Antioestrogen versus placebo

Patient or population: ovulation induction in polycystic ovarian syndrome

Setting: USA/Canada. 1 trial took place in a department of obstetrics and gynaecology; details of setting for 2 trials not provided.
Intervention: antioestrogen
Comparison: no treatment or placebo

Live birth rate ‐ not reported

Not estimable

‐

‐

No data for live birth reported for this comparison

Miscarriage rate ‐ not reported

Not estimable

‐

‐

No data for miscarriage reported for this comparison

Clinical pregnancy rate

OR 5.91
(1.77 to 19.68)

133
(3 RCTs)

⊕⊕⊝⊝
LOW ^{1 2}

Low event rates and small sample size observed in included trials

Multiple pregnancy rate ‐ not reported

Not estimable

‐

‐

No data for multiple pregnancy reported for this comparison

Ovarian hyperstimulation syndrome (OHSS) ‐ not reported

Not estimable

‐

‐

No data for OHSS reported for this comparison

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; OR: odds ratio; RCT: randomised controlled trial

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Antioestrogen versus antioestrogen

Patient or population: ovulation induction in polycystic ovarian syndrome

Setting: Egypt, USA/Canada, Iran (2 trials), Italy. Trials conducted in outpatient department, infertility clinic (2 trials), private clinic, and 1 trial did not report setting.
Intervention: antioestrogen
Comparison: antioestrogen

Clomiphene citrate versus tamoxifen ‐ Live birth rate

OR 1.24
(0.59 to 2.62)

195
(2 RCTs)

⊕⊕⊝⊝
LOW ^{1 2}

Low event rates and small sample size observed in the included studies

Clomiphene citrate versus tamoxifen ‐ Miscarriage rate

OR 1.81
(0.80 to 4.12)

653
(4 RCTs)

⊕⊕⊝⊝
LOW ^{2 3}

Low event rates observed in included studies

Clomiphene citrate versus tamoxifen ‐ Clinical pregnancy rate

OR 1.30
(0.92 to 1.85)

757
(5 RCTs)

⊕⊕⊝⊝
LOW ^{4 5}

Clomiphene citrate versus tamoxifen ‐ Multiple pregnancy

OR 2.34
(0.34 to 16.04)

567
(3 RCTs)

⊕⊝⊝⊝
VERY LOW ^{6 7}

Low event rates observed in included studies

Clomiphene citrate versus tamoxifen ‐ ovarian hyperstimulation syndrome (OHSS)

Not estimable

567
(3 studies)

‐

No events of OHSS reported in either intervention or control group in the included studies

Clomiphene citrate plus tamoxifen versus clomiphene citrate ‐ Clinical pregnancy rate

OR 3.32
(0.12 to 91.60)

20
(1 RCT)

⊕⊝⊝⊝
VERY LOW ^{7 8 9}

Very low event rates and very small sample size (n = 20 women) observed in this study

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; OR: odds ratio; RCT: randomised controlled trial

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Antioestrogen plus medical adjunct versus antioestrogen alone

Patient or population: ovulation induction in polycystic ovarian syndrome

Setting: Four studies from Iran, three from USA, two from Egypt, one from Turkey and one from India. Studies conducted in a University clinic, infertility outpatient clinic, Women's hospital clinic, Infertility and Reproductive Health Centre, private infertility clinic, Women's Health Research Institute, Infertiltiy Clinic and Research Clinic; three studies provided no information.
Intervention: antioestrogen plus medical adjunct
Comparison: antioestrogen alone

Clomiphene citrate plus ketoconazole versus clomiphene citrate

⊕⊝⊝⊝
VERY LOW ^{1 2 3}

Low event rates and small sample size in this single study

OR 0.28
(0.01 to 7.08)

80
(1 RCT)

⊕⊝⊝⊝
VERY LOW ^{1 2 3}

Low event rates and small sample size in this single study

OR 2.37
(0.88 to 6.40)

80
(1 RCT)

⊕⊝⊝⊝
VERY LOW ^{1 2 3}

Low event rates and small sample size in this single study

OR 1.18
(0.37 to 3.78)

80
(1 RCT)

Clomiphene citrate plus bromocriptine versus clomiphene citrate ‐ Clinical pregnancy rate

OR 1.03
(0.48 to 2.21)

174
(2 RCTs)

⊕⊕⊝⊝
LOW ^{2 3}

Low event rates and small sample size observed in the included studies

Clomiphene citrate plus dexamethasone versus clomiphene citrate

⊕⊝⊝⊝
VERY LOW ^{3 5 6}

OR 6.20
(2.20 to 17.48)

434
(4 RCTs)

⊕⊕⊝⊝
LOW ^{2 3}

Low event rates and small sample size observed in these studies. One study had no events in the intervention or the control group.

OR 7.71
(0.38 to 155.64)

144
(2 RCTs)

Clomiphene citrate plus combined oral contraceptive versus clomiphene citrate ‐ Miscarriage rate

⊕⊝⊝⊝
VERY LOW ^{1 2 3}

Low event rates and small sample size observed in this single study

OR 1.00
(0.06 to 16.97)

48
(1 RCT)

⊕⊝⊝⊝
VERY LOW ^{3 8}

Low event rates and small sample size observed in this single study

OR 27.18
(3.14 to 235.02)

48
(1 RCT)

⊕⊝⊝⊝
VERY LOW ^{1 2 3}

Low event rates and small sample size observed in this single study

OR 7.98
(0.39 to 163.33)

48
(1 RCT)

Clomiphene citrate plus hCG versus clomiphene citrate alone

⊕⊝⊝⊝
VERY LOW ^{1 3 9}

Low event rates and small sample size observed in this single study

OR 1.31
(0.61 to 2.80)

125
(1 RCT)

⊕⊕⊕⊝
MODERATE ²

Low event rates and small sample size observed in the included studies

OR 0.70
(0.19 to 2.62)

192
(2 RCTs)

⊕⊕⊕⊝
MODERATE ⁹

Low event rates and small sample size observed in the included studies

OR 1.18
(0.59 to 2.36)

192
(2 RCTs)

⊕⊝⊝⊝
VERY LOW ^{1 2 3}

Low event rates and small sample size observed in this single study

OR 2.21
(0.19 to 24.98)

125
(1 RCT)

Clomiphene citrate plus hormone supplementation versus clomiphene citrate alone

⊕⊝⊝⊝
VERY LOW ^{1 2 3}

Low event rates and small sample size observed in this single study

OR 1.00
(0.06 to 16.46)

96
(1 RCT)

⊕⊕⊝⊝
LOW ^{3 9}

Low event rates and small sample size observed in these studies

OR 0.81
(0.37 to 1.76)

161
(2 RCTs)

‐

No events of multiple pregnancy were observed in either the intervention or control group in this single study.

Not estimable

96
(1 RCT)

‐

No events of OHSS were observed in either the intervention or control group in this single study.

Not estimable

96
(1 RCT)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; hCG: human chorionic gonadotropin; OR: odds ratio; RCT: randomised controlled trial

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Antioestrogen regimens

Patient or population: ovulation induction in polycystic ovarian syndrome

Setting: Three studies took place in Egypt and one in Iran. One was conducted in a University Fertility Clinic, one in an Infertility Research Centre and one in a gynaecology outpatient department. The fourth research setting was not specified.
Intervention: clomiphene citrate regimen A
Comparison: clomiphene citrate regimen B

Live birth ‐ Clomiphene citrate 5 days versus clomiphene citrate 10 days

OR 0.10
(0.02 to 0.45)

220
(1 RCT)

⊕⊕⊝⊝
LOW ^{1 2}

Clinical pregnancy ‐ Clomiphene citrate 5 days versus clomiphene citrate 10 days

OR 0.18
(0.06 to 0.55)

220
(1 RCT)

⊕⊕⊝⊝
LOW ^{1 2}

Multiple pregnancy ‐ Clomiphene citrate 5 days versus clomiphene citrate 10 days

OR 0.33
(0.03 to 3.20)

220
(1 RCT)

⊕⊝⊝⊝
VERY LOW ^{1 4}

Miscarriage rate ‐ Early versus late clomiphene citrate

OR 1.25
(0.27 to 5.70)

212
(1 RCT)

⊕⊝⊝⊝
VERY LOW ^{1 3 4}

Clinical pregnancy ‐ Early versus late clomiphene citrate

OR 2.81
(1.02 to 7.75)

78
(1 RCT)

⊕⊕⊝⊝
LOW ⁴

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; OR: odds ratio; RCT: randomised controlled trial

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.