Detailed Analysis of Peripheral Blood Natural Killer Cells in Women with Repeated <scp>IVF</scp> Failure

Sacks, Gavin; Yang, Yang; Gowen, Elizabeth; Smith, Susan L.; Fay, Louise; Chapman, Michael

doi:10.1111/j.1600-0897.2012.01105.x

Cited by 58 publications

(30 citation statements)

References 34 publications

(44 reference statements)

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“…Many studies complement our hypothesis, showing that uNK and T lymphocyte rates are decreased in patients with unknown infertility reporting a dysregulation of cytokines production (Klentzeris et al, 1992;Fukui et al, 2006;Karami et al, 2012;Chernyshov et al, 2010;Sacks et al, 2012;Zhou et al, 2012;Dons'koi et al, 2013a,b). Furthermore, an interesting and recent study demonstrated that PBMCs intrauterine administration had no effect on implantation rate in patients with only one IVF failure (34 vs. 33%) but significantly increased in patients with at least three IVF failures (42 vs. 25%) (Okitsu et al, 2011).…”

Section: Resultssupporting

confidence: 77%

“…Thus immunotherapy appears to be ineffective in patients with RIF caused by an early dysregulation in the maintenance of pregnancy. Patient with unexplained recurrent spontaneous abortions (URSA) probably present with over-activation of cytotoxic uNKs characterized by up-regulation of CD69stim and CD158a as reported elsewhere (Chernyshov et al, 2010;Sacks et al, 2012;Dons'koi et al, 2013a,b;Wu et al, 2014). In these patients, another therapeutic strategy needs to be developed.…”

Section: Resultsmentioning

confidence: 93%

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Intrauterine insemination of cultured peripheral blood mononuclear cells prior to embryo transfer improves clinical outcome for patients with repeated implantation failures

Madkour

Bouamoud

Louanjli³

et al. 2015

Zygote

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Implantation failure is a major limiting factor in assisted reproduction improvement. Dysfunction of embryo-maternal immuno-tolerance pathways may be responsible for repeated implantation failures. This fact is supported by immunotropic theory stipulating that maternal immune cells, essentially uterine CD56+ natural killer cells, are determinants of implantation success. In order to test this hypothesis, we applied endometrium immuno-modulation prior to fresh embryo transfer for patients with repeated implantation failures. Peripheral blood mononuclear cells were isolated from repeated implantation failure patients undergoing assisted reproductive technology cycles. On the day of ovulation induction, cells were isolated and then cultured for 3 days and transferred into the endometrium cavity prior to fresh embryo transfer. This immunotherapy was performed on 27 patients with repeated implantation failures and compared with another 27 patients who served as controls. Implantation and clinical pregnancy were increased significantly in the peripheral blood mononuclear cell test versus control (21.54, 44.44 vs. 8.62, 14.81%). This finding suggests a clear role for endometrium immuno-modulation and the inflammation process in implantation success. Our study showed the feasibility of intrauterine administration of autologous peripheral blood mononuclear cells as an effective therapy to improve clinical outcomes for patients with repeated implantation failures and who are undergoing in vitro fertilization cycles.

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Section: Resultssupporting

confidence: 77%

Section: Resultsmentioning

confidence: 93%

Intrauterine insemination of cultured peripheral blood mononuclear cells prior to embryo transfer improves clinical outcome for patients with repeated implantation failures

Madkour

Bouamoud

Louanjli³

et al. 2015

Zygote

View full text Add to dashboard Cite

show abstract

“…However, it is important to note that the sensitivity of this test was only 11% suggesting that women with RIF might have multiple other factors that contribute to their difficulty in achieving pregnancy. Testing NK cell levels therefore cannot necessarily be used to distinguish women with RIF from the general population, but rather might be used in women with already established RIF, to determine whether the etiology of their implantation failure is related to their immunological profile [ 32 ].…”

Section: Pathophysiological Mechanisms Of Recurrent Implantation Failmentioning

confidence: 99%

Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions

Bashiri

Halper

Orvieto

2018

Reprod Biol Endocrinol

407

346

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Recurrent implantation failure (RIF) refers to cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos. The definition should also take advanced maternal age and embryo stage into consideration. The failure of embryo implantation can be a consequence of uterine, male, or embryo factors, or the specific type of IVF protocol. These cases should be investigated to determine the most likely etiologies of the condition, as this is a complex problem with several variables. There are multiple risk factors for recurrent implantation failure including advanced maternal age, smoking status of both parents, elevated body mass index, and stress levels. Immunological factors such as cytokine levels and presence of specific autoantibodies should be examined, as well as any infectious organisms in the uterus leading to chronic endometritis. Uterine pathologies such as polyps and myomas as well as congenital anatomical anomalies should be ruled out. Sperm analysis, pre-implantation genetic screening and endometrial receptivity should be considered and evaluated, and IVF protocols should be tailored to specific patients or patient populations. Treatment approaches should be directed toward individual patient cases. In addition, we suggest considering a new initial step in approach to patients with RIF, individualized planned activities to activate the brain's reward system in attempt to improve immunological balance in the body.

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“…The normal range for NK cell numbers and activity in peripheral blood from normal individuals varies widely, at ∼5–30% of mononuclear cells (Bisset et al , 2004; Sacks et al , 2012). Notably, however, pbNK are never measured routinely in any clinical condition apart from haematological disorders, such as leukaemia, because no clinically useful information is obtained.…”

Section: Nk Testingmentioning

confidence: 99%

First do no harm: uterine natural killer (NK) cells in assisted reproduction

2015

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Natural killer (NK) cells are a type of lymphocyte circulating in peripheral blood named because of their effector functions in killing target cells. Immune cells that share similar phenotypic characteristics but are poor killers populate the uterine lining at implantation and during early pregnancy when the placenta is established. The functions of these uterine NK (uNK) cells are essentially unknown but available data point to a role in regulating placentation in concert with other elements of the decidua and invading trophoblast cells. Despite the lack of scientific rationale and advice from clinical governing bodies, such as the Human Fertilisation and Embryology Authority, an increasing range of tests and therapies are still offered to women undergoing IVF or attending recurrent miscarriage clinics based on the myth that uterine NK cells need suppressing to prevent damage to the embryo. New treatments can be introduced at whim with subsequent demands for expensive trials to prove/disprove their efficacy. The evidence that targeting uNK or peripheral blood NK cells assists women with recurrent pregnancy failure is lacking. Healthcare professionals and patients should very carefully evaluate the practice of immunomodulation to enhance pregnancy outcome. A discussion on how to move towards stricter regulation of immunotherapy in non-hospital settings is now needed because it is clear that the potential risks and costs of these therapies outweigh any benefits.

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Detailed Analysis of Peripheral Blood Natural Killer Cells in Women with Repeated IVF Failure

Abstract: Peripheral blood NK cell activity is significantly higher in women with RIF than in fertile controls. Future trials of immune therapy in women undergoing IVF should target those with high NK activity.

Cited by 58 publications

References 34 publications

Intrauterine insemination of cultured peripheral blood mononuclear cells prior to embryo transfer improves clinical outcome for patients with repeated implantation failures

Intrauterine insemination of cultured peripheral blood mononuclear cells prior to embryo transfer improves clinical outcome for patients with repeated implantation failures

Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions

First do no harm: uterine natural killer (NK) cells in assisted reproduction

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