The use of an embryo transfer simulator to compare transfer techniques and pregnancy outcomes among physicians.

Objective: To evaluate the association between embryo transfer techniques and pregnancy outcomes. Design: This is a prospective observational study with a retrospective cohort. Setting: University Clinic. Patients: Patients underwent embryo transfers between 2015 and 2020. Intervention/Exposure: Fourteen physicians performed 25 mock embryo transfers on the embryo transfer simulator and completed a questionnaire assessing preferred embryo transfer techniques. Quantitative performance metrics on the embryo transfer simulator were measured. Individual physician embryo transfer success rates were retrospectively collected from all fresh and cryopreserved embryo transfers between January 1, 2015, and January 1, 2020. Associations between embryo transfer techniques (preferred technique and simulator performance metrics) and each physician's historical patient pregnancy outcomes were assessed. Main Outcome Measures: Associations between embryo transfer techniques and live births were assessed. Results: There were significant differences in embryo transfer techniques between physicians, including touches to the fundus, distance to the fundus, duration of embryo transfer, duration of the complete procedure, time spent navigating the cervical canal, velocity of embryo expulsion, time waited after embryo expulsion, and total score on the embryo transfer simulator. After controlling for confounders and multiple transfers per physician, the duration of embryo transfer was significantly associated with live birth, with longer durations associated with decreased live birth rates. Shorter placement distance to the fundus and higher velocity of embryo expulsion were both significantly associated with higher rates of ectopic pregnancy. Conclusions: This study revealed significant differences in transfer techniques among physicians. The use of the embryo transfer simulator for physicians in practice can elucidate differences and create opportunities for data-driven improvement in embryo transfer success rates.

The usefulness of peri-trigger female reproductive hormones (delta-FRH) in predicting oocyte maturation in normal ovarian reserve patients who received in vitro fertilization-embryo transfer: a retrospective study.

Objectives: To evaluate the efficacy of peri-trigger female reproductive hormones (FRHs) in the prediction of oocyte maturation in normal ovarian reserve patients during the in vitro fertilization-embryo transfer (IVF-ET) procedure. Materials and Methods: A hospital database was used to extract data on IVF-ET cases from January 2020 to September 2021. The levels of female reproductive hormones, including estradiol (E2), luteinizing hormone (LH), progesterone (P), and follicle-stimulating hormone (FSH), were initially evaluated at baseline, the day of the trigger, the day after the trigger, and the day of oocyte retrieval. The relative change in E2, LH, P, FSH between time point 1 (the day of trigger and baseline) and time point 2 (the day after the trigger and day on the trigger) was defined as E2_RoV1/2, LH_RoV1/2, P_RoV1/2, and FSH_RoV1/2, respectively. Univariable and multivariable regression were performed to screen the peri-trigger FRHs for the prediction of oocyte maturation. Results: A total of 118 patients were enrolled in our study. Univariable analysis revealed significant associations between E2_RoV1 and the rate of MII oocytes in the GnRH-agonist protocol group (p < 0.05), but not in the GnRH-antagonist protocol group. Conversely, P_RoV2 emerged as a potential predictor for the rate of MII oocytes in both protocol groups (p < 0.05). Multivariable analysis confirmed the significance of P_RoV2 in predicting oocyte maturation rate in both groups (p < 0.05), while the association of E2_RoV1 was not significant in either group. However, within the subgroup of high P_RoV2 in the GnRH-agonist protocol group, association was not observed to be significant. The C-index was 0.83 (95% CI [0.73-0.92]) for the GnRH-agonist protocol group and 0.77 (95% CI [0.63-0.90]) for the GnRH-antagonist protocol group. The ROC curve analysis further supported the satisfactory performance of the models, with area under the curve (AUC) values of 0.79 for the GnRH-agonist protocol group and 0.81 for the GnRH-antagonist protocol group. Conclusions: P_RoV2 showed significant predictive value for oocyte maturation in both GnRH-agonist and GnRH-antagonist protocol groups, which enhances the understanding of evaluating oocyte maturation and inform individualized treatment protocols in controlled ovarian hyperstimulation during IVF-ET for normal ovarian reserve patients.

Individualized luteal phase support in frozen-thawed embryo transfer after intramuscular progesterone administration might rectify live birth rate.

Background: The serum P concentrations are suggested to have an impact on pregnancy outcome. However there is no consensus about the optimal progesterone cut-off during the luteal phase. Few studies evaluated the effectiveness of a "rescue protocol" for low serum P concentrations and most of these studies used vaginal progesterone administration. There is paucity of data on the effectiveness of rescue protocol using intramuscular progesterone (IM-P) in frozen-thawed embryo transfer (FET). Methods: This study is a retrospective cohort study included 637 single or double blastocyst FETs with artificially prepared endometrium receiving 100 mg IM progesterone (P) after incremental estrogen treatment. Serum P concentrations were evaluated using blood samples obtained 117-119 hours after the first IM-P administration and 21 ± 2 hours after the last IM-P administration. Patients with serum P concentrations <20.6 ng/ml on the ET day were administrated 400 mg vaginal progesterone for rescue. Results: Demographic and cycle characteristics were similar between patients receiving rescue vaginal P (embryo transfer (ET)-day P concentration < 20.6 ng/ml) and patients who did not need rescue vaginal P (ET-day P concentration ≥ 20.6 ng/ml). Clinical pregnancy, miscarriage, and live birth rates were similar between two groups: 52.9%(45/85) vs 59.6%(326/552), p=0.287; 11.1%(5/45) vs 14.1%(46/326), p=0.583; and 47.1%(40/85) vs 50.7%(280/552), p=0.526, respectively. Logistic regression analysis revealed that the female age (p = 0.008, OR=0.942, 95% CI = 0.902-0.984) and embryo quality (ref: good quality for moderate: p=0.02, OR=0.469, 95% CI =0.269-0.760; for poor: p=0.013, OR= 0.269, 95% CI = 0.092-0.757) were independent variables for live birth. Following rescue protocol implementation, ET-day P concentration was not a significant predictor of live birth. Conclusions: Rescue vaginal P administration for low ET day serum P concentrations following IM-P yields comparable live birth rates.

Different endometrial preparation protocols on first frozen-thawed embryo transfer outcomes after hysteroscopic polypectomy: A retrospective cohort study.

OBJECTIVE: To evaluate the optimal endometrial preparation protocol for frozen-thawed embryo transfer (FET) following hysteroscopic polypectomy. METHODS: This was a retrospective clinical cohort study involving 464 patients who underwent their first FET after polyp resection between January 2021 and July 2023. The cohorts were categorized into three groups: the natural cycle (NC) group (n = 139), the ovarian induction (OI) group (n = 117), and the hormone replacement therapy (HRT) group (n = 208). RESULTS: In the initial unadjusted analysis, both NC and OI cycles exhibited similar pregnancy rates but were associated with significantly higher implantation rate (56.5%, 57.1% vs 42.0%, P < 0.001), clinical pregnancy rate (73.4%, 74.4% vs 57.2%, P = 0.001), and ongoing pregnancy rate (OPR; 67.6%, 63.2% vs 51.0%, P = 0.005) compared to the HRT group. Additionally, the three groups demonstrated comparable abortion rate (7.8%, 14.9% vs 10.9%, P = 0.299). After adjusting for potential confounders in the multiple logistic regression model, the HRT protocol resulted in a 54% significantly lower OPR compared to the NC protocol (adjusted odds ratio [aOR] = 0.46, 95% confidence interval [CI]: 0.28-0.77; P = 0.003). Meanwhile, the OPR difference between the OI protocol and the NC protocol remained insignificant (OI vs NC: aOR = 0.62, 95% CI: 0.35-1.12; P = 0.112). CONCLUSION: The ovulatory-FET scheme (NC and OI) following hysteroscopic polyp resection displayed promising clinical outcomes compared with HRT-FET scheme. The regimen without exogenous estrogen administration should be prioritized for endometrial preparation protocol after polypectomy.

[Analysis of Reproductive Tract Microecological Changes During the Frozen-Thawed Embryo Transfer Cycle and Clinical Pregnancy Outcomes]. / æ¿€ç´ æ›¿ä»£å†»èƒšç§»æ¤å‘¨æœŸç”Ÿæ®–é“å¾®ç”Ÿæ€å˜åŒ–ä¸Žå¦Šå¨ ç»“å±€åˆ†æž.

Objective: This study aims to analyze the relationship between reproductive tract microecological changes, metabolic differences, and pregnancy outcomes at different time points in the frozen-thawed embryo transfer cycle while patients are undergoing hormone replacement therapy, which will be a breakthrough point for improving outcomes. Methods: A total of 20 women undergoing frozen-thawed single blastocyst transfer for the first time at the Reproductive Medicine Center of Fujian Maternal and Child Health Hospital between July 2022 and January 2023 were recruited for this study. Their vaginal and cervical secretions were collected for 16S rRNA sequencing and non-targeted metabolomics analysis on days 2-5 of menstruation, day 7 after estrogen replacement therapy started, the day when progesterone was added, and the day of transplantation. The subjects were divided into different groups according to their clinical pregnancy status and the sequencing results were analyzed using bioinformatics methods. Results: 1) The alpha-diversity index of the vaginal and cervical microbiota was higher on days 2-5 of menstruation (P<0.01), but did not differ significantly on day 7 after oral estrogen replacement therapy started, the day of progesterone administration, and the day of transplantation (P≥0.1). 2) Both the pregnant group and the non-pregnant group showed a variety of microorganisms and metabolites with significant differences in the lower reproductive tract at different time points. 3) Microbial analysis at different time points showed that there were significant differences in vaginal flora, including Peptoniphilus, Enterocloster, Finegoldia, Klebsiella, Anaerobutyricum, Agathobaculum, Sporanaerobacter, Bilophila, Prevotella, and Anaerococcus in the pregnant group (P<0.05). 4) Metabolite analysis at different time points showed that there were significant differences in 3-hydroxybenzoic acid, linatine, (R)-amphetamine, hydroxychloroquine, and L-altarate in the vaginal secretions of the pregnant group (P<0.05), and that there were significant differences in isocitric acid, quassin, citrinin, and 12(R)-HETE in the cervical secretions (P<0.05). 5) Metabolite analysis at different time points showed that, in the non-pregnant group, there were significant differences in linatine, decanoyl-L-carnitine, aspartame, sphingosine, and hydroxychloroquine in the vaginal secretions (P<0.05), and the isocitric acid, quassin, ctrinin, and 12(R)-HETE in the cervical secretions (P<0.05). 6) Combined microbiome and metabolomics analysis showed that certain metabolites were significantly associated with microbial communities, especially Klebsiella. Conclusions: Significant differences in the microbiota genera and metabolites at different time points were found during the frozen-embryo transfer cycle of hormone replacement therapy, which may be used as potential biomarkers to predict pregnancy outcomes of embryo transfer.

Vitrification preservation of good-quality blastocysts for more than 5 years reduces implantation and live birth rates.

STUDY QUESTION: Does vitrification cryopreservation of embryos for more than 5 years affect the pregnancy outcomes after frozen embryo transfer (FET)? SUMMARY ANSWER: Vitrification cryopreservation of good-quality blastocysts for more than 5 years is associated with a decrease in the implantation rate (IR) and live birth rate (LBR). WHAT IS KNOWN ALREADY: Previous studies have predominantly focused on embryos cryopreserved for relatively short durations (less than 5 years), yet the impact of extended cryopreservation duration on pregnancy outcomes remains a controversial issue. There is a relative scarcity of data regarding the efficacy and safety of storing embryos for 5 years or longer. STUDY DESIGN, SIZE, DURATION: This retrospective study involved 36 665 eligible vitrified-thawed embryo transfer cycles from 1 January 2016 to 31 December 2022, at a single fertility center in China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were divided into three groups according to embryo storage time: Group 1 consisted of 31 565 cycles, with storage time of 0-2 years; Group 2 consisted of 4458 cycles, with a storage time of 2-5 years; and Group 3 included 642 cycles, with storage time exceeding 5 years. The main outcome measures were IR and LBR. Secondary outcome variables included rates of biochemical pregnancy, multiple pregnancy, ectopic pregnancy, and miscarriage, as well as neonatal outcomes. Reproductive outcomes were analyzed as binary variables. Multivariate logistic regression analysis was used to explore the effect of preservation time on pregnancy outcomes after correcting for confounding factors. In addition, we also assessed neonatal outcomes, such as large for gestational age (LGA) and small for gestational age (SGA). MAIN RESULTS AND THE ROLE OF CHANCE: IRs in the three groups (0-2, 2-5, and >5 years) were 37.37%, 39.03%, and 35.78%, respectively (P = 0.017), and LBRs in the three groups were 37.29%, 39.09%, and 34.91%, respectively (P = 0.028). After adjustment for potential confounding factors, compared with the 0-2 years storage group, prolonged embryo vitrification preservation time (2-5 years or >5 years) did not affect secondary outcomes such as rates of biochemical pregnancy, multiple pregnancy, ectopic pregnancy, and miscarriage (P > 0.05). But cryopreservation of embryos for more than 5 years reduced the IR (adjusted odds ratio (aOR) 0.82, 95% CI 0.69-0.97, P = 0.020) and LBR (aOR 0.76, 95% CI 0.64-0.91, P = 0.002). Multivariate stratified analysis also showed that prolonging the cryopreservation time of blastocysts (>5 years) reduced the IR (aOR 0.78, 95% CI 0.62-0.98, P = 0.033) and LBR (aOR 0.68, 95% CI 0.53-0.87, P = 0.002). However, no effect on cleavage embryos was observed (P > 0.05). We further conducted stratified analyses based on the number and quality of frozen blastocysts transferred, and the results showed that the FET results after transfers of good-quality blastocysts in the >5 years storage group were negatively affected. However, the storage time of non-good-quality blastocysts was not significantly associated with pregnancy outcomes. Regarding the neonatal outcomes (of singletons), embryo vitrification preservation time had no effect on preterm birth rates, fetal birth weight, or neonatal sex ratios. However, as the storage time increased, rates of SGA (5.60%, 4.10%, and 1.18%) decreased, while rates of LGA (5.22%, 6.75%, and 9.47%) increased (P < 0.05). After adjusting for confounding factors, the increase in LGA and the decrease in SGA were significantly correlated with the duration of storage time. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study using data from a single fertility center, even though the data had been adjusted, our findings still need to be validated in further studies. WIDER IMPLICATIONS OF THE FINDINGS: With the full implementation of the two-child policy in China, there may be more patients whose embryos have been frozen for a longer time in the future. Patients should be aware that the IR and LBR of blastocysts are negatively affected when the cryopreservation time is longer than 5 years. Couples may therefore consider shortening the time until FET treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Nature Science Foundation of China (No. 82101672), Science and Technology Projects in Guangzhou (No. 2024A03J0180), General Guidance Program for Western Medicine of Guangzhou Municipal Health Commission (No. 20231A011096), and the Medical Key Discipline of Guangzhou (2021-2023). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes.

BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. CONCLUSION: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.

Improvement of early miscarriage rates in women with adenomyosis via oxytocin receptor antagonist during frozen embryo transfer-a propensity score-matched study.

BACKGROUND: Dysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis. METHODS: Between January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses. RESULTS: The study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis. CONCLUSIONS: Administering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.

Investigation of Phosphatidylcholine by MALDI Imaging Mass Spectrometry in Normal and IVF Early-Stage Embryos.

The receptive phase of the uterus is marked by structural and functional maturation of the endometrium. During this limited time span, the blastocyst competency is superimposed on the receptive endometrium. It is a well-known fact that lipid signalling in early-stage pregnancy has a crucial role in successful embryogenesis. In our study, CD-1 mouse uteri after normal and in vitro fertilization (IVF) were investigated at 6.5, 8.5, and 10.5 days of pregnancy. Matrix-assisted laser desorption/ionization time-of-flight imaging mass spectrometry and liquid chromatography coupled tandem mass spectrometry were used for identification of phosphatidylcholine (PC) lipid structures. In the embryonal tissues, PC 32:0 and PC 34:0 were increased, while in the antemesometrial (AM) decidua the two 20:4-containing PCs, PC 36:4 and PC 38:4 were increased. In transferred uterus samples, higher expressions of PC 34:0, PC 34:1, PC 34:2, PC 36:1, and PC 36:2 in mesometrial decidua were seen, whereas the two 20:4-containing PCs, PC 36:4 and PC 38:4 showed increased expression in the AM and lateral decidua. This paper shows a significant spatio-temporal change in lipid metabolism during IVF procedures for the first time.

Hysteroscopic Management of Symptomatic Cesarean Scar Diverticulum in Patients Undergoing Frozen-Thawed Embryo Transfer: Impact on Clinical Pregnancy Rates and Pregnancy Complications.

This retrospective cohort study aimed to compare the clinical outcomes of patients with cesarean scar defect (CSD) undergoing frozen embryo transfer (FET) with or without hysteroscopic repair surgery. The study included 82 patients, with 48 patients in surgical group A (undergoing CSD repair) and 34 patients in surgical group B (undergoing hysteroscopic treatment for other uterine lesions). The results showed that patients in group A had a larger CSD volume and a different shape compared to group B. However, there was no significant difference in clinical pregnancy rates between the two groups. Additionally, there were no differences in miscarriage, live birth, or preterm birth rates, and no complications such as scar pregnancy or placental abnormalities were observed in either group. These findings suggest that hysteroscopic treatment of CSD in symptomatic patients undergoing FET does not increase the risk of pregnancy complications and can lead to comparable clinical pregnancy rates with asymptomatic patients. Further studies with larger sample sizes are needed to confirm these results and evaluate long-term reproductive outcomes following CSD repair.

Superovulating cattle with corifollitropin-alpha, a long-acting recombinant human FSH (rhFSH): Dose-response, half-life, effects on the ovaries, and embryo outcomes.

The aim of this study was to evaluate the superestimulatory and superovulatory responses of cattle treated with corifollitropin-alpha, a long-acting human recombinant FSH (rhFSH). In the first and second experiments, we used Nelore (Bos indicus) heifers previously submitted to follicular wave suppression by active immunization against GnRH. In Experiment 1 (a dose-response study), heifers (n = 20) were randomly allocated into five groups, which received placebo (saline) or a single sc dose of 7.5, 15.0, 22.5 or 30.0 µg rhFSH. The heifers were subjected to daily ovarian scan and blood sampling during 11 days. We observed group, time, and group x time effects (P<0.0001) for both average follicle size and circulating FSH concentrations, with a strong correlation (R = 0.82, P<0.0001) between the area under curve (AUC) for both parameters. The peak concentration of FSH 24h after treatment and average follicle size at all timepoints, however, were similar (P>0.05) between groups 22.5 and 30.0 µg. In Experiment 2, heifers (n = 18) were allocated into three groups, which received (0h) either placebo (control), 25 µg rhFSH or 130 mg pFSH (Folltropin). There was no difference (P>0.05) in average follicle size at any moment, as well as in intrafollicular E2 at 120h or in plasma P4 seven days later between groups rhFSH and pFSH. In Experiment 3, cycling Nelore heifers (n = 20) were subjected to a wave synchronization protocol and superovulated (day 0) using a standard pFSH protocol (120 mg split in eight decreasing im doses) or with a single sc injection of 20 µg rhFSH. The number of follicles >7 mm on day 4 did not differ (P=0.4370). Heifers receiving rhFSH had greater average follicle size on day 4 (P=0.0005), ovulation rate (P<0.0001), and number of CL (P=0.0155), as well as a trend towards a greater number of ova (P=0.07) and viable embryos (P=0.0590). In Experiment 4, superovulation was induced with a single sc injection of 25 µg rhFSH in Girolando and Nelore cows and heifers (n = 20). None of the embryo yield endpoints differed between the two breeds (P>0.05). In conclusion, cattle superstimulation and superovulation can be successfully induced with a single dose of a long-acting rhFSH (corifollitropin-alpha).

Controlled ovarian stimulation leads to cardiovascular changes in patients undergoing in vitro fertilization.

OBJECTIVE: To study hemodynamic changes along controlled ovarian stimulation in women undergoing in vitro fertilization. STUDY DESIGN: Prospective observational cohort study conducted at Mother and Child Department of University Hospital Federico II, in Naples, Italy, between April 2021 and July 2022. Sixty-eight infertile patients undergoing controlled ovarian stimulation with gonadotropin, antagonist protocol and a fresh embryo transfer were included. Haemodynamic assessment was carried out using UltraSonic Cardiac Output Monitor at baseline (T1), estradiol peak (T2), fresh embryo-transfer day (T3). To evaluate relationships between quantitative variables and groups a Student T test for independent data was assessed. One-way analysis of variance (ANOVA) was used to determine the differences between the means of three time points (T1, T2 and T3) for quantitative variables. A mixed-model analysis of variance (ANOVA) was used to determine the differences between groups, among time points (T1, T2 and T3). RESULTS: Sixty-eight patients were included. Significant differences over the three time points have been observed for CO (f = 3.78 l/min; p = 0.025), SVI (f = 3.56 ml/m2;p = 0.013), and RSVI (f = 4.84 dscm-5 m2; p = 0.009). No significant differences in trends have been found between beta hCG positive and beta hCG negative groups. There were no significant differences in maternal hemodynamic parameters at time-point T3 between patients treated with hCG 10,000 UI and with Triptorelin. Patients considered at increased risk of hyperstimulation reported a significant increase in SVI at baseline (26.9 ± 9.0 mL/m2 vs 21.9 ± 7.0 mL/m2; p = 0.010). CONCLUSION: According to the results of our study, during controlled ovarian stimulation with antagonist protocol, patients undergo significant changes in maternal cardiovascular parameters over a very short period.

Effects of high-normal fasting blood glucose on ART outcomes of frozen-thawed single blastocyst transfer in women with normal BMI.

PURPOSE: This retrospective cohort study aims to investigate whether high-normal fasting blood glucose (FBG) affects assisted reproductive technology (ART) outcomes undergoing single blastocyst frozen-thawed embryo transfer (FET) cycles in women with normal body mass index (BMI). METHODS: 944 women with normal BMI and FBG levels undergoing single blastocyst FET cycles were enrolled. Based on the median of FBG (4.97 mmol/L, 1 mmol/L = 18 mg/dL), the subjects were categorized into the low-normal group (3.90 ≤ FBG ≤ 4.97 mmol/L, n = 472) and the high-normal group (4.97 < FBG < 6.10 mmol/L, n = 472). Multivariable logistic regression and receiver operating characteristic (ROC) were used to analyze the relationship between high-normal FBG and ART outcomes. PRIMARY OUTCOME: live birth rate (LBR). RESULTS: LBR was significantly lower in the high-normal group than in the low-normal group (36.8% vs. 45.1%, p = 0.010), and the miscarriage rate was considerably higher than that in the low-normal group (23.9% vs. 16.5%, p = 0.041). High-normal FBG of female was an independent predictor of live birth (adjusted OR:0.747, 95% CI: 0.541-0.963, p = 0.027) and miscarriage (adjusted OR:1.610, 95% CI: 1.018-2.547, p = 0.042). ROC analyses showed that the cut-off values of FBG (endpoints: live birth and miscarriage) were 5.07 mmol/L, and 5.01 mmol/L, respectively. CONCLUSIONS: In women with normal BMI, high-normal FBG is an independent risk factor for lower LBR and higher miscarriage rate in single blastocyst FET cycles. Attention to preconception FBG monitoring in this particular population may allow early intervention to improve ART outcomes.

A retrospective analysis of conception per embryo transfer in dairy cattle in South Korea.

The bovine embryo production industry has seen significant growth over the past two decades, particularly in the production of in vitro produced embryos. This growth, driven by advancements in cryopreservation, in vitro culture mediums, ovum pick-up (OPU) procedures, ultrasonography devices, and embryo transfer (ET) has been notable. Particularly, ET is crucial for disseminating high genetic merit and amplifying foreign breeds by importing frozen embryos. This retrospective study aimed to assess factors affecting conception per embryo transfer (CPET) in Holstein-Friesian cattle in South Korea from October 2008 to July 2022. We evaluated type of embryo breed, type of embryo production (fresh and frozen; in vitro and in vivo production), recipient conditions including estrus type, corpus luteum quality, parity (nulliparous heifers, primiparous, and multiparous cows), and the daily mean temperature-humidity index (THI) as an index for heat stress. Type of embryo breed and estrus had no significant impact on CPET. However, we observed higher CPET in recipients with good quality corpus luteum, nulliparous heifers, and surrogates receiving fresh in vitro and frozen in vivo embryos. Importantly, CPET was not adversely affected by mild heat stress conditions (up to daily mean THI 76), indicating that using frozen in vivo embryos produced by multiple ovulation embryo transfer and fresh in vitro embryos by OPU-ET can help alleviate the subfertility issues in dairy cattle caused by global warming in Korea.

Characterization of conception rate after embryo transfer in comparison with that after artificial insemination in dairy cattle.

Artificial insemination (AI) and embryo transfer (ET) are important in the reproduction of dairy cows. The conception rate after AI or ET is an essential indicator when selecting appropriate breeding methods. However, information on the environmental factors affecting ET conception rate when compared with AI is limited. We aimed to investigate environmental factors affecting ET conception rate and characterize the differences in environmental factors between AI and ET. Records of the first AI (n = 1,870,143) and ET (n = 29,922) from Holstein nulliparous, primiparous, and multiparous cows in Hokkaido, Japan, were analyzed using separate multivariable logistic regression models. For each breeding method, we grouped primiparous and multiparous cows according to milk yield at peak lactation (PY; < 25, 25-30, 30-35, ≥ 35 kg in primiparous, < 40, 40-45, 45-50, ≥ 50 kg in multiparous) and the interval from calving to first AI or ET (CFI/CFT; < 60, 60-79, 80-99, ≥ 100 d) to evaluate the effects of PY and CFI/CFT on conception rate. AI conception rate decreased with increasing PY in primiparous and multiparous cows, whereas ET conception rate did not decrease significantly. Additionally, the ET conception rate did not decrease even in primiparous and multiparous cows slightly earlier than 60 d in CFI/CFT when compared with those in CFI/CFT after 60 d, which differed from the AI conception rate. Collectively, breeding by ET leads to the avoidance of negative effects of high milk yield and calving on the conception rate, indicating that cows are fertile by ET within 60 d after calving.

Clinical data-based modeling of IVF live birth outcome and its application.

BACKGROUND: The low live birth rate and difficult decision-making of the in vitro fertilization (IVF) treatment regimen bring great trouble to patients and clinicians. Based on the retrospective clinical data of patients undergoing the IVF cycle, this study aims to establish classification models for predicting live birth outcome (LBO) with machine learning methods. METHODS: The historical data of a total of 1405 patients undergoing IVF cycle were first collected and then analyzed by univariate and multivariate analysis. The statistically significant factors were identified and taken as input to build the artificial neural network (ANN) model and supporting vector machine (SVM) model for predicting the LBO. By comparing the model performance, the one with better results was selected as the final prediction model and applied in real clinical applications. RESULTS: Univariate and multivariate analysis shows that 7 factors were closely related to the LBO (with P < 0.05): Age, ovarian sensitivity index (OSI), controlled ovarian stimulation (COS) treatment regimen, Gn starting dose, endometrial thickness on human chorionic gonadotrophin (HCG) day, Progesterone (P) value on HCG day, and embryo transfer strategy. By taking the 7 factors as input, the ANN-based and SVM-based LBO models were established, yielding good prediction performance. Compared with the ANN model, the SVM model performs much better and was selected as the final model for the LBO prediction. In real clinical applications, the proposed ANN-based LBO model can predict the LBO with good performance and recommend the embryo transfer strategy of potential good LBO. CONCLUSIONS: The proposed model involving all essential IVF treatment factors can accurately predict LBO. It can provide objective and scientific assistance to clinicians for customizing the IVF treatment strategy like the embryo transfer strategy.

Reproductive outcomes of embryo cryopreservation and transfer at the start-up phase of fertility preservation in Japan.

Purpose: To verify the effectiveness of embryo transfer (ET) using cryopreserved embryo as fertility preservation (FP). Methods: This study was a questionnaire survey. The total number of embryo cryopreservation (EC) was investigated between 2014 and 2020. And for patients who underwent ET among study period, details of EC, outcome of ET, number of live births, and mortality were investigated. Results: Of the 150 facilities, 114 responded (76.0%). A total of 1420 EC were performed during the study period; and ET was performed for 417 patients. Breast cancer was the most common primary disease. A total of 199 live births (including prospective) were obtained by ET; 1.7 EC and 2.2 ET were performed per patient, and live birth rate was 21.4% per ET (28.1% on 35-37-year-old patients). The number of EC and ET increased with age. The final birth rate, including pregnancies other than FP, was 51.8%. Ovarian stimulation with aromatase inhibitors was commonly used, although with no effect on live birth rates. Random start stimulation was also common, experienced by 36.3% of breast cancer patients. Conclusion: Reproductive outcomes of ETs following EC as FP are acceptable. This research project was registered in the University Hospital Medical Information Network (UMIN000043664).

Clinical outcomes of fresh and frozen embryos transfer after in vitro fertilization in spouses of patients with severely low sperm count and motility. / å› é å¶é‡åº¦å°‘å¼±ç²¾å­ç—‡ä¸å­•æ‚£è€ ä½“å¤–å—ç²¾åŽç§»æ¤æ–°é²œèƒšèƒŽä¸Žå†·å†»èƒšèƒŽçš„ä¸´åºŠç»“å±€æ¯”è¾ƒ.

OBJECTIVES: To compare the pregnancy and neonatal outcomes of in vitro fertilization-embryo transfer (IVF-ET) with fresh or frozen embryos for male patients with severely low sperm count and motility. METHODS: A total of 2300 male patients with severely low sperm count and motility underwent IVT-ET in the Reproduction Medicine Center, Sir Run Run Shaw Hospital from April 2018 to April 2022. After applying the propensity score matching (PSM), 473 fresh embryo transferred cycles and 473 frozen embryo transferred cycles were selected in the study, and the pregnancy and neonatal outcomes were compared between two groups. RESULTS: There were no significant differences in pregnancy outcomes and neonatal outcomes between fresh and frozen embryo groups (all P>0.05). In the stratification analysis, the number of retrieved oocytes in the fresh good-quality embryo transfer group was significantly increased compared with the fresh poor-quality embryo group (P<0.05), but the very early pregnancy loss rates were similar between the two groups, while the rate in fresh good-quality embryo transfer group was significantly higher than that in the frozen good-quality embryo transfer group (P<0.05). Among different age groups of women, the number of retrieved oocytes and the level of estrogen in the fresh embryo transfer group was significantly higher in the 20 to <30 years old group than that in the 30 to <35 years old group (both P<0.05), but the clinical pregnancy rate was lower in the 20 to <30 years old group than that in the 30 to <35 years old group (P>0.05). Additionally, the very early pregnancy loss was significantly increased in the fresh embryo group compared with the frozen embryo group in the 20 to <30 years age group (P<0.05). CONCLUSIONS: There is no significant difference in pregnancy and neonatal outcomes between fresh embryo transfer and frozen embryo transfer for male patients with severely low sperm count and motility undergoing IVF-ET. Due to shorter transfer time, less embryo freezing damage and reduced costs, fresh embryo transfer can be considered a first choice. However, it is not necessary to pursue fresh embryo transfer if maternal oestrogen levels are too high and there is a tendency of overstimulation.

Association Between Pregnancy Outcomes and the Time of Progesterone Exposure of D6 Single-Blastocyst Transfer in Frozen-Thawed Cycles: A Retrospective Cohort Study.

Purpose: 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.

Dependency of mitochondrial quantity on blastocyst timeline obscures its actual effect to pregnancy outcomes.

Objectives: To explore the correlation between mitochondrial quantity and the blastocyst development timeline as well as their respective contributions to early pregnancy. Methods: A retrospective study was conducted using a dataset comprising 2,633 embryos that underwent preimplantation genetic testing for aneuploidy (PGT-A) between January 2016 and December 2023. The study was divided into three subsets to address distinct aspects: the representativeness of a single trophectoderm (TE) biopsy for mitochondrial quantity (n=43), the correlation between morphokinetic features and mitochondrial quantity (n=307), and the association analysis among mitochondrial quantity, blastocyst timeline factor, and reproductive outcomes (n=2,283). Distribution assessment of mitochondrial quantity across an individual blastocyst involved the identification within multiple biopsies and spent culture media. Timeline evaluation included correlating mitochondrial quantity with time-lapse datasets. Finally, multivariate logistic regression models, incorporating potential effectors alongside mitochondrial quantity, were employed to analyze their respective contributions to early pregnancy endpoints. Results: Of distribution assessment, mitochondrial quantity exhibited an even distribution across the entire trophectoderm (Spearman's ρ=0.82), while no detectable mtDNAs in the corresponding spent culture media. Then the timeline correlation study revealed significant association between mitochondrial quantity and blastocyst features of both the day of expanded blastocyst formation (95% Confidence intervals, CIs: 0.27~4.89, p=0.03) and the timing of expanded blastocyst formation (tEB) (95% CIs: -0.24~-0.01, p=0.04) in the regression model, indicating a strong dependency between mitochondrial quantity and the blastocyst development timeline. For the contribution to early pregnancy, multivariate logistic regression models showed that the day of expanded blastocyst formation contributed to four endpoints persistently: positive for HCG (odd ratio, OR: 0.71, p=0.006), gestational sac (OR: 0.78, p=0.04), fetal heartbeat (OR: 0.71, p=0.004), and progression to 14 weeks (OR: 0.69, p=0.002). Contrastingly, no notable correlation was observed between the mitochondrial quantity and these endpoints. Conclusions: Strong interaction was observed between mitochondrial quantity and the blastocyst timeline, particularly the timing of expanded blastocyst formation. It suggests that the primary determinant influencing pregnancy outcomes lies in the time-dependent parameter of blastocyst rather than in the specific mitochondrial quantity.