Teratogenicity of Progestogens Given During the First Trimester of Pregnancy

Katz, Zhanna; Lancet, M; SKORNIK, J.; Chemke, Juan; Mogilner, B.M.; KLINBERG, M.

doi:10.1097/00006254-198511000-00016

Cited by 29 publications

(41 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Katz et al [29] prospectively followed mothers who were treated with hormones because of bleeding during the first trimester. One group (n=1608) was treated with progestins (either medroxyprogesterone acetate or 17a-hydroxyprogesterone caproate) beginning in the first trimester; their outcomes were compared with those of 1146 mothers who were not exposed.…”

Section: Cardiac Anomaliesmentioning

confidence: 99%

Spermicides, hormonal contraception and congenital malformations

Simpson

Phillips

1990

Adv Contracept

View full text Add to dashboard Cite

Allegations that inadvertent pregnancies in contraceptive users are associated with congenital anomalies continue to be common. In 1985, a review by one of us concluded that there is little or no scientific basis for such claims [1]. Since then, additional data have substantiated this conclusion, particularly with respect to spermicides and hormonal contraception. The purpose of this review is to update information with respect to potential teratogenicity for these two contraceptive methods.

show abstract

Section: Cardiac Anomaliesmentioning

confidence: 99%

Spermicides, hormonal contraception and congenital malformations

Simpson

Phillips

1990

Adv Contracept

View full text Add to dashboard Cite

show abstract

“…Although a large number of studies have failed to show progesterone as a human teratogen (10,12,21). It would be pertinent to note that almost all of the major studies performed to explore the link of exogenous progesterone with birth defects were carried out in the 1970s and 1980s, when in-vitro fertilization was not as common as it is nowbeing the mechanism of conception in almost 1% of all live births in developed countries.…”

Section: Discussionmentioning

confidence: 99%

The role of folic acid in prevention of neural tube defects caused by high dose progesterone.

Iqbal

Qamar²,

Butt³

et al. 2011

Turkish Neurosurgery

View full text Add to dashboard Cite

AIm:To describe the effect of high dose progesterone (HDP) alone, or in combination with folic acid (FA), on occurrence of neural tube defects (NTDs) in chick embryo. mAterIAl and methOds: 60 Fertile, specific eggs of Fyoumi species of chick were selected at zero hr of incubation. They were incubated at 37.5 ºC and 75% relative humidity until the embryos reached stage eight of development. At this stage the eggs were divided into four groups consisting of 15 eggs/group. The 1st group was incubated without any operation. The 2nd group was injected with physiological saline. The 3rd and 4th groups were injected with HDP (20x physiologic dose of progesterone) and HDP with supplement of 5 micrograms/embryo of FA, respectively. After 48 hrs of incubation, all embryos were reviewed for the presence of NTDs under light microscopy.results: None of the eggs in the control, and saline injection groups showed NTDs, whereas 75 % (9/12) of the embryos in the 3rd group, and 58.3 % (7/12) of the chick embryos in 4th group showed NTDs. COnClusIOn: Exogenous progesterone at levels twenty times above its physiologic range in chick embryos causes NTDs. FA supplementation decreases the frequency of NTDs but does not abolish them.KeywOrds: Neural tube defects, Progesterone, Folic acid, Chick embryo, Neural tube closure ÖZ AmAÇ: Yalnızca Progesteron ve progesterona ilave olarak Folik asit ile ile kombine edilmiş uygulamanın civciv embiryosunda nöral tüp defekti oluşumu üzerine olan etkisi. yÖntem ve GereÇ: Çalışmada, inkübasyonun 0. saatinde 60 fertil Fyoumi türü civciv embiryosu kullanıldı.Tüm embiryolar gelişimlerinin 8. evresine kadar, 37,5 ºC ve 75 % nemli ortamda inkübasyona tabi tutuldu. Bu evrede embiryolar 15'erli 4 gruba ayrıldı. Birinci grup herhangi bir işleme maruz bırakılmaksızın inkübasyona tabi tutuldu. İkinci gruba serum fizyolojik injeksiyonu yapıldı. Üçüncü gruba yüksek doz progesteron (fizyolojik dozun 20 katı), dördüncü gruba yüksek doz progesterona ek olarak 5 mikrogram folik asit injeksiyonu yapıldı. Bu işlemlerden sonraki 48 saat boyunca inkübe edilen embriyolar ışık mikroskobunda nöral tüp defekti gelişimi açısından incelemeye alındı.BulGulAr: Kontrol grubunda ve serum fizyolojik injeksiyonu yapılan grupta nöral tüp defekti saptanmazken, 3. grupta % 75 oranında (9/12), 4. grupta ise % 58,3 (7/12) oranında nöral tüp defekti geliştiği görüldü.sOnuÇ: Fizyolojik dozun 20 katında uygulanan progesteron civciv embriyolarında nöral tüp defekti oluşumuna neden olmaktadır. Folik asit desteği nöral tüp defekti oluşum sıklığını azaltsa da defektin görülmesini tam olarak ortadan kaldıramamaktadır.

show abstract

“…None of the epidemiological studies described a "progestational non-genital organ teratogenic syndrome." You will also note that many of the studies with negative results were published before 1977 (Boldt, 1976;Bracken et al, 1978;Briggs and Briggs, 1979;Burstein and Wasserman, 1964;Castilla et al, 1979;Check et al, 1985Check et al, , 1986Correy et al, 1991;Czeizel et al, 1983;Czeizel and Kodaj, 1995;Darling and Hawkins, 1981;Ferencz et al, 1980;Goujard and Remeau-Roquette, 1977;Gray and Pardthaisong, 1991;Greenberg et al, 1975Greenberg et al, , 1977Katz et al, 1985;Haller, 1974;Harlap and Eldor, 1980;Harlap et al, 1975Harlap et al, , 1985Heinonen et al, 1977b;Janerich, 1979, Janerich et al, 1977, 1980Kasan and Andrews, 1980;Lammer et al, 1986;Linn et al, 1983;Martinez-Frias, 1998;Matsunaga and Shiota, 1979;Michaelis et al, 1983;Mitchell et al, 1992;Mulvihill et al, 1974;Newman et al, 1977;Oakley, 1979aOakley, , b, 1984Oakley et al, 1973;Oechsli, 1976;Pardthaisong et al, 1988…”

Section: -1987: Effect Of the Fda Package Insert Warningmentioning

confidence: 99%

“…These authors did not attribute an increased risk of fetal malformations to 17␣-HPC exposure during the critical phases of organogenesis. Katz et al (1985) published data derived from a prospective study of 2764 women who had experienced firsttrimester vaginal hemorrhage and who were treated with 17␣-HPC or 20 -30 mg of oral medroxyprogesterone acetate (MPA). The duration of therapy ranged from 1 to 33 weeks, with a mean of 48 days.…”

Section: -1987: Effect Of the Fda Package Insert Warningmentioning

confidence: 99%

“…The inclusion in the control population of women who had experienced vaginal bleeding during the first trimester is most important because the rate of malformations following first-trimester hemorrhage is increased compared to that in the general population (Brent and Franklin, 1960;Brent, 1990Brent, , 1993bBurge, 1951;Funderburk et al, 1980;Matsunaga and Shiota, 1979;Nishimura et al, 1974;Nishimura, 1970;Oakley, 1979a, b;Ornoy et al, 1976;Peckham, 1970;South, 1973;National Institute of Child Health and Human Development Workshop, 1993;Turnbull and Walker, 1956). Katz et al (1985) provided data indicating that no increase in nongenital congenital malformations was noted in women treated with progestogens compared to cohort control groups. Resseguie et al (1985) evaluated the medical records of women treated with 17␣-HPC for preeclampsia, the prevention of spontaneous abortions, premature labor, and threatened abortion, and determined the incidence of congenital malformations in the offspring.…”

Section: -1987: Effect Of the Fda Package Insert Warningmentioning

confidence: 99%

See 1 more Smart Citation

Nongenital malformations following exposure to progestational drugs: The last chapter of an erroneous allegation

Brent

2005

Birth Defect Res A

View full text Add to dashboard Cite

In the late 1960s and 1970s, a number of epidemiological studies were published indicating that pregnant women who were exposed to an array of sex steroids delivered infants with an increased incidence of nongenital congenital malformations. Because of these publications, the Food and Drug Administration (FDA), in conjunction with various pharmaceutical companies, labeled the therapeutic exposure of progestational drugs and contraceptives in pregnant women as a risk factor for limb-reduction defects (LRDs) and congenital heart defects (CHDs). Subsequently there was a rapid decrease in the exposure of pregnant women to these drugs and the initiation of numerous lawsuits alleging that a particular progestational drug was responsible for a child's nongenital congenital malformation. Wilson and Brent (1981) published an article indicating that epidemiological and animal studies of these drugs, and basic science did not support the package insert's warnings. Many new and previous animal and epidemiological studies did not support the FDA box warning. In 1987 the FDA held a hearing in which the FDA, the Teratology Society, the Centers for Disease Control and Prevention, the American College of Obstetrics and Gynecology, and other organizations supported the position that progestational agents did not result in nongenital malformations. An editorial appeared in Teratology congratulating the FDA for removing the warning label on oral contraceptives regarding nongenital malformations. In 1999 the FDA published new wording for package inserts that removed warnings for nongenital malformations for all progestational agents. In spite of the recent changes in the package inserts, lawsuits have alleged that progestational drugs cause nongenital malformations. It took 22 years from the time a box warning was required by the FDA until the warnings were removed in 1999. The 1999 FDA publication, which is a scholarly and objective document, should put an end to 2 decades of concern and anxiety for pregnant women or women of reproductive age. Could scientists, the pharmaceutical companies, or the FDA have prevented the mislabeling of progestational drugs with regard to their teratogenic risks? Was the epidemiological or teratology community at fault because they did not critique and respond to the early publications? Did the FDA act too slowly? The epidemiologic analyses, animal studies, and basic science principles have been reviewed, and it is obvious that clinically utilized progestational drugs do not cause nongenital malformations (i.e., LRDs and CHDs).

show abstract

Teratogenicity of Progestogens Given During the First Trimester of Pregnancy

Cited by 29 publications

References 0 publications

Spermicides, hormonal contraception and congenital malformations

Spermicides, hormonal contraception and congenital malformations

The role of folic acid in prevention of neural tube defects caused by high dose progesterone.

Nongenital malformations following exposure to progestational drugs: The last chapter of an erroneous allegation

Contact Info

Product

Resources

About