Table 2.
Results of their interventions
| Gonadotrophins | |||||
|---|---|---|---|---|---|
| Bordewijk et al. (45), 2017 | PCOS and anovulatory women | Live birth | FSH+metformin vs. FSH in PCOS resistant | Live birth/woman | OR: 2.31, 95% CI: 1.23 to 4.34 |
| Clinical pregnancy | FSH+metformin vs. FSH in PCOS resistant | Pregnancy/woman | OR: 2.46, 95% CI: 1.36 to 4.46 | ||
| Ovulation | |||||
| Multiple pregnancy Miscarriage | |||||
| OHSS | |||||
| Adverse effects | |||||
| Farquhar et al. (19), 2012 | CC resistant PCOS | Live birth | LOD vs. Gonadotrophins long-term | Costs | MD: -2235.0, 95% CI: -4433.16 to -36.84 |
| Pregnancy | LOD vs. Gonadotrophins short-term | Costs | MD: -1115.75, 95% CI: -1309.72 to -921.77 | ||
| Ovulation | |||||
| Miscarriage | |||||
| Multiple pregnancy | |||||
| OHSS | LOD vs. Gonadotrophins | Multiple pregnancy | OR: 0.13, 95% CI: 0.03 to 0.52 | ||
| Costs | |||||
| Moazami et al. (23), 2014 | CC-resistant PCOS | Live birth Pregnancy Miscarriage | LOD vs. Gonadotropins | Live birth/woman | OR: 0.446, 95% CI: 0.269 to 0.74 |
| Multiple pregnancies | LOD vs. Gonadotropins | Multiple pregnancy | OR: 0.127, 95% CI: 0.028 to 0.579 | ||
| Multiple pregnancy OHSS | Gonadotrophins+metformin vs. Gonadotrophins in OI | Pregnancy/woman | OR: 2.25, 95% CI: 1.50 to 3.38 | ||
| Gonadotrophins+metformin vs. Gonadotrophins in OI | Cancellation/cycle | OR: 0.41, 95% CI: 0.24 to 0.72 | |||
| Gonadotrophins+metformin vs. Gonadotrophins in OI | Gonadotrophins units | MD: 306.62, 95% CI: -500.02 to -113.22 | |||
| Gonadotrophins+metformin vs. Gonadotrophins in OI | Stimulation length | MD: -3.28, 95% CI: -6.23 to -0.32 | |||
| Palomba et al. (40), 2014 | PCOS | Live birth Pregnancy Miscarriage | Gonadotrophins+metformin vs. Gonadotrophins in OI | Live birth/woman | |
| Multiple pregnancy OHSS | Gonadotrophins+metformin vs. Gonadotrophins in OI | Pregnancy/woman | |||
| Gonadotrophins+metformin vs. Gonadotrophins in OI | Cancellation/cycle | ||||
| Gonadotrophins+metformin vs. Gonadotrophins in OI | Gonadotrophins units | ||||
| Gonadotrophins+metformin vs. Gonadotrophins in OI | Stimulation length | ||||
| Weiss et al. (29), 2015 | CC-resistant ± failure PCOS Women treated with prior metformin use +/- CCWomen with prior electro cautery of ovaries. | Live birth | rFSH vs. All urinary gonadotrophins | Gonadotrophins units | MD: -105.44, 95% CI: -154.21, -56.68 |
| rFSH vs. HMG | Gonadotrophins units | MD: -283.94, 95% CI: -449.10 to -118.78 | |||
| Clinical pregnancy Miscarriage | rFSH vs. uFSH | Gonadotrophins units | MD: -88.4, 95% CI: -139.44 to -37.36 | ||
| rFSH vs. All urinary gonadotrophins | Stimulation length | MD: -0.66, 95% CI: -1.04 to -0.28 | |||
| Multiple pregnancy OHSS | rFSH vs. HMG | Stimulation length | MD: -2.28, 95% CI: -3.49 to -1.07 | ||
| rFSH vs. uFSH | Stimulation length | MD: -0.49, 95% CI: -0.88 to -0.09 | |||
| Laparoscopic ovarian drilling (LOD) | |||||
| Farquhar et al. (19), 2012 | CC resistant PCOS | Live birth | LOD vs. Metformin | Pregnancy/woman | OR: 2.47, 95% CI: 1.05 to 5.81 |
| Pregnancy | LOD vs. Other medical treatments | Multiple pregnancy | OR: 0.21, 95% CI: 0.08 to 0.58 | ||
| Ovulation | |||||
| Miscarriage | |||||
| Multiple pregnancy | |||||
| OHSS | |||||
| Costs | |||||
| Baghdadi et a. (56), 2012 | CC resistant PCOS | Pregnancy | Lean vs. Obese PCOS | Ovulation/cycle | RR: 1.90, 95% CI: 1.46 to 2.48 |
| Lean vs. Obese PCOS | Ovulation/woman | RR: 1.43, 95% CI: 1.22 to 1.66 | |||
| Ovulation | Lean vs. Obese PCOS | Pregnancy/cycle | RR: 4.14, 95% CI: 2.08 to 8.23 | ||
| Lean vs. Obese PCOS | Pregnancy/woman | RR: 1.73, 95% CI: 1.39 to 2.17 | |||
| IUI/IVF/ICSI related interventions | |||||
| Luo et al. (57), 2014 | PCOS undergoing COS/IUI | Live birth | GnRH antagonist +IUI vs. Control IUI | LH | MD: 4.6, 95% CI: 0.9 to 8.31 |
| Clinical pregnancy | GnRH antagonist +IUI vs. Control IUI | Premature lutenization rate | OR: 4.36, 95% CI: 2.15 to 8.84 | ||
| Miscarriage | GnRH antagonist +IUI vs. Control IUI | Progesterone | MD: 0.31, 95% CI: 0.24 to 0.37 | ||
| Kollman et al. (18), 2016 | PCOS | Inositol vs. Placebo IVF | Pregnancy/woman | RR: 1.41, 95% CI: 1.05 to 1.89 | |
| Live birth/ ongoing pregnancy | Myo-inositol vs. D-chiro-inositol | Pregnancy/woman | RR: 2.86, 95% CI: 1.14 to 7.16 | ||
| Clinical pregnancy Miscarriage | Antagonist vs. Agonist | OHSS | RR: 0.63, 95% CI: 0.49 to 0.80 | ||
| OHSS | Mannitol vs. Placebo | OHSS | RR: 0.54, 95% CI: 0.39 to 0.77 | ||
| Palomba et al. (59), 2013 | PCOS undergoing IVF cycles | Live birth Pregnancy Miscarriage | Gonadotrophins+metformin vs. Gonadotrophins (Metformin stopping time until 12 weeks of gestation) | Live birth/woman | OR: 75.6, 95% CI: 8.03 to 711.5 |
| Gonadotrophins+metformin vs. Gonadotrophins | Miscarriage | OR: 0.50, 95% CI: 0.30 to 0.83 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (Metformin stopping time until 12 weeks of gestation) | Miscarriage | OR: 0.08, 95% CI: 0.02 to 0.39 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (Pretreatment length effect for long-term >3 weeks) | Miscarriage | OR: 0.41, 95% CI: 0.21 to 0.78 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (Pretreatment length effect for short-term ≤ 3 weeks) | OHSS | OR: 0.20, 95% CI: 0.07 to 0.54 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (Metformin stopping time until oocyte retrieval, ET and HCG injection) | OHSS | OR: 0.22, 95% CI: 0.11 to 0.42 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (no pretreatment period) | OHSS | OR: 0.14, 95% CI: 0.05 to 0.38 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (higher dose >1000 mg daily) | OHSS | OR: 0.40, 95% CI: 0.20 to 0.80 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (lower dose <=1000 mg/daily) | OHSS | OR: 0.15, 95% CI: 0.06 to 0.38 | |||
| OHSS | Gonadotrophins+metformin vs. Gonadotrophins | OHSS | OR: 0.27, 95% CI: 0.16 to 0.46 | ||
| Gonadotrophins+metformin vs. Gonadotrophins | Oocyte number retrieved | WMD: -1.11, 95% CI: -1.86 to -0.36 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (higher dose >1000 mg daily) | Oocyte number retrieved | WMD: -1.16, 95% CI: -1.96 to -0.37 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (Pretreatment length effect for long-term >3 weeks) | Oocyte number retrieved | WMD: -1.45, 95% CI: -2.37 to -0.53 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (Metformin stopping time until pregnancy test) | Oocyte number retrieved | WMD: -1.32, 95% CI: -2.40 to -0.23 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (Pretreatment length effect for long-term >3 weeks) | Implantation/embryo | OR: 0.28, 95% CI: 0.12 to 0.62 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (higher dose > 1000 mg daily) | Implantation/embryo | OR: 1.42, 95% CI: 1.24 to 2.75 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (Metformin stopping time until pregnancy test) | Stimulation length | WMD: 0.85, 95% CI: 0.02 to 1.68 | |||
| Gonadotrophins+metformin vs. Gonadotrophins (lower dose <=1000 mg/daily) | Gonadotrophins units | WMD: -326.84, 95% CI: -505.99 to -147.69 | |||
| Huang et al. (21), 2015 | PCOS undergoing IVF/ICSI in non-donor cycles | Live birth Clinical pregnancy | Metformin vs. Placebo | OHSS | RR: 0.44; 95%CI 0.26 to 0.77 |
| Miscarriage Multiple pregnancy | |||||
| OHSS | |||||
| Tso et al. (42), 2014 | PCOS and of reproductive age undergoing IVF or ICSI | Live birth | Metformin vs. Placebo | Pregnancy/woman | OR: 1.52, 95% CI: 1.07 to 2.15 |
| Clinical pregnancy | Metformin vs. Placebo | Side effects | OR: 4.49, 95% CI: 1.88 to 10.72 | ||
| Miscarriage OHSS | Metformin vs. Placebo | OHSS | OR: 0.29, 95% CI: 0.18 to 0.49 | ||
| Side effects | Metformin vs. Placebo (long protocol GnRH agonist) | OHSS | OR: 0.29, 95% CI: 0.16 to 0.51 | ||
| Pundir et al. (26), 2012 | PCOS undergoing IVF with or without ICSI | Live birth | GnRH antagonist vs. Agonist | Gonadotrophins units | WMD: -0.28, 95% CI: -0.43 to -0.13) |
| Clinical pregnancy | GnRH antagonist vs. Agonist | Moderate and severe OHSS | RR: 0.59, 95% CI: 0.45 to 0.76 | ||
| Ongoing pregnancy | GnRH antagonist vs. Agonist | OHSS (moderate & severe) | RR: 0.60, 95% CI: 0.48 to 0.76 | ||
| Miscarriage | GnRH antagonist vs. Agonist | Stimulation length | WMD: -0.74, 95% CI: -1.12 to -0.36 | ||
| OHSS | |||||
| Siristatidis et al. (50), 2015 | PCOS, PCO and control undergoing IVM | Live birth | IVM in (PCOS vs. Control) | Cancellation/cycle | OR: 0.15, 95% CI: 0.05 to 0.44 |
| Clinical pregnancy | IVM in (PCOS vs. Non PCOS) | Cancellation/cycle | OR: 0.18, 95% CI: 0.06 to 0.47 | ||
| Miscarriage | IVM in (PCOS vs. PCO) | Cancellation/cycle | OR: 0.25, 95% CI: 0.07 to 0.92 | ||
| Oocyte maturation | IVM in (PCOS vs. Non PCOS) | Implantation/embryo | OR: 1.73, 95% CI: 1.06 to 2.81 | ||
| IVM in (PCOS vs. Control) | Maturation/oocyte | OR: 0.74, 95% CI: 0.59 to 0.93 | |||
| IVM in (PCOS vs. Control) | Pregnancy/cycle | OR: 3.09, 95% CI: 1.46 to 6.53 | |||
| IVM in (PCOS vs. Non-PCOS) | Pregnancy/cycle | OR: 2.23, 95% CI: 1.45 to 3.43 | |||
| IVM in (PCOS vs. Control) | Pregnancy/woman | OR: 3.29, 95% CI: 1.42 to 7.62 | |||
| IVM in (PCOS vs. Non PCOS) | Pregnancy/woman | OR: 2.37, 95% CI: 1.53 to 3.68 | |||
| Xiao et al. (31), 2013 | PCOS | Clinical pregnancy | GnRH antagonist vs. GnRH agonist | Moderate-severe OHSS | OR: 0.36, 95% CI: 0.25 to 0.52 |
CC; Clomiphene citrate, COS; Controlled ovarian stimulation, ET; Embryo transfer, FSH: Follicle stimulating hormone, GnRH; Gonadotrophins releasing hormone, HCG; Human chorionic gonadotrophin, HMG; Human menopausal gonadotrophin, ICSI; Intra cytoplasmic sperm injection, IUI; Intra uterine insemination, IVF; In vitro fertilization, IVM; In vitro maturation, LH; Luteinizing hormone, LOD; Laparoscopic ovarian drilling, MD; Mean difference, OHSS; Ovarian hyper-stimulation syndrome, OI; Ovulation induction, OR; Odds ratio, PCOS; Polycystic ovary syndrome, rFSH; Recombinant follicle stimulating hormone, RR; Risk ratio, uFSH; Urinary follicle stimulating hormone, and WMD; Weighted mean difference