Reply: ovarian reserve and reproductive age may be determined from measurement of ovarian volume by transvaginal sonography
1 Department of Haematology/Oncology, Royal Hospital for Sick Children, 17 Millerfield Place, Edinburgh EH9 1LW, Scotland and 2 School of Computer Science, University of St Andrews, UK
3 To whom correspondence should be addressed. Email: hamish.wallace{at}luht.scot.nhs.uk
Sir,
We welcome the opportunity to respond to the letter of Broekmans and colleagues. We agree that the assessment of reproductive potential in women is complex and is likely to include a mathematical synthesis of a number of indicators, both hormonal [anti-Mullerian hormone (AMH), FSH, inhibin B, for example] and physiological (antral follicle count, ovarian volume). Our finding, which remains a hypothesis requiring further research to verify, clearly shows a very strong correlation between ovarian volume and primordial follicle count. This central finding of our manuscript is not challenged (Wallace and Kelsey, 2004
).
We now address the specific reservations raised about our work. We agree that there is a small declining mean for ovarian volume before age 35–40 years. However, this small decline correlates strongly with the similar small decline in primordial follicle population over the same age range.
We disagree that ovarian volume is not a useful test of ovarian reserve in survivors of childhood cancer. We have shown that survivors of childhood cancer with regular menstrual cycles, when compared to controls had elevated serum FSH levels (7.5 ± 1.4 versus 4.2 ±0.3 IU/l; P=0.02), while AMH levels were lower (13.0 ±3.0 versus 21.0 ±3.4 pmol/l; P<0.05) respectively. Ovarian volume was smaller in cancer survivors than controls (3.0 ± 0.5 versus 5.0 ± 0.8 ml; P<0.05), but antral follicle count (AFC) was similar (Bath et al., 2003).
It is simply not true that our predictions do not extend beyond 50.4 years: the legend to our example figure clearly describes an individual with a predicted age at menopause of 54 years, and other examples can be constructed with a reproductive age up to 58 years.
The work they reference on antral follicle counts was discussed in our paper. However, the study they refer to (Scheffer et al., 2003) was based on data from 162 women, whereas our results are based on data from 59 000 women over a similar age range (Pavlik et al., 2000). Statistical inference in not always improved by taking more observations, but we think it highly unlikely that, in this case, using 59 000 observations will give markedly worse results.
As we clearly state in our conclusions, reproductive age assessment will probably include measurement of several physiological and endocrine indicators; ovarian volume is one of these.
References
Wallace WH and Kelsey TW (2004) Ovarian reserve and reproductive age may be determined from measurement of ovarian volume by transvaginal sonography. Hum Reprod 19, 1612–1617.
Bath LE, Wallace WH, Shaw MP, Fitzpatrick C and Anderson RA (2003) Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-Mullerian hormone, inhibin B and ovarian ultrasound. Hum Reprod 18, 2368–2374.
Scheffer GJ, Broekmans FJM, Looman CWN, Blankenstein M, Fauser BCJM, de Jong FH and te Velde ER (2003) The number of antral follicles in normal women with proven fertility is the best reflection of reproductive age. Hum Reprod 18, 700–706.
Pavlik EJ, DePriest PD, Gallion HH, Ueland FR, Reedy MB, Kryscio RJ and van Nagell JR (2000) Ovarian volume related to age. Gynecol Oncol 77, 410–412.[CrossRef][Web of Science][Medline]
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