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

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Elonva

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 Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Division of gynecology, Department of human reproduction

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Oocytes Retrieved Per Patient	Number of oocytes obtained in the study group was compared to the number of oocytes obtained in the control group	1 month
Number of Mature Oocytes	Number of mature oocytes obtained was compared between groups	1 month
Number of Fertilized Oocytes		1 month
Number of Frozen Embryos		1 month
Biochemical Pregnancy Rate		1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	12 months

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Chair: Eda Vrtacnik Bokal, professor, Head of the department of Human reproduction

Publications and helpful links

General Publications

• Burnik Papler T, Vrtacnik Bokal E, Maver A, Kopitar AN, Lovrecic 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, Vrtacnik Bokal E, Maver A, Lovrecic 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, Vrtacnik 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. doi: 10.1016/s1472-6483(10)60420-8.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: November 6, 2015
• First Submitted That Met QC Criteria: November 16, 2015
• First Posted (Estimate): November 17, 2015

Study Record Updates

• Last Update Posted (Actual): November 26, 2018
• Last Update Submitted That Met QC Criteria: May 2, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: Merck-01