Comparing Ovarian Stimulation for Assisted Reproduction With Two Different Forms of Pituitary Suppression

NCT01565265 | Completed DMC

• 1 other identifier: UBCH001
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the non-inferiority of a multidose GnRH antagonist (cetrorelix) regimen to a GnRH agonist (triptorelin) long protocol in young infertile women undergoing ovarian stimulation with Pergoveris 150 I.U./75 I.U. (r-hFSH/ r-hLH) for ICSI treatment because of male infertility. To assess the efficacy of ovarian stimulation using either a GnRH antagonist (cetrorelix) or a GnRH agonist (triptorelin) long protocol in infertile women with good prognosis and to determine the safety of ovarian stimulation. Subsample analysis: in 10 patients of each of both arms, serum samples will be collected daily during the stimulation period and be stored frozen at -70 °C. The following hormone concentrations will be measured later in single assay batches: LH, FSH, oestradiol, progesterone, androstenedione, testosterone, inhibin A, inhibin B, AMH. Multinational, multicentre, open label, randomized, 2-arm parallel-group phase IV study. Eligible patients will be randomly allocated to one of the two groups: the agonist group will receive Decapeptyl® 0.1 mg (triptorelin) starting in the mid-luteal phase of the natural cycle until downregulation until the day of ovulation induction. The antagonist group will receive cetrorelix 0.25 mg from stimulation day 6 to ovulation induction. In both groups, Pergoveris® 150 I.U./75 I.U. (r-hFSH/r-hLH) will be used for ovarian stimulation from cycle day 2 to ovulation induction.

Conditions

Female Infertility Due to Nonimplantation of Ovum; Complications Associated With Artificial Fertilization

Keywords

ovarian hyperstimulation; GnRH antagonist; GnRH agonist; assisted reproduction; FSH; LH

Outcome Measures

Primary Outcomes (1)

• number of mature oocytes

  The primary objective of this study is to assess the non-inferiority of a multidose GnRH antagonist (cetrorelix) regimen to a GnRH agonist (triptorelin) long protocol in young infertile women undergoing ovarian hyperstimulation with Pergoveris for ICSI treatment because of male infertility. Non-inferiority is defined by the number of mature metaphase II oocytes available for ICSI.

  up to two years

Secondary Outcomes (3)

• incidence of ovarian hyperstimulation syndrome (OHSS)

  up to two years

• The number of early miscarriages.

  up to two years

• The number of participants with adverse events.

  up to two years

Study Arms (2)

GnRH agonist long protocol

ACTIVE COMPARATOR

Pergoveris will be administered daily from cycle day 2 to ovulation induction together with decapeptyl, which will be administered from the midluteal phase of the preceding menstrual cycle up to ovulation induction.

Drug: Pergoveris in long protocol with GnRH agonist

antagonist protocol

EXPERIMENTAL

Pergoveris will be administered daily from cycle day 2 to ovulation induction together with Cetrotide, which will be administered from the day six up to ovulation induction.

Drug: Pergoveris in GnRH antagonist protocol

Interventions

Pergoveris in long protocol with GnRH agonist DRUG

Ovarian hyperstimulation with recombinant FSH and recombinant FSH Ovulation induction with recombinant HCG Oocyte collection for ICSI

Also known as: Pergoveris

GnRH agonist long protocol

Pergoveris in GnRH antagonist protocol DRUG

Ovarian hyperstimulation with recombinant FSH and recombinant FSH Ovulation induction with recombinant HCG Oocyte collection for ICSI

Also known as: Cetrotide

antagonist protocol

Eligibility Criteria

• Age: 20 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female patients younger than 36 years of age with an indication for ICSI:
• to 35 years inclusive
• body mass index between 19 and 30 kg/m2
• indication for ICSI due to male infertility
• cycle length 27 to 32 days
• presence of both ovaries
• rubella immunity
• written informed consent

You may not qualify if:

• age \> 35 years
• pregnancy and breast feeding
• ovarian endometriosis
• uterine fibroids interfering with endometrial proliferation
• sperm retrieval from the epididymis or the testis
• more than one previous ART treatment with pregnancy
• known or suspected hypersensitivity to active substances
• clinically relevant systemic disease
• previous enrollment to this study
• know or suspected non-compliance, drug or alcohol abuse

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Merck Serono International SA: collaborator

Study Sites (1)

University Hospital of Basel

Basel, CH-4031, Switzerland

Location

Related Publications (11)

• Kolibianakis EM, Collins J, Tarlatzis BC, Devroey P, Diedrich K, Griesinger G. Among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth dependent on the type of analogue used? A systematic review and meta-analysis. Hum Reprod Update. 2006 Nov-Dec;12(6):651-71. doi: 10.1093/humupd/dml038. Epub 2006 Aug 18.

  PMID: 16920869 BACKGROUND

• Kolibianakis EM, Zikopoulos K, Schiettecatte J, Smitz J, Tournaye H, Camus M, Van Steirteghem AC, Devroey P. Profound LH suppression after GnRH antagonist administration is associated with a significantly higher ongoing pregnancy rate in IVF. Hum Reprod. 2004 Nov;19(11):2490-6. doi: 10.1093/humrep/deh471. Epub 2004 Aug 19.

  PMID: 15319383 BACKGROUND

• Al-Inany H, Aboulghar M. GnRH antagonist in assisted reproduction: a Cochrane review. Hum Reprod. 2002 Apr;17(4):874-85. doi: 10.1093/humrep/17.4.874.

  PMID: 11925376 BACKGROUND

• Pouly JL, Bachelot A, de Mouzon J, Devaux A; FIVNAT. [Comparison of agonists versus antagonists for i.v.f. stimulation: the French FIVNAT survey 2001-2002]. Gynecol Obstet Fertil. 2004 Sep;32(9):737-40. doi: 10.1016/j.gyobfe.2004.07.011. French.

  PMID: 15380755 BACKGROUND

• Griesinger G, Felberbaum R, Diedrich K. GnRH antagonists in ovarian stimulation: a treatment regimen of clinicians' second choice? Data from the German national IVF registry. Hum Reprod. 2005 Sep;20(9):2373-5. doi: 10.1093/humrep/dei086. Epub 2005 Jun 2.

  PMID: 15932915 BACKGROUND

• Huirne JA, Hugues JN, Pirard C, Fischl F, Sage JC, Pouly JL, Obruca A, Braat DM, van Loenen AC, Lambalk CB. Cetrorelix in an oral contraceptive-pretreated stimulation cycle compared with buserelin in IVF/ICSI patients treated with r-hFSH: a randomized, multicentre, phase IIIb study. Hum Reprod. 2006 Jun;21(6):1408-15. doi: 10.1093/humrep/del030. Epub 2006 Mar 14.

  PMID: 16537563 BACKGROUND

• Penarrubia J, Fabregues F, Creus M, Manau D, Casamitjana R, Guimera M, Carmona F, Vanrell JA, Balasch J. LH serum levels during ovarian stimulation as predictors of ovarian response and assisted reproduction outcome in down-regulated women stimulated with recombinant FSH. Hum Reprod. 2003 Dec;18(12):2689-97. doi: 10.1093/humrep/deg506.

  PMID: 14645193 BACKGROUND

• Coppola F, Poti ER, Barusi L, Ferrari B, Salvarani MC, Vadora E. Profound luteinizing hormone suppression induces a deleterious follicular environment during assisted reproduction technology. Fertil Steril. 2003 Feb;79(2):459-60. doi: 10.1016/s0015-0282(02)04671-x. No abstract available.

  PMID: 12568871 BACKGROUND

• Merviel P, Antoine JM, Mathieu E, Millot F, Mandelbaum J, Uzan S. Luteinizing hormone concentrations after gonadotropin-releasing hormone antagonist administration do not influence pregnancy rates in in vitro fertilization-embryo transfer. Fertil Steril. 2004 Jul;82(1):119-25. doi: 10.1016/j.fertnstert.2003.11.040.

  PMID: 15236999 BACKGROUND

• Burgues S; Spanish Collaborative Group on Female Hypogonadotrophic Hypogonadism. The effectiveness and safety of recombinant human LH to support follicular development induced by recombinant human FSH in WHO group I anovulation: evidence from a multicentre study in Spain. Hum Reprod. 2001 Dec;16(12):2525-32. doi: 10.1093/humrep/16.12.2525.

  PMID: 11726569 BACKGROUND

• Recombinant human luteinizing hormone (LH) to support recombinant human follicle-stimulating hormone (FSH)-induced follicular development in LH- and FSH-deficient anovulatory women: a dose-finding study. The European Recombinant Human LH Study Group. J Clin Endocrinol Metab. 1998 May;83(5):1507-14. doi: 10.1210/jcem.83.5.4770.

  PMID: 9589647 BACKGROUND

MeSH Terms

Interventions

pergoveris; Gonadotropin-Releasing Hormone; cetrorelix

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Christian De Geter, Prof.

  University of Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2012
• First Posted: March 28, 2012
• Study Start: April 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2013
• Last Updated: May 1, 2017

Record last verified: 2017-04

Locations

CH (1)