Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles

Mohamed A Youssef; Ahmed M Abou‐Setta; Wai Sun Lam

doi:10.1002/14651858.CD003719.pub4

Cochrane Database of Systematic Reviews

Gonadotrofina recombinante versus gonadotrofina coriónica humana urinaria para desencadenar la maduración final de los ovocitos en los ciclos de FIV e ICSI

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DOI:

https://doi.org/10.1002/14651858.CD003719.pub4 Copiar DOI

Base de datos:

Cochrane Database of Systematic Reviews

Versión publicada:

23 abril 2016see what's new

Tipo:

Intervention

Etapa:

Review

Grupo Editorial Cochrane:

Grupo Cochrane de Ginecología y fertilidad

Copyright:

Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

Mohamed A Youssef

Correspondencia a: Department of Obstetrics & Gynaecology, Faculty of Medicine, Cairo University, Cairo, Egypt

[email protected]

[email protected]
Ahmed M Abou‐Setta

Knowledge Synthesis Platform, George and Fay Yee Centre for Healthcare Innovation, University of Manitoba, Winnipeg, Canada
Wai Sun Lam

Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand

Contributions of authors

Mohamed AFM Youssef: performed data extraction and quality assessment of the included trials; was responsible for statistical analysis and interpretation of the data.

Ahmed M Abou‐Setta: contributed to drafts of the review.

Wai Sun Lam: screened and selected studies and entered data for the 2016 update and revised the draft text.

Sources of support

Internal sources

University of Auckland, New Zealand.

External sources

No sources of support supplied

Declarations of interest

Previous author Hesham Al‐Inany contributed to one of the trials included in this review (Study 21447).

No current author has any interest to declare.

Acknowledgements

We would like to thank Cindy Farquhar, Ruth Buist, and Sue Hall from the Cochrane Menstrual Disorders and Subfertility Group, University of Auckland, New Zealand for contributions to previous version of this review. We would also like to thank Ladan Mohammadi Yeganeh (Madani 2013); Beatrice DeMoustier (Study 21447); and the authors of Borges 2004 and Kovacs 2008 for supplying information. We would like to thank Michelle Proctor for her great efforts; she was an author on the first published version of this review.

The authors of the 2016 update thank Ragaa Mansour for contributions to previous versions of this review. They also thank Prof Hesham G Al‐Inany and Prof Mohamed Aboulghar for their contributions to all previous versions of this review.

Version history

Published

Title

Stage

Authors

Version

2016 Apr 23

Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles

Review

Mohamed A Youssef, Ahmed M Abou‐Setta, Wai Sun Lam

https://doi.org/10.1002/14651858.CD003719.pub4

2011 Apr 13

Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles

Review

Mohamed AFM Youssef, Hesham G Al‐Inany, Mohamed Aboulghar, Ragaa Mansour, Ahmed M Abou‐Setta

https://doi.org/10.1002/14651858.CD003719.pub3

2005 Apr 20

Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles

Review

Mohamed AFM Youssef, Hesham G Al‐Inany, Mohamed Aboulghar, Ragaa Mansour, Michelle Proctor

https://doi.org/10.1002/14651858.CD003719.pub2

2002 Jul 22

Recombinant versus urinary human chorionic gonadotrophin for ovulation induction in assisted conception

Protocol

Hesham G Al‐Inany, Mohamed Aboulghar, Ragaa Mansour

https://doi.org/10.1002/14651858.CD003719

Differences between protocol and review

2016 update: We added mild to moderate OHSS, moderate OHSS and undefined OHSS as outcomes and severity as a subgroup. Subgroup analysis was conducted according to the IVF protocol utilised: long GnRH agonist protocol and GnRH antagonist protocol.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Female; Humans;

PICO

Population

Intervention

Comparison

Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Figure 1

Study flow diagram.

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Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Figure 3

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 4

Forest plot of comparison: 1 rhCG versus uhCG for triggering ovulation, outcome: 1.1 Ongoing pregnancy/live birth rate per woman.

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Figure 5

Forest plot of comparison: 1 rhCG versus uhCG for triggering ovulation, outcome: 1.2 OHSS per woman.

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Figure 6

Forest plot of comparison: 1 rhCG versus uhCG for triggering ovulation, outcome: 1.3 Clinical pregnancy rate per woman.

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Figure 7

Forest plot of comparison: 1 rhCG versus uhCG for triggering ovulation, outcome: 1.4 Miscarriage rate per woman.

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Figure 8

Forest plot of comparison: 2 rhLH versus uhCG for triggering ovulation, outcome: 2.1 Ongoing pregnancy/live birth rate per woman.

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Figure 9

Forest plot of comparison: 2 rhLH versus uhCG for triggering ovulation, outcome: 2.2 OHSS per woman.

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Analysis 1.1

Comparison 1 rhCG versus uhCG for triggering ovulation, Outcome 1 Ongoing pregnancy/live birth rate per woman.

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Analysis 1.2

Comparison 1 rhCG versus uhCG for triggering ovulation, Outcome 2 OHSS per woman.

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Analysis 1.3

Comparison 1 rhCG versus uhCG for triggering ovulation, Outcome 3 Clinical pregnancy rate per woman.

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Analysis 1.4

Comparison 1 rhCG versus uhCG for triggering ovulation, Outcome 4 Miscarriage rate per woman.

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Analysis 1.5

Comparison 1 rhCG versus uhCG for triggering ovulation, Outcome 5 No of oocytes retrieved per woman.

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Analysis 1.6

Comparison 1 rhCG versus uhCG for triggering ovulation, Outcome 6 Adverse events per woman.

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Analysis 2.1

Comparison 2 rhLH versus uhCG for triggering ovulation, Outcome 1 Ongoing pregnancy/live birth rate per woman.

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Analysis 2.2

Comparison 2 rhLH versus uhCG for triggering ovulation, Outcome 2 OHSS per woman.

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Analysis 2.3

Comparison 2 rhLH versus uhCG for triggering ovulation, Outcome 3 Clinical pregnancy rate per woman.

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Analysis 2.4

Comparison 2 rhLH versus uhCG for triggering ovulation, Outcome 4 Miscarriage rate per woman.

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Analysis 2.5

Comparison 2 rhLH versus uhCG for triggering ovulation, Outcome 5 No of oocytes retrieved per woman.

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Analysis 2.6

Comparison 2 rhLH versus uhCG for triggering ovulation, Outcome 6 Adverse events per woman.

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Summary of findings for the main comparison. RhCG compared to uhCG for final oocyte maturation triggering in IVF and ICSI cycles

RhCG compared to uhCG for final oocyte maturation triggering in IVF and ICSI cycles
Population: women undergoing final oocyte maturation triggering in IVF and ICSI cycles Setting: ART Intervention: recombinant hCG (rhCG) Comparison: urinary human chorionic gonadotrophin (uhCG)
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	UhCG	RhCG
Ongoing pregnancy/live birth rate per woman	367 per 1000	396 per 1000 (344 to 454)	OR 1.15 (0.89 to 1.49)	1136 (7 studies)	⊕⊕⊕⊝ Moderate^a	—
OHSS per woman ‐ moderate to severe OHSS	10 per 1000	17 per 1000 (11 to 84)	OR 1.76 (0.37 to 8.45)	417 (3 studies)	⊕⊕⊝⊝ Low^b,c	—
Clinical pregnancy rate per woman	330 per 1000	343 per 1000 (300 to 388)	OR 1.06 (0.87 to 1.29)	1806 (13 studies)	⊕⊕⊕⊝ Moderate^a	—
Miscarriage rate per woman	51 per 1000	37 per 1000 (21 to 63)	OR 0.72 (0.41 to 1.25)	1347 (9 studies)	⊕⊕⊝⊝ Low^a,b	—
Adverse events per woman	331 per 1000	179 per 1000 (112 to 406)	OR 0.52 (0.35 to 0.76)	561 (5 studies)	⊕⊕⊕⊝ Moderate^b	Adverse events included: injection site pain, reaction, inflammation, nausea, vomiting, abdominal pain
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ART: assisted reproduction therapy; CI: confidence interval; hCG: human chorionic gonadotrophin; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilisation; OR: odds ratio; rhCG: recombinant hCG; uhCG: urinary hCG
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
^aThe pooled effect included both the line of no effect and appreciable benefit or harm. ^bTotal number of events is less than 300. ^cThe pooled effect included both the line of no effect and appreciable benefit and harm.

Summary of findings for the main comparison. RhCG compared to uhCG for final oocyte maturation triggering in IVF and ICSI cycles

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Summary of findings 2. RhLH compared to uhCG for final oocyte maturation triggering in IVF and ICSI cycles

RhLH compared to uhCG for final oocyte maturation triggering in IVF and ICSI cycles
Population: women undergoing final oocyte maturation triggering in IVF and ICSI cycles Setting: ART Intervention: rhLH (recombinant luteinising hormone) Comparison: urinary human chorionic gonadotrophin (uhCG)
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)
	Assumed risk	Corresponding risk
	UhCG	RhLH
Ongoing pregnancy/live birth rate per woman	371 per 1000	359 per 1000 (231 to 512)	OR 0.95 (0.51 to 1.78)	289 (2 studies)	⊕⊝⊝⊝ Very low^a,b,c
OHSS per woman ‐ Moderate OHSS	126 per 1000	107 per 1000 (55 to 197)	OR 0.83 (0.40 to 1.70)	289 (2 studies)	⊕⊝⊝⊝ Very low^a,b,c
Clinical pregnancy rate per woman	407 per 1000	392 per 1000 (270 to 530)	OR 0.94 (0.54 to 1.64)	289 (2 studies)	⊕⊝⊝⊝ Very low^a,b,c
Miscarriage rate per woman	36 per 1000	34 per 1000 (14 to 82)	OR 0.95 (0.38 to 2.40)	280 (2 studies)	⊕⊝⊝⊝ Very low^a,b,c
Adverse events per woman	1 study reported this outcome in this comparison; event numbers were similar in both groups.			259 (1 study)	—
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ART: assisted reproduction therapy; CI: confidence interval; hCG: human chorionic gonadotrophin; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilisation; OR: odds ratio; rhLH: recombinant luteinising hormone; uhCG: urinary hCG.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
^aThe pooled effect included both the line of no effect and appreciable benefit or harm. ^bTotal number of events is less than 300. ^c1 of the 2 included studies did not provide information about methods of randomisation, allocation concealment or blinding.

Summary of findings 2. RhLH compared to uhCG for final oocyte maturation triggering in IVF and ICSI cycles

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Comparison 1. rhCG versus uhCG for triggering ovulation

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Ongoing pregnancy/live birth rate per woman Show forest plot	7	1136	Odds Ratio (M‐H, Fixed, 95% CI)	1.15 [0.89, 1.49]

1.1 Long GnRH agonist protocol	6	1017	Odds Ratio (M‐H, Fixed, 95% CI)	1.06 [0.80, 1.39]
1.2 GnRH antagonist protocol	1	119	Odds Ratio (M‐H, Fixed, 95% CI)	2.17 [1.00, 4.68]
2 OHSS per woman Show forest plot	8		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Moderate to severe OHSS	3	417	Odds Ratio (M‐H, Fixed, 95% CI)	1.76 [0.37, 8.45]
2.2 Moderate OHSS	1	243	Odds Ratio (M‐H, Fixed, 95% CI)	0.78 [0.27, 2.27]
2.3 Mild to moderate OHSS	2	320	Odds Ratio (M‐H, Fixed, 95% CI)	1.0 [0.42, 2.38]
2.4 Undefined OHSS	3	495	Odds Ratio (M‐H, Fixed, 95% CI)	1.18 [0.50, 2.78]
3 Clinical pregnancy rate per woman Show forest plot	13	1806	Odds Ratio (M‐H, Fixed, 95% CI)	1.06 [0.87, 1.29]

3.1 Long GnRH agonist protocol	12	1687	Odds Ratio (M‐H, Fixed, 95% CI)	1.01 [0.82, 1.24]
3.2 GnRH antagonist protocol	1	119	Odds Ratio (M‐H, Fixed, 95% CI)	1.97 [0.93, 4.18]
4 Miscarriage rate per woman Show forest plot	8	1196	Odds Ratio (M‐H, Fixed, 95% CI)	0.72 [0.41, 1.25]

4.1 Long GnRH agonist protocol	7	1077	Odds Ratio (M‐H, Fixed, 95% CI)	0.73 [0.41, 1.29]
4.2 GnRH antagonist protocol	1	119	Odds Ratio (M‐H, Fixed, 95% CI)	0.5 [0.04, 5.67]
5 No of oocytes retrieved per woman Show forest plot	12	1744	Mean Difference (IV, Fixed, 95% CI)	‐0.11 [‐0.70, 0.47]

5.1 Long GnRH agonist protocol	11	1625	Mean Difference (IV, Fixed, 95% CI)	‐0.14 [‐0.73, 0.45]
5.2 GnRH antagonist protocol	1	119	Mean Difference (IV, Fixed, 95% CI)	1.20 [‐3.14, 5.54]
6 Adverse events per woman Show forest plot	5	561	Odds Ratio (M‐H, Fixed, 95% CI)	0.52 [0.35, 0.76]

Comparison 1. rhCG versus uhCG for triggering ovulation

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Comparison 2. rhLH versus uhCG for triggering ovulation

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Ongoing pregnancy/live birth rate per woman Show forest plot	2	289	Odds Ratio (M‐H, Fixed, 95% CI)	0.95 [0.51, 1.78]

2 OHSS per woman Show forest plot	2	289	Odds Ratio (M‐H, Fixed, 95% CI)	0.83 [0.40, 1.70]

2.1 Moderate OHSS	2	289	Odds Ratio (M‐H, Fixed, 95% CI)	0.83 [0.40, 1.70]
3 Clinical pregnancy rate per woman Show forest plot	2	289	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.54, 1.64]

4 Miscarriage rate per woman Show forest plot	2	289	Odds Ratio (M‐H, Fixed, 95% CI)	0.95 [0.38, 2.40]

5 No of oocytes retrieved per woman Show forest plot	2	103	Mean Difference (IV, Fixed, 95% CI)	‐1.33 [‐3.26, 0.60]

6 Adverse events per woman Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

Comparison 2. rhLH versus uhCG for triggering ovulation

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Gonadotrofina recombinante versus gonadotrofina coriónica humana urinaria para desencadenar la maduración final de los ovocitos en los ciclos de FIV e ICSI

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