What do systematic reviews say?

GnRH analogues vs GnRH antagonists

GnRH analogue showed no clear difference in postoperative amenorrhoea at 12 months or less compared with gnRH antagonist (moderate certainty).

• Pre‐operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding 2013 · Cochrane Headline outcomes only
  RR 0.95 [0.79, 1.14]
  100 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 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

Summary of findings table ‐ Progestogens vs GnRH antagonists

• Progestogens for prevention of luteinising hormone (LH) surge in women undergoing controlled ovarian hyperstimulation… 2023 · Cochrane Headline outcomes only
  no estimate extracted
  1 study · 340 participants
  GRADE not reported

Metformin vs placebo or no treatment

Metformin may leads to lower live birth rate per woman ‐ short protocol GnRH‐antagonist compared with placebo or no treatment (low certainty).

• Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome 2020 · Cochrane Headline outcomes only
  RR 0.48 [0.29, 0.79]
  1 study · 153 participants
  Low

Metformin vs placebo or no treatment

It is very uncertain whether metformin changes clinical pregnancy rate per woman ‐ short protocol GnRH‐antagonist compared with placebo or no treatment (very low certainty).

• Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome 2020 · Cochrane Headline outcomes only
  RR 1.38 [0.21, 9.14]
  2 studies · 177 participants
  Very low

GnRH agonists vs HCG

GnRH agonist probably leads to lower live birth compared with HCG (moderate certainty).

• Gonadotropin‐releasing hormone agonist versus HCG for oocyte triggering in antagonist‐assisted reproductive technology 2014 · Cochrane Headline outcomes only
  OR 0.47 [0.31, 0.7]
  5 studies · 532 participants
  Moderate

GnRH agonists vs HCG

GnRH agonist probably leads to lower OHSS (mild, moderate or severe): overall risk compared with HCG (moderate certainty).

• Gonadotropin‐releasing hormone agonist versus HCG for oocyte triggering in antagonist‐assisted reproductive technology 2014 · Cochrane Headline outcomes only
  OR 0.15 [0.05, 0.47]
  8 studies · 989 participants
  Moderate

GnRH agonists vs HCG

GnRH agonist probably leads to lower OHSS (moderate or severe): overall risk compared with HCG (moderate certainty).

• Gonadotropin‐releasing hormone agonist versus HCG for oocyte triggering in antagonist‐assisted reproductive technology 2014 · Cochrane Headline outcomes only
  OR 0.21 [0.07, 0.66]
  8 studies · 989 participants
  Moderate

GnRH agonists vs HCG

GnRH agonist probably leads to lower OHSS (mild, moderate or severe) in women at high risk of OHSS compared with HCG (moderate certainty).

• Gonadotropin‐releasing hormone agonist versus HCG for oocyte triggering in antagonist‐assisted reproductive technology 2014 · Cochrane Headline outcomes only
  OR 0.06 [0.01, 0.34]
  3 studies · 212 participants
  Moderate

GnRH agonists vs HCG

GnRH agonist may leads to lower ongoing pregnancy compared with HCG (low certainty).

• Gonadotropin‐releasing hormone agonist versus HCG for oocyte triggering in antagonist‐assisted reproductive technology 2014 · Cochrane Headline outcomes only
  OR 0.7 [0.54, 0.91]
  11 studies · 1198 participants
  Low