Results of the treatment in selected infertile patients with high density of endometrial NK cells CD56+ and CD16+ Second part

Authors: Z. Ulčová-Gallová 1,2;  M. Pešek 3;  M. Haschová 4;  P. Chaloupka 3;  P. Mukenšnabl 5;  J. Cibulka 1;  P. Lošan 1;  K. Bibková 1;  Z. Mičanová 1
Authors‘ workplace: Genetika-Plzeň, s. r. o., ředitel MUDr. P. Lošan 1;  Gynekologicko-porodnická klinika LF UK a FN, Plzeň, přednosta doc. MUDr . Z. Novotný, CSc. 2;  Mulačova nemocnice, gynekologicko-porodnické oddělení, Plzeň, přednosta MUDr. Z. Knaizl 3;  MN Privamed a. s., OKB, přednosta Ing. Z. Jeřábek 4;  Šiklův ústav patologie LF UK a FN, Plzeň, přednosta prof. MUDr. M. Michal 5
Published in: Ceska Gynekol 2018; 83(2): 115-118


This statements follows the first part of our publication entitled Screening of endometrial NK cells in selected infertile patients (First part – Methods and current results), where we dealt with methodology and endometrial findings of the natural killer cells CD16+ and CD56+. These cells are among the most important in preimplantaion, and in implantation period, in early pregnancy too, but can also negatively influence above mentioned processes.

We focused on the immunomodulatory treatment with intramuscular immunoglobulins in 21 infertile patients with a high density of endometrial NK cells CD16+ and CD56+.

Original work-prospective study.


From the originally investigated 57 women aged 25–41 (average 34) years with their history of 3–9 abortions, we target on a high selective subgroup of 21 infertile patients with pathological density of endometrial NK cells CD56+ and CD16+.

Twelve patients underwent immunomodulatory treatment with intramuscular immunoglobulin in time of positive HCG and went on the therapeutic scheme, nine infertile women continued with IVF-ET but did not achieve HCG positivity despite of initial treatment with immunoglobulins. Of the 12 treated patients, seven of them gave a birth to healthy babies, as to the next five pregnancies - one was extrauterine pregnancy, one genetically defective fetus, three pregnancies go on successfully.

Nine women from the IVF program did not get pregnat.


Immunomodulatory treatment with immunoglobulins also influences endometrial NK cells CD56+ and CD16+ associating with an overproduction of embryocytoxic cytokines. Treatment of our patients with the pathological endometrial density of NK cells must be solved strictly individually.

treatment, immunoglobulins, infertility, natural killer cells, endometrium


1. Bruton, OC., Apt, L., Gitlin, D., et al. Absence of serum gamma globulins. AMA Am J Dis Child, 1952, 84, p. 632–636.

2. Clark, DA., Coulam, CB., Stricker, RB. Is intravenous immunoglobulin [IVIG] efficacious in early pregnancy failure? A critical review and meta-analysis for patients who fail in vitro fertilization and embryo transfer. J Assist Reprod Genet, 2006, 23, p. 1–13.

3. Coulam, CB., Krzsa, LW., Bustillo, M. Intravenous immunoglobulins for in vitro fertilization failure. Human Reprod, 1994, 9, p. 2265–2269.

4. Coulam, CB., Goodman, C. Increased pregnancy rates after IVF/ET with intravenous immunoglobulin treatment in women with elevated circulating CD 56+ cells. Early Pregnancy, 2000, 4, 2, p. 90–98.

5. De Maria, A., Bozzano, F., Cantoni, C., et al. Revisiting human natural killer cell subset function revealed cytolytic CD56 CD16+ NK cells as rapid producers of abudant IFN-gamma on activation. Proc Natl Acad Sci USA, 2011, 108, p. 728–732.

6. Eshadri, S., Sunkara, SK. Natural killer cells in female infertility and recurrent miscarriage: a systemic review and meta-analysis. Human Reprod Update, 2014, 20, p. 429–438.

7. Fukui A., Funamizu, A., Fukuhara, R., et al. Expression of natural cytotoxicity receptors and cytokine production on endometrial natural killer cells in women with recurrent pregnancy loss or implantation failure, and the expression of natural cytotoxicity receptors on peripheral blood natural killer cells in pregnant women with a history of recurrent pregnancy loss. J Obstet Gynaecol Res, 2017, 43, p. 1678–1686.

8. Check, JH. The use of heparin for preventing miscarriage. Am J Reprod Immunol, 2012, 67, p. 326–333.

9. Christiansem, OB. Intravenous immunoglobulin in the prevention of recurrent spontaneous abortion. The European experience. Am J Reprod Immunol, 1998, 39, p. 77–81.

10. Králíčková, P., Krčmová, I., Krejsek, J. Imunoglobulinová substituční léčba u nemocných s primárními imunodeficity. Prakt lék, 2014, 94, s. 10–15.

11. Kuon, RJ., Vomstein, K., Weber, M., et al. The „killer cell story“ in recurrent miscarriage: Association between activated peripheral lymphocytes and uterine natural killer cells. J Reprod Immunol, 2017, 119, p. 9–14.

12. Kwak-Kim, J., Bao, S., Lee, SK., et al. Immunological models of pregnancy loss: inflammation, immune effectors, and stress. Am J Reprod Immunol, 2014, 72, p. 129–140.

13. Manaster, I., Mandelboim, O. The unique properties of uterine NK cells. Am J Reprod Immunol, 2010, 63, p. 434–444.

14. Milota, T., Šedivá, A. Nové možnosti a perspektivy imunoglobulinové terapie. Alergie, 2016, 4, s. 248–252.

15. Řezáčová, J., Malíčková, K., Mardesic, T., et al. Reprodukční medicína. Současné možnosti v asistované reprodukci. Ed. Aeskulap, 2018, v tisku.

16. Strašík, S. Praktické Lékárenství, 2014, 10, 6, s. 233–237.

17. Ulčová-Gallová, Z., Pešek, M., Chaloupka, P., et al. Screeningové vyšetření endometriálních NK buněk u vybraných infertilních pacientek. 1. část – metodika a průběžné výsledky. Čes Gynek, 2017, 82, s. 366–371.

18. Van den Heuvel, MJ., Hatta, K., Peralta, CG., et al. CD56+ cells are recruited to the uterus in two wawes: at ovulation and during the first 2 weeks after missed menses. Am J Reprod Immunol, 2008, 59, p. 90–98.

Paediatric gynaecology Gynaecology and obstetrics Reproduction medicine
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