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Endometrium immunomodulation by intrauterine insemination administration of treated peripheral blood mononuclear cell prior frozen/thawed embryos in patients with repeated implantation failure

Published online by Cambridge University Press:  19 July 2019

Fattaneh Farifteh Nobijari ,
Seyedeh Soheila Arefi ,
Ashraf Moini ,
Robabeh Taheripanah ,
Elham Fazeli ,
Hamideh Kharazi ,
Seyedeh Zeinab Hosseini ,
Ahmad Hosseini ,
Mojtaba Rezazadeh Valojerdi  and
Henri Copin
...Show all authors
Fattaneh Farifteh Nobijari
Affiliation:
Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1985717444, Iran Genetics and In Vitro Assisted Reproductive (GIVAR) Center, Erfan Hospital, Tehran 1998884349, Iran
Seyedeh Soheila Arefi
Affiliation:
Genetics and In Vitro Assisted Reproductive (GIVAR) Center, Erfan Hospital, Tehran 1998884349, Iran Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran 1941913114, Iran
Ashraf Moini
Affiliation:
Genetics and In Vitro Assisted Reproductive (GIVAR) Center, Erfan Hospital, Tehran 1998884349, Iran Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran 1665659911, Iran
Robabeh Taheripanah
Affiliation:
Infertility and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, 1985711151, Iran
Elham Fazeli
Affiliation:
Department of Anatomy and Reproductive Biology, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
Hamideh Kharazi
Affiliation:
Genetics and In Vitro Assisted Reproductive (GIVAR) Center, Erfan Hospital, Tehran 1998884349, Iran
Seyedeh Zeinab Hosseini
Affiliation:
Genetics and In Vitro Assisted Reproductive (GIVAR) Center, Erfan Hospital, Tehran 1998884349, Iran
Ahmad Hosseini
Affiliation:
Genetics and In Vitro Assisted Reproductive (GIVAR) Center, Erfan Hospital, Tehran 1998884349, Iran
Mojtaba Rezazadeh Valojerdi
Affiliation:
Genetics and In Vitro Assisted Reproductive (GIVAR) Center, Erfan Hospital, Tehran 1998884349, Iran Department of Anatomy, School of Medical Sciences, Tarbiat Modares University, Tehran, 14115111, Iran
Henri Copin
Affiliation:
IVF and Reproductive Genetics, University Hospital and School of Medicine, Picardie University Jules Verne, 80054 Amiens Sud, France
Moncef Benkhalifa*
Affiliation:
IVF and Reproductive Genetics, University Hospital and School of Medicine, Picardie University Jules Verne, 80054 Amiens Sud, France PERITOX Laboratory, CURS, Université de Picardie Jules Vernes Amiens, France
*
*Address for correspondence: Moncef Benkhalifa. University Hospital and School of Medicine, Jules Verne University of Picardie, Amiens 80054, France. Tel: +33 677 867-390. Fax:+33 130 571 934; E-mail: benkhalifamoncef78@gmail.com
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Summary

In assisted reproductive technology (ART) programmes, approximately 10% of infertile patients have at least two or three repeated implantation failures (RIFs) after an in vitro fertilization (IVF) protocol. Successful implantation mainly depends on local immune tolerance mechanisms involving a spectrum of cytokines, interleukins and growth factors. The latter have played pivotal roles in the recruitment of immune cells (and notably T-lymphocyte cells). In total, 250 couples participating in frozen–thawed embryo transfer programme were incorporated in a randomized clinical trial (peripheral blood mononuclear cells (PBMC) subgroup: n=122; control subgroup: n=128). In the PBMC group, a blood sample was collected 5 days before the scheduled frozen–thawed embryo transfer; PBMCs were isolated using Ficoll separation and then cultured for 72 h. Two days prior to embryo transfer, 0.4 ml of cultured PBMCs were transferred into the patient’s uterus. Although the clinical pregnancy rate was higher in the PBMC group (34.4%) than in the control group (23.4%), this difference was not statistically significant (P=0.05 in a chi-squared test). Nevertheless, when we limited the analysis to patients with ≥3 RIFs (n=138), there was a significant difference in the clinical pregnancy rate between the PBMC group (38.6%) and the control group (19.7%; P=0.01). Our results imply that PBMC transfer can be part of effective fertility treatment for patients with RIF.

Keywords

Corticotrophin-releasing hormoneIn vitro fertilizationPeripheral blood mononuclear cellPregnancy rateRepeated implantation failure
Type
Research Article
Information
Zygote , Volume 27 , Issue 4 , August 2019 , pp. 214 - 218
Copyright
© Cambridge University Press 2019 

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References

Benkhalifa, M, Zayani Y, Bach V, Copin H, Fek M, Benkhalifa M and Allal-Elasmi M (2018) Does the deregulation of matrix metalloproteinases contribute to recurrent implantation failure? Expert Rev Proteomics 15, 331–1323 CrossRefGoogle Scholar
Brazdova, A, Senechal, H, et al. (2016) Immune aspects of female infertility. Int J Fertil Steril 10, 1.Google ScholarPubMed
Bulmer, JN and Lash, GE (2005) Human uterine natural killer cells: a reappraisal. Mol Immunol 42, 511–521.CrossRefGoogle ScholarPubMed
Chaouat, G, Dubanchet, S, et al. (2007) Cytokines: important for implantation? J Assist Reprod Genet 24, 491–505.CrossRefGoogle ScholarPubMed
Coughlan, C, Ledger, W, et al. (2014) Recurrent implantation failure: definition and management. Reprod Biomed Online 28, 14–38.CrossRefGoogle ScholarPubMed
Fujiwara, H, Araki, Y, et al. (2016) Dual positive regulation of embryo implantation by endocrine and immune systems – step‐by‐step maternal recognition of the developing embryo. Am J Reprod Immunol 75, 281–289.CrossRefGoogle ScholarPubMed
Franasiak, JM and Scott, RT (2017) Contribution of immunology to implantation failure of euploid embryos. Fertil Steril 107, 1279–1283.CrossRefGoogle ScholarPubMed
Gleicher, N, Kushnir, VA, et al. (2017) Redirecting reproductive immunology research toward pregnancy as a period of temporary immune tolerance. J Assist Reprod Genet 34, 425–430.CrossRefGoogle ScholarPubMed
Lédée, N, Petitbarat, M, et al. (2016) The uterine immune profile may help women with repeated unexplained embryo implantation failure after in vitro fertilization. Am J Reprod Immunol 75, 388–401.CrossRefGoogle ScholarPubMed
Li, S, Wang, J, et al. (2017) Intrauterine administration of hCG-activated autologous human peripheral blood mononuclear cells (PBMC) promotes live birth rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. J Reprod Immunol 119, 15–22.CrossRefGoogle ScholarPubMed
Ly, KD, Aziz, N, et al. (2010) Evidence-based management of infertile couples with repeated implantation failure following IVF. Curr Women’s Health Rev 6, 200–218.CrossRefGoogle Scholar
Madkour, A, Bouamoud, N, et al. (2016) Intrauterine insemination of cultured peripheral blood mononuclear cells prior to embryo transfer improves clinical outcome for patients with repeated implantation failures. Zygote 24, 58–69.CrossRefGoogle ScholarPubMed
Makrigiannakis, A, Margioris, AN, et al. (1999) The decidualizing effect of progesterone may involve direct transcriptional activation of corticotrophinreleasing hormone from human endometrial stromal cells. Mol Hum Reprod 5, 789–796.CrossRefGoogle Scholar
Makrigiannakis, A, Zoumakis, E, et al. (2001) Corticotropin-releasing hormone promotes blastocyst implantation and early maternal tolerance. Nat Immunol 2, 1018–1024.CrossRefGoogle ScholarPubMed
Makrigiannakis, A, BenKhalifa, M, et al. (2015) Repeated implantation failure: a new potential treatment option. Eur J Clin Invest 45, 380–384.CrossRefGoogle ScholarPubMed
Makrigiannakis, A, Vrekoussis, T, et al. (2017) The role of HCG in implantation: a mini-review of molecular and clinical evidence. Int J Mol Sci 18, 1305.CrossRefGoogle ScholarPubMed
Nakayama, T, Fujiwara, H, et al. (2002) Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: HCG enhances the effects of PBMC. Hum Reprod 17, 207–212.CrossRefGoogle ScholarPubMed
Nastiri, CO, Lensen, S, et al. (2015) Endometrial injury and reproductive outcomes: there is more to this story than meets the horse blind eye. Hum Reprod 30, 749.CrossRefGoogle Scholar
Nederlof, I, Meuleman, T, et al. (2017) The seed to success: The role of seminal plasma in pregnancy. J Reprod Immunol 123, 24–28.CrossRefGoogle ScholarPubMed
Novembri, R, Borges, LE, et al. (2011) Impaired CRH and urocortin expression and function in eutopic endometrium of women with endometriosis. J Clin Endocrinol Metab 96, 1145–1150.CrossRefGoogle ScholarPubMed
Okitsu, O, Kiyokawa, M, et al. (2011) Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. J Reprod Immunol 92, 82–87.CrossRefGoogle ScholarPubMed
Simon, C and Bellver, J (2014) The scratching case: systemic reviews and meta analyses, the back door for evidence based medicine. Hum Reprod 29, 1618–1621.CrossRefGoogle Scholar
Vergetaki, A, Jeschke, U, et al. (2013) Differential expression of CRH, UCN, CRHR1 and CRHR2 in eutopic and ectopic endometrium of women with endometriosis. PLoS One 8, e62313.CrossRefGoogle ScholarPubMed
Vitagliano, A, Sarda, A, et al. (2018) Endometerial scratch injury for women with one or more previous failed embryo transfers: a systematic review and mata analysis of randomized controlled trials. Fertil Steril 110, 687–702.CrossRefGoogle Scholar
Yoshioka, S, Fujiwara, H, et al. (2006) Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF–embryo transfer. Hum Reprod 21, 3290–3294.CrossRefGoogle ScholarPubMed
Yu, N, Yang, J, et al. (2014) Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves endometrial receptivity in mice with embryonic implantation dysfunction. Am J Reprod Immunol 71, 24–33.CrossRefGoogle ScholarPubMed
Yu, N, Zhang, B, et al. (2016) Intrauterine administration of autologous peripheral blood mononclear cells (PBMCs) activated by HCG improves the implantation and pregnancy rates in patients with repeated implantation failure: a prospective randomized study. Am J Reprod Immunol 76, 212–216.CrossRefGoogle Scholar
Zeyneloglu, HB and Onalan, G (2014) Remedies for recurrent implantation failure. Semin Reprod Med 32, 297–305.Google ScholarPubMed