Fernanda Bertuccez Cordeiro1, Thaís Regiani Cataldi2, Beatriz Zappellini de Souza3, Raquel Cellin Rochetti3, Renato Fraietta3, Carlos Alberto Labate2, Edson Guimarães Lo Turco3. 1. Human Reproduction Section, Division of Urology, Department of Surgery, Sao Paulo Federal University, Rua Embau, 231, São Paulo, SP, 04039-060, Brazil. fernandabertuccez85@gmail.com. 2. Laboratório Max Feffer de Genética de Plantas, Departamento de Genética, Escola Superior de Agricultura Luiz de Queiroz, Universidade de São Paulo, Piracicaba, SP, 13418-900, Brazil. 3. Human Reproduction Section, Division of Urology, Department of Surgery, Sao Paulo Federal University, Rua Embau, 231, São Paulo, SP, 04039-060, Brazil.
Abstract
INTRODUCTION: During in vitro fertilization (IVF), the hyper response to controlled ovarian stimulation (COS) is a common characteristic among patients diagnosed with polycystic ovary syndrome (PCOS), although non-diagnosed patients may also demonstrate this response. OBJECTIVES: In an effort to investigate follicular metabolic characteristics associated with hyper response to COS, the present study analyzed follicular fluid (FF) samples from patients undergoing IVF. METHODS: FF samples were obtained from patients with PCOS and hyper response during IVF (PCOS group, N = 15), patients without PCOS but with hyper response during IVF (HR group, N = 44), and normo-responder patients receiving IVF (control group, N = 22). FF samples underwent Bligh and Dyer extraction, followed by metabolomic analysis by ultra-performance liquid chromatography mass spectrometry, considering two technical replicates. Clinical data was analyzed by ANOVA and chi-square tests. The metabolomic dataset was analyzed by multivariate statistics, and the significance of biomarkers was confirmed by ANOVA. RESULTS: Clinical data showed differences regarding follicles production, oocyte and embryo quality. From the 15 proposed biomarkers, 14 were of increased abundance in the control group and attributed as fatty acids, diacylglycerol, triacylglycerol, ceramide, ceramide-phosphate, phosphatidylcholine, and sphingomyelin. The PCOS patients showed increased abundance of a metabolite of m/z 144.0023 that was not attributed to a class. CONCLUSION: The clinical and metabolic similarities observed in the FF of hyper responders with and without PCOS diagnosis indicate common biomarkers that could assist on the development of accessory tools for assessment of IVF parameters.
INTRODUCTION: During in vitro fertilization (IVF), the hyper response to controlled ovarian stimulation (COS) is a common characteristic among patients diagnosed with polycystic ovary syndrome (PCOS), although non-diagnosed patients may also demonstrate this response. OBJECTIVES: In an effort to investigate follicular metabolic characteristics associated with hyper response to COS, the present study analyzed follicular fluid (FF) samples from patients undergoing IVF. METHODS: FF samples were obtained from patients with PCOS and hyper response during IVF (PCOS group, N = 15), patients without PCOS but with hyper response during IVF (HR group, N = 44), and normo-responder patients receiving IVF (control group, N = 22). FF samples underwent Bligh and Dyer extraction, followed by metabolomic analysis by ultra-performance liquid chromatography mass spectrometry, considering two technical replicates. Clinical data was analyzed by ANOVA and chi-square tests. The metabolomic dataset was analyzed by multivariate statistics, and the significance of biomarkers was confirmed by ANOVA. RESULTS: Clinical data showed differences regarding follicles production, oocyte and embryo quality. From the 15 proposed biomarkers, 14 were of increased abundance in the control group and attributed as fatty acids, diacylglycerol, triacylglycerol, ceramide, ceramide-phosphate, phosphatidylcholine, and sphingomyelin. The PCOSpatients showed increased abundance of a metabolite of m/z 144.0023 that was not attributed to a class. CONCLUSION: The clinical and metabolic similarities observed in the FF of hyper responders with and without PCOS diagnosis indicate common biomarkers that could assist on the development of accessory tools for assessment of IVF parameters.
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