Live Birth Rates Following Individualized Dosing Algorithm of Follitropin Delta in a Long GnRH Agonist Protocol

Overview

Journal Reprod Biol Endocrinol

Publisher Biomed Central

Specialties Endocrinology
Reproductive Medicine

Date 2023 May 16

PMID 37194068

Authors

Manuel Fernandez Sanchez

Per Larsson

Marcos Ferrando Serrano

Ernesto Bosch

Juan Antonio Garcia Velasco

Esther Santamaria Lopez

Bernadette Mannaerts

Affiliations

Soon will be listed here.

Abstract

Purpose: To explore the efficacy and safety of individualized follitropin delta dosing, based on serum anti-Müllerian hormone (AMH) concentration and bodyweight, in a long gonadotropin-releasing hormone (GnRH) agonist protocol.

Methods: Clinical outcomes after one treatment cycle are reported in women with AMH: 5-35 pmol/L. Oocytes were inseminated by intracytoplasmic sperm injection, blastocyst transfer was on Day 5 and remaining blastocysts were cryopreserved. Data collection included live births and neonatal health follow-up for all fresh/frozen transfers performed within one year after treatment allocation.

Results: In total, 104 women started stimulation, of whom 101 had oocyte recovery and 92 had blastocyst transfer. The average daily dose of follitropin delta was 11.0 ± 1.6 µg and the duration of stimulation was 10.3 ± 1.6 days. The mean number of oocytes was 12.5 ± 6.4, the mean number of blastocysts was 5.1 ± 3.4, and 85% had at least one good-quality blastocyst. Following mostly single blastocyst transfer (95%), the ongoing pregnancy rate was 43%, the live-birth rate was 43%, and the cumulative live-birth rate was 58% per started stimulation. There were 6 cases of early OHSS (5.8%) graded as mild (n = 3) and moderate (n = 3) and 6 cases of late OHSS (5.8%) graded as moderate (n = 3) and severe (n = 3).

Conclusion: In this first evaluation of the individualized follitropin delta dosing in a long GnRH agonist protocol, the cumulative live-birth rate was high. A randomized trial comparing follitropin delta in a long GnRH agonist protocol versus in a GnRH antagonist protocol should provide further insight into the efficacy and safety of this treatment option.

Trial Registration Number: NCT03564509; June 21, 2018.

Citing Articles

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References

Havelock J, Henningsen A, Mannaerts B, Arce J . Pregnancy and neonatal outcomes in fresh and frozen cycles using blastocysts derived from ovarian stimulation with follitropin delta. J Assist Reprod Genet. 2021; 38(10):2651-2661. PMC: 8581102. DOI: 10.1007/s10815-021-02271-5. View

Visnova H, Papaleo E, Martin F, Koziol K, Klein B, Mannaerts B . Clinical outcomes of potential high responders after individualized FSH dosing based on anti-Müllerian hormone and body weight. Reprod Biomed Online. 2021; 43(6):1019-1026. DOI: 10.1016/j.rbmo.2021.08.024. View

Qiao J, Lu G, Zhang H, Chen H, Ma C, Olofsson J . A randomized controlled trial of the GnRH antagonist ganirelix in Chinese normal responders: high efficacy and pregnancy rates. Gynecol Endocrinol. 2012; 28(10):800-4. DOI: 10.3109/09513590.2012.665103. View

Macklon N, Stouffer R, Giudice L, Fauser B . The science behind 25 years of ovarian stimulation for in vitro fertilization. Endocr Rev. 2006; 27(2):170-207. DOI: 10.1210/er.2005-0015. View

Khalaf Y, El-Toukhy T, Taylor A, Braude P . Increasing the gonadotrophin dose in the course of an in vitro fertilization cycle does not rectify an initial poor response. Eur J Obstet Gynecol Reprod Biol. 2002; 103(2):146-9. DOI: 10.1016/s0301-2115(02)00036-2. View

Toftager M, Bogstad J, Bryndorf T, Lossl K, Roskaer J, Holland T . Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol: RCT including 1050 first IVF/ICSI cycles. Hum Reprod. 2016; 31(6):1253-64. DOI: 10.1093/humrep/dew051. View

van Hooff M, Alberda A, Huisman G, ZEILMAKER G, Leerentveld R . Doubling the human menopausal gonadotrophin dose in the course of an in-vitro fertilization treatment cycle in low responders: a randomized study. Hum Reprod. 1993; 8(3):369-73. DOI: 10.1093/oxfordjournals.humrep.a138053. View

Ishihara O, Arce J . Individualized follitropin delta dosing reduces OHSS risk in Japanese IVF/ICSI patients: a randomized controlled trial. Reprod Biomed Online. 2021; 42(5):909-918. DOI: 10.1016/j.rbmo.2021.01.023. View

Arce J, Nyboe Andersen A, Fernandez-Sanchez M, Visnova H, Bosch E, Garcia-Velasco J . Ovarian response to recombinant human follicle-stimulating hormone: a randomized, antimüllerian hormone-stratified, dose-response trial in women undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2014; 102(6):1633-40.e5. DOI: 10.1016/j.fertnstert.2014.08.013. View

10.

Wirleitner B, Schuff M, Stecher A, Murtinger M, Vanderzwalmen P . Pregnancy and birth outcomes following fresh or vitrified embryo transfer according to blastocyst morphology and expansion stage, and culturing strategy for delayed development. Hum Reprod. 2016; 31(8):1685-95. DOI: 10.1093/humrep/dew127. View

11.

Al-Inany H, Youssef M, Ayeleke R, Brown J, Lam W, Broekmans F . Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016; 4:CD001750. PMC: 8626739. DOI: 10.1002/14651858.CD001750.pub4. View

12.

Tremellen K, 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):1219-24. DOI: 10.1093/humrep/deq059. View

13.

Magnusson A, Kallen K, Thurin-Kjellberg A, Bergh C . The number of oocytes retrieved during IVF: a balance between efficacy and safety. Hum Reprod. 2017; 33(1):58-64. DOI: 10.1093/humrep/dex334. View

14.

Sanchez M, Visnova H, Larsson P, Andersen C, Filicori M, Blockeel C . A randomized, controlled, first-in-patient trial of choriogonadotropin beta added to follitropin delta in women undergoing ovarian stimulation in a long GnRH agonist protocol. Hum Reprod. 2022; 37(6):1161-1174. PMC: 9156848. DOI: 10.1093/humrep/deac061. View

15.

Fatemi H, Bilger W, Denis D, Griesinger G, La Marca A, Longobardi S . Dose adjustment of follicle-stimulating hormone (FSH) during ovarian stimulation as part of medically-assisted reproduction in clinical studies: a systematic review covering 10 years (2007-2017). Reprod Biol Endocrinol. 2021; 19(1):68. PMC: 8112039. DOI: 10.1186/s12958-021-00744-x. View

16.

Copperman A, Benadiva C . Optimal usage of the GnRH antagonists: a review of the literature. Reprod Biol Endocrinol. 2013; 11:20. PMC: 3618003. DOI: 10.1186/1477-7827-11-20. View

17.

Lambalk C, Banga F, Huirne J, Toftager M, Pinborg A, Homburg R . GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Hum Reprod Update. 2017; 23(5):560-579. DOI: 10.1093/humupd/dmx017. View

18.

. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011; 26(6):1270-83. DOI: 10.1093/humrep/der037. View

19.

Nyboe Andersen A, Nelson S, Fauser B, Garcia-Velasco J, Klein B, Arce J . Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial. Fertil Steril. 2016; 107(2):387-396.e4. DOI: 10.1016/j.fertnstert.2016.10.033. View

20.

Fernandez-Sanchez M, Visnova H, Yuzpe A, Klein B, Mannaerts B, Arce J . Individualization of the starting dose of follitropin delta reduces the overall OHSS risk and/or the need for additional preventive interventions: cumulative data over three stimulation cycles. Reprod Biomed Online. 2019; 38(4):528-537. DOI: 10.1016/j.rbmo.2018.12.032. View