, 14:51 | Cite as

Hyper response to ovarian stimulation affects the follicular fluid metabolomic profile of women undergoing IVF similarly to polycystic ovary syndrome

  • Fernanda Bertuccez Cordeiro
  • Thaís Regiani Cataldi
  • Beatriz Zappellini de Souza
  • Raquel Cellin Rochetti
  • Renato Fraietta
  • Carlos Alberto Labate
  • Edson Guimarães Lo Turco
Original Article



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.


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.


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.


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.


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.


Polycystic ovary syndrome Hyper response Controlled ovarian stimulation Mtabolomics Mass Spectrometry 



This study was supported by the Sao Paulo Research Foundation (FAPESP—grant 06389-4) and by the National Council for Scientific and Technological Development (Cnpq—Brazil). The authors would like to thank Suzannah Colt for English edition of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

The authors comply with Springer’s Ethical Policies. The study received approval by the Ethics in Research Committee of São Paulo Federal University under protocol 1089/2015.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11306_2018_1350_MOESM1_ESM.pdf (113 kb)
Supplementary material 1 (PDF 113 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Fernanda Bertuccez Cordeiro
    • 1
  • Thaís Regiani Cataldi
    • 2
  • Beatriz Zappellini de Souza
    • 1
  • Raquel Cellin Rochetti
    • 1
  • Renato Fraietta
    • 1
  • Carlos Alberto Labate
    • 2
  • Edson Guimarães Lo Turco
    • 1
  1. 1.Human Reproduction Section, Division of Urology, Department of SurgerySao Paulo Federal UniversitySão PauloBrazil
  2. 2.Laboratório Max Feffer de Genética de Plantas, Departamento de Genética, Escola Superior de Agricultura Luiz de QueirozUniversidade de São PauloPiracicabaBrazil

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