Table 1.
Overview of included studies in the current meta-analysis
| Study, year | Design | Study population; cycle | Allocation | Outcomes | Luteal phase support | Results |
|---|---|---|---|---|---|---|
| tNC vs. mNC | ||||||
| Weissman A, 2009 | Retrospective cohort | Ovulatory patients; tNC = 71/mNC = 61 |
Preference | CP/LB | No LPS | No difference |
| Fatemi HM, 2010 | RCT | Ovulatory patients; tNC = 61/mNC = 63 |
Computer generated randomization | CP | No LPS | CP: tNC > mNC, p = 0.025 |
| Weissman A, 2011 | RCT | Ovulatory patients; tNC = 30/mNC = 25 |
Computer generated randomization | CP/LB | tNC: vaginal progesterone gel 1 × 90 mg or vaginal micronized progesterone 2 × 100 mg/day mNC: vaginal progesterone gel 1 × 90 mg or vaginal micronized progesterone 2 × 100 mg/day |
No difference |
| Chang EM, 2011 | Retrospective cohort | Ovulatory patients; tNC = 310/mNC = 134 |
Convenience, cost | CP | tNC: vaginal micronized progesterone 600 mg/day mNC: vaginal micronized progesterone 600 mg/day |
No difference |
| Tomas C, 2012 | Retrospective cohort | Ovulatory patients; tNC = 1168/mNC = 444 |
Preference, cycle characteristics | CP/LB | tNC: vaginal natural progesterone 3 × 200 mg/day or 2 × 400 mg/day or vaginal progesterone gel 2 × 90 mg/day mNC: No LPS |
No difference |
| tNC vs. AC without suppression | ||||||
| Loh SK, 1999 | Retrospective cohort | Ovulatory patients; tNC = 51/AC wo-s = 161 |
Preference | CP/LB | NA | LB: tNC > AC wo-s, p = 0.073 |
| Morozov V, 2007 | Retrospective cohort | Ovulatory patients; tNC = 68/AC wo-s = 174 |
Not stated | CP | tNC: vaginal micronized progesterone 4 × 200 mg/day AC wo-s: progesterone in oil 1 × 50mg/day i.m. |
CP: tNC > AC wo-s, p = 0.0298 |
| Chang EM, 2011 | Retrospective cohort | Ovulatory patients; tNC = 310/AC wo-s = 204 |
Convenience, cost | CP | tNC: vaginal micronized progesterone 600 mg/day AC wo-s: vaginal micronized progesterone 600 mg/day |
CP: tNC > AC wo-s, p = 0.008 |
| Xiao Z, 2011 | Retrospective cohort | Ovulatory and anovulatory patients; tNC = 380/AC wo-s = 646 |
Preference, cycle characteristics | CP | tNC: progesterone in oil 1 × 40 mg/day i.m. AC wo-s: progesterone in oil 1 × 40–60 mg/day i.m. |
No difference |
| Tomas C, 2012 | Retrospective cohort | Ovulatory and anovulatory patients; tNC = 1168/AC wo-s = 2858 |
Cycle characteristics | CP/LB | tNC: vaginal natural progesterone 3 × 200 mg/day or 2 × 400 mg/day or vaginal progesterone gel 2 × 90 mg/day AC wo-s: vaginal natural progesterone 2 × 400 mg/day or vaginal progesterone gel 2 × 90 mg/day |
No difference |
| Veleva Z, 2013 | Retrospective cohort | Ovulatory and anovulatory patients; tNC = 1276/AC wo-s = 312 |
Cycle characteristics | LB | tNC: No LPS: 302, with LPS: 974; vaginal micronized progesterone 200 mg/day AC wo-s: vaginal micronized progesterone 800 mg/day |
LB: tNC > AC wo-s, p < 0.0001 |
| Levron J, 2014 | Retrospective cohort | Not stated; tNC = 798/AC wo-s = 437 |
Not Stated | CP | tNC: No LPS AC wo-s: vaginal micronized progesterone 3 × 300 mg/day |
CP: tNC > AC wo-s, p < 0.02 |
| Orvieto R, 2016 | Retrospective cohort | Ovulatory and anovulatory patients; 2012–2014 tNC = 74/ 2014–2015 tNC = 59 2012–2014 AC wo-s = 113/ 2014–2015 AC wo-s = 54 |
Preference | CP | 2012–2014 tNC: vaginal micronized progesterone 600 mg/day or vaginal progesterone gel 1 × 90 mg/day 2014–2015 tNC: rhCG 250 μg the day of ET and triptorelin 0.1 mg 4 days after from ET 2012–2014 and 2014–2015 AC wo-s: vaginal micronized progesterone 3 × 300 mg/day or vaginal progesterone gel 2 × 90 mg/day |
2014–2015 tNC > 2014–2015 AC wo-s, p < 0.001 |
| tNC vs. AC-with suppression | ||||||
| Al Shawaf T, 1993 | RCT | Ovulatory and anovulatory patients; tNC = 77/AC w-s = 72 |
Age, cycle characteristics | CP/LB | tNC: No LPS AC w-s: NA |
No difference |
| Queenan JT, 1994 | Retrospective cohort | Ovulatory and anovulatory patients; tNC = 398/AC w-s = 230 |
Cycle characteristics | CP | tNC: NA AC w-s: NA |
No difference |
| Tanos V, 1996 | Quasi-randomized | Ovulatory and anovulatory patients; tNC = 219/AC w-s = 85 |
Preference, cycle characteristics | CP | tNC: NA AC w-s: NA |
No difference |
| Gelbaya TA, 2006 | Retrospective cohort | Ovulatory patients; tNC = 212/AC w-s = 205 |
Preference | CP/LB | tNC: No LPS AC w-s: micronized progesterone pessaries 200–800 mg/day |
No difference |
| Hill MJ, 2010 | Retrospective cohort | Ovulatory and anovulatory patients; NC = 240/AC w-s = 1151 |
Preference | CP/LB | tNC: progesterone in oil 1 × 50 mg/day i.m. AC w-s: progesterone in oil 1 × 50 mg/day i.m. |
CP/LB: AC w-s > tNC, p < 0.01/p < 0.01 |
| Mounce G, 2015 | RCT | Ovulatory and anovulatory patients; NC = 80/AC w-s = 79 |
Randomized using minimization algorithm | CP/LB | tNC: No LPS AC w-s: vaginal progesterone pessaries 2 × 400 mg/day |
No difference |
| mNC vs. AC-without suppression | ||||||
| Kawamura T, 2007 | Retrospective cohort | Ovulatory patients; NC = 720/AC wo-s = 136 |
CP | mNC: 2 × 0.5 mg/day chlormadinone acetate, AC wo-s: 2 × 222 mg/day vaginal progesterone and hydroxyl-progesterone caproate 1 × 125 mg/week i.m. |
No difference | |
| Givens CR, 2009 | Retrospective cohort | Ovulatory and anovulatory patients; NC = 862/AC wo-s = 205 |
Preference, cycle characteristics | CP/LB | mNC: vaginal micronized progesterone 2 × 200 mg/day AC wo-s: progesterone in oil 50 mg/day i.m. |
CP: AC wo-s > mNC, p = 0.011 |
| Chang EM, 2011 | Retrospective cohort | Ovulatory patients; mNC = 134/AC wo-s = 204 |
Convenience, cost | CP | mNC: vaginal micronized progesterone 600 mg/day AC wo-s: vaginal micronized progesterone 600 mg/day |
CP: mNC > AC wo-s, p = 0.032 |
| Tomas C, 2012 | Retrospective cohort | Ovulatory and anovulatory patients; mNC = 444/AC wo-s = 2858 |
Cycle characteristics | CP/LB | mNC: No LPS, AC wo-s: vaginal natural progesterone 2 × 400 mg/day or vaginal progesterone gel 2 × 90 mg/day |
No difference |
| Hancke K, 2012 | Retrospective cohort | Ovulatory and anovulatory patients; mNC = 148/AC wo-s = 55 |
Preference | CP/LB | mNC: vaginal micronized progesterone 3 × 200 mg/day AC wo-s: vaginal micronized progesterone 3 × 200 mg/day |
No difference |
| Groenewoud ER, 2016 | RCT | Ovulatory patients; mNC = 495/AC wo-s = 464 |
Web based randomization module | CP/LB | mNC: No LPS AC wo-s: vaginal micronized progesterone 3 × 200 mg/day |
No difference |
| mNC vs. AC-with suppression | ||||||
| Lathi RB, 2015 | Retrospective cohort | Ovulatory and anovulatory patients; mNC = 519/AC w-s = 106 |
Cycle characteristics | CP/LB | mNC: vaginal micronized progesterone 2 × 100 mg/day AC w-s: progesterone in oil 50 mg/day i.m. and vaginal micronized progesterone 3 × 200 mg/day |
No difference |
| Konc J, 2010 | Retrospective cohort | Ovulatory and anovulatory patients; mNC = 315/AC w-s = 234 |
Not stated | CP | mNC: vaginal micronized progesterone 600 mg/day AC w-s: vaginal micronized progesterone 600 mg/day |
No difference |
| AC-with suppression vs. AC-without suppression | ||||||
| Simon A, 1998 | RCT | Ovulatory and anovulatory patients; AC w-s = 53/AC wo-s = 53 |
Cycle characteristics | CP | AC w-s: vaginal micronized progesterone 3 × 300 mg/day AC wo-s: vaginal micronized progesterone 3 × 300 mg/day |
No difference |
| Dal Prato L, 2002 | Prospective randomized | Ovulatory patients; AC w-s = 146/AC wo-s = 150 |
Randomization | CP | AC w-s: progesterone in oil 100 mg/day i.m. AC wo-s: progesterone in oil 100 mg/day i.m. |
No difference |
| El Toukhy T, 2004 | RCT | Ovulatory patients; AC w-s = 117/AC wo-s = 117 |
Computer generated randomization | CP/LB | AC w-s: vaginal progesterone pessaries 2 × 400 mg/day AC wo-s: vaginal progesterone pessaries 2 × 400 mg/day |
CP/LB: AC w-s > AC wo-s, p = 0.01/p = 0.01 |
| van de Vijver A, 2014 | Retrospective cohort | Not stated; AC w-s = 280/AC wo-s = 849 |
Preference | CP/LB | AC w-s: vaginal micronized progesterone 3 × 200 mg/day AC wo-s: vaginal micronized progesterone 3 × 200 mg/day |
No difference |
| Nekoo EA, 2014 | RCT | Ovulatory patients; AC w-s = 93/AC wo-s = 83 |
Computer generated randomization | CP | AC w-s: vaginal micronized progesterone 2 × 400 mg/day AC wo-s: vaginal micronized progesterone 2 × 400 mg/day |
No difference |
| NC vs. OS with Gn | ||||||
| Dor J, 1991 | Retrospective cohort | NA; NC = 56/OS = 44 |
NA | CP/LB | NC: NA OS: NA |
No difference |
| Imthum B, 1996 | Retrospective cohort | NA; NC = 16/OS = 8 |
NA | CP | NC: NA OS: NA |
No difference |
| Tanos V, 1996 | Retrospective cohort | NA; NC = 219/OS = 77 |
NA | CP | NC: NA OS: NA |
No difference |
| Konc J, 2010 | Retrospective cohort | Ovulatory and anovulatory patients; NC = 315/OS = 282 |
Preference | CP | NC: vaginal micronized progesterone 600 mg/day OS: vaginal micronized progesterone 600 mg/day |
No difference |
| Peeraer K, 2015 | RCT | Ovulatory patients; NC = 291/OS = 288 |
Randomization | CP/LB | NC: vaginal micronized progesterone 3 × 200 mg/day OS: vaginal micronized 3 × 200 mg/day |
No difference |
| AC vs. OS with Gn or AI | ||||||
| Dor J, 1991 | Retrospective cohort | NA; AC = 42/OS = 44 |
NA | CP/LB | NA | No difference |
| Konc J, 2010 | Retrospective cohort | Ovulatory and anovulatory patients; AC = 234/OS = 282 |
Preference | CP | AC: vaginal micronized progesterone 600 mg/day OS: vaginal micronized progesterone 600 mg/day |
No difference |
| Li SJ, 2014 | RCT | Ovulatory and anovulatory patients; AC = 354/AI = 359 |
Randomization | CP/LB | AC: progesterone in oil 60 mg/day i.m. AI: dydrogesterone 2 × 10 mg/day oral plus 20–40 mg/day progestin i.m. |
CP/LB: AI > AC, p = 0.043/p = 0.002 |
| Yu J, 2015 | RCT | Ovulatory and anovulatory patients; AC = 291/OS = 285 |
Randomization | CP/LB | AC: vaginal micronized progesterone 2 × 200 mg/day OS: vaginal micronized progesterone 2 × 200 mg/day |
No difference |
RCT randomized controlled trial, NA not available, CP clinical pregnancy, LB live birth, LPS luteal phase support, tNC true natural cycle, mNC modified natural cycle, AC artificial cycle, w-s with suppression, wo-s without suppression, OS ovarian stimulation, Gn gonadotropin, AI aromatase inhibitor