Reproductive outcomes of women with recurrent pregnancy losses and repeated implantation failures are significantly improved with immunomodulatory treatment

Sung, Nak‐Ju; Khan, Shakeb A.; Yiu, Mei-Sin; Jubiz, Giovanni; Salazar, Maria D.; Skariah, Annie; Dambaeva, Svetlana; Kwak‐Kim, Joanne

doi:10.1016/j.jri.2021.103369

Cited by 27 publications

(17 citation statements)

References 41 publications

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“…Specific targeted treatment at the particular time of conception or pregnancy can be offered to control the NK cells mediated pathology. Intravenous immunoglobulin G, glucocorticoids, cyclosporin A, and vitamin D have been utilized to control NK cells for women with RPL [94,196,197]. In conclusion, women with RPL have pro-inflammatory type 1 shift in pNK and dNK cells and increased NKC in pNK.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent analysis of NKC, the receiver operating characteristic (ROC) curve analysis of NKC significantly differentiated pregnant women with RPL from normal women [75], demonstrating its value as a biomarker. When NKC and proportions were controlled before ET and throughout the pregnancy with personalized immunomodulatory therapy, the live birth rates per ET cycle and per pregnancy were significantly increased in women with RPL compared to the historical controls [94].…”

Section: Nkc In Pregnant Women With Rplmentioning

confidence: 96%

“…A detailed analysis of decidual cells by mass cytometry revealed 13 separate clusters of cells identified by mass spectrometry. Of the 13 clusters, 5 main decidual innate lymphoid cell types including decidual NK1 (dNK1), dNK2, dNK3, ILC3, and decidual proliferating NK cells (dNKp), were identified in addition to 2 subtypes of pNK cells (CD49a low /Eomes int /T-bet hi(++) /CD16 + /CD57 + and CD49a low /Eomes int /T-bet hi(++) / CD16 + /CD57 − ) [94].…”

Section: Normal Ovarian Cycle: Endometrial Nk Cellsmentioning

confidence: 99%

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Natural killer cell-mediated immunopathology in recurrent pregnancy losses

et al. 2022

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Natural killer (NK) cells have a dual role in human reproduction for maternal-fetal tolerance and protection from infection. During the ovarian cycle and pregnancy, peripheral NK (pNK) and uterine NK (uNK) cells dynamically change their proportions and cytotoxicities to prepare and accommodate invading trophoblast and maintain pregnancy. However, dysregulated pNK and uNK cell proportions and cytotoxic activities have been associated with aberrant spiral artery remodeling and trophoblast invasion, leading to implantation failures and recurrent pregnancy losses (RPLs). This review will focus on the role of NK cells in RPLs reviewing the ontogeny of NK cells, changes in pNK and uNK cell levels, and activities during the ovarian cycle, normal pregnancy, and RPL. In addition, the immunopathological role of NK cells in endometrial/decidual vascular development and killer immunoglobin-like receptor (KIR) and human leukocyte antigen (HLA)-C interactions are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Nkc In Pregnant Women With Rplmentioning

confidence: 96%

Section: Normal Ovarian Cycle: Endometrial Nk Cellsmentioning

confidence: 99%

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Natural killer cell-mediated immunopathology in recurrent pregnancy losses

et al. 2022

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“…It is not known whether both drugs are necessary for the impacts described, and further studies would be needed to investigate that. But it is worth noting that, in women with repeated IVF failure, immune therapies used in combination do appear to be more beneficial than single therapies used on their own 61 …”

Section: Discussionmentioning

confidence: 99%

Prednisolone and enoxaparin (clexane) therapy (‘the Bondi protocol’) for repeated IVF failure

Sacks

Zhang

2022

American J Rep Immunol

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Problem: What is the impact of an empirical immune therapy protocol of prednisolone and enoxaparin (clexane) (the 'Bondi protocol') on women with repeated in vitro fertilization (IVF) failure? Method of study: This was a retrospective review of live birth outcomes conducted on all transfer cycles performed by a single clinician (GS) at IVFAustralia between February 2016 and April 2020. This study consisted of 1786 transfer cycles, including 460 cycles treated with the Bondi protocol and 1326 without. Women with repeated IVF failure were given the Bondi protocol based on blood NK cell activity. Primary outcome was live birth and statistical analysis was performed with GraphPad Prism software with significance for P-values < .05.Results: Overall 'Bondi' and 'normal' protocol cycles had similar rates of IVF/ICSI, fresh/frozen transfers and use of preimplantation genetic testing (PGT). Women given the Bondi protocol were older, had more previous cycles and had higher blood NK cell activity. There was no significant difference in live birth rates (Bondi 26%, normal 28%).Bondi protocol live birth rates per transfer cycle were as high as 40% in patients under 38 years old. The Bondi protocol was more effective as NK activity increased from 'normal' to 'borderline' to 'high' . For high NK cell activity levels, live birth rates were over four times higher for women on the Bondi protocol (28%) than those on normal protocols (6%, P = .0007). Conclusion:This study describes a simple and relatively safe immune therapy protocol that may improve IVF success rates in women with evidence of immune dysfunction.

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“…Immunomodulatory or immunosuppressant agents are considered in patients with repeated implantation failure or recurrent pregnancy loss with possible immunological etiologies [ 18 , 19 ]. Women on immunomodulatory or immunosuppressant therapies such as anti-tumor necrosis factor agents and high-dose steroids for autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, and poorly controlled asthma) generally visit infertility clinics to have a baby.…”

Section: Should Women Planning To Undergo Immunomodulatory or Immunos...mentioning

confidence: 99%

Effects and safety of COVID-19 vaccination on assisted reproductive technology and pregnancy: A comprehensive review and joint statements of the KSRM, the KSRI, and the KOSAR

Han

Lee

Kim

et al. 2022

Clin Exp Reprod Med

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Humanity is in the midst of the coronavirus disease 2019 (COVID-19) pandemic, and vaccines—including mRNA vaccines—have been developed at an unprecedented speed. It is necessary to develop guidelines for vaccination for people undergoing treatment with assisted reproductive technology (ART) and for pregnancy-related situations based on the extant laboratory and clinical data. COVID-19 vaccines do not appear to adversely affect gametes, embryos, or implantation; therefore, active vaccination is recommended for women or men who are preparing for ART. The use of intravenous immunoglobulin G (IVIG) for the treatment of immune-related infertility is unlikely to impact the effectiveness of the vaccines, so COVID-19 vaccines can be administered around ART cycles in which IVIG is scheduled. Pregnant women have been proven to be at risk of severe maternal and neonatal complications from COVID-19. It does not appear that COVID-19 vaccines harm pregnant women or fetuses; instead, they have been observed to deliver antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the fetus. Accordingly, it is recommended that pregnant women receive COVID-19 vaccination. There is no rationale for adverse effects, or clinical cases of adverse reactions, in mothers or neonates after COVID-19 vaccination in lactating women. Instead, antibodies to SARS-CoV-2 can be delivered through breast milk. Therefore, breastfeeding mothers should consider vaccination. In summary, active administration of COVID-19 vaccines will help ensure the safe implementation of ART, pregnancy, and breastfeeding.

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Reproductive outcomes of women with recurrent pregnancy losses and repeated implantation failures are significantly improved with immunomodulatory treatment

Cited by 27 publications

References 41 publications

Natural killer cell-mediated immunopathology in recurrent pregnancy losses

Natural killer cell-mediated immunopathology in recurrent pregnancy losses

Prednisolone and enoxaparin (clexane) therapy (‘the Bondi protocol’) for repeated IVF failure

Effects and safety of COVID-19 vaccination on assisted reproductive technology and pregnancy: A comprehensive review and joint statements of the KSRM, the KSRI, and the KOSAR

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