The value of oral micronized progesterone in the prevention of recurrent spontaneous preterm birth: a randomized controlled trial
Authors: Sherif Ashoush
Osama El-Kady
Gehan Al-Hawwary
Ahmed Othman
Journal: Acta Obstetricia Et Gynecologica Scandinavica (2017)
Discipline: CLINICAL MEDICINE
Keywords: Preterm delivery; neonatal intensive care units; oral micronized progesterone; progesterone; randomized controlled trial.
Affiliations: Department of Obstetrics and Gynecology; Faculty of Medicine; Ain Shams University; Cairo Egypt, Department of Obstetrics and Gynecology; Ghamra Military Hospital; Cairo Egypt

Abstract:  Introduction: Progesterone is becoming universally accepted for preventing recurrent spontaneous preterm delivery. There is, however, poor consensus on the effective types and doses of progesterone to be used. Despite the encouraging available research, the role of oral micronized progesterone has not yet been thoroughly investigated. Material and methods: We randomized 212 singleton pregnancies with past history of spontaneous preterm delivery at &lt;37 weeks, into a progesterone group (receiving 100 mg oral micronized progesterone, six-hourly, starting at 14-18 weeks until 37 weeks or delivery) and an identical placebo group. The rate of spontaneous preterm delivery was the primary outcome. Secondary outcomes included gestational age at birth and admission to neonatal intensive care units. Results: The progesterone group delivered at a later gestational age, and needed longer tocolysis-to-delivery intervals (35.4 weeks vs. 33.9 weeks, p = 0.01, and 87 days vs. 36 days, p &lt; 0.001, respectively). The relative risk of spontaneous preterm delivery was 0.7 (95% confidence interval 0.54-0.92, p = 0.01), and the number needed-to-treat to prevent one case of spontaneous preterm delivery was 5 (95% confidence interval 3-20). The two groups had similar rates of operative delivery and postpartum complications. Progesterone was associated with mild maternal dizziness (29.1% vs. 9.8%, p = 0.002), somnolence (41.6% vs. 19.7%, p = 0.002), and vaginal dryness (20.8% vs. 8.7%, p = 0.03), lower neonatal mortality rates (7.3% vs. 25.2%, p &lt; 0.001), and shorter neonatal intensive care unit admissions (p = 0.008). Conclusion: Oral micronized progesterone is effective in preventing spontaneous preterm delivery. The additional advantages of oral administration, affordability, and high safety profile make it worth recommending, at least for further research. 

Retracted: No

PubPeer comments:
 According to the [retraction notice] (13 August 2018),  During further research, the authors noticed that there were some unreliable data in the experimental validations and decided to retract this paper. The authors sincerely apologize for this problem. Here is Fig 4(B):  Evaluation of the liver sections stained with Hematoxylin-eosin (H E) revealed that GS and GS GC combination treatment did not aggravate the damage of ascites to the liver tissues, which was shown in the model control group, such as inflammation or necrosis. GS = Euphorbia kansui, GC = Glycyrrhiza. ![file] Compare with Fig 6(B) from [Lin et al (2016)] :  Liver toxicity in H22 HCC ascites mice (a). Increases in ALT and AST were observed after modeling, without any significant difference between the treatment groups. (b) Evaluation of liver sections stained with H E revealed no significant pathological features such as inflammation or necrosis in any groups, but hepatic cells turned partially fatty along with liquidation, regression, or disappearance of cytoplasm.  ![file] The labeling is not consistent. , 
 Below: Fig 7, where  Lanes 1-4 in the western blot denote the Model, GS, GS GC_synergy and GS GC_antagonism groups, respectively . Above is Fig 8(c) from Lin et al (2016). Lanes are not consistent. ![file] , 
 Above: Fig 5(B),  Kidney toxicity in the H22 HCC ascites mice. ... (b) No specific pathological symptoms were detected in any of the groups. Almost all the kidney cells maintained their normal structures, degeneration and necrosis of the glomeruli and renal tubes induced by toxicants and immunological factors were not observed in any region of the kidney, and no edema or swelling were observed in the renal tubes of the kidney. Flanked by rotated flipped versions of two panels. Below: Fig 7(b) from [Lin et al (2016)] ,  Renal toxicity in H22 HCC ascites mice ...(b) No specific pathological symptoms were detected in different groups. Most kidney cells retained normal structure, without any degeneration or necrosis and edema or swelling of glomerulus and renal tubules.  ![file] Labelling of the reused panels is not consistent. , 
 The paper may be indicated as  retracted on PubMed, but not on the publisher s page, where the html and PDF versions remain, even after 2 years, in an  unretracted state. https: www.ijbs.com v12p0594.htm https: www.ijbs.com v12p0594.pdf ,