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tests in particular, is required to avoid over the ability of tests currently in

aviors, with the possible exceptioncigarette smoking (2).

RESERVE?nd qualityries signif-similar age.

tsdnnnl.neri-

ASRM PAGESWHAT IS OVARIANRESERVE?Clearly, women of the same age canhave very different responses to

In most cases, the cause(s) of DORare unknown. It is unclear whetherDOR represents a pathologic conditionresulting from abnormally rapid atresiain a normal pool of oocytes, from

Consequently, a number of tesinvolving biochemical measures anovarian imaging, collectively knowas ovarian reserve tests, have beeproposed to help predict ovariareserve and/or reproductive potentiaIn women with regular menses, ovariareserve tests do not predict wheththey are entering menopause or per

Received December 1, 2014; accepted December 2, 2014.Reprint requests: Practice Committee of the American Society for Reproductive Medicine, 1209Mont-

gomery Hwy., Birmingham, Alabama 35216 (E-mail: ASRM@asrm.org).confusion and misinterpretation, ormisuse of results.

use to predict three related, butdistinctly different, outcomes: oocytequality, oocyte quantity, and fecundity.

Although oocyte number adecline with age, fertility vaicantly among women of aof ovarian reserve testing. An under-standing of the limitations of screeningtests in general, and ovarian reserve

mary ovarian insufciency) (1).Although ovarian reserve tests havebeen applied widely, debate continues WHY MEASURE OVARIANin an individual woman. Nonetheless,clinicians often are asked for adviceon fertility potential and recommenda-tions for fertility treatments. This docu-ment reviews the evidence relating tothe clinical utility and predictive value

menses whose response to ovarianstimulation or fecundity is reducedcompared with women of comparableage. Decreased ovarian reserve isdistinct from menopause or prematureovarian failure (also referred to as pri-

genmotionnotbehofdeclines with age, it is difcult to pre-dict the pace of reproductive decline

reserve (DOR) describes womenof reproductive age having regular

ated with exposure to systemicchemotherapy, pelvic irradiation, and

etic abnormalities (e.g., 45,X chro-somal mosaicism, FMR1 premuta-s). Decreased ovarian reserve hasbeen associated with other lifestyleregenerate. Although female fertility Decreased or diminished ovarian cytes and fertility potential are associ-peak in number during fetal life, un-dergo atresia thereafter, and do not

potential as a function of the numberand quality of remaining oocytes.

population distribution of the numberof oocytes at a given age. A loss of oo-Practice Committee of the American S

American Society for Reproductive Medicin

Currently there is no uniformly accepteddistinctly different outcomes: oocyte qualmance of ovarian reserve tests is limiteddesign, analyses and outcomes, and the2015;-:--. 2015 by American SociEarn online CME credit related to this do

Discuss: You can discuss this article withfertstertforum.com/asrmpraccom-measu

T he process of reproductive agingcenters on the generally acceptedprinciple that human oocytesof ovarian recommittee oFertility and Sterility Vol.-, No.-,- 2015 0015-Copyright 2015 American Society for Reproductivehttp://dx.doi.org/10.1016/j.fertnstert.2014.12.093

VOL.- NO.- /- 2015erve: ainion

iety for Reproductive Medicine

Birmingham, Alabama

nition of decreased ovarian reserve (DORoocyte quantity, or reproductive potentiasmall sample sizes, heterogeneity amongof validated outcome measures. (Fertil Sfor Reproductive Medicine.)ment at www.asrm.org/elearn

uthors and with other ASRM members at h-ovarian-reserve/

ovarian stimulation and have differingreproductive potential. The concept ofovarian reserve views reproductive0282/$36.00Medicine, Published by Elsevier Inc.vailable evidence concerning the perfor-dyil

://

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normal atresia of an abnormally smallinitial pool of oocytes, or simply theextreme end of a normal bell-shapedeasuresmenopause or distinguish whetherthey are experiencing a decline in

e1

some have screened a general IVF population, others have tar-geted populations of older women, seeking to discriminatewomen with good prognoses from those with poor prognosesdespite their similar chronologic age.

Measures of ovarian reserve have been used to predictDOR, but DOR has been dened in different ways, includingboth reduced fecundability (the ability to achieve pregnancy)and poor ovarian response to gonadotropin stimulation. Mea-sures of ovarian response such as the number of follicles, thenumber of oocytes retrieved, the number of embryos, andcancellation rate are surrogates for the clinically importantoutcomes: pregnancy and live birth. These surrogate out-

R11.4 mIU/mL) (3). Good screening tests have validity.fertility that is pathologic or expected. When caring for acouple with infertility, clinicians use factors such as ageand diagnoses to counsel individual patients and tailor thetreatment plan. The goal of ovarian reserve testing is to addmore prognostic information to the counseling and planningprocess so as to help couples choose among treatment op-tions. However, it is important to emphasize that ovarianreserve tests are not infallible and should not be the solecriteria used to deny patients access to assisted reproductivetechnology (ART) or other treatments. Evidence of DOR doesnot necessarily equate with inability to conceive.

WHAT ARE MEASURES OF OVARIANRESERVE?Ovarian reserve tests include both biochemical tests and ul-trasound imaging of the ovaries. Biochemical tests of ovarianreserve can be divided further into basal measurements,including measurement of follicle-stimulating hormone(FSH), estradiol, inhibin B, and antimullerian hormone(AMH), and provocative tests such as the clomiphene citratechallenge test (CCCT). Biochemical measures of ovarianreserve are intended to probe and to reect the biology ofthe aging ovary, the one component of the reproductivesystem most closely related to decreased fecundity.

Inhibin B and AMH are glycoprotein hormones producedby small ovarian follicles and are therefore direct measures ofthe follicular pool. Whereas AMH is primarily secreted by pri-mary, preantral, and antral follicles, inhibin B is secreted pri-marily by preantral follicles. As the number of ovarianfollicles declines with age, both AMH and early follicularphase inhibin B concentrations decline. Decreased inhibin Bsecretion lowers the level of central negative feedback, result-ing in increased pituitary FSH secretion and in higher lateluteal and early follicular FSH concentrations (an indirectmeasure). In turn, the earlier increase in FSH levels stimulatesan earlier onset of new follicular growth and increase in estra-diol concentrations, ultimately decreasing the length of thefollicular phase and the overall cycle. Dynamic ovarianreserve tests assess the response of the hypothalamicpitui-taryovarian axis to a stimulus.

Ultrasonographic measures of ovarian reserve includeantral follicle count (AFC) and ovarian volume. The AFCdescribes the total number of follicles measuring 210 milli-meters in diameter that are observed during an early follicularphase transvaginal scan. The number of antral follicles corre-lates with the size of the remaining follicular pool and thenumber of oocytes retrieved following stimulation. Ovarianvolume declines with age and is therefore another potentialindicator of ovarian reserve.

HOW ARE OVARIAN RESERVE TESTS USED?Historically, ovarian reserve tests were intended to be used toscreen patients before beginning a cycle of in vitro fertiliza-tion (IVF) and to treat only those patients falling within anormal range as dened by each center. However, studiesexamining the performance of ovarian reserve tests have

ASRM PAGESused heterogeneous patient populations and outcome mea-sures, vastly complicating their interpretation. Whereas

e2Sensitivity and specicity are two measures of test validity(Fig. 1). A valid test correctly categorizes persons who havedisease as test positive (highly sensitive) and those withoutdisease as test negative (highly specic). In other words, ahighly sensitive test would capture all of the patients whohave DOR. Changing cutpoints to optimize sensitivity wouldminimize the number of false negatives (patients with DORcategorized as normal) but increase false-positive test results(patients with normal ovarian reserve categorized as having

FIGURE 1

Decreased ovarian reserve+ -

Ova

rian

rese

rve

test

re

sult

Test + A(True positives)B

(False positives)

Test - C(False negatives)D

(True negatives)

2 2 table to calculate test characteristics of a screening test.Sensitivity A/AC; Specicity D/BD; Positive predictive valuecomes are related to the clinically important outcomes butare not synonymous. Heterogeneity in study populationsand varied exposures and outcomes have resulted in a widerange of test characteristics for measures of ovarian reservereported in the literature. Therefore, the reported effective-ness of ovarian reserve tests as screening tests varies.Accordingly, it is important to consider study designs care-fully when applying the results of these screening studies toindividual patients.

BASIC PRINCIPLES OF SCREENING TESTSThe purpose of a screening test is to identify persons at risk fora disease. The purpose of using ovarian reserve testing as ascreening test is to identify infertility patients at risk forDOR, who are more likely to exhibit a poor response togonadotropin stimulation and to have a lesser chance ofachieving pregnancy with ART, most commonly IVF.

A screening test has a number of test characteristics,including sensitivity, specicity, positive predictive value(PPV), and negative predictive value (NPV), all of whichchange with the diagnostic threshold, or cutpoint, used toclassify an individual as being at risk for DOR (e.g., FSH A/AB; Negative predictive value D/CD.Practice Committee. Ovarian reserve testing. Fertil Steril 2015.

VOL.- NO.- /- 2015

The variability in FSH levels often prompts clinicians torepeat the test. Whereas consistently elevated FSH concentra-DOR). A highly specic test would correctly identify all of thepatients who do not have DOR. Changing cutpoints to opti-mize specicity would minimize false positives but increasefalse negatives.

Graphically, the sensitivity and specicity of differentcutpoints of a diagnostic test can be plotted as receiver oper-ating characteristic (ROC) curves. These curves help identifythe cutpoint that maximizes sensitivity and specicity. How-ever, the diagnostic threshold that optimally balances spec-icity and sensitivity for identifying patients at risk for DORnecessarily sacrices some specicity to improve sensitivityand thus may not be the best choice for clinical care.

For clinical application, the threshold for considering anovarian reserve test abnormal should have high specicityfor DOR. Specicity is the test characteristic that should beoptimized to decrease false positives, or wrongly categorizingpatients with normal ovarian reserve as having DOR. For theclinician, a highly specic test helps to avoid over-aggressivetreatment in patients with normal ovarian reserve. Addition-ally, it will avoid recommending adoption or oocyte donationto patients who may have the potential to have their owngenetic offspring. Because sensitivity is sacriced when spec-icity is optimized, a highly specic test for DOR also wouldresult in more women attempting IVF outcomes not knowingthat the prognosis is poor.

Positive predictive value and NPV are screening testcharacteristics that change with the prevalence of disease(DOR) in the study population. The PPV is the probabilitythat a woman who tests positive truly has DOR. The NPVis the probability that a woman who tests negative hasnormal ovarian reserve.

The most important test characteristics of a screeningovarian reserve test are its predictive values rather than sensi-tivity or specicity. Although predictive value is determinedby sensitivity and specicity, it also is dependent on the prev-alence of DOR in the population. This principle is important indetermining whom to screen. If the prevalence or risk of DORis low (e.g., in young women), the PPV (the probability that awoman who tests positive truly has DOR) will be low, even ifthe sensitivity and specicity are high. If the prevalence ofDOR is high (e.g., in older women), the PPV will be high if ahighly specic test cutpoint is chosen. Therefore, it is obviousthat ovarian reserve testing is most useful in identifying DORin women at high risk for DOR. Ideally, for tests of ovarianreserve to be clinically useful for patient counseling, the testcharacteristics and prevalence of DOR in a specic populationor clinic should be known. The wide range of values reportedin the literature makes it difcult to use these measuresclinically.

The use of a screening test for DOR in a population at lowrisk for the condition poses several problems. Most impor-tantly, many women will be categorized as having DORwho, in fact, have a normal ovarian reserve. The implicationsare important when screening women who have not yetreceived infertility treatment and those who may simply becurious about their reproductive potential. Ovarian reservetesting in women at low risk for DOR will yield a larger num-

ber of false-positive results (lower PPV) (4). The problem iscompounded in the use of home tests, where a qualied

VOL.- NO.- /- 2015tions confer a poor prognosis (13), a single elevated FSH valuein women

should not wait for the ideal cycle, wherein the FSH concen-tration is normal, to undergo IVF stimulation (5, 14).

It has been reported that basal FSH has limited utility as ascreening test (8, 15, 16). At high cutpoints that maximizespecicity, sensitivity is moderate for poor response tostimulation and very low for failure to achieve pregnancy.Although relatively few women with DOR will testabnormally if cutpoints are high, those who do have anabnormal test are very likely to have DOR.

In summary, a single FSH value has very limited reli-ability because of inter- and intra-cycle variability (particu-larly if it is not elevated). An elevated FSH value has goodspecicity but may represent a false positive especiallywhen used in a low-risk population. Given the inter-assayvariability of FSH, the cutpoint selected by an IVF programideally should be based on its own data or on data fromstudies using the same FSH assay (Table 1).

Estradiol

As a test of ovarian reserve, basal estradiol on day 2, 3, or 4 ofthe menstrual cycle has poor inter- and intra-cycle reliability

early follicular phase, there is limited evidence for anassociation with poor response, increased cancellation rates,or lower pregnancy rates (2830).

Clomiphene Citrate Challenge Test

The CCCT involves measurements of serum FSH before (cycleday 3) and after (cycle day 10) treatment with clomiphenecitrate (100 mg daily, cycle days 59). Whereas rising inhibinB and estradiol levels derived from a growing cohort of ovarianfollicles will suppress FSH in women with responsive ovaries,the smaller follicular cohorts that can be recruited in womenwith DOR will generate less inhibin B and estradiol, resultingin decreased negative feedback inhibition of FSH secretionand higher stimulated FSH concentrations. An elevated FSHconcentration after clomiphene stimulation therefore suggestsDOR. Studies of CCCT results have observed signicant inter-cycle variability in stimulated FSH levels and in the differencebetween basal and stimulated estradiol and inhibin B concen-trations, which limits the reliability of the CCCT (6, 31, 32). Asystematic review examined the ability of the CCCT topredict poor ovarian response or pregnancy after IVF over a

Summary of the value of screening tests of ovarian reserve.

reg

S

67100 Limited Higher sensitivitythan basal FSH

ReliabilityLimited additional value

ASRM PAGESTest Cutpoint

Poor response Non-p

Sensitivity(%)

Specicity(%)

Sensitivity(%)

FSH 1020 IU/L 1080 83100 758

AMH 0.20.7 ng/mL 4097 7892 a

AFC 310 973 73100 833

Inhibin B 4045 pg/mL 4080 6490 a

CCCT(day-10 FSH)

1022 IU/L 3598 6898 2361

Note: Laboratories ELISA.(17). The vast majority of studies have found that basalestradiol does not differ between women with and withoutDOR, regardless of whether the measured outcome is poorresponse to ovarian stimulation or failure to achieve preg-nancy (1828). Basal estradiol alone should not be used toscreen for DOR. The test has value only as an aid to correctinterpretation of a normal basal serum FSH value. Asdiscussed earlier, an early rise in serum estradiolconcentrations is a classic characteristic of reproductiveaging and can lower an otherwise elevated basal FSH levelinto the normal range, thereby causing a misinterpretationof the test. When the basal FSH concentration is normalbut the estradiol level is elevated (>6080 pg/mL) in the

TABLE 1a Insufcient evidence.

Practice Committee. Ovarian reserve testing. Fertil Steril 2015.

e4to basal FSHRequires drugadministrationrange of day-10 FSH levels (1022 IU/L) in women at low,average, and high risk for DOR. For the outcome of poorovarian response, the specicity of day-10 FSH concentrationsranged between 47% and 98% and sensitivity varied between35% and 93% (33). For the outcome of failure to achieve preg-nancy, specicity has been found to range between 67% and100% and sensitivity between 13% and 66%, depending onthe study (33). In other words, out of 10 females who do notconceive through IVF, between 1 and 7 women would havehad an abnormal day-10 FSH value (sensitivity) and of 10women who do conceive, 710 would have a normal day-10FSH value. In studies comparing the test performance of basal(cycle day 3) and stimulated (cycle day 10) FSH values,

nancy

Reliability Advantages Limitationspecicity(%)

43100 Limited Widespread use ReliabilityLow sensitivity

a Good Reliability Limit of detectabilityTwo commercial assaysDoes not predictnon-pregnancy

64100 Good ReliabilityWidespread use

Low sensitivity

Limited ReliabilityDoes not predictnon-pregnancyVOL.- NO.- /- 2015

cutpoints are neither sensitive nor specic for predicting

more useful in the general IVF population or in women at highpregnancy (19, 49, 50). The range of test characteristics andthe variable prevalence of DOR in different studies make itdifcult to use these measures clinically. Ideally, site-specicdata should be used to counsel patients.

Studies restricted to women at low risk for DOR weresmall and used exclusion criteria such as an elevated FSH,older age, anovulation, and severe male factor (51, 52).Outcomes have varied from%5 retrieved oocytes to clinicalpregnancy per oocyte retrieval. Cutpoints of 2.52.7 ng/mLstimulated FSH levels have higher sensitivity but lower speci-city than basal FSH concentrations (33). Compared with basalFSH and AFC, the clomiphene-stimulated day-10 FSH leveldoes not clearly improve test accuracy for predicting poorovarian response or pregnancy after IVF (3234).

In summary, basal measures of FSH may be preferable tothe CCCT, unless one is using the test to purposely increasesensitivity (Table 1).

Antimullerian Hormone

Serum concentrations of AMH, produced by granulosa cells ofearly follicles, are gonadotropin-independent and thereforeremain relatively consistent within and between menstrualcycles in both normal, young ovulating women and in womenwith infertility (17, 3537).

Antimullerian hormone was assayed previously using pri-marily two different assay kits (38). The current commerciallyavailable assay kit that is based on different technology has re-placed the older assays (39, 40). Although the results obtainedwith the two earlier kits are highly correlated, the standardcurves are not parallel, and there is no universally applicableconversion factor (41). Therefore, cutpoints developed andreported for one commercial AMH assay are not generalizableto the other commercial assay(s). When applying AMHcutpoints in clinical practice, clinicians must be very careful todetermine that the assay used to measure AMH is the same asthat used in the reference study population. Moreover, resultscan have a high coefcient of variation and vary amongdifferent commercial laboratories using the same assay (42).

Studies of AMH as a screening test for ovarian reservehave involved three different study populationsgeneralIVF population, subpopulation of women at low risk forDOR, and subpopulations of women at high risk for DOR.Overall, lower AMH levels have been associated with, butdo not necessarily predict, poor responses to ovarian stimula-tion, poor embryo quality, and poor pregnancy outcomes inIVF (4347). Studies that correlate different mean AMHlevels with IVF outcomes do not provide useful AMHcutpoints for clinical care (18, 44, 45, 48).

In various studies of general IVF populations, low AMHcutpoints (0.20.7 ng/mL DSL ELISA) have been found tohave sensitivities ranging between 40% and 97% and specic-ities varying from 78% to 92% for

the NPV is high (95%97%) in general IVF populations

(43, 48). In populations at high risk for DOR, PPV can be ashigh as 83% (21). The large majority of studies havedemonstrated that inhibin B does not discriminate betweenpregnancy and failure to conceive (20, 21, 24, 62, 63).

In summary, the routine use of inhibin B as a measure ofovarian reserve is not recommended (Table 1).

Ovarian Volume

Ovarian volume is calculated by measuring each ovary inthree planes and using the formula for the volume of anellipsoid (D1 D2 D3 0.52 volume). Mean ovarianvolume is the average volume of both ovaries in the sameindividual. Ovarian volume has limited reliability as anovarian reserve test. Some studies report clinically signi-cant inter-cycle variability, but this observation is notconsistent (4, 21, 64). When ovarian volume is acquiredand stored by three-dimensional (3D) ultrasound, intra-and inter-observer variability is minimized, but specializedequipment is required (65). Overall, ovarian volume corre-lates with number of follicles and retrieved oocytes butnot as well with pregnancy (22, 57, 6668). In addition,studies of ovarian volume often have excluded patientswith ovarian pathology, including those with polycysticovary syndrome, endometriomas, and large cysts (69, 70).Thus, the generalizability is limited.

Several studies have demonstrated that low ovarian vol-ume, typically

Poor ovarian response to maximal stimulation during IVF

appropriate, taking into account the needs of the individualpatient, available resources, and institutional or clinical prac-tice limitations. The Practice Committee and the Board ofreects DOR. There is insufcient evidence to indicate that the combinedtwo or more measures may be clinically useful but requirefurther validation.

SUMMARY

Currently, there is no uniformly accepted denition ofDOR, as the term may refer to three related but distinctlydifferent outcomes: oocyte quality, oocyte quantity, orreproductive potential.

Evidence of DOR does not necessarily equate with inabilityto conceive.

Available evidence concerning the performance of ovarianreserve tests is limited by small sample sizes, heterogeneityamong study design, analyses and outcomes, and by thelack of validated results. The design of published studiesmust be examined carefully before applying the results inclinical practice.

The use of a screening test for DOR in a population at lowrisk for DOR will yield a larger number of false-positive re-sults (i.e., characterizing a woman as DOR when in fact shehas normal ovarian reserve).

Overall, FSH is the most commonly used screening test forDOR, but AFC and AMH exhibit less variability and there-fore are promising predictors.

A single FSH value has very limited reliability because ofinter- and intra-cycle variability.

There is fair evidence to refute the notion that ovarianresponse and pregnancy rates will be improved in cycleswherein the FSH concentration is normal among womenpreviously exhibiting abnormally elevated values.

There is fair evidence against the use of basal estradiol con-centration as a single screening test for DOR, but there isfair evidence that the basal estradiol concentration helpsin the accurate interpretation of basal FSH concentrationsused to screen for DOR.

There is fair evidence to suggest that a clomiphene citratechallenge test has mildly increased sensitivity for detectingDOR compared with basal FSH concentration.

There is mounting evidence to support the use of AMH as ascreening test for poor ovarian response, but more data areneeded.

There is emerging evidence to suggest that a low AMH level(e.g., undetectable AMH) has high specicity as a screen forpoor ovarian response but insufcient evidence to suggestits use to screen for failure to conceive.

There is fair evidence to support that a low antral folliclecount (

ASRM PAGES8. Esposito MA, Coutifaris C, Barnhart KT. A moderately elevated day 3 FSHconcentration has limited predictive value, especially in younger women.Hum Reprod 2002;17:11823.

9. Scott RT Jr, Elkind-Hirsch KE, Styne-Gross A, Miller KA, Frattarelli JL. The pre-dictive value for in vitro fertility delivery rates is greatly impacted by themethod used to select the threshold between normal and elevated basalfollicle-stimulating hormone. Fertil Steril 2008;89:86878.

10. Thum MY, Abdalla HI, Taylor D. Relationship between women's age andbasal follicle-stimulating hormone levels with aneuploidy risk in in vitro fertil-ization treatment. Fertil Steril 2008;90:31521.

11. Massie JA, Burney RO, Milki AA, Westphal LM, Lathi RB. Basal follicle-stimulating hormone as a predictor of fetal aneuploidy. Fertil Steril 2008;90:23515.

12. Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, et al. Exec-utive summary: Stages of Reproductive Aging Workshop (STRAW). FertilSteril 2001;76:8748.

13. Roberts JE, Spandorfer S, Fasouliotis SJ, Kashyap S, Rosenwaks Z. Taking abasal follicle-stimulating hormone history is essential before initiatingin vitro fertilization. Fertil Steril 2005;83:3741.

14. Abdalla H, Thum MY. Repeated testing of basal FSH levels has no predictivevalue for IVF outcome in women with elevated basal FSH. Hum Reprod2006;21:1714.

15. Bancsi LF, Broekmans FJ, Mol BW, Habbema JD, te Velde ER. Performance ofbasal follicle-stimulating hormone in the prediction of poor ovarian responseand failure to become pregnant after in vitro fertilization: a meta-analysis.Fertil Steril 2003;79:1091100.

16. Jain T, Soules MR, Collins JA. Comparison of basal follicle-stimulating hor-mone versus the clomiphene citrate challenge test for ovarian reservescreening. Fertil Steril 2004;82:1805.

17. Fanchin R, Taieb J, Lozano DH, Ducot B, Frydman R, Bouyer J. High reproduc-ibility of serum anti-Mullerian hormone measurements suggests a multi-staged follicular secretion and strengthens its role in the assessment ofovarian follicular status. Hum Reprod 2005;20:9237.

18. Hazout A, Bouchard P, Seifer DB, Aussage P, Junca AM, Cohen-Bacrie P.Serum antimullerian hormone/mullerian-inhibiting substance appears tobe a more discriminatory marker of assisted reproductive technologyoutcome than follicle-stimulating hormone, inhibin B, or estradiol. FertilSteril 2004;82:13239.

19. Ficicioglu C, Kutlu T, Baglam E, Bakacak Z. Early follicular antimullerian hor-mone as an indicator of ovarian reserve. Fertil Steril 2006;85:5926.

20. Eldar-Geva T, Ben-Chetrit A, Spitz IM, Rabinowitz R, Markowitz E, Mimoni T,et al. Dynamic assays of inhibin B, anti-Mullerian hormone and estradiolfollowing FSH stimulation and ovarian ultrasonography as predictors ofIVF outcome. Hum Reprod 2005;20:317883.

21. McIlveen M, Skull JD, Ledger WL. Evaluation of the utility of multiple endo-crine and ultrasound measures of ovarian reserve in the prediction of cyclecancellation in a high-risk IVF population. Hum Reprod 2007;22:77885.

22. Bancsi LF, Broekmans FJ, Eijkemans MJ, de Jong FH, Habbema JD, teVelde ER. Predictors of poor ovarian response in in vitro fertilization: a pro-spective study comparing basal markers of ovarian reserve. Fertil Steril 2002;77:32836.

23. Frattarelli JL, Lauria-Costab DF, Miller BT, Bergh PA, Scott RT. Basal antral fol-licle number and mean ovarian diameter predict cycle cancellation andovarian responsiveness in assisted reproductive technology cycles. FertilSteril 2000;74:5127.

24. Hall JE, Welt CK, Cramer DW. Inhibin A and inhibin B reect ovarian functionin assisted reproduction but are less useful at predicting outcome. Hum Re-prod 1999;14:40915.

25. Penarrubia J, Balasch J, Fabregues F, Carmona F, Casamitjana R, Moreno V,et al. Day 5 inhibin B serum concentrations as predictors of assisted repro-ductive technology outcome in cycles stimulated with gonadotrophin-releasing hormone agonist-gonadotrophin treatment. Hum Reprod 2000;15:1499504.

26. Phophong P, Ranieri DM, Khadum I, Meo F, Serhal P. Basal 17beta-estradioldid not correlate with ovarian response and in vitro fertilization treatmentoutcome. Fertil Steril 2000;74:11336.e827. Ranieri DM, Quinn F, Makhlouf A, Khadum I, GhutmiW,McGarrigle H, et al.Simultaneous evaluation of basal follicle-stimulating hormone and 17 be-taestradiol response to gonadotropin-releasing hormone analogue stimula-tion: an improved predictor of ovarian reserve. Fertil Steril 1998;70:22733.

28. Evers JL, Slaats P, Land JA, Dumoulin JC, Dunselman GA. Elevated levels ofbasal estradiol-17beta predict poor response in patients with normal basallevels of follicle-stimulating hormone undergoing in vitro fertilization. FertilSteril 1998;69:10104.

29. Licciardi FL, Liu HC, Rosenwaks Z. Day 3 estradiol serum concentrations asprognosticators of ovarian stimulation response and pregnancy outcomein patients undergoing in vitro fertilization. Fertil Steril 1995;64:9914.

30. Smotrich DB, Widra EA, Gindoff PR, Levy MJ, Hall JL, Stillman RJ. Prognosticvalue of day 3 estradiol on in vitro fertilization outcome. Fertil Steril 1995;64:113640.

31. Hannoun A, Abu Musa A, Awwad J, Kaspar H, Khalil A. Clomiphene citratechallenge test: cycle to cycle variability of cycle day 10 follicle stimulatinghormone level. Clin Exp Obstet Gynecol 1998;25:1556.

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33. Hendriks DJ, Mol BW, Bancsi LF, te Velde ER, Broekmans FJ. The clomiphenecitrate challenge test for the prediction of poor ovarian response and non-pregnancy in patients undergoing in vitro fertilization: a systematic review.Fertil Steril 2006;86:80718.

34. Yanushpolsky EH, Hurwitz S, Tikh E, Racowsky C. Predictive usefulness ofcycle day 10 follicle-stimulating hormone level in a clomiphene citrate chal-lenge test for in vitro fertilization outcome in women younger than 40 yearsof age. Fertil Steril 2003;80:1115.

35. Tsepelidis S, Devreker F, Demeestere I, Flahaut A, Gervy C, Englert Y. Stableserum levels of anti-Mullerian hormone during the menstrual cycle: a pro-spective study in normo-ovulatory women. Hum Reprod 2007;22:183740.

36. La Marca A, Stabile G, Artenisio AC, Volpe A. Serum anti-Mullerian hor-mone throughout the human menstrual cycle. Hum Reprod 2006;21:31037.

37. Hehenkamp WJ, Looman CW, Themmen AP, de Jong FH, te Velde ER,Broekmans FJ. Anti-Mullerian hormone levels in the spontaneous menstrualcycle do not show substantial uctuation. J Clin Endocrinol Metab 2006;91:405763.

38. La Marca A, Sighinol G, Radi D, Argento C, Baraldi E, Artenisio AC, et al.Anti-mullerian hormone (AMH) as a predictive marker in assisted reproduc-tive technology (ART). Hum Reprod Update 2010;16:11330.

39. Coulter Beckman. AMH Gen II Elisa package insert. Brea, CA: BeckmanCoulter; 2011.

40. Nelson SM, La Marca A. The journey from the old to the new AMH assay:how to avoid getting lost in the values. Reprod Biomed Online 2011;4:41120.

41. Freour T, Mirallie S, Bach-Ngohou K, Denis M, Barriere P, Masson D. Mea-surement of serum anti-Mullerian hormone by Beckman Coulter ELISAand DSL ELISA: comparison and relevance in assisted reproduction technol-ogy (ART). Clin Chim Acta 2007;375:1624.

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Testing and interpreting measures of ovarian reserve: a committee opinionWhat is ovarian reserve?Why measure ovarian reserve?What are measures of ovarian reserve?How are ovarian reserve tests used?basic principles of screening testsBasal FSHEstradiolClomiphene Citrate Challenge TestAntimllerian HormoneAntral Follicle CountInhibin BOvarian VolumeOvarian Response

Combined ovarian reserve testsSummaryConclusionsAcknowledgmentsReferences