Table Info

Table 2.

Summary of studies evaluating pNK cell cytotoxicity (pNKC) and proportions in women with a history of RPL

Study	N	Patients	NKC	NK cell proportion/counts
Aoki et al. [66]	24	≥ 2 consecutive 1st-trimester RPL (24) vs. nonpregnant controls (44)	Increased preconception NKC with the association of miscarriage rates compared to controls (71% vs. 20%; RR 3.5, 95% CI = 1.8–6.5)	-
Kwak et al. [8]	116	≥ 3 RPL, 35 pregnant and 81 nonpregnant women. Nonpregnant controls (17) and pregnant controls (22)	-	Increased in CD56⁺ in nonpregnant RPL vs. nonpregnant controls Increased CD56⁺ and CD56⁺/CD16⁺ pNK cells in pregnant RPL vs. pregnant controls
Emmer et al. [67]	43	> 2 RPL before 16 weeks (43), 37 healthy controls	No difference in nonpregnant RPL vs. controls Increased NKC during early pregnancy in the RPL group	No difference in CD56⁺ and CD56⁺/CD16⁺ pNK prepregnancy in RPL vs. controls Increased CD56⁺/CD16⁺ pNK during early pregnancy in the RPL group
Morikawa et al. [68]	113	113 nonpregnant women with a history of RPL. 39 controls who subsequently experienced a live birth	Elevated pre-conception NKC in women who miscarried vs. women who delivered (42.8% ± 15.8% vs. 32.1% ± 13.7%; P = 0.09)	CD56⁺ pNK cells (%) not related to cause and number of RPL
Yamada et al. [69]	66	66 pregnant women with a history of RPL, no controls included	NKC subsequently decreased in the first trimester in livebirth group 32.5% ± 12.3%, 28.1% ± 12.1%, 28.0% ± 11.8% at 4–5 WG, 6–7 WG, 8–9 WG Miscarriage group with normal karyotype had significantly higher NKC at 6–7 WG 41.2% ± 19% vs. 28.1% ± 12.1%	-
Yamada et al. [70]	113	113 nonpregnant women with a history of RPL > 2, no controls included	Increased preconception NKC in women who had a SAB or biochemical pregnancy vs. livebirth (47% vs. 33%)	Increased preconception pNK % in women who had a SAB or biochemical pregnancy vs. livebirth (17.1% vs. 13.1%)
Shakhar et al. [71]	67	38 primary RPL (pRPL) 29 secondary RPL (sRPL)	Primary aborters had higher NKC than secondary aborters or controls	Primary aborters had higher pNK % and counts than secondary aborters and controls
Michou et al. [72]	99	25 RPL 30 sporadic SAB 33 infertile 11 fertile controls	-	Decreased CD56⁺CD16^–CD3^– pNK cells in sporadic aborters and infertile women
Perricone et al. [65]	53	APS with (25) and without RPL (28)	-	Increased CD56⁺ pNK % and counts in patients with RPL and APS than APS alone (15.18% ± 7.32% vs. 8.79% ± 4.68%, P ≤ 0.001)
Wang et al. [73]	85	Nonpregnant women with > 2 consecutive SABs (85) and nonpregnant women controls (27)	-	No difference in peripheral CD56⁺CD16⁺ NK cells in controls vs. RPL (16.6 ± 6.0 vs. 16.5 ± 6.5), or in CD56⁺ 16 ^– (3.8 ± 1.7 vs. 4.4 ± 2.4)
King et al. [74]	104	Nonpregnant women, with a history of ≥3 consecutive RPL in the mid-luteal phase (104) vs. controls (33)	-	Patients with RPL had higher pNK % (11.9% vs. 8.8%, P < 0.001) and lower CD56^bright:CD56^dim (0.54 vs. 0.09, P < 0.05) than controls
Karami et al. [63]	23	23, > 2 RPL patients 36, healthy controls	Increased cytotoxicity in RPL vs. controls (32.14 vs. 10.74, P < 0.001)	Increased CD56^dim pNK cell proportion in RPL vs. controls (12.94 vs. 5.37, P < 0.001)
Lee et al. [75]	95	≥3 idiopathic RPL before 20 weeks. 95 nonpregnant women 29 fertile controls	RPL patients had increased levels of NKC compared to controls	RPL patients had increased CD56⁺ pNK cells (%) compared to controls
Ahmadi et al. [76]	78	≥3 RPL with the current positive pregnancy test 38 treated with IVIg, 40 no treatment controls	IVIg treatment lowered NKC after 32 weeks of gestation (P < 0.0001)	IVIg treatment lowered NK cell percentage after 32 weeks of gestation (P < 0.0001)

CI: confidence interval; NKC: NK cell cytotoxicity; SAB: spontaneous abortion; IVIg: intravenous immunoglobulin; RR: relative risk; N: sample size

Declarations

Author contributions

TL wrote the first and final draft of the manuscript and the sections of the paper. Involved in writing various sections of the manuscript. JKK contributed to the conception and design of the paper. Additionally, she was involved in writing the final draft of various sections. KW wrote the section regarding angiogenesis. LA, AT, UG, SD and KB contributed to manuscript revision, read, and approved the submitted versions.

Conflicts of interest

The authors declare they have no conflicts of interests.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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