Efficacy of Corifollitropin Alfa in Obese Women in Terms of Clinical and Molecular Parameters of IVF Success

• ClinicalTrials.gov Identifier: NCT02606500
• Recruitment Status: Completed
• First Posted: November 17, 2015
• Results First Posted: November 26, 2018
• Last Update Posted: November 26, 2018
• Sponsor: University Medical Centre Ljubljana
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Tanja Burnik Papler, University Medical Centre Ljubljana

Study Description

Brief Summary:

The aim of the present study is to determine, whether clinical efficacy of 150 mcg of Corifollitropin alfa is the same in normal weighing and obese women. Furthermore, investigators want to determine whether oocytes retrieved from normal weighing and obese women, after COH using 150 mcg of Corifollitropin alfa, are of same quality on the molecular level.

Condition or disease	Intervention/treatment	Phase
Obesity	Drug: Elonva	Phase 4

Detailed Description:

The dosage of Corifollitropin alfa used for controlled ovarian hyperstimulation (COH) is adjusted according to the patient's body weight. Meaning, in women with a body weight ≤ 60 kg, a single dose of 100 mcg of Corifollitropin alfa is administered for COH and in women with a body weight > 60 kg, a single dose of 150 micrograms of Corifollitropin alfa is administered for COH. These two protocols are comparable in safety and efficacy of follicular stimulation.

On the other hand, knowledge about the clinical efficacy of 150 mcg of Corifollitropin alfa in obese women (BMI>30 kg/m2) is lacking.

Cumulus cells (CC) surround the oocyte and bi-directional communication between oocyte and CC is necessary for the development of mature and quality oocytes. It has been proposed, that analysis of genes, expressed in CC, can serve as an objective indicator of the oocyte's maturity and developmental potential. Expression of genes in CC as hyaluronan synthase 2 (HAS2), follicle-stimulating hormone receptor (FSHR), versican (VCAN), progesterone receptor (PR), vascular endothelial growth factor C (VEGFC), serine protease inhibitor E2 (SERPINE2), glutathione peroxidase (GPX3), pentraxin 3(PTX3) was reported to correlate with oocyte maturity and developmental potential.

The effect of Corifollitropin alfa on expression of these genes however, is unknown.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 70 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy of Corifollitropin Alfa in Obese Women in Terms of Clinical and Molecular Parameters of IVF Success
• Actual Study Start Date: March 2016
• Actual Primary Completion Date: January 2017
• Actual Study Completion Date: March 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Elonva 150 mcg; Elonva 150 mcg intramuscular daily obese	Drug: Elonva; 20 obese women will be the study group and 20 normal weighing women will be the control group. Both groups will receive 150 mcg of Elonva for controlled ovarian hyperstimulation (COH). Gonadotropin-releasing hormone (GnRH) antagonist will be used to prevent premature luteinizing hormone (LH) surge. Additional daily doses of 200 IU of recombinant follicle stimulating hormone (rFSH) will be used if necessary. Human chorionic gonadotropin (hCG) will be used for oocyte maturation. 2 mature follicles will be aspirated separately in each patient. Cumulus cell (CC) samples will be collected and stored on -80 oC for subsequent analysis. Clinical and molecular parameters of IVF success will be assessed and compared between the groups. The exclusion criteria will be: polycystic ovary syndrome, severely abnormal sperm parameters, and age > 38 years.
Active Comparator: Elonva 100 mcg; Elonva 100 mcg intramuscular daily normal weight	Drug: Elonva; 20 obese women will be the study group and 20 normal weighing women will be the control group. Both groups will receive 150 mcg of Elonva for controlled ovarian hyperstimulation (COH). Gonadotropin-releasing hormone (GnRH) antagonist will be used to prevent premature luteinizing hormone (LH) surge. Additional daily doses of 200 IU of recombinant follicle stimulating hormone (rFSH) will be used if necessary. Human chorionic gonadotropin (hCG) will be used for oocyte maturation. 2 mature follicles will be aspirated separately in each patient. Cumulus cell (CC) samples will be collected and stored on -80 oC for subsequent analysis. Clinical and molecular parameters of IVF success will be assessed and compared between the groups. The exclusion criteria will be: polycystic ovary syndrome, severely abnormal sperm parameters, and age > 38 years.

Outcome Measures

Primary Outcome Measures :

1. Number of Oocytes Retrieved Per Patient [ Time Frame: 1 month ]
   Number of oocytes obtained in the study group was compared to the number of oocytes obtained in the control group
2. Number of Mature Oocytes [ Time Frame: 1 month ]
   Number of mature oocytes obtained was compared between groups
3. Number of Fertilized Oocytes [ Time Frame: 1 month ]
4. Number of Frozen Embryos [ Time Frame: 1 month ]
5. Biochemical Pregnancy Rate [ Time Frame: 1 year ]

Secondary Outcome Measures :

1. Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level [ Time Frame: 12 months ]
   Expression of some genes that were proposed as biomarkers of oocyte quality was analysed in CC using real-time PCR. Relative expression values of genes were compared between mature oocytes derived from obese women and mature oocytes derived from normal weighing women.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 38 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• BMI > 30 kg/m2
• BMI 18.5-24.9 kg/m2

Exclusion Criteria:

• polycystic ovary syndrome, severely abnormal sperm parameters, and age > 38 years

Contacts and Locations

Locations

Slovenia

Division of gynecology, Department of human reproduction

Ljubljana, Slovenia, 1000

Sponsors and Collaborators

University Medical Centre Ljubljana

Merck Sharp & Dohme Corp.

Investigators

• Study Chair: Eda Vrtacnik Bokal, professor; Head of the department of Human reproduction

More Information

Publications:

Burnik Papler T, Vrtacnik Bokal E, Maver A, Kopitar AN, Lovrečić L. Transcriptomic Analysis and Meta-Analysis of Human Granulosa and Cumulus Cells. PLoS One. 2015 Aug 27;10(8):e0136473. doi: 10.1371/journal.pone.0136473. eCollection 2015.

Burnik Papler T, Vrtačnik Bokal E, Maver A, Lovrečić L. Specific gene expression differences in cumulus cells as potential biomarkers of pregnancy. Reprod Biomed Online. 2015 Apr;30(4):426-33. doi: 10.1016/j.rbmo.2014.12.011. Epub 2015 Jan 12.

Burnik Papler T, Vrtacnik Bokal E, Lovrecic L, Kopitar AN, Maver A. No specific gene expression signature in human granulosa and cumulus cells for prediction of oocyte fertilisation and embryo implantation. PLoS One. 2015 Mar 13;10(3):e0115865. doi: 10.1371/journal.pone.0115865. eCollection 2015.

Devjak R, Fon Tacer K, Juvan P, Virant Klun I, Rozman D, Vrtačnik Bokal E. Cumulus cells gene expression profiling in terms of oocyte maturity in controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist. PLoS One. 2012;7(10):e47106. doi: 10.1371/journal.pone.0047106. Epub 2012 Oct 17.

Vrtacnik-Bokal E, Virant Klun I, Verdenik I. Follicular oestradiol and VEGF after GnRH antagonists or GnRH agonists in women with PCOS. Reprod Biomed Online. 2009 Jan;18(1):21-8.

• Responsible Party: Tanja Burnik Papler, Principal investigator Tanja Burnik Papler, MD; PhD, University Medical Centre Ljubljana
• ClinicalTrials.gov Identifier: NCT02606500
• Other Study ID Numbers: Merck-01
• First Posted: November 17, 2015
• Results First Posted: November 26, 2018
• Last Update Posted: November 26, 2018
• Last Verified: May 2018