Preconception lifestyle advice for people with infertility

In the paper

“adverse events including gestational diabetes (RR 0.78, 95% CI 0.48 to 1.26; 1 RCT, 317 participants; very low-quality evidence)”

In the paper

“hypertension (RR 1.07, 95% CI 0.66 to 1.75; 1 RCT, 317 participants; very low-quality evidence)”

In the paper

“miscarriages (RR 1.31, 95% CI 0.21 to 8.34; 1 RCT, 37 participants; very low-quality evidence)”

In the paper

“Studies were heterogeneous with respect to participants.”

In the paper

“Due to very low-quality evidence, we are uncertain whether preconception lifestyle advice affects the percentage of weight loss, vegetable and fruit intake, alcohol abstinence, or physical activity.”

In the paper

“Compared to routine care, we are uncertain whether preconception lifestyle advice on weight affects the number of live births (RR 0.94, 95% CI 0.62 to 1.43; 2 RCTs, 707 participants; I² = 68%; very low-quality evidence)”

In the paper

“miscarriage (RR 1.50, 95% CI 0.95 to 2.37; 1 RCT, 577 participants; very low-quality evidence)”

In the paper

“Due to very low-quality evidence, we are uncertain whether preconception lifestyle advice affects the percentage of weight loss, vegetable and fruit intake, alcohol abstinence, or physical activity.”

In the paper

“Due to very low-quality evidence, we are uncertain whether preconception lifestyle advice affects the percentage of weight loss, vegetable and fruit intake, alcohol abstinence, or physical activity.”

In the paper

“alcohol abstinence (RR 1.07, 95% CI 0.99 to 1.17; 1 RCT, 607 participants)”

In the paper

“smoking cessation (RR 1.01, 95% CI 0.98 to 1.04; 1 RCT, 606 participants)”

In the paper

“Due to very low-quality evidence, we are uncertain whether preconception lifestyle advice affects the percentage of weight loss, vegetable and fruit intake, alcohol abstinence, or physical activity.”

In the paper

“Studies on preconception lifestyle advice on weight were identified only in women with infertility and obesity.”

In the paper

“We are uncertain whether preconception lifestyle advice on alcohol intake affects the number of live births (RR 1.15, 95% CI 0.53 to 2.50; 1 RCT, 37 participants; very low-quality evidence)”

In the paper

“Studies on preconception lifestyle advice on alcohol intake were identified only in at-risk drinking women with infertility.”

In the paper

“Preconception lifestyle advice on a combination of topics may result in little to no difference in the number of women with adequate folic acid supplement use (RR 0.98, 95% CI 0.95 to 1.01; 2 RCTs, 850 participants; I² = 4%)”

In the paper

“The studies included 1908 women and 222 men with a diagnosis of infertility.”

In the paper

“Studies on preconception lifestyle advice on smoking were identified only in smoking women with infertility.”

In the paper

“Studies were heterogeneous with respect to interventions and comparisons.”

In the paper

“preconception lifestyle advice on weight may slightly reduce BMI (MD -1.30 kg/m², 95% CI -1.58 to -1.02; 1 RCT, 574 participants; low-quality evidence)”

• Also stated in: § Secondary outcomes · hedged

  “Preconception lifestyle advice on weight may slightly reduce the BMI in women with infertility and obesity (MD -1.30 kg/m2, 95% CI -1.58 to -1.02; 1 RCT, 574 participants; low-quality evidence) (Analysis 2.5).”

In the paper

“For the number of participants with adequate intake of vegetables, the RR was 1.46, 95% CI 1.17 to 1.82 in 612 women with infertility, and was 1.42, 95% CI 0.96 to 2.08 in 216 male partners.”

In the paper

“Due to very low-quality evidence, we are uncertain whether preconception lifestyle advice on a combination of topics affects the number of clinical pregnancies.”

In the paper

“Oostingh 2020 reported an RR of 0.92 (95% CI 0.81 to 1.05) in 626 participants.”

What the sources say

• Not checked yetcites Oostingh 2020 source

In the paper

“Reported behavioural changes: No studies reported on lifestyle behavioural changes in caffeine intake and physical activity.”

In the paper

“Low-quality evidence suggests that preconception lifestyle advice on a combination of topics may result in little to no difference in the number of live births.”

In the paper

“or the physical quality of life in women with infertility and obesity (MD 1.63, 95% CI -0.58 to 3.85; 1 RCT, 235 participants; very low-quality evidence) (Analysis 2.14).”

In the paper

“We are uncertain whether preconception lifestyle advice on a combination of topics affects the number of men not smoking (RR 1.01, 95% CI 0.91 to 1.12; 1 RCT, 212 participants; very low-quality evidence).”

What the sources say

• Not checked yetcites Oostingh 2020 source

In the paper

“From evidence of very low quality, we are uncertain whether preconception lifestyle advice on weight affects the number of clinical pregnancies in women with infertility and obesity.”

In the paper

“We are uncertain whether preconception lifestyle advice on a combination of topics affects vegetable intake (MD 12.50 grams/ d, 95% CI -8.43 to 33.43; 1 RCT, 264 participants; very low-quality evidence) (Analysis 1.3).”

In the paper

“For the number of participants with adequate fruit intake, study authors reported an RR of 1.18, 95% CI 1.05 to 1.33 in 612 women with infertility, and an RR of 1.57, 95% CI 1.21 to 2.04 in 216 male partners.”

In the paper

“We are uncertain whether preconception lifestyle advice on weight affects the mental quality of life in women with infertility and obesity (MD -0.34, 95% CI -2.91 to 2.24; 1 RCT, 235 participants; very low-quality evidence)”

In the paper

“We are uncertain whether preconception lifestyle advice on alcohol intake affects the number of live births in at-risk drinking women with infertility (RR 1.15, 95% CI 0.53 to 2.50; 1 RCT, 37 participants; very lowquality evidence).”

In the paper

“Delaying the start of fertility treatment to give preconception lifestyle advice on weight might slightly increase the time to pregnancy in women with infertility and obesity (HR 0.79, 95% CI 0.63 to 0.99; 1 RCT, 561 participants; low-quality evidence) (Analysis 2.14).”

In the paper

“We are uncertain whether preconception lifestyle advice on weight affects the numbers of miscarriages in women with infertility and obesity (RR 1.50, 95% CI 0.95 to 2.37; 1 RCT, 577 participants; very low-quality evidence).”

In the paper

“We are uncertain whether preconception lifestyle advice on alcohol intake affects miscarriage in atrisk drinking women with infertility (RR 1.31, 95% CI 0.21 to 8.34; 1 RCT, 37 participants; very low-quality evidence).”

In the paper

“Additionally, Ng 2018 reported on fruit intake in pieces/d: MD 0.80, 95% CI 0.36 to 1.24 in 164 women with infertility.”

In the paper

“We are uncertain whether preconception lifestyle advice on weight affects the total moderate to vigorous physical activity (MD 50.76 minutes/week, 95% CI 16.77 to 84.75; 1 RCT, 254 participants; very low-quality evidence) (Analysis 2.9).”

In the paper

“For the number of participants with adequate intake of vegetables, the RR was 1.46, 95% CI 1.17 to 1.82 in 612 women with infertility, and was 1.42, 95% CI 0.96 to 2.08 in 216 male partners.”

In the paper

“Studies were heterogeneous with respect to outcomes measured.”

In the paper

“Preconception lifestyle advice on a combination of topics may result in little to no difference in the number of women with adequate use of folic acid supplement (RR 0.98, 95% CI 0.95 to 1.01; 2 RCTs, 850 participants; I2 = 4%; low-quality evidence).”

In the paper

“Two studies provided preconception lifestyle advice on a combination of weight, diet, vitamin or mineral supplement intake (folic acid), alcohol intake, physical activity, and smoking (Ng 2018, Oostingh 2020).”

In the paper

“Preconception lifestyle advice on a combination of topics may result in little to no difference in the number of live births (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.79 to 1.10; 1 RCT, 626 participants; low-quality evidence).”

In the paper

“We are uncertain whether preconception lifestyle advice on weight affects birth weight in women with infertility and obesity (MD -29.00 g, 95% CI -39.12 to -18.88; 1 RCT, 276 participants; very low-quality evidence) (Analysis 2.10).”

In the paper

“We are uncertain whether preconception lifestyle advice on weight affects gestational age in women with infertility and obesity (MD 0.45 weeks, 95% CI 0.33 to 0.57; 1 RCT, 276 participants; very low-quality evidence) (Analysis 2.11).”

In the paper

“and fruit intake (MD -7.25 grams/d, 95% CI -7.86 to -6.64; 1 RCT, 258 participants; very low-quality evidence) in women with infertility and obesity (Analysis 2.6 Analysis 2.7).”

In the paper

“We are uncertain whether preconception lifestyle advice on weight decreases alcohol intake in women with infertility and obesity (MD not estimable; 1 RCT, 239 participants; very low-quality evidence) (Analysis 2.8).”

In the paper

“Alibeigi 2020 reported an RR of 2.85 (95% CI 1.53 to 5.29) in 180 participants.”

What the sources say

• Not checked yetcites Alibeigi 2020 source

In the paper

“Preconception lifestyle advice on a combination of topics may result in little to no difference in the proportion of women abstaining from alcohol (RR 1.07, 95% CI 0.99 to 1.17; 1 RCT, 607 participants; low-quality evidence).”

In the paper

“We are uncertain whether preconception lifestyle advice on a combination of topics affects the number of men abstaining from alcohol (RR 1.08, 95% CI 0.74 to 1.58; 1 RCT, 210 participants; very low-quality evidence).”

In the paper

“Two studies provided preconception lifestyle advice on weight loss for women with infertility and obesity (Belan 2019, Mutsaerts 2016).”

In the paper

“We are uncertain whether preconception lifestyle advice on a combination of topics affects BMI in women compared to routine care (mean difference (MD) -1.06 kg/m2, 95% CI -2.33 to 0.21; 1 RCT, 180 participants; very low-quality evidence) (Analysis 1.2).”

In the paper

“We are uncertain whether preconception lifestyle advice on weight affects the numbers of live births in women with infertility and obesity (RR 0.94, 95% CI 0.62 to 1.43; 2 RCTs, 707 participants; I2 = 68%; very low-quality evidence).”

In the paper

“and hypertension (RR 1.07, 95% CI 0.66 to 1.75; 1 RCT, 317 participants; very low-quality evidence) in women with infertility and obesity.”

In the paper

“No studies reported on male factor infertility outcomes.”

In the paper

“Preconception lifestyle advice on a combination of topics may result in little to no difference in the proportion of women not smoking (RR 1.01, 95% CI 0.98 to 1.04; 1 RCT, 606 participants; low-quality evidence).”

What the sources say

• Not checked yetcites Oostingh 2020 source

In the paper

“We are uncertain whether preconception lifestyle advice on weight affects the percentage of weight loss in women with infertility and obesity (MD -3.29%, 95% CI -4.34 to -2.24; 2 RCTs, 380 participants; I2 = 24%, very low-quality evidence) (Analysis 2.4).”

In the paper

“We are uncertain whether preconception lifestyle advice on weight affects the numbers of adverse events including gestational diabetes (RR 0.78, 95% CI 0.48 to 1.26; 1 RCT, 317 participants; very lowquality evidence)”

In the paper

“For the number of participants with adequate fruit intake, study authors reported an RR of 1.18, 95% CI 1.05 to 1.33 in 612 women with infertility, and an RR of 1.57, 95% CI 1.21 to 2.04 in 216 male partners.”

In the paper

“No studies reported on reduction of caffeine intake.”

In the paper

“We are uncertain whether preconception lifestyle advice on weight affects vegetable intake (MD 0.00 grams/d, 95% CI -4.18 to 4.18; 1 RCT, 250 participants; very lowquality evidence)”

In the paper

“Consequently, we were able to add only evidence of low to very low quality to the conclusions of the first edition of this review.”

In the paper

“Remarkably, most studies were rated at high risk or at unclear risk of bias due to poor reporting of study methods.”

In the paper

“Our findings also reveal the absence of male participation in the vast majority of studies addressing this topic.”

In the paper

“Ng 2018 Fruit intake in pieces/d at 3 months (mean ± SD) 2.82 ± 1.9 in experimental group (n = 131) 2.02 ± 1.7 in control group (n = 133) MD 0.80, 95% CI 0.36 to 1.24”

What the sources say

• Not checked yetcites Ng 2018

In the paper

“Likewise, four studies reported on clinical pregnancy using a variety of definitions.”

In the paper

“Men: 67/103 in experimental group 46/111 in control group RR 1.57, 95% CI 1.21 to 2.04”

What the sources say

• Not checked yetcites Oostingh 2020 source

In the paper

“Based on the GRADE criteria, the quality of the evidence was low to very low.”

In the paper

“Women: 207/299 in experimental group 182/311 in control group RR 1.18, 95% CI 1.05 to 1.33”

What the sources say

• Not checked yetcites Oostingh 2020 source

In the paper

“Nevertheless, our search identified nine ongoing studies, reflecting increasing interest in preconception lifestyle interventions.”

In the paper

“Women: 124/299 in experimental group 89/313 in control group RR 1.46, 95% CI 1.17 to 1.82”

What the sources say

• Not checked yetcites Oostingh 2020 source

In the paper

“The predefined safety outcomes (adverse events and miscarriage) were reported in only one study (Mutsaerts 2016).”

What the sources say

• Not checked yetcites Mutsaerts 2016 source

In the paper

“1.4 Reported behavioural changes in vitamin and mineral supplement intake: use of folic acid supplement 2 850 Risk Ratio (M-H, Random,95% CI) 0.98 [0.95, 1.01]”

In the paper

“Men: 40/103 in experimental group 31/113 in control group RR 1.42, 95% CI 0.96 to 2.08”

What the sources say

• Not checked yetcites Oostingh 2020 source

In the paper

“In our review, we included only one study that had invited male participants (Oostingh 2020).”

What the sources say

• Not checked yetcites Oostingh 2020 source

In the paper

“Savoury snacks in handfuls/week at 6 months (mean ± SD) 2.17 ± 0.73 handfuls/week in experimental group (n = 100) 2.32 ± 0.81 handfuls/week in control group (n = 139) MD -0.15, 95% CI -0.35 to 0.05”

What the sources say

• Not checked yetcites Mutsaerts 2016 source

In the paper

“Sweet snacks in portions/week at 6 months (mean ± SD) 1.725 ± 0.32 portion/week in experimental group (n = 99) 2.72 ± 0.79 portion/week in control group (n = 136) MD -1, 95% CI -1.14 to -0.85”

What the sources say

• Not checked yetcites Mutsaerts 2016 source

In the paper

“Belan 2019 Composite score: healthy eating index in points at 6 months (mean ± SD) 18.2 ± 13.7 in experimental group (n = 46) 5.3 ± 12.4 in control group (n = 51) MD 12.90, 95% CI 7.68 to 18.12”

What the sources say

• Not checked yetcites Belan 2019

In the paper

“2.5 Reported behavioural changes in weight: percentage of weight loss 2 380 Mean Difference (IV, Random, 95% CI) -3.29 [-4.34, -2.24]”

In the paper

“Mutsaerts 2016 Sugary drinks in glasses/d at 6 months (mean ± SD) 0.59 ± 0.2 glasses/d in experimental group (n = 88) 0.99 ± 0.3 glasses/d in control group (n = 128) MD -0.41, 95% CI -0.47 to -0.34”

What the sources say

• Not checked yetcites Mutsaerts 2016 source

In the paper

“Belan 2019 Total leisure activity energy expenditure in kcal/kg/d at 6 months (mean ± SD) 0.77 ± 1.63 in experimental group (n = 46) 0.17 ± 1.26 in control group (n = 51) MD 0.60, 95% CI 0.02 to 1.18”

What the sources say

• Not checked yetcites Belan 2019

In the paper

“Decrease in % of drinking days in past 6 months (mean ± SD) 0.2 ± 0.3 in experimental group (n = 16) 0.1 ± 0.2 in control group (n = 21) MD 0.10, 95% CI -0.07 to 0.27”

What the sources say

• Not checked yetcites Rossi 2013 source

In the paper

“2.1 Live birth 2 707 Risk Ratio (M-H, Random, 95% CI) 0.94 [0.62, 1.43]”

In the paper

“Rossi 2013 Decrease in number of drinks on a drinking day (mean ± SD) 1 ± 1 in experimental group (n = 16) 0.4 ± 1 in control group (n = 21) MD 0.60, 95% CI -0.05 to 1.25”

What the sources say

• Not checked yetcites Rossi 2013 source

In the paper

“Maternal methylmercury exposure through eating predatory fish can affect foetal development (McDiarmid 2008).”

What the sources say

• Not checked yetcites McDiarmid 2008 source

In the paper

“Modifiable lifestyle factors such as weight, diet, alcohol intake, caffeine intake, physical activity, smoking, and other substance abuse may affect the chance of people with infertility having a live birth (Homan 2007, Rooney 2014).”

• Also stated in: § Description of the intervention · hedged

  “Lifestyle factors that may affect fertility and the chance of a live birth include weight, diet, alcohol intake, caffeine intake, physical activity, smoking, and other substance abuse (Government of South Australia 2015, Homan 2007, Practice Committee 2017, Rooney 2014, World Health Organization 2017).”

What the sources say

• Not checked yetcites Homan 2007 source
• Not checked yetcites Rooney 2014 source
• Not checked yetcites Government of South Australia 2015

In the paper

“Indeed, fertility treatment is less successful in men and women who are overweight or obese as compared with normal weight couples (Campbell 2015, Rittenberg 2011).”

What the sources say

• Not checked yetcites Campbell 2015 source
• Not checked yetcites Rittenberg 2011 source

In the paper

“Moreover, obese women are at increased risk of developing maternal and foetal complications during pregnancy (Practice Committee 2015).”

What the sources say

• Not checked yetcites Practice Committee 2015

In the paper

“However, consumption of high levels of caffeine (> 300 mg caffeine/d) during pregnancy has been associated with increased risk of spontaneous abortion (Lyngso 2017).”

What the sources say

• Not checked yetcites Lyngso 2017

In the paper

“For the first version of this review, the search identified no RCTs that assessed effects of preconception advice on the chance of live birth or other fertility outcomes in people with a diagnosis of infertility, and the need for further research into this topic was highlighted (Anderson 2010).”

What the sources say

• Not checked yetcites Anderson 2010 source

In the paper

“Regarding vitamins, excessive vitamin A consumption through supplements or through crustacean or liver products during pregnancy can cause congenital defects, so it is recommended that women avoid these both before and during pregnancy (Government of South Australia 2015).”

What the sources say

• Not checked yetcites Government of South Australia 2015

In the paper

“Evidence from observational studies suggests that higher intake of folic acid may increase a woman's chances of becoming pregnant (Gaskins 2018a).”

What the sources say

• Not checked yetcites Gaskins 2018a

In the paper

“Besides these substantial health benefits, evidence suggests a positive association between moderate physical activity and male and female fertility (Homan 2007, Ibanez-Perez 2019, McKinnon 2016).”

What the sources say

• Not checked yetcites Homan 2007 source
• Not checked yetcites Ibanez-Perez 2019 source
• Not checked yetcites McKinnon 2016 source

In the paper

“Additionally, alcohol has well-documented detrimental effects on a foetus during pregnancy (Mukherjee 2005).”

What the sources say

• Not checked yetcites Mukherjee 2005 source

In the paper

“Consuming high levels of alcohol (> 2 drinks per day, with 1 drink > 10 g of ethanol) can affect both female and male fertility and the success of fertility treatment (Hakim 1998, Klonoff-Cohen 2003, Rossi 2011).”

What the sources say

• Not checked yetcites Hakim 1998 source
• Not checked yetcites Klonoff-Cohen 2003 source
• Not checked yetcites Rossi 2011 source

In the paper

“The use of non-prescription and recreational drugs before conception has been associated with reduced fertility in both men and women (Frey 2008, Fronczak 2012, Mueller 1990).”

What the sources say

• Not checked yetcites Frey 2008 source
• Not checked yetcites Fronczak 2012 source
• Not checked yetcites Mueller 1990 source

In the paper

“Low-to very low-quality evidence suggests that antioxidant supplementation in women with infertility may increase the chance of pregnancy or live birth rate (Showell 2020).”

What the sources say

• Not checked yetcites Showell 2020 source

In the paper

“The evidence was of low to very low quality.”

In the paper

“Low-quality evidence suggests that antioxidant supplementation for men with infertility may improve live birth rates (Smits 2019).”

What the sources say

• Not checked yetcites Smits 2019 source

In the paper

“Due to the limited number of studies identified for each comparison, we were not able to perform subgroup analyses.”

In the paper

“Low-quality evidence suggests that preconception lifestyle advice on a combination of topics may result in little to no difference in the number of live births.”

In the paper

“Taking a daily folic acid (vitamin B9) supplement of 400 µg before conception and during the first three months of pregnancy has been shown to decrease the risk of neural tube defects (such as spina bifida) in the foetus (De-Regil 2017).”

What the sources say

• Not checked yetcites De-Regil 2017

In the paper

“Evidence on the association between consumption of caffeine and male and female fertility is inconclusive (Lyngso 2017, Ricci 2017).”

What the sources say

• Not checked yetcites Lyngso 2017
• Not checked yetcites Ricci 2017 source

In the paper

“Few studies have investigated the effects of caffeine intake on people with infertility as a subpopulation, but no clear associations between caffeine intake and outcomes of fertility treatment have been found (Lyngso 2017).”

What the sources say

• Not checked yetcites Lyngso 2017

In the paper

“For women undergoing fertility treatment, moderate physical activity is associated with increased pregnancy and live birth rates (Rao 2018).”

What the sources say

• Not checked yetcites Rao 2018 source

In the paper

“Moreover, evidence shows that smoking reduces the success of fertility treatments such as IVF and ICSI (Klonoff-Cohen 2005, Mínguez-Alarcón 2018, Practice Committee 2018, Waylen 2008).”

What the sources say

• Not checked yetcites Klonoff-Cohen 2005 source
• Not checked yetcites Mínguez-Alarcón 2018 source
• Not checked yetcites Practice Committee 2018

In the paper

“Five studies were rated at low risk of selection bias related to allocation concealment, as they used sequentially numbered, sealed, opaque envelopes or central randomization by a third party (Belan 2019, Hughes 2000, Mutsaerts 2016, Ng 2018, Oostingh 2020).”

In the paper

“Because the reasons for discontinuation of the intervention were well documented and were consistent with the statistical plan of 20% discontinuation of the intervention and 5% loss to follow-up, we rated this study at low risk of attrition bias (Mutsaerts 2016).”

In the paper

“Six studies were rated at low risk of selection bias related to sequence generation, as they used computer-generated randomization or a random numbers table (Belan 2019, Hughes 2000, Mutsaerts 2016, Ng 2018, Oostingh 2020, Rossi 2013).”

In the paper

“The evidence suggests that if the chance of live birth is assumed to be 49% in the control group, then the chance of live birth when preconception lifestyle advice is received would be between 30% and 70% (Analysis 2.1).”

In the paper

“Two studies failed to report the number of participants lost to follow-up (Hughes 2000, Rossi 2013).”

In the paper

“This suggests that if the proportion of women not smoking is assumed to be 95.1% in the control group, then the number of women not smoking when preconception lifestyle advice is received would be between 93% and 99% (Analysis 1.6).”

In the paper

“Therefore, we rated risk of attrition bias as unclear (Oostingh 2020).”

In the paper

“Six studies reported on patient-reported outcome measures for which the participant was the outcome assessor and was not blinded.Therefore, these studies had high risk of detection bias for these outcomes (Belan 2019, Hughes 2000, Mutsaerts 2016, Ng 2018, Oostingh 2020, Rossi 2013).”

In the paper

“In Oostingh 2020, discontinuation in the intervention group was 30.2% versus 18.2% in the control group.”

In the paper

“This suggests that if the number of women abstaining from alcohol is assumed to be 75% in the control group, then the number of women abstaining from alcohol when receiving preconception lifestyle advice would be between 74% and 88% (Analysis 1.5).”

In the paper

“We found no potential sources of within-study bias in the other studies.”

In the paper

“Deviations from the intended intervention could have arisen in all studies, for example, differential behaviours across groups such as the control group seeking preconception advice outside the study setting, or differential administration of co-interventions by personnel.”

In the paper

“Three studies reported discontinuation of the intervention and/or losses to follow-up but used intention-to-treat (ITT) analysis ( Alibeigi 2020, Mutsaerts 2016, Oostingh 2020).”

In the paper

“In two studies, it is not clear if personnel were also blinded during the intervention (Ng 2018, Oostingh 2020).”

In the paper

“However, Rossi 2013 provided data on 37 participants, whereas 161 patients with infertility were initially included.This study was rated at high risk of attrition bias.”

In the paper

“We therefore rated all studies at high risk of performance bias.”

In the paper

“This suggests that if the proportion of live births is assumed to be 48% in the control group, then the proportion of live births when preconception lifestyle advice is received would be between 38% and 53% (Analysis 1.1).”

In the paper

“Therefore, the data from these two studies were not pooled for this outcome, as this would not result in a clinically meaningful estimate of the treatment effect (Analysis 1.7).”

In the paper

“One study was rated at high risk of other bias, as it was an interim analysis (Ng 2018).”

In the paper

“Six studies were rated at high risk of reporting bias (Alibeigi 2020, Belan 2019, Hughes 2000, Ng 2018, Oostingh 2020, Rossi 2013).”

In the paper

“Not blinding outcome assessors might influence patient-reported outcome measures such as effects of reported behavioural changes on diet, vitamin or mineral supplement intake, alcohol intake, caffeine intake, physical activity, smoking, and quality of life, as participants could report more socially desirable answers for these outcomes.”

In the paper

“In the other five studies, personnel were aware of the assigned interventions (Alibeigi 2020, Belan 2019, Hughes 2000, Mutsaerts 2016, Rossi 2013).”

In the paper

“Five studies were rated at low risk of detection bias for these outcomes (Alibeigi 2020, Belan 2019, Mutsaerts 2016, Oostingh 2020, Rossi 2013).”

In the paper

“In all studies, participants were aware of the assigned interventions, as it is difficult to blind participants to behavioural interventions such as preconception lifestyle advice.”

In the paper

“Evidence from identified studies was not sufficient to justify firm conclusions on the effect of preconception lifestyle advice.”

In the paper

“This suggests that if the proportion of women with adequate use of folic acid supplement is assumed to be 93% in the control group, then the proportion of women with adequate use of folic acid supplement when preconception lifestyle advice is received would be between 89% and 94% (Analysis 1.4).”

In the paper

“In Mutsaerts 2016, discontinuation was 21.8% in the intervention group.”

In the paper

“We therefore rated Mutsaerts 2016 at low risk of reporting bias.”

In the paper

“outcome assessors were not blinded.Live birth, weight, and clinical pregnancy were not likely to be influenced, as they are observer-reported out-comes not involving judgement”

In the paper

“no blinding of participants and personnel (according to clinical tri-al register).Not clear from the paper if personnel delivering the intervention were blinded.Participants were aware of assigned intervention.Deviations from the intended intervention could have occurred”

In the paper

“Evidence was insufficient to permit a conclusion on the effects and safety of preconception lifestyle advice on adverse events, miscarriage, birth weight, gestational age, clinical pregnancy, quality of life, or male factor infertility outcomes, as no identified studies looked at these outcomes or the studies were of very low quality.”

In the paper

“Consequently, this limits the usefulness of this evidence in informing clinical practice.”

In the paper

“This inconsistency in reporting outcomes and the small number of studies covering all predefined outcomes contributed to our inability to synthesize results and compare and combine individual studies into a meta-analysis.”

In the paper

“prospectively registered study protocol is available.Most outcomes are analysed and reported in accordance with the protocol.However, tertiary outcomes are reported in the protocol and not in Netherlands Trial Register.Additionally, study authors reported an outcome not pre-specified in the protocol: lifestyle risk score, and did not (yet) report on the prespecified out-come: BIG 3 complications”

In the paper

“the primary care-giver was unblinded because he had to do the intervention and the patient was unblinded because they were given the intervention”

In the paper

“numbered, opaque, sealed envelopes”

In the paper

“participants and personnel were aware of assigned intervention; deviations from the intended intervention could have occurred”

In the paper

“study appears free of other sources of bias”

In the paper

“the women's diet and lifestyle were self reported through questionnaires and it was not possible to eliminate reporting biases”

In the paper

“outcome assessor is not blinded.Live birth, adverse events, mis-carriage, weight, birth weight, gestational age, clinical pregnancy, and time to pregnancy are not likely to be influenced, as they are observer-reported out-comes not involving judgement”

In the paper

“the allocation sequence will be concealed in corresponding sequentially numbered opaque envelopes.After a participant has completed baseline assessments, the research coordinator will open the envelope to reveal the group allocation to the participant.Participants will be informed of their group assignment at that time”

In the paper

“outcome assessor is participant and is not blinded; reported behavioural changes are likely to be influenced.Eating healthy, moving, drinking less, higher QOL are socially desirable”

In the paper

“Obviously, all studies were at high risk of detection bias for patientreported outcome measures because of the type of intervention and the impossibility of blinding participants to such types of interventions.”

In the paper

“outcome assessor is participant and is not blinded; reported behavioural changes are likely to be influenced.Eating healthy, moving, adequate use of folic acid supplement, not drinking, and not smoking are socially desir able”

In the paper

“another limitation of our study was the lack of blinding patients and physicians in our study”

In the paper

“for each stratum, a permuted block design is used and programmed before-hand.Hereby, allocation concealment is ensured”

In the paper

“as there was no description of completeness of reported data study authors were contacted for the previous version of this systematic review.They reported that all patients were accounted for and were included in follow-up”