reproductive potential and ovarian reserve: how old is too old?

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State of art technologic advances in genetic screening of embryos using CGH methodology can select the best blastocyst for implantation but also neutralizes the risk of pregnancy loss with respect to age.

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Page 1: Reproductive Potential and Ovarian Reserve: How Old is Too Old?

www.chelseafertilitynyc.com

Page 2: Reproductive Potential and Ovarian Reserve: How Old is Too Old?

Paul R. Gindoff, MD 

Paul R. Gindoff, MD 

Reproductive Potential andReproductive Potential and Ovarian Reserve Ovarian Reserve

How Old is Too Old?How Old is Too Old?

Page 3: Reproductive Potential and Ovarian Reserve: How Old is Too Old?

Conclusions

Aneuploidy is fundamental in determining implantation and IVF success.Aneuploidy increases with age.State of art technologic advances in genetic screening of embryos using CGH methodology can select the best blastocyst for implantation but also neutralizes the risk of pregnancy loss with respect to age. (An alternative to donor egg.)

Page 4: Reproductive Potential and Ovarian Reserve: How Old is Too Old?

ObjectivesObjectivesn To understand the basics of ovarian To understand the basics of ovarian

reserve testing (ORT) and how age reserve testing (ORT) and how age affects its utility affects its utility

n To understand how to develop a To understand how to develop a prognosis and counsel patients for prognosis and counsel patients for treatment optionstreatment options

n To consider the challenges of age with To consider the challenges of age with respect to aneuploidy in terms of clinical respect to aneuploidy in terms of clinical pregnancy from ART and risk of pregnancy from ART and risk of miscarriage. The role of PGS-CGS.miscarriage. The role of PGS-CGS.

Page 5: Reproductive Potential and Ovarian Reserve: How Old is Too Old?

Graphic OverviewGraphic Overview

Menstrual Cycle / Ovarian CycleMenstrual Cycle / Ovarian Cycle

Page 6: Reproductive Potential and Ovarian Reserve: How Old is Too Old?

Cross Section of OvaryCross Section of Ovary

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Follicle StructureFollicle Structure

Page 8: Reproductive Potential and Ovarian Reserve: How Old is Too Old?

• Cycle 1- Primary Secondary follicle (pre-antral) class 1 follicle.

• Cycle 2- Small antral follicle class 2 and 3 follicles.

• Cycle 3- Larger antral follicle class 3-5 follicles.

• Cycle 4- Large antral and pre-ovulatory follicle class 5-8.• Exponential growth phase.

• Ovulatory cycle.

Follicle Selection destine to OvulateFollicle Selection destine to Ovulate

Secondary follicle (pre-Secondary follicle (pre-antral) consists of:antral) consists of:h Granulosa-Granulosa-

theca-cell unit:theca-cell unit: LH and FSH LH and FSH

receptors.receptors.

Page 9: Reproductive Potential and Ovarian Reserve: How Old is Too Old?

Occurs thoughout life.

{Cycle 4

Follicular Growth:Exponential Follicular Growth:Exponential Growth PhaseGrowth Phase

n Late luteal phase prior to Late luteal phase prior to index cycle (index cycle (““classic cycleclassic cycle””) ) h class 5 follicles serve as class 5 follicles serve as

cohort for upcoming cycle:cohort for upcoming cycle:

h Heavily gonadotropin Heavily gonadotropin dependent process:dependent process:

n Follicular phase of cycle 4:Follicular phase of cycle 4:h Marked by 160 fold rise in Marked by 160 fold rise in

granulosa cell.granulosa cell.

h Follicle increases in size Follicle increases in size from 5mm to 20mm.from 5mm to 20mm.

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Ovarian ReserveOvarian Reserve

n DefinitionDefinition11

h Based on Quantity & QualityBased on Quantity & Quality

n QuantityQuantity22

h Ovarian follicles are finiteOvarian follicles are finiteh Follicular loss accelerates at age 37.5 when numbers Follicular loss accelerates at age 37.5 when numbers

reach 25,000reach 25,00033

Associated with Associated with FSH and FSH and Inhibin B Inhibin B

h Fertility decreases after 35Fertility decreases after 35

1. I van Rooij, E de Jong, F Broekmans, L Caspar, J Habbema, and E te Velde, The limited value of follicle 1. I van Rooij, E de Jong, F Broekmans, L Caspar, J Habbema, and E te Velde, The limited value of follicle stimulating hormone as a test for ovarian reserve. Fertil Steril 81 (2004), pp. 1496-97.stimulating hormone as a test for ovarian reserve. Fertil Steril 81 (2004), pp. 1496-97.

2. L Speroff, R Glass, N Kase, Clinical Gynecologic Endocrinology and Infertility. Sixth Edition. Lippincott 2. L Speroff, R Glass, N Kase, Clinical Gynecologic Endocrinology and Infertility. Sixth Edition. Lippincott Williams & Wilkins. 1999Williams & Wilkins. 1999

3. M Faddy, R Gosden, A Gougeon, S Richardson, J Nelson, Accelerated disappearance of ovarian follicles in mid-life: 3. M Faddy, R Gosden, A Gougeon, S Richardson, J Nelson, Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod 7 (1992), pp. 1342-6.implications for forecasting menopause. Hum Reprod 7 (1992), pp. 1342-6.

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Ovarian ReserveOvarian Reserve

n DefinitionDefinitionh Based on Quantity & QualityBased on Quantity & Quality

n QualityQuality44

h Oocyte abnormalitiesOocyte abnormalitiesMeiotic spindleMeiotic spindleSingle chromatid abnormalitiesSingle chromatid abnormalitiesAneuploidyAneuploidy

4. American Society for Reproductive Medicine. A Practice Committee Report. Aging and 4. American Society for Reproductive Medicine. A Practice Committee Report. Aging and Infertility in Women. January 2002.Infertility in Women. January 2002.

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Decline in Follicle Number Decline in Follicle Number With AgeWith Age

n The rise in serum concentration of FSH The rise in serum concentration of FSH in early menopause is closely related to in early menopause is closely related to the fall in inhibin B; as inhibin B plays the fall in inhibin B; as inhibin B plays an important role in FSH secretion.an important role in FSH secretion.

n Reproductive aging is also associated Reproductive aging is also associated with a decrease in anti-mullerian with a decrease in anti-mullerian hormone (AMH, MIS).hormone (AMH, MIS).

n This is most always found in women This is most always found in women already exhibiting menstrual already exhibiting menstrual irregularity.irregularity.

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Menopause TransitionMenopause Transition

n Menopause is associated with a marked decline Menopause is associated with a marked decline in oocyte number due to progressive atresia.in oocyte number due to progressive atresia.

n However, absolute oocyte is not the cause of However, absolute oocyte is not the cause of menopause.menopause.

n Biological activity of FSH changes and has Biological activity of FSH changes and has prolonged half-life due to additional prolonged half-life due to additional carbohydrates attached.carbohydrates attached.

n Purpose of ORT is to identify women of Purpose of ORT is to identify women of younger age with poor ovarian reserve for their younger age with poor ovarian reserve for their age AND older women who still have adequate age AND older women who still have adequate reserves.reserves.

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Effect of Female Age on FertilityEffect of Female Age on Fertility

n % of women not using contraception who % of women not using contraception who remained childlessremained childless44

Age 20-24Age 20-24 6%6%Age 25-29Age 25-29 9%9%Age 30-35Age 30-35 15%15%Age 35-39Age 35-39 30%30%Age 40-44Age 40-44 64%64%

4.4. American Society for Reproductive Medicine. A Practice Committee Report. Aging and Infertility American Society for Reproductive Medicine. A Practice Committee Report. Aging and Infertility in Women. January 2002.in Women. January 2002.

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Effect of Female Age on Effect of Female Age on FertilityFertility

n Risk of spontaneous abortion increases with ageRisk of spontaneous abortion increases with agen Assisted Reproductive Technology Success Assisted Reproductive Technology Success

RatesRates44 h Failure to achieve live birthFailure to achieve live birth

Under 35Under 35 14%14%35-3735-37 19%19%38-4038-40 25%25%After 40After 40 40%40%

4. American Society for Reproductive Medicine. A Practice Committee Report. Aging and Infertility in 4. American Society for Reproductive Medicine. A Practice Committee Report. Aging and Infertility in Women. January 2002.Women. January 2002.

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How old is too old to have a How old is too old to have a baby?baby?

Adriana Iliescu, the 66-y.o. single, journalist who gave birth to baby girl on Jan. 17, 2005, rests at the Giulesti Maternity

Hospital in Bucharest, Romania.

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How old is too old to have a How old is too old to have a baby?baby?

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Age GroupsAge Groups ACSACS NCHSNCHS

15-1915-19 35.635.6 44.444.4

20-2420-24 109.3109.3 105.5105.5

25-2925-29 116.0116.0 114.1114.1

30-3430-34 100.6100.6 92.592.5

35-3935-39 50.250.2 41.441.4

40-4440-44 14.214.2 8.38.3

Age Specific Fertility RatesAge Specific Fertility Rates

Births per 1000 women 15 – 44 yearsACS – American Community SurveyNCHS – National Center for Health Statistics

Retrieved October 12, 2007 from http://www.census.gov/population/www/socdemo/fertility/slideshow/ACS-MF/TextOnly/slide23.html

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Retrieved October 12, 2007 from http://www.census.gov/population/www/socdemo/fertility/slideshow/ACS-MF/slide23.html

- 50%

- 72%

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Age 30, PR 44.5%, LB 38.6%Age 35, PR 38.3%, LB 32.2%Age 40, PR 23.0%, LB 16.1%Age 43, PR 10.1%, LB 5.5%Age 45, PR 4.3%, LB 1.2%Age 47, PR 3.3%, LB 0%

Retrieved October 12, 2007 from http://www.cdc.gov/ART/ART2004/sect2_fig5-15.htm#12

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Retrieved October 12, 2007 from http://www.cdc.gov/ART/ART2004/sect2_fig5-15.htm#14

Age 30, Loss 10.8 %Age 35, Loss 13.5 %Age 40, Loss 27.8 %Age 43, Loss 45.5 %Age > 43, Loss 58.8 %

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Retrieved October 12, 2007 from http://www.cdc.gov/ART/ART2004/sect4_fig40-44.htm#f41

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Follicle DevelopmentFollicle Development

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Follicle DevelopmentFollicle Development

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Follicle DevelopmentFollicle Development

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Aging and AneuploidyAging and Aneuploidy

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Retrieved October 13, 2007 from http://fig.cox.miami.edu/~cmallery/150/devel/c7.46.11.oogenesis.jpg

Arrested at Prophase MI

Arrested atMetaphase MII

LH Surge

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Retrieved October 13, 2007 from http://fig.cox.miami.edu/~cmallery/150/devel/c7.46.11.oogenesis.jpg

LH Surge Resumption of Meiosis

How efficient is

the process?

Declines with advancing age

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From Reprogenetics

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How old is too old to How old is too old to become pregnant?become pregnant?

n Age is an independent factorAge is an independent factor

n Can we determine individual Can we determine individual ovarian reserve?ovarian reserve?

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Measurement of Ovarian Measurement of Ovarian ReserveReserve

n CD 3 FSH and EstradiolCD 3 FSH and Estradiol

n Clomiphene Citrate Challenge Test Clomiphene Citrate Challenge Test (CCCT)(CCCT)

n Inhibin-BInhibin-B

n Basal Antral Follicle CountBasal Antral Follicle Count

n AMHAMH

n Ovarian VolumeOvarian Volume

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Use of ORT in Clinical PracticeUse of ORT in Clinical Practice

n To determine ooctye quality and To determine ooctye quality and quantityquantity

n Practical outcome parameters to Practical outcome parameters to measure include: ovarian response measure include: ovarian response to stimulation and/or pregnancy.to stimulation and/or pregnancy.

n Restricted to populations of first Restricted to populations of first cycle IVF patientscycle IVF patients

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Theoretical Use of ORTTheoretical Use of ORT

n Would indicate how long current levels Would indicate how long current levels of ovarian activity can be maintained of ovarian activity can be maintained before ovarian ageing sets inbefore ovarian ageing sets in

n Predict the chances of pregnancy and Predict the chances of pregnancy and live birth with and without treatmentlive birth with and without treatment

n Individualize recommendations for Individualize recommendations for prospective patients planning treatmentprospective patients planning treatment

n Help select an optimal dose and protocol Help select an optimal dose and protocol for ovarian stimulation*for ovarian stimulation*

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Basal FSH vs. Clomiphene Basal FSH vs. Clomiphene Challenge TestChallenge Test

Jain T, Soules MR, Collins JA. Fertil Steril 2004;82:180–5

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Basal FSH vs. Clomiphene Basal FSH vs. Clomiphene Challenge TestChallenge Test

Jain T, Soules MR, Collins JA. Fertil Steril 2004;82:180–5

Abnormal Day 3 FSH3.4 – 225 times more likely to be seen in a woman who cannot conceive than one who can

Abnormal CCCT6.7 – 612 times more likely to be seen in a woman who cannot conceive than one who can

Page 37: Reproductive Potential and Ovarian Reserve: How Old is Too Old?

Day 3 FSHDay 3 FSHn Young, fertile women can have Young, fertile women can have FSH FSHn Does FSH measure quantity > quality?Does FSH measure quantity > quality?n Schipper et al 1998Schipper et al 19981313 - 38 women <35 with - 38 women <35 with

nl menses:nl menses:h 3-fold differences in FSH levels (3.6-11.2) that 3-fold differences in FSH levels (3.6-11.2) that

did not correlate with agedid not correlate with agen FSH also demonstrates intercycle variabilityFSH also demonstrates intercycle variability14,1514,15

n Intra-cycle levels are not statistically different for cycle dayIntra-cycle levels are not statistically different for cycle day 2-4 2-4

13. I Schipper, F de-Jong, B Fauser, Lack of correlation between maximum early follicular phase serum follicle-stimulating hormone levels and 13. I Schipper, F de-Jong, B Fauser, Lack of correlation between maximum early follicular phase serum follicle-stimulating hormone levels and menstrual cycle characteristics in women under the age of 35. Hum Reprod 13: 1442-1448menstrual cycle characteristics in women under the age of 35. Hum Reprod 13: 1442-1448

14. D Nikolaou, A Templeton, Early Ovarian Ageing. Eur. J. Obstet. Gynaecol. Reprod. Biol. 113 2 (2004), pp.126-133.14. D Nikolaou, A Templeton, Early Ovarian Ageing. Eur. J. Obstet. Gynaecol. Reprod. Biol. 113 2 (2004), pp.126-133.15. J Kwee, R Schats, J McDonnell, C Lambalk, J Schoemaker, Intercycle variability of ovarian reserve tests: results 15. J Kwee, R Schats, J McDonnell, C Lambalk, J Schoemaker, Intercycle variability of ovarian reserve tests: results

of a prospective randomized study. Hum Reprod 19 (2004), pp. 590-5.of a prospective randomized study. Hum Reprod 19 (2004), pp. 590-5.16. P Gindoff, P Schmidt, D Rubinow: Response to CCCT in Normal Women through Perimenopause.16. P Gindoff, P Schmidt, D Rubinow: Response to CCCT in Normal Women through Perimenopause. Gynecologic and Obstetric Investigation 43 (1997), pp. 186-91Gynecologic and Obstetric Investigation 43 (1997), pp. 186-91

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Day 3 FSHDay 3 FSH

16. I van Rooij, L Bancsi, F Broekmans, C Looman, J Habbema, E te Velde, Women older than 40 years of age and those with elevated follicle-stimulating hormone levels differ in poor response rate and embryo quality in in vitro fertilization, Fertil Steril (2003) pp. 482-8.

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Day 3 FSHDay 3 FSHn High FSH correlates with high cycle High FSH correlates with high cycle

cancellationcancellation1616

n Age is associated with decreased implantation Age is associated with decreased implantation rates rates

n IVF outcome differs between patients >40 and IVF outcome differs between patients >40 and those with elevated FSH (multifactorial)those with elevated FSH (multifactorial)

16. I van Rooij, L Bancsi, F Broekmans, C Looman, J Habbema, E te Velde, Women older than 40 years 16. I van Rooij, L Bancsi, F Broekmans, C Looman, J Habbema, E te Velde, Women older than 40 years of age and those with elevated follicle-stimulating hormone levels differ in poor response rate of age and those with elevated follicle-stimulating hormone levels differ in poor response rate and and embryo quality in in vitro fertilization, Fertil Steril (2003) pp. 482-8.embryo quality in in vitro fertilization, Fertil Steril (2003) pp. 482-8.

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Cycle Regularity is Key FactorCycle Regularity is Key Factor

In this study perimenopausal and menopausal In this study perimenopausal and menopausal women showed similar patterns of gonadotropin women showed similar patterns of gonadotropin secretion under both basal and stimulated secretion under both basal and stimulated conditions. Elevated (>20 IU/L) immunoactive FSH conditions. Elevated (>20 IU/L) immunoactive FSH levels were observed in all but two of 11 levels were observed in all but two of 11 perimenopausal women, suggesting that menstrual perimenopausal women, suggesting that menstrual cycle irregularity was evidence of perimenopausal cycle irregularity was evidence of perimenopausal gonadotropin changes in the majority of our sample. gonadotropin changes in the majority of our sample. Results of the GnRH stimulation test did not permit Results of the GnRH stimulation test did not permit better discrimination of the subject groups than did better discrimination of the subject groups than did the basal FSH levels. Similar results were found the basal FSH levels. Similar results were found when CCCT was used to unmask occult when CCCT was used to unmask occult perimenopausal women (Gindoff et al. Gynecol and perimenopausal women (Gindoff et al. Gynecol and Obstet Investigation 43:186-91, 1997)Obstet Investigation 43:186-91, 1997)

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Day 3 EstradiolDay 3 Estradiol

n Frequently evaluated along with Day 3 FSHFrequently evaluated along with Day 3 FSHn Normal <80pg/mlNormal <80pg/mln Smotrich et al 1995Smotrich et al 19951111 - prospective observational - prospective observational

study of 225 pts undergoing IVFstudy of 225 pts undergoing IVFh Evaluate prognostic value of day 3 estradiol Evaluate prognostic value of day 3 estradiol

independent of day 3 FSH on response to OI & independent of day 3 FSH on response to OI & subsequent PRsubsequent PR

11. D Smotrich, E Widra, P Gindoff, M Levy, J Hall, R Stillman, Prognostic value of day 3 estradiol 11. D Smotrich, E Widra, P Gindoff, M Levy, J Hall, R Stillman, Prognostic value of day 3 estradiol on in vitro fertilization outcome. Fertil Steril (1995) pp. 1136-40.on in vitro fertilization outcome. Fertil Steril (1995) pp. 1136-40.

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Day 3 EstradiolDay 3 Estradiol

Day 3 Estradiol >80Day 3 Estradiol >80 Day 3 Estradiol <80Day 3 Estradiol <80

PRPR 14.8%14.8% 37%37%CRCR 18.5%18.5% 0.4%0.4%

Elevated FSH excludedElevated FSH excluded

PRPR 14.8%14.8% 38.9%38.9%CRCR 18.5%18.5% 0.4%0.4%

11. D Smotrich, E Widra, P Gindoff, M Levy, J Hall, R Stillman, Prognostic value of day 3 estradiol on in vitro 11. D Smotrich, E Widra, P Gindoff, M Levy, J Hall, R Stillman, Prognostic value of day 3 estradiol on in vitro fertilization outcome. Fertil Steril (1995) pp. 1136-40.fertilization outcome. Fertil Steril (1995) pp. 1136-40.

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Multiple ScreeningMultiple Screening

AGE

FSHEstradiol*

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Elevated FSH and AgeElevated FSH and Age

AGE

Estradiol

FSH

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Ovarian Antral Follicle CountOvarian Antral Follicle Count

n Transvaginal US done on Day 3 to count Transvaginal US done on Day 3 to count antral folliclesantral follicles

n Antral follicle number can be extrapolated to Antral follicle number can be extrapolated to determine ovarian reservedetermine ovarian reserve

n Chang et al. 1998Chang et al. 199866 - 130 women & IVF - 130 women & IVFh Prospective study to evaluate predictive value of Prospective study to evaluate predictive value of

AFC on pregnancy rateAFC on pregnancy rate

6. M Chang, C Chiang, T Hsieh, Y Soong, K Hsu, Use of the Antral Follicle Count to Predict the 6. M Chang, C Chiang, T Hsieh, Y Soong, K Hsu, Use of the Antral Follicle Count to Predict the Outcome of Assisted Reproductive Technologies. Fertil Steril 69Outcome of Assisted Reproductive Technologies. Fertil Steril 69 (1998), pp. 505-10. (1998), pp. 505-10.

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Antral Follicle CountAntral Follicle Count

Ranges with diameters between 2-10 and 2-Ranges with diameters between 2-10 and 2-5 mm make this hard to compare studies.5 mm make this hard to compare studies.

Inter-cycle variability in fertile women Inter-cycle variability in fertile women confounds its utility.confounds its utility.

Not a good predictor of ovarian reserve.Not a good predictor of ovarian reserve.

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Basal Antral Follicle CountBasal Antral Follicle Count

Hendricks DJ, et al. Fertil Steril 2005;83:291–301

Abnormal AFC1.5 – 19.7 times more likely to be seen in a woman with a poor response to treatment compared to one who responds well

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Basal Antral Follicle CountBasal Antral Follicle Countn AFC in the prediction of poor ovarian AFC in the prediction of poor ovarian

response in IVF is quite adequate and response in IVF is quite adequate and superior to that of the widely used basal superior to that of the widely used basal FSH.FSH.

n The poor performance in predicting The poor performance in predicting nonpregnancy for both AFC and basal nonpregnancy for both AFC and basal FSH might be not much of a surprise FSH might be not much of a surprise because these tests merely represent the because these tests merely represent the quantitative aspect of ovarian reservequantitative aspect of ovarian reserve

Hendricks DJ, et al. Fertil Steril 2005;83:291–301

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Anti Mullerian HormoneAnti Mullerian Hormone

Fiçicioglu C, et al. Fertil Steril 2006;85:592– 6.

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Clinical ConclusionsClinical Conclusionsn The natural decline in fertility with advancing age The natural decline in fertility with advancing age

is due to oocyte not endometrial factorsis due to oocyte not endometrial factors

n Aneuploidy is the major cause of fecundity loss with Aneuploidy is the major cause of fecundity loss with age. (Long term storage of eggs and their arrest at age. (Long term storage of eggs and their arrest at MI with resumption of meiosis at ovulation result in MI with resumption of meiosis at ovulation result in large numbers of abnormal embryos.)large numbers of abnormal embryos.)

n Older women should be offered aggressive Older women should be offered aggressive treatment optionstreatment options

n Egg freezing should be offered to younger women Egg freezing should be offered to younger women to avoid fertility issues later in lifeto avoid fertility issues later in life

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Limitations of Ovarian Limitations of Ovarian Reserve TestsReserve Tests

h They sacrifice sensitivity for specificityThey sacrifice sensitivity for specificity1717 h It is impossible to sort out loss of quantity vs. decreased It is impossible to sort out loss of quantity vs. decreased

qualityqualityh Different outcome measures make it difficult to Different outcome measures make it difficult to

compare different testscompare different testsh Pregnancy is multifactorial!Pregnancy is multifactorial!44

Risk factors for decreased ovarian reserve also include Risk factors for decreased ovarian reserve also include smoking, family history of POF, ovarian pathology, & previous smoking, family history of POF, ovarian pathology, & previous ovarian surgeryovarian surgery

SpermSperm

17. T Jain, M Soules, J Collins, Comparison of basal follicle-stimulating hormone versus the clomiphene citrate 17. T Jain, M Soules, J Collins, Comparison of basal follicle-stimulating hormone versus the clomiphene citrate challenge test for ovarian reserve screening. Fertil Steril 82 (2004) pp. 180-5challenge test for ovarian reserve screening. Fertil Steril 82 (2004) pp. 180-5

4. American Society for Reproductive Medicine. A Practice Committee Report. Aging and Infertility in Women. 4. American Society for Reproductive Medicine. A Practice Committee Report. Aging and Infertility in Women. January 2002.January 2002.

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ConclusionsConclusions

n ORT weakly predictive of pregnancy ORT weakly predictive of pregnancy

n Moderately predictive of ovarian Moderately predictive of ovarian responseresponse

n May be helpful in adjusting dose for first May be helpful in adjusting dose for first cycle of IVF: maximal stimulationcycle of IVF: maximal stimulation

n Only 3 % or very few couples will be Only 3 % or very few couples will be counseled out of trying a first cyclecounseled out of trying a first cycle

n Not a substitute for trial of first cycleNot a substitute for trial of first cycle

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Conclusions continuedConclusions continued

n Used in conjunction with AGE; more usefulUsed in conjunction with AGE; more usefuln However, AGE is stand alone most important However, AGE is stand alone most important

variablevariablen Cycle regularity always pertinent and may Cycle regularity always pertinent and may

preclude use of ORTpreclude use of ORTn FSH baseline should not be used to exclude FSH baseline should not be used to exclude

patients but only for counseling purposes and patients but only for counseling purposes and cycle planningcycle planning

n The likelihood ratio needed to predict a poor The likelihood ratio needed to predict a poor response requires a very high FSH; well above response requires a very high FSH; well above currently clinically used limitscurrently clinically used limits

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Conclusions continuedConclusions continued

n After a first cycle trial with a poor After a first cycle trial with a poor response, ORT may then be used to response, ORT may then be used to counsel against further treatmentcounsel against further treatment

n Dynamic testing (CCCT) does not Dynamic testing (CCCT) does not unmask occult normal baseline test unmask occult normal baseline test resultsresults

n ORT has been studied in IVF ORT has been studied in IVF populations; making extrapolation to populations; making extrapolation to subfertile populations very precarioussubfertile populations very precarious

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