Clinical trial NCT03353948: The Effect of a Liraglutide on IVF in Obese PCOS
Official title: The Effect of Liraglutide on Pregnancy Rates in Obese Women With PCOS Undergoing in Vitro Fertilization: a Pilot Randomized Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Polycystic Ovary Syndrome
Obesity
Infertility, Female
Keywords: Polycystic Ovary Syndrome
Obesity
Infertility
IVF
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2017-11-27
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 37
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: IVF pregnancy rates
timeFrame: 14 days
measure: BMI
timeFrame: Patient's BMI was measured at the beginning and every four weeks during 12 weeks of clinical trial. ]
measure: Cumulative pregnancy rates
timeFrame: The pregnancies were collected by phone interview after one year
Secondary outcomes:
measure: Oocyte nuclear maturation
timeFrame: 2 days
measure: Embryo quality
timeFrame: 6 days
Other outcomes:
measure: The other outcomes was changes changes in fasting concentrations of glucose
timeFrame: Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial.
measure: The other outcomes was changes changes in fasting concentrations of insulin
timeFrame: Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial.
measure: Other outcome was change in blood concentration of testosterone
timeFrame: Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial. ]
measure: Other outcome was change in blood concentration in androstenedione.
timeFrame: Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial.
measure: Other outcome was change in blood concentrations of SHBG (sex hormone-binding globulin).
timeFrame: Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial. ]
Locations:
Study officials:
affiliation: UMC Ljubljana
name: Eda Vrtacnik Bokal, professor
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.