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A biochemical view: vitamin D levels do not affect in vitro fertilization outcomes following the transfer of euploid blastocysts

Published:November 24, 2014DOI:https://doi.org/10.1016/j.ajog.2014.11.022
      To the Editors:
      We read with great interest the recently published article by Franasiak et al
      • Franasiak J.M.
      • Molinaro T.A.
      • Dubel E.K.
      • et al.
      Vitamin D levels do not affect IVF outcomes following the transfer of euploid blastocysts.
      in which the authors aimed to characterize the relationship between serum 25-hydroxy vitamin D (25-OH D) levels and implantation and clinical pregnancy rates in women who undergo a euploid blastocyst embryo transfer. They concluded that vitamin D status was unrelated to pregnancy outcomes in women undergoing euploid embryo transfer. Measuring serum 25-OH D levels did not predict the likelihood that euploid blastocysts will implant and these results may not apply to women who do not undergo extended embryo culture, blastocyst biopsy for comprehensive chromosome screening, and euploid embryo transfer.
      • Franasiak J.M.
      • Molinaro T.A.
      • Dubel E.K.
      • et al.
      Vitamin D levels do not affect IVF outcomes following the transfer of euploid blastocysts.
      However, we think that there are some points that should be emphasized about this study.
      First, as seen in the “Materials and Methods” section of the study by Franasiak et al,
      • Franasiak J.M.
      • Molinaro T.A.
      • Dubel E.K.
      • et al.
      Vitamin D levels do not affect IVF outcomes following the transfer of euploid blastocysts.
      patients were selected from the electronic medical record from December 2012 through December 2013. Additionally, authors have used reference ranges, which represent clinical decision values that apply to males and females of all ages. As is known, serum 25-OH D levels are affected by many factors including pigmentation, sunlight exposure, clothing, and the season of the year. The recent study by Kasahara et al
      • Kasahara A.K.
      • Singh R.J.
      • Noymer A.
      Vitamin D (25OHD) serum seasonality in the United States.
      revealed that vitamin D levels peak in August and trough in February in the general population of the United States. However, we think that, especially in population-based studies, time of sampling, an important preanalytical factor due to the seasonality of serum vitamin D levels, should be considered for avoiding patient selection bias.
      Second, since markedly different methods are used for vitamin D testing across clinical laboratories and reliability of these methods are controversial, the importance of a variety of measurements could be specified in the conclusion. Additionally, if available, authors should have used liquid chromatography-tandem mass spectrometry, which is a state-of-the-art analytical technique for vitamin D measurement and offers advantages of improved specificity and sensitivity.
      • Kasahara A.K.
      • Singh R.J.
      • Noymer A.
      Vitamin D (25OHD) serum seasonality in the United States.
      • Singh R.J.
      Quantitation of 25-OH-vitamin D (25OHD) using liquid tandem mass spectrometry (LC-MS-MS).
      In conclusion, preanalytical factors such as time of sampling and/or seasonality of the measure and should be considered for the studies including vitamin D measurements and use of state-of-the-art methods for vitamin D measurement would improve credibility of the study.

      References

        • Franasiak J.M.
        • Molinaro T.A.
        • Dubel E.K.
        • et al.
        Vitamin D levels do not affect IVF outcomes following the transfer of euploid blastocysts.
        Am J Obstet Gynecol. 2015; 212: 315.e1-315.e6
        • Kasahara A.K.
        • Singh R.J.
        • Noymer A.
        Vitamin D (25OHD) serum seasonality in the United States.
        PloS One. 2013; 8: e65785
        • Singh R.J.
        Quantitation of 25-OH-vitamin D (25OHD) using liquid tandem mass spectrometry (LC-MS-MS).
        Methods Mol Biol. 2010; 603: 509-517

      Linked Article

      • Vitamin D levels do not affect IVF outcomes following the transfer of euploid blastocysts
        American Journal of Obstetrics & GynecologyVol. 212Issue 3
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          We sought to characterize the relationship between serum 25-hydroxy vitamin D (25-OH D) levels and implantation and clinical pregnancy rates in women who undergo a euploid blastocyst embryo transfer.
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        American Journal of Obstetrics & GynecologyVol. 212Issue 3
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          We read with interest the commentary by Sertoglu et al in response to our article in which we detail the lack of correlation between 25-hydroxy vitamin D (25-OH D) levels and in vitro fertilization outcomes when embryonic aneuploidy and quality are normalized.1 Indeed, when using either categorical ranges for 25-OH D (<20, 20-29.9, and ≥30 ng/mL) or serum 25-OH D as a continuous variable in a receiver operating characteristic analysis, a meaningful difference was not found.
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        American Journal of Obstetrics & GynecologyVol. 212Issue 3
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          We read with interest the comments by Garcia-Velasco et al in response to our article in which we detail the lack of correlation between 25-hydroxy vitamin D levels and reproductive outcomes during in vitro fertilization with euploid blastocysts. As the authors indicated, they have concomitantly published a recent article that shows similar findings in women undergoing oocyte donation, an experimental model that also makes attempts to control for embryonic factors.1 They also completed additional analyses that address some of the discussion points raised in our article regarding vitamin D binding protein and free vitamin D.
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      • Vitamin D and in vitro fertilization outcome
        American Journal of Obstetrics & GynecologyVol. 212Issue 3
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          We read with great interest the recent publication by Franasiak et al1 regarding the impact of vitamin D levels on reproductive outcome of women undergoing in vitro fertilization. As the authors mentioned, it seems that lack of vitamin D is an epidemic and its insufficiency is being associated with an increasing list of chronic conditions, adverse pregnancy outcome, and–lately–compromised fertility results. Opposed to the current trend,2,3 authors described in the largest sample analyzed so far of in vitro fertilization patients that vitamin D status was unrelated to pregnancy outcomes.
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