1. Class 15, 1st year Introdução à Medicina II 28th May 2010
Mestrado Integrado em Medicina
Progesterone supplementation can prevent preterm birth in women with short cervical length in second trimester pregnancy
Intervention
Outcome
Population
Class 15, 1st year
Introdução à Medicina II th May 2010

2. Summary Background Motivations Aims Methodology Results Conclusions
Preterm Birth
Second trimester pregnancy
Cervix
Progesterone
Motivations
Aims
Methodology
Results
Conclusions
References

3. 1. Background Preterm birth (PTB): Cervix: Second trimester pregnancy
Birth before 37 weeks of gestation [1,2]
Cervix:
Lower end of uterus
Normal:
3-5 cm [3]
Short:
Inferior to 2.5cm [2]
Second trimester pregnancy
15th-28th week
Progesterone
falar sobre os aspectos iniciais introdutórios:
_ the problem: PTB
_ defined as…
_ considered one of the main problems that lead to perinatal morbidity and mortality.
_iIt has increased in the last years (due to the delayed child bearing and the growing frequency of multifetal pregnancies from assisted reproductive technology)
_one of the possible causes: short cervix
_defined as… in second trimester
_ why? The cervix is involved in the maintenance of pregnancy:
_ the endocervix produces a mucus, which forms a mucus plug
_ the cervix remains closed through the most part of the pregnancy, assuring a sterile and safe environment for the baby. (Until the end of pregnancy, where it shortens and starts to open)
A short cervix gradually opens due to the pressure caused by the increasing weight of the, becoming thinner and widener and ultimately causing an early delivery (PTB)
_possible treatment: progesterone
_can act as an antagonist of oxytocin (which has a major role in the delivery, stimulating contractions associated with labor), inhibiting its effects, causing the uterine muscles to relax and contract less.
_ there are still controversies about its efects
[1 ] How HY,et al, [2] Lee HJ, et al,, [3] Grimes-Dennis J, et al, 2007

4. Summary Background Motivations Aims Methodology Results Conclusions
References

5. 2. Motivations
Lee HJ, MD, PhD et. al, Management of Pregnancies With Cervical Shortening: A Very Short Cervix Is a Very Big Problem, 2009
How HY, Sibai BM, Progesterone for the prevention of preterm birth: indications, when to initiate, efficacy and safety,2009

6. Summary Background Motivations Aims Methodology Results Conclusions
References

7. 3. Aims
Summarize the available information and explain the possible controversies
Assess the efficacy of progesterone supplementation in the prevention of PTB associated to short cervical length in second trimester pregnancy
Assess the effects of different types of progesterone and types of progesterone administration

8. Summary Background Motivations Aims Methodology:
4.1. Selection criteria
4.2. Query selection
4.3. Articles’ selection
4.4 Quality assessment
4.5. Data extraction
4.6. Data management
4.7. Data analysis
Results
Conclusions
References

9. 4. Methodology 4.1. Selection criteria
Type of study: Systematic Review
Inclusion Criteria
Exclusion Criteria
Progesterone
prevention of preterm birth
short cervix
Type of study:
Randomized Clinical Trials
Date:
Articles not published in the last 10 years
Language:
Other than Portuguese, English, French or Spanish
Quality rate (less than 60 points)
We will only include articles that report the association between the use of progesterone supplementation and the prevention of PTB in a population of women with short cervix in second trimester pregnancy
The quality of the articles, if too low, will also be na exclusion factor
Search in: PubMed, ISI Web of Knowledge, SCOPUS, Cochrane database of SR

10. 4. Methodology 4.2. Query selection
(progesterone OR progest*) AND (cervix or cervic*) AND (premature birth OR ((preterm OR premature) AND (birth OR delivery OR labour)) OR prematur*) AND (pregnancy OR pregnancy trimester, second OR midtrimester OR second trimester OR midpregnancy)
Intervention
Outcome
Population
We used some mesh terms (in bold), wildcards(*) and many synonyms. We didn’t limit these searches to clinical trials nor to a specific date and we also chose not to use search filters in most of them. Instead we decided to make more sensitive searches in order to obtain a higher number of articles which we will then analyze.

11. 4. Methodology 4.3. Articles’ selection
Pubmed U ISI Web U Scopus U Cochrane
202 Articles #1 #4 #3 #2
DECISION
16 Articles
7 Included articles
Primary selection:
Title
Abstract
Second selection:
Full article
After having collected all of the articles, we eliminated the duplicated ones and end up with 202 articles.
The articles were submitted to 2 selections:
_1st: they were distributed by 4 groups of 2 elements who independently analyzed the title and the abstract and decided if the article should be included or excluded. We formed another group of 3 elements which intervened when the 2 reviewers had different opinions. This last group was formed by 3 elements that reached a final decision.
_2nd : similar. However we analyzed the full article. The exclusion reasons were registered
14 articles weren’t available: we contacted the respective authors via asking the full text article. We are still waiting for the answers
We send s to some of the responsible of ongoing clinical trials in order to obtain more informations

12. 4. Methodology 4.4. Quality assessment
Criteria used extracted from Sindhu, Carpenter et al. 1997[6]
Numerical rate (0-100):
To facilitate comparisons between studies
Article to rate
Discussion and Consensus
Rating
Reader no.1
Group no. x
Reader no.2
The articles were randomly distributed to groups of 2 elements who read them and reach to a consensus about their quality, classifying them according to…
The quality of the articles was assessed using an established list16, which we find to be similar to the Consort list, having in addition a quantitative scale from 0 to 100 to classify the article, which made comparisons between articles easier and more efficient. Each article was analyzed by 2 elements independently. We didn’t exclude any article since all of them fulfilled our criteria (the score was superior to 60 points, the lowest score was 70,5).

13. 4. Methodology 4.4. Quality assessment
Sindhu, Carpenter et al. 1997[6]

14. 4. Methodology 4.5. Data extration
Participants
Number of participants
General caracteristics:
Race
Age
Singleton or twin pregnancy
Obstetrical history
Methods
How the cervical length condiction was assessed?
Main features of study :
Randomised intervention
Allocation concealment
Exclusion criteria
Outcomes
Only the ones that show relation between PTB and progesterone supplementation
Intervention
Type of progesterone
Administration aspects:
Dosages
Application moment
Application period

15. 4. Methodology 4.5. Data extration
Articles
Fonseca EB et al, 2007
DeFranco EA et al, 2007
Berghella et al, 2010
Short cervix assessment and definition
Transvaginal ultrasonography
Cervical lenght <=15mm
Cervical lenght <28mm
Cervical length<25mm
Participants
250 women (cervical length<15mm):
Vaginal progesterone group: 125
Placebo group: 125
46 women (cervical lenght <28mm)
Vaginal progesterone group:19
Placebo group:27
Women with prior preterm birth,
152 received cerclage
148 did not receive cerclage
Intervention
Vaginal progesterone: 200mg capsules
Placebo: safflower oil
Daily treatment
vaginal gel (containing 90 mg of progesterone)
placebo: identical bioadhesive delivery system, but without progesterone.
daily treatment
17 alpha-hydroxyprogesterone dose:
250mg intramusculary starting at 16 weeksand continued weekly until 36 weeks

16. 4. Methodology 4.5. Data extration
Articles
Facchinetti et al, 2007
Keeler et al, 2009
Short cervix assessment and definition
Transvaginal ultrasound
CL<=25 mm
CL<25 mm
Participants
Women with singleton pregnancy, who were hospitalized for preterm labor
30 women received 17P
30 women did not receive 17P
Patients (asymptomatic, singleton pregnancies) with a cervical length (N=75)
Intervention
Patients who were enrolled as cases received 341 mg of 17P intramuscularly every 4 days, until gestational week 36. The remaining patients were included as control subjects and received no drugs.
McDonald cerclage (N=42) or weekly intramuscular injections of 17OHP-C (N=37)
Aqui só aparecem 5 artigos porque os outros 2 são complementos. Por isso não valia a pena referir
É preciso dizer isto (oralmente)…

17. 4. Methodology 4.6. Data management
Review Manager 5
SPSS statistics 18

18. 4. Methodology 4.7. Data analysis
Based on tables and forest plot
Relative risk as effect measure
95% Confidence interval as dispersion measure
Statistical method:
Inverse variance
Heterogeneity:
Observed using Chi-Square test

19. 4. Methodology 4.7. Data analysis
Homogeneous
Heterogeneous
Metanalysis
Subgroups
Statistical Analysis of Data

20. Summary Background Motivations Aims Methodology Results Conclusions
References

21. 5. Results
Heterogeneity condition wasn’t verified. So, we will perform a metanalysis

22. 5. Results
Heterogeneity condition wasn’t verified. So, we will perform a metanalysis

23. Summary Background Motivations Aims Methodology Preliminary results
Conclusions
References

24. 6. Conclusions
The analysis of these articles suggests that progesterone might prevent preterm birth in women with short cervix on second trimester. However, there is no evidence that it has a higher effect on the prevention of PTB than cerclage.

25. 7. References
[1] How HY, Sibai BM. Progesterone for the prevention of preterm birth: indications, when to initiate, efficacy and safety. Ther Clin Risk Manag Feb;5(1):55-64.
[2] Lee HJ, Park TC, Norwitz ER. Management of Pregnancies With Cervical Shortening: A Very Short Cervix Is a Very Big Problem. Rev Obstet Gynecol Spring;2(2):
[3] Grimes-Dennis J, Berghella V. Cervical length and prediction of preterm delivery. Curr Opin Obstet Gynecol Apr ;19(2):191-5.
[4] Denney JM, Culane JF, Goldenberg RL. Prevention of preterm birth. Womens Health (Lond Engl) Nov;4(6):625-38
[5] Thornton JG. Progesterone and preterm labor--still no definite answers. N Engl J Med Aug 2;357(5):
[6] Sindhu, F., L. Carpenter, et al. (1997). "Development of a tool to rate the quality assessment of randomized controlled trials using a Delphi technique." Journal of Advanced Nursing 25: