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Objective: To evaluate whether extending embryo culture to day 5 (D5) affects pregnancy rates in women older than 38 years undergoing in vitro fertilization (IVF). Methods: This retrospective, observational cohort study included data from fresh IVF cycles of women over 38 years, during 2011–2021. The cohort was divided according to day 3 (D3) versus D5 embryo transfer (ET). Results: A total of 346 patients (ages 38–45 years) who underwent 496 IVF cycles were included, each yielding one to six embryos. A total of 374 (75%) fresh D3 ETs were compared with 122 (25%) D5 ETs. Demographically, there were more nulliparas in the D3 group (189 [50.9%] vs 47 [38.8%], P = 0.021). Higher gonadotropin dosage was used (3512 ± 1346 vs 3233 ± 1212 IU, P = 0.045) and lower maximum estradiol levels were reached in the D3 group (1129 ± 685 vs 1432 ± 708 pg/mL, P = 0.002). Thirty‐three (27%) of the D5 cycles resulted in transfer cancelation due to failure of blastocyst formation (P = 0.001). However, clinical pregnancy rates (P = 0.958), live birth rates (P = 0.988), and miscarriage rates (P = 0.710) did not differ between D3 and D5 ETs. Multivariable logistic regression for clinical pregnancy rate showed that day of transfer did not have a significant effect on the odds (P = 0.376), but maternal age (P = 0.001) and number of retrieved oocytes (P = 0.009) were significant variables. Conclusions: In older women, culturing embryos to blastocyst stage can decrease invalid ETs without reducing pregnancy rates. Cancelation rates are higher but it may avoid interventions and conserve valuable time. Synopsis: Extending embryo culture to day 5 in women over the age of 38 with fewer than six embryos did not influence clinical pregnancy rate. [ABSTRACT FROM AUTHOR]

Background: Selecting embryos with the highest implantation potential is crucial for in vitro fertilization (IVF) success.Both the timing of blastulation, day 5 (D5) or D6, and the embryo quality have been suggested as influentialfactors in determining the clinical outcome of single euploid blastocyst transfers. However, evidence supporting thesuperiority of D5 over D6 blastocysts remains inconclusive. The aim of this study was to compare clinical outcomesfollowing the transfer of euploid blastocysts with different quality and timing of blastulation.Materials and Methods: A retrospective cohort study was conducted at our Assisted Reproductive Center, analyzingthe outcome of 774 transfers with D5 euploids and 155 transfers with D6 euploids performed between January 2019and February 2022.Results: The live birth rate was significantly lower in the euploid D6 group compared to the euploid D5 group (38.71vs.55.04%, P=0.001). The outcome was significantly influenced by the quality of the embryos. Live birth rates were 62.14and 53.61% following transfers of D5 and D6 excellent embryos respectively, 45.18 and 32.21% following transfer ofD5 and D6 good embryos but only 28.64 and 19.32% following transfer of D5 and D6 fair embryos. The outcome differencewas statistically significant across embryo quality categories (P=0.001). The adjusted risk ratios (RR) of clinicaloutcomes indicated that excellent euploid D5 embryos consistently outperformed other types of embryo quality.Conclusion: The timing of blastulation and embryo quality are crucial factors in determining the success of singleeuploid blastocyst transfers. Excellent euploid D5 transfers yielded superior clinical outcomes, providing valuableinsights for IVF teams and patients when selecting embryos to be transferred.

Dan Qi,1– 9 Xi Zhang,1– 8 Fangli Li,10 Shengrui Zhao,2– 8 Qiumin Wang,1– 8 Wen Liu,2– 8 Lei Yan,1– 8 Yanbo Du1– 8 1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, People’s Republic of China; 2National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, People’s Republic of China; 3Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, People’s Republic of China; 4Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, People’s Republic of China; 5Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, People’s Republic of China; 6Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 7Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001), Jinan, Shandong, People’s Republic of China; 8Medical Integration and Practice Center, Shandong University, Jinan, Shandong, People’s Republic of China; 9Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China; 10Department of Gynecology and Obstetrics, Public Health Clinical Center Affiliated to Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yanbo Du, Center for Reproductive Medicine, Shandong University, Jinan, 250012, Shandong, People’s Republic of China, Tel +86 1 301 173 4515, Email duyanboivf@163.comPurpose: The objective of this study was to assess reproductive outcomes of D6 blastocysts transferred on day 6 in comparison to those transferred on day 7 of progesterone exposure in frozen-thawed embryo transfer cycles.Patients and Methods: This retrospective cohort study included 2029 D6 single blastocysts from the first frozen-thawed embryo transfer cycles of patients at the Hospital for Reproductive Medicine Affiliated to Shandong University from February 2017 to January 2020. Participants were divided into Group A (blastocyst transferred on the 6th day of progesterone exposure, n=1634) and Group B (blastocyst transferred on the 7th day of progesterone exposure, n=395).Results: The live birth rate was comparable between Group A and Group B (38.7% versus 38.7%, P=0.999). Subgroup analysis revealed a significantly higher preterm birth rate in D6 single blastocysts transferred on the 7th day than in those transferred on the 6th day of progesterone exposure for natural cycle frozen-thawed embryo transfer (5.2% versus 11.3%, P=0.020). After adjustment for potential confounders, the differences in the preterm birth rate in natural cycles persisted (adjusted odds ratio 2.347, 95% confidence interval 1.129– 4.877, P=0.022).Conclusion: In frozen-thawed embryo transfer cycles, transferring on the 6th or 7th day of progesterone exposure of D6 blastocysts did not affect the live birth rate; however, when a natural cycle protocol is adopted, the possible preterm risk of transferring D6 blastocysts on the 7th day of progesterone exposure should be noted.Keywords: frozen-thawed embryo transfer, blastocyst transfer, endometrium preparation, live birth rate

Background: Assisted reproductive technology (ART), offers hope for many infertile couples by increasing the chance of successful pregnancy. The success of in vitro fertilization depends on various factors, in which embryo transfer (ET) is one of the critical steps influencing in vitro fertilization success rates. Extended embryo culture and blastocyst-stage ET have been considered in ART due to their potential benefits including improved implantation rates. Objective: This study aimed to compare the outcomes of sequential ET vs single cleavage-stage ET in women undergoing a fresh ET cycle with a limited number of embryos. Materials and Methods: This randomized clinical trial was conducted on 140 women undergoing infertility treatments and candidates for fresh ET at the Research and Clinical Center for Infertility, Yazd, Iran from August 2023 to January 2024. Women with a number of embryos from 2-5 (= 2 and = 5 available embryos) were randomly divided into 2 groups: One group underwent sequential ET (one cleavage-stage ET followed by one blastocyst ET) and the other group underwent single-step 2 cleavage-stage ET. The primary outcome was clinical pregnancy, and the secondary outcome included chemical pregnancy and early abortion rates. Results: Our findings showed significantly higher rates of clinical (33.5% vs 13.6%, p = 0.003) and chemical (41.3% vs 18.2%, p = 0.004) pregnancies in the sequential ET group compared to the single-step cleavage ET group. The early abortion rate was higher in single-step cleavage ET (13% vs 44.4%, p = 0.053). Conclusion: Sequential fresh ET is a useful choice in women who have a limited number of embryos and can improve ART outcomes. [ABSTRACT FROM AUTHOR]

Abstract The sex ratio shift was observed in peoples who underwent ART treatment. Moreover, there is limited evidence on differences in sex ratio between single frozen-thawed blastocyst morphology, insemination type and transfer days. So further research is needed in this area with regard to factors possibly affecting the sex ratio. Retrospective study based on multicenter including two large assisted reproduction centers in Shanghai and Wuhan in China. A total of 6361 singleton delivery offspring after frozen-thawed blastocyst transfer. Propensity score weighting and logistic regression models were used to estimate the associations between blastocyst morphology grading and child sex ratio. The main outcome measures is singleton sex ratio. In our study, the primary outcome measure was sex ratio which was calculated as the proportion of male newborns among all live births. Higher quality blastocysts resulted in a higher sex ratio than single poor-quality frozen-thawed blastocyst transfer. Among the three blastocyst morphological parameters of trophectoderm (TE), Grade A and B were significantly associated with a higher sex ratio than Grade C. The similar trend was observed in both IVF and ICSI treated subgroups. As compared with expansion (4 + 3), expansion degree 6 achieved a higher sex ratio in overall populations and IVF treated subgroup. Transferring blastocysts of day 6 had the highest sex ratio both in IVF group and ICSI group. A 6.95% higher sex ratio in transferring blastocysts of day 5 in IVF group than those in ICSI group. No significant association between inner cell mass degree and sex ratio was observed. However, as compared with IVF treatment, all morphology parameters achieved the similar or the biased sex ratio favoring female in ICSI treated subgroup. Quality of blastocysts was positively associated with sex ratio. TE score and expansion degree rather than ICM were significantly associated with sex ratio at birth. ICSI treatment promotes the biased sex ratio favoring female.

Abstract This study aimed to examine the viability of human blastocysts after warming with fatty acids (FAs) using an in vitro outgrowth model and to assess pregnancy outcomes after a single vitrified-warmed blastocyst transfer (SVBT). For the experimental study, we used 446 discarded vitrified human blastocysts donated for research purposes by consenting couples. The blastocysts were warmed using FA‐supplemented (FA group) or non-FA-supplemented (control group) solutions. The outgrowth area was significantly larger in the FA group (P = 0.0428), despite comparable blastocyst adhesion rates between the groups. Furthermore, the incidence of outgrowth degeneration was significantly lower in the FA group than in the control group (P = 0.0158). For the clinical study, we retrospectively analyzed the treatment records of women who underwent SVBT in natural cycles between January and August 2022. Multiple covariates that affected the outcomes were used for propensity score matching as follows: 1342 patients in the FA group were matched to 2316 patients in the control group. Pregnancy outcomes were compared between the groups. The rates of implantation, clinical pregnancy, and ongoing pregnancy significantly increased in the FA group after SVBTs (P = 0.0091–0.0266). These results indicate that warming solutions supplemented with FAs improve blastocyst outgrowth and pregnancy outcomes after SVBTs.

Objective: The probability of embryo implantation in an abnormal location is significantly higher in assisted reproductive technology (ART) than in natural pregnancies. Angular pregnancy is an eccentric intrauterine pregnancy with embryo implantation in the lateral superior angle of the uterine cavity. Cycle‐level factors associated with angular pregnancy in patients conceived with ART needed to be explored. Methods: A total of 11 336 clinical pregnancies cycles were included. Angular pregnancy rate was compared among groups according to the type of embryos transferred. Among them, 53 cases of angular pregnancy and 159 cases of normal intrauterine pregnancy were screened out using propensity score matching. Risk factors of angular pregnancy were explored. Results: The angular pregnancy rate was 0.31% (14/4572) in the day 5 blastocyst transfer group, 0.58% (39/6764) in non‐day 5 embryo transfer group, with 0.55% (29/5280) in day 3 embryo transfer and 0.67% (10/1484) in the day 6 blastocyst group, respectively. A multifactor regression analysis was performed and indicated that the number of embryos transferred was significantly associated with angular pregnancy (P = 0.031, OR, 2.23, 95% CI: 1.09–4.68). Conclusion: Multiple embryo transfer could possibly be associated with an increased incidence of angular pregnancy in patients conceived with ART. Synopsis: Multiple embryo transfer could possibly be associated with an increased incidence of angular pregnancy in patients conceived with ART. [ABSTRACT FROM AUTHOR]

This study aimed to examine the viability of human blastocysts after warming with fatty acids (FAs) using an in vitro outgrowth model and to assess pregnancy outcomes after a single vitrified-warmed blastocyst transfer (SVBT). For the experimental study, we used 446 discarded vitrified human blastocysts donated for research purposes by consenting couples. The blastocysts were warmed using FA‐supplemented (FA group) or non-FA-supplemented (control group) solutions. The outgrowth area was significantly larger in the FA group (P = 0.0428), despite comparable blastocyst adhesion rates between the groups. Furthermore, the incidence of outgrowth degeneration was significantly lower in the FA group than in the control group (P = 0.0158). For the clinical study, we retrospectively analyzed the treatment records of women who underwent SVBT in natural cycles between January and August 2022. Multiple covariates that affected the outcomes were used for propensity score matching as follows: 1342 patients in the FA group were matched to 2316 patients in the control group. Pregnancy outcomes were compared between the groups. The rates of implantation, clinical pregnancy, and ongoing pregnancy significantly increased in the FA group after SVBTs (P = 0.0091–0.0266). These results indicate that warming solutions supplemented with FAs improve blastocyst outgrowth and pregnancy outcomes after SVBTs. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of an extended culture period on birth weight among singletons born after vitrified-warmed embryo transfer Methods: 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. Results: The unadjusted birth weight of singletons born after vitrified blastocyst transfer were heavier than those born after cleavage-stage transfer (b=30.28, SE=13.17, P=0.022), as were the adjusted birth weights (b=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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Abstract Background 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. Methods 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. Results 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

Jingwen Jiang,1– 3,* Na Kong,1– 3,* Qingqing Shi,1– 3,* Yuan Yan,1– 3 Xiaoyue Shen,1– 3 Jie Mei,1– 3 Haixiang Sun,1– 3 Chenyang Huang1– 3 1Center for Reproductive Medicine and Obstetrics and Gynecology, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China; 2Reproductive Medicine Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 3Center for Molecular Reproductive Medicine, Nanjing University, Nanjing, 210008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haixiang Sun; Chenyang Huang, Center for Reproductive Medicine and Obstetrics and Gynecology, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China, Tel +8625-8310-6666-70261, Fax +8625-8310-7188, Email stevensunz@163.com; dianshui19901562@126.comBackground: Previous studies suggested higher serum progesterone (P) levels were strongly associated with a lower clinical pregnancy rate (CPR) for in vitro fertilization-embryo transfer (IVF-ET). However, the effect of increased serum P levels on the day of human chorionic gonadotropin (hCG) administration on clinical outcomes in short-acting gonadotropin-releasing hormone agonist (GnRHa) downregulated IVF-ET cycles remains unclear.Methods: We conducted a retrospective cohort study from January 2017 to December 2021, which included a total of 1664 patients receiving their first short-acting GnRHa IVF-ET cycles at our reproductive medicine centre of Nanjing Drum Tower Hospital. The smooth curve fitting and interaction analysis were employed to analyse the association between the CPR and the serum P levels with different embryo types (cleavage-stage embryo or blastocyst). In addition, total cycles were grouped according to different P levels on the trigger day of hCG administration for further analysis.Results: The CPR of patients with increased serum P level (higher than 1.5 ng/mL) on the hCG day did not decrease. A smoothing curve fitting showed that the CPR did not change obviously with the increase in serum P levels. Subgroup analysis of different types of embryos transferred showed that no correlation was observed between the CPR and serum P levels on the day of hCG administration in cleavage-stage embryo transfer cycles. However, the CPR of patients receiving blastocyst transfer showed a downward trend with the increase in serum P levels. At the same time, an interaction analysis also confirmed that the CPR of blastocyst transfer was more likely to be affected by elevated serum P levels on the hCG day.Conclusion: In the luteal phase short-acting GnRHa downregulated IVF-ET cycles, the elevated serum P levels on the hCG day did not affect the CPR of cleavage-stage embryo transfer but reduced the CPR of blastocyst transfer.Keywords: short-acting GnRHa, elevated progesterone level, hCG trigger day, clinical pregnancy rate, blastocyst transfer

Background: 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. Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

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Background: ICSI (intracytoplasmic sperm injection) leads to a reduced male-tofemale ratio at birth, whereas blastocyst transfer results in an increased male-tofemale ratio. However, limited knowledge exists regarding the impact of these factors on the live birth rate for each gender. This study aimed to investigate the influence of patient characteristics and treatment parameters on the live birth rate for each gender, as well as the ultimate male-to-female ratio at birth in frozen-thawed embryo transfer (FET) cycles. Method: This retrospective cohort study involved a total of 28,376 FET cycles and 9,217 subsequent deliveries, spanning from January 2003 to December 2015. The study consisted of two parts. First, logistic regression models were constructed to determine the factors influencing the male-to-female ratio among babies born after FET. Second, we aimed to investigate the mechanisms underlying this sex ratio imbalance by analyzing data from all transfer cycles. Generalized estimated equations were employed to assess the impact of risk factors on rates of male and female live births separately. Results: ICSI resulted in a lower proportion of male offspring compared to in vitro fertilization (IVF) (50.1% vs. 53.7%, aOR: 0.87, 95% CI: 0.80-0.96). Conversely, blastocyst transfer yielded a higher proportion of male offspring than cleavagestage embryo transfer (58.7% vs. 51.6%, aOR: 1.32, 95% CI: 1.17-1.48). Analysis of all cycles indicated that ICSI resulted in a reduced likelihood of male live birth in comparison to IVF (19.8% vs. 21.6%, aOR: 0.90, 95% CI: 0.83-0.97). However, the transfer of blastocysts rather than cleavage-stage embryos not only increased the chance of male live birth (26.9% vs. 20.2%, aOR: 1.70, 95% CI:1.56-1.85) but also facilitated female live birth (20.3% vs. 19.3%, aOR: 1.26, 95% CI: 1.15-1.39). Conclusion: ICSI was associated with a reduction in the male-to-female sex ratio and a lower rate of male live births, while blastocyst transfer was associated with an increased male-to-female sex ratio at birth and a higher rate of male live births. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What are the dynamic expression features of plasma microRNAs (miRNAs) during the peri-implantation period in women with successful pregnancy via single frozen-thawed blastocyst transfer? SUMMARY ANSWER There is a significant change in the plasma miRNA expression profile before and after blastocyst transfer, during the window of implantation. WHAT IS KNOWN ALREADY The expression of miRNAs in peripheral blood has indicative functions during the peri-implantation period. Nevertheless, the dynamic expression profile of circulating miRNAs during the peri-implantation stage in women with a successful pregnancy has not been studied. STUDY DESIGN, SIZE, DURATION Seventy-six women treated for infertility with a single frozen-thawed blastocyst transfer in a natural cycle were included in this study. Among them, 57 women had implantation success and a live birth, while 19 patients experienced implantation failure. Peripheral blood samples were collected at five different time points throughout the peri-implantation period, including D0 (ovulation day), D3, D5, D7, and D9 in this cycle of embryo transfer. The plasma miRNAs in women with blastocyst transfer were isolated, sequenced, and analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS Peripheral blood samples were collected in EDTA tubes and stored at −80°C until further use. miRNAs were isolated from blood, cDNA libraries were constructed, and the resulting sequences were mapped to the human genome. The plasma miRNAs were initially analyzed in a screening cohort (n = 34) with successful pregnancy. Trajectory analysis, including a global test and pairwise comparisons, was performed to detect dynamic differentially expressed (DE) miRNAs. Fuzzy c-means clustering was conducted for all dynamic DE miRNAs. The correlation between DE miRNAs and clinical characteristics of patients was investigated using a linear mixed model. Target genes of the miRNAs were predicted, and functional annotation analysis was performed. The expression of DE miRNAs was also identified in a validation set consisting of women with successful (n = 23) and unsuccessful (n = 19) pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE Following small RNA sequencing, a total of 2656 miRNAs were determined as valid read values. After trajectory analysis, 26 DE miRNAs (false discovery rate < 0.05) were identified by the global test, while pairwise comparisons in addition identified 20 DE miRNAs. A total of seven distinct clusters representing different temporal patterns of miRNA expression were discovered. Nineteen DE miRNAs were further identified to be associated with at least one clinical trait. Endometrium thickness and progesterone level showed a correlation with multiple DE miRNAs (including two of the same miRNAs, hsa-miR-1-3p and hsa-miR-6741-3p). Moreover, the 19 DE miRNAs were predicted to have 403 gene targets, and there were 51 (12.7%) predicted genes likely involved in both decidualization and embryo implantation. Functional annotation for predicted targets of those clinically related DE miRNAs suggested the involvement of vascular endothelial growth factor and Wnt signaling pathways, as well as responses to hormones, immune responses, and cell adhesion-related signaling pathways during the peri-implantation stage. LARGE SCALE DATA The raw miRNA sequence data reported in this article have been deposited in the Genome Sequence Archive (GSA-Human: HRA005227) and are publicly accessible at https://ngdc.cncb.ac.cn/gsa-human/browse/HRA005227. LIMITATIONS, REASONS FOR CAUTION Although the RNA sequencing results revealed the global dynamic changes of miRNA expression, further experiments examining the clinical significance of the identified DE miRNAs in embryo implantation outcome and the relevant regulatory mechanisms involved are warranted. WIDER IMPLICATIONS OF THE FINDINGS Understanding the dynamic landscape of the miRNA transcriptome could shed light on the physiological mechanisms involved from ovulation to the post-implantation stage, as well as identifying biomarkers that characterize stage-related biological process. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Major clinical research project of Tangdu Hospital (2021LCYJ004) and the Discipline Platform Improvement Plan of Tangdu Hospital (2020XKPT003). The funders had no influence on the study design, data collection, and analysis, decision to publish, or preparation of the article. There are no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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 groupwas 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. Conclusions: Sequential embryo transfer in FET cycles could improve the clinical outcomes of patients with RIF. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical outcomes of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles using frozen–thawed blastocyst transfers derived from zygotes with no (0PN) or one pronucleus (1PN). Methods: This retrospective study included 7084 0PN, 2238 1PN, and 72,266 two pronuclear (2PN) embryos cultured to the blastocyst stage from 19,631 IVF and 12,377 ICSI cycles between March 2018 and December 2021. Developmental potential and clinical outcomes of 0PN, 1PN, and 2PN embryos were analyzed. A total of 290 0PN-, 92 1PN-, and 1906 2PN-derived single frozen–thawed blastocyst transfers were performed. Chromosome euploid rates of 0PN-, 1PN-, and 2PN-derived blastocysts were analyzed by next-generation sequencing. Euploid 0PN- and 1PN-derived blastocysts underwent subsequent Infinium Asian Screening Array gene chip analysis to detect ploidy alterations. Results: Available blastocyst rates of 0PN and 1PN embryos were significantly lower than those of 2PN embryos in both IVF and ICSI cycles. Single 0PN and 1PN blastocysts transferred in frozen–thawed cycles resulted in a similar clinical pregnancy rate, miscarriage rate, live birth rate, and neonatal outcome to 2PN blastocysts in IVF and ICSI cycles. Genetic analysis showed that euploid rates of 0PN- and 1PN-derived blastocysts used for ICSI cycles were similar to that of 2PN-derived blastocysts. Conclusion: Our study indicated that 0PN- and 1PN-derived blastocysts resulted in similar clinical outcomes to 2PN-derived blastocysts. The 0PN- and 1PN-derived blastocysts from ICSI cycles can be transferred as well as those from IVF cycles when the number of 2PN-derived blastocysts is insufficient. [ABSTRACT FROM AUTHOR]

Background: Twin pregnancies carry significant fetal, perinatal and maternal risks. Thus, it is important to evaluate clinical outcomes of in vitro fertilization with donor sperm (IVFD) in the first attempt with double cleavage-stage embryos and explore optimal number of day 3 high-quality embryos for the blastocyst transfer on day 5. Methods: We retrospectively identified all IVFD embryo transfers (IVFD-ETs) for the initial time between 2014 and 2021 at our hospital. We mainly analyzed the twin pregnancy rates for double day 3 embryo transfers and clinical outcomes of day 5 blastocyst transfers by prolonged culture with different numbers of day 3 high-quality embryos. Results: Among 1512 IVFD-ETs, 834 were day 3 embryo transfers and 678 were day 5 blastocyst transfers. Our data indicated that the twin pregnancy rates reached up to 40% in the 674 double cleavage-stage embryo transfers and it was not due to the quality of the transferred embryos. For prolonged culture with 2, 3 and 4 day 3 high-quality embryos, the cycle rates of no high-quality blastocysts obtained were 30.43%, 19.80% and 7.91%, respectively. The clinical pregnancy rates were 56.52%, 74.26% and 72.32%, respectively. The twin pregnancies rates were 7.69%, 14.67% and 6.77%, respectively. Conclusions: Transferring double cleavage-stage embryos had high risks of twin pregnancies in the IVFD-ETs. Blastocyst transfer was safe and recommended for the patients with three or more high-quality embryos on day 3.

The ability to predict the likelihood of a live birth after single fresh embryo transfer is an important part of fertility treatment. While past studies have examined the likelihood of live birth based on the number of oocytes retrieved and cleavage-stage embryos available, the odds of a live birth based on the number of supernumerary blastocysts cryopreserved following a fresh embryo transfer has not been rigorously studied. We performed a retrospective analysis, stratified by age, on patients undergoing their first fresh autologous single day 5 blastocyst transfer to assess relationship between the likelihood of a live birth and number of supernumerary blastocysts cryopreserved. In patients aged <35 years and 35–39 years old, the likelihood of a live birth increased linearly between 1 and 6 supplementary blastocysts and non-linearly if 10 or more blastocysts were cryopreserved. When aged 40 years and above, the likelihood of a live birth increased linearly up to 4 cryopreserved blastocysts and then non-linearly if 10 or more blastocysts were cryopreserved. The present study demonstrated a non-linear relationship between the number of supernumerary blastocysts cryopreserved and the likelihood of a live birth after single blastocyst transfer in the first autologous fresh IVF/ICSI cycle across different age groups. [ABSTRACT FROM AUTHOR]

Abstract Background Letrozole treatment is considered an effective option in endometrial preparation for frozen embryo transfers in patients with ovulation disorders or irregular menstruation; however, the effectiveness of letrozole-induced endometrial preparation remains unclear in ovulatory patients. Furthermore, there is no comparative study reporting on pregnancy complications and congenital anomalies after frozen embryo transfers comparing natural and letrozole-assisted cycles. This study examined whether letrozole-induced endometrial preparation affected pregnancy outcomes, perinatal outcomes, and congenital anomalies after single vitrified-warmed blastocyst transfers (SVBTs) in ovulatory patients, as compared with the natural cycle. Methods This historic cohort study included only patients with unexplained infertility. Overall, 14,611 patients who underwent SVBTs between July 2015 and June 2020, comprising both natural and letrozole-assisted cycles, were included. Multiple covariates that impact outcomes were used for propensity score matching; 1,911 patients in the letrozole group were matched to 12,700 patients in the natural group, and the clinical records of 1,910 patients in each group were retrospectively analysed. Cycle characteristics, pregnancy outcomes (clinical pregnancy, ongoing pregnancy, and live birth), and incidence of pregnancy complications and congenital anomalies were statistically compared between the two groups. Results Multivariate logistic regression analysis showed that letrozole administration during SVBT cycles significantly improved the live birth rate (P = 0.0355). Gestational age, birth length, birth weight, and infant sex, as well as the incidence of pregnancy complications and birth defects, were statistically comparable between the two groups. Furthermore, multivariate logistic regression analysis revealed that the perinatal outcomes were not affected by letrozole-induced endometrial preparation. Conclusions Letrozole-induced endometrial preparation improved the live birth rate compared with the natural cycle, without adverse effects on perinatal outcomes and congenital anomalies after SVBTs. Therefore, letrozole-induced endometrial preparation might be a safe and more effective strategy, especially for patients with insufficient luteal function.

Abstract Background It remains unclear whether polycystic ovary syndrome (PCOS) is an independent risk factor for pregnancy complications in women undergoing assisted reproductive technology (ART) treatment. For the integrative treatment of PCOS patients, it is still important to investigate the pregnancy outcomes of PCOS patients after adjusting for potential biases, such as body mass index, embryo quality and endometrial preparation method. Methods This retrospective cohort study ultimately included a total of 336 PCOS patients who conceived after single thawed blastocyst transfer in the PCOS group and 2,325 patients in the control group from January 2018 to December 2020. A propensity score matching (PSM) model was used, and 336 PCOS patients were matched with 336 patients in the control group. Results Before PSM, no differences in the miscarriage rate, pregnancy complication rate, preterm birth rate, or live birth rate were found between the PCOS group and the control group. After PSM, the late miscarriage rate of the PCOS group was significantly higher than that of the control group (3.3% vs. 0.6%, P = 0.040), although the early miscarriage rates were similar (14.0% vs. 13.7%). The rates of pregnancy complications, preterm birth and live birth in the PCOS group were comparable to those in the matched control group (P = 0.080, P = 0.105, P = 0.109, respectively). The neonatal weights of male infants and female infants were similar between the two groups (P = 0.219, P = 0.169). Subgroup analysis showed that PCOS patients with homeostasis model assessment of insulin resistance (HOMA-IR) levels ≥ 2.49 had a significantly increased risk of preterm birth compared with those with HOMA-IR levels

The rate of monozygotic twinning (MZT) has seen a gradual increase in recent years. Numerous parameters involved in ART procedures are blamed for this surge, even though the exact explanation is as yet unknown. Our study's objectives were to determine the risk variables for monozygotic twinning after ART and to estimate their prevalence. We examined 25,794 IVF cycles for the incidence of monozygotic twinning in this observational analysis. Our study, which was carried out across seven tertiary IVF centres over the course of four years, found an overall MZT rate of 0.37% per embryo transfer procedure and 0.88% of all pregnancies. Monozygotic twinning was more commonly seen in fresh single-embryo transfer (SET) and blastocyst transfer cycles. Larger multicentre studies are needed to explore the potential risk variables. [ABSTRACT FROM AUTHOR]

Background: There are few studies evaluating the effects of number and quality of transferred blastocysts on birth outcomes in frozen-thawed transfer cycles. Methods: A retrospective study was conducted, encompassing 5493 frozen-thawed blastocyst transfer cycles from January 2019 to June 2021. The cycles were categorized into five groups based on the number and quality of transferred blastocysts, as well as trichotomized based on maternal age brackets. Pregnancy outcomes such as implantation rate (IR), clinical pregnancy rate (CPR), multiple pregnancy rate (MPR), abortion rate (AR), live birth rate (LBR), and neonatal characteristics were compared and statistically analyzed. Results: The data revealed that maternal age, quality and number of the transferred blastocysts exerted a demonstrable impact on both pregnancy and birth outcomes. Within the same blastocyst transfer groups, it was noted that IR, CPR, and LBR exhibited a progressive decline as a function of advancing maternal age. Amplifying the number of homogeneously graded blastocysts for transfer did not conspicuously elevate CPR and LBR; however, it led to a statistically significant escalation in MPR (p < 0.01). In instances of dual blastocyst transfers, better-quality blastocysts yielded higher IR, CPR, MPR and LBR. Furthermore, neonatal outcomes were most favorable in singleton births, followed in sequence by dizygotic twins and monozygotic twins. A positive correlation was observed between sex ratio and the proportion of good-quality blastocysts, with a statistically significant difference between good-quality and poor-quality blastocyst groups (1.34 vs 1.00, p/odds ratio (OR)/95% confidence interval (95% CI)

Background: Assisted reproductive technology treatment is recommended to overcome endometriosis-associated infertility but current evidence is controversial. Endometriosis is associated with lower antral follicle count (AFC) and oocyte yield but similar clinical outcomes compared to controls. Unaffected ovarian stimulation response and embryological outcomes but lower clinical pregnancy and live birth rates and higher miscarriage rates have been reported, implying direct impact on endometrial receptivity. With evidence emerging on the benefit of frozen-warmed and blastocyst stage transfer, we investigated ART outcomes in endometriosis using homogeneous case-control groups.Methods: This is a retrospective observational case-control study including n = 66 frozen-warmed unbiopsied single blastocyst transfers of patients with endometriosis and n = 96 of women exhibiting idiopathic sterility. All frozen-warmed transfers followed artificial endometrial preparation.Results: In control women, the mean number of oocytes recovered at oocyte pick up was higher compared to women with endometriosis (15.3 ± 7.1 vs. 12.7 ± 5.2, p = 0.025) but oocyte maturation index (mature oocytes/total oocytes at oocyte pick up) was significantly higher for endometriosis (48.2% vs. 34.0%, p = 0.005). The same was shown for the subgroup of 44 endometriosis patients after endometrioma surgery when compared with controls (49.1% vs. 34.0%, p = 0.014). Clinical pregnancy rate was not higher in endometriosis but was close to significance (47.0% vs. 32.3%, p = 0.059) while live birth rate was comparable (27.3% vs. 32.3%, p = 0.746). Miscarriage rate was higher in the endometriosis group (19.7% vs. 7.3%, p = 0.018). A significantly higher AFC was observed in the control group in comparison with the endometriosis group (16.3 ± 7.6 vs. 13.4 ± 7.0, p = 0.014). Live birth rate did not differ when comparing all endometriosis cases (p = 0.746), ASRM Stage I/II and Stage III/IV (p = 0.348 and p = 0.888) with the control group but the overall pregnancy rate was higher in ASRM Stage I/II (p = 0.034) and miscarriage rate was higher in ASRM Stage III/IV (p = 0.030) versus control.Conclusion: Blastocyst transfers in women with endometriosis originate from cycles with lower AFC but higher share of mature oocytes than in control women, suggesting that endometriosis might impair ovarian reserve but not stimulation response. A higher miscarriage rate, independent of blastocyst quality may be attributed to an impact of endometriosis on the endometrium beyond the timing of implantation.

Purpose: To investigate the effect of climatic parameters in the mesothermal climate area on clinical pregnancy and live birth following fresh single blastocyst transfer. Methods: This study investigated clinical pregnancies and live births that resulted from 555 ovarian stimulation cycles followed by fresh single blastocyst transfer. The samples were stratified according to climatic conditions (low T, temperature < 12.9 °C; middle T, 12.9 °C ≤ temperature < 22.6 °C; high T, temperature ≥ 22.6 °C; low H, relative humidity < 62.1%; middle H, 62.1% ≤ relative humidity < 66.5%; high H, relative humidity ≥ 66.5%; short S, sunlight duration < 5.2 h; middle S, 5.2 h ≤ sunlight duration < 6.7 h; long S, sunlight duration ≥ 6.7 h). Clinical pregnancy and live birth rates among three groups from each climatic parameter were compared. Multivariable analyses were performed to investigate the effects of climatic conditions on blastocyst development, endometrial thickness, clinical pregnancy, and live birth. Results: A statistically significant difference was found in pregnancy rates among low T (48.8%), middle T (37.3%), and high T (36.6%) groups. Multivariable analyses revealed that temperature was associated with clinical pregnancy and live birth rates with adjustment for patient age, BMI, type of ovarian stimulation, endometrial thickness, and expansion grade of the transferred blastocyst. The association between climatic parameters and blastocyst development and endometrial thickness was not confirmed. Conclusions: This study suggests that lower temperatures in the mesothermal climate area could favorably affect the rates of clinical pregnancy and live birth achieved by fresh single blastocyst transfer. [ABSTRACT FROM AUTHOR]

In patients with 1–3 embryos available on day 3, does blastocyst transfer reduce the chances of a clinical pregnancy by cancelling transfer cycles compared with cleavage transfer? This retrospective observational study included 423 IVF cycles performed from 1 January 2019 to 31 December 2020 at the Center for Reproduction and Fertility of the Second Affiliated Hospital of Kunming Medical University. Cleavage transfer was performed in 267 cycles and blastocyst transfer was performed in 156 cycles. The primary outcome was the ongoing pregnancy rate, and the secondary outcomes were clinical pregnancy rate and embryo cessation rate. Univariate analysis was performed to compare outcomes. A logistic regression analysis was performed to explore the association between transfer stage and ongoing pregnancy rate. No differences were observed in the ongoing pregnancy rate (25.84% versus 26.92%; odds ratio [OR] 0.95; 95% confidence interval [CI] 0.61–1.50; P = 0.82) and embryo cessation rate (83.48% versus 85.75%; OR 1.19; 95% CI 0.82–1.75; P = 0.40) between the two groups. Logistic regression analysis showed no association between transfer stage and ongoing pregnancy rate (OR 1.06; 95% CI 0.64–1.73). Blastocyst transfer does not reduce the chances of a clinical pregnancy. These results support the proposal of blastocyst transfer in patients with 1–3 embryos available on day 3. [ABSTRACT FROM AUTHOR]

How do perinatal outcomes differ between programmed and modified natural frozen embryo transfer (FET) cycles? A retrospective cohort study of 839 patients was undertaken at a university-affiliated fertility practice undergoing single blastocyst FET cycles between 2014 and 2020. The primary outcome measures were the incidence of ischaemic placental disease, small for gestational age (SGA), intrauterine growth restriction (IUGR), preterm delivery, birth weight, and mode of delivery. When comparing programmed FET cycles with modified natural FET cycles, there was no increased risk of ischaemic placental disease [adjusted risk ratio (aRR) 0.83, 95% CI 0.61–1.14], IUGR (unadjusted RR 0.50, 95% CI 0.14–1.77), preterm delivery (aRR 1.11, 95% CI 0.72–1.70) or SGA (aRR 0.69, 95% CI 0.40–1.19). Patients in the programmed cohort had increased risk of caesarean delivery (aRR 1.32, 95% CI 1.10–1.59). These outcomes were unchanged when limited to patients undergoing their first FET cycle. There are no differences in patient and neonatal clinical outcomes between programmed and modified natural FET cycles. The choice of FET protocol should remain a shared decision between patient and provider. [ABSTRACT FROM AUTHOR]

Background: High responders are characterized by a large number of retrieved oocytes and/or a high level of estradiol on the day of administration of human chorionic gonadotropin. There is controversy in the literature regarding live birth rates from fresh day-5 single blastocyst transfer (day-5 SBT) compared to cleavage-stage fresh day-3 embryo transfer (day-3 ET) in high responders. The aim of this study was therefore to compare reproductive outcomes between day-5 SBT and day-3 ET using high-quality embryos and gonadotropin-releasing hormone (GnRH) antagonist protocols in high responders undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Methods: This was a single-center retrospective study of 282 high responders who underwent fresh day-5 SBT (day-5 SBT group, n = 142) or two cleavage-stage fresh day-3 embryo transfer (day-3 ET group, n = 140) between 2015 and 2019. Results: No significant differences were observed between the day-5 SBT and day-3 ET groups in terms of clinical pregnancy rate (51.41% vs. 59.29%, p = 0.183) or live birth rate (41.55% vs. 52.86%, p = 0.057). The incidence of multiple pregnancy (1.37% vs. 36.14%) and of low birth weight (5.00% vs. 32.26%) were significantly less frequent in the day-5 SBT group than in the day-3 ET group (p < 0.001 and p < 0.001, respectively). Conclusions: SBT may be the preferred choice for high-quality embryos in high responders undergoing IVF/ICSI during GnRH antagonist cycles with fresh embryo transfers. This is due to the lower incidence of obstetric complications compared to day-3 ET, although the clinical outcomes for the two groups are comparable.

Background: The presence of only morphologically poor embryos (MPEs) on day3 is common in autologous in vitro fertilization (IVF), particularly among p Tel: 886-7-7317123 Ext. 8916. Fax: 886-7-7322915.atients who have advanced maternal age or are poor responders. However, there are limited data regarding the disposition of embryos from patients who only produced MPEs on day3. The present study was designed to investigate the possible benefits of extended culturing MPEs. Try to detect whether the extended culture (day4 or day5 culture) can improve the live birth rate per cycle? Methods: This retrospective, observational, single-center, cohort study examined 224 IVF/intracytoplasmic sperm injection (ICSI) cycles between January 2010 and June 2015, in which women only produced MPEs on day3. A total of 544 MPEs were analyzed. The defines a day3 embryo as an MPE if it fails to develop to eight cells, blastomeres of equal size, and less than 20% cytoplasmic fragments. Of the 224 cycles, 89 (39.7%) underwent fresh embryo transfer on day3, and 135 (60.3%) underwent extended culture. Of the 135 extended cultures, 54 cycles (40.0%) experienced day4, or day5 embryo transfer, 16 cycles (11.9%) had all embryos frozen, and 65 cycles (48.1%) had total embryo arrest. Results: Analysis of patient baseline demographic data, cycle characteristics, and cycle outcomes for day3 transfer group and extended culture group indicated that a higher body mass index in the day3 transfer group was the only significant difference (p = 0.006). Both fresh transfer groups had low live birth rates (LBRs) (4.5% vs. 7.4% p = 0.46). After extended culture, 65 cycles (48.1%) were cancelled because the embryos exhibited developmental arrest and 70 cycles (51.9%) grew to day4 or day5. Thirteen frozen embryo transfer (FET) cycles and 22 frozen blastocysts derived from MPEs were thawed. There were more high-quality embryos (p

Objective: To know whether sperm DNA fragmentation (SDF) affects the clinical outcomes in the cumulative transfers of an intracytoplasmic sperm injection (ICSI) cycle along with blastocyst transfers in couples with normozoospermic males. Methods: The study included 252 couples who underwent their first ICSI cycles along with blastocyst transfer and whose male partner semen samples were normozoospermic according to the World Health Organization 2010 criteria. All the couples were classified into two groups based on the SDF: the low SDF group (SDF≤30%, n=162) and the high SDF group (SDF>30%, n=90). Clinical as well as laboratory outcomes were correlated between the two groups. Sperm DNA fragmentation was assessed on the post-wash semen samples by acridine orange test. The main outcome measures were the live birth rate and miscarriage rate. Results: A significant decrease in the live birth rates was observed in the high SDF group compared to the low SDF group in fresh embryo transfer cycles (P0.05). No significant difference was observed in the laboratory outcomes between the two SDF groups. A remarkable decrease in sperm motility was observed in the high SDF group compared to the low SDF group (P

Background: Letrozole treatment is considered an effective option in endometrial preparation for frozen embryo transfers in patients with ovulation disorders or irregular menstruation; however, the effectiveness of letrozole-induced endometrial preparation remains unclear in ovulatory patients. Furthermore, there is no comparative study reporting on pregnancy complications and congenital anomalies after frozen embryo transfers comparing natural and letrozole-assisted cycles. This study examined whether letrozole-induced endometrial preparation affected pregnancy outcomes, perinatal outcomes, and congenital anomalies after single vitrified-warmed blastocyst transfers (SVBTs) in ovulatory patients, as compared with the natural cycle.Methods: This historic cohort study included only patients with unexplained infertility. Overall, 14,611 patients who underwent SVBTs between July 2015 and June 2020, comprising both natural and letrozole-assisted cycles, were included. Multiple covariates that impact outcomes were used for propensity score matching; 1,911 patients in the letrozole group were matched to 12,700 patients in the natural group, and the clinical records of 1,910 patients in each group were retrospectively analysed. Cycle characteristics, pregnancy outcomes (clinical pregnancy, ongoing pregnancy, and live birth), and incidence of pregnancy complications and congenital anomalies were statistically compared between the two groups.Results: Multivariate logistic regression analysis showed that letrozole administration during SVBT cycles significantly improved the live birth rate (P = 0.0355). Gestational age, birth length, birth weight, and infant sex, as well as the incidence of pregnancy complications and birth defects, were statistically comparable between the two groups. Furthermore, multivariate logistic regression analysis revealed that the perinatal outcomes were not affected by letrozole-induced endometrial preparation.Conclusions: Letrozole-induced endometrial preparation improved the live birth rate compared with the natural cycle, without adverse effects on perinatal outcomes and congenital anomalies after SVBTs. Therefore, letrozole-induced endometrial preparation might be a safe and more effective strategy, especially for patients with insufficient luteal function. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare the outcomes of three endometrial preparation methods prior to frozen embryo transfer (FET): Natural cycle (NC), modified natural cycle (mNC), and programmed/artificial cycle (AC) protocols. Primary outcomes investigated were clinical pregnancy rate (CPR) and live birth rate (LBR). Methods: A retrospective study on 2080 FET cycles including patients ≤ 35 years with a BMI ≤ 30 who underwent FET with a single autologous blastocyst stage embryo at Aarhus University Hospital or Horsens Regional Hospital in the period 2013–2019. Only blastocysts frozen by vitrification were included. No luteal phase support (LPS) was used in natural cycles. Results: In NC, mNC and AC, CPRs were 34.9%, 40.6% and 32.0%, while LBRs were 32.3%, 36.3% and 26.6%, respectively. There were no significant differences in main outcomes when comparing AC with NC [LBR: OR = 0.9 (0.6; 1.2), p = 0.4]. Compared to NC, mNC-FET displayed significantly higher positive hCG, implantation rate, CPR and LBR [LBR: OR = 1.4 (1.0; 1.9), p = 0.03]. An analysis with mNC as reference group demonstrated significantly better outcomes in the mNC group compared to AC [LBR: OR 0.6 (0.5; 0.8), p = < 0.01]. Conclusion: The present study overall demonstrated better outcomes including LBR with mNC protocol as compared to NC and AC protocol, while comparison of AC and NC showed both protocols to be equally effective. A programmed cycle may be necessary for women with anovulatory cycles; however, normo-ovulating women may be offered a natural cycle protocol. Trial registration number: 3-3013-3047/1 and 31-1522-44. Date of registration: June 24, 2019 and April 23, 2020. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether there is an association between extended in vitro culture based on embryo developmental stage at transfer and pre-malignant gestational trophoblastic disease (GTD) risk of molar pregnancy during assisted reproduction. Methods: A retrospective study was carried out using Human Fertilization and Embryology Authority (HFEA) anonymized register from 1999 to 2016. A total of 540,376 cycles were eligible to be included in the study after excluding any kind of donor treatment or surrogacy, frozen embryo transfers, and cycles with incomplete data. Subgroup analysis was carried out in subjects with primary infertility aiming to exclude an increased risk in those with a previous GTD. Multivariate logistic regression analysis was used to adjust for possible confounders, and the effect of day of embryo transfer in IVF (in vitro fertilization)/ICSI (intracytoplasmic sperm injection) treatment on a molar pregnancy GTD outcome was analyzed. Results: The prevalence of a molar pregnancy GTD among the study population was 3.4/10,000 livebirths (53/156,683) with a higher risk in the over 40 age category. No significant difference of pre-malignant GTD incidence was seen between IVF and ICSI (0.01% vs 0.009% respectively). No association was seen with GTD based on type/cause of infertility or number of embryos transferred. Crude (1.06; 95% CI 0.852–1.31) and adjusted (1.07; 95% CI (0.857–1.32) odds ratios were calculated to see an association between day of embryo transfer and the occurrence of a GTD. There was no association between day of embryo transfer and molar GTD risk after adjusting for age and secondary infertility. Conclusion: No significant association between pre-malignant molar gestational trophoblastic disease and extended in vitro embryo culture was found after analyzing 540,376 cycles of IVF and ICSI. [ABSTRACT FROM AUTHOR]

Background: It remains unclear whether polycystic ovary syndrome (PCOS) is an independent risk factor for pregnancy complications in women undergoing assisted reproductive technology (ART) treatment. For the integrative treatment of PCOS patients, it is still important to investigate the pregnancy outcomes of PCOS patients after adjusting for potential biases, such as body mass index, embryo quality and endometrial preparation method.Methods: This retrospective cohort study ultimately included a total of 336 PCOS patients who conceived after single thawed blastocyst transfer in the PCOS group and 2,325 patients in the control group from January 2018 to December 2020. A propensity score matching (PSM) model was used, and 336 PCOS patients were matched with 336 patients in the control group.Results: Before PSM, no differences in the miscarriage rate, pregnancy complication rate, preterm birth rate, or live birth rate were found between the PCOS group and the control group. After PSM, the late miscarriage rate of the PCOS group was significantly higher than that of the control group (3.3% vs. 0.6%, P = 0.040), although the early miscarriage rates were similar (14.0% vs. 13.7%). The rates of pregnancy complications, preterm birth and live birth in the PCOS group were comparable to those in the matched control group (P = 0.080, P = 0.105, P = 0.109, respectively). The neonatal weights of male infants and female infants were similar between the two groups (P = 0.219, P = 0.169). Subgroup analysis showed that PCOS patients with homeostasis model assessment of insulin resistance (HOMA-IR) levels ≥ 2.49 had a significantly increased risk of preterm birth compared with those with HOMA-IR levels < 1.26 and 1.26 ≤ HOMA-IR levels < 2.49 (26.0% vs. 6.0% vs. 9.8%, P = 0.005). PCOS patients with total testosterone levels ≥ 0.7 ng/ml had a higher early miscarriage rate but a lower late miscarriage rate than those with total testosterone levels < 0.7 ng/ml (29.4% vs. 12.3%, 0% vs. 3.6%, respectively, P = 0.032).Conclusions: PCOS is an independent risk factor for late miscarriage in patients conceived after a single thawed blastocyst transfer, even after adjusting for biases. Among PCOS patients, insulin resistance and hyperandrogenism are associated with a higher risk of preterm birth and early miscarriage, respectively. [ABSTRACT FROM AUTHOR]

Objective: Dose an elevated serum progesterone (P) level on the human chorionic gonadotropin (hCG) trigger day have a negative effect on clinical pregnancy outcomes for embryos transferred at different stages of development in long-acting gonadotropin-releasing hormone agonist (GnRHa) in vitro fertilization-embryo transfer (IVF-ET) cycles?Study Design: This was a noninterventional, retrospective, observational, single-centre cohort study. A total of 1951 patients received long-acting GnRHa for pituitary downregulation in IVF-ET cycles at Nanjing Drum Tower Hospital from January 2018 to December 2020. The serum P levels on the day of hCG administration were measured, together with other cycle parameters, to explore the relationship between P levels and the clinical pregnancy rate (CPR) of different embryos transferred.Results: When the serum P level on the hCG day was higher than 1.5 ng/mL, the CPR did not decrease significantly. There was no correlation between the CPR of cleavage-stage embryo transfer and the serum P level on the hCG day. In addition, the interaction analysis suggested that the CPR of patients undergoing blastocyst transfer decreased as serum P levels on the hCG day increased. Progesterone levels on the day of hCG administration were closely related to the CPR of blastocyst transfer rather than cleavage-stage embryo transfer.Conclusion: An increased serum P level on the day of hCG administration did not affect the CPR of cleavage-stage embryo transfer, but it reduced the CPR of blastocyst transfer cycles. [ABSTRACT FROM AUTHOR]

Purpose: Several studies investigated endometrial patterns, with respect to pregnancy rates following the transfer of embryos but did not distinguish between single- and multiple-blastocyst procedures. We clarified how the endometrial pattern imaged to transfer a frozen embryo is associated with pregnancy outcomes in single-blastocyst frozen-embryo transfer (sbFET)., Methods: Patients ≤35 years who underwent sbFET on the hormone replacement protocol. We analyzed endometrial patterns' associations with pregnancy outcomes in relation to blastocyst grade and pregnancy-related factors., Results: Of the 1383 cycles, 483 were Lf, 840 were partial-Lf, and 60 were non-Lf. Leaf pattern (Lf): central echogenic line present and continuous. Overall, decreasing distinctness of the central echogenic line was associated with significantly lower rates of clinical pregnancy (Lf: 70.4%; partial-Lf: 58.1%; non-Lf: 28.3%) and live birth (56.3%, 45.5%, and 15.0%) and a higher miscarriage rate (20.0%, 21.7%, and 47.1%). Logistic regressions showed pregnancy and live birth to be significantly more likely and miscarriage less likely in Lf than non-Lf: OR (95% CI): 6.07 (3.24-11.37), 7.43 (3.47-15.39), and 0.20 (0.07-0.57)., Conclusions: Non-Lf presentation was associated with lower rates of pregnancy and live birth, suggesting it signals unsuitable conditions for embryo transfer. We provide information on the pregnancy outcomes of sbFET for endometrial patterns., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s). Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Purpose: To determine whether granulocyte–macrophage colony-stimulating factor (GM-CSF)-containing medium could improve embryo-transfer outcomes in frozen-thawed blastocyst transfer. Methods: Patients who underwent frozen-thawed blastocyst transfer (430 women, aged 30–39 years, 566 cycles) were analyzed. Frozen-thawed blastocysts were cultured in GM-CSF-containing medium or control medium for 3–5 h, followed by transfer to the uterus. The embryo-transfer outcomes in the two groups were measured and compared, and a propensity score matching (1:1) method was used to balance the differences in baseline characteristics. We analyzed 213 matched samples. Results: In patients who underwent frozen-thawed blastocyst transfer with GM-CSF, the percentage of human chorionic gonadotropin-positive cases, biochemical pregnancies, clinical pregnancies, ongoing pregnancies, and live birth rates was 60.6%, 7.98%, 52.6%, 42.9%, and 40.9%, respectively, as compared with 45.1%, 3.29%, 41.8%, 31.1%, and 30.5%, respectively, for the control groups. The rates of human chorionic gonadotropin positivity (odds ratio [OR]: 1.87, 95% confidence interval: [CI]: 1.27–2.75), biochemical pregnancy (2.55, 1.04–6.29), clinical pregnancy (1.54, 1.05–2.27), ongoing pregnancy (1.64, 1.13–2.41), and live birth (1.67, 1.14–2.45) were significantly higher in the GM-CSF group than the control group. The incidence of pregnancy loss (22.3% vs. 27.0%) did not significantly differ between the groups. Conclusion: The use of a GM-CSF-containing medium for blastocyst-recovery culture improved the live birth rate as a result of increased implantation rate in the frozen-thawed blastocyst-transfer cycle. The use of GM-CSF-containing medium following blastocyst thawing could be an effective choice for improving the blastocyst-transfer outcomes. [ABSTRACT FROM AUTHOR]

Does artificial shrinkage before fresh blastocyst transfer improve clinical pregnancy rates in IVF? In this monocentric prospective, randomized, double-blind, controlled pilot study, 150 couples undergoing fresh single-blastocyst transfer were randomized between 20 May 2018 and 22 February 2022. In the artificial shrinkage group (AS group), a single laser pulse was directed to the cellular junction of the trophectoderm on the opposite side of the inner cell mass in each blastocyst. IVF outcomes were clinical pregnancy, multiple pregnancy and live birth rates. Cell-free DNA (cfDNA) concentration was also measured by quantitative real-time PCR in the blastocyst culture medium. In total, 142 couples underwent fresh single-blastocyst transfer: control group, no artificial shrinkage, n = 47; and AS group, artificial shrinkage, n = 95; An intention-to-treat (ITT) analysis was employed. After a reassessment and the exclusion of patients with major protocol deviations, 139 couples underwent fresh single-blastocyst transfer under optimal conditions: control group, n = 47; and AS group, n = 92; a per-protocol analysis was used here. The clinical and laboratory characteristics were not significantly different between the groups. The clinical pregnancy rate was similar in the control and AS groups (ITT: 48.9% versus 49.5%, P = 0.97; per protocol: 48.94% versus 51.1%, P = 0.89). The multiple pregnancy rate and the live birth rate were also similar between the groups. No significant differences in gestational age, birthweight or proportion of male/female newborns were observed. The concentration of cfDNA in the blastocyst culture medium was not associated with IVF outcome. Large-scale randomized controlled trials are required to confirm these preliminary results. [ABSTRACT FROM AUTHOR]

Introduction: embryo implantation is a crucial step for assisted reproductive technology (ART) achievement. Human chorionic gonadotropin (hCG) is one of the main regulators of the implantation process. Studies focusing on the impact of intrauterine hCG infusion at the time of embryo transfer on clinical ART outcomes have shown controversial results, mainly at blastocyst stage. In this study, we aimed to investigate whether intrauterine hCG infusion one day before human blastocyst transfer in fresh invitro fertilization (IVF) cycles enhances implantation and pregnancy rates. Methods: a total of 174 subfertile women undergoing autologous fresh blastocyst transfer were enrolled in this randomized prospective study. Patients were randomly divided into three groups; group 1 (n = 54) and group 2 (n = 59) received an intrauterine injection of respectively 500 IU and 1000 IU of hCG one day before blastocyst transfer and the control group (n= 61) did not receive any intrauterine injection. The pregnancy and implantation rates were compared between the three study groups. Results: significant difference was found between the study groups. The bio chemical pregnancy rates were 25.9%, 30.5% and 29.5%, the clinical pregnancy rates were 24.1%, 27.1% and 27.9% and the implantation rates were 14.9%, 17.9% and 18.7% respectively in group 1,2 and control group. Conclusion: our results have shown that clinical outcomes in fresh IVF cycles cannot be improved through intrauterine hCG administration one day prior to blastocyst transfer, neither with 500 IU of hCG nor with a higher dose of 1000 IU of hCG. [ABSTRACT FROM AUTHOR]

Objective To investigate the application of laser-assisted hatching (AH) in the frozen-thawed blastocyst transfer. Methods A total of 444 patients with vitrified blastocyst transfer were divided into the laser AH group (n=250) and non-laser AH group (n=194). Blastocyst hatching degree, pregnancy outcome indexes (embryo implantation rate, bio-chemical pregnancy rate, clinical pregnancy rate, live birth rate, and abortion rate) and neonatal outcome indexes (new-born birth weight, proportion of premature infants, proportion of infants with low birth weight and proportion of macrosomia) were compared between the two groups. Results Before transplantation, the proportion of blastocyst in stage 4, 5 and 6 between AH group and NAH group was significantly different (P<0. 01). Totally 310 embryos were transplanted into NAH group and 388 embryos were transplanted into AH group. The embryo implantation rate, biochemical pregnancy rate, clinical pregnancy rate, total live birth rate and single live birth rate in the AH group were significantly higher than those in the NAH group (all P<0. 05), and there was no statistical significance in the live birth rate and abortion rate between the two groups (all P>0. 05). The proportion of macrosomia in the AH group was lower than that in NAH group (P< 0. 05), and there were no significant differences in birth weight, preterm proportion or low birth weight proportion between the two groups (all P>0. 05). Conclusion Laser AH can promote blastocyst hatching, improve pregnancy outcome of vitrified-warmed blastocyst transfer, and do not increase the risk of adverse outcome in newborns. [ABSTRACT FROM AUTHOR]

Purpose: Assisted reproductive technology (ART) has an impact on secondary sex ratio (SSR), which is seemed to be elevated after blastocyst transfer (BT) but decreased following ICSI procedure. We aim to assess whether the higher SSR associated with BT could be influenced by fertilization method used. Methods: All consecutive IVF/ICSI cycles (fresh and frozen) involving single embryo transfer (SET) resulting in a live birth between 2015 and 2019 were retrospective analyzed. Logistic regression was used to model the effect on the SSR of maternal and specific ART characteristics. Results: Six thousand nine hundred twenty-two women were included with the crude SSR of 54.8%. The impact of BT on SSR is influenced by the fertilization method used. After adjustment for potential confounders, the SSR in the ICSI BT group was significantly higher when compared to ICSI cleavage-stage embryo SET (aOR 1.24; 95% CI 1.10–1.40, P < 0.001). However, this effect was not detected among SBT with IVF treatment (aOR 1.04; 95% CI 0.97–1.12, P = 0.260). Assessing blastocyst morphological parameters, high trophectoderm quality was significantly associated with elevated SSR (aOR 1.76, 95% CI 1.34–2.31 [A vs. C], and aOR 1.28, 95% CI 1.14–1.44 [B vs. C]). No significant difference was shown in expansion, inner cell mass, or days of blastocyst formation between male and female blastocysts. Conclusions: The impact of BT on SSR could be influenced by the fertilization method used. The higher SSR was observed after BT with ICSI procedures but not with IVF. Interpretation of the findings is limited by the potential for selection and confounding bias. [ABSTRACT FROM AUTHOR]

Background: The risk of developing gestational diabetes mellitus (GDM) is higher in women undergoing assisted reproductive treatment than in women conceiving spontaneously. Objectives: To determine whether the GDM risk after day-3 embryo transfer differs from the GDM risk after day-5 blastocyst transfer. Methods: Prospective observational study in women becoming pregnant after first fresh embryo or blastocyst transfer. Results: A total of 1579 women got pregnant and had live birth; 1300 women got day-3 embryo transfer only, whereas 279 women received at least 1 blastocyst. Of 1579 women, 252 developed GDM. Age, body mass index, baseline estradiol, baseline high-density lipoprotein, and progesterone on the day of human chorionic gonadotropin injection were not different in women receiving day-3 embryos only vs women receiving at least 1 blastocyst. The number and quality of retrieved oocytes were not different in women receiving day-3 embryo transfer from those receiving blastocysts. Our study confirmed already established GDM risk factors such as age and body mass index, baseline estradiol, and high-density lipoprotein, as well as progesterone after ovarian stimulation. We furthermore demonstrate that the GDM incidence in women receiving day-5 blastocyst transfer was significantly higher than those who received day-3 embryo transfer (21.15% vs 14.85%; P = 0.009). Considering confounding factors, we likewise saw that blastocyst transfer was an independent procedure-related GDM risk factor [P = 0.009, Exp (B): 1.56, 95% CI: 1.12-2.18]. Conclusion: Blastocyst transfer after in vitro fertilization/intracytoplasmic sperm injection increases the risk of developing GDM. [ABSTRACT FROM AUTHOR]

Purpose: This randomized controlled trial is aiming to compare the clinical pregnancy rate of immediate versus delayed post thawing embryo transfer in frozen embryo transfer (FET) cycles. Materials and Methods: The study was conducted on 150 FET cycles in which embryos were vitrified on day 2 or 3. After thawing, cases with more than 50% blastomere loss were excluded as well as cases with recurrent implantation. The endometrium was prepared by programmed estrogen/progesterone method. After thawing, cases were randomized to immediate embryo transfer or extended culture for 18-72 hours before transfer. Results: Number of cryopreserved embryos and survival rates were similar in both groups. Survival rates was above 95% in both groups and in the extended culture group 72.1% of embryos resumed miosis. Clinical pregnancy rate was 50.7% in immediate transfer group and 41.3% in the extended culture group. Conclusion: Extended culture after thawing helps in embryo selection but does not increase clinical pregnancy rate.

Culturing of human embryos in optimal conditions is crucial for a successful in vitro fertilisation (IVF) programme. In addition, the capacity to assess and rank embryos correctly for quality will allow for transfer of the potentially ‘best’ embryo first, thereby shortening the time to pregnancy, although not improving cumulative pregnancy and live birth rates. It will also encourage and facilitate the implementation of single embryo transfers, thereby increasing safety for mother and offspring. Time-lapse technology introduces the concept of stable culture conditions, in connection with the possibility of continuous viewing and documenting of the embryo throughout development. However, so far, even when embryo quality scoring is based on large datasets, or when using the time-lapse technology, the morphokinetic scores are still mainly based on subjective and intermittent annotations of morphology and timings. Also, the construction of powerful algorithms for widespread use is hampered by large variations in culture conditions between individual IVF laboratories. New methodology, involving machine learning, where every image from the time-lapse documentation is analysed by a computer programme, looking for patterns that link to outcome, may in the future provide a more accurate and non-biased embryo selection.

Abstract Background With improvements in in vitro culture techniques there has been a steady shift in practice to transfer embryos at the blastocyst stage (post fertilization day (p.f.d.) 5–7), when embryos reach the endometrial cavity during natural conception. For patients with > 5 zygotes on day 1 of embryo development, fresh blastocyst embryo transfer (ET) increases live birth rates when compared to cleavage stage (p.f.d. 3) transfer. In poorer prognosis patients (≤ 5 zygotes) cleavage stage ET is commonly performed to reduce the risk of cycle cancellation if no embryo survives to the blastocyst stage. However, there is a dearth of randomized controlled trial (RCT) data demonstrating improved live birth rates per cycle for cleavage vs blastocyst stage ET in this subgroup of patients. The hypothesis of the PRECiSE (PooR Embryo Yield Cleavage Stage Versus blaStocyst Embryo Transfer) trial is that blastocyst ET is not inferior to cleavage stage ET with regard to live birth rates per retrieval in poorer prognosis patients. The adoption of routine blastocyst culture for all patients would result in higher rates of single embryo transfers (SET), reduced incidence of multiple pregnancies and simplified laboratory protocols, thereby reducing costs. Methods/design Multicenter, non-inferiority randomized controlled trial (RCT) comparing blastocyst to cleavage stage embryo transfer in poorer prognosis patients with ≤5 zygotes on day 1 after fertilization. The primary outcome is live birth per retrieval. Secondary outcomes include: time to pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and multiple pregnancy rate (per retrieval). This trial will enroll 658 women with ≤5 zygotes on day 1 at 6 IVF centers over the course of 22 months. Discussion If the hypothesis is proven true, the data from this trial may facilitate the adoption of uniform blastocyst culture in all IVF patients. Trial registration ClinicalTrials.gov Identifier: NCT03764865. Registered 5 December 2019, Protocol issue date: 4 December 2018, Original.

Objective: To compare the effectiveness of blastocyst elective single embryo transfer (eSET) and double embryo transfer (DET) in reducing low birth weight, preterm birth, and perinatal mortality in in vitro fertilization (IVF) cycles of Indonesian women. Methods: A retrospective observational study was conducted at Morula IVF Clinic, Jakarta, Indonesia. A total of 179 women who underwent either eSET or DET and had met the eligibility criteria were included. Seventy-six women underwent eSET while 103 underwent DET in their IVF cycles. Low birth-weight rate, preterm birth rate, and perinatal mortality rate of both groups were measured as the primary study outcomes. Neonatal intensive care unit (NICU) admission rate, Apgar score, multiple pregnancy, and maternal complications during pregnancy were also evaluated. Results: The risk of low birth weight [odds ratio (OR)=0.21, 95% confidential interval (CI): 0.10-0.45, P< 0.001] and preterm birth (0R=0.25, 95% CI: 0.13-0.49, P< 0.001) was significantly lower in the eSET group compared with the DET group. Furthermore, eSET efficiently reduced the incidence of NICU admission and multiple pregnancy (P=0.01 and P< 0.001, respectively). No significant difference was observed in terms of perinatal mortality rate, Apgar score, and maternal complications including gestational diabetes, preeclampsia as well as pregnancy-induced hypertension (P>0.05). However, a lower incidence of antepartum hemorrhage was noticed in the eSET group than in the DET group (P=0.03). Conclusions: Compared with DET, infants conceived through IVF cycles with eSET have a significantly lower risk of low birth weight, preterm birth, and NICU admissions. Moreover, eSET is shown to reduce multiple pregnancy rate, yet no significant differences are observed in the perinatal mortality rates, Apgar score and maternal complications (except for the incidence of antepartum hemorrhage) between both groups.