Table 1 Characteristics of included studies

De Leo et al[18]

Sample size:

- N. of ampoules of huFSH.

Crossover study.

20 subjects

- Serum E₂ levels.

No data on live-births.

Exclusion:

- Days of treatment.

No blind design.

- Abnormal FSH and/or prolactin levels.

- Cancelled cycles.

No criteria for defining OHSS.

- Abnormal thyroid function.

- Incidence of OHSS.

No criteria for cycle cancellation.

- Congenital adrenal hyperplasia.

- Pregnancy rate.

- Abnormal partner’s seminal parameters.

- Side effects.

- Drug assumption 2 mths prior to the study.

Yarali et al[19]

Sample size:

- N. of ampoules of rFSH.

Data of spontaneous ovulation during the pre-treatment phase were excluded.

32 subjects

- Serum E₂ levels.

Exclusion:

- Days of treatment.

No criteria for defining OHSS.

- Any infertility factor other than PCOS (by semen analysis, hysterosalpingography, and/or laparoscopy).

- Cancelled cycles.

No data on OHSS.

- Endocrinopathies.

- Pregnancy rate.

No data on live-births.

- Abnormal glucose tolerance, IGT or type-2 DM.

- Endometrial thickness.

Cycle was cancelled in presence of more than 3 follicles ≥15 mm, or in absence of ovarian response after 35 days of treatment.

- Use of medications known to alter insulin secretion or action.

- Side effects.

Tasdemir et al[20]

Sample size:

- rFSH IU.

No blind design.

32 subjects

- serum E₂ levels.

No criteria for cycle cancellation.

Exclusion:

- N. dominant follicles.

No criteria for defining OHSS.

- Age <20 > 34.

- Days of treatment.

No data on live-births.

- Congenital adrenal hyperplasia.

- Endometrial thickness.

Not specified n. of side effects.

- Hyperprolactinemia.

- Cancelled cycles.

- Hypothyroidism.

- Incidence of OHSS.

- Abnormal renal and liver tests.

- Pregnancy rate.

- Use of drugs with possible effect on endogenous sex hormones.

- Multiple pregnancies.

- Type 1-2 DM.

- Side effects.

- Hypophysal insufficiency.

- Any infertility factor other than PCOS (by semen analysis, hysterosalpingography, and/or laparoscopy).

Palomba et al[21]

Sample size:

- N. of ampoules of hpFSH.

Only insulin-resistant women were included.

70 subjects

- Serum E₂ levels.

IUI was performed in ovulating women who failed to conceive.

Exclusion:

- N. dominant follicles.

TI was performed in non-ovulating women.

- Age <20 or >34 years.

- Days of treatment.

Cycle was cancelled in presence of more than 3 follicles ≥14 mm, or in absence of ovarian response after 35 days of treatment.

- BMI >30 and <18 kg/m².

- Cancelled cycles.

- Neoplastic, metabolic (including glucose intolerance), hepatic, and cardiovascular disorder or other concurrent medical illness.

- Incidence of OHSS.

- Hypothyroidism.

- Ovulation rate.

- Hyperprolactinaemia.

- Rate of mono-ovulatory cycles.

- Cushing’s syndrome; non-classical congenital adrenal

- Pregnancy rate.

- hyperplasia.

- Multiple pregnancy rate (primary end-point).

- Abuse of alcohol.

- Abortion.

- Current or previous (within 6 mths) use of oral contraceptives, glucocorticoids, antiandrogens, antidiabetic, and anti-obesity and hormonal drugs.

- Live-birth rate.

- Organic pelvic diseases.

- Side effects.

- Previous pelvic surgery.

- Suspected peritoneal factor infertility.

- Tubal or male factor infertility (by hysterosalpingogram and semen analysis).

- Intention to start a diet or a specific program of physical activity.

van Santbrink et al[22]

Sample size:

- Units of rFSH (primary end-point).

Only insulin-resistant women were included.

20 subjects

- Serum E₂ levels.

No clear definition for CC-resistance and CC-failure.

Exclusion:

- Days of treatment (primary end-point).

- Age ≤18 ≥ 37 yrs

- Cancelled cycles.

No specific definition for PCOS.

- Abnormal serum E₂ and FSH levels.

- Incidence of OHSS.

No criteria for defining OHSS.

- Abnormal serum prolactin and thyroxine levels.

- Ovulation rate.

No specification of the time of metformin and placebo administration.

- DM.

- Rate of mono-ovulatory cycles.

- Signs of liver or kidney insufficiency and heart or vascular disease.

- Pregnancy rate.

The study was divided into two phases. Only the 2^nd phase was considered in the analysis.

- Multiple pregnancy rate.

- Abortion.

No data on live-births.

- Serious side effects.

Cycle was cancelled in presence of more than 3 follicles ≥15 mm, or in absence of ovarian response at the maximum dosage (225IU rFSH daily).

Cheng et al[23]

Sample size:

- N. of ampoules of HMG.

No data on the days of treatment.

60 subjects

- Serum E₂ levels.

No data of the multiple pregnancies.

Exclusion:

- N. dominant follicles.

No data on live-births.

- Age ≥ 40 yrs.

- Cancelled cycles.

No data on side effects.

- Endometrial pathology.

- Incidence of OHSS.

No criteria for defining OHSS.

- Abnormal glucose tolerance (75g OGTT).

- Ovulation rate.

Cycle was cancelled in presence of more than 4 dominant follicles.

- Any infertility factor other than PCOS.

- Rate of mono-ovulatory cycles.

- Other common causes of hyperandrogenism.

- Pregnancy rate (primary end-point).

- Prolactinoma.

- Congenital adrenal hyperplasia.

- Cushing syndrome.

- Virilizing ovarian or adrenal tumours.

- Hormonal drugs assumption 3 mths prior to the study.

Begum et al[24]

Sample size:

- Ovulation rate.

No blind design.

110 subjects

- Miscarriage.

No criteria for defining OHSS.

Exclusion:

- Perinatal outcome.

No criteria for cycle cancellation due to hyper-response.

-DM.

- Pregnancy rate (primary end-point).

- Altered glucose metabolism.

- Live-birth rate (primary end-point).

No clear strategy (TI or IUI).

- Hyperprolactinemia.

- Hypothyroidism.

- Endometriosis.

- Pelvic inflammatory disease.

- Tubal factor infertility.

- Partner abnormal semen parameters.