Embryo Transfer Failure Research Articles

Application of disposable digital hysteroscope for outpatient hysteroscopy in women undergoing artificial assisted reproductive procedures: a clinical research

BackgroundHysteroscopy is the preferred method for the diagnosis and treatment of uterine diseases. With the increasing demand for outpatient hysteroscopy, disposable digital hysteroscopy has emerged, which can meet the requirements of diagnosis and treatment integration, and greatly reduce the labour and storage costs.MethodsA total of 108 outpatients who underwent hysteroscopy using disposable digital hysteroscope were divided into two groups: the non-porous group (group A, n=49) and the married with child group (group B, n=59). The patients’ general information and clinical data were recorded and statistical analysis was performed.ResultsNo differences were found between the age, weight, body mass index, menopausal status and indication for hysteroscopy of the two groups. The most common indication was embryo transfer failure. The surgical success rate of 108 patients was 100%, the concordance rate between hysteroscopic diagnosis of chronic endometritis and pathological diagnosis was 94.44% (68/72), while the false positive rate stood at 38.89% (14/36). Additionally, incidental findings rate for endometrial polyps was 92.00% (23/25) with a low false positive rate of only 6% (5/83). The mean visual analogue scale score of group A was 2.285±0.180, which was not significantly different from group B (p=0.483, 95% CI(−0.60-0.44)). The pregnancy rate among patients who received assisted reproductive technology and were followed up for 1 year after surgery was 66.67% (40/60), while the abortion rate stood at 5.00% (3/60).ConclusionsThe disposable digital hysteroscope is a valuable and effective tool for outpatient hysteroscopy.

Structural and functional features of the endometrium in chronic endometritis and implantation failure in IVF cycles

BACKGROUND: Implantation failure of the endometrium in women with chronic endometritis remains a subject of discussion, despite certain progress in the diagnosis and treatment of this pathology. It has been proven that chronic endometritis is a predictor of endometrial dysfunction, which contributes to the disruption of the morphogenesis of the endometrium necessary for its implantation capacity. Implantation disorders associated with chronic endometritis are related to pathology of the receptor profile and vascular bed, as well as dysregulation of proliferative and apoptotic mechanisms. AIM: The aim of this study was to evaluate the expression of estrogen and progesterone receptors, endothelial marker and apoptosis-inducing factor in the endometrium of patients with chronic endometritis and ineffective embryo transfer in IVF protocols. MATERIALS AND METHODS: This study enrolled 50 patients with ineffective embryo transfers in IVF protocols and 25 women in the control group with positive reproductive outcomes. All patients underwent a comprehensive morphological study of the endometrium including histological examination, immunohistochemical study with assessment of the receptor profile [estrogen (ERα) and progesterone (PR) receptor expression], chronic endometritis (CD8+, CD4+, CD20+, CD138+), apoptosis [antibodies to apoptosis-inducing factor (anti-AIF [E20])], and angiogenesis (CD34+), with microscopic, morphometric and statistical methods used as well. RESULTS: Endometrial implantation failure is associated with a history of urogenital infection, benign cervical diseases, high incidence of endometrial pathology and reproductive loss. It is characterized by the presence of follicle-like mononuclear infiltrates in the endometrium, fibroplastic changes in the stromal component, vascular sclerosis, abnormal increase in the pro-inflammatory cell count, multifocal decrease in estrogen (ERα) and progesterone (PR) receptor expression, as well as activation of pathological neoangiogenesis and apoptosis in the stroma. CONCLUSIONS: Chronic endometritis leads to disruption of the structural and functional characteristics of the endometrium, stimulates pathological neoangiogenesis and dysregulates proliferative and apoptotic mechanisms, which forms a vicious circle of endometrial implantation failure and inefficiency of embryo transfer in IVF protocols.

P-635 Effect of intrauterine autologous platelet-rich plasma on women with repeated implantation failure undergoing IVF: a systematic review

Abstract Study question In women with repeated implantation failure(RIF), according to the ESHRE definition, does intrauterine autologous platelet-rich plasma(PRP) increase the probability of pregnancy after IVF? Summary answer Using the ESHRE definition of RIF, no RCTs exist to accept or refute a beneficial role of intrauterine PRP on the probability of pregnancy. What is known already Ten meta-analyses of RCTs evaluating intrauterine infusion of PRP in patients reported as being RIF have been published until today, suggesting an increase in pregnancy rates. However, due to the significant heterogeneity and low quality of the included studies, no solid conclusions can be drawn. Importantly, the variability in the definition of RIF in the literature renders extrapolation of research results problematic. In this respect, ESHRE has recently published a RIF definition to facilitate evaluation of interventions in these patients. A systematic review on the effect PRP in patients meeting the ESHRE criteria for RIF has not yet been performed. Study design, size, duration A literature search (according to a predefined search protocol) in MEDLINE, Embase and CENTRAL was performed until 12/2023 aiming to identify eligible RCTs. Subsequently, the search results were scrutinized independently by two reviewers and demographic, methodological and clinical data from eligible RCTs were extracted. The main outcome measure was achievement of live birth. Secondary outcomes measures included clinical pregnancy, ongoing pregnancy, implantation and miscarriage rates. Study quality was assessed using the RoB2 tool by Cochrane. Participants/materials, setting, methods Data from the identified RCTs were extracted to examine whether the ESHRE definition of RIF was met. Specifically, whether RCTs were performed in patients <35 years of age with three unsuccessful embryo transfers(ETs) or in patients between 35 and 39 years of age with four unsuccessful ETs, or in patients aged 40 and above with six unsuccessful ETs, when embryos of unknown euploidy were used or in patients with >2 failed ETs of euploid embryos. Main results and the role of chance Systematic review: Twelve RCTs published between 2019 and 2022 were identified, evaluating the effect of intrauterine infusion of PRP in women with RIF, undergoing IVF, transferring embryos of unknown euploidy(1596 women). Although, the majority of the RCTs identified suggested a positive effect of intrauterine PRP infusion on the probability of pregnancy in patients with RIF, a great heterogeneity was present regarding the definition of RIF, especially considering the number of previous failed ETs, that range from at least one to more than three. Moreover, the number of failed ETs used to define RIF did not take into consideration female age, as suggested in the ESHRE definition of RIF. In two out of the twelve RCTs, patients evaluated were less than 35 years of age, which is one the age groups used by ESHRE for the definition of RIF. However, in these studies, patient with less than three failed ETs were included (1-5). Overall, in none of the RCTs identified, the ESHRE definition of RIF was met and thus, a meta-analysis to accept or refute a beneficial role of intrauterine infusion of PRP was not possible. Limitations, reasons for caution Although it is expected that RCTs published prior to the ESHRE definition of RIF are unlikely to meet the criteria proposed, it should be clear that currently no RCTs exist to accept or refute the beneficial role of intrauterine PRP on the probability of pregnancy in these patients. Wider implications of the findings It is likely that the beneficial role of intrauterine PRP infusion on the probability of pregnancy, observed in the relevant RCTs, included in previously published meta-analyses, does not apply to patients with RIF, according to the definition criteria proposed by ESHRE. Therefore, additional RCTs conforming to this definition are required. Trial registration number Under process in Prospero

P-446 Personalization of the euploid embryo transfer guided by the endometrial receptivity analysis in patients with >1 previous failed transfer

Abstract Study question Does personalized embryo transfer (pET) guided by Endometrial Receptivity Analysis (ERA) increase reproductive outcome in patients with >1 previous failed transfer of an euploid embryo? Summary answer pET guided by ERA resulted in a significantly higher Pregnancy Rate (PR), Ongoing Pregnancy Rate (OGPR) and Live Birth Rate (LBR) versus standard embryo transfer. What is known already pET consists of synchronizing embryo transfer with the optimal endometrial receptivity status by the transcriptomics identification of the personalized window of implantation (WOI). Euploid transfers improve reproductive outcome controlling the embryo contribution in the implantation. Controversial results have been published regarding the clinical usefulness of pET in a range of clinical indications. Here we present data from patients with >1 previous failed embryo transfer (ET) in a subsequent euploid ET. Study design, size, duration Multicenter retrospective study involving 270 patients with at least one previous implantation failure between 2017 and 2021. These patients were divided into two groups according to their subsequent transfer: study group (pET guided by ERA) (n = 200), and control group (standard transfer) (n = 70). All the ET were done in Hormone Replacement Therapy cycles (HRT). PR, OGPR and LBR were compared between the two groups. Participants/materials, setting, methods Age, body mass index, previous failed attempts, inner cell mass (ICM) and trophectoderm (TE) quality of the transferred embryos were compared between the groups. Study group had an ERA result as standard WOI or displaced WOI and pET of an euploid embryo was carried out in a subsequent HRT cycle (following the same conditions and recommendations provided by ERA). Wilcoxon rank sum test was applied to quantitative comparations. Chi-square test was done for categorical variables. Main results and the role of chance Clinical results in terms of PR, OGPR and LBR were significantly higher when pET guided by ERA was performed when compared to the non-ERA group. PR was 65% (130/200) in pET versus 37.14% (26/70) in control group (P = 0.000088); OGPR was 49% (98/200) in pET versus 27.14% (19/70) in control group (P = 0.0024); and LBR was 48.20% (95/197) in pET versus 26.09% (18/69) in control group (P = 0.0022). Control and demographics variables did not show differences between the two groups: Age: 35.27 ± 3.86 versus 35.77 ± 3.35 (P = 0.31); BMI: 22.99 ± 3.02 versus 23.25 ± 3.72 (P = 0.52); Previous failed attempts: 2.42 ±1.78 versus 2.17 ±1.81 (P = 0.32); P values where 0.1 and 0.36 for comparisons of optimal quality of ICM and TE, respectively. Limitations, reasons for caution This is a retrospective study, having the limitations of its nature. Wider implications of the findings These results show that pET guided by the ERA test of an euploid embryo significantly increases the reproductive outcomes (PR, OGPR and LBR) in patients with ≥1 previous failed transfer compared to the standard frozen ET. Trial registration number Hospital Clínico de Valencia Ethic Committee approval nº. 2021/018.

P-662 Effect of rescue-dose progesterone in patients with low serum progesterone levels on the day of embryo transfer in frozen embryo transfer cycles

Abstract Study question What is the effect of rescue-dose progesterone in patients with low serum progesterone on the day of embryo transfer in frozen embryo transfer cycles? Summary answer In patients with low serum progesterone on the day of embryo transfer, rescue dose progesterone results in significantly higher clinical pregnancy rates. What is known already Frozen embryo transfer (FET) has become more common lately with many centers utilizing hormone replacement therapy (HRT) to electively plan embryo transfer with improved compliance rates. Serum progesterone level on the day of embryo transfer is a very simple, useful investigation which can be used as a predictor of clinical outcomes. Patients with lower progesterone levels (<5ng/ml) are associated with lower clinical pregnancy and ongoing pregnancy rates. Progesterone levels of > 10ng/ml are considered optimal by various studies. There is limited data on the efficacy of progesterone supplementation in patients with low progesterone levels. Study design, size, duration This study was conducted to assess the effect of rescue dose progesterone in patients with low serum progesterone levels on the day of embryo transfer in patients with HRT-FET cycles. This was a retrospective study and data was collected from prospectively maintained records of patients undergoing treatment at Miracles IVF and fertility center, Gurgaon, India between December, 2021 to November, 2023. Participants/materials, setting, methods All were HRT-FET cycles with vaginal progesterone supplementation of 800 mg/day. Serum progesterone levels were done on day of embryo transfer and if 5-10 ng/ml, rescue dose progesterone (100 mg intramuscular) was given. Single blastocyst embryo transfer was done. Inclusion criteria: 1.Age 25-35 years, 2.Endometrial thickness >7.5mm on day of start of progesterone. Exclusion criteria: 1.Transfer day progesterone <5ng/ml, 2. BMI > 30, 3. Previously failed embryo transfer The primary outcome was clinical pregnancy rate. Main results and the role of chance A total of 121 patients underwent 165 cycles during the study period with 93 patients included in the study after fulfilling the inclusion and exclusion criteria. 35 patients (37.6%) received rescue dose progesterone (RD group) and remaining 58 patients (62.4%) received no rescue dose (NRD group) as per their serum progesterone levels. All these patients were followed as per protocol and serum bhcg was done after 14 days of embryo transfer. Patients with positive values were monitored till positive clinical pregnancy. Biochemical pregnancy rates were 20 out of 35 (57.1%), 35 out of 58 ( 60.3%) and 55 out of 93 ( 59.1%) in RD group, NRD group and overall respectively. Clinical pregnancy rates were 18 out of 35 (51.4%), 34 out of 58 ( 58.6%) and 52 out of 93 ( 55.9%) in RD group, NRD group and overall respectively. RD group had significantly improved outcomes in terms of clinical pregnancy rates which were comparable to NRD group Limitations, reasons for caution Limitations, reasons for caution: Ours was a single center retrospective study with limited sample size. Though, our study revealed comparable outcome between the two groups but large volume multicenter studies are needed for making conclusive recommendations. Wider implications of the findings This study provides an insight into the role of serum progesterone levels on the day of embryo transfer. Rescue progesterone dosage for patients with sub-optimal serum progesterone levels may help in achieving similar clinical pregnancy rates and improving overall outcomes. Trial registration number not applicable

P-441 Comparative analysis of endometrial receptivity analysis guided embryo transfer and sequential embryo transfer Strategies in implantation failures patients

Abstract Study question Do patients with previous in vitro fertilization (IVF) implantation failures benefit more from endometrial receptivity analysis(ERA)-guided embryo transfer(ET) or sequential ET compared to traditional ET? Summary answer Our research suggests that both ERA-guided and sequential ET methods may lead to improved pregnancy outcomes compared to traditional ET in IVF-failure patients. What is known already In the field of IVF, achieving successful outcomes heavily relies on two crucial factors - embryo genetics and implantation in a receptive endometrium. The use of ERA-guided and sequential ET strategies has emerged in clinical practice as potential solutions to overcome embryo transfer failures. However, the controversy surrounding their advantages over traditional transplantation calls for a comprehensive comparative study. Study design, size, duration A retrospective cohort study was conducted in two private fertility clinics in Southwestern China (Dec 1, 2019 - Jun 30, 2024). Individuals experienced at least one IVF implantation failure were categorized into ERA-guided ET group (group A), sequential ET group(group B), or traditional ET group (group C) based on embryo transfer strategies. Analysis was restricted to patients who completed subsequent frozen-thawed embryo transplantation and were followed up at least 3 months to assess clinical outcomes Participants/materials, setting, methods A total of 6814 participants, with a mean age of 33.7 years were included. Among them, 15% (n = 1022) underwent ERA-guided ET (group A), which involved individualized ET guided by ERA testing. Another 10.3% (n = 703) utilized sequential transfer (group B), where two embryos were transferred at different timepoints. The remaining 74.7% (n = 5089) underwent traditional embryo transfer (group C) Main results and the role of chance The ongoing pregnancy rate was significantly higher in both group A (45.5%) and group B (44.8%) compared to group C (28.9%); however, there was no significant difference between group A and B (p = 0.79). Group A and B exhibited better clinical outcomes in terms of biochemical pregnancy (63.2%, 69.0%, 53.2%), clinical pregnancy (53.2%, 65.1%, 38.3%), implantation rate (46.6%, 38.5%, 34.6%), and spontaneous abortion rate (14.9%, 17.1%, 24.5%), compared to group C. The differences among three groups for multiple birth rate were significant (30.9%, 20.4%, 25.1%). In multivariate logistical regression, after adjusting for age, BMI, infertile type, IVF-failure times, and endometrium thickness, group A and B had odds ratios (OR) of achieving a successful ongoing pregnancy of 2.88 times [95% CI, 1.88-4.41] and 3.45 times [95% CI, 2.67-4.45], respectively. Among patients transferred at least two embryos, this beneficial effect was only significant in group A [OR, 1.90, 95% CI, 1.60-2.27]. Additionally, when comparing two blastocysts (D5+D5/D6, D6+D6) ET to two cleavage (D3+D3) ET, two blastocysts ET had a significantly higher chance [OR, 1.42, 95% CI, 1.22-1.65] of achieving an ongoing pregnancy. Similarly in one cleavage embryo plus one blastocyst (D3+D5/D6) ET [OR, 1.20, 95% CI, 1.58- 2.45] Limitations, reasons for caution The study has several limitations, including its retrospective observational nature, limited generalizability due to the study population being from two fertility centers in the same region, and potential biases from EHRs data source. Further studies are needed to validate these findings and explore the underlying mechanisms. Wider implications of the findings Overall, these findings suggest that both ERA-guided embryo transfer and sequential transfer methods may lead to better pregnancy outcomes compared to standard timing transfer in patients who have experienced IVF failures. Early adoption of these strategies and the transfer of two blastocysts are recommended. Trial registration number 2023(08)

O-130 The spatial conformational features of blastocysts can serve as a new basis for selection

Abstract Study question Can spatial conformational features become a new basis for blastocyst selection? Summary answer The spatial conformational features of blastocysts can be associated with clinical outcomes, which is a new basis for blastocyst selection. What is known already At present, the quality evaluation of blastocysts is two-dimensional, and there are relatively few evaluation indicators. There are now methods for exploring three-dimensional reconstruction of blastocysts, including fluorescence staining to obtain three-dimensional structures or artificial rotation to obtain images and restore three-dimensional conformations. However, one drawback of these methods is that they are far from true clinical applications. There are no reports on the reconstruction techniques that can be used in clinical blastocyst selection techniques, and there are no reports on the spatial conformational features related to them. Study design, size, duration This study included 2,141 frozen thaw single blastocyst transfer cycles at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2020 to 2021. Simultaneously collect multi-focal plane (11) image data for each blastocyst (EmbryoScope+). The inclusion criteria for patients are those under 40 years old, with an endometrial thickness of 7-16mm, and a history of embryo transfer failure of less than or equal to 1 time. Participants/materials, setting, methods This study iteratively interpolated the 11 focal planes using a multi focal plane generation network model. The contour and spatial information of blastocyst TE and ICM were obtained through deep-learning and segmentation networks. Texture information was extracted using depth estimation and image fusion and mapped to a 3D model to obtain a complete blastocyst spatial model. Then calculate a series of new spatial conformational features of the blastocyst and analyze their correlation with clinical outcomes. Main results and the role of chance We validated the model using the fluorescence reconstruction of human blastocysts as the gold standard (key indicator accuracy>90%). The obtained spatial conformational parameters of blastocysts include: Blastocyst: overall volume (BOV), cystic cavity volume (BCV), surface area (BSA); ICM: volume (IV), surface area (ISA), spatial aspect ratio (ISAr), surface sphericity (ISS), relative distance from ICM to TE (IRD), contact area with TE (ICA); TE cells: number (TN), density (TD), distribution difference (TDD), TE cell roundness (TR), circumference (TC), area (TA) and variance, TE cell aspect ratio (TMM) and variance. The BOV, BCV, and BSA of the blastocyst were positively correlated with clinical pregnancy rate (CPR). The quartile results showed significant differences in CPR when the values were >179 wμm3, 165 wμm3, and 25.8 wμm2, respectively. In terms of ICM, there was no significant difference in CPR among the IV, ISA, IRD, and ICA. However, we found ISAr and ISS had higher CPR in the range of 0.715-0.912 and 0.920-0.943, respectively. In terms of TE, TN is positively correlated with CPR. TD, TDD, TR were not significantly associated with CPR. The pleasing finding is that TC, TA, TMM, and their variances are significantly correlated with CPR. Limitations, reasons for caution The overall quality of blastocysts is relatively good, which is related to the priority thawing of the best blastocysts. Some blastocysts may appear partially out of view, leading to data unavailability and potentially affecting 3D reconstruction. Further exploration and discovery are needed for the spatial conformational features of blastocysts. Wider implications of the findings This work provides a 3D reconstruction system for blastocysts that is closer to clinical applications and discovers new spatial features that are related to clinical outcomes. This enables the study of more dimensional biological characteristics of blastocysts, and our research further promotes the development of embryo reconstruction technology. Trial registration number not applicable

Inflammatory Changes after Medical Suppression of Suspected Endometriosis for Implantation Failure: Preliminary Results.

Unexplained euploid embryo transfer failure (UEETF) is a frustrating and unanswered conundrum accounting for 30 to 50% of failures in in vitro fertilization using preimplantation genetic testing for aneuploidy (PGT-A). Endometriosis is thought by many to account for most of such losses and menstrual suppression or surgery prior to the next transfer has been reported to be beneficial. In this study, we performed endometrial biopsy in a subset of women with UEETF, testing for the oncogene BCL6 and the histone deacetylase SIRT1. We compared 205 PGT-A cycles outcomes and provide those results following treatment with GnRH agonist versus controls (no treatment). Based on these and previous promising results, we next performed a pilot randomized controlled trial comparing the orally active GnRH antagonist, elagolix, to oral contraceptive pill (OCP) suppression for 2 months before the next euploid embryo transfer, and monitored inflammation and miRNA expression in blood, before and after treatment. These studies support a role for endometriosis in UEETF and suggest that medical suppression of suspected disease with GnRH antagonist prior to the next transfer could improve success rates and address underlying inflammatory and epigenetic changes associated with UEETF.

Predicting personalized cumulative live birth rate after a complete in vitro fertilization cycle: an analysis of 32,306 treatment cycles in China

BackgroundThe cumulative live birth rate (CLBR) has been regarded as a key measure of in vitro fertilization (IVF) success after a complete treatment cycle. Women undergoing IVF face great psychological pressure and financial burden. A predictive model to estimate CLBR is needed in clinical practice for patient counselling and shaping expectations.MethodsThis retrospective study included 32,306 complete cycles derived from 29,023 couples undergoing IVF treatment from 2014 to 2020 at a university-affiliated fertility center in China. Three predictive models of CLBR were developed based on three phases of a complete cycle: pre-treatment, post-stimulation, and post-treatment. The non-linear relationship was treated with restricted cubic splines. Subjects from 2014 to 2018 were randomly divided into a training set and a test set at a ratio of 7:3 for model derivation and internal validation, while subjects from 2019 to 2020 were used for temporal validation.ResultsPredictors of pre-treatment model included female age (non-linear relationship), antral follicle count (non-linear relationship), body mass index, number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, tubal factor, male factor, and scarred uterus. Predictors of post-stimulation model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. Predictors of post-treatment model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), cumulative Day-3 embryos live-birth capacity (non-linear relationship), number of previous IVF attempts, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. The C index of the three models were 0.7559, 0.7744, and 0.8270, respectively. All models were well calibrated (p = 0.687, p = 0.468, p = 0.549). In internal validation, the C index of the three models were 0.7422, 0.7722, 0.8234, respectively; and the calibration P values were all greater than 0.05. In temporal validation, the C index were 0.7430, 0.7722, 0.8234 respectively; however, the calibration P values were less than 0.05.ConclusionsThis study provides three IVF models to predict CLBR according to information from different treatment stage, and these models have been converted into an online calculator (https://h5.eheren.com/hcyc/pc/index.html#/home). Internal validation and temporal validation verified the good discrimination of the predictive models. However, temporal validation suggested low accuracy of the predictive models, which might be attributed to time-associated amelioration of IVF practice.

Unlocking Infertility: Enhancing Pregnancy Rates With Personalized Embryo Transfers Using Optimal Time for Endometrial Receptivity Analysis in Recurrent Implantation Failure Patients Undergoing In Vitro Fertilization.

Background Infertility remains a significant global challenge, and recurrent implantation failure (RIF) poses a considerable concern in assisted reproductive technology. Understanding the factors contributing to implantation failure is essential for developing accurate diagnostic tools and treatment strategies. Endometrial receptivity (ER) during the window of implantation is crucial for successful embryo implantation in in vitro fertilization (IVF) procedures. Molecular-based endometrial receptivity analysis and next-generation sequencing provide insights into ER, but there is a lack of research on these in the Indian population, particularly in patients with RIF. This retrospective cohort study evaluates the effectiveness of Optimal Timing for Endometrial Receptivity Analysis (OpERA)-guided personalized embryo transfer (pET) in Indian patients with a history of RIF. Methodology The study includes 158 female patients with a history of failed embryo transfers who underwent OpERA testing before frozen embryo transfer. Patients were categorized based on the number of previous failed transfers. OpERA outcomes were assessed, and clinical outcomes were compared between groups undergoing preimplantation genetic testing for aneuploidy (PGT-A) with and without OpERA. Endometrial preparation involved hormone replacement therapy, and OpERA testing was performed at the Neuberg Centre for Genomic Medicine using RNA extraction, cDNA conversion, and sequencing. Results OpERA outcomes showed no significant differences in receptive rates among patient groups. Group 3, with three or more failed transfers, exhibited significantly higher biochemical pregnancy rates (BPRs), clinical pregnancy rates (CPRs), and abortion rates (ARs) compared to Groups 1 and 2. OpERA with PGT-A showed significantly higher BPR, implantation rate, CPR, and lower AR compared to OpERA without PGT-A. Conclusions OpERA-guided pET, especially with PGT-A, demonstrated improved pregnancy outcomes, particularly in patients with a history of RIF. The study emphasizes the importance of OpERA in determining optimal transfer timing, moving beyond the traditional reliance on embryo quality alone.OpERA presents promise in predicting pregnancy outcomes for Indian patients with previous IVF failures. The integration of OpERA and PGT-A represents a significant advancement in personalized reproductive medicine, offering new hope for individuals grappling with infertility complexities.

Clinical effectiveness of spindle-view intracytoplasmic sperm injection compared to conventional intracytoplasmic sperm injection in patients with poor ovarian response and previous implantation failure.

This study aimed to determine the clinical advantage of spindle-view intracytoplasmic sperm injection (SVICSI; a novel technology) over conventional intracytoplasmic sperm injection (cICSI) in patients with poor ovarian response (POR) and previous implantation failure. The study included 37 patients who underwent SVICSI followed by fresh embryo transfer (FET) at a single fertility clinic from January to December 2022, 58 patients who underwent cICSI followed by FET at the same fertility clinic from January to December 2021 as a control group. All study participants met the Bologna criteria for POR and had at least three or more previous failed embryo transfers. The number of blastocyst transfers was significantly higher in the SVICSI group than in the cICSI group. A good-quality cleavage embryo rate, blastocyst rate, and good-quality blastocyst rate were also significantly higher in the SVICSI group than in the cICSI group. There were no significant differences in the rates of fertilization, implantation, clinical pregnancy, or clinical abortion between the two groups. In patients with POR, those who underwent SVICSI appeared to have better embryos than those who underwent cICSI. However, whether SVICSI improved clinical outcomes such as implantation and pregnancy rates cannot be proven.

#196 : Office Hysteroscopy Results in Patients with Recurrent Implantation Failure at Tam Anh General Hospital

Background and Aims: To describe the clinical characteristics and evaluate the results of office hysteroscopy in patients with recurrent implantation failure at Tam Anh General Hospital. Methods: A descriptive study on 151 patients at Tam Anh General Hospital who had failed embryo transfer twice or more consecutively was carried out from January 2021 to March 2023. Results: 151 patients were included in the study, 41,1% of which had unexplained infertility. The mean age and duration of infertility were 34,5 ± 5,2 years and 5,7 ± 3,4 years, respectively. 55,0% of patients exhibited uterine cavity abnormalities during office hysteroscopy, with the most common is endometritis accounting for 29.8%. The median time to perform the procedure was 3 (2) minutes, the mean VAS pain score was 3,2 ± 1,1 points. No complications related to office hysteroscopy were noted. Conclusions: A office hysteroscopy was able to detect intrauterine pathologies which were missed by other investigative modalities. In individuals who have experienced repeated implantation failure, office hysteroscopy is a safe and practical approach that should be recognized as a crucial tool for intrauterine evaluation.

#130 : Food Intolerance and Conception in Women Suffering Repeated Implantation Failure

Background and Aims: Food-specific immunoglobulins, in combination with the elevated reactive oxygen species and other inflammatory components, have been indicated to represent immunological response to food consumed. This study aimed to investigate the relationship of food intolerance and conception in women receiving IVF treatments. Method: Infertile women who had experienced at least two failed embryo transfer treatments were investigated between June 2017 and August 2021 in TUBE Fertility Clinic. The whole blood 20 mL was taken from cubital vein and complete food panel examination employing ELISA analyses were designed to assay food-specific IgG and IgE antibodies. The levels of IgG antibodies were presented through spectrophotometric analysis (Table 1). The IgG tests included 5 dairy components, 25 grains/legumes/nuts, 18 vegetables, 9 egg/meat/poultry, 21 fruits, 9 herbs/spices, 18 fish/crustacea/mollusk, and 9 miscellaneous foods including baker’s yeast. Infertile women were asked to refrain from those foods according to the level of hypersensitivity, six months were required for those with reaction class III to IV, and three months for those with reaction class II. Further IVF and embryo transfer cycles were then carried out afterwards. Results: In total, 67 infertile women enrolled in this study. Their mean age was 38.2 ± 4.3 years old. They had received 2.7 ± 1.6 previous IVF/ET cycles. All 67 women showed positive IgG and 14 (21%) women with positive IgE investigated. Grains/legumes/nuts (90%) and dairy products (86.6%) were the most common hypersensitive foods (Table 2). Thirty-one (46.3%) women conceived in their successive ET cycles after refraining from hypersensitive foods. Lower pregnancy rates were noted in those with hypersensitivity to fish/crustacea/mollusk and eggs/meat/poultry, even after refraining from those foods. Conclusion: High percentage of infertile women suffering repeated failed IVF/ET cycles presented with different levels of hypersensitivity to foods. Avoidance of hypersensitive foods may help them achieve future conception.

#141 : Enhanced Luteal Support Following IVF/ICSI for Women with Two or More Good-Quality Embryo Transfer Failures Using Both Subcutaneous and Vaginal Progesterone: A Retrospective Cohort Study

Background and Aims: Utilizing progesterone to support the luteal phase (LP) in in vitro fertilization is a well-established practice. Subcutaneous progesterone (SC-P) administration has shown pregnancy rates comparable to vaginal progesterone (Vag-P). However, data are not available regarding the efficacy of combining SC-P with Vag-P for women with multiple good-quality embryo transfer (ET) failures. Therefore, this study aims to evaluate the effectiveness of adding SC-P to Vag-P in women who had not conceived following two or more good-quality ETs. Method: A retrospective cohort analysis of data collected from a university-affiliated fertility centre in the UK between January 2020 to May 2022. A total of 224 embryo transfer cycles, including 65 fresh embryo transfer (fresh-ET) cycles and 159 frozen embryo transfer (FET) cycles in women who had not conceived or experienced miscarriages following two or more good-quality ETs, were analysed. The luteal support protocol was either micronized Vag-P (gel 90mg daily in fresh-ET cycles or pessaries 800mg daily in FET cycles) plus SC-P 25mg once daily (enhanced group) or Vag-P alone (control group). The pregnancy outcomes between the two groups were compared. Clinical pregnancy rates (CPR) represented the primary outcome. Results: In fresh-ET cycles, the enhanced group resulted in higher CPR than the control group. However, statistical significance was not achieved (40% (14/35) vs. 30% (9/30), p=0.40; multivariate analysis adjusted OR 1.54, 95% CI 0.48–4.93, p=0.468). In FET cycles, CPRs were comparable between the enhanced group and the control group (32.3% (21/65) vs. 31.9 % (30/94), p=0.958; multivariate analysis adjusted OR 0.98, 95% CI 0.47–2.03, p=0.953). In both fresh and frozen cycles, no significant difference was observed regarding the positive pregnancy test and miscarriage rates between the two groups. Conclusion: Adding SC-P to Vag-P did not improve pregnancy outcomes for women who had not conceived following two or more good-quality ETs.

Evaluation of the effect of endometrial scratch by hysteroscopic scissors on frozen embryo transfer outcomes: A historical cohort study

Background: Endometrial scratch (ES) has been suggested to improve assisted reproductive techniques success rates by investigating implantation failure.
 Objective: In this study, we evaluated the effect of ES on the outcomes of frozen embryo transfer (FET) in women with at least 2 failed embryo transfer cycles.
 Materials and Methods: In this historical cohort study, medical data of 236 infertile women who underwent in-vitro fertilization-FET at Ebne-sina Infertility Center, Tehran, Iran, from January 2015-December 2021 was extracted from their medical records. Based on having ES before FET, they were assigned to either the scratch (n = 118) or the no-scratch group (n = 118). We compared these groups regarding pregnancy rates and outcomes.
 Results: The demographic characteristics were similar in both groups regarding weight, body mass index, the number of previous embryo transfers, and the duration of infertility. However, the scratch group had a slightly higher mean age (32.31 vs. 29.96 yr, p < 0.001). No statistically significant difference was observed between groups regarding pregnancy rate (p = 0.89). No significant association was observed between scratch, infertility duration, the number of previous FET attempts, and the likelihood of pregnancy in a logistic regression model. No major complications were observed.
 Conclusion: Hysteroscopic endometrial scratching with scissors probably has no effect on FET outcomes, including pregnancy or live birth rates.
 Key words: Hysteroscopy, Infertility, Pregnancy rate, Live birth.

Comparative effectiveness and safety of 36 therapies or interventions for pregnancy outcomes with recurrent implantation failure: a systematic review and network meta-analysis.

To investigate the effectiveness and safety of 36 different therapies for recurrent implantation failure (RIF) patients. We searched PubMed, Embase, the Cochrane Library (CENTRAL), Web of Science, and China National Knowledge Internet (CNKI) from inception to August 24, 2022, with language in both English and Chinese. Randomized controlled trials (RCTs) and observational studies that provided data with one of pregnancy outcomes on RIF patients were included in the network meta-analysis (NMA). The odds ratios (OR) and 95% credible interval (CrI) on pregnancy outcomes were summarized by NMA with a random-effects model. We also analyzed data from only RCTs and compared whether the optimal treatment is the same for different failed embryo transfer attempts. The total of 29,906 RIF patients from 154 clinical studies (74 RCTs and 80 non-RCTs) were included in the NMA. In terms of implantation rate (IR), growth hormone (GH) (OR: 3.32, 95% CrI: 1.95-5.67) is the best treatment in all included studies; IVIG+PBMC (5.84, 2.44-14.1) is the best for clinical pregnancy rate (CPR); hyaluronic acid (HA) (12.9, 2.37-112.0) for live birth rate (LBR); and aspirin combined with glucocorticoids (0.208, 0.0494-0.777) for miscarriage rate (MR). The two-dimensional graphs showed that GH could maximize IR and CPR simultaneously; HA and GH could simultaneously increase IR and LBR to a large extent; HA could maximize IR and minimize MR. IVIG+PBMC, GH, and embryo medium enriched with HA could significantly improve pregnancy outcomes in patients with RIF. It appears that combination therapy is a potential administration strategy. This study has been registered on PROSPERO (CRD42022353423).

The effect of chronic endometritis on the clinical outcomes of patients with failure of first embryo transfer

Objective: To investigate the effect of chronic endometritis (CE) on the clinical outcomes of patients with failure of first embryo transfer. Methods: A total of 5 605 cycles of frozen-thawed single blastocyst transfer in the reproductive center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to June 2021 were retrospectively collected. After the failure of first embryo transfer, all patients underwent hysteroscopy, and when necessary, endometrial pathology and immunohistochemistry were combined to diagnose CE. Patients were divided into two groups: non-CE group (5 033 cycles) and CE treatment group (572 cycles). The main outcome was live birth rate and the secondary outcomes included clinical pregnancy rate and early abortion rate. The quantitative data were represented by Median (Q1, Q3). The rank sum test was used for comparison between groups. The factors related to live birth rate were analyzed by binary logistic regression model. Results: The incidence of CE was 10.21% (572 cycles) in patients with the failure of first embryo transfer. The maternal age in the non-CE group was 31.0 (29.0, 34.0) years old, and that in the CE treatment group was 31.0 (29.0, 34.0) years old (P<0.001). There was a statistically significant difference in endometrial preparation between the two groups (P=0.010). The endometrial thickness in the CE group was 9.0 (8.2, 10.3) mm on progesterone transformation day, which was higher than that of [9.5 (8.6, 11.0) mm] in the non-CE group (P<0.001). There was no significant difference in clinical pregnancy rate (60.3% (3 035 cycles) vs 63.1% (361 cycles), P=0.193), early abortion rate (17.1% (520 cycles) vs 20.5% (74 cycles), P=0.112) and live birth rate (49.2% (2 477 cycles) vs 49.3% (282 cycles), P=0.969) between the non-CE group and the CE treatment group. The maternal age, endometrial thickness on progesterone transformation day and blastocyst grade were related factors of the live birth rate, and the OR(95%CI) were 0.94 (0.93-0.96), 1.10 (1.06-1.14) and 2.07 (1.84-2.32)), respectively (all P<0.001). Compared with the non-CE group, the CE treatment group did not affect the live birth rate after transplantation, the aOR (95%CI) was 0.99 (0.82-1.18), P=0.882. Conclusions: For patients who underwent the failure of first embryo transfer, hysteroscopy is recommended before single frozen blastocyst transfer, and if necessary, combined with immunohistochemical screening for CE. After standardized treatment, CE patients could obtain similar clinical pregnancy rate, early miscarriage rate and live birth rate as non-CE patients.

O-145 From mathematical modeling to real-life clinical data: live birth rates up until the tenth blastocyst transfer without PGT-A

Abstract Study question What is the cumulative live birth rate (CLBR) from the first until the tenth consecutive blastocyst transfer, across all age-groups, if no PGT-A is applied? Summary answer Our clinical data confirm existing mathematical models: without PGT-A, a CLBR of 70.0% after three, 88.9% after seven and 95.9% after ten transfers was observed. What is known already The rate of ‘true’ repeated implantation failure (RIF) from endometrial origin is an important topic of debate in our scientific community. Its existence was challenged with the reporting of CLBRs &amp;gt;90% after three consecutive euploid blastocyst transfers. These findings are not directly applicable when PGT-A is not routinely performed. Mathematical models have been developed to tackle this issue by taking into account (1) the anticipated euploidy rate based on the oocyte’s age and (2) the probability of an euploid embryo to implant. So far, no actual patient data have confirmed the validity of this model. Study design, size, duration This is a single-center, retrospective, observational cohort study including 4320 unique women who underwent up to ten consecutive blastocyst transfers between 2010 and 2020. All age categories were included, as well as fresh/frozen and single/double embryo transfers. Patients using donor oocytes, PGT or cleavage stage embryo transfers were excluded or led to drop-out in the study. Participants/materials, setting, methods Patient characteristics were retrieved and cumulative outcomes were analyzed. A Kaplan-Meier curve was plotted for CLBR. For each transfer cycle the live birth rate (LBR), double embryo transfer rate (DET) and multiple pregnancy rate were calculated. Main results and the role of chance The mean age of the patients included in the study was 31.8 (±4.5) years at the time of the first ovarian stimulation. The mean body mass index was 23.7 (± 4.3) kg/m2 and mean basal FSH 6.8 (±2.3) IU/L. The mean number of stimulations per patient was 1.21 (±0.5) and a total mean number of 4.6 (±3.2) blastocysts were obtained per patient. The mean time to the pregnancy leading to live birth was less than one year (0.3±0.7). We observed the highest LBR (46.3%, 2002/4320) after the first blastocyst transfer followed by 35.4% (593/1672), 32.3% (275/851), 32.2% (147/456), 32.8% (78/238), 21.3% (26/122), 23.9% (17/71), 25.6% (10/39), 31.8% (7/22), 18.2% (2/11) for the second until the 10th transfer, respectively. The Kaplan-Meier curve showed CLBRs to mount from 70.0% after the third, up to 88.9% after the seventh and 95.9% after the tenth blastocyst transfer. We noticed a steady increase in DET rate from only 6.4% in the first up to &amp;gt; 27% as of the fourth and &amp;gt;44% as of the seventh transfer with acccompanied multiple pregnancy rates of 1.3% over 10.9% and 11.8%, respectively. Limitations, reasons for caution The main limitation is the study’s retrospective nature. As our center performs cleavage stage and blastocyst transfer, the included population is a good prognosis one as embryology allowed to perform extended culture. Nevertheless, to investigate RIF due to endometrial causes, this could also be seen as an asset. Wider implications of the findings These patient data confirm mathematical models and further question the prevalence of insurmountable, endometrial origin RIF. Preserved LBRs (even in higher cycle ranks) and a CLBR &amp;gt;95% provide hope and reassurance to couples with failed embryo transfers and encourage them to continue treatment if blastocysts are available. Trial registration number NA

P-506 Administration of low molecular weight heparin alleviate immune physiology in recurrent implantation failure modulating CCL2-CCR2 axis during frozen embryo transfer: effort from clinic to bench

Abstract Study question Does low molecular-weight heparin (LMWH) administration modulate CCL2-CCR2 axis in recurrent implantation failure (RIF) patients undergoing frozen embryo transfer (FET) to improve pregnancy salvage? Summary answer LMWH treatment attests beneficial immunological tolerance in vivo and in vitro through modulation of CCL2-CCR2 axis suggesting possible restoration of weak pro-inflammatory response in RIF. What is known already Immune imbalance in proportion of activated macrophages (M1) and alternatively activated macrophages (M2) impede endometrial receptivity and contribute to RIF. CCL2 (M2-asscociated) - CCR2 (t-helper-2 associated) axis orders macrophage polarization by influencing expression of functionally relevant and polarization associated genes and down-modulate pro-inflammatory cytokine production. Immunological effects of LMWH regulate pregnancy-promoting processes at foetal-maternal interface to provide an appropriate implantation process; outcomes being controversial. We aim to investigate the potential immunoregulatory properties of LMWH in patients with RIF undergoing FET, with particular regard to effects on macrophages and T-helper (Th) cells; two key players in promoting immune tolerance during pregnancy. Study design, size, duration This prospective cohort study constituted 121 women with RIF (≥3 failed embryo transfer) undergoing FET at Institute of Reproductive Medicine between January to October 2022. An incremental dose (4-12mg/day) of estradiol with (Group A; n = 62) or without (Group B; n = 59) LMWH (40 mg/day) from d2 to d12 with sequential ultrasound following intra-muscular progesterone (100mg/day) for 4 days was administered in all participants. Blood samples were collected to isolate plasma and peripheral-blood-mononuclear-cells (PBMCs). Participants/materials, setting, methods Monocytes were purified from PBMCs and cultured with GM-CSF or M-CSF to analyze factor/s which control CCL2-CCR2 expression along macrophage polarization by flow cytometry. Influence of CCL2 on GM-CSF-cultured macrophages (GM-MØ) and M-CSF-cultured macrophages (M-MØ) specific gene markers was analysed using quantitative RT-PCR (qRT-PCR). To assess immunological effects of LMWH in-vivo, Th-specific cytokine profile/s and respective chemokines were measured from plasma by Luminex xMAP technology. Statistical significance was set at p &amp;lt; 0.05. Main results and the role of chance The clinical pregnancy rate was higher in group A. (A vs B: 37.09% vs. 27.11%, p = 0.24). LMWH exposure significantly decreased the secretion of CCL2 (p &amp;lt; 0.01) and CCL22 (p &amp;lt; 0.001) in GM-CSF-cultured macrophages, while it increased CCL2, CCL20 production (p &amp;lt; 0.001) in both GM-MØ and M-MØ. However, expression of CCL7 was significantly lower (p &amp;lt; 0.01) in M-MØ and GM-MØ generated from CD14+ CD16+ monocytes and CD14 ++ CD16- monocytes respectively under LMWH exposure. qPCR analysis revealed a significant increase (p &amp;lt; 0.01) in the expression of various GM-MØ–specific genes including EGLN3, and SERPINE1 in macrophage supernatant post LMWH treatment. Expression of various M-MØ-specific marker/s such as IGF1, FOLR2, and HTR2B, is significantly up-regulated (p &amp;lt; 0.01) in Group B. Group A, although documented a decreased concentration/s (pg/ml) of Th17-type cytokine/s (IL-6 (1.88 ± 0.65 vs. 0.91 ± 0.43; p &amp;lt; 0.04 and IL-23 (17.94 ± 9.76 vs. 7.78 ± 3.43; p &amp;lt; 0.01)), at end of treatment, concentration of TGF-β was significantly higher (3909.05 ± 1248.35 vs. 2469.83 ± 1058.71; p &amp;lt; 0.01) which cue to probable maintenance in balance of inflammatory response at the time of implantation. No differences were observed in Th1-type cytokine level/s (IFN-γ and TNF-α). CXCL10, CXCL11, CXCL1, CXCL8, CCL17, CCL22 do not differ in vivo. Limitations, reasons for caution Beneficial effects of LMWH administration with a good sample size are clearly needed to confirm this hypothesis; hence result/s should be dealt with caution. Further to this, inclusion of other arm/s (corticosteroids, intralipid and/or intravenous immunoglobulin) will make the study much robust and conclusive. Wider implications of the findings The identification of atypical Th1-associated pro-inflammatory effects of LMWH drives to evaluate modulation of CCL2 expression to limit or potentiate macrophage activation in RIF; especially where anticoagulant effect is not the primary goal. Further, modification of cytokine expression/s might potentiate novel strategy derived from deregulated macrophage polarization. Trial registration number Not Applicable

P-368 Clinical impact of personalized embryo transfer (pET) guided by endometrial receptivity analysis (ERA) in patients with ≥ 1 failed transfers

Abstract Study question Does pET following ERA increase pregnancy (PR), ongoing pregnancy per transfer (OGPR) and live birth rates (LBR) in patients with ≥ 1 previous failed transfer? Summary answer In this group of patients, pET guided by ERA obtained a significantly higher PR, OGPR and LBR versus standard embryo transfer. What is known already pET consists of synchronizing embryo transfer with the optimal endometrial receptivity status of the patient by the transcriptomics identification of her personalized window of implantation (WOI). Controversial results have been published regarding the clinical usefulness of this precision medicine diagnosis in a range of clinical indications. Here we present data from patients with ≥ 1 previous failed transfer undergoing pET guided by ERA. Study design, size, duration Multicenter retrospective study involving 526 patients with at least one previous failed embryo transfer (ET) between 2017 and 2021. These patients were divided into two groups: cases (pET guided by ERA) (n = 385), or controls (standard blind ET) (n = 141). Clinical outcomes compared were PR, OGPR and LBR for each group. Participants/materials, setting, methods Age, body mass index (BMI), previous failed attempts, proportion of embryos with PGT-A and transferred embryo quality were compared between the two groups. ERA test was performed in HRT cycles and subsequent embryo transfer was carried out replicating the same conditions and following the recommendation given for pET. Standard ET was also performed in HRT cycles. Wilcoxon rank sum test was applied to quantitative comparations. Chi-square test was done for categorical variables. Main results and the role of chance In this retrospective analysis, age and number of previous failed ET was higher in the ERA group (p &amp;lt; 0.05). Clinical results in terms of PR, OGPR and LBR were significantly higher when pET guided by ERA was performed when compared to the non-ERA group. Limitations, reasons for caution This is a retrospective study, having limitations of its nature. Wider implications of the findings These results show that pET guided by ERA in patients with ≥ 1 failed transfers increased significantly PR, OGPR and LBR versus standard blind ET. Trial registration number Hospital Clínico de Valencia Ethic Committee approval nº. 2021/018.