PMID- 31761720 OWN - NLM STAT- MEDLINE DCOM- 20210407 LR - 20210407 IS - 1472-6491 (Electronic) IS - 1472-6483 (Linking) VI - 40 IP - 1 DP - 2020 Jan TI - Ovarian stimulation does not influence the uterine immune environment in healthy infertile women. PG - 113-123 LID - S1472-6483(19)30698-4 [pii] LID - 10.1016/j.rbmo.2019.08.004 [doi] AB - RESEARCH QUESTION: There is some controversy regarding the impact of ovarian stimulation on immune cells in women undergoing IVF. The study's aim was to determine whether ovarian stimulation affected immune uterine cells in healthy women undergoing IVF. DESIGN: This prospective cohort study included 28 patients undergoing IVF and 47 healthy oocyte donors. Endometrial biopsies were taken in a natural cycle and after ovarian stimulation. All participants had a normal karyotype, pelvic ultrasound and cervical cytology results and thyroid-stimulating hormone concentration, as well as normal glucose and insulin concentrations and inherited and acquired thrombophilia test results. Screening tests including human papillomavirus were normal. Immune cells were analysed using three techniques: fluorescence-activated cell sorting, immunohistochemistry and gene expression. A human leukocyte antigen (HLA)-C tetramer was used as an 'artificial embryo'. The expression of genes including those for tumour necrosis factor (TNF)-alpha and interleukin-10 (IL-10) was analysed. RESULTS: A comparison was made of the percentage and gene expression of CD56(bright)CD16(-) uterine natural killer (uNK), CD56(dim)CD16(+) natural killer cells, CD56(-)CD16(+) natural killer cells and TregCD25(+)CD4(+)FoxP3(+) cells, uNK binding to the HLA-C tetramer, and TNF-alpha and IL-10 expression. No between- or within-group differences were observed in natural versus ovarian stimulation cycles. CONCLUSIONS: Ovarian stimulation does not affect the uterine immune cell population or HLA-C binding in healthy women undergoing ovarian stimulation. Further studies are underway to find out if different responses might be seen in women with previous autoimmune disorders. CI - Copyright (c) 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. FAU - Alecsandru, D AU - Alecsandru D AD - Department of Immunology, IVI RMA, Madrid, Spain; Rey Juan Carlos University, Madrid, Spain; Health Research Institute La Fe, Valencia, Spain. Electronic address: diana.alecsandru@ivirma.com. FAU - Pacheco, A AU - Pacheco A AD - Health Research Institute La Fe, Valencia, Spain; Department of Andrology, IVI RMA, Madrid, Spain; Alfonso X 'El Sabio' University, Madrid, Spain. FAU - Guerrero-Mayo, A AU - Guerrero-Mayo A AD - Universidad de Valencia, IVI Learning Center. FAU - Fabris, A AU - Fabris A AD - Department of Reproductive Endocrinology and Infertility, IVI RMA, Madrid, Spain. FAU - Aparicio, P AU - Aparicio P AD - Department of Immunology, IVI RMA, Madrid, Spain. FAU - Barrio, A AU - Barrio A AD - Department of Reproductive Endocrinology and Infertility, IVI RMA, Madrid, Spain. FAU - Pellicer, A AU - Pellicer A AD - Health Research Institute La Fe, Valencia, Spain; Universidad de Valencia, IVI Learning Center; Department of Reproductive Endocrinology and Infertility, IVI RMA, Roma, Italy. FAU - Garcia-Velasco, Juan A AU - Garcia-Velasco JA AD - Rey Juan Carlos University, Madrid, Spain; Health Research Institute La Fe, Valencia, Spain; Universidad de Valencia, IVI Learning Center; Department of Reproductive Endocrinology and Infertility, IVI RMA, Madrid, Spain. LA - eng PT - Journal Article DEP - 20190822 PL - Netherlands TA - Reprod Biomed Online JT - Reproductive biomedicine online JID - 101122473 SB - IM MH - Adult MH - Embryo Implantation/immunology MH - Female MH - Humans MH - Infertility, Female/*immunology MH - Killer Cells, Natural/*immunology MH - Menstrual Cycle/immunology MH - *Ovulation Induction MH - Prospective Studies MH - Uterus/*immunology OTO - NOTNLM OT - Endometrial biopsies OT - Immune cell populations OT - Natural cycles OT - Ovarian stimulation OT - Peripheral blood natural killer cells OT - Uterine natural killer cells EDAT- 2019/11/26 06:00 MHDA- 2021/04/10 06:00 CRDT- 2019/11/26 06:00 PHST- 2019/01/16 00:00 [received] PHST- 2019/07/15 00:00 [revised] PHST- 2019/08/14 00:00 [accepted] PHST- 2019/11/26 06:00 [pubmed] PHST- 2021/04/10 06:00 [medline] PHST- 2019/11/26 06:00 [entrez] AID - S1472-6483(19)30698-4 [pii] AID - 10.1016/j.rbmo.2019.08.004 [doi] PST - ppublish SO - Reprod Biomed Online. 2020 Jan;40(1):113-123. doi: 10.1016/j.rbmo.2019.08.004. Epub 2019 Aug 22.