The Effectiveness and Safety of the Prolonged Down-regulation Protocol for Controlled Ovarian Hyperstimulation

Summary

Since the first "tube baby", Louise Brown, was born in the United Kingdom in 1978, many infertile couples have been benefitted from in vitro fertilization and embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI). Although a late starter, China is developing rapidly in ART and playing a more and more important role in the area of reproductive medicine. In spite of the continuous development in ART, so far, the overall success rate of IVF/ICSI is still hovering around 25-40%. There are many factors influencing the success rate of IVF/ICSI. Among them, an appropriate controlled ovarian hyperstimulation (COH) protocol is directly associated with the number of oocyte retrieved, as well as the number and quality of embryos, which exert an important influence on the success rate of IVF/ICSI. The luteal phase pituitary down-regulation protocol is one of the most widely used COH protocols in clinical practice, particularly in China. Though effective, it may lead to an increased incidence of ovarian hyperstimulation syndrome (OHSS), as well as a negative impact on endometrial receptivity. The coping strategy is to freeze all the embryos and transfer in the next cycle. Though avoiding the above mentioned adverse effects, such strategy increases the time to pregnancy (TTP) and therefore results in certain psychological and economic burdens for infertile couples. In recent years, some Chinese researches applied the early follicular full-dose down-regulation protocol that is always performed to women with endometriosis to a more general IVF/ICSI population and found a clinical pregnancy rate of 64% in the fresh embryo transfer cycle, much higher than that of the luteal phase down-regulation protocol. Furthermore, since this protocol decrease the risk of progesterone elevation on hCG day, it increases the fresh embryo transfer rate and shortens TTP. Given most studies regarding the effectiveness and safety of the early follicular phase full-dose down-regulation protocol are retrospective studies, the results may be biased by several confounding factors. Therefore, we would like to conduct a multicenter, randomized controlled trial to compare the pregnancy outcome and safety indicators between the early follicular phase full-dose down-regulation protocol and the luteal phase down-regulation protocol.

Timeline

Start

2019-02-01

Primary completion

2020-09-01

Completion

2020-12-31

Publications

• Background The United Kingdom national data. Human Fertility and Embryology Authority. 2015
• Background The United States national assisted reproductive technology(ART) data. Centers for Disease Control and Prevention.2015
• Background Chinese Reproductive Medicine Society national assisted reproductive technology (ART) data. 2015
• Background L Hu, Y Sun. The impact of various controlled ovarian hyperstimulation (COS) protocols on the outcome of in vitro fertilization and embryo transfer (IVF-ET). Journal of Practical Obstetrics and Gynecology. 2014;30(10);723-725.
• Background Y Hu, T Ding, Y Zhao, Q Wu. The comparison of the birth outcome of in vitro fertilization and embryo transfer (IVF-ET) after two different down-regulation protocols. Maternal and Child Health Care of China.2017;32(4):808-810.
• Background D Xu, Q Wu. The comparison of the application of ultra-long down-regulation protocol and antagonist protocol in in vitro fertilization and embryo transfer (IVF-ET). Jiangxi Medical Journal. 2015;50(1):13-15.
• Background Q Su, Q Wu, L Tian, Y Li. The clinical analysis of different controlled ovarian hyperstimulation (COS) protocols in in vitro fertilization and embryo transfer (IVF-ET). Jiangxi Medical Journal. 2014;49(8):723-725.
• Background Y Li, Q Wu, Y Yi. The impact of the follicular phase ultra-long long down-regulation protocol on PCOS patients' outcome after in vitro fertilization and embryo transfer (IVF-ET). Jiangxi Medical Journal. 2014;49(2):117-120.
• Background L Nie, Q Wu, Y Zhang, J Chen. The analysis of the application of the follicular phase ultra-long down-regulation protocol in patients with fine ovarian reserve but a failed previous in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) and embryo transfer. Progress in Obstetrics and Gynecology. 2011;20(6):470-472.
• Background F Gong, K Luo, G Lu. The effectiveness of the modified ultra-long down-regulation protocol in PCOS patients receiving in vitro fertilization and embryo transfer (IVF-ET). Basic and Clinical Medicine. 2010，30(9)：984-987.
• Background Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG; Consolidated Standards of Reporting Trials Group. CONSORT 2010 Explanation and Elaboration: Updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol. 2010 Aug;63(8):e1-37. doi: 10.1016/j.jclinepi.2010.03.004. Epub 2010 Mar 25.

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