The Effect of a Liraglutide on IVF in Obese PCOS

The Effect of Liraglutide on Pregnancy Rates in Obese Women With PCOS Undergoing in Vitro Fertilization: a Pilot Randomized Study

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.

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

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.

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.

Patient's BMI was defined as the patient's body mass in kilograms divided by the square of their height in meters.

Patient's BMI was measured at the beginning and every four weeks during 12 weeks of clinical trial. ]

The embryo quality assessed by standard cleavage stage embryo grading system on day 3 of embryo culture. For any embryos grown to day 5, the embryo quality assessed by standard blastocyst grading system on day 5 of embryo culture

Patient's blood was drawn between 8 and 9 a.m. Concentrations of fasting glucose was measured in mmol/L.

Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial.

Patient's blood was drawn between 8 and 9 a.m. Fasting concentrations of insulin was measured in mU/L.

Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial.

Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial. ]

Patient's blood was drawn between 8 and 9 a.m. Blood concentrations of androstenedione was measured in nmol/L.

Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial.

Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial. ]

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

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.

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.