Frozen-thawed embryo transfer cycles: clinical outcomes of single and double blastocyst transfers

Purpose  

To evaluate clinical outcomes of frozen-thawed embryo transfer cycles when one or two blastocysts are transferred.     

Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer

The objective of this study was to compare the implantation rate, pregnancy rate and endometrial thickness of frozen-thawed embryo transfers using endometrial preparation with either an artificial cycle or stimulated cycle. This was a prospective randomized trial at a single academic IVF centre. Seventy-seven patients undergoing artificial cycles received oral oestradiol; patients with endometrium < 7 mm on day 9-10 were switched to vaginal oestradiol. Eighty-six patients undergoing stimulated cycles received recombinant FSH followed by human gonadotrophin hormone injection. Vaginal progesterone was begun 2 or 3 days prior to embryo transfer. There was no difference in implantation rate (8.5% versus 7.3%), pregnancy rate (16% versus 13%), cancellation rate (both 23%) or endometrium thickness (8.7 +/- 1.1 mm versus 8.7 +/- 1.0 mm) between artificial and stimulated cycles. Stimulated cycles had a higher incidence of thin endometrium (27% versus 5%, P < 0.01). In artificial cycles, patients switched to vaginal oestradiol had improved pregnancy rate (31%) versus patients who received oral oestradiol alone (13%) (P = 0.05). It is concluded that artificial and stimulated cycles produce comparable pregnancy rates, implantation rates, cancellation rates and endometrial thickness, although stimulated cycles have a higher incidence of thin endometrium. Vaginal oestradiol supplementation improved implantation rates.     

Study on the incidence and influences on heterotopic pregnancy from embryo transfer of fresh cycles and frozen-thawed cycles

Purpose

The purpose of this study was to determine the heterotopic pregnancy rate using fresh versus frozen-thawed embryo transfers and factors associated with heterotopic pregnancy (HP). Management and clinical outcomes after heterotopic pregnancy were also evaluated.

Methods

In this retrospective cohort study, we included 12,484 women who had clinical pregnancies after in vitro fertilization treatment at our fertility center between 2012 and 2017. Patients received fresh day 3 embryos (F-D3 group), fresh day 5 blastocysts (F-D5 group), frozen-thawed day 3 embryos (T-D3 group), or frozen-thawed day 5 or 6 blastocysts (T-D5/6 groups) transfers. The primary outcome measure was the occurrence of heterotopic pregnancy. Factors associated with heterotopic pregnancy were analyzed using logistic regression.

Results

The heterotopic pregnancy rates were 0.58% in the F-D3, 0.39% in F-D5, 0.56% in T-D3, and 0.33% in T-D5/6 groups, but no differences were found between groups. The risk factors of HP included a history of previous ectopic pregnancy (odds ratio [OR] 5.805, 95% CI 4.578–9.553, P?=?0.016) and pelvic inflammation diseases (OR 1.129, 95% CI 1.021–3.178, P?=?0.047). Salpingectomy was performed in 62.9% patients either through laparoscopy or through laparotomy. The early abortion rate and late abortion rate were 29.03% and 1.61%, respectively. In total, 66.13% of the patients had a live birth, either a singleton (90.24%) or twins (9.76%).

Conclusion

No significant difference in the incidence of heterotopic pregnancy in fresh IVF cycles vs. frozen-thawed cycles could be demonstrated in a large cohort of patients. The risk factors of HP included history of ectopic pregnancy and PID. The clinical outcome after heterotopic pregnancy appears to be favorable.

     

Elevated progesterone and its impact on birth weight after fresh embryo transfers

Purpose

The purpose of the study was to examine the association between serum progesterone levels on the day of hCG administration and birth weight among singleton live births after fresh embryo transfer.

Methods

This study was conducted as a retrospective cohort database analysis on patients who underwent IVF treatment cycles from January 2004 to April 2012. The study was performed at a University affiliated private infertility practice. All cycles that had achieved a singleton live birth after fresh embryo transfer and for which progesterone was measured on the day of hCG administration were examined. Generalized linear models were used to calculate mean birth weight and z-scores.

Results

We analyzed 817 fresh IVF embryo transfers in which birth weight, gestational age, and progesterone (ng/mL) level on day of hCG administration were documented. While there was a decrease in birth weight as progesterone quartile [≤0.54; >0.54 to ≤0.81; >0.81 to ≤1.17; >1.17 ng/mL] increased, the difference in mean birth weights among the four quartiles was not statistically significant (p = 0.11) after adjusting for maternal age and peak estradiol levels. When dichotomizing based on a serum progesterone considered clinically elevated, cycles with progesterone >2.0 ng/mL had a significantly lower mean singleton birth weight (2860 g (95% CI 2642 g, 3079 g)) compared to cycles with progesterone ≤2.0 ng/mL (3167 g (95% CI 3122 g, 3211 g) p = 0.007)) after adjusting for maternal age and estradiol.

Conclusion

We demonstrated that caution should be exercised when performing fresh embryo transfers with elevated progesterone levels and in particular with levels (>2.0 ng/mL) as this may lead to lower birth weight.

     

Cumulative live birth rate after two single frozen embryo transfers (eSFET) versus a double frozen embryo transfer (DFET) with cleavage stage embryos: a retrospective cohort study

Purpose

According to the latest ART report for Europe, about 13 % of pregnancies after frozen embryo transfer are multiple. Our objective was to analyse the impact on the multiple pregnancy rate of two eSFET (elective single frozen embryo transfers) versus a DFET (double frozen embryo transfer) in women aged under 38 years, who had not achieved pregnancy in their fresh transfer and who had at least two vitrified embryos of A/B quality.

Methods

This study was conducted from January 2010 to June 2013 at a public hospital. The couples were divided into three groups. Group DFET: the first cryotransfer of two embryos (105 women); cSFET group: the only cryotransfer of a single vitrified embryo (60 women); eSFET group, individually vitrified embryos: 20 patients included in a clinical trial of single-embryo fresh and frozen transfer and 21 patients who chose to receive eSFET.

Results

The clinical pregnancy rate was 38.1 % in the DET group and the cumulative clinical pregnancy rate was 43.3 % in the eSFET group. There were no significant differences between the DFET and eSFET groups (30.0 vs 34.1 %) in cumulative live birth delivery rate. The rate of multiple pregnancies varied significantly between the DFET and eSFET groups (32.5 vs 0 %, p < 0.05).

Conclusions

For good-prognosis women aged under 38 years, taking embryo quality as a criterion for inclusion, an eSFET policy can be applied, achieving acceptable cumulative clinical pregnancy and live birth rates and reducing multiple pregnancy rates.     

Elective single embryo transfer versus double embryo transfer in assisted reproduction

High numbers of embryos transferred during assisted reproduction have become implicated as the cause of higher than normal twinning and multiple gestation rates following this form of therapy. However, reducing the number to a single embryo transferred has been shown to carry unfavourable results in the first cycle, but with similar cumulative live birth rates. This study tested the theory by performing a randomized controlled trial of elective single embryo transfer (SET) versus double embryo transfer (DET) in young women, and follow them up for 1 year to determine the result of cryo-embryo transfer cycles in the two cohorts. The results showed that the probability of a live birth was not significantly different between the two groups, but with a higher rate of twins in the DET group. In addition, during the 1-year follow-up period, the live birth, clinical pregnancy and multiple pregnancy rates were also similar, and in line with the results of the randomized trial. In conclusion, the results of this prospective randomized trial and 1-year follow-up show that in young women, elective SET should be the first line of choice. Even so, these results should be confirmed by larger randomized studies.     

101例IVF-ET新鲜周期移植未见原核来源胚胎临床结局分析

目的评估体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)新鲜周期移植完全来源未见原核(non-pronuclear,0PN)胚胎的临床结局。方法回顾分析了2009年1月至2012年9月,在北京大学第三医院生殖中心接受IVF-ET治疗(包括常规IVF和常规ICSI),移植完全来源0PN的胚胎的新鲜移植周期共计101例。结果 101例新鲜移植完全来源于0PN胚胎中,99例移植分裂期胚胎,临床妊娠率为:9.09%(9/99),着床率:7.09%(9/127);截止到2013年1月,妊娠结局:1例胎停育,2例继续,6个健康婴儿出生。移植囊胚2例,没有妊娠。结论 IVF-ET新鲜周期中,在没有正常2PN受精来源的胚胎时,0PN来源的胚胎可用于移植。     

Impact of assisted hatching on fresh and frozen-thawed embryo transfer cycles: a prospective, randomized study

The aim of this study was to determine if assisted hatching (AH) could improve the rates of pregnancy and implantation for both fresh and frozen-thawed embryo transfer cycles. A total of 760 fresh embryo transfer cycles and 200 frozen-thawed embryo transfer cycles were randomly assigned to either the treatment group (AH) or the control group (no AH). Zona thinning by laser was performed just before embryo transfer. In fresh embryo transfer cycles, the AH group and control group results were comparable. There were no significant differences in the rates of positive human chorionic gonadotrophin (HCG; 47.5 versus 48.8%), clinical pregnancy (42.4 versus 42.6%), or implantation (26.3 versus 25.2%) between the two groups. However, in frozen-thawed embryo transfer cycles, the rates of positive HCG (32.0 versus 17.0%), clinical pregnancy (25.0 versus 14.0%) and implantation (16.7 versus 7.3%) were significantly greater in the AH group than in the control group (P <: 0.05). The results of this investigation show that in the fresh embryo transfer cycles, laser-assisted hatching by zona thinning has no impact on the rates of positive HCG, clinical pregnancy and implantation, whereas in frozen-thawed cycles, assisted hatching by zona thinning significantly increases all three of these rates.     

Higher clinical pregnancy rates from frozen-thawed blastocyst transfers compared to fresh blastocyst transfers: a retrospective matched-cohort study

Purpose

The purpose of this matched-cohort study was to assess endometrial receptivity to blastocyst implantation in fresh embryo transfer by comparing implantation outcomes of fresh embryo transfer with frozen embryo transfer, where two blastocysts of good quality were transferred in good prognosis patients.

Method(s)

Fresh embryo transfer from intracytoplasmic sperm injection cycles and artificial frozen embryo transfer cycles performed from January 2012 to December 2013 at a private clinic were retrospectively analyzed and the pregnancy, clinical pregnancy, and implantation rates statistically compared. Cycles were stratified and matched according to the blastocyst expansion grade (grade 2, 3, 4, or 5) of the two blastocysts transferred. Five hundred ninety-eight fresh embryo transfer cycles were matched with 545 frozen embryo transfer cycles across four blastocyst cohorts.

Result(s)

In this study of 1143 blastocyst transfer cycles, fresh embryo transfer resulted in reduced pregnancy, clinical pregnancy, and fetal heart implantation rates in all four blastocyst cohorts. The fetal heart implantation rates for fresh embryo transfer ranged from 16.7 % in the grade 2 to 47.3 % in the grade 5 cohort, compared to 23.1 % in the grade 2 to 57.4 % in the grade 5 cohort for frozen embryo transfer. The trends in increasing pregnancy outcomes relative to increasing blastocyst expansion were similar in fresh embryo transfer and frozen embryo transfer.

Conclusion(s)

Blastocysts of good quality transferred in frozen embryo transfer had a significantly greater chance of implantation and clinical pregnancy compared to blastocysts of matched quality transferred in fresh embryo transfer, suggesting reduced endometrial receptivity in fresh embryo transfer.     

The role of angiogenic markers in adverse perinatal outcomes: fresh versus frozen embryo transfers

Purpose

We aimed to investigate the angiogenic balance in fresh compared to frozen embryo transfers, and among neonates with adverse perinatal outcomes.

Methods

This was a retrospective cohort study. All IVF cycles resulting in a singleton live birth at a university academic fertility center from January 1, 2011, to December 31, 2013, were examined. Concentrations of sFLT-1 and PlGF were measured in previously frozen serum specimens collected during early gestation at approximately 5 weeks gestation. Patients completed an electronic survey to detail perinatal outcome.

Results

We identified 152 singleton live births (103 fresh, 49 frozen). Demographic characteristics were similar between the two groups. Ratios of sFlt-1:PlGF were not different between fresh and frozen transfers. Neonates from fresh cycles had a mean birth weight 202 g lighter (p = 0.01) than frozen cycles, after adjusting for gestational age. Among babies born with poor perinatal outcomes, there was a difference in sFlt-1:PlGF ratios after adjusting for race. In non-Asians, infants born small for gestational age (SGA) (< 10th percentile) had significantly higher sFLT-1:PLGF ratio, median ratio (0.21 vs 0.12, p = 0.016).

Conclusions

Fresh transfers were associated with lower birth weight infants compared to frozen transfers. While there was no difference in sFlt-1:PlGF ratios between fresh and frozen transfers, these ratios were significantly lower in SGA infants, suggesting an imbalance in angiogenic markers during placentation.

     

Effect of mid-luteal phase GnRH agonist on frozen-thawed embryo transfers during natural menstrual cycles: a randomised clinical pilot study

This prospective randomised crossover study evaluated the effect of mid-luteal single-dose gonadotropin-releasing hormone agonist (triptoreline) on pregnancy outcomes in natural-cycle frozen embryo transfers (FETs). Ninety-eight women were randomised to receive either standard luteal support with vaginal micronised progesterone or an additional single dose of 0.1?mg triptoreline at the time of implantation. The intervention group was composed of 65 FET cycles and the control group of 62 cycles. In the intervention group, there were more positive pregnancy tests, clinical pregnancies and live births, but the differences did not reach statistical significance. The mean beta human chorionic gonadotropin (β-hCG) concentration of singleton pregnancies was significantly lower in the intervention group compared to the control group (p?=?0.048). No difference was detected in the median birth weight of the newborns.     

Influence of cleavage-stage embryo quality on the in-vitro fertilization outcome after single embryo transfer in fresh cycles

ObjectiveEmbryo quality is crucial for determining the outcome of embryo implantation. This study aimed to assess the impact of embryo quality on the outcome of in vitro fertilization/single-embryo transfer (IVF-SET).Materials and methodsThis retrospective study included 2531 fresh IVF-SET cycles, including 277 poor-quality and 2254 top-quality embryos. The clinical pregnancy rate, miscarriage rate, live birth, implantation rate, pregnancy outcome and complication were analyzed and compared. Risk factors associated with miscarriage rate and pregnancy complication were identified using logistics regression analysis.ResultsTop-quality embryos resulted in higher clinical pregnancy rate (30.5% vs. 12.6%, P < 0.001) and live birth rate (23.9% vs. 9.7%, P < 0.001) compared with poor-quality embryos. Logistics regression analysis revealed that embryo quality was not correlated with miscarriage rate (95% CI 0.33–1.89) and pregnancy complications (95% CI 0.12–7.84). Maternal age and body mass index was a risk factor for miscarriage rate (95% CI 1.05–1.22) and pregnancy complication (95% CI 1.01–1.29), respectively.ConclusionClinical miscarriage rate and pregnancy complication were embryo quality independent. Maternal age was the risk factor for miscarriage rate. Embryo quality did not affect miscarriage once a clinical pregnancy is achieved.     

冷冻前胚胎因素对冻融胚胎移植结局的影响

目的:探讨冻融胚胎移植周期中冷冻前胚胎因素对临床结局的影响。方法:回顾分析本生殖中心2009年1月～9月的589个冻融胚胎移植周期,根据冷冻前受精方式、胚胎培养时间、胚胎卵裂球数目、冷冻前≥6细胞胚胎个数分组。结果:589例冻融移植周期中共解冻胚胎2185枚,复苏率为69.5%,临床妊娠率26.5%。不同受精方式的临床妊娠率分别为23.4%,33.2%,差异有统计学意义;D2胚胎和D3胚胎冷冻后复苏率和临床妊娠率差异有统计学意义(71.4%vs69.1%和20.2%vs30.1%);冷冻前胚胎≥6细胞和6细胞,两组的临床妊娠率(31.8%,22.0%)和卵裂球完全存活复苏率(23.7%,45.4%)比较,差异均有统计学意义;冷冻前3个及以上≥6细胞的胚胎复苏率最高为56.0%、卵裂球完全存活复苏率最低为20.9%,与冷冻前少于3个胚胎组相比差异有统计学意义。若冷冻前仅余1个≥6细胞胚胎,冷冻后复苏率显著高于仅余1个6细胞胚胎,但卵裂球完全存活复苏率显著降低;和仅余2个胚胎相比,组间临床妊娠率无统计学差异。结论:冷冻前≥6细胞胚胎的妊娠结局优于6细胞的胚胎;若冷冻前仅余1个6细胞的胚胎,虽然冻融后复苏率较低,但仍有妊娠的可能,因此仍然建议冻存这部分胚胎,提高患者的累积妊娠率。     

Blastocyst culture: toward single embryo transfers

The routine culture and transfer of viable human blastocysts has been made possible by the development of sequential culture media, formulated to account for the changes in nutrient requirements of the embryo as it develops and differentiates. Resultant implantation rates of blastocysts transferred on day 5 are significantly higher than those obtained by the transfer of cleavage stage embryos transferred on day 2 or day 3 within the same programme. As a direct result of this increase in implantation rate, fewer blastocysts than cleavage stage embryos need to be transferred to obtain acceptable pregnancy rates, thereby reducing the incidence of multiple gestations. Blastocysts developed in sequential culture media are readily cryopreserved. The efficiency of in vitro fertilization (IVF) in a general patient population can be calculated using a model that takes into account the number of embryos transferred and cryopreserved, together with their respective implantation rates. Blastocyst transfer is associated with about a 20% increase in the efficiency of IVF compared with the transfer of cleavage stage embryos on day 3. The development of a suitable scoring system has enabled identification of those blastocysts with the highest developmental potential (70% implantation rate). The culmination of this work should be the move to the transfer of a single blastocyst for a significant number of patients.     

Blastocyst culture: Toward single embryo transfers

The routine culture and transfer of viable human blastocysts has been made possible by the development of sequential culture media, formulated to account for the changes in nutrient requirements of the embryo as it develops and differentiates. Resultant implantation rates of blastocysts transferred on day 5 are significantly higher than those obtained by the transfer of cleavage stage embryos transferred on day 2 or day 3 within the same programme. As a direct result of this increase in implantation rate, fewer blastocysts than cleavage stage embryos need to be transferred to obtain acceptable pregnancy rates, thereby reducing the incidence of multiple gestations. Blastocysts developed in sequential culture media are readily cryopreserved. The efficiency of in vitro fertilization (IVF) in a general patient population can be calculated using a model that takes into account the number of embryos transferred and cryopreserved, together with their respective implantation rates. Blastocyst transfer is associated with about a 20% increase in the efficiency of IVF compared with the transfer of cleavage stage embryos on day 3. The development of a suitable scoring system has enabled identification of those blastocysts with the highest developmental potential (70% implantation rate). The culmination of this work should be the move to the transfer of a single blastocyst for a significant number of patients.     

Application of atosiban in frozen-thawed cycle patients with different times of embryo transfers

This prospective cohort study aimed to examine the effects of atosiban, given before transfer of frozen-thawed embryo to women with different number of embryo transfer (ET) cycles. Atosiban treatment significantly increased implantation rate and clinical pregnancy rate in the third and more than three ET groups. However, there were no significant increases in the above parameters in the first and second ET groups. Our study showed that patients those who underwent the third or more than three ET cycles were inclined to higher uterine contractions and serum oxytocin level, thus atosiban treatment starting from the third ET cycle may be effective in improving embryo implantation. This is the first study to evaluate the optimal atosiban treatment window corresponding to the number of ET cycles of the patients.     

注射人绒毛膜促性腺激素日雌激素水平对体外受精新鲜及冻融周期妊娠结局影响

目的探讨体外受精(IVF)周期中注射人绒毛膜促性腺激素(HCG)日不同血清雌二醇(E2)水平对新鲜周期及随后胚胎冻融移植(FET)周期妊娠结局的影响。方法对2008年1月至2010年12月在上海交通大学医学院附属瑞金医院生殖医学中心接受常规IVF或卵胞浆内单精子注射(ICSI)助孕的820个周期进行回顾性分析,根据注射HCG日血清E2水平分为6组:A组(<7340pmol/L),B组(7340～<11010pmol/L),C组(11010～<14680pmol/L),D组(14680～<18350pmol/L),E组(18350～<22020pmol/L)和F组(≥22020pmol/L);为预防严重卵巢过度刺激综合征(OHSS)而放弃移植随后进行的首次FET周期,根据其取卵周期注射HCG日血清E2水平分为4组:Ⅰ组(14680～<18350pmol/L),Ⅱ组(18350～<22020pmol/L),Ⅲ组(22020～<25690pmol/L),Ⅳ组(≥25690pmol/L),比较各组妊娠结局。结果随着E2水平的增加,受精率、卵裂率均呈增高趋势(P<0.05);新鲜移植(ET)周期临床妊娠率、种植率及继续妊娠率A、B组略低,C、D、E、F组较高,但各组比较差异均无统计学意义(P>0.05)。全胚冻存后的首次FET周期,Ⅰ～Ⅳ组临床妊娠率、种植率和继续妊娠率差异无统计学意义(P>0.05)。总FET周期临床妊娠率(51.09%)和种植率(31.68%)明显高于总ET周期(38.90%,25.32%)(P<0.05)。结论促排卵周期中HCG日血清E2水平与IVF结局没有显著相关性,与随后FET结局也没有显著相关性。     

Blastocyst-stage versus cleavage-stage embryo transfer in the first frozen cycles of OHSS-risk patients who deferred from fresh embryo transfer

Abstract

Elective cryopreservation of all embryos has been the most effective means to avoid developing ovarian hyperstimulation syndrome (OHSS). However, it is still unknown which stage is optimal for freezing and transferring into uterus in OHSS-risk patients. This study was undertaken to evaluate whether OHSS-risk patients could benefit from transferring blastocysts. A total of 162 women were allocated to cleavage-stage embryo transfer (ET) (group A?=?70) and blastocysts transfer (group B?=?92) on the basis of patients’ voluntary in their first frozen cycles. Although the mean number of transferred embryos in group A was significantly more than those in group B (2.37?±?0.52 versus 2.11?±?0.52, p?<?0.05), the clinical pregnancy rates, implantation rates and live birth rates in group B were significantly higher than those in group A (47.83% versus 31.43%, p?<?0.05; 31.44% versus 18.67%, p?<?0.05; 40.21% versus 27.14%, p?<?0.05), and the multiple pregnancy rates in both groups were comparable (34.09% versus 36.36%, p?>?0.05). The observed results in OHSS-risk population allow us to take a position in favor of blastocyst transfer, thus pregnancy and live birth could be achieved with fewer ETs and in a shorter time frame.