Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-745bb68f8f-v2bm5 Total loading time: 0 Render date: 2025-01-24T14:31:42.188Z Has data issue: false hasContentIssue false

Chapter 4 - Diagnostic Testing of Reproductive Aging

from Section 4 - Rethinking and Redefining “Family Planning” for the Twenty-First Century

Published online by Cambridge University Press:  15 September 2022

By
Tanya L. Glenn  and
David B. Seifer
Edited by
Dimitrios S. Nikolaou  and
David B. Seifer
Dimitrios S. Nikolaou
Affiliation:
Chelsea and Westminster Hospital, London
David B. Seifer
Affiliation:
Yale Reproductive Medicine, New Haven, CT
Get access

Summary

Recently there has been an increase in age-related infertility, termed ‘reproductive aging’, in which both quantity and quality of oocytes decline. Various established ways to analyze oocyte quantity include assessing age, follicle stimulating hormone, antral follicle count, and anti-Mullerian hormone. Each test has strengths and weaknesses inherent to the test itself and there can be concern when the tests are discordant. Additionally, several algorithms have been proposed that assess multiple elements to predict live birth rates per transfer and most recently cumulative live birth rates per retrieval. Knowledge about fertility has been assessed in several survey-based studies. These surveys illustrate a limited understanding of the participants regarding the impact of age-related fertility decline and a lack of realistic expectations regarding the limitations of IVF or egg cryopreservation to preserve the age-related decline in fertility. Additionally, there are inconsistencies in whether women would choose to have ovarian reserve testing and whether this would alter management. Lastly, emotional response after receiving ovarian reserve testing is also highly variable. This encourages providers to have a conversation about potential ramifications of testing.

Keywords

Age-related infertilityovarian reserveoocyte quantityoocyte qualityageAFCAMHalgorithmsfertility knowledgeemotional response
Type
Chapter
Information
Optimizing the Management of Fertility in Women over 40 , pp. 39 - 55
Publisher: Cambridge University Press
Print publication year: 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Tal, R, Seifer, DB. Ovarian reserve testing: a user’s guide. American Journal of Obstetrics & Gynecology. 2017;217(2):129–40.Google Scholar
Steiner, AZ, Jukic, AM. Impact of female age and nulligravidity on fecundity in an older reproductive age cohort. Fertility & Sterility. 2016;105(6):1584–8.e1.Google Scholar
Liu, KE, Case, A. No. 346-Advanced reproductive age and fertility. Journal of Obstetrics & Gynaecology Canada. 2017;39(8):685–95.Google Scholar
Fleming, R, Seifer, DB, Frattarelli, JL, Ruman, J. Assessing ovarian response: antral follicle count versus anti-Mullerian hormone. Reproductive Biomedicine Online. 2015;31(4):486–96.CrossRefGoogle ScholarPubMed
Ripley, M, Lanes, A, Leveille, MC, Shmorgun, D. Does ovarian reserve predict egg quality in unstimulated therapeutic donor insemination cycles? Fertility & Sterility. 2015;103(5):1170–5.e2.CrossRefGoogle ScholarPubMed
Nelson, SM, Telfer, EE, Anderson, RA. The ageing ovary and uterus: new biological insights. Human Reproduction Update. 2012;19(1):67–83.CrossRefGoogle ScholarPubMed
Devine, K, Mumford, SL, Wu, M, DeCherney, AH, Hill, MJ, Propst, A. Diminished ovarian reserve in the United States assisted reproductive technology population: diagnostic trends among 181,536 cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Fertility & Sterility. 2015;104(3):612–19.e3.Google Scholar
Toner, JPS, Seifer DB Why we may abandon basal follicle-stimulating hormone testing: a sea change in determining ovarian reserve using antimullerian hormone. Fertility & Sterility. 2013;99(7):1825–30.CrossRefGoogle ScholarPubMed
van Rooij, IA, Broekmans, FJ, Scheffer, GJ, Looman, CW, Habbema, JD, de Jong, FH, et al. Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: a longitudinal study. Fertility & Sterility. 2005;83(4):979–87.Google Scholar
Winslow, KL, Toner, JP, Brzyski, RG, Oehninger, SC, Acosta, AA, Muasher, SJ. The gonadotropin-releasing hormone agonist stimulation test—a sensitive predictor of performance in the flare-up in vitro fertilization cycle. Fertility & Sterility. 1991;56(4):711–7.Google Scholar
Fanchin, R, de Ziegler, D, Olivennes, F, Taieb, J, Dzik, A, Frydman, R. Endocrinology: Exogenous follicle stimulating hormone ovarian reserve test (EFORT): a simple and reliable screening test for detecting ‘poor responders’ in in-vitro fertilization. Human Reproduction. 1994;9(9):1607–11.Google Scholar
McTavish, KJ, Jimenez, M, Walters, KA, Spaliviero, J, Groome, NP, Themmen, AP, et al. Rising follicle-stimulating hormone levels with age accelerate female reproductive failure. Endocrinology 2007;148(9):4432–9.CrossRefGoogle ScholarPubMed
Lass, A, Skull, J, McVeigh, E, Margara, R, Winston, RM. Measurement of ovarian volume by transvaginal sonography before ovulation induction with human menopausal gonadotrophin for in-vitro fertilization can predict poor response. Human Reproduction. 1997;12(2):294–7.CrossRefGoogle ScholarPubMed
Chang, M-Y. Use of the antral follicle count to predict the outcome of assisted reproductive technologies. Fertility & Sterility. 1997;69(3):505–10.Google Scholar
Hansen, KR, Morris, JL, Thyer, AC, Soules, MR. Reproductive aging and variability in the ovarian antral follicle count: application in the clinical setting. Fertility & Sterility. 2003;80(3):577–83.Google Scholar
Landersoe, SK, Birch Petersen, K, Sorensen, AL, Larsen, EC, Martinussen, T, Lunding, SA, et al. Ovarian reserve markers after discontinuing long-term use of combined oral contraceptives. Reproductive Biomedicine Online 2020;40(1):176–86.Google Scholar
Seifer, DB, MacLaughlin, DT, Christian, BP, Feng, B, Shelden, RM. Early follicular serum mullerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles. Fertility & Sterility. 2002;77(3):468–71.CrossRefGoogle ScholarPubMed
Styer, AK, Gaskins, AJ, Brady, PC, Sluss, PM, Chavarro, JE, Hauser, RB, et al. Dynamic antimullerian hormone levels during controlled ovarian hyperstimulation predict in vitro fertilization response and pregnancy outcomes. Fertility & Sterility. 2015;104(5):1153–61.e1-7.CrossRefGoogle ScholarPubMed
Nelson, SM, Pastuszek, E, Kloss, G, Malinowska, I, Liss, J, Lukaszuk, A, et al. Two new automated, compared with two enzyme-linked immunosorbent, antimüllerian hormone assays. Fertility & Sterility. 2015;104(4):1016–21.Google Scholar
Leader, B, Baker, VL. Maximizing the clinical utility of antimullerian hormone testing in women’s health. Current Opinion in Obstetrics & Gynecology. 2014;26(4):226–36.Google Scholar
Seifer, DB, Baker, VL, Leader, B. Age-specific serum anti-Mullerian hormone values for 17,120 women presenting to fertility centers within the United States. Fertility & Sterility. 2011;95(2):747–50.Google Scholar
Burks, HR, Ross, L, Opper, N, Paulson, E, Stanczyk, FZ, Chung, K. Can highly sensitive antimullerian hormone testing predict failed response to ovarian stimulation? Fertility & Sterility. 2015;104(3):643–8.CrossRefGoogle ScholarPubMed
Seifer, DB, Tal, O, Wantman, E, Edul, P, Baker, VL. Prognostic indicators of assisted reproduction technology outcomes of cycles with ultralow serum antimullerian hormone: a multivariate analysis of over 5,000 autologous cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for 2012–2013. Fertility & Sterility. 2016;105(2):385–93.e3.Google Scholar
Seifer, DB, Golub, ET, Lambert-Messerlian, G, Benning, L, Anastos, K, Watts, DH, et al. Variations in serum mullerian inhibiting substance between white, black, and Hispanic women. Fertility & Sterility. 2009;92(5):1674–8.Google Scholar
Tal, R, Seifer, DB, Wantman, E, Baker, V, Tal, O. Antimullerian hormone as a predictor of live birth following assisted reproduction: an analysis of 85,062 fresh and thawed cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for 2012–2013. Fertility & Sterility. 2018;109(2):258–65.Google Scholar
Tal, R, Tal, O, Seifer, BJ, Seifer, DB. Antimullerian hormone as predictor of implantation and clinical pregnancy after assisted conception: a systematic review and meta-analysis. Fertility & Sterility. 2015;103(1):119–30.e3.Google Scholar
Tal, R, Seifer, DB, Tal, R, Granger, E, Wantman, E, Tal, O. AMH highly correlates with cumulative live birth rate in women with diminished ovarian reserve independent of age. The Journal of Clinical Endocrinology and Metabolism. 2021;106(9):2754–66.Google Scholar
Lyttle Schumacher, BM, Jukic, AMZ, Steiner, AZ. Antimullerian hormone as a risk factor for miscarriage in naturally conceived pregnancies. Fertility & Sterility. 2018;109(6):1065–71.e1.CrossRefGoogle ScholarPubMed
McCormack, CD, Leemaqz, SY, Furness, DL, Dekker, GA, Roberts, CT. Anti-Mullerian hormone levels in recurrent embryonic miscarriage patients are frequently abnormal, and may affect pregnancy outcomes. Journal of Obstetrics and Gynaecology. 2019;39(5):623–7.Google Scholar
Shebl, O, Ebner, T, Sir, A, Schreier-Lechner, E, Mayer, RB, Tews, G, et al. Age-related distribution of basal serum AMH level in women of reproductive age and a presumably healthy cohort. Fertility & Sterility. 2011;95(2):832–4.CrossRefGoogle Scholar
Tarasconi, B, Tadros, T, Ayoubi, JM, Belloc, S, de Ziegler, D, Fanchin, R. Serum antimullerian hormone levels are independently related to miscarriage rates after in vitro fertilization-embryo transfer. Fertility & Sterility. 2017;108(3):518–24.CrossRefGoogle ScholarPubMed
Zarek, SM, Mitchell, EM, Sjaarda, LA, Mumford, SL, Silver, RM, Stanford, JB, et al. Antimüllerian hormone and pregnancy loss from the Effects of Aspirin in Gestation and Reproduction trial. Fertility & Sterility. 2016;105(4):946–52.e2.CrossRefGoogle ScholarPubMed
Freeman, EW, Sammel, MD, Lin, H, Gracia, CR. Anti-mullerian hormone as a predictor of time to menopause in late reproductive age women. The Journal of Clinical Endocrinology and Metabolism. 2012;97(5):1673–80.Google Scholar
Khan, HL, Bhatti, S, Suhail, S, Gul, R, Awais, A, Hamayun, H, et al. Antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) are the predictors of natural fecundability have similar trends irrespective of fertility status and menstrual characteristics among fertile and infertile women below the age of 40 years. Reproductive Biology & Endocrinology. 2019;17(1):20.Google Scholar
Wang, S, Zhang, Y, Mensah, V, Huber, WJ, 3rd, Huang, YT, Alvero, R. Discordant anti-mullerian hormone (AMH) and follicle stimulating hormone (FSH) among women undergoing in vitro fertilization (IVF): which one is the better predictor for live birth? Journal of Ovarian Research. 2018;11(1):60.Google Scholar
Leader, B, Hegde, A, Baca, Q, Stone, K, Lannon, B, Seifer, DB, et al. High frequency of discordance between antimullerian hormone and follicle-stimulating hormone levels in serum from estradiol-confirmed days 2 to 4 of the menstrual cycle from 5,354 women in U.S. fertility centers. Fertility & Sterility. 2012;98(4):1037–42.Google Scholar
Ligon, S, Lustik, M, Levy, G, Pier, B. Low antimullerian hormone (AMH) is associated with decreased live birth after in vitro fertilization when follicle-stimulating hormone and AMH are discordant. Fertility & Sterility. 2019;112(1):73–81.e1.CrossRefGoogle ScholarPubMed
Hipp, HS, Kawwass, JF. Discordant ovarian reserve testing: what matters most? Fertility & Sterility. 2019;112(1):34.CrossRefGoogle ScholarPubMed
Centers for Disease Control and Prevention. IVF Success Estimator. 2019. https://www.cdc.gov/art/ivf-success-estimator/index.htmlGoogle Scholar
Kushnir, VA, Choi, J, Darmon, SK, Albertini, DF, Barad, DH, Gleicher, N. CDC-reported assisted reproductive technology live-birth rates may mislead the public. Reproductive Biomedicine Online. 2017;35(2):161–4.Google Scholar
Centers for Disease Control and Prevention. 2017 Assisted Reproductive Technology Fertility Clinic Success Rates Report. 2018. https://www.cdc.gov/art/reports/2017/fertility-clinic.htmlGoogle Scholar
Goldman, RJF. BWH Egg Freezing Counseling Tool (EFCT). MD Calc. 2019. https://www.mdcalc.com/bwh-egg-freezing-counseling-tool-efctGoogle Scholar
Society for Assisted Reproductive Technology. What are my chances with ART. 2020. https://www.sartcorsonline.com/Predictor/PatientGoogle Scholar
Venturella, R, Lico, D, Sarica, A, Falbo, MP, Gulletta, E, Cannataro, M, et al. A new algorithm to predict ovarian age combining clinical, biochemical and 3D-ultrasonographic parameters. Fertility & Sterility. 2014;102(3):e145.Google Scholar
ReproSource I. ReproSource Ovarian Assessment Report Clinical Data Update from Multiple US Fertility Centers. 2019.Google Scholar
Univfy Inc. Univfy PreIVF Report. 2013. https://www.univfy.com/ivf-successGoogle Scholar
Nyboe Andersen, A, Nelson, SM, Fauser, BCJM, García-Velasco, JA, Klein, BM, Arce, J-C, et al. Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial. Fertility & Sterility. 2017;107(2):387–96.e4.CrossRefGoogle ScholarPubMed
Friis Petersen, J, Løkkegaard, E, Andersen, LF, Torp, K, Egeberg, A, Hedegaard, L, et al. A randomized controlled trial of AMH-based individualized FSH dosing in a GnRH antagonist protocol for IVF. Human Reproduction Open. 2019;2019(1):hoz003-hoz.Google Scholar
Hickman, LC, Fortin, C, Goodman, L, Liu, X, Flyckt, R. Fertility and fertility preservation: knowledge, awareness and attitudes of female graduate students. The European Journal of Contraception & Reproductive Health Care. 2018;23(2):130–8.CrossRefGoogle ScholarPubMed
Hurley, EG, Ressler, IB, Young, S, Batcheller, A, Thomas, MA, DiPaola, KB, et al. Postponing childbearing and fertility preservation in young professional women. Southern Medical Journal. 2018;111(4):187–91.Google Scholar
Azhar, E, Seifer, DB, Melzer, K, Ahmed, A, Weedon, J, Minkoff, H. Knowledge of ovarian reserve and reproductive choices. Journal of Assisted Reproduction and Genetics. 2015;32(3):409–15.Google Scholar
O’Brien, Y, Kelleher, C, Wingfield, M. “So what happens next?” exploring the psychological and emotional impact of anti-Mullerian hormone testing. Journal of Psychosomatic Obstetrics and Gynaecology. 2020;41(1):30–7.Google ScholarPubMed
ACOG Committee. Opinion No. 773 Summary: The use of antimüllerian hormone in women not seeking fertility care. Obstetrics and Gynecology. 2019;133:e275–9.Google Scholar
Steiner, AZ, Pritchard, D, Stanczyk, FZ, Kesner, JS, Meadows, JW, Herring, AH, et al. Association between biomarkers of ovarian reserve and infertility among older women of reproductive age. Journal of the American Medical Association. 2017;318(14):1367–76.Google Scholar
Seifer, DB, Minkoff, H, Merhi, Z. Putting ‘family’ back in family planning. Human Reproduction. 2015;30(1):16–9.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×