Dataset Information

Effects of preconception lifestyle intervention in infertile women with obesity: The FIT-PLESE randomized controlled trial.

ABSTRACT:

Background

Women with obesity and infertility are counseled to lose weight prior to conception and infertility treatment to improve pregnancy rates and birth outcomes, although confirmatory evidence from randomized trials is lacking. We assessed whether a preconception intensive lifestyle intervention with acute weight loss is superior to a weight neutral intervention at achieving a healthy live birth.

Methods and findings

In this open-label, randomized controlled study (FIT-PLESE), 379 women with obesity (BMI ≥ 30 kg/m2) and unexplained infertility were randomly assigned in a 1:1 ratio to 2 preconception lifestyle modification groups lasting 16 weeks, between July 2015 and July 2018 (final follow-up September 2019) followed by infertility therapy. The primary outcome was the healthy live birth (term infant of normal weight without major anomalies) incidence. This was conducted at 9 academic health centers across the United States. The intensive group underwent increased physical activity and weight loss (target 7%) through meal replacements and medication (Orlistat) compared to a standard group with increased physical activity alone without weight loss. This was followed by standardized empiric infertility treatment consisting of 3 cycles of ovarian stimulation/intrauterine insemination. Outcomes of any resulting pregnancy were tracked. Among 191 women randomized to standard lifestyle group, 40 dropped out of the study before conception; among 188 women randomized to intensive lifestyle group, 31 dropped out of the study before conception. All the randomized women were included in the intent-to-treat analysis for primary outcome of a healthy live birth. There were no significant differences in the incidence of healthy live births [standard 29/191(15.2%), intensive 23/188(12.2%), rate ratio 0.81 (0.48 to 1.34), P = 0.40]. Intensive had significant weight loss compared to standard (-6.6 ± 5.4% versus -0.3 ± 3.2%, P < 0.001). There were improvements in metabolic health, including a marked decrease in incidence of the metabolic syndrome (baseline to 16 weeks: standard: 53.6% to 49.4%, intensive 52.8% to 32.2%, P = 0.003). Gastrointestinal side effects were significantly more common in intensive. There was a higher, but nonsignificant, first trimester pregnancy loss in the intensive group (33.3% versus 23.7% in standard, 95% rate ratio 1.40, 95% confidence interval [CI]: 0.79 to 2.50). The main limitations of the study are the limited power of the study to detect rare complications and the design difficulty in finding an adequate time matched control intervention, as the standard exercise intervention may have potentially been helpful or harmful.

Conclusions

A preconception intensive lifestyle intervention for weight loss did not improve fertility or birth outcomes compared to an exercise intervention without targeted weight loss. Improvement in metabolic health may not translate into improved female fecundity.

Trial registration

ClinicalTrials.gov NCT02432209.

SUBMITTER: Legro RS

PROVIDER: S-EPMC8765626 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Lifestyle modification is recommended in women with polycystic ovary syndrome (PCOS) prior to conception but there are few randomized trials to support its implementation or benefit.This study aimed to determine the relative efficacy of preconception intervention on reproductive and metabolic abnormalities in overweight/obese women with PCOS.This was a randomized controlled trial of preconception and infertility treatment at Academic Health Centers in women with infertility due to PCOS, age 18-40 y and body mass index 27-42 kg/m(2).Women were randomly assigned to receive either 16 weeks of 1) continuous oral contraceptive pills (OCPs) (ethinyl estradiol 20 mcg/1 mg norethindrone acetate) ("OCP"); 2) lifestyle modification consisting of caloric restriction with meal replacements, weight loss medication (either sibutramine, or orlistat), and increased physical activity to promote a 7% weight loss ("Lifestyle"); or 3) combined treatment with both OCP and lifestyle modification ("Combined"). After preconception intervention, women underwent standardized ovulation induction with clomiphene citrate and timed intercourse for four cycles. Pregnancies were followed with trimester visits until delivery.Weight, ovulation, and live birth were measured.We consented 216 and randomly assigned 149 women (Lifestyle: n = 50; OCP: n = 49; Combined: n = 50). We achieved significant weight loss with both Lifestyle (mean weight loss, -6.2%; 95% confidence interval (CI), -7.4--5.0; and Combined (mean weight loss, -6.4%; 95% CI, -7.6--5.2) compared with baseline and OCP (both P < .001). There was a significant increase in the prevalence of metabolic syndrome at the end of preconception treatment compared with baseline within OCP (odds ratio [OR, 2.47; 95% CI, 1.42-4.27) whereas no change in metabolic syndrome was detected in the Lifestyle (OR, 1.18; 95% CI, 0.63-2.19) or Combined (OR, 0.72; 95% CI, 0.44-1.17) groups. Cumulative ovulation rates were superior after weight loss: OCP, 46%; Lifestyle, 60%; and Combined, 67% (P < .05). Live birth rates were OCP, 12%; Lifestyle, 26%; and Combined, 24% (P = .13).A preconception weight loss intervention eliminates the adverse metabolic oral contraceptive effects and, compared with oral contraceptive pretreatment, leads to higher ovulation rates.

Project description:BACKGROUND:The preconceptional period may be an optimal window of opportunity to improve lifestyle. We previously showed that a 6?month preconception lifestyle intervention among women with obesity and infertility was successful in decreasing the intake of high caloric snacks and beverages, increasing physical activity and in reducing weight in the short term. We now report the effects of the preconception lifestyle intervention on diet, physical activity and body mass index (BMI) at 5.5?years (range?=?3.7-7.0?years) after the intervention. METHODS:We followed women who participated in the LIFEstyle study, a multicentre RCT in which women with obesity and infertility were assigned to a six-month lifestyle intervention program or prompt infertility treatment (N?=?577). Diet and physical activity 5.5?years later were assessed with an 173-item food frequency questionnaire (N?=?175) and Actigraph triaxial accelerometers (N?=?155), respectively. BMI was calculated from self-reported weight and previously measured height (N?=?179). Dietary intake, physical activity, and BMI in the intervention and control group were compared using multivariate regression models. Additionally, dietary intake, physical activity and BMI of women allocated to the intervention arm with successful weight loss during the intervention (i.e. BMI?<?29?kg/m2 or???5% weight loss), unsuccessful weight loss and the control group were compared with ANCOVA. RESULTS:Although BMI did not differ between the intervention and control group 5.5?years after the intervention (-?0.5?kg/m2 [-?2.0;1.1]; P?=?0.56), the intervention group did report a lower energy intake (-?216?kcal/day [-?417;-16]; P?=?0.04). Women in the intervention arm who successfully lost weight during the intervention had a significantly lower BMI at follow-up compared to women in the intervention arm who did not lose weight successfully (-?3.4?kg/m2 [-?6.3;-0.6]; P?=?0.01), and they reported a significantly lower energy intake compared to the control group (-?301?kcal [-?589;-14]; P?=?0.04). Macronutrient intake, diet quality, and physical activity did not differ between the intervention and control group, irrespective of successful weight loss during the intervention. CONCLUSIONS:In our study population, a preconception lifestyle intervention led to reduced energy intake 5.5?years later. Additionally, women allocated to the intervention group who were successful in losing weight during the intervention also had a lower BMI at follow-up. This shows the potential sustainable effect of a preconception lifestyle intervention. TRIAL REGISTRATION:This trial was registered on 16 November 2008 in the Dutch trial register; clinical trial registry number NTR1530 .

Project description:BACKGROUND:The prevalence of obesity, an important cardiometabolic risk factor, is rising in women. Lifestyle improvements are the first step in treatment of obesity, but the success depends on factors like timing and motivation. Women are especially receptive to advice about lifestyle before and during pregnancy. Therefore, we hypothesize that the pre-pregnancy period provides the perfect window of opportunity to improve cardiometabolic health and quality of life of obese infertile women, by means of a lifestyle intervention. METHODS AND FINDINGS:Between 2009-2012, 577 infertile women between 18 and 39 years of age, with a Body Mass Index of ? 29 kg/m2, were randomized to a six month lifestyle intervention preceding infertility treatment, or to direct infertility treatment. The goal of the intervention was 5-10% weight loss or a BMI < 29 kg/m2. Cardiometabolic outcomes included weight, waist- and hip circumference, body mass index, systolic and diastolic blood pressure, fasting glucose and insulin, HOMA-IR, hs-CRP, lipids and metabolic syndrome. All outcomes were measured by research nurses at randomization, 3 and 6 months. Self-reported quality of life was also measured at 12 months. Three participants withdrew their informed consent, and 63 participants discontinued the intervention program. Intention to treat analysis was conducted. Mixed effects regression models analyses were performed. Results are displayed as estimated mean differences between intervention and control group. Weight (-3.1 kg 95% CI: -4.0 to -2.2 kg; P < .001), waist circumference (-2.4 cm 95% CI: -3.6 to -1.1 cm; P < .001), hip circumference (-3.0 95% CI: -4.2 to -1.9 cm; P < .001), BMI (-1.2 kg/m2 95% CI: -1.5 to -0.8 kg/m2; P < .001), systolic blood pressure (-2.8 mmHg 95% CI: -5.0 to -0.7 mmHg; P = .01) and HOMA-IR (-0.5 95% CI: -0.8 to -0.1; P = .01) were lower in the intervention group compared to controls. Hs-CRP and lipids did not differ between groups. The odds ratio for metabolic syndrome in the intervention group was 0.53 (95% CI: 0.33 to 0.85; P < .01) compared to controls. Physical QoL scores were higher in the lifestyle intervention group (2.2 95% CI: 0.9 to 3.5; P = .001) while mental QoL scores did not differ. CONCLUSIONS:In obese infertile women, a lifestyle intervention prior to infertility treatment improves cardiometabolic health and self-reported physical quality of life (LIFEstyle study: Netherlands Trial Register: NTR1530).

Project description:BackgroundObesity in infertile women increases the costs of fertility treatments, reduces their effectiveness and increases significantly the risks of many complications of pregnancy and for the newborn. Studies suggest that even a modest loss of 5-10 % of body weight can restore ovulation. However, there are gaps in knowledge regarding the benefits and cost-effectiveness of a lifestyle modification program targeting obese infertile women and integrated into the fertility clinics. This study will evaluate clinical outcomes and costs of a transferable interdisciplinary lifestyle intervention, before and during pregnancy, in obese infertile women. We hypothesize that the intervention will: 1) improve fertility, efficacy of fertility treatments, and health of mothers and their children; and 2) reduce the cost per live birth, including costs of fertility treatments and pregnancy outcomes.Methods/designObese infertile women (age: 18-40 years; BMI ≥30 kg/m(2) or ≥27 kg/m(2) with polycystic ovary syndrome) will be randomised to either a lifestyle intervention followed by standard fertility treatments after 6 months if no conception has been achieved (intervention group) or standard fertility treatments only (control group). The intervention and/or follow-up will last for a maximum of 18 months or up to the end of pregnancy. Evaluation visits will be planned every 6 months where different outcome measures will be assessed. The primary outcome will be live-birth rates at 18 months. The secondary outcomes will be sub-divided into four categories: lifestyle and anthropometric, fertility, pregnancy complications, and neonatal outcomes. Outcomes and costs will be also compared to similar women seen in three fertility clinics across Canada. Qualitative data will also be collected from both professionals and obese infertile women.DiscussionThis study will generate new knowledge about the implementation, impacts and costs of a lifestyle management program in obese infertile women. This information will be relevant for decision-makers and health care professionals, and should be generalizable to North American fertility clinics.Trial registrationClinicalTrials.gov NCT01483612. Registered 25 November 2011.

Project description:PurposeTo identify demographic, (bio)physical, behavioral, and psychological determinants of successful lifestyle change and program completion by performing a secondary analysis of the intervention arm of a randomized-controlled trial, investigating a preconception lifestyle intervention.MethodsThe 6-month lifestyle intervention consisted of dietary counseling, physical activity, and behavioral modification, and was aimed at 5-10% weight loss. We operationalized successful lifestyle change as successful weight loss (??5% weight/BMI???29 kg/m2), weight loss in kilograms, a reduction in energy intake, and an increase in physical activity during the intervention program. We performed logistic and mixed-effect regression analyses to identify baseline factors that were associated with successful change or program completion.ResultsWomen with higher external eating behavior scores had higher odds of successful weight loss (OR 1.10, 95% CI 1.05-1.16). Women with the previous dietetic support lost 0.94 kg less during the intervention period (95% CI 0.01-1.87 kg). Women with higher self-efficacy reduced energy intake more than women with lower self-efficacy (p?<?0.01). Women with an older partner had an increased energy intake (6 kcal/year older, 95% CI 3-13). A high stage of change towards physical activity was associated with a higher number of daily steps (p?=?0.03). A high stage of change towards weight loss was associated with completion of the intervention (p?=?0.04).ConclusionsDeterminants of lifestyle change and program completion were: higher external eating behavior, not having received previous dietetic support, high stage of change. This knowledge can be used to identify women likely to benefit from lifestyle interventions and develop new interventions for women requiring alternative support.Trial registrationThe LIFEstyle study was registered at the Dutch trial registry (NTR 1530; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1530 ).

Project description:Background: Preconception lifestyle interventions appear promising to reduce pregnancy complications, prevent adult cardiometabolic diseases, and prevent childhood obesity. These interventions have almost exclusively been studied in populations of obese infertile women. The development of preconception lifestyle interventions targeting a broader population of overweight and obese women without a history infertility and their partners is needed. Methods: This study is a multicenter open label parallel group randomized controlled trial. Sixty-eight non-infertile women with overweight or obesity in the preconception period and their partners will be recruited from the Sherbrooke and Quebec City regions. The couples will be randomized in a 1:1 ratio to receive the Healthy for my Baby intervention or standard care in the preconception period and pregnancy. Women and their partners will be invited to take part in this lifestyle intervention which includes motivational interviews and daily self-monitoring of lifestyle goals through a mobile phone application. The primary endpoint of this study is the diet quality of women during the preconception period, which will be evaluated using the C-HEI 2007 score at baseline, 2, 4- and 6-months following study enrolment. Women's dietary quality will also be evaluated through the measure of urinary biomarkers of habitual dietary intake at baseline and 2 months in preconception, and 24-26 weeks in pregnancy. Additional indicators of women's lifestyle as well as anthropometric measures will be documented in preconception and pregnancy. For the pregnancy period, the main secondary endpoint is the pattern of gestational weight gain. Pregnancy and neonatal complications will also be evaluated. For partners, diet quality, other lifestyle habits, and anthropometric measures will be documented in the preconception and pregnancy periods. Discussion: This study will evaluate the effectiveness of a low-cost intervention designed to improve diet and other lifestyle characteristics of women in the preconception period who are overweight or obese. If the Healthy for my Baby intervention is efficacious regarding dietary measures, larger trials will be needed to evaluate the impact of this intervention on the rates of pregnancy complications, childhood obesity, and adult cardiometabolic disease. Clinical Trial Registration:clinicaltrials.gov (NCT04242069).

Project description:BACKGROUND: Intensive lifestyle intervention significantly reduces the progression to diabetes in high-risk individuals. OBJECTIVE: It is not known whether a program of moderate intervention might effectively reduce metabolic abnormalities in the general population. DESIGN: Two-arm randomized controlled 1-year trial. PATIENTS: Three hundred and thirty-five patients participated from a dysmetabolic population-based cohort of 375 adults aged 45-64 years in northwestern Italy. MEASUREMENTS: We compared the effectiveness of a general recommendation-based program of lifestyle intervention carried out by trained professionals versus standard unstructured information given by family physicians at reducing the prevalence of multiple metabolic and inflammatory abnormalities. RESULTS: At baseline, clinical/anthropometric/laboratory and lifestyle characteristics of the intervention (n = 169) and control (n = 166) groups were not significantly different. The former significantly reduced total/saturated fat intake and increased polyunsaturated fat/fiber intake and exercise level compared to the controls. Weight, waist circumference, high-sensitivity C-reactive protein, and most of the metabolic syndrome components decreased in the intervention group and increased in the controls after 12 months. Lifestyle intervention significantly reduced metabolic syndrome (odds ratio [OR] = 0.28; 95% CI 0.18-0.44), with a 31% (21-41) absolute risk reduction, corresponding to 3.2 (2-5) patients needing to be treated to prevent 1 case after 12 months. The intervention significantly reduced the prevalence of central obesity (OR = 0.33; 0.20-0.56), and hypertriglyceridemia (OR = 0.48; 0.31-0.75) and the incidence of diabetes (OR = 0.23; 0.06-0.85). CONCLUSION: A lifestyle intervention based on general recommendations was effective in reducing multiple metabolic/inflammatory abnormalities. The usual care by family physicians was ineffective at modifying progressive metabolic deterioration in high-risk individuals.