P-429 The prevalence and assessment of uterine natural killer cells (uNK) by Immunohistochemistry (IHC) in women undergoing IVF
Authors: Sharma S , Asif S , Fenning N.R 
Published: June 2022

Abstract

Study question
What is the prevalence of raised uNK cells in an IVF population?
Identifying demographic factors that are predictive of a raised uNK result?

Summary answer
The prevalence of uNK was high for those with RIF and history of miscarriage. Age was the only statistically significant factor for predicting positive results.

What is known already
uNK cells play two important roles in implantation; regulation of trophoblastic invasion and spiral artery modelling. Both these crucial mechanisms are required for bringing about a state of endometrial receptivity. The current evidence is centred on raised uNK status in women undergoing IVF being associated with a detrimental pregnancy outcome. This could be either due to NK cells being cytotoxic to embryo endometrium complex or causing aberrant placentation. Their exact function is unclear and the prevalence has only been determined in small observational studies.

Study design, size, duration
This was a prospective analysis of 203 patients who had uNK testing through immunohistochemistry and subsequently embarked on IVF treatment. Patients undergoing both fresh and frozen in vitro fertilisation (IVF) cycles at NURTURE fertility, Nottingham, UK were approached over a period of 6 months at different stages of their fertility history.

Participants/materials, setting, methods
uNK biopsy was arranged one month before undergoing IVF to ensure results before embryo transfer.
The procedure was carried out in the mid-luteal phase of the menstrual cycle (day 19-24). Samples were fixed and analyzed by IHC.
The age, BMI, timing of the biopsy, cause of infertility was recorded. The details of the subsequent IVF cycle, embryo quality, and pregnancy outcome were also collected prospectively.
The data was analyzed using SPSS version 25.

Main results and the role of chance
The prevalence of raised uNK status was noted to be 61.6% (CI 54.9-68.3) in the IVF population. Furthermore the prevalence in women with no previous IVF treatment (primary infertility) was also high 66.7% (CI 54.4-78.9).
One of the main strengths of this work was women were recruited from a highly successful IVF center. The clinical pregnancy rates are 2-3 fold higher than the national average e.g. 65% for women aged under 35 versus 29% respectively (HFEA 2018). This is mainly due to stringent laboratory processes leading to the creation of optimal quality embryos and their transfer. Therefore if IVF did not result in a pregnancy, then endometrial receptivity or adverse maternal immunology could be contributory factors.
Although the prevalence of raised uNK status was high for those with RIF and a history of miscarriage, there were only statistically significant associations found for age in terms of predicting a positive result.
Therefore IHC has to be complimented with another technique such as flow cytometry to determine if uNK is significant in implantation and pregnancy success.

Limitations, reasons for caution
uNK status is influenced by hormonal, menstrual cycle variability, pathogenic and laboratory interpretation. Therefore to gauge an accurate assessment of whether immune cells are implicated in pregnancy, a functional aspect of study or repeat sampling in the same cycle is required.

Wider implications of the findings
It is known that immune cell function declines with age. They may also be detrimental to pregnancy outcomes and contribute to the age-related decline in fertility.
Designing a randomized controlled trial whereby patients tested for uNK are allocated to therapy such as prednisolone. This may address both issues.

Trial registration number
N/A