25576320
OBJECTIVE	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 .
METHODS	Multicentre , open label , three arm , parallel group , randomised controlled non-inferiority trial .
METHODS	17 centres in the Netherlands .
METHODS	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 .
METHODS	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 .
METHODS	The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation .
METHODS	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 .
RESULTS	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 .
RESULTS	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 .
RESULTS	These 95 % confidence intervals do not extend below the predefined threshold of 0.69 for inferiority .
RESULTS	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 .

