Intravenous immunoglobulin treatment in women with four or more recurrent pregnancy losses: A double-blind, randomised, placebo-controlled trial

Yamada, Hideto; Deguchi, Masashi; Saito, Shigeru; Takeshita, Toshiyuki; Mitsui, Mari; Saito, Tsuyoshi; Nagamatsu, Takeshi; Takakuwa, Koichi; Nakatsuka, Mikiya; Yoneda, Satoshi; Egashira, Kensuke; Tachibana, Masahito; Matsubara, Keiichi; Honda, Ritsuo; Fukui, Atsushi; Sengoku, Kazuo; Endo, Toshiaki; Yata, Hiroaki

doi:10.1016/j.eclinm.2022.101527

Cited by 31 publications

(23 citation statements)

References 32 publications

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“…However, the recent meta-analysis of 54 RCTs comprising 4957 participants supports the efficacy of treatment with hydroxychloroquine, IVIG, and prednisone when prescribed in addition to the first-line therapy with low-dose aspirin and LMWH [ 114 ]. Based on a recent RCT [ 188 ], ESHRE suggested the administration of “repeated and high doses of IVIG very early in pregnancy” that could be beneficial for the improvement of live birth rates in women with four or more idiopathic pregnancy losses [ 5 ].…”

Section: Resultsmentioning

confidence: 99%

Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box

Turesheva,

Aimagambetova,

Ukybassova

et al. 2023

JCM

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Recurrent pregnancy loss is a complex health challenge with no universally accepted definition. Inconsistency in definitions involves not only the number of spontaneous abortions (two or three) that are accepted for recurrent pregnancy loss but the types of pregnancy and gestational age at miscarriage. Due to the heterogeneity of definitions and criteria applied by international guidelines for recurrent pregnancy loss, the true incidence of recurrent miscarriage, which is reported to range from 1% to 5%, is difficult to estimate. Moreover, the exact etiology of recurrent pregnancy loss remains questionable; thus, it is considered a polyetiological and multifactorial condition with many modifiable and non-modifiable factors involved. Even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors, up to 75% of cases remain unexplained. This review aimed to summarize and critically analyze accumulated knowledge on the etiology, risk factors, relevant diagnostic options, and management approach to recurrent pregnancy loss. The relevance of various factors and their proposed roles in recurrent pregnancy loss pathogenesis remains a matter of discussion. The diagnostic approach and the management largely depend on the etiology and risk factors taken into consideration by a healthcare professional as a cause of recurrent miscarriage for a particular woman or couple. Underestimation of social and health consequences of recurrent pregnancy loss leads to compromised reproductive health and psychological well-being of women after miscarriage. Studies on etiology and risk factors for recurrent pregnancy loss, especially idiopathic, should be continued. The existing international guidelines require updates to assist clinical practice.

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Section: Resultsmentioning

confidence: 99%

Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box

Turesheva,

Aimagambetova,

Ukybassova

et al. 2023

JCM

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“…Unfortunately, both normal pregnancy mice and GDM mice lost their pregnancies when treated with NK cells at GD5.5 (not shown). To avoid the impact of immunotherapy on embryo implantation, immunotherapy or intrauterine infusion therapy is normally administered before pregnancy or in the very early stages of pregnancy in clinical practice ( 66 , 69 , 70 ). Therefore, performing intrauterine infusion at a very early stage is safer and will have a smaller impact on the miscarriage rate of embryos.…”

Section: Discussionmentioning

confidence: 99%

Aberrant NK cell profile in gestational diabetes mellitus with fetal growth restriction

Xiong,

Wang,

et al. 2024

Front. Immunol.

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Gestational diabetes mellitus (GDM) is a gestational disorder characterized by hyperglycemia, that can lead to dysfunction of diverse cells in the body, especially the immune cells. It has been reported that immune cells, specifically natural killer (NK) cells, play a crucial role in normal pregnancy. However, it remains unknown how hyperglycemia affects NK cell dysfunction thus participates in the development of GDM. In this experiment, GDM mice were induced by an intraperitoneal injection of streptozotocin (STZ) after pregnancy and it has been found that the intrauterine growth restriction occurred in mice with STZ-induced GDM, accompanied by the changed proportion and function of NK cells. The percentage of cytotoxic CD27-CD11b+ NK cells was significantly increased, while the proportion of nourished CD27-CD11b- NK cells was significantly reduced in the decidua of GDM mice. Likewise, the same trend appeared in the peripheral blood NK cell subsets of GDM patients. What’s more, after intrauterine reinfusion of NK cells to GDM mice, the fetal growth restriction was alleviated and the proportion of NK cells was restored. Our findings provide a theoretical and experimental basis for further exploring the pathogenesis of GDM.

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“…In the former studies, medium-dose IVIG was administered; the dosage was 20−50 g several times before or after pregnancy was confirmed [ 16 , 17 , 18 ]. A recent randomized controlled trial revealed that high-dose IVIG treatment (100 g) for RPL can improve pregnancy outcomes, including ongoing pregnancy and live birth rates [ 19 ]. In addition, Christiansen et al described that high-dose IVIG effectively prevented RPL in a randomized, double-blind, placebo-controlled trial [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Successful Pregnancy and Delivery at Term Following Intravenous Immunoglobulin Therapy with Heparin for Unexplained Recurrent Pregnancy Loss Suspected of Immunological Abnormalities: A Case Report and Brief Literature Review

Mitsui

Ota

Takayanagi

et al. 2023

JCM

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About 60% of cases of recurrent pregnancy loss have unexplained etiology. Immunotherapy for unexplained recurrent pregnancy loss is still unestablished. A 36-year-old woman, not obese, had a stillbirth at 22 gestational weeks and a spontaneous abortion at 8 weeks. She had been examined for recurrent pregnancy loss at previous clinics with no significant findings. When she visited our clinic, a hematologic test showed a Th1/Th2 ratio imbalance. Ultrasonography, hysteroscopy, and semen analysis showed no abnormalities. She successfully conceived by embryo transfer in hormone replacement therapy cycle. However, she had a miscarriage at 19 weeks. The baby had no deformities, but a chromosomal test was not performed, according to the parents’ will. The placenta pathologically suggested hemoperfusion problems. Her and her husband’s chromosomal tests showed normal karyotypes. Other examinations revealed a repeated Th1/Th2 ratio imbalance and a high resistance index of uterine radial artery blood flow. She was administered low-dose aspirin, intravenous immunoglobulin, and unfractionated heparin after the second embryo was transferred. Her baby was healthily born by cesarean section at 40 weeks. Intravenous immunoglobulin therapy can be a choice for recurrent miscarriage without risk factors because it has clinically beneficial influences on the patient’s immunological aberration.

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Intravenous immunoglobulin treatment in women with four or more recurrent pregnancy losses: A double-blind, randomised, placebo-controlled trial

Cited by 31 publications

References 32 publications

Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box

Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box

Aberrant NK cell profile in gestational diabetes mellitus with fetal growth restriction

Successful Pregnancy and Delivery at Term Following Intravenous Immunoglobulin Therapy with Heparin for Unexplained Recurrent Pregnancy Loss Suspected of Immunological Abnormalities: A Case Report and Brief Literature Review

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