Pregnancy-related complications and perinatal outcomes following progesterone supplementation before 20 weeks of pregnancy in spontaneously achieved singleton pregnancies: a systematic review and meta-analysis

Abstract

Background Progesterone supplementation is widely performed in women with threatened miscarriage or a history of recurrent miscarriage; however, the effects of early progesterone supplementation on pregnancy-related complications and perinatal outcomes in later gestational weeks remain unknown. Methods Ovid MEDLINE, the Cochrane Library, Embase and ClinicalTrials.gov were searched until April 3rd, 2021. Randomized controlled trials regarding spontaneously achieved singleton pregnancies who were treated with progestogen before 20 weeks of pregnancy and were compared with those women in unexposed control groups were selected for inclusion. We performed pairwise meta-analyses with the random-effects model. The risk of bias was assessed according to the Cochrane Collaboration tool. The primary outcomes included preeclampsia (PE), and gestational diabetes mellitus (GDM), with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs). Results We identified nine eligible studies involving 6439 participants. The pooled OR of subsequent PE following early progestogen supplementation was 0.64 (95% CI 0.42–0.98, moderate quality of evidence). A lower OR for PE was observed in the progestogen group when the subgroup analysis was performed in the vaginal subgroup (OR 0.62, 95%CI 0.40–0.96). There was insufficient evidence of a difference in the rate of GDM between pregnant women with early progestogen supplementation and unexposed pregnant women (OR 1.02, 95% CI 0.79–1.32, low quality of evidence). The pooled OR of low birth weight (LBW) following oral dydrogesterone was 0.57 (95% CI 0.34–0.95, moderate quality of evidence). The results were affected by a single study and the total sample size of enrolled women did not reach the required information size. Conclusion Use of vaginal micronized progesterone (Utrogestan) in spontaneously achieved singleton pregnancies with threatened miscarriage before 20 weeks of pregnancy may reduce the risk of PE in later gestational weeks. Among spontaneously achieved singleton pregnancies with threatened miscarriage or a history of recurrent miscarriage, use of oral dydrogesterone before 20 weeks of pregnancy may result in a lower risk of LBW in later gestational weeks. However, the available data were not sufficient to reach definitive conclusions, which highlighted the need for future studies.

Monitoring medicine prescriptions before, during and after pregnancy in Italy

“…As regard to progestogens, a proportion of 19.0% of women was exposed to progesterone during pregnancy, mainly concentrated in the 1 st TP (14.8%), probably in an attempt to prevent miscarriages. The use of progestogens, in particular in the prevention of non-recurrent miscarriage, is worthy of attention because its efficacy is still unsupported by conclusive evidence [ 42 , 43 ]. In 2009 the World Health Organization (WHO) recommended not to prescribe progestogens for preventing miscarriages.…”

Uterine Deletion of Bmal1 Impairs Placental Vascularization and Induces Intrauterine Fetal Death in Mice

“…Allowing for a higher concentration of serum P4 in P4-supplemented cKO mice compared to WT mice, the possibility that expression of CD161 on uNK cells in the spongiotrophoblast layer was mediated through a glucocorticoid receptor pathway. As clinical evidence, progesterone supplement was demonstrated to prevent miscarriage in women with recurrent miscarriage of unclear etiology [ 41 ] and protect the onset of HDP [ 42 ]. Recently, it was also reported that progesterone supplement therapy is clinically effective for the functional failure of the placenta with structural abnormalities [ 43 ].…”

Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis

“…I 2 was used to evaluate heterogeneity, and values of 25, 50, and 75% were used for classification of low, moderate, and high heterogeneity, respectively ( Higgins et al, 2003 ). The meta-analysis was performed using a random-effects model that was weighted according to the sample size of studies ( Wu et al, 2021 ). A difference with a p value below 0.05 was considered statistically significant.…”