Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparison Between Letrozole and Urinary Purified FSH in Women With Clomiphene Citrate Resistant Polycystic Ovarian Syndrome: A Randomised Controlled Trial
Brief Summary: 210 women with clomiphene resistant PCOS will be randomly divided into 3 equal groups using computer generated random numbers. Group 1 will receive FSH, group 2 will have Letrozole and group 3 will act as the control group with no intervention.


Options:
A: Inclusion criteria

1. Age of women between 20 and 40 years.
2. Chronic oligomenorrhea or amenorrhea: oligomenorrhea is defined as an intermenstrual interval \> 35 days or \< 8 menstrual bleedings in the past year. Amenorrhea is defined as an intermenstrual interval \>90 days.
3. Hyperandrogenism (either hirsutism or hyperandrogenemia) or polycystic ovaries on ultrasound. Hirsutism is determined by a modified Ferriman-Gallwey Score ≥ 5 at screening examination, and biochemical hyperandrogenism is defined as total testosterone (T) \> 2.6 nmol/L and free testosterone ≥ 6.0 pg/mL. Polycystic ovaries are present when there are ≥ 12 antral follicles (2 - 9 mm) or ovarian volume \> 10 mL on transvaginal scanning.
4. At least one patent tube shown by hysterosalpingogram or diagnostic laparoscopy within 3 years if the patient does not have a history of abortion or pelvic operation. If the patient has a history of pregnancy and no history of pelvic operation within the past 5 years, she is not required to undergo a tubal patency test.
5. Sperm concentration ⩾ 15 × 106/mL and total motility ⩾ 40% or total motile sperm count ⩾ 9 million in the semen analysis of the husband. Agree to have regular intercourse i.e. 2-3 times per week during the study period.

Exclusion criteria

1. Exclusion of other endocrine disorders: a. patients with hyperprolactinemia (defined as two prolactin levels at least one week apart ≥ 25 ng/mL); b. Patients with FSH levels \> 15 mIU/mL. A normal level within the last year is adequate for entry; c. Patients with uncorrected thyroid disease (defined as TSH \< 0.2 mIU/mL or \> 5.5 mIU/mL). A normal level within the last year is adequate for entry. d. Patients diagnosed with Type I or Type II diabetes who are poorly controlled (defined as HbA1c level \> 7.0%), or patients receiving antidiabetic medications such as metformin, insulin, thiazolidinediones, acarbose, or sulfonylureas. e. Patients with suspected Cushing's syndrome.
2. Use of other TCM treatments including Chinese herbal prescriptions and acupuncture in the past 3 months.
3. Use of other western medications known to affect reproductive function or metabolism in the past 2 months.
4. Pregnancy within the past 6 weeks.
5. Within 6 weeks postabortion or postpartum.
6. Breastfeeding within the last 6 months.
7. Not willing to give written consent to the study.
8. Additional exclusion criteria are as follows.

   1. Patients taking other medications known to affect reproductive function or metabolism. These medications include oral contraceptives, depot progestins, hormonal implants (including Implanon), GnRH agonists and antagonists, antiandrogens, gonadotropins, antiobesity drugs, antidiabetic drugs such as metformin and thiazolidinediones, somatostatin, diazoxide, angiotensin-converting-enzyme (ACE) inhibitors, and calcium channel blockers. The washout period on these medicationswill be two months, longer washouts may be necessary for certain depot contraceptive forms or implants, especially where the implants are still in place. A one-month washout will be required for patients on depot progestins.
   2. Patients with liver disease defined as AST or ALT \> 2 times normal or total bilirubin \> 2.5 mg/dL. Patients with renal disease defined as BUN \> 30 mg/dL or serum creatinine \> 1.4 mg/dL.
   3. Patients with hemoglobin \< 10 g/dL.
   4. Patients with a history of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident.
   5. Patients with known heart disease that is likely to be exacerbated by pregnancy.
   6. Patients with a history of, or suspected cervical carcinoma, endometrial carcinoma, or breast carcinoma. A normal Pap smear result will be required for women 21 and over.
   7. Patients with a current history of alcohol abuse. Alcohol abuse is defined as \>14 drinks/week or binge drinking.
   8. Patients enrolled into other investigative studies that require medications, prescribe the study medications, limit intercourse, or otherwise prevent compliance with the protocol.
   9. Patients who anticipate taking longer than a one-month break during the protocol should not be enrolled.
   10. Patients with a suspected adrenal or ovarian tumor secreting androgens.
   11. Couples with previous sterilization procedures (vasectomy, tubal ligation), which have been reversed. The prior procedure may affect study outcomes, and patients with both a reversed sterilization procedure and PCOS are rare enough that exclusion should not adversely affect recruitment.
   12. 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.
   13. Patients with untreated poorly controlled hypertension defined as a systolic blood pressure 160 mmHg or a diastolic 100 mm Hg obtained on two measures obtained at least 60 minutes apart.
   14. Patients with known congenital adrenal hyperplasia.
B: Inclusion Criteria:

* 20-40 years old
* PCOS infertile women resistant to CC for3 cycles

Exclusion Criteria:

* presence of medical disorders as diabetes, hypertension, cardiac problems, liver or kidney diseases, hyperprolactinemia or thyroid dysfunction.
* use of gonadotropins before
* previous ovarian drilling
* presence of urinary symptoms especially bloody urine
C: Inclusion Criteria:

1. Women aged between 20 and 40 years.
2. Confirmed diagnosis of PCOS according to 2003 modified Rotterdam criteria
3. According to World Health Organization standards (2010), semen analysis of the husband must meet ① or ②. ①sperm concentration ≥15\*106/ml and total motility ≥40% . ② Total motile sperm count ≥9 million, i.e. semen volume\*sperm density\*percentage of motile sperm ≥9 million.
4. At least one patent tube shown by hysterosalpingogram or diagnostic laparoscopy. The results will be valid for 3 years if the patients do not have a history of abortion or pelvic operation.

Exclusion Criteria:

1) Exclusion of other endocrine disorders:

* Patients with hyperprolactinemia (defined as two prolactin levels at least one week apart 25 ng/mL or greater or as determined by local normative values). The goal of eliminating patients with documented hyperprolactinemia is to decrease the heterogeneity of the PCOS population. These patients may be candidates for ovulation induction with alternate regimens (dopamine agonists). A normal level within the last year or on treatment is adequate for entry.

  * Patients with FSH levels \> 15 mIU/mL. A normal level within the last year is adequate for entry.

    * Patients with uncorrected thyroid disease (defined as TSH \< 0.2 mIU/mL or \>5.5 mIU/mL). A normal level within the last year is adequate for entry.

      * Patientsdiagnosed with Type I or Type II diabetes who are poorly controlled (defined as a Hb A1c level \> 7.0%), or patients receiving antidiabetic medications such as insulin, thiazolidinediones, acarbose, or sulfonylureas likely to confound the effects of study medication; Patients currently receiving metformin XR (extended release) for a diagnosis of Type I or Type II diabetes or for PCOS are also specifically excluded.

        ⑤Patients with suspected Cushing's syndrome. 2) Use of hormonal or other medication including Chinese Herbal prescriptions which may affect the outcome at least in the past 2 months.

        3) Acupuncture the last 2 months. 4) Pregnancy within the past 6 weeks. 5) Within 6 weeks post-abortion or postpartum. 6) Breastfeeding within the last 6 months. 7) Not willing to give written consent to the study. 8) Additional exclusion criteria

        1. Patients with a suspected adrenal or ovarian tumor secreting androgens. 2. Couples with previous sterilization procedures (vasectomy, tubal ligation) which have been reversed. The prior procedure may affect study outcomes, and patients with both a reversed sterilization procedure and PCOS are rare enough that exclusion should not adversely affect recruitment.

        3. 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.

        4. 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.

        5. Patients with known congenital adrenal hyperplasia. 6. Patients on oral contraceptives, depot 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 where the implants are still in place. A one-month washout will be required for patients on oral cyclic progestins.

        7. Patients with liver disease defined as AST or ALT \> 2 times normal or totalbilirubin \>2.5 mg/dL. Patients with renal disease defined as BUN \> 30 mg/dL or serum creatinine\> 1.4 mg/dL.

        8. Patients with significant anemia (Hemoglobin \< 10 g/dL). 9. Patients with a history of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident.

        10. Patients with known heart disease that is likely to be exacerbated by pregnancy.

        11. Patients with a history of, or suspected cervical carcinoma, endometrial carcinoma, or breast carcinoma. A normal Pap smear or TCT result will be required for women 21 and over.

        12. Patients with a current history of alcohol abuse. Alcohol abuse is defined as \>14 drinks/week or binge drinking.

        13. Patients enrolled simultaneously into other investigative studies that require medications, proscribe the study medications, limit intercourse, or otherwise prevent compliance with the protocol.

        14. Patients who anticipate taking longer than a one month break during the protocol should not be enrolled.

        15. Patients taking other medications known to affect reproductive function or metabolism. These medications include oral contraceptives, GnRH agonists and antagonists, antiandrogens, gonadotropins, anti-obesity drugs, Chinese herbal formula, anti-diabetic drugs such as metformin and thiazolidinediones, somatostatin, diazoxide, ACE inhibitors, and calcium channel blockers. The washout period on all these medications will be two months.
D: Inclusion Criteria:

* Clomiphene resistant PCOS.

Exclusion Criteria:

* Other causes of infertility.
* Hyperprolactinaemia.
* Allergy to Letrozole or FSH.

Answer: D