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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02606500
• Other study ID #: Merck-01
• Status: Completed
• Phase: Phase 4
• Start date: March 2016
• Est. completion date: March 2017

Study information

• Verified date: May 2018
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: March 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 38 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity

Intervention

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.

Locations

Country	Name	City	State
Slovenia	Division of gynecology, Department of human reproduction	Ljubljana

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Slovenia, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of Mature Oocytes	Number of mature oocytes obtained was compared between groups	1 month
Primary	Number of Fertilized Oocytes		1 month
Primary	Number of Frozen Embryos		1 month
Primary	Biochemical Pregnancy Rate		1 year
Secondary	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