Improving Reproductive Fitness Through Pretreatment With Lifestyle Modification in Obese Women With Unexplained Infertility
Condition: Infertility, Female
MeSH terms: Infertility; Infertility, Female
Intervention: Caloric Restriction; Orlistat; Moderate physical activity
Intervention description: 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.
Intervention MeSH terms: Orlistat
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 379.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: No

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).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Women ≥18 to ≤ 40 years of age, with one or more years infertility history, desirous
             of conceiving, regularly ovulating (defined as 9 or more menses per year), at
             initiation of participation.

          2. BMI ≥ 30 kg/m2.

          3. Normal uterine cavity and at least one open fallopian tube confirmed by
             hysterosalpingography (HSG), sonohysterography (SHG), or laparoscopy/hysteroscopy in
             the last three years preceding enrollment into the study. An uncomplicated
             intrauterine non-IVF pregnancy and uncomplicated delivery and postpartum course
             resulting in live birth within the last three years will also serve as sufficient
             evidence of a patent tube and normal uterine cavity as long as the subject did not
             have, during the pregnancy or subsequently, risk factors for Asherman's syndrome or
             serious pelvic infection or other disorder leading to an increased suspicion for
             intrauterine abnormality or tubal occlusion.

          4. Evidence of ovarian function/reserve as assessed by menstrual cycle day 3 (+/-2 days)
             FSH ≤10 IU/L with estradiol ≤ 70 pg/mL OR AMH ≥ 1 ng/mL within one year prior to study
             initiation.

          5. Normal or corrected thyroid function within one year of study initiation.

          6. Normal or corrected prolactin level within one year of study initiation.

          7. In general good health, not taking any medications which could interfere with the
             study (e.g., FSH, insulin sensitizers).

          8. Ability to have inseminations following hCG administration.

          9. Male partner with total motile sperm in the ejaculate of at least 5 million sperm,
             within one year of study initiation.

         10. Able to comply with intercourse instructions and collection of semen for insemination.

        Exclusion Criteria:

          1. Currently pregnant or successful pregnancies within 12 months of initiating
             participation. Clinical intrauterine miscarriages prior to initiating participation,
             within ASRM guidelines: subjects over 35 must wait six months, while subjects under 35
             must wait 12 months. No exclusion for biochemical pregnancies.

          2. Undiagnosed abnormal uterine bleeding.

          3. Suspicious ovarian mass.

          4. Subjects on oral contraceptives, depo-progestins, or hormonal implants (including
             Implanon). A two month washout period will be required prior to screening for patients
             on these agents. Longer washouts may be necessary for certain depot contraceptive
             methods or implants, especially when the implants are still in place. A one-month
             washout will be required for patients taking oral cyclic progestins.

          5. Known 21-hydroxylase deficiency or other enzyme defect causing congenital adrenal
             hyperplasia.

          6. Type I or Type II diabetes mellitus, or if receiving antidiabetic medications.

          7. Known significant anemia (Hemoglobin <10 g/dL).

          8. History of deep venous thrombosis, pulmonary embolus, or cerebrovascular event.

          9. Known heart disease (New York Heart Association Class II or higher).

         10. Known Liver disease (defined as AST or ALT>2 times normal, or total bilirubin >2.5
             mg/dL).

         11. Known Renal disease (defined as BUN >30 mg/dL or serum creatinine > 1.4 mg/dL).

         12. History of, or suspected cervical carcinoma, endometrial carcinoma or breast
             carcinoma.

         13. History of alcohol abuse (defined as >14 drinks/week) or binge drinking of ≥ 6 drinks
             at one time).

         14. Known Cushing's disease.

         15. Known or suspected adrenal or ovarian androgen secreting tumors.

         16. Allergy or contraindication to the treatment medications: CC or hCG.

         17. Couples with previous sterilization procedures (e.g. vasectomy, tubal ligation)
             whether or not it has been reversed.

         18. Subjects with untreated poorly controlled hypertension defined as a systolic blood
             pressure ≥ 160 mm Hg or a diastolic ≥ 100 mm Hg obtained on two measures at least 60
             minutes apart.

         19. Subjects who have undergone a bariatric surgery procedure in the past or are in a
             period of acute weight loss (defined as a weight loss of greater than 5 kgs in the
             last 6 months).

         20. Known moderate or severe endometriosis.

         21. Anovulation or oligo-ovulation including hypothalamic amenorrhea, polycystic ovary
             syndrome, etc.

         22. Donated semen.

         23. Couples in which either partner is legally married to someone else.

         24. Medical conditions that are contraindications to pregnancy.

         25. Presence of severe, untreated psychiatric illness (major depression, substance abuse,
             eating disorder, etc.) that would, in the opinion of the site investigator, interfere
             with the patient's ability to successfully complete the study.

         26. Any additional medical conditions that would be a contraindication to orlistat. (This
             includes patients with chronic malabsorption syndrome or cholestasis or known
             hypersensitivity to any of the drugs used in this study.)

         27. Any contraindication to study requirements including diet recommendations and activity
             requirements.

         28. Currently participating in a lifestyle intervention program (such as Weight Watchers,
             Atkins Diet, Curves) or lost more than 5% body weight within the last 6 months.

         29. History of Gout.