Clinical trial: Improving Reproductive Fitness Through Pretreatment With Lifestyle Modification in Obese Women With Unexplained Infertility (NCT02432209)

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.
Female
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 40 Years

Patient description (medical language): A 32-year-old woman comes to the hospital with vaginal spotting.  Her last menstrual period was 10 weeks ago. She has regular menses lasting for 6 days and repeating every 29 days. Medical history is significant for appendectomy and several complicated UTIs. She has multiple male partners, and she is inconsistent with using barrier contraceptives. Vital signs are normal.  Serum β-hCG level is 1800 mIU/mL, and a repeat level after 2 days shows an abnormal rise to 2100 mIU/mL.  Pelvic ultrasound reveals a thin endometrium with no gestational sac in the uterus.

Patient description (patient's own words): I just turned 32 and last morning I woke up with strange blood stains on my underwear. My last periods were more than 2 months ago, which is unusual for me because I used to have regular periods lasting for 6 days every 29 days, more or less. I had several UTIs in the past. I also had appendicitis. I'm currently seeing several men and, to be honest, some of them do struggle to wear a condom. I went to the hospital to check myself up and they told me that my vitals were normal. I also had a blood test on Monday, and my β-hCG level was 1800 mIU/mL, and then on Wednesday, it went up to 2100 mIU/mL. The gynecologist also did an ultrasound and she told me that, hopefully, there was no ovule.

Does the patient match the trial criteria? Contradiction