Improving Reproductive Fitness Through Pretreatment With Lifestyle Modification in Obese Women With Unexplained Infertility
Condition: Infertility, Female
MeSH terms: Infertility; Infertility, Female
Study type: Interventional
Phase: Phase 3

Summary: 
      A two-arm, multicenter, prospective, randomized clinical trial of a lifestyle modification
      program with tracked increased physical activity and weight loss (intensive) compared to
      recommendations to tracking of increased physical activity alone with weight maintenance
      (standard) in women with obesity and unexplained infertility. This 16 week period of
      lifestyle modification will be followed by an open label empiric infertility treatment
      regimen consisting of three cycles of ovarian stimulation with oral medication (clomiphene
      citrate (CC)), triggering of ovulation with human chorionic gonadotropin (hCG) and
      intrauterine insemination (IUI).
    

Detailed description: 
      Study Objective An intensive lifestyle modification intervention (which includes caloric
      restriction, use of an over-the-counter weight loss medication, and moderate physical
      activity with tracking) designed to promote a weight loss of approximately 7% of initial body
      weight is more likely to achieve a good perinatal outcome (i.e. a healthy term normal weight
      infant) than a recommendation to standard lifestyle modification with moderate physical
      activity with tracking (based on publically available activity recommendations) in obese
      women with unexplained infertility.

      Patient Population The population will consist of 380 obese women with unexplained
      infertility, age 18-40 years old. Subjects must have normal ovulatory function and normal
      ovarian reserve. Additionally, the couple will have no other major infertility factor: the
      subject will have at least one patent fallopian tube and a normal uterine cavity, and a
      partner total motile sperm count of at least 5 million in at least one ejaculate.

      Study Design This will be a two-arm, multicenter, prospective, randomized clinical trial of a
      lifestyle modification program with tracked increased physical activity and weight loss
      (intensive) compared to recommendations to tracking of increased physical activity alone with
      weight maintenance (standard) in women with obesity and unexplained infertility. This 16 week
      period of lifestyle modification will be followed by an open label empiric infertility
      treatment regimen consisting of three cycles of ovarian stimulation with oral medication
      (clomiphene citrate (CC)), triggering of ovulation with human chorionic gonadotropin (hCG)
      and intrauterine insemination (IUI).

      Treatment The intensive lifestyle modification intervention will consist of caloric
      restriction (consumption of approximately 1200-1500 kcal/d), use of an over-the-counter
      weight loss medication (Alli, which is brand name Orlistat, a gastric lipase inhibitor that
      limits gut fat absorption), and moderate physical activity (goal of reaching 10,000 steps a
      day). The pretreatment intervention will last 16 weeks and is designed to promote a weight
      loss of approximately 7% of total body weight. Women in the standard lifestyle intervention
      (standard) will receive publicly available written materials that promote engagement in
      moderate physical activity with target of 10,000 steps a day. Detailed instruction of
      physical activity will not be provided. Participants in both groups will receive activity
      tracking devices (Fitbit Wireless Activity Tracker) and wireless scales (Fitbit Aria Wireless
      Activity Scale) to promote adherence to the inventions and to allow monitoring for compliance
      by study personnel. The pretreatment intervention will last 16 weeks. Both groups will aim
      for activity levels of 10,000 steps/day, with a recommendation to increase steps from
      baseline by 500 steps/per week. The investigators will monitor subjects monthly during this
      preconception intervention. After 16 weeks of lifestyle modification, all subjects randomized
      will receive a standardized empiric infertility treatment, regardless of adherence or success
      in achieving treatment goals. This treatment will consist of ovarian stimulation with CC
      followed by ultrasound follicular monitoring, hCG trigger of ovulation, and a single partner
      intrauterine insemination (IUI) per treatment cycle for up to three treatment cycles. The
      goal for both treatment groups will be to maintain levels of physical activity and weight
      achieved during the pretreatment phase during the empiric infertility treatment phase.
      Subjects who conceive will be followed throughout pregnancy with the wireless activity
      monitor and wireless scale. Additionally there will be three brief onsite visits during
      pregnancy (per trimester at 16, 24, and 32 weeks) for onsite determination of weight,
      glycemic, and blood pressure changes and collection of biospecimens. All pregnancy outcomes
      will be tracked. Subjects who deliver will be encouraged to donate placenta and cord blood to
      the study repository and then to enroll in our Pregnancy Registry for continued infant
      follow-up. The investigators will also expand the number and variety of specimens that are
      collected for the repository from both partners including urine and serum, semen, saliva,
      placenta and cord blood.
    

Intervention name(s): Caloric Restriction; Orlistat; Moderate physical activity
Intervention type(s): Other; Drug; Other
Intervention description(s): Subjects on Active comparator will have Caloric Restriction to a 1200-1500 kcal/day diet through use of Nutrisystem Meal Plan.; Subjects on Active comparator will use an over-the-counter weight loss medication, Orlistat, a gastric lipase inhibitor that limits gut fat absorption.; All subjects in both arms will be encouraged to engage in moderate physical activity with target of 10,000 steps a day.
Other intervention name(s): Nutrisystem; Alli
Intervention MeSH terms: Orlistat
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment