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. 2022 Mar 9;28(4):548–582. doi: 10.1093/humupd/dmac006

Table VI.

Uterine NK cell activity by effect on uterine vasculature.

Author/year Study design Study groups and sample number Tissue sampled Method of analysis Outcome measure Direction of effect of in RM/RIF patients
Lédée et al. (2004) Prospective case control

  • RIF (n = 35)

  • vs

  • controls (n = 12)

 Endometrial tissue at luteal phase, either on Day 20 under oestrogen–progesterone replacement or Day 6 post-urinary LH surge IHC; USS No clear correlation between cytokine staining/depletion of IL-12 and IL-18, number of NK cells and ultrasound Doppler in RIF or controls Qualitative analysis
Lédée-Bataille et al. (2005) Prospective case control

  • RIF (n = 37)

  • vs

  • controls (n = 8)

 Endometrial tissue at luteal phase, either on Day 21 under oestrogen–progesterone replacement IHC; USS; qRT-PCR • Mean UA PI ↑
• Mean number of NK cells ↑
• Mean ET ↓
• Endometrial (IL-12; IL-15; IL-18) cytokine mRNA ratio ↔
Lédée et al. (2008) Prospective case control

  • RIF (n = 40)

  • vs

  • Controls (n = 8)

 Endometrial tissue D7-9 post-LH surge IHC, rtPCR, USS • Sub-endometrial flow
• Uterine artery pulsatility
Correlation of cytokine mRNA ratio:
with sub-endometrial flow and CD56+ count
• IL-15 POSITIVE*
With mean UA PI
• IL-15
• IL-18
• IL-18BP NEGATIVE*
Junovich et al. (2013) Prospective case control

  • RIF (n = 26)

  • vs

  • controls (n = 18)

 Endometrial tissue on Day 5–9 after ovulation (by ultrasound) FC; ELISA Correlation of CD16+ uNK with endometrial cell culture supernatant protein expression:
• IL-6 (n = 28) Inline graphic NEGATIVE*
• VEGF (n = 31) RIF and controls
Almasry et al. (2015) Prospective case control

  • RM (n = 40)

  • vs

  • controls (n = 30)

 Decidual samples at time of miscarriage/TOP between 6 and 10 weeks gestation IHC; TEM Non-remodelling score POSITIVE*
RM and controls
El-Azzamy et al. (2018) Prospective case control

  • 15 RM (n = 14)

  • controls (n = 7)

 Endometrial tissue taken on in mid-luteal phase Day 7–9 post-ovulation IHC; western blot; qRT-PCR Correlation of CD56+ cell count with:
• VSMC expressing SMM ↔*
• CD31+ endothelial cells ↔*
Chen et al. (2018) Prospective case control

  • RM (n = 18)

  • vs

  • controls (n = 10)

 Endometrial samples on Day 7 post-LH surge. Angiogenic array; ELISA Expression of:
• angiogenin Inline graphic↑
• bFGF
• VEGF-A

Effect direction in relation to RM/RIF group: ↑increase;↓decrease; ↔no difference between the groups.

*

P < 0.05.

bFGF, basic fibroblast growth factor; ET, endometridal thickness; IHC, immunohistochemistry; IL-18BP, Interleukin-18 binding protein; qRT-PCR, real-time quantitative PCR; RIF, current implantation failure; RM, recurrent miscarriage; SMM, smooth muscle myosin; TEM, transmission electron microscopy; TOP, termination of pregnancy; UA PI, uterine artery pulsatility index; USS, ultrasound scan; VSMC, vascular smooth muscle cells.