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

Array comparative genomic hybridization screening in IVF significantly reduces number of embryos available for cryopreservation

Objective During IVF, non-transferred embryos are usually selected for cryopreservation on the basis of morphological criteria. This investigation evaluated an application for array comparative genomic hybridization (aCGH) in assessment of surplus embryos prior to cryopreservation. Methods First-time IVF patients undergoing elective single embryo transfer and having at least one extra non-transferred embryo suitable for cryopreservation were offered enrollment in the study. Patients were randomized into two groups: Patients in group A (n=55) had embryos assessed first by morphology and then by aCGH, performed on cells obtained from trophectoderm biopsy on post-fertilization day 5. Only euploid embryos were designated for cryopreservation. Patients in group B (n=48) had embryos assessed by morphology alone, with only good morphology embryos considered suitable for cryopreservation. Results Among biopsied embryos in group A (n=425), euploidy was confirmed in 226 (53.1%). After fresh single embryo transfer, 64 (28.3%) surplus euploid embryos were cryopreserved for 51 patients (92.7%). In group B, 389 good morphology blastocysts were identified and a single top quality blastocyst was selected for fresh transfer. All group B patients (48/48) had at least one blastocyst remaining for cryopreservation. A total of 157 (40.4%) blastocysts were frozen in this group, a significantly larger proportion than was cryopreserved in group A (p=0.017, by chi-squared analysis). Conclusion While aCGH and subsequent frozen embryo transfer are currently used to screen embryos, this is the first investigation to quantify the impact of aCGH specifically on embryo cryopreservation. Incorporation of aCGH screening significantly reduced the total number of cryopreserved blastocysts compared to when suitability for freezing was determined by morphology only. IVF patients should be counseled that the benefits of aCGH screening will likely come at the cost of sharply limiting the number of surplus embryos available for cryopreservation

Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study

Background Single embryo transfer (SET) remains underutilized as a strategy to reduce multiple gestation risk in IVF, and its overall lower pregnancy rate underscores the need for improved techniques to select one embryo for fresh transfer. This study explored use of comprehensive chromosomal screening by array CGH (aCGH) to provide this advantage and improve pregnancy rate from SET. Methods First-time IVF patients with a good prognosis (age <35, no prior miscarriage) and normal karyotype seeking elective SET were prospectively randomized into two groups: In Group A, embryos were selected on the basis of morphology and comprehensive chromosomal screening via aCGH (from d5 trophectoderm biopsy) while Group B embryos were assessed by morphology only. All patients had a single fresh blastocyst transferred on d6. Laboratory parameters and clinical pregnancy rates were compared between the two groups. Results For patients in Group A (n=55), 425 blastocysts were biopsied and analyzed via aCGH (7.7 blastocysts/patient). Aneuploidy was detected in 191/425 (44.9%) of blastocysts in this group. For patients in Group B (n=48), 389 blastocysts were microscopically examined (8.1 blastocysts/patient). Clinical pregnancy rate was significantly higher in the morphology+aCGH group compared to the morphology-only group (70.9 and 45.8%, respectively; p=0.017); ongoing pregnancy rate for Groups A and B were 69.1 vs. 41.7%, respectively (p=0.009). There were no twin pregnancies. Conclusion Although aCGH followed by frozen embryo transfer has been used to screen at risk embryos (e.g., known parental chromosomal translocation or history of recurrent pregnancy loss), this is the first description of aCGH fully integrated with a clinical IVF program to select single blastocysts for fresh SET in good prognosis patients. The observed aneuploidy rate (44.9%) among biopsied blastocysts highlights the inherent imprecision of SET when conventional morphology is used alone. Embryos randomized to the aCGH group implanted with greater efficiency, resulted in clinical pregnancy more often, and yielded a lower miscarriage rate than those selected without aCGH. Additional studies are needed to verify our pilot data and confirm a role for on-site, rapid aCGH for IVF patients contemplating fresh SET

Conservative Management of Type 2 Endoleaks is not Associated with Increased Risk of Aneurysm Rupture

AbstractObjectiveEndovascular repair (EVAR) of abdominal aortic aneurysms (AAAs) has led to a reduction in the perioperative mortality when compared with open repair. However, re-intervention for complications, such as endoleak, may be required in up to 20% of the cases. Controversy exists over the management of Type 2 endoleaks. This study examined the outcomes of patients with Type 2 endoleaks treated conservatively to inform the ongoing management debate.MethodsAll patients with a confirmed Type 2 endoleak after EVAR for an infrarenal AAA were included in the study. Data regarding device details, endoleak and time point, aneurysm sac growth, intervention and outcome were collected retrospectively from case notes and the vascular research database.ResultsForty-one Type 2 endoleaks were seen in 369 EVARs performed for infrarenal AAA between March 1994 and June 2006. Twenty-five were isolated Type 2 endoleaks and 16 occurred in conjunction with other endoleaks. Of the 25 isolated Type 2 endoleaks, 18 (72%) patients demonstrated no increase in sac size, six (24%) patients showed an enlargement of the sac and one patient was lost to follow-up. Only one patient underwent intervention for an isolated Type 2 endoleak. After a mean follow-up period of 4 years, approximately half of the patients (48%) remain under observation (with an enlarging or stable sac), whilst the others (48%) have spontaneously sealed. Only five patients under surveillance (20%) have an enlarging sac. There were no ruptured aneurysms or aneurysm-related deaths and no patients required conversion to open repair.ConclusionsIn this study, a policy of regular surveillance for Type 2 endoleaks was not associated with any adverse events. We therefore advocate the conservative approach for Type 2 endoleaks

Bivariate analysis of basal serum anti-Müllerian hormone measurements and human blastocyst development after IVF

Background To report on relationships among baseline serum anti-Müllerian hormone (AMH) measurements, blastocyst development and other selected embryology parameters observed in non-donor oocyte IVF cycles. Methods Pre-treatment AMH was measured in patients undergoing IVF (n = 79) and retrospectively correlated to in vitro embryo development noted during culture. Results Mean (+/- SD) age for study patients in this study group was 36.3 ± 4.0 (range = 28-45) yrs, and mean (+/- SD) terminal serum estradiol during IVF was 5929 +/- 4056 pmol/l. A moderate positive correlation (0.49; 95% CI 0.31 to 0.65) was noted between basal serum AMH and number of MII oocytes retrieved. Similarly, a moderate positive correlation (0.44) was observed between serum AMH and number of early cleavage-stage embryos (95% CI 0.24 to 0.61), suggesting a relationship between serum AMH and embryo development in IVF. Of note, serum AMH levels at baseline were significantly different for patients who did and did not undergo blastocyst transfer (15.6 vs. 10.9 pmol/l; p = 0.029). Conclusions While serum AMH has found increasing application as a predictor of ovarian reserve for patients prior to IVF, its roles to estimate in vitro embryo morphology and potential to advance to blastocyst stage have not been extensively investigated. These data suggest that baseline serum AMH determinations can help forecast blastocyst developmental during IVF. Serum AMH measured before treatment may assist patients, clinicians and embryologists as scheduling of embryo transfer is outlined. Additional studies are needed to confirm these correlations and to better define the role of baseline serum AMH level in the prediction of blastocyst formation

Level Sets of the Takagi Function: Local Level Sets

The Takagi function \tau : [0, 1] \to [0, 1] is a continuous non-differentiable function constructed by Takagi in 1903. The level sets L(y) = {x : \tau(x) = y} of the Takagi function \tau(x) are studied by introducing a notion of local level set into which level sets are partitioned. Local level sets are simple to analyze, reducing questions to understanding the relation of level sets to local level sets, which is more complicated. It is known that for a "generic" full Lebesgue measure set of ordinates y, the level sets are finite sets. Here it is shown for a "generic" full Lebesgue measure set of abscissas x, the level set L(\tau(x)) is uncountable. An interesting singular monotone function is constructed, associated to local level sets, and is used to show the expected number of local level sets at a random level y is exactly 3/2.Comment: 32 pages, 2 figures, 1 table. Latest version has updated equation numbering. The final publication will soon be available at springerlink.co

Isolation and Monitoring of the Endohedral Metallofullerenes Y@C82 and Sc3@C82:On-Line Chromatographic Separation with EPR Detection

The direct coupling of high-performance liquid chromatography (HPLC) with on-line electron paramagnetic resonance (EPR) detection is demonstrated for monitoring separations of endohedral metallofullerenes (M@C2n). The HPLC-EPR approach readily permits detection of the paramagnetic species, such as Y@C82 and Sc3@C82, in the presence of the dominant empty-cage fullerenes (C60, C70) and diamagnetic metallofullerenes (e.g., M2@C2n). The results indicate that on-line EPR provides a noninvasive, selective detector for HPLC metallofullerene separations that is readily adaptable to air-sensitive and/or labile compounds. Specifically, the “EPR-active” metallofullerenes, Y@C82 and Sc3@C82, are selectively monitored on-line for an initial separation of the metallofullerene fraction from the dominant empty-cage fullerenes utilizing a combination of polystyrene columns. This preparative “cleanup” procedure is followed by HPLC-EPR separation and monitoring of Y@C82 and Sc3@C82 species using a selective tripodal π-acidic-phase column (Trident-Tri-DNP) for the final stages of isolation