Please select the eligibility criteria that correspond to the clinical trial below.
Title: Pregnancy in Polycystic Ovary Syndrome: A 30 Week Double-Blind Randomized Trial of Clomiphene Citrate, Metformin XR, and Combined Clomiphene Citrate/Metformin XR For the Treatment of Infertility in Women With Polycystic Ovary Syndrome
Brief Summary: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting up to 10% of women. The primary symptoms of PCOS are menstrual irregularities, increased body and facial hair, acne, and infertility. This study will test a combination of medications in women with PCOS to determine which works best to overcome infertility.


Options:
A: 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. Normal uterine cavity and at least one open fallopian tube confirmed by hysterosalpingography (HSG), sonohysterography, 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.
3. Evidence of ovarian function/reserve as assessed by day 3 (+/-2 days) FSH ≤12 IU/L within one year prior to study initiation.
4. Normal or corrected thyroid function within one year of study initiation.
5. Normal prolactin level within one year of study initiation.
6. In general good health, not taking any medications which could interfere with the study (e.g., FSH, insulin sensitizers).
7. Ability to have inseminations following hCG administration.
8. Male partner with total motile sperm in the ejaculate of at least 5 million sperm, within one year of study initiation.

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. Patients 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 on 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: AI, gonadotropins, CC or hCG.
17. Couples with previous sterilization procedures (e.g. vasectomy, tubal ligation) which have been reversed.
18. Patients 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 recent past (\< 12 months) and are in a period of acute weight loss or have been advised against pregnancy by their bariatric surgeon.
20. Known moderate or severe endometriosis
21. Known polycystic ovarian syndrome as evidenced by anovulation or oligoovulation, hirsutism and/or elevated testosterone levels, and ovarian morphology on ultrasound examination.
22. Donated semen.
23. Couples in which either partner is legally married to someone else.
24. Medical conditions that are contraindications to pregnancy.
B: Inclusion Criteria:

* Fulfilling Rotterdam criteria for PCOS
* Infertility more than 1 year
* First or second cycle of IVF/ICSI treatment
* Age below 38 years at inclusion
* BMI below 28 kg/m3 at inclusion
* Willing to be randomised to 4 months metformin or placebo
* Signed written informed consent

Exclusion Criteria:

* Not suitable for starting dose 112.5 IE
* Basal FSH above 10 IU/L
* Known renal disease or s-creatinine above 110 umol/L
* Known liver disease or s-ALAT above 80 IU/L
* Known alcoholism or drug abuse
* Known diabetes mellitus or fasting plasma glucose above 7 mmol/L
* Corticosteroid treatment (oral)
* Treatment with cimetidine, anticoagulants, erythromycin or other macrolides
* Hyperprolactinemia (PRL above 700 mIU/L)
* Abnormal thyroid function tests
* Known congenital adrenal hyperplasia
* Androgen secreting tumours
* Cushing syndrome
* Metformin treatment within the last one month prior to screening
* Unfit to participate for any other reason
C: Inclusion Criteria

* Eight or fewer menstrual cycles in the past year or intermenstrual periods of 45 days or longer
* Elevated testosterone level
* Good general health
* Sperm concentration in partner of 20 million/ml or greater
* Ability to have intercourse 2-3 times per week
* One functional fallopian tube and normal uterine cavity
D: Inclusion Criteria:

* Women between the age of 18 and 39 years inclusive.
* Anovulatory infertility of duration at least 12 months.
* Polycystic ovary syndrome, based on Rotterdam consensus criteria.
* Normal serum prolactin, thyroid function and 17-hydroxyprogesterone.
* Normal serum prolactin, thyroid function and 17-hydroxyprogesterone;

Exclusion Criteria:

* Presence of any other significant infertility factor including male factor, known tubal disease or history of an ectopic pregnancy, known endometriosis affecting the fallopian tubes or ovaries.
* Already taking oral hypoglycaemics.
* Diabetics receiving treatment.
* Renal impairment
* Chronic hepatic disease
* Cardiac Disease
* Alcohol dependency
* Pre-disposition to lactic acidosis
* Previous ovarian drilling procedure, gonadotrophin injection therapy, IUI (intrauterine insemination) or IVF ( in vitro fertilisation).
* For those women who have had previous fertility treatment, the following would be excluded:

  * Women who have had \> 5 cycles of clomiphene citrate
  * Women who have had \> 5 months metformin treatment previously
  * Women who have proven to be resistant to 100mg or more of clomiphene citrate.

Answer: C