Comparative analysis of cumulus cell transcripts when using different ovulation triggers in IVF/ICSI programs
Objective. To investigate the transcriptional profile (transcripts) of cumulus cells when using a gonadotropin-releasing hormone (GnRH) agonist or human chorionic gonadotropin (hCG) as an ovulation trigger.Ipen S.M., Burmenskaya O.V., Pavlovich S.V., Levkov L.A., Syrkasheva A.G., Kodyleva T.A., Abubakirov A.N., Mishieva N.G., Trofimov D.Yu.
Subjects and methods. The investigation analyzed 179 cumulus cell samples from 35 patients who had undergone an IVF/ICSI program. The patients were divided into 2 groups according to the injected ovulation trigger: 1) hCG at a dose of 10,000 IU (n = 17); 2) a GnRH agonist 0.2 mg (n = 18). The mRNA expression of 13 genes in the cumulus cells was investigated by a real-time RT-PCR assay.
Results. Differences were found in the expression of CALM2 (0.08 vs 0.05; P < 0.0001), TRPM7 (0.82 vs 0.70; P = 0.007), ALCAM (0.26 vs 0.37; P = 0.0008), and PFKP (3.46 vs 4.70; P = 0.0005). All changes were less than 2 times. The mRNA expression of the TP53I3 gene was higher in the cumulus cells of oocytes that later formed blastocyst (0.3 vs 0.23; P = 0.0304).
Keywords
cumulus cells
gene expression
gonadotropin-releasing hormone (GnRH) agonist as a trigger
in vitro fertilization
blastocyst
References
1. Homburg R. The physiology of ovulation. In: Homburg R. Ovulation induction and controlled ovarian stimulation. A practical guide. Springer;2014: 7-23.
2. Humaidan P., Papanikolaou E.G., Tarlatzis B.C. Reply: GnRHa to trigger final oocyte maturation: a time to reconsider. Hum. Reprod. 2010; 25(3): 807-8.
3. Acevedo B., Gomez-Palomares J.L., Ricciarelli E., Hernández E.R. Triggering ovulation with gonadotropin-releasing hormone agonists does not compromise embryo implantation rates. Fertil. Steril. 2006; 86(6): 1682-7.
4. Casper R.F. Reducing the risk of OHSS by GnRH agonist triggering. J. Clin. Endocrinol. Metab. 2015; 100(12): 4396-8.
5. Ding L.J., Wang B., Shen X.Y., Yan G.J., Zhang N.Y., Hu Y.L. et al. Withdrawal of GnRH agonist decreases oestradiol and VEGF concentrations in high responders. Reprod. Biomed. Online. 2013; 27(2): 131-9.
6. Andersen C., Humaidan P., Ejdrup H., Bungum L., Grondahl M., Westergaard L. Hormonal characteristics of follicular flluid from women receiving either GnRH agonist or hCG for ovulation. Hum. Reprod. 2006; 21(8): 2126-30.
7. Humaidan P., Westergaard L., Mikkelsen L., Fukuda A., Yding Andersen C. Levels of the epidermal growth factor-like peptide amphiregulin in follicular fluid reflect the mode of triggering ovulation: a comparison between gonadotrophin-releasing hormone agonist and urinary human chorionic gonadotrophin. Fertil. Steril. 2011; 95(6): 2034-8.
8. Cerrillo M., Pacheco A., Rodriguez S., Delgado F., Pellicer A., García-Velasco J. Effect of GnRH agonist and hCG treatment on VEGF, angiopoietin-2, and VE-cadherin: trying to explain the link to ovarian hyperstimulation syndrome. Fertil. Steril. 2011; 95(8): 2517-9.
9. Haas J., Ophir L., Barzilay E., Yerushalmi G.M., Yung Y., Kedem A. et al. GnRH agonist vs. hCG for triggering of ovulation – differential effects on gene expression in human granulosa cells. PLoS One. 2014; 9(3): e90359.
10. Gebhardt K.M., Feil D.K., Dunning K.R., Lane M., Russell D.L. Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer. Fertil. Steril. 2011; 96(1): 47-52. e2.
11. Ekart J., Mcnatty K., Hutton J., Pitman J. Ranking and selection of MII oocytes in human ICSI cycles using gene expression levels from associated cumulus cells. Hum. Reprod. 2013; 28(11): 2930-42.
12. Martazanova B.A., Mishieva N.G., Abubakirov A.N. Ovulation trigger replacement as a method for preventing ovarian hyperstimulation syndrome. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2014; (5): 15-8. (in Russian)
13. Martazanova B.A., Mishieva N.G., Vedikhina I.A., Aksenenko A.A., Eapen S.M., Ibragimova M.Kh., Ivanets T.Yu., Abubakirov A.N. The hormonal profile in women at high risk for ovarian hyperstimulation syndrome after replacement of an ovulation trigger. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2015; 6: 84-90. (in Russian)
14. Engmann L., DiLuigi A., Schmidt D., Nulsen J., Maier D., Benadiva C. The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study. Fertil. Steril. 2008; 89(1): 84-91.
15. Gurbuz A.S., Gode F., Uzman M.S., Ince B., Kaya M., Ozcimen N. et al. GnRH agonist triggering affects the kinetics of embryo development: a comparative study. J. Ovarian Res. 2016; 9: 22.
16. Anderson R.A., Sciorio R., Kinnell H., Bayne R.A., Thong K.J., de Sousa P.A., Pickering S. Cumulus gene expression as a predictor of human oocyte fertilisation, embryo development and competence to establish a pregnancy. Reproduction. 2009; 138(4): 629-37.
17. Fragouli E., Wells D., Iager A.E., Kayisli U.A., Patrizio P. Alteration of gene expression in human cumulus cells as a potential indicator of oocyte aneuploidy. Hum. Reprod. 2012; 27(8): 2559-68.
18. Assou S., Haouzi D., De Vos J., Hamamah S. Human cumulus cells as biomarkers for embryo and pregnancy outcomes. Mol. Hum. Reprod. 2010; 16(8): 531-8.
19. Wathlet S., Adriaenssens T., Segers I., Verheyen G., Van de Velde H., Coucke W. et al. Cumulus cell gene expression predicts better cleavage-stage embryo or blastocyst development and pregnancy for ICSI patients. Hum. Reprod. 2011; 26(5): 1035-51.
20. Fujiwara H., Tatsumi K., Kosaka K., Sato Y., Higuchi T., Yoshioka S. et al. Human blastocysts and endometrial epithelial cells express activated leukocyte cell adhesion molecule (ALCAM/CD166). J. Clin. Endocrinol. Metab. 2003; 88(7): 3437-43.
21. Borgbo T., Povlsen B.B., Andersen C.Y., Borup R., Humaidan P., Grøndahl M.L. Comparison of gene expression profiles in granulosa and cumulus cells after ovulation induction with either human chorionic gonadotropin or a gonadotropin-releasing hormone agonist trigger. Fertil. Steril. 2013; 100(4): 994-1001.
22. Yerushalmi G.M., Salmon-Divon M., Yung Y., Maman E., Kedem A., Ophir L. et al. Characterization of the human cumulus cell transcriptome during final follicular maturation and ovulation. Mol. Hum. Reprod. 2014; 20(8): 719-35.
23. de los Santos M.J., García-Láez V., Beltrán-Torregrosa D., Horcajadas J.A., Martínez-Conejero J.A., Esteban F.J. et al. Hormonal and molecular characterization of follicular fluid, cumulus cells and oocytes from pre-ovulatory follicles in stimulated and unstimulated cycles. Hum. Reprod. 2012; 27(6): 1596-605.
Received 16.12.2017
Accepted 23.12.2017
About the Authors
Eapen S.М., graduate student, I.M. Sechenov First Moscow State Medical University.Address: 119991, Russia, Moscow, Bolshaya Pirogovskaya str. 2-4. Тel.: 8 (926) 003-26-00. Е-mail: dr.snehaeapen@gmail.com
Burmenskaya O.V., MD, Senior Researcher of Laboratory molecular genetic factors, Research Center of Obstetrics, Gynecology, and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381341. E-mail: bourmenska@mail.ru
Pavlovich S.V., PhD, Associate Professor, scientific secretary of Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79104244197. E-mail: st.pavlovich@mail.ru
Levkov L.A., MD, PhD, Consultant embryologist of 1st gynecological department, Research Center of Obstetrics, Gynecology, and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79858616344. Е-mail: l_levkov@oparina4.ru
Syrkasheva A.G., MD, Researcher of R&D Department, Research Center of Obstetrics, Gynecology and Perinatology.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954382501. E-mail: anast.syrkasheva@gmail.com
Kodyleva T.A., embryologist 1st gynecology department, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954382622. E-mail: t_kodyleva@oparina4.ru
Abubakirov A.N., PhD, Head of 1st gynecology department, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954382622. Е-mail: nondoc555@yahoo.com
Mishieva N.G., MD, Senior researcher of 1st gynecology department, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79104244197. E-mail: nondoc555@mail.ru
Trofimov D.Y., Ph.D., The Head of molecular-genetical laboratory, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381341. E-mail: d_trofimov@oparina4.ru
For citations: Eapen S.M., Burmenskaya O.V., Pavlovich S.V., Levkov L.A., Syrkasheva A.G., Kodyleva T.A., Abubakirov A.N., Mishieva N.G., Trofimov D.Yu. Comparative analysis of cumulus cell transcripts when using different ovulation triggers in IVF/ICSI programs. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (5): 82-8. (in Russian)
http://dx.doi.org/10.18565/aig.2017.5.82-8
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