Progesterone supplementation can prevent preterm birth in women with short cervical length in second trimester pregnancy

1
Progesterone supplementationcan prevent preterm
birth in women with short cervical length in
second trimester pregnancy
Mestrado Integrado em Medicina

• Class 15, 1st year
• Introdução à Medicina II
  28th May 2010

2
Summary

• Background
• Preterm Birth
• Second trimester pregnancy
• Cervix
• Progesterone
• Motivations
• Aims
• Methodology
• Results
• Conclusions
• References

3
1. Background

• Preterm birth (PTB)
• 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

1 How HY,et al, 2009 2
Lee HJ, et al,, 2009 3
Grimes-Dennis J, et al, 2007
4
Summary

1. Background
2. Motivations
3. Aims
4. Methodology
5. Results
6. Conclusions
7. 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

1. Background
2. Motivations
3. Aims
4. Methodology
5. Results
6. Conclusions
7. 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)

Search in PubMed, ISI Web of Knowledge, SCOPUS,
Cochrane database of SR
10
4. Methodology4.2. 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)

11
4. Methodology4.3. Articles selection
12
4. Methodology 4.4. Quality assessment

• Criteria used extracted from Sindhu, Carpenter et
  al. 19976
• Numerical rate (0-100)
• To facilitate comparisons between studies

13
4. Methodology 4.4. Quality assessment
Sindhu, Carpenter et al. 19976
14
4. Methodology 4.5. Data extration
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 lt15mm Transvaginal ultrasonography Cervical lenght lt28mm Transvaginal ultrasonography Cervical lengthlt25mm
Participants 250 women (cervical lengthlt15mm) Vaginal progesterone group 125 Placebo group 125 46 women (cervical lenght lt28mm) Vaginal progesterone group19 Placebo group27 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 CLlt25 mm Transvaginal ultrasound CLlt25 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 (N75)
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 (N42) or weekly intramuscular injections of 17OHP-C (N37)
17
4. Methodology4.6. Data management

• Review Manager 5
• SPSS statistics 18

18
4. Methodology4.7. 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. Methodology4.7. Data analysis
20
Summary

• Background
• Motivations
• Aims
• Methodology
• Results
• Conclusions
• References

21
5. Results
22
5. Results
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. 2009 Feb5(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.2009 Spring2(2)107-15.
• 3 Grimes-Dennis J, Berghella V. Cervical length
  and prediction of preterm delivery. Curr Opin
  Obstet Gynecol. 2007 Apr 19(2)191-5.
• 4 Denney JM, Culane JF, Goldenberg RL.
  Prevention of preterm birth. Womens Health (Lond
  Engl). 2008 Nov4(6)625-38
• 5 Thornton JG. Progesterone and preterm
  labor--still no definite answers. N Engl J Med.
  2007 Aug 2357(5)499-501.
• 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 1262-1268.