International Journal of Infertility & Fetal Medicine

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VOLUME 15 , ISSUE 1 ( January-April, 2024 ) > List of Articles


A Prospective Cohort Study on the Impact of Delaying Ovulation Trigger on Assisted Reproductive Technology Outcomes

Anu Manivannan, Radha Vembu, Monna Pandurangi, Sanjeeva R Nellepalli

Keywords : Assisted reproductive technology outcome, Follicle size, Oocyte maturation, Ovulation trigger

Citation Information : Manivannan A, Vembu R, Pandurangi M, Nellepalli SR. A Prospective Cohort Study on the Impact of Delaying Ovulation Trigger on Assisted Reproductive Technology Outcomes. Int J Infertil Fetal Med 2024; 15 (1):1-5.

DOI: 10.5005/jp-journals-10016-1328

License: CC BY-NC 4.0

Published Online: 29-02-2024

Copyright Statement:  Copyright © 2024; The Author(s).


Aims and background: The optimal size of the leading follicle at which ovulation trigger should be given in the gonadotropin-releasing hormone (GnRH) antagonist protocol has not been validated yet. We carried out this study to assess the role of delaying ovulation triggering, with the leading follicle beyond 20 mm, in enabling the maturation of medium-sized follicles during controlled ovarian stimulation (COS). Materials and methods: A total of 427 infertile women between the age-group 21 and 45 years, undergoing COS with flexible GnRH antagonist protocol were included, and before stimulation, they were categorized into three groups, namely predicted poor (group I), normal (group II), and hyper (group III) responders. On the day of the trigger, all three groups were further split into two subgroups based on the leading follicle diameter (subgroup A: <20 mm and subgroup B: ≥20 mm), and assisted reproductive technology (ART) outcomes were analyzed between the subgroups. Results: The number of oocytes retrieved [6.8 ± 3.9 vs 4.0 ± 2.7, 95% confidence interval (CI): 1.10–4.44; p = 0.001], the number of metaphase II oocytes among them (4.6 ± 3.1 vs 2.8 ± 1.9; 95% CI: 0.48–3.06; p = 0.008) and the resultant total number of embryos available for freezing (3.5 ± 2.6 vs 2.2 ± 1.7; 95% CI: 0.17–2.41; p = 0.024) and the number of grade I embryos (2.0 ± 1.9 vs 1.1 ± 1.4; 95% CI: 0.15–1.77; p = 0.021) were significantly increased in group IB when compared to group IA. The cycle outcomes were marginally improved, though not significant, in subgroups IIB and IIIB when compared to subgroups IIA and IIIA, respectively. Oocyte maturation rate and fertilization rate were comparable between the subgroups. Conclusion: Delaying the trigger for oocyte maturation has a role in improving the outcomes in poor responders. Clinical significance: Delaying the ovulation trigger in enabling the maturation of medium-sized follicles leads to clinically better yield of oocytes and good quality embryos in predicted poor responders.

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  1. Ectors FJ, Vanderzwalmen P, Van Hoeck J, et al. Relationship of human follicular diameter with oocyte fertilization and development after in-vitro fertilization or intracytoplasmic sperm injection. Hum Reprod 1997;12(9):2002–2005. DOI: 10.1093/humrep/12.9.2002
  2. Wittmaack FM, Kreger DO, Blasco L, et al. Effect of follicular size on oocyte retrieval, fertilization, cleavage, and embryo quality in in vitro fertilization cycles: a 6-year data collection. Fertil Steril 1994;62(6):1205–1210. DOI: 10.1016/s0015-0282(16)57186-6
  3. Abbara A, Vuong LN, Ho VNA, et al. Follicle size on day of trigger most likely to yield a mature oocyte. Front Endocrinol (Lausanne) 2018;9:193. DOI: 10.3389/fendo.2018.00193
  4. Orvieto R, Mohr-Sasson A, Blumenfeld S, et al. Does a large (>24 mm) follicle yield a competent oocyte/embryo? Gynecol Obstet Invest 2020;85(5):416–419. DOI: 10.1159/000510876
  5. Triwitayakorn A, Suwajanakorn S, Pruksananonda K, et al. Correlation between human follicular diameter and oocyte outcomes in an ICSI program. J Assist Reprod Genet 2003;20(4):143–147. DOI: 10.1023/a:1022977002954
  6. Dubey AK, Wang HA, Duffy P, et al. The correlation between follicular measurements, oocyte morphology, and fertilization rates in an in vitro fertilization program. Fertil Steril 1995;64(4):787–790. DOI: 10.1016/s0015-0282(16)57855-8
  7. Miller KF, Goldberg JM, Falcone T. Follicle size and implantation of embryos from in vitro fertilization. Obstet Gynecol 1996;88(4 Pt 1):583–586. DOI: 10.1016/0029-7844(96)00241-4
  8. Kahraman S, Cetinkaya CP, Cetinkaya M, et al. The effect of follicle size and homogeneity of follicular development on the morphokinetics of human embryos. J Assist Reprod Genet 2017;34(7):895–903. DOI: 10.1007/s10815-017-0935-1
  9. McCulloh DH, Kutchukhidze N, Charkviani T, et al. Follicle size indicates oocyte maturity and blastocyst formation but not blastocyst euploidy following controlled ovarian hyperstimulation of oocyte donors. Hum Reprod 2020;35(3):545–556. DOI: 10.1093/humrep/dez291
  10. Rosen MP, Shen S, Dobson AT, et al. A quantitative assessment of follicle size on oocyte developmental competence. Fertil Steril 2008;90(3):684–690. DOI: 10.1016/j.fertnstert.2007.02.011
  11. Mohr-Sasson A, Orvieto R, Blumenfeld S, et al. The association between follicle size and oocyte development as a function of final follicular maturation triggering. Reprod Biomed Online 2020;40(6):887–893. DOI: 10.1016/j.rbmo.2020.02.005
  12. Shapiro BS, Rasouli MA, Verma K, et al. The effect of ovarian follicle size on oocyte and embryology outcomes. Fertil Steril 2022;117(6):1170–1176. DOI: 10.1016/j.fertnstert.2022.02.017
  13. Jirge PR, Patil MM, Gutgutia R, et al. Ovarian stimulation in assisted reproductive technology cycles for varied patient profiles: an indian perspective. J Hum Reprod Sci 2022;15(2):112–125. DOI: 10.4103/jhrs.jhrs_59_22
  14. Vembu R, Nellepalli SR, Pandurangi M, et al. Impact of two doses of agonist trigger on assisted reproductive technology outcome. Int J Infertil Fetal Med 2022;13(1):1–4. DOI: 10.5005/jp-journals-10016-1255
  15. Alpha Scientists in Reproductive Medicine ESHRE Special Interest Group of Embryology,. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 2011;26(6):1270–1283. DOI: 10.1093/humrep/der037
  16. Baerwald A, Pierson R. Ovarian follicular waves during the menstrual cycle: physiologic insights into novel approaches for ovarian stimulation. Fertil Steril 2020;114(3):443–457. DOI: 10.1016/j.fertnstert.2020.07.008
  17. Sunkara SK, Rittenberg V, Raine-Fenning N, et al. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod 2011;26(7):1768–1774. DOI: 10.1093/humrep/der106
  18. De Geyter C, Fehr P, Moffat R, et al. Twenty years’ experience with the Swiss data registry for assisted reproductive medicine: outcomes, key trends and recommendations for improved practice. Swiss Med Wkly 2015;145:w14087. DOI: 10.4414/smw.2015.14087
  19. Labarta E, Bosch E, Mercader A, et al. A higher ovarian response after stimulation for IVF is related to a higher number of euploid embryos. Biomed Res Int 2017;2017:5637923. DOI: 10.1155/2017/5637923
  20. Venetis CA, Tilia L, Panlilio E, et al. Is more better? A higher oocyte yield is independently associated with more day-3 euploid embryos after ICSI. Hum Reprod 2019;34(1):79–83. DOI: 10.1093/humrep/dey342
  21. Law YJ, Zhang N, Kolibianakis EM, et al. Is there an optimal number of oocytes retrieved at which live birth rates or cumulative live birth rates per aspiration are maximized after ART? A systematic review. Reprod Biomed Online 2021;42(1):83–104. DOI: 10.1016/j.rbmo.2020.10.008
  22. Vandekerckhove F, Gerris J, Vansteelandt S, et al. Delaying the oocyte maturation trigger by one day leads to a higher metaphase II oocyte yield in IVF/ICSI: a randomised controlled trial. Reprod Biol Endocrinol 2014;12:31. DOI: 10.1186/1477-7827-12-31
  23. Mochtar MH, Custers IM, Koks CA, et al. Timing oocyte collection in GnRH agonists down-regulated IVF and ICSI cycles: a randomized clinical trial. Hum Reprod 2011;26(5):1091–1096. DOI: 10.1093/humrep/der048
  24. Morley L, Tang T, Yasmin E, et al. Timing of human chorionic gonadotrophin (hCG) hormone administration in IVF protocols using GnRH antagonists: a randomized controlled trial. Hum Fertil (Camb) 2012;15(3):134–139. DOI: 10.3109/14647273.2012.712739
  25. Chen Y, Zhang Y, Hu M, et al. Timing of human chorionic gonadotropin (hCG) hormone administration in IVF/ICSI protocols using GnRH agonist or antagonists: a systematic review and meta-analysis. Gynecol Endocrinol 2014;30(6):431–437. DOI: 10.3109/09513590.2014.895984
  26. Mizrachi Y, Horowitz E, Farhi J, et al. Ovarian stimulation for freeze-all IVF cycles: a systematic review. Hum Reprod Update 2020;26(1):118–135. DOI: 10.1093/humupd/dmz037
  27. Tremellen KP, Lane M. Avoidance of weekend oocyte retrievals during GnRH antagonist treatment by simple advancement or delay of hCG administration does not adversely affect IVF live birth outcomes. Hum Reprod 2010;25(5):1219–1224. DOI: 10.1093/humrep/deq059
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