The Effect of a Liraglutide on IVF in Obese PCOS

NCT ID: NCT03353948

Last Updated: 2017-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-01
• Study Completion Date: 2016-09-01

Brief Summary

The aim of this study was to evaluate the impact of low dose liraglutide in combination with metformin compared to metformin alone on IVF pregnancy rate (PR) and cumulatively PR (IVF and spontaneous) in infertile obese women with PCOS who had been previously poor responders regarding weight reduction with lifestyle modification and resistant to first line reproductive treatments.

Detailed Description

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, in particular when PCOS is linked to obesity. Obese PCOS has poor IVF outcomes associated with impaired oocyte and embryo parameters and morphology. The purpose of this pilot prospective study was to investigate the effect of the novel medical therapy (combination of metformin and liraglutide (COMBI)) in the specific infertile obese PCOS population. GLP-1 has been investigated in regulation of reproductive system in animal models. Current observations suggest that it directly regulates kisspeptin and GnRH expression and that ovaries express GLP-1 mRNA. In obese PCOS, GLP-1 receptor agonist liraglutide provided positive effects on weight reduction and glucose homeostasis

Conditions

Polycystic Ovary Syndrome; Obesity; Infertility, Female

Keywords

Polycystic Ovary Syndrome; Obesity; Infertility; IVF

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metfrormin group (MET)

Drug: Metformin

Group Type: ACTIVE_COMPARATOR

MET

Intervention Type: DRUG

In the MET group metformin was initiated at a dose of 500 mg once per day and increased by 500 mg every 3 days up to 1000 mg BID per os for 12 weeks. After 1 month IVF was done.

COMBI group (COMBI)

Drug: liraglutide

Group Type: ACTIVE_COMPARATOR

COMBI

Intervention Type: DRUG

In the COMBI group the initial dose of MET was 500 mg for at least 2 wk and gradually increased to a final dose of 1000 mg BID. Liraglutide 1.2 mg QD s.c. was added after first two weeks of monotherapy with MET. After 1 month IVF was done.

Interventions

MET

In the MET group metformin was initiated at a dose of 500 mg once per day and increased by 500 mg every 3 days up to 1000 mg BID per os for 12 weeks. After 1 month IVF was done.

Intervention Type: DRUG

COMBI

In the COMBI group the initial dose of MET was 500 mg for at least 2 wk and gradually increased to a final dose of 1000 mg BID. Liraglutide 1.2 mg QD s.c. was added after first two weeks of monotherapy with MET. After 1 month IVF was done.

Intervention Type: DRUG

Other Intervention Names

Glucophage tbl; Victoza 6 mg/ml solution for injection in pre-filled pen

Eligibility Criteria

Inclusion Criteria

• 18 years old to 38 years old
• polycystic ovary syndrome (rotterdam criteria)
• BMI of 30 kg/m² or higher
• Infertility
• Before IVF

Exclusion Criteria

• type 1 or type 2 diabetes mellitus

• history of carcinoma
• Cushing's syndrome or congenital (non-classic) adrenal hyperplasia
• personal or family history of MEN 2
• significant cardiovascular, kidney or hepatic disease
• the use of medications known or suspected to affect reproductive or metabolic functions
• the use of statins, within 90 days prior to study entry no other ovarian pathology normal male semen

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 37 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Medical Centre Ljubljana

OTHER

Sponsor Role: lead

Responsible Party

Vesna Salamun

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eda Vrtacnik Bokal, professor

Role: STUDY_CHAIR

UMC Ljubljana

References

Jensterle Sever M, Kocjan T, Pfeifer M, Kravos NA, Janez A. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol. 2014 Feb 7;170(3):451-9. doi: 10.1530/EJE-13-0797. Print 2014 Mar.

Reference Type: BACKGROUND

PMID: 24362411 (View on PubMed)

Salamun V, Rizzo M, Lovrecic L, Hocevar K, Papler Burnik T, Janez A, Jensterle M, Vrtacnik Bokal E, Peterlin B, Maver A. The Endometrial Transcriptome of Metabolic and Inflammatory Pathways During the Window of Implantation Is Deranged in Infertile Obese Polycystic Ovarian Syndrome Women. Metab Syndr Relat Disord. 2022 Sep;20(7):384-394. doi: 10.1089/met.2021.0149. Epub 2022 Jul 13.

Reference Type: DERIVED

PMID: 35834645 (View on PubMed)

Other Identifiers

Obese PCOS IVF

Identifier Type: -

Identifier Source: org_study_id