Abstract
In the controlled ovarian hyperstimulation (COH) cycle of the in vitro fertilization-embryo transfer (IVF-ET) therapy, the clinicians observe the patients’ responses to gonadotropin dosages through closely monitoring their physiological states, to balance the trade-off between pregnancy rate and ovarian hyperstimulation syndrome (OHSS) risk. In this paper, we model the clinical practice in the COH treatment cycle as a stochastic dynamic program, to capture the dynamic decision process and to account for each individual patient’s stochastic responses to gonadotropin administration. We discretize the problem into a Markov decision process and solve it using a slightly modified backward dynamic programming algorithm. We then evaluate the policies using simulation and explore the impact of patient misclassification. More specifically, we focus on patients with polycystic ovary syndrome (PCOS) or potential, that is, the patients that tend to be more sensitive to gonadotropin administration.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aboulghar, M. A., & Mansour, R. T. (2003). Ovarian hyperstimulation syndrome: classifications and critical analysis of preventive measures. Human Reproduction Update, 9(3), 275–289.
Al-Shawaf, T., & Grudzinskas, J. G. (2003). Prevention and treatment of ovarian hyperstimulation syndrome. Best Practice & Research Clinical Obstetrics & Gynaecology, 17(2), 249–261.
Alagoz, O., Maillart, L. M., Schaefer, A. J., & Roberts, M. S. S. (2004). The optimal timing of living-donor liver transplantation. Management Science, 50(10), 1420–1430.
Alagoz, O., Maillart, L. M., Schaefer, A. J., & Roberts, M. S. S. (2007a). Choosing among living-donor and cadaveric livers. Management Science, 53(11), 1702–1715.
Alagoz, O., Maillart, L. M., Schaefer, A. J., & Roberts, M. S. S. (2007b). Determining the acceptance of cadaveric livers using an implicit model of the waiting list. Operations Research, 55(1), 24–36.
Allahbadia, G. N. (2005). Manual of ovulation induction Anshan Ltd.
Asch, R. H., Li, H.-P., Balmaceda, J. P., Weckstein, L. N., & Stone, S. C., (1991). Severe ovarian hyperstimulation syndrome in assisted reproductive technology, definition of high risk groups. Human Reproduction, 6(10), 1395–1399.
Balasch, J., Fábregues, F., Creus, M., Puerto, B., Peñarrubia, J., & Vanrell, J. A. (2001). Follicular development and hormone concentrations following recombinant FSH administration for anovulation associated with polycystic ovarian syndrome: prospective, randomized comparison between low-dose step-up and modified step-down regimens. Human Reproduction, 16(4), 652–656.
Banks, J., Carson, J., Nelson, B. L., & Nicol, D. (2004). Discrete-event system simulation, 4th edn. New York: Prentice Hall.
Barbieri, R. L., & Hornstein, M. D. (1999). Assisted reproduction-In Vitro Fertilization success is improved by ovarian stimulation with exogenous gonadotropins and pituitary suppression with gonadotropin-releasing hormone analogues. Endocrine Reviews, 20(3), 249–252.
Biller, B., & Nelson, B. L. (2003). Modeling and generating multivariate time-series input processes using a vector autoregressive technique. ACM Transactions on Modeling and Computer Simulation, 13(3), 211–237.
Biller, B., & Nelson, B. L. (2005). Fitting time series input processes for simulation. Operations Research, 53(3), 549–559.
Cai, J., Huang, H., & Zhu, Y. (2005). Poor responder-high responder: The importance of follicle stimulating hormone receptor in ovarian stimulation protocols. Fertility and Sterility (Supplement 1), 84(1), 44.
Cario, M. C., & Nelson, B. L. (1996). Autoregressive to anything: time-series input processes for simulation. Operations Research Letters, 19(2), 51–58.
Cario, M. C., & Nelson, B. L. (1998). Numerical methods for fitting and simulating autoregressive-to-anything processes. INFORMS Journal on Computing, 10(1), 72–81.
Chang, M.-Y., Chiang, C.-H., Hsieh, T.-T., Soong, Y.-K., & Hsu, K.-H. (1998). Use of the antral follicle count to predict the outcome of assited reproductive technologies. Fertility and Sterility, 69(3), 505–510.
Chen, C.-H., Zhang, X., Barnes, R., Confino, E., Milad, M., Puscheck, E., & Kazer, R. R. (2003). Relationship between peak serum estradiol levels and treatment outcome in in vitro fertilization cycles after embryo transfer on day 3 or day 5. Fertility and Sterility, 80(1), 75–79.
Delvigne, A., & Rozenberg, S. (2002). Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): A review. Human Reproduction Update, 8(6), 559–577.
Delvigne, A., & Rozenberg, S. (2003). Review of clinical course and treatment of ovarian hyperstimulation syndrome(OHSS). Human Reproduction Update, 9(1), 77–96.
Fauser, B. C. J. M., Devroey, P., Yen, S. S. C., Gosden, R., Jr, W. F. C., Baird, D. T., & Bouchard, P. (1999). Minimal ovarian stimulation for IVF: appraisal of potential benefits and drawbacks. Human Reproduction, 14(11), 2681–2686.
He, N. (2004). An introduction to assisted reproductive technology, part 1. China Science & Technology Education, 6, 48–50 (in Chinese).
Heijnen, E. M. E. W., Macklon, N. S., & Fauser, B. C. J. M. (2004). What is the most relevant standard of success in assisted reproduction? The next step to improving outcomes of IVF: consider the whole treatment. Human Reproduction, 19(9), 1936–1938.
Hofmann, G. E., Toner, J. P., Muasher, S. J., & Jones, G. S. (1989). High-dose follicle-stimulating hormone (FSH) ovarian stimulation in low-responder patients for in vitro fertilization. Journal of in Vitro Fertilization and Embryo Transfer, 6(5), 285–289.
Hoomans, E. H. M., Andersen, A. N., Loft, A., Leerentveld, R. A., Kamp, A. A. V., & Zech, H. (1999). A prospective, randomized clinical trial comparing 150 IU recombinant follicle stimulating hormone (Puregon®) and 225 IU highly purified urinary follicle stimulation hormone (Metrodin-HP®) in a fixed-dose regimen in women undergoing ovarian stimulation. Human Reproduction, 14(10), 2442–2447.
Klemetti, R., Sevón, T., Gissler, M., & Hemminki, E. (2005). Complications of IVF and ovulation induction. Human Reproduction, 20(12), 3293–3300.
Ku, S.-Y., Kim, S. D., Jee, B. C., Suh, C. S., Choi, Y. M., Kim, J. G., Moon, S. Y., & Kim, S. H. (2006). Clinical efficacy of body mass index as predictor of in vitro fertilization and embryo transfer outcomes. Journal of Korean Medical Science, 21(2), 300–303.
Martin, J. R., Mahutte, N. G., Arici, A., & Sakkas, D. (2006). Impact of duration and dose of gonadotrophins on IVF outcomes. Reproductive Biomedicine Online, 13(5), 645–650.
Mathur, R. S., Akande, A. V., Keay, S. D., Hunt, L. P., & Jenkins, J. M. (2000). Distinction between early and late ovarian hyperstimulation syndrome. Fertility and Sterility, 73(5), 901–907.
Norman, R. J., Dewailly, D., Legro, R. S., & Hickey, T. E. (2007). Polycystic ovary syndrome. The Lancet, 370(9588), 685–697.
Oyesanya, O. A., Parsons, J. H., Collins, W. P., & Campbell, S. (1995). Total ovarian volume before human chorionic gonadotrophin administration for ovulation induction may predict the hyperstimulation syndrome. Human Reproduction, 10(12), 3211–3212.
Papageorgiou, T., Guibert, J., Goffinet, F., Patrat, C., Fulla, Y., Janssens, Y., & Zorn, J.-R. (2002). Percentile curves of serum estradiol levels during controlled ovarian stimulation in 905 cycles stimulated with recombinant FSH show that high estradiol is not detrimental to IVF outcome. Human Reproduction, 17(11), 2846–2850.
Peña, J. E., Chang, P. L., Chan, L.-K., Zeitoun, K., Thornton, M. H., & Sauer, M. V. (2002). Supraphysiological estradiol levels do not affect oocyte and embryo quality in oocyte donation cycles. Human Reproduction, 17(1), 83–87.
Pittaway, D. E., & Wentz, A. C. (1983). Evaluation of the exponential rise of serum estradiol concentrations in human menopausal gonadotropin-induced cycles. Fertility and Sterility, 40(6), 763–767.
Powell, W. B. (2007). Approximate dynamic programming. New York: Wiley.
Reid, P. P., Compton, W. D., Grossman, J. H., & Fanjiang, G. (2005). Building a better delivery system: a new engineering/health care partnership. Committee on Engineering and the Health Care System, National Academy of Engineering, Institute of Medicine. National Academies Press.
Rombauts, L. (2007). Is there a recommended maximum starting dose of FSH in IVF? Journal of Assisted Reproduction and Genetics, 24(8), 343–349.
Schmidt, A., Hahn, S., White, L., Russell, D., Kelk, D., & Smith, D. (2004). High peak serum estradiols during IVF-ET impair pregnancy and implantation rates. Fertility and Sterility (Supplement 2), 82(2), 14.
Schmittlein, D. C., & Morrison, D. G. (2003). A live baby or your money back: The marketing of in vitro fertilization procedures. Management Science, 49(12), 1617–1635.
Seifer, D. B., & Collins, R. L. (2002). Office-based infertility practice. Berlin: Springer.
Tarlatzis, B. (2002). Ovulation induction. Amsterdam: Elsevier.
Thomas, K., Searle, T., Quinn, A., Wood, S., Lewis-Jones, L., & Kingsland, C. (2002). The value of routine estradiol monitoring in assisted conception cycles. Acta Obstetricia et Gynecologica Scandinavica, 81(6), 551–554.
Wely, M. V., Fauser, B. C. J. M., Laven, J. S. E., Eijkemans, M. J., & Veen, F. V. D. (2006). Validation of a prediction model for the follicle-stimulating hormone response dose in women with polycystic ovary syndrome. Fertility and Sterility, 86(6), 1710–1715.
Wikland, M., Bergh, C., Borg, K., Hillensjö, T., Howles, C. M., Knutsson, A., Nilsson, L., & Wood, M. (2001). A prospective, randomized comparison of two starting doses of recombinant FSH in combination with cetrorelix in women undergoing ovarian stimulation for IVF/ICSI. Human Reproduction, 16(8), 1676–1681.
Wilson, E. A., Jawad, M. J., & Hayden, T. L. (1982). Rates of exponential increase of serum estradiol concentrations in normal and human menopausal gonadotropin-induced cycles. Fertility and Sterility, 37(1), 46–49.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
He, M., Zhao, L. & Powell, W.B. Optimal control of dosage decisions in controlled ovarian hyperstimulation. Ann Oper Res 178, 223–245 (2010). https://doi.org/10.1007/s10479-009-0563-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10479-009-0563-y