Interest of Estrogen Scheduling Before Ovarian Stimulation With Corifollitropin Alfa

NCT02884245 | Completed Phase 3

• 1 other identifier: PRESCORI
• Study Type: interventional
• Target: 334
• Locations: 1 country
• Sites: 3

Brief Summary

E2 given in late luteal phase can be extended beyond the onset of menses for a period of at least eight days before the start of the stimulation, allowing scheduling of stimulation in order to limit oocytes retrievals during weekends . Administration of corifollitropin alfa, a Follicule stimulating Hormone (FSH) with extended release kinetics, seems particularly interesting for a synchronous recruitment of follicles after homogenization of the cohort. The objective of this study is to evaluate the impact on the response to ovarian stimulation with corifollitropin alfa of E2 scheduling versus no scheduling for women over 38 years, age at which declining of ovarian reserve usually begins. The management of these patients in terms of organization of the center is also evaluated. The scheduling of IVF cycles represents a double benefit. On one hand, to enable a "synchronization" of the follicular cohort for a best response and a higher number of mature oocytes. On the other hand, a more efficient organization for both the center (avoiding retrievals on weekends and public holidays, organize and distribute equally the activity, reduce cost operations) and couples (personal and professional organization).

Conditions

Infertility

Keywords

Fertility; Reproductive processes; In vitro fertilization; Intracytoplasmic sperm injection; Estrogens; Follicule Stimulating Hormon

Outcome Measures

Primary Outcomes (1)

• Number of selected oocytes

  At time of ovarian puncture

Secondary Outcomes (14)

• Number of days of pretreatment

  From inclusion visit date to the beginning of stimulation, up to 15 days

• Cancellation rate

  From date of inclusion visit until the date of embryo transfer, up to 90 days

• Number of days of antagonist

  From date of stimulation until the date of the trigger, up to 30 days

• The day of the trigger

  At time of the trigger

• Estradiol rate

  8 days from the beginning of stimulation and the day of the trigger

Study Arms (2)

Arm E2: With estrogens pretreatment

EXPERIMENTAL

The estrogens pretreatment will began between the day 20 and the day 24 of an ovarian cycle and should be continued until Wednesday beyond the onset of menses

Drug: Estrogens

Arm S: without estrogens pretreatment

NO INTERVENTION

No estrogen pretreatment will be delivered

Interventions

Estrogens DRUG

The estrogens pretreatment will began between the day 20 and the day 24 of an ovarian cycle and should be continued until Wednesday beyond the onset of menses

Arm E2: With estrogens pretreatment

Eligibility Criteria

• Age: 38 Years - 47 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patient of 38 years or more
• Planned in invitro fertilization or intracytoplasmic sperm injection rank 1 or 2 (rank = retrieval with transfer)
• With regular cycles from 26 to 35 days
• Weight \> 50 kg and body mass index\< or equal to 32
• Affiliation to the general system of French social security and reimbursement for fertility problems

You may not qualify if:

• Irregular cycles and/or polycystic ovarian syndrome
• Previous History of ovarian hyperstimulation syndrome
• Rank puncture \> 2
• Uterine malformation
• Presence of hydrosalpinges
• Endometriosis stage III or IV

Sponsors & Collaborators

• Centre Hospitalier Intercommunal Creteil: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Hôpital Jean Verdier

Bondy, 93140, France

Location

CHI Creteil

Créteil, 94000, France

Location

Clinique de la Sagesse

Rennes, 35043, France

Location

Related Publications (13)

• Blockeel C, Engels S, De Vos M, Haentjens P, Polyzos NP, Stoop D, Camus M, Devroey P. Oestradiol valerate pretreatment in GnRH-antagonist cycles: a randomized controlled trial. Reprod Biomed Online. 2012 Mar;24(3):272-80. doi: 10.1016/j.rbmo.2011.11.012. Epub 2011 Nov 30.

  PMID: 22296973 BACKGROUND

• Boostanfar R, Shapiro B, Levy M, Rosenwaks Z, Witjes H, Stegmann BJ, Elbers J, Gordon K, Mannaerts B; Pursue investigators. Large, comparative, randomized double-blind trial confirming noninferiority of pregnancy rates for corifollitropin alfa compared with recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist controlled ovarian stimulation protocol in older patients undergoing in vitro fertilization. Fertil Steril. 2015 Jul;104(1):94-103.e1. doi: 10.1016/j.fertnstert.2015.04.018. Epub 2015 May 21.

  PMID: 26003273 BACKGROUND

• Cedrin-Durnerin I, Bstandig B, Parneix I, Bied-Damon V, Avril C, Decanter C, Hugues JN. Effects of oral contraceptive, synthetic progestogen or natural estrogen pre-treatments on the hormonal profile and the antral follicle cohort before GnRH antagonist protocol. Hum Reprod. 2007 Jan;22(1):109-16. doi: 10.1093/humrep/del340. Epub 2006 Aug 26.

  PMID: 16936304 BACKGROUND

• Cedrin-Durnerin I, Guivarc'h-Leveque A, Hugues JN; Groupe d'Etude en Medecine et Endocrinologie de la Reproduction. Pretreatment with estrogen does not affect IVF-ICSI cycle outcome compared with no pretreatment in GnRH antagonist protocol: a prospective randomized trial. Fertil Steril. 2012 Jun;97(6):1359-64.e1. doi: 10.1016/j.fertnstert.2012.02.028. Epub 2012 Mar 28.

  PMID: 22464760 BACKGROUND

• Chang X, Wu J. Effects of luteal estradiol pre-treatment on the outcome of IVF in poor ovarian responders. Gynecol Endocrinol. 2013 Mar;29(3):196-200. doi: 10.3109/09513590.2012.736558. Epub 2012 Nov 30.

  PMID: 23194136 BACKGROUND

• Escriva AM, Diaz-Garcia C, Monterde M, Rubio JM, Pellicer A. Antral Follicle Priming Before Intracytoplasmic Sperm Injection in Previously Diagnosed Low Responders: A Randomized Controlled Trial (FOLLPRIM). J Clin Endocrinol Metab. 2015 Jul;100(7):2597-605. doi: 10.1210/jc.2015-1194. Epub 2015 May 8.

  PMID: 25955224 BACKGROUND

• Fanchin R, Salomon L, Castelo-Branco A, Olivennes F, Frydman N, Frydman R. Luteal estradiol pre-treatment coordinates follicular growth during controlled ovarian hyperstimulation with GnRH antagonists. Hum Reprod. 2003 Dec;18(12):2698-703. doi: 10.1093/humrep/deg516.

  PMID: 14645194 BACKGROUND

• Guivarc'h-Leveque A, Homer L, Arvis P, Broux PL, Moy L, Priou G, Vialard J, Colleu D, Dewailly D. Programming in vitro fertilization retrievals during working days after a gonadotropin-releasing hormone antagonist protocol with estrogen pretreatment: does the length of exposure to estradiol impact on controlled ovarian hyperstimulation outcomes? Fertil Steril. 2011 Oct;96(4):872-6. doi: 10.1016/j.fertnstert.2011.07.1138. Epub 2011 Aug 24.

  PMID: 21868004 BACKGROUND

• Hauzman EE, Zapata A, Bermejo A, Iglesias C, Pellicer A, Garcia-Velasco JA. Cycle scheduling for in vitro fertilization with oral contraceptive pills versus oral estradiol valerate: a randomized, controlled trial. Reprod Biol Endocrinol. 2013 Sep 28;11:96. doi: 10.1186/1477-7827-11-96.

  PMID: 24074027 BACKGROUND

• Nielsen AP, Korsholm AS, Lemmen JG, Sylvest R, Sopa N, Nyboe Andersen A. Selective use of corifollitropin for controlled ovarian stimulation for IVF in patients with low anti-Mullerian hormone. Gynecol Endocrinol. 2016 Aug;32(8):625-628. doi: 10.3109/09513590.2016.1147548. Epub 2016 Feb 18.

  PMID: 26891977 BACKGROUND

• Polyzos NP, De Vos M, Corona R, Vloeberghs V, Ortega-Hrepich C, Stoop D, Tournaye H. Addition of highly purified HMG after corifollitropin alfa in antagonist-treated poor ovarian responders: a pilot study. Hum Reprod. 2013 May;28(5):1254-60. doi: 10.1093/humrep/det045. Epub 2013 Feb 26.

  PMID: 23442756 BACKGROUND

• Reynolds KA, Omurtag KR, Jimenez PT, Rhee JS, Tuuli MG, Jungheim ES. Cycle cancellation and pregnancy after luteal estradiol priming in women defined as poor responders: a systematic review and meta-analysis. Hum Reprod. 2013 Nov;28(11):2981-9. doi: 10.1093/humrep/det306. Epub 2013 Jul 25.

  PMID: 23887073 BACKGROUND

• Cedrin-Durnerin I, Carton I, Massin N, Chevalier N, Dubourdieu S, Bstandig B, Michelson X, Goro S, Jung C, Guivarc'h-Leveque A. Pretreatment with luteal estradiol for programming antagonist cycles compared to no pretreatment in advanced age women stimulated with corifollitropin alfa: a non-inferiority randomized controlled trial. Hum Reprod. 2024 Sep 1;39(9):1979-1986. doi: 10.1093/humrep/deae167.

  PMID: 39008826 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

Estrogens

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Anne GUIVARC'H - LEVEQUE, MD

  Clinique de la Sagesse

  PRINCIPAL INVESTIGATOR

• Isabelle CEDRIN - DURNERIN, MD

  CHU Jean Verdier - APHP

  PRINCIPAL INVESTIGATOR

• Nathalie MASSIN, MD

  CHI Créteil

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Reproductive Endocrinologist

Study Record Dates

• First Submitted: August 22, 2016
• First Posted: August 30, 2016
• Study Start: November 4, 2016
• Primary Completion: July 1, 2022
• Study Completion: January 4, 2023
• Last Updated: February 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)