The M-OVIN study: Does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate - a randomised controlled trial

Marleen J. Nahuis, Nienke S. Weiss, Fulco van der Veen, Ben Willem J Mol, Peter G. Hompes, Jur Oosterhuis, Nils B. Lambalk, Jesper M J Smeenk, Carolien A M Koks, Ron J T van Golde, Joop S E Laven, Ben J. Cohlen, Kathrin Fleischer, Angelique J. Goverde, Marie H. Gerards, Nicole F. Klijn, Lizka C M Nekrui, Ilse A J van Rooij, Diederik A. Hoozemans, Madelon Van Wely

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60% to 85% of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI. Methods/Design: We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI. Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included. Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40% after CC, 55% after addition of IUI and 55% after ovulation induction with gonadotrophins, with an alpha of 5% and a power of 80%, we need to recruit 200 women per arm (800 women in total).An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm). Discussion: The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women. Trial registration number: Netherlands Trial register NTR1449.

LanguageEnglish
Article number42
JournalBMC Women's Health
Volume13
Issue number1
DOIs
Publication statusPublished - 25 Oct 2013

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynaecology

Cite this

Nahuis, Marleen J. ; Weiss, Nienke S. ; van der Veen, Fulco ; Mol, Ben Willem J ; Hompes, Peter G. ; Oosterhuis, Jur ; Lambalk, Nils B. ; Smeenk, Jesper M J ; Koks, Carolien A M ; van Golde, Ron J T ; Laven, Joop S E ; Cohlen, Ben J. ; Fleischer, Kathrin ; Goverde, Angelique J. ; Gerards, Marie H. ; Klijn, Nicole F. ; Nekrui, Lizka C M ; van Rooij, Ilse A J ; Hoozemans, Diederik A. ; Van Wely, Madelon. / The M-OVIN study : Does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate - a randomised controlled trial. In: BMC Women's Health. 2013 ; Vol. 13, No. 1.
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abstract = "Background: Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60{\%} to 85{\%} of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI. Methods/Design: We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI. Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included. Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40{\%} after CC, 55{\%} after addition of IUI and 55{\%} after ovulation induction with gonadotrophins, with an alpha of 5{\%} and a power of 80{\%}, we need to recruit 200 women per arm (800 women in total).An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm). Discussion: The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women. Trial registration number: Netherlands Trial register NTR1449.",
author = "Nahuis, {Marleen J.} and Weiss, {Nienke S.} and {van der Veen}, Fulco and Mol, {Ben Willem J} and Hompes, {Peter G.} and Jur Oosterhuis and Lambalk, {Nils B.} and Smeenk, {Jesper M J} and Koks, {Carolien A M} and {van Golde}, {Ron J T} and Laven, {Joop S E} and Cohlen, {Ben J.} and Kathrin Fleischer and Goverde, {Angelique J.} and Gerards, {Marie H.} and Klijn, {Nicole F.} and Nekrui, {Lizka C M} and {van Rooij}, {Ilse A J} and Hoozemans, {Diederik A.} and {Van Wely}, Madelon",
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Nahuis, MJ, Weiss, NS, van der Veen, F, Mol, BWJ, Hompes, PG, Oosterhuis, J, Lambalk, NB, Smeenk, JMJ, Koks, CAM, van Golde, RJT, Laven, JSE, Cohlen, BJ, Fleischer, K, Goverde, AJ, Gerards, MH, Klijn, NF, Nekrui, LCM, van Rooij, IAJ, Hoozemans, DA & Van Wely, M 2013, 'The M-OVIN study: Does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate - a randomised controlled trial', BMC Women's Health, vol. 13, no. 1, 42. https://doi.org/10.1186/1472-6874-13-42

The M-OVIN study : Does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate - a randomised controlled trial. / Nahuis, Marleen J.; Weiss, Nienke S.; van der Veen, Fulco; Mol, Ben Willem J; Hompes, Peter G.; Oosterhuis, Jur; Lambalk, Nils B.; Smeenk, Jesper M J; Koks, Carolien A M; van Golde, Ron J T; Laven, Joop S E; Cohlen, Ben J.; Fleischer, Kathrin; Goverde, Angelique J.; Gerards, Marie H.; Klijn, Nicole F.; Nekrui, Lizka C M; van Rooij, Ilse A J; Hoozemans, Diederik A.; Van Wely, Madelon.

In: BMC Women's Health, Vol. 13, No. 1, 42, 25.10.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The M-OVIN study

T2 - BMC Women's Health

AU - Nahuis, Marleen J.

AU - Weiss, Nienke S.

AU - van der Veen, Fulco

AU - Mol, Ben Willem J

AU - Hompes, Peter G.

AU - Oosterhuis, Jur

AU - Lambalk, Nils B.

AU - Smeenk, Jesper M J

AU - Koks, Carolien A M

AU - van Golde, Ron J T

AU - Laven, Joop S E

AU - Cohlen, Ben J.

AU - Fleischer, Kathrin

AU - Goverde, Angelique J.

AU - Gerards, Marie H.

AU - Klijn, Nicole F.

AU - Nekrui, Lizka C M

AU - van Rooij, Ilse A J

AU - Hoozemans, Diederik A.

AU - Van Wely, Madelon

PY - 2013/10/25

Y1 - 2013/10/25

N2 - Background: Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60% to 85% of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI. Methods/Design: We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI. Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included. Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40% after CC, 55% after addition of IUI and 55% after ovulation induction with gonadotrophins, with an alpha of 5% and a power of 80%, we need to recruit 200 women per arm (800 women in total).An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm). Discussion: The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women. Trial registration number: Netherlands Trial register NTR1449.

AB - Background: Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60% to 85% of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI. Methods/Design: We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI. Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included. Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40% after CC, 55% after addition of IUI and 55% after ovulation induction with gonadotrophins, with an alpha of 5% and a power of 80%, we need to recruit 200 women per arm (800 women in total).An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm). Discussion: The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women. Trial registration number: Netherlands Trial register NTR1449.

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