Single Embryo Transfer Research Articles

Maternal age-related declines in live birth rate following single euploid embryo transfer: a retrospective cohort study

PurposeTo assess whether maternal age influences the pregnancy outcomes after single frozen euploid embryo transfer.MethodsThis retrospective analysis was conducted on 1037 cycles of single euploid embryo transfer performed at Nanjing Women and Children’s Healthcare Hospital between January 2016 and April 2023. Patients with severe uterine pathologies, immune disorders, or endocrine diseases were excluded. The cycles were categorized into three age groups: <35 years, 35–37 years, and ≥ 38 years. Primary outcomes included live birth rate, clinical pregnancy rate, early pregnancy loss, and miscarriage rate. Data were analyzed using multivariable logistic regression with generalized estimating equations (GEE) to account for confounding factors and restricted cubic splines to visualize the relationship between maternal age and pregnancy outcomes.ResultsWomen aged ≥ 38 years demonstrated a significantly diminished live birth rate (41.7%) ,which was lower than that observed in women aged < 35 years (54.5%) and 35–37 years (54.0%), with statistical significance (P < 0.05). Multivariable regression analysis revealed that compared with women aged ≥ 38 years, younger women had reduced risk of miscarriage (aOR = 0.371, 95% CI: 0.139–0.988 for the < 35 years group; aOR = 0.317, 95% CI: 0.106–0.954 for the 35–37 years group) and increased likelihood of live birth (aOR = 2.188, 95% CI: 1.154–4.147 for the < 35 years group; aOR = 2.239, 95% CI: 1.0103–4.548 for the 35–37 years group) after adjusting for relevant confounders. Additionally, the analysis showed that embryos biopsied on day 5 were linked to higher clinical pregnancy rates than those biopsied on day 6, and high-grade blastocysts were associated with superior pregnancy outcomes.ConclusionAdvanced maternal age is associated with a higher miscarriage rate and lower live birth rate following euploid embryo transfer. Despite the exclusion of aneuploidy, age-related factors beyond chromosomal abnormalities appear to impact reproductive outcomes.

Risk factors associated with pregnancy loss after single euploid blastocysts transfer

ObjectiveTo detect primary factors influencing pregnancy loss(PL) following the transfer of euploid blastocysts?DesignRetrospective cohort study.MethodsTo identify potential factors influencing PL, we analyzed multiple variables in both the PL group and the live birth group. In order to minimize the impact of confounding factors, various variables were included in a binary logistic regression analysis.ResultsThe PL rate after the transfer of euploid embryos is 13.3% (36 cases of PL out of 270 cases of single embryo transfer). Compared to the live birth group, the PL group had lower E2 levels (2376.03 ± 1553.25 vs 3412.88 ± 2116.47, P=0.007), higher LH levels (2.66 ± 2.47 vs 1.96 ± 1.52, P=0.023) on trigger day of fresh cycle, fewer retrieved oocytes (10.08 ± 5.01 vs 12.77 ± 7.20, P=0.044), higher female BMI (23.26 ± 3.27 vs 22.05 ± 2.69, P=0.016), higher proportion of maternal smokers (50% vs 20.51%, P&amp;lt;0.001), and more day 6 blastocyst transfers ((38.89% vs14.53, P=0.001). Logistic regression analysis revealed that higher LH levels(OR=1.304, 95%CI=1.054-1.613, P=0.015), low E2 levels (OR=0.438, 95%CI=0.242-0.794, P=0.007) on trigger day of fresh cycle, maternal smoking(OR=4.574, 95%CI=1.974-10.601, P&amp;lt;0.001), and day 6 blastocyst transfer(OR=4.610, 95%CI=1.907-11.141, P=0.001) appeared to be associated with increased risk of PL following the transfer of euploid embryos.ConclusionsMaternal smoking, day of blastocyst transferred, estradiol (E2) and Luteinizing hormone (LH) levels on trigger day of corresponding fresh cycle for transferred blastocysts are all associated with PL following transfer of euploid embryos.

One carbon metabolism supplementation in maturation medium but not embryo culture medium improves the yield of blastocysts from bovine oocytes

Optimizing oocyte maturation and embryo culture media could enhance in vitro embryo production. The purpose of the present study was to investigate the role of supplementing one carbon metabolism (OCM) substrates and its cofactors (Cystine, Zinc, Betaine, B2, B3, B6, B12 and 5-methyltetrahydrofolate) in maturation and/or embryo culture media on the rate of blastocyst formation and pregnancy outcomes following the transfer of the resulting blastocysts in bovines. In the first experiment, 2537 bovine oocytes were recovered from slaughterhouse ovaries and then matured either in conventional maturation medium (IVM) or IVM supplemented with OCM substrates (Sup-IVM). After in vitro fertilization, the putative zygotes from each treatment (IVM or Sup-IVM) were cultured in the media either without (IVM/IVC or Sup-IVM/IVC) or with (IVM/Sup-IVC or Sup-IVM/Sup-IVC) OCM supplementation. The blastocyst rate, assessed on day 8, was significantly increased in Sup-IVM/IVC group (34.90 ± 2.52) as compared to IVM/IVC (17.06 ± 1.69; P = 0.0001) and Sup-IVM/Sup-IVC (20.29 ± 2.75; P = 0.004) and non-significantly as compared to IVM/Sup-IVC (24.86 ± 5.37). In the second experiment, non-matured bovine oocytes were collected by transvaginal ovum pick up after FSH stimulation, randomly allocated into IVM/IVC (n = 275) and Sup-IVM/IVC (n = 260) and the blastocysts achieved at day 7 were transferred in recipient cattle. The blastocyst rate was significantly higher in Sup-IVM/IVC group (38.85%) as compared to the IVM/IVC group (23.64%; P < 0.0001). After single embryo transfer, the supplemented blastocysts were at least as competent as non-supplemented ones with a non-significantly higher (20% vs. 14%) pregnancy rate and the advantage of several good quality blastocysts available for future use. In conclusion, optimizing the maturation medium with OCM substrates and its cofactors could enhance the formation of viable blastocysts with the potential to increase the cumulative birth rate in cattle.

New treatment strategies in assisted reproduction

This review elucidates the roles of vitrification and blastocyst culture in assisted reproductive technology. Vitrification exploits ultra-fast cooling rates to preserve embryos and avoid cell-damaging ice crystals. With the cultivation of the embryo to the blastocyst stage, survival- and pregnancy rates are now comparable to those achieved with fresh embryos. This has provided numerous advantages, and this review will focus on the management of ovarian hyperstimulation syndrome, the use of gonadotropin-releasing hormone-agonist trigger, elective single embryo transfer, and preimplantation genetic testing.

Endometrial scratching before euploid embryo transfer: a case-control study.

To evaluate the effect of endometrial scratching on in vitro fertilization (IVF) success rates in women undergoing frozen embryo transfer with preimplantation genetic testing for aneuploidy (PGT-A). Biopsy was performed at oocyte retrieval in cases and compared to those who did not undergo scratching (controls). Endpoints included pregnancy loss, total pregnancy, clinical pregnancy rate (CPR), ongoing pregnancy rate/live birth rate (OPR), and the incidence of chronic endometritis (CE). Women in case and control groups had similar characteristics, such as age, body mass index, and parity. Overall total pregnancy rate was 82.43% following single euploid embryo transfer in cases compared to 85.7% in controls (p = 0.57; OR = 1.27; 95% CI = 0.565 to 2.78). CPR was 73.3% and 76.2% (p = 0.62; OR = 1.18; 95% CI = 0.594 to 2.29), and OPR between groups was 64.8% and 72.3% (p = 0.28; OR = 1.42; 95% CI = 0.74 to 2.7). First trimester loss rate was similar at 16.9%% and 15.5%%, respectively (p = 0.82). Subjects who underwent scratching closer to their frozen embryo transfer (≤ 3months) had a similar overall pregnancy rate to those with a longer delay between retrieval and frozen embryo transfer (> 3months 81.4% vs.87.5%; p = 0.56). CE incidence was 10.8% (8 out of 74; 95% CI = 5.5% to 19.9%). The odds of having a second trimester loss were significantly higher in the scratch group compared to controls (p = 0.03; OR = infinity; 95% CI = 1.3 to infinity). Endometrial scratching before frozen euploid embryo transfer did not influence pregnancy outcome but increased the chances of second trimester loss. CE was a frequent finding in those undergoing endometrial scratching at the time of retrieval.

Could cleaved embryo morphology and morphokinetics be associated with prenatal and neonatal outcomes?

To evaluate if morphology and morphokinetics of cleaved embryos affect prenatal and perinatal outcomes. This retrospective cohort study included 734 single fresh embryo transfer (SET) from ICSI from January 2014 to December 2020 at the Dijon University Hospital. Using time-lapse technology, embryos were defined as TOP or non-TOP according to morphological/morphokinetic criteria. Linear regression, adjusted for maternal factors, explored the association between cleaved-embryo quality and implantation rate, miscarriage rate, live birth rate, term, birthweight, and birthweight Z-score. Multivariate analyses showed that non-implanted embryos were significantly more often out of the interquartile range than implanted embryos for cell events t2 (p = 0.019), t3 (p = 0.038), t4 (p = 0.013), ECC1 (p = 0.047), and ECC2 (p = 0.001). After implantation, the morphokinetics was significantly different for non-TOP embryos ending in miscarriage or live birth. A significant high risk of miscarriage was found for embryos with a short or long ECC1 (3.27 [95% CI: 1.44;8.37]. There was no significant difference in birthweight, birthweight Z-score, or term between TOP and non-TOP embryos. An association with increased birthweight was observed in multivariate analysis for pronuclei appearance (tPNa) (p = 0.001out of the range. Late tPNa was associated with a higher birthweight Z-score (p < 0.0001) while late pronuclei disappearance (tPNf) was associated with a lower Z-score (p = 0.006). Morphological and morphokinetic parameters significantly influence implantation rates and the likelihood of a live birth from embryos with non-optimal morphological features. Birthweight Z-scores were significantly higher with late tPNa and lower with late tPNf.

Impact of previous cesarean delivery on pregnancy and neonatal outcomes in subsequent in vitro fertilization/intracytoplasmic sperm injection and single frozen-thawed embryo transfer: a historical cohort study with a large sample size.

This study aims to explore the impact of a woman's previous cesarean delivery (CD) on pregnancy and neonatal outcomes for subsequent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and single frozen-thawed embryo transfer (FET), compared with vaginal delivery (VD). This was a retrospective cohort study that included a total of 5817 patients who desired to transfer a single vitrified-thawed blastocyst from the same oocyte retrieval cycle as their last live birth between January 2011 and January 2021 at a single reproductive medicine center. Patients with a single previous CD were classified in the CD group, while those with a single VD were assigned to the VD group. All patients underwent single blastocyst transfer. To minimize the effect of confounding factors, modified Poisson regression analyses with different adjustment models and propensity score matching (PSM) analyses were performed. Women with a previous CD had significantly lower rates of biochemical pregnancy, clinical pregnancy, and live births than those with a previous VD. Meanwhile, the CD rate was significantly higher in the CD group. There were no significant differences in the rates of multiple pregnancies, miscarriage, ectopic pregnancy, multiple live births, maternal complications, or preterm and neonatal outcomes. A previous CD is associated with a significant reduction in the rates of biochemical pregnancy, clinical pregnancy, and live birth in patients undergoing subsequent single frozen-thawed blastocyst transfer. Additionally, it increases the rates of repeat CD.

Exploring key embryonic developmental morphokinetic parameters that affect clinical outcomes during the PGT cycle using time-lapse monitoring systems

Research questionIs it possible to predict blastocyst quality, embryo chromosomal ploidy, and clinical pregnancy outcome after single embryo transfer from embryo developmental morphokinetic parameters?DesignThe morphokinetic parameters of 1011 blastocysts from 227 patients undergoing preimplantation genetic testing were examined. Correlations between the morphokinetic parameters and the quality of blastocysts, chromosomal ploidy, and clinical pregnancy outcomes following the transfer of single blastocysts were retrospectively analyzed.ResultsThe morphokinetic parameters of embryos in the high-quality blastocyst group were significantly shorter than those in the low-quality blastocyst group (p < 0.05). In contrast, the CC2 time was significantly prolonged (p < 0.05). On chromosomal analysis of biopsy blastocysts nourished by trophectoderm cells, in comparison to euploid embryos, aneuploid embryos exhibited significant extensions in tPNa, S3, tSC, tM, tSB, and tB (p < 0.05), with a simultaneous significant reduction in CC2 time (p < 0.05). After adjusting for age and body mass index through logistic regression analysis, late morphokinetic parameters, namely tM (OR 0.96; 95% CI 0.93–0.99), tSB (OR 0.94; 95% CI 0.90–0.97), and tB (OR 0.93; 95% CI 0.90–0.97), emerged as independent risk factors influencing the development of embryos into high-quality blastocysts. S3 (< 12.01 h), t8 (< 62.48 h), and tPB2 (< 3.36 h) were potential predictors of a successful clinical pregnancy after blastocyst transfer.ConclusionMorphokinetic parameters showed correlations with blastocyst quality, chromosomal status, and clinical pregnancy outcomes post-transfer, making them effective predictors for clinical results. Embryos with relatively rapid development tended to exhibit better blastocyst quality, chromosomal ploidy, and improved clinical pregnancy outcomes. The late morphokinetic parameter, S3, demonstrated a strong predictive effect on blastocyst quality, chromosomal ploidy, and clinical pregnancy outcomes.

How to balance the live birth rate and the multiple pregnancy rate by selecting the cleavage-stage embryo number and quality for POSEIDON Group 1 and Group 2? A retrospective study.

For unexpected low-prognosis patients (Group 1 and Group 2) defined by POSEIDON criteria, how to maximize the live birth rate while controlling the multiple birth rate by tailoring the embryo transfer number and quality? This was a retrospective study, including patients from Poseidon Group 1 (N = 672) and Group 2 (N = 503) who underwent cleavage-stage embryo transfer. Logistic regression was used for the comparative analysis of clinical outcomes among subgroups divided by the number and quality of embryos. For Group 1, compared to transferring a single good-quality embryo (GQE), a good-quality embryo with a poor-quality embryo (GQE + PQE) did not significantly improve the live birth rate, although increasing in value (40.5% vs 31.9%, P = 0.272), meanwhile obviously raised the multiple birth rate to 28.1% (P = 0.042). For Group 2, double embryo transfer (DET) was associated with a higher live birth rate than single embryo transfer (SET) (22.4% vs 6.3%, P = 0.001) and further analysis indicated that the similar trend observed in the GQE + PQE group compared to the GQE group (26.1% vs 8.5%, P = 0.017) with statistical significance, but without a significant increase in the multiple birth rate (8.3%, P = 1.000). The study indicated that asingle good-quality cleavage-stageembryo was an option for patients in Poseidon Group 1 to avoid the risk of multiple pregnancies. DET with mixed quality cleavage-stageembryo might be an alternative for Poseidon Group 2, given that it improved the pregnancy outcomes while controlling the multiple birth rates.

Adenomyosis, especially in its focal nature, hampers implantation and live birth rate after single euploid embryo transfer.

The primary objective of this study was to assess if uterine adenomyosis impacts live birth rate per euploid embryo transfer. The secondary objectives included addressing obstetric and perinatal outcomes in the study group. This was a multicenter and retrospective cohort study in which 228 patients diagnosed with adenomyosis undergoing single euploid embryo transfer between 2016 and June 2023 were included and matched on 1:1 ratio to control patients without ultrasonographic diagnostic criteria for adenomyosis. A significant higher live birth rate per embryo transfer was observed in controls compared to women with adenomyosis: 107/228 (46.9%) versus 56/228 (24.6%), respectively (odds ratio (OR) = 2.71, 95% confidence interval [CI]: 1.73-4.13, p < 0.001). When dividing adenomyotic patients regarding the nature of the disease, a higher live birth rate per transfer was described in diffuse adenomyosis compared to focal adenomyosis: 47/166 (28.3%) versus 9/62 (15%), respectively (OR = 2.32, 95% CI: 1.03-5.78, p = 0.034). Described differences were constant even when correcting for multiple variables. There was no statistically significant difference in childbirth delivery method (vaginal vs. cesarean section) between the adenomyosis and control groups. Mean gestational age at the time of delivery, newborn size and weight, and incidences of low birth weight, preterm birth, and admission to the neonatal intensive care unit did not differ between the two groups. In addition, invitro fertilization (IVF) and perinatal outcomes were similar in patients with diffuse compared with focal adenomyosis. Adenomyosis, especially focal adenomyosis, affects clinical but may not affect perinatal outcomes after single euploid embryo transfer.

Embryo Cryopreservation Strategy May Improve Live Birth for Women Underwent In Vitro Maturation After Early Oocyte Retrieval: A Retrospective Cohort Study.

There is limited clinical research investigating the optimal transplantation strategy in early oocyte retrieval cycles. We aimed to assess whether the maturation of oocytes from early oocyte retrieval influenced pregnancy outcomes, and to find the optimal embryo transfer strategy (fresh or frozen-thawed embryo transfers) for patients who had early oocyte retrieval and underwent in vitro maturation (IVM). A retrospective cohort study was conducted in a university-based reproductive medical center. A total of 234 women who underwent single embryo transfer after early oocyte retrieval were included. The primary outcome was live birth rate. The live birth rate (12.5% vs. 27.5%, p = 0.005, adjusted p = 0.010) was significantly lower in IVM cycles compared with no IVM cycles. There was a significant decrease in live birth (3.6% vs. 19.0%, p = 0.008, adjusted p = 0.011) and a markedly elevated early pregnancy loss rate (62.5% vs. 11.1%, p = 0.014, adjusted p = 0.012) for IVM fresh cycles compared with no IVM fresh cycles. However, these findings were not repeated in subgroup analysis when frozen-thaw embryos were transferred. These results indicate that patients who underwent early oocyte retrieval and then IVM-intracytoplasmic sperm injection should be recommended the embryo cryopreservation strategy. Resynchronization of the embryo and the endometrium in frozen-thaw embryo transfer cycles may optimize live birth and decrease early pregnancy loss in IVM-intracytoplasmic sperm injection cycles after early oocyte retrieval.

Is Artificial Intelligence (AI) currently able to provide evidence-based scientific responses on methods that can improve the outcomes of embryo transfers? No.

The rapid development of Artificial Intelligence (AI) has raised questions about its potential uses in different sectors of everyday life. Specifically in medicine, the question arose whether chatbots could be used as tools for clinical decision-making or patients' and physicians' education. To answer this question in the context of fertility, we conducted a test to determine whether current AI platforms can provide evidence-based responses regarding methods that can improve the outcomes of embryo transfers. We asked nine popular chatbots to write a 300-word scientific essay, outlining scientific methods that improve embryo transfer outcomes. We then gathered the responses and extracted the methods suggested by each chatbot. Out of a total of 43 recommendations, which could be grouped into 19 similar categories, only 3/19 (15.8%) were evidence-based practices, those being "ultrasound-guided embryo transfer" in 7/9 (77.8%) chatbots, "single embryo transfer" in 4/9 (44.4%) and "use of a soft catheter" in 2/9 (22.2%), whereas some controversial responses like "preimplantation genetic testing" appeared frequently (6/9 chatbots; 66.7%), along with other debatable recommendations like "endometrial receptivity assay", "assisted hatching" and "time-lapse incubator". Our results suggest that AI is not yet in a position to give evidence-based recommendations in the field of fertility, particularly concerning embryo transfer, since the vast majority of responses consisted of scientifically unsupported recommendations. As such, both patients and physicians should be wary of guiding care based on chatbot recommendations in infertility. Chatbot results might improve with time especially if trained from validated medical databases; however, this will have to be scientifically checked.

Effects of preimplantation genetic testing for aneuploidy on embryo transfer outcomes in women of advanced reproductive age with no more than three retrieved oocytes.

To evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) benefits women of advanced reproductive age (≥38 years old) with a diminished ovarian reserve (DOR; not more than three retrieved oocytes). A retrospective analysis comparing two groups: (a) PGT-A group: women who chose PGT-A and subsequent single re-warmed embryo transfers (ETs) and (b) non-PGT-A group: women who chose not to genetically test their embryos and underwent subsequent fresh or re-warmed ETs of one to two embryos on days 3 or 5. Two hundred and thirty patients underwent PGT-A therapy, with 49 of these individuals undergoing more than one PGT-A cycle. Meanwhile, 309 patients received non-PGT-A treatment, among whom 89 underwent more than one cycle of this type. Collectively, this study encompassed a total of 298 PGT-A cycles and 429 non-PGT-A cycles from a single center (April 2019-June 2023). All women had a DOR and advanced reproductive age. The exposure variable was the use of PGT-A. The primary outcome was live birth rates (per cycle and retrieval). Secondary outcomes were clinical pregnancy rates (per cycle and retrieval), miscarriage rates (per pregnancy and retrieval). While PGT-A cycles had lower transfer rates (14.1% vs. 73.2%), they achieved significantly higher pregnancy (66.7% vs. 12.4%) (adjusted odds ratio [aOR] = 11.474; 95% confidence interval [95% CI], 5.462, 24.102; p < 0.001) and live birth rates (57.1% vs. 7.5%) per transfer (aOR = 13.065; 95% CI, 5.987, 28.510; p < 0.001). The PGT-A group also had lower miscarriage rates (14.3% vs. 40.0%) (aOR = 0.142; 95% CI, 0.030, 0.661; p = 0.013). However, overall pregnancy and live birth rates were similar, and the PGT-A group required fewer cycles for live birth (p = 0.023). While PGT-A improved clinical pregnancy and live birth rates per transfer cycle in women of advanced reproductive age with a low oocyte yield, it did not impact these rates per retrieval.

Impact of follicle size before luteal progesterone supplementation on clinical outcomes of modified natural cycle single frozen embryo transfer

Impact of follicle size before luteal progesterone supplementation on clinical outcomes of modified natural cycle single frozen embryo transfer

Effect of day 3 embryo cell number on the pregnancy and neonatal outcomes of day 4 single embryo transfer from fresh cycles

BackgroundThe aim of this retrospective cohort study was to assess the impact of day 3(D3) embryo cell number on the clinical pregnancy and neonatal outcomes of day 4(D4) single embryo transfer in fresh cycles.MethodsThe study included 431 day 4 single embryo transfer in fresh cycles conducted between December 2018 and June 2023. These cycles were divided into three groups according to the day 3 embryo cell number: 248 cycles in the 7 ~ 9-cell group, 149 cycles in the 10 ~ 13-cell group and 34 cycles in the >13-cell group, and clinical pregnancy outcomes and neonatal outcomes were compared among the three groups.ResultsThe clinical outcomes with 10 ~ 13-cell were significantly higher than those of the 7 ~ 9-cell group, regardless of whether the female age was < 30 or ≥ 30 years. The same result could be found when the insemination pattern was IVF, and when the transferred embryos were the grade of complete fusion. There were no differences in neonatal outcomes between different groups.After adjusting for confounding factors, the 7 ~ 9-cell group was associated with lower clinical pregnancy rates(CBR) and live birth rates(LBR) compared with the 10 ~ 13-cell group (CPR: aOR 0.527, 95% CI 0.317 ~ 0.874, P = 0.013; LBR: aOR 0.499, 95% CI 0.308 ~ 0.807, P = 0.005).ConclusionThe cell number of D3 embryos can be an important reference indicator for D4 embryo selection. When performing day 4 single embryo transfer in fresh cycles, embryos with 10 ~ 13-cell on D3 can be preferentially selected for transplantation to enhance clinical outcomes, especially when the insemination pattern is IVF, and when the transferred embryos are the grade of compaction stage.

In vitro fertilization and long-term child health and development: nationwide birth cohort study in Japan

The aim of this study is to compare long-term health outcomes between IVF-conceived children and non-IVF-conceived children in Japan, in the context of strong recommendation for single embryo transfer. Using data from a nationwide birth cohort linked with perinatal database, this study analyzed 2140 children born in Japan in May 2010. It compared child health and development outcomes up to 9 years of age between IVF-conceived and non-IVF-conceived children (binary exposure). A Poisson regression with robust variance to estimate the risk ratios for the association between IVF and various long-term child health and developmental outcomes. After adjusting for confounding factors, no significant differences were observed between IVF-conceived and naturally conceived children for most outcomes, including hospitalization, obesity, and developmental milestones. IVF-conceived children showed a slightly lower risk of attention problems at 8 years (adjusted Risk Ratio [aRR]: 0.73, 95% CI: 0.53–1.00). In subgroup analyses, IVF-conceived term children and singletons demonstrated reduced risk of cognitive delays at 5.5 years (aRR: 0.31, 95% CI: 0.10–0.96 and aRR: 0.37, 95% CI: 0.14–0.98, respectively).Conclusion: In this Japanese cohort, IVF conception was not associated with adverse long-term health or developmental outcomes. These findings provide reassurance about the safety of IVF, particularly in the context of single embryo transfer policies. Further research is needed to explore specific IVF protocols and subgroups.What is known:• Long-term health and developmental outcomes of IVF-conceived children remain inconsistent across studies and populations, despite the widespread use of this technology.What is new:• A nationwide population-based cohort study in Japan did not show adverse effects of IVF on long-term child health and development through age 9.• These findings provide reassurance about the safety of IVF, while indicating the need for careful monitoring in specific subgroups such as preterm and multiple births.

One fresh cleavage-stage single embryo transfer (SET) plus one frozen-thawed blastocyst-stage SET or one fresh cleavage-stage double embryo transfer? A retrospective matched cohort study.

Are there significant differences in fertility outcomes between transferring two cleavage-stage embryos in a single fresh cycle and transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle? In women aged <38 years with two embryos available, transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle increased live birth rates and decreased multiple live birth rates compared to transferring two cleavage-stage embryos in a single fresh cycle. The strategy of repeated single embryo transfer (SET) has emerged as a solution to address the reduced live birth rates associated with SET per cycle. There is substantial evidence indicating that the cumulative live birth rate after repeated SET is comparable to that of double embryo transfer (DET), while significantly reducing the incidence of multiple pregnancies. Evidence regarding the outcomes of transferring two cleavage-stage embryos in a single fresh cycle versus transferring one cleavage-stage embryo in one fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle is scarce. This study is a retrospective matched cohort study, where data were gathered from the clinical database of women who underwent IVF treatment at the Reproductive Center of Peking University Third Hospital between January 2011 and December 2019, with follow-up extending until December 2021. The study group included cycles with a fresh cleavage-stage SET and a subsequent frozen-thawed blastocyst-stage SET (2xSET, N = 976). Fresh cleavage-stage DET was the control group (DET, N = 976). Included cycles were divided into subgroups based on age (≥38 years vs <38 years) and total number of utilizable (transferred or cryopreserved) embryos (=2 vs >2). The duration of infertility, prevalence of unexplained infertility, and controlled ovarian stimulation regimes differed significantly between the two groups and were adjusted for in the further analysis. We observed a significant increase in clinical pregnancies (55.5% vs 42%, adjusted odds ratio (OR) 1.87 [1.55-2.26]) and live births (44.8% vs 34.5%, adjusted OR 1.63 [1.35-1.97]) in favor of the 2xSET group. The preterm birth rate was lower in the study group (adjusted OR 0.64 [0.42-0.96]). Neonatal birth weight of singletons was similar between the two groups (adjusted B 4.94 g [-84.5 to 94.4]). The beneficial effect on the live birth rate disappeared in cases where aged 38 years and older or when only two embryos were utilizable. This study is limited by differences in baseline characteristics of the two groups. Analyzing two consecutive SETs at the cleavage stage was not feasible. Additionally, the homogeneous population limits generalizability to other ethnic groups, which should be considered when interpreting the results broadly. We recommend a combination strategy for women under 38 years old and with more than two embryos available: transfer one cleavage-stage embryo in the fresh cycle, followed by one blastocyst-stage embryo in the subsequent frozen-thawed cycle. This strategy reduces the risk of blastocyst culture failure while maintaining a high success rate. It offers hope to families seeking additional children and avoids unnecessary embryo disposal. B.W.M. had received grants from NHMRC, Ferring, Merck, and Guerbet, consulting fees and stock options from ObsEva, is on the advisory board of ObsEva, and reports consultancy for Guerbet, none of which are in relation to the present manuscript. All other authors have no conflict of interest to declare. N/A.

Assisted reproductive technology and the risk of birth defects mediated by multifetal pregnancy: evidence from the China Birth Cohort Study

BackgroundBoth assisted reproductive technology (ART) and multifetal pregnancy have been reported to be associated with an increased risk of birth defects (BDs). However, it is unclear whether multifetal pregnancy is a mediator that increases the risk of BDs in ART-conceived pregnancies. ObjectivesTo investigate the risk of BDs associated with ART, and to quantify the mediating effect of multifetal pregnancy between ART and BDs. Study DesignFrom November 2017 to August 2021, 132,386 pregnant women from 50 study sites in 17 provinces of China were monitored from their first trimester until delivery (or miscarriage/termination). BDs were detected in both live births and stillbirths. Directed acyclic graph was drawn to understand the causal relationship between ART and BDs, and inverse probability of treatment weighting was used to adjust for confounders. Then, log-binomial generalized estimating equation was established in the inverse probability weighted cohort to estimate the adjusted relative risk (RR) of BDs associated with ART compared to natural conception, while addressing the cluster effect of study sites. Mediation analysis was performed to assess the mediating effect of multifetal pregnancy between ART and BDs. Number needed to harm was calculated for multifetal pregnancy versus singleton pregnancy among ART-conceived pregnancies. ResultsA total of 126,035 naturally conceived and 5124 ART-conceived pregnancies were included in the analysis. The incidence of BDs in the ART conception group (4.2%) was significantly higher than that in the natural conception group (2.5%), with an adjusted RR of 1.48 (95% CI, 1.24 to 1.78). Multifetal pregnancies were also more common in the ART conception group (21.4%) than the natural conception group (1.1%). Mediation through multifetal pregnancy accounted for 25% of the risk of BDs associated with ART. Notably, if ART-conceived pregnant women could have singleton pregnancy rather than multifetal pregnancy, one case of BDs could be potentially avoided for every 52 (95% CI, 29 to 233) pregnancies. ConclusionsMultifetal pregnancy mediated the effect of ART on BDs. Therefore, when ART treatment is needed, single embryo transfer should be considered under clinically feasible conditions for the prevention of BDs.

IMPACT OF BLASTOCYST GRADES TO IMPLANTATION AND LIVE-BIRTH RATES IN WOMEN LESS THAN 30 YEARS WITH SINGLE EMBRYO TRANSFERS

Background:Morphological evaluation of blastocysts focusing on key factors such as expansion, inner cell mass (ICM) quality, and trophectoderm (TE) quality have been most widely used for embryo selection. The study emphasizes the importance of detailed blastocyst evaluation, highlighting that morphological variations can have substantial implications for ART outcomes. Methods:A total of 115women aged less than 30 years undergoing SET from from January 2023 to June 2023 were included in this study.The patients were divided into three groups based on their morphologic grading before embryo transfer: good-quality (n = 53), average-quality (n = 52) and poor-quality blastocysts (n = 10). The three morphologic groups pregnancy outcomes were examined, and the implantation rate was logistically regressed. Results:Good-quality blastocysts yielded a statistically significantly higher implantation rate (77%) than average / poor-quality blastocysts (44% and 20% respectively). Average-quality blastocysts still yielded in higher implantation rates (44%) compared to poor-quality blastocysts (20%). The baseline characteristics were analysed for significance using the Pearsons Chi-squared test. A P-value &lt; 0.05 was considered statistically significant. All the statistical analyses were performed using the social science statistics website with SPSS software. Conclusions:Higher blastocyst morphologic grading was associated with increased implantation rate for single embryo transfers. These findings suggest that evaluating blastocyst morphology is critical when selecting the best blastocyst.

Determining Factors Influencing The Successful Embryo Transfer and Pregnancy during The Frozen Cycle of In Vitro Fertilization: A Retrospective Cohort Study.

Frozen embryo transfer (FET) has been increasingly used due to advancements in cryopreservation techniques and the safety advantages. This study aims to determine various factors influencing the successful FET. Retrospective cohort analysis included 1112 women who underwent programmed FET between January 2012 and October 2022, at King Chulalongkorn Memorial Hospital, Thailand. Patient characteristics, embryo characteristics, endometrial preparation protocol, endometrial characteristics (thickness, pattern), embryo transfer procedure (tip and flow during transfer, embryo placement location, the difficulty of the procedure, presence of blood and mucous at catheter), and operator factor were analyzed. Multiple logistic regression analysis was used to assess the relationship between collected variables and successful embryo transfer which is defined by clinical pregnancy. The overall clinical pregnancy rate was 34.2%. Women aged 35-40 years and >40 years were less likely to have a clinical pregnancy compared to those aged <35 years [adjusted odds ratio (aOR): 0.523; 95% confidence intervals (CI): 0.360-0.757, P<0.001 and aOR: 0.260; 95% CI: 0.152-0.434, P<0.001, respectively]. Obese women with body mass index (BMI) ≥25 kg/m2 were significantly associated with decreased clinical pregnancy (aOR: 0.632; 95% CI: 0.403-0.978, P=0.042) compared to those with normal BMI. Day-3 and day-4 embryo transfer showed a significant decrease in clinical pregnancy compared to blastocyst transfer (aOR: 0.294; 95% CI: 0.173-0.485, P<0.001 and aOR: 0.497; 95% CI: 0.265-0.900, P=0.024). Double embryo transfer (DET) was 1.78 times more likely to have a clinical pregnancy than women with single embryo transfer (SET) (aOR: 1.779; 95% CI: 1.293-2.458, P<0.001). The cycles with endometrial thickness <8 mm were associated with a decrease in clinical pregnancy compared with those with a thickness ≥8 mm (aOR: 0.443; 95% CI: 0.225-0.823, P=0.013). Older age, obesity, non-blastocyst transfer, single embryo transfer, and endometrial thickness of <8 mm were significantly associated with a decreased clinical pregnancy in programmed FET.