Cost-effectiveness analysis of GnRH-agonist long-protocol and GnRH-antagonist protocol for in vitro fertilization

Abstract

The gonadotropin releasing hormone agonist (GnRH-a) long-protocols and the GnRH-antagonist protocols are two commonly used protocols for in vitro fertilization (IVF), but their cost-effectiveness has not been studied, especially in China. A retrospective study involving 1638 individuals in GnRH-a long-protocol and 621 in GnRH-antagonist protocol were conducted and a decision tree model analysis was used to analyze the cost-effectiveness. Both direct and indirect costs were calculated. As a result, during the fresh embryo transplantation cycles, there was no significant difference in the rate of ongoing pregnancy between the two protocols, the average cost of per ongoing pregnancy in the GnRH-antagonist protocol was $ 16970.85, and that in the GnRH-agonist long-protocol was $19902.24. The probability of cumulative ongoing pregnancy per start cycle was estimated at 60.65% for the GnRH-antagonist protocol and 71.6% for the GnRH-agonist long-protocol (P < 0.01). Considering the cumulative ongoing pregnancy rate, the mean costs per ongoing pregnancy were estimated at $8176.76 and at $7595.28 with GnRH-antagonist protocol and GnRH-agonist long protocol, respectively. In conclusion, in fresh embryo transplantation cycle, the GnRH-antagonist protocol has economic advantage. However, the GnRH-agonist long protocol is more cost effective considering the cumulative ongoing pregnancy rate in the fresh embryo and frozen embryo transplantation cycles. According to a World Health Organization (WHO) report, about 48.5 million couples are affected by infertility worldwide in 2010 1. With the refinement and development of assisted reproductive technology (ART), increasing number of infertile couples seek ART. The European Society of Human Reproduction and Embryology (ESHRE) reported that the worldwide number of babies born as a result of ART has reached an estimated total of 8 million since the world's first, Louise Brown, was born in July 1978 2. Up to now, ART is the most important method to treat infertility in the world. Study has shown that cumulative live birth rates are increased with the number of oocytes obtained 3. Therefore, controlled ovarian hyperstimulation (COH) is an important process to obtain a set number of oocytes for IVF. The GnRH-agonists were introduced into IVF in the late 1980s and the GnRH-agonist long-protocol is still the most frequently used protocol in most centers worldwide 4. The basic principle is to use gonadotropin-releasing hormone agonist (GnRH-a) to regulate pituitary and stimulate follicular growth with exogenous gonadotropin hormone, and avoid endogenous luteinizing hormone (LH) surge before oocyte retrieval 5,6. Since 1990s, GnRH antagonists were used in COH, this protocol competitively blocks pituitary GnRH receptors, inducing a rapid, reversible suppression of gonadotrophin secretion and preventing and interrupting LH surges 6-8. The GnRH-antagonist protocol have been widely adopted in IVF due to these advantages.

The (decision) tree of fertility: an innovative decision-making algorithm in assisted reproduction technique

“…Specifically in the ART setting, the decision tree model has been previously applied mainly in cost-effectiveness analyses, for instance to identify the most cost-effective ovarian stimulation drug for intra-uterine insemination (IUI) [42]; to evaluate the clinical utility for preimplantation genetic assessment for aneuploidy after IVF in the USA [43], and in Germany [44]; to highlight anti-Müllerian hormone (AMH) serum levels as informative for stimulation dose management for optimizing blastocyst development [45]; and to identify the most cost-effective policy in terms of ART success in case of female age below 38 years comparing expectant management, IUI with ovarian stimulation and IVF [46]. Moreover, a decision tree was applied to develop a model combining AMH, antral follicle counts, FSH basal levels and female age to obtain the true ovarian reserve [47], and to compare GnRH-agonist long protocol to GnRH-antagonist protocol in IVF, highlighting that GnRH-antagonist introduces an economic advantage in case of fresh embryos, while the GnRH-agonist long protocol is preferable considering the cumulative pregnancy rate using both fresh and frozen embryos [48]. Here, we applied for the first time this statistical approach to new clinical question that should be increasingly relevant in ART practice.…”

Retrospective study of rescue intra cytoplasmic sperm injection (ICSI) as an emergency procedure aimed at salvaging the IVF ET cycle

“…Miaomiao Jing et al in a retrospective study of 1638 individuals in long agonist cycle and 621 patients of antagonist cycle concluded that Antagonist cycle are more economical. This was because of lower doses of gonadotropin were required as well as less hospitalization due to OHSS [13] .…”

The trends of assisted reproductive technologies and cost for ovarian stimulation protocols in Ukraine

“…The cost of tree-based therapy regimens for the long protocol using GnRH antagonists was $16,970.85, and with agonists was $2,902.24. The GnRH-agonist protocol has been found to be more cost-effective (Jing et. al.…”