One Plus One is Better than Two: An Approach Towards a Single Blastocyst Transfer Policy for All IVF Patients / Um mais um é melhor que dois: Uma abordagem pela prática da transferência de embrião único para todos os pacientes de FIV

Abstract Objective It is known that the single embryo transfer (SET) is the best choice to reduce multiples and associated risks. The practice of cryopreserving all embryos for posterior transfer has been increasingly performed for in vitro fertilization (IVF) patients at the risk of ovarian hyperstimulation syndrome or preimplantation genetic testing for aneuploidy. However, its widespread practice is still controverse. The aim of this study was to evaluate how effective is the transfer of two sequential SET procedures compared with a double embryo transfer (DET) in freeze-only cycles. Methods This retrospective study reviewed 5,156 IVF cycles performed between 2011 and 2019, and 506 cycles using own oocytes and freeze-only policy with subsequent elective frozen-thawed embryo transfers (eFET) were selected for this study. Cycles having elective SET (eSET, n = 209) comprised our study group and as control group we included cycles performed with elective DET (eDET, n = 291). In the eSET group, 57 couples who had failed in the 1st eSET had a 2nd eFET, and the estimated cumulative ongoing pregnancy rate was calculated and compared with eDET. Results After the 1st eFET, the ongoing pregnancy rates were similar between groups (eSET: 35.4% versus eDET: 38.5%; p =0.497), but the estimated cumulative ongoing pregnancy rate after a 2nd eFET in the eSET group (eSET + SET) was significantly higher (48.8%) than in the eDET group (p < 0.001). Additionally, the eSET +SET group had a 2.7% rate of multiple gestations, which is significantly lower than the eDET group, with a 30.4% rate (p < 0.001). Conclusion Our study showed the association of freeze-only strategy with until up to two consecutive frozen-thawed eSETs resulted in higher success rates than a frozenthawed DET, while drastically reducing the rate of multiple pregnancies.

Resumo Objetivo Sabe-se que a transferência de embrião único (SET) é a melhor escolha para reduzir as gestações múltiplas e riscos associados. A prática da criopreservação de todos os embriões para transferência posterior tem sido cada vez mais utilizada para fertilização in vitro (FIV), em especial quando há risco de síndrome de hiperestimulação ovariana ou realização de teste genético pré-implantacional. Entretanto, sua utilização disseminada ainda é controversa. O objetivo deste estudo foi avaliar a eficácia de duas SET sequenciais em comparação com uma transferência de embrião dupla (DET) em ciclos de FIV onde todos os embriões foram criopreservados. Métodos Neste estudo retrospectivo foram revisados 5.156 ciclos de FIV realizados entre 2011 e 2019, e 506 ciclos usando oócitos próprios e criopreservação de todos os embriões com transferências eletivas subsequentes de embriões descongelados, foram selecionados para este estudo. Ciclos com transferência eletiva de embrião único (eSET, n = 209) compuseram nosso grupo de estudo e como grupo de controle incluímos os ciclos com transferência eletiva de dois embriões (eDET, n = 291). No grupo eSET, 57 casais que falharam na 1ª tentativa de eSET tiveram uma 2ª eFET e a taxa de gravidez em curso cumulativa foi estimada para o grupo eSET e comparada com o grupo eDET. Resultados Após a 1ª eFET, as taxas de gravidez em curso foram semelhantes entre os grupos (eSET: 35,4% versus eDET: 38,5%; p = 0,497), mas a taxa de gravidez em curso cumulativa estimada após a 2ª eFET no grupo eSET (eSET + SET) foi significativamente maior (48,8%) do que no grupo eDET (p <0,001). Além disso, as taxas de gestação múltipla foram expressivamente inferiores no grupo eSET + SET (2,7%) quando comparado ao grupo eDET (30,4%; p < 0,001). Conclusão Nosso estudo mostrou que a associação das estratégias de congelamento de todos os embriões com até duas eSETs sequenciais resultou em maiores taxas de sucesso do que uma DET com embriões descongelados, além de reduzir drasticamente a ocorrência de gestações múltiplas.

Analysis of pregnancy outcomes of single top-quality blastocyst transfer developed from cleavage embryos with different grading / 中华妇产科杂志

Objective:To explore the clinical outcomes of top-quality blastocysts transfer developed from cleavage embryos with different grading and determine whether the cleavage stage embryo morphology grading should be taken into consideration when transferring the embryo at the blastocyst stage.Methods:A number of 3 059 cycles were included with single top-quality blastocyst transfer dating from January 2017 to May 2021 in Henan Provincial People′s Hospital. According to the number of cleavage sphere and degree of fragmentation, all cleavage stage embryos were divided into three groups: top D3 embryo (8 cells, ≤5% fragments)-TB group, suboptimal D3 embryo (8 cells, 5%<fragments≤10%; 7 cells or 9 cells, ≤10%)-TB group, and normal D3 embryo-TB group. Univariate analysis, multivariate logistic regression analysis and threshold effect analysis were performed on the data.Results:The clinical pregnancy rates of top D3 embryo-TB group(1 326 cycles), suboptimal D3 embryo-TB group (830 cycles) and normal D3 embryo-TB group (903 cycles) were 69.53%, 70.12% and 66.67%, respectively ( P>0.05); and the early abortion rate were 10.74%, 12.54% and 12.62%, respectively ( P>0.05). After adjusting for confounders, logistic regression showed that no significant associations were found between cleavage stage embryo morphology grading and clinical pregnancy rate (suboptimal D3 embryo-TB group: OR=1.02, 95% CI: 0.76-1.38, P=0.879; normal D3 embryo-TB group: OR=0.84, 95% CI: 0.61-1.14, P=0.262) and early abortion rate (suboptimal D3 embryo-TB group: OR=1.18, 95% CI: 0.77-1.82, P=0.445; normal D3 embryo-TB group: OR=1.26, 95% CI: 0.81-1.98, P=0.309). The results of threshold effect analysis showed that when a single top-quality blastocysts was transferred, the effect of age on the clinical pregnancy rate showed a curve relationship, when the age was≥33 years old, the clinical pregnancy rate decreased significantly with age increased ( OR=0.89, 95% CI: 0.83-0.95, P=0.007); and there was no significant change in early abortion rate ( OR=1.01, 95% CI: 0.97-1.06, P=0.628). Conclusions:Cleavage stage embryo grading is not found to correlate with clinical outcomes in single top-quality blastcyst tranfer. Therefore, when considering blastocyst transfer, its morphology at blastocyst stage is more relevant. The effect of age on pregnancy outcomes of single blastocyst transfer should be considered.

Relación entre la ubicación de la burbuja de aire en la transferencia embrionaria y las tasas de implantación y gestación evolutiva / Relationship between air bubble location at embryo transfer and implantation and ongoing pregnancy rates

Resumen OBJETIVO: Evaluar la relación entre la ubicación de la burbuja de aire que contiene los embriones y las tasas de implantación y de gestación clínica. El secundario: estudiar la relación entre la posición de la punta de la cánula, el grosor endometrial y el desplazamiento de la burbuja con esos desenlaces reproductivos. MATERIALES Y MÉTODOS: Estudio retrospectivo, observacional y de análisis de imágenes ecográficas de transferencias de embrión único en estadio de blastocisto practicadas por un mismo especialista en la Fundación IVI, Valencia, España, entre septiembre de 2013 y febrero de 2021. Criterios de selección: grosor endometrial ≥ 6 mm en el último control ecográfico, ausencia de miomas, IMC menor de 30 kg/m2, transferencias atraumáticas efectuadas por el mismo especialista. En función de la ubicación de la burbuja de aire se establecieron tres grupos de estudio (alta: mayor de 0.98 cm, media: 0.98 a 1.44 cm y baja: mayor de 1.44 cm) y para evaluar la asociación entre las categorías se aplicó el cálculo de razón de momios (OR) e IC95%. RESULTADOS: Se estudiaron 342 transferencias de embrión único. La edad media de las pacientes fue 39.70 ± 4.5 años. La relación entre la distancia de la burbuja de aire al fondo uterino y la tasa de implantación fue de 61 ± 9% en el grupo de ubicación alta, 64 ± 9% en el grupo de ubicación media, y de 56 ± 1% en el grupo de ubicación baja (p = 0.437). No se observaron diferencias en la tasa de gestación evolutiva analizada mediante probabilidad de ocurrencia entre grupos, con frecuencias de 0.60 en comparación con 0.64 (OR: 1.42; IC95%: 0.83 a 2.44; p: 0.199) y en la ubicación alta con media, y frecuencias de 0.60 en comparación con 0.56 (OR: 1.22; IC95%: 0.72-2.08; p: 0.462) entre alta y baja. CONCLUSIONES: No se encontró asociación entre la ubicación de la burbuja y las tasas de implantación y de gestación evolutiva. El mayor desplazamiento de la burbuja se asoció con mayores tasas de gestación evolutiva.

Abstract OBJECTIVE: To evaluate the relationship between the location of the air bubble containing the embryos and the implantation and clinical gestation rates. Secondary: to study the relationship between the position of the cannula tip, the endometrial thickness and the displacement of the bubble with these reproductive outcomes. MATERIALS AND METHODS: Retrospective, observational, ultrasound image analysis study of single embryo transfers at blastocyst stage performed by the same specialist at the IVI Foundation, Valencia, Spain, between September 2013 and February 2021. Selection criteria: endometrial thickness ≥ 6 mm at the last ultrasound control, absence of fibroids, BMI less than 30 kg/m2, atraumatic transfers, performed by the same specialist. Based on the location of the air bubble, three study groups were established (high: greater than 0.98 cm, medium: 0.98 to 1.44 cm and low: greater than 1.44 cm) and the odds ratio (OR) and 95%CI were used to evaluate the association between the categories. RESULTS: A total of 342 single embryo transfers were studied. The mean age of the patients was 39.70 ± 4.5 years. The relationship between the distance of the air bubble to the uterine fundus and the implantation rate was 61 ± 9% in the high placement group, 64 ± 9% in the medium placement group, and 56 ± 1% in the low placement group (p = 0.437). No differences were observed in the evolutionary gestation rate analyzed by probability of occurrence between groups, with frequencies of 0.60 compared to 0.64 (OR: 1.42; 95%CI: 0.83 to 2.44; p: 0.199) and high to medium location, and frequencies of 0.60 compared to 0.56 (OR: 1.22; 95%CI: 0.72-2.08; p: 0.462) between high and low. CONCLUSIONS: No association was found between the air bubble localization and implantation or ongoing pregnancy rates. However, a greater displacement of the bubble was associated with higher ongoing pregnancy rates.

The strategy of frozen-thawed blastocyst transfer in women over 40 years / 中国医师杂志

Objective:To explore the selection strategy of blastocyst transfer number in freeze-thaw cycle for women over 40 years old, so as to provide reference for reducing twin rate and improving perinatal clinical outcome.Methods:A retrospective analysis was made of 377 patients who underwent freeze-thaw blastocyst transplantation in the reproductive center of Guangdong Maternal and Child Health Hospital from January 2017 to December 2019. They were divided into single blastocyst and double blastocyst transplantatio groups according to the number of blastocyst transplantation. The clinical pregnancy rate, implantation rate, abortion rate, live birth rate, premature delivery rate, twin rate and singleton delivery rate were compared between the two groups.Results:⑴There was no significant difference between two groups regarding the majority of baseline characteristics, including age at retrieval, age at transfer, body mass index (BMI), antral follicle count (AFC), basal follicle stimulating hormone (FSH), anti Mullerian hormone (AMH), endometrial thickness at transfer day, number of oocytes retrieved, Gn starting dose, Gn days, Gn dosage, embryos at cleavage stage and top-quality embryos ( P>0.05). ⑵ There was no significant difference in the rate of implantation, early pregnancy loss, late pregnancy loss and live birth between two groups ( P>0.05). ⑶ The preterm birth rate was higher in the double blastocyst transplantation group compared with the single blastocyst transplantation group, albeit not reaching significant difference (31.7% vs 12.5%, P=0.083). ⑷ The clinical pregnancy rate and the twin pregnancy rate was significantly higher in the double blastocyst transplantation group compared with the single blastocyst transplantation group ( P<0.05). ⑸ The singleton birth rate was significantly lower in the double blastocyst transplantation group compared with the single blastocyst transplantation group (75.61% vs 95.83%, P<0.05). Conclusions:In women ≥40 years old, transferring a single blastocyst can result in live birth rate that is similar as transferring two blastocysts while dramatically reducing the risk of twin pregnancy rate and increasing singleton birth rate.

Modelo de impacto orçamentário da aplicação do single embryo transfer consecutivo comparado com o double embryo transfer em tratamentos de fertilização in vitro no Sistema de Saúde Suplementar / Budget impact model of the use of consecutive single embryo transfers compared to double embryo transfer in in vitro fertilization procedures in the Brazilian Private Healthcare System

Objetivo: Estimar o impacto orçamentário em cinco anos da incorporação da técnica de SET (single embryo transfer) sequencial no Sistema de Saúde Suplementar brasileiro (SSSB). Métodos: Foram consideradas taxas de nascidos vivos de 41% e de gemelaridade de 2% e 30% para SET e DET (double transfer embryo), respectivamente. Os custos dos procedimentos foram, em sua maioria, obtidos das tabelas SIMPRO, CBHPM e CMED. Para a estimativa da população elegível, foram consideradas mulheres de 20 a 35 anos registradas no Datasus e taxas de infertilidade e de uso de fertilização in vitro (FIV) da literatura. Estimou-se em 20% e 80% o uso de SET sequencial e DET, respectivamente, com incorporação da primeira em 45%, 50%, 55%, 65% e 75% dos casos nos cinco anos subsequentes. Resultados: Considerando cenários com reembolso de um a dois ciclos de SET sequencial e inclusão ou não do valor dos medicamentos, o impacto orçamentário em cinco anos seria entre R$ 10.231.387 e R$ 16.123.874 em operadoras de grande porte, R$ 1.054.174 e R$ 1.661.297 em operadoras de médio porte e R$ 173.700 e R$ 273.738 em operadoras de pequeno porte. Em cenário com aumento progressivo do uso de SET sequencial sem alteração no modelo de reembolso atual, foi estimada economia de R$ 59.319.276 para o SSSB em cinco anos. Conclusões: O uso de SET sequencial (vs. DET) em procedimentos de FIV é potencialmente menos oneroso para o SSSB referente a custos de pré-natal, parto e complicações. Em cenário de incorporação progressiva, o custo incremental foi estimado em R$ 8-13 mil/paciente.

Objective: To estimate the five-year budget impact of incorporating the sequential single embryo transfer (SET) technique into the Brazilian Supplementary Healthcare System (BSHS). Methods: Live birth rates of 41% and multiple pregnancy rates of 2% and 30% were considered for SET and DET (double transfer embryo), respectively. The costs of the procedures were mostly obtained from e SIMPRO, CBHPM and CMED tables. To estimate the eligible population, we considered women aged 20-35 years registered in DATASUS, and infertility and in vitro fertilization (IVF) rates from the literature. The use of sequential SET and DET was estimated as 20% and 80%, respectively, with incorporation of the first in 45%, 50%, 55%, 65% and 75% of cases in the subsequent five years. Results: Considering scenarios with reimbursement of 1 to 2 cycles of sequential SET and inclusion or not of the drugs in the reimbursement, the budget impact in five years would be between BRL 10,231,387-16,123,874 in large operators, BRL 1,054,174-1,661,297 in midsize operators and BRL 173,700-273,738 in small operators. In a scenario of progressive increase of the use of sequential SET with no change in the current reimbursement model, we estimated a saving of BRL 59,319,276 for the BSHS in five years. Conclusions: The use of sequential SET (vs. DET) in IVF procedures is potentially less costly for BSHS for prenatal, child-birth and complication costs. In the scenario of progressive incorporation and full reimbursement of the procedure, the incremental cost was estimated at BRL 8-13 thousands/patient.

Single embryo transfer and multifetal pregnancy reduction: perception and attitude of women seeking assisted reproduction in Nigeria

Background: In-vitro fertilization (IVF) is associated with increased multiple pregnancy and its attendant complications. This study evaluates the attitude and acceptance of single embryo transfer (SET) and multifetal pregnancy reduction (MFPR) by clients assessing assisted reproduction in this region.Methods: A cross sectional survey of patients selected for IVF was conducted. Information on demography, knowledge of IVF procedure and their perception, attitude and acceptability of multiple pregnancy as well as their knowledge, attitude and perception to single embryo transfer and multifetal pregnancy reduction were extracted for statistical analysis.Results: Seventy-three women participated in the study. The mean age was 39 years and mean duration of infertility was 8.6 years. Only 3 (4.1%) respondents agreed to have SET as the overwhelming majority (70) 95.9% preferred 2 or more and they felt the more number of embryo transferred the better the chances of achieving pregnancy. Similarly most respondents, 38.4% (28) did not accept MFPR. Most respondents considered age (63%) and duration of infertility (78.1%) as major influencing factor for rejecting SET. Over 75% of respondents said they will still accept multiple embryos transferred despite knowledge of the possible complications.Conclusions: While most infertile women in our sub region appear to recognize the risks with multiple pregnancy, they are less interested in SET or MFPR because they perceive more embryos transferred as a means to maximize treatment outcome. Government funding, client education and a blastocyst transfer protocol may improve acceptability as well as overall preference for less number of embryos transferred in our environment.

Las contracciones en blastocistos humanos se correlacionan con aneuploidía, menor implantación y mayor tiempo de llegada a blastocisto: estudio retrospectivo con incubadora Time-Lapse

Objectives:To identify contraction (CT) patterns in human blastocysts using a Time-Lapse incubator and to correlate them with their ploidy status by PGT-A analysis, the time they took to reach blastocyst state, implantation rate and clinical pregnancy rate. Design: Retrospective cohort study. Interventions: From October 2016 through May 2018, 270 patients were evaluated, 912 embryos were cultivated in the Time-Lapse (Embryoscope™, Vitrolife) incubator; 778 of them were tested for aneuploidy using an NGS platform in a reference laboratory. Vitrification was performed according to the result of embryo development and awaiting the NGS result, followed by devitrification and transfer of a single embryo. Blastocyst contractions (CT) were determined using the EmbryoViewer (EmbryoViewer™ drawing tools) in order to obtain area, percentage of contraction and the various types of contractions, and these were compared with the NGS genetic study result. 182 transfers were performed to patients with an average age of 30.4 years, range 24 to 39 years. Finally, we obtained the correlation of implantation rate and clinical pregnancy of euploid embryos transferred in the program of assisted reproduction. Results: Embryos were separated into two groups according to contraction during their development: those that contracted (CT) and those that did not, named "only expanding" (OE). OE embryos were euploid in 58.3%, while 53.6% of CT embryos were aneuploid, with a statistically significant difference (p=0.029), meaning that OE embryos had higher chances of being euploid than CT embryos. Pregnancy rate was also higher in OE embryos (63.1% vs. 46.7% in CT embryos; p=0.012). CT embryos took longer to reach the blastocyst stage compared to OE embryos (p=0.004). Women's age had no correlation with embryo contraction. Conclusions: In this study, embryos who showed contractions had a higher chance of aneuploidy, a lower implantation rate, and required longer to reach the blastocyst stage. The simple fact of observing contractions in an embryo could be useful to decide to transfer another embryo without contractions. Further studies are necessary to prove these findings.

Objetivos. Estudiar los patrones de contracciones en blastocistos humanos mediante el uso de una incubadora time-lapse y correlacionarlos con su estado de ploidía por análisis PGT-A, el tiempo para alcanzar el estado blastocisto, la tasa de implantación y de embarazo clínico. Diseño. Estudio de cohortes retrospectivo. Intervenciones. Entre octubre 2016 y mayo 2018, se evaluó 270 pacientes; se hizo cultivo extendido de 5 a 6 días a 912 embriones en la incubadora time-lapse (Embryoscope, Vitrolife), y a 778 se les estudió para aneuploidía usando una plataforma NGS en un laboratorio de referencia. Hubo posterior vitrificación, según resultado del desarrollo embrionario y en espera del resultado del NGS, seguido de desvitrificación y transferencia de embrión único. Se determinó las contracciones del blastocisto (CTB) mediante la herramienta de dibujo del embrión EmbryoViewer (EmbryoViewer drawing tools), de manera de obtener el área, porcentaje de contracción y los diferentes tipos de contracciones, y se comparó los embriones con el resultado del estudio genético mediante NGS. Se transfirió 182 embriones en pacientes de 30,4 años promedio, rango entre 24 y 39 años. Finalmente, se correlacionó la tasa de implantación y embarazo clínico de los embriones euploides que fueron transferidos, en el programa de reproducción asistida. Resultados. Se separó los embriones en dos grupos de acuerdo a las contracciones durante su desarrollo, en aquellos que las tuvieron (CT) y aquellos que no, denominados 'solo expanding' (SE). Los embriones SE fueron euploides en 58,3%, mientras los embriones CT fueron aneuploides en 53,6%, con significancia estadística (p=0,012). Ello indica que la mayoría de los embriones euploides hacen 'solo expanding' durante su desarrollo, mientras que la mayoría de los embriones aneuploides (53,9%) hacen contracciones durante su desarrollo (p=0,029). Del mismo modo, la tasa de embarazo clínico de los embriones SE euploides fue 63,1% frente a 46,7% de los embriones CT, p=0.012. Finalmente, los embriones euploides CT tardaron más en convertirse en blastocistos tempranos que los embriones SE, p=0.004. La edad de la mujer no representó un factor para contracción embrionaria. Conclusiones. Los resultados obtenidos en este estudio muestran que los embriones que muestran contracciones, sin importar que tan intensas sean, están relacionados con mayor probabilidad de aneuploidías, menor tasa de implantación y ritmos de división lentos. El simple hecho de observar contracciones en un embrión podría ser útil para decidir transferir otro embrión que no las haya tenido. Se requiere más estudios para comprobar estos hallazgos.

Primer embarazo en América Latina utilizando la técnica Piezo-ICSI: reporte de caso

Intracytoplasmic sperm injection (ICSI) is an in vitro fertilization technique in which a sperm is injected through a micropipette to achieve fertilization. This technique, widely used in assisted reproduction, causes a moderate deformation of the oocyte membrane, which becomes harmful in some cases. The Piezo-ICSI technique minimizes this deformation because the Piezo device generates submicron vibration in the ICSI micropipette that crosses the zona pellucida without generating any resistance. There is no prior evidence of a pregnancy obtained through this technique in Latin America. Therefore, we present this report as the first case of a 16-week clinical pregnancy with present heartbeat from an embryo fertilized using the Piezo-ICSI technique.

La inyección intracitoplasmática del espermatozoide al ovulo (ICSI) es una técnica de fertilización in vitro en la que un espermatozoide es inyectado al ovocito utilizando una micropipeta biselada, para conseguir la fecundación. Esta técnica, ampliamente usada en reproducción asistida, genera una deformación moderada de la membrana del ovocito, llegando a ser, en algunos casos, nocivo para este. Utilizando la técnica Piezo-ICSI, esta deformación se minimiza, ya que el dispositivo Piezo genera vibración submicrónica en la micropipeta de ICSI, y atraviesa la zona pelúcida sin generar resistencia alguna. No existe evidencia que esta técnica haya logrado un embarazo en América Latina, por lo tanto, se presenta el siguiente reporte como el primer caso de embarazo clínico con actividad cardiaca de 16 semanas de gestación proveniente de un embrión fecundado con la técnica de Piezo-ICSI.

El uso de la tecnología Time-Lapse y algoritmo predictivo KIDScore 5 ayuda a mejorar la selección de embriones euploides para la transferencia

Objectives: To determine if the use of the KIDScore 5 algorithm (known implantation data) can help select between euploid embryos in order to improve pregnancy and implantation rates in patients undergoing assisted reproductive procedures. Methods: Retrospective cohort study in a fertility clinic, from October 2016 to December 2018, of 1 049 embryos from 328 patients. All the embryos were cultured in the Time-Lapse, Embryoscope® incubator (Vitrolife®, Canada) for 5-6 days. Of these, 896 embryos (85.4%) were biopsied and analyzed by NGS, and assessed with the predictive KIDScore 5 algorithm (Vitrolife®, Canada). The 153 remaining embryos (14.6%) were assessed with the predictive KIDScore 5 algorithm only. 256 single euploid embryos were transferred in couples undergoing IVF treatments at the Inmater clinics laboratory of assisted reproduction in Lima - Peru. Results: The implantation rate was significantly higher (p = 0.004) in euploid embryos transferred when selected by the KIDScore 5 algorithm (Group 2) versus those selected using only genetic study by NGS technology (Group 1) (71.2% vs. 48.8%). The rate of implantation of the euploid embryos transferred with KIDScore value = 6 versus those transferred with KIDScore = 1 was statistically different (73.5% vs. 50.8%; p = 0.030). When assessing the relationship between the rate of euploid embryos versus the result of the KIDScore 5 value, we found highly significant differences in the rates of euploid embryos with values 6 and 5 versus those with KIDScore 0 and 1 (60.5% vs. 45.7%; p = 0.0004). Conclusions: The embryo selection with the KIDScore 5 algorithm offers advantage on implantation and pregnancy rates only when euploid embryos are transferred. Its use as an additional criterion to embryo selection should be considered when accompanied by genetic study of the embryos to be transferred. Euploid embryos with a higher value in the KIDScore 5 algorithm scale have better rates of implantation and euploidy than embryos with the minimum value of this algorithm.

Objetivos. Evaluar si el uso del algoritmo KIDScore 5 (known implantation data) puede ayudar a seleccionar entre los embriones euploides, para mejorar las tasas de embarazo e implantación en pacientes sometidas a procedimientos de reproducción asistida. Métodos. Estudio de cohorte retrospectivo en una clínica de fertilidad, desde octubre 2016 a diciembre 2018. Se estudió 1 049 embriones provenientes de 328 pacientes. Todos los embriones fueron cultivados en la incubadora Time-Lapse, Embryoscope® (Vitrolife®, Canadá) durante 5 a 6 días. De estos, 896 embriones (85,4%) fueron biopsiados y analizados mediante NGS y recibieron una valoración otorgada por el algoritmo predictivo KIDScore 5 (Vitrolife®, Canadá). Los 153 embriones restantes (14,6%) únicamente recibieron la valoración mediante el algoritmo predictivo KIDScore 5. Se realizó 256 transferencias únicas de embriones euploides en parejas sometidas a tratamientos de FIV en el laboratorio de reproducción asistida de la Clínica Inmater, Lima - Perú. Resultados. La tasa de implantación de los embriones euploides transferidos con valores de KIDScore = 6 versus los transferidos con valores de KIDScore = 1 tuvo diferencia estadísticamente significativa (73,5% vs. 50,8%; p=0,030). Al evaluar la relación entre la tasa de euploidia embrionaria versus el resultado del valor de KIDScore 5, se obtuvo diferencias altamente significativas en las tasas de euploidia en los embriones con resultados de KIDScore 6 y 5 versus los de KIDScore 0 y 1 (60,5% vs. 45,7%; p=0,0004). Conclusiones. La selección embrionaria con ayuda del algoritmo KIDScore 5 ofrece ventaja en las tasas de implantación y embarazo únicamente cuando se transfieren embriones euploides. Su uso como criterio adicional a la selección embrionaria debiera ser considerado siempre que se acompañe estudio genético a los embriones a transferir. Los embriones euploides con valor más alto en la escala del algoritmo KIDScore 5, tienen mejores tasas de implantación y euploidía que los embriones con el valor mínimo de dicho algoritmo.

Clinical Outcome Analysis of Single Embryo Transfer / 中山大学学报(医学科学版)

@#【Objective】To explore the application prospect of single embryo transfer（SET）in assisted reproduction. 【Methods】A total of 5 130 cases of fresh and frozen embryo transfer in the Reproductive Center of the First Affiliated Hospital，Sun Yat-sen University in the recent two years were analyzed retrospectively. To analyze the main outcome of clinical pregnancy in different age groups，we classified the SET cycles into 4 groups of fresh or frozen，elective or obliged.【Results】In non-preimplantation genetic testing（PGT）elective SET cycles，the clinical pregnancy rate of the day 3 embryos（D3）and day 6 embryos（D6）in patients under 35 were as high as 35%. The clinical pregnancy rate of day 5 embryos（D5）was 50% approximately. While in PGT cycles，the clinical pregnancy rate of patients less than 42 years old was 45%，especially implantation rate of D5 embryos was close to 60% in all patients under 40. With the increase of age，the pregnancy rate of SET decreased. In non-PGT group，D3 embryos showed significant difference in either elective/obliged or fresh/frozen cycles（P < 0.001 for all）. In general，elective SET showed a higher pregnancy rate than obliged cycles. There was no significant difference between the elective and obliged frozen cycles of D5 or D6 embryos regarding clinical pregnancy rate（P = 0.074 and P = 0.596，respectively）. Elective D5 embryo transfer group had a higher pregnancy rate than that of the obliged group（P = 0.011）. However，there was no significant difference of clinical pregnancy rate between elective and obliged groups of D6 embryos（P = 0.979）. In non-PGT cycles，clinical pregnancy rate was significantly different among different age groups of either elective/obliged or fresh/ frozen cycles（P < 0.001）. Obliged D3 and D6 embryo transfer groups showed the lowest pregnancy rate，and in PGT cycles of patients under 40，D5 embryo showed a higher pregnancy rate than that of D6 group as a whole（P < 0.001）.【Conclusion】The outcome of SET strategy seemed good in the last 2 years. In order to avoid perinatal complications caused by multiple fetuses，clinicians and patients should actively promote and choose SET.

Live birth outcomes of vitrified embryos generated under growth hormone stimulation are improved for women categorized as poor-prognosis / 대한생식의학회지

OBJECTIVE: To determine the clinical pregnancy (CP) and live birth (LB) rates arising from frozen embryo transfers (FETs) that had been generated under the influence of in vitro fertilization (IVF) adjuvants given to women categorized as poor-prognosis.METHODS: A registered, single-center, retrospective study. A total of 1,119 patients with first FETs cycle include 310 patients with poor prognosis (109 treated with growth hormone [GH], (+)GH group vs. 201 treated with dehydroepiandrosterone, (–)GH group) and 809 patients with good prognosis (as control, (–)Adj (Good) group).RESULTS: The poor-prognosis women were significantly older, with a lower ovarian reserve than the (–)Adj (Good) group, and demonstrated lower chances of CP (p<0.005) and LB (p<0.005). After adjusting for confounders, the chances of both CP and LB in the (+)GH group were not significantly different from those in the (–)Adj (Good) group, indicating that the poor-prognosis patients given GH had similar outcomes to those with a good prognosis. Furthermore, the likelihood of LB was significantly higher for poor-prognosis women given GH than for those who did not receive GH (p<0.028). This was further confirmed in age-matched analyses.CONCLUSION: The embryos cryopreserved from fresh IVF cycles in which adjuvant GH had been administered to women classified as poor-prognosis showed a significant 2.7-fold higher LB rate in subsequent FET cycles than a matched poor-prognosis group. The women with a poor prognosis who were treated with GH had LB outcomes equivalent to those with a good prognosis. We therefore postulate that GH improves some aspect of oocyte quality that confers improved competency for implantation.

Analysis of pregnancy outcomes and influencing factors of single embryo transfer and double embryo transfer by in vitro fertilization and embryo transfer / 上海交通大学学报（医学版）

Objective • To compare the pregnancy outcomes between the patients undergoing single embryo transfer and double embryo transfer by in vitro fertilization and embryo transfer, and analyze the influencing factors. Methods • From Jan. 2011 to Jun. 2016, women who underwent single embryo transfer or double embryo transfer with in vitro fertilization and embryo transfer and successfully conceived in Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine were followed up to the pregnancy outcomes. According to the number of embryo transfer, the patients were divided into single embryo transfer group and double embryo transfer group. Univariate analysis (t test, Chi-square test) and multivariate Logistic regression analysis were used to compare the pregnancy outcomes between two groups, and analyze the influencing factors of adverse outcomes. Results • A total of 19 030 patients (98.69%) were followed up to the pregnancy outcomes. Stratified analysis showed that there were significant differences in the composition of pregnancy outcomes (P=0.000) and the number of live births (P=0.000) between two groups. For the neonatal birth quality, the infants born by the patients with single embryo transfer had higher birth weights than those born by the patients with double embryo transfer (P=0.000), and the proportions of newborns with low birth weights and full-term newborns with low birth weights were higher among the patients with double embryo transfer compared to those with single embryo transfer (P=0.000). In addition, there was no statistically significant difference in he incidence of birth defects between the infants born by the patients with single embryo transfer and double embryo transfer. Multivariate Logistic regression analysis showed that the risk of abortion or labor induction among the patients with double embryo transfer was higher than those with single embryo transfer with age, infertility causes and embryo type adjusted (OR=0.88, P=0.025). Conclusion • The risk of adverse pregnancy outcomes is higher among the patients with double embryo transfer than those with single embryo transfer.

Estudio genético preimplantación para aneuploidias: resultados de la transición entre diferentes tecnologías / Preimplantation genetic testing for aneuploidies PGT-A: Results of the transition between different technologies

Resumen OBJETIVO Comunicar los resultados obtenidos del análisis del estudio genético preimplantación para aneuploidias en dos centros de reproducción asistida de México en un periodo de tres años, utilizando dos diferentes técnicas moleculares. MATERIALES Y MÉTODOS Estudio observacional, retrospectivo, en donde se reporta el resultado de blastocistos sometidos a preimplantación para aneuploidias durante 2014-2017, en dos centros de reproducción asistida (Ciudad de México y Guadalajara). RESULTADOS Se analizaron 404 blastocistos de 129 pacientes (edad promedio 39 ± 4 años). Los embriones se dividieron en dos grupos según la técnica aplicada: 76 por a-CGH y 328 por secuenciación de nueva generación. El porcentaje de embriones euploides fue de 33%. Las aneuploidias numéricas fueron las más frecuentes. Hasta la terminación del estudio se habían transferido 69 embriones euploides con tasas de implantación de 78% para secuenciación de nueva generación y de 57% para a-CGH. CONCLUSIONES La tasa de implantación reportada en este estudio fue mayor con el análisis de preimplantación para aneuploidias por secuenciación de nueva generación. Los resultados reportados en nuestra experiencia soportan la necesidad de favorecer una opción de transferencia de embrión único. Es importante reconocer los retos de las nuevas tecnologías y la necesidad de técnicas moleculares más sensibles.

Abstract OBJECTIVE Communicate the results obtained from the analysis of the preimplantation genetic study for aneuploidy in two centers of assisted reproduction in Mexico in a period of three years, using two differentmolecular techniques. MATERIALS AND METHODS Descriptive, retrospective study, which reports the blastocysts PGT-A results, over 2014-2017, in two Fertility Centers (Ciudad de México and Guadalajara). The embryos where divided in two groups by their molecular techniques studied: 76 by a-CGH and 328 by NGS RESULTS We analyzed a total of 404 blastocysts from 129 patients (mean age 39 ± 4 years), with two different molecular techniques: a-CGH and NGS. The euploid embryos percentage was 33%. The numerical aneuploidies were the most frequent. Up to the ending of the study, 69% of the euploid embryos had been transferred. The implantation rates were 78% for those analyzed by NGS and 57% with a-CGH. CONCLUSIONS The implantation rate was bigger with the PGT-A by NGS. Our results reported, supports a single embryo transfer policy. It is important to recognize the challenges of new technologies and the need for more sensitive molecular techniques.

Retrospective study of single vitrified-warmed blastocyst transfer cycles according to the presence of morphokinetic variables / 대한생식의학회지

This study retrospectively assessed whether time-lapse data relating to developmental timing and morphology were associated with clinical outcomes, with the eventual goal of using morphokinetic variables to select embryos prospectively for cryopreservation. In this study, we examined the clinical outcomes of single vitrified-warmed blastocyst transfer cycles that were cultured in a time-lapse incubation system. The morphokinetic variables included uneven pronuclei, an uneven blastomere, multinucleation, and direct, rapid, and irregular division. A total of 164 single vitrified-warmed blastocyst transfer cycles were analyzed (102 cycles of regularly developed blastocysts and 62 cycles of blastocysts with morphokinetic variables). No significant differences in the age of females or the standard blastocyst morphology were found between these two groups. The regularly developed blastocysts showed significantly higher implantation and clinical pregnancy rates than the blastocysts exhibiting morphokinetic variables (30.4% vs. 9.7% and 37.3% vs. 14.5%, respectively; p < 0.01). The blastocysts that exhibited morphokinetic variables showed different mean development times compared with the regularly developed blastocysts. Although morphokinetic variables are known to have fatal impacts on embryonic development, a considerable number of embryos developed to the blastocyst stage. Morphokinetic variables had negative effects on the implantation and clinical pregnancy rates in vitrified-warmed blastocyst transfer cycles. These findings suggest that blastocysts cultured in a time-lapse incubation system should be considered for selective cryopreservation according to morphokinetic variables.

Comparación de resultados posterior a la transferencia electiva de embrión único euploide en ciclos frescos vs criopreservados / Results after elective single embryo transfer: Fresh euploid embryo transfer versus frozen-thawed transfer cycles

Resumen OBJETIVO: analizar las tasas de implantación y embarazo en ciclos de fertilización in vitro con transferencia electiva de un solo blastocisto, con control del factor embriónico mediante transferencia de embriones euploides. MATERIALES Y MÉTODOS: estudio retrospectivo de pacientes atendidas entre los años 2010 a 2015 en un centro privado, en protocolo de fertilización in vitro y que tuvieron, por lo menos, un embrión euploide disponible para transferencia. Para fines de estudio las pacientes se dividieron en dos grupos: 1) transferencia de embriones frescos y 2) embriones desvitrificados. Las variables categóricas se analizaron con χ2 y prueba exacta de Fisher; las variables continuas con t de Student. Se estableció significación estadística con un valor de p < 0.05. Para el análisis estadístico se usó SAS-STAT versión 9.4. RESULTADOS: se incluyeron 637 ciclos (frescos: 243 vs criopreservados: 394). La tasa de embarazo fue de 75.5% (n = 289) vs 66.3% (n = 159), embarazo clínico 62.5% (n = 235) vs 53.1% (n = 127) que fue estadísticamente significativo a favor de los ciclos criopreservados. Las tasas de embarazo múltiple fueron bajas (1.7 vs 1.6%) en ambas cohortes. CONCLUSIONES: la transferencia de un solo embrión disminuye significativamente la incidencia de embarazos múltiples y la morbilidad materna y neonatal. El mejor pronóstico en ciclos de fertilización in vitro homólogos se consigue con la transferencia de un solo embrión genéticamente equilibrado, en un ciclo posterior de preparación endometrial sintética o natural.

Abstract OBJECTIVE: To analyze the implantation and pregnancy rates in cycles of in vitro fertilization with elective transfer of a single blastocyst, with control of the embryonic factor by transfer of euploid embryos. MATERIALS AND METHODS: Retrospective analysis who included patients that underwent IVF and had at least one euploid embryo available for transfer between 2010 and 2015 on a single academic private practice. Cohorts were segregated in fresh embryo transfers (ET) vs frozen/thawed ET. Categorical variables were analyzed with χ2 and Fisher test when appropriate. Continuous variables were analyzed with Students t test. P value < 0.5 was established as statistically significant. SAS/STAT 9.4 was used for analysis. RESULTS: Six hundred and thirty-seven euploid SETs cycles (fresh cycle: n = 243; frozen/thaw cycle: n = 394) were identified. Pregnancy (75.5% (n=289) vs 66.3% (n = 159)) and clinical pregnancy rates (PR) (62.5% (n = 235) vs 53.1% (n = 127)) were statistically higher in the frozen/thaw cycles. Low rates of multiple pregnancies (1.7 and 1.6%) were observed in both cohorts. CONCLUSIONS: In one of the largest studies to date, a euploid SET during a frozen/thaw cycle showed significantly improved pregnancy and clinical PR compared to embryo transfer in fresh cycles. Single embryo transfer significantly reduces the incidence of multiple gestation and improves maternal and neonatal outcomes. An optimal outcome is achieved by the performance of a SET in FET cycles.

Heterotopic pregnancy after a single embryo transfer

Heterotopic pregnancy is a rare and life-threatening condition which is defined as coexistent intrauterine and ectopic gestation. The risk of ectopic and heterotopic pregnancy is increasing due to the increased risk of multiple pregnancies with the aid of assisted reproductive technologies. However, it hardly happens in the setting of single embryo transfer, since single embryo transfer significantly reduces the incidence of multiple pregnancies. Surprisingly, we experienced a case of heterotopic pregnancy after a single embryo transfer caused by coincidental natural pregnancy during assisted reproductive technologies. An infertile woman who underwent, during her natural cycle, transfer of a single embryo that had been cryopreserved for 3 years was found to be heterotopically pregnant. After an early and successful management with laparoscopic right salpingectomy, she finally reached at full-term vaginal delivery.

Clinical outcomes of single versus double blastocyst transfer in fresh and vitrified-warmed cycles / 대한생식의학회지

OBJECTIVE: Assisted reproductive technology has been associated with an increase in multiple pregnancies. The most effective strategy for reducing multiple pregnancies is single embryo transfer. Beginning in October 2015, the National Supporting Program for Infertility in South Korea has limited the number of embryos that can be transferred per in vitro fertilization (IVF) cycle depending on the patient's age. However, little is known regarding the effect of age and number of transferred embryos on the clinical outcomes of Korean patients. Thus, this study was performed to evaluate the effect of the number of transferred blastocysts on clinical outcomes. METHODS: This study was carried out in the Fertility Center of CHA Gangnam Medical Center from January 2013 to December 2014. The clinical outcomes of 514 women who underwent the transfer of one or two blastocysts on day 5 after IVF and of 721 women who underwent the transfer of one or two vitrified-warmed blastocysts were analyzed retrospectively. RESULTS: For both fresh and vitrified-warmed cycles, the clinical pregnancy rate and live birth or ongoing pregnancy rate were not significantly different between patients who underwent elective single blastocyst transfer (eSBT) and patients who underwent double blastocyst transfer (DBT), regardless of age. However, the multiple pregnancy rate was significantly lower in the eSBT group than in the DBT group. CONCLUSION: The clinical outcomes of eSBT and DBT were equivalent, but eSBT had a lower risk of multiple pregnancy and is, therefore, the best option.

A retrospective study of single frozen-thawed blastocyst transfer / 대한생식의학회지

OBJECTIVE: To study the clinical outcomes of single frozen-thawed blastocyst transfer cycles according to the hatching status of frozen-thawed blastocysts. METHODS: Frozen-thawed blastocysts were divided into three groups according to their hatching status as follows: less-than-expanded blastocyst (≤EdB), hatching blastocyst (HgB), and hatched blastocyst (HdB). The female age and infertility factors of each group were evaluated. The quality of the single frozen-thawed blastocyst was also graded as grade A, tightly packed inner cell mass (ICM) and many cells organized in the trophectoderm epithelium (TE); grade B, several and loose ICM and TE; and grade C, very few ICM and a few cells in the TE. The clinical pregnancy and implantation rate were compared between each group. The data were analyzed by either t-test or chi-square analysis. RESULTS: There were no statistically significant differences in average female ages, infertility factors, or the distribution of blastocyst grades A, B, and C in each group. There was no significant difference in the clinical pregnancy and implantation rate of each group according to their blastocyst grade. However, there was a significant difference in the clinical pregnancy and implantation rate between each group. In the HdB group, the clinical pregnancy and implantation rate were similar regardless of the blastocyst quality. CONCLUSION: There was an effect on the clinical outcomes depending on whether the blastocyst hatched during single frozen-thawed blastocyst transfer. When performing single frozen-thawed blastocyst transfer, the hatching status of the frozen-thawed blastocyst may be a more important parameter for clinical outcomes than the quality of the frozen-thawed blastocyst.

Comparison of elective single cleavage-embryo transfer to elective single blastocyst-embryo transfer in human IVF-ET / 대한생식의학회지

OBJECTIVE: This study was carried out to compare the clinical outcome of elective single cleavage-embryo transfer (eSCET) to that of elective single blastocyst-embryo transfer (eSBET) in human IVF-ET. METHODS: This study was a retrospective study which analyzed for 614 women who visited the Daegu Maria Clinic from August 2008 to December 2009. All were under 37 years old and had more than 8 mm of endometrial thickness on the day of hCG administration and at least one good quality embryo on day 3. The eSCETs were performed on day 3 (n=450) and the eSBETs were conducted on day 5 (n=164). RESULTS: The numbers of retrieved oocytes, fertilized oocytes, and day 3 good quality embryos were significantly lower in the eSCET group (12.1+/-6.0, 8.2+/-4.6, and 4.2+/-3.1, respectively) compared to the eSBET group (16.7+/-7.2, 12.1+/-5.0, and 8.5+/-4.5, respectively; p<0.001). However, the clinical pregnancy, implantation, on-going pregnancy, and live birth rates of the eSCET group (46.7, 46.9, 40.0, and 36.7%, respectively) were not statistically different from those of the eSBET group (51.2, 51.8, 45.1, and 43.9%, respectively; p=0.318, 0.278, 0.254, and 0.103, respectively). CONCLUSION: These results suggested that elective single embryo transfer should be performed regardless of the developmental stage to women less than 37 years old who had more than 8 mm of endometrial thickness on the hCG administration day and at least one good quality embryo on day 3 in order to reduce the twin pregnancy rate without reducing the whole pregnancy rate.

Comparison of elective single cleavage-embryo transfer to elective single blastocyst-embryo transfer in human IVF-ET / 대한생식의학회지

OBJECTIVE: This study was carried out to compare the clinical outcome of elective single cleavage-embryo transfer (eSCET) to that of elective single blastocyst-embryo transfer (eSBET) in human IVF-ET. METHODS: This study was a retrospective study which analyzed for 614 women who visited the Daegu Maria Clinic from August 2008 to December 2009. All were under 37 years old and had more than 8 mm of endometrial thickness on the day of hCG administration and at least one good quality embryo on day 3. The eSCETs were performed on day 3 (n=450) and the eSBETs were conducted on day 5 (n=164). RESULTS: The numbers of retrieved oocytes, fertilized oocytes, and day 3 good quality embryos were significantly lower in the eSCET group (12.1+/-6.0, 8.2+/-4.6, and 4.2+/-3.1, respectively) compared to the eSBET group (16.7+/-7.2, 12.1+/-5.0, and 8.5+/-4.5, respectively; p<0.001). However, the clinical pregnancy, implantation, on-going pregnancy, and live birth rates of the eSCET group (46.7, 46.9, 40.0, and 36.7%, respectively) were not statistically different from those of the eSBET group (51.2, 51.8, 45.1, and 43.9%, respectively; p=0.318, 0.278, 0.254, and 0.103, respectively). CONCLUSION: These results suggested that elective single embryo transfer should be performed regardless of the developmental stage to women less than 37 years old who had more than 8 mm of endometrial thickness on the hCG administration day and at least one good quality embryo on day 3 in order to reduce the twin pregnancy rate without reducing the whole pregnancy rate.