TY - JOUR
T1 - Intravenous immunoglobulin treatment in women with four or more recurrent pregnancy losses
T2 - A double-blind, randomised, placebo-controlled trial
AU - Yamada, Hideto
AU - Deguchi, Masashi
AU - Saito, Shigeru
AU - Takeshita, Toshiyuki
AU - Mitsui, Mari
AU - Saito, Tsuyoshi
AU - Nagamatsu, Takeshi
AU - Takakuwa, Koichi
AU - Nakatsuka, Mikiya
AU - Yoneda, Satoshi
AU - Egashira, Katsuko
AU - Tachibana, Masahito
AU - Matsubara, Keiichi
AU - Honda, Ritsuo
AU - Fukui, Atsushi
AU - Tanaka, Kanji
AU - Sengoku, Kazuo
AU - Endo, Toshiaki
AU - Yata, Hiroaki
N1 - Funding Information:
Study drugs were packaged and provided by the Japan Blood Products Organization. We thank all participants for their contributions to this study and thank Tomoyuki Fujii, M.D. Kiyoko Kato, M.D. Hidetaka Katabuchi, M.D. for study design, study management, and oversight. The study was funded by The Japan Blood Products Organization.
Funding Information:
Study drugs were packaged and provided by the Japan Blood Products Organization. We thank all participants for their contributions to this study and thank Tomoyuki Fujii, M.D., Kiyoko Kato, M.D., Hidetaka Katabuchi, M.D., for study design, study management, and oversight. The study was funded by The Japan Blood Products Organization.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/8
Y1 - 2022/8
N2 - Background: There is no effective treatment for women with unexplained recurrent pregnancy loss (RPL). We aimed to investigate whether treatment with a high dose of intravenous immunoglobulin (IVIG) in early pregnancy can improve pregnancy outcomes in women with unexplained RPL. Methods: In a double-blind, randomised, placebo-controlled trial, women with primary RPL of unexplained aetiology received 400 mg/kg of IVIG daily or placebo for five consecutive days starting at 4–6 weeks of gestation. They had experienced four or more miscarriages except biochemical pregnancy loss and at least one miscarriage of normal chromosome karyotype. The primary outcome was ongoing pregnancy rate at 22 weeks of gestation, and the live birth rate was the secondary outcome. We analysed all women receiving the study drug (intention-to-treat, ITT) and women except those who miscarried due to fetal chromosome abnormality (modified-ITT). This study is registered with ClinicalTrials.gov number, NCT02184741. Findings: From June 3, 2014 to Jan 29, 2020, 102 women were randomly assigned to receive IVIG (n = 53) or placebo (n = 49). Three women were excluded; therefore 50 women received IVIG and 49 women received placebo in the ITT population. The ongoing pregnancy rate at 22 weeks of gestation (31/50 [62·0%] vs. 17/49 [34·7%]; odds ratio [OR] 3·07, 95% CI 1·35–6·97; p = 0·009) and the live birth rate (29/50 [58·0%] vs. 17/49 [34·7%]; OR 2·60, 95% CI 1·15–5·86; p = 0·03) in the IVIG group were higher than those in the placebo group in the ITT population. The ongoing pregnancy rate at 22 weeks of gestation (OR 6·27, 95% CI 2·21–17·78; p < 0·001) and the live birth rate (OR 4·85, 95% CI 1·74–13·49; p = 0·003) significantly increased in women who received IVIG at 4–5 weeks of gestation as compared with placebo, but these increases were not evident in women who received IVIG at 6 weeks of gestation. Four newborns in the IVIG group and none in the placebo group had congenital anomalies (p = 0·28). Interpretation: A high dose of IVIG in very early pregnancy improved pregnancy outcome in women with four or more RPLs of unexplained aetiology. Funding: The Japan Blood Products Organization.
AB - Background: There is no effective treatment for women with unexplained recurrent pregnancy loss (RPL). We aimed to investigate whether treatment with a high dose of intravenous immunoglobulin (IVIG) in early pregnancy can improve pregnancy outcomes in women with unexplained RPL. Methods: In a double-blind, randomised, placebo-controlled trial, women with primary RPL of unexplained aetiology received 400 mg/kg of IVIG daily or placebo for five consecutive days starting at 4–6 weeks of gestation. They had experienced four or more miscarriages except biochemical pregnancy loss and at least one miscarriage of normal chromosome karyotype. The primary outcome was ongoing pregnancy rate at 22 weeks of gestation, and the live birth rate was the secondary outcome. We analysed all women receiving the study drug (intention-to-treat, ITT) and women except those who miscarried due to fetal chromosome abnormality (modified-ITT). This study is registered with ClinicalTrials.gov number, NCT02184741. Findings: From June 3, 2014 to Jan 29, 2020, 102 women were randomly assigned to receive IVIG (n = 53) or placebo (n = 49). Three women were excluded; therefore 50 women received IVIG and 49 women received placebo in the ITT population. The ongoing pregnancy rate at 22 weeks of gestation (31/50 [62·0%] vs. 17/49 [34·7%]; odds ratio [OR] 3·07, 95% CI 1·35–6·97; p = 0·009) and the live birth rate (29/50 [58·0%] vs. 17/49 [34·7%]; OR 2·60, 95% CI 1·15–5·86; p = 0·03) in the IVIG group were higher than those in the placebo group in the ITT population. The ongoing pregnancy rate at 22 weeks of gestation (OR 6·27, 95% CI 2·21–17·78; p < 0·001) and the live birth rate (OR 4·85, 95% CI 1·74–13·49; p = 0·003) significantly increased in women who received IVIG at 4–5 weeks of gestation as compared with placebo, but these increases were not evident in women who received IVIG at 6 weeks of gestation. Four newborns in the IVIG group and none in the placebo group had congenital anomalies (p = 0·28). Interpretation: A high dose of IVIG in very early pregnancy improved pregnancy outcome in women with four or more RPLs of unexplained aetiology. Funding: The Japan Blood Products Organization.
KW - Abortion
KW - Intravenous immunoglobulin
KW - Pregnancy outcome
KW - Recurrent miscarriage
KW - Recurrent pregnancy loss
KW - Unknown aetiology
UR - http://www.scopus.com/inward/record.url?scp=85133167150&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85133167150&partnerID=8YFLogxK
U2 - 10.1016/j.eclinm.2022.101527
DO - 10.1016/j.eclinm.2022.101527
M3 - Article
AN - SCOPUS:85133167150
SN - 2589-5370
VL - 50
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 101527
ER -