Fresh In Vitro Fertilization Cycles Research Articles

P-440 Idiopathic infertility does not increase rates of placental abnormalities among singleton pregnancies conceived with either in-vitro fertilization (IVF) or ovulation induction±intrauterine insemination (OI±IUI)

Abstract Study question Is there an adverse impact of idiopathic infertility diagnosis on placental pathology among singleton pregnancies conceived with fertility treatments? Summary answer Idiopathic infertility does not increase rates of placental abnormalities and exhibits distinctive associations within the inflammatory and vascular spectrum of placental pathology. What is known already Pregnancies resulting from fertility treatments are often considered to be at higher risk for placenta-mediated obstetric complications and subsequent adverse perinatal outcomes. Treatment induced hormonal changes altering the endometrial milieu, along with embryo manipulation and culture conditions, may impact the processes of implantation, decidualization, trophoblast invasion, and placental vascularization. Nevertheless, the impact of infertility diagnoses on placental pathology among singleton pregnancies conceived with fertility treatments has not been elucidated, and whether idiopathic infertility alters the risk of placental abnormalities remains unknown. Study design, size, duration Retrospective review of placental pathology data from 1205 singleton livebirths conceived with fertility treatments (899 IVF, and 306 OI±IUI cycles) between 01/2004 and 04/2022. Placenta pathology was reviewed by one expert pathologist and classified as anatomic, inflammatory, infectious, and vascular [including any features of fetal (FVM) or maternal (MVM) vascular malperfusion], using the Amsterdam Workshop Consensus definitions. Placental abnormalities were compared between idiopathic infertility (IdI, n: 269) and all other, non-idiopathic infertility (non-IdI, n:936) diagnoses. Participants/materials, setting, methods Primary outcomes: anatomic, inflammatory, infectious, and vascular placental abnormalities. Parametric, and non-parametric tests were used as appropriately; odds ratios (OR) with 95% confidence intervals (95%CI) were assessed through logistic regression, adjusting for maternal age, body mass index (BMI, kg/m2), race, parity, gestational age, neonatal gender, treatment type, gestational diabetes, and hypertensive disorders. Analyses were further stratified by OI±IUI vs IVF treatments [the latter further stratified into fresh and frozen embryo transfers (FET)]. Main results and the role of chance Mean age, BMI, and AMH did not differ between groups, and neither did placental weight at term. Overall, unadjusted rates of inflammatory, infectious, and vascular abnormalities did not differ between groups (12.6% vs 11.4%, p 0.568; 22.0% vs 19.1%, p 0.256; 54.5% vs 58.6%, p 0.186, respectively). However, a higher rate of anatomic abnormalities was noted among IdI patients (32.8% vs 27.1%, p 0.044, IdI vs. non-IdI, respectively). When adjusting for potential confounders, no differences were noted between groups regarding inflammatory, infectious, and vascular abnormalities, and the observed difference in anatomic abnormalities lost its significance [adjOR(95%CI); inflammatory: 0.98(0.94-1.03), infectious: 1.03(0.98-1.09), vascular: 0.96(0.90-1.02), and anatomic: 1.02(0.96-1.08), non-IdI: ref]. Similarly, when separating OI±IUI from FET and fresh IVF cycles, adjOR(95%CI) revealed no differences in anatomic, infectious, and vascular abnormalities between groups [OI±IUI: 0.97(0.85-1.1), 0.97(0.87-1.08), 0.99(0.87-1.12); FET: 1.08(0.94-1.24), 1.07(0.94-1.23), 1.04(0.98-1.11) and, fresh IVF: 1.06(0.98-1.15), 1.04(0.96-1.13), 0.96(0.87-1.07), for anatomic, infectious, and vascular, respectively]. However, lower odds of inflammatory abnormalities were noted among fresh IVF but not among FET or OI±IUI cycles in IdI [adjOR (95%CI); fresh IVF: 0.95(0.91-0.99), FET: 1.09(0.98-1.21), OI±IUI: 0.97(0.87-1.08), non-IdI: ref]. Interestingly, among vascular abnormalities studied in the programmed FET cycles, MVM showed a difference between the groups [adjOR(95%CI) 0.90(0.85-0.96), non-IdI: ref]. Limitations, reasons for caution This study is limited by its retrospective design. The reported findings are from an infertile population undergoing treatments and thus not easily generalizable to natural conceptions. Other factors, such as environmental, nutritional, and lifestyle, might alter a patient’s individual pregnancy risk for placental abnormalities. Wider implications of the findings Overall, idiopathic infertility does not appear to increase the risk for placental abnormalities. However, it may impact placental pathology in a unique way, within the vascular and inflammatory spectrum, which might differ from that of other infertility diagnoses, and might be further altered by the treatment protocol. Trial registration number Not Applicable

The details matter: personalized prediction of live birth after in vitro fertilization in women with polycystic ovary syndrome

ObjectiveTo derive and internally validate a clinical prediction model for live birth in women with polycystic ovary syndrome (PCOS) undergoing in-vitro fertilization (IVF) DesignRetrospective cohort study SettingFour academic reproductive endocrinology clinics Patients207 women with PCOS confirmed by Rotterdam criteria undergoing their first fresh IVF cycle InterventionsNone Main Outcome MeasureThe primary outcome was cumulative live birth (LB) per IVF cycle start. This included any LB that resulted from either fresh embryo transfer or any subsequent frozen embryo transfer from embryos obtained at the index oocyte retrieval. A prediction model was derived using multivariable logistic regression. Covariates considered for inclusion in the prediction model included demographic characteristics, medical history, and prior fertility treatment. Predicted probabilities for live birth were calculated using the prediction model which included the 90% shrinkage factor for each adjusted OR. ResultsThe final model, based on maximization of the area under the receiver operating characteristic curve (AUROC), included age <35 years, White race, presence of polycystic ovaries on ultrasound (PCOM), normal BMI (<25 kg/m2), being metabolically healthy (no metabolic risk factors), and being a non-responder to ovulation induction (OI) agents including letrozole and clomiphene citrate. The AUROC for the model was 0.68 (95% CI: 0.60, 0.77). Predicted probabilities of live birth ranged from 8.1% (95% CI 2.8, 21.5) for a woman who had no favorable predictors to 74.2% (95% CI: 59.5, 84.9) for a woman who had all favorable predictors. ConclusionOur study demonstrates that in addition to anovulation, the underlying pathophysiology and associated co-morbidities alter the likelihood of a successful pregnancy in women with PCOS undergoing IVF. Further validation of this model is needed before it, can serve as a tool to personalize prediction estimates for probability of live birth in women with PCOS.

Leukemia Inhibitory Factor, Tissue Factor, Thrombomodulin, P-Selectine, D-Dimer, Thrombin Generation and Procoagulant Phospholipid Dependent Clotting Time Are Predictive for in Vitro Fertilization Outcome. the Prospective Roadmap-IVF Study

Background The link between blood hypercoagulability, endothelial cell activation and infertility or in vitro fertilization (IVF) failure is a puzzling issue. Activation of platelets, endothelial cells and blood coagulation, proinflammatory and angiogenetic potential play important role in implantation and early embryonic development. Biomarkers of cellular hypercoagulability are associated with high risk of IVF failure. Soluble Leukemia Inhibitory Factor (LIF), an interleukin 6 class cytokine expressed in the trophectoderm of the developing embryo is an important regulator in the establishment of pregnancy. Endoglin (Eng), a co-receptor for TGF-β1 and TGF-β3 is implicated in vascular complications of pregnancy and particularly in preeclampsia. Aim: The prospective longitudinal monocentric observational cohort study ROADMAP-IVF, evaluated the synergistic prognostic value of LIF and Eng with the biomarkers of cellular hypercoagulability in predicting the endometrial receptivity of fresh IVF cycles. Materials and Methods. The ROADMAP-IVF enrolled 40 women eligible for IVF with normal blood count, PT, aPTT, Fg, renal and liver function. The control group (CG) consisted of 30 healthy women with history of uncomplicated pregnancies. Exclusion criteria: Use of anticoagulant or antiplatelet agents during the last 30 days before inclusion. Known cardiovascular disease, active cancer. Active corticosteroid treatment. Primary end-point: Echographically documented pregnancy at 7 weeks from implantation. Blood was collected on day 2 (D2) from the natural cycle and 6 days after hormone treatment initiation corresponding to D8 of the cycle. Procoagulant phospholipid-dependent clotting time (PPL-ct), tissue factor (TF), thrombomodulin (TM), von Willebrand factor (vWF) and D-Dimers (DDi) were measured with assays from Diagnostica Stago (Asnieres, France). P- and E-Selectin, LIF and Eng were measured with ELISA. Thrombin generation (TG) with the TF 5 pM PPP-Reagent ® was assessed on Calibrated Automated Thrombogram (Stago, France). The cut-off values for studied biomarkers have been selected on the basis of ROC analysis. Univariate and multivariate logistic regression analysis examined the associations between the biomarkers and the study outcome. Results: 40 women were enrolled in the study. In 11 women pregnancy was confirmed with ultrasound and in 23 women no pregnancy was echographically documented. Age was not significantly different between the IVF (41 ys; range 22 - 48 ys) and the control group (40 ys; range 20 - 46 ys). At D2 and D8 the DDi and LIF were significantly higher in IVFG as compared to the CG. At D2 most of the patients had PPL-ct, DDi and MRI of TG higher than the upper normal limit (UNL). At D8 only TF was significantly increased as compared to the CG. Analytical data are presented in Table 1. Age did not correlate with the levels of the studied biomarkers. Significant correlations (p&amp;lt;0.05) were found between DDi and ETP (r=0.35); TM, TF and P-Selectin (r=0.4) at D2; TF, LIF and Eng (r=0.5) at D2 and D8; P-Selectin and PPL-ct (r=-0.4) at D2; P-Selectin and TM (r=0.4), E-Selectin (r=0.5), LIF (0.4) at D2; E-Selectin and P-Selectin (r=0.5), TF (r=0.3), and LIF (r=0.4) at D2. The ROC analysis showed that IVF failure was associate with DDi increase at D2 (AUC = 0.64); P-Selectin increase at D2(AUC = 0.57) and D8 (AUC = 0.61); TM increase at D8 (AUC = 0.61); TF increase at D8 (AUC = 0.57); LIF increase at D8 (AUC = 0.59); ETP increase at D2 (AUC = 0.67) and D8 (AUC = 0.67); Peak increase at D2 (AUC = 0.64) and D8 (AUC = 0.61). Prolongation of PPL-ct on D8 was predictive for positive pregnancy outcome(AUC 0.64). Conclusion The ROADMAP-IVF study showed that at least one out of four women eligible for IVF present biological evidence of activation of platelets, endothelial cells, blood coagulation or LIF upregulation. Hormone treatment administration does not significantly alter the proinflammatory or the hypercoagulable state. Among the studied biomarkers the levels of LIF, DDi, P-Selectine, TM and TF as well as the status of thrombin generation and PPL-ct showed a significant predictive value for the IVF outcome, particularly when measured at 6 days after hormone treatment administration. These findings will lead to the elaboration of an risk assessment model for IVF failure combining the selected biomarkers of hypercoagulability with LIF.

The association between body mass index and live birth and maternal and perinatal outcomes after in-vitro fertilization: a national cohort study.

To investigate the association between female body mass index (BMI) and live birth rates and maternal and perinatal outcomes after in-vitro fertilization (IVF). We performed a national, population-based cohort study including women undergoing IVF between 2002 and 2020. The cohort included 126,620 fresh cycles and subsequent frozen embryo transfers between 2007 and 2019 (subpopulation 1) and 58,187 singleton deliveries between 2002 and 2020 (subpopulation 2). Exposure was female BMI (kg/m2) categorized according to the World Health Organization as underweight (<18.5), normal weight (18.5-24.9, reference), overweight (25.0-29.9), class I obesity (30.0-34.9), class II obesity (35.0-39.9), and class III obesity (≥40.0). The primary outcome in subpopulation 1 was cumulative live birth per started fresh IVF cycle, including fresh and subsequent frozen embryo transfers. Primary outcomes in subpopulation 2 were hypertensive disorders of pregnancy and preterm birth at less than 37 weeks. Risk ratios (RRs) with 95% confidence intervals (CIs) for the association between BMI class and outcomes were calculated using generalized linear models after adjustment for relevant confounders. The cumulative live birth rate decreased significantly with increasing BMI from 32.6% in normal-weight women to 29.4% in overweight women, 27.0% in women in obesity class I, 21.8% in women in obesity class II, and 7.6% in women in obesity class III. The risk of hypertensive disorders of pregnancy increased significantly and progressively with increasing BMI, from 4.6% in normal-weight women to 7.8% in overweight women and 12.5%, 17.9%, and 20.3% in women in obesity classes I, II, and III. The risk of preterm birth followed a similar pattern, from 6.3% in normal-weight women to 7.5% in overweight women and 8.9%, 9.9%, and 15.3% in women in obesity classes I, II, and III. The risks of other perinatal complications, such as perinatal death, showed an even more pronounced increase. Using a large and complete national cohort of women undergoing IVF, we demonstrate a dose-dependent decrease in live birth rate and a substantial increase in maternal and perinatal complications with increasing BMI. Strategies to improve this situation are warranted.

O-214 interaction of air pollution and meteorological factors on IVF outcomes: a multicenter study in China

Abstract Study question Is there an interaction between air pollution and meteorological factors on IVF outcomes? Summary answer The correlation between air-pollutant exposure and IVF outcomes was modified by meteorological conditions, especially temperature and wind speed. What is known already Previous studies revealed associations between air-pollutant exposure and in vitro fertilization (IVF) outcomes. However, modification effects of air pollution on IVF outcomes by meteorological conditions remain elusive. Study design, size, duration Multicenter retrospective cohort study, 2015–2020. Participants/materials, setting, methods This multicenter retrospective cohort study included 15,217 women from five northern Chinese cities during 2015–2020. Daily average concentrations of air pollutants (PM2.5, PM10, O3, NO2, SO2, and CO) and meteorological factors (temperature, relative humidity, wind speed, and sunshine duration) during different exposure windows were calculated as individual approximate exposure. Generalized estimating equations and stratification models were used to assess the associations of air pollution and meteorological conditions with IVF outcomes and estimated potential interactions. Main results and the role of chance Exposure to PM2.5, SO2, and O3 was adversely correlated with pregnancy outcomes in fresh IVF cycles. Positive associations of wind speed and sunshine duration with pregnancy outcomes were detected. In addition, we observed that embryo transfer in spring and summer had a higher likelihood to achieve a live birth compared with winter. In stratified models, pieces of evidence of interaction between meteorological factors and air pollutants on pregnancy outcomes were detected. Negative associations of PM2.5 with clinical pregnancy were only significant at lower temperatures and wind speeds. Moreover, the effects of O3 on live birth were enhanced by higher quartiles of wind speed. Limitations, reasons for caution First of all, we used the data from monitoring stations to estimate the individual exposure, which was inaccurate and may introduce bias. Second, due to data limitations, this study did not discuss socio-economic factors, which were reported to be associated with spatial-temporal variations of air pollutants and reproductive outcomes. Wider implications of the findings Pregnant women should be advised to reduce outdoor time when the air quality was poor, particularly at lower temperatures. Trial registration number not applicable

P-245 Birth of twenty-seven healthy babies following transfer of fresh and frozen-thawed embryos derived from monopronuclear zygotes: a retrospective study

Abstract Study question What are the neonatal outcomes of fresh/frozen-thawed embryos derived from monopronuclear zygotes (1PN)? Is there any influence of the method of fertilization? Summary answer A total of 231 monoembryonic transfers (TF) of fresh or frozen/thawed embryos derived from 1PN zygotes allows to the birth of twenty-seven healthy babies. What is known already Zygotes were classified 16 to 18 hours post insemination according to the extrusion of the second polar body and the number of pronuclei (PN). The «normally fertilized» zygotes display 2 PN and those with 0, 1 or more than 2 PN (&amp;gt; 2PN) are considered as abnormal. If some zygotes are always discarded (&amp;gt;2PN) due to the increased risk of aneuploidy, the transfer of embryos derived from 1PN zygotes remains more controversial. Study design, size, duration Our retrospective study included all conventional in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and frozen embryo transfer (FET) cycles performed between january 2018 and december 2022. Embryo and pregnancy outcomes were analyzed in a first group of 781 fresh cycles (731 patients) and in a second group of 167 FET (150 patients) with embryos derived from 1PN zygote. Only monoembryonic transfers were analyzed for live birth rate (LBR). Participants/materials, setting, methods Only embryos derived from 1PN zygotes were analyzed in our study. For fresh cycles (n = 2762), embryo outcome was analyzed for 1234 (1PN) zygotes (IVF = 648 and ICSI = 586). Fresh embryo TF was performed in 64 cycles. For frozen cycles, TF was achieved in 167 cases. For a total of 231 TF on day 2, 3 or 5, pregnancy and live birth rates were analyzed. Main results and the role of chance At first, 46% of 1PN zygotes from fresh IVF cycles gave rise to embryos of sufficient quality to be transferred or frozen (day 3 or 5/6). This rate decreased to 33% in the fresh ICSI cycles. Blastulation rate was also more important in IVF group (44%) in comparison to ICSI group (20%) without signification (p = 0.1). Fresh TF of 64 patients (32 in each fertilization group) allowed 7 pregnancies in the IVF group (PR = 22%) as compared to 4 pregnancies in the ICSI group (PR = 12%). The 7 IVF pregnancies ended in 4 deliveries of healthy newborns, 2 miscarriages and one pregnancy still ongoing. In the ICSI group, 1 birth of a healthy newborn and 3 miscarriages were observed. Secondary, thirty-six pregnancies were obtained in the 167 FET cycles. A non significative difference was observed between embryos derived from IVF cycles (PR = 26%) and ICSI cycles (PR = 16%) with respectively 15 and 6 healthy babies born. Two pregnancies in each group are still ongoing. Limitations, reasons for caution The main limitation of this study is that it was a retrospective, single-center study with a relatively small number of births. Wider implications of the findings In conclusion, we observed better outcomes in IVF cycles in comparison to ICSI cycles and our center policy to transfer a good quality embryo developed from 1PN zygotes allowed 26 deliveries of 27 healthy newborns during the period analyzed. Trial registration number not applicable

Interaction of air pollution and meteorological factors on IVF outcomes: A multicenter study in China

BackgroundPrevious studies revealed associations between air-pollutant exposure and in vitro fertilization (IVF) outcomes. However, modification effects of air pollution on IVF outcomes by meteorological conditions remain elusive. MethodsThis multicenter retrospective cohort study included 15,217 women from five northern Chinese cities during 2015–2020. Daily average concentrations of air pollutants (PM2.5, PM10, O3, NO2, SO2, and CO) and meteorological factors (temperature, relative humidity, wind speed, and sunshine duration) during different exposure windows were calculated as individual approximate exposure. Generalized estimating equations models and stratified analyses were conducted to assess the associations of air pollution and meteorological conditions with IVF outcomes and estimate potential interactions. ResultsPositive associations of wind speed and sunshine duration with pregnancy outcomes were detected. In addition, we observed that embryo transfer in spring and summer had a higher likelihood to achieve a live birth compared with winter. Exposure to PM2.5, SO2, and O3 was adversely correlated with pregnancy outcomes in fresh IVF cycles, and the associations were modified by air temperature, relative humidity, and wind speed. The inverse associations of PM2.5 and SO2 exposure with biochemical pregnancy were stronger at lower temperatures and humidity. Negative associations of PM2.5 with clinical pregnancy were only significant at lower temperatures and wind speeds. Moreover, the effects of O3 on live birth were enhanced by higher wind speed. ConclusionsOur results suggested that the associations between air-pollutant exposure and IVF outcomes were modified by meteorological conditions, especially temperature and wind speed. Women undergoing IVF treatment should be advised to reduce outdoor time when the air quality was poor, particularly at lower temperatures.

Premature progesterone elevation during the early and mid-follicular phases in fresh in vitro fertilization (IVF) cycles is associated with lower live birth, clinical pregnancy, and implantation rates.

Evaluate follicular phase progesterone elevation (≥ 1.5ng/mL) prior to trigger during IVF stimulation and its effects on live birth rate (LBR), clinical pregnancy rate (CPR), and implantation rate (IR) in fresh IVF cycles. This was a retrospective cohort study within an academic clinic. A total of 6961 fresh IVF and IVF/ICSI cycles from October 1, 2015 to June 30, 2021 were included and grouped by progesterone (PR) prior to trigger: PR < 1.5ng/mL (low PR group) and PR ≥ 1.5ng/mL (high PR group). Main outcome measures included LBR, CPR, and IR. Among all cycle starts, 1568 (22.5%) were in the high PR group and 5393 (77.5%) were in the low PR group. Of the cycles which proceeded to an embryo transfer, 416 (11.1%) were in the high PR group and 3341 (88.9%) were in the low PR group. The high PR group had significantly lower IR (RR 0.75; 95% CI 0.64-0.88), CPR (aRR 0.74; 95% CI 0.64-0.87), and LBR (aRR 0.71; 95% CI 0.59-0.85) compared to the low PR group. When stratified by progesterone on the day of trigger (TPR), there was a clinically notable decrease in IR (16.8% vs 23.3%), CPR (28.1% vs 36.0%), and LBR (22.8% vs 28.9%) in the high PR group compared to the low PR group even when TPR < 1.5ng/mL. In fresh IVF cycles in which TPR < 1.5ng/mL, progesterone elevation ≥ 1.5ng/mL at any point in time prior to trigger negatively impacts IR, CPR, and LBR. This data supports testing of serum progesterone in the follicular phase prior to trigger, as these patients may benefit from a freeze-all approach.

Impact of Insulin Resistance on Ovarian Sensitivity and Pregnancy Outcomes in Patients with Polycystic Ovary Syndrome Undergoing IVF.

Ovarian sensitivity index (OSI) is an accurate index to reflect the ovarian sensitivity to exogenous gonadotropins in in vitro fertilization (IVF). How insulin resistance (IR) affects OSI and pregnancy outcomes during IVF remains unclear. This was a large retrospective, cohort study. A total of 2055 women with polycystic ovary syndrome (PCOS) undergoing the first fresh IVF cycle were enrolled. They were grouped into terciles based on the homeostasis model assessment of insulin resistance (HOMA-IR) values as control, medium and IR group for comparison. Multivariate regression analysis was also conducted. HOMA-IR had a significantly negative impact on OSI (adjusted β = -0.24; 95% CI, -0.35 to -0.13), especially in lean patients with an adjusted β of -0.33 (95% CI, -0.51 to -0.16). The interaction analysis revealed an interactive association between HOMA-IR and body mass index (BMI) (p = 0.017). IR was related to an increased early miscarriage risk independently with an odds ratio (OR) of 2.21 (95% CI, 1.13 to 4.33), without significant impact on pregnancy and live birth rate. IR decreased the ovarian response in PCOS patients undergoing IVF, especially in the lean subgroup. IR may result in a higher risk of early miscarriage, but did not impair pregnancy and live birth rate.

High initial FSH dosage reduces the number of available cleavage-stage embryos in a GnRH-antagonist protocol: Real-world data of 8,772 IVF cycles from China.

To evaluate the relationship between the initial follicle stimulating hormone (FSH) dose and the number of available cleavage-stage embryos in in vitro fertilization (IVF) cycles.We included 8772 fresh IVF cycles using a GnRH antagonist protocol at the Genetic and Reproductive Institution of Chongqing, P. R. China, from January 2016 to June 2021.Univariate linear regression was used to evaluate the associations between the initial FSH dosage (≤ 150, 187.5-200, 225, 250, or 300 IU) with the number of available cleavage-stage embryos on day 3.A two-factor linear regression model was applied to calculate the threshold effect of the initial FSH dosage on the number of available cleavage-stage embryos based on a smoothing plot. The initial FSH dose was negatively correlated with the number of available cleavage-stage embryos, independent of female age, body mass index, infertility factors, duration of infertility, anti-Müllerian hormone and basal FSH levels, antral follicle count and the proportions of patients with poor ovarian response or polycystic ovarian syndrome. Using a two-factor linear regression model, we calculated the inflection point to be 200 IU of FSH. The relationship between the initial FSH dose and the number of available cleavage-stage embryos was nonlinear. The initial FSH dose was negatively associated with the number of available cleavage-stage embryos when the initial FSH dose was > 200 IU. Therefore, clinicians should try to avoid unnecessarily increasing the initial FSH dose.

Adaptive data-driven models to best predict the likelihood of live birth as the IVF cycle moves on and for each embryo transfer

PurposeTo dynamically assess the evolution of live birth predictive factors’ impact throughout the in vitro fertilization (IVF) process, for each fresh and subsequent frozen embryo transfers.MethodsIn this multicentric study, data from 13,574 fresh IVF cycles and 6,770 subsequent frozen embryo transfers were retrospectively analyzed. Fifty-seven descriptive parameters were included and split into four categories: (1) demographic (couple’s baseline characteristics), (2) ovarian stimulation, (3) laboratory data, and (4) embryo transfer (fresh and frozen). All these parameters were used to develop four successive predictive models with the outcome being a live birth event.ResultsEight parameters were predictive of live birth in the first step after the first consultation, 9 in the second step after the stimulation, 11 in the third step with laboratory data, and 13 in the 4th step at the transfer stage. The predictive performance of the models increased at each step. Certain parameters remained predictive in all 4 models while others were predictive only in the first models and no longer in the subsequent ones when including new parameters. Moreover, some parameters were predictive in fresh transfers but not in frozen transfers.ConclusionThis work evaluates the chances of live birth for each embryo transfer individually and not the cumulative outcome after multiple IVF attempts. The different predictive models allow to determine which parameters should be taken into account or not at each step of an IVF cycle, and especially at the time of each embryo transfer, fresh or frozen.

P-523 rs2277698 Single nucleotides polymorphisms in tissue inhibitors of metalloproteinases 2 (TIMP2) affected clinical outcomes of women undergoing in vitro fertilization

Abstract Study question Is there any association between clinical outcomes of women undergoing in vitro fertilization (IVF) and the polymorphic variants of matrix metalloproteinases (MMPs) or tissue inhibitors of metalloproteinases (TIMPs)? Summary answer Our findings suggested that clinical outcomes of women undergoing IVF were associated with rs2277698 SNPs in TIMP2. What is known already The extracellular matrix proteolytic machinery is one of the most important mechanisms for regulating trophoblast invasion. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), which are involved in the extracellular matrix proteolysis process, have the ability to regulate the degradation of the extracellular matrix and play a critical role in trophoblast invasion. Study design, size, duration A prospective study was composed of 1014 women undergoing their first fresh IVF cycle with non-donor from January 2014 to December 2015. Participants/materials, setting, methods The present study was carried out in Lee Women’s Hospital, Taiwan. DNA was extracted from the peripheral blood of all participants, and the SNPs were genotyped by real-time polymerase chain reaction. The effects of the following three single nucleotide polymorphisms (SNPs) on IVF outcomes were explored: TIMP1 (rs4898 C/T), TIMP2 (rs2277698 C/T) and MMP2 (rs243865 C/T). The SNP genotype, correlation with clinical pregnancy, embryo implantation, abortion and live birth rates of IVF were analyzed. Main results and the role of chance In the analysis of 1014 patients attempting their first cycle of IVF, the genotypes frequencies of the study population showed a statistically significant association between TIMP2 (rs2277698 C/T) and clinical outcome. For TIMP2 polymorphisms, women with wild genotype (CC) hadhigher clinical pregnancy rate (34.8% v.s 28.0%; p = 0.032), embryo implantation rate (19.4% v.s 15.4%; p = 0.009), live birth rate (29.8% v.s 22.1%; p = 0.006), and lower abortion rate (7.0% v.s 17.1%; p = 0.005) compared women with CT/TT genotype. On the other hand, the clinical outcomes in different TIMP1 or MMP2 gene polymorphisms groups were no statistically significant difference. Limitations, reasons for caution The size number of the study samples. Wider implications of the findings This study showed that the TIMP2 SNP polymorphisms CT/TT was associated with low trend of clinical outcomes. The mechanism of TIMP2 gene T allele affected the outcomes of IVF remains to be determined. Further studies should focus on the mechanism of these associations in a larger, more heterogeneous cohort. Trial registration number CS13194

P-650 Partial premature ovulation detection during follicular aspiration compromises the quantity but not the quality of the retrieved oocytes in stimulated fresh IVF cycles

Abstract Study question Is partial premature ovulation (PPO) detection during the oocyte pick-up (OPU) a sign of poor prognosis in in vitro fertilization (IVF) cycles with own oocytes? Summary answer PPO halves the number of metaphase II oocytes available for an IVF treatment without reducing their quality, demonstrated by unaltered fertilization and top-quality blastocyst rates. What is known already PPO detected during the OPU procedure has not been extensively studied in the literature. This phenomenon may result in a reduction in the number and/or competence of the oocytes retrieved, due to the potential loss of the already expelled oocytes, as well as the likely dominance exerted by the ruptured follicle/s in the rest of the cohort. Despite this, several authors have demonstrated that competent oocytes can be retrieved from these already ruptured follicles, suggesting that oocyte extrusion frequently does not occur after follicle rupture. The potential negative effect exerted in the rest of sibling oocytes remains unknown. Study design, size, duration Retrospective cohort analysis performed in IVIRMA Valencia (Spain), including 8994 cycles of controlled ovarian stimulation (COS) for an IVF treatment with fresh own oocytes, between January 2016 and May 2021. OPU procedures for oocyte cryopreservation, as well as mixed cycles with both fresh and frozen oocytes, were discarded. PPO diagnosis was based on ultrasound visualization of any already formed corpus luteum structure/s, a lower follicular count than expected, and/or free fluid. Participants/materials, setting, methods Female patients undergoing OPU after COS for a fresh IVF treatment. Cycles in which PPO has been detected will be compared with a random, and of the same size, sample without PPO. Mean number of oocytes, metaphase II, fertilized oocytes and top-quality embryos, as well as IVF success rates, will be compared between both groups. Patients’ basal characteristics and COS parameters will be analyzed in order to detect any potential early indicator of PPO. Main results and the role of chance PPO was detected in 123 of the 8994 cycles (1.37%) performed. A random control group of 123 cycles without PPO was selected. Patients’ mean age was 37.6±3.6, with a BMI of 23.3±4.1 kg/m2 and an anti-mullerian hormone of 1.62±1.3 ng/mL. Patient’s basal characteristics and COS parameters were statistically comparable among groups (p &amp;gt; 0.05), except for lower serum estradiol levels (2037.64 vs. 1582.24 pg/mL; p = 0.004) in the PPO group on the last ultrasound prior to OPU. Patients with PPO showed lower aspiration rates (88.95% vs. 55.78% in the PPO gr.), as well as a reduced mean number of oocytes (10.69 vs. 5.68 in the PPO gr.), metaphase II (8.41 vs. 4.33 in the PPO gr.), fertilized oocytes (6.23 vs. 3.26 in the PPO gr.) and top-quality blastocysts (2.77 vs. 1.35 in the PPO gr.) (p = 0.000). In contrast, maturation (80.72% vs. 76.57% in the PPO gr.), fertilization (73.52% vs. 75.18% in the PPO gr.) and top-quality blastocyst rates (44.03% vs. 38.68% in the PPO gr.) were statistically similar between both groups (p &amp;gt; 0.05). Limitations, reasons for caution The main limitations of the present study are its retrospective design and its small sample size, derived from the low frequency of the PPO phenomenon in our clinic. Larger prospective studies should be proposed in order to accurately define the negative impact of PPO in IVF success rates. Wider implications of the findings PPO clearly reduces the number of oocytes available for an IVF treatment, although it does not seem to impair the competence of the remaining cohort. Once PPO is detected, cycle cancellation may not be worth the associated loss of money, time and morale, especially given its low prevalence (around 1%). Trial registration number Not applicable

Supraphysiological hCG day estradiol levels can predict pregnancy-associated plasma protein A levels in maternal serum in the first trimester

Objective To investigate the effect of hCG day estradiol (hCG-E2) used in Down Syndrome screening on maternal serum levels of PAPP-A in fresh in vitro fertilization (IVF) cycles. Methods This study was a retrospective analysis of a cohort that resulted in a single pregnancy after a total of 92 fresh IVF cycles. The primary outcome of this study was to determine the effect of fresh IVF cycle parameters on the PAPP-A level and the cutoff value for hCG-E2 predicting a low PAPP-A level, while the secondary outcome was to determine whether the effect of IVF parameters on the PAPP-A level was significant. Results There was a negative correlation between PAPP-A levels and the number of hCG-E2 and grade 1 embryos (respectively, p = .049; .047), while a positive correlation was observed between baby weight at birth and the PAPP-A (p < .05). At a PAPP-A value of 0.82, the difference between the two groups, in terms of hCG-E2, the number of grade 1 embryos, and pregnancy-related complications was significant (p = .050; .029; .033, respectively). The threshold value of hCG-E2 affecting PAPP-A levels was statistically significant (AUC = 0.618; p = .050; hCG-E2 = 4869.5 pg/ml). In the model, an increase in the number of grade 1 embryos resulted in higher PAPP-A levels (OR = 2.26; p = .044). Conclusion The fact that the hCG-E2 cutoff value, which lowers PAPP-A, reflects excessive ovarian stimulation argues for the correction of the dual screening test in a subset of patients with high response to the first-trimester screening test.

Risk factors for twin pregnancy in women undergoing double cleavage embryo transfer

BackgroundTwo or more embryo transfers have been used to increase the success rate of live birth in traditional in vitro fertilization (IVF) strategy at the expense of increased risks of multiple pregnancy and adverse perinatal outcomes. The decision regarding the elective single embryo transfer or double embryo transfer remains inconclusive. The aim of this study was to investigate the risk factors for twin pregnancy in IVF.MethodsParticipants who underwent their first fresh IVF cycle where two cleavage stage embryos were transferred in Women’s Hospital of Zhejiang University between January 2010 and December 2018 were included in this retrospective cohort study. The primary outcome was twin delivery. Secondary outcomes included preterm birth and low birth weightResultsFifteen thousand four hundred fifty-nine women were available for final analysis, in which 1511 women resulted in twin delivery and 4788 women had singleton delivery. Female age over 35 was associated with reduced rates of twin pregnancy compared with female age at or less than 35 (9.5% vs 25.1%, aRR = 0.38 (0.27. 0.55)). Poor-type endometrium was associated with reduced rates of twin pregnancy (19.2% vs 27.5%, aRR = 0.75 (0.58. 0.96)). Two good-quality embryos for transfer was associated with significantly higher rates of twin pregnancy compared with one good-quality or none good-quality embryo (26% vs 12.8% vs 9.3%, aRR = 0.56 (0.45. 0.70), aRR = 0.44(0.26. 0.74)). Female age over 35 and none or one good-quality embryo for transfer were associated with reduced rate of low birth weight and preterm birth.ConclusionWomen with age over 35, poor-type endometrium, one good-quality embryo or none good-quality embryo were associated with reduced rate for twin pregnancy.

Role of three-dimensional Doppler ultrasonography and leukemia inhibitory factor from endometrial secretion in predicting endometrial receptivity in IVF treatment: a pilot study

PurposeThis pilot study aimed to evaluate the potential synergistic role of three-dimensional power Doppler angiography ultrasound and the expression of Leukemia Inhibitory Factor (LIF) protein in predicting the endometrial receptivity of fresh In-Vitro Fertilization (IVF) cycles.Materials and methodsThis prognostic cohort study involved 29 good prognosis women who underwent fresh IVF cycles with fresh blastocysts transfer. Serial measurements of sub-endometrial parameters including vascularity index (VI), flow index (FI), and vascularization flow index (VFI) were conducted consecutively via power Doppler angiography on the day of oocyte maturation trigger, oocyte retrieval, and blastocyst transfer. Aspiration of endometrial secretion was performed on the day of embryo transfer.ResultsThe mean index of VI and VFI on the trigger and oocyte retrieval day and also LIF protein concentration at the window of implantation were significantly higher in clinically pregnant women than that of the non-pregnant women (p < 0.05). The area under the curve (AUC) of VI and VFI was shown to have a powerful predictive value to forecast receptive endometrium on either trigger day (0.788 and 0.813, respectively) or oocyte retrieval day (0.813 and 0.818). Likewise, LIF concentration on the day of embryo transfer was adequate to become a predictor for endometrial receptivity (AUC 0.874). A combination of the VI and VFI on the trigger day and LIF concentration at specific cut-off values (VI > 5.381, VFI > 1.483, LIF 703.5 pg/mL) produced an algorithm with high AUC (0.881) and high specificity (94.4%) for an adequate prediction of non-receptive endometrium.ConclusionVI and VFI index assessed on maturation trigger day and the expression of LIF protein concentration at the window of implantation provided sufficient information to predict endometrial receptivity. A large randomized control trial is needed to validate these findings.

No Effect of Inactivated SARS-CoV-2 Vaccination on in vitro Fertilization Outcomes: A Propensity Score-Matched Study.

PurposeTo investigate the impact of inactivated SARS-CoV-2 vaccination on in vitro fertilization (IVF) outcomes.Patients and MethodsThis retrospective cohort study included 2185 patients undergoing fresh IVF cycles from June 1st to September 13th 2021 in a single university-affiliated hospital. Vaccine administration information was collected and ascertained via immunization records. Patients with two dosages of inactivated SARS-CoV-2 vaccines (Sinopharm or Sinovac) were categorized into the vaccinated group (n = 150), while those unvaccinated were classified as control (n = 2035). Propensity score matching was performed to balance the baseline characteristics (14 covariates) between the two groups at a ratio of 1:4. The main outcome measures were the number of oocytes retrieved, good-quality embryo rate and clinical pregnancy rate.ResultsThere were 146 women in the vaccinated group and 584 in the control group after matching. The number of oocytes retrieved (9.9 ± 7.1 vs 9.9 ± 6.7; P = 0.893), good-quality embryo rate (33.5 ± 29.8% vs 29.9 ± 28.6%; P = 0.184) and clinical pregnancy rate (59.1% vs 63.6%; P = 0.507) were all similar between the two groups. In addition, no significant differences were observed regarding other cycle characteristics, laboratory parameters and pregnancy outcomes. The results were also comparable when vaccinated patients were subdivided into three categories based on the time interval from complete vaccination to cycle initiation: ≤1 month, >1–2 months, and >2 months.ConclusionOur study provided the first-time evidence that inactivated SARS-CoV-2 vaccination in females did not result in any measurable detrimental effects on IVF treatment. Owing to the present limitations, further prospective studies with larger cohort size and longer follow-up are warranted to validate our conclusion.

Effect of intrauterine administration of human chorionic gonadotropin one day before fresh blastocyst transfer on clinical outcomes: a quasi-experimental study.

Introductionembryo implantation is a crucial step for assisted reproductive technology (ART) achievement. Human chorionic gonadotropin (hCG) is one of the main regulators of the implantation process. Studies focusing on the impact of intrauterine hCG infusion at the time of embryo transfer on clinical ART outcomes have shown controversial results, mainly at blastocyst stage. In this study, we aimed to investigate whether intrauterine hCG infusion one day before human blastocyst transfer in fresh invitro fertilization (IVF) cycles enhances implantation and pregnancy rates.Methodsa total of 174 subfertile women undergoing autologous fresh blastocyst transfer were enrolled in this randomized prospective study. Patients were randomly divided into three groups; group 1 (n = 54) and group 2 (n = 59) received an intrauterine injection of respectively 500 IU and 1000 IU of hCG one day before blastocyst transfer and the control group (n= 61) did not receive any intrauterine injection. The pregnancy and implantation rates were compared between the three study groups.Resultssignificant difference was found between the study groups. The bio chemical pregnancy rates were 25.9%, 30.5% and 29.5%, the clinical pregnancy rates were 24.1%, 27.1% and 27.9% and the implantation rates were 14.9%, 17.9% and 18.7% respectively in group 1,2 and control group.Conclusionour results have shown that clinical outcomes in fresh IVF cycles cannot be improved through intrauterine hCG administration one day prior to blastocyst transfer, neither with 500 IU of hCG nor with a higher dose of 1000 IU of hCG.

Association of the microbial culture of follicular fluid, vaginal swab and catheter tip with β–hCG IVF positive and negative

Objective: To find out the association of microbial contamination with β-human chorionic gonadotropin ( β-hCG) in-vitro fertilization (IVF) positive and negative.Methods: A total of 73 fresh IVF cycle women were included in the retrospective study. Vaginal swab culture samples were collected prior to ovum pick-up and embryo transfer. The follicular fluids were collected during ovum pick-up and catheter tip culture samples were collected after successful embryo transfer. After 14 days of the embryo transfer, women were classified into β-hCG IVF positive and negative. The comparative statistical analyses of aerobic microbial culture reports were done between β-hCG IVF positive and negative women.Results: Out of 73 women, 42(57.5%) were found to be β-hCG IVF positive and 31(43.5%) were negative. In the aerobic culture of ovum pick-up vaginal swab, follicular fluid, embryo transplantation vaginal swab and catheter tip, Enterococcus faecalis was found to be higher compared to other bacteria (Streptococcus spp., Candida, Escherichia coli and Klebsiella). Regarding the comparison between IVF positive and negative, the overall microbial infection rate of vaginal swab culture during ovum pick-up and embryo transplantation was found to be higher in IVF negative women than in IVF positive women (38.71% vs. 28.57%); however, it was not statistically significant (P>0.05). The follicular fluid and catheter tip culture microbial infection rate was found to slightly higher in IVF positive women than in IVF negative women (54.76% vs. 41.94% and 19.05% vs. 9.68%, respectively), but there were not significant differences (P>0.05).Conclusions: The aerobic microbial culture reports of follicular fluid, vaginal swab culture, and catheter tip culture are not statistically significantly with β-hCG IVF positive.

Do vitrified frozen-thawed embryos generated from successful fresh cycles have higher potential for favorable outcome?

Many variables, including woman's age, embryo quality and endometrial receptivity, influence the success rate of either fresh embryo transfer (ET) or frozen-thawed ET (FT-ET) cycles. This study aims to examine whether the results of a fresh in-vitro fertilization (IVF) cycle correlate with its frozen-thawed embryos transfer outcomes. A retrospective cohort study conducted in a tertiary medical center single IVF unit between 2014-2017. The study population was comprised of women who underwent fresh ET with the remaining embryos frozen using vitrification and at least one consecutive FT-ET cycle. Comparison of FT-ET cycle's details and outcomes were assessed in relation to the outcome of preceding fresh ET cycle. A total of 599 women underwent fresh ET and at least one consecutive FT-ET cycle. Significantly higher rates of successful FT-ET cycle outcomes were observed in the group of patients with a successful fresh cycle compared to the group with an unsuccessful fresh cycle (48.9% vs. 20.8%, P<0.001). Logistic regression demonstrated an adjusted OR of 5.02 for successful FT-ET after a successful fresh cycle. Frozen-thawed embryos generated from successful fresh IVF cycles have higher potential to implant when compared to frozen-thawed embryos obtained in an unsuccessful fresh cycle.