DOI: http://dx.doi.org/10.18203/2320-1770.ijrcog20205215

Analysis of 14-bp HLA-G polymorphism in middle-eastern women with recurrent implantation failure

Rand Sulaiman, Tharaa Mohammad, Marwan Alhalabi

Abstract


Background: Implantation appears to be the major rate-limiting step in assisted reproductive techniques success. Recurrent implantation failure (RIF) is a common condition, being the failure to achieve a clinical pregnancy after transfer of four or more good-quality embryos in a minimum of two IVF cycles in a woman under the age of 40. Human leukocyte antigen G (HLA-G) is thought to play a key role in implantation by modulating cytokine secretion to enable the semi-allogeneic embryo to implant into the maternal endometrium. The aim of this study was to investigate the association between the 14-bp ins/del HLA-G polymorphism and rates of RIF. No similar studies were conducted nationally or regionally.

Methods: The study was designed as a case-control study. A proportion of 30 patients with RIF were selected as the experimental group. The control group included 15 patients with at least one pregnancy following IVF procedure. Peripheral blood samples were collected from both groups. DNA was extracted and the polymorphism analysis was performed using (AMPLI - HLA-G polymorphism) kit, then PCR products were electrophoresed on 2% agarose gel. statistical analysis was performed using SPSS statistics software.

Results: A total of 45 middle-eastern patients were recruited in this case-control study. High frequency of the polymorphism was found in both case (76.6%) and control (86.67%) groups, but with no significant difference between the two groups (p=0.429).

Conclusions: There is no correlation between the 14-bp ins/del HLA-G polymorphism and RIF, thus it may be considered as a normal polymorphism and might not affect the level of HLA-G.


Keywords


Assisted reproductive techniques, Recurrent implantation failure, Implantation, HLA-G polymorphism, middle east

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References


Cao H, You D, Yuan M, Xi M. Hysteroscopy after repeated implantation failure of assisted reproductive technology: A meta‐analysis. J Obstet Gynaecol Res. 2018;44(3):365-73.

Sharif K, Ghunaim S. Management of 273 cases of recurrent implantation failure: results of a combined evidence-based protocol. Reproduct Biomedic. 2010;21(3):373-80.

Potdar N, Gelbaya TA, Konje JC, Nardo LG. Adjunct low-molecular-weight heparin to improve live birth rate after recurrent implantation failure: a systematic review and meta-analysis. Human reproduction update. 2013;19(6):674-84.

Li Z, Wang X, Guan Y, Yu X, Liu J, Zhang Z. Uterine artery blood flow and microvessel density by vaginal color Doppler ultrasonography in embryo implantation failure. Experiment Therapeut Medic. 2017;14(5):4797-800.

Al-Turki HA. Hysteroscopy as an investigation tool in recurrent implantation failure in vitro fertilization. Sau Medic J. 2018;39(3):243.

Boudjenah R, Molina-Gomes D, Wainer R, de Mazancourt P, Selva J, Vialard F. The vascular endothelial growth factor (VEGF)+ 405 G/C polymorphism and its relationship with recurrent implantation failure in women in an IVF programme with ICSI. J Assist Reproduct Genet. 2012;29(12):1415-20.

Lashley LEELO, Van Der Westerlaken L, Haasnoot G, Drabbels J, Spruyt‐Gerritse M, Scherjon S, et al. Maternal HLA‐C2 and 14 bp insertion in HLA‐G is associated with recurrent implantation failure after in vitro fertilization treatment. Tissue Antige. 2014;84(6):536-44.

Fan W, Huang Z, Li S, Xiao Z. The HLA-G 14-bp polymorphism and recurrent implantation failure: a meta-analysis. J Assist Reproduct Genet. 2017;34(11):1559-65.

Vianna P, Dalmáz CA, Veit TD, Tedoldi C, Roisenberg I, Chies JAB. Immunogenetics of pregnancy: role of a 14-bp deletion in the maternal HLA-G gene in primiparous pre-eclamptic Brazilian women. Hum Immunol. 2007;68(8):668-74.

Aghdaie MH, Azarpira N, Kazemi K, Geramizadeh B, Darai M, Malekhoseini SA. Frequency of HLA-G exon 8 polymorphisms and kidney allograft outcome in Iranian population. Molecul Biol Report. 2011;38(5):3593-7.

Lynge Nilsson L, Djurisic S, Hviid TVF. Controlling the immunological crosstalk during conception and pregnancy: HLA-G in reproduction. Frontiers in immunology. 2014;5:198.

Niu Z, Wang L, Pang RT, Guo Y, Yeung WS, Yao Y. A meta-analysis of the impact of human leukocyte antigen-G on the outcomes of IVF/ICSI. Reproduct Bio Medic. 2017;34(6):611-8.

Nardi FdS, Slowik R, Wowk PF, da Silva JS, Gelmini GF, Michelon TF, et al. Analysis of HLA‐G polymorphisms in couples with implantation failure. Am J Reproduct Immunol. 2012;68(6):507-14.

Mosaferi E, Majidi J, Mohammadian M, Babaloo Z, Monfaredan A, Baradaran B. HLA-G expression pattern: Reliable assessment for pregnancy outcome prediction. Advanc Pharmaceut Bullet. 2013;3(2):443.

Hviid TVF, Hylenius S, Rørbye C, Nielsen LG. HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels. Immunogenet. 2003;55(2):63-79.

Hviid T, Hylenius S, Lindhard A, Christiansen O. Association between human leukocyte antigen‐G genotype and success of in vitro fertilization and pregnancy outcome. Tissue Antige. 2004;64(1):66-9.

Kuroshli Z, Gourabi H, Bazrgar M, Sanati M, Esteki MZ. The Relationship between HLA-G Gene Polymorphisms and Repeated Implantation Failure in Infertile Couples Undergoing Assisted Reproductive Technique Repeated Implantation Failure in Infertile Couples Undergoing Assisted Reproductive Technique. Iran J Aller, Asthm Immunol. 2015;14(5):535-42.

Rizzo R, Fuzzi B, Stignani M, Criscuoli L, Melchiorri L, Dabizzi S, et al. Soluble HLA-G molecules in follicular fluid: a tool for oocyte selection in IVF? J Reproduct Immunol. 2007;74(1-2):133-42.

Ouji-Sageshima N, Yuui K, Nakanishi M, Takeda N, Odawara Y, Yamashita M, et al. sHLA-G and sHLA-I levels in follicular fluid are not associated with successful implantation. J Reproduct Immunol. 2016;113:16-21.

Sipak‐Szmigiel O, Cybulski C, Wokołorczyk D, Lubiński J, Kurzawa R, Bączkowski T, et al. HLA‐G polymorphism and in vitro fertilization failure in a Polish population. Tissue Antig. 2009;73(4):348-52.

Enghelabifar M, Allafan S, Khayatzadeh J, Abadi KS, Nazarabadi MH, Moradi F, et al. Association of the maternal 14-bp insertion/deletion polymorphism in the histocompatibility leukocyte antigen G gene with recurrent implantation failure. Iran J Reproduct Medic. 2014;12(9):641.

Desai N, Filipovits J, Goldfarb J. Secretion of soluble HLA-G by day 3 human embryos associated with higher pregnancy and implantation rates: assay of culture media using a new ELISA kit. Reproduct Biomedic. 2006;13(2):272-7.