Fetal Medicine · Congenital Anomalies
Rock JA et al., 1985 · Fertil Steril
This report presents the outcome of pregnancies of 93 women who conceived while taking progesterone (P) suppositories (n = 42) or P in oil intramuscularly (n = 51). The dosage and duration of treatment varied according to the indication. The total dose (in milligrams) increased with the duration of treatment and ranged from 75 to 13,500 mg. Two of 75 term pregnancies (2.6%) were noted to have congenital anomalies. Both women had been treated with P in oil. No patient treated with P suppositories gave birth to a malformed infant. An increased spontaneous abortion rate (28.6%) was noted among women treated with P suppositories. The authors recommend that a national registry be created to document fetal outcome after P therapy.
Fetal Medicine · Congenital Anomalies
Resseguie LJ et al., 1985 · Fertil Steril
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.
Preterm Birth · Progesterone Prophylaxis
Hilgers TW et al., 2015 · Issues Law Med
Progesterone support in pregnancy has been in use for over 60 years, having received its start in the 1940s. Its initial use was in patients who had habitual spontaneous abortion caused by luteal phase deficiency. More recently, the administration of progesterone later in pregnancy has been considered to be justified because of an observed decrease in circulating progesterone with the onset of labor, an association of premature labor with decreased progesterone concentrations, and the observation that progesterone has a tocolytic effect. A considerable boost to the use of progestational agents to reduce preterm delivery was received with the publication of two papers which showed a significant reduction in preterm delivery rates with the prophylactic administration of either progesterone or 17-a hydroxyprogesterone caproate. Recently it has been shown, however, that its use is not universal. This may be related to the significant late sequelae that were documented following the in utero exposure of the fetus to the potent steroid diethylstilbestrol (DES) and that this bad experience cast “a long shadow,” In spite of this, the use of progesterone, at least in early pregnancy, is widespread in the various artificial reproductive programs and is growing in its use as an agent to reduce prematurity. Over the years, there has been an extraordinary amount of confusion related to the use of progesterone support in pregnancy. The Food & Drug Administration (FDA) created some of this confusion. In various labeling of progesterone products by the FDA, one of the contraindications to the use of oral progesterone is listed as “known or suspected pregnancy.” And, yet, no such contraindication is identified for the use of progesterone gel. In fact, progesterone gel is indicated for progesterone supplementation or replacement as a part of an assisted reproductive technology (ART) treatment program for infertile women with a progesterone deficiency. To make this even more confusing, oral progesterone, while it was contraindicated in “known or suspected pregnancy,” its official labeling stated that it “should be used during pregnancy only if indicated (see contraindications).” Also, up until very recently, there was a dire “warning” contained in the labeling for USP progesterone injection in sesame seed oil regarding an increased possibility of birth defects. An analysis of the fetal safety of isomolecular progesterone (Pregn-4-ene-3,20-dione) administration during the course of 1,310 pregnancies over a 35-year period of time (1979-2014) was undertaken to address this confusion.
Early Pregnancy · Progesterone Support
Katz Z et al., 1985 · Obstet Gynecol
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.
