Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction (review)

Abha Maheshwari, Ahmed Gibreel, Charalambos Siristatidis, Siladitya Bhattacharya

Research output: Contribution to journalLiterature review

Abstract

A B S T R A C T
Background
Gonadotrophin-releasing hormone agonists (GnRHa) are used in assisted reproduction technology (ART) cycles to prevent a luteinizing
hormone surge. Various protocols have been described in the literature, such as long protocols (continuous and stop or reduce dose,
long luteal, or long follicular protocol); short protocols and ultrashort protocols.
Objectives
To determine the most effective GnRHa protocol as an adjuvant to gonadotrophins in ART cycles.
Search strategy
We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled
Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINHAHL and PsycINFO. Reference lists of relevant articles
were also searched. All the searches were updated to August 2010.
Selection criteria
Only randomised controlled trials comparing any two protocols of GnRHa in in vitro fertilization (IVF) or intra-cytoplasmic sperm
injection (ICSI) cycles were included.
Data collection and analysis
The primary outcome measure was live births per women. Secondary outcome measures were pregnancy rate, ongoing pregnancy rate,
number of oocytes retrieved and amount of gonadotrophins used. Data were independently extracted in 2 x 2 tables by two authors.
Odds ratios (OR) with 95% confidence intervals (CI) were calculated after verifying the presence of homogeneity of treatment effect
across all trials. For continuous variables mean differences (MD) were calculated.
Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction (Review) 1
Copyright © 2011 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd.
Main results
Of 29 included studies, 17 compared long with short protocols; two compared long with ultrashort protocols; four compared a follicular
versus luteal start of GnRHa; three compared continuation versus stopping the GnRHa at the start of stimulation; three compared
continuation of the same dose versus reduced dose of GnRHa and one compared a short versus short stop protocol.
There was no evidence of a difference in the live birth rate but this outcome was only reported by three studies.
There was evidence of a significant increase in clinical pregnancy rate (OR 1.50, 95% CI 1.16 to 1.93) in a long protocol when
compared to a short protocol. That is there is a 50% increase in chance of achieving pregnancy if a long protocol is used as compared to
a short protocol, although this difference could range from 16% to 93% increased chance of pregnancy. This difference did not persist
when the meta-analysis was done only on the studies with adequate randomisation (OR 1.38, 95% CI 0.93 to 2.05).
There was evidence of an increased number of oocytes (MD 1.61, 95% CI 0.18 to 3.04) obtained when a long protocol was used
as compared to a short protocol. That is there is a 60% increase in the number of oocytes retrieved when a long protocol is used as
compared to a short protocol, although this difference could range from 18% to 304% more oocytes.
There was evidence of an increase (MD 12.90, 95% CI 3.29 to 22.51) in the requirement for gonadotrophins in long as compared
to short protocols. That is approximately 12.9 more ampoules of gonadotrophins were consumed when a long protocol was used as
compared to a short protocol. This difference could range from 3.29 to 22.51 more gonadotrophin ampoules.
There was no evidence of a difference in any of the outcome measures for luteal versus follicular start of GnRHa and stopping versus
continuation of GnRHa at the start of stimulation.
Authors’ conclusions
The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol.
There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence
of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was
associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.
Original languageEnglish
Article numberCD006919
Number of pages93
JournalCochrane Database of Systematic Reviews
Issue number8
DOIs
Publication statusPublished - 2011

Fingerprint

Pregnancy Rate
Gonadotropins
Gonadotropin-Releasing Hormone
Reproduction
Oocytes
Confidence Intervals
Corpus Luteum
Live Birth
Birth Rate
Odds Ratio
Outcome Assessment (Health Care)
Technology
Pregnancy
Fertilization in Vitro
Random Allocation
Nuclear Family
MEDLINE
Infertility
Libraries
Meta-Analysis

Cite this

Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction (review). / Maheshwari, Abha; Gibreel, Ahmed; Siristatidis, Charalambos; Bhattacharya, Siladitya.

In: Cochrane Database of Systematic Reviews, No. 8, CD006919, 2011.

Research output: Contribution to journalLiterature review

@article{17a5c72a2f2a40868f8fee4955287f62,
title = "Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction (review)",
abstract = "A B S T R A C T Background Gonadotrophin-releasing hormone agonists (GnRHa) are used in assisted reproduction technology (ART) cycles to prevent a luteinizing hormone surge. Various protocols have been described in the literature, such as long protocols (continuous and stop or reduce dose, long luteal, or long follicular protocol); short protocols and ultrashort protocols. Objectives To determine the most effective GnRHa protocol as an adjuvant to gonadotrophins in ART cycles. Search strategy We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINHAHL and PsycINFO. Reference lists of relevant articles were also searched. All the searches were updated to August 2010. Selection criteria Only randomised controlled trials comparing any two protocols of GnRHa in in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) cycles were included. Data collection and analysis The primary outcome measure was live births per women. Secondary outcome measures were pregnancy rate, ongoing pregnancy rate, number of oocytes retrieved and amount of gonadotrophins used. Data were independently extracted in 2 x 2 tables by two authors. Odds ratios (OR) with 95{\%} confidence intervals (CI) were calculated after verifying the presence of homogeneity of treatment effect across all trials. For continuous variables mean differences (MD) were calculated. Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction (Review) 1 Copyright {\circledC} 2011 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. Main results Of 29 included studies, 17 compared long with short protocols; two compared long with ultrashort protocols; four compared a follicular versus luteal start of GnRHa; three compared continuation versus stopping the GnRHa at the start of stimulation; three compared continuation of the same dose versus reduced dose of GnRHa and one compared a short versus short stop protocol. There was no evidence of a difference in the live birth rate but this outcome was only reported by three studies. There was evidence of a significant increase in clinical pregnancy rate (OR 1.50, 95{\%} CI 1.16 to 1.93) in a long protocol when compared to a short protocol. That is there is a 50{\%} increase in chance of achieving pregnancy if a long protocol is used as compared to a short protocol, although this difference could range from 16{\%} to 93{\%} increased chance of pregnancy. This difference did not persist when the meta-analysis was done only on the studies with adequate randomisation (OR 1.38, 95{\%} CI 0.93 to 2.05). There was evidence of an increased number of oocytes (MD 1.61, 95{\%} CI 0.18 to 3.04) obtained when a long protocol was used as compared to a short protocol. That is there is a 60{\%} increase in the number of oocytes retrieved when a long protocol is used as compared to a short protocol, although this difference could range from 18{\%} to 304{\%} more oocytes. There was evidence of an increase (MD 12.90, 95{\%} CI 3.29 to 22.51) in the requirement for gonadotrophins in long as compared to short protocols. That is approximately 12.9 more ampoules of gonadotrophins were consumed when a long protocol was used as compared to a short protocol. This difference could range from 3.29 to 22.51 more gonadotrophin ampoules. There was no evidence of a difference in any of the outcome measures for luteal versus follicular start of GnRHa and stopping versus continuation of GnRHa at the start of stimulation. Authors’ conclusions The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.",
author = "Abha Maheshwari and Ahmed Gibreel and Charalambos Siristatidis and Siladitya Bhattacharya",
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T1 - Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction (review)

AU - Maheshwari, Abha

AU - Gibreel, Ahmed

AU - Siristatidis, Charalambos

AU - Bhattacharya, Siladitya

PY - 2011

Y1 - 2011

N2 - A B S T R A C T Background Gonadotrophin-releasing hormone agonists (GnRHa) are used in assisted reproduction technology (ART) cycles to prevent a luteinizing hormone surge. Various protocols have been described in the literature, such as long protocols (continuous and stop or reduce dose, long luteal, or long follicular protocol); short protocols and ultrashort protocols. Objectives To determine the most effective GnRHa protocol as an adjuvant to gonadotrophins in ART cycles. Search strategy We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINHAHL and PsycINFO. Reference lists of relevant articles were also searched. All the searches were updated to August 2010. Selection criteria Only randomised controlled trials comparing any two protocols of GnRHa in in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) cycles were included. Data collection and analysis The primary outcome measure was live births per women. Secondary outcome measures were pregnancy rate, ongoing pregnancy rate, number of oocytes retrieved and amount of gonadotrophins used. Data were independently extracted in 2 x 2 tables by two authors. Odds ratios (OR) with 95% confidence intervals (CI) were calculated after verifying the presence of homogeneity of treatment effect across all trials. For continuous variables mean differences (MD) were calculated. Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction (Review) 1 Copyright © 2011 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. Main results Of 29 included studies, 17 compared long with short protocols; two compared long with ultrashort protocols; four compared a follicular versus luteal start of GnRHa; three compared continuation versus stopping the GnRHa at the start of stimulation; three compared continuation of the same dose versus reduced dose of GnRHa and one compared a short versus short stop protocol. There was no evidence of a difference in the live birth rate but this outcome was only reported by three studies. There was evidence of a significant increase in clinical pregnancy rate (OR 1.50, 95% CI 1.16 to 1.93) in a long protocol when compared to a short protocol. That is there is a 50% increase in chance of achieving pregnancy if a long protocol is used as compared to a short protocol, although this difference could range from 16% to 93% increased chance of pregnancy. This difference did not persist when the meta-analysis was done only on the studies with adequate randomisation (OR 1.38, 95% CI 0.93 to 2.05). There was evidence of an increased number of oocytes (MD 1.61, 95% CI 0.18 to 3.04) obtained when a long protocol was used as compared to a short protocol. That is there is a 60% increase in the number of oocytes retrieved when a long protocol is used as compared to a short protocol, although this difference could range from 18% to 304% more oocytes. There was evidence of an increase (MD 12.90, 95% CI 3.29 to 22.51) in the requirement for gonadotrophins in long as compared to short protocols. That is approximately 12.9 more ampoules of gonadotrophins were consumed when a long protocol was used as compared to a short protocol. This difference could range from 3.29 to 22.51 more gonadotrophin ampoules. There was no evidence of a difference in any of the outcome measures for luteal versus follicular start of GnRHa and stopping versus continuation of GnRHa at the start of stimulation. Authors’ conclusions The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

AB - A B S T R A C T Background Gonadotrophin-releasing hormone agonists (GnRHa) are used in assisted reproduction technology (ART) cycles to prevent a luteinizing hormone surge. Various protocols have been described in the literature, such as long protocols (continuous and stop or reduce dose, long luteal, or long follicular protocol); short protocols and ultrashort protocols. Objectives To determine the most effective GnRHa protocol as an adjuvant to gonadotrophins in ART cycles. Search strategy We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINHAHL and PsycINFO. Reference lists of relevant articles were also searched. All the searches were updated to August 2010. Selection criteria Only randomised controlled trials comparing any two protocols of GnRHa in in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) cycles were included. Data collection and analysis The primary outcome measure was live births per women. Secondary outcome measures were pregnancy rate, ongoing pregnancy rate, number of oocytes retrieved and amount of gonadotrophins used. Data were independently extracted in 2 x 2 tables by two authors. Odds ratios (OR) with 95% confidence intervals (CI) were calculated after verifying the presence of homogeneity of treatment effect across all trials. For continuous variables mean differences (MD) were calculated. Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction (Review) 1 Copyright © 2011 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd. Main results Of 29 included studies, 17 compared long with short protocols; two compared long with ultrashort protocols; four compared a follicular versus luteal start of GnRHa; three compared continuation versus stopping the GnRHa at the start of stimulation; three compared continuation of the same dose versus reduced dose of GnRHa and one compared a short versus short stop protocol. There was no evidence of a difference in the live birth rate but this outcome was only reported by three studies. There was evidence of a significant increase in clinical pregnancy rate (OR 1.50, 95% CI 1.16 to 1.93) in a long protocol when compared to a short protocol. That is there is a 50% increase in chance of achieving pregnancy if a long protocol is used as compared to a short protocol, although this difference could range from 16% to 93% increased chance of pregnancy. This difference did not persist when the meta-analysis was done only on the studies with adequate randomisation (OR 1.38, 95% CI 0.93 to 2.05). There was evidence of an increased number of oocytes (MD 1.61, 95% CI 0.18 to 3.04) obtained when a long protocol was used as compared to a short protocol. That is there is a 60% increase in the number of oocytes retrieved when a long protocol is used as compared to a short protocol, although this difference could range from 18% to 304% more oocytes. There was evidence of an increase (MD 12.90, 95% CI 3.29 to 22.51) in the requirement for gonadotrophins in long as compared to short protocols. That is approximately 12.9 more ampoules of gonadotrophins were consumed when a long protocol was used as compared to a short protocol. This difference could range from 3.29 to 22.51 more gonadotrophin ampoules. There was no evidence of a difference in any of the outcome measures for luteal versus follicular start of GnRHa and stopping versus continuation of GnRHa at the start of stimulation. Authors’ conclusions The pregnancy rate was found to be higher when GnRHa was used in a long protocol as compared to a short or ultrashort protocol. There was no evidence of a difference in live birth rate, but this outcome was only reported by three studies. There was no evidence of a difference in the outcomes amongst various long protocols; nor that stopping or reducing GnRHa at the start of stimulation was associated with a reduced pregnancy rate. For all comparison, except a long versus short protocol, there was a lack of power.

U2 - 10.1002/14651858.CD006919.pub3

DO - 10.1002/14651858.CD006919.pub3

M3 - Literature review

JO - Cochrane Database of Systematic Reviews

JF - Cochrane Database of Systematic Reviews

SN - 1469-493X

IS - 8

M1 - CD006919

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