Impact of luteal-phase support with a GnRH agonist on the outcomes of IVF programs


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Abstract

Subjects and methods. A randomized controlled clinical trial was conducted in 207 patients with tuboperitoneal, male, or mixed factor infertility. Ovarian function was stimulated according to a fixed-dose GnRH antagonists (GnRH-ant) protocol using recombinant follicle-stimulating gonadotropins. According to a LP support regimen in the stimulated cycle, the patients were divided into 2 groups: 1) 92 patients received micronized progesterone (P) in a dose of 600 mg/day on day 1 after transvaginal puncture (TVP) of ovaries and triptorelin in a single subcutaneous dose of 0.1 mg on day 6 after fertilization; 2) 115 had micronized P only in a dose of 600 mg/day on day 1 after TVP. Dynamic monitoring of the levels of Е2, Р, luteinizing hormone (LH), and chorionic gonadotropin β-subunit (CG-β) was made on days 5, 7, and 15 after fertilization. The rate of biochemical pregnancy, implantation, clinical pregnancy, and progressive pregnancy was estimated as criteria for the efficiency of the IVF program. Results. Analysis of the results of hormonal monitoring on day 5 following fertilization revealed no significant difference between the groups in LH, P, and E2 concentrations (p > 0.05). In patents with pregnancy, the concentrations of CG-β were not statistically significantly different on days 5 and 7 after fertilization in both examined groups (p = 0.66) and p = 0.763). On day 7 following fertilization, those of E2 (median 5126 and 3501 pmol/l; p = 0,002, Р (median 335 and 170 nmol/l; р = 0.0001), and LH (median 13.9 and 0.1 IU/l; р = 0.0001) were substantially higher in Group 1. On day 15 after fertilization, the concentrations of LH (median 0.3 and 0.1 IU/l; р = 0.003) and Р (median 206 and 108 nmol/l; р = 0.043) were also significantly higher in Group 1. On the same day following fertilization, in the patients with pregnancy showed higher level of CG-β in the GnRH-a group than that in the control group (p = 0.0001). On day 15 after fertilization, the patients with single and double pregnancy had also much higher CG-β concentrations in Group 1 (p < 0.05). In the latter group, the rate of biochemical pregnancy, implantation, and clinical pregnancy was significantly higher than that in the control group (51.1 and 34.8%; р = 0.018), (30.6 and 16.6%; р < 0.05), and (40.2 and 27%; р = 0.044). That of progressive pregnancy was higher in the GnRH-a group (37 and 21%), but the difference was not statistically significant (p = 0.349). No significant group difference was found in abortion rates (8.1 and 22.5%; p = 0.309). The rate of multiple pregnancy was also significantly higher in the GnRH-a group (35.1 and 12.9%;p = 0.049). Conclusion. The use of GnRH-a for LP support has a favorable impact on the clinical outcomes of IVF programs in the GnRH-ant protocols.

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About the authors

Elena Maratovna Gallyamova

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: elena-galliamova@rambler.ru
graduate student

Svetlana Grigorievna Perminova

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: perisvet@list.ru
MD, Leading Researcher 1st gynecological department

Elena Viktorovna Mityurina

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: mity-elena@yandex.ru
graduate student

Daria Andreevna Strelchenko

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: da_strelchenko@mail.ru
graduate student

References

  1. Macklon N.S., Fauser B.C. Impact of ovarian hyperstimulation on the luteal phase. J. Reprod. Fertil. 2000; 55(Suppl.): 101-8.
  2. Beckers N.G., Macklon N.S., Eijkemans M.J., Ludwig M., Felberbaum R.E., Diedrich K. et al. Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment. J. Clin. Endocrinol. Metab. 2003; 8899): 4186-92.
  3. Kolibianakis E.M., Bourgain C., Platteau P., Albano C., Van Streiteghem A.C., Devroey P. Abnormal endometrial development occurs during the luteal phase of nonsupplemented donor cycles treated with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonists. Fertil. Steril. 2003; 80(2): 464-6.
  4. Tesarik J., Hazout A., Mendoza-Tesarik R., Mendoza N., Mendoza C. Beneficial effect of luteal-phase GnRH agonist administration on embryo implantation after ICSI in both GnRH agonist- and antagonist-treated ovarian stimulation cycles. Hum. Reprod. 2006; 21(10): 2572-9.
  5. Kyrou D., Kolibianakis E.M., Fatemi H.M., Tarlatzi T.B., Devroey P., Tarlatzis B.C. Increased live birth rates with GnRH agonist addition for luteal support in ICSI/IVF cycles: a systematic review and meta-analysis. Hum. Reprod. Update. 2011; 17(6): 734-40. doi: 10.1093/humupd/dmr029.
  6. Oliveira J.B., Baruffi R., Petersen C.G., Mauri A.L., Cavagna M., Franco J.G. Jr. Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis. Reprod. Biol. Endocrinol. 2010; 8: 107. doi: 10.1186/1477-7827-8-107.
  7. van der Linden M., Buckingham K., Farquhar C., Kremer J.A., Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst. Rev. 2011; (10): CD009154.
  8. Isik A.Z., Caglar G.S., Sozen E., Akarsu C., Tuncay G., Ozbicer T., Vicdan K. Single-dose GnRH agonist administration in the luteal phase of GnRH antagonist cycles: a prospective randomized study. Reprod. Biomed. Online. 2009; 19(4): 472-7.
  9. Fujii S., Sato S., Fukui A., Kimura H., Kasai G., Saito Y. Continuous administration of gonadotrophin-releasing hormone agonist during the luteal phase in IVF. Hum. Reprod. 2001; 16(8): 1671-5.
  10. Qublan H., Amarin Z., Al-Quda M., Diab F., Nawasreh M., Malkawi S. et al. Luteal phase support with GnRH-a improves implantation and pregnancy rates in IVF cycles with endometrium of [less-than or equal to]7 mm on day of egg retrieval. Hum. Fertil. 2008; 11(1): 43-7.
  11. Razieh D.F., Maryam A.R., Nasim T. Beneficial effect of luteal-phase gonadotropin-releasing hormone agonist administration on implantation rate after intracytoplasmic sperm injection. Taiwan J. Obstet. Gynecol. 2009; 48(3): 245-8.
  12. Pirard C., Donnez J., Loumaye E. GnRH agonist as novel luteal support: results of a randomized, parallel group, feasibility study using intranasal administration of buserelin. Hum. Reprod. 2005; 20(7): 1798-804.
  13. Tesarik J., Hazout A., Mendoza C. Enhancement of embryo developmental potential by a single administration of GnRH agonist at the time of implantation. Hum. Reprod. 2004; 19(5): 1176-80.
  14. Inamdar D.B., Majumdar A. Evaluation of the impact of gonadotropin-releasing hormone agonist as an adjuvant in luteal-phase support on IVF outcome. J. Hum. Reprod. Sci. 2012; 5(3): 279-84.
  15. Casan E.M., Raga F., Polan M.L. GnRH mRNA and protein expression in human preimplantation embryos. Mol. Hum. Reprod. 1999; 5(3): 234-9.
  16. Kawamura K., Fukuda J., Kumagai J., Shimizu Y., Kodama H., Nakamura A., Tanaka T. Gonadotropin-releasing hormone I analog acts as an antiapop-totic factor in mouse blastocysts. Endocrinology. 2005; 146(9): 4105-16.
  17. Nam D.H., Lee S.H., Kim H.S., Lee G.S., Jeong Y.W., Kim S. et al. The role of gonadotropin-releasing hormone (GnRH) and its receptor in development of porcine preimplantation embryos derived from in vitro fertilization. Theriogenology. 2005; 63(1): 190-201.
  18. Raga F., Casan E.M., Kruessel J., Wen Y., Bonilla-Musoles F., Polan M.L. The role of gonadotropin-releasing hormone in murine preimplantation embryonic development. Endocrinology. 1999; 140(8): 3705-12.
  19. Klemmt P.A., Liu F., Carver J.G., Jones C., Brosi D., Adamson J. et al. Effects of gonadotrophin releasing hormone analogues on human endometrial stromal cells and embryo invasion in vitro. Hum. Reprod. 2009; 24(9): 2187-92.
  20. Iwashita M., Kudo Y., Shinozaki Y., Takeda Y. Gonadotropin-releasing hormone increases serum human chorionic gonadotropin in pregnant women. Endocr. J. 1993; 40(5): 539-44.
  21. Lin L.S., Roberts V.J., Yen S.S. Expression of human gonadotropin-releasing hormone receptor gene in the placenta and its functional relationship to human chorionic gonadotropin secretion. J. Clin. Endocrinol. Metab. 1995; 80(2): 580-5.
  22. Siler-Khodr T.M., Smikle C.B., Sorem K.A., Grayson M.A., Spencer D.K., Yoder B.A., Khodr G.S. Effect of excessive GnRH-binding substance on circulating maternal hCG in human pregnancy. Early Pregnancy. 1997; 3(1): 10-4.
  23. Raga F., Casan E.M., Kruessel J.S., Wen Y., Huang H.Y., Nezhat C., Polan M.L. Quantitative gonadotropin-releasing hormone gene expression and immunohistochemical localization in human endometrium throughout the menstrual cycle. Biol. Reprod. 1998; 59(3): 661-9.
  24. Chou C.S., Tai C.J., MacCalman C.D., Leung P.C. Dose-dependent effects of gonadotropin releasing hormone on matrix metalloproteinase (MMP)-2, and MMP-9 and tissue specific inhibitor of metalloproteinases-1 messenger ribonucleic acid levels in human decidual stromal cells in vitro. J. Clin. Endocrinol. Metab. 2003; 88(2): 680-8.
  25. Raga F., Casan E.M., Wen Y., Huang H.Y., Bonilla-Musoles F., Polan M.L. Independent regulation of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-3 in human endometrial stromal cells by gonadotropin-releasing hormone: implications in early human implantation. J. Clin. Endocrinol. Metab. 1999; 84(2): 636-42.
  26. Zhang X., Bocca S., Franchi A., Anderson S., Kaur M., Bajic V.B., Oehninger S. Do GnRH analogues directly affect human endometrial epithelial cell gene expression? Mol. Hum. Reprod. 2010; 16(5): 347-60.

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