Hilgers, T. W., Keefe, C. E., & Pakiz, K. A. (2015). The Use of Isomolecular Progesterone in the Support of Pregnancy and Fetal Safety. Issues in Law & Medicine, 30(2), 159-168.
Hilgers TW, Keefe CE, Pakiz KA. The Use of Isomolecular Progesterone in the Support of Pregnancy and Fetal Safety. Issues Law Med. 2015;30(2):159-168.
Hilgers, T. W., et al. "The Use of Isomolecular Progesterone in the Support of Pregnancy and Fetal Safety." Issues in Law & Medicine, vol. 30, no. 2, 2015, pp. 159-168.
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Pope Paul VI Institute for the Study of Human Reproduction, Omaha, Nebraska.027jqx654
One clinic's birth defect rates matched with and without progesterone
A chart review of 1,763 pregnancies at one clinic found that birth defects occurred in about 2 out of 100 pregnancies with or without progesterone. The clinic treats fertility problems and high-risk pregnancy. Of these, 1,310 had progesterone support and 453 did not.
Key Findings
Fetal anomalies occurred in 29 of 1,310 pregnancies on progesterone (2.2%) and 10 of 453 pregnancies not on progesterone (2.2%), p=0.99.
Chromosomal anomalies: 14 (1.1%) on progesterone versus 3 (0.7%) without, p=0.45. Non-chromosomal anomalies: 15 (1.1%) versus 7 (1.5%), p=0.51.
Women on progesterone were older (29.9 versus 26.3 years) and more often had a history of infertility (45.2% versus 12.7%).
No individual anomaly differed significantly between groups. The authors concluded there is no credible evidence that progesterone used to support pregnancy is teratogenic (harmful to fetal development) or responsible for genital malformations.
Interpretation
This chart review covered 1,763 pregnancies at the Pope Paul VI Institute from 1979 to 2014. All of the women got isomolecular (bioidentical) progesterone or none at all. The authors say this is the largest group of pregnancies studied with isomolecular progesterone on record. The findings support larger studies of progesterone's safety in pregnancy.
RRM Context
The paper comes from the Pope Paul VI Institute, where NaProTechnology was developed. The authors keep progesterone the body makes separate from synthetic look-alike drugs. They call US drug labeling for progesterone confusing. They also cite an earlier review that found little reason to suspect harm to a developing baby from progesterone. That review named one exception: some synthetic drugs at high doses.
Our editorial summary of this paper, not the article's abstract.
Abstract
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.
