Ovarian reserve and reproductive age may be determined from measurement of ovarian volume by transvaginal sonography

Frank J. Broekmans1,3, Malcolm Faddy2 and Egbert R. te Velde1

1 Department of Reproductive Medicine, Division of Obstetrics, Gynecology and Neonatology, University Medical Center Utrecht, Utrecht, The Netherlands 2 School of Mathematical Sciences, Queensland University of Technology, Brisbane, Australia

3 To whom correspondence should be addressed. Email: f.broekmans{at}azu.nl

Sir,

We read with interest the recent paper by Wallace and Kelsey (2004)Go on the role of ovarian volume measured by ultrasound in the assessment of female reproductive status. The authors linked ovarian volume to primordial follicle numbers, by arguing that ovarian volume declined with age in a similar way to total follicle numbers in the analysis of Faddy and Gosden (1996)Go. Then they concluded that ovarian volume could thus be used instead of follicle numbers to predict reproductive potential. We feel that both the methodology used in the paper and the relative value of ovarian volume compared with other predictors of ovarian reserve are open to criticism.

First, our data on ovarian volume based on the studies by Scheffer et al. (2003)Go and those in Pavlik et al. (2000)Go that Wallace and Kelsey used, do not indicate much in the way of a declining mean before age 35–40 years, while follicle numbers decline from ~100 000 at age 25 to ~20 000 at age 40. So, predictions of reproductive potential based on ovarian volume should not differ by much more than chronological age at these young ages, and ovarian volume can be looked upon more as a late marker of ovarian ageing, much like basal FSH (Van Rooij et al., 2004Go). The applicability of ovarian volume as a test for ovarian reserve in survivors of childhood cancer might therefore be doubtful. Also, there is little change in mean ovarian volume after the age of 50 years, and Wallace and Kelsey's predictions of ‘reproductive age’ do not seem to extend beyond age 50.4 years. This is curious as ~50% of women experience menopause after this age!

Second, Faddy and Gosden (1996)Go linked the age-dependent decline in (total) follicle numbers to age at menopause via a threshold number of follicles ‘triggering’ menopause. A similar methodology can be applied to data on ovarian volume, and our data (Scheffer et al., 2003Go) suggest a (mean) threshold ovarian volume of 4.38 cm3 (based on two ovaries) which is remarkably close to twice Pavlik et al.'s reported mean ovarian volume [based on a single ovary (Pavlik et al., 2000Go)] of 2.2 cm3 from post-menopausal women. However, just like Faddy and Gosden's (1996)Go estimated menopausal threshold number of follicles, a threshold ovarian volume is not constant but will vary between women (median 4.1 cm3, and quartiles 3.3 and 5.2 cm3) so that predictions of reproductive potential based on ovarian volume will have additional uncertainties to those inherent to any indirect method.

Third, the methodology used by Wallace and Kelsey in constructing the predictions of ‘reproductive age’ is essentially based on percentiles of the distributions of (age-dependent) ovarian volume and menopausal age (at least for points A and B in their Figure 5) although the method is rather crude (e.g. straight-line segmented plots) and the use of a fixed point (C in their Figure 5), which has no interpretation in terms of percentiles, would seem rather peculiar. We have made similar percentile-based predictions of reproductive events based on antral follicle counts (Broekmans et al., 2004Go) which we feel will be as useful as those of Wallace and Kelsey, if not more so, as antral follicle counts show more substantial changes than ovarian volume over all age ranges from 25 to 50 years. Moreover, in direct comparisons between volume and count the antral follicle number has proven to be the best indicator of reproductive age (Bancsi et al., 2002Go; Scheffer et al., 2003Go). Also, from re-analysis of data on the prediction of the occurrence of the menopausal transition it has been shown that ovarian volume had lesser predictive power than antral follicle counts (Van Rooij et al., 2004Go).

If the authors are right in their last sentence that an easily reproducible test for reproductive status opens possibilities for screening for early ovarian ageing, we feel the antral follicle count must be considered a better candidate than ovarian volume.

References

Bancsi LF, Broekmans FJ, Eijkemans MJ, de Jong FH, Habbema JD and te Velde ER (2002) Predictors of poor ovarian response in in vitro fertilization: a prospective study comparing basal markers of ovarian reserve. Fertil Steril 77, 328–336.[CrossRef][ISI][Medline]

Broekmans FJ, Faddy MJ, Scheffer GJ and te Velde ER (2004) Antral follicle counts are related to age at natural fertility loss and age at menopause. Menopause 11, 607–614.[CrossRef][Medline]

Faddy MJ and Gosden RG (1996) A model conforming the decline in follicle numbers to the age of menopause in women. Hum Reprod 11, 1484–1486.[Abstract/Free Full Text]

Pavlik EJ, DePriest PD, Gallion HH et al. (2000) Ovarian volume related to age. Gynecol Oncol 77, 410–412.[CrossRef][ISI][Medline]

Scheffer GJ, Broekmans FJ, Looman CW et al. (2003) The number of antral follicles in normal women with proven fertility is the best reflection of reproductive age. Hum Reprod 18, 700–706.[Abstract/Free Full Text]

van Rooij IA, den Tonkelaar I, Broekmans FJ, Looman CW, Themmen AP and te Velde ER (2004) Anti-mullerian hormone is a promising marker for the prediction of the menopausal transition. Menopause 11, 601–606.[CrossRef][Medline]

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.[Abstract/Free Full Text]





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