Double Blastocyst Transfer Research Articles

Sequential Transfer of Blastocysts on Day 5 and Day 6 in Patients with Repeated Implantation Failure in Frozen Embryo Transfer Cycle.

The aim of this study was to evaluate which frozen embryo transfer (FET) strategy benefits the recurrent implantation failure (RIF) population. A retrospective study of 336 women with RIF was performed from July 2020 to October 2023. The patients were divided into three groups according to the FET protocol. The three FET protocols included transferring a blastocyst on both days 5 and 6 (Group 1, n = 138); transferring a cleavage-stage embryo on day 3 and a blastocyst on day 5 (Group 2, n = 55); and transferring double blastocysts on day 5 (Group 3, n = 143).The sequential day 5 and day 6 blastocyst ET strategy significantly improved in vitro fertilization success rates compared with those of both the traditional double-blastocyst day 5 transfer strategy and the strategy involving one cleavage-stage embryo transfer on day 3 and one blastocyst transfer on day 5 in RIF patients. Compared with those observed in Day 5 double-blastocyst transfer, the rates of clinical pregnancy and implantation increased (51.75% vs. 64.49%, P < 0.001 and 37.06% vs. 41.3%, P = 0.005, respectively), while the rates of biochemical pregnancy and multiple gestation decreased (18.18% vs. 12.32%, P = 0.006 and 43.24% vs. 28.09%, P = 0.044, respectively) with the new protocol.Blastocysts from sequential embryo transfer on day 5 and day 6 were more effective than those from the traditional FET protocol at improving pregnancy outcomes and lowering the multiple pregnancy rate in RIF patients. When only one or zero good-quality blastocysts are available, sequential blastocyst ET on days 5 and 6 should be considered.

P-763 Twin births in Belgium: a national cohort analysis of 35 523 double fresh embryo transfers between 2012 and 2021

Abstract Study question Should a national embryo transfer (ET) policy designed in the era of cleavage stage transfers be adapted for blastocyst transfers to avoid twin pregnancies? Summary answer Double embryo transfer policy results in unacceptable high twin rates at all ages and treatment ranks which is significantly more pronounced after double blastocyst transfer. What is known already In 2003, authorities in Belgium implemented a law to reduce multiple pregnancies after ART by tailoring ET policies based on age, embryo quality, and cycle rank. A choice between SET or Double Embryo Transfer (DET) depending on embryo quality is allowed in the second cycle for patients under 36y with SET being mandatory with top quality embryos. DET is allowed as of the first cycle for patients aged 36y or more regardless of embryo quality. Blastocyst transfer results in significantly higher live birth rates, implying an increased risk of multiple pregnancies after multiple blastocyst transfers. Study design, size, duration A analysis of 35,523 double embryo fresh transfer cycles over a period of 10 years from 2012 to 2021 from the Belgian national BELRAP (Belgian Registry on Assisted Procreation) registry was performed. The study included 26,930 double cleavage stage transfers (DET-CL) and 8,593 double blastocyst transfers (DET-BL). Participants/materials, setting, methods The primary outcomes were delivery rate (DR) per transfer and twin delivery rate (TDR). DR includes all deliveries with a least one live birth per transfer; the TDR includes all twin deliveries as a proportion of all deliveries. For analysis, the data were categorized into the following age groups: 18-25 years, 26-29 years, 30-35 years, 36-39 years and 40-45 years. Cycle ranks were categorized as follows: rank 1, rank 2 and cycle 3- ≥ 6. Main results and the role of chance For all age groups and cycle ranks, delivery rate per transfer and twin delivery rate per delivery were significantly higher after DET-Bl compared to DET-Cl (26.0% versus 19.9%; p &amp;lt; 0.0001 and 28.0% versus 20.6%; p &amp;lt; 0.0001, respectively). In the age groups 26-29 years, 30-35 years and 36-39 years, a significantly higher TDR was observed in DET-Bl compared to DET-Cl, respectively (34.4% versus 24.2%, p = 0.0005; 33.5% versus 24.9%, p &amp;lt; 0.0001 and 24.3% versus 17.3%, p = 0.0002). TDR after DET-Bl was significantly lower in women aged 40-45 years compared to all other age groups, 18-25 years, 26-29 years, 30-35 years and 36-39 years, respectively (11.3% versus 32.8%, p &amp;lt; 0.0001; 11.3% versus 34.4%; p &amp;lt; 0.0001; 11.3% versus 33.5%; p &amp;lt; 0.0001 and 11.3% versus 24.3%; p &amp;lt; 0.0001), respectively). DR was significantly lower in cycle rank 1 compared to cycle rank 2 (22.5% versus 25.5%; p &amp;lt; 0.0001) and compared to cycle rank 3 - &amp;gt; 6 rank 1 and (22.5% versus 27.1%; p &amp;lt; 0.0001). After DET-Bl, a significantly lower TDR was observed in cycle rank 1 compared to cycle rank 2 (15.6% versus 30.0%; p &amp;lt; 0.0001) and compared to cycle rank 3 - &amp;gt; 6 (15.6% versus 29.7%; p &amp;lt; 0.0001). Limitations, reasons for caution The retrospective design is a limitation. Outcomes might be influenced by clinical and laboratory improvements over the years. The registry does not collect embryo quality data making it impossible to assess the effect of embryo quality on the ET policy and outcome. Wider implications of the findings This data indicates that a double blastocyst transfer should only be considered from the age of 40 onwards. In the first cycle, regardless of age, we observe a significantly lower twin delivery rate, suggesting that a double ET is performed when only poor-quality blastocysts are available. Trial registration number Not applicable

P-605 Effectiveness of follitropin delta in patients with potential poor response: A post hoc analysis from the ESTHER-1 trial

Abstract Study question What is the effectiveness of individualised follitropin delta dosing compared to conventional follitropin alfa dosing in patients with potential poor response undergoing ovarian stimulation? Summary answer Individualised follitropin delta dosing provides a favourable efficacy and safety balance and is as good as follitropin alfa in patients with potential poor ovarian response. What is known already Poor ovarian response to controlled ovarian stimulation constitutes a challenge in in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment. The dosing algorithm of follitropin delta incorporates the prediction of ovarian response based on anti-Müllerian hormone (AMH), an accurate marker of ovarian reserve, and body weight, for an individualised dosing. In the general IVF/ICSI population and potential high responders, individualised follitropin delta reduces the risk of ovarian hyperstimulation syndrome (OHSS) and/or preventive interventions for OHSS, with sustained efficacy compared to conventional follitropin alfa. However, the performance of follitropin delta in the subpopulation of patients with potential poor response has not been evaluated. Study design, size, duration Post hoc analysis of 332 patients with potential poor response from the ESTHER-1 trial (determined by AMH level at screening &amp;lt;9 pmol/L). Patients received the maximum daily dose of 12 µg follitropin delta (fixed dosing throughout stimulation) as stipulated by the dosing algorithm for patients with AMH &amp;lt;15 pmol/l, or follitropin alfa at a starting dose of 150 IU, with potential dose adjustments from stimulation day 6 and onwards (maximum daily dose of 450 IU). Participants/materials, setting, methods Participants were women, 18–40 years, undergoing their first IVF/ICSI cycle in a GnRH antagonist protocol, including triggering with human chorionic gonadotrophin, IVF/ICSI insemination, and single or double blastocyst transfer on Day 5. Ultrasound was performed 10–11 weeks after transfer to confirm ongoing pregnancy. All pregnancies were followed until birth. Study outcomes include number of oocytes retrieved and number of good quality blastocysts, ongoing pregnancy and live birth rates, cycle cancellation and OHSS rates. Main results and the role of chance A total of 332 patients (25.0% of the overall ESTHER-1 population) had serum AMH at screening of &amp;lt; 9 pmol/l and were included in the analysis: 168 were treated with follitropin delta and 164 were treated with follitropin alfa. Baseline characteristics were similar between the treatment groups, with a mean age of 34.8 years, a median AMH of 5.7 pmol/l and a mean weight of 64.5 kg. With follitropin delta, the mean daily dose was 12.0 µg and with follitropin alfa 12.4 µg, resulting in mean total doses of 104.6 µg and 112.3 µg, respectively. The mean number of oocytes retrieved was 5.8 ± 3.5 with follitropin delta and 5.5 ± 3.6 with follitropin alfa and the mean number of good-quality blastocysts was 1.2 ± 1.4 with both treatments. The ongoing pregnancy rate was 29.8% with follitropin delta and 29.3% with follitropin alfa and the live birth rates were 29.2% and 28.7%, respectively. Thirteen patients (7.7%) treated with follitropin delta and 14 (8.5%) treated with follitropin alfa had their cycles cancelled due to poor response. One case of OHSS (0.6%) was observed in the follitropin delta group, and 3 cases (1.8%) were observed in the follitropin alfa group. Limitations, reasons for caution The main limitation of the study is its post hoc nature. Furthermore, the study is based on a relatively small number of patients. Wider implications of the findings This subgroup analysis, alongside the normoresponder and the potential hyperresponder subgroup of the ESTHER-1 trial, adds evidence for the effectiveness of follitropin delta across all ovarian reserve subgroups of the infertile population. Trial registration number NCT01956110

O-014 Cumulative live birth associated with number of oocytes in ovarian stimulation with follitropin delta: an individual patient data meta-analysis

Abstract Study question What is the optimum number of oocytes retrieved to maximise cumulative live birth rates in the fresh and subsequent frozen cycles following follitropin delta stimulation? Summary answer The cumulative live birth rate increased steadily with number of oocytes retrieved up to a plateau starting at ∼21 oocytes retrieved. What is known already Live birth rate (LBR) per fresh ovarian stimulation cycle is the conventionally reported outcome of in vitro fertilisation (IVF). In recent years, there has been a marked increase in number and successful outcomes of cryopreserved cycles, suggesting that the cumulative live birth rate (CLBR) has emerged as a more clinically relevant outcome. In the fresh cycle, the number of oocytes retrieved is regarded as a prognostic factor for LBR. A similar association has been shown for CLBR implying that CLBR increases with the number of oocytes and continues to increase beyond the plateau observed for fresh cycle LBR. Study design, size, duration Individual patient data meta-analysis of 1746 patients from 4 randomised controlled trials using follitropin delta for ovarian stimulation. The analysis included patients with ≥1 oocyte retrieved following stimulation. The CLBR in the fresh and subsequent frozen cycles was evaluated. Predicted CLBR was obtained using a logistic regression analysis with fractional polynomials to assess the association between number of oocytes retrieved and CLBR. Subgroup analyses were performed based on age, AMH and number of oocytes retrieved. Participants/materials, setting, methods Participants were women, 18–42 years, undergoing their first or second in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycle in a GnRH antagonist/long agonist protocol with human chorionic gonadotrophin or GnRH agonist triggering and IVF/ICSI insemination. Single or double blastocyst transfer was performed on Day 5 and all viable surplus blastocysts were cryopreserved. All pregnancies from the fresh cycle and frozen cycles initiated within 1 year after start of stimulation were followed until birth. Main results and the role of chance The study included 1746 patients who underwent a total of 2948 cycles; 1746 fresh and 1202 frozen. In total, 740 patients (42.4%) initiated frozen cycles (maximum of 6). The study population had a mean age of 33.8 years and a median AMH level of 17.0 pmol/l. The mean number of oocytes retrieved was 12.4, the fresh cycle LBR was 29.1% and the CLBR was 51.4%. The CLBR steadily increased with number of oocytes retrieved, reaching above 60% at &amp;gt; 15 oocytes and above 70% at &amp;gt; 20 oocytes. The CLBR started to plateau at ∼21 oocytes. Subgroup analyses by number of oocytes retrieved, age group or AMH group demonstrated that the CLBR decreased with increasing age (57.1%, 51.6% and 35.8% at &amp;lt; 35, 35-37 and ≥38 years). In comparison it was similar for AMH &amp;lt;15 and ≥15 pmol/l (52.0% and 50.9%, respectively). A continued increase in CLBR from 15 oocytes retrieved was observed in older patients (≥38 years); from 41.3% to 53.4% to 58.7% at 15-19, 20-24 and ≥25 oocytes. No equivalent benefit was observed in younger patients, where corresponding rates were 72.5%, 68.0% and 78.8% in patients &amp;lt;35 years, and 70.3%, 73.1% and 71.5% in patients 35-37 years. Limitations, reasons for caution A limitation of this study is the small number of patients with &amp;gt;20 oocytes retrieved. The individual pooled studies were heterogenous regarding number of blastocysts transferred and hCG/agonist trigger. Wider implications of the findings The current individual patient data meta-analysis suggests an increase in CLBR with number of oocytes retrieved up to a plateau starting at ∼21 oocytes following ovarian stimulation cycles with follitropin delta and subsequent frozen cycles. An increase in CLBR from 20 oocytes was evident in older but not younger patients. Trial registration number NCT01956110, NCT03564509, NCT03740737, NCT03738618

The effect of an extended culture period on birth weight among singletons born after single or double vitrified embryo transfer.

To evaluate the effect of an extended culture period on birth weight among singletons born after vitrified-warmed embryo transfer. A retrospective cohort study was performed among 12400 women who gave birth to 1015, 1027, 687, and 9671 singletons after single blastocyst transfer, single cleavage-stage embryo transfer, double blastocyst transfer, and double cleavage-stage embryo transfer, respectively. The unadjusted birth weight of singletons born after vitrified blastocyst transfer were heavier than those born after cleavage-stage transfer (β=30.28, SE=13.17, P=0.022), as were the adjusted birth weights (β=0.09, SE=0.03, P=0.007). In addition, there was a 37% increased odd of having an infant with high birth weight after vitrified blastocyst transfer compared with vitrified cleavage stage transfer (OR=1.37, 95% CI:1.07-1.77). The unadjusted and adjusted birth weight and odds of having an infant with high birth weight significantly increased after blastocyst transfer compared with cleavage-stage embryo transfer in vitrified-warmed cycles.

Single versus double blastocyst transfer in first and second frozen-thawed embryo transfer cycle in advance-aged women: a two-center retrospective cohort study.

The present evidence is deficient for the trade-offs between the pros and cons of single blastocyst transfer (SBT) versus double blastocyst transfer (DBT) in frozen-thawed embryo transfer cycles for women in advanced reproductive age, especially in the second cycle. The current study aimed to investigate the impact of transferred blastocyst numbers on pregnancy outcomes in the first and second embryo transfer for women ≥ 35 years. This was a retrospective cohort study including 1284 frozen-thawed blastocyst transfer (FBT) cycles from two reproductive centers. We analyzed the pregnancy outcomes after SBT and DBT in the first and second FBT cycles. Moreover, stratified analysis was conducted by maternal age. In the first FBT cycle, the LBR was higher in the DBT group than that in the SBT group [52.3% vs. 33.9%; adjusted odds ratio (aOR), 1.65; 95% confidence interval (CI), 1.26-2.15, P < 0.001]. However, the LBR of the DBT group showed no remarkable difference compared with that of the SBT group in the second cycle of FBT (44.3% vs. 33.3%; aOR, 1.30; 95% CI, 0.81-2.08; P = 0.271). Furthermore, stratified analysis by age showed a higher LBR for the DBT group than the SBT group in patients aged 38-42 years (43.1% vs. 33.9%; aOR, 2.27; 95% CI, 1.05-4.90; P = 0.036). The present study demonstrated that the SBT regimen is a better choice for both, the first and second frozen-thawed embryo transfer cycles, for women aged 35-37 years. Additionally, the DBT regimen is still recommended to achieve a high LBR in women aged 38-42 years in the second FBT cycle. These findings may be beneficial for deciding the embryo transfer regimens in women of advanced reproductive age.

#82 : Does Apoptotic Body Impair Pregnancy Outcome

Background: Morphologically suboptimal blastocyst is often associated with poorer pregnancy outcomes. Apoptotic body is one of the abnormal findings in blastocysts characterised by cellular shrinkage and a darker appearance. The presence of apoptotic bodies may be suggestive of ongoing cellular degeneration. Cellular degeneration in the blastocyst is part of its self-corrective mechanism. The degenerated cells will deplete through the phagocytosis process. Aims: This is a retrospective study that aims to analyse whether the presence of apoptotic body has a significant impact on pregnancy outcomes. Method: We compare the outcome of the frozen-thawed embryo transfer (FET) cycle of blastocysts with apoptotic body and without it as a control. We further divide the cases into single blastocyst transfer and double blastocyst transfer. The data was collected from Vistana Fertility Centre from January to December 2022. Results: Conclusion: Data analysis showed that there is no significant difference between the study group and the control group. Hence, the presence of dead cells did not negatively impact the pregnancy outcomes.

Reproductive outcomes following abdominal repair for cesarean scar defect in women who desire subsequent pregnancies: A single-center retrospective study

ObjectiveTo clarify the reproductive outcomes of women who underwent abdominal repair surgery for cesarean scar defect (CSD). Study designThis is a retrospective observational study performed in a tertiary center. We retrospectively reviewed 20 women who underwent abdominal repair between 2007 and 2021. The indication for the repair was a minimal residual myometrial thickness (RMT) of ≦3.0 mm. We investigated surgical complications, changes in minimal RMT before and three-months after the repair, and reproductive outcomes. ResultsThe median age at the time of repair was 36 years (27–40), with a median body mass index of 21.0 (17.7–28.7) and a median of 1 prior cesarean section (1–5). Twelve women reported secondary infertility, while eight women were concerned about the potential risk of uterine rupture in future pregnancies due to thin RMT. Additionally, one woman had a co-existing vesicouterine fistula, two had abscess and hematoma formation at the precedent cesarean section, and three showed remarkable dehiscence of the defect. The median minimal RMT significantly increased to 5.05 mm (range; 2.5–14.2 mm) after the repair. Seven women had a total of eight live births, with a median duration from the repair to a live-birth pregnancy of 11.5 months (range; 4–20 months). No surgical complications occurred during the repair, and there were no instances of uterine rupture in subsequent pregnancies. However, one woman who became pregnant with twins following double blastocyst transfer required a cesarean section at 25 weeks of pregnancy due to bulging towards the bladder side of the repaired CSD. ConclusionAbdominal repair for CSD is feasible in women with thin RMT who experience secondary infertility. Twin pregnancies can promote thinning of the CSD repair site, potentially increasing the risk of uterine rupture.

Sequential embryo transfer versus double cleavage-stage embryo or double blastocyst transfer in patients with recurrent implantation failure with frozen-thawed embryo transfer cycles: a cohort study.

Recurrent implantation failure (RIF) is more common among patients receiving assisted reproductive treatment. Many efforts have been made to increase the incidence of clinical pregnancy among patients with RIF. The effect of the sequential transfer procedure, a two-step interval transfer of a cleavage-stage embryo followed by a blastocyst in one transfer cycle, on the clinical outcomes of RIF patients remains controversial. In total, 1774 frozen-thawed embryo transfer (FET) cycles in RIF patients were included. Of these cycles, 302 were sequential embryo transfer (ET) cycles, 979 were double day 3 cleavage-stage ET cycles, and 493 were double blastocyst ET cycles. The primary outcomes were the rates of implantation, clinical pregnancy and multiple pregnancy, and the secondary outcomes were the rates of hCG positive, early miscarriage and ectopic pregnancy. The implantation, hCG positive, and clinical pregnancy rates in the sequential ET group (32.1%, 58.9%, 50.7%) were significantly higher than those in the day 3 cleavage-stage ET group (24.9%, 46.5%, 40.4%) and were similar to those in the blastocyst transfer group (30.1%, 56.4%, 47.1%). The early miscarriage rate in the blastocyst transfer group was significantly higher than that in the cleavage-stage ET group (17.2% vs. 8.1%, P <0.05), while the ectopic pregnancy rate in the blastocyst transfer group was significantly lower than that in the cleavage-stage ET group (0.4% vs. 3.0%, P <0.05). The multiple pregnancy rate in the sequential ET group was significantly lower than that in the cleavage-stage ET group (17.0% vs. 25.5%, P <0.05) and the blastocyst transfer group (17.0% vs. 27.6%, P <0.05). When cycles of blastocyst culture failure were excluded, the clinical pregnancy rate was significantly higher (55.7% vs. 47.1%, P <0.05), and the early miscarriage rate and multiple pregnancy rate were significantly lower (8.5% vs. 17.2%, 17.7% vs. 27.6%; P <0.05, respectively) in the sequential ET group than in the double blastocyst ET group. Sequential embryo transfer in FET cycles could improve the clinical outcomes of patients with RIF.

P-766 Re-assessment of the Belgian legislation on embryo transfer in a blastocyst transfer policy

Abstract Study question How does a multiple fresh blastocyst transfer policy impacts live birth rate (LBR) and multiple live birth rates (MLBR) in relation to maternal age ? Summary answer Fresh transferring of ≥ 2 blastocysts only increases LBR in women above the age of 36 and substantially increases risk of multiples in all age categories. What is known already Multiple pregnancies after ART are recognized as a major complication as it significantly contributes to extreme preterm and very low-birthweight births. Even in the presence of a strict Belgian embryo transfer law in some subgroups in which double embryo transfer (DET) is allowed (women aged &amp;lt;36 years in cycle rank 3 up to 6 and in women aged 36-40 years in cycle rank 2), twining rates remain above 10%. A study by Tannus et al., (2017) concluded that double blastocyst transfer (DBT) is associated with both higher LBR and higher twin birth rates compared to elective single blastocyst transfer (eSBT). Study design, size, duration A single center retrospective, observational cohort study was conducted between July 2010 and December 2020. Both fresh IVF and ICSI cycles were included. A total of 8,402 fresh transfers were performed (2,948 on day 3 and 5,454 on day 5) over the course of the study period. SET was performed in 6,108 cases, DET in 2,077 cases, triple embryo transfer (TET) in 202 cases and multiple embryo transfers (MET) in 15 cases. Participants/materials, setting, methods The primary outcomes of this study were LBR per transfer and twin pregnancy rate. Generalized estimating equations (GEE) with the patient as subject was applied to account for clustering of cycles within women. An interaction analysis between the number of embryos transferred and age categories in the day 5 group was performed. A P-value of &amp;lt; 0.05 was considered statistically significant. Main results and the role of chance In women aged &amp;lt;36 years, chances of a live birth were not significantly higher when two or more vs. a single blastocyst were transferred (OR: 1.014; 95%% CI 0.791 - 1.299; p = 0.91). However, transferring more than one blastocyst in women aged 36-40 years and &amp;gt;40 years did result in a higher chance of live birth compared to SBT (OR: 1.631; 95% CI: 1.218 - 2.185; p = 0.0008 and OR: 1.634; CI: 1.219-2.190; p = 0.0008, respectively).` Women aged 36-40 years and &amp;gt; 40 years had an estimated 19.3% and 66.3% lower odds respectively of a live birth after the transfer of a day 5 embryo, vs. women aged &amp;lt;36 years (OR: 0.800, 95% CI: 0.687-0.931; p = 0.0034 and OR: 0.337, CI: 0.268-0.424; p &amp;lt; 0.0001, respectively). Overall, live births were 28.5% higher when 2 or more blastocysts were transferred compared to an SBT (OR: 1.285 95% CI 1.1.077 – 1.533) (p = 0.0046). The estimated odds for a twin pregnancy were 17.8 times higher for DBT/MBT compared to SBT (OR 17.814; 95% CI: 10.74 - 29.55) (p &amp;lt; 0.0001). Limitations, reasons for caution This study is limited by its retrospective design and no interaction analysis between number of twin pregnancies and age categories was possible due to the low number of twins. Wider implications of the findings The data indicates that in women younger than 36 years only one blastocyst should be transferred regardless the embryo quality or the cycle rank. Only for patients older than 40 years, transfer of two blastocyst(s) could be considered. Trial registration number Not applicable

Comparison of frozen-thaw blastocyst transfer strategies in women aged 35-40 years: a retrospective study.

To compare the effects of five different frozen-thaw embryo transfer (FET) strategies in women aged 35-40 years. Data from 1,060 patients were divided into five groups according to the number and quality of transferred blastocysts: a high-quality single blastocyst group (group A, n= 303), a high-quality double blastocysts group (group B, n= 176), a high-quality plus poor-quality double blastocysts group (group C, n= 273), a poor-quality double blastocysts group (group D, n= 189), and a poor-quality single blastocyst group (group E, n= 119). Comparative analyses were then performed between groups with regard to primary conditions, pregnancy, and neonatal outcomes. Group A had the lowest twin pregnancy rate (1.97%) and incidence of low-birth-weight infants (3.45%), which were significantly different from groups B, C, and D. In addition, the preterm birth rate (7.89%), neonatal birth weight (3300g [3000, 3637.5]), and neonatal birth age (39.14 weeks [38.43, 39.61]) in group A were different from those in groups B and C. Double blastocyst transfer (DBT) was associated with a 20.558-fold (Risk Ratio [RR]=20.558, 95% confidence interval [CI], 6.628-63.763) and 3.091-fold (RR=3.091, 95% CI, 1.69-5.653) increased risk of twin pregnancy and preterm delivery in unadjusted analysis, respectively, when compared with single blastocyst transfer (SBT). In the adjusted analysis, we observed similar risk estimates (adjusted RR=26.501, 95% CI, 8.503-82.592; adjusted RR=3.586, 95% CI, 1.899-6.769). Although, high-quality SBT resulted in a lower live birth rate than high-quality DBT, it also significantly reduced the risk of adverse pregnancies, thus resulting in more benefits for both the mother and baby. Collectively, our data indicate that high-quality SBT remains the optimal FET strategy for women aged 35-40 years and warrants further clinical application.

Blastocyst Transplantation Strategies in Women of Different Ages

(1) Background: Single blastocyst transfers (SBT) and double blastocyst transfers (DBT) are widely used in clinical practice. The objective of this study was to investigate the application of these two strategies in women of different ages. (2) Methods: Analysis was carried out on 5477 frozen embryo transfer cycles of women in different ages. All the cycles were divided into three groups according to the age of the included women: <35, 35-39, and >39. The live birth rate (LBR) and multiple birth rate (MBR) between the SBT and DBT among these groups, respectively, were compared. (3) Results: In the women < 35 group, the LBR was similar in SBT and DBT, but the MBR was higher in DBT than SBT. In women 35-39, with >10 oocytes retrieved, the MBR in DBT was significantly higher than SBT, but there was no significant difference in LBR between the two groups; with ≤10 oocytes retrieved, the LBR in DBT were significantly higher than SBT, but the MBT was not significantly different between the two groups. In women > 39, the LBR and MBR were lower in the SBT than DBT, but the differences were not statistically significant. (4) Conclusions: Selective SET is appropriate for most young women, whereas older women are advised to make individualized choices based on the number of oocytes retrieved and blastocyst quality.

Elective single versus double blastocyst-stage embryo transfer in women aged 36 years or older: a retrospective cohort study

We evaluated if elective single-blastocyst transfer (eSBT) could be adopted in women aged 36 or older. In this retrospective cohort, women aged ≥36 years received IVF ovarian stimulation cycles and had ≥ two blastocysts. A total of 240 women underwent eSBT and 189 double-blastocyst transfer (DBT) in the first transfer cycle. The subsequent frozen-thawed embryo transfer cycles were a combination of single- and double- blastocyst transfers. Analysis was stratified for patients in age groups 36–37, 38–39 and ≥40, considering the quality of the blastocyst transferred. The cumulative live birth rates (cLBR) were 74.2% (178/240) versus 63.0% (119/189) after eSBT versus DBT, respectively (aOR: 1.09 (0.68, 1.75)). Time to live birth did not vary significantly between the two groups (HR: 0.85 (0.68, 1.08)). The total number of children born was 194 after eSBT (162 singletons and 16 pairs of twins) versus 154 (84 singletons and 35 twins) after DBT. The odds ratios for preterm birth (0.37 (0.21–0.64)), and low birth weight (0.31 (0.16, 0.60)) were all lower in eSBT. In women aged ≥36 years, cLBR following single- versus double- blastocyst transfer was comparable while the odds of multiple live births and adverse perinatal outcomes were reduced.

Obstetrics and perinatal outcomes between elective single versus double blastocyst transfer in women younger than 35 years: A cross-sectional study

IntroductionClinicians have a positive attitude towards multiple embryo transfer in in vitro fertilization (IVF) cycles, considering increased live birth rates compared to single embryo transfer. We aimed to evaluate obstetric and perinatal outcomes among young women who became clinically pregnant after single & double blastocyst transfer. Material-method545 women under 35 years who became clinically pregnant after fresh blastocyst transfer was evaluated retrospectively. The participants were divided11The participants divided into two groups according to.according to the transferred embryo number - the elective single blastocyst transfer group (eSBT) (n=112) and the double blastocyst transfer group (DBT group) (n=433). Obstetric and perinatal outcomes were recorded. ResultsLive birth and abortion rates per pregnancy and per gestational sac, having a fetus with congenital anomaly per pregnancy and per neonate, and gestational complications were comparable between the groups. Multiple pregnancy, Cesarean section, and admission to neonatal intensive care unit (NICU) and hospitalization day in NICU per neonate were higher in the DBT group than in the eSBT group. Mean gestational week, birth weight, birth height decreased with the embryo transfer number. ConclusionDBT transfer appears to be associated with increased multiple pregnancies, Cesarean section, prematurity, decreased fetal anthropometric measurements, and admission to NICU without an increase in live birth and abortion rates. Therefore, it will be easier for clinicians to choose eSBT by providing young couples undergoing IVF treatment with detailed information about multiple pregnancies and prematurity.

Comparison of frozen-thawed embryo transfer strategies for the treatment of infertility in young women: a retrospective study.

To investigate transfer strategies in the frozen-thawed embryo transfer (FET) cycle. The clinical data of 1,652 FET patients were divided into five groups according to the number and quality of the transferred blastocyst: high-quality single blastocyst group (group A, n=558), high-quality plus poor-quality double blastocyst group (group B, n=435), poor-quality double blastocyst group (group C, n=241), high-quality double blastocyst group (group D, n=298), and poor-quality single blastocyst group (group E, n=120). Inter-group comparison analyses of primary conditions, pregnancy outcomes and neonatal outcomes were then performed. Group A had the highest embryo implantation rate (67.38%), significantly different from the implantation rates of the other four groups. The gemellary pregnancy rate (1.60%), preterm birth rate (5.58%), neonatal birth weight (3,350g [3,000g, 3,650g]), neonatal birth age (39.57 weeks [38.71, 40.34]), and incidence of low birth weight (7.02%) in group A were different from those in groups B, C, and D, but did not significantly differ from those in group E. Moreover, the proportions of male infants born in groups A (56.86%) and D (59.41%) were significantly higher than those in the other three groups. Double blastocyst transfer (0.528, 95% CI [0.410-0.680], P<0.001) and high-quality blastocyst transfer (0.609, 95% CI [0.453-0.820], P=0.001) were found to be protective factors for live birth. In addition, double blastocyst transfer was also the largest risk factor for pregnancy complications (3.120, 95% CI [2.323-4.190], P<0.001) and neonatal complications (2.230, 95% CI [1.515-3.280], P<0.001), especially for gemellary pregnancy (59.933, 95% CI [27.298-131.58], P<0.001) and preterm birth (3.840, 95% CI [2.272-6.489], P<0.001). Based on the ROC curves, a double blastocyst transfer could predict gemellary pregnancy reliably with a high area under the curve (AUC = 78.53%). Additionally, a double blastocyst transfer could effectively predict a high risk of pregnancy complications (AUC = 65.90%), neonatal complications (AUC = 64.80%) and preterm birth (AUC = 66.20%). The live birth rate of frozen-thawed high-quality single blastocyst transfer is lower than that of double high-quality blastocyst transfer, which can significantly increase the embryo implantation rate. High-quality single blastocyst transfer also significantly lowers the risk of gemellary pregnancy, preterm birth, and low birth weight, and can significantly improve maternal and infant outcomes. After weighing the pros and cons of live birth with pregnancy and neonatal complications, the authors believe that high-quality single blastocyst transfer is the optimal FET strategy for young women and is worthy of further clinical application. Despite this recommendation, high-quality single blastocyst transfer can increase the risk of monozygotic twins, as well as significantly increase the proportion of male infants born.

Effectiveness and Safety of Two Consecutive Cycles of Single Embryo Transfer Compared With One Cycle of Double Embryo Transfer: A Systematic Review and Meta-Analysis.

ObjectiveTo date, evidence regarding the effectiveness and safety of two consecutive cycles of single embryo transfer (2SETs) compared with one cycle of double embryo transfer (DET) has been inadequate, particularly considering infertile women with different prognostic factors. This study aimed to comprehensively summarize the evidence by comparing 2SETs with DET.MethodsPubMed, Embase, Cochrane Library databases, ClinicalTrails.gov, and the WHO International Clinical Trials Registry Platform were searched up to March 22, 2022. Peer-reviewed, English-language randomized controlled trials (RCTs) and observational studies (OS) comparing the outcomes of 2SETs with DET in infertile women with their own oocytes and embryos were included. Two authors independently conducted study selection, data extraction, and bias assessment. The Mantel–Haenszel random-effects model was used for pooling RCTs, and a Bayesian design-adjusted model was conducted to synthesize the results from both RCTs and OS.Main ResultsTwelve studies were finally included. Compared with the DET, 2SETs were associated with a similar cumulative live birth rate (LBR; 48.24% vs. 48.91%; OR, 0.97; 95% credible interval (CrI), 0.89–1.13, τ2 = 0.1796; four RCTs and six observational studies; 197,968 women) and a notable lower cumulative multiple birth rate (MBR; 0.87% vs. 17.72%; OR, 0.05; 95% CrI, 0.02–0.10, τ2 = 0.1036; four RCTs and five observational studies; 197,804 women). Subgroup analyses revealed a significant increase in cumulative LBR (OR, 1.33; 95% CrI, 1.29–1.38, τ2 = 0) after two consecutive cycles of single blastocyst transfer compared with one cycle of double blastocyst transfer. Moreover, a lower risk of cesarean section, antepartum hemorrhage, preterm birth, low birth weight, and neonatal intensive care unit admission but a higher gestational age at birth and birth weight were found in the 2SETs group.ConclusionCompared to the DET strategy, 2SETs result in a similar LBR while simultaneously reducing the MBR and improving maternal and neonatal adverse outcomes. The 2SETs strategy appears to be especially beneficial for women aged ≤35 years and for blastocyst transfers.

P-128 Role of PGT-A and ERA to optimise reproductive outcomes of couples with recurrent implantation failure

Abstract Study question In couples with Recurrent Implantation Failure (RIF), can Pre-implantation Genetic Testing for Aneuploidy (PGT-A) or Endometrial Receptive Array (ERA) help to optimise the reproductive outcomes? Summary answer In RIF patients PGT-A or ERA individually do not seem to optimize outcomes. PGT-A in-combination with ERA seems to be a beneficial intervention. What is known already Role of PGT-A and ERA to optimize reproductive outcomes has been ambigious. In this current study we wanted to evaluate their efficacy in RIF patients. Study design, size, duration This is a retrospective data of couples undergone treatment for RIF at our private fertility centre from January 2014 to July 2019. The study population was divided to four groups based on the treatments offered: Group A: ERA (n = 47) Group B: PGT-A (n = 54) Group C: ERA+PGT-A (n = 49) Group D: No PGT-A/ No ERA (n = 189) Participants/materials, setting, methods Couples with minimum two failed transfers were recruited. ICSI was the method of insemination. Blastocysts were subjected to genetic testing through Next-Generation Sequencing(NGS). All embryo transfers performed in a Frozen Embryo Replacement Cycle(FET). ERA was done as per our institutes Standard Operating Procedures(SOP) and for ERA patients ET was done as per the receptivity status. Elective Single Euploid Blastocyst transfer (eSET) was done in grpB&amp;C un-screened double Blastocyst Transfer (DET) was done in grpA&amp;D. Main results and the role of chance Clinical Pregnancy Rate (CPR), Miscarriage Rate (MR) Implantation Rate (IR), Multiple Pregnanacy rates (MPR) and Live Birth Rate (LBR) was evaluated in all groups. Outcomes of groups A, B, C &amp; D were as follows: CPR – 68.09% Vs 62% Vs 68.42% Vs 70% IR – 48.89% Vs 47.50% Vs 65.22% Vs 45% MR – 12.77% Vs 9.25% Vs 5.26% Vs 17.89% MPR – 16% Vs 0% Vs 0% Vs 17% LBR – 51.06% Vs 46.8% Vs 63.16% Vs 45% CPR was comaparble between all groups ERA &amp; PGT-A group seems to have the best IR, LBR with least miscarriage rates. For RIF patients role of PGT or ERA when offered individually, doesn’t seem to optimize outcomes. PGT-A in-combination with ERA seems to be beneficial to optimize outcomes. Limitations, reasons for caution This data is retrospective and there is a need for a well designed RCT to further validate the conclusion of this study. Caution needs to be exercised while offering PGT and ERA as they incurr additional financial burden to the patients. Wider implications of the findings Embryo Transfer cycles with a personalised window of implantation and transfer of a single Euploid embryo can help RIF patinets to have the best reproductive outcomes and can also help shorten the time to pregnancy. Trial registration number Not applicable

ENDOMETRIAL THICKNESS AND OBSTETRICAL OUTCOME IN ASSISTED REPRODUCTIVE TECHNOLOGY

Mounting evidence suggests that assisted reproductive technology (ART) alters certain obstetrical parameters as compared to natural pregnancies. Endometrial thickness (EMT) is one possible parameter which could impact on the depth of placentation – either too shallow, or too deep. While the impact of EMT on actual pregnancy rates has been studied in ART, little is known on whether EMT affects the quality of placentation. Therefore, we studied the impact of EMT on obstetrical outcomes following fresh and frozen embryo transfers (ET). Retrospective cohort study including patients who obtained a live birth (LB) after autologous ART in our center, between January 2017 and December 2019. Single and double blastocyst transfers were included. Fresh and frozen ET with singleton and twin pregnancies were analyzed separately. We divided them into 4 groups according to the last measured EMT before ET : <7mm,7 to 9 mm; 9 to 12 mm; ≥ 12 mm. Primary outcome was pregnancy duration in days. Secondary outcomes were the birth weight, obstetrical complications and the delivery mode. Associations between the 4 EMT groups were assessed using ANOVA and Fisher tests. 120 patients obtained single LB after fresh ET and 19 patients obtained twin LB. After frozen ET 571 patients had single LB and 75 patients had twin LB. No significant difference was reported between the 4 EMT groups when compared for pregnancy duration in fresh or frozen ET, and in singleton or twin pregnancies. In fresh ET with singleton pregnancies, more obstetrical complications and medically induced deliveries before 41 gestational weeks (GW) were reported in the groups<7 mm and >12mm.Table 1Results for singleton pregnancies<7 mm7-9 mm9-12 mm≥12 mmpvalueFresh ETN=5N=25N=68N=22Pregnancy Duration256.7±20.3262.7±13.4260.7±18.5263.3±10.20.78Birth Weight3153±744.73263.7±407.13196.1±509.23128.2±507.70.83SpontaneousInduced<41GWInduced≥41GW1 (20)2 (40)2 (40)19 (76)5 (20)1 (4)49 (72)14 (21)5 (7)9 (41)10 (45)3 (14)0.01Complications4 (80)4 (16)20 (29)7 (32)0.04Frozen ETN=19N=324N=202N=26Pregnancy Duration256.7±20.3262.7±13.4260.7±18.5263.3±10.20.23Birth Weight3139.2±777.03326.7±535.73271.3±635.23422.7±469.50.29SpontaneousInduced<41GWInduced≥41GW9 (47)7 (37)3 (16)147 (45)126 (39)51 (16)89 (44)78 (39)35 (17)12 (46)10 (38)4 (15)0.99Complications4 (21)87 (27)49 (24)7 (27)0.88 Open table in a new tab Our findings report no difference in the pregnancy duration (in days) or in birth weight related to endometrial thickness at the time of fresh or frozen ET. This suggests that EMT does not impact the quality of placentation.

RECURRENT IMPLANTATION FAILURE – ROLE OF PGT AND ERA TO OPTIMIZE REPRODUCTIVE OUTCOMES?

To assess the role of Pre-Implantation Genetic Testing for Aneuploidy (PGT-A) and Endometrial Receptivity Assay (ERA) in couples with Recurrent Implantation failure (RIF) to optimize reproductive outcomes. This is retrospective data of couples at our private fertility clinic during January 2014 to July 2019. Study population was divided into three groups; All women with history of RIF were only recruited or this study. Group A – Both PGT-A and ERA done (n=79) Group B – only PGT-A done, no ERA done – (n=54) Group C – No PGT-A / No ERA done (n=189) INCLUSION CRITERIA Women with at least two fresh/frozen embryos transfers with minimum 4 blastocysts transferred in total and never conceived were considered as RIF. Only women with one euploid embryo, who underwent frozen embryo transfers (FET) were recruited in this study in group A&B. Women of all age groups who had Blastocysts available for transfer were included in Group- C. Only self-gamete cycles were considered in this study. All the women with RIF underwent controlled ovarian stimulation and oocyte retrieval as per our clinic’s standard operating protocol (SOP). ICSI was the choice of insemination considering history of failed implantation, fertilized oocytes were cultured till blastocysts and freeze all policy was adopted. Blastocysts were biopsied and trophectoderm tissue was subjected to genetic testing through Next-Generation Sequencing (NGS). ERA was done as per our institutes SOP. The biopsy was done using a endometrial biopsy pipette supplied by the company at 120 hours (day 5) of the start of the progesterone supplementation. This procedure was repeated at 144 hours (day 6) also. This was done to cater for the reduction in the error that could occur due to the extrapolation of results in cases of pre-receptive samples. The samples that were collected were stored and transported in the prescribed method of the company. The same conditions were replicated in the (FET) transfer cycle. Group A women underwent elective Single Euploid Blastocyst transfer (eSET) in an artificial cycle as per the ERA timing. Group B underwent eSET of a Euploid Blastocyst in a FET cycle on 6th day post progesterone support, no ERA was done. Group C women underwent transfer with un-screened double Blastocyst Transfer (DET) in a FET cycle. Primary Outcome was Implantation Rate (IR). Mean of IR of all subjects were calculated: Group A - 53% Group B - 47% Group C - 42% Odds ratio and p value was calculated for IR between the groups and showed no statistical significance. Though Group A had the best implantation rates, there was no statistical significance with the other two groups. Role of PGT-A and ERA as an intervention to improve reproductive outcomes is still debatable and needs well designed RCTs to further infer. PGT-A and ERA for RIF couples do not seem to offer beneficial reproductive outcomes. Couples need to be counselled appropriately while offering treatment options for RIF.

P–774 Clinical effectiveness of elective single versus double blastocyst transfer in women aged 36 years or older

Abstract Study question If the elective single-blastocyst transfer (eSBT) strategy can be applied to women aged 36 or older. Summary answer In women ≥36 years old with at least two blastocysts, eSBT increased cumulative livebirth rate (LBR) while minimizing twins compared with double blastocyst transfer (DBT). What is known already: In young women with a good prognosis, eSBT policy is an accepted strategy to maintain LBR while decreasing multiple gestation. However, in many areas of the world DBT is still applied in older women. Study design, size, duration We performed a retrospective cohort study of 429 women aged ≥36 years or older who received IVF ovarian stimulation cycles between Jan 2015 and Oct 2018 and who had at least two blastocysts. Women were followed up until Oct 2020 for their fertility outcomes including cumulative live birth and multiple pregnancies. The study was performed at the Northwest Women and Children’s Hospital, Xi’an, China. Participants/materials, setting, methods Out of 429 women, 240 underwent a fresh cycle of eSBT and 189 DBT. The subsequent frozen-thawed embryo transfer cycles were a combination of single- and double- blastocyst transfers, more commonly the latter. Analysis was stratified for patients in age groups 36–37, 38–39 and ≥40 and quality of the blastocyst transferred, as graded by morphological examination. Outcomes were the LBR in the fresh cycle, cumulative LBR and multiple rate after fresh and frozen embryo transfers. Main results and the role of chance The cumulative LBR was 74.2% (178/240) for eSBT versus 63.0% (119/189) for DBT (OR = 1.69, 95%CI 1.12–2.56), irrespective of female age. The multiple rate was 9% (16/178) after eSBT versus 29.4% (35/119) after DBT (P- value &amp;lt; .001). The total number of children born was 194 after eSBT versus 154 after DBT. Stratified by female age, the cumulative LBRs in women aged 36–37 (78.9 vs 70.5%), 38–39 (68.9 and 61.1%) and ≥ 40 years (59.3 and 47.5%), were higher after eSBT compared with DBT, however, the differences did not reach statistical significance in each subgroups. LBRs in the fresh cycles were comparable for patients with eSBT compared with DBT (52.1% vs. 52.4%, OR = 0.99, 95%CI 0.68–1.45). In women &amp;lt; 40 years, DBT resulted in a small non-significant increase in LBR in the fresh transfer (63.2% vs. 61.2%, 95%CI=0.64–1.85, 36–37 years; 48.1% vs. 41.0%, 95%CI=0.64–2.80, 38–39 years) at the expense of a marked increase in twinning rate (0–5.4% vs. 31.7–34.6%). For women ≥40 years, no significant differences were observed in the LBR (37.0% vs 45%, 95%CI 0.47–4.07) or twinning rate (0 vs 7.7%) between eSBT and DBT group. The findings persisted with and without accounting for quality of the blastocyst transferred. Limitations, reasons for caution This study is limited by its observational character. Wider implications of the findings: In women ≥36 years with two blastocysts, eSBT should be the preferred treatment which maximizes the cumulative LBR for a decrease in the rate of multiple pregnancies. Trial registration number Not applicable