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Dairy herds have adopted sexed semen (SS) and beef semen (BS) to control heifer inventory and increase calf sales revenue. Beef in vitro-produced embryo transfer (beef IVP-ET) may be an alternative to increase calf sales revenue. Additionally, raising those Jersey-beef crossbred or pure beef animals in a dairy system may be a new source of revenue. We aimed to evaluate the effects of breed strategies combining dairy conventional semen (CS), SS, BS, and beef IVP-ET on herd dynamics and profitability with strategies of marketing those animals at 1 d old or raising them to a weight of 180 kg. A Markov chain model was developed to maximize the profitability of Jersey herds by changing the number of dairy heifers sold at birth and the culling rate of cows in their third parity or greater. The model presents inputs on the reproductive and productive performance of heifers and cows over time. The last year's data (year 10, steady state) was used to calculate accrual operational cost and revenue per cow per year. We varied the breeding strategy by breeding order and parities, the embryo transfer cost ($85 or $170), the pure beef calf market price ($200 or $300), and the marketing strategy. A total of 8 scenarios plus a default scenario were simulated. Overall, the proportion of SS use was 47.3 ± 0.6% (mean ± SD). For the scenarios replacing all CS breedings with BS breedings, the percentage of BS used was 52.3 ± 0.6%. When beef IVP-ET was used, the percentages of BS and beef IVP-ET used were 22.4 ± 0.1% and 31.0 ± 0.1%, respectively. We observed that when we compared the combination of BS and dairy SS with the default scenario, the production of purebred Jersey male calves was reduced by 83.5%, and profit per cow per year was increased from $113.50 to $203.30. When a beef IVP-ET cost of $85 per transfer was used (scenarios 2 and 3), profit per cow per year was $145.50 and $176.20 for pure beef calf prices of $200 and $300, respectively. In scenario 4, with a beef IVP-ET cost of $170, the lowest profit ($52.90 per cow per year) was found when marketing 1-d-old pure beef calves at $200. The highest profit was achieved for the scenario of raising the Jersey-beef crossbred animals to 180 kg ($232.90, scenario 6), followed by scenario 7 ($222.90, using the combination of BS, dairy SS, and beef IVP-ET) with an embryo transfer cost of $85. Under the current market conditions, combining SS and BS in the reproductive program was a feasible economic opportunity for Jersey herds, yielding the highest net return. The adoption of beef IVP-ET in a reproductive program can potentially increase profit per cow per year, but its profitability will depend on the beef IVP-ET pregnancy cost, the pure beef market price, calf performance, and herd reproductive performance. In conclusion, raising the Jersey-beef crossbred calves may be a profitable strategy, and dairy producers need to evaluate the best option to invest in, as it will take extra risk to produce high-quality animals., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

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.)

Background: Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception., Methods: Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs'). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis., Results: IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate., Conclusions: IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers., (© 2021. The Author(s).)

Objective: To compare the live birth rate and cost effectiveness of artificial cycle-prepared frozen embryo transfer (AC-FET) with or without GnRH agonist (GnRH-a) pretreatment for women with polycystic ovary syndrome (PCOS)., Design: Open-label, randomised, controlled trial., Setting: Reproductive centre of a university-affiliated hospital., Sample: A total of 343 women with PCOS, aged 24-40 years, scheduled for AC-FET and receiving no more than two blastocysts., Methods: The pretreatment group (n = 172) received GnRH-a pretreatment and the control group (n = 171) did not. Analysis followed the intention-to-treat (ITT) principle., Main Outcome Measures: The primary outcome measure was live birth rate. Secondary outcome measures included clinical pregnancy rate, implantation rate, early pregnancy loss rate and direct treatment costs per FET cycle., Results: Among the 343 women randomised, 330 (96.2%) underwent embryo transfer and 328 (95.6%) completed the protocols. Live birth rate according to ITT did not differ between the pretreatment and control groups [85/172 (49.4%) versus 92/171 (53.8%), absolute rate difference -4.4%, 95% CI -10.8% to 2.0% (P = 0.45). Implantation rate, clinical pregnancy rate and early pregnancy loss rate also did not differ between groups, but median direct cost per FET cycle was significantly higher in the pretreatment group (7799.2 versus 4438.9 RMB, OR = 1.9, 95%CI 1.2-3.4, P < 0.001). Median direct cost per live birth was also significantly higher in the pretreatment group (15663.1 versus 8189.9 RMB, odds ratio [OR] = 1.9, 95% CI 1.2-3.8, P < 0.001)., Conclusions: Pretreatment with GnRH-a does not improve pregnancy outcomes for women with PCOS receiving AC-FET, but significantly increases patient cost., Tweetable Abstract: For women with PCOS, artificial cycle-prepared FET with GnRH agonist pretreatment provides no pregnancy outcome benefit but incurs higher cost., (© 2020 John Wiley & Sons Ltd.)

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.)

In vitro fertilization and embryo transplantation (IVF-ET) technology is one of the main treatments for infertility. But IVF-ET is expensive and has not be covered by health insurance in most developing countries. Therefore, how to obtain the maximum success rate with the minimum cost is a common concern of clinicians and patients. At present, the economic studies on IVF-ET mainly focus on different ovulation stimulating drugs, different ovulation stimulating protocols, different transplantation methods and the number of transplants. But the process of IVF-ET is complex, the relevant methods of economic study are diverse, and there are no unified standard for outcome indicators, so there is no unified conclusion for more economical and effective protocol by now. Therefore, to analyze the economic studies of IVF-ET, and to explore appropriate evaluation methods and cost-effective protocols will be helpful for reasonable allocation of medical resources and guidance of clinical selection. It would provide policy reference to include the costs of IVF-ET treatment in health insurance in the future.

Objective: To evaluate the economical benefit of preimplantation genetic testing of aneuploidies (PGT-A) when applied in an extended culture and stringent elective single ET framework., Design: Theoretical cost-effectiveness study., Setting: Not applicable., Patients/animal(s): None., Intervention(s): Comparison of the cost-effectiveness between two IVF treatment strategies: serial transfer of all available blastocysts without genetic testing (first fresh transfer and subsequent frozen-thawed transfer); and systematic use of genetic testing (trophectoderm biopsy, freeze-all, and frozen-thawed transfers of euploid blastocysts). The costs considered for this analysis are based on regional public health system provider., Main Outcome Measure(s): Costs per live birth., Result(s): Cost-effectiveness profile of PGT-A improves with female age and number of available blastocysts. Sensitivity analyses varying the costs of ET, the costs of genetic analyses, the magnitude of the detrimental impact of PGT-A on live birth rate, and the crude live birth rates change to some extent the thresholds for effectiveness but generally confirm the notion that PGT-A can be economically advantageous in some specific subgroups., Conclusion(s): PGT-A can be cost-effective in specific clinical settings and population groups. Economic considerations deserve attention in the debate regarding the clinical utility of PGT-A., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

In vitro embryo production (IVP) in cattle has gained worldwide interest in recent years, but the efficiency of using IVP embryos for calf production is far from optimal. This review will examine the pregnancy retention rates of IVP embryos and explore causes for pregnancy failures. Based on work completed over the past 25 yr, only 27% of cattle receiving IVP embryos will produce a live calf. Approximately 60% of these pregnancies fail during the first 6 wk of gestation. When compared with embryos generated by superovulation, pregnancy rates are 10% to 40% lower for cattle carrying IVP embryos, exemplifying that IVP embryos are consistently less competent than in vivo-generated embryos. Several abnormalities have been observed in the morphology of IVP conceptuses. After transfer, IVP embryos are less likely to undergo conceptus elongation, have reduced embryonic disk diameter, and have compromised yolk sac development. Marginal binucleate cell development, cotyledon development, and placental vascularization have also been documented, and these abnormalities are associated with altered fetal growth trajectories. Additionally, in vitro culture conditions increase the risk of large offspring syndrome. Further work is needed to decipher how the embryo culture environment alters post-transfer embryo development and survival. The risk of these neonatal disorders has been reduced by the use of serum-free synthetic oviductal fluid media formations and culture in low oxygen tension. However, alterations are still evident in IVP oocyte and embryo transcript abundances, timing of embryonic cleavage events and blastulation, incidence of aneuploidy, and embryonic methylation status. The inclusion of oviductal and uterine-derived embryokines in culture media is being examined as one way to improve the competency of IVP embryos. To conclude, the evidence presented herein clearly shows that bovine IVP systems still must be refined to make it an economical technology in cattle production systems. However, the current shortcomings do not negate its current value for certain embryo production needs and for investigating early embryonic development in cattle., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to explore the benefits of in vitro fertilization (IVF) for patients and hospitals under different protocols and if IVF treatment should be incorporated into health care., Perspective: The government should consider including IVF treatment in health insurance. Hospitals and patients could obtain the best benefit by following the hospital's recommended protocol., Setting: This retrospective study was conducted from January 2014 to August 2017 at an academic hospital., Methods: A total of 7440 patients used gonadotropin-releasing hormone agonists (GnRHa) protocol, 2619 patients used, gonadotropin-releasing hormone antagonists (GnRHant) protocol, and 1514 patients used GnRHa ultra-long protocol. Primary outcomes were live birth rate (LBR), cost-effectiveness, hospital revenue, and government investment., Results: The cycle times for the GnRHa protocol and the GnRHa ultra-long protocol were significantly higher than the GnRHant protocol. Patients who were ≤29 years chose the GnRHant protocol. The cost of a successful cycle was 67,579.39 ± 9,917.55 ¥ and LBR was 29.25%. Patients who were >30 years had the GnRHa protocol as the dominant strategy, as it was more effective at lower costs and higher LBR. When patients were >30 to ≤34 years, the cost of a successful cycle was 66,556.7 ± 8,448.08 ¥ and the LBR was 31.05%. When patients were >35 years, the cost of a successful cycle was 83,297.92 ± 10,918.05 ¥ and the LBR was 25.07%. The government reimbursement for a cycle ranged between 11,372.12 ± 2,147.71 ¥ and 12,753.67 ± 1,905.02 ¥., Conclusions: The government should consider including IVF treatment in health insurance. Hospitals recommend the GnRHant protocol for patients <29 years old and the GnRHa protocol for patients >30 years old, to obtain the best benefits. Patients could obtain the best benefit by using the protocol recommended by the hospital.

Embryo biopsy for fetal sexing has clinical application, but few reports are available of its use within an active embryo transfer program. We evaluated results on biopsy of 459 embryos over one breeding season. There were no significant differences in pregnancy rate between biopsied and non-biopsied embryos (72% vs 73%) or for biopsied embryos recovered at the centre (73%) compared with those shipped overnight (72%). However, the pregnancy rate decreased significantly in shipped embryos biopsied ≥20h after collection. Overall, 86% of biopsies provided a sex diagnosis. The likelihood of a positive genomic (g) DNA result was significantly higher for biopsies from large blastocysts (96%) than from smaller embryos (70-85%). In total, 38% of biopsies were positive for Y chromosome DNA (Y-DNA) and were diagnosed as male. Subsequently, 95% of Y-DNA-positive embryos were confirmed as male and 78% of Y-DNA-negative embryos were confirmed as female. The accuracy of prediction of female (Y-DNA negative) was significantly higher when the biopsy sample was probed for Y-DNA only compared with probing for both gDNA and Y-DNA. We estimate that by transferring only Y-DNA-negative embryos, 3% of potential female pregnancies may have been lost, and production of male pregnancies was reduced by 72%.

Research Question: Does delaying IVF for 6 months in couples with unexplained infertility, compared with immediate IVF treatment, decrease the cost of IVF without compromising success rates?, Design: Decision modelling was used to evaluate the cost and outcomes of immediate IVF versus delayed IVF for a cohort of women aged <40 years suffering unexplained infertility. Australian data and costs were used in the analysis. For different age groups, three scenarios were tested where 10%, 50% and 90% of couples with unexplained infertility delayed IVF for 6 months if they had a good prognosis for natural conception. The study included a total of 8781 couples aged <40 years, diagnosed with unexplained infertility and who had IVF in 2013., Results: The studied couples underwent 27,648 fresh and frozen embryo transfers, for an estimated total cost of $141 million. Potential out-of-pocket cost savings if 90% of couples delayed IVF ranged from $4.7 to $12.2 million, with Medicare cost savings of up to $15.1 million. The impact on the total pregnancy and live birth rates after 18 months was minimal., Conclusions: In couples with unexplained infertility and a good prognosis for natural conception, delaying IVF for 6 months could substantially decrease out-of-pocket costs without compromising pregnancy and live birth rates over an 18-month period., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine if preimplantation genetic testing for aneuploidy (PGT-A) is cost-effective for patients undergoing in vitro fertilization (IVF)., Design: Decision analytic model comparing costs and clinical outcomes of two strategies: IVF with and without PGT-A., Setting: Genetics laboratory., Patients: Women ≤ 42 years of age undergoing IVF., Intervention(s): Decision analytic model applied to the above patient population utilizing a combination of actual clinical data and assumptions from the literature regarding the outcomes of IVF with and without PGT-A., Main Outcome Measure(s): The primary outcome was cumulative IVF-related costs to achieve a live birth or exhaust the embryo cohort from a single oocyte retrieval. The secondary outcomes were time from retrieval to the embryo transfer resulting in live birth or completion of treatment, cumulative live birth rate, failed embryo transfers, and clinical losses., Results: 8,998 patients from 74 IVF centers were included. For patients with greater than one embryo, the cost differential favored the use of PGT-A, ranging from $931-2411 and depending upon number of embryos screened. As expected, the cumulative live birth rate was equivalent for both groups once all embryos were exhausted. However, PGT-A reduced time in treatment by up to four months. In addition, patients undergoing PGT-A experienced fewer failed embryo transfers and clinical miscarriages., Conclusion: For patients with > 1 embryo, IVF with PGT-A reduces healthcare costs, shortens treatment time, and reduces the risk of failed embryo transfer and clinical miscarriage when compared to IVF alone., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Study Question: Is a freeze-only strategy more cost-effective from a patient perspective than fresh embryo transfer (ET) after one completed In Vitro Fertilization/ Intracytoplasmic Sperm Injection (IVF/ICSI) cycle in women without polycystic ovary syndrome (PCOS)?, Summary Answer: There is a low probability of the freeze-only strategy being cost-effective over the fresh ET strategy for non-PCOS women undergoing IVF/ICSI., What Is Known Already: Conventionally, IVF embryos are transferred in the same cycle in which oocytes are collected, while any remaining embryos are frozen and stored. We recently evaluated the effectiveness of a freeze-only strategy compared with a fresh ET strategy in a randomized controlled trial (RCT). There was no difference in live birth rate between the two strategies., Study Design, Size, Duration: A cost-effectiveness analysis (CEA) was performed alongside the RCT to compare a freeze-only strategy with a fresh ET strategy in non-PCOS women undergoing IVF/ICSI. The effectiveness measure for the CEA was the live birth rate. Data on the IVF procedure, pregnancy outcomes and complications were collected from chart review; additional information was obtained using patient questionnaires, by telephone., Participants/materials, Setting, Methods: For all patients, we measured the direct medical costs relating to treatment (cryopreservation, pregnancy follow-up, delivery), direct non-medical costs (travel, accommodation) and indirect costs (income lost). The direct cost data were calculated from resources obtained from patient records and prices were applied based on a micro-costing approach. Indirect costs were calculated based on responses to the questionnaire. Patients were followed until all embryos obtained from a single controlled ovarian hyperstimulation cycle were used or a live birth was achieved. The incremental cost-effectiveness ratio (ICER) was based on the incremental cost per couple and the incremental live birth rate of the freeze-only strategy compared with the fresh ET strategy. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were also performed., Main Results and the Role of Chance: Between June 2015 and April 2016, 782 couples were randomized to a freeze-only (n = 391) or a fresh ET strategy (n = 391). Baseline characteristics including mean age, Body Mass Index (BMI), anti-Mullerian hormone, total dose of Follicle Stimulating Hormone (FSH), number of oocytes obtained, good quality Day 3 embryos, fertility outcomes and treatment complications were comparable between the two groups. The live birth rate (48.6% vs. 47.3%, respectively; risk ratio, 1.03; 95% Confidence Interval [CI], 0.89, 1.19; P = 0.78) and the average cost per couple (3906 vs. 3512 EUR, respectively; absolute difference 393.6, 95% CI, -76.2, 863.5; P = 0.1) were similar in the freeze-only group versus fresh ET. Corresponding costs per live birth were 8037 EUR versus 7425 EUR in the freeze-only versus fresh ET group, respectively. The incremental cost for the freeze-only strategy compared with fresh ET was 30 997 EUR per 1% additional live birth rate. The direct non-medical costs and indirect costs of infertility treatment strategies represented ~45-52% of the total cost. PSA shows that the 95% CI of ICERs was -263 901 to 286 681 EUR. Out of 1000 simulations, 44% resulted in negative ICERs, including 13.0% of simulations in which the freeze-only strategy was dominant (more effective and less costly than fresh ET), and 31% of simulations in which the fresh embryo strategy was dominant. In the other 560 simulations with positive ICERs, the 95% CI of ICERs ranged from 2155 to 471 578 EUR. The CEAC shows that at a willingness to pay threshold of 300 000 EUR, the probability of the freeze-only strategy being cost-effective over the fresh ET strategy would be 58%., Limitations, Reasons for Caution: Data were collected from a single private IVF center study in Vietnam where there is no public or insurance funding of IVF. Unit costs obtained might not be representative of other settings. Data obtained from secondary sources (medical records, financial and activity reports) could lack authenticity, and recall bias may have influenced questionnaire responses on which direct costs were based., Wider Implications of the Findings: In non-PCOS women undergoing IVF/ICSI, the results suggested that the freeze-only strategy was not cost-effective compared with fresh ET from a patient perspective. These findings indicate that other factors could be more important in deciding whether to use a freeze-only versus fresh ET strategy in this patient group., Study Funding/competing Interest(s): This study was funded by My Duc Hospital; no external funding was received. Ben Willem J. Mol is supported by an NHMRC Practioner Fellowship (GNT 1082548) and reports consultancy for Merck, ObsEva and Guerbet. Robert J. Norman has shares in an IVF company and has received support from Merck and Ferring. All other authors have no conflicts of interest to declare., Trial Registration Number: Not applicable.

Purpose: To determine the expected out-of-pocket costs of IVF with preimplantation genetic testing for aneuploidy (PGT-A) to attain a 50%, 75%, or 90% likelihood of a euploid blastocyst based on individual age and AMH, and develop a personalized counseling tool., Methods: A cost analysis was performed and a counseling tool was developed using retrospective data from IVF cycles intended for PGT or blastocyst freeze-all between January 1, 2014 and August 31, 2017 (n = 330) and aggregate statistics on euploidy rates of > 149,000 embryos from CooperGenomics. Poisson regression was used to determine the number of biopsiable blastocysts obtained per cycle, based on age and AMH. The expected costs of attaining a 50%, 75%, and 90% likelihood of a euploid blastocyst were determined via 10,000 Monte Carlo simulations for each age and AMH combination, incorporating age-based euploidy rates and IVF/PGT-A cost assumptions., Results: The cost to attain a 50% likelihood of a euploid blastocyst ranges from approximately $15,000 U.S. dollars (USD) for younger women with higher AMH values (≥ 2 ng/mL) to > $150,000 for the oldest women (44 years) with the lowest AMH values (< 0.1 ng/mL) in this cohort. The cost to attain a 75% versus 90% likelihood of a euploid blastocyst is similar (~ $16,000) for younger women with higher AMH values, but varies for the oldest women with low AMH values (~ $280,000 and > $450,000, respectively). A typical patient (36-37 years, AMH 2.5 ng/mL) should expect to spend ~ $30,000 for a 90% likelihood of attaining a euploid embryo., Conclusions: This tool can serve as a counseling adjunct by providing individualized cost information for patients regarding PGT-A.

The objective of this study was to find the optimal proportions of pregnancies from an in vitro-produced embryo transfer (IVP-ET) system and artificial insemination (AI) so that profitability is maximized over a range of prices for embryos and surplus dairy heifer calves. An existing stochastic, dynamic dairy model with genetic merits of 12 traits was adapted for scenarios where 0 to 100% of the eligible females in the herd were impregnated, in increments of 10%, using IVP-ET (ET0 to ET100, 11 scenarios). Oocytes were collected from the top donors selected for the trait lifetime net merit (NM$) and fertilized with sexed semen to produce IVP embryos. Due to their greater conception rates, first ranked were eligible heifer recipients based on lowest number of unsuccessful inseminations or embryo transfers, and then on age. Next, eligible cow recipients were ranked based on the greatest average estimated breeding values (EBV) of the traits cow conception rate and daughter pregnancy rate. Animals that were not recipients of IVP embryos received conventional semen through AI, except that the top 50% of heifers ranked for EBV of NM$ were inseminated with sexed semen for the first 2 AI. The economically optimal proportions of IVP-ET were determined using sensitivity analysis performed for 24 price sets involving 6 different selling prices of surplus dairy heifer calves at approximately 105 d of age and 4 different prices of IVP embryos. The model was run for 15 yr after the start of the IVP-ET program for each scenario. The mean ± standard error of true breeding values of NM$ of all cows in the herd in yr 15 was greater by $603 ± 2 per cow per year for ET100 when compared with ET0. The optimal proportion of IVP-ET ranged from ET100 (for surplus dairy heifer calves sold for ≥$300 along with an additional premium based on their EBV of NM$ and a ≤$100 embryo price) to as low as ET0 (surplus dairy heifer calves sold at $300 with a $200 embryo price). For the default assumptions, the profit/cow in yr 15 was greater by $337, $215, $116, and $69 compared with ET0 when embryo prices were $50, $100, $150, and $200. The optimal use of IVP-ET was 100, 100, 62, and 36% of all breedings for these embryo prices, respectively. At the input price of $165 for an IVP embryo, the difference in the net present value of yr 15 profit between ET40 (optimal scenario) and ET0 was $33 per cow. In conclusion, some use of IVP-ET was profitable for a wide range of IVP-ET prices and values of surplus dairy heifer calves., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Purpose: Adding preimplantation genetic screening to in vitro fertilization has been shown to increase live birth rate in women older than 37. However, preimplantation genetic screening is an expensive procedure. Information on the cost-effectiveness of preimplantation genetic screening can help inform clinical decision making., Methods: We constructed a decision analytic model for a hypothetical fresh, autologous in vitro fertilization cycle (with versus without preimplantation genetic screening) for women older than age 37 who had a successful oocyte retrieval and development of at least one blastocyst. The model incorporated probability and cost estimates of relevant clinical events based on data from published literature. Sensitivity analyses were performed to examine the impact of changes in model input parameters., Results: In base-case analysis, IVF-PGS offered a 4.2 percentage point increase in live birth rate for an additional cost of $4509, yielding an incremental cost-effectiveness ratio (ICER) of $105,489 per additional live birth. This ICER was below the expected cost of $145,063 for achieving one live birth with IVF (assuming an average LBR of 13.4% and $19,415 per cycle for this patient population). Sensitivity analysis suggested that ICER improved substantially with decreases in PGS cost and increases in PGS effectiveness. Monte Carlo simulation showed PGS to be cost-effective in 93.9% of iterations at an acceptability cutoff of $145,063., Conclusions: Considering the expected cost of achieving one live birth with IVF, PGS is a cost-effective strategy for women older than 37 undergoing IVF. Additional research on patients' willingness-to-pay per live birth would further inform our understanding regarding the cost-effectiveness of PGS.

Belgian legislation limiting the number of embryos for transfer has been shown to result in a 50% reduction of the multiple live birth rate (MLBR) per cycle without having a negative impact on the cumulative delivery rate per patient within six cycles or 36 months. The objective of the current study was to evaluate the cost saving associated with a 50% reduction in MLBR. A retrospective cost analysis was performed of 213 couples, who became pregnant and had a live birth after one or more assisted reproductive technology treatment cycles, and their 254 children. The mean cost of a singleton (n = 172) and multiple (n = 41) birth was calculated based on individual hospital invoices. The cost analysis showed a significantly higher total cost (assisted reproductive technology treatment, pregnancy follow-up, delivery, child cost until the age of 2 years) for multiple births (both children: mean €43,397) than for singleton births (mean: €17,866) (Wilcoxon-Mann-Whitney P < 0.0001). A 50% reduction in MLBR resulted in a significant cost reduction related to hospital care of 13%., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Study Question: What is the cost-effectiveness of lifestyle intervention preceding infertility treatment in obese infertile women?, Summary Answer: Lifestyle intervention preceding infertility treatment as compared to prompt infertility treatment in obese infertile women is not a cost-effective strategy in terms of healthy live birth rate within 24 months after randomization, but is more likely to be cost-effective using a longer follow-up period and live birth rate as endpoint., What Is Known Already: In infertile couples, obesity decreases conception chances. We previously showed that lifestyle intervention prior to infertility treatment in obese infertile women did not increase the healthy singleton vaginal live birth rate at term, but increased natural conceptions, especially in anovulatory women. Cost-effectiveness analyses could provide relevant additional information to guide decisions regarding offering a lifestyle intervention to obese infertile women., Study Design, Size, Duration: The cost-effectiveness of lifestyle intervention preceding infertility treatment compared to prompt infertility treatment was evaluated based on data of a previous RCT, the LIFEstyle study. The primary outcome for effectiveness was the vaginal birth of a healthy singleton at term within 24 months after randomization (the healthy live birth rate). The economic evaluation was performed from a hospital perspective and included direct medical costs of the lifestyle intervention, infertility treatments, medication and pregnancy in the intervention and control group. In addition, we performed exploratory cost-effectiveness analyses of scenarios with additional effectiveness outcomes (overall live birth within 24 months and overall live birth conceived within 24 months) and of subgroups, i.e. of ovulatory and anovulatory women, women <36 years and ≥36 years of age and of completers of the lifestyle intervention. Bootstrap analyses were performed to assess the uncertainty surrounding cost-effectiveness., Participants/materials, Settings, Methods: Infertile women with a BMI of ≥29 kg/m2 (no upper limit) were allocated to a 6-month lifestyle intervention programme preceding infertility treatment (intervention group, n = 290) or to prompt infertility treatment (control group, n = 287). After excluding women who withdrew informed consent or who were lost to follow-up we included 280 women in the intervention group and 284 women in the control group in the analysis., Main Results and the Role of Chance: Total mean costs per woman in the intervention group within 24 months after randomization were €4324 (SD €4276) versus €5603 (SD €4632) in the control group (cost difference of -€1278, P < 0.05). Healthy live birth rates were 27 and 35% in the intervention group and the control group, respectively (effect difference of -8.1%, P < 0.05), resulting in an incremental cost-effectiveness ratio of €15 845 per additional percentage increase of the healthy live birth rate. Mean costs per healthy live birth event were €15 932 in the intervention group and €15 912 in the control group. Exploratory scenario analyses showed that after changing the effectiveness outcome to all live births conceived within 24 months, irrespective of delivery within or after 24 months, cost-effectiveness of the lifestyle intervention improved. Using this effectiveness outcome, the probability that lifestyle intervention preceding infertility treatment was cost-effective in anovulatory women was 40%, in completers of the lifestyle intervention 39%, and in women ≥36 years 29%., Limitations, Reasons for Caution: In contrast to the study protocol, we were not able to perform the analysis from a societal perspective. Besides the primary outcome of the LIFEstyle study, we performed exploratory analyses using outcomes observed at longer follow-up times and we evaluated subgroups of women; the trial was not powered on these additional outcomes or subgroup analyses., Wider Implications of the Findings: Cost-effectiveness of a lifestyle intervention is more likely for longer follow-up times, and with live births conceived within 24 months as the effectiveness outcome. This effect was most profound in anovulatory women, in completers of the lifestyle intervention and in women ≥36 years old. This result indicates that the follow-up period of lifestyle interventions in obese infertile women is important. The scenario analyses performed in this study suggest that offering and reimbursing lifestyle intervention programmes in certain patient categories may be cost-effective and it provides directions for future research in this field., Study Funding/competing Interest(s): The study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). The department of obstetrics and gynaecology of the UMCG received an unrestricted educational grant from Ferring pharmaceuticals BV, The Netherlands. B.W.J.M. is a consultant for ObsEva, Geneva., Trial Registration Number: The LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530). http://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 1530., (© 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)

Competing Interests: Conflict of Interest: All authors stated no conflict of interest.

Objective: To evaluate the cost-effectiveness of single embryo transfer followed by an additional frozen-thawed single embryo transfer, if more embryos are available, as compared to double embryo transfer in relation to female age., Study Design: We used a decision tree model to evaluate the costs from a healthcare provider perspective and the pregnancy rates of two embryo transfer policies: one fresh single embryo transfer followed by an additional frozen-thawed single embryo transfer, if more embryos are available (strategy I), and double embryo transfer (strategy II). The analysis was performed on an intention-to-treat basis. Sensitivity analyses were carried out to evaluate the robustness of our model and to identify which model parameters had the strongest impact on the results., Results: SET followed by an additional frozen-thawed single embryo transfer if available was dominant, less costly and more effective, over DET in women under 32 years. In women aged 32 or older DET was more effective than SET followed by an additional frozen-thawed single embryo transfer if available but also more costly., Conclusion: SET followed by an additional frozen-thawed single embryo transfer should be the preferred strategy in women under 32 undergoing IVF. The choice for SET followed by an additional frozen-thawed single embryo transfer or DET in women aged 32 or older depends on individual patient preferences and on how much society is willing to pay for an extra child. There is a strong need for a randomized clinical trial comparing the cost and effects of SET followed by an additional frozen-thawed single embryo transfer and DET in the latter category of women., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The objective of this study was to implement an in vitro-produced embryo transfer (IVP-ET) system in an existing stochastic dynamic dairy simulation model with multitrait genetics to evaluate the genetic, technical, and financial performance of a dairy herd implementing an exclusive IVP-ET or artificial insemination (AI) system. In the AI system, sexed semen was used on the genetically best heifers only. In the IVP-ET system, all of the animals in the herd were impregnated with female sexed embryos created through in vitro fertilization of oocytes collected from animals of superior genetics for different traits of interest. Each donor was assumed to yield on average 4.25 transferable embryos per collection. The remaining animals in the herd were used as recipients and received either a fresh embryo or a frozen embryo when fresh embryos were not available. Selection of donors was random or based on the greatest estimated breeding value (EBV) of lifetime net merit (NM$), milk yield, or daughter pregnancy rate. For both the IVP-ET and AI systems, culling of surplus heifer calves not needed to replace culled cows was based on the lowest EBV for the same traits. A herd of 1,000 milking cows was simulated 15 yr over time after the start of the IVP-ET system. The default cost to produce and transfer 1 embryo was set at $165. Prices of fresh embryos at which an exclusive IVP-ET system financially breaks even with the comparable AI system in yr 15 and for an investment period of 15 yr were also estimated. More surplus heifer calves were sold from the IVP-ET systems than from the comparable AI systems. The surplus calves from the IVP-ET systems were also genetically superior to the surplus calves from the comparable AI systems, which might be reflected in their market value as a premium price. The most profitable scenario among the 4 IVP-ET scenarios in yr 15 was the one in which NM$ was maximized in the herd. This scenario had an additional profit of $8/cow compared with a similar AI scenario that maximized NM$, provided that surplus heifer calves could be sold at a premium price based on the superiority of the EBV of NM$. For the IVP-ET system to be at least as profitable as the comparable AI system during a 15-yr investment period, the surplus calves from the IVP-ET system needed to be sold at the premium prices. The break-even price of fresh embryos was estimated to be $84 for the exclusive IVP-ET system. This resulted in the same profit as the AI system, which maximized NM$ for a 15-yr investment period and in which heifer calves were sold at a premium price., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

A cost analysis covering direct healthcare costs relating to IVF freeze-all policy was conducted. Normal- and high- responder patients treated with a freeze-all policy (n = 63) compared with fresh transfer IVF (n = 189) matched by age, body mass index, duration and cause of infertility, predictive factors for IVF (number of oocytes used for fertilization) and study period, according to a 1:3 ratio were included. Total costs per patient (€6952 versus €6863) and mean costs per live birth were similar between the freeze-all strategy (€13,101, 95% CI 10,686 to 17,041) and fresh transfer IVF (€15,279, 95% CI 13,212 to 18,030). A mean per live birth cost-saving of €2178 (95% CI -1810 to 6165) resulted in a freeze-all strategy owing to fewer embryo transfer procedures (1.29 ± 0.5 versus 1.41 ± 0.7); differences were not significant. Sensitivity analysis revealed that the freeze-all strategy remained cost-effective until the live birth rate is either higher or only slightly lower (≥-0.59%) in the freeze-all group compared with fresh cycles. A freeze-all policy does not increase costs compared with fresh transfer, owing to negligible additional expenses, i.e. vitrification, endometrial priming and monitoring, against fewer embryo transfer procedures required to achieve pregnancy., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Study Question: What is the cost-effectiveness of elective single embryo transfer (eSET) versus double embryo transfer (DET) strategies from a societal perspective, when applying a time horizon of 1, 5 and 18 years?, Summary Answer: From a short-term perspective (1 year) it is cost-effective to replace DET with single embryo transfer; however when intermediate- (5 years) and long-term (18 years) costs and consequences are incorporated, DET becomes the most cost-effective strategy, given a ceiling ratio of €20 000 per quality-adjusted life years (QALY) gained., What Is Already Known: According to previous cost-effectiveness research into embryo transfer strategies, DET is considered cost-effective if society is willing to pay around €20 000 for an extra live birth. However, interpretation of those studies is complicated, as those studies fail to incorporate long-term costs and outcomes and used live birth as a measure of effectiveness instead of QALYs. With this outcome, both multiple and singletons were valued as one live birth, whereas costs of all children of a multiple were incorporated., Study Design, Size, Duration: A Markov model (cycle length: 1 year; time horizon: 1, 5 and 18 years) was developed comparing a maximum of: (i) three cycles of eSET in all patients; (ii) four cycles of eSET in all patients; (iii) five cycles of eSET in all patients; (iv) three cycles of standard treatment policy (STP), i.e. eSET in women <38 years with a good quality embryo, and DET in all other women; and (v) three cycles of DET in all patients., Participants/materials, Setting, Methods: Expected life years (LYs), child QALYs and costs were estimated for all comparators. Input parameters were derived from a retrospective cohort study, in which hospital resource data were collected (n=580) and a parental questionnaire was sent out (431 respondents). Probabilistic sensitivity analysis (5000 iterations) was performed., Main Results and the Role of Chance: With a time horizon of 18 years, DETx3 is most effective (0.54 live births, 10.2 LYs and 9.8 QALYs) and expensive (€37 871) per couple starting IVF. Three cycles of eSET are least effective (0.43 live births, 7.1 LYs and 6.8 QALYs) and expensive (€25 563). We assumed that society is willing to pay €20 000 per QALY gained. With a time horizon of 1 year, eSETx3 was the most cost-effective embryo transfer strategy with a probability of being cost-effective of 99.9%. With a time horizon of 5 or 18 years, DETx3 was most cost-effective, with probabilities of being cost-effective of 77.3 and 93.2%, respectively., Limitations, Reasons for Caution: This is the first study to use QALYs generated by the children in the economic evaluation of embryo transfer strategies. There remains some disagreement on whether QALYs generated by new life should be used in economic evaluations of fertility treatment. A further limitation is that treatment ends when it results in live birth and that only child QALYs were considered as measure of effectiveness. The results for the time horizon of 18 years might be less solid, as the data beyond the age of 8 years are based on extrapolation., Wider Implications of the Findings: The current Markov model indicates that when child QALYs are used as measure of outcome it is not cost-effective on the long term to replace DET with single embryo transfer strategies. However, for a balanced approach, a family-planning perspective would be preferable, including additional treatment cycles for couples who wish to have another child. Furthermore, the analysis should be extended to include QALYs of family members., Study Funding/competing Interests: This study was supported by a research grant (grant number 80-82310-98-09094) from the Netherlands Organization for Health Research and Development (ZonMw). There are no conflicts of interest in connection with this article., Trial Registration Number: Not applicable., (© The Author 2016. 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.)

ET is a critical step in an assisted reproduction cycle. Over the past decade there has been an increasing trend to extending culture from cleavage-stage to blastocyst transfer. There has also been a trend to single ET and reporting the success of an assisted reproductive cycle as a cumulative live-birth rate after using both fresh and frozen embryos. There is low evidence that fresh blastocyst transfer is associated with improved live-birth rates compared with fresh cleavage-stage embryos. However, in the few studies that report cumulative pregnancy rates after fresh and frozen transfers, no significant difference was found. Cleavage-stage transfer is associated with greater numbers of embryos available for freezing, and blastocyst transfer is associated with increased number of cycles with no embryos to transfer. Further well-designed studies are warranted to evaluate the outcomes for blastocyst transfer including cumulative live-birth rate after fresh and frozen transfers, time to live birth, costs of the different transfer strategies, and perinatal mortality and severe perinatal morbidity., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Study Question: Are live birth rates (LBRs) after artificial cycle frozen-thawed embryo transfer (AC-FET) non-inferior to LBRs after modified natural cycle frozen-thawed embryo transfer (mNC-FET)?, Summary Answer: AC-FET is non-inferior to mNC-FET with regard to LBRs, clinical and ongoing pregnancy rates (OPRs) but AC-FET does result in higher cancellation rates., What Is Already Known: Pooling prior retrospective studies of AC-FET and mNC-FET results in comparable pregnancy and LBRs. However, these results have not yet been confirmed by a prospective randomized trial., Study Design, Size and Duration: In this non-inferiority prospective randomized controlled trial (acronym 'ANTARCTICA' trial), conducted from February 2009 to April 2014, 1032 patients were included of which 959 were available for analysis. The primary outcome of the study was live birth. Secondary outcomes were clinical and ongoing pregnancy, cycle cancellation and endometrium thickness. A cost-efficiency analysis was performed., Participant/materials, Setting, Methods: This study was conducted in both secondary and tertiary fertility centres in the Netherlands. Patients included in this study had to be 18-40 years old, had to have a regular menstruation cycle between 26 and 35 days and frozen-thawed embryos to be transferred had to derive from one of the first three IVF or IVF-ICSI treatment cycles. Patients with a uterine anomaly, a contraindication for one of the prescribed medications in this study or patients undergoing a donor gamete procedure were excluded from participation. Patients were randomized based on a 1:1 allocation to either one cycle of mNC-FET or AC-FET. All embryos were cryopreserved using a slow-freeze technique., Main Results and the Role of Chance: LBR after mNC-FET was 11.5% (57/495) versus 8.8% in AC-FET (41/464) resulting in an absolute difference in LBR of -0.027 in favour of mNC-FET (95% confidence interval (CI) -0.065-0.012; P = 0.171). Clinical pregnancy occurred in 94/495 (19.0%) patients in mNC-FET versus 75/464 (16.0%) patients in AC-FET (odds ratio (OR) 0.8, 95% CI 0.6-1.1, P = 0.25). 57/495 (11.5%) mNC-FET resulted in ongoing pregnancy versus 45/464 (9.6%) AC-FET (OR 0.7, 95% CI 0.5-1.1, P = 0.15). χ(2) test confirmed the lack of superiority. Significantly more cycles were cancelled in AC-FET (124/464 versus 101/495, OR 1.4, 95% CI 1.1-1.9, P = 0.02). The costs of each of the endometrial preparation methods were comparable (€617.50 per cycle in NC-FET versus €625.73 per cycle in AC-FET, P = 0.54)., Limitations, Reasons for Caution: The minimum of 1150 patients required for adequate statistical power was not achieved. Moreover, LBRs were lower than anticipated in the sample size calculation., Wider Implications of the Findings: LBRs after AC-FET were not inferior to those achieved by mNC-FET. No significant differences in clinical and OPR were observed. The costs of both treatment approaches were comparable., Study Funding/competing Interests: An educational grant was received during the conduct of this study. Merck Sharpe Dohme had no influence on the design, execution and analyses of this study. E.R.G. received an education grant by Merck Sharpe Dohme (MSD) during the conduct of the present study. B.J.C. reports grants from MSD during the conduct of the study. A.H. reports grants from MSD and Ferring BV the Netherlands and personal fees from MSD. Grants from ZonMW, the Dutch Organization for Health Research and Development. J.S.E.L. reports grants from Ferring, MSD, Organon, Merck Serono and Schering-Plough during the conduct of the study. F.J.M.B. receives monetary compensation as member of the external advisory board for Merck Serono, consultancy work for Gedeon Richter, educational activities for Ferring BV, research cooperation with Ansh Labs and a strategic cooperation with Roche on automated anti Mullerian hormone assay development. N.S.M. reports receiving monetary compensations for external advisory and speaking work for Ferring BV, MSD, Anecova and Merck Serono during the conduct of the study. All reported competing interests are outside the submitted work. No other relationships or activities that could appear to have influenced the submitted work., Trial Registration Number: Netherlands trial register, number NTR 1586., Trial Registration Date: 13 January 2009., First Patient Included: 20 April 2009., (© The Author 2016. 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 estimate the national cost savings resulting from reductions in higher-order multiple (HOM) live births (defined as three or more fetuses), following the initial publication of the Society for Assisted Reproductive Technology (SART) guidelines on ET in 1998., Design: Descriptive use and cost analysis., Setting: Not applicable., Patient(s): Not applicable., Intervention(s): Not applicable., Main Outcome Measure(s): Estimates of the total number of HOM deliveries prevented (from 1998-2012) following the publication of SART guidelines; the associated healthcare savings (2014 US dollars)., Result(s): A singleton live birth was estimated to cost $17,100-$24,200. A twin live birth was estimated at $66,000-$117,500. A triplet live birth was estimated at $190,800-$456,300. The percentage of HOM gestations among all ART pregnancies decreased from 11.4% in 1997 to 2.0% in 2012, with the sharpest year-over-year decline of 20.3% occurring in the year following the publication of the guidelines. The number of prevented HOM deliveries from 1998 through 2012 was estimated to be between 13,500 and 16,300, corresponding to cost savings of $6.02B (billion) (range, $2.35B-$7.03B, 2014 US dollars)., Conclusion(s): Iatrogenic HOM gestations represent a substantial economic burden to our healthcare system. The introduction of guidelines for ET in 1998 coincided with a dramatic decrease in the HOM rate in subsequent years and an associated cumulative cost savings of more than $6B. Further reductions in HOM gestations could save up to an additional $2B annually., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: In states in the USA without in vitro fertilzation coverage (IVF) insurance coverage, more embryos are transferred per cycle leading to higher risks of multi-fetal pregnancies and adverse pregnancy outcomes., Objective: To determine frequency and cost of selected adverse perinatal complications based on number of embryos transferred during IVF, and calculate incremental cost per IVF live birth., Methods: Medical records of patients who conceived with IVF (n = 116) and delivered at >20 weeks gestational age between 2007 and 2011 were evaluated. Gestational age at delivery, low birth weight (LBW) term births, and delivery mode were tabulated. Healthcare costs per cohort, extrapolated costs assuming 100 patients per cohort, and incremental costs per infant delivered were calculated., Results: The highest prematurity and cesarean section rates were recorded after double embryo transfers (DET), while the lowest rates were found in single embryo transfers (SET). Premature singleton deliveries increased directly with number of transferred embryos [6.3 % (SET), 9.1 % (DET) and 10.0 % for ≥3 embryos transferred]. This trend was also noted for rate of cesarean delivery [26.7 % (SET), 36.6 % (DET), and 47.1 % for ≥3 embryos transferred]. The proportion of LBW infants among deliveries after DET and for ≥3 embryos transferred was 3.9 and 9.1 %, respectively. Extrapolated costs per cohort were US$718,616, US$1,713,470 and US$1,227,396 for SET, DET, and ≥3 embryos transferred, respectively., Conclusion: Attempting to improve IVF pregnancy rates by permitting multiple embryo transfers results in sharply increased rates of multiple gestation and preterm delivery. This practice yields a greater frequency of adverse perinatal outcomes and substantially increased healthcare spending. Better efforts to encourage SET are necessary to normalize healthcare expenditures considering the frequency of very high cost sequela associated with IVF where multiple embryo transfers occur.

Objectives: The hypothesis that shared decision-making (SDM) reduces medical practice variations is increasingly common, but no evidence is available. We aimed to elaborate further on this, and to perform a first exploratory analysis to examine this hypothesis. This analysis, based on a limited data set, examined how SDM is associated with variation in the choice of single embryo transfer (SET) or double embryo transfer (DET) after in vitro fertilisation (IVF). We examined variation between and within hospitals., Design: A secondary analysis of a randomised controlled trial., Setting: 5 hospitals in the Netherlands., Participants: 222 couples (woman aged <40 years) on a waiting list for a first IVF cycle, who could choose between SET and DET (ie, ≥2 embryos available)., Intervention: SDM via a multifaceted strategy aimed to empower couples in deciding how many embryos should be transferred. The strategy consisted of decision aid, support of IVF nurse and the offer of reimbursement for an extra treatment cycle. Control group received standard IVF care., Outcome Measure: Difference in variation due to SDM in the choice of SET or DET, both between and within hospitals., Results: There was large variation in the choice of SET or DET between hospitals in the control group. Lower variation between hospitals was observed in the group with SDM. Within most hospitals, variation in the choice of SET or DET appeared to increase due to SDM. Variation particularly increased in hospitals where mainly DET was chosen in the control group., Conclusions: Although based on a limited data set, our study gives a first insight that including patients' preferences through SDM results in less variation between hospitals, and indicates another pattern of variation within hospitals. Variation that results from patient preferences could be potentially named the informed patient rate. Our results provide the starting point for further research., Trial Registration Number: NCT00315029; Post-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

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.

Objective: To assess treatment and pregnancy/infant-associated medical costs and birth outcomes for assisted reproductive technology (ART) cycles in a subset of patients using elective double embryo (ET) and to project the difference in costs and outcomes had the cycles instead been sequential single ETs (fresh followed by frozen if the fresh ET did not result in live birth)., Design: Retrospective cohort study using 2012 and 2013 data from the National ART Surveillance System., Setting: Infertility treatment centers., Patient(s): Fresh, autologous double ETs performed in 2012 among ART patients younger than 35 years of age with no prior ART use who cryopreserved at least one embryo., Intervention(s): Sequential single and double ETs., Main Outcome Measure(s): Actual live birth rates and estimated ART treatment and pregnancy/infant-associated medical costs for double ET cycles started in 2012 and projected ART treatment and pregnancy/infant-associated medical costs if the double ET cycles had been performed as sequential single ETs., Result(s): The estimated total ART treatment and pregnancy/infant-associated medical costs were $580.9 million for 10,001 double ETs started in 2012. If performed as sequential single ETs, estimated costs would have decreased by $195.0 million to $386.0 million, and live birth rates would have increased from 57.7%-68.0%., Conclusion(s): Sequential single ETs, when clinically appropriate, can reduce total ART treatment and pregnancy/infant-associated medical costs by reducing multiple births without lowering live birth rates., (Published by Elsevier Inc.)

Study Question: What is the cost-effectiveness of in vitro fertilization (IVF) with conventional ovarian stimulation, single embryo transfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) as a first-line treatment in couples with unexplained subfertility and an unfavourable prognosis on natural conception?., Summary Answer: Both IVF strategies are significantly more expensive when compared with IUI-COH, without being significantly more effective. In the comparison between IVF-MNC and IUI-COH, the latter is the dominant strategy. Whether IVF-SET is cost-effective depends on society's willingness to pay for an additional healthy child., What Is Known Already: IUI-COH and IVF, either after conventional ovarian stimulation or in a MNC, are used as first-line treatments for couples with unexplained or mild male subfertility. As IUI-COH is less invasive, this treatment is usually offered before proceeding to IVF. Yet, as conventional IVF with SET may lead to higher pregnancy rates in fewer cycles for a lower multiple pregnancy rate, some have argued to start with IVF instead of IUI-COH. In addition, IVF in the MNC is considered to be a more patient friendly and less costly form of IVF., Study Design, Size, Duration: We performed a cost-effectiveness analysis alongside a randomized noninferiority trial. Between January 2009 and February 2012, 602 couples with unexplained infertility and a poor prognosis on natural conception were allocated to three cycles of IVF-SET including frozen embryo transfers, six cycles of IVF-MNC or six cycles of IUI-COH. These couples were followed until 12 months after randomization., Participants/materials, Setting, Methods: We collected data on resource use related to treatment, medication and pregnancy from the case report forms. We calculated unit costs from various sources. For each of the three strategies, we calculated the mean costs and effectiveness. Incremental cost-effectiveness ratios (ICER) were calculated for IVF-SET compared with IUI-COH and for IVF-MNC compared with IUI-COH. Nonparametric bootstrap resampling was used to investigate the effect of uncertainty in our estimates., Main Results and the Role of Chance: There were 104 healthy children (52%) born in the IVF-SET group, 83 (43%) the IVF-MNC group and 97 (47%) in the IUI-COH group. The mean costs per couple were €7187 for IVF-SET, €8206 for IVF-MNC and €5070 for IUI-COH. Compared with IUI-COH, the costs for IVF-SET and IVF-MNC were significantly higher (mean differences €2117; 95% CI: €1544-€2657 and €3136, 95% CI: €2519-€3754, respectively).The ICER for IVF-SET compared with IUI-COH was €43 375 for the birth of an additional healthy child. In the comparison of IVF-MNC to IUI-COH, the latter was the dominant strategy, i.e. more effective at lower costs., Limitations, Reasons for Caution: We only report on direct health care costs. The present analysis is limited to 12 months., Wider Implications of the Findings: Since we found no evidence in support of offering IVF as a first-line strategy in couples with unexplained and mild subfertility, IUI-COH should remain the treatment of first choice., Study Funding/competing Interests: The study was supported by a grant from ZonMw, the Netherlands Organization for Health Research and Development, (120620027) and a grant from Zorgverzekeraars Nederland, the Netherlands' association of health care insurers (09-003)., Trial Registration Number: Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939., (© 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.)

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.)

The present assay attempts to evaluate the feasibility of using embryo transfer in small community farmers by in vivo study and by modelling the results obtained. From the total of 59 donor cows, 62.7% responded to treatment, with a significant difference (p = 0.002) in the percentage of the response between breeds, being 90.5% (19/21) in Holstein and 47.4% (18/38) in Brahman. A total of 283 embryos were graded as transferable, while 141 as non-transferable, without difference in the percentage of transferable embryo by breed (p = 0.18). The mean of transferable embryos graded as class I and II was not different between Holstein and Brahman (p = 0.96 and p = 0.92, respectively); besides, no differences were observed in the other grades (non-transferable). The highest difference in costs, regardless of its quality by breed, was seen in the lower levels of probable fertility of the embryo transferred, even reaching several hundred dollars. When modelling the expected costs for embryo produced and transferred, values can reach nearly $2000.00 when the probable fertility is only 10%. However, when the probable fertility was 60%, embryo cost was close to $300.00. This technology seems to be viable on average or high-scale systems, having a superovulatory response between 60 and 80% with 4-6 transferrable embryos. Yet, in small-scale farming, due to the reduced number of donors and/or recipients, the costs surpass the economical feasibility of the technique., (© 2015 Blackwell Verlag GmbH.)

Objective: To use linked assisted reproductive technology (ART) surveillance and birth certificate data to compare ET practices and perinatal outcomes for a state with a comprehensive mandate requiring coverage of IVF services versus states without a mandate., Design: Retrospective cohort study., Setting: Not applicable., Patient(s): Live-birth deliveries ascertained from linked 2007-2009 National ART Surveillance System and birth certificate data for a state with an insurance mandate (Massachusetts) and two states without a mandate (Florida and Michigan)., Intervention(s): None., Main Outcome Measure(s): Number of embryos transferred, multiple births, low birth weight, preterm delivery., Result(s): Of the 230,038 deliveries in the mandate state and 1,026,804 deliveries in the nonmandate states, 6,651 (2.9%) and 8,417 (0.8%), respectively, were conceived by ART. Transfer of three or more embryos was more common in nonmandate states, although the effect was attenuated for women 35 years or older (33.6% vs. 39.7%; adjusted relative risk [RR], 1.46; 95% confidence interval [CI], 1.17-1.81) versus women younger than 35 (7.0% vs. 26.9%; adjusted RR, 4.18; 95% CI, 2.74-6.36). Lack of an insurance mandate was positively associated with triplet/higher order deliveries (1.0% vs. 2.3%; adjusted RR, 2.44; 95% CI, 1.81-3.28), preterm delivery (22.6% vs. 30.7%; adjusted RR, 1.31; 95% CI, 1.20-1.42), and low birth weight (22.3% vs. 29.5%; adjusted RR, 1.28; 95% CI, 1.17-1.40)., Conclusion(s): Compared with nonmandate states, the mandate state had higher overall rates of ART use. Among ART births, lack of an infertility insurance mandate was associated with increased risk for adverse perinatal outcomes., (Published by Elsevier Inc.)

Conventional controlled ovarian stimulation (cCOS) can cause significant discomfort, including ovarian hyperstimulation syndrome (OHSS). Clearly, management of OHSS and poor responder patients requires new strategies to overcome these problems and facilitate the birth of a healthy child with the fewest stimulation cycles. Several alternative methods have been developed. Non-conventional controlled ovarian stimulation (non-cCOS) is based on low-dose stimulation regimens and is often termed "light", "soft", "mini", "minimal", "mild", "low cost", or "low dose IVF". Non-controlled ovarian stimulation therapies (non-COS) include natural cycle IVF or a mixture between non-controlled and non-cCOS, termed "modified natural IVF" or "antiestrogen/aromatase inhibitor/low dose FSH-cycles", in which cycles are monitored but not controlled. These approaches promise to reduce the physical, emotional, and financial burden of IVF therapy while maintaining acceptable pregnancy rates. Such approaches might reduce the risk of OHSS. However, the overall cost per baby increases due to the higher number of stimulation cycles required, and the inconvenience of ovum pick-up still remains. The primary focus should be to obtain several good quality blastocysts after a single cCOS cycle. Thus, adequate numbers of mature oocytes are mandatory. What is more difficult and expensive for patients: several non-COS/non-cCOS cycles to obtain a baby or a single cCOS cycle with a high probability to obtain more than one child? Classic cCOS using the GnRH agonist long protocol followed by single embryo transfer (SET) at the blastocyst stage and aseptic vitrification of surplus embryos optimizes the IVF outcome. This strategy, combined with outpatient management in the case of OHSS, minimizes inconvenience and risks of OHSS. Accumulation cycles (AC) by repeated COS with subsequent freezing of blastocysts, combined with preimplantation genetic screening (PGS), is a promising new approach for low responders, especially in cases of advanced maternal age (AMA).

What role should legislation or policy play in avoiding the complications of in-vitro fertilization? In this article, we focus on single versus double embryo transfer, and assess three arguments in favour of mandatory single embryo transfer: risks to the mother, risks to resultant children, and costs to society. We highlight significant ethical concerns about each of these. Reproductive autonomy and non-paternalism are strong enough to outweigh the health concerns for the woman. Complications due to non-identity cast doubt on the extent to which children are harmed. Twinning may offer an overall benefit rather than burden to society. Finally, including the future health costs for children (not yet born) in reproductive policy is inconsistent with other decisions. We conclude that mandatory single embryo transfer is not justified and that a number of countries should reconsider their current embryo transfer policy.

Background: New techniques in assessing oocytes and embryo quality are currently explored to improve pregnancy and delivery rates per embryo transfer. While a better understanding of embryo quality could help optimize the existing "in vitro fertilization" (IVF) therapy schemes, it is essential to address the economic viability of such technologies in the healthcare setting., Methods: An Embryo-Dx economic model was constructed to assess the cost-effectiveness of 3 different IVF strategies from a payer's perspective; it compares Embryo-Dx with single embryo transfer (SET) to elective single embryo transfer (eSET) and to double embryo transfer (DET) treatment practices., Results: The introduction of a new non-invasive embryo technology (Embryo-Dx) associated with a cost up to €460 is cost-effective compared to eSET and DET based on the cost per live birth. The model assumed that Embryo-Dx will improve ongoing pregnancy rate/realize an absolute improvement in live births of 9% in this case., Conclusions: This study shows that improved embryo diagnosis combined with SET may have the potential to reduce the cost per live birth per couple treated in IVF treatment practices. The results of this study are likely more sensitive to changes in the ongoing pregnancy rate and consequently the live birth rate than the diagnosis costs. The introduction of a validated Embryo-Dx technology will further support a move towards increased eSET procedures in IVF clinical practice and vice versa.

Multiple pregnancies are an undesirable complication of IVF and of ovulation induction and/or ovulation enhancement without IVF. Studies based on published population data and data from the Centers for Disease Control and Prevention indicate that savings from the mitigation of iatrogenic multiples would save money in the billions (10(9)) of US dollars on a national basis. The aim of this study was to determine whether, using real data from a major regional insurance carrier for the interval 2005-2009 covering obstetric costs requiring hospitalization and neonatal costs through the first year, it was possible to show that the cost saved by eliminating iatrogenic multiple births would be adequate to fund a protocol to minimize iatrogenic multiple births. The net savings on an annual basis for the study group of 13,478 was about US$4.4 million. Applying the regional findings to national data suggests savings of approximately US$6.3 billion if national iatrogenic multiples were eliminated. These findings indicate that the health insurance industry should be able to offer infertility coverage at a lower rate by requiring a treatment algorithm designed to essentially eliminate iatrogenic multiple pregnancies. It is concluded that efforts should be made to assure a singleton birth when treating infertility., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Although efficient transcervical transfer of embryos in mice would provide many advantages over a surgical method, the low success rate of transcervical transfer has hampered its acceptance and use. Here, we describe a novel device and protocol for transcervical embryo transfer in mice. Blastocysts from CD1 female mice were transferred into the uteri of 2.5-d pseudopregnant CD1 mice by using this method resulted in the successful development of 66.7% to 73.5% of the transferred blastocysts into live-born fetuses. Our method is as efficient as surgical embryo transfer yet is much simpler, easier, and markedly less traumatic to the recipient. In addition, our method provides hygienic and economic advantages and conforms to the principles of humane experimental technique. More importantly, our method provides a model for studying transcervical embryo transfer in cattle, other large animals, and humans.

Objective: To systematically quantify the impact of consumer cost on assisted reproduction technology (ART) utilization and numbers of embryos transferred., Design: Ordinary least squared (OLS) regression models were constructed to measure the independent impact of ART affordability-measured as consumer cost relative to average disposable income-on ART utilization and embryo transfer practices., Setting: Not applicable., Patient(s): Women undergoing ART treatment., Intervention(s): None., Main Outcome Measure(s): OLS regression coefficient for ART affordability, which estimates the independent effect of consumer cost relative to income on utilization and number of embryos transferred., Result(s): ART affordability was independently and positively associated with ART utilization with a mean OLS coefficient of 0.032. This indicates that, on average, a decrease in the cost of a cycle of 1 percentage point of disposable income predicts a 3.2% increase in utilization. ART affordability was independently and negatively associated with the number of embryos transferred, indicating that a decrease in the cost of a cycle of 10 percentage points of disposable income predicts a 5.1% increase in single-embryo transfer cycles., Conclusion(s): The relative cost that consumers pay for ART treatment predicts the level of access and number of embryos transferred. Policies that affect ART funding should be informed by these findings to ensure equitable access to treatment and clinically responsible embryo transfer practices., (Copyright © 2014 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.

Study Question: What is the effect of a legal limitation of the number of embryos that can be transferred in an assisted reproductive technology (ART) cycle on the multiple delivery rate?, Summary Answer: The Belgian national register shows that the introduction of reimbursement of ART laboratory costs in July 2003, and the imposition of a legal limitation of the number of embryos transferred in the same year, were associated with a >50% reduction of the multiple pregnancy rate from 27 to 11% between 2003 and the last assessment in 2010, without any reduction of the pregnancy rate per cycle., What Is Known Already: Individual Belgian IVF centres have published their results since the implementation of the law, and these show a decrease in the multiple pregnancy rate on a centre by centre basis. However, the overall national picture remains unpublished., Study Design, Size, Duration: Cohort study from 1990 to 2010 of all ART cycles in Belgium (2685 cycles in 1990 evolving to 19 110 cycles in 2010), with a retrospective analysis from 1990 to 2000 and prospective online data collection since 2001., Participants/materials, Setting, Methods: Registration evolved from paper written reports per centre to a compulsory online registration of all ART cycles. From 2001 up to mid-2009, data were collected from Excel spread sheets or MS Access files into an MS Access database. Since mid-2009, data collection is done via a remote and secured web-based system (www.belrap.be) where centres can upload their data and get immediate feedback about missing data, errors and inconsistencies., Main Results and the Role of Chance: National Belgian registration data show that reimbursement of IVF laboratory costs in July 2003, coupled to a legal limitation in the number of embryos transferred in utero, were associated with a 50% reduction of the multiple pregnancy rate from 27 to 11% without reduction of the pregnancy rate per cycle, and with an increase in the number of fresh and frozen ART cycles due to improved access to treatment., Limitations, Reasons for Caution: There is potential underreporting of complications of ART treatment, pregnancy outcome and neonatal health., Wider Implications of the Findings: Over the 20 years of registration, the pregnancy rate has remained constant, despite the reduction in the number of embryos transferred, optimization of laboratory procedures and stimulation protocols, introduction of quality systems and implementation of the EU Tissue Directive over the period 2004-2010., Study Funding/competing Interest(s): No external funding was sought for this study. None of the authors has any conflict of interest to declare.

Objective: To compare cost-effectiveness between pituitary down-regulation with a GnRH agonist (GnRHa) short regimen on alternate days and GnRH antagonist (GnRHant) multidose protocol on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcome., Design: Prospective, randomized., Setting: A private center., Patient(s): Patients were randomized into GnRHa (n = 48) and GnRHant (n = 48) groups., Intervention(s): GnRHa stimulation protocol: administration of triptorelin on alternate days starting on the first day of the cycle, recombinant FSH (rFSH), and recombinant hCG (rhCG) microdose. GnRHant protocol: administration of a daily dose of rFSH, cetrorelix, and rhCG microdose., Main Outcome Measure(s): ICSI outcomes and treatment costs., Result(s): A significantly lower number of patients underwent embryo transfer in the GnRHa group. Clinical pregnancy rate was significantly lower and miscarriage rate was significantly higher in the GnRHa group. It was observed a significant lower cost per cycle in the GnRHa group compared with the GnRHant group ($5,327.80 ± 387.30 vs. $5,900.40 ± 472.50). However, mean cost per pregnancy in the GnRHa was higher than in the GnRHant group ($19,671.80 ± 1,430.00 vs. $11,328.70 ± 907.20)., Conclusion(s): Although the short controlled ovarian stimulation protocol with GnRHa on alternate days, rFSH, and rhCG microdose may lower the cost of an individual IVF cycle, it requires more cycles to achieve pregnancy., Clinical Trial Registration Number: NCT01468441., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

As fertility rates among women of advanced reproductive age have steadily increased, so has the utilization of fertility services. National health policies provide infertility treatment coverage in several developed countries; however, in the United States infertility treatment is largely privately funded, resulting in limited access to care. In response to the lack of insurance coverage, many practices offer fertility treatment on a risk-sharing or contingency fee basis. The ethical delivery of care under the auspices of these programs requires adherence to core principles including transparency, patient autonomy, and the delivery of appropriate medical care. Moreover, concerns regarding patient understanding and decision making have also been of foremost concern. Patients must be able to fully appreciate the financial and clinical implications of contingency fee programs. To further explore patient comprehension and satisfaction, we surveyed participants in our shared risk assisted reproductive technology program. The overwhelming majority of respondents felt adequately informed of and fairly charged for their treatment. Our results demonstrate that shared risk programs can receive strong endorsement from participants, which may lead to improved utilization of and perseverance with fertility treatment., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Frozen thawed embryo transfer (FET) is a cost-effective adjunct to IVF or IVF-ICSI treatment. In order to optimize treatment outcome, FET should be carried out during a period of optimal endometrial receptivity. To optimize implantation several methods for endometrium preparation have been proposed. In natural cycle FET (NC-FET), the endometrium develops under endogenous hormonal stimulation. The development of the dominant follicle and endometrium is monitored by ultrasound and FET is timed after triggering ovulation induction or determination of the spontaneous LH surge. In an artificial cycle FET (AC-FET) estrogens and progesterone are administered to prepare the endometrium for implantation. While the currently available data show no significant difference in pregnancy rates between these methods, well designed randomized controlled trials are lacking. Moreover there is little literature on difference in cancellation rates, cost-efficiency and adverse events., Methods and Design: In this randomized, multi-centre, non-inferiority trial we aim to test the hypothesis that there is no significant difference in live birth rates between patients undergoing NC-FET versus AC-FET. The primary outcome will be live birth rate per embryo transfer procedure. Secondary outcomes will be ongoing and clinical pregnancy rate, cancellation rate, (serious) adverse events and cost-efficiency. Based on a live birth rate of 20% and a minimal clinical important difference of 7.5% (one-sided alpha 2.5%, beta 20%) a total of 1150 patients will be needed. Analyzes will be performed using both per protocol as well as intention to treat analyses., Discussion: This prospective, randomized, non-inferiority trial aims to address the hypothesis that there is no significant difference in live birth rates between patients undergoing NC-FET versus patients undergoing AC-FET. Moreover it addresses cost-efficiency as well as the perceived burden of both treatments., Trial Register: Netherlands trial register (NTR): 1586.