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 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.
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.
To determine if natural selection and follicular stimulation produces a lower risk for embryonic aneuploidy than that attained following superovulation with exogenous gonadotropins.
Prospective ...observational with historical control group.
Large academically affiliated private practice.
All patients presenting for their evaluation for infertility were offered participation in the study.
All participants in the natural cycle group underwent an unstimulated in vitro fertilization (IVF) cycle. A subsequent frozen embryo transfer was performed if a euploid blastocyst was attained.
Rates of embryonic aneuploidy attained in unstimulated IVF cycles were compared to those observed in age-controlled historical cohort undergoing conventional stimulated IVF cycles with exogenous gonadotropins.
Aneuploidy rates were equivalent in unstimulated and stimulated IVF cycles. The prevalence of aneuploidy in natural cycles increased with the age of the female partner in a manner identical to that seen in stimulated IVF cycles. Finally, sustained implantation rates of euploid blastocysts were equivalent in natural and stimulated IVF cycles.
Rates of embryonic aneuploidy are not impacted by follicular stimulation with exogenous gonadotropins. Prior concerns of inducing a higher risk of embryonic aneuploidy are not supported by this data.
NCT01866618.
Las tasas de aneuplodía embrionaria son equivalentes en los ciclos naturales y en los ciclos estimulados con gonadotropinas
Determinar si la selección natural y la estimulación folicular producen un riesgo más bajo de aneuplodía embrionaria en comparación con aquel conseguido siguiendo la superovulación con gonadotropinas exógenas.
Prospectivo observacional con grupo de control histórico.
Practica privada grande académicamente afiliada.
A todos los pacientes que se presentaron para su evaluación por infertilidad se les ofreció participar en el estudio.
Todos los pacientes en el grupo de ciclo natural fueron sometidos a un ciclo de fecundación in vitro (IVF) sin estimulación. Se realizó posteriormente una transferencia de embriones congelados si un blastocisto euploide fuese obtenido.
Las tasas de aneuplodía embrionaria obtenidas en ciclos de IVF sin estimulación fueron comparadas con aquellas observadas en una cohorte histórica de edad-control la cual fue sometida a ciclos de IVF convencional estimulados con gonadotropinas exógenas.
Las tasas de aneuploidías fueron equivalentes en los ciclos de IVF estimulados y no estimulados. La prevalencia de aneuploidía en ciclos naturales aumentó con la edad de la pareja femenina de manera idéntica a aquellos vistos en ciclos de IVF estimulados. Finalmente la tasa de implantación sostenida de embriones euploides fue equivalente en los ciclos de IVF estimulados y no estimulados.
Las tasas de aneuplodía embrionaria no se ven impactadas por la estimulación folicular con gonadotropinas exógenas. Las previas preocupaciones de inducir un alto riesgo de aneuplodía embrionaria no son respaldadas por estos datos.
To study the prevalence of celiac disease in the infertile population undergoing in vitro fertilization (IVF) and assess outcomes.
Prospective cohort study.
A single infertility center from January ...2016 to March 2017.
Women 18–45 years of age participating in IVF.
Patients had serum tissue transglutaminase (tTG) and endomysial (EMA) IgA testing to screen for celiac disease and completed a 10-question “yes or no” survey to assess their medical history, previous testing, dietary habits, and pertinent symptoms.
IVF cycle outcomes were compared between seronegative and seropositive patients.
Of 1,000 patients enrolled, 995 completed serologic screening and 968 underwent oocyte retrieval. Eighteen patients screened positive for both tTG and EMA (1.8%) and 10 additional patients (1.0%) screened positive for one of the two antibodies. The number of mature oocytes retrieved, fertilization rates, and blastulation rates were equivalent between seronegative and seropositive patients. There were 987 patients who completed the questionnaire (98.7%), and 84 reported being gluten free (8.5%). Those who reported being gluten free were no more likely to be antibody positive than the general population. Furthermore, a low-gluten diet was not associated with markers of ovarian reserve, oocytes retrieved, fertilization, blastulation, sustained implantation and pregnancy loss rates.
The prevalence of seropositive celiac disease was consistent with that of the general population (2.8%). Patients who were seropositive for celiac disease–related antibodies had outcomes equivalent to seronegative patients, and patients with a gluten-free diet did not have improved outcomes.
La enfermedad celíaca no es más prevalente en las pacientes que realizan fertilización in vitro y no afecta los resultados reproductivos con o sin tratamiento: Un amplio estudio de cohorte
Estudiar la prevalencia de la enfermedad celíaca en la población infértil que realiza fertilización in vitro (FIV) y evaluar los resultados.
Estudio prospectivo de cohorte.
Un único centro de infertilidad desde enero de 2016 hasta marzo de 2017.
Mujeres de 18-45 años que realizan FIV.
A las pacientes se les realizó estudio de la transglutaminasa sérica (tTG) y de anticuerpos IgA antiendomisio (EMA) para cribado de enfermedad celíaca, y se les pidió completar un cuestionario de 10 preguntas con respuestas “Sí o No” para evaluar su historia médica, exámenes previos, hábitos nutricionales y síntomas pertinentes.
Se compararon los resultados de los ciclos FIV de pacientes seronegativas y seropositivas.
De 1000 pacientes incluidas, 995 completaron el estudio serológico, y en 968 se llegó a realizar aspiración de ovocitos. Dieciocho pacientes resultaron positivas tanto para tTG como para EMA (1,8%), y 10 pacientes adicionales fueron positivas para uno de los dos anticuerpos. El número de ovocitos maduros obtenidos, y las tasas de fecundación y blastulación fueron equivalentes entre las pacientes seronegativas y seropositivas. 987 pacientes completaron el cuestionario (98,7%), y 84 reportaron ser libres de gluten (8,5%). Aquellas que informaron ser libres de gluten no tuvieron más probabilidades de ser positivas para anticuerpos que la población general. Además, una dieta baja en gluten no se asoció con marcadores de reserva ovárica, ovocitos obtenidos, ni con las tasas de fecundación, blastulación, implantación sostenida y aborto.
La prevalencia de enfermedad celíaca seropositiva fue consistente con la de la población general (2,8%). Las pacientes que resultaron seropositivas para anticuerpos relacionados con la enfermedad celíaca tuvieron resultados equivalentes a los de las pacientes seronegativas, y las pacientes con dieta libre de gluten no tuvieron mejores resultados.
To determine if a dynamic embryo culture system affects the reproductive potential of human embryos resulting from in vitro fertilization (IVF).
Paired randomized controlled trial (RCT).
IVF center.
...IVF patients with normal ovarian reserve eligible for two-embryo transfer.
IVF care was routine until fertilization was confirmed. Two-pronuclear embryos (2PNs) were then randomized: One-half of each patient’s 2PNs were cultured in dynamic culture and one-half in static culture. Preimplantation genetic testing for embryonic aneuploidy was used to control for aneuploidy and allow for DNA fingerprinting. The best euploid blastocyst from each culture system was selected and patients underwent a frozen two-embryo transfer. If a singleton gestation resulted, DNA-fingerprinting was used to determine which of the two blastocysts implanted. The dynamic platform used was the NSSB-300 (Nepagene).
The primary outcome was the proportion of usable blastocysts obtained. The secondary outcome was sustained implantation rate (SIR).
One hundred participants completed oocyte retrieval and blastocyst vitrification for frozen-thawed embryo transfer; 609 dynamic 2PNs and 615 static 2PNs were followed; and 304 blastocysts developed in dynamic culture and 333 blastocysts developed in static culture. In the paired analysis, the rate of usable blastulation was similar between dynamic and static culture (58.3% vs. 57.1%). In addition, there was no difference in the rate of aneuploidy (20.0% vs. 33.3%) or SIR (67.1% vs. 63.1%) between groups.
In this paired RCT, dynamic culture did not improve usable blastulation rate or SIR.
NCT02467725
Movimiento natural del embrión (enMotion): un ensayo controlado aleatorio pareado que evalúa un sistema dinámico de cultivo de embriones
determinar si un sistema dinámico de cultivo de embriones afecta el potencial reproductivo de los embriones humanos resultantes de la fertilización in vitro (FIV).
ensayo controlado aleatorio pareado (ECA).
centro de FIV.
pacientes de FIV con reserva ovárica normal elegibles para transferencia de dos embriones.
el manejo de la FIV fue de rutina hasta que se confirmó la fertilización. Luego, los embriones de dos pronucleos (2PN) se aleatorizaron: la mitad de los 2PN de cada paciente se cultivaron en cultivo dinámico y la otra mitad en cultivo estático. Las pruebas genéticas previas a la implantación para la aneuploidía embrionaria se utilizaron para controlar la aneuploidía y permitir la toma de huellas digitales de ADN. Se seleccionó el mejor blastocisto euploide de cada sistema de cultivo y los pacientes se sometieron a una transferencia congelada de dos embriones. Si se producía una gestación singleton, se utilizaban las huellas digitales de ADN para determinar cuál de los dos blastocistos se implantaba. La plataforma dinámica utilizada fue el NSSB-300 (Nepagene).
El resultado primario fue la proporción de blastocitos utilizables obtenidos. El resultado secundario fue la tasa de implantación sostenida (SIR).
Cien participantes completaron la recuperación de ovocitos y la vitrificación de blastocistos para la transferencia de embriones congelados y descongelados; Se siguieron 609 2PN dinámicos y 615 2PN estáticos; y 304 blastocistos se desarrollaron en cultivo dinámico y 333 blastocistos se desarrollaron en cultivo estático. En el análisis pareado, la tasa de blastulación utilizable fue similar entre el cultivo dinámico y el estático (58.3% vs. 57.1%). Además, no hubo diferencias en la tasa de aneuploidía (20.0% vs. 33.3%) o SIR (67.1% vs. 63.1%) entre los grupos. Conclusión (es): en este ECA pareado, el cultivo dinámico no mejoró la tasa de blastulación utilizable o SIR.
cultivo dinámico, plataforma de microvibración, competencia embrionaria.
Purpose
The ideal thyroid-stimulating hormone (TSH) range for infertile women attempting conception has not been determined. Current recommendations include optimizing the preconception TSH value to ...≤2.5 mIU/L, which is the established goal for pregnant women. The aim of this study was to determine if there is a distinct range of TSH ≤2.5 mIU/L for infertile women undergoing in vitro fertilization (IVF) that improves reproductive outcomes.
Methods
One thousand five hundred ninety-nine euploid blastocyst transfer cycles were evaluated in which TSH measurements were obtained 8 days after embryo transfer. Only euploid embryo transfers were included in an effort to control for embryo quality. Patients were separated into TSH groups utilizing 0.5 mIU/L increments. Implantation, live birth, and miscarriage rates among the TSH groups were compared. Outcomes for individuals on thyroid hormone supplementation and those not requiring supplementation were evaluated.
Results
There was no difference in implantation (
p
= 0.56), live birth (
p
= 0.36), or miscarriage rates (
p
= 0.10) between TSH groups. Receiver operating characteristic (ROC) curves for implantation, live birth, and miscarriage approached the line of no discrimination, signifying that there is no value of TSH within the recommended range for pregnancy (≤2.5 mIU/L) that predicts IVF outcomes better than other values in this range. Live birth rates for patients requiring thyroid hormone supplementation and those not on medication were similar (
p
= 0.86).
Conclusions
The recommended TSH range for pregnancy (≤2.5 mIU/L) may be applied to infertile patients attempting conception without a need for further adjustment.
(Abstracted from Fertil Steril 2019;112:670–676)It is unclear whether controlled ovarian hyperstimulation (COH) using exogenous gonadotrophins during the in vitro fertilization (IVF) process elevates ...risk of meiotic or mitotic error, leading to aneuploidy. Several studies with mouse models have suggested that follicle-stimulating hormone (FSH) administration in vitro results in higher rates of aneuploidy, although studies utilizing mouse models are limited due to significantly different rates of aneuploidy and mechanistic differences between mice and humans.
Abstract The relationship between FMR1 CGG premutation status and decreased ovarian responsiveness is well established. The association between FMR1 CGG repeat number in the currently defined normal ...range (less than 45 repeats) and ovarian reserve, however, is controversial. This retrospective study examined whether variation in CGG repeat number in the normal range was associated with markers of ovarian response in IVF cycles. The first IVF cycle of 3006 patients with FMR1 CGG repeat analysis was examined. Only patients carrying two alleles with less than 45 CGG repeats were included for analysis. The CGG repeat number furthest from the modal peak was plotted against number of mature oocytes retrieved and no correlation was identified. Patients were also separated into biallelic genotype groups, based on the recently proposed narrower “new normal” range of 26–34 CGG repeats. A linear regression showed that none of the biallelic genotype groups were associated with a decreased oocyte yield. The euploidy rates after comprehensive chromosomal screening were equivalent among the genotype groups. No difference was found in the rate of cycle cancellation for poor response. Despite increasing use, FMR1 CGG repeats in the normal range cannot be used as a predictor of ovarian response to gonadotrophin stimulation.
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