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.

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).

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.

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.

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.

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.

[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.

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.

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.

EFFECTS OF BEEF SEMEN AND BEEF EMBRYO STRATEGIES ON PROFITABILITY: Economics of using beef semen and beef in vitro produced embryo transfer in Jersey herds.

Dairy herds have adopted sexed semen (SS) and beef semen (BS) to control heifer inventory and increase calf sales revenue. Beef in vitro-produced embryo transfer (beef IVP-ET) may be an alternative to increase calf sales revenue. Besides, raising those Jersey beef crossbred and/or pure beef animals in a dairy system may be a new source of revenue. We aimed to evaluate breed strategies combining dairy conventional semen (CS), SS, BS, and beef IVP-ET on herd dynamics and profitability by marketing those animals with one-day-old or raising them to 180 kg. A Markov chain model was developed to maximize the profitability of Jersey herds by changing the number of dairy heifers sold at birth and the culling rate of 3rd and greater parity cows. The model presents inputs on the reproductive and productive performance of heifers and cows over time. The last year's data (year 10 - steady state) was used to calculate accrual operational cost and revenue per cow per year. We varied the breeding strategy by breeding order and parities, the embryo transfer cost ($85 or $170), the pure beef calf market price ($200 or $300), and by marketing Jersey-beef and pure beef animals with one-day-old or raising them to 180 kg. A total of 8 scenarios + default scenario were simulated. Overall, the proportion of SS use was 47.3 ± 0.6%. For the scenarios replacing all CS breedings with BS breedings, the proportion of CS and BS used was 52.3 ± 0.6. When beef IVP-ET was used, the percentage of BS and beef IVP-ET used was 22.4 ± 0.1% and 31.0 ± 0.1%, respectively. We observed that when we compared SS:BS with the default scenario, the production of purebred Jersey male calves was reduced by 83.5%, and profit/cow per year was increased from $113.5 to $203.3 with SS:BS. When a beef IVP-ET of $85 per transfer was used (scenarios 2 and 3), profit/cow per year was $145.5 and $176.2 for a pure-beef calf price of $200 and $300, respectively. In scenario 4, with a beef IVP-ET cost of $170, the lowest profit ($52.9 per cow per year) was found when marketing one-day-old pure-beef calves at $200. The highest profit was achieved for scenario raising the Jersey-beef crossbred animals to 180 kg ($232.9, scenario 6), followed by scenario 7 ($222.9, SS:BS:IVP-ET) with an embryo transfer cost of $85. Under the current market conditions, combining SS and BS in the reproductive program was a feasible economic opportunity for Jersey herds, yielding the highest net return. The adoption of beef IVP-ET in a reproductive program can potentially increase profit/cow per year, but its profitability will depend on the beef IVP-ET pregnancy cost, the pure-beef market price, calf performance, and the herd reproductive performance. In conclusion, raising the Jersey-beef crossbred calves may be a profitable strategy, and dairy producers need to evaluate the best option to invest in since it will take an extra risk to produce high-quality animals to the market.

Premature Progesterone Rise Is Associated with Higher Cumulative Live Birth Rate with Freeze-All Strategy.

Background/Objectives: This paper undertakes an investigation into the implications of premature progesterone rise (PPR) on pregnancy outcomes in freeze-all strategy cycles. Methods: A retrospective cohort study encompassing 675 IVF/ICSI cycles using a freeze-all strategy was enrolled. The cycles were categorized into two groups based on serum progesterone levels at the time of hCG administration: 526 cycles had levels below 1.5 ng/mL, while 149 cycles had levels equal to or above 1.5 ng/mL. Results: The findings revealed a significantly higher number of mature follicles and retrieved oocytes in patients with PPR across all AMH categories. Multiple analyses revealed factors influencing PPR, including the duration of induction and the number of retrieved oocytes. Within the same oocyte retrieval number group, patients with PPR demonstrated non-inferior pregnancy outcomes compared to non-PPR patients. Upon adjustment for age, AMH, and total follicle-stimulating hormone (FSH) dosage, PPR maintained a positive correlation with the cumulative live birth rate (LBR). Conclusions: The study showed that PPR correlates with an increase in retrieved oocytes while maintaining similar embryo quality and oocyte retrieval rates and results in a higher cumulative LBR.

Combined analysis of estradiol and ß-hCG to predict the early pregnancy outcome of FET: a retrospective study.

BACKGROUND: The accurate prediction of pregnancy outcomes in in vitro fertilization (IVF) cycles is crucial. While several studies have been conducted on the predictive power of serum estradiol (E2) and ß-hCG concentrations post-embryo transfer (ET) for pregnancy outcomes, there is debate on the predictive value of E2. The objective of this study was to investigate the predictive efficacy of combining serum E2 and ß-hCG levels on early reproductive outcomes 12 days after embryo transfer. METHODS: A total of 1521 patients with ß-hCG positive values on day 12 following frozen-thawed embryo transfer (FET) with natural endometrial preparation cycles (NCs) were gathered in affiliated Women's Hospital of Jiangnan University. Using logistic regression, the relationship between pregnancy outcome and early serum E2 and ß-hCG concentrations was examined. The receiver-operating characteristic (ROC) analysis was used to assess the predictive accuracy of the serum E2 and ß-hCG concentrations. RESULTS: Notable distinctions were observed in the serum E2 and ß-hCG levels on the twelfth day following FET with NCs between the groups classified as clinical pregnancy group (CP Group) and biochemical pregnancy group (BP Group). In addition, the cutoff values for E2 and ß-hCG on day 12 following FET with NCs in cleavage embryo group (CE Group) were 129.25 pg/mL and 156.60 mIU/mL, respectively. The threshold values for E2 and ß-hCG for the blastocyst group (B Group) were 174.45 pg/mL and 217.70 mIU/mL. Serum E2 day12 and ß-hCG day12 were found to be substantially linked with clinical pregnancy by logistic regression analysis. CONCLUSIONS: Serum E2 and ß-hCG concentrations were found to be significantly different between the CP Group and BP Group in infertility women underwent FET with NCs. Our retrospective cohort study's findings suggest that the combination of early E2 and ß-hCG levels on day 12 post-FET could be used as a predictive tool to evaluate the likelihood of both positive and negative pregnancy outcomes in FET with NCs.

Pretreatment with or without GnRH-agonist before frozen-thawed embryo transfer in patients with PCOS: a systematic review and meta-analysis.

PURPOSE: This study was aimed to systematically evaluate the efficacy of artificial cycle-prepared frozen-thawed embryo transfer (FET) with or without gonadotrophin-releasing hormone agonist (GnRH-a) pretreatment for women with polycystic ovary syndrome (PCOS). METHODS: The analysis was carried out by searching the PubMed, EMBASE, and CNKI databases with a combination of keywords before October 2021. The available studies of the effects of GnRH-a pretreatment or no pretreatment on FET in PCOS patients were considered. The risk ratios (RRs) or standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated with using subgroups and sensitivity analysis. The quality evaluation for this analysis was followed. RESULTS: Seventeen studies including 3646 women were analyzed. GnRH-a pretreatment was significantly associated with a higher implantation rate (RR = 1.12, 95%CI: 1.00-1.24) and clinical pregnancy rate (RR = 1.19, 95%CI: 1.08-1.32) than the placebo. Moreover, in the GnRH-a pretreatment group, significant differences were detected for increasing the endometrium thickness among PCOS patients (SMD = 0.56, 95%CI: 0.20-0.92). However, for RCTs subgroup, no differences were observed, even after sensitivity analyses. In addition, the miscarriage rates, ectopic pregnancy rates, multiple pregnancy rates, and live birth rates were similar in both two groups. CONCLUSIONS: Endometrial preparation using GnRH agonist pretreatment prior to FET seems to be the better choice for PCOS patients. However, well-designed RCTs are required for confirmation.

Influence of COVID-19 infection on early pregnancy outcomes in different periods around frozen embryo transfer.

PURPOSE: The study aimed to investigate the potential influence of COVID-19 infection on embryo implantation and early development in women undergoing frozen embryo transfer (FET), with a specific focus on infections occurring at different periods around FET. METHODS: A retrospective analysis was performed on women who had undergone FET during a period marked by a significant surge in COVID-19 infection in Shanghai. All enrolled women experienced their first documented COVID-19 infection around the time of FET, ensuring that infections did not occur prior to oocyte retrieval. Participants were categorized into six groups based on the timing of infection: uninfected, ≥ 60 days, < 60 days before FET, 0-14 days, 15-28 days, and 29-70 days after FET. Clinical outcomes were compared across these groups. RESULTS: The infection rate among the total of 709 cases was 78.28%. Infected individuals exhibited either asymptomatic or mild symptoms. The ongoing pregnancy rates for the first four groups were 40.7%, 44.4%, 40.5%, and 34.2% (P = 0.709) respectively, biochemical pregnancy rates (59.1% vs. 61.1% vs. 67.6% vs. 55.7%, P = 0.471) and clinical pregnancy rates (49.6% vs. 55.6% vs. 55.4% vs. 48.1%, P = 0.749), all showed no significant differences. Early spontaneous abortion rates across all six groups were 18.3%, 20.0%, 25.0%, 28.9%, 5.4%, and 19.0% respectively, with no significant differences (P = 0.113). Multivariable logistic analysis revealed no significant correlation between the infection and ongoing pregnancy. CONCLUSION: Asymptomatic or mild COVID-19 infections occurring around FET do not appear to have a significant adverse impact on early pregnancy outcomes.

Letrozole ovulation regimen for frozen-thawed embryo transfer in women with polycystic ovary syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the frozen-thawed embryo transfer (FET) during their IVF/ICSI treatment. The programmed regimen permits flexible scheduling of embryo transfer but requires long-term usage of exogenous estrogen and higher dosages of luteal support while the letrozole ovulation regimen needs lower dosages of luteal support only. Recently, multiple studies have shown that the letrozole ovulation regimen can improve pregnancy outcomes of FET in women with PCOS compared with the programmed regimen. However, most of these studies are retrospective, and prospective studies are urgently needed the evidence from the perspective study is insufficient. METHODS/DESIGN: We are undertaking a multicentre, randomized, controlled clinical trial of an endometrial preparation regimen for FET in women with PCOS. The eligible women are randomly assigned to either the letrozole ovulation regimen or the programmed regimen for endometrial preparation. The primary outcome is the clinical pregnancy rate. DISCUSSION: The results of this study will provide evidence for whether the letrozole ovulation regimen for endometrial preparation could improve pregnancy outcomes in PCOS women undergoing FET. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200062244. Registered on 31 July 2022.

Effects of hormone sources on developmental competence of oocytes by ovum pickup in Japanese black cattle.

Japanese Black (Wagyu) cattle donors were primed with different protocols and sources of follicle-stimulating hormone (FSH) for successive ovum pickup (OPU) and embryo development after in vitro fertilization (IVF). Following OPU, retrieved cumulus oocyte complexes (COCs) were subjected to IVF, and resulting blastocysts were transferred into recipients to evaluate implantation capability. Experiment 1: The best blastocyst development (45.3 %) and embryo yields (5.0/donor/OPU) were found with oocytes retrieved from donors treated with FSH (STIMUFOL®, Belgium) at a dosage of 150 IU per donor, compared to two others commercial FSH sources. Experiment 2: There were no differences in embryo development or yield with STIMUFOL FSH (total FSH 150 IU/donor) at a priming duration of either 60-h (Regime 1, six FSH injections) or 36-h (Regime 2, four FSH injections). Experiment 3: Compacted COCs required 22-26-h maturation in vitro (IVM) before IVF for optimal blastocyst development (36.1-41.1 %); however, short (18-h) and prolonged (30-h) IVM duration resulted in lower embryonic development. In contrast, expanded COCs resulted in inferior blastocyst development compared to compacted COCs. Immunofluorescence microscopy revealed that the ratio of 89.8 % cumulus compacted COCs were at the germinal vesicle (pachytene) phase while 98.9 % cumulus expanded COCs went through spontaneous meiosis from meiotic metaphase I, anaphase I, telophase I to metaphase II upon OPU retrieval (P<0.05). Pregnancy rates were not different among three FSH sources or different FSH treatments as long as embryos reached the blastocyst stage. Our study found that different sources of FSH used for Wagyu donor priming prior to OPU resulted in differential embryo development potentials, but those embryos that reached out to blastocysts had a competent implantation ability.

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.

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.

Gonadotropin-Releasing Hormone (GnRH) and Its Agonists in Bovine Reproduction II: Diverse Applications during Insemination, Post-Insemination, Pregnancy, and Postpartum Periods.

The administration of GnRH and its agonists benefits various aspects of bovine reproductive programs, encompassing physiological stages such as estrous synchronization, post-insemination, pregnancy, and the postpartum period. The positive impact of GnRH administration in overcoming challenges like repeat breeder cows, early embryonic loss prevention, and the management of cystic ovarian disease (COD) is thoroughly surveyed. Furthermore, this review focuses on the significance of GnRH administration during the postpartum period, its role in ovulation induction, and how it enhances the productivity of embryo transfer (ET) programs. An emerging feature of this field is introduced, focusing on nano-drug delivery systems for GnRH agonists, and the potential benefits that may arise from such advancements are highlighted. While this review offers valuable insights into various applications of GnRH in bovine reproduction, it emphasizes the crucial need for further research and development in this field to advance reproductive efficiency and health management in dairy cattle.