Effect of Prolonged Ovarian Stimulation (24 and 48 Hours) Compared to Conventional Duration on IVF/ICSI Outcomes: A Single-Blind Randomized Clinical Trial

Effect of Prolonged Ovarian Stimulation on IVF/ICSI

Authors

  • Nasim Jabbari Asl Women Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  • Laya Farzadi Women Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  • Aliye Ghasemzadeh Women Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  • Kobra Hamdi Women Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  • Parvin Hakimi Women Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  • Hamed Hajipour Women Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  • Nazli Navali Women Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

DOI:

https://doi.org/10.31661/gmj.v14i.3840

Keywords:

Controlled Ovarian Stimulation; in vitro Fertilization; Intracytoplasmic Sperm Injection; Infertility; Assisted Reproductive Technology

Abstract

Background: Infertility is a global public health concern, and controlled ovarian stimulation (COS) plays a crucial role in assisted reproductive technologies (ART) by facilitating the retrieval of multiple oocytes. This single-blind randomized clinical trial aimed to evaluate whether extending the duration of COS by 24 and 48 hours beyond the conventional protocol would affect pregnancy rates in couples undergoing IVF/ICSI. Materials and Methods: Ninety patients were randomized into three groups: control (GC), 24-hours longer (G24), and 48-hours longer (G48), using block randomization. The GC group followed the standard COS protocol, while G24 and G48 received extended COS for their respective durations. Primary outcomes included imaging-proven pregnancy at six weeks gestation, chemical pregnancy, and clinical pregnancy post-embryo transfer. Secondary outcomes included follicle, oocyte, and embryo counts. Results: Baseline characteristics were comparable across groups. Antral follicle count (AFC) and anti-Müllerian hormone (AMH) levels were positively correlated with pregnancy outcomes. Significant associations were observed between AFC/AMH and follicle/oocyte/embryo counts. Although embryo counts varied among groups, no significant differences in primary or secondary outcomes were found. A trend towards improved outcomes was noted from GC to G48, but without statistical significance. Conclusion: The study did not find significant differences in pregnancy rates or other outcomes with prolonged COS durations compared to conventional protocols. However, the results suggest a need for further research to explore the effects of extended COS in specific patient subsets, as existing literature indicates potential benefits.

References

Ombelet W. Global access to infertility care in developing countries: a case of human rights, equity and social justice. Facts Views Vis Obgyn. 2011;3(4):257-66.

Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015 Jul 1;21(4):411-26.

https://doi.org/10.1093/humupd/dmv016

PMid:25801630

Duffy JMN, Adamson GD, Benson E, Bhattacharya S, Bhattacharya S, Bofill M, et al. Top 10 priorities for future infertility research: an international consensus development study. Hum Reprod Oxf Engl. 2020 Nov 30;35(12):2715-24.

Azami R, Farshbaf-Khalili A, Mahdipour M, Ghazi Firozsalar F, Shahnazi M. Effect of Nigella sativa Oil on early menopausal symptoms and serum levels of oxidative markers in menopausal women: A randomized, triple-blind clinical trial. Nurs midwifery stud. 2022; 11(2): 103-111.

Gallos ID, Eapen A, Price MJ, Sunkara SK, Macklon NS, Bhattacharya S, et al. Controlled ovarian stimulation protocols for assisted reproduction: a network meta‐analysis. Cochrane Database Syst Rev. 2017 Mar 9;2017(3):CD012586.

https://doi.org/10.1002/14651858.CD012586

Howie R, Kay V. Controlled ovarian stimulation for in-vitro fertilization. Br J Hosp Med Lond Engl 2005. 2018 Apr 2;79(4):194-9.

https://doi.org/10.12968/hmed.2018.79.4.194

PMid:29620984

Pal L, Jindal S, Witt BR, Santoro N. Less is more ‥‥ Increased gonadotropin use for ovarian stimulation adversely influences clinical pregnancy and live birth following IVF. Fertil Steril. 2008 Jun;89(6):1694-701.

https://doi.org/10.1016/j.fertnstert.2007.05.055

PMid:18440515 PMCid:PMC2601677

Glujovsky D, Pesce R, Miguens M, Sueldo CE, Lattes K, Ciapponi A. How effective are the non-conventional ovarian stimulation protocols in ART? A systematic review and meta-analysis. J Assist Reprod Genet. 2020; 37(12): 2913-2928.

https://doi.org/10.1007/s10815-020-01966-5

PMid:33219862 PMCid:PMC7714798

Ryan A, Wang S, Alvero R, Polotsky AJ. Prolonged gonadotropin stimulation for assisted reproductive technology cycles is associated with decreased pregnancy rates for all women except for women with polycystic ovary syndrome. J Assist Reprod Genet. 2014 Jul;31(7):837-42.

https://doi.org/10.1007/s10815-014-0253-9

PMid:24865669 PMCid:PMC4096873

Purandare N, Emerson G, Kirkham C, Harrity C, Walsh D, Mocanu E. The duration of gonadotropin stimulation does not alter the clinical pregnancy rate in IVF or ICSI cycles. Ir J Med Sci. 2017 Aug;186(3):653-7.

https://doi.org/10.1007/s11845-016-1526-3

PMid:27822908

Chuang M, Zapantis A, Taylor M, Jindal SK, Neal-Perry GS, Lieman HJ, et al. Prolonged gonadotropin stimulation is associated with decreased ART success. J Assist Reprod Genet. 2010 Dec;27(12):711-7.

https://doi.org/10.1007/s10815-010-9476-6

PMid:20821043 PMCid:PMC2997954

Ryan A, Wang S, Alvero R, Polotsky AJ. Prolonged gonadotropin stimulation for assisted reproductive technology cycles is associated with decreased pregnancy rates for all women except for women with polycystic ovary syndrome. J Assist Reprod Genet. 2014; 31(7): 837-42.

https://doi.org/10.1007/s10815-014-0253-9

PMid:24865669 PMCid:PMC4096873

Ovarian Stimulation TEGGO, Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI†. Hum Reprod Open. 2020; 2020(2): hoaa009. open, 2020(2), hoaa009.

https://doi.org/10.1093/hropen/hoaa009

PMid:32395637 PMCid:PMC7203749

Kolibianakis EM, Albano C, Kahn J, Camus M, Tournaye H, Van Steirteghem AC, et al. Exposure to high levels of luteinizing hormone and estradiol in the early follicular phase of gonadotropin-releasing hormone antagonist cycles is associated with a reduced chance of pregnancy. Fertil Steril. 2003 Apr 1;79(4):873-80.

https://doi.org/10.1016/S0015-0282(02)04920-8

PMid:12749423

Alport B, Case A, Lim H, Baerwald A. Does the Ovarian Stimulation Phase Length Predict In vitro Fertilization Outcomes? Int J Fertil Steril. 2011;5(3):134-41.

Zhao X, Zhang X, Wu S, Tan J. Association Between the Ratio of Ovarian Stimulation Duration to Original Follicular Phase Length and In Vitro Fertilization Outcomes: A Novel Index to Optimise Clinical Trigger Time. Front Endocrinol (Lausanne). 2022; 13: 862500.

https://doi.org/10.3389/fendo.2022.862500

PMid:35957813 PMCid:PMC9361069

Keane K, Cruzat VF, Wagle S, Chaudhary N, Newsholme P, Yovich J. Specific ranges of anti-Mullerian hormone and antral follicle count correlate to provide a prognostic indicator for IVF outcome. Reprod Biol. 2017 Mar 1;17(1):51-9.

https://doi.org/10.1016/j.repbio.2016.12.002

PMid:28132758

Broer SL, Mol BWJ, Hendriks D, Broekmans FJM. The role of antimullerian hormone in prediction of outcome after IVF: comparison with the antral follicle count. Fertil Steril. 2009 Mar 1;91(3):705-14.

https://doi.org/10.1016/j.fertnstert.2007.12.013

PMid:18321493

Huang JYJ, Rosenwaks Z. In vitro fertilisation treatment and factors affecting success. Best Pract Res Clin Obstet Gynaecol. 2012 Dec;26(6):777-88.

https://doi.org/10.1016/j.bpobgyn.2012.08.017

PMid:23059403

Martin JR, Mahutte NG, Arici A, Sakkas D. Impact of duration and dose of gonadotrophins on IVF outcomes. Reprod Biomed Online. 2006 Nov;13(5):645-50.

https://doi.org/10.1016/S1472-6483(10)60654-2

PMid:17169173

Baker VL, Brown MB, Luke B, Smith GW, Ireland JJ. Gonadotropin dose is negatively correlated with live birth rate: analysis of more than 650,000 assisted reproductive technology cycles. Fertil Steril. 2015 Nov 1;104(5):1145-1152.e5.

https://doi.org/10.1016/j.fertnstert.2015.07.1151

PMid:26297646 PMCid:PMC4896751

Pereira N, Friedman C, Hutchinson AP, Lekovich JP, Elias RT, Rosenwaks Z. Increased odds of live birth in fresh in vitro fertilization cycles with shorter ovarian stimulation. Fertil Steril. 2017 Jan 1;107(1):104-109.e2.

https://doi.org/10.1016/j.fertnstert.2016.09.044

PMid:27793370

Baker VL, Brown MB, Luke B, Conrad KP. Association of number of retrieved oocytes with live birth rate and birth weight: an analysis of 231,815 cycles of in vitro fertilization. Fertil Steril. 2015 Apr 1;103(4):931-938.e2.

https://doi.org/10.1016/j.fertnstert.2014.12.120

PMid:25638421 PMCid:PMC4415984

Briggs R, Kovacs G, MacLachlan V, Motteram C, Baker HWG. Can you ever collect too many oocytes? Hum Reprod Oxf Engl. 2015 Jan;30(1):81-7.

https://doi.org/10.1093/humrep/deu272

PMid:25362088

Downloads

Published

2025-08-02

How to Cite

Jabbari Asl, N., Farzadi, L., Ghasemzadeh, A., Hamdi, K., Hakimi, P., Hajipour, H., & Navali, N. (2025). Effect of Prolonged Ovarian Stimulation (24 and 48 Hours) Compared to Conventional Duration on IVF/ICSI Outcomes: A Single-Blind Randomized Clinical Trial: Effect of Prolonged Ovarian Stimulation on IVF/ICSI. Galen Medical Journal, 14, e3840. https://doi.org/10.31661/gmj.v14i.3840

Issue

Vol. 14 (2025): 2025: In Progress

Section

Original Article

License

Copyright (c) 2025 Galen Medical Journal

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

https://creativecommons.org/licenses/by/4.0/