To determine if preimplantation genetic testing for aneuploidy (PGT-A) is cost-effective for patients undergoing in vitro fertilization (IVF).
Decision analytic model comparing costs and clinical ...outcomes of two strategies: IVF with and without PGT-A.
Genetics laboratory.
Women ≤ 42 years of age undergoing IVF.
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.
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.
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.
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.
La fecundación in vitro (FIV) con test genético preimplantacional para aneuploidías es coste-efectivo, acorta el tiempo de tratamiento y reduce el riesgo de transferencia embrionaria fallida y aborto clínico en pacientes seleccionadas comparado con FIV solo
Determinar si el test genético preimplantacional para aneuploidías (TGP-A) es coste-efectivo para pacientes que se someten a fecundación in vitro (FIV).
Modelo analítico de decisión comparando costes y resultados clínicos de dos estrategias: FIV con y sin TGP-A.
Laboratorio de genética.
Mujeres ≤ 42 años de edad que se someten a FIV.
Modelo analítico de decisión aplicado a la población de pacientes antedicha utilizando una combinación de datos clínicos reales y suposiciones de la literatura con respecto a los resultados de FIV con y sin TGP-A.
El resultado primario fue el coste acumulado relacionado con FIV para lograr un nacido vivo o agotar la cohorte embrionaria de una única captación ovocitaria. Los resultados secundarios fueron tiempo desde la captación ovocitaria hasta la transferencia embrionaria que resultara en un nacido vivo o terminación del tratamiento, tasa acumulada de nacido vivo, transferencias embrionarias fallidas y pérdidas clínicas.
8998 pacientes de 74 centros de FIV fueron incluídas. Para pacientes con más de un embrión, el diferencial de costes favoreció el uso de TGP-A, desde $931-2411 y dependiendo del número de embriones estudiados. Como se esperaba, la tasa acumulada de nacido vivo fue equivalente en ambos grupos una vez que todos los embriones fueron agotados. Sin embargo, el TGP-A redujo el tiempo en tratamiento hasta cuatro meses. Además, las pacientes sometidas a TGP-A experimentaron menos transferencias embrionarias fallidas y abortos clínicos.
Para pacientes con más de un embrión, FIV con TGP-A reduce los costes sanitarios, acorta el tiempo de tratamiento y reduce el riesgo de transferencia embrionaria fallida y aborto clínico comparado con FIV solo.
Chromosomal rearrangements have long been known to significantly impact fertility and miscarriage risk. Advancements in molecular diagnostics are challenging contemporary clinicians and patients in ...accurately characterizing the reproductive risk of a given abnormality. Initial attempts at preimplantation genetic diagnosis were limited by the inability to simultaneously evaluate aneuploidy and missed up to 70% of aneuploidy in chromosomes unrelated to the rearrangement. Contemporary platforms are more accurate and less susceptible to technical errors. These techniques also offer the ability to improve outcomes through diagnosis of uniparental disomy and may soon be able to consistently distinguish between normal and balanced translocation karyotypes. Although an accurate projection of the anticipated number of unbalanced embryos is not possible at present, confirmation of normal/balanced status results in high pregnancy rates (PRs) and diagnostic accuracy.
There has been much debate regarding the optimal oxygen tension in clinical embryo culture. The majority of the literature to date has compared 5% oxygen to atmospheric levels (20–21%). While the ...majority of modern IVF labs have accepted the superiority of 5% oxygen tension, a new debate has emerged regarding whether a further reduction after day 3 of development represents the most physiologic system. This new avenue of research is based on the premise that oxygen tension is in fact lower in the uterus than in the oviduct and that the embryo crosses the uterotubal junction sometime on day 3. While data are currently limited, recent experience with ultra-low oxygen (2%) after day 3 of development suggests that the optimal oxygen tension in embryo culture may depend on the stage of development. This review article will consider the current state of the literature and discuss ongoing efforts at studying ultra-low oxygen tension in extended culture.
ABSTRACT Despite the lack of a shear-rich tachocline region, low-mass fully convective (FC) stars are capable of generating strong magnetic fields, indicating that a dynamo mechanism fundamentally ...different from the solar dynamo is at work in these objects. We present a self-consistent three-dimensional model of magnetic field generation in low-mass FC stars. The model utilizes the anelastic magnetohydrodynamic equations to simulate compressible convection in a rotating sphere. A distributed dynamo working in the model spontaneously produces a dipole-dominated surface magnetic field of the observed strength. The interaction of this field with the turbulent convection in outer layers shreds it, producing small-scale fields that carry most of the magnetic flux. The Zeeman-Doppler-Imaging technique applied to synthetic spectropolarimetric data based on our model recovers most of the large-scale field. Our model simultaneously reproduces the morphology and magnitude of the large-scale field as well as the magnitude of the small-scale field observed on low-mass FC stars.
Abstract
STUDY QUESTION
What is the predictive value of trophectoderm mitochondrial DNA (mtDNA) quantity for blastocyst reproductive potential?
SUMMARY ANSWER
This study demonstrates that, within a ...given cohort, mtDNA quantitation does not distinguish between embryos that implant and embryos that do not implant after double embryo transfer (DET).
WHAT IS ALREADY KNOWN
An association between implantation failure and increased quantities of mtDNA has been observed in two studies but not in a third.
STUDY DESIGN, SIZE AND DURATION
A total of 187 patients (nine who received donor oocytes) with DET of one male and one female euploid blastocyst were included in this retrospective study, with 69 singleton deliveries providing the primary dataset to evaluate the predictive value of mtDNA for reproductive potential between January 2010 and July 2016.
PARTICIPANTS/MATERIALS, SETTING AND METHOD
MtDNA was quantified in cell lines to validate the quantitative PCR assay on limited quantities of starting material and then applied to 374 blastocyst biopsies. Pregnancies resulting in a singleton outcome were analyzed and newborn gender was utilized as a means to identify the implanted embryo. MtDNA quantity was then compared between implanted and non-implanted embryos in order to define the predictive value of mtDNA content for reproductive potential in this subset of patients.
MAIN RESULTS AND THE ROLE OF CHANCE
An initial comparison of mtDNA levels between all successful and unsuccessful embryos revealed no significant differences. In order to control for patient-specific variables, gender was subsequently used to identify the implanted embryo in DETs resulting in a singleton (n = 69). No systematic difference in relative mtDNA quantity was detected between implanted and non-implanted embryos.
LIMITATIONS, REASONS FOR CAUTION
This study was conducted at a single center and did not evaluate the entire cohort of embryos from each patient to evaluate cohort specific variation in mtDNA quantity. Although the largest of its kind so far, the sample size of DETs leading to a singleton was relatively small.
WIDER IMPLICATIONS OF THE FINDINGS
These data highlight the importance of control over patient-specific variables when evaluating candidate biomarkers of reproductive potential. All current available data suggest that mtDNA quantification needs further study before its clinical use to augment embryo selection.
STUDY FUNDING/COMPETING INTERESTS
The authors have no potential conflict of interest to declare. No external funding was obtained for this study.
TRIAL REGISTRATION NUMBER
Not applicable.
Objective To evaluate the association between relative DNA content of the trophectoderm biopsy and pregnancy outcomes. Design Retrospective cohort study. Setting Academic-affiliated private practice. ...Patient(s) This study included patients undergoing their first single embryo transfer after trophectoderm biopsy and comprehensive chromosome screening (CCS) at a single center between January 2010 and February 2014. Intervention(s) In phase 1 of the study, a standard curve was developed to estimate the relative DNA content of trophectoderm biopsies. Phase 2 of the study examined reproductive outcomes in patients undergoing single embryo transfer after trophectoderm biopsy and CCS. Samples were divided into quartiles according to their relative DNA content, and clinical outcomes were compared. Main Outcome Measure(s) Chemical pregnancy rate, clinical implantation rate, ongoing pregnancy rate, live birth rate. Result(s) The quartile of highest relative DNA content had a significantly lower live birth rate when compared with the other three quartiles (relative risk 0.84, 95% confidence interval 0.75–0.95). There was no difference between the quartiles regarding age, body mass index, ovarian response, or endometrial thickness. Among those patients who had a live birth, there was no difference in hCG levels, gestational age at delivery, or birth weight with respect to biopsy DNA content. Conclusion(s) Trophectoderm biopsies with the highest relative DNA content are associated with lower live birth rates after single embryo transfer. Possible explanations for this phenomenon include diminished accuracy of the euploid diagnosis vs. a mechanical impact of the biopsy. Regardless of the cause, the outcomes emphasize the importance of obtaining appropriately sized trophectoderm biopsies for CCS.
This is a retrospective cohort study comparing blastocyst transfer outcomes following intracytoplasmic sperm injection utilizing epididymal versus testicular sperm for men with obstructive ...azoospermia. All cases at a single center between 2012 and 2016 were included. Operative approach was selected at the surgeon's discretion and included microepididymal sperm aspiration or testicular sperm extraction. Blastocyst culture was exclusively utilized prior to transfer. The primary outcome was live birth rate. Secondary outcomes included fertilization rate, blastulation rate, euploidy rate, and implantation rate. A mixed effects model was performed. Seventy-six microepididymal sperm aspiration cases and 93 testicular sperm extraction cases were analyzed. The live birth rate was equivalent (48.6% vs 50.5%, P = 0.77). However, on mixed effects model, epididymal sperm resulted in a greater likelihood of fertilization (adjusted OR: 1.37, 95% CI: 1.05-1.81, P = 0.02) and produced a higher blastulation rate (adjusted OR: 1.41, 95% CI: 1.1-1.85, P = 0.01). As a result, the epididymal sperm group had more supernumerary blastocysts available (4.3 vs 3, P < 0.05). The euploidy rate was no different. Pregnancy rates were no different through the first transfer cycle. However, intracytoplasmic sperm injection following microepididymal sperm aspiration resulted in a greater number of usable blastocysts per patient. Thus, the true benefit of epididymal sperm may only be demonstrated via a comparison of cumulative pregnancy rates after multiple transfers from one cohort.
Objective To compare maternal uterine natural killer cell immunoglobulin receptor (KIR) genotype and haplotype frequencies between patients whose euploid single-embryo transfer resulted in pregnancy ...loss and those that resulted in delivery and to determine if the risk of pregnancy loss was affected by the HLA-C genotype content in the embryo. Design Retrospective cohort. Setting Academic research center. Patient(s) Autologous fresh IVF cycles resulting in positive serum β-hCG during 2009–2014. Intervention(s) None. Main outcome measure(s) 1) Relative risk of pregnancy loss according to maternal KIR genotypes and haplotypes. 2) Comparison of pregnancy loss rates within each KIR haplotype according to HLA-C ligand present in trophectoderm biopsy samples. Result(s) A total of 668 euploid single-embryo transfers with stored maternal DNA and available preamplification DNA from prior trophectoderm biopsy samples were studied. KIR2DS1, KIR3DS1, and KIR2DS5 were more common in patients who experienced pregnancy loss. Carriers of KIR A haplotype exhibited a decreased risk of pregnancy loss compared with KIR B haplotype carriers. However, among KIR A haplotype carriers, the risk of loss was significantly influenced by whether the transferred embryo carried a C1 allele versus no C1 alleles. Conclusion(s) KIR A haplotype carriers experienced fewer pregnancy losses than KIR B haplotype carriers after euploid single-embryo transfer. However, this risk was modified by HLA-C alleles present in the embryo. High-risk combinations (KIR A/homozygous C2 and KIR B/homozygous C1) resulted in a 51% increased risk of loss over all other combinations.
The majority of offspring born following assisted reproductive technology (ART) achieve equivalent development milestones and demonstrate comparable health as spontaneously conceived children. Yet, ...multiple studies have suggested offspring conceived with ART have slightly increased risk of metabolic derangements, cardiovascular disease, and malignancy. However, the associations observed in these studies often inadequately control for a variety of confounding variables, such as multiple gestation, premature birth, and low birth weight. Furthermore, many studies fail to account for the increased risk of many of these pathologies in the offspring of subfertile women in general. Lastly, the absolute risk of most of the ailments studied is extremely low. In nearly all examples, the number of women who would need to be treated to observe one additional diagnosis is substantially high. When compared with the number of couples who would have remained childless due to severe male factor infertility or would have been exposed to the risk of passing on a severe monogenic disorder, the general increased risks to ART-exposed children is very small.
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