In Vitro Fertilization Outcomes Research Articles

Optimizing trigger timing in minimal ovarian stimulation for In Vitro fertilization using machine learning models with random search hyperparameter tuning

Various studies have emphasized the importance of identifying the optimal Trigger Timing (TT) for the trigger shot in In Vitro Fertilization (IVF), which is crucial for the successful maturation and release of oocytes, especially in minimal ovarian stimulation treatments. Despite its significance for the ultimate success of IVF, determining the precise TT remains a complex challenge for physicians due to the involvement of multiple variables. This study aims to enhance TT by developing a machine learning multi-output model that predicts the expected number of retrieved oocytes, mature oocytes (MII), fertilized oocytes (2 PN), and useable blastocysts within a 48-h window after the trigger shot in minimal stimulation cycles. By utilizing this model, physicians can identify patients with possible early, late, or on-time trigger shots. The study found that approximately 27 % of treatments administered the trigger shot on a suboptimal day, but optimizing the TT using the developed Artificial Intelligence (AI) model can potentially increase useable blastocyst production by 46 %. These findings highlight the potential of predictive models as a supplementary tool for optimizing trigger shot timing and improving IVF outcomes, particularly in minimal ovarian stimulation. The experimental results underwent statistical validation, demonstrating the accuracy and performance of the model. Overall, this study emphasizes the value of AI prediction models in enhancing TT and making the IVF process safer and more efficient.

Artificial intelligence system for outcome evaluations of human in vitro fertilization-derived embryos.

In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on days or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for aneuploidy prediction and consequent live-birth outcomes. These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709-0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Our study underscores the AI model's ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

Exposure of women undergoing in-vitro fertilization to per-and polyfluoroalkyl substances: Evidence on negative effects on fertilization and high-quality embryos

In April 2023, the World Health Organization (WHO) reported that 17.5% of the global adult population experience infertility. What may be the contribution of per-and polyfluoroalkyl (PFAS) to this global public health problem?This study explored the associations between in vitro fertilization (IVF) outcomes and plasma concentrations of individual PFAS and PFAS mixtures in women undergoing in vitro fertilization and embryo transfer (IVF-ET) and how these exposures might affect IVF outcomes. We analyzed 8 PFASs in plasma samples from women (N = 259) who underwent IVF treatment. In multivariable generalized linear mixed models, there were statistically significant associations of higher plasma concentrations of PFNA with reduced numbers of total retrieved oocytes [12.486 (95%CI: 0.446,25.418), p trend = 0.017], 2 PN zygotes [6.467(95%CI: 2.034,14.968), p trend = 0.007], and cleavage embryos [6.039(95%CI: 2.162,14.240), p trend = 0.008]. Similarly, there was a continuous decline in the numbers of retrieved 2 PN zygotes and cleavage embryos with increasing concentration of PFOS [6.467(95%CI: 2.034,14.968), p trend = 0.009 and 6.039(95%CI: 2.162,14.240), p trend = 0.031,respectively] and a negative association between PFHxS concentrations and clinical pregnancy during the initial cycles of frozen ET [0.525(95%CI:0.410,0.640), p trend = 0.021]. To investigate the joint effect of PFAS mixtures, a confounder-adjusted BKMR model analysis showed inverse relationship between PFAS mixtures and the number of high-quality embryos, 2 PN zygotes and cleavage embryos, to which the greatest contributors to the mixture effect are PFDeA and PFBS, respectively. It demonstrated that PFAS exposure might exert negative effects on oocyte yield, fertilization and high-quality embryo in women undergoing IVF. These findings suggest that exposure to PFAS may increase the risk of female infertility and further studies are needed to uncover the potential mechanisms underlying the reproductive effects associated with PFAS.

Association of ambient PM2.5 and its components with in vitro fertilization outcomes: The modifying role of maternal dietary patterns

Despite the associations of dietary patterns and air pollution with human reproductive health have been demonstrated, the interaction of maternal preconception diet and PM2.5 and its components exposure on in vitro fertilization (IVF) treatment outcomes has not been investigated. A total of 2688 couples from an ongoing prospective cohort were included. Principle component analysis with varimax rotation was performed to determine dietary patterns. One-year and 85-day average PM2.5 and its components exposure levels before oocyte retrieval were estimated. Generalized linear regression models were conducted to assess the association of dietary patterns and PM2.5 and its components exposure with IVF outcomes. Interactive effects of dietary patterns on the association between PM2.5 and its components and IVF outcomes were evaluated by stratified analyses based on different dietary patterns. A positive association between the “Fruits-Vegetables-Dairy” pattern and normal fertilization (p-trend = 0.009), Day 3 available embryos (p-trend = 0.048), and top-quality embryos (p-trend = 0.041) was detected. Conversely, women with higher adherence to the “Puffed food-Bakery-Candy” pattern were less likely to achieve Day 3 available embryos (p-trend = 0.042) and top-quality embryos (p-trend = 0.030), clinical pregnancy (p-trend = 0.049), and live birth (p-trend = 0.020). Additionally, increased intake of animal organs and seafood improved the odds of live birth (p-trend = 0.048). Exposure to PM2.5, SO42-, organic matter (OM), and black carbon (BC) had adverse effects on embryo development and pregnancy outcomes. Furthermore, our findings indicated that the effects of PM2.5 components exposure on normal fertilization and embryo quality were modified by the “Grains-Tubers-Legumes”. Moreover, moderate intake of animal organs and seafood appeared to attenuate the effect of NO3- and NH4+ on the risk of early abortion. Our findings provide human evidence of the interaction between dietary patterns and PM2.5 exposure on IVF outcomes during preconception, implicating the potential for dietary interventions in infertile women to improve reproductive outcomes under conditions of unavoidable ambient air-pollutant exposure.

O-157 The effect of growth hormone on the euploid rate and morphokinetic signature of blastocysts in patients with advanced maternal age : a randomized controlled trial

Abstract Study question Does growth hormone (GH) supplementation during ovarian stimulation affect the euploid rate and morphokinetic characteristics of euploid embryos in patients with advanced maternal age (AMA)? Summary answer GH supplementation improved the probability of obtaining euploid blastocysts in women with AMA, while did not affect the morphokinetic parameters of the euploid embryos. What is known already Studies have demonstrated that supplementation with GH during ovarian stimulation (OS) has positive impact on the clinical outcomes of in vitro fertilization (IVF). However, few studies have investigated the association of GH supplementation with the ploidy status of embryos. Meanwhile, it is unclear whether GH supplementation affects the morphokinetic signatures and the transfer outcomes of euploid blastocysts. Therefore, the underlying reason for the effect of GH on IVF outcomes remains largely unknown. Study design, size, duration This is a single centre open-labelled randomized controlled trial conducted at single IVF center from August 2022 to August 2023. A total of 441 patients were screened for eligibility and 309 patients were enrolled and allocated. The primary outcome was the proportion of cycles which obtained euploid blastocysts. Secondary outcomes included euploid blastocyst rate per cohort, euploid blastocyst rate per cycle and morphokinetic parameters of euploid embryos obtained with or without GH supplementation. Participants/materials, setting, methods A total of 309 patients aged 38–46 years who underwent their first preimplantation genetic testing for aneuploidy (PGT-A) cycle using antagonist protocol were randomized into the GH group or the control group at 1:1 ratio, with all embryos cultured in the time-lapse monitoring system. Patients in the GH group received 2 IU/day subcutaneous GH from the 2nd day of the previous menstrual period until the day of trigger, for a total of approximately 6 weeks. Main results and the role of chance The baseline and cycle characteristics between the two groups were similar. The proportion of cycles which obtained euploid blastocysts was significantly higher in the GH group (44.74% vs 31.85%, p = 0.02). The GH group had a significantly higher euploid blastocyst rate per cohort (38.46% vs 28.01%, p = 0.01) and mean euploid blastocyst rate per cycle (per biopsy cycle 0.38±0.43 vs. 0.26±0.39, p = 0.02; per OS cycle 0.29±0.41 vs. 0.19±0.36, p = 0.03). Multivariate logistic regression indicated GH supplement was an independent factor for acquisition of euploid embryos (adjusted risk ratio=1.79, 95%CI [1.06-2.99], p = 0.03). We did not observe a statistically significant difference in the morphokinetic parameters and transfer outcomes of the euploid embryos acquired with or without GH supplemented. Limitations, reasons for caution This was a single center study which limited the sample size, further limiting the number of patients with euploid blastocysts analyzed for the morphokinetic parameters and transfer outcomes. Meanwhile, affordability may also introduce selection bias since patients were required to pay for GH. Wider implications of the findings Our research presents new evidence that GH supplementation AMA patients increased the probability of obtaining euploid blastocysts, and explains the underlying reason for the positive effect of GH on IVF outcomes in existing studies. The effect of GH on morphokinetic parameters and transfer outcomes of euploid embryos warrants further investigation. Trial registration number NCT05447208, www.clinicaltrials.gov.

O-257 Comparing the accuracy of the novel clustering model versus phenotype classification in predicting live birth in polycystic ovary syndrome women undergoing In-Vitro fertilization

Abstract Study question Is the clustering model more accurate than phenotype classification in predicting live birth in polycystic ovary syndrome (PCOS) women undergoing in vitro fertilization (IVF)? Summary answer Novel PCOS clusters, identified by patients’ endocrine and metabolic profiles, more accurately predict live birth rates in women undergoing IVF than the traditional phenotype classification What is known already PCOS is a heterogeneous condition that affects fertility and IVF success. It is classified based on three factors: hyperandrogenism (HA), ovulatory dysfunction (OD), and polycystic ovaries (PCOM). The ESHRE/ASRM classification system identifies four phenotypes: A (including all three factors), B (HA and OD), C (HA and PCOM), and D (OD and PCOM). Although this classification is widely used, its focus solely on clinical signs and symptoms, while neglecting underlying endocrine and metabolic factors, may limit its effectiveness in predicting fertility outcomes in PCOS patients. Therefore, classifying PCOS patients may require a more comprehensive and inclusive assessment approach. Study design, size, duration This prospective cohort study was conducted from June 2020 to August 2022 at a tertiary IVF center in Ho Chi Minh City, Vietnam. Clustering models were built based on the endocrine and metabolic profiles of 731 PCOS patients. Patients were grouped into novel clusters based on their endocrine and metabolic profiles and compared with traditional phenotypes classification. The primary outcome measured was the live birth rate. Participants/materials, setting, methods Patients aged 18–45, diagnosed with PCOS according to the Rotterdam 2003 criteria, and undergoing IVF treatment were included in the study. Patients with hypothyroidism, Cushing’s syndrome, congenital adrenal hyperplasia, or contraindications to hormonal treatment were excluded. We employed Gaussian Mixture Models for clustering, using endocrine and metabolic data as the key features. We then compared the accuracy of the clustering model with phenotype classification in predicting IVF outcomes using a logistic regression model. Main results and the role of chance We identified three distinct clusters among polycystic ovary syndrome (PCOS) patients. Cluster 0 (n = 298) was characterized by significant insulin resistance and dyslipidemia. Cluster 1 (n = 219) displayed the lean PCOS phenotype, and Cluster 2 (n = 214) had moderate insulin resistance with severe hyperandrogenism. Our findings indicated that Clusters 1 and 2 had a higher cumulative live birth rate (CLBR) (39.7% and 37.9% versus 28.5% in Cluster 0, p = 0.015) and lower gestational diabetes rates (8.68% and 6.07%, respectively) compared to Cluster 0 (12.4%, p = 0.048). Additionally, the prevalence of hypertensive disorders during pregnancy showed differences across clusters (3.69% in Cluster 1, 0.46% in Cluster 2, and 2.8% in Cluster 0, p = 0.059). In contrast, the traditional phenotype classification did not demonstrate significant differences in CLBR, gestational diabetes, and hypertensive disorders. The cluster-based method provided a more accurate prediction of CLBR using logistic regression, with an AUC of 0.67 (95% CI: 0.57-0.76) compared to 0.49 (95% CI: 0.41-0.59) for traditional classifications (p = 0.001) Limitations, reasons for caution This is a single-center study conducted on Vietnamese patients. Therefore, the generalizability may be limited. The novel clustering’s predictive value for IVF outcomes in PCOS patients requires further validation in prospective studies. Wider implications of the findings This study suggests a potential shift towards personalized IVF treatment strategies for PCOS, using machine learning-based PCOS clustering identified by patients’ endocrine and metabolic profiles. Trial registration number NCT04364087

O-163 The effect of ambient exposure to air pollutants on live birth rates in frozen embryo transfer cycles

Abstract Study question Do air pollutants during oocyte retrieval (OPU) and frozen embryo transfer (FET) affect in vitro fertilization (IVF) outcomes? Summary answer Environmental exposure to increased concentrations of CO either on oocyte retrieval or embryo transfer day negatively influences clinical outcomes in FET cycles. What is known already Exposure to air pollution is linked to adverse perinatal outcomes and reduced fecundity, yet its effect on fertility and IVF cycles is inconclusive. Previous studies explored associations between air pollutant concentrations and IVF outcomes with conflicting results. Nevertheless, few assessed different pollutants’ effects either on oocyte retrieval or embryo transfer days on live birth rates. While Asian and American studies suggest that pollutants affect pregnancy rates, from European studies failed to show meaningful differences in live birth rates. Considering varying pollutant levels globally, we aimed to evaluate their impact on a European population’s fertility outcomes. Study design, size, duration A retrospective cohort study analysed 1960 FET cycles conducted by a university affiliated fertility center in Europe between January 2017 to December 2022. Participants/materials, setting, methods Daily average ambient concentrations of five air pollutants (PM2.5, NO, SO2, CO, and O3) were obtained from an urban air quality monitoring station on the day of oocyte retrieval and the day of FET. Tertiles (T1, T2, T3) of each pollutant served as cut-off levels. Multiple logistic regression analysis assessed associations between pollutant exposure and pregnancy outcomes, adjusted for confounders. Main results and the role of chance Overall pregnancy and live birth rates following FET were 52.55% and 40.71%, respectively. When analysis the results according to air pollutants on the day of FET, ambient exposure to CO was significantly associated with up to 36% lower live birth (T2, OR: 0.64, 95% CI: 0.49—0.84; T3, OR: 0.67, 95% CI: 0.51—0.88; both compared to T1). Higher CO concentrations on the FET day were positively associated with increased miscarriage rates of up to 75% (T2, OR: 1.75, 95% CI: 1.12—2.75; T3, OR: 1.63, 95% CI: 1.04—2.56; both compared to T1). Limitations, reasons for caution The retrospective nature of the study and the omission of various potential covariates including environmental and patient factors that could affect IVF outcomes, limit our findings. Exposure assessment exclusively considered specific IVF days, and reliance on data from one air quality station reduces accuracy. Caution advised when interpreting the results. Wider implications of the findings This study highlights the potential impact of air quality on IVF cycle outcomes. Further investigations are needed to determine vulnerable IVF cycle phases and clarify mechanisms underlying fertility impairment. Trial registration number not applicable

P-793 New approaches for treating diminished ovarian reserve: MSC-derived extracellular vesicles and autologous platelet rich plasma

Abstract Study question Does intraovarian injection of MSC-Derived Extracellular Vesicles (EVs) and autologous platelet rich plasma (PRP) improves the outcome of IVF in women with Diminished Ovarian reserve? Summary answer EVs and PRP therapies increse Antral follicle count (AFC), lower FSH level and result in higher amount of mature oocytes and blastocysts What is known already Diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI) are significant impediments to the success of in vitro fertilization (IVF). Current strategies for ovarian stimulation primarily affects only the growth of antral follicles. Even in scenarios where ovarian ovulatory function is compromised, a reservoir of dormant follicles persists, which could potentially be activated by stem cells. Mesenchymal stem cells (MSCs), owing to their multipotent differentiation capabilities and paracrine signaling properties, have emerged as leading candidates for innovative therapeutic approaches. Recent scientific inquiries have highlighted the paracrine impact of EVs secreted by stem cells, underscoring their prospective therapeutic relevance. Study design, size, duration This prospective interventional study was conducted at the V.I. Kulakov Scientific Research Center for Obstetrics, Gynecology, and Perinatology in Russia. It involved 60 infertile female participants aged 20 to 38 years, each with DOR and a history of at least two unsuccessful IVF cycles. These participants were enrolled in the study during their subsequent IVF cycle. Prior to inclusion, all patients provided written informed consent. Participants/materials, setting, methods Patients in group 1 (n = 30) received treatment with exosomes derived from human umbilical cord mesenchymal stem cells (HUC-MSCs-Exos) prior to initiating their in vitro fertilization (IVF) cycle. In contrast, participants in group 2 (n = 30) underwent intraovarian therapy with autologous platelet-rich plasma (PRP) in preparation for their IVF cycle. The comparative analysis encompassed antral follicle count (AFC), anti-Müllerian hormone (AMH) levels, follicle-stimulating hormone (FSH) levels, ovarian stimulation outcomes, and the primary characteristics of oogenesis and embryogenesis. Main results and the role of chance After transplantation of EVs and PRP the ovarian function-related hormone levels and the AFC returned to nearly normal parameteres.Meanwhile, after exosomal treatment the improvement in reproductive outcomes was more significant. FSH concentration was significantly different before and 30 days after the procedure in both groups. In group 1 FSH values were less than the initial data In 95% of cases, in group 2 – in 72% of cases. AMH levels did not change significantly in both groups. The AFC increased in group 1 compared to group 2. All Patients underwent an IVF antagonist cycle after 3 months from the treatment. The number of obtained oocytes in group 1 ranged from 2 to 8, MII from 1 to 6; in group 2: from 0-5, MII – 0-5. The number of blastocysts in group 1 ranged from 1 to 5, in group 2 – from 0 to 3. In group 1, pregnancy occurred in 9 patients (30%): 1 women ( 3,3%) conceived spontaneously in the cycle of procedures, 8 (26,7%) attempted IVF, in group 2 pregnancy occurred in 4 patients (13,3%): 4 attempted IVF. EVs and PRP injections improve outcomes of IVF results in women with low ovarian reserve. Limitations, reasons for caution Limitations may include the fact that the study is single-center and has a rather small amount of patients enrolled in the study. Fundamental approaches to further research in this area are also required to better understand the obtained results. Wider implications of the findings EVs and PRP therapies appear to enhance ovarian reserve metrics and the success rates of IVF programs in patients with DOR. The clinical implementation of these interventions may offer improved reproductive prospects for patients whose sole option was previously oocyte donation. Trial registration number 121040600410-7

O-043 Con

Abstract Dual and/or double trigger improve IVF success - CON The improvement of in vitro fertilization (IVF) outcomes remains a pivotal area of reproductive medicine research, with the dual trigger approach emerging as a significant innovation. This con abstract explores the scientific basis, methodology, and outcomes associated with the dual trigger strategy, juxtaposed with conventional triggering methods in IVF protocols. The dual trigger, incorporating both Gonadotropin-Releasing Hormone Agonist (GnRHa) and Human Chorionic Gonadotropin (hCG), has been posited to improve oocyte maturation, retrieval-, and live birth rates. By scrutinizing recent studies, clinical trials, and meta-analyses, this debate aims to delineate the efficacy, safety, and application scope of this approach. Initial investigations into the dual trigger method have highlighted its potential to ameliorate oocyte quality and maturity, which are crucial determinants of IVF success. The mechanism underlying this improvement involves the simultaneous activation of LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hormone) receptors, enhancing follicular response and oocyte developmental competence. Studies have demonstrated an increase in the number of mature oocytes retrieved, attributed to the more synchronized and comprehensive follicular stimulation afforded by the dual trigger. This augmentation in oocyte quality and quantity directly correlates with enhanced embryo development profiles, and higher implantation and clinical pregnancy rates. Furthermore, the dual trigger method has shown promise in reducing the incidence of Ovarian Hyperstimulation Syndrome (OHSS), a severe complication of IVF treatments. By leveraging the luteolytic effects of GnRHa, this strategy minimizes the risk associated with exogenous hCG administration, thus offering a safer alternative for patients predisposed to OHSS. The application of the dual trigger in specific patient cohorts, such as those with PCOS or poor ovarian responders, has been underlined, indicating its potential for personalized reproductive medicine. However, the implementation of the dual trigger strategy is not without challenges. Variability in patient response necessitates a highly individualized approach, with precise dosing and timing adjustments to optimize outcomes. The existing literature presents a heterogeneity in study designs, populations, and outcome measures, which complicates the direct comparison of dual trigger efficacy against traditional methods. Furthermore, the long-term safety and potential impacts on offspring warrant further investigation, given the recent adoption of this approach. In conclusion, the dual trigger strategy may offer significant benefits in enhancing IVF outcomes. Its potential to improve oocyte maturity and quality could increase the number of retrievable oocytes and reduce the incidence of OHSS. However, it is important to acknowledge that, while the GnRH agonist trigger combined with a freeze-all strategy eliminates the risk of OHSS in women with PCOS, the dual trigger approach followed by fresh embryo transfer does not. Further research is imperative to refine its application, understand its mechanisms fully, and establish comprehensive guidelines for its use. The promise of the dual trigger approach underscores the importance of continuous innovation and evidence-based practices in enhancing the efficacy and safety of IVF treatments.

P-277 Focal rather than diffuse nature of adenomyosis might be more detrimental to IVF outcomes after single euploid embryo transfer

Abstract Study question Is the nature of adenomyosis a factor to consider after a single euploid embryo transfer? Summary answer Focal adenomyosis was associated with lower live birth rate per transfer when compared to diffuse adenomyosis. What is known already Adenomyosis is widely described to hamper reproductive potential of women who suffer it. This uterine pathology has a detrimental impact on in vitro fertilization (IVF) clinical outcomes, as described by a series of recent metanalysis. Nevertheless, there is scarce evidence regarding clinical studies that address the impact of adenomyosis depending either on its diffuse or focal nature. Study design, size, duration A multicenter retrospective cohort study in which 229 patients undergoing IVF treatment were included. Patients with single embryo transfer (SET) in blastocyst stage after pregestational testing for aneuploidy (PGT-A) between years 2015 and May 2023 were divided into two groups: diffuse adenomyosis (n = 167) and focal adenomyosis (n = 62). Participants/materials, setting, methods Inclusion criteria consisted of patients in a PGT-A program who had a cryotransfer of a single euploid blastocyst-stage embryo. Patients were diagnosed within our facilities using transvaginal ultrasonography (TVUS) prior to their IVF cycle. Diffuse adenomyosis was diagnosed when irregular endometrial-myometrial junction, increased uterine volume, ill-defined myometrial heterogeneity, presence of anechoic round myometrial cysts, hyperechoic islands, fan-shaped shadows and/or echogenic subendometrial lines were detected. Focal adenomyosis was diagnosed when foci with adenomyotic characteristics were observed. Main results and the role of chance Clinical pregnancy rate per embryo transfer was 81/167 (48.5%) in those women diagnosed with diffuse adenomyosis versus 23/62 (37.1%) in the focal adenomyosis group (OR = 0.63 95% CI [0.33-1.18], NS). Differences found in clinical miscarriage rate were not statistically significant, being 33/81 (40.7%) for diffuse adenomyosis and 14/23 (60.1%) for the focal adenomyosis group (OR = 2.24 95% CI [0.79-6.63], NS). A lower live birth rate per euploid embryo transfer was observed in women diagnosed with focal adenomyosis, being 9/62 (14.5%) and 48/167 (28.7%) for women who presented diffuse adenomyosis (OR = 0.42 95% CI [0.17-0.95], p=0.027). There were no statistically significant differences between childbirth delivery method (vaginal versus caesarean section). Furthermore, means of gestational age at the time of delivery, newborn size and weight and incidences of low birth weight did not differ between the two groups. Limitations, reasons for caution The retrospective nature of this observational study implies that possible confounders cannot be completely excluded. Also, the accurate diagnostic of adenomyosis is not without complexity and although gynecologists were equally trained to identify direct and indirect markers, different criteria may have been used Wider implications of the findings To our knowledge this is the first study to use an euploid model to assess the impact of the focal versus diffuse nature of adenomyosis in IVF patients. This model permits to correct for numerous covariables attributed to patient’s age and embryo genetic constitution. Trial registration number Not applicable

Effect of Body Mass Index (BMI) on In Vitro Fertilization (IVF) Outcomes in Women with Polycystic Ovary Syndrome (PCOS)

Objective: Obesity is known to have negative impaction on reproductive health and ovarian functions. It may alter endocrine axis and quality of oocytes, and indirectly effect the success of in vitro fertilization (IVF). Methods: Medical records of patients with polycystic ovary syndrome (PCOS) who were applied for IVF between 2018 and 2024 were reviewed. Demographics, indications for reproductive treatment, IVF outcome parameters and the factors contributing to morbidity of treatment were recorded. Student’s test with one-way analysis of variance (ANOVA) and Kruskal-Wallis tests were used to compare the variables. P<0.05 was considered statistically significant. Results: 186 patients with PCOS were divided as lean (BMI<25 kg/m2, control), overweight (BMI 25-30 kg/m2) and obese (BMI>30 kg/m2). Mean ages and primary infertility rates were similar (both, p>0.05), but duration of infertility was longer in overweight and obese patients (p<0.05). Although patients with higher BMI required more induction dose for the cycle, number of retrieved oocytes did not change significantly, with achieved chemical and clinical pregnancy (each, p>0.05). Moreover, fertilization rates of transferred oocytes and rates of adverse outcomes during pregnancies were similar in the groups (each, p>0.05). Although overweight and obese patients with PCOS required more gonadotropin induction for IVF cycle (2311 vs 1920 vs 1752 IU, respectively, p<0.05), the numbers of metaphase II and fertilized oocytes were seen to be similar with increasing BMI (each, p>0.05). Conclusion: There is longer infertility duration and a higher requirement for gonadotropins in overweight and obese patients with no effect of BMI on most of IVF parameters such as retrieved oocyte, clinical pregnancy, obstetric complication and delivery rate.

Predicting the Outcomes of In Vitro Fertilization Using Baseline Maternal Serum Inflammatory Markers: A Retrospective Cohort Study.

Achieving pregnancy through in vitro fertilization (IVF) remains a challenge, with less than one-third of women succeeding. There is a pressing need for reliable predictive tools to assess the likelihood of post-IVF pregnancy. While some serum inflammatory biomarkers have been investigated for their predictive potential, substantial knowledge gaps persist. This study examined the utility of different inflammatory markers in predicting IVF outcomes. Inflammatory markers including the white blood cell count, neutrophil-to-lymphocyte ratio (NLR), platelet count, mean platelet volume, platelet distribution width, platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), erythrocyte sedimentation rate, and vitamin D3 were assessed. Study outcomes were chemical pregnancy (positive serum beta-human chorionic gonadotropin 2 weeks post-embryo transfer), clinical pregnancy (detection of pregnancy sac via transvaginal ultrasonography), and viable pregnancy (detection of fetal heart rate). Univariate and multivariate logistic regression analyses were conducted, with multivariate analysis incorporating age, body mass index, infertility duration, type, and etiology, as well as all studied serum inflammatory markers, embryo count, stage, quality, and endometrial thickness. Lower NLR (p<0.001, odds ratio [OR]=0.372 [0.247-0.559]) and CRP (p=0.035, odds ratio=0.956 [0.916-0.997]) predicted chemical pregnancy in univariate analysis, with NLR maintaining significance in multivariate analysis (p=0.022, OR=0.319 [0.120-0.848]). Lower NLR (p<0.001, OR=0.309 [0.198-0.482]) and PLR (p=0.013, OR =0.994 [0.990-0.999]) predicted clinical pregnancy, with NLR surviving multivariate analysis (p=0.005, OR = 0.217 [0.075-0.626]). Lower NLR (p<0.001, OR = 0.320 [0.198-0.516]) also predicted viable pregnancy, maintaining statistical significance in multivariate analysis (p = 0.002, OR = 0.177 [0.058-0.541]). Other studied inflammatory markers did not predict IVF outcomes. NLR emerged as a robust independent predictor of pregnancy attainment after IVF.

Correlation of Sperm DNA Fragmentation Index With Semen Parameters, Lifestyle and Clinical Pregnancy Outcome After Intracytoplasmic Injection.

This study aimed to measure the correlation of sperm DNA fragmentation with semen parameters, lifestyle, and fertility outcomes after intracytoplasmic injection (ICSI). The partners who were candidates for ICSI with a history of one In vitro fertilization (IVF) failure or male factor were recruited in the study. Semen parameters including sperm count, motility, and morphology as well as DNA fragmentation index (DFI) (that were divided into 2 groups as high (>15%), and low (≤15%) fragmentation scales) were evaluated either. The correlation of DFI with semen parameters, lifestyle, and clinical pregnancy after ICSI were compared between groups. In 120 included couples, 59 men (49.2%) had DFIs ≤ 15% and 61 (50.8%) cases had DFIs >15%. In the group with higher DFI, abnormal morphology (p=0.010) was higher whereas, progressive motility (p=0.001), total motility (p<0.001), and total count (p<0.001) of sperm were significantly lower. In addition, the DFI was significantly higher in the subgroup of male infertility (0.012). Logistic regression showed that a lower risk of DFI>15% was associated with higher values of progressive motility (OR=0.97, p=0.001), total motility (OR=0.96, p=<0.001), count (OR=0.96, p=<0.001) and even clinical pregnancy (OR=0.27, p=0.011). However, a history of testicular surgery was associated with a higher risk of DFI>15% (OR=3.37, p=0.046). Although no correlation was found between male age and lifestyle components with DFI, the number of embryos was lower in DFI≥15% (p<0.001). DFI provide a clinically important measurement of sperm quality and have an impact on IVF outcomes; however, lifestyle components may not correlate with DFI.

Low and High-Normal FMR1 Triplet Cytosine, Guanine Guanine Repeats Affect Ovarian Reserve and Fertility in Women Who Underwent In Vitro Fertilization Treatment? Results from a Cross-Sectional Study.

Dynamic mutations in the 5' untranslated region of FMR1 are associated with infertility. Premutation alleles interfere with prenatal development and increase infertility risks. The number of CGG repeats that causes the highest decrease in ovarian reserves remains unclear. We evaluated the effect of FMR1 CGG repeat lengths on ovarian reserves and in vitro fertilization (IVF) treatment outcomes in 272 women with alleles within the normal range. FMR1 CGG repeat length was investigated via PCR and capillary electrophoresis. Alleles were classified as low-normal, normal, and high-normal. Serum levels of follicle-stimulating hormone and anti-Mullerian hormone (AMH) in the follicular phase of the menstrual cycle were measured, and antral follicles (AFC) were counted. IVF outcomes were collected from medical records. Regarding FMR1 CGG repeat length alleles, 63.2% of women presented at least one low-normal allele. Those carrying low-normal alleles had significantly lower AMH levels than women carrying normal or high-normal alleles. Low-normal/low-normal genotype was the most frequent, followed by low-normal/normal and normal/normal. A comparison of ovarian reserve markers and reproductive outcomes of the three most frequent genotypes revealed that AFC in the low-normal/normal genotype was significantly lower than the low-normal/low-normal genotype. The low number of FMR1 CGG repeats affected AMH levels and AFC but not IVF outcomes per cycle of treatment.

Serum copper assessment in patients with polycystic ovary syndrome and tubal infertility: A retrospective 5-year study.

The association between serum copper and polycystic ovary syndrome (PCOS) lacks definitive conclusions, and the intricate interactions with invitro fertilization (IVF) cycle characteristics in infertility remain insufficiently explored. This retrospective study included 560 patients with tubal infertility (no-PCOS) and 266 patients with PCOS undergoing IVF at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2018 to December 2022. Patients' basic characteristics, hormonal and metabolic parameters, essential trace elements, and IVF cycle characteristics were measured and analyzed. The results revealed a significantly elevated serum copper level in the PCOS group compared to the control group [17.27 (15.54, 19.67) vs 15.4 (13.87, 17.35), μmol/L; p < .001]. Spearman correlation analyses revealed a significant positive correlation between serum copper concentration and body mass index (BMI), fasting glucose (FG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) in the no-PCOS group. Additionally, a notable negative correlation with high-density lipoprotein (HDL) was observed (r = -.184, p < .001). Within the PCOS group, serum copper concentration correlated significantly with BMI (r = .198, p = .004) and TG (r = .214, p = .002). The linear trend analysis indicated no significant relationship between serum copper concentration and ovarian response as well as preimplantation outcomes in both groups after adjusting for confounding factors. Our study provided evidence of elevated serum copper concentration in PCOS patients, closely associated with lipid metabolism but showing no correlation with IVF outcomes. These findings provide valuable real-world data, enriching our nuanced understanding of the role of copper in female fertility.

Impact of COVID-19 Vaccination on In Vitro Fertilization Outcomes: A Systematic Review.

COVID-19 vaccination, especially vaccines that mimic the structure of the COVID-19 virus (mRNA vaccines), may be wrongly assumed to be disrupting factors affecting in vitro fertilization (IVF) outcome. This study aims to evaluate any significant impact of COVID-19 vaccination in women undergoing IVF to improve vaccine compliance and promote COVID-19 eradication. This was a systematic review study. We searched studies published between 2020 and 2022 using databases such as PubMed, Cochrane, PMC, and CINAHL. Selected studies were carefully analyzed to review the impact of the COVID-19 vaccine on IVF outcomes. Seven retrospective and prospective cohort studies, which involved 3232 female patients undergoing IVF, who also received full doses of COVID-19 vaccinations (mRNA), were included. All studies in the present review showed that despite presenting anti-SARS-CoV-2 antibodies after vaccination, there were no significant differences in IVF outcomes, implantation rates, and pregnancy rates. Contrary to the theory that presumed cross-reactivity between anti- SARS-CoV-2 antibodies and the human syncytin-1 protein could affect syncytiotrophoblast formation and embryo implantation. The present review concluded that COVID-19 vaccination does not result in any detrimental effects on IVF outcomes and is safe for women undergoing IVF treatment. The results of our study are important to tackle misinformation regarding COVID-19 vaccination and infertility that may cause vaccine hesitancy in women of reproductive age.

Immunomodulatory Treatment Impact on IVF Outcomes in KIR AA Genotype: Personalized Fertility Insights.

Background and Objectives: Recurrent implantation failure (RIF) affects 10% of couples undergoing in vitro fertilization (IVF), spurring exploration into tailored treatments to enhance implantation rates. Maternal immune tolerance towards embryos, particularly killer-cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells, is a focal point in RIF research. Materials and Methods: This retrospective cohort study, conducted at fertility clinic in Oradea, Romania, involved 65 infertile couples undergoing IVF treatment between January 2022 and December 2023. Couples were divided into two groups: KIR AA (Group A) and KIR Bx (Group B). Results: Factors such as age, type of infertility, oocytes retrieved, embryos produced, pregnancy rates in Group A without and with immunomodulatory treatment were documented. Group A, receiving immunomodulatory treatment, achieved a pregnancy rate of 47.8%, significantly higher than the 23.73% rate without treatment (p = 0.008). Group B had a higher mean patient age than Group A. However, miscarriage rates did not significantly differ between Group A with treatment and Group B (p = 0.2457), suggesting comparable outcomes with immunomodulation. Conclusions: The impact of immunological factors on recurrent implantation failure is being more and more emphasized and warrants the attention of specialists in human reproduction. Uterine natural killers and their function though KIR receptors deserve particular attention as immunomodulatory treatment may improve pregnancy rates in patients with KIR AA haplotype.

Impact of Body Mass Index (BMI) and Age on in Vitro Fertilization (IVF) Outcome in Indian Patients with Polycystic Ovary Syndrome (PCOS)

Aim: The study evaluated the effect of body mass index (BMI) and age on in vitro fertilization (IVF) outcomes in women with polycystic ovary syndrome (PCOS). Methods: A retrospective study of 412 IVF cycles in PCOS patients aged between 20 and 40 years from January 2019 to 2022. Patients were divided into three groups based on their BMI-normal (18.5–24.9[Formula: see text]kg/m2), overweight (25–29.9[Formula: see text]kg/m2), and obese ([Formula: see text][Formula: see text]kg/m2). The patients were divided into two groups based on their age [Formula: see text] and [Formula: see text] years. The IVF cycle outcomes, clinical pregnancy (CPR), and live birth rates (LBR) were studied. The Mantel–Haenszel Chi-square test was used for statistics. Results: The oocyte yield and endometrial thickness, fertilization, CPR, and LBR were significantly higher in the normal BMI group. Similarly, oocyte yield, mature oocytes, and endometrial thickness were significantly higher in the younger age-group. Comparing the CPR in younger and older normal, overweight, and obese groups, it was observed to be highest in the younger, normal BMI group and lowest in the older, obese group. The LBR were significantly higher in the younger, normal-BMI group compared to the older, obese patients. Conclusion: Oocyte yield, CPR, and LBR were higher in the normal-BMI PCOS patients. The oocyte yield, endometrial thickness, and fertilization rates were higher in the younger age group. The CPR and LBR were significantly lower in the older obese patients. Patients with PCOS must be encouraged to normalize BMI before embarking on IVF. Timely treatment must be encouraged for better IVF outcomes.

In vitro fertilization and perinatal outcomes of patients with advanced maternal age after single frozen euploid embryo transfer: a propensity score-matched analysis of autologous and donor cycles

ObjectiveTo evaluate in vitro fertilization (IVF) and perinatal outcomes of donor egg and autologous cycles in advanced reproductive-aged patients after undergoing single, frozen euploid embryo transfer (SET/FET). DesignA retrospective, multicenter cohort study. SettingUniversity-affiliated and private IVF centers. Patient(s)Patients between 39-46 years old undergoing IVF with intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidy (PGT-A) using whole-chromosome sequencing with donor (n=278) or autologous (n=278) oocytes between October 2017 and October 2021. Intervention(s)SET/FET with donor or autologous euploid embryo Main outcome measure(s)The live birth rate after the first embryo transfer, calculated per embryo transfer. Secondary outcomes included implantation rate, ectopic pregnancy rate, miscarriage rate, and gestational age and birthweight at the time of delivery. Result(s)Patients using donor or autologous oocytes had a similar likelihood of implantation57.91% (51.87-63.78) versus 57.19% (51.15-63.09), p=0.93 and live birth rate 41.01% (95% CI:35.17-47.04) versus 42.45% (95% CI:36.56-48.49), p=0.86. Furthermore, there were no significant differences in ectopic pregnancy rate [0.72% (0.09-2.57) versus 0.36% (0.01-1.99), p=1] or miscarriage rate [16.19% (12.06-21.05) versus 14.39% (95% CI:10.48-19.08), p=0.98], gestational age [38.50 weeks (38.08-38.92) versus 39.16 weeks (38.25-40.07), p=0.19], or birthweight of infants [2982.25 kg (2606.69-3357.81) versus 3128.24 kg (2962.30-3294.17), p=0.95]. The univariate analysis showed no association of advanced maternal age on the live birth rate [risk relative (RR) 1.03 (IC95%: 0.84-1.25); p=0.79]. Multivariate analysis using putative confounders for embryo competency found no associations with live birth rate [adjusted risk relative (aRR) 1.22 (IC95%: 0.75-1.98); p=0.42] Conclusion(s)Patients with euploid blastocysts derived from donor or autologous oocytes did not reveal statistically significant differences in live birth rate, implantation rate, ectopic pregnancy rate, miscarriage rate, duration of gestation, or infant birthweight. These findings suggest that age-related reproductive decline and/or poor IVF outcomes associated with advanced reproductive-aged women undergoing IVF are heavily driven by embryonic aneuploidy.

The features of endometrial receptivity in women underwent in vitro fertilization procedure

The objective: to determine the endometrial receptivity markers in women who underwent the procedure of in vitro fertilization (IVF). Materials and methods. The study included 191 patients who applied to the reproductive department of Caspian International Hospital from 2020 to 2022 for an examination for infertility.The main group included 50 patients with infertility who underwent endometrial biopsy during the implantation window (7th–9th days after ovulation in the cycle preceding the IVF stage); the control group – 20 women who underwent treatment for male infertility with a positive program result.The patients underwent IVF according to the standard method. The following expression levels were determined: leukemia inhibiting factor (LIF); vascular endothelial growth factor (VEGF); transforming growth factor-β1 (TGF-β1). The percentage expression of area indices was estimated.Results. In the women of the main group absence of embryo transfer was in 5 (10%) cases, no pregnancy – 27 (54%) cases, presence of pregnancy – 23 (46%) cases, cycle disruption – 3 (6%) cases.According to the results of a histological examination in women of the control group, complete secretory transformation of the endometrium was determined in 85% of cases. In the main group complete secretory transformation of the endometrium was detected in 48%, defective secretory transformation – in 42%, morphological signs of endometrial changes corresponding to the average secretory phase of the cycle – in 10% of women.A significant decrease (p&lt;0.001) in the expression of LIF in the histological structures (stroma) of the endometrium was revealed in the main study group compared to the control one. The most pronounced differences were observed in the expression level of TGF-β1 in the stroma (approximately 10-fold; p&lt;0.001).Conclusions. Thus, infertile women who underwent IVF have multidirectional changes in endometrial receptivity markers: decrease in LIF expression in the stroma and epithelium, increase in VEGF expression in the stroma, and a significant increase in TGF-β1 expression in the stroma and epithelium. These changes indicate an abnormal functional state of the endometrium and affect the results of IVF in patients (absence of oocyte transfer and failure to conceive).