The Pregnancy Outcomes Among Women Receiving Individualized Algorithm Dosing with Follitropin Delta: a Systematic Review of Randomized Controlled Trials

Overview

Journal J Assist Reprod Genet

Publisher Springer

Specialties Genetics
Reproductive Medicine

Date 2024 May 29

PMID 38809330

Authors

Bogdan Doroftei

Ovidiu-Dumitru Ilie

Ana-Maria Dabuleanu

Theodora Armeanu

Radu Maftei

Affiliations

Soon will be listed here.

Abstract

Purpose: To investigate whether the ovarian stimulation with follitropin delta in an individualized algorithm-based manner is inferior to recombinant human-follicle stimulating's follitropin alfa or follitropin beta conventional dosing regarding a series of established primary endpoints.

Methods: We conducted a registered systematic review (CRD42024512792) on PubMed-MEDLINE, Web of Science™, Cochrane Database of Systematic Reviews, and Scopus. Our search was designed to cover all relevant literature, particularly randomized controlled trials. We critically and comparatively analyzed the outcomes for each primary endpoint based on the intervention, reflected by the positive βhCG test, clinical pregnancy, vital pregnancy, ongoing pregnancy, live birth, live birth at 4 weeks, and multiple pregnancies.

Results: Six randomized controlled trials were included in the quality assessment as priority manuscripts, revealing an 83.3% low risk of bias. Follitropin delta led to non-significant differences in each parameter of interest from positive βhCG test (691; 53.44% vs. 602; 46.55%), ongoing pregnancies (603; 53.79% vs. 518; 46.20%), clinical and vital pregnancies (1,073; 52.80% vs. 959; 47.19%), to live birth and at 4 weeks (595; 54.14% vs. 504; 45.85%) with only 2 losses, and even multiple pregnancies (8; 66.66% vs. 4; 33.33%). However, follitropin delta was well-tolerated among hypo- and hyper-responders without significant risk of ovarian hyperstimulation syndrome and/or preventive interventions in contrast with follitropin alfa or follitropin beta.

Conclusion: The personalized individualized-based algorithm dosing with follitropin delta is non-inferior to conventional follitropin alfa or follitropin beta. It is as effective in promoting a similar response in women without significant comparable adverse effects.

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

Baldini G, Mastrorocco A, Sciorio R, Palini S, Dellino M, Cascardi E . Inadvertent Administration of 72 µg of Follitropin-Δ for Three Consecutive Days Does Not Appear to Be Dangerous for Poor Responders: A Case Series. J Clin Med. 2023; 12(16). PMC: 10456029. DOI: 10.3390/jcm12165202. View

Broekmans F, Kwee J, Hendriks D, Mol B, Lambalk C . A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Reprod Update. 2006; 12(6):685-718. DOI: 10.1093/humupd/dml034. View

Dias J, Ulloa-Aguirre A . New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect. Front Endocrinol (Lausanne). 2021; 12:636038. PMC: 8018285. DOI: 10.3389/fendo.2021.636038. View

Sterne J, Savovic J, Page M, Elbers R, Blencowe N, Boutron I . RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366:l4898. DOI: 10.1136/bmj.l4898. View

Lunenfeld B, Bilger W, Longobardi S, Alam V, DHooghe T, Sunkara S . The Development of Gonadotropins for Clinical Use in the Treatment of Infertility. Front Endocrinol (Lausanne). 2019; 10:429. PMC: 6616070. DOI: 10.3389/fendo.2019.00429. View

Iliodromiti S, Salje B, Dewailly D, Fairburn C, Fanchin R, Fleming R . Non-equivalence of anti-Müllerian hormone automated assays-clinical implications for use as a companion diagnostic for individualised gonadotrophin dosing. Hum Reprod. 2017; 32(8):1710-1715. PMC: 5850658. DOI: 10.1093/humrep/dex219. View

Koechling W, Plaksin D, Croston G, Jeppesen J, Macklon K, Andersen C . Comparative pharmacology of a new recombinant FSH expressed by a human cell line. Endocr Connect. 2017; 6(5):297-305. PMC: 5510450. DOI: 10.1530/EC-17-0067. View

La Marca A, Sunkara S . Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice. Hum Reprod Update. 2013; 20(1):124-40. DOI: 10.1093/humupd/dmt037. View

10.

Magnusson A, Olerod G, Thurin-Kjellberg A, Bergh C . The correlation between AMH assays differs depending on actual AMH levels. Hum Reprod Open. 2019; 2017(4):hox026. PMC: 6277007. DOI: 10.1093/hropen/hox026. View

11.

Bergandi L, Canosa S, Carosso A, Paschero C, Gennarelli G, Silvagno F . Human Recombinant FSH and Its Biosimilars: Clinical Efficacy, Safety, and Cost-Effectiveness in Controlled Ovarian Stimulation for In Vitro Fertilization. Pharmaceuticals (Basel). 2020; 13(7). PMC: 7407829. DOI: 10.3390/ph13070136. View

12.

Melado L, Lawrenz B, Sibal J, Abu E, Coughlan C, Navarro A . Anti-müllerian Hormone During Natural Cycle Presents Significant Intra and Intercycle Variations When Measured With Fully Automated Assay. Front Endocrinol (Lausanne). 2018; 9:686. PMC: 6278633. DOI: 10.3389/fendo.2018.00686. View

13.

Bissonnette F, Minano Masip J, Kadoch I, Librach C, Sampalis J, Yuzpe A . Individualized ovarian stimulation for in vitro fertilization: a multicenter, open label, exploratory study with a mixed protocol of follitropin delta and highly purified human menopausal gonadotropin. Fertil Steril. 2020; 115(4):991-1000. DOI: 10.1016/j.fertnstert.2020.09.158. View

14.

Duarte-Filho O, Miyadahira E, Matsumoto L, Yamakami L, Tomioka R, Podgaec S . Follitropin delta combined with menotropin in patients at risk for poor ovarian response during in vitro fertilization cycles: a prospective controlled clinical study. Reprod Biol Endocrinol. 2024; 22(1):7. PMC: 10759374. DOI: 10.1186/s12958-023-01172-9. View

15.

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

16.

Arab S, Frank R, Ruiter J, Dahan M . How to dose follitropin delta for the first insemination cycle according to the ESHRE and ASRM guidelines; a retrospective cohort study. J Ovarian Res. 2023; 16(1):24. PMC: 9883945. DOI: 10.1186/s13048-022-01079-w. View

17.

Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71. PMC: 8005924. DOI: 10.1136/bmj.n71. View

18.

Gorkem U, Togrul C . Is There a Need to Alter the Timing of Anti-Müllerian Hormone Measurement During the Menstrual Cycle?. Geburtshilfe Frauenheilkd. 2019; 79(7):731-737. PMC: 6620182. DOI: 10.1055/a-0840-3817. View

19.

Haakman O, Liang T, Murray K, Vilos A, Vilos G, Bates C . In vitro fertilization cycles stimulated with follitropin delta result in similar embryo development and quality when compared with cycles stimulated with follitropin alfa or follitropin beta. F S Rep. 2021; 2(1):30-35. PMC: 8244387. DOI: 10.1016/j.xfre.2020.12.002. View

20.

Rose T, Roshammar D, Erichsen L, Grundemar L, Ottesen J . Characterisation of Population Pharmacokinetics and Endogenous Follicle-Stimulating Hormone (FSH) Levels After Multiple Dosing of a Recombinant Human FSH (FE 999049) in Healthy Women. Drugs R D. 2016; 16(2):165-72. PMC: 4875921. DOI: 10.1007/s40268-016-0126-z. View