Objective To determine the relationship between the age of the female partner and the prevalence and nature of human embryonic aneuploidy. Design Retrospective. Setting Academic. Patient(s) ...Trophectoderm biopsies. Intervention(s) Comprehensive chromosomal screening performed on patients with blastocysts available for biopsy. Main Outcome Measure(s) Evaluation of the impact of maternal age on the prevalence of aneuploidy, the probability of having no euploid embryos within a cohort, the complexity of aneuploidy as gauged by the number of aneuploid chromosomes, and the trisomy/monosomy ratio. Result(s) Aneuploidy increased predictably after 26 years of age. A slightly increased prevalence was noted at younger ages, with >40% aneuploidy in women 23 years and under. The no euploid embryo rate was lowest (2% to 6%) in women aged 26 to 37, was 33% at age 42, and was 53% at age 44. Among the biopsies with aneuploidy, 64% involved a single chromosome, 20% two chromosomes, and 16% three chromosomes, with the proportion of more complex aneuploidy increasing with age. Finally, the trisomy/monosomy ratio approximated 1 and increased minimally with age. Conclusion(s) The lowest risk for embryonic aneuploidy was between ages 26 and 30. Both younger and older age groups had higher rates of aneuploidy and an increased risk for more complex aneuploidies. The overall risk did not measurably change after age 43. Trisomies and monosomies are equally prevalent.
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.
Objective We sought to characterize the relationship between serum 25-hydroxy vitamin D (25-OH D) levels and implantation and clinical pregnancy rates in women who undergo a euploid blastocyst embryo ...transfer. Study Design This retrospective cohort study, conducted in an academic setting, included 529 cycles in which comprehensive chromosome screening was performed as part of routine infertility care with an autologous transfer of 1 or 2 euploid blastocysts. After excluding repeat cycles there were 517 unique cycles representing 517 women for evaluation. Vitamin D levels from serum samples obtained on the day of ovulation trigger in the fresh in vitro fertilization cycle were analyzed. The primary outcome was ongoing pregnancy rate as defined by sonographic presence of fetal heart rate at >8 weeks’ gestation. Results For the population as a whole, serum vitamin D ranges and pregnancy outcomes did not correlate. Furthermore, pregnancy rates did not differ when comparing women in different strata of vitamin D levels (<20, 20-29.9, and ≥30 ng/mL). No meaningful breakpoint for vitamin D levels and ongoing pregnancy rate was identified using receiver operating characteristic analysis with the resultant line possessing an area under the curve of 0.502. Multivariate logistic regression controlling for age, transfer order, race, season, and body mass index did not yield a different result. The study was powered to detect an 18% difference in ongoing pregnancy rates between patients grouped by the 3 vitamin D ranges. Conclusion In women undergoing euploid embryo transfer, vitamin D status was unrelated to pregnancy outcomes. Measuring serum 25-OH vitamin D levels does not predict the likelihood that euploid blastocysts will implant. These results may not apply to women who do not undergo extended embryo culture, blastocyst biopsy for comprehensive chromosome screening, and euploid embryo transfer.
Purpose
To evaluate if sperm DNA fragmentation (SDF) in the sample used for intracytoplasmic sperm injection (ICSI) impacts outcomes after euploid blastocyst transfer.
Methods
Prospective cohort ...study of couples undergoing IVF with preimplantation genetic testing for aneuploidy from December 2014–June 2017. Sperm collected on the day of ICSI was analyzed for SDF using the sperm chromatin structure assay (SCSA®). Semen analysis parameters, embryologic outcomes, and clinical outcomes after euploid blastocyst transfer were compared between groups with DNA fragmentation index (DFI) ≤ 15% and DFI > 15% using Mann–Whitney
U
,
t
tests, and generalized linear mixed effects models.
Results
Two hundred thirty-four patients were included. One hundred seventy-nine men had DFI ≤ 15% (low DFI group) and 55 men had DFI > 15% group (high DFI group). Total motile sperm and sperm concentration were significantly lower in the group with DFI > 15% vs. DFI ≤ 15%. There was no difference in fertilization (86.3 vs. 84.2%, adjusted OR (95% CI) 0.86 (0.63–1.18)), blastulation (49.5 vs. 48.8%, adjusted OR 1.02 (0.75–1.36)), or euploidy (55.7 vs. 52.1%, adjusted OR 0.96 (0.7–1.31)) between the low and high DFI groups, respectively. Clinical outcomes were similar between low and high DFI groups, including implantation rate (68.8 vs. 79.8%), ongoing pregnancy rate (65.9 vs. 72.6%), and miscarriage rate (4.2 vs. 8.8%), respectively.
Conclusion
Sperm DNA fragmentation on the day of ICSI is not associated with embryologic or clinical outcomes after euploid blastocyst transfer. Increasing levels of SDF are associated with low sperm concentration and total motile sperm count.
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.
Objective To compare monozygotic twinning (MZT) rates in patients undergoing blastocyst or cleavage-stage ET. Design Retrospective cohort. Setting Academic research center. Patient(s) Autologous, ...fresh IVF cycles resulting in a clinical pregnancy from 1999 to 2014. Intervention(s) None. Main Outcome Measure(s) Monozygotic twin pregnancy in blastocyst-stage transfer vs. cleavage-stage transfer when controlling for patient prognosis and embryo cohort quality factors. Result(s) There were a total of 9,969 fresh transfer cycles resulting in a pregnancy during the study period. Of these pregnancies, 234 monozygotic twin pregnancies were identified (2.4%). Of all transfers, 5,191 were cleavage-stage and 4,778 were blastocyst-stage transfers. There were a total of 99 MZT identified in the cleavage-stage group (1.9%) and 135 MZT in the blastocyst ET group (2.4%), which was significant. Multivariable logistic regression revealed that increasing age was associated with a significant reduction in MZT, regardless of transfer order. Embryo cohort quality factors, including the number and proportion of six- to eight-cell embryos and availability of supernumerary embryos, were also significant. When controlling for patient age, time period during which the cycle took place, the number and proportion of six- to eight-cell embryos, and availability of supernumerary embryos, there was no longer a difference in MZT rate between blastocyst and cleavage transfer. Conclusion(s) Patient prognosis and embryo cohort quality seem to be major factors in MZT rate in women undergoing blastocyst transfer. Although technology-based effects cannot be excluded, patient and embryo characteristics play an important role.
Objective To determine whether endometrial hCG infusion at the time of human blastocyst transfer impacts implantation rates. Design Randomized double-blinded placebo-controlled trial. Setting ...Academic. Patient(s) Infertile couples with the female partner less than 43 years old (n = 300) undergoing fresh or frozen ET of one or two blastocysts. Intervention(s) Patients undergoing ET were randomized into either a treatment or a control group. The treatment group received an infusion of 500 IU of hCG diluted in ET media. The control group received a sham infusion of ET media. Infusions were done using a separate catheter less than 3 minutes before actual ET. Main Outcome Measure(s) Sustained implantation rate: ongoing viable gestation (primary outcome) and ongoing pregnancy rate (secondary outcome). Result(s) A total of 473 blastocysts were transferred into 300 patients. There were no differences between the two groups in sustained implantation rate (48.1% in the hCG group, 44.2% in the control group) or ongoing pregnancy rate (58.8% in the hCG group, 52.0% in the control group). Conclusion(s) Endometrial infusion of hCG at the time of blastocyst ET does not improve sustained implantation rates. Clinical Trial Registration Number NCT01643993.
Objective To determine whether sequential or monophasic media is the more optimal formulation for blastocyst development and sustained implantation rates (SIR) in IVF. Design Paired randomized ...controlled trials. Setting Academic. Patient(s) Infertile couples (N = 192) with female partner ≤42 years old and normal ovarian reserve. Intervention(s) Fertilized zygotes from each patient were randomly divided into two groups: 1 cultured in sequential media and 2 cultured in monophasic medium. Sequential media consisted of Quinn's Advantage Cleavage Medium (SAGE) followed by Blast Assist (Origio). The monophasic medium used was Continuous Single Culture (Irvine Scientific). Paired ETs were accomplished by transferring the best euploid blastocyst from each media group. DNA fingerprinting was used to link outcomes. Main Outcome Measure(s) The primary outcome measure was the proportion of blastocysts suitable for clinical use. Secondary outcome measures included timing of blastulation, aneuploidy rates, and SIR. Sustained implantation rate is defined as the number fetal heart beats at 8–9 weeks of gestation, divided by the number of embryos transferred. Result(s) A total of 192 patients had their 2PN embryos (N = 2,257) randomized to each culture system. Sequential media had higher blastulation rate than monophasic medium (55.2% vs. 46.9%). No differences were found in the day of blastulation or aneuploidy rate. Of the 168 patients who had euploid blastocysts suitable for transfer, 126 completed a paired ET. Among the double ETs, there was no difference in implantation between groups. Conclusion(s) This is the first randomized controlled trial to examine paired euploid transfers of sibling zygotes cultured in sequential versus monophasic media. This study demonstrates that the usable blastocyst rate is greatest after culture in the sequential media tested in comparison with the monophasic formulation selected for study. However, no difference exists in timing of blastulation, aneuploidy, or SIR. Whether these observations are generalizable to other media systems remains to be determined. Clinical Trial Registration Number NCT01917240.
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