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.

Estrategia combinada en fertilización in vitro: mínima estimulación y transferencia de embrión único con diagnóstico genético. Experiencia de 3 años en dos centros de reproducción en México / A combined in-vitro fertilization strategy: minimal stimulation IVF, PGT-A and SET. Results from 3 years' experience at two IVF centers in Mexico

Resumen OBJETIVO: Evaluar los desenlaces de una estrategia combinada para fertilización in vitro: mínima estimulación ovárica, diagnóstico genético preimplantación para aneuploidias y transferencia de un solo embrión. MATERIALES Y MÉTODOS: Estudio de cohorte, retrospectivo, efectuado en dos centros de reproducción de México, en un periodo de tres años. Se incluyeron pacientes entre 25 y 45 años, en protocolo de fertilización in vitro, con mínima estimulación, diagnóstico genético preimplantación para aneuploidias (PGT-A) y transferencia de embrión único. El diagnóstico genético preimplantación se estableció mediante microarreglos y secuenciación de nueva generación (NGS). Para el análisis estadístico se integraron 5 grupos, según la edad de las pacientes: menores de 35 años; 35 a 37 años; 38 a 40 años; 41 a 42 años; y mayores de 42 años. Mediante estadística descriptiva se analizaron las variables numéricas y categóricas. RESULTADOS: Se analizaron 175 ciclos, en 125 pacientes (edad promedio: 39 años ± 5). Se obtuvieron, en promedio, 5 óvulos por ciclo. La tasa de fertilización fue de 86.5% y la de blastocisto por óvulo fertilizado de 50.7%. Se tomó biopsia para diagnóstico genético preimplantación para aneuploidias a 404 embriones. La tasa general de euploidia fue de 33%. Se efectuaron 69 transferencias de embrión único, con una tasa de embarazo por transferencia de 71%. La tasa de nacimiento por transferencia fue de 60.8% (42 nacimientos). CONCLUSIONES: La combinación de mínima estimulación, diagnóstico genético preimplantación para aneuploidias y transferencia de embrión único, es un procedimiento adecuado para alcanzar una tasa de nacimiento alta.

Abstract OBJECTIVE: To evaluate results of a combined approach in IVF, using minimal stimulation, preimplantation genetic testing for aneuploidy, and single blastocyst transfer. MATERIALS AND METHODS: Retrospective cohort study over a three years' period in two fertility centers in Mexico. A total of 125 patients were included, between 25 and 45 years old, with minimal stimulation IVF, preimplantation genetic testing for aneuploidy (PGT-A) and single euploid embryo transfer. PGT was performed using microarrays and next generation sequencing (NGS). RESULTS: A total of 175 cycles (mean age: 39 years old) were analyzed in 125 patients. On average, five eggs were collected per cycle; fertilization rate was 86.57%; blastocyst rate was 50.7% per fertilized egg. Only 33% of embryos were euploid. Pregnancy rate per transferred embryo was 71%. Live birth rate was 60.8% (42 births). CONCLUSIONS: A combination of minimal stimulation, PGT-A and single blastocyst embryo transfer can yield a high live birth rate.

Influence of the Single Live Birth Outcome Following Transfer of Vitrified Blastocyst and Blastocyst Cultured from Thawing Cleavage Embryo / 中山大学学报(医学科学版)

[Objective]To compare the single live birth outcomes of blastocyst transfer between vitrified blastocyst and blastocyst cultured from thawing cleavage embryo,so as to choose the best scheme of blastocyst transfer.[Methods]Retrospective analysis of the single live birth clinical data of 1 037 vitrified blastocyst compared with 690 blastocyst cul-tured from thawing cleavage embryo undergoing frozen embryo transplantation(FET)from January 2014 to October 2016 was performed.Mail outcome were including gestational age,neonatal weight,proportion of male neonate,preterm birth rate,very preterm birth rate,low birthweight rate,very low birthweight rate,congenital anomalies rate.[Results]There were no differences between the two groups for gestational age,neonatal weight,proportion of Live birth,health baby and stillbirth(P>0.05). There were no differences in proportion of male neonate(AOR 1.07,95% CI 0.86~1.34),preterm birth rate(AOR 0.7,95% CI 0.49~1.01),very preterm birth rate(AOR 1.47,95% CI 0.55~3.96),low birthweight rate (AOR 1.38,95% CI 0.86~2.22),very low birthweight rate(AOR 0.76,95% CI 0.20~2.83),congenital anomalies rate (AOR 1.58,95% CI 0.66~3.76,P>0.05).[Conclusion]The blastocyst may be the preferable stage for vitrifying and transfer currently which can obtain good neonatal outcomes.

Influence of blastocysts morphological score on pregnancy outcomes and neonate′s condition in vitrified-warmed transfer cycles / 实用医学杂志

Objective To estimate the effect of blastocysts morphological score on pregnancy outcomes and neonate′s condition in vitrified-warmed single-blastocyst transfer cycles. Methods A retrospective analysis of 586 cycles of vitrified-warmed single-blastocyst transfer from Mar. 2010 to Feb.2016 was performed and the influ-ence of day of vitrification,inner cell mass(ICM)and trophectoderm(TE)scores on pregnancy outcomes and neo-nate′s condition were observed. Results There were no significant differences in clinical pregnancy rate,birth weight and sex ration of newborn between different vitrification day,ICM score and TE score.The day of vitrifica-tion and ICM score can significantly influence pregnancy loss rate,and were the two primary predictors of pregnan-cy loss rate. Vitrification day,ICM score and TE score exerted significant influence on live birth rate(P < 0.05) and TE score was the primary factor of live birth rate. Conclusions Day 5 vitrified blastocysts with higher quality of ICM and TE can provide high live birth rate and low pregnancy loss rate,but it could not predict the weight and gender of the newborn.

Predictive Value of Initial Serum Human Chorionic Gonadotropin Levels for Pregnancies after Single Fresh and Frozen Blastocyst Transfer / 华中科技大学学报（医学）（英德文版）

As one of the earliest markers for predicting pregnancy outcomes,human chorionic gonadotropin (hCG) values have been inconclusive on reliability of the prediction after frozen and fresh embryo transfer (ET).In this retrospective study,patients with positive hCG (day 12 after transfer) were included to examine the hCG levels and their predictive value for pregnancy outcomes following 214 fresh and 1513 vitrified-warmed single-blastocyst transfer cycles.For patients who got clinical pregnancy,the mean initial hCG value was significantly higher after frozen cycles than fresh cycles,and the similar result was demonstrated for patients with live births (LB).The difference in hCG value existed even after adjusting for the potential covariates.The area under curves (AUC) and threshold values calculated by receiver operator characteristic curves were 0.944 and 213.05 mIU/mL for clinical pregnancy after fresh ET,0.894 and 399.50 mIU/mL for clinical pregnancy after frozen ET,0.812 and 222.86 mIU/mL for LB after fresh ET,and 0.808 and 410.80 mIU/mL for LB after frozen ET with acceptable sensitivity and specificity,respectively.In conclusion,single frozen blastocyst transfer leads to higher initial hCG values than single fresh blastocyst transfer,and the initial hCG level is a reliable predictive factor for predicting IVF outcomes.

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.

Clinical outcomes of different transferring methods in patients who received different numbers of oocytes / 西安交通大学学报(医学版)

Objective To compare the clinical outcomes of two D3 embryo and single blastocyst transfer in patients retrieving different oocytes, so as to provide data support for selecting a clinical transfer strategy. Methods We made a retrospective analysis of patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI)between January and December 2014 in the Reproductive Medicine Center,the Third Affiliated Hospital of Zhengzhou University.The patients were divided into three groups according to the number of oocytes received:Group A (5-9 oocytes),Group B (10 - 14 oocytes)and Group C (≥ 1 5 oocytes).Patients in each group all received four different transfer methods as follows:transfer of two fresh D3 embryos (a ),transfer of one fresh blastocyst (b ),transfer of two D3 frozen embryos (c ),and transfer of one frozen blastocyst (d ).We compared the 2PN fertilization rate of oocytes,rate of available embryos and rate of good embryos among the three groups.We also compared the embryo implantation rate,biochemical pregnancy rate,clinical pregnancy rate, multiplets rate and abortion rate among the four transfer methods in each group.Results ① There were 667, 573,and 479 transfer cycles in Group A,Group B and Group C,respectively.The 2PN fertilization rate of IVF and available embryos rate was significantly higher in Group A than in Group B and Group C (P =0.003/P 0.05),but the implantation rate of c was significantly lower than that of a and d (P =0.027/0.020),d had a higher implantation rate than a and c in Group B (P =0.005/0.001).In Group C,the biochemical pregnancy rate and clinical pregnancy rate of d were significantly higher than those of a (P =0.048/0.027)and c (P =0.003/0.001).Patients in Group C also had a higher implantation rate than D3 embryos (P <0.05).③ The multiple pregnancy rate of single blastocyst transfer decreased compared with D3 embryos transfer in the three groups (P <0.05).Conclusion Single blastocyst transfer has both higher implantation rate and lower multiple pregnancy rate in high response patients (1 5 or more oocytes received).For patients who received 5-9 and 10-14 oocytes,D3 embryos have a similar clinical pregnancy rate with that of single blastocyst but a higher multiple pregnancy rate.Single vitrified-warmed blastocyst transfer has a higher clinical pregnancy rate.It is the best transfer method for patients who received more than 10 oocytes.

Clinical value of blastocyst transfer in vitrified-thawed cycles / 重庆医学

Objective To evaluate the clinical value of frozen-thawed blastocyst transfer and the blastocyst derived from frozen-thawed cleavage stage embryo transfer.Methods The data of 5 1 8 cycles in reproductive medicine center of the hospital from Sep-tember 2012 to August 2013 were analyzed retrospectively.According to the frozen-embryos type,all patients were divided into three groups,group A:frozen-thawed blastocyst transfer,129 cycles;group B:blastocysts derived from frozen-thawed cleavage stage embryos transfer,123 cycles;group C:frozen-thawed cleavage embryos transfer,266 cycles.The clinical outcomes of all groups were compared with each other,and the rates of blastocyst formation and cancellation were compared between group A and group B.Re-sults The rates of biochemical pregnancy,clinical pregnancy and embryo implantation in group A(70.5%,61.2%,42.3%)and group B(67.5%,58.2%,40.2%)were significantly higher than group C(53.0%,42.5%,23.1%)(P0.05);there were no significant differences in the blastocyst formation rates of the high quality cleavage embryos at D3 in fresh cycles and the frozen-thawed cleavage embryos(62.5%vs.57.7%)(P>0.05)and those two groups were both significantly higher than the poor quality cleavage embryos at D3 in fresh cycles(20.3%)(P<0.05).Conclusion Blastocyst transfer in vitrified-thawed cycles could get rel-atively satisfactory clinical outcomes.There are higher blastocyst formation rate and better clinical outcomes of transfer blastocyst derived from frozen-thawed cleavage embryo.

A Comparative Study Between Cleavage Stage Embryo Transfer at Day 3 and Blastocyst Stage Transfer at Day 5 in IVF/ICSI on Clinical Pregnancy Rates.

Objective: To evaluate the efficacy of blastocyst transfer in comparison with cleavage stage transfer. Study design: A randomized, prospective study was conducted in Infertility Clinic, Dept. of Obstetrics and Gynecology, Mahatma Gandhi Hospital, Jaipur on 300 patients aged 25-40 years undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ ICSI) cycle from May 2010 to April 2011. When three or more Grade I embryos were observed on Day 2 of culture, patients were divided randomly into two study groups, cleavage stage transfer and blastocyst transfer group having 150 patients each. Primary outcomes evaluated were, clinical pregnancy rate and implantation rate. The results were analyzed using proportions, standard deviation and Chi-square test. Results: Both the groups were similar for age, indication and number of embryos transferred. Clinical pregnancies after blastocyst transfer were significantly higher 66 (44.0%) compared to cleavage stage embryo transfer 44 (29.33%) (p < 0.01). Implantation rate for blastocyst transfer group was also significantly higher (p < 0.001). Conclusion: Blastocyst transfer having higher implantation rate and clinical pregnancy rate leads to reduction in multiple pregnancies.

Preliminary clinical outcome of novel strategy for the maximization of cumulative pregnancy rates per retrieval in normal responders / 대한생식의학회지

OBJECTIVE: We devised a novel strategy, a GnRH antagonist protocol with a GnRH agonist trigger followed by frozen-thawed blastocyst transfers with long zona dissection (LZD). The purpose of this study was to investigate the clinical outcomes of this new strategy according to age. METHODS: Ninety women aged less than 35 (group A) and 32 women aged 35 to 39 (group B) underwent the GnRH antagonist protocol with a GnRH agonist trigger in order to obtain many oocytes and prevent early-onset ovarian hyperstimulation syndrome (OHSS). All oocytes were cultured to the blastocyst stage and all blastocysts grade 3BB or better were cryopreserved. Embryo transfers were only performed in freeze-thaw cycles to prevent late-onset OHSS and to overcome embryo-endometrium dyssynchrony. LZD was performed just after thawing to improve hatching and implantation rates. RESULTS: The average numbers of retrieved oocytes and blastocysts grade 3BB or better were 12.8+/-5.5 and 4.4+/-2.6 in group A and 10.9+/-7.4 and 2.5+/-2.2 in group B, respectively, and OHSS did not occur in any of the women. Implantation rates were 46.7% in group A and 39.3% in group B. Cumulative clinical pregnancy rates per retrieval were 77.8% in group A and 62.5% in group B. Cumulative ongoing pregnancy rates per retrieval were 71.1% in group A and 53.1% in group B. CONCLUSION: GnRH antagonist protocol with GnRH agonist trigger followed by frozen-thawed blastocyst transfers with LZD can generate many blastocysts without OHSS and maximize cumulative pregnancy rates per retrieval. This strategy is more effective in young women aged less than 35 than in women aged 35 to 39.

Comparative study between natural cycles and programmed cycles using exogenous steroid hormones for endometrial preparation in cryopreserved-thawed blastocyst transfer / 대한산부인과학회지

OBJECTIVE: The objective of this study was to compare the outcomes of cryopreserved-thawed blastocyst transfer (CT-BT) in natural or programmed cycles using exogenous steroid hormones. METHODS: A total of 221 CT-BT cycles were included and divided into two groups according to endometrial preparation protocols. In natural cycle group (n=116), monitoring was performed by transvaginal ultrasonography to detect ovulation. In programmed cycle group (n=105), oral estradiol valerate, 6 mg/day, was started on the third day of the menstrual cycle and administered continuously, and progesterone in oil 100 mg i.m. daily injection was started on cycle day 15. CT-BTs were performed on five days after ovulation in natural cycles and five days after the initiation of progesterone administration in programmed cycles. Pregnancy rates, implantation rates, and other clinical characteristics of the two groups were compared. RESULTS: Clinical characteristics of study subjects did not differ between the two groups. Post-thaw survival rates, number of transferred blastocysts, and number of good-quality blastocysts were not different. There were no statistically significant differences in implantation rates (21.1% vs. 19.4%), clinical pregnancy rates (36.2% vs. 36.2%), and ongoing pregnancy rates (28.4% vs. 27.6%) between the two groups. CONCLUSIONS: No statistically significant differences were found in pregnancy rates and implantation rates between the two protocols. Our results suggest that both protocols are equally effective for endometrial preparation in CT-BT cycles.

A Case of Two Sets of Monozygotic Twins after ICSI and Blastocyst Transfer / 대한산부인과학회지

One of the most important complications in assisted reproductive technology (ART) is multiple pregnancy, which is associated with an increased risk of maternal and perinatal complications. There have been several attempts to achieve the highest pregnancy rates while minimizing multiple pregnancy rates in in vitro fertilization and embryo transfer (IVF-ET). One approach for this purpose is extended embryo culture and transfer of fewer (one or two) blastocysts. However, there are emerging concerns about the increase of the risk for embryo splitting and subsequent monozygotic multiple pregnancy with this approach. Recently, there have been several reports on the possible increased risk of monozygotic twinning after extended embryo culture and blastocyst transfer. We have experienced a case of two sets of monozygotic twins after intracytoplasmic sperm injection (ICSI) and transfer of two blastocysts. We report the first case of pregnancy of monozygotic twins after blastocysts transfer with a brief review of literature in Korea.

Blastulation and the clinical outcome of the blastocyst transfer in the COH cycles with premature progesterone elevation / 대한산부인과학회잡지

OBJECTIVES: To determine the effect of increased plasma Progesterone(P) level on the day of hCG administration on oocyte /embryo development and implantation after blastocyst transfer in controlled ovarian hyperstimulation (COH) cycle with premature progesterone elevation for IVF-ET. METHODS: Seventy controlled ovarian hyperstimulation cycles for IVF-ET were underwent with GnRH agonist and hMG/FSH in 70 women. Embryos were cocultured up to the blastocyst stage and transferred into the uterine cavity. The cycles were devided into two groups depending on the levels of plasma P on the day of hCG administration, and the clinical results in both groups were analysed and compared each other. High P group was defined when the level of plasma P was higher than 0.9 ng/mL. RESULTS: Fertilization rates, cleavage rates and blastulation rates were similar in the low and high P groups. Blastulation rates were increased in high quality (morphological characteristics) D 2-3 preembryo regardless of the P levels during the late follicular phase(p <0.001). However, clinical pregnancy rate, ongoing pregnancy rate and implantation rate were higher in low P group compared with high P group(p <0.01). CONCLUSIONS: Premature P elevation did not deteriorate the developmental potential of oocyte, but had a harmful effect on pregnancy rate and implantation rate. So we suggest that early ET on the day 2-3 (after ovum pick-up) without delaying another several days to avoid the advanced maturation of secretory endometrium might be better than blastocyst transfer in patients with premature P elevation.

Successful sequential single embryo transfer: A local experience

Our first test tube baby was born about 9 years ago1 and since then we have done about 127 patients resulting in 37 babies with a multiple pregnancy rate of 40 percent. The primary major risk of IVF that it shares with ovulation induction is the unacceptable rate of multiple pregnancy which is associated with high neonatal and maternal adverse outcomes. In order to reduce this risk, this case series aims to present clinical data of our two recent successful ongoing pregnancies from sequential single embryo transfer relating to improvement of culture media and changes that make embryo transfer more efficient especially when ultrasonographically guided. It is high time that Philippine Society of Reproductive Endocrinology and Infertility (PSREI) create guidelines in the practice of ART and collaborate in the submission of data to international organizations. The balance of risk and benefit is intrinsic to medical practice. Optimization of outcomes of IVF requires minimization of risk while maintaining or improving success rates. The use of single embryo transfer is a step in the right direction for ART in delivering a healthy baby.