Abstract

Nitric oxide, a key regulatory molecule in the follicular fluid, has been suggested as a possible biomarker to predict ovarian response in stimulated cycles and the potential of the retrieved oocytes for developing high-quality embryos. Nevertheless, a consensus on whether or not nitric oxide can help in this context has not been reached. We simultaneously measured the oxidation products of nitric oxide, nitrite, and nitrate, via high-performance liquid chromatography (HPLC)-UV in follicular fluid samples from 72 oocyte donors. We found no associations of follicular fluid nitrite, nitrate, total nitric oxide, or nitrate/nitrite ratio with total or metaphase II (MII) oocyte yield. However, nitrite and nitrate levels were related to the yield of MII oocytes when this outcome was expressed as a proportion of all oocytes retrieved. The adjusted MII proportion in the lowest and highest nitrite levels were 68% (58–77%) and 79% (70–85%), respectively (p, linear trend = 0.02), whereas the adjusted MII proportion in extreme tertiles of nitrate levels were 79% (70–85%) and 68% (57–77%) (p, linear trend = 0.03). In addition, nitrate levels showed a suggestive inverse correlation with embryos with maximum or high potential of implantation (p = 0.07). These results suggest that the follicular fluid concentrations of nitrite and nitrate may be a useful tool in predicting how healthy oocyte donors respond to superovulation and the implantation potential of the embryos produced from their oocytes.

Highlights

  • A large number of couples of reproductive age struggle with infertility issues, the causes of which are not always clear (Agarwal and Allamaneni, 2004)

  • The following data regarding the donation cycle were collected from IVI-RMA Global (Murcia, Spain) for all participants: total and metaphase II (MII) oocyte yield, number of stimulation days, 17β-estradiol (E2) peak, total dose of follicle-stimulating hormone (FSH), oocyte fate, and quality of the blastocyst derived from their oocytes

  • follicular fluid (FF) was obtained at oocyte retrieval in 93 oocyte donation cycles to measure NO2 and NO3 levels by HPLCUV (Figure 2)

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Summary

Introduction

A large number of couples of reproductive age struggle with infertility issues, the causes of which are not always clear (Agarwal and Allamaneni, 2004). For this reason, several studies have tried to identify new biochemical markers that can affect gamete and embryo quality and may predict the outcome of infertility treatment with in vitro fertilization (IVF) (Yalçınkaya et al, 2013). Nitric oxide (NO) has emerged as a candidate predictor of ovarian response and IVF outcomes (Barroso et al, 1999). When investigating the relation of intrafollicular levels of NO with oocyte recruiting, fertilization potential, embryo quality, implantation, and pregnancy rates in patients undergoing IVF, the results are contradictory. The relationship between FF, NO, and pregnancy outcome is uncertain (Lee et al, 2000; Kim et al, 2004; Yalçınkaya et al, 2013)

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