Does sexual intercourse during IVF/ICSI cycle affect endometrial thickness in the presence of immunohormonal markers of stress in the seminal plasma?


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Men’s stress may alter the concentration of immunological and hormonal factors in seminal plasma, which, on entering the female reproductive tract during sexual intercourse, may affect endometrial development. Objective: To investigate the relationship between endometrial thickness in women having intercourse during the proliferative phase of the IVF/ICSI cycle and the content of immunological and endocrine stress markers in the partner's seminal plasma. Materials and methods: This prospective study included 71 couples with tubal infertility factor having unprotected intercourse during the proliferative phase of IVF/ICSI cycle, supplemented with intravaginal injection of seminal plasma on the day of transvaginal ovarian puncture. The retrospective pilot study included couples with IVF/ICSI success (group 1, n=7) and IVF/ICSI failure (group 2, n=9). They were comparable by clinical, demographic and laboratory parameters, but differed in the content of immunohormonal stress markers in the partner's seminal plasma. The groups were formed based on the content of cytokines IL-18 and IL-1P, steroid hormones, their precursors and seminal plasma metabolites. Endometrial thickness was measured by transvaginal ultrasound on the day of ovulation trigger. The cytokine content in seminal plasma was assessed by flow cytofluorometry and fluorescent microspheres using FlowCytomix technology. The concentration and total amount of steroids in seminal plasma were determined using a combination of high-performance liquid chromatography and tandem mass spectrometry. Results: Prospective and retrospective studies revealed a reduced endometrial thickness in the group of patients with an increased content of immunoendocrine stress markers in seminal plasma. There was a negative correlation between endometrial thickness and concentration and/or total amount of 17-a-hydroxypregnenolone, testosterone, progesterone, and cytokines IL-18, IL-1P in seminal plasma. The cortisol/DHEA ratio was positively associated with endometrial thickness. Conclusion: The study's finding suggested that stress-related seminal immunological and hormonal factors in the seminal plasma entering the female reproductive tract during sexual intercourse in the proliferative phase of the IVF/ICSI cycle may negatively impact endometrial development. However, further research is necessary to establish a causal link between the composition of seminal plasma and the endometrial status.

Full Text

Restricted Access

About the authors

Marina A. Nikolaeva

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: mnikolaeva@oparina4.ru
Dr. Bio. Sci., Leading Researcher at the Laboratory of Clinical Imunology

Alina A. Babayan

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: a_babayan@oparina4.ru
PhD, Researcher at the IVF Department named after Prof. BV. Leonov

Alla S. Arefieva

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: a_arefyeva@oparina4.ru
Researcher at the Laboratory of Clinical Imunology

Vitaliy V. Chagovets

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: v_chagovets@oparina4.ru
PhD, Head of the laboratory of Metabolomics and Bioinformatics of the Department of Systems Biology in Reproductive Medicine of the Institute of Translational Medicine

Natalia L. Starodubtseva

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: aurum19@mail.ru
PhD, Head of the laboratory of Clinical Proteomics of the Department of Systems Biology in Reproductive Medicine of the Institute of Translational Medicine

Vladimir E. Frankevich

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: v_frankevich@oparina4.ru
Dr. Sci. (Physics and Mathematics), Deputy Director for Research, Head of the Department of Systems Biology in Reproduction

Elena A. Kalinina

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: e_kalinina@oparina4.ru
Dr. Med. Sci., Professor, Head of the IVF department named after Prof. BV. Leonov

Lyubov V. Krechetova

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: l_krechetova@oparina4.ru
Dr. Med. Sci., Head of the Laboratory of Clinical Imunology

Gennady T. Sukhikh

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: g_sukhikh@oparina4.ru
Academician of the RAS, Dr. Med. Sci., Professor, Director

References

  1. Wyns C., De Geyter C., Calhaz-Jorge C., Kupka M.S., Motrenko T., Smeenk J. et al.; European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2017: results generated from European registries by ESHRE. Hum. Reprod. Open. 2021; 2021(3): hoab026. https://dx.doi.org/10.1093/hropen/hoab026.
  2. Kayisli U.A., Guzeloglu-Kayisli O., Arici A. Endocrine-immune interactions in human endometrium. Ann. N. Y. Acad. Sci. 2004; 1034: 50-63. https://dx.doi.org/10.1196/annals.1335.005.
  3. Robertson S.A., Sharkey D.J. Seminal fluid and fertility in women. Fertil. Steril. 2016; 106(3): 511-9. https://dx.doi.org/10.1016/j.fertnstert.2016.07.1101.
  4. Chen J.C., Johnson B.A., Erikson D.W., Piltonen T.T., Barragan F., Chu S. et al. Seminal plasma induces global transcriptomic changes associated with cell migration, proliferation and viability in endometrial epithelial cells and stromal fibroblasts. Hum. Reprod. 2014; 29(6): 1255-70. https://dx.doi.org/10.1093/humrep/deu047.
  5. Rodriguez-Caro H., Dragovic R., Shen M., Dombi E., Mounce G., Field K. et al. In vitro decidualisation of human endometrial stromal cells is enhanced by seminal fluid extracellular vesicles. J. Extracell. Vesicles. 2019; 8(1): 1565262. https://dx.doi.org/10.1080/20013078.2019.1565262.
  6. George A.F., Jang K.S., Nyegaard M., Neidleman J., Spitzer T.L., Xie G. et al. Seminal plasma promotes decidualization of endometrial stromal fibroblasts in vitro from women with and without inflammatory disorders in a manner dependent on interleukin-11 signaling. Hum. Reprod. 2020; 35(3): 617-40. https://dx.doi.org/10.1093/humrep/deaa015.
  7. Moharrami T., Ai J., Ebrahimi-Barough S., Nouri M., Ziadi M., Pashaiefar H., Yazarlou F. et al. Influence of follicular fluid and seminal plasma on the expression of endometrial receptivity genes in endometrial cells. Cell J. 2021; 22(4): 457-66. https://dx.doi.org/10.22074/cellj.2021.6851.
  8. 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. https://dx.doi.org/10.1016/s0015-0282(16)49521-x.
  9. Chicea R., Ispasoiu F., Focsa M. Seminal plasma insemination during ovum-pickup-a method to increase pregnancy rate in IVF/ICSI procedure. A pilot randomized trial. J. Assist. Reprod. Genet. 2013; 30(4): 569-74. https://dx.doi.org/10.1007/s10815-013-9955-7.
  10. Fishel S., Webster J., Jackson P., Faratian B. Evaluation of high vaginal insemination at oocyte recovery in patients undergoing in vitro fertilization. Fertil. Steril. 1989; 51(1): 135-8. https://dx.doi.org/10.1016/s0015-0282(16)60442-9.
  11. Jafarabadi M., Sasani A., Ramezanzadeh F., Zandieh Z., Shariat M., Haghollahi F. Intracervical application of seminal plasma at the time of oocyte pickup during in vitro fertilization. Acta Medica Mediterranea. 2016; 32: 2085-90.
  12. Coulam C.B., Stern J.J. Effect of seminal plasma on implantation rates. Early Pregnancy. 1995; 1(1): 33-6.
  13. von Wolff M., Rosner S., Thone C., Pinheiro R.M., Jauckus J., Bruckner T. et al. Intravaginal and intracervical application of seminal plasma in in vitro fertilization or intracytoplasmic sperm injection treatment cycles - a doubleblind, placebo-controlled, randomized pilot study. Fertil. Steril. 2009; 91(1): 167-72. https://dx.doi.org/10.1016/j.fertnstert.2007.11.036.
  14. Friedler S., Ben-Ami I., Gidoni Y., Strassburger D., Kasterstein E., Maslansky B. et al. Effect of seminal plasma application to the vaginal vault in in vitro fertilization or intracytoplasmic sperm injection treatment cycles-a doubleblind, placebo-controlled, randomized study. J. Assist. Reprod. Genet. 2013; 30(7): 907-11. https://dx.doi.org/10.1007/s10815-013-0033-y.
  15. Marconi G., Auge L., Oses R., Quintana R., Raffo F., Young E. Does sexual intercourse improve pregnancy rates in gamete intrafallopian transfer? Fertil. Steril. 1989; 51(2): 357-9. https://dx.doi.org/10.1016/s0015-0282(16)60507-1.
  16. 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. https://dx.doi.org/10.1093/humrep/15.12.2653.
  17. Aflatoonian A., Ghandi S., Tabibnejad N. The effect of intercourse around embryo transfer on pregnancy rate in assisted reproductive technology cycles. Int. J. Fertil. Steril. 2009; 2(4): 169-72.
  18. Ata B., Abou-Setta A.M., Seyhan A., Buckett W. Application of seminal plasma to female genital tract prior to embryo transfer in assisted reproductive technology cycles (IVF, ICSI and frozen embryo transfer). Cochrane Database Syst. Rev. 2018; (2): CD011809. https://dx.doi.org/10.1002/14651858.CD011809.pub2.
  19. Ilacqua A., Izzo G., Emerenziani G.P., Baldari C., Aversa A. Lifestyle and fertility: the influence of stress and quality of life on male fertility. Reprod. Biol. Endocrinol. 2018; 16(1): 115. https://dx.doi.org/10.1186/s12958-018-0436-9.
  20. Zaidouni A., Fatima O., Amal B., Si ham A., Houyam H., Jalal K. et al. Predictors of infertility stress among couples diagnosed in a public center for assisted reproductive technology. J. Hum. Reprod. Sci. 2018; 11(4): 376-83. https://dx.doi.org/10.4103/jhrs.JHRS_93_18.
  21. Pedro J., Vassard D., Malling G.M.H., Hougaard C.0., Schmidt L., Martins M.V. Infertility-related stress and the risk of antidepressants prescription in women: a 10-year register study. Hum. Reprod. 2019; 34(8): 1505-13. https://dx.doi.org/10.1093/humrep/dez110.
  22. Sejbaek C.S., Pinborg A., Hageman I., Sorensen A.M., Koert E., Forman J.L. et al. Depression among men in ART treatment: a register-based national cohort study. Hum. Reprod. Open. 2020; 2020(3): hoaa019. https://dx.doi.org/10.1093/hropen/hoaa019.
  23. Roozitalab S., Rahimzadeh M., Mirmajidi S.R., Ataee M., Esmaelzadeh Saeieh S. The relationship between infertility, stress, and quality of life with posttraumatic stress disorder in infertile women. J. Reprod. Infertil. 2021; 22(4): 282-8. https://dx.doi.org/10.18502/jri.v22i4.7654.
  24. Nguyen A.D., Conley A.J. Adrenal androgens in humans and nonhuman primates:production, zonation and regulation. Endocr. Dev. 2008; 13: 33-54. https://dx.doi.org/10.1159/000134765.
  25. Sze Y., Brunton P.J. Sex, stress and steroids. Eur. J. Neurosci. 2020; 52(1): 2487-2515. https://dx.doi.org/10.1111/ejn.14615.
  26. Chichinadze K., Chichinadze N. Stress-induced increase of testosterone: contributions of social status and sympathetic reactivity. Physiol. Behav. 2008; 94(4): 595-603. https://dx.doi.org/10.1016/j.physbeh.2008.03.020.
  27. Elenkov I.J., Wilder R.L., Chrousos G.P., Vizi E.S. The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol. Rev. 2000; 52(4): 595-638.
  28. Sekiyama A., Ueda H., Kashiwamura S., Nishida K., Kawai K., Teshima-Kondo S. et al. IL-18; a cytokine translates a stress into medical science. J. Med. Invest. 2005; 52(Suppl.): 236-9. https://dx.doi.org/10.2152/jmi.52.236.
  29. Goshen I., Yirmiya R. Interleukin-1 (IL-1): a central regulator of stress responses. Front. Neuroendocrinol. 2009; 30(1): 30-45. https://dx.doi.org/10.1016/j.yfrne.2008.10.001.
  30. Nikolaeva M.A., Babayan A.A., Stepanova E.O., Smolnikova V.Y., Kalinina E.A., Fernández N., Krechetova L.V., Vanko L.V., Sukhikh G.T. The relationship of seminal transforming growth factor-β1 and interleukin-18 with reproductive success in women exposed to seminal plasma during IVF/ICSI treatment. J. Reprod. Immunol. 2016; 117: 45-51. https://dx.doi.org/10.1016/ j.jri.2016.03.006
  31. Nikolaeva M., Arefieva A., Babayan A., Chagovets V., Kitsilovskaya N., Starodubtseva N., Frankevich V., Kalinina E., Krechetova L., Sukhikh G. Markers of stress in seminal plasma at IVF/ICSI failure: a preliminary study. Reprod. Sci. 2021; 28(1): 144-58. https://dx.doi.org/10.1007/s43032-020-00253-z.
  32. Pantos K., Grigoriadis S., Maziotis E., Pistola K., Xystra P., Pantou A. et al. The role of interleukins in recurrent implantation failure: a comprehensive review of the literature. Int. J. Mol. Sci. 2022; 23(4): 2198. https://dx.doi.org/10.3390/ijms23042198.
  33. Mackens S., Santos-Ribeiro S., Racca A., Daneels D., Koch A., Essahib W. et al. The proliferative phase endometrium in IVF/ICSI: an in-cycle molecular analysis predictive of the outcome following fresh embryo transfer. Hum. Reprod. 2020; 35(1): 130-44. https://dx.doi.org/10.1093/humrep/dez218.
  34. Багдасарян Л.А., Корнеева И.Е. Толщина эндометрия: предиктор эффективности программ ЭКО/ICSI (обзор литературы). Гинекология. 2018; 20(1): 113-6.
  35. Краснопольская К.В., Оразов М.Р., Ершова И.Ю., Федоров А.А. Тонкий эндометрий и бесплодие. М.: ГЭОТАР-Медиа; 2022. 208с.
  36. Gardner D.K., Schoolcraft W.B. Culture and transfer of human blastocysts. Curr. Opin. Obstet. Gynecol. 1999; 11(3): 307-11. https://dx.doi.org/10.1097/00001703-199906000-00013.
  37. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: WHO; 2010.
  38. Hacker-Klom U.B., Gohde W., Nieschlag E., Behre H.M. DNA flow cytometry of human semen. Hum. Reprod. 1999; 14(10): 2506-12. https://dx.doi.org/10.1093/humrep/14.10.2506.
  39. Antoniassi M.P., Intasqui P., Camargo M., Zylbersztejn D.S., Carvalho V.M., Cardozo K.H. et al. Analysis of the functional aspects and seminal plasma proteomic profile of sperm from smokers. BJU Int. 2016; 118(5): 814-22. https://dx.doi.org/10.1111/bju.13539.
  40. Leisegang K., Henkel R., Agarwal A. Obesity and metabolic syndrome associated with systemic inflammation and the impact on the male reproductive system. Am. J. Reprod. Immunol. 2019; 82(5): e13178. https://dx.doi.org/10.1111/aji.13178.
  41. Petracco R.G., Kong A., Grechukhina O., Krikun G., Taylor H.S. Global gene expression profiling of proliferative phase endometrium reveals distinct functional subdivisions. Reprod. Sci. 2012; 19(10): 1138-45. https://dx.doi.org/10.1177/1933719112443877.
  42. Цховребова Л.Т., Шевцова М.А., Аксененко А.А., Дуринян Э.Р., Гависова А.А. Андрогенные рецепторы и их уникальность. Акушерство и гинеко логия. 2020; 12: 62-6. https://dx.doi.org/10.18565/aig.2020.12.62-66.
  43. Jiang N.X., Li X.L. The disorders of endometrial receptivity in PCOS and its mechanisms. Reprod. Sci. 2022; 29(9): 2465-76. https://dx.doi.org/10.1007/s43032-021-00629-9.
  44. Simitsidellis I., Saunders P.T.K., Gibson D.A. Androgens and endometrium: New insights and new targets. Mol. Cell. Endocrinol. 2018; 465: 48-60. https://dx.doi.org/10.1016/j.mce.2017.09.022.
  45. Gibson D.A., Simitsidellis I., Collins F., Saunders P.T. Evidence of androgen action in endometrial and ovarian cancers. Endocr. Relat. Cancer. 2014; 21(4): T203-18.
  46. Perrone A.M., Cerpolini S., Maria Salfi N.C., Ceccarelli C., De Giorgi L.B., Formelli G. et al. Effect of long-term testosterone administration on the endometrium of female-to-male (FtM) transsexuals. J. Sex. Med. 2009; 6(11): 3193-200. https://dx.doi.org/10.1111/j.1743-6109.2009.01380.x.
  47. Palomba S., Piltonen T.T., Giudice L.C. Endometrial function in women with polycystic ovary syndrome: a comprehensive review. Hum. Reprod. Update. 2021; 27(3): 584-618. https://dx.doi.org/10.1093/humupd/dmaa051.
  48. Semeniuk L.M., Likhachov V.K., Yuzvenko T.Y., Dobrovolska L.M., Makarov O.G. Risk markers of reproductive loss in women with hyperandrogenism. Wiad. Lek. 2018; 71(8): 1550-3.
  49. 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. https://dx.doi.org/10.1093/humupd/5.4.365.
  50. Beral V., Bull D., Reeves G.; Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the million women study. Lancet. 2005; 365(9470): 1543-51. https://dx.doi.org/10.1016/S0140-6736(05)66455-0.
  51. Halasz M., Szekeres-Bartho J. The role of progesterone in implantation and trophoblast invasion. J. Reprod. Immunol. 2013; 97(1): 43-50. https://dx.doi.org/10.1016/j.jri.2012.10.011.
  52. Brenner R.M., Slay den O.D. Progesterone receptor antagonists and the endometrial antiproliferative effect. Semin. Reprod. Med. 2005; 23(1): 74-81. https://dx.doi.org/10.1055/s-2005-864035.
  53. Critchley H.O., Saunders P.T. Hormone receptor dynamics in a receptive human endometrium. Reprod. Sci. 2009; 16(2): 191-9. https://dx.doi.org/10.1177/1933719108331121.
  54. Babayev S.N., Park C.W., Keller P.W., Carr B.R., Word R.A., Bukulmez O. Androgens upregulate endometrial epithelial progesterone receptor expression: potential implications for endometriosis. Reprod. Sci. 2017; 24(10): 1454-61. https://dx.doi.org/10.1177/1933719117691145.
  55. Nikolaeva M., Babayan A., Stepanova E., Arefieva A., Dontsova T., Smolnikova V., Kalinina E., Krechetova L., Pavlovich S., Sukhikh G. The link between seminal cytokine interleukin 18, female circulating regulatory T. cells, and IVF/ICSI success. Reprod. Sci. 2019; 26(8): 1034-44. https://dx.doi.org/10.1177/1933719118804404.
  56. Robertson S.A., Mau V.J., Tremellen K.P., Seamark R.F. Role of high molecular weight seminal vesicle proteins in eliciting the uterine inflammatory response to semen in mice. J. Reprod. Fertil. 1996; 107(2): 265-77. https://dx.doi.org/10.1530/jrf.0.1070265.
  57. Cermik D., Selam B., Taylor H.S. Regulation of HOXA-10 expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 2003; 88(1): 238-43. https://dx.doi.org/10.1210/jc.2002-021072.
  58. Frolova A.I., O’Neill K., Moley K.H. Dehydroepiandrosterone inhibits glucose flux through the pentose phosphate pathway in human and mouse endometrial stromal cells, preventing decidualization and implantation. Mol. Endocrinol. 2011; 25(8): 1444-55. https://dx.doi.org/10.1210/me.2011-0026.
  59. Quant H.S., Zap antis A., Nihsen M., Bevilacqua K., Jindal S., Pal L. Reproductive implications of psychological distress for couples undergoing IVF. J. Assist. Reprod. Genet. 2013; 30(11): 1451-8. https://dx.doi.org/10.1007/s10815-013-0098-7.
  60. Ryan M., Ryznar R. The molecular basis of resilience: a narrative review. Front. Psychiatry. 2022; 13: 856998. https://dx.doi.org/10.3389/fpsyt.2022.856998.

Supplementary files

Supplementary Files
Action
1. JATS XML

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies