University of Oulu

Kangasniemi, M. H., Komsi, E. K., Rossi, H.-R., Liakka, A., Khatun, M., Chen, J. C., Paulson, M., Hirschberg, A. L., Arffman, R. K., & Piltonen, T. T. (2022). Artificial intelligence deep learning model assessment of leukocyte counts and proliferation in endometrium from women with and without polycystic ovary syndrome. F&S Science, 3(2), 174–186.

Artificial intelligence deep learning model assessment of leukocyte counts and proliferation in endometrium from women with and without polycystic ovary syndrome

Saved in:
Author: Kangasniemi, Marika H.1; Komsi, Elina K.1; Rossi, Henna-Riikka1;
Organizations: 1Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
2Department of Pathology, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
3Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California
4Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
5Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.7 MB)
Persistent link:
Language: English
Published: Elsevier, 2022
Publish Date: 2022-10-03


Objective: To study whether artificial intelligence (AI) technology can be used to discern quantitative differences in endometrial immune cells between cycle phases and between samples from women with polycystic ovary syndrome (PCOS) and non-PCOS controls. Only a few studies have analyzed endometrial histology using AI technology, and especially, studies of the PCOS endometrium are lacking, partly because of the technically challenging analysis and unavailability of well-phenotyped samples. Novel AI technologies can overcome this problem.

Design: Case-control study.

Setting: University hospital-based research laboratory.

Patient(s): Forty-eight women with PCOS and 43 controls. Proliferative phase samples (26 control and 23 PCOS) and luteinizing hormone (LH) surge timed LH+ 7–9 (10 control and 16 PCOS) and LH+ 10–12 (7 control and 9 PCOS) secretory endometrial samples were collected during 2014–2019.

Intervention(s): None.

Main Outcome Measure(s): Endometrial samples were stained with antibodies for CD8+ T cells, CD56+ uterine natural killer cells, CD68+ macrophages, and proliferation marker Ki67. Scanned whole slide images were analyzed with an AI deep learning model. Cycle phase differences in leukocyte counts, proliferation rate, and endometrial thickness were measured within the study populations and between the PCOS and control samples. A subanalysis of anovulatory PCOS samples (n = 11) vs. proliferative phase controls (n = 18) was also performed.

Results: Automated cell counting with a deep learning model performs well for the human endometrium. The leukocyte numbers and proliferation in the endometrium fluctuate with the menstrual cycle. Differences in leukocyte counts were not observed between the whole PCOS population and controls. However, anovulatory women with PCOS presented with a higher number of CD68+ cells in the epithelium (controls vs. PCOS, median [interquartile range], 0.92 [0.75–1.51] vs. 1.97 [1.12–2.68]) and fewer leukocytes in the stroma (CD8%, 3.72 [2.18–4.20] vs. 1.44 [0.77–3.03]; CD56%, 6.36 [4.43–7.43] vs. 2.07 [0.65–4.99]; CD68%, 4.57 [3.92–5.70] vs. 3.07 [1.73–4.59], respectively) compared with the controls. The endometrial thickness and proliferation rate were comparable between the PCOS and control groups in all cycle phases.

Conclusions: Artificial intelligence technology provides a powerful tool for endometrial research because it is objective and can efficiently analyze endometrial compartments separately. Ovulatory endometrium from women with PCOS did not differ remarkably from the controls, which may indicate that gaining ovulatory cycles normalizes the PCOS endometrium and enables normalization of leukocyte environment before implantation. Deviant endometrial leukocyte populations observed in anovulatory women with PCOS could be interrelated with the altered endometrial function observed in these women.

see all

Series: F&S science
ISSN: 2666-335X
ISSN-E: 2666-335X
ISSN-L: 2666-335X
Volume: 3
Issue: 2
Pages: 174 - 186
DOI: 10.1016/j.xfss.2022.01.006
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Funding: M.H.K. reports grants from the Orion research foundation sr and the Finnish Medical Association for the submitted work. E.K.K. has nothing to disclose. H.R.R. has nothing to disclose. A.L. has nothing to disclose. M.K. has nothing to disclose. J.C.C. has nothing to disclose. M.P. has nothing to disclose. A.L.H. has nothing to disclose. R.K.A. has nothing to disclose. T.T.P. reports grant from Academy of Finland, Sigrid Juselius Foundation for the submitted work. Supported by the Sigrid Juselius Foundation, Academy of Finland (nos. 315921 and 321763), Orion Research Foundation sr, Finnish Medical Association, and Swedish Research Council. Funding sources were not involved in the study design.
Academy of Finland Grant Number: 315921
Detailed Information: 315921 (Academy of Finland Funding decision)
321763 (Academy of Finland Funding decision)
Copyright information: © 2022 The Authors. Published by Elsevier Inc. on behalf of American Society for Reproductive Medicine. This is an open access article under the CC BY-NC-ND license (