Fit-for-Fertility Multicenter Randomized Controlled Trial: Improving Reproductive, Maternal and Neonatal Outcomes in Obese and Infertile
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 408
- 试验地点
- 6
- 主要终点
- Live birth rate
研究概览
简要总结
Infertility affects approximately 10-15% of couples and one of its important modifiable risk factor is obesity, which affects 19% of Canadian women of reproductive age. Accordingly, many organizations have recommended that women should be assisted to adopt a healthy lifestyle prior to conception and maintain it during pregnancy. We therefore propose to conduct a multicenter randomized controlled trial (RCT) assessing the lifestyle intervention Fit-For-Fertility in women with infertility and obesity. Our hypothesis is that the Fit-For-Fertility program is an efficient and low cost solution to improve access to motherhood for women suffering from obesity and infertility.
To test our hypothesis, seven fertility clinics having a good ethnic diversity will participate in this RCT and recruit a total of 408 women with obesity (BMI according to ethnicity) who consult at the fertility clinic. Participants will be randomly allocated to one of these two groups: the intervention group will be invited to participate in the Fit-for Fertility Program alone for 6 months and then in combination with usual fertility treatments; while the control group will receive standard fertility treatments from randomisation. The aim of the Fit-for Fertility Program will be to implement progressive and sustainable lifestyle changes, using 1) individual sessions with a dietitian and a kinesiologist every 6-12 weeks, for a total of 18 months or until the end of pregnancy; and 2) eight educational group sessions. Evaluation visits will take place prior to randomisation and then every 6 months for 18 months. Women who become pregnant will be evaluated early during pregnancy and at 26 weeks of gestation. Clinical outcomes will be assessed after a total follow up of 24 months.
Anticipated contributions: The results of our multicenter RCT will provide important data on the importance of a lifestyle program supporting women with obesity consulting in fertility clinics, in order to improve their fertility and response to ART, as well as helping them to have a healthy baby. This study will also provide valuable information on potential cost savings for individuals and the healthcare system.
详细描述
- BACKGROUND
Infertility affects approximately 10-15% of couples and costs associated with medically assisted reproduction (MAR) are growing, such that equitable access to high quality reproductive care is a challenge for the Canadian health care system. This is especially true for women with obesity. A modifiable risk factor for infertility is obesity (body mass index (BMI) >= 30 kg/m2), which accounts for as many as 19% of Canadian women of reproductive age. Moreover, obesity increases the costs of fertility treatments, reduces their effectiveness and predisposes to several pregnancy and neonatal complications. As important, maternal pre-pregnancy BMI and excessive gestational weight gain were consistently associated with early development of obesity and diabetes in the offspring. Childhood obesity is closely linked to adult obesity, which perpetuates the intergenerational cycle of obesity. Accordingly, we strongly believe that targeting women with obesity prior to conception may be essential to reduce the burden of infertility and MAR costs in Canada, as well as obesity and cardiometabolic diseases.
To prevent these adverse effects, many organizations have recommended that obese women should be assisted to adopt a healthy lifestyle prior to conception and maintain it during pregnancy. In a recent survey, all women who were obese or overweight and considering pregnancy were interested in adopting a healthy lifestyle pre-conception and 91% reported their willingness to participate in a lifestyle program. However, most Canadian women with obesity do not have access to such targeted lifestyle programs integrated with their fertility care. Our solution is therefore to give these women access to the Fit-for-Fertility Program, an interdisciplinary lifestyle intervention, integrated into the fertility clinic care pathway. This program supports participants in their adoption of sustainable healthy behaviours, prior conception and during pregnancy.
To fill these gaps, in 2010 Dr. Baillargeon set up the Canadian network on reproductive and maternal health of women with obesity and infertility. Through this network, our team has conducted a CIHR-funded RCT evaluating the impact of the Fit-for-Fertility Program, which was implemented at the fertility clinic of the Centre hospitalier universitaire de Sherbrooke (CHUS), on 130 obese women randomized to 1) Control group: standard fertility treatments right away; or 2) Intervention group: follow the Fit-for-Fertility program alone for 6 months, then in combination with fertility treatments if not pregnant. The analysis of the 108 women who completed at least 6 months in the study (83%) shows that after a maximum follow-up of 18 months and in comparison with the standard fertility treatments (n = 57), the Fit-for-Fertility program (n = 51) significantly increased the rates of total pregnancy (61% vs. 39%, p = 0.02) and spontaneous pregnancy (31% vs. 12%, p = 0.01), as well as a tendency to increase live birth (51% vs. 37%, p = 0.14). Such results from the pilot study are highly clinically significant. The total cost of this intervention was only $870 per participant, as compared to standard fertility care costs averaging $4,400 per woman with obesity in the above-mentioned trial. As such, these preliminary results thus suggest that our low-cost lifestyle intervention for women who are obese and infertile may significantly improve their fertility and reduce the need for expensive MAR. These promising findings provide strong justification for further validation in diverse Canadian populations using a multicenter trial.
The general goals of our research program are therefore to i) improve the fertility of women with obesity, ii) reduce costs associated with their fertility treatments, and iii) promote the health of mothers and their offspring. To achieve this goal, we ask the question: Does the Fit-for-Fertility Program improve in a cost-effective manner the live birth rate and other fertility outcomes, as well as pregnancy and neonatal outcomes, in women with obesity and infertility who consult a fertility clinic, as compared to usual care? 2. OBJECTIVES
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Infertility defined as (a) failure to achieve a clinical pregnancy after ≥12 months of regular unprotected sexual intercourse, (b) not conceiving after having tried ≥6 months in women with irregular menstrual cycles or ≥35 years of age; or (c) women with an established cause of infertility;
- •Aged between 18 and 40 years; and
- •Obesity (BMI ≥ 30 kg/m² or 27 kg/m² for Asian and Latin American), or overweight for women with PCOS (BMI ≥ 27 kg/m²).
排除标准
- •Any uncontrolled medical or mental condition that contra-indicates fertility treatments, based on clinical judgment of the fertility specialist;
- •If the only clinically indicated MAR procedure is IVF (e.g. bilateral tubal factor, severe male factor, etc.) or in case of insemination with donor, because natural conception is impossible or highly unlikely;
- •Recurrent spontaneous abortions (>2 miscarriages at less than 22 weeks of gestation) within the last 12 months (with evidence of conception, such as positive β-hCG), because these women do not have difficulty to conceive.
- •Previously diagnosed uncontrolled eating disorder or major depression that would contra-indicate the initiation of a lifestyle intervention;
- •A high level of depressive state, as determined by a score for depression on the Hospital Anxiety and Depression Scale (HADS) ≥ 15, since that would contra-indicate the initiation of a lifestyle intervention;
- •Planning for or past history of bariatric surgery;
- •Planning for or engaging in another intensive lifestyle intervention (that includes face-to-face visits every 8 weeks or less, which would be similar to the intervention tested);
- •Inability to understand the language in which group sessions will be provided in the participating center, i.e. French in Quebec province and English in other provinces; and
- •Planning to be unable to attend research visits at the participating center for the next 18 months, due to moving in another region, for example.
结局指标
主要结局
Live birth rate
时间窗: 24 months
Cumulative incidence of live birth, based on medical record/questionnaire.
次要结局
- Fertility Outcomes - Rate of biochemical pregnancy(24 months)
- Fertility Outcomes - Rate of ongoing pregnancy(24 months)
- Blood markers - Endocrine panel(18 months or end of pregnancy)
- Fertility Outcomes - Rate of spontaneous miscarriage(24 months)
- Fertility Outcomes - Rate of multiple gestation(24 months)
- Fertility Outcomes - Rate of spontaneous pregnancy(24 months)
- Lifestyle outcomes - Nutrient intake(18 months or end of pregnancy)
- Lifestyle outcomes - Physical activity behaviours(18 months or end of pregnancy)
- Lifestyle outcomes - Measures of physical activity(18 months or end of pregnancy)
- Fertility Outcomes - Rate of pregnancy following MAR procedures(24 months)
- Fertility Outcomes - Doses of fertility medications per participant(24 months)
- Fertility Outcomes - Number of MAR and/or ART cycles per participant(24 months)
- Fertility Outcomes - Frequency of embryo transfers(24 months)
- Fertility Outcomes - Frequency of complications due to MAR procedures(24 months)
- Lifestyle outcomes - Physical fitness level(18 months or end of pregnancy)
- Lifestyle outcomes - Other lifestyles(18 months or end of pregnancy)
- Lifestyle outcomes - Sleep duration and quality(18 months or end of pregnancy)
- Lifestyle outcomes - Sleep stages(18 months or end of pregnancy)
- Lifestyle outcomes - Perceived competence(18 months or end of pregnancy)
- Lifestyle outcomes - Readiness(18 months or end of pregnancy)
- Lifestyle outcomes - Anxiety/depression(18 months or end of pregnancy)
- Anthropometric measures - BMI(18 months or end of pregnancy)
- Anthropometric measures - Fat percentage(18 months or end of pregnancy)
- Blood markers - Sex steroids(18 months or end of pregnancy)
- Blood markers - Metabolic panel(18 months or end of pregnancy)
- Neonatal outcomes - Birth trauma(24 months)
- Incremental health-related cost-effectiveness ratio of live birth(24 months)
- Pregnancy outcomes - Gestational weight gain(24 months)
- Pregnancy outcomes - Gestational complications(24 months)
- Neonatal outcomes - Birth weight(24 months)
- Neonatal outcomes - Apgar score(24 months)
- Neonatal outcomes - Hypoglycemia(24 months)
- Neonatal outcomes - Jaundice(24 months)
- Neonatal outcomes - Admission to neonatal intensive care unit(24 months)
- Neonatal outcomes - Death(24 months)
研究者
Jean-Patrice Baillargeon
Professor of Medicine
Université de Sherbrooke