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. Author manuscript; available in PMC: 2021 Nov 22.
Published in final edited form as: Fertil Steril. 2021 Aug 17;116(5):1341–1348. doi: 10.1016/j.fertnstert.2021.06.019

Table 1.

Description of included studies

Author,
Country, Year		 Study
Setting		 Study
recruitment
duration,
Number of
study sites		 RPL definition RPL
(n)		 Control
(n)		 Primary
Outcome		 Description of Participants Description of Comparator
Ahmed, S, Bahrain (2015) Outpatient OB/GYN clinics Jan 12-Apr 13, Single site 3 or more consecutive early pregnancy losses 275 290 Association of RPL with serum CRP and genetic variation in CRP gene Non-pregnant women mean age 31.6 [5.4], with u- RPL. Additional exclusion criteria included women over 40 years at first pregnancy, Rh incompatibility, preeclampsia and biochemical pregnancy. Women, mean age 31.6 [4.9], with at least two live births, no personal or family history of miscarriage, preeclampsia, ectopic pregnancy or preterm delivery. Controls were matched to cases according to age and self-identified ethnic origin.
Almawi, W, Bahrain (2013) OBGYN clinics Jan 11 – Apr 12, Single site 3 or more consecutive miscarriages before 24 weeks 296 305 VEGF polymorphism in RPL Non-pregnant women mean age 31.6 [5.4], with u- RPL. Age matched, multiparous women, mean age 31.6 [4.9] with no previous miscarriages and at least two LB.
Al-Shaikh, F, Bahrain, (2013) OBGYN clinics NM, Single site 3 or more consecutive miscarriages before 24 weeks 287 308 Protien Z variants in I-RPL Non-pregnant women mean age 31.6 [5.4], with u- RPL. Age matched, multiparous women, mean age 31.7 [3.9] with no previous miscarriages and at least two LB.
Al-Khateeb, G, Bahrain (2011) Outpatient OB/GYN clinics NM, Two sites 3 or more consecutive early pregnancy losses 282 289 Association of RPL with IL-18 genotyping Non-pregnant women mean age 31.6 [5.4], with u- RPL. Additional exclusion criteria included women over 40 years at first pregnancy, Rh incompatibility, preeclampsia and biochemical pregnancy. Women, mean age 31.7 [4.5], with at least two live births, no personal or family history of miscarriage, preeclampsia, ectopic pregnancy or preterm delivery. Controls were matched to cases according to age and self-identified ethnic origin.
Bagheri, A, India (2017) ART clinic NM, Single site At least 2 pregnancy losses before 20 weeks 90 70 Investigate the relationship between serum level of VEGF and URM Non-pregnant women mean age 30.6 [6.3], with u- RPL. Age matched women, mean age 28.9 [5.8], without history of recurrent abortion with at least one LB.
Bahia, W, 2017, Tunisia OB/GYN clinics Jan 2014-Apr 2016, two sites 3 or more miscarriages 396 361 Genetic variation in progesterone receptor gene in RPL Non-pregnant women mean age 32.4 [6.2], with u- RPL. Hospital employees or volunteer women, mean age 36.1 [7.9] with 2 or more natural pregnancies
Bennett, S, UK, 2014 RM Clinic Mar 11 – Oct 12, Single site 3 or more miscarriages ≤14 weeks or 1 or more miscarriages >14 weeks 50 41 Pro-coagulation potential in RPL Non-pregnant women mean age 36.4 [5.3], with u- RPL. Parous women, mean age 34.9 [5.6], with no miscarriages.
Bussen, S, Germany, 1999 RM Clinic NM, Single site 3 or more miscarriages 42 42 Endocrine abnormalities in RPL Non-pregnant women, mean age 33.2 [4.2] with u- RSA Nulligravid women attending ART clinic, mean age 33.3 (4.7] with no previous miscarriage, and no clinical evidence of endocrine abnormality.
Cao, Y, China, 2013 Maternal and Child Health Center NM, Two sites At least two consecutive pregnancy losses before 20 weeks 94 169 Hemostasis-related gene polymorphism in RPL Women, mean age 28.4 [3.7] with RPL Ethnically matched healthy women, mean age 28.1 [3.6] with regular menstrual cycles, at least one naturally conceived pregnancy and no history of pregnancy loss or other pregnancy complication
Chin, J, USA, 2013 OB/GYN tissue bank NM, Two sites At least two consecutive pregnancy losses before 20 weeks 99 108 Leptin receptor polymorphism in RPL Non-pregnant women mean age 30.6 [5.1], with u- RPL. Women, mean age 30.5 [4.8] with a history of at least two live births and no pregnancy losses
Comba, C, Turkey, 2015 Gyn and Infertility clinics NM, Single site 2 or more consecutive failed clinical pregnancies 21 20 Inflammatory mediators in RPL Non-pregnant women mean age 36.4 [5.3], with u- RPL. Fertile women, mean age 28 [2.6], who had regular menstrual cycles with a history of at least one live birth, no history of abortion or infertility, and who were admitted for annual gynecologic examination.
Dundar, O, Turkey, 2015 OBGYN clinic Jan 01 – Jan 14, Single site 3 or more consecutive first trimester miscarriages, two or more second third trimester fetal loss combined with at least one first-trimester miscarriage 60 60 RBC and Platelet distribution width in RPL Women, mean age 27 [5.2], with history of RPL. Healthy parous women, mean age 27.6 [5.3], with no history of previous miscarriage.
Eser, A, Turkey, 2016 OBGYN clinic NM, Single site 2 or more miscarriages prior to 12 weeks 42 36 Carboxypeptidase B2 in RPL Caucasian women mean age 33.3 [7.9], with RPL and normal thrombophilia panel test. Healthy Caucasian women mean age 32.7[4], who had no history of miscarriage or obstetric morbidity.
Granfors, M, Sweden, 2012 OBGYN clinics Apr 09 – Jun 10, Four sites 3 or more verified consecutive miscarriages in the first or second trimester of pregnancy (5–21 completed weeks of gestation). 188 391 Phosphodiesterase 8B gene polymorphism in RPL Women, mean age 30.1[5.8], with RPL Age matched women, mean age 30.1 [5.8], with no previous history of miscarriage and 74.9% had at least two spontaneous pregnancies, including the ongoing pregnancy, resulting in LB.
Ispasoiu, CA, Romania, 2013 Obstetrics and Fertility clinics Jan 11 – Dec 12, Single site 2 or more pregnancy losses 65 53 High Fasting Insulin Levels and Insulin Resistance Women, mean age 30.1 [4.9], with RPL. Women, mean age 29.3 [5.2], with no pregnancy loss, with at least one live birth.
Jiao, Y 1, China, 2016 OBGYN clinics 2012-2014 3 or more consecutive pregnancies prior to 20 weeks 154 155 Toll-like receptor 4 gene in Uygur women with RPL Women, mean age 35.2 [3.7], with u- RPL. Age-matched healthy women, mean age 35.1 [4.5] with no history of abortions or fertility treatments.
Jiao, Y 2, China, 2016 OBGYN clinics 2012-2014 3 or more consecutive pregnancies prior to 20 weeks 152 151 Toll-like receptor 4 gene in Han women with RPL Women, mean age 35.6 [4.1], with u- RPL. Age-matched healthy women, mean age 35.7 [3.8] with no history of abortions or fertility treatments.
Krause, M, Germany & Switzerland, 2005 Obstetric clinics Jan 98-Dec 03, Four sites 3 or more abortions < 23 gestational weeks with the same partner 133 133 Lipoprotein (a) and other prothrombotic risk factors in RPL Caucasian women, median age 29 [range=17-40], with u- RM Age-matched healthy women, median age 28.5 [range=18-40], who had delivered at least one child without complications and who had no history of spontaneous abortion.
Li, L, China, 2018 OBGYN in-patients and outpatient clinics Jan 14 – May 16 2 or more spontaneous abortion; the couple without abnormal karyotype or thrombotic diseases. 129 116 Polymorphism in promoter region of MMP2 and MMP9 in RPL. Women, mean age 28.1 [4.5], with u- RPL. Women, mean age [27.4 [4.2], with history of normal pregnancy without complications in the age of 17 to 43 years.
Li, S, China, 2017 Maternal and Child Care Service Centre Jan 15 – Dec 15 2 or more miscarriages less than 12 weeks 80 100 TNF-α in decidual tissue and peripheral blood in RPL Women, mean age 29.03 [4.4], with u-RSA. Women, mean age 28.5 [5.2], with a normal early pregnancy but who voluntarily decided to terminate the pregnancy
Park, H, Korea, 2019 Obstetrics and Fertility clinics Mar 99-Feb 10, Two sites At least 2 consecutive pregnancy losses 375 276 MicroRNA polymorphism in miR-150 and miR-1179 in RPL Women, mean age 33.02 [4.2], with idiopathic RPL. Pregnant women, mean age 33.01 [5.3], previous regular menstrual cycles, history of LB, no history of pregnancy loss, and karyotype 46, XX.
Pekcan, M, Turkey, 2017 Infertility OP clinic Feb 15 – Jan 16 2 or more clinically diagnosed unexplained pregnancy loss before 20 weeks 45 41 ADAMTS-3, −13, −16, and −19 levels in RPL Women, median age [range=20-45], with u- RPL. Women, median age 31 [range=21-41], with at least two healthy children, regular menstrual cycles, requesting contraception, no history of recurrent miscarriage, no acute or chronic illness, and no drug use.
Romero, S, USA, 2016 OBGYN and Internal Medicine clinics NM, Two sites 2 or more clinically diagnosed unexplained pregnancy loss before 20 weeks 117 117 Serum fructosamine and RPL Women, mean age 30.1 [4.5], with idiopathic RPL. Women, mean age 30.1 [4.6], with at least one LB and no miscarriage or major medical obstetric history.
Sater, M, Bahrain, 2011 OBGYN clinics Oct 07 – May 09, Single site 3 or more miscarriages before 12 weeks 265 283 Anti-PZ IgM and IgG level in RPL Non-pregnant women mean age 31.6 [5.4], with u- RPL. Age matched, multiparous women, mean age 31.7 [4.5], with no previous miscarriages.
Sater, M, Bahrain, 2012 OBGYN clinics Feb 10 – Oct 10, Single site 3 or more miscarriages with the same partner 277 288 Anti-β2 GP1 antibodies in RPL Non-pregnant women mean age 31.6 [5.4], with u- RPL. Age matched, multiparous women, mean age 31.7 [4.5], with no previous miscarriages.
Sharshiner, R, USA, 2013 OBGYN and Internal Medicine clinics NM, Two sites 2 or more clinically diagnosed unexplained pregnancy loss before 20 weeks 116 116 Celiac disease serum markers and RPL Women, mean age 30.1 [4.4], with idiopathic RPL. Women, mean age 30.1 [4.5], with at least one LB and no miscarriage or major medical obstetric history.
Trifonova, E.A, Russia, 2019 Genetic clinics 2010-2014, Single site At least 2 or more miscarriages before 20 weeks 253 339 Angiogenesis and endothelial dysfunction related gene variants in RPL Women, mean age 29.5 [4.5], with idiopathic RPL Women, mean age 27.3 [4.6], with at least 2 live births and no history of miscarriage.
Xu, Z, China, 2017 Gyn clinic Aug 16-Sep 16, Single site 3 or more consecutive miscarriages before 24 weeks 30 30 Expression of LRH-1 in RPL Women, mean age 27.6 [2.9], in early pregnancy after a diagnosis of u-RPL Women, mean age 27.2 [1.5], in early pregnancy with no previous history of miscarriages.
Zahraei, M, Iran, 2014 Infertility clinic NM, Single site 2 or more miscarriages with no previous LB 100 100 Sulf1 gene polymorphism in RPL Women, mean age 30.9 [5.1], with u- RM. Age-matched healthy women, mean age 29 [4.4] with two LB and no history of abortions or fertility treatments.