Day 3 embryo metabolomics in the spent culture media is altered in obese women undergoing in vitro fertilization

We discuss how the global metabolomic profile of the spent culture media from day-3 embryos is different when obese and normoweight women are compared.

José Bellver, M.D., María J. De los Santos, Ph.D., Pilar Alamá, M.D., Damià Castelló, Ph.D., Laura Privitera, M.D., Daniela Galliano, M.D., Elena Labarta, M.D., Carmen Vidal, M.D., Antonio Pellicer, M.D., Francisco Domínguez, Ph.D.

Volume 103, Issue 6, Pages 1407-1415


To determine whether the global metabolomic profile of the spent culture media (SCM) of day-3 embryos is different in obese and normoweight women undergoing in vitro fertilization (IVF).

Prospective cohort analysis.

IVF clinic.

Twenty-eight young, nonsmoking women with normoweight, nonsmoking male partners with mild/normal sperm factors undergoing a first IVF attempt for idiopathic infertility, tubal factor infertility, or failed ovulation induction: obese ovulatory women (n = 12); obese women with polycystic ovary syndrome (PCOS; n = 4); normoweight ovulatory women (n = 12).

Fifty μl of SCM collected from two day-3 embryos of each cohort.

Main Outcome Measure(s):
Metabolomic profiling via ultrahigh performance liquid chromatography coupled to mass spectrometry of SCM from a total of 56 embryos.

The untargeted metabolomic profile was different in obese and normoweight women. Partial least squares discriminant analysis resulted in a clear separation of samples when a total of 551 differential metabolites were considered. A prediction model was generated using the most consistent metabolites. Most of the metabolites identified were saturated fatty acids, which were detected in lower concentrations in the SCM of embryos from obese women. The metabolomic profile was similar in obese women with or without PCOS.

The metabolomic profile in the SCM of day-3 embryos is different in normoweight and obese women. Saturated fatty acids seem to be reduced when embryos from obese patients are present.

Clinical Trial Registration Number:

  • As this study demonstrates, metabolomics are likely to play a major role in embryo assessment in the future. They may also assist with our understanding of the pathophysiology of reproduction. The finding of decreased saturated fatty acids in the metabolomics profile of obese patients is intriguing. Do the authors think this may be the earliest evidence of the Barker hypothesis?

    • Jose Bellver

      We think it could be another evidence of the Barker hypothesis. It is well known that the offspring of obese women presents an increased risk of several metabolic diseases (obesity, diabetes, cardiovascular diseases, metabolic syndrome…) and of other non-metabolic conditions (autisim, cancer, osteoporosis…) according to recent epidemilogical studies. Therefore, some alterations occurring at the level of the embryo and during the fetal growth may be determining factors for the future health of the baby. Lipid abnormal metabolism at the initial stages of embryo development may impact on this.

      • Thank you for your reply- I am looking forward to future research on this topic, and in the area of metabolomics.

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