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.
PMID 3175947 3175947 DOI 10.1002/tera.1420380206 10.1002/tera.1420380206 Yovich et al. 1988, Yovich 1988
Cite this article
Yovich, J. L., Turner, S. R., & Draper, R. (1988). Medroxyprogesterone acetate therapy in early pregnancy has no apparent fetal effects. Teratology, 38(2), 135-144. https://doi.org/10.1002/tera.1420380206
Yovich JL, Turner SR, Draper R. Medroxyprogesterone acetate therapy in early pregnancy has no apparent fetal effects. Teratology. 1988;38(2):135-144. doi:10.1002/tera.1420380206
Yovich, J. L., et al. "Medroxyprogesterone acetate therapy in early pregnancy has no apparent fetal effects." Teratology, vol. 38, no. 2, 1988, pp. 135-144.
From 1964 to 1976, a cohort study was performed in West Germany to study the possible influence of various factors on pregnancy and child development. Results of the evaluation of 13,643 pregnancies are given with respect to possible teratogenetic effects of antiemetic drugs and sex hormones administered in early pregnancy. There was no evidence of an increased risk of major malformations following the intake of certain antiemetic drugs and progesterone. Also, the use of a hormonal pregnancy test was not significantly associated with an increase of major malformations.
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.
therapeutics/prescribing-safety/medication-safety-in-pregnancygenetics-and-immunology/reproductive-immunology/antiphospholipid-and-thrombophiliapregnancy/pregnancy-complications/hypertensive-disorders
Open Access
Murvai VR et al., 2025·BMC pregnancy and childbirth
Antiphospholipid syndrome (APS) is an autoimmune disorder associated with thrombotic events and adverse obstetric outcomes, particularly in its obstetric form (OAPS). Affecting approximately 0.5% of the population, APS is a leading contributor to recurrent pregnancy loss (RPL), preeclampsia (PE), and fetal growth restriction ((FGR). Despite advancements in understanding its pathophysiology and management, optimal treatment strategies for APS in pregnancy remain challenging and require systematic evaluation. This review synthesizes current evidence on APS mechanisms, diagnostic criteria, and therapeutic interventions, with a focus on maternal and fetal outcomes in OAPS. A comprehensive search of PubMed, was conducted to identify studies exploring APS pathogenesis, diagnostic standards, and treatment efficacy in obstetric settings. Inclusion criteria prioritized randomized controlled trials, cohort studies, and systematic reviews with a clear focus on APS and pregnancy. The review confirmed that APS current accepted pathogenesis is governed by a "two-hit" model, where antiphospholipid antibodies (aPLs) initiate endothelial damage, culminating in thrombosis and placental insufficiency. Epidemiological analysis underscores the prevalence and severity of APS in obstetric contexts, with lupus anticoagulant (LA) emerging as a significant predictor of adverse outcomes. Evidence supports the use of low-dose aspirin (LDA) and heparin to reduce miscarriage rates, while adjunctive treatments, such as hydroxychloroquine (HCQ), have shown promise in improving live birth rates and reducing preterm delivery in high-risk cases. Emerging therapies, including tumoral necrosis factor (TNF-alpha) inhibitors and nitric oxide modulators, may offer additional benefits in refractory cases. APS remains a critical determinant of adverse pregnancy outcomes, necessitating precise diagnostic criteria and tailored management approaches. This systematic review emphasizes the importance of individualized therapeutic regimens to optimize maternal and fetal health in OAPS and highlights areas for future research, particularly regarding novel pharmacological approaches. Further studies are essential to refine treatment protocols and improve clinical guidelines for managing APS in pregnancy.
contraception/adverse-effects/cardiovascular-effectstherapeutics/prescribing-safety/medication-safety-in-pregnancy
Open Access
To evaluate the association between contemporary hormonal contraceptive use and the risk of incident ischaemic stroke and myocardial infarction.
Real-world, nationwide, prospective cohort study.
Denmark, by use of national registries. All women aged 15-49 years residing in Denmark between 1996 and 2021, with no history of arterial or venous thrombosis, antipsychotics use, cancer, thrombophilia, liver disease, kidney disease, polycystic ovary syndrome, endometriosis, infertility treatment, hormone therapy use, oophorectomy, and hysterectomy. First time diagnosis of ischaemic stroke or myocardial infarction at discharge. Among 2 025 691 women followed up for 22 209 697 person years, 4730 ischaemic strokes and 2072 myocardial infarctions occurred. Standardised ischaemic stroke rate per 100 000 person years were 18 (95% confidence interval 18 to 19) for no use, 39 (36 to 42) for combined oral contraception, 33 (25 to 44) for progestin-only pills, and 23 (17 to 29) for intrauterine device. Standardised myocardial infarction rate per 100 000 person years were 8 (8 to 9) for no use, 18 (16 to 20) for combined oral contraception, 13 (8 to 19) for progestin-only pills, and 11 (7 to 16) for intrauterine device. Compared with no use, current use of combined oral contraception was associated with an adjusted rate ratio of 2.0 (1.9 to 2.2) for ischaemic stroke and 2.0 (1.7 to 2.2) for myocardial infarction. These corresponded to standardised rate differences of 21 (18 to 24) extra ischaemic strokes and 10 (7 to 12) extra myocardial infarctions per 100 000 person years. Compared with no use, current use of progestin-only pills was associated with an adjusted rate ratio of 1.6 (95% CI 1.3 to 2.0) for ischaemic stroke and 1.5 (1.1 to 2.1) for myocardial infarction, equating to 15 (6 to 24) extra ischaemic strokes and four (-1 to 9) extra myocardial infarctions per 100 000 person years. Increased arterial thrombotic risk was also observed with use of the combined vaginal ring (adjusted incidence rate ratio of 2.4 (1.5 to 3.7) for ischaemic stroke and 3.8 (2.0 to 7.3) for myocardial infarction), patch (3.4 (1.3 to 9.1) and no myocardial infarctions), and progestin-only implant (2.1 (1.2 to 3.8) and ≤3 myocardial infarctions), whereas no increased risk was observed with progestin-only intrauterine device (1.1 (1.0 to 1.3) for ischaemic stroke and 1.1 (0.9 to 1.3) for myocardial infarction). Use of contemporary oestrogen-progestin and progestin-only contraceptives was associated with an increased risk of ischaemic stroke and, in some cases, myocardial infarction except for the levonorgestrel-releasing intrauterine device, which was not associated with either. Although absolute risks were low, clinicians should include the potential risk of arterial thrombosis in their assessment of the benefits and risks when prescribing a hormonal contraceptive method.