LETTER TO THE EDITOR REPLY OF THE AUTHORS: We appreciated reading the thoughtful commentary by Kollmann and colleagues in response to our article. They brought forth several issues relating to the definition and significance of polycystic ovarian morphology (PCOM) that warrant further and more widespread dialogue. First, they too acknowledge the urgent need to implement a higher follicle threshold for PCOM than the outdated value of R12 follicles per ovary, which unfortunately continues to be recommended (1). Similar to those of other investigators (2), our data using newer imaging technology clearly support a substantially higher follicle threshold—26 versus 12 follicles—to distinguish between the normal and polycystic ovary syndrome (PCOS) condition (3). Indeed, in our recent review of follicle counts reported for healthy women of reproductive age (4), there is evidence of a technology-dependent increase in the number of follicles that are now visible using higher frequency transducers (R8 MHz), which afford better image resolution. Second, Kollmann et al. recommend that thresholds for PCOM be based on normative data. This is consistent with the approach taken by the Androgen Excess and PCOS Society, whose recently proposed threshold of R25 follicles per ovary was based on the estimated 95th percentile of follicle counts made in >1,000 healthy women of which our control series was included (4). We agree that a comprehensive evaluation of ovarian morphology in healthy women across all ages is urgently needed in light of advancements in imaging technology. As for proposing thresholds based on an upper limit of normal, this is certainly an acceptable approach if and when the control population is carefully defined. Unlike the receiver operating characteristic curve analysis we employed, this approach is limited by a preselected falsepositive rate and no indication of the sensitivity of the marker to detect the diseased condition. However, we acknowledge that in the case of PCOS, where there is controversy regarding the actual clinical spectrum of PCOS, consideration of a normative series may be most prudent. Third, they urge that follicle patterning continue to be considered in the detection of PCOM. We agree that a peripheral distribution of follicles can be reliably assessed and is highly predictive of PCOS. However, our study did not show this marker to have greater specificity than follicle counts nor did it add appreciable diagnostic power when coupled

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with other sonographic markers. Moreover, follicle patterning lacked sensitivity to detect PCOS (only 27%). This might have reflected the broad definition for hyperandrogenism employed by our study (that is, either biochemical or clinical hyperandrogenism was sufficient). However, this hypothesis was not tested. Last, while there is the potential for follicle patterning to be less variable than follicle counts across the lifespan, we are unaware of any study that has prospectively evaluated this notion. In closing, we agree that the term ‘‘polycystic ovary’’ should be abandoned for a more appropriate description of the actual anatomical anomaly. The ovary is multi- or polyfollicular, and we must continue to educate our peers and patients on this point until there is sufficient consensus to support a name change for PCOS—which at present seems looming (5). Marla E. Lujan, Ph.D. Human Metabolic Research Unit, Division of Nutritional Sciences, Cornell University, Ithaca, New York January 9, 2014 http://dx.doi.org/10.1016/j.fertnstert.2014.01.013

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Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, et al. Diagnosis and treatment of polycystic ovary syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2013;98:4565–92. Dewailly D, Gronier H, Poncelet E, Robin G, Leroy M, Pigny P, et al. Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries. Hum Reprod 2011;26:3123–9. Lujan ME, Jarrett BY, Brooks ED, Reines JK, Peppin AK, Muhn N, Escobar Morreale HF. Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume. Hum Reprod 2013;28:1361–8. Dewailly D, Lujan ME, Carmina E, Cedars MI, Laven J, Norman RJ, Escobar Morreale HF. Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update 2013 Dec 16. [Epub ahead of print]. PMID: 24345633. Teede H, Gibson-Helm M, Norman RJ, Boyle J. Polycystic ovary syndrome: perceptions and attitudes of women and primary health care physicians on features of PCOS and renaming the syndrome. J Clin Endocrinol Metab 2014;99: E107–11.

VOL. 101 NO. 4 / APRIL 2014