Novel approaches to the management of recurrent pregnancy loss: The OPTIMUM (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu) treatment strategy

Kuroda, Keiji; Ikemoto, Yuko; Horikawa, Takashi; Moriyama, Azusa; Ojiro, Yuko; Takamizawa, Satoru; Uchida, Toyoyoshi; Nojiri, Shuko; Nakagawa, Koji; Sugiyama, Rikikazu

doi:10.1002/rmb2.12412

Cited by 13 publications

(25 citation statements)

References 73 publications

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“…Cytokines such as tumor necrosis factor‐α, interleukin‐6 and interferon‐γ are synthesized in large quantities by Th1 cells in RSA patients, causing an excessive inflammatory response in the body 34 . In addition, Kuroda et al 36 . showed that the Th1/Th2 ratio was obviously lower in RSA patients after vitamin D treatment, which validated the relationship between serum vitamin D concentrations and the Th1/Th2 ratio.…”

Section: Discussionmentioning

confidence: 87%

Association between serum vitamin D level during pregnancy and recurrent spontaneous abortion: A systematic review and meta‐analysis

Chen

Wang

Zhang

et al. 2022

American J Rep Immunol

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Problem Previous studies had shown that there might be an association between serum vitamin D concentrations and the occurrence of recurrent spontaneous abortion (RSA). However, the conclusions remained controversial. The objective of this study was to systematically review the evidence for an epidemiological association between vitamin D and RSA. Method of study The literature search was performed in the following databases: PubMed, Web of Science, Embase and Chinese databases. The I2 statistic was used to evaluate heterogeneity. Effect sizes were calculated using fixed or random effects models, including standardized mean difference (SMD), odds ratios (OR) and their 95% confidence intervals (95% CI). Then, we performed subgroup analysis, sensitivity analysis and publication bias analysis. Results Fourteen studies from five countries were included. Based on the results, patients with RSA had lower vitamin D levels than controls (SMD = ‐1.48, 95% CI: ‐2.01, ‐.94, P < .001), and pregnant women with vitamin D deficiency (VDD) had a higher risk of developing RSA (OR = 4.02, 95% CI: 2.23, 7.25, P < .001). There was remarkable heterogeneity between studies (I2SMD = 97.3%, P < .001; I2OR = 82.2%, P < .001). The results of the subgroup analysis suggested that heterogeneity may be caused by the assay method, age and region. Sensitivity analysis showed the analysis results were robust. Conclusion Patients with RSA had lower serum vitamin D levels than normal pregnant women, and pregnant women with VDD might be at higher risk for RSA.

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Section: Discussionmentioning

confidence: 87%

Association between serum vitamin D level during pregnancy and recurrent spontaneous abortion: A systematic review and meta‐analysis

Chen

Wang

Zhang

et al. 2022

American J Rep Immunol

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“…There was also no difference in the chromosomal aberration rate between the factors for recurrent pregnancy loss, with or without thrombophilia, and antithrombotic therapy; only advancing maternal age was significantly correlated with increased embryo chromosomal aberration rates. 19 On the contrary, according to Kurodawa, 20 the live birth rate in thrombophilia patients treated with low‐dose aspirin increased in all patients, except for those older than 40 years old. Our patients were treated with low‐molecular‐weight heparin, not aspirin, but there was no difference regarding age.…”

Section: Discussionmentioning

confidence: 98%

The postpartum uterine ultrasonographic scale in assessment of uterine involution after cesarean section in treated thrombophilia pregnant patients at term

Filip

Covali

Socolov

et al. 2022

Clinical Laboratory Analysis

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Background Pregnancy is a prothrombotic condition which can be abnormally exaggerated in women with thrombophilia. Methods In a prospective study, patients who delivered at term, by cesarean section, between 1 October 2017 and 1 December 2021, who already had a diagnosis of thrombophilia before coming to our hospital, were included in the study group ( n = 80). A similar number of nonthrombophilia patients ( n = 80) without any history of thrombotic events, age‐ and para‐matched with the study group, were included in the control group. The postpartum uterine ultrasonographic scale (PUUS) values, in the first 24–48 h, were correlated with the patients' data. Results The P‐LCR (platelet large cell ratio), was significantly higher in the treated thrombophilia group ( p = 0.042). There was no correlation between PUUS and complete blood count values, coagulation factors, maternal characteristics, or fetal outcomes, except for postpartum neutrophils ( p = 0.047) and postpartum platelet count ( p = 0.046). Conclusions Postpartum uterine involution was not significantly different, after cesarean section, between treated thrombophilia patients and nonthrombophilia patients. Involution correlated only with postpartum neutrophils and postpartum platelet count.

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“…The diagnosis of CE was defined as five or more CD138‐positive cells in 10 random areas at ×10 magnification based on our previous studies. 26 , 27 …”

Section: Methodsmentioning

confidence: 99%

“…None of the patients had chronic endometritis (CE) resulting from CD138 immunostaining of the endometrium or abnormal complete blood count data. The diagnosis of CE was defined as five or more CD138‐positive cells in 10 random areas at ×10 magnification based on our previous studies 26,27 …”

Section: Methodsmentioning

confidence: 99%

Transcriptomic profiling analysis of human endometrial stromal cells treated with autologous platelet‐rich plasma

Kuroda

Matsumoto

Horikawa

et al. 2023

Reprod Medicine & Biology

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Purpose To clarify the mechanisms of intrauterine platelet‐rich plasma (PRP) infusion that support embryo implantation in in vitro fertilization treatment. Methods Blood and endometrial samples were collected from four infertile women. Human endometrial stromal cells (HESCs) were cultured and passaged equally into four cell culture dishes in each patient. Two were treated with PRP twice, and the other two were treated with vehicle. Subsequently, two cultures with and without PRP were decidualized with 8‐bromoadenosine 3′,5′‐cyclic AMP and progesterone for 5 days. Results The gene expression in undifferentiated or decidualized HESCs with and without PRP was compared. In the microarray analysis, 381 and 63 differentially expressed genes were detected in undifferentiated and decidualized HESCs, respectively. In the undifferentiated HESCs, PRP was found to promote the gene expression associated with cell growth, tissue regeneration, proinflammatory response, and antibiotic effects. In decidualized HESCs, PRP was found to attenuate the gene expression involved in cell proliferation and inflammation by inhibiting the expression of phosphoinositide 3‐kinase signaling. Conclusions Platelet‐rich plasma regulates the reprogramming of cell proliferation and inflammation depending on menstrual cycle phases in an appropriate manner, suggesting that PRP has the potential to increase endometrial thickness in the proliferative phase and improve immune tolerance in the secretory phase.

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Novel approaches to the management of recurrent pregnancy loss: The OPTIMUM (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu) treatment strategy

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 13 publications

References 73 publications

Association between serum vitamin D level during pregnancy and recurrent spontaneous abortion: A systematic review and meta‐analysis

Association between serum vitamin D level during pregnancy and recurrent spontaneous abortion: A systematic review and meta‐analysis

The postpartum uterine ultrasonographic scale in assessment of uterine involution after cesarean section in treated thrombophilia pregnant patients at term

Transcriptomic profiling analysis of human endometrial stromal cells treated with autologous platelet‐rich plasma

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