Does it all come down to postnatal aging of the primary oocyte?

Abstract

I read with interest the article by Chuang et al. (1Chuang C.C. Chen C.D. Chao K.H. Chen S.U. Ho H.N. Yang Y.S. Age is a better predictor of pregnancy potential than basal follicle-stimulating hormone levels in women undergoing in vitro fertilization.Fertil Steril. 2003; 79: 63-68Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar). We have reached similar conclusions that when evaluating outcome of IVF-ET, advanced age is a better prognosticator of poor outcome than elevated early follicular phase serum FSH (2Check J.H. Nazari P. Check M.L. Choe J.K. Liss J.R. Prognosis following in vitro fertilization embryo transfer (IVF-ET) in patients with elevated day 2 or 3 serum follicle stimulating hormone (FSH) is better in younger vs older patients.Clin Exp Obstet Gynecol. 2002; 29: 42-44PubMed Google Scholar). Our study similarly concluded that elevated FSH in younger patients is more associated with decreased number of oocytes retrieved (2Check J.H. Nazari P. Check M.L. Choe J.K. Liss J.R. Prognosis following in vitro fertilization embryo transfer (IVF-ET) in patients with elevated day 2 or 3 serum follicle stimulating hormone (FSH) is better in younger vs older patients.Clin Exp Obstet Gynecol. 2002; 29: 42-44PubMed Google Scholar). It is attractive to attribute the poorer prognosis with increased FSH with advanced age to different etiologies for the diminished oocyte reserve; that is, that natural selection of recruitment of the best follicles leaves behind not only fewer but the worst oocytes with physiologic aging versus some damaging process in younger women that leaves diminished reserve but similar quality of oocytes to peers with normal FSH (1Chuang C.C. Chen C.D. Chao K.H. Chen S.U. Ho H.N. Yang Y.S. Age is a better predictor of pregnancy potential than basal follicle-stimulating hormone levels in women undergoing in vitro fertilization.Fertil Steril. 2003; 79: 63-68Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar). However, there is another hypothesis that could explain this phenomenon. Data suggest that controlled ovarian hyperstimulation (COH) can create an adverse uterine environment inhibiting implantation (3Check J.H. Choe J.K. Katsoff D. Summers-Chase D. Wilson C. Controlled ovarian hyperstimulation adversely affects implantation following in vitro fertilization-embryo transfer.J Assist Reprod Genet. 1999; 16: 416-420Crossref PubMed Scopus (113) Google Scholar). In addition, studies indicate that the older uterus is more susceptible to the adverse effects of COH based on higher or similar implantation rates in older patients (but not younger patients) with deselected frozen–thawed embryos compared to fresh ET (4Check J.H. Katsoff D. Brittingham D. Summers-Chase D. Wilson C. Comparable implantation rates with fresh vs frozen embryo transfer suggests that controlled ovarian hyperstimulation has an adverse effect on conception outcome.Clin Exp Obstet Gynecol. 2000; 27: 173-175PubMed Google Scholar). One way to support the authors’ hypothesis would be to evaluate the effect of age and FSH in the absence of COH. Such a study of patients not undergoing IVF-ET has been published (5Check J.H. Peymer M. Lurie D. Effect of age on pregnancy outcome without assisted reproductive technology in women with elevated early follicular phase serum follicle-stimulating hormone levels.Gynecol Obstet Invest. 1998; 45: 217-220Crossref PubMed Scopus (44) Google Scholar). The results showed a 6-month clinical and ongoing pregnancy rate of 46.1% and 34.6%, respectively, in women younger than 40 years of age 10.5% and 5.3% in those 40 years of age or older despite similar (about 20 mIU/mL) serum FSH levels (P < .05) (5Check J.H. Peymer M. Lurie D. Effect of age on pregnancy outcome without assisted reproductive technology in women with elevated early follicular phase serum follicle-stimulating hormone levels.Gynecol Obstet Invest. 1998; 45: 217-220Crossref PubMed Scopus (44) Google Scholar). These data from this latter study thus eliminates the possibility that the COH effect on the uterus rather than lesser-quality oocytes could account for the demonstrated age related decreased pregnancy rate in women with increased FSH. Thus, this study supports the authors’ hypothesis (5Check J.H. Peymer M. Lurie D. Effect of age on pregnancy outcome without assisted reproductive technology in women with elevated early follicular phase serum follicle-stimulating hormone levels.Gynecol Obstet Invest. 1998; 45: 217-220Crossref PubMed Scopus (44) Google Scholar).