The cumulative live birth rate and cost-effectiveness of the clomiphene and gonadotropin cotreatment protocol versus the mid-luteal GnRH agonist protocol in women over 35 years old.

The decrease in assisted reproductive technology success among older women, attributed to decreased oocyte quantity and quality, poses a significant challenge. Currently, no consensus on the optimal ovarian stimulation protocol for older women undergoing IVF exists. This retrospectively registered cohort study aimed to compare the cumulative live birth rate (CLBR), time to live birth (TTLB), and cost-effectiveness among women older than 35 years who were receiving either the gonadotropin-releasing hormone agonist (GnRHa) or clomiphene citrate and gonadotropin cotreatment with ovarian stimulation (CC cotreatment) protocol. To compare treatment outcomes, we performed propensity score matching (PSM) on 2871 IVF cycles in women older than 35 years who received either the GnRHa or CC cotreatment protocol, resulting in 375 cycles in each group. Additionally, a decision tree model was utilized to assess the cost-effectiveness of the two protocols. Following PSM, both groups had similar baseline characteristics. The CC cotreatment protocol resulted in a greater rate of cycle cancellation (13.07% vs. 8.00%, p = 0.032), but the groups maintained comparable fertilization rates and embryo quality. Although the TTLB was longer in the CC cotreatment group, the CLBR per initial cycle (41.07% vs. 45.33%, p = 0.269) and delivery outcomes were similar between the two groups at the 24 months follow-up. Additionally, the average cost per live birth in the CC cotreatment group was 21.27% lower than in the GnRHa group (¥32,301.42 vs. ¥39,174.22). In conclusion, for women older than 35 years undergoing IVF, the CC cotreatment protocol offered a comparable CLBR to the GnRHa protocol but with reduced costs, indicating its potential as a viable and cost-effective ovarian stimulation option.Clinical trial registration: https://www.chictr.org.cn/ , identifier [ChiCTR2300076537].

A randomized controlled trial to evaluate the use of a web-based application to manage medications during in vitro fertilization.

OBJECTIVE: To evaluate the use of a web-based application that assists in medication management during in vitro fertilization (IVF) treatment. DESIGN: Multicenter randomized controlled trial. SETTING: University hospitals. PATIENT(S): Women undergoing IVF. INTERVENTION(S): Subjects were recruited to assess quality of life during IVF and were randomly assigned to use either the OnTrack application to assist with medication management or conventional medication management. Surveys were administered at four time points. MAIN OUTCOME MEASURE(S): Medication surplus, incidence of medication errors, amount of patient-initiated communication, and patient satisfaction. RESULT(S): A total of 153 women participated. The average number of portal messages and telephone calls was similar between groups. Twelve patients in the control group (12/69, 17.4%) and 8 patients in the case group (8/72, 11.1%) made medication errors. There were similar amounts of medication surplus in the two groups. The estimated cost of medication waste was $2,578 ± $2,056 in the control group and $2,554 ± $1,855 in the case group. Patient satisfaction was similar between the two groups. CONCLUSION(S): Use of a web-based application did not decrease medication errors, medication surplus, or patient-initiated messages. Many patients had a medication surplus, which can be an area of cost reduction during IVF. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT03383848.

Short communication: Economic impact among 7 reproductive programs for lactating dairy cows, including a sensitivity analysis of the cost of hormonal treatments.

Although hormonal synchronization programs can improve reproductive efficiency of dairy herds, some farmers question the economics of these programs based on the upfront cost of hormonal treatments as opposed to the economic value of the resulting reproductive performance. Our aim was to compare the economic impact of reproductive management programs that incorporate varying degrees of detection of estrus and timed artificial insemination (AI) in dairy herds with year-round calving in confinement total mixed ration systems. A reproductive economic analysis simulation model was used to compare the economic impact of pairs of reproductive management programs. We simulated sets of scenarios for 2 analyses. In the first analysis, we calculated the economic impact of switching from a Presynch-Ovsynch program to a Double-Ovsynch program that included a second PGF2α treatment during the Breeding-Ovsynch portion of the program (Double-Ovsynch+PGF). In the second analysis, we conducted a break-even analysis in which the cost of hormonal treatments was incrementally increased within various reproductive management programs. Our analyses revealed that a Double-Ovsynch+PGF program, the most intensive program evaluated, was more profitable than other programs compared, including a Presynch-Ovsynch program with 100% timed AI or a Presynch-Ovsynch program that incorporated detection of estrus, despite the higher upfront cost incurred by using more hormonal treatments. This advantage remained until the cost of hormones was increased 5 to 14 times current US market prices and 2 to 6 times current European market prices. The cost of GnRH had a greater impact on net profit gain than the cost of PGF2α. In conclusion, more intensive reproductive programs that use more hormonal treatments but result in substantially increased reproductive performance are more profitable than less intensive programs and remain so even if hormone prices are unusually high.

Cumulative Live Birth Rate and Cost-Effectiveness Analysis of Gonadotropin Releasing Hormone-Antagonist Protocol and Multiple Minimal Ovarian Stimulation in Poor Responders.

Background: The overall cumulative live birth rate (CLBR) of poor ovarian responders (POR) is extremely low. Minimal ovarian stimulation (MOS) provides a relatively realistic solution for ovarian stimulation in POR. Our study aimed to investigate whether multiple MOS strategies resulted in higher CLBR compared to conventional gonadotropin releasing hormone (GnRH) antagonists in POR. Methods: This retrospective study included 699 patients (1,058 cycles) from one center, who fulfilled the Bologna criteria between 2010 and 2018. Overall, 325 women (325 cycles) were treated with one-time conventional GnRH antagonist ovarian stimulation (GnRH-antagonist). Another 374 patients (733 cycles) were treated with multiple MOS including natural cycles. CLBR and time-and-cost-benefit analyses were compared between these two groups of women. Results: GnRH antagonists provided more retrieved oocytes, meiosis II oocytes, fertilized oocytes, and more viable embryos compared to both the first MOS (p < 0.001) and the cumulative corresponding numbers in multiple MOSs (p < 0.001). For the first in vitro fertilization (IVF) cycle, GnRH antagonists resulted in higher CLBR than MOS [12.92 versus 4.54%, adjusted OR (odds ratio) 2.606; 95% CI (confidence interval) 1.386, 4.899, p = 0.003]. The one-time GnRH-antagonist induced comparable CLBR (12.92 versus 7.92%, adjusted OR 1.702; 95% CI 0.971, 2.982, p = 0.063), but a shorter time to live birth [9 (8, 10.75) months versus 11 (9, 14) months, p = 0.014] and similar financial expenditure compared to repeated MOS [20,838 (17,953, 23,422) ¥ versus 21,261.5 (15,892.5, 35,140.25) ¥, p = 0.13]. Conclusion: Both minimal ovarian stimulation (MOS) and GnRH-antagonists provide low chances of live birth in poor responders. The GnRH antagonist protocol is considered a suitable choice for PORs with comparable CLBR, shorter times to live birth, and similar financial expenditure compared to repeated MOS.

Evaluation of estrous synchronization protocols on ewe reproductive efficiency and profitability.

A 2-year experiment was conducted to determine the effect of a single injection of prostaglandin after initiation of the breeding season on ewe estrous synchronization. Rambouillet ewes (n = 101; Year 1 = 52; Year 2 = 49) assigned to one of three treatments: untreated (CON); 12-d CIDR insert (CIDR); or 1 injection of prostaglandin at d 2.5 (1 PG) after rams were placed with ewes. Rams were placed with ewes at the time of CIDR removal (d 0) and remained with ewes during a 35-d breeding season. Both the CIDR- (94%) and 1 PG (73.5%) treatment groups had a larger number (P ≤ 0.01) of ewes bred in the first 5 d of the breeding season compared to ewes of the control (33%) group. As expected, CIDR-treated ewes had a shorter time to mating, than 1 PG-treated ewes and ewes of the control group had a longer interval to mating than both CIDR- and 1 PG-treated ewes (P ≤ 0.01). The number of lambs born per ewe and kg of lamb weaned per ewe was not different (P ≥ 0.31) among treatment groups. Additionally, there was no difference (P =  0.78) in net profit per ewe among treatment groups. Based on these data, utilizing a single injection of PG 2.5 d after initiation of the breeding season resulted in similar pregnancy rates at d 5 of the breeding season when compared with CIDR-treated ewes indicating the potential utilization of the 1PG protocol in a confinement setting as a viable method for estrous synchronization.

Decision analysis about the cost-effectiveness of different in vitro fertilization-embryo transfer protocol under considering governments, hospitals, and patient.

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 ±â€Š9,917.55 ¥ 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 ±â€Š8,448.08 ¥ and the LBR was 31.05%. When patients were >35 years, the cost of a successful cycle was 83,297.92 ±â€Š10,918.05 ¥ and the LBR was 25.07%. The government reimbursement for a cycle ranged between 11,372.12 ±â€Š2,147.71 ¥ and 12,753.67 ±â€Š1,905.02 ¥. 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.

Cost-effectiveness of elagolix versus leuprolide acetate for treating moderate-to-severe endometriosis pain in the USA.

AIM: To assess the cost-effectiveness of elagolix versus leuprolide acetate in women with moderate to severe endometriosis pain. METHODS: A Markov model was developed. The efficacy of leuprolide acetate was derived from statistical prediction models using elagolix trial data. Model inputs were extracted from Phase III clinical trials and published literature. RESULTS: Compared with leuprolide acetate, elagolix generated positive net monetary benefit (NMB) assuming a payer's willingness-to-pay threshold of US$100,000 per quality-adjusted life year over a 1-year time horizon: US$5660 for elagolix 150 mg and US$6443 for elagolix 200 mg. The 2-year NMBs were also positive. CONCLUSION: Elagolix was cost effective versus leuprolide acetate in the management of moderate to severe endometriosis pain over 1- and 2-year time horizons. Results were robust in sensitivity analyses.

Gonadotrophins versus clomiphene citrate with or without IUI in women with normogonadotropic anovulation and clomiphene failure: a cost-effectiveness analysis.

STUDY QUESTION: Are six cycles of ovulation induction with gonadotrophins more cost-effective than six cycles of ovulation induction with clomiphene citrate (CC) with or without IUI in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC? SUMMARY ANSWER: Both gonadotrophins and IUI are more expensive when compared with CC and intercourse, and gonadotrophins are more effective than CC. WHAT IS KNOWN ALREADY: In women with normogonadotropic anovulation who ovulate but do not conceive after six cycles with CC, medication is usually switched to gonadotrophins, with or without IUI. The cost-effectiveness of these changes in policy is unknown. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation of ovulation induction with gonadotrophins compared with CC with or without IUI in a two-by-two factorial multicentre randomized controlled trial in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC. Between December 2008 and December 2015 women were allocated to six cycles with gonadotrophins plus IUI, six cycles with gonadotrophins plus intercourse, six cycles with CC plus IUI or six cycles with CC plus intercourse. The primary outcome was conception leading to a live birth achieved within 8 months of randomization. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed a cost-effectiveness analysis on direct medical costs. We calculated the direct medical costs of ovulation induction with gonadotrophins versus CC and of IUI versus intercourse in six subsequent cycles. We included costs of medication, cycle monitoring, interventions, and pregnancy leading to live birth. Resource use was collected from the case report forms and unit costs were derived from various sources. We calculated incremental cost-effectiveness ratios (ICER) for gonadotrophins compared to CC and for IUI compared to intercourse. We used non-parametric bootstrap resampling to investigate the effect of uncertainty in our estimates. The analysis was performed according to the intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: We allocated 666 women in total to gonadotrophins and IUI (n = 166), gonadotrophins and intercourse (n = 165), CC and IUI (n = 163), or CC and intercourse (n = 172). Mean direct medical costs per woman receiving gonadotrophins or CC were €4495 versus €3006 (cost difference of €1475 (95% CI: €1457-€1493)). Live birth rates were 52% in women allocated to gonadotrophins and 41% in those allocated to CC (relative risk (RR) 1.24:95% CI: 1.05-1.46). The ICER was €15 258 (95% CI: €8721 to €63 654) per additional live birth with gonadotrophins. Mean direct medical costs per woman allocated to IUI or intercourse were €4497 versus €3005 (cost difference of €1510 (95% CI: €1492-€1529)). Live birth rates were 49% in women allocated to IUI and 43% in those allocated to intercourse (RR = 1.14:95% CI: 0.97-1.35). The ICER was €24 361 (95% CI: €-11 290 to €85 172) per additional live birth with IUI. LIMITATIONS, REASONS FOR CAUTION: We allowed participating hospitals to use their local protocols for ovulation induction and IUI, which may have led to variation in costs, but which increases generalizability. Indirect costs generated by transportation or productivity loss were not included. We did not evaluate letrozole, which is potentially more effective than CC. WIDER IMPLICATIONS OF THE FINDINGS: Gonadotrophins are more effective, but more expensive than CC, therefore, the use of gonadotrophins in women with normogonadotropic anovulation who have not conceived after six ovulatory CC cycles depends on society's willingness to pay for an additional child. In view of the uncertainty around the cost-effectiveness estimate of IUI, these data are not sufficient to make recommendations on the use of IUI in these women. In countries where ovulation induction regimens are reimbursed, policy makers and health care professionals may use our results in their guidelines. STUDY FUNDING/COMPETING INTEREST(S): This trial was funded by the Netherlands Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). The Eudract number for this trial is 2008-006171-73. The Sponsor's Protocol Code Number is P08-40. CBLA reports unrestricted grant support from Merck and Ferring. BWM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for Merck, ObsEva and Guerbet. TRIAL REGISTRATION NUMBER: NTR1449.

Cost-effectiveness of ovarian stimulation with gonadotrophin and clomiphene citrate in an intrauterine insemination programme for subfertile couples.

Ovarian stimulation with low-dose human menopausal gonadotrophin (HMG) is superior to clomiphene citrate in intrauterine insemination (IUI) cycles with respect to clinical pregnancy rate, but it is unclear whether HMG is also the more cost-effective option. The aim of this study was to compare the cost-effectiveness of ovarian stimulation with low-dose subcutaneously administred HMG (37.5-75 IU per day) to orally administred clomiphene citrate (50 mg/day from day 3-7) in an IUI programme for subfertile couples. A cost-effectiveness analysis was conducted using the results of a randomized trial, including 620 IUI cycles. The primary outcome was the incremental cost-effectiveness ratio (ICER) of using HMG versus clomiphene citrate. Results are presented from the healthcare payer perspective. The total cost per patient associated with one IUI treatment with HMG is €764, whereas it is €558 if clomiphene citrate is used, resulting in an incremental cost of €206 for HMG per treatment. The incremental clinical pregnancy rate of using HMG instead of clomiphene citrate, however, is also 5.7 percentage points higher, resulting in an ICER of HMG versus clomiphene citrate of €3615 per additional clinical pregnancy achieved. On average, HMG was found to be more cost-effective than clomiphene citrate.

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

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

Gonadotropin Therapy versus Laparoscopic Ovarian Drilling in Clomiphene Citrate-Resistant Polycystic Ovary Syndrome Patients: A Retrospective Cost-Effectiveness Analysis.

BACKGROUND: Gonadotropin therapy and laparoscopic ovarian drilling (LOD) are treatment options for ovulation induction (OI) in clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS) patients. The current evidence of the cost-effectiveness of both treatments is scarce, conflicting and performed from different health-economic perspectives. METHODS: A retrospective health-economic evaluation was performed from a societal perspective in which human menopausal gonadotropin (hMG) therapy (n = 43) was compared with LOD (n = 35), followed by OI with CC and/or hMG if spontaneous ovulation did not occur within 2 months. Data were collected until the patients were pregnant, with a time limit of 6 months after the onset of treatment. Outcomes were expressed as ongoing pregnancy rate and number of live-born children. RESULTS: The ongoing pregnancy rate was 21/35 (60%) after LOD and 30/43 (69.8%) after hMG treatment (relative risk 0.85, 95% CI 0.61-1.19). The societal cost per patient, up to an ongoing pregnancy, was significantly higher after LOD versus hMG treatment (adjusted mean difference EUR 1,073, 95% CI 180-1,967). CONCLUSION: This economic evaluation based on real-life data shows that the societal cost up to an ongoing pregnancy is less after hMG treatment when compared with LOD surgery in CC-resistant PCOS patients.

A retrospective evaluation of prognosis and cost-effectiveness of IVF in poor responders according to the Bologna criteria.

STUDY QUESTION: Do the Bologna criteria for poor responders successfully identify women with poor IVF outcome? SUMMARY ANSWER: The Bologna criteria effectively identify a population with a uniformly low chance of success. WHAT IS ALREADY KNOWN: Women undergoing IVF who respond poorly to ovarian hyper-stimulation have a low chance of success. Even if improving IVF outcome in this population represents a main priority, the lack of a unique definition of the condition has hampered research in this area. To overcome this impediment, a recent expert meeting in Bologna proposed a new definition of poor responders ('Bologna criteria'). However, data supporting the relevance of this definition in clinical practice are scanty. STUDY DESIGN, SIZE, DURATION: Retrospective study of women undergoing IVF-ICSI between January 2010 and December 2012 in two independent infertility units. Women could be included if they fulfilled the definition of poor ovarian response (POR) according to Bologna criteria prior to initiation of the cycle. Women were included only for one cycle. The main outcome was the live birth rate per started cycle. The perspective of the cost analysis was the one of the health provider. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three-hundred sixty-two women from two independent Infertility Units were selected. A binomial distribution model was used to calculate the 95% CI of the rate of success. Characteristics of women who did and did not obtain a live birth were compared. A logistic regression model was used to adjust for confounders. The economic analysis included costs for pharmacological compounds and for the IVF procedure. The benefits were estimated on quality-adjusted life years (QALY). To develop the model, we used the local life-expectancy tables, we applied a 3% discount of life years gained and we used a 0.07 improvement in quality of life associated with parenthood. Sensitivity analyses were performed varying the improvement of the quality of life and including/excluding the male partner. The reference values for cost-effectiveness were the Italian and the local (Lombardy) gross domestic product (GDP) pro capita per year in the studied period and the upper and lower limits suggested by NICE. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 23 women had a live birth (6%, 95% CI: 4-9%), in line with the previous evidence. This proportion did not significantly differ in the different subgroups of poor responders. Positive predictive factors of success were previous deliveries (adjusted OR = 3.0, 95% CI: 1.1-8.7, P = 0.039) and previous chemotherapy (adjusted OR = 13.9, 95% CI: 2.5-77.2, P = 0.003). Age, serum AMH, serum FSH and antral follicle count were not significantly associated with live birth. The total cost per live birth was 87 748 Euros, corresponding to 49 919 Euros per QALY. This is above both the limits suggested by NICE for cost-effectiveness and the Italian and local GDP pro capita. Sensitivity analyses mainly support the robustness of the conclusion. LIMITATIONS, REASONS FOR CAUTION: We lack a control group and we cannot thus exclude that an alternative definition of poor responders may be equally if not more valid. Moreover, independent validations are warranted prior to concluding that IVF is not cost-effective. Women should thus not be denied treatment based on our findings. Noteworthy, there is also not yet a consensus on the most appropriate economic model to be used. WIDER IMPLICATIONS OF THE FINDINGS: We recommend the use of the Bologna criteria when designing future studies on poor responders. Large multi-centred international studies are now required to draw definite conclusions on the economic profile of IVF in this situation.

Cost-effectiveness analysis comparing continuation of assisted reproductive technology with conversion to intrauterine insemination in patients with low follicle numbers.

OBJECTIVE: To compare the cost effectiveness of proceeding with oocyte retrieval vs. converting to intrauterine insemination (IUI) in patients with ≤4 mature follicles during assisted reproductive technology (ART) cycles. DESIGN: Probabilistic decision analysis. The cost effectiveness of completing ART cycles in poor responders was compared to that for converting the cycles to IUI. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Cost-effectiveness analysis. MAIN OUTCOME MEASURE(S): Cost effectiveness, which was defined as the average direct medical costs per ongoing pregnancy. RESULT(S): In patients with 1-3 mature follicles, completing ART was more cost effective if the cost of a single ART cycle was between $10,000 and $25,000. For patients with 4 mature follicles, if an ART cycle cost<$18,025, it was more cost effective to continue with oocyte retrieval than to convert to IUI. CONCLUSION(S): In patients with ≤4 mature follicles following ovarian stimulation in ART cycles, it was on average more cost effective to proceed with oocyte retrieval rather than convert to IUI. However, important factors, such as age, prior ART failures, other fertility factors, and medications used in each individual case need to be considered before this analysis model can be adapted by individual practices.

Use of fertility treatment modalities in a large United States cohort of professional women.

OBJECTIVE: To evaluate the use of fertility treatments among a large cohort of women in the United States. DESIGN: Cohort study. SETTING: Nurses' Health Study II. PATIENT(S): Ten thousand thirty-six women who reported having used fertility treatment on biennial questionnaires from 1993-2009. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Data on patterns of treatment modality were collected via self-report from validated mailed questionnaires. Information on clomiphene, gonadotropin injections alone, and gonadotropin injections as part of intrauterine insemination (IUI) and in vitro fertilization (IVF) was queried. RESULT(S): Most women who reported fertility treatment used clomiphene (94%), with a large majority reporting clomiphene as their only form of treatment (73%). Of women who reported treatment more advanced than clomiphene, 13% had used gonadotropin injections alone, 11% IUI treatment, and 11% IVF. Several subgroups were more likely to use multiple treatment modalities and to initiate treatment with gonadotropins rather than clomiphene, including women living in states with insurance coverage of fertility procedures, with higher household income, younger in age, who remained nulliparous at the study close, and treated after 2000. CONCLUSION(S): Results should be interpreted cautiously, but to our knowledge, this represents the first study of fertility treatment patterns in the United States and could inform public health planning.

Cost-effectiveness of treatment strategies in women with PCOS who do not conceive after six cycles of clomiphene citrate.

This study evaluated the cost-effectiveness of treatments for women with polycystic ovary syndrome (PCOS) who ovulate on clomiphene citrate but do not conceive after six cycles. A decision-analytic framework was developed for six scenarios: (1) three cycles of IVF; (2) continuation of clomiphene citrate for six cycles, followed by three cycles of IVF in case of no birth; (3) six cycles of gonadotrophins and three cycles of IVF; (4) 12 cycles of gonadotrophins and three cycles of IVF; (5) continuation of clomiphene citrate for six cycles, six cycles of gonadotrophins and three cycles of IVF; (6) continuation of clomiphene citrate for six cycles, 12 cycles of gonadotrophins and three cycles of IVF. Two-year cumulative birth rates were 58%, 74%, 89%, 97%, 93% and 98% and costs per couple were € 9518, € 7530, € 9711, € 9764, € 7651 and € 7684 for scenarios 1-6, respectively. Scenario 2 was the lowest cost option. The extra cost for at least one live birth in scenario 5 was € 629 and in scenario 6 € 630. In these subjects, continuation of treatment for six cycles of clomiphene citrate, 6 or 12 cycles of gonadotrophins and IVF is potentially cost-effective. These results should be confirmed in a randomized clinical trial.

Low dose of rFSH [100 IU] in controlled ovarian hyperstimulation response: a pilot study.

BACKGROUND: The initial dose of recombinant Follicle Stimulating Hormone [rFSH] to be used in assisted reproduction treatment depends on several factors, mainly the cause of the infertility and the patient's age. For young patients [≤35 years] usually an initial dose of around 150 IU of rFSH is recommended, but there are no studies proving that this should actually be the standard initial dose. We aimed to report the experience of a low-cost Human Reproduction Center where a dose of 100 IU of rFSH was used for controlled ovarian hyperstimulation [COH]. FINDINGS: An observational prospective study was performed on 212 women aged ≤38 years old that underwent high-complexity assisted reproduction treatments. The patients' infertility was mainly caused by tuboperitoneal, idiopathic or male factors. Controlled ovarian stimulation was performed using 100 IU of rFSH. Regarding the COH, 53.8% of the patients presented a satisfactory response, 25.9% low response, 14.2% hyper-response, and 6.1% developed ovarian hyperstimulation syndrome. Of the 55 patients with poor response, 20 started a new cycle with an initial dose of 200 IU of rFSH; 65% showed a satisfactory response, 10% a poor response, 20% a hyper-response, and 5% developed OHSS. CONCLUSION: The initial dose of 100 IU of rFSH was considered adequate for controlled ovarian hyperstimulation, meeting the aim to reduce the costs of the assisted reproduction treatment.

Sequential clomiphene citrate/hMG versus hMG for ovulation induction in clomiphene citrate-resistant women.

OBJECTIVE: This study was designed to compare sequential clomiphene citrate/hMG regimen to hMG regimen for ovulation induction in clomiphene citrate-resistant women. STUDY DESIGN: A comparative prospective study. PATIENTS AND METHODS: Ninety infertile women were randomized to receive either sequential CC/hMG regimen (45 women) or low-dose step-up protocol of hMG (45 women). All participants had received at least six consecutive cycles of clomiphene citrate for ovulation induction within the last year before inclusion in this study, but they did not conceive. The CC/hMG regimen group received clomiphene citrate 100 mg/day for 5 days, followed by hMG 75 IU for 4 days. The hMG group received low-dose step-up protocol for 10-14 days. To detect the number and size of the follicles, TVS was done on cycle day 8 and repeated daily or every other day according to follicular development. When one to three follicles reached a diameter ≥18 mm, hCG injection was scheduled. Before hCG injection, the E2 level and endometrial thickness were evaluated. ß-hCG levels were measured on cycle day 22. RESULTS: There was no significant difference between the two studied groups regarding the demographic data, sperm parameters, and day 3 FSH, LH and estradiol. Also, there was no significant difference between the two studied groups regarding endometrial thickness, number of mature follicles, peak of E2 before hCG injection and number of cases that developed ovarian cyst or OHSS. The dose of gonadotropins used was significantly low in the CC/hMG group compared to the hMG group (295.2 ± 75.5 vs. 625.3 ± 65.0, respectively), and the pregnancy rate was significantly high in the CC/hMG group compared to the hMG group [12 (26.7 %) vs. 3 (6.7 %), respectively, p < 0.05]. CONCLUSION: The sequential CC/hMG regimen is as effective as hMG regimen for ovulation induction, produces satisfactory pregnancy results and reduces the treatment cost.

Balancing selected medication costs with total number of daily injections: a preference analysis of GnRH-agonist and antagonist protocols by IVF patients.

BACKGROUND: During in vitro fertilization (IVF), fertility patients are expected to self-administer many injections as part of this treatment. While newer medications have been developed to substantially reduce the number of these injections, such agents are typically much more expensive. Considering these differences in both cost and number of injections, this study compared patient preferences between GnRH-agonist and GnRH-antagonist based protocols in IVF. METHODS: Data were collected by voluntary, anonymous questionnaire at first consultation appointment. Patient opinion concerning total number of s.c. injections as a function of non-reimbursed patient cost associated with GnRH-agonist [A] and GnRH-antagonist [B] protocols in IVF was studied. RESULTS: Completed questionnaires (n = 71) revealed a mean +/- SD patient age of 34 +/- 4.1 yrs. Most (83.1%) had no prior IVF experience; 2.8% reported another medical condition requiring self-administration of subcutaneous medication(s). When out-of-pocket cost for [A] and [B] were identical, preference for [B] was registered by 50.7% patients. The tendency to favor protocol [B] was weaker among patients with a health occupation. Estimated patient costs for [A] and [B] were $259.82 +/- 11.75 and $654.55 +/- 106.34, respectively (p < 0.005). Measured patient preference for [B] diminished as the cost difference increased. CONCLUSIONS: This investigation found consistently higher non-reimbursed direct medication costs for GnRH-antagonist IVF vs. GnRH-agonist IVF protocols. A conditional preference to minimize downregulation (using GnRH-antagonist) was noted among some, but not all, IVF patient sub-groups. Compared to IVF patients with a health occupation, the preference for GnRH-antagonist was weaker than for other patients. While reducing total number of injections by using GnRH-antagonist is a desirable goal, it appears this advantage is not perceived equally by all IVF patients and its utility is likely discounted heavily by patients when nonreimbursed medication costs reach a critical level.

A case-control pilot study of low-intensity IVF in good-prognosis patients.

Low-intensity IVF (LI-IVF) is rapidly gaining in popularity. Yet studies comparing LI-IVF to standard IVF are lacking. This is a case-control pilot study, reporting on 14 first LI-IVF and 14 standard IVF cycles in women with normal age-specific ovarian reserve under age 38, matched for age, laboratory environment, staff and time of cycle. LI-IVF cycles underwent mild ovarian stimulation, utilizing clomiphene citrate, augmented by low-dose gonadotrophin stimulation. Control patients underwent routine ovarian stimulation. LI-IVF and regular IVF patients were similar in age, body mass index, FSH and anti-Müllerian hormone. Standard IVF utilized more gonadotrophins (P<0.001), yielded more oocytes (P<0.001) and cryopreserved more embryos (P<0.001). With similar embryo numbers transferred, after ethnicity adjustments, standard IVF demonstrated better odds for pregnancy (OR 7.07; P=0.046) and higher cumulative pregnancy rates (63.3% versus 21.4%; OR 6.6; P=0.02). Adjustments for age, ethnicity and diagnosis maintained significance but oocyte adjustment did not. Cost assessments failed to reveal differences between LI-IVF and standard IVF. In this small study, LI-IVF reduced pregnancy chances without demonstrating cost advantages, raising questions about its utility. In the absence of established clinical and/or economic foundations, LI-IVF should be considered an experimental procedure. Low-intensity IVF (LI-IVF) is increasingly propagated as an alternative to standard IVF. LI-IVF has, however, never been properly assessed in comparison to standard IVF. Such a comparison is presented in the format of a small pilot study, matching LI-IVF cycles with regular IVF cycles and comparing outcomes as well as costs. The study suggests that LI-IVF, at least in this setting, is clinically inferior and economically at best similar to standard IVF. LI-IVF should, therefore, as of this point not be offered as routine IVF treatment but only as an experimental procedure.