FIT-PLESE

Principal Investigator: Erica  Johnstone
Keywords: Overweight , Infertility , BMI , Weight loss , Free , Reproductive medicine , IUI cycles Department: Obstetrics And Gynecology (Dept)
IRB Number: 00091533 Co Investigator:  
Specialty: OB/Gyn, General, Reproductive Endocrinology and Infertility, OB/Gyn, General, Reproductive Endocrinology and Infertility, OB/Gyn, General, OB/Gyn, General, OB/Gyn, General
Sub Specialties: General Gynecology, In Vitro Fertilization, In Vitro Fertilization, General Obstetrics, Women's Health, Contraception and Family Planning
Recruitment Status: Recruiting

Contact Information

Samantha Nielsen
sam.nielsen@hsc.utah.edu
801-585-7617

Brief Summary

Primary Aim

Our primary goal is to examine the efficacy of an intensive lifestyle modification intervention, which includes caloric restriction by using meal replacements, a weight loss medication (over the counter orlistat) and physical activity recommendations versus a standard lifestyle intervention consisting of increasing physical activity alone on improving good birth outcomes in obese women with unexplained infertility.  Implicit in the primary aim is the goal of tracking safety of our interventions at all Phases of the study (through lifestyle modification to infertility treatment to pregnancy to infant).

Secondary Aim

We will assess secondary outcomes including live birth rate, time to pregnancy, pregnancy loss rate [including ectopics and Pregnancies of Unknown Location (PULs)], multiple pregnancy rate, pregnancy complication rate including development of gestational hypertension and diabetes, birth weight, mode of delivery, neonatal complication rate, predictive factors for response including DNA polymorphisms, stool and vaginal microbiome composition, psychosocial outcomes, and cost effectiveness.

Tertiary Aims

  1. Is there a relationship between amount of weight loss or amount of physical activity during lifestyle modification and ovulatory response and pregnancy?
  2. Does physical activity alone lead to healthier pregnancies (i.e. better gestational weight gain, blood pressure change, glycohemoglobin levels)?
  3. Is there a biphasic effect of either weight loss or physical activity on conception and pregnancy?
  4. Does lifestyle modification affect the menstrual cycle of regularly ovulating women?
  5. Is this treatment more cost effective than immediately proceeding with empiric infertility treatment? (compare with AMIGOS data)
  6. Does weight loss or physical activity increase sexual function and amount of intercourse?
  7. Can sperm microarray identify couples more or less likely to conceive?
  8. Does perceived stress and self-reported quality of life by husband and wife influence success?  [Assess by SF-12 and PHQ-9]]
  9. Is length of luteal phase predictive of pregnancy outcome?
  10. Is there a relationship between length of infertility and conception?
  11. Is there a difference in pregnancy rate in the first vs. second vs. third vs. fourth cycle?
  12. Does weight loss or physical activity reduce the rate of metabolic syndrome?
  13. Does the baseline vaginal or stool microbiome effect response to treatment and outcomes.
  14. Does treatment effect the stool or vaginal microbiome?
  15. Is the stool microbiome heritable to offspring?
  16. Are there changes in stress as determined by salivary biomarker of stress according to treatments?

 

Inclusion 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 obtained at screening visit.
  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 tubal disease or other disorder leading to an increased suspicion for intrauterine abnormality or tubal occlusion.
  4. Evidence of ovarian function/reserve as assessed by day 3 (+/-2 days) FSH ≤ 10 IU/L with Estradiol ≤ 70 pg/mL OR serum 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 - see Appendix for full list). 
  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 have intercourse and collect semen for insemination

Exclusion Criteria

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 35 and over 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 forms or implants, especially when the implants are still in place.A one-month washout will be required for patients who have taken 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 >15 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, known hypersensitivity or contraindication to the treatment medications used in this study including orlistat (This will include patients with chronic malabsorption syndrome or cholestasis or clomiphene (previous change in vision).

  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 obtained 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% body weight in the last 6 months).

  20. Known 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.

  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)

  29. History of Gout.

  30. History of pelvic radiation

Study Termination Criteria

  1. Development or suspicion of an allergic or serious adverse reaction to any of the medications in the study.

  2. Uncontrolled hypertension.

  3. Persistent ovarian cyst > 30 mm mean diameter that does not resolve in two cycles.

  4. Serious or severe Ovarian Hyperstimulation Syndrome (OHSS).