Role of the immunoregulatory potential of seminal plasma in the IVF treatment of infertility
Objective. To assess the relationship of an IVF program to seminal plasma application on the levels of the cytokines IL-18 and TGF-β1 in the seminal plasma ((SP) of partners.Babayan A.A., Nikolaeva M.A., Smolnikova V.Yu., Stepanova E.O., Dontsova T.V., Vanko L.V., Ivanets T.Yu., Kalinina E.A., Krechetova L.V., Sukhikh G.T.
Subjects and methods. The investigation included married couples (n = 71) who were treated for infertility by in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) via SP application on the day of transvaginal puncture. According to the treatment result, the patients were divided into 2 groups: 1) 32 patients with incipient pregnancy; 2) 39 patients with negative treatment results. The levels of the cytokines IL-18 and TGF-β1 in the sexual partners’ seminal plasma were estimated by flow cytofluorometry and fluorescent microspheres using the special kits Human TGF-β1 and IL-18 FlowCytomix Simplex Kits (Bender MedSystems, Vienna, Austria). Statistical data processing was carried out using MedCalc software version 12.3.0.
Results. In the patients with incipient pregnancy, whose partners had significantly lower seminal plasma IL-18 concentrations and total ejaculate IL-18 and TGF-β1 levels than in those with an unsuccessful treatment outcome. The TGF-β1/IL-18 ratio was significantly higher in the sexual partners of patients with a successful treatment outcome.
Conclusion. The seminal plasma level of the cytokines IL-18 and TGF-β1 is associated with reproductive success when implementing an IVF program through seminal plasma application.
Keywords
in vitro fertilization
seminal plasma
cytokines
Supplementary Materials
- Table. Characteristics of patients in the study groups
- Fig . 1. Comparative characteristics of the concentrations of TGF-β1 (A) and IL-18 (B), the TGF-β1 (B) and IL-18 (D) contents in the entire ejaculate volume and the concentration ratio of TGF-β1 / IL-18 (D) in JV partners of patients of the main group with successful and unsuccessful outcomes of the IVF / ICSI program
- Fig . 2. ROC curves of IL-18 content in ejaculate, concentration of IL-18 in SP, TGF-β1 / IL-18 ratio, TGF-β1 content in ejaculate for predicting the success of IVF / ICSI program
References
1. Корсак В.С., Смирнова А.А., Шурыгина О.В. ВРТ в России. Отчет за 2013 год. Регистр ВРТ. СПб.: Российская Ассоциация Репродукции Человека; 2015: 26-9. [Korsak V.S., Smirnova A.A., Shurygina O.V. ART in Russia. The report for 2013. Register of ART. St. Petersburg: Russian Association of Human Reproduction; 2015: 26-9. (in Russian)]
2. Kupka M.S., Ferraretti A.P., de Mouzon J., Erb K., D’Hooghe T., Castilla J.A. et al.; European IVF-Monitoring Consortium, for the European Society of Human Reproduction and Embryology. Assisted reproductive technology in Europe 2010: results generated from European registers by ESHRE. Hum. Reprod. 2014; 29(10): 2099-113.
3. Edwards R.G. Human implantation: the last barrier in assisted reproduction technologies? Reprod. Biomed. Online. 2006; 13(6): 887-904.
4. Boomsma C.M., Kavelaars A., Eijkemans M.J., Lentjes E.G., Fauser B.C., Heijnen C.J., Macklon N.S. Endometrial secretion analysis identifies a cytokine profile predictive of pregnancy in IVF. Hum. Reprod. 2009; 24(6): 1427-35.
5. Robertson S.A., Sharkey D.J. Seminal fluid and fertility in women. Fertil. Steril. 2016; 106(3): 511-9.
6. Robertson S.A., Prins J.R., Sharkey D.J., Moldenhauer L.M. Seminal fluid and the generation of regulatory T cells for embryo implantation. Am. J. Reprod. Immunol. 2013; 69(4): 315-30.
7. Crawford G., Ray A., Gudi A., Shah A., Homburg R. The role of seminal plasma for improved outcomes during in vitro fertilization treatment: review of the literature and meta-analysis. Hum. Reprod. Update. 2015; 21(2): 275-84.
8. von Wolff M., Rösner S., Germeyer A., Jauckus J., Griesinger G., Strowitzki T. Intrauterine instillation of diluted seminal plasma at oocyte pick-up does not increase the IVF pregnancy rate: a double-blind, placebo controlled, randomized study. Hum. Reprod. 2013; 28(12): 3247-52.
9. Bellinge B.S., Copeland C.M., Thomas T.D., Mazzucchelli R.E., O’Neil G., Cohen M.J. The influence of patient insemination on the implantation rate in an in vitro fertilization and embryo transfer program. Fertil. Steril. 1986; 46(2): 252-6.
10. Chicea R., Ispasoiu F., Focsa M. Seminal plasma insemination during ovum-pickup-a method to increase pregnancy rate in IVF/ICSI procedure Apilot randomized trial. J. Assist. Reprod. Genet. 2013; 30(4): 569-74.
11. Coulam C.B., Stern J.J. Effect of seminal plasma on implantation rates. Early Pregnancy. 1995; 1(1): 33-6.
12. Politch J.A., Tucker L., Bowman F.P., Anderson D.J. Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men. Hum. Reprod. 2007; 22(11): 2928-35.
13. Schjenken J.E., Robertson S.A. Seminal fluid signaling in the female reproductive tract: implications for reproductive success and offspring health. Adv. Exp. Med. Biol. 2015; 868: 127-58.
14. Sharkey D.J., Tremellen K.P., Briggs N.E., Dekker G.A., Robertson S.A. Seminal plasma transforming growth factor-β, activin A and follistatin fluctuate within men over time. Hum. Reprod. 2016; 31(10): 2183-91.
15. Sharkey D.J., Macpherson A.M., Tremellen K.P., Mottershead D.G., Gilchrist R.B., Robertson S.A. TGF-β mediates pro-inflammatory seminal fluid signaling in human cervical epithelial cells. J. Immunol. 2012; 189(2): 1024-35.
16. Keogan S., Siegert K., Wigdahl B., Krebs F.C. Variability in human semen content and its potential effects in the female reproductive tract. J. Reprod. Biol. Health. 2016; 4(1): 1-8.
17. ?outoulaki A., Langley M., Sloan A.J., Aeschlimann D., Wei X.Q. TNF-alphaand TGF-beta1 influence IL-18-induced IFN-gamma production through regulation of IL-18 receptor and T-bet expression. Cytokine. 2010; 49(2):177-84.
18. Massagué J. How cells read TGF-beta signals. Nat. Rev. Mol. Cell. Biol. 2000; 1(3): 169-78.
19. Matalliotakis I.M., Cakmak H., Fragouli Y., Kourtis A., Arici A., Huszar G. Increased IL-18 levels in seminal plasma of infertile men with genital tract infections. Am. J. Reprod. Immunol. 2006; 55(6): 428-33.
20. Qian L., Zhou Y., Du C., Wen J., Teng S., Teng Z. IL-18 levels in the semen of male infertility: semen analysis. Int. J. Biol. Macromol. 2014; 64: 190-2.
21. Lédée-Bataille N., Olivennes F., Kadoch J., Dubanchet S., Frydman N., Chaouat G., Frydman R. Detectable levels of interleukin-18 in uterine luminal secretions at oocyte retrieval predict failure of the embryo transfer. Hum. Reprod. 2004; 19(9): 968-73.
22. Anderson D.J., Politch J.A. Role of seminal plasma in human female reproductive failure: immunomodulation, inflammation, and infections. Adv. Exp. Med. Biol. 2015; 868: 159-69.
23. Tremellen K.P., Valbuena D., Landeras J., Ballesteros A., Martinez J., Mendoza S. et al. The effect of intercourse on pregnancy rates during assisted human reproduction. Hum. Reprod. 2000; 15(12): 2653-8.
24. Cicinelli E., de Ziegler D. Transvaginal progesterone: evidence for a new functional ‘portal system’ flowing from the vagina to the uterus. Hum. Reprod. Update. 1999; 5(4): 365-72.
Received 09.06.2017
Accepted 23.06.2017
About the Authors
Babayan Alina Anatolievna, Ph.D., doctor of the department of auxiliary technologies in the treatment of infertility named after prof. B.V. Leonov, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954382501. E-mail: alinababayan@yandex.ruNikolaeva Marina Arkadevna, Doctor of Biological Sciences, Leading Researcher of the Laboratory of Clinical Immunology, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381183. E-mail: nikolaeva_ma@mail.ru
Smolnikova Veronika Yuryevna, MD, leading research assistant of the Department of Auxiliary Technologies in the treatment of infertility named after prof. B.V. Leonov, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954382501. E-mail: v_smolnikova@oparina4.ru
Stepanova Elena Olegovna, Junior Researcher, Laboratory of Clinical Immunology, Research Center of Obstetrics, Gynecology, and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79629544421. E-mail: elena2404.07@mail.ru
Dontsova Tatyana Vladimirovna, postgraduate student of the Department of Auxiliary Technologies in Infertility Treatment, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954382501. E-mail: dr.dontsova@gmail.com
Kalinina Elena Anatolievna, MD, associate professor, head of the department of auxiliary technologies in the treatment of infertility named after prof. B.V. Leonov,
Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381342. E-mail: e_kalinina@oparina4.ru
Vanko Lyudmila Viktorovna, MD, Professor, Leading Researcher, Laboratory of Clinical Immunology, Research Center of Obstetrics, Gynecology, and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381183. E-mail: LVanko@oparina4.ru
Ivanets Tatyana Yurievna, Candidate of Medical Science, Head of the department, clinical diagnostic laboratory, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381183. E-mail: t_ivanets@oparina4.ru
Krechetova Lyubov Valentinovna, Ph.D., Head of the Laboratory of Clinical Immunology, Research Center of Obstetrics, Gynecology, and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381183. E-mail: l_krechetova@oparina4.ru
Sukhikh Gennady Tikhonovich, Academician of the Russian Academy of Sciences, Doctor of Medicine, Professor, Director of the Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: g_sukhikh@oparina4.ru
For citations: Babayan A.A., Nikolaeva M.A., Smolnikova V.Yu., Stepanova E.O.,
Dontsova T.V., Vanko L.V., Ivanets T.Yu., Kalinina E.A., Krechetova L.V., Sukhikh G.T. Role
of the immunoregulatory potential of seminal plasma in the IVF treatment of infertility.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (3): 76-82. (in Russian)
https://dx.doi.org/10.18565/aig.2018.3.76-82
Similar Articles
