Embryo Transfer Outcomes Research Articles

Comparison of efficacy of long follicular phase regimen and antagonist regimen on pregnancy outcome of fresh cycle or freeze-thawed cycle embryo transfer

Objective: To compare the pregnancy outcome of the fresh cycle or freeze-thaw cycle embryo transfer of patients treated with a long follicular phase regimen and antagonist regimen, and explore the clinical therapeutic effect of the two regimens. Methods: This was a retrospective study. The data of a total of 543 patients who underwent in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) or frozen-thawed embryo transfer (FET) in Baoding Maternal and Child Health Care Hospital from January 2020 to December 2022 were retrospectively analyzed in this study and were divided into four group to analyze the basic conditions, medication, laboratory indicators and clinical outcomes after embryo transfer of patients in each group. Results: The pregnancy rate and implantation rate in Groups A, B and C were higher than those in Group-D, and the differences were statistically significant (p<0.05). The difference in multiple pregnancy rate and abortion rate among groups was not statistically significant (p>0.05). The influencing factors of clinical pregnancy rate were identified by binary Logistic regression analysis. Advanced age was found to be a risk factor for improving the pregnancy rate, while the increase in the number of oocytes retrieved is a protective factor for improving the pregnancy rate. The differences were statistically significant (p<0.05). Conclusion: The antagonist regimen has a low dosage and short medication time and can achieve a high embryo utilization rate and blastula formation rate, saving time and cost for patients. doi: https://doi.org/10.12669/pjms.40.10.9050 How to cite this: Li P, Zhai J, Liu T, Guo M, Wang Y. Comparison of efficacy of long follicular phase regimen and antagonist regimen on pregnancy outcome of fresh cycle or freeze-thawed cycle embryo transfer. Pak J Med Sci. 2024;40(10):2170-2175. doi: https://doi.org/10.12669/pjms.40.10.9050 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

"Try until the last?"-the relevance of fresh embryo transfer outcomes for subsequent same-cohort vitrified-warmed cycles.

Taking into consideration earlier attempts at assisted reproduction and previous pregnancies allows a more differentiated approach when counseling couples regarding their chances in assisted reproductive treatments. The aim of this study was to investigate whether the outcome of fresh embryo transfers affects subsequent same-cohort vitrified-warmed cycles. This retrospective cohort study analyzes the outcome of all fresh and frozen embryo transfers (n = 8118) between January 1, 2011, and December 31, 2022. All women who received fresh or frozen embryo transfers at Kepler University Hospital Linz were included. The use of donor eggs, previously cryopreserved oocytes, and freeze-all cycles were excluded from the analysis. Positive serum βhCG after a fresh cycle has a significant impact on the chances of positive βhCG in a subsequent vitrified-warmed cycle (36.3% [33.2%, 39.5%]; P = 0.002). Negative βhCG after a fresh cycle does not predict the outcome of the following same-cohort embryo transfer (33.1% [30.7%, 35.7%], P = 0.726). Pregnancy rates of the first, second, third, and fourth same-cohort vitrified-warmed embryo transfer remain continuously high, with 32.8%, 30.8%, 28.9%, and 27.1%, respectively. Positive serum βhCG after a fresh embryo transfer has a positive predictive value for the outcome of a subsequent vitrified-warmed embryo transfer. Couples with a negative fresh cycle should not be discouraged from continuing fertility treatment using same-cohort frozen embryos. This study was prospectively registered at the German Clinical Trials Register on September 5, 2023 (DRKS00032552).

High androgen level during controlled ovarian stimulation cycle impairs endometrial receptivity in PCOS patients

PCOS is one of the most common endocrine disorders among women of reproductive age. While the mechanism involved is not yet fully characterized. Our study aims to examine the pregnancy outcomes of embryo transfers in women with PCOS after pretreatment, and to explore the possible effect of high androgen levels on endometrial receptivity. Retrospective cohort study was conducted to analyze pregnancy outcomes among 2714 infertile women with tubal factor and 452 PCOS women. Endometrium samples were collected from 6 controls and 6 PCOS patients to detect the expression of endometrial receptivity marks. The implantation rate, clinical and ongoing pregnancy rates and live birth rate in women with PCOS followed fresh embryo transfers were obviously decreased even after the pretreatment. Similar pregnancy outcomes were found in frozen-thawed embryo transfer cycles between women with or without PCOS. Strikingly, serum total testosterone (TT) levels on trigger day were significantly higher in PCOS women. Women with high TT levels presented significantly lower clinical and ongoing pregnancy rates, and the expression of insulin-like growth factor binding protein 1 (IGFBP-1), and leukemia inhibitory factor (LIF) in the endometria decreased significantly as well. High doses of testosterone significantly down-regulated the expression of IGFBP-1 and LIF in Ishikawa cells. Although endocrine abnormalities had been improved before the controlled ovarian stimulation (COS) cycle started, higher serum TT levels were detected on the trigger day of the COS cycle in PCOS patients, which may contribute to the decreased fresh embryo implantation by impairing endometrial receptivity.

Effect of blastomere cell number on ART outcome of fresh single day 3 embryo transfer

PurposeExplore the effect of blastomere cell number on ART outcome of fresh embryo transfer on day 3.MethodsRetrospective analysis of 540 fresh single day 3 embryo transfer cycles at the Reproductive Center of the Third Affiliated Hospital of Guangzhou Medical University from January 1, 2018 to October 31, 2022. Patients were divided into 5–6 cell group (n = 55), 7–9 cell group (n = 457), and ≥ 10 cell group(n = 28) based on the number of blastomeres. Single factor analysis of variance and Pearson's chi square test were used to compare the basic data, cycle information, pregnancy outcome and neonatal outcome. Univariate logistic regression was used to correct for confounding factors and analyze the influencing factors of pregnancy outcome.ResultsThe positive HCG rate were 20%, 43%, 25% for the 5–6-cell, 7–9 cell and ≥ 10 cell groups respectively, with statistically significant differences (P < 0.001). The clinical pregnancy rate was 18%, 42%,21%, respectively (P < 0.001). The live birth rates were 13%, 34%,21% with P-value less than 0.05 which is statistically significant. In order to exclude the influence of confounding factors, multivariable logistic regression analysis was performed, and the outcomes were consistent with previous findings. There were no significant differences found in neonatal outcome between groups (P > 0.05).ConclusionThe results suggested that intermediate cleaving embryos (7–9 cell) still presents the highest clinical potential. Fast and slow cleaving embryos are not conducive to the ART outcome.

Uncovering the association between embryo development and early pregnancy loss using artificial intelligence annotated kinetic events

Research questionCan artificial intelligence powered annotation of numerous biological events help uncover an association between embryonic kinetics and early pregnancy loss? DesignA multicentric retrospective analysis was conducted on 37717 embryos (7028 egg retrievals, 13 centers in France and Spain, three different time-lapse systems). The videos of developing embryos were analyzed with artificial intelligence to detect developmental events, including t2, t5, t8 (cleavage from 2 cells to 8 cells), tSB (start blastulation) and tB (blastocyst). The association between embryo kinetics and transfer outcome (lack of early pregnancy, early pregnancy loss and clinical pregnancy) was investigated using univariate and multivariate logistic regressions. ResultsAn optimal kinetics for clinical pregnancy was identified as being statistically different from that of embryos which led to an early pregnancy loss (p<0.01). As much as overall faster developing embryos (tB-t2=77.18±8.33 hours) were the most likely to lead to an early pregnancy, it appeared that beyond early pregnancy, embryos that showed a deceleration during cleavage (tsB-t5=46.05±13.60 hours) followed by a subsequent acceleration during blastulation (tB-tSB=9.81±5.04 hours) were the most likely to lead to clinical pregnancy. Conversely, embryos that presented the fastest cleavage and longest blastulation kinetics were the most likely to lead to an early pregnancy loss. ConclusionsAnalyzing numerous kinetic combinations annotated with artificial intelligence reveals patterns which can help distinguish embryos that are competent enough for early pregnancy but not for clinical pregnancy. Detecting such subtle kinetic differences could add transparency to algorithms by pinpointing which phases of an embryo development might be predictive of a pregnancy loss.

Progestin-primed ovarian stimulation

The use of progestins for the prevention of premature ovulation during ovarian stimulation is called progestin-primed ovarian stimulation (PPOS). Response to ovarian stimulation with PPOS and gonadotropin-releasing hormone (GnRH) analogs seem to be similar with the clinically insignificant differences being explained by endocrine characteristics as expected. PPOS has the advantage of oral administration and lower medication cost than GnRH analogs, but the mandatory cancellation of an otherwise possible fresh embryo transfer can render PPOS less cost-effective if a fresh transfer would have been possible. Oocytes collected in PPOS cycles have similar developmental potential, including blastocyst euploidy rates. Frozen embryo transfer outcomes of PPOS and GnRH analog cycles seem similar both in terms of ongoing pregnancy/live birth rates and obstetric and perinatal outcomes. While some studies reported lower cumulative live birth rates with PPOS, they suffer from methodological issues, including arbitrary definitions of cumulative live birth rates. PPOS has been used in all patient types with consistent results and seems a patient-friendly and cost-effective choice when a fresh embryo transfer is not intended.

The outcome of embryo transfer after three different procedures for laparoscopic correction of hydrosalpinx.

To compare the effect of three different surgical approaches: simple terminal salpingostomy, bilateral proximal tubal ligation plus terminal salpingostomy, and bilateral salpingectomy. A retrospective analysis was conducted on the clinical data of 292 patients who underwent laparoscopic surgery for hydrosalpinx and embryo transfer within 2 years postoperatively from January 2018 to August 2021. The patients were divided into three groups: Group A (68 cases) underwent simple terminal salpingostomy, Group B (199 cases) underwent ligation plus terminal salpingostomy, and Group C (25 cases) underwent bilateral salpingectomy. Age, body mass index, surgical time, intraoperative bleeding, length of hospital stay, and infertility type showed no significant differences among the different surgical groups (P > 0.05), except for the age 30-39 group, which showed statistically significant differences in surgical time (P < 0.001) and length of hospital stay (P < 0.001); the age 40 or above group showed statistically significant differences in intraoperative bleeding (P = 0.008). A total of 336 oocyte retrievals and 451 embryo transfers were successfully performed in the 292 patients within 2 years postoperatively. The choice of surgical approach for hydrosalpinx does not affect pregnancy rates after embryo transfer within the same age group.

Reproductive outcomes in fresh transfer cycles and antagonists with premature luteinizing and/or progesterone surge: a single center retrospective cohort study.

The optimal outcome of assisted reproductive technology is a successful live birth after fresh embryo transfer. However, the success pregnancy rate of fresh embryo transfer cycle in antagonist protocol is lower than that observed in other protocols. Despite the use of antagonists (GnRH-ant), the incidence of luteinizing hormone surge and elevated progesterone levels remain at approximately 5%-38%. Progesterone is widely recognized to exert adverse effects on fresh embryo transfer outcomes. This study aimed to investigate the impact of luteinizing hormone surge and progesterone levels on live birth rate following fresh embryo transfer and explore appropriate progesterone thresholds to enhance pregnancy outcomes. This retrospective cohort study included a total of 1,177 antagonist protocol cycles with fresh embryo transfer. The patients were divided into four groups based on the presence of premature LH surge and progesterone level on trigger day>1.5ng/ml. Then, the relationship between the variables and the pregnancy outcome was analyzed and compared in each group. The transient rise of luteinizing hormone did not impact pregnancy outcomes (P=0.345; P=0.3; P=0.787), in contrast to progesterone levels on the day of hCG administration (P=0.047*; P=0.015*; P=0.021*). In cases with luteinizing hormone surge, elevated progesterone levels were correlated with higher antral follicle count (AFC), and as progesterone levels increased, a greater quantity of oocytes and embryos were obtained. However, there was no statistically significant difference in pregnancy outcomes. In cases without luteinizing hormone surge, elevated progesterone levels led to significantly poorer pregnancy outcomes. Furthermore, the curve-fitting and threshold-effect analysis revealed a notable decline in live birth rates when progesterone exceeded or equaled 1.10ng/ml (OR, 0.25; 95% CI, 0.09-0.66; P = 0.005*). The GnRH-ant dosage addition should be carefully selected in flexible antagonist protocols. The presence of elevated progesterone levels may be associated with improved embryo quality when luteinizing hormone surge occurred. In the absence of a luteinizing hormone surge, progesterone levels showed a larger impact on the pregnancy outcome, and fresh embryo transfer should not be performed if the progesterone level on the day of hCG administration is higher than 1.10ng/ml.

Effects of intrauterine infusion of autologous platelet-rich plasma gel on endometrial thickness and outcomes of frozen-thawed embryo transfer in women with thin endometrium.

The purpose of this study is to determine whether intrauterine infusion of autologous platelet-rich plasma (PRP) gel increases endometrial thickness (EMT) and improves the outcomes of frozen-thawed embryo transfer (FET) in women with thin endometrium. This study included 111 women (aged 25-44years) who had thin endometrium. All patients had at least one previous cycle canceled because of thin endometrium or previous embryo transfer cycles and an EMT < 7mm. Forty-seven women underwent intrauterine infusion of autologous PRP gel on three occasions during endometrial preparation and the remaining women served as controls. The final EMT was measured by ultrasound before the start of the luteal phase, and FET-related outcome parameters were monitored. Mean EMT was greater in women who received PRP gel than in those who did not (6.7mm vs. 6.3mm, respectively, p < 0.05). FET was attempted in all women. The 47 women who underwent infusion of PRP had a significantly higher pregnancy rate (18 pregnancies (38.3%), with 17 (36.2%) ongoing) compared with 64 control women (ten pregnancies (18.5%), nine (16.7%) ongoing). However, there was no significant reduction in the miscarriage rate. Intrauterine infusion of autologous PRP gel during endometrial preparation for FET cycles can improve the EMT, clinical pregnancy rate, and ongoing pregnancy rate in women with thin endometrium.

Is Artificial Intelligence (AI) currently able to provide evidence-based scientific responses on methods that can improve the outcomes of embryo transfers? No.

The rapid development of Artificial Intelligence (AI) has raised questions about its potential uses in different sectors of everyday life. Specifically in medicine, the question arose whether chatbots could be used as tools for clinical decision-making or patients' and physicians' education. To answer this question in the context of fertility, we conducted a test to determine whether current AI platforms can provide evidence-based responses regarding methods that can improve the outcomes of embryo transfers. We asked nine popular chatbots to write a 300-word scientific essay, outlining scientific methods that improve embryo transfer outcomes. We then gathered the responses and extracted the methods suggested by each chatbot. Out of a total of 43 recommendations, which could be grouped into 19 similar categories, only 3/19 (15.8%) were evidence-based practices, those being "ultrasound-guided embryo transfer" in 7/9 (77.8%) chatbots, "single embryo transfer" in 4/9 (44.4%) and "use of a soft catheter" in 2/9 (22.2%), whereas some controversial responses like "preimplantation genetic testing" appeared frequently (6/9 chatbots; 66.7%), along with other debatable recommendations like "endometrial receptivity assay", "assisted hatching" and "time-lapse incubator". Our results suggest that AI is not yet in a position to give evidence-based recommendations in the field of fertility, particularly concerning embryo transfer, since the vast majority of responses consisted of scientifically unsupported recommendations. As such, both patients and physicians should be wary of guiding care based on chatbot recommendations in infertility. Chatbot results might improve with time especially if trained from validated medical databases; however, this will have to be scientifically checked.

Increasing dominant follicular proportion was associated with adverse IVF/ICSI outcomes in low-prognosis women undergoing GnRH antagonist protocol: a retrospective cohort study

PurposeThis study aimed to examine the correlation between different dominant follicle proportions (DFPs) and outcomes of in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) among patients classified under POSEIDON Groups 3 and 4, who underwent gonadotropin-releasing hormone antagonist (GnRH-ant) protocols. Additionally, it sought to determine the optimal DFP threshold for trigger timing.MethodsA retrospective analysis was performed on patients classified under POSEIDON Groups 3 (n = 593) and 4 (n = 563) who underwent GnRH-ant protocols for controlled ovarian hyperstimulation (COH) between 2016 and 2022. These patients were categorized into two groups based on their DFPs, defined as the ratio of ≥ 18-mm dominant follicles to ≥ 12-mm follicles on the trigger day (DFP ≤ 40% and DFP ≥ 40%). Statistical analyses, including restricted cubic spline (RCS) and multivariate logistic regression, were employed to assess the relationship between DFP and IVF/ICSI outcomes.ResultsDemographic characteristics of patients were similar across groups. In POSEIDON Groups 3 and 4, DFP > 40 was associated with a significant decrease in the number (No.) of oocytes retrieved, cleaved embryos, and available embryos. Moreover, following the GnRH-ant cycle, the clinical pregnancy and live birth rates in fresh embryo transfer (ET) were notably reduced in the DFP > 40 group compared with the DFP ≤ 40 group, whereas no significant differences were observed in the pregnancy outcomes of the first frozen-thawed embryo transfer (FET) between the groups. In POSEIDON Group 3, the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLRB) were significantly higher in the DFP ≤ 40 subgroup than in the DFP > 40 subgroup, with a notable decrease in CLRB observed with increasing DFP levels. However, in POSEIDON Group 4, no significant differences in CCPR and CLRB were found between the groups. Logistic regression analysis identified age and the No. of oocytes retrieved as pivotal factors influencing CLRB in Group 4.ConclusionFor patients in POSEIDON Group 3, maintaining a DFP ≤ 40 mm is crucial to achieve optimal laboratory and pregnancy outcomes by avoiding delayed triggering. However, for patients in POSEIDON Group 4, age remains a critical factor influencing CLRB regardless of DFP, although a higher No. of oocytes retrieved and available embryos with DFP ≤ 40 is beneficial.

Vaginal and endometrial microbiome dysbiosis associated with adverse embryo transfer outcomes

BackgroundAssisted reproductive technology (ART) is the most effective method to treat infertility and the pathogenesis of implantation failure after in vitro fertilization-embryo transfer (IVF-ET) is a challenging filed in infertility. Microbes in the female reproductive tract are considered to be associated with gynecological and obstetric diseases. However, its effects on embryo implantation failure are unsured.PurposeThis study aimed to investigate reproductive tract dysbiosis, identify different bacteria in reproductive tract as potential biomarkers of embryo implantation failure and demonstrate the pathogenesis through metabolites analysis.MethodsWe compared the data from 16S rRNA gene and metagenome in reproductive tracts through QIIME2 and HUMAnN2 by the times of embryo implantation failure on 239 infertile patients and 17 healthy women.ResultsOur study revealed a strong positive correlation between Lactobacillus abundance and embryo implantation success (IS) after IVF-ET. The microbial community composition and structure in reproductive tract showed substantially difference between the embryo implantation failure (IF) and healthy control. Moreover, we established a diagnostic model through receiver operating characteristic (ROC) with 0.913 area under curve (AUC) in IS and multiple implantation failures (MIF), verified its effectiveness with an AUC = 0.784 demonstrating microbial community alterations could efficiently discriminate MIF patients. Metagenome functional analyses of vaginal samples from another independent infertile patients after IVF-ET revealed the L-lysine synthesis pathway enriched in IF patients, along with ascended vaginal pH and decreased Lactobacillus abundance.ConclusionsThis study clarifies several independent relationships of bacteria in vagina and endometrial fluid on embryo implantation failure and undoubtedly broadens the understanding about female reproductive health.

Effect of LH level on HCG trigger day on clinical outcomes in patients with diminished ovarian reserve undergoing GnRH-antagonist protocol

Research questionDoes luteinizing hormone (LH) levels on human chorionic gonadotropin (HCG) trigger day (LHHCG) affect the clinical outcomes of patients with diminished ovarian reserve (DOR) undergoing gonadotropin-releasing hormone antagonist (GnRH-ant) protocol?MethodsRetrospective analysis fresh embryo transfer cycles of DOR patients who underwent GnRH-ant protocol from August 2019 to June 2023. The participants were divided into different groups according to LHHCG level and age. The clinical data and outcomes were compared between groups.ResultsIn patients with DOR, the HCG positive rate (59.3% versus 39.8%, P = 0.005), embryo implantation rate (34.5% versus 19.7%, P = 0.002), clinical pregnancy rate (49.2% versus 28.4%, P = 0.003), live birth rate (41.5% versus 22.7%, P = 0.005) in LHHCG < 2.58 IU/L group were significantly higher than LHHCG ≥ 2.58 IU/L group. There was no significant correlation between LHHCG level and clinical pregnancy in POSEIDON group 3. In POSEIDON group 4, the HCG positive rate (52.8% versus 27.0%, P = 0.015), embryo implantation rate (29.2% versus 13.3%, P = 0.023), clinical pregnancy rate (45.3% versus 18.9%, P = 0.010) in LHHCG < 3.14 IU/L group were significantly higher than LHHCG ≥ 3.14 IU/L group. Logistic regression analysis indicated that LHHCG level was an independent influencing factor for clinical pregnancy in POSEIDON group 4 patients (OR = 3.831, 95% CI: 1.379–10.643, P < 0.05).ConclusionsLHHCG level is an independent factor affecting pregnancy outcome of fresh embryo transfer in DOR patients undergoing GnRH-ant protocol, especially for advanced-aged women. LHHCG had a high predictive value for POSEIDON group 4 patients, and LHHCG ≥ 3.14 IU/L predicts poor pregnancy outcomes.

Impact of elevated serum estradiol levels before progesterone administration on pregnancy outcomes in frozen-thawed embryo transfer for hormone replacement therapy

ObjectiveThe objective of this retrospective cohort study is to investigate the impact of monitoring serum estradiol (E2) levels before progesterone administration within hormone replacement therapy (HRT) on pregnancy outcomes in women undergoing frozen-thawed embryo transfer (FET).MethodsAnalyzed HRT-FET cycles conducted at a reproductive center from 2017 to 2022. Serum E2 levels were measured prior to progesterone administration. Multivariate stratified and logistic regression analyses were performed on 26,194 patients grouped according to terciles of serum E2 levels before progesterone administration.ResultsThe clinical pregnancy rate (CPR) and live birth rate (LBR) exhibited a gradual decline with increasing serum E2 levels across the three E2 groups. Even after controlling for potential confounders, including female age, body mass index, infertility diagnosis, cycle category, number of embryos transferred, fertilization method, indication for infertility, and endometrial thickness, both CPR and LBR persistently showed a gradual decrease as serum E2 levels increased within the three E2 groups. The same results were obtained by multivariate logistic regression analysis.ConclusionsThis large retrospective study indicates that elevated serum E2 levels before progesterone administration during HRT-FET cycles are associated with reduced CPR and LBR post-embryo transfer. Therefore, it is advisable to monitor serum E2 levels and adjust treatment strategies accordingly to maximize patient outcomes.

Antibiotics improve reproductive outcomes after frozen-thaw embryo transfer for chronic endometritis treatment, especially in those with repeated implantation failure

PurposeTo investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE.MethodsA retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up.ResultsOut of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P < 0.05). Analysis of the effect of CE on pregnancy outcomes in FET cycles after antibiotic treatment indicated that treated CE patients exhibited a significantly lower miscarriage rate (8.7%) and early miscarriage rate (2.9%) than untreated non-CE patients (20.2%, 16.8%). Moreover, the singleton live birth rate (45.5%) was significantly higher in treated CE patients than in untreated non-CE patients (32.7%). Survival analysis revealed a statistically significant difference in the first clinical pregnancy time between treated CE and untreated non-CE patients after hysteroscopy (P = 0.0019). Stratified analysis based on the presence of recurrent implantation failure (RIF) demonstrated that in the RIF group, treated CE patients were more likely to achieve clinical pregnancy than untreated non-CE patients (P = 0.0021). Among hysteroscopy-positive patients, no significant difference was noted in pregnancy outcomes between the treatment and control groups (P > 0.05).ConclusionInfertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF.

Pregnancy and perinatal outcomes in pregnancies following frozen embryo transfer (FET) after transcervical resection of adhesions (TCRA): A retrospective cohort study with propensity score matching analysis.

To compare the pregnancy and perinatal outcomes of frozen-thawed embryo transfer (FET) in patients following transcervical resection of adhesions (TCRA) versus patients with normal uterine morphology, and to investigate the factors influencing pregnancy outcomes in patients undergoing FET after TCRA. We retrospectively analyzed FET cycles from September 2014 to September 2023, comparing patients with normal uterine morphology to those with intrauterine adhesions (IUAs) treated with TCRA. Propensity score matching (PSM) adjusted for confounding factors. LASSO regression and multivariate logistic regression identified predictors of outcomes, which were visually represented in nomograms. Model performance was assessed using calibration curves, ROC curves, and DCA, with bootstrap method for internal validation. Post-PSM analysis showed higher live birth rates in patients with normal uterine morphology after clinical pregnancy (75.1% vs. 61.7%, P < 0.001). No significant differences were noted in clinical pregnancy rates and perinatal outcomes between the groups. Factors influencing clinical pregnancy in FET after TCRA included basal progesterone levels, endometrial thickness, parity, infertility cause, embryo stage at transfer, number and quality of embryos transferred, IUA severity, and TCRA surgical procedures. Body mass index, basal LH levels, and day 14 HCG levels post-embryo transfer were determinants of live birth outcome. FET cycles following TCRA showed a lower rate of successful live births, but TCRA did not increase adverse perinatal outcome risks. Our study introduces an innovative predictive model for clinical pregnancy and live birth outcomes in patients undergoing FET following TCRA, addressing a significant void in existing research.

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

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

P-382 Clinical case studies of women achieving successful pregnancy outcomes in natural cycle endometrial preparation while continuing breastfeeding: a gap in the existing literature

Abstract Study question Existing research in assisted reproductive technology excludes women who are breastfeeding.The influence of lactation on embryo transfer outcomes remains underexplored. Summary answer This collection of clinical cases underscores the viability of natural cycle endometrial preparation for women who wish to continue breastfeeding while pursuing fertility treatments. What is known already Endometrial preparation for embryo transfer often involves hormonal regimens and synchronization with the menstrual cycle. However, little attention has been given to women who choose to continue breastfeeding while pursuing fertility treatments. This study presents clinical case reports of women who successfully achieved ongoing pregnancies by utilizing natural cycle endometrial preparation during continued lactation, shedding light on a crucial gap in the current literature regarding embryo transfers in lactating women. Study design, size, duration A series of clinical case reports were analyzed, focusing on women who maintained breastfeeding while undergoing natural cycle endometrial preparation for embryo transfer. The cases encompass various age groups and underlying fertility issues. Data collected includes menstrual regularity, hormonal profile, and outcomes of embryo transfers. Participants/materials, setting, methods Retrospective review of a group of women of varying ages and fertility backgrounds who opted to continue breastfeeding while pursuing embryotransfer. We performed frozen embryo transferchoosing natural cycle endometrial preparation. Clinical data were collected from the participants, including menstrual regularity, hormonal assesment, and outcomes of embryo transfers. Patients were monitored to determine the timing of natural ovulation. The women continued breastfeeding throughout their cycle, and embryo transfers were performed according to standard protocols. Main results and the role of chance Our preliminary findings indicate that women who continued breastfeeding during natural cycle endometrial preparation achieved successful pregnancies with evolving embryos. These case reports highlight the potential feasibility of this approach in fertility treatments, despite the limited scientific literature examining the impact of breastfeeding on embryo transfer outcomes. Limitations, reasons for caution Limited number of clinical cases, which may not fully represent the diversity of patient experiences. Additionally, the absence of a control group makes it challenging to draw definitive conclusions about the sole influence of breastfeeding on the outcomes. Future investigations should involve larger cohorts and controlled studies to provide evidence. Wider implications of the findings This collection of clinical cases underscores the viability of natural cycle endometrial preparation for women who wish to continue breastfeeding while pursuing fertility treatments.. These cases advocate for a broader understanding of reproductive options and potential adaptations to existing protocols for lactating women in the field of assisted reproductive technology. Trial registration number not aplicable

P-328 Uterine Fluid microbiome composition in fertile controls and infertile women

Abstract Study question Is the microbiome of the Uterine Fluid (UF) related to outcomes of frozen-thawed blastocyst transfer? Summary answer Microbiome of UF collected by double-sheated catheter shows Lactobacilli as the most abundant species but does not relate to outcomes of frozen-thawed blastocyst transfer. What is known already The microbiome of UF has been described to be largely dominated (&amp;gt;90%) by Lactobacilli and has been shown to be markedly associated with the outcomes of embryo transfer. Nonetheless, previous reports have not collected UF by avoiding vaginal/cervical contamination through a double-sheated catheter. Study design, size, duration Observational study conducted at Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico and IRCCS Ospedale San Raffaele, Milan, Italy. n = 13 fertile controls underwent UF sampling in the pre-receptive (LH + 2) and receptive (LH + 7) phase of a monitored natural cycle and n = 48 infertile women underwent UF sampling on day LH + 7 of the monitored natural cycle preceding that of their first frozen-thawed blastocyst transfer. UF was sampled by aspiration with a double-sheated catheter (commonly used for embryo transfer. Participants/materials, setting, methods Microbiome analysis was conducted following the Illumina protocol for V3-V5 regions of the 16S rRNA and using the Illumina MiSeq instrument. Raw sequencing data processing encompassed quality controls, and QIIME 2 scripts were employed to obtain taxonomic abundances (taxonomic levels L2-L7). Alpha (within sample), and beta (among samples) diversity and differential expression at taxonomic level (using limma, Bioconductor library) were calculated. Main results and the role of chance UF microbiome analysis showed lack of separation between samples from the two Centres, confirming the reproducibility of the technique. UF microbiome was also found to be stable throughout the menstrual cycle, with no diversity observed between LH + 2 and LH + 7 samples in the population of fertile controls (p = 0.9, Adonis test on beta diversity; confirmed by differential abundance tests based on linear regression models at taxonomic levels). UF of fertile controls showed Lactobacillus Helveticus as the most abundant species (16.2%), followed by other Lactobacilli (unspecified) (12.1 %), Lactobacillus Iners (11.8%), Streptococcus (unspecified) (6.8%), Bifidobacterium (4.7%) and Gardnerella (1.9 %). In women who achieved successful implantation after FET, the most abundant species was L. Helveticus (58.1%) followed by L. Iners (9.8%), Acinetobacter lwoffii (5.9%) and other Lactobacilli (unspecified) (4.0%). No statistically significant differences were found in linear regression comparisons at taxonomic level with UF of women with failed implantation, in whom most abundant species were L. Helveticus (50.4%, p = 0.11), L. Iners (15.8%, p = 0.95), other Lactobacilli (unspecified) (13.7%, p = 0.17) and Garnderella (6.5%, p = 0.19). The proportion of Lactobacillus- dominated (&amp;gt;90%) samples was 50% (n = 10/20) in infertile women achieving successful implantation and 46% (n = 13/28) in infertile women with failed implantation (p = 0.8). Limitations, reasons for caution These results are preliminary and only include the first n = 48 patients of the total n = 249 patients that will be enrolled. A larger sample is required to further investigate possible relations between UF microbiome composition and implantation outcomes. Wider implications of the findings As UF microbiome was found to be stable between cycle phases and it is non-invasively collected, it could be analysed in the same cycle in which ET is scheduled. This might increase accuracy compared to current tests for endometrial receptivity, that have to be performed in the cycle before ET. Trial registration number RF-2019-12369460

O-291 Sonographic Symphony: a systematic review and network meta-analysis of the use of 2D, 3D, 4D ultrasound’s influence on embryo transfer outcomes

Abstract Study question To comprehensively evaluate and compare pregnancy and live birth rates following clinical touch, 2D, 3D or 4D ultrasound guided embryo transfer of a blastocyst. Summary answer The use of 3D and 4D ultrasound is not superior to 2D transabdominal ultrasound, but all forms of ultrasound are superior to clinical touch alone. What is known already While several factors contribute to the overall success of embryo transfer, the accurate placement of the embryo within the uterine cavity remains a critical determinant of implantation and subsequent pregnancy. While two-dimensional (2D) ultrasound provides basic imaging during embryo transfer, assisting with catheter placement, three-dimensional (3D) ultrasound adds volume and spatial information, aiding in assessing the endometrial cavity and embryo positioning. Meanwhile, four-dimensional (4D) ultrasound introduces real-time visualisation, offering dynamic insights into embryo movement and potential implantation. Although 2D remains a standard for most transfers, there is a growing interest in leveraging advanced imaging technologies to improve assisted reproductive outcomes. Study design, size, duration We searched bibliographical databases, including the Cochrane Central Register of Controlled Trials, EMBASE and Medline, from inception until August 2023. Randomised controlled trials that compared 2D transabdominal (2D TAUS), 2D transvaginal (2D TVUS), 3D and 4D ultrasound guided embryo transfer with one another or with clinical touch were included. The primary outcome was live birth rate (LBR), and the secondary outcome was clinical pregnancy rate (CPR) per transfer. Participants/materials, setting, methods Two reviewers independently screened selected studies and extracted the data. Pairwise and network meta-analyses (NMA) were conducted according to the technique used. Effect estimates were odds ratio (OR) with 95% confidence interval (CI) for each outcome respectively. Summary estimates were calculated using random-effects methods and quality assessment was performed using GRADE. Main results and the role of chance Twenty-eight trials, reporting data from 10,521 embryo transfer procedures, were included. Four different ultrasound modalities were evaluated: 2D transabdominal guided embryo transfer (2D TAUS) (21 trials), 2D transvaginal guided embryo transfer (2D TVUS) (four trials), 3D transabdominal guided embryo transfer (one trial) and 4D transabdominal guided embryo transfer (one trial). Compared to 2D TAUS, there was no difference in LBR in the network meta-analysis when using 2D TVUS (OR 1.14; 95% CI: 0.75-1.74), 3D ultrasound (OR 0.98; 95% CI: 0.49-1.97) or 4D ultrasound modality (OR 1.28; 95% CI: 0.56- 2.94). The use of clinical touch was associated with lower LBR (OR 0.71; 95% CI: 0.49-1.03). Compared to 2D TAUS, there was no difference in clinical pregnancy rate in the network meta-analysis when using 2D TVUS (OR 1.17; 95% CI: 0.86-1.58), 3D ultrasound (OR 0.97; 95% CI: 0.57-1.63) or 4D ultrasound modality (OR 1.30; 95% CI: 0.71- 2.38). The use of clinical touch was associated with lower CPR (OR 0.74; 95% CI: 0.64-0.85). Limitations, reasons for caution Variability in study designs, methodologies, and participant characteristics across primary studies can complicate the synthesis of results. There was only one study directly comparing 3D and 4D interventions which resulted in sparse data, affecting the precision and reliability of estimates. Wider implications of the findings Published evidence supports the continued use of 2D transabdominal ultrasound guided embryo transfer in routine clinical practice. There is insufficient evidence to support the introduction of 3D and 4D ultrasound when performing embryo transfers. Larger randomised controlled trials specifically assessing the superiority of these modalities are recommended. Trial registration number not applicable