What do systematic reviews say?

Metformin combined with clomiphene citrate vs clomiphene

Metformin combined with clomiphene citrate showed no clear difference in miscarriage rate per woman compared with clomiphene citrate alone (low certainty).

• Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome 2019 · Cochrane Headline outcomes only
  OR 1.35 [0.91, 2]
  10 studies · 1206 participants
  Low
• Insulin‐sensitising drugs (metformin, rosiglitazone, pioglitazone, D‐chiro‐inositol) for women with polycystic ovary… 2017 · Cochrane Headline outcomes only
  OR 1.59 [1.03, 2.46]
  9 studies · 1096 participants
  Low

Metformin combined with clomiphene citrate vs clomiphene

Metformin combined with clomiphene citrate showed no clear difference in live birth rate per woman compared with clomiphene citrate alone (low certainty).

• Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome 2019 · Cochrane Headline outcomes only
  OR 1.27 [0.98, 1.65]
  10 studies · 1219 participants
  Low
• Insulin‐sensitising drugs (metformin, rosiglitazone, pioglitazone, D‐chiro‐inositol) for women with polycystic ovary… 2017 · Cochrane Headline outcomes only
  OR 1.21 [0.92, 1.59]
  9 studies · 1079 participants
  Low

Metformin combined with clomiphene citrate vs clomiphene

Metformin combined with clomiphene citrate probably leads to higher adverse events (gastrointestinal) per woman compared with clomiphene citrate alone (moderate certainty).

• Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome 2019 · Cochrane Headline outcomes only
  OR 4.26 [2.83, 6.4]
  6 studies · 852 participants
  Moderate
• Insulin‐sensitising drugs (metformin, rosiglitazone, pioglitazone, D‐chiro‐inositol) for women with polycystic ovary… 2017 · Cochrane Headline outcomes only
  OR 3.97 [2.59, 6.08]
  3 studies · 591 participants
  Moderate

Metformin combined with clomiphene citrate vs clomiphene

Metformin combined with clomiphene citrate probably leads to higher clinical pregnancy rate per woman compared with clomiphene citrate alone (moderate certainty).

• Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome 2019 · Cochrane Headline outcomes only
  OR 1.62 [1.32, 1.99]
  19 studies · 1790 participants
  Moderate
• Insulin‐sensitising drugs (metformin, rosiglitazone, pioglitazone, D‐chiro‐inositol) for women with polycystic ovary… 2017 · Cochrane Headline outcomes only
  OR 1.59 [1.27, 1.99]
  16 studies · 1529 participants
  Moderate

Metformin combined with clomiphene citrate vs clomiphene

Metformin combined with clomiphene citrate may leads to higher ovulation rate per woman compared with clomiphene citrate alone (low certainty).

• Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome 2019 · Cochrane Headline outcomes only
  OR 1.65 [1.35, 2.03]
  22 studies · 1601 participants
  Low
• Insulin‐sensitising drugs (metformin, rosiglitazone, pioglitazone, D‐chiro‐inositol) for women with polycystic ovary… 2017 · Cochrane Headline outcomes only
  OR 1.57 [1.28, 1.92]
  21 studies · 1624 participants
  Moderate

Metformin combined with clomiphene citrate vs clomiphene

The review found no eligible studies for this question.

• Insulin‐sensitising drugs (metformin, rosiglitazone, pioglitazone, D‐chiro‐inositol) for women with polycystic ovary… 2017 · Cochrane Headline outcomes only
  no estimate extracted
  Studies not reported
  No studies found

Clomiphene citrate or letrozole with or without gonadotropins (with or without midcycle antagonist) vs gonadotropins (with GnRH agonists or midcycle antagonist)

Clomiphene citrate or letrozole with or without gonadotropins (with… showed no clear difference in live birth per woman compared with gonadotropins (with GnRH agonists or midcycle antagonist) (low certainty).

• Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian… 2017 · Cochrane Headline outcomes only
  RR 0.92 [0.66, 1.27]
  4 studies · 493 participants
  Low

Clomiphene citrate or letrozole with or without gonadotropins (with or without midcycle antagonist) vs gonadotropins (with GnRH agonists or midcycle antagonist)

• Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian… 2017 · Cochrane Headline outcomes only
  no estimate extracted
  3 studies · 136 participants
  Moderate

Clomiphene citrate or letrozole with or without gonadotropins (with or without midcycle antagonist) vs gonadotropins (with GnRH agonists or midcycle antagonist)

• Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian… 2017 · Cochrane Headline outcomes only
  no estimate extracted
  8 studies · 1203 participants
  Moderate

Clomiphene citrate or letrozole with or without gonadotropins (with or without midcycle antagonist) vs gonadotropins (with GnRH agonists or midcycle antagonist)

Clomiphene citrate or letrozole with or without gonadotropins (with… may leads to lower ovarian hyperstimulation syndrome per woman compared with gonadotropins (with GnRH agonists or midcycle antagonist) (low certainty).

• Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian… 2017 · Cochrane Headline outcomes only
  Peto OR 0.21 [0.11, 0.41]
  5 studies · 1067 participants
  Low

Clomiphene citrate or letrozole with or without gonadotropins (with or without midcycle antagonist) vs gonadotropins (with GnRH agonists or midcycle antagonist)

Clomiphene citrate or letrozole with or without gonadotropins (with… showed no clear difference in clinical pregnancy rate per woman compared with gonadotropins (with GnRH agonists or midcycle antagonist) (moderate certainty).

• Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian… 2017 · Cochrane Headline outcomes only
  RR 1 [0.86, 1.16]
  12 studies · 1998 participants
  Moderate

Clomiphene citrate or letrozole with or without gonadotropins (with or without midcycle antagonist) vs gonadotropins (with GnRH agonists or midcycle antagonist)

Clomiphene citrate or letrozole with or without gonadotropins (with… may leads to higher cancellation rate per woman compared with gonadotropins (with GnRH agonists or midcycle antagonist) (low certainty).

• Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian… 2017 · Cochrane Headline outcomes only
  RR 1.87 [1.43, 2.45]
  9 studies · 1784 participants
  Low

Clomiphene citrate or letrozole with or without gonadotropins (with or without midcycle antagonist) vs gonadotropins (with GnRH agonists or midcycle antagonist)

• Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian… 2017 · Cochrane Headline outcomes only
  no estimate extracted
  6 studies · 1098 participants
  Moderate

Clomiphene citrate or letrozole with or without gonadotropins (with or without midcycle antagonist) vs gonadotropins (with GnRH agonists or midcycle antagonist)

• Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian… 2017 · Cochrane Headline outcomes only
  no estimate extracted
  8 studies · 1481 participants
  Moderate

Clomiphene citrate or letrozole with or without gonadotropins (with or without midcycle antagonist) vs gonadotropins (with GnRH agonists or midcycle antagonist)

Clomiphene citrate or letrozole with or without gonadotropins (with… showed no clear difference in live birth per woman compared with gonadotropins (with GnRH agonist or midcycle antagonist) (low certainty).

• Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian… 2017 · Cochrane Headline outcomes only
  RR 1.16 [0.49, 2.79]
  2 studies · 357 participants
  Low

Clomiphene citrate or letrozole with or without gonadotropins (with or without midcycle antagonist) vs gonadotropins (with GnRH agonists or midcycle antagonist)

Clomiphene citrate or letrozole with or without gonadotropins (with… showed no clear difference in clinical pregnancy rate per woman compared with gonadotropins (with GnRH agonist or midcycle antagonist) (low certainty).

• Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian… 2017 · Cochrane Headline outcomes only
  RR 0.85 [0.64, 1.12]
  8 studies · 1462 participants
  Low

Clomiphene citrate or letrozole with or without gonadotropins (with or without midcycle antagonist) vs gonadotropins (with GnRH agonists or midcycle antagonist)

Clomiphene citrate or letrozole with or without gonadotropins (with… may leads to higher cancellation rate per woman compared with gonadotropins (with GnRH agonist or midcycle antagonist) (low certainty).

• Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian… 2017 · Cochrane Headline outcomes only
  RR 1.46 [1.18, 1.81]
  10 studies · 1601 participants
  Low

IUI in a stimulated cycle vs TI or expectant management

IUI in a stimulated cycle probably leads to higher live birth rate per couple (all cycles)‐ clomiphene citrate or… compared with TI or expectant management (moderate certainty).

• Intra‐uterine insemination for unexplained subfertility 2020 · Cochrane Headline outcomes only
  OR 4.48 [2, 10.01]
  1 study · 201 participants
  Moderate

IUI in a stimulated cycle vs TI or expectant management

IUI in a stimulated cycle showed no clear difference in live birth rate per couple (all cycles)‐ clomiphene citrate or… compared with TI or expectant management (low certainty).

• Intra‐uterine insemination for unexplained subfertility 2020 · Cochrane Headline outcomes only
  OR 0.82 [0.45, 1.49]
  1 study · 253 participants
  Low

IUI in a stimulated cycle vs TI or expectant management

IUI in a stimulated cycle probably leads to higher pregnancy rate per couple (all cycles)‐ clomiphene citrate or… compared with TI or expectant management (moderate certainty).

• Intra‐uterine insemination for unexplained subfertility 2020 · Cochrane Headline outcomes only
  OR 4.68 [2.22, 9.86]
  1 study · 201 participants
  Moderate