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Chapter 5 - The Case against Mild Stimulation Protocols

from Section 1 - Mild Forms of Ovarian Stimulation

Published online by Cambridge University Press:  14 April 2022

By
Carlotta Zacà ,
Francesca Pennetta  and
Andrea Borini
Edited by
Mohamed Aboulghar  and
Botros Rizk
Mohamed Aboulghar
Affiliation:
University of Cairo IVF Centre
Botros Rizk
Affiliation:
University of South Alabama
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Summary

The number of retrieved oocytes is one of the major parameters by which the intensity of ovarian stimulation is estimated. While conventional stimulation protocols in in vitro fertilization (IVF) are designed to obtain maximum oocytes yields, they have often been associated with increased risk of complications, increased costs derived from higher gonadotropin dosage, and lower embryo quality. For these reasons, physicians have introduced a milder approach to ovarian stimulation, focusing on a more patient-friendly and safe method, while attempting to improve IVF outcomes. Typically, the strengths of mild stimulation include: reduced mean number of days of stimulation, smaller total amount of gonadotropins, smaller mean number of oocytes retrieved balanced by possibly better embryo quality, decreased treatment discomfort, and reduced risk of complications. However, to date there are still unanswered questions about the possibility that a milder approach to ovarian stimulation is clinically superior to conventional regimens.

Type
Chapter
Information
Ovarian Stimulation , pp. 47 - 54
Publisher: Cambridge University Press
Print publication year: 2022

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References

Zegers-Hochschild, F, Adamson, D, Dyer, S, et al. The International Glossary on Infertility and Fertility Care, 2017. Hum Reprod 2017;32(9):1786–1801.Google Scholar
Nargund, G, Fauser, BC, Macklon, NS, et al. The ISMAAR proposal on terminology for ovarian stimulation for IVF. Hum Reprod 2007;22:2801–2804.Google Scholar
Alper, MM, Fauser, BC. Ovarian stimulation protocols for IVF: is more better than less? Reprod Biomed Online 2017;34(4):345–353.CrossRefGoogle ScholarPubMed
Siristatidis, C, Salamalekis, G, Dafopoulos, K, et al. Mild versus conventional ovarian stimulation for poor responders undergoing IVF/ICSI. In Vivo 2017;31(2):231–237.Google Scholar
Orvieto, R, Vanni, VS, Gleicher, N. The myths surrounding mild stimulation in vitro fertilization (IVF). Reprod Biol Endocrinol 2017;15(1):48.Google Scholar
Verberg, MFG, Eijkemans, MJC, Machlon, NS, et al. The clinical significance of the retrieval of a low number of oocytes following mild ovarian stimulation for IVF: a meta-analysis. Hum Reprod Update 2009;15:5–12.Google Scholar
Practice Committee of the American Society for Reproductive Medicine. Comparison of pregnancy rates for poor responders using IVF with mild ovarian stimulation versus conventional IVF: a guideline. Fertil Steril 2018;109(6):993–999.Google Scholar
Hillier, SG, Afnan, AM, Margara, RA, Winston, RM. Superovulation strategy before in vitro fertilization. Clin Obstet Gynaecol 1985;12(3):687–723.Google Scholar
Sunkara, SK, Rittenberg, V, Raine-Fenning, N, et al. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod 2011;26:1768–1774.Google Scholar
Ji, J, Liu, Y, Tong, XH, et al. The optimum number of oocytes in IVF treatment: an analysis of 2455 cycles in China. Hum Reprod 2013;28(10):2728–2734.Google Scholar
Beckers, NGM, Macklon, NS, Eijkemans, MJC, Fauser, BCJM. Women with regular menstrual cycles and a poor response to ovarian hyperstimulation for in vitro fertilization exhibit follicular phase characteristics suggestive of ovarian aging. Fertil Steril 2002;78:291–297.Google Scholar
Briggs, R, Kovacs, G, MacLachlan, V, Motteram, C, Baker, HW. Can you ever collect too many oocytes? Hum Reprod 2015;30(1):81–87.CrossRefGoogle ScholarPubMed
Fauser, BC, Devroey, P, Macklon, NS. Multiple birth resulting from ovarian stimulation for subfertility treatment. Lancet 2005;365:1807–1816.Google Scholar
Macklon, NS, Stouffer, RL, Giudice, LC, Fauser, BC. The science behind 25 years of ovarian stimulation for in vitro fertilization. Endocr Rev 2006;27:170–207.CrossRefGoogle ScholarPubMed
Zacà, C, Spadoni, V, Patria, G, et al. How do live birth and cumulative live birth rate in IVF cycles change with the number of oocytes retrieved? EC Gynaecol 2017;20:391–401.Google Scholar
Fauser, BC, Devroey, P, Yen, SS, et al. Minimal ovarian stimulation for IVF: appraisal of potential benefits and drawbacks. Hum Reprod 1999;14:2681–2686.Google Scholar
McAvey, B, Zapantis, A, Jindal, SK, Lieman, HJ, Polotsky, AJ. How many eggs are needed to produce an assisted reproductive technology baby: is more always better? Fertil Steril 2011;96:332–335.Google Scholar
Polyzos, NP, Drakopoulos, P, Parra, J, et al. Cumulative live birth rates according to the number of oocytes retrieved after the first ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection: a multicenter multinational analysis including 15,000 women. Fertil Steril 2018;110(4):661–670.Google Scholar
Devesa, M, Tur, R, Rodríguez, I, et al. 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):2010–2017.Google Scholar
Baart, EB, Martini, E, Eijkemans, MJ, et al. Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Hum Reprod 2007;22:980–988.Google Scholar
Verpoest, W, Fauser, BC, Papanikolaou, E, et al. Chromosomal aneuploidy in embryos conceived with unstimulated cycle IVF. Hum Reprod 2008;23(10):2369–2371.CrossRefGoogle ScholarPubMed
Gleicher, N, Kim, A, Weghofer, A, Barad, DH. Lessons from elective in vitro fertilization (IVF) in, principally, non-infertile women. Reprod Biol Endocrinol 2012;10:48.Google Scholar
Labarta, E, Bosch, E, Alama, P, et al. Moderate ovarian stimulation does not increase the incidence of human embryo chromosomal abnormalities in in vitro fertilization cycles. J Clin Endocrinol Metab 2012;97:1987–1994.Google Scholar
Rubio, C, Mercader, A, Alamá, P, et al. Prospective cohort study in high responder oocyte donors using two hormonal stimulation protocols: impact on embryo aneuploidy and development. Hum Reprod 2010;25:2290–2297.CrossRefGoogle ScholarPubMed
Labarta, E, Bosh, E, Mercader, A, et al. A higher ovarian response after stimulation for IVF is related to a higher number of euploid embryos. Biomed Res Int 2017;2017:5637923.Google Scholar
Sekhon, L, Shaia, K, Santistevan, A, et al. The cumulative dose of gonadotropins used for controlled ovarian stimulation does not influence the odds of embryonic aneuploidy in patients with normal ovarian response. J Assist Reprod Genet 2017;34(6):749–758.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;25:2–14.Google Scholar
Maheshwari, A, McLernon, D, Bhattacharya, S. Cumulative live birth rate: time for a consensus? Hum Reprod 2015;30(12):2703–2707.Google Scholar
Sunkara, SK, Khalaf, Y, Maheshwari, A, Seed, P, Coomarasamy, A. Association between response to ovarian stimulation and miscarriage following IVF: an analysis of 124 351 IVF pregnancies. Hum Reprod 2014;29(6):1218–1224.Google Scholar
Cai, QF, Wan, F, Huang, R, Zhang, HW. Factors predicting the cumulative outcome of IVF/ICSI treatment: a multivariable analysis of 2450 patients. Hum Reprod 2011;26(9):2532–2540.Google Scholar
Vaughan, DA, Leung, A, Resetkova, N, et al. How many oocytes are optimal to achieve multiple live births with one stimulation cycle? The one-and-done approach. Fertil Steril 2017;107(2):397–404.Google Scholar
Fauser, BC, Nargund, G, Andersen, AN, et al. Mild ovarian stimulation for IVF: 10 years later. Hum Reprod 2010;25(11):2678–2684.Google Scholar
Drakopoulos, P, Blockeel, C, Stoop, D, et al. Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos? Hum Reprod 2016;31(2):370–376.Google Scholar
Baker, VL. Mild ovarian stimulation for in vitro fertilization: one perspective from the USA. J Assist Reprod Genet 2013;30(2):197–202.Google Scholar
Delvigne, A. Symposium: update on prediction and management of OHSS. Epidemiology of OHSS. Reprod Biomed Online 2009;19:8–13.Google Scholar
Papanikolaou, EG, Tournaye, H, Verpoest, W, et al. Early and late ovarian hyperstimulation syndrome: early pregnancy outcome and profile. Hum Reprod 2005;20:636–641.Google Scholar
Matsaseng, T, Kruger, T, Steyn, W. Mild ovarian stimulation for in vitro fertilization: are we ready to change? A meta-analysis. Gynecol Obstet Invest 2013;76:233–240.Google Scholar
Steward, RG, Lan, L, Shah, AA, et al. Oocyte number as a predictor for ovarian hyperstimulation syndrome and live birth: an analysis of 256,381 in vitro fertilization cycles. Fertil Steril 2014;101(4):967–973.Google Scholar
Zacà, C, Bazzocchi, A, Pennetta, F, et al. Cumulative live birth rate in freeze-all cycles is comparable to that of a conventional embryo transfer policy at the cleavage stage but superior at the blastocyst stage. Fertil Steril 2018;110(4):703–709.Google Scholar
Devroey, P, Polyzos, NP, Blockeel, C. An OHSS-free clinic by segmentation of IVF treatment. Hum Reprod 2011;26:2593–7.Google Scholar
Wong, KM, van Wely, M, Mol, F, Repping, S, Mastenbroek, S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev 2017;3:CD011184.Google Scholar

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