Improving Reproductive Fitness Through Pretreatment With Lifestyle Modification in Obese Women With Unexplained Infertility

• Status: Completed
• Trial end date: 2020-05-01
• Target enrollment: 0
• Participant gender: Female

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).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University
• Collaborators: Augusta University; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Penn State University; University of California, San Francisco; University of North Carolina; University of Oklahoma; University of Pennsylvania
• Treatments: Orlistat

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.