***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: OBJECTIVE To determine whether a crossover design results in a different estimate of treatment effect compared with a parallel design . DESIGN With the aid of a computer program , data sets of subfertile patients were simulated under different assumptions . These patients were subjected to 2 treatments that were compared in either a parallel- design or a crossover- design trial . Results were analyzed using logistic regression . SETTING University hospital . PATIENT(S ) Simulated patients of a heterogeneous subfertile population . INTERVENTION(S ) Two treatment modalities with a pregnancy rate of 10 % and of 20 % in the first cycle were offered for 6 cycles to simulated heterogeneous population s. MAIN OUTCOME MEASURE(S ) After 1,000 simulations for each assumption , median pregnancy rates and odds ratios were compared between the crossover- and parallel- design trials . RESULT ( S ) No relevant difference in estimated treatment effect was found between the design s. The crossover design result ed in more pregnancies overall than the parallel design . CONCLUSION ( S ) In infertility research , parallel and crossover design s will lead to about the same results . Although the crossover design showed a slight tendency to overestimate the treatment effect of the most effective treatment , this overestimation is clinical ly not relevant and is small in relation to the r and om error . Because of its practical advantages and because more pregnancies are achieved , a crossover design should be the first choice in infertility research 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 , r and omised controlled non-inferiority trial . Setting 17 centres in the Netherl and s. 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 r and omisation . Main outcome measures The primary outcome was birth of a healthy child result ing from a singleton pregnancy conceived within 12 months after r and omisation . 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 r and omly 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 IS RCT N52843371 ; Nederl and s Trial Register NTR939 BACKGROUND The st and ard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate . Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates . METHODS We enrolled couples with unexplained infertility in a multicenter , r and omized trial . Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were r and omly assigned to ovarian stimulation ( up to four cycles ) with gonadotropin ( 301 women ) , clomiphene ( 300 ) , or letrozole ( 299 ) . The primary outcome was the rate of multiple gestations among women with clinical pregnancies . RESULTS After treatment with gonadotropin , clomiphene , or letrozole , clinical pregnancies occurred in 35.5 % , 28.3 % , and 22.4 % of cycles , and live birth in 32.2 % , 23.3 % , and 18.7 % , respectively ; pregnancy rates with letrozole were significantly lower than the rates with st and ard therapy ( gonadotropin or clomiphene ) ( P=0.003 ) or gonadotropin alone ( P<0.001 ) but not with clomiphene alone ( P=0.10 ) . Among ongoing pregnancies with fetal heart activity , the multiple gestation rate with letrozole ( 9 of 67 pregnancies , 13 % ) did not differ significantly from the rate with gonadotropin or clomiphene ( 42 of 192 , 22 % ; P=0.15 ) or clomiphene alone ( 8 of 85 , 9 % ; P=0.44 ) but was lower than the rate with gonadotropin alone ( 34 of 107 , 32 % ; P=0.006 ) . All multiple gestations in the clomiphene and letrozole groups were twins , whereas gonadotropin treatment result ed in 24 twin and 10 triplet gestations . There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications . CONCLUSIONS In women with unexplained infertility , ovarian stimulation with letrozole result ed in a significantly lower frequency of multiple gestation but also a lower frequency of live birth , as compared with gonadotropin but not as compared with clomiphene . ( Funded by the National Institutes of Health and others ; Clinical Trials.gov number , NCT01044862 . ) Objective To compare the effectiveness of clomifene citrate and unstimulated intrauterine insemination with expectant management for the treatment of unexplained infertility .  Design Three arm parallel group , pragmatic r and omised controlled trial . Setting Four teaching hospitals and a district general hospital in Scotl and . Participants Couples with infertility for over two years , confirmed ovulation , patent fallopian tubes , and motile sperm . Intervention Expectant management , oral clomifene citrate , and unstimulated intrauterine insemination . Main outcome measures The primary outcome was live birth . Secondary outcome measures included clinical pregnancy , multiple pregnancy , miscarriage , and acceptability . Results 580 women were r and omised to expectant management ( n=193 ) , oral clomifene citrate ( n=194 ) , or unstimulated intrauterine insemination ( n=193 ) for six months . The three r and omised groups were comparable in terms of age , body mass index , duration of infertility , sperm concentration , and motility . Live birth rates were 32/193 ( 17 % ) , 26/192 ( 14 % ) , and 43/191 ( 23 % ) , respectively . Compared with expectant management , the odds ratio for a live birth was 0.79 ( 95 % confidence interval 0.45 to 1.38 ) after clomifene citrate and 1.46 ( 0.88 to 2.43 ) after unstimulated intrauterine insemination . More women r and omised to clomifene citrate ( 159/170 , 94 % ) and unstimulated intrauterine insemination ( 155/162 , 96 % ) found the process of treatment acceptable than those r and omised to expectant management ( 123/153 , 80 % ) ( P=0.001 and P<0.001 , respectively ) . Conclusion In couples with unexplained infertility existing treatments such as empirical clomifene and unstimulated intrauterine insemination are unlikely to offer superior live birth rates compared with expectant management . Trial registration IS RCT No : OBJECTIVE To determine whether crossover trials with simple pooling of data over different study periods leads to a different estimate of treatment effect compared with parallel group trials in infertility research using pregnancy as the outcome measure . DESIGN An observational study using nine overviews that included trials with both crossover and parallel group design s. These overviews comprised 17 crossover and 17 parallel group trials . In total , there were 5,291 outcomes including 775 pregnancies . The association between study design and treatment effect estimate was analyzed using multiple logistic regression , controlling for differences in the therapeutic interventions and variations in the method ological quality of the trials . SETTING Infertile patients in an academic research environment . PATIENTS Infertile patients undergoing treatment efficacy evaluation in controlled trials . INTERVENTIONS R and om allocation to a variety of treatments including clomiphene citrate , hCG , IUI , tamoxifen , and bromocriptine . MAIN OUTCOME MEASURE Estimate of bias between study design s , based on the interaction of study design and treatment in the logistic regression model . RESULTS Crossover trials produced a larger average estimate of treatment effect compared with trials with a parallel group design , overestimating the odds ratio by 74 % ( 95 % confidence interval , 2 % to 197 % ) . CONCLUSION The use of a crossover design for evaluating infertility treatments with outcomes that prevent patients from completing later phases of the trial should be avoided because it leads to exaggerated estimates of treatment effect and may result in erroneous inferences and clinical decisions . Furthermore , the type of study design should be taken into account when assessing the method ological quality of therapy trials in infertility The aim of this prospect i ve r and omized controlled study was to determine the possible role of ovulation induction with intrauterine insemination ( IUI ) in the treatment of  unexplained infertility .  A total of 100 patients were r and omized to receive ovulation induction with or without IUI . All patients were treated with long-course gonadotrophin-releasing hormone analogue ( GnRHa ) , starting in the luteal phase , and exogenous follicle stimulating hormone ( FSH ) to induce follicular growth . Ovulation was induced using human chorionic gonadotrophin and timed intercourse ( TI ) was advised 24 - 48 h later or IUI was effected 36 - 48 h later . Both the cycle fecundities ( 21.8 and 8.5 % ) and the cumulative ongoing pregnancy rates after three cycles ( 42 and 20 % ) were significantly higher ( P < 0.03 ) in the IUI group than in the TI group respectively . This is a clear indication that ovulation induction with  IUI  is an effective treatment method for unexplained infertility , but ovulation induction with TI has a negligible impact in this large group of patients BACKGROUND The high iatrogenic multiple pregnancy rate associated with intrauterine insemination ( IUI ) in hyperstimulated cycles is becoming less acceptable . Therefore we investigated data from an earlier prospect i ve trial with regard to the specific question of whether the application of mild hyperstimulation in IUI cycles could be an alternative strategy for obtaining acceptable pregnancy rates while preventing a high multiple pregnancy rate , compared with natural cycles for IUI . METHODS Pregnancy outcome of 310 natural and 334 mildly hyperstimulated cycles for IUI in 171 couples with unexplained or mild male factor subfertility was analysed on a patient level with r and om coefficient models . RESULTS Pregnancy rates were similar : 35 and 39.8 % per couple in the natural and mildly hyperstimulated cycles respectively ( P = 0.60 ) . Multiple pregnancies , all twin pregnancies , were conceived significantly more frequently in the mild hyperstimulation group ( 27 % of the pregnancies ) than in the natural cycle group ( 4 % of the pregnancies ) ( P = 0.01 ) . All multiple pregnancies in the hyperstimulation group 
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Quality ranged from low to moderate , the main limitation being imprecision in the findings for both live birth and multiple pregnancy .. AUTHORS ' CONCLUSIONS This systematic review did not find conclusive evidence of a difference in live birth or multiple pregnancy in most of the comparisons for couples with unexplained subfertility treated with intra-uterine insemination ( IUI ) when compared with timed intercourse ( TI ) , both with and without ovarian hyperstimulation ( OH ) .