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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 (￥29 146.26 (US$4333.17) vs ￥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%; ￥30 703.02 (US$4564.62) vs ￥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 ￥65 420 (US$9726) and ￥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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

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., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

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., (© 2021. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

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., Competing Interests: The authors declare no conflict of interest., (Thieme. All rights reserved.)

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.

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 ∼7.3% 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., (Published by Elsevier Inc.)

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., (© 2018 American Medical Association. All Rights Reserved.)

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., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

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., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

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., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.

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.

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., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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.

Objective: To determine the cost-effectiveness of split IVF-intracytoplasmic sperm injection (ICSI) for the treatment of couples with unexplained infertility., Design: Adaptive decision model., Setting: Academic infertility clinic., Patient(s): A total of 154 couples undergoing a split IVF-ICSI cycle and a computer-simulated cohort of women <35 years old with unexplained infertility undergoing IVF., Intervention(s): Modeling insemination method in the first IVF cycle as all IVF, split IVF-ICSI, or all ICSI, and adapting treatment based on fertilization outcomes., Main Outcome Measure(s): Live birth rate, incremental cost-effectiveness ratio (ICER)., Result(s): In a single cycle, all IVF is preferred as the ICER of split IVF-ICSI or all ICSI ($58,766) does not justify the increased live birth rate (3%). If two cycles are needed, split IVF/ICSI is preferred as the increased cumulative live birth rate (3.3%) is gained at an ICER of $29,666., Conclusion(s): In a single cycle, all IVF was preferred as the increased live birth rate with split IVF-ICSI and all ICSI was not justified by the increased cost per live birth. If two IVF cycles are needed, however, split IVF/ICSI becomes the preferred approach, as a result of the higher cumulative live birth rate compared with all IVF and the lesser cost per live birth compared with all ICSI., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Clinical efficacy of human-derived follicle-stimulating hormone (FSH) versus recombinant FSH (rFSH) in IVF-ICSI cycles has long been compared, but no clear evidence of the superiority of a preparation over the other has been found. Human gonadotropins have been often grouped together, but a different glycosylation may be present in each preparation, therefore influencing the specific bioactivity. To exclude confounding factors, a meta-analysis and a cost-effectiveness analysis were designed to compare effectiveness and cost-effectiveness of a specific highly purified human FSH (HP-hFSH) (Fostimon®) versus rFSH (Gonal-F®) in IVF/ICSI cycles. Research methodology filters were applied in MEDLINE, Current Contents and Web of Science from 1980 to February 2012. Eight randomized trials met selection criteria. The meta-analysis showed no significant differences between rFSH and HP-hFSH treatment in live-birth rate (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.63-1.11), clinical pregnancy rate (OR 0.85, 95% CI 0.68-1.07), number of oocytes retrieved, number of mature oocytes and days of stimulation. The cost-effectiveness ratio was € 7174 in the rFSH group and € 2056 in the HP-hFSH group. HP-hFSH is as effective as rFSH in ovarian stimulation for IVF-ICSI cycles, but the human preparation is more cost-effective.

The Dutch Minister of Health has proposed reducing the number of reimbursed in vitro fertilisation (IVF) cycles per couple from 3 to 1, in order to save 30 million euro per year. In the Netherlands, the number of IVF cycles has increased by 50% in the past 13 years, resulting in, on average, one child conceived through IVF in every classroom today. The increase in the number of IVF treatments is also caused by expansion of the indications for IVF, despite the lack of evidence proving the effectiveness of IVF for some of these indications. In a time of financial constraint, the restriction of reimbursed indications would be fairer than reducing the number of reimbursed treatments with IVF or intracytoplasmic sperm injection (ICSI) for all couples.

Objective: To identify clinical and embryological factors that may predict success in rescue intracytoplasmic sperm injection (ICSI) cycles (after total fertilization failure has occurred) and to evaluate the cost effectiveness of rescue ICSI strategy. Additionally, follow-up of 20 rescue ICSI pregnancies is reported., Design: Retrospective analysis of total fertilization failure cycles., Setting: University-based tertiary medical center., Material and Methods: In total, 92 patients who had undergone conventional in-vitro fertilization (IVF) cycles with total fertilization failure were included. The patients were divided into two subgroups: those who conceived through rescue ICSI and those who did not., Results: The pregnant members of the rescue ICSI subgroup were found to be significantly younger (32.9 ± 4.2 vs. 36.3 ± 4.5, respectively, p = 0.0035,) and to have better-quality embryos than those who did not conceive (cumulative embryo score: 38.3 ± 20.4 vs. 29.3 ± 14.7, p = 0.025). Cost effectiveness analysis showed 25% reduction in the cost per live birth when rescue ICSI is compared to cycle cancellation approach. The pregnancies follow-up did not show adverse perinatal outcome., Conclusions: Rescue ICSI is an option for salvaging IVF cycles complicated by total fertilization failure. Success in rescue ICSI was found to be associated with younger age and higher quality of embryos. Furthermore, the cost effectiveness of rescue ICSI in terms of total fertilization failure was found to be worthwhile.

Objective: Evaluation of the results after the first 105 cycles in private IVF centres in Bosnia and Herzegovina., Study Design: Retrospective analysis of one hundred and five infertile couples who underwent IVF procedures., Results: The mean age of women who underwent IVF/ ICSI was 34.1 +/- 5.1. The male factor was the cause of infertility in 50 (47.6%), tubal factor in 24 (22.2%), idiopathic infertility in 14 (13.3%), advanced age in 14 (13.3%) and PCOS in 4 (3.8%) infertile couples. The average number of retrieved oocyte was 7.84 +/- 5.30. In 96.2% cycles ICSI was performed and in 3.8% IVF/ICSI. The average number of transferred embryos per cycle was 2.49 +/- 0.9. The pregnancy rate per aspiration was 26.7%. The clinical pregnancy rate per transfer was 26.3%. The percentage of live births per transfer to date was 13.1% and 7 of them are still pregnant. In the entire group of pregnant women 40% had twin pregnancies, 1 of them had an ectopic pregnancy (1.01%) and 4 (4.04%) had spontaneous abortions., Conclusions: The pregnancy and delivery rates are not satisfactory. The twin pregnancy rate is higher than is acceptable. Low-cost hormonal stimulation, natural cycles and freezing of embryos could be a possible way to make IVF affordable to a larger number of infertile couples.

Background: Authorities concerned by rising healthcare costs have a tendency to target reproductive treatments because of the perception that infertility is a low priority. In 2004 German health authorities introduced a 50% co-payment for patients, in an effort to save cost. We explored the impact of this pricing policy on the utilization of reproductive treatments in Germany., Methods: Using aggregated annual in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycle data in Germany, we evaluated the relationship between changes in the number of cycles in relation to changes in costs faced by consumers following the introduction of a patient co-payment from 'no fees' to 1500-2000 euros by estimating the short-run price-elasticity of demand. The impact of introducing patient co-payments for IVF/ICSI on the likelihood of switching to other low-cost fertility treatments was evaluated using the cross-price elasticity methodology. RESULTS The reduction in demand for IVF and ICSI cycles in the year following the introduction of patient co-payments resulted in elasticities of -0.41 and -0.34, respectively. The price-elasticity for the combined reduction of IVF/ICSI in relation to the co-payment was estimated to be -0.36. The cross-price elasticity for clomifene was close to zero (-0.01) suggesting that demand for these interventions are independent of each other and no substitution occurred., Conclusions: We report price elasticities for IVF and ICSI of -0.41 and -0.34 after introducing a 500-2000 euros co-payment. These findings likely represent short-run elasticities that are likely to vary over time as factors that influence the supply and demand for fertility treatments change.

The consensus view among relevant professional societies opposing the offering of elective oocyte cryopreservation for potential future self-donation withstands neither clinical nor ethical scrutiny. The favorable risk-benefit ratio of this technology mandates both the prioritization of patient autonomy for informed women seeking to maximize-not guarantee-their chances of having genetically related children, and a justification for viewing egg freezing differently from intracytoplasmic sperm injection.

Cost and outcome estimates based on clinical trial data may not reflect usual clinical practice, yet they are often used to inform service provision and budget decisions. To expand understanding of assisted reproduction treatment in clinical practice, an economic evaluation of IVF/intracytoplasmic sperm injection (ICSI) data from a single assisted conception unit (ACU) in England was performed. A total of 1418 IVF/ICSI cycles undertaken there between October 2001 and January 2006 in 1001 women were analysed. The overall live birth rate was 22% (95% CI: 19.7-24.2), with the 30- to 34-year age group achieving the highest rate (28%). The average recombinant FSH (rFSH) dose/cycle prescribed was 1855 IU. Average cost of rFSH/cycle was 646 pound(SD: 219 pound), and average total cost/cycle was 2932 pound (SD: 422 pound). Economic data based on clinical trials informing current UK guidance assumes higher doses of rFSH dose/cycle (1750-2625 IU), higher average cost of drugs/cycle (1179 pound), and higher average total cost/cycle (3266 pound). While the outcomes in this study matched UK averages, total cost/cycle was lower than those cited in UK guidelines. Utilizing the protocols and (lower) rFSH dosages reported in this study may enable other ACU to provide a greater number of IVF/ICSI cycles to patients within given budgets.

Background: Although elective single embryo transfer (eSET) minimizes the multiple birth rate after in vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI), there remain concerns in many countries that it is less effective and more expensive than conventional double embryo transfer (DET)., Methods: We compared the clinical outcome achieved in the years 1995-1999, in which eSET was rarely used (4.2% of women, DET period) with that of the years 2000-2004, in which eSET was more widely used (46.2%, eSET period). In the DET period, 826 women had 1359 fresh embryo cycles followed by 589 frozen-thawed embryo transfer (FET) cycles. In the eSET period, 684 women had 1027 fresh and 683 FET cycles. The cumulative term live birth rate/woman was the primary clinical outcome measure. An incremental cost-effectiveness ratio of a term live birth was also calculated based on hospital charges and medication prices of IVF/ICSI treatment., Results: The cumulative pregnancy rate/oocytes pickup (38.2 versus 33.1%, P = 0.01), cumulative live birth rate/oocytes pickup (28.0 versus 22.5%, P = 0.002) and cumulative live birth rate/woman (41.7 versus 36.6%, P = 0.04) were all higher in the eSET period than in the DET period. The cumulative multiple birth rate was significantly lower in the eSET period than in the DET period (8.9 versus 19.6%, P < 0.0001). A term live birth in the eSET period was 19 889 euros less expensive than in the DET period., Conclusions: This study shows that eSET with cryopreservation is more effective and less expensive than DET and should be adopted as a treatment of choice.

Purpose of Review: To review the role of varicocele repair in the treatment of male infertility., Recent Findings: Varicocele is a common finding among men with infertility and its repair has been a mainstay of surgical therapy in these men. Although each year multiple discoveries are made concerning the mechanism of varicocele-induced infertility, the exact pathophysiologic mechanism remains unknown. This study will update significant findings in regard to the pathophysiology of varicocele-induced infertility, such as increased expression of the aquaporin receptor and new findings related to testicular blood flow and vas deferens motility. Recent information concerning the effects of apoptosis and oxidative stress are also reviewed. With regard to the efficacy of varicocele repair, previous meta-analysis of the available data has been misleading due to improper selection criteria. Available clinical data are critically evaluated, with a focus on new meta-analyses that contradict the findings of the Cochrane database review, a study that has been accepted by many as evidence against varicocele repair., Summary: We conclude that varicocele repair not only is an effective treatment for appropriately selected patients but can also be the most cost effective option.

Objective: To provide detailed information about costs of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment stages and to estimate the cost per IVF and ICSI treatment cycle and ongoing pregnancy., Design: Descriptive micro-costing study., Setting: Four Dutch IVF centers., Patient(s): Women undergoing their first treatment cycle with IVF or ICSI., Intervention(s): IVF or ICSI., Main Outcome Measure(s): Costs per treatment stage, per cycle started, and for ongoing pregnancy., Result(s): Average costs of IVF and ICSI hormonal stimulation were euro 1630 and euro 1585; the costs of oocyte retrieval were euro 500 and euro 725, respectively. The cost of embryo transfer was euro 185. Costs per IVF and ICSI cycle started were euro 2381 and euro 2578, respectively. Costs per ongoing pregnancy were euro 10,482 and euro 10,036, respectively., Conclusion(s): Hormonal stimulation covered the main part of the costs per cycle (on average 68% and 61% for IVF and ICSI, respectively) due to the relatively high cost of medication. The costs of medication increased with increasing age of the women, irrespective of the type of treatment (IVF or ICSI). Fertilization costs (IVF laboratory) constituted 12% and 20% of the total costs of IVF and ICSI. The total cost per ICSI cycle was 8.3% higher than IVF.

Purpose: To estimate the incremental cost effectiveness of ICSI, and total costs for the population of Australia., Methods: Treatment effects for three patient groups were drawn from a published systematic review and meta-analysis of trials comparing fertilisation outcomes for ICSI. Incremental costs derived from resource-based costing of ICSI and existing practice comparators for each patient group., Results: Incremental cost per live birth for patients unsuited to IVF is estimated between A$8,500 and 13,400. For the subnormal semen indication, cost per live birth could be as low as A$3,600, but in the worst case scenario, there would just be additional incremental costs of A$600 per procedure. Multiplying out the additional costs of ICSI over the relevant target populations in Australia gives potential total financial implications of over A$31 million per annum., Conclusion: While there are additional benefits from ICSI procedure, particularly for those with subnormal sperm, the additional cost for the health care system is substantial.

Background: Intracytoplasmic sperm injection (ICSI) was initially developed as part of in vitro fertilization (IVF) to treat male-factor infertility. However, despite the added cost, uncertain efficacy, and potential risks of ICSI, its use has been extended to include some patients without documented male-factor infertility., Methods: We analyzed national data on assisted reproductive technology reported to the Centers for Disease Control and Prevention, to determine temporal trends in the use of ICSI and IVF in the United States, and we examined differences in the use of ICSI between states with and those without mandated insurance coverage., Results: From 1995 to 2004, the number of fertility clinics and fresh-embryo cycles and the rates of IVF-related pregnancies and live births increased. The percentage of IVF cycles with the use of ICSI also increased dramatically (from 11.0% to 57.5%), while the percentage of diagnoses of infertility attributed to male-factor conditions remained stable. The ratio of ICSI procedures to diagnoses of male-factor infertility steadily increased each year, suggesting an increasing use of ICSI for conditions other than male-factor infertility. From 1999 to 2004, there was an increasing use of ICSI relative to the percentage of patients with male-factor infertility in states with and those without mandated insurance coverage. For any given year, however, states with insurance coverage had a higher ratio of ICSI use to diagnoses of male-factor infertility than did states without insurance coverage (P<0.001)., Conclusions: Since 1995, the use of ICSI in the United States has increased dramatically, while the proportion of patients receiving treatment for male-factor infertility has remained stable. State-mandated health insurance coverage for IVF services is associated with greater use of ICSI for infertility that is not attributed to male-factor conditions., (Copyright 2007 Massachusetts Medical Society.)

Objective: To study the impact of the introduction of reimbursement of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) laboratory costs in Belgium which is linked to an embryo transfer strategy leading to prevention of multiple pregnancies. The impact on the incidence of multiple and twin pregnancy rate as well as on ongoing pregnancy rate in our centre is calculated., Study Design: Observational cohort study of all patients in the first year (July 1, 2003-June 30, 2004) since the implementation of the law and comparison of ongoing pregnancy rate and multiple pregnancy rate of our centre with Belgian data., Results: Our results of one year of IVF/ICSI since reimbursement of laboratory costs show a total conception rate of 42.2% with 29.7% ongoing pregnancies beyond 25 weeks amenorrhea. The multiple pregnancy rate was 8.5% including five monozygotic twin pregnancies. These data show an important decline of multiple pregnancy rate when compared to Belgian data (2002) with 24.4% multiple pregnancy rate in the year prior to reimbursement., Conclusion: The introduction of reimbursement of IVF/ICSI laboratory costs coupled to a restriction in the number of embryos for transfer has reached the goal of halving the multiple pregnancy rate since its introduction while maintaining an optimal ongoing pregnancy rate.

Assisted reproductive technology with intracytoplasmic sperm injection (ICSI) is becoming an international panacea for couples struggling with infertility. The increasing popularity of these techniques and the data generated has given us a better understanding of the efficacy, consequences and costs of these procedures. There still remain many unanswered questions and controversies surrounding the use of IVF and ICSI. Increased experience, better refinement of these techniques and clearer indications for IVF and ICSI will inevitably minimize the risks associated with this procedure.

Health plans often deliberate covering technologies with challenging purposes, effects, or costs. They must integrate quantitative evidence (e.g., how well a technology works) with qualitative, normative assessments (e.g., whether it works well enough for a worthwhile purpose). Arguments from analogy and precedent help integrate these criteria and establish standards for their policy application. Examples of arguments are described for three technologies (ICSI, genetic tests, and Viagra). Drawing lessons from law, ethics, philosophy, and the social sciences, a framework is developed for case-based evaluation of new technologies. The decision-making cycle includes (1) taking stock of past decisions and formulating precedents, (2) deciding new cases, and (3) assimilating decisions into the case history and evaluation framework. Each stage requires distinctive decision maker roles, information, and methods.

There is general agreement that intracytoplasmic sperm injection (ICSI) should be used in male factor infertility cases, such as oligoasthenoteratozoospermia, presence of anti-sperm antibodies, or azoospermia, these cases being diagnosed through abnormal semen analysis. There are no randomized clinical trials comparing ICSI with IVF (or other interventions) where semen quality is so poor that IVF would not achieve fertilization. It is accepted that ICSI is the only treatment option in those circumstances. The role of ICSI where IVF can be expected to give a reasonable fertilization rate is the question that needs to be answered. The argument is whether or not ICSI should be used for all cases of infertility. This paper proposes and strongly supports the use of ICSI for all indications. Considerations of fertilization and embryo development, cost effectiveness and safety will be clearly discussed.

Objective: To compare clinical outcome and costs of CC + gonadotropins with GnRHa + gonadotropins during IVF/ICSI cycles., Materials and Methods: Clinical outcome and expenses of 382 CC + gonadotropin and 964 GnRHa + gonadotropin cycles were compared. Medication costs were calculated on the basis of the mean number of ampoules and the proportion of various gonadotropins. Costs per clinical pregnancy were calculated on the basis of expenses and clinical pregnancy rates., Results: Women in the CC + gonadotropin group were younger, and had fewer follicles, oocytes, embryos, and embryos transferred. Clinical pregnancy rates were higher in the GnRHa group (35.9 % vs 26.2%, p < 0.001). More ampoules of gonadotropins were used in the GnRHa group (24.0 +/- 0.3 vs 20.0 +/- 0.5, p < 0.001). Medication costs per cycle were higher in the GnRHa group (US dollars 357 vs 248). Expenses per pregnancy however were lower in the GnRHa group (USdollars 4197 vs 5335 with IVF; USdollars 5590 vs 7244 with ICSI). When different age subgroups with similar baseline characteristics and stimulation parameters were compared, pregnancy rates were significantly higher in the GnRHa groups. Medication cost per cycle was higher in the GnRHa subgroups, and the expense per pregnancy was lower with GnRHa protocol., Conclusions: Cost per cycle is higher with GnRHa + gonadotropin. However, because of the better performance of the GnRHa + gonadotropin stimulation, the cumulative costs are reduced by the time a clinical pregnancy is achieved.

Every practitioner active in the field of assisted reproduction treatment is aware of the risks and complications related to twin and higher-order multiple pregnancies. Introduction of single embryo transfer (SET) into IVF/intracytoplasmic sperm injection (ICSI) is one of the possible ways of reducing the rate of twin pregnancy. Careful selection of patients, in combination with elective SET, has been shown to decrease the twin pregnancy rate while maintaining a stable ongoing pregnancy rate. The combination of a woman younger than 38 years of age, in her first or second IVF/ICSI cycle and with an embryo with a high implantation potential is the key to successful SET. This article will discuss embryo selection and patient selection and review the data published on SET. In the Centre for Reproductive Medicine at Middelheim Hospital, 39% of all transfers in 2002 were SET; the ongoing pregnancy rate remained stable at 30.6%. The twin (multiple) pregnancy rate declined to 11.7%. Particular attention should be drawn to the augmenting effect of the pregnancy rate of frozen-thawed cycles. Health economic data available so far subscribe the plea for SET.

Objective: To evaluate the cost effectiveness of a clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/GnRH antagonist protocol versus a long-acting GnRH agonist/hMG protocol., Participants and Methods: One hundred eighty nine couples having their first trial of ICSI for male factor infertility were divided into two groups. Group I (no = 33) received CC 100-150 mg/day for five days starting from day 2 of the cycle and 150 IU of hMG/day on days 6-10. GnRH antagonist (Centrorelix) 0.25 mg/day was started when the leading follicle reached 16 mm in the absence of an LH surge. Group II (no = 156) received 0.1 mg Deacapeptyl/day as our standard long protocol., Results: Clinical pregnancy was observed in 8 out of the 33 cases in group I (24%) while in group II, 92 out of 156 achieved clinical pregnancy (59%), the difference was statistically significant (P = 0.019). The cost of medications/cycle was estimated to be 1110+/-492 E.P in group I, while it was 1928+/-456 E.P. in group II. However, the total cost per pregnancy was 19653 EP in group I and 10047 EP in group II., Conclusion: The use of the clomid/hMG/antagonist protocol is not a cost effective strategy and should not be recommended in IVF-ICSI cycles.

Background: Approximately one in six couples experiences problems with their fertility at some point in their reproductive lives. The economic implications of the use of assisted reproductive techniques require consideration. Herein, the health economics research in this area are critically appraised., Methods: Multiple strategies were used to identify relevant studies. Each title and abstract was independently reviewed by two members of the study team and categorized according to perceived relevance. The selected papers were then assessed for quality and data were extracted, converted to UK pounds sterling at 1999/2000 prices, tabulated and critically appraised., Results: A total of 2547 papers was identified through the searches; this resulted in 30 economic evaluations, 22 cost studies and five economic benefit studies that met the selection criteria. The quality of these studies was mixed; many failed to disaggregate costs, discount future costs or conduct sensitivity analyses. Consistent findings included the following: initiating treatment with intrauterine insemination appeared to be more cost-effective than IVF; vasectomy reversal appeared to be more cost-effective than ICSI; factors associated with poor prognosis decreased the cost-effectiveness of interventions., Conclusions: The cost-effectiveness of different interventions should be considered when making decisions about treatment. Future economic appraisals of assisted reproductive techniques would benefit from more robust methodology than is evident in much of the published literature to date.

The health economics of IVF and ICSI involve assessments of utilization, cost, cost-effectiveness and ability to pay. In 48 countries, utilization averaged 289 IVF/ICSI cycles per million of population per annum, ranging from two in Kazachstan, to 1657 in Israel. Higher national utilization of IVF/ICSI was associated with higher quality of health services, as indicated by lower infant mortality rates. IVF and ICSI are scientifically demanding and personnel-intensive, and are therefore expensive procedures. The average cost per IVF/ICSI cycle in 2002 would be US$9547 in the USA, and US$3518 in 25 other countries. Price elasticity estimates suggest that a 10% decrease in IVF/ICSI cost would generate a 30% increase in utilization. The average cost-effectiveness ratios in 2002 would be US$58,394 per live birth in the USA, and US$22,048 in other countries. In three randomized controlled trials, incremental costs per additional live birth with IVF compared with conventional therapy were US$ -26,586, $79,472 and $47,749. The national costs of IVF/ICSI treatment would be US$1.00 per capita in one current model, but the costs to individual couples range from 10% of annual household expenditures in European countries to 25% in Canada and the USA.

Objective: To compare the cost effectiveness of recombinant human FSH (Gonal-F; Serono, Inc., Randolph, MA) and urinary FSH (Fertinex; Serono, Inc.) for ovarian stimulation during IVF with or without intracytoplasmic sperm injection for the treatment of infertility., Design: Clinical decision analysis techniques (the Markov model) were used to model the direct medical costs per patient during assisted reproductive technology., Main Outcome Measure(s): Clinical and economic outcomes of two different ovarian stimulation protocols (recombinant human FSH or urinary FSH) during three treatment cycles were considered., Result(s): More ongoing pregnancies were achieved, with fewer stimulation cycles, after recombinant human FSH (Gonal-F) than after urinary FSH (Fertinex) (40,665 versus 37,890). In addition, recombinant human FSH was also found to be more cost effective per ongoing pregnancy. From a societal perspective, the mean cost per pregnancy was $40,688 for recombinant human FSH versus $47,096 for urinary FSH. From the insurers' perspective, the mean cost/pregnancy for recombinant human FSH was $28,481 versus $32,967 for urinary FSH., Conclusion(s): Recombinant human FSH (Gonal-F) is not only more efficient clinically than urinary FSH (Fertinex), but also more cost effective. This analysis illustrates the point that the economic effectiveness of a drug depends less on its acquisition costs and rather more on the clinical outcomes associated with its use.