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Comparison of early versus late initiation of GnRH antagonist co-treatment for controlled ovarian stimulation in IVF: a randomized controlled trial

Comparison of early versus late initiation of GnRH antagonist co-treatment for controlled ovarian stimulation in IVF: a randomized controlled trial
Comparison of early versus late initiation of GnRH antagonist co-treatment for controlled ovarian stimulation in IVF: a randomized controlled trial
study question: what is the impact of initiating GnRH antagonist co-treatment for in vitro fertilization (IVF) on cycle day (CD) 2 compared with CD 6 on live birth rate (LBR) per started cycle and on the cumulative live birth rate (CLBR)?

Summary answer: early initiation of GnRH antagonist does not appear to improve clinical outcomes of IVF compared with midfollicular initiation.

What is known already: during ovarian stimulation for IVF, GnRH antagonist co-treatment is usually administered from the midfollicular phase onwards. Earlier initiation may improve the follicular phase hormonal milieu and therefore overall clinical outcomes.

Study design, size, duration: this open-label, multicentre randomized controlled trial was conducted between September 2009 and July 2011. A web-based program was used for randomization and 617 IVF-intracytoplasmic sperm injection (ICSI) patients were included.

Participants/materials, setting, methods: recombinant FSH (150–225 IU) was administered daily from CD 2 onwards in both groups. The study group (CD2; n = 308) started GnRH antagonist co-treatment on CD 2, whereas the control group (CD6; n = 309) started on CD 6.

Main results and the role of chance: there were no significant differences in clinical outcomes between the two groups. A non-significant trend towards a higher LBR per started cycle and CLBR was observed in the CD6 group compared with the CD2 group (LBR: 24.0 versus 21.5%, P = 0.5; CLBR: 29.9 versus 26.7%, P = 0.6).

Limitations, reasons for caution: the study was terminated prematurely because no significant difference was observed in clinical outcomes after 617 inclusions. A much larger study population would be needed to detect a small significant difference in favour of either study arm, which raises the question of whether this would be relevant for clinical practice.

Wider implications of the findings: the present study shows that the additional treatment burden and costs of starting GnRH antagonist on CD 2 instead of on CD 6 are not justified, as early initiation of GnRH antagonist does not improve LBRs.

Study funding/competing interests: this study was partially supported by a grant from Merck Serono. O.H., M.J.C.E, A.V., P.A.D., R.E.B., G.J.E.O., C.A.G.H., G.C.D.M., H.J.V., P.F.M.H. and A.B. have nothing to declare. F.J.B. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gedeon Richter, Merck Serono, MSD and Roche. B.J.C. has received fees and grant support from the following companies (in alphabetic order): Ferring, Merck Serono and MSD. C.B.L has received fees and grant support from the following companies (in alphabetic order): Auxogen, Ferring, Merck Serono and MSD. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order): Andromed, Ardana, Ferring, Genovum, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono and Wyeth. J.S.E.L. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gennovum, MSD, Merck Serono, Organon, Schering Plough and Serono. N.S.M. has received fees and grant support from the following companies (in alphabetic order): Anecova, Ferring, Merck Serono, MSD, Organon and Serono
1-9
Hamdine, O.
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Macklon, N.S.
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Eijkemans, M.J.
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Laven, J.S.
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Cohlen, B.J.
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Verhoeff, A.
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van Dop, P.A.
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Bernardus, R.E.
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Lambalk, C.B.
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Oosterhuis, G.J.
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Holleboom, C.A.
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van den Dool-Maasland, G.C.
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Verburg, H.J.
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van der Heijden, P.F.
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Blankhart, A.
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Fauser, B.C.
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Broekmans, F.J.
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Hamdine, O.
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Macklon, N.S.
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Eijkemans, M.J.
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Laven, J.S.
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Cohlen, B.J.
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Verhoeff, A.
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van Dop, P.A.
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Bernardus, R.E.
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Lambalk, C.B.
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Oosterhuis, G.J.
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Holleboom, C.A.
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van den Dool-Maasland, G.C.
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Verburg, H.J.
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van der Heijden, P.F.
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Blankhart, A.
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Fauser, B.C.
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Broekmans, F.J.
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Hamdine, O., Macklon, N.S., Eijkemans, M.J., Laven, J.S., Cohlen, B.J., Verhoeff, A., van Dop, P.A., Bernardus, R.E., Lambalk, C.B., Oosterhuis, G.J., Holleboom, C.A., van den Dool-Maasland, G.C., Verburg, H.J., van der Heijden, P.F., Blankhart, A., Fauser, B.C. and Broekmans, F.J. (2013) Comparison of early versus late initiation of GnRH antagonist co-treatment for controlled ovarian stimulation in IVF: a randomized controlled trial. Human Reproduction, 1-9. (doi:10.1093/humrep/det374). (PMID:24129613)

Record type: Article

Abstract

study question: what is the impact of initiating GnRH antagonist co-treatment for in vitro fertilization (IVF) on cycle day (CD) 2 compared with CD 6 on live birth rate (LBR) per started cycle and on the cumulative live birth rate (CLBR)?

Summary answer: early initiation of GnRH antagonist does not appear to improve clinical outcomes of IVF compared with midfollicular initiation.

What is known already: during ovarian stimulation for IVF, GnRH antagonist co-treatment is usually administered from the midfollicular phase onwards. Earlier initiation may improve the follicular phase hormonal milieu and therefore overall clinical outcomes.

Study design, size, duration: this open-label, multicentre randomized controlled trial was conducted between September 2009 and July 2011. A web-based program was used for randomization and 617 IVF-intracytoplasmic sperm injection (ICSI) patients were included.

Participants/materials, setting, methods: recombinant FSH (150–225 IU) was administered daily from CD 2 onwards in both groups. The study group (CD2; n = 308) started GnRH antagonist co-treatment on CD 2, whereas the control group (CD6; n = 309) started on CD 6.

Main results and the role of chance: there were no significant differences in clinical outcomes between the two groups. A non-significant trend towards a higher LBR per started cycle and CLBR was observed in the CD6 group compared with the CD2 group (LBR: 24.0 versus 21.5%, P = 0.5; CLBR: 29.9 versus 26.7%, P = 0.6).

Limitations, reasons for caution: the study was terminated prematurely because no significant difference was observed in clinical outcomes after 617 inclusions. A much larger study population would be needed to detect a small significant difference in favour of either study arm, which raises the question of whether this would be relevant for clinical practice.

Wider implications of the findings: the present study shows that the additional treatment burden and costs of starting GnRH antagonist on CD 2 instead of on CD 6 are not justified, as early initiation of GnRH antagonist does not improve LBRs.

Study funding/competing interests: this study was partially supported by a grant from Merck Serono. O.H., M.J.C.E, A.V., P.A.D., R.E.B., G.J.E.O., C.A.G.H., G.C.D.M., H.J.V., P.F.M.H. and A.B. have nothing to declare. F.J.B. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gedeon Richter, Merck Serono, MSD and Roche. B.J.C. has received fees and grant support from the following companies (in alphabetic order): Ferring, Merck Serono and MSD. C.B.L has received fees and grant support from the following companies (in alphabetic order): Auxogen, Ferring, Merck Serono and MSD. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order): Andromed, Ardana, Ferring, Genovum, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono and Wyeth. J.S.E.L. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gennovum, MSD, Merck Serono, Organon, Schering Plough and Serono. N.S.M. has received fees and grant support from the following companies (in alphabetic order): Anecova, Ferring, Merck Serono, MSD, Organon and Serono

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e-pub ahead of print date: 15 October 2013
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 359602
URI: http://eprints.soton.ac.uk/id/eprint/359602
PURE UUID: 868c2740-e304-43c5-bec0-56f7a469a1b6

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Date deposited: 07 Nov 2013 11:39
Last modified: 08 Jan 2022 18:06

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Contributors

Author: O. Hamdine
Author: N.S. Macklon
Author: M.J. Eijkemans
Author: J.S. Laven
Author: B.J. Cohlen
Author: A. Verhoeff
Author: P.A. van Dop
Author: R.E. Bernardus
Author: C.B. Lambalk
Author: G.J. Oosterhuis
Author: C.A. Holleboom
Author: G.C. van den Dool-Maasland
Author: H.J. Verburg
Author: P.F. van der Heijden
Author: A. Blankhart
Author: B.C. Fauser
Author: F.J. Broekmans

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