Administration of Follicle-stimulating Hormone (FSH) and Low Dose Human Chorionic Gonadotropin (hCG) for Oocyte Maturity While Decreasing hCG Exposure in In Vitro Fertilization (IVF) Cycles

NCT02310919 | Completed Phase 3 Results DMC

• 1 other identifier: P0503461
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, single center clinical trial study to compare oocyte competence and risk of ovarian hyperstimulation syndrome (OHSS) after receiving the standard dose of human chorionic gonadotropin (hCG) ovulation trigger or a lower dose of hCG plus concomitant follicle stimulating hormone (FSH) co-trigger in women undergoing in vitro fertilization (IVF).

Conditions

Infertility

Keywords

Infertility; In vitro fertilization; IVF

Outcome Measures

Primary Outcomes (1)

• Total Fertilization Proportion (i.e. Total Competent Proportion)

  The number of fertilized oocytes (2-pronuclei) after standard in vitro fertilization or intra-cytoplasmic sperm injection divided by the total number of oocytes retrieved as a measure of oocyte competence.

  2 days

Secondary Outcomes (28)

• Number of Oocytes Retrieved

  1 day

• Number of MII Oocytes

  1 day

• Total Oocyte Maturity Rate

  1 day

• Mature Oocyte Recovery Proportion

  1 day

• ICSI Fertilization Rate

  2 days

Study Arms (2)

Low dose hCG plus FSH co-trigger

EXPERIMENTAL

On the day of ovulation trigger the patient will receive hCG 1,500 IU SQ plus FSH 450 IU SQ

Drug: Low dose hCG plus FSH co-trigger

Standard dose of hCG alone

ACTIVE COMPARATOR

On the day of ovulation trigger the patient will receive standard dose of hCG (10,000 or 5,000 IU SQ)

Drug: Standard dose of hCG

Interventions

Low dose hCG plus FSH co-trigger DRUG

Low dose hCG (1,500 IU) plus FSH (450 IU) co-trigger

Low dose hCG plus FSH co-trigger

Standard dose of hCG DRUG

Standard dose of hCG (10,000 or 5,000 IU) trigger

Standard dose of hCG alone

Eligibility Criteria

• Age: 18 Years - 41 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Age \>41 years old
• Antral Follicle Count (AFC; 2-10 mm) \< 8
• Body Mass Index \> 30 kg/m2
• History of ≥ 2 prior canceled IVF cycles secondary to poor response
• Diagnosis of cancer
• Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up, or interpretation of study results
• Undergoing embryo co-culture
• Use of any of the following medications: Growth Hormone, Sildenafil, or Aspirin (except if being used for hypercoagulable state)
• Severe male factor infertility diagnosis. Male factor infertility diagnosis should be cleared for eligibility by the PI based on previous patient history of fertilization outcomes and/or expected fertilization outcomes of the cause of male factor infertility based on known scientific data.
• Ovulation trigger less than or greater than 36 hours to oocyte retrieval
• Serum estradiol level \>5,000 pg/ml on the day of expected trigger due to high risk of OHSS

Sponsors & Collaborators

• University of California, San Francisco: lead
• Ferring Pharmaceuticals: collaborator

Study Sites (1)

University of California at San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (16)

• Lamb JD, Shen S, McCulloch C, Jalalian L, Cedars MI, Rosen MP. Follicle-stimulating hormone administered at the time of human chorionic gonadotropin trigger improves oocyte developmental competence in in vitro fertilization cycles: a randomized, double-blind, placebo-controlled trial. Fertil Steril. 2011 Apr;95(5):1655-60. doi: 10.1016/j.fertnstert.2011.01.019.

  PMID: 21315341 BACKGROUND

• Navot D, Bergh PA, Laufer N. Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment. Fertil Steril. 1992 Aug;58(2):249-61. doi: 10.1016/s0015-0282(16)55188-7.

  PMID: 1633889 BACKGROUND

• Klemetti R, Sevon T, Gissler M, Hemminki E. Complications of IVF and ovulation induction. Hum Reprod. 2005 Dec;20(12):3293-300. doi: 10.1093/humrep/dei253. Epub 2005 Aug 26.

  PMID: 16126753 BACKGROUND

• McClure N, Healy DL, Rogers PA, Sullivan J, Beaton L, Haning RV Jr, Connolly DT, Robertson DM. Vascular endothelial growth factor as capillary permeability agent in ovarian hyperstimulation syndrome. Lancet. 1994 Jul 23;344(8917):235-6. doi: 10.1016/s0140-6736(94)93001-5.

  PMID: 7913160 BACKGROUND

• Kashyap S, Parker K, Cedars MI, Rosenwaks Z. Ovarian hyperstimulation syndrome prevention strategies: reducing the human chorionic gonadotropin trigger dose. Semin Reprod Med. 2010 Nov;28(6):475-85. doi: 10.1055/s-0030-1265674. Epub 2010 Nov 16.

  PMID: 21082506 BACKGROUND

• Tsoumpou I, Muglu J, Gelbaya TA, Nardo LG. Symposium: Update on prediction and management of OHSS. Optimal dose of HCG for final oocyte maturation in IVF cycles: absence of evidence? Reprod Biomed Online. 2009 Jul;19(1):52-8. doi: 10.1016/s1472-6483(10)60045-4.

  PMID: 19573290 BACKGROUND

• Schmidt DW, Maier DB, Nulsen JC, Benadiva CA. Reducing the dose of human chorionic gonadotropin in high responders does not affect the outcomes of in vitro fertilization. Fertil Steril. 2004 Oct;82(4):841-6. doi: 10.1016/j.fertnstert.2004.03.055.

  PMID: 15482757 BACKGROUND

• Kolibianakis EM, Papanikolaou EG, Tournaye H, Camus M, Van Steirteghem AC, Devroey P. Triggering final oocyte maturation using different doses of human chorionic gonadotropin: a randomized pilot study in patients with polycystic ovary syndrome treated with gonadotropin-releasing hormone antagonists and recombinant follicle-stimulating hormone. Fertil Steril. 2007 Nov;88(5):1382-8. doi: 10.1016/j.fertnstert.2006.12.058. Epub 2007 Apr 18.

  PMID: 17445806 BACKGROUND

• Chen X, Chen SL, He YX, Ye DS. Minimum dose of hCG to trigger final oocyte maturation and prevent OHSS in a long GnRHa protocol. J Huazhong Univ Sci Technolog Med Sci. 2013 Feb;33(1):133-136. doi: 10.1007/s11596-013-1085-z. Epub 2013 Feb 8.

  PMID: 23392722 BACKGROUND

• Zelinski-Wooten MB, Hutchison JS, Hess DL, Wolf DP, Stouffer RL. A bolus of recombinant human follicle stimulating hormone at midcycle induces periovulatory events following multiple follicular development in macaques. Hum Reprod. 1998 Mar;13(3):554-60. doi: 10.1093/humrep/13.3.554.

  PMID: 9572409 BACKGROUND

• Bianchi V, Dal Prato L, Maccolini A, Mazzone S, Borini A. Inadvertent recombinant human follicle stimulating hormone bolus instead of human chorionic gonadotrophin leads to the retrieval of competent oocytes in IVF program. Fertil Steril. 2009 Nov;92(5):1747.e1-3. doi: 10.1016/j.fertnstert.2009.07.998. Epub 2009 Sep 3.

  PMID: 19732874 BACKGROUND

• Wikland M, Borg J, Forsberg AS, Jakobsson AH, Svalander P, Waldenstrom U. Human chorionic gonadotrophin self-administered by the subcutaneous route to induce oocyte maturation in an in-vitro fertilization and embryo transfer programme. Hum Reprod. 1995 Jul;10(7):1667-70. doi: 10.1093/oxfordjournals.humrep.a136152.

  PMID: 8582958 BACKGROUND

• Hoff JD, Quigley ME, Yen SS. Hormonal dynamics at midcycle: a reevaluation. J Clin Endocrinol Metab. 1983 Oct;57(4):792-6. doi: 10.1210/jcem-57-4-792.

  PMID: 6411753 BACKGROUND

• Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv. 1989 Jun;44(6):430-40. doi: 10.1097/00006254-198906000-00004. No abstract available.

  PMID: 2660037 BACKGROUND

• Egbase PE, Sharhan MA, Masangcay M, Egbase E. Follicle stimulating hormone (FSH) administer with trigger dose human chorionic gonadotropin (hCG) completely prevents ovarian hyperstimulation (OHSS): Randomised controlled study. [Abstract] Fertil Steril 2011; 96(3): S20.

  BACKGROUND

• Anaya Y, Cakmak H, Mata DA, Letourneau J, Zhang L, Lenhart N, Juarez-Hernandez F, Jalalian L, Cedars MI, Rosen M. Triggering with 1,500 IU of human chorionic gonadotropin plus follicle-stimulating hormone compared to a standard human chorionic gonadotropin trigger dose for oocyte competence in in vitro fertilization cycles: a randomized, double-blinded, controlled noninferiority trial. Fertil Steril. 2022 Aug;118(2):266-278. doi: 10.1016/j.fertnstert.2022.05.006. Epub 2022 Jun 12.

  PMID: 35705380 DERIVED

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Results Point of Contact

• Title: Dr. Yanett Anaya, Assistant Professor
• Organization: UCSF Center for Reproductive Health

Yanett.anaya2@ucsf.edu

832-654-8361

Study Officials

• Mitchell Rosen, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2014
• First Posted: December 8, 2014
• Study Start: September 1, 2014
• Primary Completion: June 20, 2018
• Study Completion: June 20, 2018
• Last Updated: April 29, 2022
• Results First Posted: April 29, 2022

Record last verified: 2022-04

Locations

US (1)