Please select the eligibility criteria that correspond to the clinical trial below.
Title: Intrauterine Insemination With Letrozole Versus Intrauterine Insemination in Natural Cycle. A Randomised Controlled Trial
Brief Summary: Rationale: Intrauterine insemination (IUI) is the treatment of first choice for couples with unexplained and mild male factor infertility in many countries, but it is controversial whether ovarian stimulation improves fertility outcomes. In recent retrospectively collected data, investigators found that in couples with unexplained and mild male factor infertility undergoing IUI, ovarian stimulation with letrozole increased live birth rate as compared to natural cycle IUI without substantially increasing the multiple pregnancy rate. Investigators therefore perform a randomized clinical trial (RCT) on the subject in the Centre of Reproductive Medicine, Peking University Third Hospital, Beijing, China.

Objective: To test the hypothesis that in couples with unexplained or mild male factor infertility scheduled for an IUI program ovarian stimulation with letrozole increases the live birth rate as compared to natural cycle treatment.

Study design Randomized clinical trial.

Study population Women diagnosed with unexplained or mild male factor infertility scheduled for treatment with IUI.

Intervention Women will be randomized for ovarian stimulation with letrozole or to natural cycle IUI. In the group allocated to ovarian stimulation, women will receive oral tablets letrozole 5 mg daily from cycle day 3-5 for 5 days. Investigators will treat the couples for 3 cycles, with a time horizon of 4 months.

Main study parameters/endpoints Primary outcome is ongoing pregnancy leading to live birth. Secondary endpoints are clinical pregnancy, multiple pregnancy, miscarriage rates, pregnancy complications and patients' costs.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness The strategies compared are already broadly applied in current practice. No additional risks are expected. There is no benefit for participants, but the results may benefit future subfertile couples.


Options:
A: 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
B: Inclusion Criteria:

* Being diagnosed with unexplained or mild male subfertility
* At least one sided tubal patency, established according to local protocol
* Normal or mild impairment of semen quality defined as a TMSC of 3 million or more based on at least one semen analysis

Exclusion Criteria:

* Woman with double sided tubal pathology
* Women with irregular cycles, PCOS or other endocrine disorders
* Impaired semen quality: pre-wash TMSC \<3 million.
C: 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.
D: Inclusion Criteria:

* all women with PCOS trying to conceive who are between 18 and 37 years of age (PCOS will be defined using the Rotterdam criteria)

Exclusion Criteria:

* women who have already began fertility treatment
* women who are taking myo-inositol or have taken it in the past three months
* women being treated for or who have a history of an eating disorder

Answer: B