Embryo Transfer Outcomes Research Articles

Influence of maternal obesity on embryonic vitrification injury and subsequent pregnancy outcomes: A retrospective cohort study

BackgroundWe previously reported that obese mice had significantly high lipid content in embryos, and excessive lipids are detrimental to embryonic development. However, whether maternal obesity has an effect on embryonic vitrification injury and subsequent pregnancy outcomes is still controversial. This study was conducted to clarify the influence of maternal obesity on embryonic vitrification injury and subsequent pregnancy outcomes by in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). MethodsWe retrospectively collected medical record of IVF/ICSI patients from reproductive medicine centers in two tertiary hospitals. The patients were classified into a low-weight group (<18.5 kg/m2), normal-weight group (18.5–23.9 kg/m2), overweight group (24.0–27.9 kg/m2) and obese group (≥28.0 kg/m2) according to their body mass index (BMI). Multivariable logistic regression analysis was performed to compare pregnancy outcomes in fresh and frozen embryo transfer among different BMI groups to define the correlation between BMI and embryonic vitrification injury. ResultsA total of 44 773 women among 20–40 years old were recruited in this study, of which 27 797 underwent their first fresh embryo transfer and 16 976 underwent their first frozen embryo transfer. For fresh embryo transfer, there was no significant difference in the clinical pregnancy rate, live birth rate, and miscarriage rate of 4 BMI groups. For frozen-thawed embryo transfer, there was a significant increase in the clinical pregnancy rate of the overweight group (AOR = 1.14, 95% CI: 1.05–1.25) and the obese group (AOR = 1.24, 95% CI: 1.03–1.50), while the miscarriage rate (AOR = 1.42, 95% CI: 1.05–1.92) also showed a significant increase in the obese group compared to the normal-weight group. ConclusionThis study provided a new understanding of the effect of maternal obesity on embryonic vitrification injury. Maternal obesity does not worsen the outcome of IVF/ICSI, particularly in the frozen-thawed group.

Methods to improve frozen-thawed blastocyst transfer outcomes- the IVF laboratory perspective

During the last few years, the number of frozen-thawed embryo transfer cycles (FET) significantly increased due to the universal application of more efficient cryopreservation techniques in the IVF laboratory and the improved survival rates of blastocyst stage embryos and the wide implementation of “freeze all” IVF cycles to prevent OHSS, or for preimplantation genetic testing for aneuploidy (PGT-A). Blastocyst cryopreservation allows single embryo transfers to reduce the rate of multiple pregnancies and improve perinatal outcomes. There is no consensus regarding the optimal laboratory protocol for blastocyst cryopreservation, and research is ongoing for its amelioration. This review summarizes different laboratory methods that may improve frozen-thawed blastocyst embryo transfer outcomes, alone or in combination. Some of the techniques relate to embryo survival; some of them work on endometrial receptivity.

Euploid programmed frozen embryo transfer cycles are associated with a higher live birth rate when estradiol levels more closely mimic physiology

To determine whether peak estradiol (E2) levels above the usual physiologic range (300-500 pg/mL) will impact programmed frozen embryo transfer (FET) outcomes in an ideal study population of those using good-quality single euploid blastocysts. Retrospective cohort study. University-based clinic. Single euploid-programmed FET done at a single academic institution from January 2016 to December 2019. The population was divided into three groups on the basis of peak serum E2 levels during endometrial preparation: group A (E2 <300 pg/mL), group B (300-500 pg/mL), and group C (>500 pg/mL). Group B was used as the reference range for statistical analysis. Frozen embryo transfer cycles. The primary outcome was the live birth rate (LBR). Secondary outcomes included implantation, biochemical,ectopic, and miscarriage rates. A total of 750 FET cycles were included in this study. Poisson regression analysis showed a negative impact of higher peak E2 on the LBR. A decrease in LBR was noted between group C and referent group B (50.2% vs. 63.4%, risk ratio 0.79 [0.68-0.91]) and group A and referent group B (42.5% vs. 63.4%, risk ratio 0.67 [0.46-0.98]). Secondary outcomes were notable for a lower implantation rate when groups A and C were compared with group B and a higher biochemical rate between group C and group B. There was no notable difference between groups in ectopic or miscarriage rates. Limiting peak serum E2 levels to 300-500 pg/mL during programmed FET cycles is associated with improved LBRs compared with cycles with peak E2 levels of <300 pg/mL or >500 pg/mL in an ideal study population.

Impact of Lactobacillus in the uterine microbiota on in vitro fertilization outcomes

Abundant intrauterine Lactobacillus is associated with good in vitro fertilization (IVF) outcomes; however, whether specific species of Lactobacillus have any benefit remains unclear. So we examine the effect of Lactobacillus on the clinical outcomes of IVF at the species level. Uterine microbiota were classified as either Lactobacillus-dominant (LD) or non-Lactobacillus-dominant. In the LD group, we further investigated the clinical results for each Lactobacillus species and evaluated them in relation to IVF outcomes. In Uterine microbiome analysis, Lactobacillus was the most abundant, with the four species of L. crispatus, L. iners, L. gasseri, and L. jensenii accounting for the great majority. We compared the clinical outcomes of single frozen-thawed embryo transfer conducted by Lactobacillus species and found that the implantation rate was lowest in those in whom L. iners was dominant. This study is the first to conduct a species-level analysis of the uterine microbiota and report on a detailed investigation of Lactobacillus, which was believed to be particularly helpful for pregnancy.

The comparison of pregnancy outcomes in fresh and frozen embryo transfer: A cross-sectional study.

The benefits of frozen embryo transfer (FET) vs. fresh embryo transfer for in vitro fertilization (IVF) have been discussed in previous studies. To determine and compare the pregnancy outcomes following FET and frozen embryo transfer in women who underwent assisted reproductive techniques. In this cross-sectional study, 233 women candidates for IVF/intra cytoplasmic sperm injection who referred to the Kamali Training Medical Center, Karaj, Iran during 2019-2020 were evaluated in 2 groups of fresh (n = 127) and frozen (n = 106) embryo transfers. The rates of pregnancy outcomes including chemical and clinical pregnancy, live birth, preeclampsia, ectopic pregnancy, still birth, and pregnancy loss were compared between groups in 3 age subgroups ( 25, 25-35, and 35-40 yr old). No significant difference in terms of chemical and clinical pregnancy and live birth rates were observed between groups in women aged 25 yr. Chemical and clinical pregnancy and live birth rates were significantly higher in the FET group compared to fresh group in 25-35-yr-old women (p = 0.01, p = 0.03, and p = 0.01, respectively). In 35-40-yr-old women, no significant differences were observed in terms of chemical and clinical pregnancy rates, but live birth rate was found to be significantly higher in the FET group (p = 0.02). The pregnancy loss was lower in the FET group (p = 0.038). In conclusion, the FET method in women aged 25-35 yr significantly increases the chance of successful IVF/intra cytoplasmic sperm injection.

Effect of obstructive sleep apnea on invitro fertilization outcomes in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) confers a high risk of obstructive sleep apnea (OSA). Here we investigated the effect of OSA on first invitro fertilization (IVF) cycle metrics and outcomes in patients with PCOS. This was a prospective cohort study of patients with PCOS undergoing their first IVF at a single tertiary center between October 1, 2021, and September 30, 2022. Patients were screened for OSA before IVF and grouped accordingly. Clinical and IVF cycle data were compared between groups. OSA was found in 37.2% of 156 patients with PCOS, with longer infertility duration (4.3 ± 2.5 vs. 3.4 ± 2.0 years) and lower levels of anti-Müllerian and luteinizing hormones than patients without OSA (6.44 ± 2.96 vs 8.69 ± 4.03 µg/L and 6.30 ± 5.02 vs 8.46 ± 6.09 U/L). Antral follicle count was lower in patients with OSA (28.9 ± 12.4 vs 33.2 ± 12.9). During ovarian stimulation, patients with OSA required significantly higher doses of gonadotropin (2080.8 ± 1008.7 vs 1682.8 ± 619.9 U) and had lower peak estradiol level (4473.5 ± 2693.0 vs 5455.7 ± 2955.1 pmol/L) and fewer retrieved oocytes, high-quality, and available embryos (17.8 ± 7.2 vs 21.9 ± 10.5, 4.5 ± 4.4 vs 6.2 ± 4.6, 5.2 ± 4.3 vs 7.4 ± 5.0). Eleven patients were excluded for having no embryos or missing transfer. Therefore, we analyzed the outcome of the first embryo transfer in 145 patients. The biochemical and clinical pregnancy rates were lower in patients with OSA than patients without OSA (51.9% vs 66.7% and 42.3% vs 60.2%). OSA was independently associated with clinical pregnancy rate after controlling for several confounders (P = .043). OSA impairs female fertility in patients with polycystic ovary syndrome, suggesting an adverse effect on invitro fertilization cycle stimulation characteristics and clinical outcomes. Zhang Q, Wang Z, Ding J, etal. Effect of obstructive sleep apnea on invitro fertilization outcomes in women with polycystic ovary syndrome. J Clin Sleep Med. 2024;20(1):31-38.

Retracted: Correlation between Endometrial Vascular Endothelial Growth Factor Expression and Pregnancy Outcome of Frozen-Thawed Embryo Transfer in Patients with Repeated Implantation Failure.

[This retracts the article DOI: 10.1155/2022/1937714.].

Impact of dienogest pretreatment on IVF-ET outcomes in patients with endometriosis: a systematic review and meta-analysis

BackgroundTo comprehensively evaluate the influence of dienogest (DNG) versus non-DNG pretreatment on in vitro fertilization and embryo transfer (IVF-ET) outcomes for patients with endometriosis.MethodsPubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP were comprehensively searched for relevant publications until September 14, 2022. Primary outcomes included clinical pregnancy rate and live birth rate. Secondary outcomes included retrieved oocytes, mature oocytes, blastocysts, growing follicles, transferrable embryos, fertilization rate, implantation rate, and miscarriage rate. Subgroup analysis was performed according to different grouping methods and embryo types.ResultsFive studies of 568 females with endometriosis were involved in this systematic review and meta-analysis. DNG treatment exhibited similar effects to non-DNG treatment on either the primary or the secondary outcomes (all P > 0.05). The DNG group had a significantly greater clinical pregnancy rate than the non-hormonal treatment group (pooled relative risk [RR]: 2.055, 95% confidence interval [CI]: 1.275, 3.312, P = 0.003), and exhibited a significantly lower clinical pregnancy rate than the long gonadotropin-releasing hormone agonist (GnRH-a) group (RR: 0.542, 95%CI: 0.321, 0.916, P = 0.022). For patients undergoing fresh embryo transfer, the DNG group displayed a significantly greater clinical pregnancy rate versus the non-DNG group (pooled RR: 1.848, 95%CI: 1.234, 2.767, P = 0.003). Patients receiving DNG had a significantly greater live birth rate than those with non-hormonal treatment (pooled RR: 2.136, 95%CI: 1.223, 3.734, P = 0.008), while having a significantly lower live birth rate than the long GnRH-a group (RR: 0.441, 95%CI: 0.214, 0.907, P = 0.026). While using fresh embryos, patients with DNG treatment had an increased live birth rate, compared with those without DNG treatment (pooled RR: 2.132, 95%CI: 1.090, 4.169, P = 0.027).ConclusionDNG treatment may have similar effects to non-DNG treatment on IVF-ET outcomes. The clinical pregnancy rate and live birth rate after DNG treatment may be significantly higher than those after non-hormonal treatment. More evidence is warranted to corroborate these findings.

Frozen embryo transfer outcomes decline with increasing female body mass index in female but not male factor infertility: analysis of 56,564 euploid blastocyst transfers

ObjectiveTo evaluate the association of body mass index (BMI) with cycle outcomes after euploid frozen blastocyst transfer. DesignRetrospective cohort study. SettingNot applicable. Patient(s)A total of 56,564 first single autologous euploid frozen embryo transfers (FET) from the 2016-2019 Society for Assisted Reproductive Technology database were analyzed by BMI and by World Health Organization BMI cohorts. Sub-analyses were performed on cycles among patients with a sole diagnosis of polycystic ovary syndrome (PCOS) (n = 4,626) and among patients with only male factor (n = 10,854). Intervention(s)None. Main outcome measure(s)Clinical pregnancy, pregnancy loss, and live birth. Results(s): Success rates and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for all outcomes were most favorable among those with normal BMI and progressively worsened with increasing BMI. These trends persisted among patients with PCOS for clinical pregnancy (aOR 0.99, 95% CI 0.98-0.997, p 0.003), pregnancy loss (aOR 1.02, 95% CI 1.01-1.04, p 0.01), and live birth (aOR 0.98, 95% CI 0.97-0.99, p <0.001), but not among patients with male factor only for clinical pregnancy (aOR 1.00, 95% CI 0.99-1.01, p 0.425), pregnancy loss (aOR 1.01, 95% CI 0.99-1.03, p 0.07), or live birth (aOR 0.99, 95% CI 0.98-1.00, p 0.08). Conclusion(s): In the largest cohort to date, increasing BMI was associated with decreased pregnancy and live birth and increased pregnancy loss following euploid FET among the entire cohort and among patients with a sole diagnosis of PCOS; however, these results were attenuated among patients with a sole diagnosis of male factor infertility, suggesting that associated female infertility diagnoses and not BMI alone may underly this trend.

Effects of the Severe Acute Respiratory Syndrome Coronavirus 2 Inactivated Vaccine on the Outcome of Frozen Embryo Transfers: A Large Scale Clinical Study.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a life-threatening infectious disease that has become a global pandemic. This study aimed to explore the effects of SARS-CoV-2 inactivated vaccine on the outcome of frozen embryo transfer (FET). We grouped patients who underwent FET between August 2021 and March 2022 based on their vaccination status, number of doses, and the interval between the last dose and the FET, and then compared the differences in pregnancy outcomes among the groups. There were 1084 vaccinated patients and 1228 non-vaccinated ones. There were significant differences in the live birth rate between the vaccination and non-vaccination groups (16.61% vs 28.26%), among the one-dose, two-dose, and three-dose groups (22.28% vs 19.51% vs 7.27%), and among the groups with interval ≤ 1 month, 1-2 months, and ≥ 2 months (38.38% vs 27.27% vs 12.03%). There were significant differences in the persistent pregnancy rate between the vaccination and non-vaccination groups (22.88% vs 14.09%), among the one-dose, two-dose, and three-dose groups (14.51% vs 23.80% vs 38.18%), and among the groups with interval ≤ 1 month, 1-2 months, and ≥ 2 months (1.01% vs 8.44% vs 28.16%). There were significant differences in the neonatal weight between the vaccination and non-vaccination groups [3805.50 (3746.00-3863.50) vs 2970.00 (2500.00-3400.00)]. There were significant differences in the premature birth rate among the one-dose, two-dose, and three-dose groups (23.26% vs 34.59% vs 100.00%), and among the groups with interval ≤ 1 month, 1-2 months, and ≥ 2 months (15.79% vs 21.43% vs 37.00%). Pregnancy outcomes were not affected by taking the SARS-CoV-2 inactivated vaccine before FET, the number of doses, and the interval between doses. These findings provide evidence supporting the safety of administering the SARS-CoV-2 inactivated vaccine during pregnancy, which can be used as a guide for vaccinating patients undergoing ART.

Reply: Artificial cycle frozen embryo transfer and obstetric adverse outcomes: association or causation?

Reply: Artificial cycle frozen embryo transfer and obstetric adverse outcomes: association or causation?

Pregnancy outcomes after vaginal probiotic supplementation before frozen embryo transfer: a randomized controlled study

In women receiving assisted reproductive treatment, intrauterine lactobacilli dominance has been associated with higher rates of pregnancy achievement. This randomized controlled trial conducted in the fertility clinic of the university hospital from 7 August 2019 to May 2021, aimed to compare the clinical outcome of embryo transfer in frozen-thaw cycles with Lactobacillus supplementation prior to embryo transfer and the standard treatment. A total of 340 infertile women underwent randomization. The biochemical and clinical pregnancy rates were comparable between the groups (39.9 and 34.2% in the study group vs. 41.8 and 31.7% in the control group); however, the miscarriage rate was significantly decreased in the study group (9.5 vs. 19.1%, respectively, p = 0.02), [OR = 0.44, 95% CI (0.23, 0.86)]. Among 49 women diagnosed with bacterial vaginosis, the live birth rate in the study group was higher than the control group (42.31 vs. 26.09%, p = 0.23), [OR = 2.08, 95% CI (0.62, 6.99)]. In the blastocyst transfer group (n = 206), the live birth rate was significantly higher in the study group than in the control group (35.71 vs. 22.22%, p = 0.03) [OR = 1.9, 95% CI (1.05, 3.59)]. Therefore, intravaginal lactobacilli supplementation before embryo transfer in the frozen-thaw cycle did not improve the biochemical and clinical pregnancy rate in the general population but significantly reduced the miscarriage rate.Trial Registration: TCTR20190429001 (29/04/2019) @ www.thaiclinicaltrials.org.

The duration of estrogen treatment before progesterone application does not affect neonatal and perinatal outcomes in frozen embryo transfer cycles.

To explore whether the duration of estrogen treatment before progesterone application affects neonatal and perinatal outcomes in artificial frozen embryo transfer (FET) cycles. This was a retrospective cohort study. Patients who underwent FET via artificial cycles and delivered a singleton live birth between January 2015 and August 2019 were included in the analysis. According to the duration of estrogen treatment before progesterone application, we divided the cycles into four groups: ①≤12 days, ②13-15 days, ③16-19 days, and ④≥20 days. The '≤12 days group' was considered the reference group. The main outcome measures were preterm birth (PTB), small-for-gestational age (SGA), low birth weight (LBW), macrosomia, large-for-gestational age (LGA), gestational diabetes mellitus (GDM), gestational hypertension, premature rupture and placenta previa. Overall, 2010 FET cycles with singleton live births were included for analysis. Cycles were allocated to four groups according to the duration of estrogen treatment before progesterone application: ①≤12 days (n=372), ②13-15 days (n=745), ③16-19 days (n=654), ④≥20 days (n=239). The neonatal outcomes, including PTB, SGA, LBW, macrosomia and LGA, were comparable among the groups (P=0.328, P=0.390, P=0.551, P=0.565, P=0.358). The rates of gestational hypertension, premature rupture and placenta previa (P=0.676, P=0.662, P=0.211) were similar among the groups. The rates of GDM among the four groups were 4.0% (15/372), 6.7% (50/745), 6.4% (42/654), and 11.3% (27/239), with statistical significance (P=0.006). After multiple logistic regression analysis, the duration of estrogen treatment did not affect the rate of GDM or other outcomes. The estrogen treatment duration before progesterone application does not affect neonatal and perinatal outcomes in single frozen blastocyst transfer cycles.

Correlation between abnormal energy metabolism of ovarian granulosa cells and in vitro fertilization–embryo transfer outcomes in patients with polycystic ovary syndrome and obesity

ContextGranulosa cells (GCs) that surround oocytes in mammalian reproduction play an active role in oocyte differentiation through proliferation and energy production.AimsThis study aimed to investigate the characteristics of the energy metabolism of ovarian GCs and the influence of GCs on the early embryonic development in polycystic ovary syndrome (PCOS).MethodsThe clinical characteristics and in vitro fertilization-embryo transfer treatment outcomes of 39 patients with PCOS and 68 patients with simple tubal factor infertility who underwent controlled ovarian hyperstimulation were analyzed and summarized. The mitochondrial function and glucose metabolism level of the GCs were determined, as well as the content of oxidative stress markers in the follicular fluid (FF) of patients with and without PCOS.Key resultsWhen compared to the non-PCOS group, patients with PCOS had a significantly increased number of retrieved oocytes but a significantly decreased number of high-quality embryos, available embryos, and high-quality blastocyst formation (P < 0.05). Furthermore, the mitochondrial membrane potential, adenosine triphosphate level, and mitochondrial DNA (mtDNA) copy number decreased in the GCs, whereas the levels of reactive oxygen species increased (P < 0.01). The levels of malondialdehyde and 8-oxo-deoxyguanosine (8-OHdG) in the follicular fluid (FF) of the patients with PCOS were higher than those of the control group (P < 0.05), and superoxide dismutase was increased by compensation (P < 0.05). In the PCOS group, the expressions of GLUT1, LDHA, and PFKP were lower than those in the non-PCOS group, and glucose levels were higher.ConclusionsThe low oocyte competence of PCOS may be associated with mitochondrial dysfunction and abnormal glycolysis.ImplicationsThis research offers explanations for the possible connections influencing human ovarian folliculogenesis.

Coronavirus Disease 2019 (COVID-19) Vaccination and Assisted Reproduction Outcomes: A Systematic Review and Meta-analysis.

To assess the association between coronavirus disease 2019 (COVID-19) vaccination and female assisted reproduction outcomes through a systematic review and meta-analysis. We searched Medline (OVID), EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov on January 11, 2023, for original articles on assisted reproduction outcomes after COVID-19 vaccination. The primary outcome was rates of clinical pregnancy; secondary outcomes included number of oocytes retrieved, number of mature oocytes retrieved, fertilization rate, implantation rate, ongoing pregnancy rate, and live-birth rate. Two reviewers independently screened citations for relevance, extracted pertinent data, and rated study quality. Only peer-reviewed published studies were included. Our query retrieved 216 citations, of which 25 were studies with original, relevant data. Nineteen studies reported embryo transfer outcomes, with a total of 4,899 vaccinated and 13,491 unvaccinated patients. Eighteen studies reported data on ovarian stimulation outcomes, with a total of 1,878 vaccinated and 3,174 unvaccinated patients. There were no statistically significant results among our pooled data for any of the primary or secondary outcomes: clinical pregnancy rate (odds ratio [OR] 0.94, 95% CI 0.88-1.01, P =.10), number of oocytes retrieved (mean difference -0.26, 95% CI -0.68 to 0.15, P =.21), number of mature oocytes retrieved (mean difference 0.31, 95% CI -0.14 to 0.75, P =.18), fertilization rate (OR 0.99, 95% CI 0.87-1.11, P =.83), implantation rate (OR 0.92, 95% CI 0.84-1.00, P =.06), ongoing pregnancy rate (OR 0.95, 95% CI 0.86-1.06, P =.40), or live-birth rate (OR 0.95, 95% CI 0.78-1.17, P =.63). A subanalysis based on country of origin and vaccine type was also performed for the primary and secondary outcomes and did not change the study results. Vaccination against COVID-19 is not associated with different fertility outcomes in patients undergoing assisted reproductive technologies. PROSPERO, CRD42023400023.

Season at the time of oocyte collection and frozen embryo transfer outcomes.

Does the meteorological season at the time of oocyte retrieval affect live birth rates in subsequent frozen embryo transfers? Frozen embryo transfers resulting from oocytes retrieved in summer have 30% increased odds of live birth compared to frozen embryo transfers resulting from oocytes retrieved in autumn, regardless of the season at the time of embryo transfer. Season at the time of frozen embryo transfer does not appear to be associated with live birth rate. One study in the northern hemisphere found increased odds of live birth with frozen embryo transfer resulting from oocytes collected in summer when compared to those collected in winter. Retrospective cohort study including all frozen embryo transfers performed by a single clinic over eight years, from January 2013 to December 2021. There were 3659 frozen embryo transfers with embryos generated from 2155 IVF cycles in 1835 patients. Outcome data were missing for two embryo transfers, which were excluded from analysis. Outcomes were analysed by the season, temperatures, and measured duration of sunshine at the time of oocyte collection and at the time of frozen embryo transfer. There were no significant differences between patients with oocyte collection or embryo transfers in different seasons. Meteorological conditions on the day of oocyte collection and the day of frozen embryo transfer, and in the preceding 14- and 28-day periods, were collected including mean, minimum, and maximum temperatures, and recorded duration of sunshine hours. Clinical and embryological outcomes were analysed for their association with seasons, temperatures, and duration of sunshine with correction for repeated cycles per participant, age at the time of oocyte retrieval, and quadratic age. Compared to frozen embryo transfers with oocyte retrieval dates in autumn, transfers with oocyte retrieval dates in summer had 30% increased odds of live birth (odds ratio (OR): 1.30, 95% CI: 1.04-1.62) which remained consistent after adjustment for season at the time of embryo transfer. A high duration of sunshine hours (in the top tertile) on the day of oocyte retrieval was associated with a 28% increase in odds of live birth compared to duration of sunshine hours in the lowest tertile (OR 1.28, 95% CI: 1.06-1.53). Temperature on the day of oocyte retrieval did not independently affect the odds of live birth. The odds of live birth were decreased by 18% when the minimum temperature on the day of embryo transfer was high, compared with low (OR: 0.82, 95% CI: 0.69-0.99), which was consistent after correction for the conditions at the time of oocyte retrieval. This was a retrospective cohort study, however, all patients during the study period were included and data was missing for only two patients. Given the retrospective nature, causation is not proven and there are other factors that may affect live birth rates and for which we did not have data and were unable to adjust, including pollutants and behavioural factors. We were also not able to stratify results based on specific patient populations (such as poor- or hyper-responders) nor report the cumulative live birth rate per commenced cycle. These findings may be particularly relevant for patients planning oocyte or embryo cryopreservation. Given the increasing utilization of cryopreservation, identification of factors that influence outcomes in subsequent frozen embryo transfers has implications for future therapeutic and management options. Further studies to clarify the physiology underlying the influence of sunshine hours or season on subsequent frozen embryo transfer outcomes are required, including identification of specific populations that may benefit from these factors. No funding was provided for this study. S.L. has received educational travel assistance from Besins, Merck and Organon outside the submitted work. R.H. is National Medical Director of City Fertility and Medical Director of Fertility Specialists of Western Australia, has received honoraria from MSD, Merck Serono, Origio and Ferring outside the submitted work, and has equity interests in CHA SMG. C.R., M.W., and E.N. declare that they have no conflicts of interest. N/A.

Effect of hyaluronic acid-enriched transfer medium on frozen-thawed embryo transfer outcomes in RIF patients: a single-centre retrospective study.

Many patients who undergo assisted reproductive technology (ART) suffer from recurrent implantation failure (RIF). The addition of hyaluronic acid (HA) to the transfer medium is one of several methods to improve pregnancy outcomes. We investigated whether HA could improve the live birth and clinical pregnancy rates of RIF patients. This study included 248 RIF patients, who were divided into two groups: the control (CTL) group (n=137), which received transfer medium without HA, and the HA group (n=111), which received transfer medium with HA. The two groups were compared according to the ART outcome. The primary outcomes were the clinical pregnancy and live birth rates. Secondary outcomes include a positive urine pregnancy test, the implantation, ongoing pregnancy, multiple pregnancy, clinical miscarriage, and ectopic pregnancy rates, foetal or congenital defects, obstetric complications, infant birth weight and any related adverse events. Regarding the primary outcomes, the clinical pregnancy rate was significantly higher in the HA group than in the control group, and there was no significant difference in the live birth rate (LBR) between the HA and control groups. Regarding the secondary outcomes, the implantation, multiple pregnancy and ectopic pregnancy rates were similar between the two groups. Our findings supported the conclusion that HA can improve the clinical pregnancy rate of patients with RIF undergoing FET cycles, but the live birth rate was not significantly improved with the addition of HA to the traditional transfer medium.

P-073 Comparison of human preimplantation embryo development after sperm selection for ICSI using the microfluidic ZyMōt device versus density gradient centrifugation

Abstract Study question Does microfluidic sperm selection using ZyMōt device has a significant effect on blastocyst development, ploidy, and improves pregnancy outcomes when compared with density-gradient centrifugation. Summary answer The study demonstrated that sperm selection using a microfluidic device had no impact on euploid blastocyst rates or clinical pregnancy outcomes. What is known already Selecting competent spermatozoa with the highest genomic integrity for ICSI is a key to achieving normal embryo development and a healthy live birth. Several sperm preparation techniques have long been scrutinized with varied success. The novel microfluidic ZyMōt device appears promising for improving the quality of sperm used in Assisted Reproductive Technologies. Preliminary tests have shown that ZyMōt may increase sperm motility and considerably decrease DNA fragmentation, which could potentially enhance euploid blastocyst development rates. However, the impact of this sperm selection method on clinical outcomes has not been fully investigated. Study design, size, duration This is a retrospective cohort study performed in a single academic IVF centre (IRB # 16367). Data were collected from 1286 ICSI cycles in 2020-2021 (730 with ZyMōt and 556 with DGC), including 867 cycles with PGT-A outcomes. Morphological grading of 6640 blastocysts cultured in a time lapse imaging incubator (Embryoscope™) and ploidy of 4783 blastocysts using high resolution NGS (Illumina platform and Blue Gnome) were compared between the two study groups. Participants/materials, setting, methods All male partners were normo-spermic according to standard semen analysis. ICSI results for a total of 7277 mature oocytes injected with spermatozoa processed with ZyMōt device and 5977 oocytes injected with spermatozoa processed by gradient-density centrifugation were compared. For the analysis of 1478 euploid embryo transfer outcomes, all cases included a single blastocyst transferred in a frozen-thaw cycle. Associated patient characteristics, including age and fertility diagnosis were collected. Main results and the role of chance A significantly higher fertilization rate was observed with ZyMōt compared to the gradient prepared sperm (83.4% vs 81.0%, P = 0.0004, respectively). The blastocyst rates (61.3%, vs 60.4%, P = 0.34) as well as the proportion of high-quality blastocysts were similar in both groups (P = 0.20). Euploidy rates were not different between all female age groups, including young egg donors (≤ 30y of age) to patients with advanced maternal age (&amp;gt;40 y of age). Microfluidic sperm selection did not improve clinical pregnancy rates after euploid embryo transfer (42.9% vs 41.4%; P = 0.58). Limitations, reasons for caution Although this is the largest study to date evaluating application of the ZyMōt device, the retrospective nature and cohort design limited the interpretation of our results. The patient population did not include male factor cases and sperm DFI data was not available. Embryo transfer outcomes were limited to clinical pregnancies. Wider implications of the findings The ZyMōt device offers a convenient alternative to standard sperm processing by density gradient method. Further studies are needed to fully determined the impact of ZyMōt on embryo quality and clinical outcomes in different age and diagnosis groups of patients; particularly for those with high DFI and poor IVF/ICSI outcomes. Trial registration number not applicable

P-257 Transcriptomic signature of live birth revealed in cumulus cells of women undergoing an ICSI cycle for infertility treatment

Abstract Study question Is the transcriptome of cumulus cells surrounding an oocyte that was fertilised and transferred predictive of live birth? Summary answer Live birth is associated with a distinct transcriptomic signature in cumulus cells isolated from an oocyte that was fertilised and transferred. What is known already The selection of the best embryo for transfer is currently based on standard morphological assessment, which is intrinsically subjective, and time-lapse monitoring, which fails to show benefit in predicting pregnancy. Alternative non-invasive selection methods are in development including analysis of cumulus cells (CCs) isolated from oocytes that resulted in an eligible embryo for transfer. However the majority of the existing studies were conducted using outdated methodologies such as transcriptomic analysis with PCR and microarrays. Moreover, the studies associating CCs’ transcriptome with clinical and embryological outcomes lack consensus due to non-homogenous cohorts while the outcome of live birth is inadequately explored. Study design, size, duration CC samples (n = 17), collected between 2018 and 2021 and biobanked, were retrospectively selected for RNA sequencing on the basis of their embryo transfer outcome. Thus, we analysed CCs associated with an oocyte that resulted in pregnancy (n = 6), no pregnancy (n = 7), live birth (n = 5) and pregnancy without live birth (n = 5). Differential gene expression analysis identified the differentially expressed genes (DEGs) between the groups in relation to pregnancy and live birth. Participants/materials, setting, methods The samples were retrieved from subfertile couples undergoing controlled ovarian stimulation and intracytoplasmic sperm injection with subsequent unbiopsied fresh or frozen embryo transfer at the IVF centre of University Hospital Zurich. Maternal age was below 43 years. Libraries from CCs were prepared using the Smart-seq2 pipeline and the RNA sequencing was performed on the NovaSeq 6000 system. The DESeq2 workflow was conducted and the threshold for the adjusted p-values (FDR) was set to 0.05. Main results and the role of chance No DEGs emerged when comparing the transcriptomic profiles of cumulus cells between the “no pregnancy” and “pregnancy” groups. However, 139 DEGs were identified in the comparison between the “pregnancy without live birth” and “live birth” groups. 28 DEGs were familiar and relevant to competent cumulus-oocyte-complexes: CTGF (fold change: 4.38, FDR: 0.005), SERPINE2 (fc: 3.08, FDR: 0.0002), PCK1 (fc:3.04, FDR: 0.0001), HHIP (fc:2.69, FDR: 0.006), HS3ST (fc:2.45, FDR: 0.009) and BIRC5 (fc: -2.69, FDR 0.0001) among others. Functional enrichment analysis of DEGs revealed that the incidence of live birth is associated with promotion of pathways such as runt-related transcription factor 1 (RUNX1/2) signalling, glycosaminoglycan biosynthesis and sonic hedgehog signalling (SHH), and reduction in pathways such as glycosphingolipid biosynthesis and pyrimidine metabolism in cumulus cells. Limitations, reasons for caution We reveal the transcriptome associated with live birth in CCs analysed with RNAseq on a limited number of samples. Consolidation of these findings via utilisation of a validation prospective cohort is pending. Wider implications of the findings CCs’ transcriptome could inform the development of non-invasive biomarkers to predict the chance of live birth across a group of embryos eligible for transfer. The transcriptomic findings inspire further explorations in the field of cumulus-oocyte bidirectional communication and establishment of oocyte competence. Trial registration number N/A

P-544 Biochemical markers as a predictor of clinical pregnancy on day 6 after embryo transfer

Abstract Study question Is it possible to predict clinical pregnancy using Machine Learning models on day 6 after embryo transfer to an acceptable degree of certainty? Summary answer Using selected biochemical markers it is possible to build a machine learning model to predict clinical pregnancy. What is known already Human chorionic gonadotropin (β-hCG) is considered the main early predictor of pregnancy. Due to the fact that the highest percentage of spontaneous abortions occurs in the first trimester predicting clinical pregnancy outcomes at the early stages of pregnancy is particularly difficult. The level of B-hcg measured at the early stages of implantation and the dynamics of its increase can help predict clinical pregnancy and predict its further development. However, the specific cut-off points at which pregnancy can be determined vary from study to study, and a different factor is often suggested to increase the certainty of β-hCG-based predictions. Study design, size, duration 1474 single frozen embryo transfers (1205 patients between 23 and 47 years of age), January 2019 -December 2022 were used for data modelling and statistical testing. The dataset consisted of endocrinal markers:β-hCG, PRG (progesterone), E (estradiol) measured on the 6th day after ET and other practitioner-chosen data: age, PGD results, embryo quality status, RIF or RPL history, embryo maturation days as well as pregnancy outcomes. Exclusion criteria were: PRG &amp;gt; 50ng/ml, β-hCG &amp;gt;70 mIU/ml. Participants/materials, setting, methods A machine learning model for predicting clinical pregnancy was trained using the gradient boosting technique. The model used 100 decision trees with 8 leaves, maximal depth of 2 nodes and a learning rate of 0.1. The performance of the model was measured using the accuracy score metric and area under ROC (AUC). Feature importance was based on Shapley values. Additional analysis was performed using statistical testing using a two-sided Student’s t-test. Main results and the role of chance A Machine Learning naive model employed chosen variables to predict clinical pregnancy. The most important variables turned out to be the serum level of β-hCG and PRG on day 6 after embryo-transfer. The final model, limited to those variables, performs with an accuracy of around 83 % (accuracy score = 0.834), the area under ROC (AUC) was 0.927. Based on Shapley values, β-hCG followed by PRG are the most relevant for the model’s predictions. Low PRG concentrations increased the chances of clinical pregnancy. The findings were confirmed by additional statistical analysis. Observations were divided into two groups for which the cut-off point was the level of PRG of 24 ng/ml – the median for the whole group. The probability of clinical pregnancy is higher in the group where the serum PRG is below 24 ng/ml even if β-hCG levels are the same. A statistically significant difference between these groups regarding β-hCG (P value &amp;lt; 0.001) was noticed. In order for serum β-hCG to be used as a more accurate clinical pregnancy predictor its level should be interpreted in the context of PRG serum levels. Limitations, reasons for caution Since in the dataset, only data regarding frozen embryo transfers were included, fresh ETs need to be explored further. The model was based on endocrinal markers as measured on day six after ET hence it cannot be used to interpret those markers as measured on any other date. Wider implications of the findings In order to most accurately inform patients regarding the possible outcomes of embryo-transfers, practitioners should not limit themselves to monitoring β-hCG serum levels but also include PRG as an important prognostic of clinical pregnancy. Trial registration number Not Applicable