterone acetate (MPA). In the first experiment the animals received 5-900 mg/kg of the hormone before implantation (day 2 of pregnancy). CA treatment on day 2 caused a dose-dependent decrease in fetal weight and a significant dose-dependent increase in the rates of cleft palate and urinary tract abnormalities. Exencephaly and heart abnormalities were also significantly more frequent, but this increase was not dose-dependent. MPA treatment on day 2 was followed by sporadic increases in dead and resorbed fetuses, a decrease in fetal weight and an increase in the rates of cleft palate, and malformed or abnormally developed fetuses. None of these effects, however, was dose-dependent. In the second experiment the mice were given one single injection (30 mg/kg) of CA or MPA on any one of days 1-12 of gestation. Treatment with CA on one day between days 1 and 12 revealed that the specific sensitivity for abnormalities of the urinary tract was on days 5 and 6, for the respiratory tract on days 8 and 9, and for cleft palate on days 10 and 11. Treatment with MPA on one day between days 1 and 12 only revealed a high rate of respiratory and urinary tract abnormalities on day 9. After treatment with MPA cleft palate was again significantly more frequent in all treated groups, however, days of peak sensitivity were not detected. The long half-life of CA (60 hours) explains the teratogenic effect of high doses of this progestin after treatment on day 2 and also the pattern of abnormal development found after treatment with a single dose of CA on one of the days between day 1 and day 12.
Comparison of a cohort of 988 offspring exposed in utero to exogenous progestins with a matched cohort of unexposed offspring did not result in detection of an association of congenital anomalies with exposure. The conclusions are based primarily on outcomes of pregnancy with exposure to progesterone and 17 alpha-hydroxyprogesterone caproate, and may not apply to androgenic progestins. Offspring exposed to combinations of progestins and estrogens were excluded from this study and may have a different distribution of anomalies.
The incidence of congenital anomalies in infants born to 382 women treated with P was noted. Only five anomalies occurred in the infants born to women who had taken P. This study supports the data of Rock et al. by demonstrating a similar low incidence of birth defects in a much larger series of patients who also took a much higher dosage of P. Similarly, because only 1 of 189 patients treated with both P and 17-OHP developed anomalies, the data supports the study by Katz et al., suggesting no increase in anomalies related to 17-OHP therapy.
Pregnancy › Early Pregnancy › Progesterone Support · Therapeutics › Hormonal Agents › Progesterone and Progestins
PMID 3158848 3158848 Katz et al. 1985, Katz 1985
Cite this article
Katz, Z., Lancet, M., Skornik, J., Chemke, J., Mogilner, B. M., & Klinberg, M. (1985). Teratogenicity of progestogens given during the first trimester of pregnancy. Obstetrics and gynecology, 65(6), 775-780.
Katz Z, Lancet M, Skornik J, Chemke J, Mogilner BM, Klinberg M. Teratogenicity of progestogens given during the first trimester of pregnancy. Obstet Gynecol. 1985;65(6):775-780.
Katz, Z., et al. "Teratogenicity of progestogens given during the first trimester of pregnancy." Obstetrics and gynecology, vol. 65, no. 6, 1985, pp. 775-780.
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