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.

One Plus One is Better than Two: An Approach Towards a Single Blastocyst Transfer Policy for All IVF Patients.

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 frozen-thawed DET, while drastically reducing the rate of multiple pregnancies.

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.

Effectivity of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) when male factor is absent: a perspective point of view.

An objective and individualized approach of in vitro fertilization techniques tends to decrease costs and improve the experience of infertile couples during treatment. The use of available technologies to diagnose and treat infertility based on scientific evidence seems to be the best practice, which is the guideline that motivates this review on the available techniques for laboratory oocyte insemination. Conventional IVF, the pioneering technique, was initially used in the treatment of tubal obstruction infertility, successfully expanding the treatment of infertile couples presenting with several other factors. However, it was less effective in cases of severe male factor infertility. Intracytoplasmic sperm injection, which was developed in 1992, proved to be the method of choice for treating couples with severe male factor infertility. Since then, it has been increasingly used regardless of the infertility factor. This review discusses the effectiveness of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) when the male factor is absent in all aspects, as technical and clinical outcomes, associated risks, adjustments for using with other technologies and costs. Finally we discuss the advantages and disadvantages of each one, with all aspects reviewed.

Delivering embryos following 10 years of cryopreservation, using unpaired freeze/thaw techniques: A case report.

Although frozen embryo transfer is a widely established route for assisted reproduction, successful frozen embryo transfer using embryos that have undergone long term cryopreservation remains relatively unexplored, and its efficacy remains a matter of some debate. This case report describes two successful frozen embryo transfer conceptions in the same patient, one after 3 months of cryopreservation and the second 10 years after cryopreservation. These embryos were cryopreserved using the slow freezing technique and were thawed using an unpaired technique (ultra-rapid warming) after 10 years of storage.

A review of initial data on pregnancy during the COVID-19 outbreak: implications for assisted reproductive treatments.

The current outbreak of the novel 2019 coronavirus disease (COVID-19) started in China in December 2019 and has since spread to several other countries. On March 25, 2020, a total of 375,498 cases had been confirmed globally with 2,201 cases in Brazil, showing the urgency of reacting to this international public health emergency. While in most cases, mild symptoms are observed, in some cases the infection leads to serious pulmonary disease. As a result, the possible consequences of the COVID-19 outbreak for pregnant women and its potential effects on the management of assisted reproductive treatments, demand attention. In this review, we summarize the latest research progress related to COVID-19 epidemiology and the reported data of pregnant women, and discuss the current evidence of COVID-19 infections during pregnancy and its potential consequences for assisted reproductive treatments. Reported data suggest that symptoms in pregnant women are similar to those in other people, and that there is no evidence for higher maternal or fetal risks. However, considering the initial data and lack of comprehensive knowledge on the pathogenesis of SARS-CoV-2 during pregnancy, human reproduction societies have recommended postponing the embryo transfers and do not initiate new treatment cycles. New evidence must be considered carefully in order to adjust these recommendations accordingly at any time and to guide assisted reproductive treatments.

A review of initial data on pregnancy during the COVID-19 outbreak: implications for assisted reproductive treatments

The current outbreak of the novel 2019 coronavirus disease (COVID-19) started in China in December 2019 and has since spread to several other countries. On March 25, 2020, a total of 375,498 cases had been confirmed globally with 2,201 cases in Brazil, showing the urgency of reacting to this international public health emergency. While in most cases, mild symptoms are observed, in some cases the infection leads to serious pulmonary disease. As a result, the possible consequences of the COVID-19 outbreak for pregnant women and its potential effects on the management of assisted reproductive treatments, demand attention. In this review, we summarize the latest research progress related to COVID-19 epidemiology and the reported data of pregnant women, and discuss the current evidence of COVID-19 infections during pregnancy and its potential consequences for assisted reproductive treatments. Reported data suggest that symptoms in pregnant women are similar to those in other people, and that there is no evidence for higher maternal or fetal risks. However, considering the initial data and lack of comprehensive knowledge on the pathogenesis of SARS-CoV-2 during pregnancy, human reproduction societies have recommended postponing the embryo transfers and do not initiate new treatment cycles. New evidence must be considered carefully in order to adjust these recommendations accordingly at any time and to guide assisted reproductive treatments.(AU)

Should single embryo transfer be used in patients with any kind of infertility factor? Preliminary outcomes.

OBJECTIVE: Multiple embryos have been transferred to compensate for low implantation rates, which in turn, increase the likelihood of multiple pregnancies. Despite the publication of clinical guidelines and a reduction in the number of embryos transferred, double embryo transfer still is the most common practice. There is no clear evidence of who should receive the single embryo transfer (SET), and it is more commonly indicated for patients of good prognosis. However, it is not clear how much the presence of other infertility factors can affect the SET prognosis. The aim of this study was to evaluate differences in clinical pregnancy rates (CPR) of frozen-thawed SET cycles for women presenting with different infertility factors. METHODS: Retrospective cohort study evaluating 305 frozen-thawed SET cycles performed in the last 10 years in a private IVF center. We included patients undergoing ovarian stimulation cycles, using ejaculated sperm and a frozen-thawed ET. Embryos were routinely vitrified and warmed up, and the blastocysts were transferred after endometrium preparation. The cycles were categorized according to the infertility factor classified by the Society for Assisted Reproductive Technologies (SART) as anatomic female factor (n=55), endocrine female factor (n=26), endometriosis (n=37), male factor (n=60), ovarian insufficiency (n=26), unexplained (n=24), multiple factors (n=45) and other (n=32). CPR were compared between the groups and the multivariate analysis was performed to evaluate the association of each infertility factor and the CPR, adjusted for confounders. RESULTS: The women varied in age from 18 to 44 years (35.9±3.8), presented Body Mass Index of 22.4±3.1kg/m2, baseline serum FSH of 7.4±8.3 IU/ml, and had a mean of 11.0±8.4 MII oocytes recovered and 6.4±5.3 embryos cryopreserved. The CPR, according to infertility factors were: anatomic female factor (25.9%), endocrine female factor (30.8%), endometriosis (27.8%), male factor (20.7%), ovarian insufficiency (21.7%), unexplained (9.5%), multiple factors (17.1%) and other (20.7%). Multivariate analysis did not show significant association of infertility factors and CPR adjusted for confounders. CONCLUSIONS: Patients presenting different infertility factors seem to have a satisfactory CPR for a SET cycle, except those with unexplained infertility. This is a preliminary outcome and the number of patients by category is small; in addition, the retrospective characteristics of the study are its limitations. Overall, our findings suggest that patients presenting any infertility factor, except unexplained infertility, are suitable to receive a SET with satisfactory outcomes.

The impact of balanced reciprocal translocation - 46,XX,t(7;17) (p13;q24) probably involving the SOX9 gene in the in vitro fertilization with own oocytes evaluated by preimplantation genetic testing or donated oocytes.

Preimplantation genetic testing (PGT) for in vitro fertilization (IVF) - also known as PGT for Structural Rearrangements (PGT-SR) - has emerged as an option for at-risk couples carrying balanced translocations. The female in the couple featured in this case report is a carrier of a balanced reciprocal translocation who underwent IVF. PGT showed all her embryos were aneuploid. She subsequently had two cycles using donor oocytes, which ended in miscarriages.

Comparação entre menotropina altamente purificada e folitropina alfa para hiperestimulação ovariana controlada após supressão hipofásica nos ciclos de ICSI / A comparison of menotropin, highly-purified menotropin and follitropin alfa for controlled ovarian stimulation after pituitary down-regulation in ICSI cycles

OBJETIVO: Comparar a eficácia clínica entre três tipos de gonadotrofinas para a estimulação ovariana após a supressão hipofisária nos ciclos de ICSI. MATERIAL E MÉTODOS: Analisou-se retrospectivamente 865 ciclos consecutivos de ICSI envolvendo supressão hipofisária previamente à hiperestimulação ovariana controlada (HOC). A HOC foi realizada com menotropina (HMG: Menogon, Ferring; n=299), menotropina altamente purificada (HMG-HP: Menopur, Ferring; n=330) e FSH recombinante (r-hFSH: Gonal-F, Serono; n=236). Os protocolos laboratoriais e clínicos permaneceram inalterados ao longo do tempo, os últimos diferindo apenas no tipo de gonadotrofina utilizada, que foram introduzidas seqüencialmente na prática clínica, iniciando com o HMG, seguido pelo HMG-HP, e finalmente o r-hFSH. Os parâmetros de interesse primário foram a taxa de nascidos vivos e as doses totais de gonadotrofina utilizadas por ciclo, por gestação e por nascido vivo. Análise comparativa foi realizada com ANOVA, Kruskal-Wallis e Chi-quadrado quando apropriado. RESULTADOS: As taxas de nascidos vivos não foram significativamente diferentes entre os grupos HMG (26,4%), HMG-HP (34,6%) e r-hFSH (32,4%; p igual a 0,09). A dose total de gonadotrofina utilizada por ciclo foi significativamente superior nos grupos HMG (2.685±720UI) e HMG-HP (2.903 mais ou menos 867UI) em comparação com o r-hFSH (2.268 mais ou menos 747UI; p menor que 0,001). Diferenças relativas de 15,7% e 45,2%, e de 11% e 19,8% foram observadas a favor do r-hFSH em comparação ao HMG e HMG-HP, respectivamente, no que se refere às quantidades de gonadotrofina necessárias para se obter cada gestação e cada nascido vivo. CONCLUSÕES: Taxas de nascidos vivos similares foram obtidas com HMG, HMG-HP e r-hFSH quando utilizadas para HOC após supressão hipofisária nos ciclos de ICSI. Doses totais significativamente menores de r-hFSH foram utilizadas por ciclo em comparação às menotropinas. Para cada nascido vivo, quantidades consideravelmente maiores d...