Table I.
Characteristics of the studies for chromosomal abnormalities, uterine anomalies, antiphospholipid syndrome, thrombophilia and thyroid disorders identified in a systematic review of RPL.
| Author | Year | Study type | Study population | Prevalence 2 pregnancy losses | Prevalence ≥ 3 pregnancy losses | Outcome measures |
|---|---|---|---|---|---|---|
| Chromosomal abnormalities | ||||||
| Michels et al. | 1982 | Cohort | 122 couples 2 PL n = 48 ≥ 3 PL n = 74 | Balanced translocations 8.4% (4/48) | Balanced translocations 5.4% (4/74) | Cytogenetic analysis from peripheral blood lymphocyte cultures showed no significant difference between 2 versus 3 or more pregnancy losses. |
| Diedrich et al. | 1983 | Cohort | 136 couples 2 PL n = 59 ≥ 3 PL n = 77 | Abnormal karyotype 10.2% (6/59) | Abnormal karyotype 11.9% (9/77) | Chromosomal analysis from peripheral blood lymphocyte cultures showed no significant difference between 2 versus 3 or more pregnancy losses. |
| FitzSimmons et al. | 1983 | Cohort | 645 couples 2 PL n = 340 ≥ 3PL n = 305 | Abnormal karyotype 1.8% (6/340) | Abnormal karyotype 2.3% (7/305) | Chromosomal analysis from peripheral blood lymphocyte cultures showed no significant difference between 2 versus 3 or more pregnancy losses. |
| Schwartz et al. | 1983 | Cohort | 164 couples 2 PL n = 71 ≥ 3 PL n = 93 | Abnormal karyotype 5.6% (4/71) | Abnormal karyotype 5.4% (5/93) | Chromosomal analysis from peripheral blood lymphocyte cultures showed no significant difference between 2 versus 3 or more pregnancy losses. |
| Sachs et al. | 1985 | Cohort | 371 couples 2 PL n = 182 ≥ 3PL n = 189 | Abnormal karyotype 9.3% (17/182) | Abnormal karyotype 9.5% (18/189) | Chromosomal analysis from peripheral blood lymphocyte cultures showed no significant difference between 2 versus 3 or more pregnancy losses. |
| Sider et al. | 1988 | Cohort | 187 couples 2 PL n = 99 ≥ 3PL n = 88 | Abnormal karyotype 3.0% (3/99) | Abnormal karyotype 6.8% (6/88) | Chromosomal analysis from peripheral blood lymphocyte cultures showed no significant difference between 2 versus 3 or more pregnancy losses. |
| Goddijn et al. | 2004 | Cohort | 95 couples 2 PL n = 55 ≥ 3PL n = 40 | Abnormal karyotype 32.7% (18/55) | Abnormal karyotype 37.5% (15/40) | Chromosomal analysis from peripheral blood lymphocyte cultures showed no significant difference between 2 versus 3 or more pregnancy losses. |
| Jaslow et al. | 2010 | Cohort | 561 women 2 PL n = 281 ≥ 3PL n = 280 | Abnormal karyotype 2.8% (8/281) | Abnormal karyotype 5.4% (15/280) | Parental karyotypes showed no significant difference between 2 versus 3 or more pregnancy losses. |
| Bashiri et al. | 2012 | Cohort | 114 couples 2 PL n = 34 ≥ 3 PL n = 80 | Abnormal karyotype (0/34) | Abnormal karyotype 4.0% (4/80) | Parental genetics (significant rearrangements (balanced translocations) showed no significant difference between 2 versus 3 or more pregnancy losses. |
| Asgari et al. | 2013 | Cohort | 140 couples 2 PL n = 65 ≥ 3PL n = 75 | Abnormal karyotype 3.1% (2/65) | Abnormal karyotype 5.3% (4/75) | Chromosomal analysis from peripheral blood lymphocyte cultures showed no significant difference between 2 versus 3 or more pregnancy losses. |
| Uterine anomalies | ||||||
| Weiss et al. | 2005 | Cohort | 165 women 2 PL n = 67 ≥ 3 PL n = 98 | 22.4% (15/67) | 17.3% (17/98) | Identified by hysteroscopy. Considered abnormal were congenital anomalies. No difference in prevalence was found between 2 versus 3 or more pregnancy losses. |
| Bohlmann et al. | 2010 | Cohort | 206 women 2 PL n = 78 ≥ 3 PL n = 119 | 9.2% (8/78) | 16.8% (20/119) | Identified by hysteroscopy. Considered abnormal were congenital abnormalities. No difference in prevalence was found between 2 versus 3 or more pregnancy losses. |
| Jaslow et al. | 2010 | Cohort | 875 women 2 PL n = 401 ≥ 3PL n = 303 | 18.7% (75/401) | 18.2% (55/303) | Identified by hysterosalpingogram, hysteroscopy, sonohysterography. Considered abnormal were congenital anomalies, fibroids, polyps and septa, Asherman’s syndrome adhesions. No difference in prevalence was found between 2 versus 3 or more pregnancy losses. |
| De Souza et al. | 2011 | Cohort | 66 women 2 PL n = 23 ≥ 3 PL n = 43 | 17.3% (4/23) | 11.6% (5/43) | Identified by hysteroscopy. Considered abnormal was congenital anomalies. No difference in prevalence was found between 2 versus 3 or more pregnancy losses. |
| Seckin et al. | 2012 | Cohort | 220 women 2 PL n = 151 ≥ 3 PL n = 69 | 26.5% (40/151) | 30.4% (21/69) | Diagnostic hysteroscopy. Considered abnormal was congenital anomaly. No difference in prevalence was found between 2 versus 3 or more pregnancy losses. |
| Bashiri et al. | 2012 | Cohort | 114 women 2 PL n = 38 ≥ 3 PL n = 78 | 31.6% (12/38) | 23.1% (18/78) | Hysteroscopy or 3D ultrasound. Considered abnormal were septate uterus, unicornuate, bicornuate, fibroids, polyps and Asherman’s syndrome. No difference in prevalence was found between 2 versus 3 or more pregnancy losses. |
| Jaslow et al. | 2013 | Cohort | 875 women 2 PL n = 389 ≥ 3 PL n = 486 | 6.7% (26/389) | 7.2% (35/486) | Three dimensional sonohysterography. Considered abnormal were congenital and acquired abnormalities. No difference in prevalence was found between 2 versus 3 or more pregnancy losses. |
| Antiphospholipid syndrome | ||||||
| Jaslow et al. | 2010 | Cohort | 729 women 2 PL n = 409 ≥ 3 PL n = 320 | 15.6% (64/409) | 13.1% (42/320) | Lupus anticoagulant levels, Anticardiolipin IgG and IgM were measured. No difference was found between 2 versus 3 or more pregnancy losses. |
| Bashiri et al. | 2012 | Cohort | 120 women 2 PL n = 39 ≥ 3 PL n = 81 | 10.3% (4/39) | 13.6 (11/81) | Lupus anticoagulant. No difference in prevalence was found between 2 versus 3 or more pregnancy losses. |
| Van den Boogaard et al. | 2013 | Cohort | 2444 women 2 PL n = 1526 ≥ 3 PL n = 918 | 17.4% (265/1526) | 17.3% (159/918) | Lupus anticoagulant levels, Anticardiolipin IgG and IgM were measured. No difference was found between 2 versus 3 or more pregnancy losses. |
| Thrombophilia | ||||||
| Sotiriadis et al. | 2007 | Cohort | 99 women 2 PL n = 56 ≥ 3 PL n = 43 | 2 PL = 56 | 3 PL = 43 | There was no difference in the distribution of Factor V Leiden, FII G20210A and MTHFR between patients with 2 and 3 or more PLs. |
| Jaslow et al. | 2010 | Cohort | 243 women | Factor V Leiden 4.2% (6/144) Prothrombin gene mutation 2.6% (3/115) Protein S 3.5% (4/115) Protein S 0.9% (1/115) | Factor V Leiden 8.1% (8/99) Prothrombin gene mutation (0/85) Protein S 2.4% (2/85) Protein C (0/85) | Factor V Leiden mutation, prothrombin gene mutation, protein C activity, protein S activity. No difference was found between 2 versus 3 or more pregnancy losses. |
| Bashiri et al. | 2012 | Cohort | 120 women | Factor V Leiden 4.8% (1/21) Prothrombin gene mutation 13.6% (3/22) Protein S 3.8% (1/26) Protein C 7.7% (2/26) | Factor V Leiden 17.0% (8/47) Prothrombin gene mutation 4.5% (2/44) Protein S 13.6% (8/59) Protein C 8.2% (5/61) | Factor V Leiden mutation, prothrombin gene mutation, Protein S activity, Protein C activity. No difference was found between 2 versus 3 or more pregnancy losses. |
| Karadeniz et al. | 2012 | Cohort | 108 women 2 PL n = 42 ≥ 3 PL n = 66 | Factor V Leiden 9.5% (4/42) Prothrombin gene mutation (0/42) Protein S 16.6% (7/42) Protein C 16.6% (7/42) | Factor V Leiden 7.5% (5/66) Prothrombin gene mutation 1.5% (1/66) Protein S 12.2% (8/66) Protein C 18.2% (12/66) | Factor V Leiden mutation, prothrombin gene mutation, Protein S activity, Protein C activity. No difference was found between 2 versus 3 or more pregnancy losses. |
| Baumann et al. | 2013 | Cohort | 641 women 2 PL n = 240 ≥ 3 PL n = 401 | Factor V Leiden 8.3% (20/240) Prothrombin gene mutation 2.9% (7/240) | Factor V Leiden 7.2% (29/401) Prothrombin gene mutation 3.5% (14/401) | Factor V Leiden, prothrombin gene mutation. No difference was found between 2 versus 3 or more pregnancy losses. |
| Ali et al. | 2014 | Cohort | 250 patients 2 PL n = 125 ≥ 3 PL n = 125 | Factor V Leiden (0/23) Prothrombin gene mutation (0/175) Protein S 1.1% (2/175) Protein C 1.1% (2/175) | Factor V Leiden 11.5% (3/26) Prothrombin gene mutation 1.4% (2/140) Protein S 4.3% (6/140) Protein C 4.3% (6/140) | Factor V Leiden mutation, prothrombin gene mutation, protein C activity, protein S activity. No difference was found between 2 versus 3 or more pregnancy losses. |
| Guzel et al. | 2015 | Cohort | 252 women 2 PL n = 72 ≥ 3 PL n = 180 | Protein S deficiency (84.18 ± 11.69) Protein C deficiency (90.91 ± 23.35) | Protein S deficiency (89.02 ± 22.47) Protein C deficiency (106.57 ± 68.79) | Protein S deficiency and protein C deficiency. No difference was found between 2 versus 3 or more pregnancy losses. |
| Thyroid disorders | ||||||
| Jaslow et al. | 2010 | Cohort | 687 women 2 PL n = 396 ≥ 3 PL n = 291 | Abnormal TSH 8.0% (32/396) | Abnormal TSH 6.5% (19/291) | Serum levels of TSH < 0.45 mU/ml or > 4.5 mU/ml |
| Bashiri et al. | 2012 | Cohort | 118 women 2 PL n = 38 ≥ 3 PL n = 80 | Abnormal TSH 2.6% (1/38) | Abnormal TSH 16.3%(13/80) | Serum levels of TSH < 0.45 mU/ml or > 4.5 mU/ml. |
PL, pregnancy loss; TSH: thyroid-stimulating hormone, MTHFR: methylenetetrahydrofolate reductase.