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-cd9895bd7-dk4vv Total loading time: 0 Render date: 2024-12-23T16:01:22.077Z Has data issue: false hasContentIssue false

Chapter 6 - When to Use ART beyond 40: How Often, How Many Attempts, When to Stop

from Section 5 - Optimal Deployment of ART beyond 40

Published online by Cambridge University Press:  15 September 2022

By
Steven D. Spandorfer  and
Pietro Bortoletto
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

ART in women over 40 years of age is a fundamentally complex undertaking fraught with many challenges. This chapter carefully reviews the data for effective ovarian reserve assessment and preconception counseling. For women undergoing IVF, we discuss the evidence base for the different stimulation regimens and the multitude of adjunctive treatments proposed for poor responders. Finally, we discuss expected treatment success and when to consider stopping further IVF attempts with autologous oocytes.

Keywords

Advanced maternal ageART40 and olderIVF
Type
Chapter
Information
Optimizing the Management of Fertility in Women over 40 , pp. 71 - 80
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

Martin, JA, Hamilton, BE, Osterman, MJ, Curtin, SC, Matthews, TJ. Births: final data for 2013. Natl Vital Stat Rep 2015;64(1):1–65.Google ScholarPubMed
Seifer, DB, Baker, VL, Leader, B. Age-specific serum anti-Müllerian hormone values for 17,120 women presenting to fertility centers within the United States. Fertil Steril 2011;95(2):747–50.Google Scholar
Reichman, DE, Goldschlag, D, Rosenwaks, Z. Value of antimüllerian hormone as a prognostic indicator of in vitro fertilization outcome. Fertil Steril 2014;101(4):1012–18.e1.Google Scholar
Tokura, Y, Yoshino, O, Ogura-Nose, S, Motoyama, H, Harada, M, Osuga, Y, et al. The significance of serum anti-Müllerian hormone (AMH) levels in patients over age 40 in first IVF treatment. J Assist Reprod Genet 2013;30(6):821–5.Google Scholar
Scott, RT, Toner, JP, Muasher, SJ, Oehninger, S, Robinson, S, Rosenwaks, Z. Follicle-stimulating hormone levels on cycle day 3 are predictive of in vitro fertilization outcome. Fertil Steril 1989;51(4):651–4.CrossRefGoogle ScholarPubMed
Klipstein, S, Regan, M, Ryley, DA, Goldman, MB, Alper, MM, Reindollar, RH. One last chance for pregnancy: a review of 2,705 in vitro fertilization cycles initiated in women age 40 years and above. Fertil Steril 2005;84(2):435–45.Google Scholar
Rooij van, IAJ, Bancsi, LFJMM, Broekmans, FJM, Looman, CWN, Habbema, JDF, Velde te, ER. 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;79(3):482–8.CrossRefGoogle Scholar
Yih, MC, Spandorfer, SD, Rosenwaks, Z. Egg production predicts a doubling of in vitro fertilization pregnancy rates even within defined age and ovarian reserve categories. Fertil Steril 2005;83(1):24–9.Google Scholar
Nelson, SM, Klein, BM, Arce, J-C. Comparison of antimüllerian hormone levels and antral follicle count as predictor of ovarian response to controlled ovarian stimulation in good-prognosis patients at individual fertility clinics in two multicenter trials. Fertil Steril 2015;103(4):923–30.e1.Google Scholar
Khan, HL, Bhatti, S, Suhail, S, Gul, R, Awais, A, Hamayun, H, et al. Antral follicle count (AFC) and serum anti-Müllerian 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. Reprod Biol Endocrinol 2019;17(1):20.Google Scholar
Hendriks, DJ, Mol, B-WJ, Bancsi, LFJMM, Te Velde, ER, Broekmans, FJM. Antral follicle count in the prediction of poor ovarian response and pregnancy after in vitro fertilization: a meta-analysis and comparison with basal follicle-stimulating hormone level. Fertil Steril 2005;83(2):291–301.Google Scholar
Tsakos, E, Tolikas, A, Daniilidis, A, Asimakopoulos, B. Predictive value of anti-müllerian hormone, follicle-stimulating hormone and antral follicle count on the outcome of ovarian stimulation in women following GnRH-antagonist protocol for IVF/ET. Arch Gynecol Obstet 2014;290(6):1249–53.Google Scholar
Creanga, AA, Syverson, C, Seed, K, Callaghan, WM. Pregnancy-related mortality in the United States, 2011–2013. Obstet Gynecol 2017;130(2):366–73.Google Scholar
Sheen, J-J, Wright, JD, Goffman, D, Kern-Goldberger, AR, Booker, W, Siddiq, Z, et al. Maternal age and risk for adverse outcomes. Am J Obstet Gynecol 2018;219(4):390.e1–390.e15.Google Scholar
Wennberg, AL, Opdahl, S, Bergh, C, Aaris Henningsen, A-K, Gissler, M, Romundstad, LB, et al. Effect of maternal age on maternal and neonatal outcomes after assisted reproductive technology. Fertil Steril 2016;106(5):1142–9.e14.Google Scholar
Sullivan-Pyke, CS, Senapati, S, Mainigi, MA, Barnhart, KT. In vitro fertilization and adverse obstetric and perinatal outcomes. Semin Perinatol 2017;41(6):345–53.CrossRefGoogle ScholarPubMed
du Fossé, NA, van der Hoorn, M-LP, van Lith, JMM, le Cessie, S, Lashley, EELO. Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis. Hum Reprod Update 2020;26(5):650–69.CrossRefGoogle ScholarPubMed
Sharma, R, Agarwal, A, Rohra, VK, Assidi, M, Abu-Elmagd, M, Turki, RF. Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring. Reprod Biol Endocrinol 2015;13:35.CrossRefGoogle ScholarPubMed
Tsafrir, A, Simon, A, Revel, A, Reubinoff, B, Lewin, A, Laufer, N. Retrospective analysis of 1217 IVF cycles in women aged 40 years and older. Reprod Biomed Online 2007;14(3):348–55.Google Scholar
Corsan, G, Trias, A, Trout, S, Kemmann, E. Ovulation induction combined with intrauterine insemination in women 40 years of age and older: is it worthwhile? Hum Reprod 1996;11(5):1109–12.CrossRefGoogle ScholarPubMed
Evans, MB, Stentz, NC, Richter, KS, Schexnayder, B, Connell, M, Healy, MW, et al. Mature follicle count and multiple gestation risk based on patient age in intrauterine insemination cycles with ovarian stimulation. Obstet Gynecol 2020;135(5):1005–14.Google Scholar
Gunnala, V, Irani, M, Melnick, A, Rosenwaks, Z, Spandorfer, S. One thousand seventy-eight autologous IVF cycles in women 45 years and older: the largest single-center cohort to date. J Assist Reprod Genet 2018;35(3):435–40.Google Scholar
van Tilborg, TC, Torrance, HL, Oudshoorn, SC, Eijkemans, MJC, Koks, CAM, Verhoeve, HR, et al. Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 1: The predicted poor responder. Hum Reprod 2017;32(12):2496–505.CrossRefGoogle ScholarPubMed
Stimpfel, M, Vrtačnik-Bokal, E, Pozlep, B, Kmecl, J, Virant-Klun, I. Gonadotrophin-releasing hormone agonist protocol of controlled ovarian hyperstimulation as an efficient treatment in Bologna-defined poor ovarian responders. Syst Biol Reprod Med 2016;62(4):290–6.Google Scholar
Boza, A, Cakar, E, Boza, B, Api, M, Kayatas, S, Sofuoglu, K. Microdose flare-up gonadotropin-releasing hormone (GnRH) agonist versus GnRH antagonist protocols in poor ovarian responders undergoing intracytoplasmic sperm injection. J Reprod Infertil 2016;17(3):163–8.Google Scholar
Orvieto, R, Kruchkovich, J, Rabinson, J, Zohav, E, Anteby, EY, Meltcer, S. Ultrashort gonadotropin-releasing hormone agonist combined with flexible multidose gonadotropin-releasing hormone antagonist for poor responders in in vitro fertilization/embryo transfer programs. Fertil Steril 2008;90(1):228–30.CrossRefGoogle ScholarPubMed
Reichman, DE, Zakarin, L, Chao, K, Meyer, L, Davis, OK, Rosenwaks, Z. Diminished ovarian reserve is the predominant risk factor for gonadotropin-releasing hormone antagonist failure resulting in breakthrough luteinizing hormone surges in in vitro fertilization cycles. Fertil Steril 2014;102(1):99–102.CrossRefGoogle ScholarPubMed
Dragisic, KG, Davis, OK, Fasouliotis, SJ, Rosenwaks, Z. Use of a luteal estradiol patch and a gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation for in vitro fertilization in poor responders. Fertil Steril 2005;84(4):1023–6.Google Scholar
Elassar, A, Engmann, L, Nulsen, J, Benadiva, C. Letrozole and gonadotropins versus luteal estradiol and gonadotropin-releasing hormone antagonist protocol in women with a prior low response to ovarian stimulation. Fertil Steril 2011;95(7):2330–4.CrossRefGoogle ScholarPubMed
Rubio, C, Bellver, J, Rodrigo, L, Castillón, G, Guillén, A, Vidal, C, et al. In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study. Fertil Steril 2017;107(5):1122–9.CrossRefGoogle ScholarPubMed
Deng, J, Hong, HY, Zhao, Q, Nadgauda, A, Ashrafian, S, Behr, B, et al. Preimplantation genetic testing for aneuploidy in poor ovarian responders with four or fewer oocytes retrieved. J Assist Reprod Genet 2020;37(5):1147–54.CrossRefGoogle ScholarPubMed
Zhou, P, Baumgarten, SC, Wu, Y, Bennett, J, Winston, N, Hirshfeld-Cytron, J, et al. IGF-I signaling is essential for FSH stimulation of AKT and steroidogenic genes in granulosa cells. Mol Endocrinol 2013;27(3):511–23.CrossRefGoogle ScholarPubMed
Duffy, JM, Ahmad, G, Mohiyiddeen, L, Nardo, LG, Watson, A. Growth hormone for in vitro fertilization. Cochrane Database Syst Rev 2010;1:CD000099.Google Scholar
Garcia-Velasco, JA, Moreno, L, Pacheco, A, Guillén, A, Duque, L, Requena, A, et al. The aromatase inhibitor letrozole increases the concentration of intraovarian androgens and improves in vitro fertilization outcome in low responder patients: a pilot study. Fertil Steril 2005;84(1):82–7.Google Scholar
Nagels, HE, Rishworth, JR, Siristatidis, CS, Kroon, B. Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction. Cochrane Database Syst Rev 2015;11:CD009749.Google Scholar
Özcan, P, Fıçıcıoğlu, C, Kizilkale, O, Yesiladali, M, Tok, OE, Ozkan, F, et al. Can coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage? J Assist Reprod Genet 2016;33(9):1223–30.Google Scholar
Fragouli, E, Wells, D. Mitochondrial DNA assessment to determine oocyte and embryo viability. Semin Reprod Med 2015;33(6):401–9.Google Scholar
Xu, Y, Nisenblat, V, Lu, C, Li, R, Qiao, J, Zhen, X, et al. Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial. Reprod Biol Endocrinol 2018;16(1):29.Google Scholar
Khosravi, P, Kazemi, E, Zhan, Q, Malmsten, JE, Toschi, M, Zisimopoulos, P, et al. Deep learning enables robust assessment and selection of human blastocysts after in vitro fertilization. NPJ Digit Med 2019;2:21.Google Scholar
Farquhar, CM, Wang, YA, Sullivan, EA. A comparative analysis of assisted reproductive technology cycles in Australia and New Zealand 2004–2007. Hum Reprod 2010;25(9):2281–9.Google Scholar
Smith, ADAC, Tilling, K, Lawlor, DA, Nelson, SM. Live birth rates and perinatal outcomes when all embryos are frozen compared with conventional fresh and frozen embryo transfer: a cohort study of 337,148 in vitro fertilisation cycles. BMC Med 2019;17(1):202.Google Scholar
Maheshwari, A, Pandey, S, Amalraj Raja, E, Shetty, A, Hamilton, M, Bhattacharya, S. Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer? Hum Reprod Update 2018;24(1):35–58.Google Scholar
Roque, M, Haahr, T, Geber, S, Esteves, SC, Humaidan, P. Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes. Hum Reprod Update 2019;25(1):2–14.Google Scholar
Marozio, L, Picardo, E, Filippini, C, Mainolfi, E, Berchialla, P, Cavallo, F, et al. Maternal age over 40 years and pregnancy outcome: a hospital-based survey. J Matern Fetal Neonatal Med 2019;32(10):1602–8.CrossRefGoogle ScholarPubMed
Penzias, A, Bendikson, K, Butts, S, Coutifaris, C, Fossum, G, Falcone, T, et al. Guidance on the limits to the number of embryos to transfer: a committee opinion. Fertil Steril 2017;107(4):901–3.CrossRefGoogle Scholar
Gunnala, V, Reichman, DE, Meyer, L, Davis, OK, Rosenwaks, Z. Beyond the American Society for Reproductive Medicine transfer guidelines: How many cleavage-stage embryos are safe to transfer in women ≥43 years old? Fertil Steril 2014;102(6):1626–32.e1.Google Scholar
Singh, B, Reschke, L, Segars, J, Baker, VL. Frozen-thawed embryo transfer: the potential importance of the corpus luteum in preventing obstetrical complications. Fertil Steril 2020;113(2):252–7.Google Scholar
Devesa, M, Tur, R, Rodríguez, I, Coroleu, B, Martínez, F, Polyzos, NP. Cumulative live birth rates and number of oocytes retrieved in women of advanced age. A single centre analysis including 4500 women ≥38 years old. Hum Reprod 2018;33(11):2010–7.Google Scholar
Sneeringer, R, Klipstein, S, Ryley, DA, Alper, MM, Reindollar, RH. Pregnancy loss in the first in vitro fertilization cycle is not predictive of subsequent delivery in women over 40 years. Fertil Steril 2008;89(2):364–7.CrossRefGoogle Scholar
Ethics Committee of American Society for Reproductive Medicine. Fertility treatment when the prognosis is very poor or futile: a committee opinion. Fertil Steril 2012;98(1):e6–9.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
×