Live Birth Outcomes Research Articles

Initial β-hCG levels and 2-day-later increase rates effectively predict pregnancy outcomes in single blastocyst transfer in frozen-thawed or fresh cycles: A retrospective cohort study.

To investigate whether the initial beta-human chorionic gonadotropin (β-hCG) levels and their rate of increase differ after single fresh and frozen blastocyst transfers, and whether these values effectively predict pregnancy outcomes. This retrospective cohort study was conducted at the Sisli Memorial Hospital, assisted reproductive technology, and Reproductive Genetics Center in Istanbul, Turkey, between January 2016 and January 2022. Three thousand two hundred thirty-eight single blastocyst transfers with positive pregnancy test results were evaluated. Of these, 738 were fresh transfer cycles and 2500 were frozen-thawed embryo transfer (FET) cycles. β-hCG test results from 9 days after fresh and FET cycles were compared between the groups with biochemical pregnancy, early pregnancy loss, and live birth outcomes. The threshold values were determined for each pregnancy outcome. The rate of increase between the first and second β-hCG tests performed 2 days apart was determined for each pregnancy outcome. Finally, the listed values were compared between the FET and fresh cycle. Mean baseline β-hCG levels were significantly higher in FET cycles than in fresh cycles, regardless of pregnancy outcomes (P < .005). Baseline β-hCG levels were higher in fresh cycles with live births (171.76 ± 109.64 IU/L) compared to biochemical and clinical pregnancy losses (50.37 ± 24.31 and 114.86 ± 72.42, respectively) (P < .001). Live births in FET cycles resulted in higher baseline β-hCG levels (193.57 ± 100.38 IU/L) compared to biochemical and clinical pregnancy loss groups (68.41 ± 51.85 and 149.29 ± 96.99 IU/L, respectively) (P < .001). The β-hCG threshold for live birth for fresh cycles was 116.5 IU/L (sensitivity 80%, specificity 70%, positive predictive value 90%, negative predictive value 54%) and 131.5 IU/L for FET cycles (sensitivity 71%, specificity 68%, positive predictive value 87%, negative predictive value 50%). The percentage of the area under the curve for single fresh blastocyst transfers was 0.81 and 0.76 for frozen transfers. The rate of increase in β-hCG was similar in fresh and FET cycles. Initial β-hCG levels and 2-day increases are effective parameters for diagnosing pregnancy in fresh and FET cycles. The initial β-hCG level was significantly higher in the FET cycles than in the fresh cycles. Predicting outcomes earlier helps clinicians to manage and follow high-risk pregnancies.

Clinical Features of Severe Ovarian Hyperstimulation Syndrome with Hydrothorax.

Does the presence of hydrothorax suggest that severe ovarian hyperstimulation syndrome (OHSS) is associated with more severe conditions and worse pregnancy outcomes? The clinical data for 868 hospital patients with severe OHSS following IVF-ET at Peking University Third Hospital between 1 January 2016 and 21 July 2021 were retrospectively analysed. The patients were divided into two groups, the ascites alone group (n = 417) and the ascites combined with hydrothorax group (n = 451), to investigate the clinical features and pregnancy outcomes of patients with severe ovarian hyperstimulation syndrome (OHSS) combined with hydrothorax plus ascites. The clinical data for 868 hospital patients with severe OHSS following IVF-ET were included. A total of 51.96% of patients with severe OHSS had hydrothorax plus ascites, mainly bilateral and moderate hydrothorax. Most cases with hydrothorax could be monitored and observed, and only 2.66% of the cases required thoracentesis and pleural drainage. Clinically, the time to visit due to worsening symptoms was longer; the hospital stay was shorter; and the OHSS-related laboratory tests, such as white blood cells (WBC), haematocrit (HCT), and ovarian diameter, were less severe in the ascites combined with hydrothorax group than in the ascites alone group. For live-birth outcomes of IVF-ET, the presence and the volume of hydrothorax were not independent risk factors, while the late onset of OHSS (odds ratio [OR]: 0.857 95% confidence interval [CI]: 0.795, 0.925) and a history of foetal reduction (OR: 13.796 95% CI: 1.808, 105.288) were independent protective factors for live birth. Patients with severe OHSS combined with hydrothorax plus ascites have less severe clinical manifestations and laboratory tests than those with ascites alone. The presence and the volume of hydrothorax are unrelated to live-birth outcomes following in vitro fertilization and embryo transfer (IVF-ET).

Epigenetic determinants of reproductive potential augment the predictive ability of the semen analysis

To investigate the power of DNA methylation variability in sperm cells in assessing male fertility potential. Retrospective cohort. Fertility care centers. Male patients seeking infertility treatment and fertile male sperm donors. None. Sperm DNA methylation data from 43 fertile sperm donors were analyzed and compared with the data from 1344 men seeking fertility assessment or treatment. Methylation at gene promoters with the least variable methylation in fertile patients was used to create 3 categories of promoter dysregulation in the infertility treatment cohort: poor, average, and excellent sperm quality. After controlling for female factors, there were significant differences in intrauterine insemination pregnancy and live birth outcomes between the poor and excellent groups across a cumulative average of 2-3 cycles: 19.4% vs. 51.7% (P=.008) and 19.4% vs. 44.8% (P=.03), respectively. Live birth outcomes from invitro fertilization, primarily with intracytoplasmic sperm injection, were not found to be significantly different among any of the 3 groups. Methylation variability in a panel of 1233 gene promoters could augment the predictive ability of semen analysis and be a reliable biomarker for assessing intrauterine insemination outcomes. Invitro fertilization with intracytoplasmic sperm injection appears to overcome high levels of epigenetic instability in sperm.

Comparison of 1-year cumulative live birth and perinatal outcomes following single blastocyst transfer with or without preimplantation genetic testing for aneuploidy: a propensity score-matched study.

We evaluated whether preimplantation genetic testing for aneuploidy (PGT-A) could increase the cumulative live birth rate (CLBR) in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL). The clinical records of 7,668 patients who underwent oocyte retrieval (OR) with or without PGT-A were reviewed for 365days and retrospectively analyzed. Using propensity score matching, 579 patients in the PGT-A group were matched one-to-one with 7,089 patients in the non-PGT-A (control) group. Their pregnancy and perinatal outcomes and CLBRs were statistically compared. The live birth rate per single vitrified-warmed blastocyst transfers (SVBTs) significantly improved in the PGT-A group in all age groups (P < 0.0002, all). Obstetric and perinatal outcomes were comparable between both groups regarding both RIF and RPL cases. Cox regression analysis demonstrated that in the RIF cases, the risk ratio per OR was significantly lower in the PGT-A group than in the control group (P = 0.0480), particularly in women aged < 40years (P = 0.0364). However, the ratio was comparable between the groups in RPL cases. The risk ratio per treatment period was improved in the PGT-A group in both RIF and RPL cases only in women aged 40-42years (P = 0.0234 and P = 0.0084, respectively). Increased CLBR per treatment period was detected only in women aged 40-42years in both RIF and RPL cases, suggesting that PGT-A is inappropriate to improve CLBR per treatment period in all RIF and RPL cases.

Using blastocyst re-expansion rate for deciding when to warm a new blastocyst for single vitrified–warmed blastocyst transfer

Research questionCan predictive post-warm parameters that support the decision to transfer a warmed blastocyst or to warm another blastocyst be identified in women with multiple frozen–vitrified blastocysts? DesignRetrospective single-centre observational cohort analysis. A total of 1092 single vitrified–warmed blastocyst transfers (SVBT) with known Gardner score, maternal age and live birth were used to develop live birth prediction models based on logistic regression, including post-warm re-expansion parameters. Time-lapse incubation was used for pre-vitrification and post-warm embryo culture. A dataset of 558 SVBT with the same inclusion criteria was used to validate the model, but with known clinical pregnancy outcome instead of live birth outcome. ResultsThree different logistic regression models were developed for predicting live birth based on post-warm blastocyst re-expansion. Different post-warm assessment times indicated that a 2-h post-warm culture period was optimal for live birth prediction (model 1). Adjusting for pre-vitrification Gardner score (model 2) and in combination with maternal age (model 3) further increased predictability (area under the curve [AUC] = 0.623, 0.633, 0.666, respectively). Model validation gave an AUC of 0.617, 0.609 and 0.624, respectively. The false negative rate and true negative rate for model 3 were 2.0 and 10.1 in the development dataset and 3.5 and 8.0 in the validation dataset. ConclusionsClinical application of a simple model based on 2 h of post-warm re-expansion data, pre-vitrification Gardner score and maternal age can support a standardized approach for deciding if warming another blastocyst may increase the likelihood of live birth in SVBT.

Effect of preimplantation genetic testing for aneuploidies on pregnancy outcome in patients with unexplained recurrent spontaneous abortion

Objective: To investigate the effect of preimplantation genetic testing for aneuploidies (PGT-A) on pregnancy outcome and perinatal outcome of single live birth in patients with unexplained recurrent spontaneous abortion (URSA). Methods: The clinical data of 351 cycles of the first transfer of a blastocyst through whole embryo freezing in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from 2019 to 2021 were retrospectively analyzed. According to whether PGT-A was performed before the transfer, the patients were divided into two groups: the PGT-A group (160 cycles) and the control group (191 cycles) were treated with in vitro fertilization/intracytoplasmic sperm microinjection (IVF/ICSI). To adjust for confounding factors, propensity score matching (PSM) was carried out in a 1∶1 ratio between the two groups of patients. After matching, 98 patients in the PGT-A group and 98 patients in the control group were compared for pregnancy outcome and perinatal outcome of singleton live births. Results: Before PSM, the female age in the PGT-A group was (33.6±4.0) years, lower than that in the control group (34.5±4.5) years (P=0.049). Male age in the PGT-A group was (33.6±4.1) years, lower than that in the control group (35.3±5.1) years (P<0.001). There were statistically significant differences between the two groups in infertility factors, female body mass index (BMI), years of infertility, number of spontaneous abortions, basal follicle stimulating hormone (FSH), endometrial thickness on the day of transfer and the percentage of high-quality blastocysts (all P values<0.05); After PSM, there was a statistically significant difference in fertilization methods and infertility factors between the two groups (P<0.05), while other differences were not statistically significant (all P values>0.05); There were statistically significant differences between the two groups in implant rate [63.3% (62 cycles) vs. 49.0% (48 cycles), P=0.044], clinical pregnancy rate [63.3% (62 cycles) vs. 49.0% (48 cycles), P=0.044], and live birth rate [42.9% (42 cycles) vs. 28.6% (28 cycles), P=0.037]. There was no statistically significant difference in perinatal outcomes between the PGT-A group and the control group in obtaining single birth live births (P>0.05). Conclusion: Compared with conventional IVF/ICSI assisted pregnancy, PGT-A assisted pregnancy significantly improves implantation rate, clinical pregnancy rate, and live birth rate in URSA patients. PGT-A improves the pregnancy outcomes in URSA patients but not perinatal outcomes in patients with singleton live births.

SUMO1 and Defective Spermatozoa Correlate with Endogenous Hydrogen Peroxide and Live Birth Outcome in Intrauterine Insemination Cycles for Unexplained Infertility.

This study aimed to investigate the correlation between hydrogen peroxide (H2O2), small ubiquitin-like modifier molecules (SUMO), and pregnancy outcomes in couples with unexplained infertility (UI) undergoing intrauterine insemination (IUI) treatment. We prospectively collected semen samples from 56 couples with UI and divided the spermatozoa into motile and immotile fractions by density gradient centrifugation (DSC). Immunofluorescence staining was used to examine the immunostaining and localization of nuclear pore complex (NPC), SUMO1, and SUMO2/3 in spermatozoa. We detected H2O2 levels by chemiluminescence methods. We found that H2O2 levels correlated with NPC (neck) (r = 0.400) and NPC (tail) (r = 0.473) in motile sperm fractions. In immotile fractions, H2O2 positively correlated with NPC (tail) (r = 0.431) and SUMO1 (neck) (r = 0.282). Furthermore, the positive NPC (tail) group had a significantly lower live birth rate than the negative NPC group (17.9% = 5/28 vs. 42.9% = 12/28). In conclusion, H2O2 positively correlated with SUMO1 (neck) and NPC (tail) in human spermatozoa. The DSC may partially eliminate defective spermatozoa (positive NPC staining); however, if defective spermatozoa remain in the motile fraction, this scenario is associated with a low live birth rate following IUI treatment.

Association of HCG Level with Ultrasound Visualization of the Gestational Sac in Early Viable Pregnancies

Our primary objective is to verify or refute a 2013 study by Connolly et al. which showed that in early pregnancy, a gestational sac was visualized 99% of the time on transvaginal ultrasound when the HCG level reached 3510 mIU/mL. Our secondary objective was to make clinical correlations by assessing the relationship between human chorionic gonadotropin (HCG) level in early pregnancy when a gestational sac is not seen and pregnancy outcomes of live birth, spontaneous abortion, and ectopic pregnancy. This retrospective study includes 144 pregnancies with an outcome of live birth, 87 pregnancies with an outcome of spontaneous abortion, and 59 ectopic pregnancies. Logistic regression is used to determine the probability of visualizing a gestational sac and/or yolk sac based on the HCG level. A gestational sac is predicted to be visualized 50% of the time at an HCG level of 979 mIU/mL, 90% at 2421 mIU/mL, and 99% of the time at 3994 mIU/mL. A yolk sac was predicted to be visualized 50% of the time at an HCG level of 4626 mIU/mL, 90% at 12,892 mIU/mL, and 99% at 39,454 mIU/mL. A total of 90% of ectopic pregnancies presented with an HCG level below 3994 mIU/mL. These results are in agreement with the study by Connolly et al. Since most early ectopic pregnancies had an HCG value below the discriminatory level for gestational sac visualization, other methods for the evaluation of pregnancy of unknown location such as repeat HCG values are clinically important.

Follicular phase length is not related to live birth outcome in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination cycles in a multicenter trial

To evaluate the effect of follicular phase length (FPL) on pregnancy outcomes and endometrial thickness (ET) among women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination (OS-IUI) with clomiphene citrate, letrozole, or gonadotropins. Cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation randomized controlled trial. Multicenter randomized controlled trial. A total of 869 couples with unexplained infertility who underwent OS-IUI treatment cycles as part of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation study. FPL was evaluated as a categorical variable defined by quintiles (q1: ≤11 days, q2: 12 days, q3: 13 days, q4: 14-15 days, and q5: ≥16 days). Clinical pregnancy, live birth rates, and ET. Decreasing FPL quintiles did not reduce clinical pregnancy or live birth rates in unadjusted or adjusted models with all treatment groups combined or when stratified by the ovarian stimulation medication. All FPL categories had significantly thinner ET compared with the 5th quintile (≥16 days) among women treated with clomiphene citrate or letrozole. Similar but diminished associations were observed among women who underwent ovarian stimulation with gonadotropins, but the observed differences were limited to those with FPL of 12 days or shorter when compared with FPL ≥16 days. Although shorter FPL was associated with reduced ET, it was not associated with the outcomes of clinical pregnancy or live birth in women with unexplained infertility undergoing OS-IUI in all treatment groups combined. Similar patterns existed when analyses of clinical pregnancy and live birth rates were stratified by treatment. NCT01044862.

Reproductive history does not compromise subsequent live birth and perinatal outcome following in-vitro fertilization: analysis of 25 329 first frozen-thawed embryo transfer cycles without preimplantation genetic testing for aneuploidy.

To investigate the effect of women's reproductive history on live-birth rate and perinatal outcome after first frozen-thawed embryo transfer (FET) without preimplantation genetic testing for aneuploidy. This was a retrospective cohort study of women who had undergone their first FET cycle between January 2014 and December 2020 at a university-affiliated fertility center. No transferred embryo underwent preimplantation genetic testing for aneuploidy. The women were categorized into five groups based on their reproductive history: no previous pregnancy; previous termination of pregnancy (TOP); previous pregnancy loss; previous ectopic pregnancy (EP); and previous live birth. The women with no previous pregnancy were considered as the reference group. The primary outcome was the live-birth rate and secondary endpoints included rates of positive pregnancy test, clinical pregnancy, pregnancy loss and EP as well as perinatal outcomes such as birth weight and preterm birth. Multivariable logistic regression analyses were used to control for a number of potential confounders, including age, body mass index, education level, duration and cause of infertility, insemination method, type of endometrial preparation, number of embryos transferred, embryo developmental stage, quality of the embryos transferred, year of treatment and endometrial thickness. Additionally, propensity score matching (PSM) was used to check the robustness of the main findings. In total, 25 329 women were included in the final analysis. On univariate analysis, each reproductive-history type except for previous EP was significantly associated with worse pregnancy outcome following in-vitro fertilization (IVF), including rates of positive pregnancy test, clinical pregnancy, pregnancy loss and live birth, when compared with the group of women with no previous pregnancy. However, after correcting for several potential confounders, the differences in rates of live birth, pregnancy loss, positive pregnancy test and clinical pregnancy were no longer significant between the study and control groups on multivariable regression models, while the risk of EP after embryo transfer was elevated among women with a previous TOP or EP. There was no increased risk of adverse perinatal outcome associated with reproductive history compared with the control group. Notably, similar results were obtained from the PSM models, confirming the robustness of the main findings. Relative to women without a previous pregnancy, those with a prior TOP, pregnancy loss, EP or live birth did not have compromised live-birth rate or perinatal outcomes following FET without preimplantation genetic testing for aneuploidy, with the exception of an increased risk of EP in those with prior TOP or EP. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Comparison of the effect of two commercialized vitrification carriers on pregnancy outcomes in freeze-thaw cycles.

This study aimed to compare the effects of two brands of commercial vitrification carriers on pregnancy outcomes in freeze-thaw cycles. We included 4871 patients who underwent a "freeze all" strategy using the commercial carriers J.Y. straw and OYASHIPS straw in the Reproductive Center of the First Hospital of Jilin University. The pregnancy outcomes of cleavage-stage embryos and blastocysts were studied separately. Detailed data and the safety of children born from mothers with the two types of carriers were also compared. Patients who used J.Y. straw had similar clinical pregnancy and live birth rates with one and two cleavage-stage embryo transplantation to those who used OYASHIPS straw. In patients who had blastocyst transplantation, the clinical pregnancy rate of one blastocyst transplanted in those who used OYASHIPS straw was significantly higher than that in those who used J.Y. straw (57.85% vs 47.09%). Among children born from mothers who used J.Y. straw, the congenital disability rate was significantly higher than that in those with OYASHIPS straw. The OYASHIPS straw carrier is cheap and can achieve clinical pregnancy and live birth outcomes comparable to those of J.Y. straw. Therefore, OYASHIPS straw is a good alternative option.

Systematic review and meta-analysis: does pre-implantation genetic testing for aneuploidy at the blastocyst stage improve live birth rate?

PurposeTo establish if preimplantation genetic testing for aneuploidy (PGT-A) at the blastocyst stage improves the composite outcome of live birth rate and ongoing pregnancy rate per embryo transfer compared to conventional morphological assessment.MethodsA systematic literature search was conducted using PubMed, EMBASE and Cochrane database from 1st March 2000 until 1st March 2022. Studies comparing reproductive outcomes following in vitro fertilisation using comprehensive chromosome screening (CCS) at the blastocyst stage with traditional morphological methods were evaluated.ResultsOf the 1307 citations identified, six randomised control trials (RCTs) and ten cohort studies fulfilled the inclusion criteria. The pooled data identified a benefit between PGT-A and control groups in the composite outcome of live birth rate and ongoing pregnancy per embryo transfer in both the RCT (RR 1.09, 95% CI 1.02–1.16) and cohort studies (RR 1.50, 95% CI 1.28–1.76). Euploid embryos identified by CCS were more likely to be successfully implanted amongst the RCT (RR 1.20, 95% CI 1.10–1.31) and cohort (RR 1.69, 95% CI 1.29–2.21) studies. The rate of miscarriage per clinical pregnancy is also significantly lower when CCS is implemented (RCT: RR 0.73, 95% CI 0.56–0.96 and cohort: RR 0.48, 95% CI 0.32–0.72).ConclusionsCCS-based PGT-A at the blastocyst biopsy stage increases the composite outcome of live births and ongoing pregnancies per embryo transfer and reduces the rate of miscarriage compared to morphological assessment alone. In view of the limited number of studies included and the variation in methodology between studies, future reviews and analyses are required to confirm these findings.

Tissue-specific DNA methylation variability and its potential clinical value.

Complex diseases have multifactorial etiologies making actionable diagnostic biomarkers difficult to identify. Diagnostic research must expand beyond single or a handful of genetic or epigenetic targets for complex disease and explore a broader system of biological pathways. With the objective to develop a diagnostic tool designed to analyze a comprehensive network of epigenetic profiles in complex diseases, we used publicly available DNA methylation data from over 2,400 samples representing 20 cell types and various diseases. This tool, rather than detecting differentially methylated regions at specific genes, measures the intra-individual methylation variability within gene promoters to identify global shifts away from healthy regulatory states. To assess this new approach, we explored three distinct questions: 1) Are profiles of epigenetic variability tissue-specific? 2) Do diseased tissues exhibit altered epigenetic variability compared to normal tissue? 3) Can epigenetic variability be detected in complex disease? Unsupervised clustering established that global epigenetic variability in promoter regions is tissue-specific and promoter regions that are the most epigenetically stable in a specific tissue are associated with genes known to be essential for its function. Furthermore, analysis of epigenetic variability in these most stable regions distinguishes between diseased and normal tissue in multiple complex diseases. Finally, we demonstrate the clinical utility of this new tool in the assessment of a multifactorial condition, male infertility. We show that epigenetic variability in purified sperm is correlated with live birth outcomes in couples undergoing intrauterine insemination (IUI), a common fertility procedure. Men with the least epigenetically variable promoters were almost twice as likely to father a child than men with the greatest number of epigenetically variable promoters. Interestingly, no such difference was identified in men undergoing in vitro fertilization (IVF), another common fertility procedure, suggesting this as a treatment to overcome higher levels of epigenetic variability when trying to conceive.

The effect of peak serum estradiol level during ovarian stimulation on cumulative live birth and obstetric outcomes in freeze-all cycles.

To determine whether the peak serum estradiol (E2) level during ovarian stimulation affects the cumulative live birth rate (CLBR) and obstetric outcomes in freeze-all cycles. This retrospective cohort study involved patients who underwent their first cycle of in vitro fertilization followed by a freeze-all strategy and frozen embryo transfer cycles between January 2014 and June 2019 at a tertiary care center. Patients were categorized into four groups according to quartiles of peak serum E2 levels during ovarian stimulation (Q1-Q4). The primary outcome was CLBR. Secondary outcomes included obstetric and neonatal outcomes of singleton and twin pregnancies. Poisson or logistic regression was applied to control for potential confounders for outcome measures, as appropriate. Generalized estimating equations were used to account for multiple cycles from the same patient for the outcome of CLBR. A total of 11237 patients were included in the analysis. Cumulatively, live births occurred in 8410 women (74.8%). The live birth rate (LBR) and CLBR improved as quartiles of peak E2 levels increased (49.7%, 52.1%, 54.9%, and 56.4% for LBR; 65.1%, 74.3%, 78.4%, and 81.6% for CLBR, from the lowest to the highest quartile of estradiol levels, respectively, P<0.001). Such association remained significant for CLBR after accounting for potential confounders in multivariable regression models, whereas the relationship between LBR and peak E2 levels did not reach statistical significance. In addition, no significant differences were noticed in adverse obstetric and neonatal outcomes (gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, placental disorders, preterm birth, low birthweight, and small for gestational age) amongst E2 quartiles for either singleton or twin live births, both before and after adjustment. In freeze-all cycles, higher peak serum E2 levels during ovarian stimulation were associated with increased CLBR, without increasing the risks of adverse obstetric and neonatal outcomes.

The effects of high risk of ovarian hyperstimulation syndrome and duration of embryo cryopreservation on perinatal outcomes of single live births in the first frozen embryo transfer cycle after whole embryo cryopreservation

Objective: To investigate the effects of high risk of ovarian hyperstimulation syndrome (OHSS) and duration of embryo cryopreservation on perinatal outcomes of the first frozen-thawed cycle after whole embryo cryopreservation. Methods: The clinical data of 1 804 patients who underwent the first frozen-thawed cycle after whole embryo cryopreservation and achieved singleton live births in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to June 2021 were retrospectively analyzed. According to whether there was high risk of OHSS in the oocyte retrieval cycle, the patients were divided into high-risk group (n=790) and non-high-risk group (n=1 014). The baseline data and perinatal outcomes were compared between the two groups. Multivariate linear regression was applied to analyze the relative factors affecting neonatal weight. And the high-risk group was divided into three subgroups according to different cryopreservation time: the embryos of 96 cycles with a cryopreservation time less than 60 days were defined as group A; the embryos of 587 cycles with a cryopreservation time around 60 to 120 days were defined as group B; the embryos of 107 cycles with a cryopreservation time more than 120 days were defined as group C. The perinatal outcomes were compared among the three groups. The measurement data in this study were represented by［M（Q1，Q3）］. Results: The female age in the high-risk group was 30.0 (27.0, 32.0) years old, which was lower than that in the non-high-risk group 31.0 (29.0, 34.0) (P<0.001). The male age in high-risk group was 30.0 (28.0, 33.0), lower than that in non-high-risk group 32.0 (29.0, 35.0) (P<0.001). The birth weight of high-risk group [3 500.0 (3 200.0,3 800.0) g] was higher than that of control group [3 400.0 (3 150.0,3 800.0) g](P=0.045). Multivariate linear regression analysis showed that female BMI was correlated with neonatal weight, β (95%CI) was 15.37(8.33, 22.41) (P<0.001), and the high risk of OHSS was not correlated with neonatal weight, β (95%CI) was 19.40 (-38.07, 76.87) (P=0.508). There was significant difference in the incidence of low birth weight and very low birth weight among groups A, B and C (all P values<0.05), and the incidence of low birth weight and very low birth weight in group C was higher than that in group B (all P values<0.017). Conclusions: The risk of adverse perinatal outcomes in high-risk OHSS patients who underwent the first frozen-thawed cycle after whole embryo cryopreservation was not increased. However, prolonged cryopreservation of embryos may lead to increased risk of low birth weight and very low birth weight.

Embryo development, pregnancy and live birth outcomes following IVF treatment were not compromised during the COVID-19 pandemic.

To evaluate whether outcomes of in vitro fertilization (IVF) are affected during the coronavirus disease-19 (COVID-19) pandemic. This was a single-center, retrospective study. Embryo development, pregnancy, and live birth outcomes were compared between COVID-19 and pre-COVID-19 groups. Blood samples from patients during the COVID-19 pandemic were tested for COVID-19. After 1:1 random matching, 403 cycles for each group were included in the study. The rates of fertilization, normal fertilization, and blastocyst formation were higher in the COVID-19 group than in the pre-COVID-19 group. No difference was observed in the rates of day 3 good-quality embryos and good-quality blastocysts between the groups. A multivariate analysis showed that the live birth rate in the COVID-19 group was higher than that in the pre-COVID-19 group (51.4% vs. 41.4%, P = 0.010). In fresh cleavage-stage embryo and blastocyst transfer cycles, there were no differences between the groups in terms of pregnancy, obstetric, and perinatal outcomes. In the freeze-all cycles, the live birth rate was higher during the COVID-19 pandemic (58.0% vs. 34.5%, P = 0.006) than during the pre-COVID-19 period following frozen cleavage stage embryo transfer. The rate of gestational diabetes during the COVID-19 pandemic was higher than that during the pre-COVID-19 period (20.3% vs. 2.4%, P = 0.008) following frozen blastocyst transfer. All the serological results of the patients during the COVID-19 pandemic were negative. Our results indicate that embryo development, pregnancy, and live birth outcomes in uninfected patients were not compromised during the COVID-19 pandemic at our center.

Time-lapse imaging: Morphokinetic analysis of in vitro fertilization outcomes

Time-lapse imaging (TLI) allows continuous monitoring of embryo development without disturbing culture conditions by removing embryos from the incubator. The study of embryo kinetics using TLI has given rise to some new markers for embryo selection that are able to document and evaluate embryo morphology and the timing of developmental events through continuous live image tracking. Time-lapse imaging has emerged as a powerful tool for creating predictive models of invitro fertilization outcomes. Fourty-seven articles were included in the present review to investigate the current situation of TLI in invitro fertilization laboratories. Morphokinetics of the embryo during its invitro development have been described using parameters indicative of the different events capable of predicting the ability to reach blastocyst stage, implantation and pregnancy rates, live birth outcome, and embryo ploidy.

The Effect of Hormonal Contraception Use on Ovarian Reserve Markers and the Uptake of Assisted Reproductive Technology in Individuals Seeking an Infertility Evaluation.

Background and objective The effects of hormonal contraception (HC) use on ovarian reserve (OR) markers in individuals seeking an infertility evaluation and the success of assisted reproductive technology (ART) warrantfurther investigation. Therefore, the aim of this study was to determine if women seeking an evaluation for unexplained infertility who used long-term (≥2 years) HC have lower ovarian reserve (OR) markers and higher uptake of ART compared to short-term (<2 years) or never HC users. Methods We performed a cross-sectional patient survey involving a retrospective medical chart review of patients seeking an evaluation for unexplained infertility at the University of Colorado Advanced Reproductive Medicine (CU ARM) clinic. Results Most participants (87%; 107/123) reported a history of HC use with 98 (79.7%) reporting long-term continuous use for two or more years. Median OR markers were similar between long-term and short-term/never HC users [anti-Müllerian hormone (AMH): 2.4 vs. 3.2, p=0.20; antral follicle count (AFC): 18 vs. 26, p=0.10; follicle-stimulating hormone (FSH): 7.6 vs. 6.3, p=0.26] and remained so after adjusting for age and diagnosis of polycystic ovarian syndrome (PCOS) or primary ovarian insufficiency (POI) in linear regression models. However, amongHC users aged less than 30 years(n=9), those who had discontinued HC between two and three years prior to the assessment of their OR markers had a 6.20 ng/mL increase in AMH level compared to those whohad discontinued HCless than two years prior to the assessment (p=0.02). Additionally, there was a marginally increased use of ART overall among long-term HC users compared to short-term/never HC users (64.3% vs. 44.0%, p=0.06), specifically in the use of in vitro fertilization (IVF) (58.7% vs. 18.2%, p=0.01). Among long-term HC users, ovulation induction was less likely to result in live birth compared to short-term/never HC users (8.9% vs. 62.5%, p<0.001); however, after adjusting for age, PCOS, POI, and type of ART used, there was no difference in the odds of live birth after ART between long-term HC users and short-term/never users. Conclusion While long-term HC users report increased use of ART, in particular IVF, the overall conception rates and live birth outcomes among ART users do not appear to be significantly affected by a history of long-term HC use.

O-087 Patient-centric, machine learning (ML)-based personalised prognostics supports fertility specialists to improve access to assisted reproductive technology (ART) and increase overall live birth (LB) outcomes

Abstract Study question Does the use of patient-centric, ML-prognostics counselling report (Univfy® PreIVF Report) affect assisted reproductive technology (ART) conversion (first ART cycle usage) and LB rate (LBR)? Summary answer The use of patient-centric, ML-prognostics counselling report (Univfy® PreIVF Report) by fertility specialists is associated with higher ART conversion and LBR among new patients. What is known already ART is a highly effective and safe treatment for clinical infertility. However, ART remains vastly underutilised resulting in missed opportunities to help more people build families. Commonly used age-based trends often do not address patients' perceived risks including their own ART success probability and ART cost burden as related to their personalised LB probabilities. We previously reported the use of artificial intelligence (AI)/ML to generate patient-centric counselling reports based on ART success prediction models developed and validated for each fertility centre to address their local patient populations in ways that are personalised, relevant and actionable. Study design, size, duration Retrospective cohort analysis. Eight fertility centres from 22 locations across 9 states (US) and Ontario, Canada contributed to the research design, compilation of outcomes data, and interpretation of results. Five centres provided ART utilisation and outcomes data for 15,289 new patients seen in each centre's study period when the Univfy® PreIVF Report was available and data were submitted for aggregated research analysis. Each centre provided 4-6 years of data within the period 2016-2022. Participants/materials, setting, methods The effect of Univfy or No-Univfy Group on ART conversion was analyzed by Chi square tests using aggregated data and separately for each centre's data, for 3 timed analyses, 180-Day, 360-Day and “Ever” (no restriction) after new patient visit. Patients who received the Univfy® PreIVF Report prior to IUI or ART conversion, or had no such conversion after receiving it were placed into the Univfy Group. The No-Univfy Group comprises patients who did not receive a report. Main results and the role of chance Univfy report usage was associated with higher conversions to Direct-ART (by 2.6-, 2.4-, 1.9-folds) and Any-ART (by 2.9-, 3.0-, 2.4-folds) in the aggregated data when analyzed for 180-Day, 360-Day and Ever, respectively; p-value &amp;lt; 0.001. Direct-ART is ART conversion without prior IUI(s); Any-ART conversion includes ART conversion with or without prior IUI(s). In the centre-specific analyses, the fold increase in Direct-ART and Any-ART conversions ranged from 1.8 to 4.5 and 2.2 to 4.7, respectively, in the 360-Day period; p-value &amp;lt;0.001. Univfy® PreIVF Report usage was associated with an increase in estimated LBR ranging from 2.1 to 1.3 folds for the Univfy Group compared to No-Univfy Group (360-Day analysis, p &amp;lt; 0.001) based on conservative versus liberal scenarios. Similar ART conversion and LBR results were observed for 180-Day and Ever analyses, p &amp;lt; 0.001. We used conservative to liberal assumptions for IUI-LBR and NC-LBR because IUI and NC outcomes were not readily available. (Conservative: IUI-LBR 15%, natural conception (NC)-LBR 5%; Liberal: IUI-LBR 25%, NC-LBR 20%). Estimated LBR for ART used clinical ongoing pregnancies and documented live births as LBs and the following LBR assumptions: freeze-all with no transfers yet (50%); gestational carrier ART (45%); ART with unknown outcomes (0%). Limitations, reasons for caution This study was not prospective or randomised. The intended report usage was to support physicians when counselling patients. Although we observed comparable report and ART usage across predicted ART-LB probabilities, there is potential unintentional bias towards higher report or ART utilisation among patients with more favorable clinical characteristics. Wider implications of the findings These results represent our retrospective experience in diverse geographies in North America. We endeavor to collaborate with additional centres to test the reproducibility of AI/ML-driven, validated personalized IVF prognostics on improved overall live birth outcomes and ART access when counselling patients about treatment options. Trial registration number not applicable

P-115 Clinical prognosis of abnormally cleaved embryos: time-lapse evidence of self-correction before blastulation

Abstract Study question What is the clinical prognosis of embryos displaying abnormal cleavage (ABNCL) observed via time-lapse videography (TLV) and the role of blastulation in embryo self-correction? Summary answer ABNCL leads to reduced blastulation rate, but not live birth rates and neonatal outcomes once blastulation has been achieved. What is known already It is widely accepted that ABNCL is associated with reduced viability in cleavage stage human embryos. However, evidence is scarce in literature reporting birth outcomes from blastocysts arising from such embryos, mostly because they are ranked low priority for transfer. Knowledge is also limited regarding the potential self-correction mechanism in those leading to live births. In this study, using a large dataset of blastocysts with known live birth outcomes, we aimed to explore the role of blastulation in the self-correction process of ABNCL embryos, and their subsequent live birth rates as well as neonatal outcomes following intrauterine transfer. Study design, size, duration This retrospective study involved 1562 consecutive autologous in vitro fertilization cycles (maternal age 35.1 ± 4.7 years) performed at Fertility North between January 2017 and June 2022. Fresh transfers were routinely performed on Day 3 with remaining embryos cultured up to Day 6. A total of 9451 embryos were subject to blastocyst culture, with a subset of 664 resulting blastocysts (following single frozen transfers up to August 2021) included for live birth and neonatal outcome analysis. Participants/materials, setting, methods A total of 6019 out of 9451 embryos were annotated for ABNCL up to Day 3, including direct cleavage (DC), reverse cleavage (RC) and &amp;lt;4 intercellular contact points at 4-cell stage (&amp;lt;4ICCP). The remaining 3432 embryos were excluded from TLV annotation due to poor quality as per the 2011 Istanbul consensus. For DC and RC, the number of affected blastomeres was also recorded for the 1st (1-cell), 2nd (2-3-cell), and 3rd cleavage cycles (4-8-cell), respectively. Main results and the role of chance Embryos showing DC (19.5%), RC (41.7%), &amp;lt;6ICCP (58.8%), and Mixed (affected by 2 or 3 ABNCL types, 26.4%) had lower blastulation rates than those without ABNCL (67.2%, P &amp;lt; 0.01 respectively). Subgroup analysis showed increasing blastulation rates along cleavage cycles of DC/RC occurrence, from 1st through 2nd to 3rd cleavage cycles (DC 6.3%, 20.7% and 41.0%, P &amp;lt; 0.001; and RC 10.0%, 32.3% and 45.8%, P &amp;lt; 0.05). Negative correlation (P &amp;lt; 0.05 respectively) was also identified between the number of blastomeres affected by DC/RC and subsequent blastulation. However, once blastulation was achieved, clinical results were comparable between blastocysts with DC, RC, &amp;lt;6ICCP and No ABNCL; including live birth rates (25.9%, 33.0%, 36.0% vs 30.8%, P &amp;gt; 0.05 respectively), gestational age (38.7 ± 1.6, 38.5 ± 1.2, 38.3 ± 3.5 vs 38.5 ± 1.8 weeks, P &amp;gt; 0.05 respectively) and birthweight (3343.0 ± 649.1, 3378.2 ± 538.4, 3352.6 ± 841.3 vs 3313.9 ± 509.6 grams, respectively). Above findings held true following multivariate regression (logistic or linear as appropriate); adjusting for maternal age and BMI, vitrification day, blastocyst expansion stage, ICM/TE grades, insemination methods and sperm types. Also, no difference was detected using either Z-score as endpoint combining birthweight, baby sex and gestational age; or preterm delivery (&amp;lt;37 weeks) or low birthweight (&amp;lt;2500 grams) incidences as endpoints. Live-birth embryo TLV indicated self-correction mechanisms by excluding/extruding DC/RC cells before blastulation. Limitations, reasons for caution Our study is limited by its retrospective nature, making it impossible to control all known/unknown confounders. Embryos in our dataset, being surplus after selection for those with no or minimum ABNCL for fresh transfer on Day 3, may not represent the full embryo cohort. Wider implications of the findings Our findings further support the embryo self-correction mechanism where DC/RC affected blastomere is excluding/extruded at blastulation, which is evidenced by TLV of live-birth embryos. The assuring live birth rates and neonatal outcomes in ABNCL blastocysts provide valuable guidance to clinical practice and patient counselling. Trial registration number not applicable