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Meta-Analysis
. 2011 Feb 16;2011(2):CD005354.
doi: 10.1002/14651858.CD005354.pub2.

Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles

Madelon van Wely  1 , Irene Kwan, Anna L Burt, Jane Thomas, Andy Vail, Fulco Van der Veen, Hesham G Al-Inany
Affiliations
Meta-Analysis

Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles

Madelon van Wely et al. Cochrane Database Syst Rev. .

Abstract

Background: Several systematic reviews compared recombinant gonadotrophin with urinary gonadotrophins (HMG, purified FSH, highly purified FSH) for ovarian hyperstimulation in IVF and ICSI cycles and these reported conflicting results. Each of these reviews used different inclusion and exclusion criteria for trials. Our aim in producing this review is to bring together all randomised studies in this field under common inclusion criteria with consistent and valid statistical methods.

Objectives: To compare the effectiveness of recombinant gonadotrophin (rFSH) with the three main types of urinary gonadotrophins (i.e. HMG, FSH-P and FSH-HP) for ovarian stimulation in women undergoing IVF or ICSI treatment cycles.

Search strategy: An extended search was done according to Cochrane guidelines including the Menstrual Disorders & Subfertility Group's Specialised Register of controlled trials, The Cochrane Central Register of Controlled Trials, MEDLINE (1966 to May 2010), EMBASE (1980 to May 2010), CINAHL (1982 to May 2010), National Research Register, and Current Controlled Trials.

Selection criteria: All randomised controlled trials reporting data comparing clinical outcomes for women undergoing IVF/ICSI cycles and using recombinant FSH in comparison with HMG or highly purified HMG, purified urinary FSH (FSH-P), and highly purified urinary FSH (FSH-HP) for ovarian hyperstimulation in IVF or ICSI cycles were included.

Data collection and analysis: Primary outcome measure was live birth rate and OHSS per randomised woman.Binary outcomes were analysed using odds ratios and also reported in absolute terms. Grouped analyses were carried out for all outcomes to explore whether relative effects differed due to key features of the trials.

Main results: We included 42 trials with a total of 9606 couples. Comparing rFSH to any of the other gonadotrophins irrespective of the down-regulation protocol used, did not result in any evidence of a statistically significant difference in live birth rate (28 trials, 7339 couples, odds ratio 0.97, 95% CI 0.87 to 1.08). This suggests that for a group with a 25% live birth rate using urinary gonadotrophins the rate would be between 22.5% and 26.5% using rFSH. There was also no evidence of a difference in the OHSS rate (32 trials, 7740 couples, OR 1.18, 95% CI 0.86 to 1.61). This means that for a group with 2% risk of OHSS using urinary gonadotrophins, the risk would be between 1.7% and 3.2% using rFSH.

Authors' conclusions: Clinical choice of gonadotrophin should depend on availability, convenience and costs. Further research on these comparisons is unlikely to identify substantive differences in effectiveness or safety.

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Conflict of interest statement

None known

Figures

1
1
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Funnel plot of comparison: 1 rFSH versus urinary gonadotrophins, outcome: 1.1 Live birth (or pregnancy ongoing beyond 20 weeks).
4
4
Funnel plot of comparison: 1 rFSH versus urinary gonadotrophins, outcome: 1.5 Ovarian Hyperstimulation Syndrome (OHSS).
5
5
Funnel plot of comparison: 1 rFSH versus urinary gonadotrophins, outcome: 1.9 Clinical pregnancy.
6
6
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.1 Live birth (or ongoing pregnancy) by urinary gonadotrophin.
7
7
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.2 Live birth (or ongoing pregnancy) by down regulation protocol.
8
8
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.3 Live birth (or ongoing pregnancy) by fresh/frozen policy.
9
9
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.4 Live birth (or ongoing pregnancy) by sponsor.
10
10
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.5 OHSS by urinary gonadotrophin.
11
11
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.6 OHSS by down regulation protocol.
12
12
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.8 OHSS by sponsor.
13
13
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.9 Clinical pregnancy by urinary gonadotrophin.
14
14
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.10 Clinical pregnancy by down regulation protocol.
15
15
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.11 Clinical pregnancy by fresh/frozen policy.
16
16
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.12 Clinical pregnancy by sponsor.
17
17
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.15 Multiple pregnancy (per woman).
18
18
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.16 Multiple pregnancy (per pregnancy).
19
19
Forest plot of comparison: 1 rFSH versus urinary gonadotrophins: primary analyses, outcome: 1.17 Miscarriage (per woman).
1.1
1.1. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 1 Live birth (or ongoing pregnancy) by urinary gonadotrophin.
1.2
1.2. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 2 Live birth (or ongoing pregnancy) by down regulation protocol.
1.3
1.3. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 3 Live birth (or ongoing pregnancy) by fresh/frozen policy.
1.4
1.4. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 4 Live birth (or ongoing pregnancy) by sponsor.
1.5
1.5. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 5 OHSS by urinary gonadotrophin.
1.6
1.6. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 6 OHSS by down regulation protocol.
1.7
1.7. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 7 OHSS by sponsor.
1.8
1.8. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 8 Clinical pregnancy by urinary gonadotrophin.
1.9
1.9. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 9 Clinical pregnancy by down regulation protocol.
1.10
1.10. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 10 Clinical pregnancy by fresh/frozen policy.
1.11
1.11. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 11 Clinical pregnancy by sponsor.
1.12
1.12. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 12 Multiple pregnancy (per woman).
1.13
1.13. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 13 Multiple pregnancy (per pregnancy).
1.14
1.14. Analysis
Comparison 1 rFSH versus urinary gonadotrophins: primary analyses, Outcome 14 Miscarriage (per woman).
2.1
2.1. Analysis
Comparison 2 Sensitivity analyses excluding lower quality trials, Outcome 1 Live birth (or pregnancy ongoing) by urinary gonadotrophin.
2.2
2.2. Analysis
Comparison 2 Sensitivity analyses excluding lower quality trials, Outcome 2 Live birth (or pregnancy ongoing) rFSH vs FSH‐P by down‐regulation.
2.3
2.3. Analysis
Comparison 2 Sensitivity analyses excluding lower quality trials, Outcome 3 Live birth (or ongoing pregnancy) by fresh/frozen policy.
2.4
2.4. Analysis
Comparison 2 Sensitivity analyses excluding lower quality trials, Outcome 4 Live birth (or ongoing pregnancy) by sponsor.
2.5
2.5. Analysis
Comparison 2 Sensitivity analyses excluding lower quality trials, Outcome 5 OHSS by urinary gonadotrophin.
2.6
2.6. Analysis
Comparison 2 Sensitivity analyses excluding lower quality trials, Outcome 6 OHSS by down regulation protocol.
2.7
2.7. Analysis
Comparison 2 Sensitivity analyses excluding lower quality trials, Outcome 7 OHSS by sponsor.
2.8
2.8. Analysis
Comparison 2 Sensitivity analyses excluding lower quality trials, Outcome 8 Clinical pregnancy by urinary gonadotrophin.
2.9
2.9. Analysis
Comparison 2 Sensitivity analyses excluding lower quality trials, Outcome 9 Clinical pregnancy by down regulation protocol.
2.10
2.10. Analysis
Comparison 2 Sensitivity analyses excluding lower quality trials, Outcome 10 Clinical pregnancy by fresh/frozen policy.
2.11
2.11. Analysis
Comparison 2 Sensitivity analyses excluding lower quality trials, Outcome 11 Clinical pregnancy by sponsor.
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References

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