Prevention of multiple pregnancies in couples with unexplained or mild male subfertility: Randomised controlled trial of in vitro fertilisation with single embryo transfer or in vitro fertilisation in modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation

A. J. Bensdorp, R. I. Tjon-Kon-Fat, P. M M Bossuyt, C. A M Koks, G. J E Oosterhuis, A. Hoek, P. G A Hompes, F. J M Broekmans, H. R. Verhoeve, J. P. De Bruin, R. Van Golde, S. Repping, B. J. Cohlen, M. D A Lambers, P. F. Van Bommel, E. Slappendel, D. Perquin, J. M. Smeenk, M. J. Pelinck, J. Gianotten & 6 others D. A. Hoozemans, J. W M Maas, M. J C Eijkemans, F. Van Der Veen, B. W J Mol, M. Van Wely

Research output: Contribution to journalArticle

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Abstract

Objectives: To compare the effectiveness of in vitro fertilisation with single embryo transfer or in vitro fertilisation in a modified natural cycle with that of intrauterine insemination with controlled ovarian hyperstimulation in terms of a healthy child. Design: Multicentre, open label, three arm, parallel group, randomised controlled non-inferiority trial. Setting: 17 centres in the Netherlands. Participants: Couples seeking fertility treatment after at least 12 months of unprotected intercourse, with the female partner aged between 18 and 38 years, an unfavourable prognosis for natural conception, and a diagnosis of unexplained or mild male subfertility. Interventions: Three cycles of in vitro fertilisation with single embryo transfer (plus subsequent cryocycles), six cycles of in vitro fertilisation in a modified natural cycle, or six cycles of intrauterine insemination with ovarian hyperstimulation within 12 months after randomisation. Main outcome measures: The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation. Secondary outcomes were live birth, clinical pregnancy, ongoing pregnancy, multiple pregnancy, time to pregnancy, complications of pregnancy, and neonatal morbidity and mortality Results: 602 couples were randomly assigned between January 2009 and February 2012; 201 were allocated to in vitro fertilisation with single embryo transfer, 194 to in vitro fertilisation in a modified natural cycle, and 207 to intrauterine insemination with controlled ovarian hyperstimulation. Birth of a healthy child occurred in 104 (52%) couples in the in vitro fertilisation with single embryo transfer group, 83 (43%) in the in vitro fertilisation in a modified natural cycle group, and 97 (47%) in the intrauterine insemination with controlled ovarian hyperstimulation group. This corresponds to a risk, relative to intrauterine insemination with ovarian hyperstimulation, of 1.10 (95% confidence interval 0.91 to 1.34) for in vitro fertilisation with single embryo transfer and 0.91 (0.73 to 1.14) for in vitro fertilisation in a modified natural cycle. These 95% confidence intervals do not extend below the predefined threshold of 0.69 for inferiority. Multiple pregnancy rates per ongoing pregnancy were 6% (7/121) after in vitro fertilisation with single embryo transfer, 5% (5/102) after in vitro fertilisation in a modified natural cycle, and 7% (8/119) after intrauterine insemination with ovarian hyperstimulation (one sided P=0.52 for in vitro fertilisation with single embryo transfer compared with intrauterine insemination with ovarian hyperstimulation; one sided P=0.33 for in vitro fertilisation in a modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation). Conclusions: In vitro fertilisation with single embryo transfer and in vitro fertilisation in a modified natural cycle were non-inferior to intrauterine insemination with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable, low multiple pregnancy rates. Trial registration: Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939.

LanguageEnglish
Article numberg7771
JournalBMJ (Online)
Volume350
DOIs
Publication statusPublished - 9 Jan 2015

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bensdorp, A. J. ; Tjon-Kon-Fat, R. I. ; Bossuyt, P. M M ; Koks, C. A M ; Oosterhuis, G. J E ; Hoek, A. ; Hompes, P. G A ; Broekmans, F. J M ; Verhoeve, H. R. ; De Bruin, J. P. ; Van Golde, R. ; Repping, S. ; Cohlen, B. J. ; Lambers, M. D A ; Van Bommel, P. F. ; Slappendel, E. ; Perquin, D. ; Smeenk, J. M. ; Pelinck, M. J. ; Gianotten, J. ; Hoozemans, D. A. ; Maas, J. W M ; Eijkemans, M. J C ; Van Der Veen, F. ; Mol, B. W J ; Van Wely, M. / Prevention of multiple pregnancies in couples with unexplained or mild male subfertility : Randomised controlled trial of in vitro fertilisation with single embryo transfer or in vitro fertilisation in modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation. In: BMJ (Online). 2015 ; Vol. 350.
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title = "Prevention of multiple pregnancies in couples with unexplained or mild male subfertility: Randomised controlled trial of in vitro fertilisation with single embryo transfer or in vitro fertilisation in modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation",
abstract = "Objectives: To compare the effectiveness of in vitro fertilisation with single embryo transfer or in vitro fertilisation in a modified natural cycle with that of intrauterine insemination with controlled ovarian hyperstimulation in terms of a healthy child. Design: Multicentre, open label, three arm, parallel group, randomised controlled non-inferiority trial. Setting: 17 centres in the Netherlands. Participants: Couples seeking fertility treatment after at least 12 months of unprotected intercourse, with the female partner aged between 18 and 38 years, an unfavourable prognosis for natural conception, and a diagnosis of unexplained or mild male subfertility. Interventions: Three cycles of in vitro fertilisation with single embryo transfer (plus subsequent cryocycles), six cycles of in vitro fertilisation in a modified natural cycle, or six cycles of intrauterine insemination with ovarian hyperstimulation within 12 months after randomisation. Main outcome measures: The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation. Secondary outcomes were live birth, clinical pregnancy, ongoing pregnancy, multiple pregnancy, time to pregnancy, complications of pregnancy, and neonatal morbidity and mortality Results: 602 couples were randomly assigned between January 2009 and February 2012; 201 were allocated to in vitro fertilisation with single embryo transfer, 194 to in vitro fertilisation in a modified natural cycle, and 207 to intrauterine insemination with controlled ovarian hyperstimulation. Birth of a healthy child occurred in 104 (52{\%}) couples in the in vitro fertilisation with single embryo transfer group, 83 (43{\%}) in the in vitro fertilisation in a modified natural cycle group, and 97 (47{\%}) in the intrauterine insemination with controlled ovarian hyperstimulation group. This corresponds to a risk, relative to intrauterine insemination with ovarian hyperstimulation, of 1.10 (95{\%} confidence interval 0.91 to 1.34) for in vitro fertilisation with single embryo transfer and 0.91 (0.73 to 1.14) for in vitro fertilisation in a modified natural cycle. These 95{\%} confidence intervals do not extend below the predefined threshold of 0.69 for inferiority. Multiple pregnancy rates per ongoing pregnancy were 6{\%} (7/121) after in vitro fertilisation with single embryo transfer, 5{\%} (5/102) after in vitro fertilisation in a modified natural cycle, and 7{\%} (8/119) after intrauterine insemination with ovarian hyperstimulation (one sided P=0.52 for in vitro fertilisation with single embryo transfer compared with intrauterine insemination with ovarian hyperstimulation; one sided P=0.33 for in vitro fertilisation in a modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation). Conclusions: In vitro fertilisation with single embryo transfer and in vitro fertilisation in a modified natural cycle were non-inferior to intrauterine insemination with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable, low multiple pregnancy rates. Trial registration: Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939.",
author = "Bensdorp, {A. J.} and Tjon-Kon-Fat, {R. I.} and Bossuyt, {P. M M} and Koks, {C. A M} and Oosterhuis, {G. J E} and A. Hoek and Hompes, {P. G A} and Broekmans, {F. J M} and Verhoeve, {H. R.} and {De Bruin}, {J. P.} and {Van Golde}, R. and S. Repping and Cohlen, {B. J.} and Lambers, {M. D A} and {Van Bommel}, {P. F.} and E. Slappendel and D. Perquin and Smeenk, {J. M.} and Pelinck, {M. J.} and J. Gianotten and Hoozemans, {D. A.} and Maas, {J. W M} and Eijkemans, {M. J C} and {Van Der Veen}, F. and Mol, {B. W J} and {Van Wely}, M.",
year = "2015",
month = "1",
day = "9",
doi = "10.1136/bmj.g7771",
language = "English",
volume = "350",
journal = "BMJ (Online)",
issn = "0959-8146",
publisher = "BMJ Publishing Group",

}

Bensdorp, AJ, Tjon-Kon-Fat, RI, Bossuyt, PMM, Koks, CAM, Oosterhuis, GJE, Hoek, A, Hompes, PGA, Broekmans, FJM, Verhoeve, HR, De Bruin, JP, Van Golde, R, Repping, S, Cohlen, BJ, Lambers, MDA, Van Bommel, PF, Slappendel, E, Perquin, D, Smeenk, JM, Pelinck, MJ, Gianotten, J, Hoozemans, DA, Maas, JWM, Eijkemans, MJC, Van Der Veen, F, Mol, BWJ & Van Wely, M 2015, 'Prevention of multiple pregnancies in couples with unexplained or mild male subfertility: Randomised controlled trial of in vitro fertilisation with single embryo transfer or in vitro fertilisation in modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation', BMJ (Online), vol. 350, g7771. https://doi.org/10.1136/bmj.g7771

Prevention of multiple pregnancies in couples with unexplained or mild male subfertility : Randomised controlled trial of in vitro fertilisation with single embryo transfer or in vitro fertilisation in modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation. / Bensdorp, A. J.; Tjon-Kon-Fat, R. I.; Bossuyt, P. M M; Koks, C. A M; Oosterhuis, G. J E; Hoek, A.; Hompes, P. G A; Broekmans, F. J M; Verhoeve, H. R.; De Bruin, J. P.; Van Golde, R.; Repping, S.; Cohlen, B. J.; Lambers, M. D A; Van Bommel, P. F.; Slappendel, E.; Perquin, D.; Smeenk, J. M.; Pelinck, M. J.; Gianotten, J.; Hoozemans, D. A.; Maas, J. W M; Eijkemans, M. J C; Van Der Veen, F.; Mol, B. W J; Van Wely, M.

In: BMJ (Online), Vol. 350, g7771, 09.01.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prevention of multiple pregnancies in couples with unexplained or mild male subfertility

T2 - BMJ (Online)

AU - Bensdorp, A. J.

AU - Tjon-Kon-Fat, R. I.

AU - Bossuyt, P. M M

AU - Koks, C. A M

AU - Oosterhuis, G. J E

AU - Hoek, A.

AU - Hompes, P. G A

AU - Broekmans, F. J M

AU - Verhoeve, H. R.

AU - De Bruin, J. P.

AU - Van Golde, R.

AU - Repping, S.

AU - Cohlen, B. J.

AU - Lambers, M. D A

AU - Van Bommel, P. F.

AU - Slappendel, E.

AU - Perquin, D.

AU - Smeenk, J. M.

AU - Pelinck, M. J.

AU - Gianotten, J.

AU - Hoozemans, D. A.

AU - Maas, J. W M

AU - Eijkemans, M. J C

AU - Van Der Veen, F.

AU - Mol, B. W J

AU - Van Wely, M.

PY - 2015/1/9

Y1 - 2015/1/9

N2 - Objectives: To compare the effectiveness of in vitro fertilisation with single embryo transfer or in vitro fertilisation in a modified natural cycle with that of intrauterine insemination with controlled ovarian hyperstimulation in terms of a healthy child. Design: Multicentre, open label, three arm, parallel group, randomised controlled non-inferiority trial. Setting: 17 centres in the Netherlands. Participants: Couples seeking fertility treatment after at least 12 months of unprotected intercourse, with the female partner aged between 18 and 38 years, an unfavourable prognosis for natural conception, and a diagnosis of unexplained or mild male subfertility. Interventions: Three cycles of in vitro fertilisation with single embryo transfer (plus subsequent cryocycles), six cycles of in vitro fertilisation in a modified natural cycle, or six cycles of intrauterine insemination with ovarian hyperstimulation within 12 months after randomisation. Main outcome measures: The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation. Secondary outcomes were live birth, clinical pregnancy, ongoing pregnancy, multiple pregnancy, time to pregnancy, complications of pregnancy, and neonatal morbidity and mortality Results: 602 couples were randomly assigned between January 2009 and February 2012; 201 were allocated to in vitro fertilisation with single embryo transfer, 194 to in vitro fertilisation in a modified natural cycle, and 207 to intrauterine insemination with controlled ovarian hyperstimulation. Birth of a healthy child occurred in 104 (52%) couples in the in vitro fertilisation with single embryo transfer group, 83 (43%) in the in vitro fertilisation in a modified natural cycle group, and 97 (47%) in the intrauterine insemination with controlled ovarian hyperstimulation group. This corresponds to a risk, relative to intrauterine insemination with ovarian hyperstimulation, of 1.10 (95% confidence interval 0.91 to 1.34) for in vitro fertilisation with single embryo transfer and 0.91 (0.73 to 1.14) for in vitro fertilisation in a modified natural cycle. These 95% confidence intervals do not extend below the predefined threshold of 0.69 for inferiority. Multiple pregnancy rates per ongoing pregnancy were 6% (7/121) after in vitro fertilisation with single embryo transfer, 5% (5/102) after in vitro fertilisation in a modified natural cycle, and 7% (8/119) after intrauterine insemination with ovarian hyperstimulation (one sided P=0.52 for in vitro fertilisation with single embryo transfer compared with intrauterine insemination with ovarian hyperstimulation; one sided P=0.33 for in vitro fertilisation in a modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation). Conclusions: In vitro fertilisation with single embryo transfer and in vitro fertilisation in a modified natural cycle were non-inferior to intrauterine insemination with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable, low multiple pregnancy rates. Trial registration: Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939.

AB - Objectives: To compare the effectiveness of in vitro fertilisation with single embryo transfer or in vitro fertilisation in a modified natural cycle with that of intrauterine insemination with controlled ovarian hyperstimulation in terms of a healthy child. Design: Multicentre, open label, three arm, parallel group, randomised controlled non-inferiority trial. Setting: 17 centres in the Netherlands. Participants: Couples seeking fertility treatment after at least 12 months of unprotected intercourse, with the female partner aged between 18 and 38 years, an unfavourable prognosis for natural conception, and a diagnosis of unexplained or mild male subfertility. Interventions: Three cycles of in vitro fertilisation with single embryo transfer (plus subsequent cryocycles), six cycles of in vitro fertilisation in a modified natural cycle, or six cycles of intrauterine insemination with ovarian hyperstimulation within 12 months after randomisation. Main outcome measures: The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation. Secondary outcomes were live birth, clinical pregnancy, ongoing pregnancy, multiple pregnancy, time to pregnancy, complications of pregnancy, and neonatal morbidity and mortality Results: 602 couples were randomly assigned between January 2009 and February 2012; 201 were allocated to in vitro fertilisation with single embryo transfer, 194 to in vitro fertilisation in a modified natural cycle, and 207 to intrauterine insemination with controlled ovarian hyperstimulation. Birth of a healthy child occurred in 104 (52%) couples in the in vitro fertilisation with single embryo transfer group, 83 (43%) in the in vitro fertilisation in a modified natural cycle group, and 97 (47%) in the intrauterine insemination with controlled ovarian hyperstimulation group. This corresponds to a risk, relative to intrauterine insemination with ovarian hyperstimulation, of 1.10 (95% confidence interval 0.91 to 1.34) for in vitro fertilisation with single embryo transfer and 0.91 (0.73 to 1.14) for in vitro fertilisation in a modified natural cycle. These 95% confidence intervals do not extend below the predefined threshold of 0.69 for inferiority. Multiple pregnancy rates per ongoing pregnancy were 6% (7/121) after in vitro fertilisation with single embryo transfer, 5% (5/102) after in vitro fertilisation in a modified natural cycle, and 7% (8/119) after intrauterine insemination with ovarian hyperstimulation (one sided P=0.52 for in vitro fertilisation with single embryo transfer compared with intrauterine insemination with ovarian hyperstimulation; one sided P=0.33 for in vitro fertilisation in a modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation). Conclusions: In vitro fertilisation with single embryo transfer and in vitro fertilisation in a modified natural cycle were non-inferior to intrauterine insemination with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable, low multiple pregnancy rates. Trial registration: Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939.

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U2 - 10.1136/bmj.g7771

DO - 10.1136/bmj.g7771

M3 - Article

VL - 350

JO - BMJ (Online)

JF - BMJ (Online)

SN - 0959-8146

M1 - g7771

ER -