Hum. Reprod. Advance Access originally published online on November 9, 2006
Human Reproduction 2007 22(3):901; doi:10.1093/humrep/del437
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Letters to the editor |
Reactive oxygen species and oocyte fertilization
1 Institute of Biotechnology and 2 Center for Biological and Health Sciences, University of Caxias do Sul, RS, Brazil
3 To whom correspondence should be addressed at: Institute of Biotechnology, University of Caxias do Sul, RS, Brazil. E-mail: fabio.conception{at}terra.com.br/ fabio{at}conception-rs.com.br
Sir,
The oocyte resides in a metabolically active environment consisting of steroid hormones, growth factors, cytokines, granulosa cells and leukocytes. Even though the impact of follicular fluid oxidative stress on oocyte maturation, fertilization and pregnancy is not clear, in bovine oocytes, the formation of reactive oxygen species (ROS) is reported to increase the developmental potential during in vitro maturation to produce embryos. Attaran et al. reported a beneficial role for ROS, with higher levels in follicular fluid in IVF conception cycles compared with non-conception cycles (Attaran et al., 2000
). It appears that ROS may have different effects at different stages of embryo development. The results demonstrated that women who became pregnant had higher levels of ROS than those who did not leading the authors to suggest that ROS, at low concentrations, may be a potential marker for predicting success of IVF patients. On the contrary, Ho et al. (1998) in genetic manipulation studies in mice found that mice that were made deficient in SOD had decreased litter size and decreased the number of litters per month.
We evaluated 41 women undergoing IVF (n = 26) or ICSI (n = 15). The main indications for IVF were male factor infertility (n = 16; 39%), tubo-peritoneal factors (n = 17; 42%), idiopathic infertility (n = 3; 7%) and ovulatory factors (n = 5; 12%) (Pasqualotto et al., 2004). After adjusting for age, the patients who did not become pregnant had significantly lower levels of lipid peroxidation (LPO) and total antioxidant capacity (TAC) compared with the patients who became pregnant. A positive correlation was seen between the grade 2 embryos and the TAC levels. After adjusting for age, a positive correlation was seen between the pregnancy rate and LPO and the pregnancy rate and TAC.
We read with great interest the recent article by Das et al. (2006) who suggested that high levels of ROS in follicular fluid obtained from women with tubal infertility tend to decrease the fertilization potential of oocytes. Higher percentage of embryo formation as well as good embryo quality was observed corresponding to follicular fluid with ROS levels <100 cps. This result is inconsistent with Attaran et al. (2000) and Pasqualotto et al. (2004) where interference of low ROS with pregnancy outcome is suggested.
One of the possible reasons for such different results regarding embryo quality/pregnancy rates between the studies from Pasqualotto and Attaran with the study published by Das is that Das et al. recruited only patients with tubal ligation and the other two studies enrolled patients with endometriosis, male factor infertility, tubo/peritoneal reasons, idiopathic infertility and ovulatory disorders. In patients with tubal ligation, no differences were detected in ROS and TAC levels between patients who got pregnant and who did not get pregnant. However, in patients with endometriosis, ROS levels were higher in patients who got pregnant compared with patients who did not get pregnant. In addition, the ROS/TAC score was higher in patients who did not get pregnant compared with patients who got pregnant.
Therefore, we believe, based on Attaran and Pasqualotto results, that follicles with lower levels of oxygen available (in hypoxia) could contain lower levels of LPO and TAC, but at the same time, they would have a smaller chance of establishing a pregnancy because of the hypoxaemic status. We argue that this may be associated with the intense metabolism of the developing follicle. Follicular fluid from patients with endometriosis must have higher content of ROS in order to have a better chance to a woman undergoing IVF cycle to get pregnant.
References
Attaran M, Pasqualotto E, Falcone T, Goldberg JM, Miller KF, Agarwal A, Sharma RK. (2000) The effect of follicular fluid reactive oxygen species on the outcome of in vitro fertilization. Int J Fertil Womens Med 45:314–320.[Web of Science][Medline]
Das S, Chattopadhyay R, Ghosh S, Goswami SK, Chakravarty BN, Chaudhury K. (2006) Reactive oxygen species level in follicular fluid – embryo quality marker in IVF? Hum Reprod 21:2403–2407.
Ho JS, Gargano M, Cao J, Bronson RT, Heimler I, Hutz RJ. (1998) Reduced fertility in female mice lacking copper ± zinc superoxide dismutase. J Biol Chem 273:7765–7769.
Pasqualotto EB, Agarwal A, Sharma RK, Izzo VM, Pinotti JA, Joshi NJ, Rose BI. (2004) Effect of follicular fluid on the outcome of assisted reproductive procedures. Fertil Steril 81:973–976.[CrossRef][Web of Science][Medline]
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