Background: Serum luteinizing hormone (LH) levels are measured on trigger day and 12 hours post-gonadotropin releasing hormone (GnRH) agonist trigger for final oocyte maturation. The impact of 12-hour serum LH on the prediction of suboptimal response and outcome of assisted reproductive technology (ART) is controversial.
Aim: To evaluate the impact of two doses of agonist trigger 12 hours apart irrespective of 12-hour serum LH levels on ART outcome.
Settings and design: Retrospective cohort study at a tertiary care university hospital.
Subjects and methods: Eighty-six infertile women with predicted hyper-response, administered agonist trigger 12 hours apart, and have undergone Intracytoplasmic Sperm Injection (ICSI) with frozen embryo transfer (FET) over 3 years were included. They were grouped based on 12-hour serum LH into <15 IU/L, 15–30 IU/L, and >30 IU/L. The baseline characteristics and ART outcome were compared among the three groups.
Statistical analysis: SPSS 23.0 version, Chi-square test, One-way ANOVA with post hoc test.
Results: The study groups were comparable with regard to baseline characteristics, oocytes retrieved, mature oocytes metaphase II (MII) (p = 0.421), day three grade-I embryos and embryos available for freezing (p = 0.419). The cumulative pregnancy rate (p = 0.753), miscarriage rate (p = 0.421) and ongoing pregnancy/cumulative live birth rate (CLBR) per retrieval (p = 0.892) were comparable.
Conclusion: Administration of two doses of agonist trigger 12 hours apart is an effective solution in low-resource settings to avoid suboptimal response without compromising the ART outcome.
Clinical significance: Administration of two doses of agonist trigger is an effective way to avoid suboptimal response in low-resource setting and can avoid LH estimation 12 hours post-trigger.
Itskovitz-Eldor J, Kol S, Mannaerts B. Use of a single bolus of GnRH agonist triptorelin to trigger ovulation after GnRH antagonist ganirelix treatment in women undergoing ovarian stimulation for assisted reproduction, with special reference to the prevention of ovarian hyper- stimulation syndrome: preliminary report: short communication. Hum Reprod 2000;15:1965–1968. DOI: 10.1093/humrep/15.9.1965
Honnma H, Hashiba Y, Asada Y, et al. Failure of triggering oocyte maturation with a GnRH agonist in polycystic ovary syndrome: two case reports. Eur J Obstet Gynecol Reprod Biol 2011;157:239–240. DOI: 10.1016/j.ejogrb.2011.03.002
Chang FE, Beall SA, Cox JM, et al. Assessing the adequacy of gonadotropin-releasing hormone agonist leuprolide to trigger oocyte maturation and management of inadequate response. Fertil Steril 2016;106(5):1093–1100.e3. DOI: 10.1016/j.fertnstert.2016.06.013
ALPHA Scientists in Reproductive Medicine, ESHRE Special Interest Group Embryology. Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Reprod Biomed Online 2011;22:632–646. DOI: 10.1093/humrep/der037
Azziz R. Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: the Rotterdam criteria are premature. J Clin Endocrinol Metab 2006;91:781–785. DOI: 10.1210/jc.2005-2153
Nakano RT, Mizuno F, Kotsuji K et al. “Triggering“ of ovulation after infusion of synthetic luteinizing hormone releasing factor (LRF). Acta Obstet Gynecol Scand 1973;52:269–272. DOI: 10.3109/00016347309158325
Itskovitz J, Boldes R, Levron J, et al. Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist. Fertil Steril 1991;56:213–220. PMID: 1906406.
Hoff JD, Quigley ME, Yen SS. Hormonal dynamics at mid cycle: a reevaluation. J Clin Endocrinol Metab 1983;57:792–796. DOI: 10.1210/jcem-57-4-792
Zelinski-Wooten MB, Lanzendorf SE, Wolf DP, et al. Titrating luteinizing hormone surge requirements for ovulatory changes in primate follicles. I. Oocyte maturation and corpus luteum function. J Clin Endocrinol Metab 1991;73:577–583. DOI: 10.1210/jcem-73-3-577
Seibel MM, Smith DM, Levesque L, et al. The temporal relationship between the luteinizing hormone surge and human oocyte maturation. Am J Obstet Gynecol 1982;142:568–572. DOI: 10.1016/0002-9378(82)90763-3
Zelinski-Wooten MB, Hutchison JS, Chandrasekher YA, et al. Administration of human luteinizing hormone (hLH) to macaques after follicular development: further titration of LH surge requirements for ovulatory changes in primate follicles. J Clin Endocrinol Metab 1992;75(2):502–507. DOI: 10.1210/jcem.75.2.1639951
Shapiro BS, Daneshmand ST, Restrepo H, et al. Efficacy of induced luteinizing hormone surge after “trigger” with gonadotropin-releasing hormone agonist. Fertil Steril 2011;95:826–828. DOI: 10.1016/j.fertnstert.2010.09.009
Deepika K, Baiju P, Gautham P, et al. Repeat dose of gonadotropin-releasing hormone agonist trigger in polycystic ovarian syndrome undergoing in vitro fertilization cycles provides a better cycle outcome - a proof-of-concept study. J Hum Reprod Sci 2017;10:271–280. DOI: 10.4103/jhrs.JHRS_102_17
Griesinger G, Schultz L, Bauer T, et al. Ovarian hyperstimulation syndrome prevention by gonadotropin-releasing hormone agonist triggering of final oocyte maturation in a gonadotropin-releasing hormone antagonist protocol in combination with a “freeze-all” strategy: a prospective multicentric study. Fertil Steril 2011;95:2029–2033. DOI: 10.1016/j.fertnstert.2011.01.163
Kummer NE, Feinn RS, Griffin DW, et al. Predicting successful induction of oocyte maturation after gonadotropin-releasing hormone agonist (GnRHa) trigger. Hum Reprod 2013;28:152–159. DOI: 10.1093/humrep/des361
B. Popovic-Todorovic B, Santos-Ribeiro S, Drakopoulos P, et al. Predicting suboptimal oocyte yield following GnRH agonist trigger by measuring serum LH at the start of ovarian stimulation. Hum Rep 2019;34:2027–2035. DOI: 10.1093/humrep/dez132
Youssef MAF, Abdelmoty HI, Ahmed MAS, et al. GnRH agonist for final oocyte maturation in GnRH antagonist co-treated IVF/ICSI treatment cycles: systematic review and meta-analysis. J Adv Res 2015;6:341–349. DOI: 10.1016/j.jare.2015.01.005