PMID- 31993049 OWN - NLM STAT- MEDLINE DCOM- 20201204 LR - 20201214 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 10 DP - 2019 TI - Association of Soluble HLA-G Plasma Level and HLA-G Genetic Polymorphism With Pregnancy Outcome of Patients Undergoing in vitro Fertilization Embryo Transfer. PG - 2982 LID - 10.3389/fimmu.2019.02982 [doi] LID - 2982 AB - Infertility is currently a growing problem observed around the world and is estimated to affect between 8 and 12% of reproductive-aged couples worldwide. Artificial reproductive techniques are the last chance for couples seeking their own child. Human leukocyte antigen (HLA)-G expression has been suggested as an immunomodulatory molecule that influences pregnancy outcome. The HLA-G gene encodes either membrane-bound or/and soluble proteins. The aim of this study was the evaluation of the role of soluble HLA-G (sHLA-G) and its gene polymorphism in successful implantation after in vitro fertilization embryo transfers (IVF-ETs) in different clinical protocols. We tested the HLA-G polymorphism in three positions: rs1632947: c.-964G>A; rs1233334: c.-725G>C/T in promoter region; rs371194629: c.(*)65_(*)66insATTTGTTCATGCCT in 3' untranslated region of exon 8, in 389 patients who underwent IVF-ETs and 320 women with healthy children born after natural conception. Among the patient group, 239 women were with recurrent implantation failure and 117 women had an ongoing pregnancy or a child born after IVF-ET. We found that certain rs1632947-rs1233334-rs371194629 HLA-G haplotypes and diplotypes were associated with infertility, while others were protective. The lowest secretors of sHLA-G were G-C-ins haplotype carriers (37.21 IU/ml), while the highest -G-C-del carriers (73.80 IU/ml). Other haplotype carriers were intermediate secretors. In our study, regardless of possessed haplotype by the patient, 59.73 IU/ml sHLA-G was the threshold value with the best sensitivity (58.82%) and specificity (66.10%) to discriminate patients who achieved and maintained pregnancy from those who did not conceive or they had miscarriage (p = 0.0085; likelihood ratio, 1.74; 95% CI = 0.55-0.78). However, we do not exclude that factors other than sHLA-G may also contribute to complications in pregnancy. In addition, we found that IVF patients in cycles when frozen/thawed embryo was transferred secreted higher soluble HLA-G levels than patients with fresh embryo transferred (p = 0.021). Moreover, correlation analysis of sHLA-G concentration measured before and after embryo transfer for particular patients indicated short ovarian stimulation with gonadotropin-releasing hormone antagonist as more beneficial than long protocol with gonadotropin-releasing hormone agonist. Our study confirms a role of HLA-G polymorphism in infertility and soluble HLA-G in the early stages of pregnancy. CI - Copyright (c) 2020 Nowak, Wilczynska, Radwan, Wisniewski, Krasinski, Radwan, Wilczynski, Malinowski and Kusnierczyk. FAU - Nowak, Izabela AU - Nowak I AD - Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. FAU - Wilczynska, Karolina AU - Wilczynska K AD - Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. FAU - Radwan, Pawel AU - Radwan P AD - Department of Reproductive Medicine, Gameta Hospital, Rzgow, Poland. AD - Biogeno-Regional Science-Technology Centre, Podzamcze, Poland. FAU - Wisniewski, Andrzej AU - Wisniewski A AD - Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. FAU - Krasinski, Rafal AU - Krasinski R AD - Department of Reproductive Medicine, Gameta Hospital, Rzgow, Poland. FAU - Radwan, Michal AU - Radwan M AD - Department of Reproductive Medicine, Gameta Hospital, Rzgow, Poland. AD - Faculty of Health Sciences, The State University of Applied Sciences in Plock, Plock, Poland. FAU - Wilczynski, Jacek R AU - Wilczynski JR AD - Department of Surgical and Oncological Gynecology, Medical University of Lodz, Lodz, Poland. FAU - Malinowski, Andrzej AU - Malinowski A AD - Department of Surgical, Endoscopic and Oncologic Gynecology, Polish Mothers' Memorial Hospital-Research Institute, Lodz, Poland. FAU - Kusnierczyk, Piotr AU - Kusnierczyk P AD - Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200114 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (3' Untranslated Regions) RN - 0 (HLA-G Antigens) SB - IM MH - 3' Untranslated Regions MH - Embryo Transfer MH - Female MH - Fertilization in Vitro MH - HLA-G Antigens/*blood/*genetics MH - Haplotypes MH - Humans MH - Infertility, Female/blood/*genetics/physiopathology/*therapy MH - *Polymorphism, Genetic MH - Pregnancy MH - Pregnancy Outcome PMC - PMC6971053 OTO - NOTNLM OT - HLA-G polymorphism OT - fresh or frozen cycle OT - in vitro fertilization embryo transfer OT - ovarian stimulation protocol OT - recurrent implantation failure OT - sHLA-G EDAT- 2020/01/30 06:00 MHDA- 2020/12/15 06:00 PMCR- 2019/01/01 CRDT- 2020/01/30 06:00 PHST- 2019/09/24 00:00 [received] PHST- 2019/12/04 00:00 [accepted] PHST- 2020/01/30 06:00 [entrez] PHST- 2020/01/30 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2019.02982 [doi] PST - epublish SO - Front Immunol. 2020 Jan 14;10:2982. doi: 10.3389/fimmu.2019.02982. eCollection 2019.