Table 4 Primary and secondary endpoints for each specific intervention according to different population/ clinical situations
| Â | Total OHSS | Moderate-severe OHSS | Live-births | Clinical pregnancies | Ongoing pregnancy rate | Pregnancy rate | Miscarriages | Oocytes retrieved |
|---|---|---|---|---|---|---|---|---|
Predictive models | No difference 4 RCTs; OR 0.58, 95% CI 0.34 to 1.00, n = 2823; I2 = 0% | / | No difference 4 RCTs; OR 1.04, 95% CI 0.88 to 1.23, n = 2823; I2 = 34% | No difference 4 RCTs; OR 0.96, 95% CI 0.82 to 1.13, n = 2823; I2 = 0% | No difference 4 RCTs; OR 1.04, 95% CI 0.88 to 1.23, n = 2823; I2 = 34% | / | / | / |
Monitoring and surveillance | No difference 6 RCTs; OR 1.03, 95% CI 0.48 to 2.20, n = 781; I2 = 0% | / | / | / | / | No difference 4 RCTs; OR 1.10, 95% CI 0.79 to 1.54, n = 617; I2 = 5% | / | No difference 4 RCTs; OR 0.32, 95% CI -0.60 to 1.24; n = 596; I2 = 17% |
Natural IVF cycles | No difference 1 RCT; OR 0.19, 95% CI 0.01 to 4.06, n = 60 | / | / | No difference 4 RCTs; OR 0.52, 95% CI 0.17 to 1.61, n = 351; I2 = 63% | No difference 3 RCTs; OR 0.72, 95% CI 0.50 to 1.05, n = 458; I2 = 0% | / | / | Reduction 1 RCT; MD -4.40, 95% CI -7.87 to -0.93, n = 60 |
Pre-treatment with oral contraceptives + GnRH analogues | ||||||||
vs. GnRH antagonists | No difference 2 RCTs; OR 0.98, 95% CI 0.28 to 3.40, n = 642; I2 = 0% | / | Reduction 6 RCTs; OR 0.74, 95% CI 0.58 to 0.95, n = 1335; I2 = 0% | / | Reduction 6 RCTs; OR 0.74, 95% CI 0.58 to 0.95, n = 1335; I2 = 0% | / | No difference 5 RCTs; OR 1.36, 95% CI 0.82 to 2.26, n = 868; I2 = 0% | / |
vs. GnRH agonists | No difference 2 RCTs; OR 0.63, 95% CI 0.20 to 1.96, n = 290; I2 = 0% | / | No difference 4 RCTs; OR 0.89, 95% CI 0.64 to 1.25, n = 724; I2 = 0% | / | No difference 4 RCTs; OR 0.89, 95% CI 0.64 to 1.25, n = 724; I2 = 0% | / | Reduction 5 RCTs; OR 0.40, 95% CI 0.22 to 0.72, n = 780; I2 = 0% | / |
GONADOTROPIN STARTING DOSE | ||||||||
Personalization (In high-responders) | / | Reduction 1 RCT; OR 2.31, 95% CI 0.80 to 6.67, n = 521; | No difference 1 RCT; OR 0.98, 95% CI 0.66 to 1.46, n = 521 | No difference 1 RCT; OR 1.14, 95% CI 0.78 to 1.66, n = 521 | / | / | / | / |
 Mild ovarian stimulation | ||||||||
Normal-responders | Reduction 9 RTCs; RR 0.26, CI 0.14 to 0.49, n = 1925; I2 = 0% | / | No difference 3 RCTs; OR 0.88, 95% CI 0.69 to 1.12, n = 573; I2 = 0% | / | No difference 7 RCTs; OR 1.10, 95% CI 0.88 to 1.12, n = 573; I2 = 0% | / | / | Reduction 13 RTCs; SMD-1.34, CI -1.94 to -0.75, n = 3499; I2 = 98% |
Hyper-responders | Reduction 2 RTCs; RR 0.47, 95% CI 0.31 to 0.72, n = 931; I2 = 0% | / | No difference 2 RCTs; OR 0.98, 95% CI 0.79 to 1.22, n = 931; I2 = 0% | / | No difference 1 RCT; OR 0.86, 95% CI 0.61 to 1.23, n = 521; | / | / | No difference 2 RTCs; SMD-0.31, CI -0.74 to -0.13, n = 931, I2 = 91% |
PROTOCOL OF INDUCTION: GNRH AGONISTS VS. ANTAGONIST | ||||||||
 DRUG FORMULATION FOR OVARIAN STIMULATION | ||||||||
Urinary vs. recombinant gonadotropin | No difference 32 RCTs; OR 1.18, 95% CI 0.86 to 1.61, n = 7740; I2 = 0% | / | No difference   28 RCTs; OR 0.97, 95% CI 0.87 to 1.08, n = 7339; I2 = 0% | / | No difference 28 RCTs; OR 0.97, 95% CI 0.87 to 1.08, n = 7339; I2 = 0% | / | / | / |
Corifollitropin alfa (including poor- and normal-responders) | No difference 5 RCTs; RR 1.15, 95% CI 0.83 to 1.57, n = 3749; I2 = 0% | No difference 4 RCTs; RR 1.17, 95% CI 0.54 to 2.56, n = 3349; I2 = 0% | No difference 8 RCTs; RR 0.92, 95% CI 0.80–1.05, n = 4340; I2 = 23% | No difference 7 RCTs; RR 0.96, 95% CI 0.88 to 1.05, n = 4340; I2 = 0% | No difference 8 RCTs; RR 0.92, 95% CI 0.80–1.05, n = 4242; I2 = 23% | / | No difference 4 RCTs; RR, 0.94; 95% CI, 0.71–1.25, n = 4242; I2 = 0% | / |
 REGIMENS OF OVARIAN STIMULATION | ||||||||
Clomiphene citrate or letrozole | Reduction 5 RCTs; OR 0.21, 95% CI 0.11 to 0.41, n = 1067; I2 = 0% | / | No difference 4 RCTs; RR 0.92, 95% CI 0.66 to 1.27, n = 493; I2 = 0% | No difference 12 RCTs; RR 1.00, 95% CI 0.86 to 1.16, n = 1998; I2 = 3% | / | / | / | / |
Clomiphene citrate | Reduction 4 RTCs; OR 0.2, 95% CI, 0.1 to 0.3, n = 1251; I2 = 0% | / | No difference 4 RCTs; RR 0.9, 95% CI 0.7 to 1.1, n = 1207; I2 = 36% | No difference 8 RCTs; RR 1.0, 95% CI 0.9 to 1.1, n = 1764; I2 = 0% | / | / | No difference 4 RCTs; RR 0.83, 95% 0.59 to 1.19, n = 610 | Reduction 8 RCTs; MD − 4.6, 95% CI − 6.1 to − 3, n = 1631; I2 = 95% |
Letrozole | Reduction 1 RTC; OR 0.1, 95% CI, 0.0 to 0.6 n = 94 | / | / | / | / | / | / | / |
Metformin GnRH agonists GnRH antagonists | Reduction 9 RCTs; RR 0.40, 95% CI 0.26 to 0.60, n = 898; I2 = 23% No difference 2 RCTs; RR 0.97, 95% CI 0.32 to 2.98, n = 193; I2 = 25% | / / | No difference 6 RCTs; RR 1.30, 95% CI 0.94 to 1.79, n = 651; I2 = 23% Reduction 1 RCT; RR 0.48, 95% CI 0.29 to 0.79, n = 153 | Increase 10 RCT; RR 1.32, 95% CI 1.08 to 1.63, n = 915; I2 = 13% No difference 2 RCTs; RR 1.38, 95% CI 0.21 to 9.19, n = 177; I2 = 87% | / / | / / | No difference 7 RCTs; RR 0.80, 95% CI 0.51 to 1.26, n = 668; I2 = 0% No difference 1 RCT; RR 0.86, 95% CI 0.56 to 1.32, n = 153 | / / |
Melatonin | Reduction 1 RCT; RR 1.01; 95% CI 0.33 to 3.08, n = 358 | / | / | No difference 5 RCTs; RR 0.6; 95% CI 0.2–2.22, n = 680; l2 = 0% | / | / | No difference 2 RCTs; RR 1.7; 95% CI 0.43–2.68, n = 143; l2 = 0% | No difference 5 RCTs; MD 0.6; -02 to -1.4, n = 680; I2 = 69% |
Coasting | Reduction 2 RCTs; OR 0.11, 95% CI 0.05 to 0.24, n = 207; I2 = 0% | / | No difference 1 RCT; OR 0.48, 95% CI 0.14 to 1.62, n = 68 | No difference 2 RCTs; OR 0.82, 95% CI 0.46 to 1.44, n = 207; I2 = 0% | / | / | No difference 2 RCTs; OR 0.85, 95% CI 0.25 to 2.86, n = 207, I2 = 0% | / |
 STRATEGIES FOR CONTROLLING LH SURGE | ||||||||
GnRH agonist vs. antagonists: overall population | Reduction in antagonists 36 RCTs; OR 0.61, 95% C 0.51 to 0.72, n = 7944; I2 = 31% | / | No difference 12 RCTs; OR 1.02, 95% CI 0.85 to 1.23, n = 2303; I2 = 27% | No difference 54 RCT; OR 0.91, 95% CI 0.83 to 1, n = 9959; I2 = 31% | No difference 37 RCT; OR 0.92, 95% CI 0.83 to 1.01, n = 8311; I2 = 0% | / | No difference 34 RCTs; OR 1.03, 95% CI 0.82 to 1.29, n = 7082; I2 = 0% | / |
GnRH agonists vs. antagonists: general population | Reduction in antagonists 22 RCTs; OR 0.63, 95% C 0.50 to 0.81, n = 5598; I2 = 0% | / | No difference 10 RCTs; OR 0.91, 95% CI 0.79 to 1.04, n = 2590; I2 = 0% | No difference 34 RCT; OR 0.90, 95% CI 0.84 to 0.96, n = 8084; I2 = 0% | Reduction 26 RCT; OR 0.89, 95% CI 0.82 to 96, n = 7191; I2 = 0% | / | No difference 34 RCTs; OR 1.03, 95% CI 0.82 to 1.29, n = 7082; I2 = 0% | Increase in agonists 31 RCTs; WMD − 1.04, CI -1.56 to -0.52, n = 7080 I2 = 81% |
GnRH agonists vs. antagonists: PCOS | Reduction in antagonists 9 RCTs; OR 0.58, 95% C 0.44 to 0.77, n = 994, I2 = 0% | Reduction in antagonist 9 RCTs; OR 0.65, 95% C 0.52 to 0.82, n = 1114, I2 = 0% | No difference 1 RCT; OR 0.78, 95% CI 0.46 to 1.32, n = 74 | No difference 8 RCTs; OR 0.96, 95% CI 0.77 to 1.19, n = 840; I2 = 30% | No difference 5 RCTs; OR 0.92, 95% CI 0.78 to 1.08, n = 785; I2 = 0% | / | No difference 7 RCTs; OR 0.93, 95% CI 0.61 to 1.43, n = 997; I2 = 1% | / |
GnRH agonists vs. antagonists: normal responder | Reduction in antagonists 21 RCTs; OR 0.69, 95% CI 0.57 to 0.83 n = 5763; I2 = 15% | / | No difference 6 RCTs; OR 0.95, 95% CI 0.74 to 1.09, n = 2237; I2 = 0% | No difference 8 RCTs; OR 0.90, 95% CI 0.80 to 1.01, n = 5814; I2 = 0% | No difference 18 RCTs; OR 0.88, 95% CI 0.77 to 1.00, n = 5119; I2 = 0% | / | No difference 14 RCTs; OR 0.98, 95% CI 0.69 to 1.40, n = 3198; I2 = 0% | Reduction in antagonists 22 RTCs; SMD-1.14, CI -1.84 to -0.99, n = 4914, I2 = 45% |
GnRH agonists vs. antagonists: poor responder | / | / | No difference 3 RCTs; OR 0.89, 95% CI 0.56 to 1.41, n = 544; I2 = 0% | No difference 6 RCTs; OR 0.85, 95% CI 0.66 to 1.10, n = 780; I2 = 0% | No difference 6 RCTs; OR 0.87, 95% CI 0.65 to 1.17, n = 780; I2 = 0% | / | / | Increase in agonist 6 RCTs; WMD − 0.08, CI -1.09 to -0.43, n = 7080 I2 = 57% |
Progestin-primed ovarian stimulation | Reduction 6 RCT; OR 0.52, 95% CI 0.36 to 0.75, n = 1238; I2 = 0% | / | No difference 6 RCTs; RR 1.06, 95% CI 0.94 to 1.19, n = 1442; I2 = 0% | No difference 8 RCTs; RR 0.99, 95% CI 0.85 to 1.15, n = 1782; I2 = 56% | No difference 6 RCTs; RR 1.06, 95% CI 0.94 to 1.19, n = 1442; I2 = 0% | / | No difference 8 RCTs; RR -0.03, 95% CI -0.35 to 0.29, n=; I2 = 0% | / |
LH addition | No difference 6 RCTs; OR 0.38, 95% CI 0.14 to 1.01, n = 2178; I2 = 10 | / | No difference 4 RCTs OR 1.32, 95% CI 0.85 to 2.06; n = 499; I2 = 63% | / | Reduction 19 RCTs; OR 1.20, 95% CI 1.01 to 1.42, n = 3129; I2 = 2% | / | No difference 13 RCTs; OR 0.93, 95% CI 0.63 to 1.36, n = 1711; I2 = 0% | / |
 OVULATION TRIGGERING STRATEGIES | ||||||||
hCG type r-HCG vs. u-HCG | No difference 3 RCTs; OR 1.18, 95% CI 0.50 to 2.78, n = 495; I2 = 0% | No difference 3 RCTs; OR 1.76, 95% CI 0.37 to 8.45, n = 417; I2 = 0% | No difference 7 RCTs; OR 1.15, 95% CI 0.89 to 1.49, n = 1136; I2 = 0% | No difference 13 RCTs; OR 1.06, 95% CI 0.87 to 1.29, n = 1806; I2 = 0% | No difference 7 RCTs; OR 1.15, 95% CI 0.89 to 1.49, n = 1136; I2 = 0% | / | No difference 8 RCTs; OR 0.72, 95% CI 0.41 to 1.25, n = 1196 I2 = 0% | / |
GnRH agonists | Reduction 8 RCTs; OR 0.15, 95% CI 0.05 to 0.47, n = 989; I2 = 42% | Reduction 8 RCTs; OR 0.21, 95% CI 0.07 to 0.66, n = 989; I2 = 73% | Reduction 5 RCTs; OR 0.47, 95% CI 0.31 to 0.70, n = 532; I2 = 56% | / | Reduction 11 RCTs; OR 0.70, 95% CI 0.54 to 0.91, n = 198; I2 = 59% | / | Increase 11 RCTs; RR 1.74, 95% CI 1.10 to 2.75, n = 1198; I2 = 1% | / |
r-hLH | No difference 2 RCTs; OR 0.83, 95%CI 0.40 to 1.70, n = 289; I2 = 6% | / | No difference 2 RCTs; OR 0.95, 95% CI 0.51 to 1.78, n = 289; I2 = 0% | No difference 2 RCTs; OR 0.94, 95% CI 0.54 to 1.64, n = 289; I2 = 0% | No difference 2 RCTs; OR 0.95, 95% CI 0.51 to 1.78, n = 289; I2 = 0% | / | No difference 2 RCTs; OR 0.95, 95% CI 0.38 to 2.40, n = 289; I2 = 0% | No difference 2 RCTs; MD − 1.33, 95%CI − 3.26 to 0.60, n = 103; I2 = 0% |
Elective cryopreservation | Reduction 6 RCTs; OR 0.26, 95% CI 0.17 to 0.39, n = 4478; I2 = 0% | / | No difference 8 RCTs; OR 0.95, 95% CI 0.75 to 1.22, n = 4712; I2 = 31% | / | No difference 4 RCTs; OR 0.95, 95% CI 0.75 to 1.19, n = 1245; I2 = 31% | / | No difference 2 RCTs; OR 1.06, 95% CI 0.72 to 1.55, n = 986; I2 = 55% | / |
In vitro maturation of oocytes | No cases of OHSS 2 RCTs; OR: not estimable; n = 71; I2: not applicable | / | / | Increase 2 RCTs; OR 3.10, 95% CI 1.06 to 9.00, n = 71; I2 = 0% | / | / | / | / |
 OTHER TREATMENTS OR PROCEDURES | ||||||||
Dopaminergic agonists vs. no treatment | / | Reduction 10 RCTs; OR 0,32, 95% CI 0.23 to 0,44, n = 1202; I2 = 13% | No difference 3 RCTs; OR 0.92, 95% CI 0.63 to 1.37, n = 530; I2 = 0% | No difference 3 RCTs; OR 0.96, 95% CI 0.60 to 1.55, n = 362; I2 = 0% | / | / | No difference 2 RCTs; OR 0.66, 95% CI 0.19 to 2.28, n = 168; I2 = 0% | / |
Dopamine agonists plus co-intervention | / | Reduction 4 RCTs; OR 0,48, 95% CI 0.28 to 0,84, n = 748; I2 = 40% | No difference 2 studies; OR 1.21, 95% CI 0.81 to 1.80, n = 400; I2 = 0% | No difference 4 RCTs; OR 1.11, 95% CI 0.83 to 1.49, n = 748; I2 = 0% | / | / | No difference 3 RCTs; OR 0.65, 95% CI 0.30 to 1.42, n = 548; I2 = 0% | / |
Diosmin | No difference 1 RCT; OR 2.85, 95% CI 1.35 to 6.00, n = 200 | / | / | No difference 1 RCT; OR 0.89, 95% CI 0.51 to 1.55, n = 200 | / | / | No difference 1 RCT; OR 1.21, 95% CI 0.36 to 4.11, n = 200 | / |
olume expander Albumin Hydroxyethyl starch | Reduction 7 RCTs; OR 0.67, 95% CI 0.47 to 0.95, n = 1452; I2 = 69% Reduction 2 RCTs; OR 0.27, 95% CI 0.12 to 0.59, n = 272; I2 = 0% | / / | / / | / / | / / | Reduction 7 RCTs; RR 0.72, 95% CI 0.55 to 0.94, n = 1069; I2 = 42% No difference 1 RCTs; RR 1.20, 95% CI 0.49 to 2.93, n = 168 | / / | / / |
Glucocorticoid | No difference 3 RTCs; OR 1.07, 95% CI 0.60 to 1.90, n = 370; I2 = 0% | / | No difference 2 RCTs; OR 1.37,95% CI: 0.69 to 2.71, n = 366; I2 = 7% | No difference 13 RTCs; OR 1.17, 95% CI 0.95 to 1.44, n = 1967; I2 = 0% | No difference 3 RCTs; OR 1.19, 95% CI 0.80 to 1.76, n = 476; I2 = 0% | / | No difference 6 RCTS; OR 1.09, 95% CI 0.63 to 1.87, n = 821; I2 = 0% | / |
Luteal phase support hCG Progesterone GnRH agonist (vs. progesterone) | Increase 1 RCT; OR 4.28, 95% CI 1.91 to 9.6, n = 387 Reduction 5 RCTs; OR 0.46, 95% CI 0.30 to 0.71, n = 1293; I2 = 48% No difference 1 RCT; OR 1.00; 95% CI 0.33 to 3.01, n = 300 | / / / | Increase 3 RCTs; OR 1.76, 95% CI 1.08 to 2.86, n = 527; I2 = 24% No difference 5 RCTs; OR 0.95, 95% CI 0.65 to 1.38, n = 833; I2 = 24% Increase 9 RCTs; OR 0.62, 95% CI 0.48 to 0.81, n = 2861; I2 = 55% | No difference 5 RTCs; OR 1.3, 95% CI 0.9 to 1.88, n = 746; I2 = 0% No difference 16 RTCs; OR 1.08, 95% CI 0.90 to 1.30 n = 2355; I2 = 0% Increase 8 RTCs; OR 0.66, 95% CI 0.51 to 0.85 n = 2435; I2 = 0% | Increase 3 RCTs; OR 1.76, 95% CI 1.08 to 2.86, n = 527; I2 = 24% No difference 5 RCTs; OR 0.95, 95% CI 0.65 to 1.38, n = 833; I2 = 24% Increase 9 RCTs; OR 0.62, 95% CI 0.48 to 0.81, n = 2861; I2 = 55% | / / / | No difference 2 RTCs; OR 1.51, 95% CI 0.37 to 6.21, n = 140; I2 = 0% No difference 5 RTCs; OR 1.24, 95% CI 0.66 to 2.31, n = 832; I2 = 0% No difference 2 RTCs; OR 1.37, 95% CI 0.53 to 3.52, n = 240; I2 = 0% | / / / |
ntensified luteal phase support: GnRH-a | No difference 2 RCTs; RR 0.96; 95% CI 0.32–2.89, n = 523; l2 = 0% | / | Increase 6 RTCs; RR 1.52, 95% CI 1.20 to 1.94, n = 1674; l2 = 62% | Increase 11 RTCs; RR 1.21, 95% CI 1.11 to 1.33, n = 3038; l2 = 62% | Increase 6 RTCs; RR 1.18, 95% CI 1.06 to 1.32, n = 2537; l2 = 0% | Increase 6 RTCs; RR 1.36, 95% CI 1.01 to 1.82 n = 1164; l2 = 60% | / | / |
Calcium infusion | No difference 2 RCTs; OR 1.83, 95% CI 0.88 to 3.81, n = 230; I2 = 81% | / | No difference 1 RCT; OR 1.11, 95% CI 0.66 to 1.89, n = 230; I2 = not applicable | No difference 2 RCTs; OR 1.00, 95% CI 0.67 to 1.49, n = 400; I2 = 0% | / | / | No difference 1 RCT; OR 1.21, 95% CI 0.27 to 1.48, n = 230; I2 = not applicable | / |
Ovarian drilling | No difference 1 RCT; OR 0.27, 95% CI 0.04 to 1.69; n=50 | / | No difference 1 RCT; OR 1.26, 95% CI 0.33 to 4.84, n=50 | No difference 1 RCT; OR 1.20, 95% CI 0.37 to 3.86, n=50 | / | / | No difference 1 RCT; OR 1.00, 95% CI 0.18 to 5.51, n=50 | / |