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Journal of Assisted Reproduction and Genetics

Published in:

01-03-2015 | Assisted Reproduction Technologies

Efficacy and safety of late-start Corifollitropin-alfa administration for controlled ovarian hyperstimulation in IVF: a cohort, case–control study

Authors: Alberto Revelli, Giulia Pittatore, Simona Casano, Stefano Canosa, Francesca Evangelista, Chiara Benedetto

Published in: Journal of Assisted Reproduction and Genetics | Issue 3/2015

Abstract

Objective

To investigate efficacy and safety of a controlled ovarian stimulation (COS) protocol in which a single dose of Corifollitropin-alfa (CFα) was administered on day 4 of a GnRH-antagonist cycle.

Design

Cohort case–control study.

Setting

University Hospital.

Patients

One hundred twenty-two normally cycling women expected to be normal responders to COS.

Interventions

In 61 patients, CFα (100–150 μg) was injected subcutaneously on day 4 of a spontaneous menstrual cycle; a GnRH-antagonist was added from day 8 (fixed protocol; 0.25 mg/day). If needed to complete follicular maturation, recombinant FSH (rFSH) daily injections (150/200 IU/day) were given from day 11. A control group of 61 matched women was stimulated with daily subcutaneous injections of rFSH (100–150 U/day) from day 4 of the cycle, and received GnRH-antagonist (0.25 mg/day) from day 8. IVF or ICSI was performed according to the sperm characteristics, and 1–2 embryos were transferred in utero under US guidance on day 2.

Main outcome measures

Number of retrieved cumulus-oocyte complexes (COCs), clinical pregnancy rate (PR), implantation rate (IR), ongoing PR at 10 weeks, number of injections/cycle, ovarian hyperstimulation syndrome (OHSS) rate.

Results

No cycle was cancelled and the mean number of retrieved COCs was comparable in patients and controls. About 60 % of CF-alfa treated women had no need of daily rFSH addition, and the mean number of injections/cycle was significantly lower in the CF-alfa group than in controls (p < 0.05). The ongoing PR/transfer was 36.8 % in CF-alfa group and 37.5 % in controls. No patient developed severe OHSS, and the incidence of moderate OHSS was similar in cases and controls.

Conclusions

CFα may be started on day 4 of the cycle obtaining results comparable to those of a COS using day 4-start daily rFSH, with significantly less injections and a similar risk of OHSS.

Nargund G, Fauser BC, Macklon NS, Ombelet W, Nygren K, Frydman R. The ISMAAR proposal on terminology for ovarian stimulation for IVF.; Rotterdam ISMAAR consensus group on terminology for ovarian stimulation for IVF. Hum Reprod. 2007;22:2801–4.PubMedCrossRef

Verberg MF, Macklon NS, Nargund G, Frydman R, Devroey P, Broekmans FJ, et al. Mild ovarian stimulation for IVF. Hum Reprod Update. 2009;15:13–29.PubMedCrossRef

Revelli A, Casano C, Salvagno F, Delle PL. Mild is better? Advantages and disadvantages of mild ovarian stimulation for human in vitro fertilization. Reprod Biol Endocrinol. 2011;9:25–33.PubMedCentralPubMedCrossRef

Blockeel C, Polyzos NP, Derksen L, De Brucker M, Vloeberghs V, van de Vijver A, et al. Administration of corifollitropin alfa on day 2 versus day 4 of the cycle in a GnRH antagonist protocol: a randomized controlled pilotstudy. Hum Reprod. 2014;29:1500–7.PubMedCrossRef

Fares FA, Suganuma N, Nishimori K, LaPolt PS, Hsueh AJ, Boime I. Design of a long-acting follitropin agonist by fusing the C-terminal sequence of the chorionic gonadotropin beta subunit to the follitropin beta subunit. Proc Natl Acad Sci U S A. 1992;89:4304–8.PubMedCentralPubMedCrossRef

LaPolt PS, Nishimori K, Fares FA, Perlas E, Boime I, Hsueh AJ. Enhanced stimulation of follicle maturation and ovulatory potential by long acting follicle-stimulating hormone agonists with extended carboxyl-terminal peptides. Endocrinology. 1992;131:2514–20.PubMed

Fauser BCJM, Mannaerts BMJL, Devroey P, Leader A, Boime I, Baird DT. Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency. Hum Reprod Update. 2009;15:309–21.PubMedCrossRef

Duijkers IJM, Klipping C, Boerrigter PJ, Machielsen CSM, de Bie JJ, Voortman G. Single dose pharmacokinetics and effects on follicular growth and serum hormones of a long-acting recombinant FSH preparation (FSH-CTP) in healthy pituitary-suppressed females. Hum Reprod. 2002;17:1987–93.PubMedCrossRef

Devroey P, Fauser BC, Platteau P, Beckers NG, Dhont M, Mannaerts BM. Induction of multiple follicular development by a single dose of long-acting recombinant follicle-stimulating hormone (FSH-CTP, corifollitropin alfa) for controlled ovarian stimulation before in vitro fertilisation. J Clin Endocrinol Metab. 2004;89:2062–70.PubMedCrossRef

10.

De Greef R, Struijs M, de Haan A, Marintcheva-Petrova M, Mannaerts BMJL. Dose selection of Org 36286 (corifollitropin alfa) using pharmacokinetic and dynamic modeling and simulation. Hum Reprod. 2007;22:i39.CrossRef

11.

Verbost P, Sloot WN, Rose UM, de Leeuw R, Hanssen RG, Verheijden GF. Pharmacologic profiling of corifollitropin alfa, the first developed sustained follicle stimulant. Eur J Pharmacol. 2011;651:227–33.PubMedCrossRef

12.

Devroey P, Boostanfar R, Koper NP, Mannaerts BMJL, Ijzerman-Boon PC, Fauser BCJM, et al. A double-blind, non inferiority RCT comparing Corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. 2009;24:3063–72.PubMedCentralPubMedCrossRef

13.

The corifollitropin alfa Ensure study group. Corifollitropin alfa for ovarian stimulation in IVF: a randomized trial in lower-body-weight women. Reprod BioMed Online. 2010;21:66–76.CrossRef

14.

Requena A, Cruz M, Collado D, Izquierdo A, Ballesteros A, Muñoz M, et al. Evaluation of the degree of satisfaction in oocyte donors using sustained-release FSH corifollitropin α. Reprod BioMed Online. 2013;26:253–9.PubMedCrossRef

15.

de Klerk C, Macklon NS, Heijnen EM, Eijkemans MJ, Fauser BC, Passchier J, et al. The psychological impact of IVF failure after two or more cycles of IVF with a mild versus standard treatment strategy. Hum Reprod. 2007;22:2554–8.PubMedCrossRef

16.

Holte J, Berglund L, Milton K, Garello C, Gennarelli G, Revelli A, et al. Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval. Hum Reprod. 2007;22:548–57.PubMedCrossRef

17.

Fauser BC, Nargund G, Andersen AN, Norman R, Tarlatzis B, Boivin J, et al. Mild ovarian stimulation for IVF: 10 years later. Hum Reprod. 2010;25:2678–84.PubMedCrossRef

18.

Heijnen EMEW, Macklon NS, Fauser BCJM. What is the most relevant standard of success in assisted reproduction? The next step to improving outcomes of IVF: consider the whole treatment. Hum Reprod. 2004;19:1936–8.PubMedCrossRef

19.

Polyzos NP, Devos M, Humaidan P, Stoop D, Ortega-Hrepich C, Devroey P, et al. Corifollitropin alfa followed by rFSH in a GnRH antagonist protocol for poor ovarian responder patients: an observational pilot study. Fertil Steril. 2013;99:422–6.PubMedCrossRef

20.

Polyzos NP, De Vos M, Corona R, Vloeberghs V, Ortega-Hrepich C, Stoop D, et al. Addition of highly purified HMG after corifollitropin alfa in antagonist-treated poor ovarian responders: a pilot study. Hum Reprod. 2013;28:1254–60.PubMedCrossRef

21.

Schipper I, Hop WC, Fauser BC. The follicle-stimulating hormone (FSH) threshold/window concept examined by different interventions with exogenous FSH during the follicular phase of the normal menstrual cycle: duration, rather than magnitude, of FSH increase affects follicle development. J Clin Endocrinol Metab. 1998;83:1292–8.PubMed

22.

Macklon NS, Stouffer RL, Giudice LC, Fauser BCJM. The science behind 25 years of ovarian stimulation for in vitro fertilization. Endocr Rev. 2006;27:170–207.PubMedCrossRef

23.

Hohmann FP, Laven JSE, de Jong FH, Eijkemans, Fauser BCJM. Low dose exogenous FSH initiated during the early mid or late follicular phase can induce multiple dominant follicle development. Hum Reprod. 2001;16:846–54.PubMedCrossRef

24.

Hohmann FP, Macklon NS, Fauser BCJM. A randomized comparison of two ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) antagonist cotreatment for in vitro fertilization commencing recombinant follicle-stimulating hormone on cycle day 2 or 5 with the standard long GnRH agonist protocol. J Clin Endocrinol Metab. 2003;88:166–73.PubMedCrossRef

25.

de Jong D, Macklon NS, Fauser BC. A pilot study involving minimal ovarian stimulation for in vitro fertilization: extending the “follicle-stimulating hormone window” combined with the gonadotropin-releasing hormone antagonist cetrorelix. Fertil Steril. 2000;73:1051–4.PubMedCrossRef

26.

Tarlatzis BC, Griesinger G, Leader A, Rombauts L, Ijzerman-Boon PC, Mannaerts BM. Comparative incidence of ovarian hyperstimulation syndrome following ovarian stimulation with corifollitropin alfa or recombinant FSH. Reprod BioMed Online. 2012;24:410–9.PubMedCrossRef

27.

Casano S, Guidetti D, Pittatore G, Gennarelli G, Revelli A. Mild ovarian stimulation with GnRH antagonist vs. long protocol with low dose FSH for non-PCO high responders undergoing IVF: a prospective, randomized study including thawing cycles. J Assist Reprod Genet. 2012;29:1343–51.PubMedCentralPubMedCrossRef

28.

Norman RJ, Zegers-Hochschild F, Salle BS, Elbers J, Heijnen E, Marintcheva-Petrova M, et al. Repeated ovarian stimulation with corifollitropin alfa in patients in a GnRH antagonist protocol: no concern for immunogenicity. Hum Reprod. 2011;26:2200–8.PubMedCentralPubMedCrossRef

Title: Efficacy and safety of late-start Corifollitropin-alfa administration for controlled ovarian hyperstimulation in IVF: a cohort, case–control study
Authors: Alberto Revelli
Giulia Pittatore
Simona Casano
Stefano Canosa
Francesca Evangelista
Chiara Benedetto
Publication date: 01-03-2015
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 3/2015
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-014-0426-6

At a glance: The STEP trials

Springer Medicine

Efficacy and safety of late-start Corifollitropin-alfa administration for controlled ovarian hyperstimulation in IVF: a cohort, case–control study

Abstract

Objective

Design

Setting

Patients

Interventions

Main outcome measures

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Design

Setting

Patients

Interventions

Main outcome measures

Results

Conclusions

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