Economic Evaluation of Three Frequently Used Gonadotrophins in Assisted Reproduction Techniques in the Management of Infertility in the Netherlands.

BACKGROUND AND OBJECTIVE: Subfertility represents a multidimensional problem associated with significant distress and impaired social well-being. In the Netherlands, an estimated 50,000 couples visit their general practitioner and 30,000 couples seek medical specialist care for subfertility. We conducted an economic evaluation comparing recombinant human follicle-stimulating hormone (follitropin alfa, r-hFSH, Gonal-F®) with two classes of urinary gonadotrophins-highly purified human menopausal gonadotrophin (hp-HMG, Menopur®) and urinary follicle-stimulating hormone (uFSH, Fostimon®)-for ovarian stimulation in women undergoing in vitro fertilization (IVF) treatment in the Netherlands. METHODS: A pharmacoeconomic model was developed, simulating each step in the IVF protocol from the start of therapy until either a live birth, a new IVF treatment cycle or cessation of IVF, following a long down-regulation protocol. A decision tree combined with a Markov model details progress through each health state, including ovum pickup, fresh embryo transfer, up to two subsequent cryo-preserved embryo transfers, and (ongoing) pregnancy or miscarriage. A health insurer perspective was chosen, and the time horizon was set at a maximum of three consecutive treatment cycles, in accordance with Dutch reimbursement policy. Transition probabilities and costing data were derived from a real-world observational outcomes database (from Germany) and official tariff lists (from the Netherlands). Adverse events were considered equal among the comparators and were therefore excluded from the economic analysis. A Monte Carlo simulation of 5000 iterations was undertaken for each strategy to explore uncertainty and to construct uncertainty intervals (UIs). All cost data were valued in 2013 Euros. The model's structure, parameters and assumptions were assessed and confirmed by an external clinician with experience in health economics modelling, to inform on the appropriateness of the outcomes and the applicability of the model in the chosen setting. RESULTS: The mean total treatment costs were estimated as €5664 for follitropin alfa (95 % UI €5167-6151), €5990 for hp-HMG (95 % UI €5498-6488) and €5760 for uFSH (95 % UI €5256-6246). The probability of a live birth was estimated at 36.1 % (95 % UI 27.4-44.3 %), 33.9 % (95 % UI 26.2-41.5 %) and 34.1 % (95 % UI 25.9-41.8 %) for follitropin alfa, hp-HMG and uFSH, respectively. The costs per live birth estimates were €15,674 for follitropin alfa, €17,636 for hp-HMG and €16,878 for uFSH. Probabilistic sensitivity analysis indicated a probability of 72.5 % that follitropin alfa is cost effective at a willingness to pay of €20,000 per live birth. The probabilistic results remained constant under several analyses. CONCLUSION: The present analysis shows that follitropin alfa may represent a cost-effective option in comparison with uFSH and hp-HMG for IVF treatment in the Netherlands healthcare system.

Cost-saving treatment strategies in in vitro fertilization: a combined economic evaluation of two large randomized clinical trials comparing highly purified human menopausal gonadotropin and recombinant follicle-stimulating hormone alpha.

OBJECTIVE: To assess the cost-effectiveness of two gonadotropin treatments that are available in the United Kingdom in light of limited public funding and the fundamental role of costs in IVF treatment decisions. DESIGN: An economic evaluation based on two large randomized clinical trials in IVF patients using a simulation model. SETTING: Fifty-three fertility clinics in 13 European countries and Israel. PATIENT(S): Women indicated for treatment with IVF (N = 986), aged 18-38, participating in double-blind, randomized controlled trials. INTERVENTION(S): Highly purified menotropin (HP-hMG, Menopur) or recombinant follitropin alpha (rFSH, Gonal-F). MAIN OUTCOME MEASURE(S): Cost per IVF cycle and cost per live birth for HP-hMG and rFSH alpha. RESULT(S): HP-hMG was more effective and less costly versus rFSH for both IVF cost per live birth and for IVF cost per baby (incremental cost-effectiveness ratio was negative). The mean costs per IVF treatment for HP-hMG and rFSH were 2408 pounds (95% confidence interval [CI], 2392 pounds, 2421 pounds) and 2660 pounds (95% CI 2644 pounds, 2678 pounds), respectively. The mean cost saving of 253 pounds per cycle using HP-hMG allows one additional cycle to be delivered for every 9.5 cycles. CONCLUSION(S): Treatment with HP-hMG was dominant compared with rFSH in the United Kingdom. Gonadotropin costs should be considered alongside live-birth rates to optimize outcomes using scarce health-care resources.

Comparison of controlled ovarian stimulation with human menopausal gonadotropin or recombinant follicle-stimulating hormone.

OBJECTIVE: To carefully examine the features of controlled ovarian stimulation performed with recombinant FSH-alpha or hMG. DESIGN: Controlled, prospective, randomized comparison of fixed gonadotropin regimens. SETTING: Academic research institution. PATIENT(S): Fifty infertile patients who were candidates for IUI. INTERVENTION(S): Patients were randomized to receive a fixed regimen of recombinant FSH-alpha (150 IU/day, 25 patients) or hMG (150 IU/day, 25 patients), after GnRH-agonist suppression (long regimen). MAIN OUTCOME MEASURES: Daily measurements of serum LH, immunoreactive FSH, hCG, E(2), P, and T. Transvaginal pelvic ultrasound every 2 days. Pregnancy and abortion rates. Cost of medications. Two recombinant FSH-alpha-treated patients did not respond. Despite matched daily FSH dose, duration of treatment (hMG 10.8 +/- 0.4 vs. recombinant FSH-alpha 12.4 +/- 0.5 days), gonadotropin dose (21.7 +/- 0.8 vs. 25.3 +/- 1.3 ampoules), gonadotropin cost (288 +/- 10 vs. 1,299 +/- 66 /cycle), serum P levels, and small preovulatory follicle number were significantly lower, and LH, hCG, immunoreactive FSH levels, and larger follicles on day 8 were significantly higher in hMG-treated patients. The pregnancy, abortion, and twin pregnancy rates did not differ. CONCLUSION: The hMG administration was associated with: [1]. increased serum LH activity and immunoreactive FSH levels during treatment; [2]. reduced signs of premature luteinization; [3]. differential modulation of folliculogenesis; [4]. lower treatment duration, gonadotropin dose, and cost; and [5]. clinical outcome comparable to recombinant FSH-alpha.