Probability Of Live Birth Research Articles

Predictions of live birth in IVF programs of patients with recurrent implantation failure

BackgroundWhen a high-quality embryo is implanted into the uterus, but the pregnancy is not established as shown by the ultrasound visualization of an intrauterine gestational sac, this is known as “implantation failure.” Cases when more than two times implantation failure occurred was defined as recurrent implantation failure (RIF). Additional testing is done at this stage of infertility treatment to avoid a repeat of the same result with a future in vitro fertilization (IVF) effort. Aim of the studyThe study aimed to evaluate predictive value of using embryo transfer personalization because of the implantation window study in combination with preimplantation genetic testing in patients with recurrent implantation attempts. MethodsBriefly describe the main methods or treatments applied: Ninety-three infertile women make up the sample for this prospective cohort study. In regard to treatment results, the study intends to assess the predictive importance of patient characteristics, screening indicators, and several features of IVF cycles, such as the quantity, quality, and developmental stage of the transferred embryos. Statistical methods employed include the calculation of the median (Me) and interquartile range (IQR) for continuous variables. The Mann-Whitney U test was used to discern differences between unrelated samples, while categorical variables were presented as absolute and percentage values. The Pearson’s Chi-squared test assessed differences between groups. Logistic regression, utilizing both enter and backward Wald methods, was applied to establish associations with binary outcomes. ResultsThe integration of individualized embryo transfer and preimplantation genetic testing (PGT) significantly enhanced the likelihood of live births by 3.4 times in patients experiencing recurrent implantation failure (RIF), with a statistical significance of p = 0.026. In contrast, employing PGT alone increased the probability of live births by 1.5 times; however, this result was not statistically significant (p = 0.439). The predictive model for live birth in patients with RIF, based on our study findings, is defined as follows: the probability of live birth = 1.936 + [1.014 if PGT-A embryos are utilized for transfer] + [1.742 if endometrial preparation is tailored according to the Wellbeing Index (WI)] − [1.860 in cases of secondary infertility] − [1.891 when a male factor is involved]. ConclusionsThe determination of the implantation window (IW) and PGT of the embryo are efficient methods of live birth achievement for patients with RIF.

Higher serum progesterone level has no negative impact on live birth rate in frozen embryo transfer

Optimal synchronisation between the endometrium and the embryo is key to the success of frozen embryo transfers (FET). It is achieved by administering different doses of exogenous oestrogen and progesterone (P4). The negative impact of low levels of P4 on FET has been reported, but there is a lack of knowledge about which levels are most appropriate. We aimed to evaluate whether high serum P4 levels measured on FET day affect the probability of having a baby at home. This retrospective cohort study includes 7546 FET cycles performed with hormone replacement therapy (HRT) for artificial endometrial preparation. Patients were divided into three groups according to P level on FET day (ng/mL): P4 < 20(n = 6623), P4 ≥ 20–40 (n = 770) and P > 40 (n = 146). Female age was per group P4 < 20 = 38.7 ± 3.1, P ≥ 20–40 = 39.0 ± 3.0, and P4 > 40 = 38.1 ± 2.9 years old (p = 0.53). The group with the highest progesterone levels found lower ongoing pregnancy rates without statistical significance (56.3 % (P4 < 20) vs 56.8 % (P4 ≥ 20-<40) vs 51.4 % (P4 > 40); p = 0.5). Miscarriage rate was also higher, although not significantly: 16.2 % (P4 < 20) vs 15.0 % (P4 ≥ 20-<40) vs 18.0 % (P4 > 40) (p = 0.6). These findings were explored with an adjusted analysis. A higher, but not significant, odds of miscarriage was observed when P4 > 40 ng/ml, aOR = 1.14 (0.75–1.74) (p = 0.55) whereas no such association was found with P4 ≥ 20–40 ng/ml (aOR = 0.92 (0.74–1.15) (p = 0.46)). The probability of livebirth is similar when the patient was P4 > 40 (aOR = 0.77 (0.51–1.15) (p = 0.20)) than when P4 ≥ 20-<40 (aOR = 0.94 (0.79–1.11) (p = 0.47). In conclusion, women with elevated serum P4 levels on the day of FET after HRT do not find their probability of live birth impaired.

Is there a relationship between morphokinetic parameters and obstetrical complications? An analysis of singleton live births after single fresh embryo transfer

BackgroundWith the advancement in embryology and the introduction of time-lapse monitoring system, the embryologists' goal might be to find not only the embryo with the highest probability of live birth, but also the embryo with the highest probability to progress to a healthy full-term delivery. Thus, we aimed to investigate the association between morphokinetic time-lapse parameters and obstetrical and perinatal complications.MethodsA cohort study reviewing fertility and delivery files of all singletone births from IVF patients whose embryos were cultured in a time-lapse monitoring system and had a single fresh embryo transfer at our center between 2013–2019. We conducted multiple comparisons between complicated and uncomplicated pregnancies of each perinatal complication, including: gestational diabetes mellitus (GDM); small for gestational age (SGA); pre-eclamptic toxemia (PET); preterm labor < 37 weeks of gestation (PTL); and third stage of labor complications. A comparison between pregnancies with and without a composite outcome of placental complications including GDM, SGA, PET and PTL was also conducted. Baseline characteristics, treatment and morphokinetic parameters in complicated and uncomplicated gestations were compared. Logistic regression analysis was utilized to adjust results for potential confounders.ResultsOne hundred seventy-six single embryo transfers resulted in 176 live births. Morphokinetic time-lapse parameters were similar between the groups, except for a shorter time to full blastulation in the SGA group (tB-tPNf = 75.5 ± 1.3 h vs. 79.5 ± 4.8 in the non-SGA group, p < 0.001), and shorter third cell cycle duration in the PET group (CC3 = 12.4 ± 1.1 h vs. 13.6 ± 2.9 in the non-PET group, p = 0.02). On multivariate regression analysis, none of the morphokinetic parameters were found to be significantly correlated with any of the perinatal complications.ConclusionTime-lapse morphokinetic parameters of the embryo transferred are not associated with adverse obstetric and perinatal outcomes.

Nomogram for predicting live birth in ovulatory women undergoing frozen-thawed embryo transfer

BackgroundStudy objectives included the development of a practical nomogram for predicting live birth following frozen-thawed embryo transfers in ovulatory women.MethodsTotally, 2884 patients with regular menstrual cycles in our center were retrospectively enrolled. In an 8:2 ratio, we randomly assigned patients to training and validation cohorts. Then we identified risk factors by multivariate logistic regression and constructed nomogram. Finally, receiver operating characteristic curve analysis, calibration curve and decision curve analysis were performed to assess the calibration and discriminative ability of the nomogram.ResultsWe identified five variables which were related to live birth, including age, anti-Müllerian hormone (AMH), protocol of frozen-thawed embryo transfer (FET), stage of embryos and amount of high-quality embryos. We then constructed nomograms that predict the probabilities of live birth by using those five parameters. Receiver operating characteristic curve analysis (ROC) showed that the area under the curve (AUC) for live birth was 0.666 (95% CI: 0.644–0.688) in the training cohort. The AUC in the subsequent validation cohorts was 0.669 (95% CI, 0.625–0.713). The clinical practicability of this nomogram was demonstrated through calibration curve analysis and decision curve analysis.ConclusionsOur nomogram provides a visual and simple tool in predicting live birth in ovulatory women who received FET. It could also provide advice and guidance for physicians and patients on decision-making during the FET procedure.

Pregnancy outcome predictors in systemic lupus erythematosus: a systematic review and meta-analysis

To enhance patient-tailored preconception risk assessment for women with systemic lupus erythematosus (SLE), knowledge on risk factors associated with adverse pregnancy outcomes is required. Therefore, we did a systematic review and meta-analysis to identify and provide unambiguous effect sizes of preconception predictors of pregnancy outcomes in women with SLE. In this systematic review and meta-analysis, we searched PubMed and Embase for studies reporting preconception predictors of pregnancy outcomes in women with SLE, from database inception to Aug 22, 2023. Studies were included if they presented original, quantitative data on pregnant women with SLE and reported on preconception risk factors on at least one of the outcomes as defined in the protocol. Studies were excluded if they had a sample size of less than 20 patients, were restricted to multiple pregnancies, had unclear timing of prognostication, or exclusively reported a composite outcome. Literature screening, data extraction, and risk-of-bias assessment (quality in prognostic studies tool) were done by two reviewers independently, in a blinded, standardised manner. The reported outcomes included livebirth, pre-eclampsia, small for gestational age, preterm birth, pregnancy loss before and after 20 weeks of gestation, and SLE flares. We computed pooled univariate odds ratios (ORs) and 95% CIs using a random effects model. We assessed heterogeneity using the I2 statistic and prediction intervals. This study is registered with PROSPERO, CRD42022344732. Of the 6705 unique articles identified, 72 (1·1%) were included in the meta-analysis, comprising 10 355 pregnancies in 8065 women with SLE. One potentially eligible study was retracted and therefore removed from our analysis. Previous lupus nephritis was associated with decreased livebirth probability (OR 0·62 [95% CI 0·47-0·81]; I2=0%), increased risk of preterm birth (2·00 [1·55-2·57]; I2=17%), and increased risk of pre-eclampsia (3·11 [2·35-4·12]; I2=0%). Chronic hypertension was associated with increased risk of disease flare (2·50 [1·74-3·58]; I2=0%), preterm birth (2·65 [1·87-3·77]; I2=0%), and pre-eclampsia (5·86 [3·41-10·06]; I2=33%). SLE disease activity at conception or preconception was associated with increased risk of preterm birth (2·91 [1·96-4·33]; I2=21%) and pre-eclampsia (2·32 [1·40-3·83]; I2=0%). Secondary antiphospholipid syndrome was associated with decreased livebirth probability (0·40 [0·27-0·58]; I2=0%), increased risk of pregnancy loss after 20 weeks of gestation (2·77 [1·44-5·31]; I2=0%), and increased risk of preterm birth (1·65 [1·29-2·11]; I2=0%). Across studies, risk-of-bias assessment suggested considerable bias in study attrition and confounding. We identified previous lupus nephritis, chronic hypertension, SLE disease activity before and at conception, and secondary antiphospholipid syndrome as predictors of adverse pregnancy outcomes in women with SLE. These findings contribute to an optimal patient-tailored risk assessment in preconception counselling. None.

O-063 How does the exclusion of blastomeres affect the outcome of euploid blastocysts?

Abstract Study question Do euploid blastocysts with excluded blastomere(s) have the same probability of live birth when compared to euploid blastocysts without excluded blastomere(s)? Summary answer Euploid blastocysts with excluded blastomere(s) have significantly worse pregnancy outcomes, with the live birth rate being 10% lower than those without any exclusion pattern. What is known already Blastomeres that have arisen at any time throughout cleavage-stage are sometimes excluded from the formation of the blastocyst and once isolated, those cells do not take further part in preimplantation development. Embryos harboring cell exclusion were found to have altered morphokinetic profiles; S2(second synchrony) and ECC3(embryonic cell cycle 3) were described as useful in identifying increased odds of FHB when a cell exclusion event was present (Kakulavarapua et al., 2023). Besides, pregnancy and live birth rates were reported to progressively decrease in a non-PGT-A (preimplantation genetic testing for aneuploidy) tested cohort with excluded or extruded blastomere(s) (Coticchio et al., 2021). Study design, size, duration This retrospective study included 667 euploid blastocysts with excluded blastomere(s) and 3830 euploid blastocysts without excluded blastomere(s). All were transferred between 2017 and 2023. No discrimination was made between cells failing to compact because of their exclusion from the compaction process (excluded from a partially compacted morula), and cells extruded after an initial inclusion in the compacted embryonic mass (extruded from a partially compacted morula). Participants/materials, setting, methods A total of 4497 IVF patients treated in a single private clinic were included in this retrospective study. Their blastocysts were subjected to PGT-A mainly for advanced maternal age. The analysis was done by next generation sequencing (NGS) (Ion Torrent S5, Thermo Fisher). Vitrified-warmed euploid blastocysts were then transferred in a next cycle. Pregnancy and miscarriage rates were compared between blastocysts with and without excluded blastomere(s) by chi-square test. Main results and the role of chance The outcomes of euploid blastocysts with excluded blastomeres (n = 667) were compared to euploid blastocysts without excluded blastomeres (n = 3830). The biochemical pregnancy rate was 71.6% and 77%, respectively (p = 0.0026). The clinical pregnancy rate was 61.3% and 70.6%, respectively (p = 0.0001). The ongoing pregnancy rate was 53.7% and 63.3%, respectively (p = 0.0001). The biochemical miscarriage rate nearly doubled with the presence of excluded blastomere(s) (14% vs. 8.3%, respectively; p = 0.0001). The clinical miscarriage rate was 12.7% and 10.4%, respectively (ns). Ultimately, the live birth rate was 46.3% for the blastocysts with excluded blastomere(s), compared to 57.6% for the blastocysts without excluded blastomere(s) (p = 0.0001). Limitations, reasons for caution No discrimination was made between cells excluded from a partially compacted morula and cells extruded after an initial inclusion in the compacted embryonic mass. Wider implications of the findings Although blastocysts with excluded blastomere(s) are not the first choice for transfer, our results show that, although at lower rate, successful pregnancies and live births occur. A complete time-lapse culture evaluation not limited to cell division time points may propose indicators to identify higher implantation potential blastocysts with excluded blastomere(s). Trial registration number N/A

O-250 Never a lost cause: can artificial intelligence (AI)-powered ranking help decrease time to pregnancy when only poor-quality embryos are available?

Abstract Study question Can an objectively trained AI system complement embryologists in their ranking of embryos and minimize time to pregnancy, when only poor-quality embryos are available? Summary answer An objective AI algorithm could have decreased cycle to pregnancy by 18% in cohorts of embryos where only poor-quality embryos were available. What is known already Morphokinetics is a key criterion for embryologists to rank embryos as good, fair, or poor quality, with the latter frequently being discarded. Although poor-quality embryos can still lead to a pregnancy, selection of a viable embryo remains challenging to embryologists due to their depleted morphological characteristics. Unlike embryologists, an AI can be trained to see beyond embryo morphological quality, on data that includes many poor-quality embryos that resulted in a pregnancy. As such, AI has the potential to recognize viable poor-quality embryos, which becomes especially crucial in cases where good or fair embryos are unavailable from the embryo pool. Study design, size, duration Data from a French center was acquired through a MIRI® (ESCO) time-lapse system and uploaded on EMBRYOLY, between January 2022 and March 2023. For a total of 204 patients (women’s average age 35 y.o.), embryologists were faced with having to choose an embryo to transfer among 4.3 ± 1.7 poor-quality embryos either because the cohort was composed of only poor-quality embryos or because higher quality embryos had already been transferred. Participants/materials, setting, methods A previously described deep learning algorithm trained on videos of developing embryos with known pregnancy outcome was used to score embryos according to their chances of leading to a clinical pregnancy (fetal heartbeat between 6-9 weeks). A 2D ResNet model was trained, validated and tested on 8138 images of day 5 embryos annotated by senior embryologists to identify those of poor-quality (Gardner grade ICM and/or TE = C, corresponding to 44.7% of the dataset). Main results and the role of chance The association between video predictions and pregnancy was assessed with a logistic regression. A McNemar test was used to compare cycle to pregnancy (CTP) with and without EMBRYOLY’s hypothetical impact. EMBRYOLY’s AI was able to rank poor-quality embryos, as illustrated by a 2-7% relative increase in likelihood of clinical pregnancy observed with an increase in the video score (logistic regression with unit level +0.02, OR = 1.04, 95CI = [1.02-1.07], N = 261 transferred embryos, p &amp;lt; 0.05). EMBRYOLY’s first choice was concordant with the embryologists’ first choice in 74% of the cases that led to a pregnancy (N = 42 embryos). For patients who had two poor-quality embryos transferred with at least one pregnancy (N = 14 cycles), the results show that if the embryologist had first transferred the highest EMBRYOLY-ranked embryo, the number of cycles to pregnancy would have been reduced by 18% (from 1.7 to 1.4, McNemar, p &amp;lt; 0.05), corresponding to a median of 2.3 months. Limitations, reasons for caution The endpoint used was clinical pregnancy as measured by fetal heartbeat, and does not indicate the probability of live birth. The current investigation was performed with retrospective data from a single center. In the future, a multi-centre evaluation should be performed to generalize our findings. Wider implications of the findings Our findings support that an objectively trained AI can help embryologists not miss out on poor-quality embryos that can lead to a pregnancy, which is all the more important to target when good or fair embryos are unavailable from the embryo pool. Trial registration number not applicable

P-093 The effect of antioxidant supplementation on sperm quality in infertile men: a randomized placebo-controlled clinical trial

Abstract Study question Is sperm quality improved in infertile men after administration for three months of a combination of antioxidants as compared to placebo? Summary answer Administration in infertile men for three months of a combination of antioxidants as compared to placebo does not improve sperm quality. What is known already In infertile men, limited evidence exists to support treatment with a combination of antioxidants for improving sperm quality. A recent Cochrane meta-analysis suggested that treatment of these patients with combinations of antioxidants as compared to placebo or no treatment results in an increase in sperm motility (MD + 12.71 95%CI +11.33 to + 14.08, 7 studies, 684 patients), while no beneficial effect was observed on DNA fragmentation index (DFI) and on the probability of live birth. Nevertheless, combinations of antioxidants are widely used in clinical practice at present. Study design, size, duration This randomized placebo-controlled trial evaluated the effect of a combination of antioxidants on sperm motility (primary outcome). Secondary outcomes were sperm concentration, morphology, DFI and levels of reactive oxygen species (ROS). For this purpose, 79 infertile men, were randomized, using a computer-generated randomization list, between 2019-2022, to receive either a combination of antioxidants (n = 40) or placebo (n = 39) for three months. This was a quadruple-blind trial (participants, clinicians, outcome assessors, data analyst). Participants/materials, setting, methods Sperm variables were evaluated according to WHO criteria, ROS levels by the detection of 8-hydroxy-2-deoxy-guanosine peroxidation product on sperm and DFI by flow cytometry. For all outcomes, the changes between treatment initiation and completion were assessed in both the antioxidant and the placebo groups and compared statistically. Values are expressed as mean (95%CI of the mean) and statistical significance was set at p = 0.05. Main results and the role of chance Nine patients dropped out from the study, since they did not perform the second sperm analysis for personal reasons and thus did not complete the study process. No differences were observed between the antioxidants and the placebo group regarding male age {mean difference (MD) -1.3 years, 95%CI -1.4 to + 4.1}, smoking (antioxidants: 41.6%, 95%CI 25.5 to 59.2 vs placebo: 43.5%, 95%CI 27.8 to 60.3), exercise (antioxidants: 45.4%, 95%CI 28.1 to 63.6 vs placebo: 16.1%, 95%CI 5.4 to 33.7) and primary infertility (antioxidants: 82.3%, 95%CI 65.4 to 93.2 vs placebo: 85.7%, 95%CI 69.7 to 95.1). No statistically significant differences were observed in infertile men who received a combination of antioxidants or placebo, between the changes of pre and post treatment values, regarding sperm motility (-3.5%, 95%CI: -13 to + 5.9, p = 0.742), concentration (-1.9%, 95%CI: -15.7 to + 11.8, p = 0.0.77), morphology (-0.10%, 95%CI: -0.8 to 0.6, p = 0.793), DFI (0.2%, 95%CI: -3.8 to + 4.4, p = 0.891) and levels of ROS (-1.2%, 95%CI: -3.2 to + 0.8, p = 0.231). No side effects were reported in antioxidants combination treated patients for the duration of follow-up. Limitations, reasons for caution The current RCT did not explicitly include men with abnormal DFI, limiting the extrapolation of the results obtained in this group of patients. Moreover, it was not designed to evaluate the probability of pregnancy either spontaneously or after Medically Assisted Reproduction (MAR). Wider implications of the findings The current study does not support the use of antioxidants for enhancing male infertility. Future relevant studies should focus on identifying the optimal population and duration of treatment. Trial registration number NCT04256278

P-412 Elevated progesterone levels after hormone replacement therapy (HRT) for frozen embryo transfer (FET) does not impair IVF outcomes, a retrospective study

Abstract Study question Does high serum progesterone (P) level on the day of FET after hormone replacement therapy affect IVF outcomes? Summary answer The supraphysiological serum progesterone levels on the day of FET after HRT do not impair reproductive outcomes. What is known already A proper synchronization between embryo and the endometrium is still required by controlling the timing and the dosage of exposure to exogenous hormones. Previous observational studies have highlighted the negative effects of serum hormone levels at the minimum threshold during FET cycles. However, based on existing research, the relationship between progesterone levels on FET day and pregnancy outcomes as well as the certain dose of progesterone ideally to achieve pregnancy and a live birth are debatable topics Study design, size, duration This is an observational, retrospective and cohort study including 7539 FET cycles that were performed under artificial endometrial preparation with HRT using exogenous estradiol and progesterone (vaginal, subcutaneous and intramuscular) between January 2017 and December 2022. Both euploid FET from autologous oocyte ICSI-PGT-A cycles (n = 1822) or FET from ICSI cycles using donated oocytes (n = 5724) were considered. Participants/materials, setting, methods Women were divided into three groups according to P4 level on the day of FET:P&amp;lt;20 ng/ml (n = 6623),P≥20-40 ng/ml (n = 770) and P &amp;gt; 40 ng/ml (n = 146).All ET were performed at the blastocyst stage.The primary outcome was live birth rate (LBR). Secondary outcomes evaluated were biochemical, clinical, and ongoing pregnancy, and miscarriage rate (MR) calculated per FET.Categorical variables were compared between groups with Fisher’s exact test. Logistic regression models adjusted (AOR) with several confounders. Main results and the role of chance There were no significant differences in baseline characteristics of the study population. The mean of P4 level was 15,66 ng/ml. Female age was P &amp;lt; 20:38.7 ±3.1, P ≥ 20-40: 39.0 ±3.0, and P &amp;gt; 40: 38.1 ±2.9 (p = 0.53) years old. The group with the highest progesterone levels always found lower biochemical pregnancy even no statistically significant [64.6% (P &amp;lt; 20) vs 63.7% (P ≥ 20-&amp;lt;40) vs 61.1% (P &amp;gt; 40); p = 0.62]; in clinical pregnancy [56.3% (P &amp;lt; 20) vs 56.8% (P ≥ 20-&amp;lt;40) vs 51.4% (P &amp;gt; 40); p = 0.5] and in ongoing [47.0% (P &amp;lt; 20) vs 47.0% (P ≥ 20-&amp;lt;40) vs 41.8% (P &amp;gt; 40); p = 0.47] pregnancy rates. The MR was also higher in the group with higher progesterone, although not significantly: 16.2% (P &amp;lt; 20) vs 15.0% (P ≥ 20-&amp;lt;40) vs 18.0% (P &amp;gt; 40) (p = 0.60). No statistically significant differences were reported for live birth rate, 41.8% (P &amp;lt; 20) vs 40.3% (P ≥ 20-&amp;lt;40) vs 34.2% (P &amp;gt; 40) (p = 0.2). The multivariate analysis showed an increased risk of miscarriage when P &amp;gt; 40ng/ml, aOR= 1.14 (0.75-1.74) (p = 0.55) whereas no such association was found with P4 ≥20-40 ng/ml, aOR=0.92 (0.74-1.15) (p = 0.46). Additionally, the probability of live birth is similar when the patient was P &amp;gt; 40 (aOR= 0.77 (0.51-1,15) (p = 0.20)) than when P ≥ 20-&amp;lt;40 (aOR=0.94 (0.79-1,11) (p = 0.47) compared with the references group. Limitations, reasons for caution The retrospective design and different female factors for IVF were included in the study leading to a possible biased population although the adjusted analysis. Different routes of progesterone administration were considered in the study. Currently, we don’t report the timing between the last P4 administration and dosage on the FET. Wider implications of the findings This information is useful for clinicians who monitor progesterone levels prior to FET to avoid reaching high levels that would undermine the chances of achieving a newborn. Trial registration number Not Applicable

O-129 Live birth of Day 7 blastocyst transfers. Another chance to succeed

Abstract Study question Does the reproductive potential, especially live birth probability, of embryos decrease when blastocyst development takes longer than the traditionally accepted 5 and 6 days?. Summary answer The reproductive potential decreases with blastulation time. Day 7 had the worst live birth (LB), aneuploidy and miscarriage rates compared to Day 5 and 6. What is known already Ending culture on Day 6 is current practice in most clinics, it is important to elucidate whether or not this is a good practice. It has been reported that Day 7 blastocysts represent only 5% of useable blastocysts, although slower growing compared to Day 5 and 6 blastocysts.Day 7 blastocysts can be viable, they can be of top morphological grade, euploid and result in a LB. Furthermore, the effects of prolonged culture to Day 7 in regards to embryo development and their reproductive potential are not well established. Study design, size, duration Retrospective cohort study of patients from US RMA clinics attempting conception through ICSI and utilizing preimplantation genetic testing for aneuploidy screening (PGT-A) from January 2022 to January 2023. A total of 6,132 ICSI PGT-A cycles were included in the analysis; three thousand six hundred and eighty frozen single embryo transfer (SET) from those resulting ICSI cycles occurred during that period of time were included in the study. Participants/materials, setting, methods Patients that performed an ICSI cycle with autologous oocytes were included in the study. Patients with frozen oocytes, donor egg recipients, non PGT-A cases, and conventional insemination were excluded. The main outcome measures include euploidy rates, miscarriage rates and LB rates between Days 5, 6 and 7. Statistical tests were conducted through Chi-Square Test and logistic regression methods adjusted for maternal age at time of transfer and morphological quality of the blastocyst. Main results and the role of chance Euploidy rate was worse on D7 than D5 or D6, with 45.5%95%CI(43,46%-47,50%), 78.1% 95%CI(77,02%-79,13%), and 63.2%95%CI(62,42%-63,96%) respectively, p&amp;gt;0.0001. LB rate per ET (embryo transfer) was also worse on D7, 21.6%95%CI(15.05-28.09), than D5, 62.3%95%CI(59.73-64.95), and D6, 53.3%95%CI(51.23-55.40). We found D5 and D6 statistically significant vs D7, p&amp;lt;0.0001. When adjusted for potential confounders, and establishing D7 as reference, for LB AdjORD5=4.127,95%CI(2.671-6.378), and AdjORD6=3.241, 95%CI(2.145-4.898). Clinical miscarriage was 20.8%, 95%CI(9.84-31.67) on D7, and 11.2%, 95%CI(9.38-13.09) and 14.1%, 95%CI(12.41-15.75) for D5 and D6 respectively, with AdjORD5=0.478, 95%CI(0.230-0.994) and AdjORD6, 95%CI(0.619, 95%CI(0.310-1.239), being statistically different only for AdjORD5 (p=0.048). Finally, when we analyzed the quality of the inner cell mass (ICM) and the trophectoderm among Day 7 ETs, we found that blastocysts with an A quality ICM had a higher chance of LB (40%) when compared with B (25%) and C (7.1%) ICM. The adjusted OR comparing A vs C revealed significant difference (p=0.005), when A ICM is established as reference. Also, ET of blastocysts graded with an A trophectoderm had higher probability of a LB (44%) when compared with B and C (17.3% and17%, respectively). The adjusted OR, with A trophectoderm as reference, B and C trophectoderm revealed significant difference (p=0.012 and p=0.007, respectively). Limitations, reasons for caution The primary limitation is the low number of Day 7 blastocyst transfers. To determine whether Day 7 blastocysts are intrinsically worse from Day 5/6 embryos, prospective randomized studies with patients who have at least one embryo developed on day 5, 6 and 7 suitable for transfer are needed. Wider implications of the findings Expanding blastocyst culture increases the number of useable embryos per cycle and provides further opportunity of LB for patients, especially those with a few or low-quality blastocysts. This study demonstrates that Day 7 blastocysts can achieve live births and challenges the predominant practice of ending culture before Day 7. Trial registration number 2206-SFR-079-MC

The Association of Female and Male Preconception Dyslipidemia with Live Birth in Couples Seeking Fertility Treatment.

Dyslipidemia is common, and resultant endothelial dysfunction may impact reproductive outcomes. No prospective study has examined the effect of preconception lipid parameters in both female and male partners or their interaction on live birth. To determine whether live birth is associated with preconception lipids in both partners by planned fertility treatment. Secondary analysis of the Folic Acid and Zinc Supplementation Trial, conducted between June 2013-December 2017. Couples were followed for nine months after randomization and until delivery. Multicenter study. Couples seeking fertility treatment (n = 2370; females 18-45 years, males ≥18 years). Female, male, and couple abnormal versus normal preconception lipid concentrations (total cholesterol [TC], low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglycerides [TG]). Live birth. Among 2370 couples, most males (84%) and females (76%) had at least one abnormal lipid parameter. Males planning in vitro fertilization (IVF, n = 373) with elevated LDL had lower probability of live birth than those with normal levels (47.4% vs. 59.7%, aRR 0.79, 95% CI 0.65-0.98). In couples planning IVF where both partners had elevated TC or LDL, live birth was lower than those with normal levels (TC: 32.4% vs. 58.0%, aRR 0.53, 95% CI 0.36-0.79; and LDL: 41.9% vs. 63.8%, aRR 0.69, 95% CI 0.55-0.85). Lipid parameters were not associated with live birth for couples planning non-IVF treatments. Couples planning IVF where both partners had elevated TC or LDL and males planning IVF with elevated LDL had decreased probability of live birth. These findings may support lipid screening in patients seeking fertility treatment for prognostic information for reproductive outcomes.

A heatmap for expected cumulative live birth rate in preimplantation genetic testing for monogenic disorders and chromosomal structural rearrangements

PurposeOur objective is to predict the cumulative live birth rate (CLBR) and identify the specific subset within the population undergoing preimplantation genetic testing for monogenic disorders (PGT-M) and chromosomal structural rearrangements (PGT-SR) which is likely to exhibit a diminished expected CLBR based on various patient demographics.MethodsWe performed a single-centre retrospective cohort study including 1522 women undergoing 3130 PGT cycles at a referral centre for PGT. A logistic regression analysis was performed to predict the CLBR per ovarian stimulation in women undergoing PGT-M by polymerase chain reaction (PCR) or single-nucleotide polymorphism (SNP) array, and in women undergoing PGT-SR by SNP array, array comparative genomic hybridization (CGH) or next-generation sequencing (NGS).ResultsThe mean age of women was 32.6 years, with a mean AMH of 2.75 µg/L. Female age and AMH significantly affected the expected CLBR irrespective of the inheritance mode or PGT technology. An expected CLBR < 10% was reached above the age of 42 years and AMH ≤ 1.25 µg/L. We found no significant difference in outcome per ovarian stimulation between the different PGT technologies, i.e. PCR, SNP array, array CGH and NGS. Whereas per embryo transfer, we noticed a significantly higher probability of live birth when SNP array, array CGH and NGS were used as compared to PCR.ConclusionIn a PGT-setting, couples with an unfavourable female age and AMH should be informed of the prognosis to allow other reproductive choices. The heatmap produced in this study can be used as a visual tool for PGT couples.

Women's preconception psychological stress and birth outcomes in a fertility clinic: the EARTH study.

The epidemiologic literature on women's perceived stress in relation to perinatal outcomes has been inconclusive and does not consider the preconception window of exposure. To evaluate whether women's preconception perceived stress is related to live birth, gestational age, and birthweight in a cohort receiving fertility treatment. This observational study included women seeking fertility care at the Massachusetts General Hospital (2004-2019). During preconception, women provided information on their psychological stress using the short version of the validated Perceived Stress Scale 4 (PSS-4). We used regression models to evaluate the associations of stress with live birth (N = 768 attempting to conceive) and perinatal outcomes (N = 413 live births) while adjusting for confounders. Stratified analyses by mode of conception [natural, intrauterine insemination (IUI), and IVF (in vitro fertilization)] and selected socioeconomic factors (race, education, and income) were also conducted. Higher psychological stress was negatively associated with the overall probability of live birth (adjusted RR = 0.95, 95% CI: 0.92, 0.98), particularly among women conceiving using IVF. However, we found no association between women's psychological stress and gestational age and birth weight in the overall analyses and also stratified by mode of conception. Similarly, we observed no differences in women's psychological stress with any of the measured outcomes by socioeconomic factors. These results highlight the importance of considering the preconception window and mode of conception when evaluating the relationship between women's preconception stress and live birth.

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.

Associations between the artificial intelligence scoring system and live birth outcomes in preimplantation genetic testing for aneuploidy cycles

BackgroundSeveral studies have demonstrated that iDAScore is more accurate in predicting pregnancy outcomes in cycles without preimplantation genetic testing for aneuploidy (PGT-A) compared to KIDScore and the Gardner criteria. However, the effectiveness of iDAScore in cycles with PGT-A has not been thoroughly investigated. Therefore, this study aims to assess the association between artificial intelligence (AI)-based iDAScore (version 1.0) and pregnancy outcomes in single-embryo transfer (SET) cycles with PGT-A.MethodsThis retrospective study was approved by the Institutional Review Board of Chung Sun Medical University, Taichung, Taiwan. Patients undergoing SET cycles (n = 482) following PGT-A at a single reproductive center between January 2017 and June 2021. The blastocyst morphology and morphokinetics of all embryos were evaluated using a time-lapse system. The blastocysts were ranked based on the scores generated by iDAScore, which were defined as AI scores, or by KIDScore D5 (version 3.2) following the manufacturer’s protocols. A single blastocyst without aneuploidy was transferred after examining the embryonic ploidy status using a next-generation sequencing-based PGT-A platform. Logistic regression analysis with generalized estimating equations was conducted to assess whether AI scores are associated with the probability of live birth (LB) while considering confounding factors.ResultsLogistic regression analysis revealed that AI score was significantly associated with LB probability (adjusted odds ratio [OR] = 2.037, 95% confidence interval [CI]: 1.632–2.542) when pulsatility index (PI) level and types of chromosomal abnormalities were controlled. Blastocysts were divided into quartiles in accordance with their AI score (group 1: 3.0–7.8; group 2: 7.9–8.6; group 3: 8.7–8.9; and group 4: 9.0–9.5). Group 1 had a lower LB rate (34.6% vs. 59.8–72.3%) and a higher rate of pregnancy loss (26% vs. 4.7–8.9%) compared with the other groups (p < 0.05). The receiver operating characteristic curve analysis verified that the iDAScore had a significant but limited ability to predict LB (area under the curve [AUC] = 0.64); this ability was significantly weaker than that of the combination of iDAScore, type of chromosomal abnormalities, and PI level (AUC = 0.67). In the comparison of the LB groups with the non-LB groups, the AI scores were significantly lower in the non-LB groups, both for euploid (median: 8.6 vs. 8.8) and mosaic (median: 8.0 vs. 8.6) SETs.ConclusionsAlthough its predictive ability can be further enhanced, the AI score was significantly associated with LB probability in SET cycles. Euploid or mosaic blastocysts with low AI scores (≤ 7.8) were associated with a lower LB rate, indicating the potential of this annotation-free AI system as a decision-support tool for deselecting embryos with poor pregnancy outcomes following PGT-A.

Factors Affecting the Birth Outcome Among Women with Eclampsia at Mardan Medical Complex, Mardan, Pakistan.

Background: Eclampsia is a life-threatening complication of pregnancy. Identifying the factors affecting birth outcome in eclamptic patients allows for targeted interventions to enhance maternal and fetal well-being.Objectives: To identify the risk factors that adversely affect birth outcomes among women with eclampsia.Material and Methods: This Cross-Sectional Descriptive study was conducted at Gynae Unit in Mardan Medical Complex, Mardan, from 1st January to 31st Dec 2018. A total of 157 antenatal patients who presented with eclampsia and live fetuses were enrolled for the study through non probability sampling technique. The data on their demographic variables, gestational age at presentation, mode of delivery, and birth outcome were recorded.The logistic regression model was used to investigate the dependence of birth outcome on maternal age, gestational age, mode of delivery, Parity and Booking Status. Results: Our analyses indicate that maternal age, mode of delivery, and parity significantly affect the birth outcome in women suffering from eclampsia. These three factors had a significantly negative impact on the birth outcome as their estimates are less than 1 at 5% level of significance indicating the probability of live birth decreases for the Normal Vaginal Delivery, Parity (multigravida), and advanced maternal age.Conclusion: Increased maternal age, normal vaginal delivery and multiparity increased the probability of still births in patients with eclampsia. Compared to the Cesarean section mode, normal vaginal delivery had a lower probability of live birth. Multigravida had a lower probability of live birth in eclampsia patients. Keywords: Cesarean Section, Eclampsia, Live birth, Normal vaginal delivery, Stillbirth.

Higher live birth rates are associated with a normal body mass index in preimplantation genetic testing for aneuploidy frozen embryo transfer cycles: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System study

To determine whether body mass index (BMI) was associated with live birth in patients undergoing transfer of frozen-thawed preimplantation genetic testing for aneuploidy (PGT-A) embryos. Retrospective cohort study of cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. All autologous and donor recipient PGT-A-tested cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System from 2014 to2017. Body mass index. The primary outcome measure was the live birth rate, and the secondary outcome measures were the clinical pregnancy and biochemical pregnancy rates. Multivariable generalized additive mixed models and log-binomial models were used to model the relationship between BMI and outcome measures. A total of 77,018 PGT-A cycles from 55,888 patients were analyzed. Of these cycles, 70,752 were autologous, and 6,266 were donor recipient. In autologous cycles, a statistically significant and clear nonlinear relationship was observed between the BMI and live birth rates, with the highest birth rates observed for the BMI range of 23-24.99 kg/m2. When using 23-24.99 kg/m2 as the referent, other BMI ranges demonstrated a lower probability of live birth and clinical pregnancy that continued to decrease as the BMI moved further from the reference value. Patients with a BMI of <18.5 kg/m2 had a 11% lower probability of live birth, whereas those with a BMI of ≥40 kg/m2 had a 27% lower probability than the referent. A normal-weight BMI range of 23-24.99 kg/m2 was associated with the highest probability of clinical pregnancy and live birth after a frozen-thawed PGT-A-tested blastocyst transfer in both autologous and donor recipient cycles. A BMI outside the range of 23-24.99 kg/m2 is likely associated with a malfunction in the implantation process, which is presumed to be related to a uterine factor and not an oocyte factor, as both autologous and donor recipient cycle outcomes were associated similarly with the BMI of the intended parent.

Neighborhood deprivation and racial differences in in vitro fertilization outcomes

BACKGROUNDThere are significant racial disparities in in vitro fertilization outcomes, which are poorly explained by individual-level characteristics. Environmental factors such as neighborhood-level socioeconomic factors may contribute to disparities in in vitro fertilization outcomes; however, few studies have directly addressed this research question in a large, racially diverse cohort. OBJECTIVETo investigate whether neighborhood deprivation is associated with differences in in vitro fertilization outcomes. STUDY DESIGNOur retrospective cohort study included 1110 patients who underwent 2254 autologous in vitro fertilization cycles between 2014 and 2019 at an academic fertility center in the Southeastern United States. Neighborhood deprivation was estimated using the neighborhood deprivation index, a composite variable measuring community levels of material capital based off poverty, occupation, housing, and education domains. Using multivariable log-binomial generalized estimating equations with cluster weighting, risk ratios (RR) and 95% confidence intervals (CI) were estimated for cycle cancellation, miscarriage (defined as spontaneous pregnancy loss before twenty weeks after a confirmed intrauterine gestation), and live birth according to patient neighborhood deprivation index. RESULTSThere were positive associations between increasing neighborhood deprivation index (indicating worsening neighborhood deprivation) and body mass index, as well as increasing prevalence of tubal and uterine factor infertility diagnoses. The crude probability of live birth per cycle was lower in Black (24%) versus White patients (32%) and the crude probability of miscarriage per clinical pregnancy was elevated in Black (22%) as compared to White patients (12%). After adjustment, neighborhood deprivation index was not significantly associated with risk of cycle cancellation or live birth. Results were consistent when analyses were stratified by race. CONCLUSIONOur research demonstrates racial disparities between Black and White women in the incidence of miscarriage and live birth following in vitro fertilization. While level of neighborhood deprivation was closely related to race, it did not have strong associations with in vitro fertilization outcomes in our population as a whole or within strata of race.

Fertility outcomes following surgery and multiagent chemotherapy in malignant ovarian germ cell tumor survivors: a survey study

ObjectiveTo assess fertility outcomes in long-term survivors of malignant ovarian germ cell tumors treated with fertility-sparing surgery with or without additional chemotherapy.MethodsWomen diagnosed and treated for malignant ovarian germ cell...

The role of endometrial scratching prior to in vitro fertilization: an updated systematic review and meta-analysis

Research questionTo evaluate the role of endometrial scratching performed prior to an embryo transfer cycle on the probability of pregnancy compared to placebo/sham or no intervention.DesignA computerized literature (using a specific search strategy) search was performed across the databases MEDLINE, EMBASE, COCHRANE CENTRAL, SCOPUS and WEB OF SCIENCE up to June 2023 in order to identify randomized controlled trials (RCTs) evaluating the effect of endometrial scratching prior to an embryo transfer cycle on the probability of pregnancy, expressed either as live birth, ongoing pregnancy or clinical pregnancy (in order of significance) compared to placebo/sham or no intervention. Data were pooled using random-effects or fixed-effects model, depending on the presence or not of heterogeneity. Heterogeneity was assessed using the I2 statistic. Subgroup analyses were performed based on the population studied in each RCT, as well as on the timing and method of endometrial biopsy. Certainty of evidence was assessed using the GRADEPro tool.ResultsThe probability of live birth was significantly higher in embryo transfer cycles after endometrial scratching as compared to placebo/sham or no intervention (relative risk-RR: 1.12, 95% CI: 1.05–1.20; heterogeneity: I2=46.30%, p<0.001, 28 studies; low certainty). The probability of ongoing pregnancy was not significantly difference between the two groups (RR: 1.07, 95% CI: 0.98–1.18; heterogeneity: I2=27.44%, p=0.15, 11 studies; low certainty). The probability of clinical pregnancy was significantly higher in embryo transfer cycles after endometrial scratching as compared to placebo/sham or no intervention (RR: 1.12, 95% CI: 1.06–1.18; heterogeneity: I2=47.48%, p<0.001, 37 studies; low certainty).A subgroup analysis was performed based on the time that endometrial scratching was carried out. When endometrial scratching was performed during the menstrual cycle prior to the embryo transfer cycle a significantly higher probability of live birth was present (RR: 1.18, 95% CI:1.09-1.27; heterogeneity: I2=39.72%, p<0.001, 21 studies; moderate certainty). On the contrary, no effect on the probability of live birth was present when endometrial injury was performed during the embryo transfer cycle (RR: 0.87, 95% CI: 0.67-1.15; heterogeneity: I2=65.18%, p=0.33, 5 studies; low certainty).In addition, a higher probability of live birth was only present in women with previous IVF failures (RR: 1.35, 95% CI: 1.20-1.53; heterogeneity: I2=0%, p<0.001, 13 studies; moderate certainty) with evidence suggesting that the more IVF failures the more likely endometrial scratching to be beneficial (p=0.004). The number of times endometrial scratching was performed, as well as the type of instrument used did not appear to affect the probability of live birth.ConclusionsEndometrial scratching during the menstrual cycle prior to an embryo transfer cycle can lead to a higher probability of live birth in patients with previous IVF failures.PROSPERO registrationPROSPERO CRD42023433538 (18 Jun 2023)