RESUMEN
OBJECTIVE: This paper uses health economics methods to discuss the cost-effectiveness value of long protocol and antagonist protocol for in vitro fertilisation and embryo transfer (ET) in the Chinese population. DESIGN: Health economic evaluation study. SETTING: The data needed to construct the model for this study were derived from published studies and other secondary sources in China. PARTICIPANTS: No patients participated in the study. MEASURES: The main outcomes were live birth rate (LBR) and cost. From the societal perspective, we considered the direct and indirect costs over the course of the treatment cycles. A cost-effectiveness was measured using the incremental cost-effectiveness ratio and the probability that a protocol has higher net monetary benefit. Sensitivity analysis was carried out to verify the reliability of the simulation results. RESULTS: For the Chinese population, the long protocol resulted in a higher LBR than the antagonist protocol (29.33% vs 20.39%), but at the same time, it was more expensive (ï¿¥29 146.26 (US$4333.17) vs ï¿¥23 343.70 (US$3470.51)), in the case of considering only one fresh ET cycle. It was the same when considering subsequent frozen ET (FET) cycles (51.78% vs 42.81%; ï¿¥30 703.02 (US$4564.62) vs ï¿¥24 740.95 (US$3678.24)). The results of most subgroups were consistent with the results of the basic analysis. However, for certain populations, the long protocol was the inferior protocol (less effective and more expensive). CONCLUSION: For the Chinese population, when the monetary value per live birth was greater than ï¿¥65 420 (US$9726) and ï¿¥66 400 (US$9872), respectively, considering only one fresh cycle and considering subsequent frozen cycles, the long protocol is the preferred protocol. This threshold also varies for women of different ages and ovarian response capacities. For women in POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) group 2, group 3 and group 4, antagonist protocol is recommended as the preferred protocol. The results of this study need to be verified by further large-scale randomised controlled trials.
Asunto(s)
Análisis Costo-Beneficio , Hormona Liberadora de Gonadotropina , Humanos , China , Femenino , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Embarazo , Adulto , Fertilización In Vitro/economía , Fertilización In Vitro/métodos , Inyecciones de Esperma Intracitoplasmáticas/economía , Transferencia de Embrión/economía , Transferencia de Embrión/métodos , Economía Farmacéutica , Modelos Económicos , Tasa de Natalidad , Pueblos del Este de AsiaRESUMEN
STUDY QUESTION: Which assited reproductive technology (ART) interventions in high-income countries are cost-effective and which are not? SUMMARY ANSWER: Among all ART interventions assessed in economic evaluations, most high-cost interventions, including preimplantation genetic testing for aneuploidy (PGT-A) for a general population and ICSI for unexplained infertility, are unlikely to be cost-effective owing to minimal or no increase in effectiveness. WHAT IS KNOWN ALREADY: Approaches to reduce costs in order to increase access have been identified as a research priority for future infertility research. There has been an increasing number of ART interventions implemented in routine clinical practice globally, before robust assessments of evidence on economic evaluations. The extent of clinical effectiveness of some studied comparisons has been evaluated in high-quality research, allowing more informative decision making around cost-effectiveness. STUDY DESIGN, SIZE, DURATION: We performed a systematic review and searched seven databases (MEDLINE, PUBMED, EMBASE, COCHRANE, ECONLIT, SCOPUS, and CINAHL) for studies examining ART interventions for infertility together with an economic evaluation component (cost-effectiveness, cost-benefit, cost-utility, or cost-minimization assessment), in high-income countries, published since January 2011. The last search was 22 June 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two independent reviewers assessed publications and included those fulfilling the eligibility criteria. Studies were examined to assess the cost-effectiveness of the studied intervention, as well as the reporting quality of the study. The chosen outcome measure and payer perspective were also noted. Completeness of reporting was assessed against the Consolidated Health Economic Evaluation Reporting Standard. Results are presented and summarized based on the intervention studied. MAIN RESULTS AND THE ROLE OF CHANCE: The review included 40 studies which were conducted in 11 high-income countries. Most studies (n = 34) included a cost-effectiveness analysis. ART interventions included medication or strategies for controlled ovarian stimulation (n = 15), IVF (n = 9), PGT-A (n = 7), single embryo transfer (n = 5), ICSI (n = 3), and freeze-all embryo transfer (n = 1). Live birth was the mostly commonly reported primary outcome (n = 27), and quality-adjusted life years was reported in three studies. The health funder perspective was used in 85% (n = 34) of studies. None of the included studies measured patient preference for treatment. It remains uncertain whether PGT-A improves pregnancy rates compared to IVF cycles managed without PGT-A, and therefore cost-effectiveness could not be demonstrated for this intervention. Similarly, ICSI in non-male factor infertility appears not to be clinically effective compared to standard fertilization in an IVF cycle and is therefore not cost-effective. Interventions such as use of biosimilars or HMG for ovarian stimulation are cheaper but compromise clinical effectiveness. LIMITATIONS, REASONS FOR CAUTION: Lack of both preference-based and standardized outcomes limits the comparability of results across studies. The selection of efficacy evidence offered for some interventions for economic evaluations is not always based on high-quality randomized trials and systematic reviews. In addition, there is insufficient knowledge of the willingness to pay thresholds of individuals and state funders for treatment of infertility. There is variable quality of reporting scores, which might increase uncertainty around the cost-effectiveness results. WIDER IMPLICATIONS OF THE FINDINGS: Investment in strategies to help infertile people who utilize ART is justifiable at both personal and population levels. This systematic review may assist ART funders decide how to best invest to maximize the likelihood of delivery of a healthy child. STUDY FUNDING/COMPETING INTEREST(S): There was no funding for this study. E.C. and R.W. receive salary support from the National Health and Medical Research Council (NHMRC) through their fellowship scheme (EC GNT1159536, RW 2021/GNT2009767). M.D.-T. reports consulting fees from King Fahad Medical School. All other authors have no competing interests to declare. REGISTRATION NUMBER: Prospero CRD42021261537.
Asunto(s)
Análisis Costo-Beneficio , Países Desarrollados , Técnicas Reproductivas Asistidas , Humanos , Técnicas Reproductivas Asistidas/economía , Femenino , Embarazo , Países Desarrollados/economía , Infertilidad/terapia , Infertilidad/economía , Inyecciones de Esperma Intracitoplasmáticas/economía , Inyecciones de Esperma Intracitoplasmáticas/métodos , Diagnóstico Preimplantación/economía , Diagnóstico Preimplantación/métodos , Índice de EmbarazoRESUMEN
OBJECTIVE: To assess the potential costs and benefits of preimplantation genetic testing for aneuploidy (PGT-A) across age groups, considering financial costs, total euploidy rates and the potential for morphology grading to predict a euploid embryo. METHODS: This study is a blinded retrospective chart review of patients who incorporated PGT-A as part of their in vitro fertilization (IVF) treatment cycle at a university-affiliated fertility clinic. Patients between 25-44 years of age undergoing IVF with intracytoplasmic sperm injection and PGT-A with autologous oocytes (n = 220) were included in this study. Number of blastocysts achieved, euploidy rates and PGT-A costs were compared between 3 age groups: <35 years, 35-37, and ≥38. Additionally, agreement on the top-quality embryo based on morphology assessment alone versus PGT-A selection was analyzed and further compared based on the number of blastocysts achieved. RESULTS: A significant negative correlation between patient age and number of embryos produced, PGT-A costs, and euploidy rates (P < 0.001) was observed. Additionally, morphology alone ratings were able to predict the top-quality euploid embryo 78% of the time in the <35 age group, but only 32% of the time in the ≥38 age group (P < 0.05), with a trend toward even lower agreement when 3 or fewer blastocysts were produced. CONCLUSION: Based on our cost analysis, it may be advantageous to incorporate PGT-A when maternal age is ≥38, given the lower financial costs associated with each cycle and the low likelihood of transferring a euploid embryo on the first attempt for this age group. Nevertheless, we acknowledge that PGT-A remains a complex decision influenced by a multitude of factors.
Asunto(s)
Aneuploidia , Análisis Costo-Beneficio , Diagnóstico Preimplantación , Humanos , Diagnóstico Preimplantación/economía , Femenino , Adulto , Estudios Retrospectivos , Fertilización In Vitro/economía , Factores de Edad , Canadá , Embarazo , Pruebas Genéticas/economía , Inyecciones de Esperma Intracitoplasmáticas/economíaRESUMEN
BACKGROUND: Assisted reproductive technology (ART) insurance mandates promote more selective utilization of ART clinic resources including intracytoplasmic sperm injection (ICSI). Our objective was to examine whether ICSI utilization differs by state insurance mandates for ART coverage and assess if such a difference is associated with male factor, preimplantation genetic testing (PGT), and/or live birth rates. METHODS: In this retrospective analysis of the Centers for Disease Control (CDC) data from 2018, ART clinics in ART-mandated states (n = 8, AR, CT, HI, IL, MD, MA, NJ, RI) were compared individually to one another and with non-mandated states in aggregate (n = 42) for use of ICSI, male factor, PGT, and live birth rates. ANOVA was used to evaluate differences between ART-mandated states and non-mandated states. Individual ART-mandated states were compared using Welch t-tests. Statistical significance was determined by Bonferroni Correction. RESULTS: There were significant differences in ICSI rates (%, mean ± SD) between MA (53.3 ± 21.3) and HI (90.7 ± 19.6), p = 0.028; IL (86.5 ± 18.7) and MA, p = 0.002; IL and MD (57.2 ± 30.8), p = 0.039; IL and NJ (62.0 ± 26.8), p = 0.007; between non-mandated states in aggregate (79.9 ± 19.9) and MA, p = 0.006, and NJ (62.0 ± 26.8), p = 0.02. Male factor rates of HI (65.8 ± 16.0) were significantly greater compared to CT (18.8 ± 8.7), IL (26.0 ± 11.9), MA (26.9 ± 6.6), MD (29.3 ± 9.9), NJ (30.6 ± 17.9), and non-mandated states in aggregate (29.7 ± 13.7), all p < 0.0001. No significant differences were reported for use of PGT and/or live birth rates across all age groups regardless of mandate status. CONCLUSIONS: ICSI use varied significantly among ART-mandated states while demonstrating no differences in live birth rates. These data suggest that the prevalence of male factor and the presence of a state insurance mandate are not the only factors influencing ICSI use. It is suggested that other non-clinical factors may impact the rate of ICSI utilization in a given state.
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Cobertura del Seguro , Aceptación de la Atención de Salud/estadística & datos numéricos , Técnicas Reproductivas Asistidas/estadística & datos numéricos , Inyecciones de Esperma Intracitoplasmáticas/estadística & datos numéricos , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Técnicas Reproductivas Asistidas/economía , Estudios Retrospectivos , Inyecciones de Esperma Intracitoplasmáticas/economíaRESUMEN
OBJECT: We have previously reported that cumulative live birth rates (CLBRs) are higher in the freeze-all group compared with controls (64.3% vs. 45.8%, p = 0.001). Here, we aim to determine if the freeze-all policy is more cost-effective than fresh embryo transfer followed by frozen-thawed embryo transfer (FET). MATERIALS AND METHODS: The analysis consisted of 704 ART (Assisted reproductive technology) cycles, which included in IVF (In vitro fertilisation) and ICSI (Intra Cytoplasmic Sperm Injection) cycles performed in Taichung Veterans General Hospital, Taiwan between January 2012 and June 2014. The freeze-all group involved 84 patients and the fresh Group 625 patients. Patients were followed up until all embryos obtained from a single controlled ovarian hyper-stimulation cycle were used up, or a live birth had been achieved. The total cost related to treatment of each patient was recorded. The incremental cost-effectiveness ratio (ICER) was based on the incremental cost per couple and the incremental live birth rate of the freeze-all strategy compared with the fresh ET strategy. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed. RESULTS: The total treatment cost per patient was significantly higher for the freeze-all group than in the fresh group (USD 3419.93 ± 638.13 vs. $2920.59 ± 711.08 p < 0.001). However, the total treatment cost per live birth in the freeze-all group was US $5319.89, vs. US $6382.42 in the fresh group. CEAC show that the freeze-all policy was a cost-effective treatment at a threshold of US $2703.57 for one additional live birth. Considering the Willingness-to-pay threshold per live birth, the probability was 60.1% at the threshold of US $2896.5, with the freeze-all group being more cost-effective than the fresh-ET group; or 90.1% at the threshold of $4183.8. CONCLUSION: The freeze-all policy is a cost-effective treatment, as long as the additional cost of US $2703.57 per additional live birth is financially acceptable for the subjects.
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Criopreservación/economía , Transferencia de Embrión/economía , Nacimiento Vivo/economía , Políticas , Técnicas Reproductivas Asistidas/economía , Adulto , Análisis Costo-Beneficio , Transferencia de Embrión/métodos , Femenino , Fertilización In Vitro/economía , Fertilización In Vitro/métodos , Humanos , Recién Nacido , Embarazo , Estudios Retrospectivos , Inyecciones de Esperma Intracitoplasmáticas/economía , Inyecciones de Esperma Intracitoplasmáticas/métodos , TaiwánRESUMEN
Intracytoplasmic sperm injection (ICSI) was first introduced as a supplemental method to conventional in vitro fertilization (c-IVF) for couples with severe male factor infertility to overcome the poor fertilization rate, while its indications expanded in current clinical practice and gained worldwide popularity. However, ICSI is invasive and crosses all natural barriers, raising several unresolved concerns regarding procedure-dependent and procedure-independent risks, as well as the characteristic of being labor-intensive and more expensive than c-IVF. This review is aimed to draw readers' attention, to the widespread use of ICSI worldwide, with its effectiveness in different indications of infertility, especially in those with unexplained infertility, as well as the cost-effectiveness of the ICSI-for-all strategy. Also, we covered current evidence on the short- and long-term safety of children born thanks to ICSI-aided conception. Further well-designed, adequately powered, and randomized controlled clinical trials are absolutely needed to arrive at a consensus on the use of ICSI over c-IVF in different populations.
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Infertilidad Femenina/terapia , Infertilidad Masculina/terapia , Inyecciones de Esperma Intracitoplasmáticas/métodos , Femenino , Fertilización/fisiología , Humanos , Masculino , Embarazo , Resultado del Embarazo , Inyecciones de Esperma Intracitoplasmáticas/efectos adversos , Inyecciones de Esperma Intracitoplasmáticas/economíaRESUMEN
This study retrospectively examined the degree to which success within a commercial ovum pick-up (OPU)-intracytoplasmic sperm injection (ICSI) program varied between individual mares and stallions. Over 2 years, 552 OPU sessions were performed on 323 privately owned warmblood mares. For mares that yielded at least one blastocyst during the first OPU-ICSI cycle, there was a 77% likelihood of success during subsequent attempts; conversely, when the first cycle yielded no blastocyst, the likelihood of failure (no embryo) in subsequent cycles was 62%. In mares subjected to four or more OPU sessions, the mean percentage of blastocysts per injected oocyte was 20.5% (range 1.4-46.7%), whereas the mean number of blastocysts per OPU-ICSI session was 1.67 (0.2-4.2). Age did not differ significantly between mares that yielded good or poor results. The number of recovered oocytes per OPU was positively associated with the likelihood of success (P<0.001). Although there were considerable between-stallion differences, most stallions (14/16) clustered between 15.6% and 26.8% blastocysts per injected oocyte, and the number of blastocysts per OPU (mean 1.4; range 0.2-2.2) was less variable than among mares. In conclusion, although both mare and stallion affect the success of OPU-ICSI, mare identity and the number of oocytes recovered appear to be the most reliable predictors of success.
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Blastocisto/citología , Cruzamiento , Caballos/fisiología , Recuperación del Oocito , Inyecciones de Esperma Intracitoplasmáticas , Animales , Cruzamiento/economía , Cruzamiento/métodos , Recuento de Células/economía , Recuento de Células/veterinaria , Células Cultivadas , Comercio , Técnicas de Cultivo de Embriones/economía , Técnicas de Cultivo de Embriones/veterinaria , Embrión de Mamíferos/citología , Femenino , Masculino , Recuperación del Oocito/economía , Recuperación del Oocito/métodos , Recuperación del Oocito/veterinaria , Oocitos/citología , Estudios Retrospectivos , Inyecciones de Esperma Intracitoplasmáticas/economía , Inyecciones de Esperma Intracitoplasmáticas/métodos , Inyecciones de Esperma Intracitoplasmáticas/veterinaria , Medicina Veterinaria Deportiva/economía , Medicina Veterinaria Deportiva/organización & administraciónRESUMEN
Reproductive health services, including infertility care, are important in countries with infrastructure deficits, such as Lebanon, which now hosts more than one million Syrian refugees. Islamic prohibitions on child adoption and third-party reproductive assistance (donor eggs, sperm, embryos, and surrogacy) mean that most Muslim couples must turn to in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) to overcome their childlessness. Attempts to bring low-cost IVF-ICSI to underserved populations might help infertile couples where no other services are available. However, a low-cost IVF-ICSI protocol for male infertility remains technically challenging and thus may result in two standards of clinical care. Nonetheless, low-cost IVF-ICSI represents a form of reproductive justice in settings with infrastructure deficits and is clearly better than no treatment at all.
Asunto(s)
Costos y Análisis de Costo , Países en Desarrollo , Ética Clínica , Infertilidad Masculina/terapia , Calidad de la Atención de Salud , Servicios de Salud Reproductiva , Inyecciones de Esperma Intracitoplasmáticas , Servicios de Planificación Familiar , Fertilización In Vitro , Recursos en Salud , Accesibilidad a los Servicios de Salud , Humanos , Infertilidad Masculina/etnología , Islamismo , Líbano , Masculino , Refugiados , Religión y Medicina , Servicios de Salud Reproductiva/economía , Servicios de Salud Reproductiva/ética , Servicios de Salud Reproductiva/normas , Inyecciones de Esperma Intracitoplasmáticas/economía , Inyecciones de Esperma Intracitoplasmáticas/ética , Siria , Poblaciones VulnerablesRESUMEN
OBJECTIVE: To compare indications and trends in intracytoplasmic sperm injection (ICSI) use for in vitro fertilization (IVF) cycles among residents of states with and without insurance mandates for IVF coverage. DESIGN: Cross-sectional analysis of the National Assisted Reproductive Technology Surveillance System from 2011 to 2015 for the main outcome and from 2000 to 2015 for trends. SETTING: IVF cycles performed in U.S. fertility clinics. PATIENT(S): Fresh IVF cycles. INTERVENTION(S): Residency in a state with an insurance mandate for IVF (n = 8 states) versus no mandate (n = 43 states, including DC). MAIN OUTCOME MEASURE(S): ICSI use by insurance coverage mandate status stratified by male-factor infertility diagnosis. RESULT(S): During 2000-2015, there were 1,356,377 fresh IVF cycles, of which 25.8% (n = 350,344) were performed for residents of states with an insurance coverage mandate for IVF. ICSI use increased significantly during 2000-2015 in states both with and without a mandate; however, for non-male-factor infertility cycles, the percentage increase in ICSI use was greater among nonmandate states (34.6% in 2000 to 73.9% in 2015) versus mandate states (39.5% in 2000 to 63.5% in 2015). For male-factor infertility cycles, this percentage increase was â¼7.3% regardless of residency in a state with an insurance mandate for IVF. From 2011 to 2015, ICSI use was lower in mandate versus nonmandate states, both for cycles with (91.5% vs. 94.5%), and without (60.3% vs. 70.9%) male-factor infertility. CONCLUSION(S): Mandates for IVF coverage were associated with lower ICSI use for non-male-factor infertility cycles.
Asunto(s)
Disparidades en Atención de Salud/tendencias , Infertilidad Femenina/terapia , Infertilidad Masculina/terapia , Cobertura del Seguro/tendencias , Seguro de Salud/tendencias , Programas Obligatorios/tendencias , Pautas de la Práctica en Medicina/tendencias , Inyecciones de Esperma Intracitoplasmáticas/tendencias , Adulto , Estudios Transversales , Femenino , Encuestas de Atención de la Salud , Disparidades en Atención de Salud/economía , Humanos , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/economía , Infertilidad Femenina/fisiopatología , Infertilidad Masculina/diagnóstico , Infertilidad Masculina/economía , Infertilidad Masculina/fisiopatología , Cobertura del Seguro/economía , Seguro de Salud/economía , Masculino , Programas Obligatorios/economía , Embarazo , Inyecciones de Esperma Intracitoplasmáticas/economía , Factores de Tiempo , Estados UnidosRESUMEN
STUDY QUESTION: Does a reduced FSH dose in women with a predicted hyper response, apparent from a high antral follicle count (AFC), who are scheduled for IVF/ICSI lead to a different outcome with respect to cumulative live birth rate and safety? SUMMARY ANSWER: Although in women with a predicted hyper response (AFC > 15) undergoing IVF/ICSI a reduced FSH dose (100 IU per day) results in similar cumulative live birth rates and a lower occurrence of any grade of ovarian hyperstimulation syndrome (OHSS) as compared to a standard dose (150 IU/day), a higher first cycle cancellation rate and similar severe OHSS rate were observed. WHAT IS KNOWN ALREADY: Excessive ovarian response to controlled ovarian stimulation (COS) for IVF/ICSI may result in increased rates of cycle cancellation, the occurrence of OHSS and suboptimal live birth rates. In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can be used to predict response to COS. No consensus has been reached on whether ORT-based FSH dosing improves effectiveness and safety in women with a predicted hyper response. STUDY DESIGN SIZE, DURATION: Between May 2011 and May 2014, we performed an open-label, multicentre RCT in women with regular menstrual cycles and an AFC > 15. Women with polycystic ovary syndrome (Rotterdam criteria) were excluded. The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. Secondary outcomes included the occurrence of OHSS and cost-effectiveness. Since this RCT was embedded in a cohort study assessing over 1500 women, we expected to randomize 300 predicted hyper responders. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with an AFC > 15 were randomized to an FSH dose of 100 IU or 150 IU/day. In both groups, dose adjustment was allowed in subsequent cycles (maximum 25 IU in the reduced and 50 IU in the standard group) based on pre-specified criteria. Both effectiveness and cost-effectiveness were evaluated from an intention-to-treat perspective. MAIN RESULTS AND THE ROLE OF CHANCE: We randomized 255 women to a daily FSH dose of 100 IU and 266 women to a daily FSH dose of 150 IU. The cumulative live birth rate was 66.3% (169/255) in the reduced versus 69.5% (185/266) in the standard group (relative risk (RR) 0.95 [95%CI, 0.85-1.07], P = 0.423). The occurrence of any grade of OHSS was lower after a lower FSH dose (5.2% versus 11.8%, RR 0.44 [95%CI, 0.28-0.71], P = 0.001), but the occurrence of severe OHSS did not differ (1.3% versus 1.1%, RR 1.25 [95%CI, 0.38-4.07], P = 0.728). As dose reduction was not less expensive (4.622 versus 4.714, delta costs/woman 92 [95%CI, -479-325]), there was no dominant strategy in the economic analysis. LIMITATIONS, REASONS FOR CAUTION: Despite our training programme, the AFC might have suffered from inter-observer variation. Although strict cancellation criteria were provided, selective cancelling in the reduced dose group (for poor response in particular) cannot be excluded as observers were not blinded for the FSH dose and small dose adjustments were allowed in subsequent cycles. However, as first cycle live birth rates did not differ from the cumulative results, the open design probably did not mask a potential benefit for the reduced dosing group. As this RCT was embedded in a larger cohort study, the power in this study was unavoidably lower than it should be. Participants had a relatively low BMI from an international perspective, which may limit generalization of the findings. WIDER IMPLICATIONS OF THE FINDINGS: In women with a predicted hyper response scheduled for IVF/ICSI, a reduced FSH dose does not affect live birth rates. A lower FSH dose did reduce the incidence of mild and moderate OHSS, but had no impact on severe OHSS. Future research into ORT-based dosing in women with a predicted hyper response should compare various safety management strategies and should be powered on a clinically relevant safety outcome while assessing non-inferiority towards live birth rates. STUDY FUNDING/COMPETING INTEREST(S): This trial was funded by The Netherlands Organization for Health Research and Development (ZonMW, Project Number 171102020). SCO, TCvT and HLT received an unrestricted research grant from Merck Serono (the Netherlands). CBL receives grants from Merck, Ferring and Guerbet. BWJM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. FJMB receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV and Merck Serono for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. TRIAL REGISTRATION NUMBER: Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number: NTR2657. TRIAL REGISTRATION DATE: 20 December 2010. DATE OF FIRST PATIENT'S ENROLMENT: 12 May 2011.
Asunto(s)
Fertilización In Vitro/métodos , Hormona Folículo Estimulante/administración & dosificación , Folículo Ovárico/fisiología , Ovario/fisiología , Inyecciones de Esperma Intracitoplasmáticas/métodos , Adulto , Tasa de Natalidad , Criopreservación , Femenino , Fertilización In Vitro/economía , Hormona Liberadora de Gonadotropina/administración & dosificación , Humanos , Infertilidad/terapia , Variaciones Dependientes del Observador , Síndrome de Hiperestimulación Ovárica , Reserva Ovárica/efectos de los fármacos , Inducción de la Ovulación/métodos , Seguridad del Paciente , Embarazo , Resultado del Embarazo , Índice de Embarazo , Estudios Prospectivos , Inyecciones de Esperma Intracitoplasmáticas/economía , Factores de Tiempo , Resultado del TratamientoRESUMEN
STUDY QUESTION: Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? SUMMARY ANSWER: In women with a predicted poor ovarian response (AFC < 11) undergoing IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). WHAT IS KNOWN ALREADY: In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. STUDY DESIGN, SIZE, DURATION: Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC < 11 (Dutch Trial Register NTR2657). The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. We needed 300 women to assess whether an increased dose strategy would increase the cumulative live birth rate from 25 to 40% (two-sided alpha-error 0.05, power 80%). PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with an AFC ≤ 7 were randomized to an FSH dose of 450 IU/day or 150 IU/day, and women with an AFC 8-10 were randomized to 225 IU or 150 IU/day. In the standard group, dose adjustment was allowed in subsequent cycles based on pre-specified criteria. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 511 women were randomized, 234 with an AFC ≤ 7 and 277 with an AFC 8-10. The cumulative live birth rate for increased versus standard dosing was 42.4% (106/250) versus 44.8% (117/261), respectively [relative risk (RR): 0.95 (95%CI, 0.78-1.15), P = 0.58]. As an increased dose strategy was more expensive [delta costs/woman: 1099 (95%CI, 562-1591)], standard FSH dosing was the dominant strategy in our economic analysis. LIMITATIONS, REASONS FOR CAUTION: Despite our training programme, the AFC might have suffered from inter-observer variation. As this open study permitted small dose adjustments between cycles, potential selective cancelling of cycles in women treated with 150 IU could have influenced the cumulative results. However, since first cycle live birth rates point in the same direction we consider it unlikely that the open design masked a potential benefit for the individualized strategy. WIDER IMPLICATIONS OF THE FINDINGS: Since an increased dose in women scheduled for IVF/ICSI with a predicted poor response (AFC < 11) does not improve live birth rates and is more expensive, we recommend using a standard dose of 150 IU/day in these women. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by The Netherlands Organisation for Health Research and Development (ZonMW number 171102020). T.C.T., H.L.T. and S.C.O. received an unrestricted personal grant from Merck BV. H.R.V. receives monetary compensation as a member on an external advisory board for Ferring pharmaceutical BV. B.W.J.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. F.J.M.B. receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV (the Netherlands) and Merck Serono (the Netherlands) for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. TRIAL REGISTRATION NUMBER: Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number NTR2657. TRIAL REGISTRATION DATE: 20 December 2010. DATE OF FIRST PATIENT'S ENROLMENT: 12 May 2011.
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Fertilización In Vitro/métodos , Hormona Folículo Estimulante/administración & dosificación , Folículo Ovárico/fisiología , Ovario/fisiología , Inyecciones de Esperma Intracitoplasmáticas/métodos , Adulto , Tasa de Natalidad , Criopreservación , Femenino , Fertilización In Vitro/economía , Hormona Liberadora de Gonadotropina/administración & dosificación , Humanos , Infertilidad/terapia , Reserva Ovárica/efectos de los fármacos , Inducción de la Ovulación/métodos , Embarazo , Resultado del Embarazo , Índice de Embarazo , Estudios Prospectivos , Inyecciones de Esperma Intracitoplasmáticas/economía , Factores de Tiempo , Resultado del TratamientoRESUMEN
STUDY QUESTION: Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment? SUMMARY ANSWER: In women initiating IVF/ICSI, AFC-based individualized FSH dosing does not improve live birth rates or reduce costs as compared to a standard FSH dose. WHAT IS KNOWN ALREADY: In IVF or ICSI, ovarian reserve testing is often used to adjust the FSH dose in order to normalize ovarian response and optimize live birth rates. However, no robust evidence for the (cost-)effectiveness of this practice exists. STUDY DESIGN, SIZE, DURATION: Between May 2011 and May 2014 we performed a multicentre prospective cohort study with two embedded RCTs in women scheduled for IVF/ICSI. Based on the AFC, women entered into one of the two RCTs (RCT1: AFC < 11; RCT2: AFC > 15) or the cohort (AFC 11-15). The primary outcome was ongoing pregnancy achieved within 18 months after randomization resulting in a live birth (delivery of at least one live foetus after 24 weeks of gestation). Data from the cohort with weight 0.5 were combined with both RCTs in order to conduct a strategy analysis. Potential half-integer numbers were rounded up. Differences in costs and effects between the two treatment strategies were compared by bootstrapping. PARTICIPANTS/MATERIALS, SETTING, METHODS: In both RCTs women were randomized to an individualized (RCT1:450/225 IU, RCT2:100 IU) or standard FSH dose (150 IU). Women in the cohort all received the standard dose (150 IU). Anti-Müllerian hormone (AMH) was measured to assess AMH post-hoc as a biomarker to individualize treatment. For RCT1 dose adjustment was allowed in subsequent cycles based on pre-specified criteria in the standard group only. For RCT2 dose adjustment was allowed in subsequent cycles in both groups. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. MAIN RESULTS AND THE ROLE OF CHANCE: We included 1515 women, of whom 483 (31.9%) entered the cohort, 511 (33.7%) RCT1 and 521 (34.4%) RCT2. Live births occurred in 420/747 (56.3%) women in the individualized strategy and 447/769 (58.2%) women in the standard strategy (risk difference -0.019 (95% CI, -0.06 to 0.02), P = 0.39; a total of 1516 women due to rounding up the half integer numbers). The individualized strategy was more expensive (delta costs/woman = 275 (95% CI, 40 to 499)). Individualized dosing reduced the occurrence of mild and moderate ovarian hyperstimulation syndrome (OHSS) and subsequently the costs for management of these OHSS categories (costs saved/woman were 35). The analysis based on AMH as a tool for dose individualization suggested comparable results. LIMITATIONS, REASONS FOR CAUTION: Despite a training programme, the AFC might have suffered from inter-observer variation. In addition, although strict cancel criteria were provided, selective cancelling in the individualized dose group (for poor response in particular) cannot be excluded as observers were not blinded for the FSH dose and small dose adjustments were allowed in subsequent cycles. However, as both first cycle live birth rates and cumulative live birth rates show no difference between strategies, the open design probably did not mask a potential benefit for the individualized group. Despite increasing consensus on using GnRH antagonist co-treatment in women predicted for a hyper response in particular, GnRH agonists were used in almost 80% of the women in this study. Hence, in those women, the AFC and bloodsampling for the post-hoc AMH analysis were performed during pituitary suppression. As the correlation between AFC and ovarian response is not compromised during GnRH agonist use, this will probably not have influenced classification of response. WIDER IMPLICATIONS OF THE FINDINGS: Individualized FSH dosing for the IVF/ICSI population as a whole should not be pursued as it does not improve live birth rates and it increases costs. Women scheduled for IVF/ICSI with a regular menstrual cycle are therefore recommended a standard FSH starting dose of 150 IU per day. Still, safety management by individualized dosing in predicted hyper responders is open for further research. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by The Netherlands Organisation for Health Research and Development (ZonMW number 171102020). AMH measurements were performed free of charge by Roche Diagnostics. TCT, HLT and SCO received an unrestricted personal grant from Merck BV. AH declares that the department of Obstetrics and Gynecology, University Medical Centre Groningen receives an unrestricted research grant from Ferring pharmaceutics BV, The Netherlands. CBL receives grants from Merck, Ferring and Guerbet. BWJM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. FJMB receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV (the Netherlands) and Merck Serono (the Netherlands) for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development (Switzerland) and for a research cooperation with Ansh Labs (USA). All other autors have nothing to declare. TRIAL REGISTRATION NUMBER: Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number: NTR2657.
Asunto(s)
Fertilización In Vitro/métodos , Hormona Folículo Estimulante/administración & dosificación , Reserva Ovárica , Inyecciones de Esperma Intracitoplasmáticas/métodos , Adulto , Hormona Antimülleriana/metabolismo , Tasa de Natalidad , Análisis Costo-Beneficio , Femenino , Fertilización In Vitro/economía , Costos de la Atención en Salud , Humanos , Folículo Ovárico/patología , Síndrome de Hiperestimulación Ovárica , Ovario/fisiología , Inducción de la Ovulación/métodos , Embarazo , Resultado del Embarazo , Índice de Embarazo , Estudios Prospectivos , Inyecciones de Esperma Intracitoplasmáticas/economía , Factores de Tiempo , Resultado del TratamientoRESUMEN
The cost of fertility treatment is expensive and interventions that reduce cost can lead to greater efficiency and fewer embryos transferred. Endometrial polyps contribute to infertility and are frequently removed prior to infertility treatment. It is unclear whether polypectomy reduces fertility treatment cost and if so, the magnitude of cost reduction afforded by the procedure. The aim of this study was to determine whether performing office or operative hysteroscopic polypectomy prior to infertility treatment would be cost-effective. PubMed, Embase, and Cochrane libraries were used to identify publications reporting pregnancy rates after hysteroscopic polypectomy. Studies were required to have a polypectomy treatment group and control group of patients with polyps that were not resected. The charges of infertility treatments and polypectomy were obtained through infertility organizations and a private healthcare cost reporting website. These charges were applied to a decision tree model over the range of pregnancy rates observed in the representative studies to calculate an average cost per clinical or ongoing pregnancy. A sensitivity analysis was conducted to assess cost savings of polypectomy over a range of pregnancy rates and polypectomy costs. Pre-treatment office or operative hysteroscopic polypectomy ultimately saved 6658 ($7480) and 728 ($818), respectively, of the average cost per clinical pregnancy in women treated with four cycles of intrauterine insemination. Polypectomy prior to intrauterine insemination was cost-effective for clinical pregnancy rates greater than 30.2% for office polypectomy and 52.6% for operative polypectomy and for polypectomy price <4414 ($4959). Office polypectomy or operative polypectomy saved 15,854 ($17,813) and 6644 ($7465), respectively, from the average cost per ongoing pregnancy for in vitro fertilization/intracytoplasmic sperm injection treated women and was cost-effective for ongoing pregnancy rates greater than 26.4% (office polypectomy) and 31.7% (operative polypectomy) and polypectomy price <6376 ($7164). These findings suggested that office or operative hysteroscopic polypectomy was cost-effective when performed prior to both intrauterine insemination and in vitro fertilization over a range of plausible pregnancy rates and procedural costs.
Asunto(s)
Costos y Análisis de Costo , Histeroscopía/economía , Infertilidad/economía , Infertilidad/terapia , Pólipos/cirugía , Enfermedades Uterinas/cirugía , Análisis Costo-Beneficio , Femenino , Fertilización In Vitro/economía , Humanos , Histeroscopía/métodos , Inseminación Artificial/economía , Embarazo , Índice de Embarazo , Inyecciones de Esperma Intracitoplasmáticas/economíaRESUMEN
We demonstrated the IVF-ICSI results, perinatal outcomes and cost-effectivity of the patients with advanced age at a tertiary centre. A total of 456 patients categorised into two groups according to age: group 1 (n = 158) (≥39years) and group 2 (n = 298) (<39years) were analysed retrospectively. In addition, subgroup analysis was performed according to the 40 years cut-off. Clinical pregnancy rate was significantly different between the groups (p< .001). Preterm delivery (< 37 gestational week) and low birth weight (< 2500 g) were significantly higher in advanced aged women than youngsters (p< .001). Mean expense per cycle for hormonal stimulation of IVF-ICSI was 1058.9 and 723.5 USD in groups 1 and 2, respectively (p< .001). Mean expense per pregnancy was 9294.7 and 1874.8 USD in groups 1 and 2, respectively (p< .001). Our study showed that perinatal outcomes and cost-effectivity might be adversely affected with increasing age.
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Peso al Nacer/fisiología , Edad Materna , Resultado del Embarazo , Índice de Embarazo , Inyecciones de Esperma Intracitoplasmáticas/economía , Adulto , Factores de Edad , Análisis Costo-Beneficio , Femenino , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo/economía , Estudios Retrospectivos , Inyecciones de Esperma Intracitoplasmáticas/estadística & datos numéricosRESUMEN
The Authors present a new methodological approach in stochastic regime to determine the actual costs of an healthcare process. The paper specifically shows the application of the methodology for the determination of the cost of an Assisted reproductive technology (ART) treatment in Italy. The reason of this research comes from the fact that deterministic regime is inadequate to implement an accurate estimate of the cost of this particular treatment. In fact the durations of the different activities involved are unfixed and described by means of frequency distributions. Hence the need to determine in addition to the mean value of the cost, the interval within which it is intended to vary with a known confidence level. Consequently the cost obtained for each type of cycle investigated (in vitro fertilization and embryo transfer with or without intracytoplasmic sperm injection), shows tolerance intervals around the mean value sufficiently restricted as to make the data obtained statistically robust and therefore usable also as reference for any benchmark with other Countries. It should be noted that under a methodological point of view the approach was rigorous. In fact it was used both the technique of Activity Based Costing for determining the cost of individual activities of the process both the Monte Carlo simulation, with control of experimental error, for the construction of the tolerance intervals on the final result.
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Costos y Análisis de Costo/métodos , Transferencia de Embrión/economía , Fertilización In Vitro/economía , Método de Montecarlo , Transferencia de Embrión/métodos , Fertilización In Vitro/métodos , Humanos , Italia , Inyecciones de Esperma Intracitoplasmáticas/economía , Inyecciones de Esperma Intracitoplasmáticas/métodos , Procesos EstocásticosRESUMEN
Infertility care has improved remarkably over the last few decades and has received growing attention from health care providers. Several treatments, including expensive options such as Assisted Reproductive Techniques, are now widely available for routine clinical use. In most cases, adoption of these treatments has occurred without robust cost-effective analyses. IVF for unexplained infertility and ICSI in the absence of semen abnormalities are two examples of this gradual technology creep. More in-depth economic analyses in the field of infertility are undoubtedly warranted. However, performing these analyses is challenging because infertility care poses a number of unique challenges. Studies of cost-effectiveness are open to criticism because there is a lack of consensus about the outcomes of choice and the appropriate perspective. The use of quality adjusted life years (QALYs) to allow comparisons with other clinical conditions is also controversial because the value associated with infertility care cannot be easily captured in QALYs. Moreover, their use triggers the crucial question of whose QALYs merit consideration-an individual's, a couple's or a child's. In conclusion, economic analysis in infertility represents a peculiar but crucial challenge. If management of infertility is to become an integral part of publicly or privately funded health care systems worldwide, better quality data and a shared vision about the costs and benefits of infertility treatments are needed.
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Infertilidad/economía , Medicina Reproductiva/economía , Investigación Biomédica/economía , Análisis Costo-Beneficio , Transferencia de Embrión/economía , Femenino , Fertilización In Vitro/economía , Humanos , Recién Nacido , Masculino , Modelos Económicos , Embarazo , Resultado del Embarazo , Años de Vida Ajustados por Calidad de Vida , Técnicas Reproductivas Asistidas/economía , Semen , Inyecciones de Esperma Intracitoplasmáticas/economíaAsunto(s)
Preservación de la Fertilidad/psicología , Esperanza , Neoplasias/psicología , Adulto , Canadá , Consejo , Femenino , Preservación de la Fertilidad/economía , Preservación de la Fertilidad/métodos , Preservación de la Fertilidad/enfermería , Humanos , Masculino , Neoplasias/complicaciones , Rol de la Enfermera , Oocitos , Bancos de Esperma , Inyecciones de Esperma Intracitoplasmáticas/efectos adversos , Inyecciones de Esperma Intracitoplasmáticas/economía , Bancos de Tejidos , Adulto JovenAsunto(s)
Infertilidad Masculina/terapia , Evaluación de Procesos y Resultados en Atención de Salud/normas , Paquetes de Atención al Paciente/normas , Seguridad del Paciente/normas , Resultado del Embarazo/epidemiología , Inyecciones de Esperma Intracitoplasmáticas/normas , Evaluación de la Tecnología Biomédica/normas , Ensayos Clínicos como Asunto/economía , Ensayos Clínicos como Asunto/normas , Análisis Costo-Beneficio , Toma de Decisiones , Femenino , Humanos , Infertilidad Masculina/economía , Difusión de la Información/métodos , Masculino , Evaluación de Procesos y Resultados en Atención de Salud/economía , Evaluación de Procesos y Resultados en Atención de Salud/métodos , Paquetes de Atención al Paciente/economía , Seguridad del Paciente/economía , Embarazo , Resultado del Embarazo/economía , Vigilancia de Productos Comercializados/economía , Vigilancia de Productos Comercializados/normas , Mecanismo de Reembolso/normas , Mecanismo de Reembolso/tendencias , Inyecciones de Esperma Intracitoplasmáticas/economía , Inyecciones de Esperma Intracitoplasmáticas/estadística & datos numéricos , Evaluación de la Tecnología Biomédica/economía , Estados UnidosRESUMEN
OBJECTIVE: To analyze the cost-effectiveness of IVF-ICSI cycles with elective single-embryo transfer (eSET), plus elective single frozen embryo transfer (eSFET) if pregnancy is not achieved, compared with double-embryo transfer (DET). DESIGN: Cost-effectiveness analysis. SETTING: Public hospital. PATIENT(S): A population of 121 women (<38 years old), undergoing their first or second IVF cycles. INTERVENTION(S): We conducted a cost-effectiveness analysis using the results of a prospective clinical trial. The women in group 1 received eSET plus eSFET, and those in group 2 received DET. A probabilistic sensitivity analysis was performed. MAIN OUTCOME MEASURE(S): Live birth delivery rate. RESULT(S): The cumulative live birth delivery rate was 38.60% in the eSET+eSFET group versus 42.19% in the DET group. The mean costs per patient were 5,614.11 in the eSET+eSFET group and 5,562.29 in the DET group. These differences were not statistically significant. The rate of multiple gestation was significantly lower in the eSET group than in the DET group (0 vs. 25.9%). CONCLUSION(S): This study does not show that eSET is superior to DET in terms of effectiveness or of costs. The lack of superiority of the results for the eSET+eSFET and the DET groups corroborates that the choice of strategy to be adopted should be determined by the context of the health care system and the individual prognosis.
Asunto(s)
Fertilización In Vitro/economía , Transferencia de un Solo Embrión/economía , Transferencia de un Solo Embrión/métodos , Inyecciones de Esperma Intracitoplasmáticas/economía , Adulto , Análisis Costo-Beneficio , Parto Obstétrico/estadística & datos numéricos , Procedimientos Quirúrgicos Electivos , Embrión de Mamíferos , Femenino , Fertilización In Vitro/métodos , Congelación , Humanos , Recién Nacido , Embarazo , Índice de Embarazo , Adulto JovenRESUMEN
STUDY QUESTION: Can modified natural cycle IVF or ICSI (MNC) be a cost-effective alternative for controlled ovarian hyperstimulation IVF or ICSI (COH)? SUMMARY ANSWER: The comparison of simulated scenarios indicates that a strategy of three to six cycles of MNC with minimized medication is a cost-effective alternative for one cycle of COH with strict application of single embryo transfer (SET). WHAT IS KNOWN ALREADY: MNC is cheaper per cycle than COH but also less effective in terms of live birth rate (LBR). However, strict application of SET in COH cycles reduces effectiveness and up to three MNC cycles can be performed at the same costs as one COH cycle. STUDY DESIGN, SIZE, DURATION: The cost-effectiveness of MNC versus COH was evaluated in three simulated treatment scenarios: three cycles of MNC versus one cycle of COH with SET or double embryo transfer (DET) and subsequent transfer of cryopreserved embryos (Scenario 1); six cycles of MNC versus one cycle of COH with strictly SET and subsequent transfer of cryopreserved embryos (Scenario 2); six cycles of MNC with minimized medication (hCG ovulation trigger only) versus one cycle of COH with SET or DET and subsequent transfer of cryopreserved embryos (Scenario 3). We used baseline data obtained from two retrospective cohorts of consecutive patients (2005-2008) undergoing MNC in the University Medical Center Groningen (n = 499, maximum six cycles per patient) or their first COH cycle with subsequent transfer of cryopreserved embryos in the Academic Medical Center Amsterdam (n = 392). PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 1994 MNC cycles (958 MNC-IVF and 1036 MNC-ICSI) and 392 fresh COH cycles (one per patient, 196 COH-IVF and 196 COH-ICSI) with subsequent transfer of cryopreserved embryos (n = 72 and n = 94 in MNC and COH cycles, respectively) in ovulatory, subfertile women <36 years of age served as baseline for the three simulated scenarios. To compare the scenarios, the incremental cost-effectiveness ratio (ICER) was calculated, defined as the ratio of the difference in IVF costs up to 6 weeks postpartum to the difference in LBR. Live birth was the primary outcome measure and was defined as the birth of at least one living child after a gestation of ≥25 weeks. MAIN RESULTS AND THE ROLE OF CHANCE: In the baseline data, MNC was not cost-effective, as COH dominated MNC with a higher cumulative LBR (27.0 versus 24.0%) and lower cost per patient (3694 versus 5254). The simulations showed that in scenario 1 three instead of six cycles lowered the costs of MNC to below the level of COH (3390 versus 3694, respectively), but also lowered the LBR per patient (from 24.0 to 16.2%, respectively); Scenario 2: COH with strict SET was less effective than six cycles MNC (LBR 17.5 versus 24.0%, respectively), but also less expensive per patient (2908) than MNC (5254); Scenario 3: improved the cost-effectiveness of MNC but COH still dominated MNC when medication was minimized in terms of costs, i.e. 855 difference in favor of COH and 3% difference in LBR in favor of COH (ICER: 855/-3.0%). LIMITATIONS, REASONS FOR CAUTION: Owing to the retrospective nature of the study, the analyses required some assumptions, for example regarding the costs of pregnancy and delivery, which had to be based on the literature rather than on individual data. Furthermore, costs of IVF treatment were based on tariffs and not on actual costs. Although this may limit the external generalizability of the results, the limitations will influence both treatments equally, and would therefore not bias the comparison of MNC versus COH. WIDER IMPLICATIONS OF THE FINDINGS: The combined results suggest that MNC with minimized medication might be a cost-effective alternative for COH with strict SET. The scenarios reflect realistic alternatives for daily clinical practice. A preference for MNC depends on the willingness to trade off effectiveness in terms of LBR against the benefits of a milder stimulation regimen, including a very low rate of multiple pregnancies and hyperstimulation syndrome and ensuing lower costs per live birth. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by research grants from Merck Serono and Ferring Pharmaceuticals. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.