Predictor Of Clinical Pregnancy Research Articles

P-668 Progesterone levels on the thawed embryo transfer day in artificial cycles with vaginal progesterone are not a predictor of clinical pregnancy: a prospective study

Abstract Study question Are serum progesterone (P) levels on the thawed embryo transfer day a good predictor of clinical pregnancy with own oocytes in artificial endometrial preparation cycles? Summary answer In artificial endometrial preparation cycles, serum P levels on the thawed embryo transfer day are not a good predictor of clinical pregnancy with own oocytes. What is known already Some studies have shown that low serum P levels on the thawed embryo transfer (ET) day are associated with a lower pregnancy rate after artificial endometrial preparation (AEP) cycles. Other studies have shown that serum P is not a good predictor of pregnancy rates. Furthermore, studies are inconclusive about which cutoff level for P on ET day correlates with better gestational outcomes. Study design, size, duration Prospective cohort study with 235 patients who underwent ET after AEP cycle with estradiol valerate and vaginal micronized P (200 mg/ 8 h). All patients underwent blastocyst-stage or cleavage-stage ET with embryos from their own oocytes, without preimplantation genetic testing for aneuploidies, after AEP cycle, with a triple layer endometrium > 7 mm. The study was carried out at the Human Reproduction Center of Ribeirão Preto Clinical Hospital from November 2021 to June 2023. Participants/materials, setting, methods Blood was collected between 8–10 am on the thawed ET day and serum P concentration was measured. The primary outcome was clinical pregnancy (CP) beyond pregnancy week 8. A ROC curve detected the best P cutoff level that correlated with higher CP rate. Thereafter, patients were categorized into those with serum P above and below the cutoff level. Multivariate logistic regression was performed to verify which variables were predictors of CP and P levels. Main results and the role of chance Serum P measured on the ET day showed no significant difference between patients who had CP and those who did not (12.76 +4.1 versus 11.9 + 5.6, p 0.3318). The cutoff level for serum P measured on the ET day above which correlates with higher CP rate was 10.6 ng/mL (AUC 0.58), with a sensibility of 72% and specificity of 44%. Patients who had serum P on the day of ET above this value had a significantly higher CP rate than those who had it below this value (25.9% versus 14.6%) (p 0.0372). However, when the multivariate logistic regression model was performed, there was no significant difference in the CP between the groups (OR 2, 95%IC: 0.9-5). Predictors of CP in the study were the presence of at least one top-quality embryo transferred (OR 2.6, 95%IC: 1-6.6) and the transfer of embryo at the blastocyst-stage (OR 5.2, 95%IC: 1.9-14). The presence of endometriosis was negatively associated with CP (OR 0.2, 95%IC: 0.09-0.9). Limitations, reasons for caution The small sample size is a limitation. We included the blastocyst-stage and the cleavage-stage embryo transfer. Only women with vaginal micronized P were included. Extrapolation to other P administration forms needs to be evaluated. Wider implications of the findings Monitoring serum P levels on the day of ET in AEP cycles with vaginal micronized P is not justified as serum P levels are not a good predictor of CP in cycles with own oocytes. Trial registration number Not applicable

O-255 Ovarian Response Prediction Index (ORPI) as a predictor tool for ovarian response and clinical pregnancy in IVF/ICSI cycle : A Prospective Cohort Study

Abstract Study question Can incorporation of the Ovarian Response Prediction Index (ORPI), integrating AMH, AFC and age, offer a reliable prognostication of ovarian stimulation response in ART cycles? Summary answer The study affirms that ORPI, a three-variable index, emerges as a robust predictor for both ovarian response and clinical pregnancy rates within IVF/ICSI cycles. What is known already In the realm of individualized Controlled Ovarian Stimulation, precision in forecasting ovarian response proves pivotal. Ovarian reserve, influenced by age, AMH, and AFC, exhibits considerable heterogeneity among women of analogous age. While AMH and AFC function as pivotal markers, a holistic approach, exemplified by ORPI, stands out as a more comprehensive tool for predicting ovarian response. Study design, size, duration This prospective cohort study enrolled 302 subjects undergoing IVF cycles at a tertiary infertility center spanning from 1st January 2022 to 31st December 2023. Rigorous inclusion criteria mandated age ≤38 years, a BMI between 20–25 kg/m2, regular menstrual cycles, intact bilateral ovaries, no history of ovarian surgeries, absence of severe endometriosis, and no evidence of endocrine disorders. Participants/materials, setting, methods Subjects adhering to the inclusion criteria underwent venous blood sampling for AMH measurement and transvaginal ultrasound for AFC assessment. The ORPI was meticulously computed as (AMH × AFC) / patient age. Key endpoints encompassed the total oocytes retrieved, mature MII oocytes, and occurrences of clinical pregnancy. Rigorous statistical methodologies were employed for robust analysis. Main results and the role of chance The mean values for age (years), AMH (ng/mL), ORPI, AFC, and fertilized oocytes were 31.75 ± 4, 3.75 ± 3.39, 1.06 ± 1.22, 7.1 ± 2.94, and 6.11 ± 3.26, respectively. A highly significant positive correlation (p-value < 0.0001) was observed between ORPI and the numbers of oocytes and MII oocytes, with correlation coefficients of 0.714 and 0.746, respectively. Interpretation of the area under the ROC curve revealed that ORPI was a significant predictor of obtaining ≥4 oocytes at a cutoff point of > 0.2, with an area under the curve of 0.907. Similarly, for MII oocytes ≥4, ORPI was a significant predictor at a cutoff point of > 0.2, with an area under the curve of 0.937. In the case of positive clinical pregnancy, ORPI emerged as a significant predictor at a cutoff point of > 0.75, with an area under the curve of 0.822. The study underscored a substantial positive correlation between ORPI and both oocyte and MII oocyte counts, affirming ORPI’s pivotal role as a predictor for clinical pregnancy. Limitations, reasons for caution Limitations due to the constraint of sample size temper the generalizability of findings. The study did not account for live birth rates, and a comparative analysis with alternative markers was omitted. A more expansive, meticulously designed study is imperative. Wider implications of the findings ORPI, an innovative ovarian response biomarker, showcases considerable potential for predicting both ovarian response and clinical pregnancy rates. Its integration into individualized Controlled Ovarian Stimulation regimens holds promise for augmenting the counselling and prognostication process for patients embarking on IVF/ICSI cycles. Trial registration number MCDH/2023/28

Analysis of predictors of clinical pregnancy and live birth in patients with RIF treated with IVF-ET technology: a cohort study based on a propensity score approach.

To investigate the predictors of clinical pregnancy and live birth rate in patients with recurrent embryo implantation failure (RIF) treated with in vitro fertilization-embryo transfer (IVF-ET) technique. This retrospective cohort study was conducted in Jinjiang District Maternal and Child Health Hospital, Chengdu City, Sichuan Province, China. Patients were recruited who were enrolled at this hospital between November 1, 2019 and August 31, 2022, and who met the following criteria: a frozen embryo transfer (FET) at day 5 or 6 blastocyst stage was performed and the number of transfer cycles was not less than two. We collected information on age, height, weight, number of embryo transfer cycles, and information related to clinical outcomes. We used the group of patients who underwent ERA testing as the study group and those who underwent FET only as the control group, and matched baseline characteristics between the two groups by propensity score to make them comparable. We compared the differences in clinical outcomes between the two groups and further explored predictors of pregnancy and live birth using survival analysis and COX regression modeling. The success rate of clinical pregnancy in RIF patients was 50.74% and the live birth rate was 33.09%. Patients in the FET group were less likely to achieve clinical pregnancy compared to the ERA group (HR = 0.788, 95%CI 0.593-0.978, p < 0.05). Patients with >3 previous implantation failures had a lower probability of achieving a clinical pregnancy (HR = 0.058, 95%CI 0.026-0.128, p < 0.05) and a lower likelihood of a live birth (HR = 0.055, 95%CI 0.019-0.160, p < 0.05), compared to patients with ≤3 previous implantation failures. Patients who had two embryos transferred were more likely to achieve a clinical pregnancy (HR = 1.357, 95%CI 1.079-1.889, p < 0.05) and a higher likelihood of a live birth (HR = 1.845, 95%CI 1.170-2.910, p < 0.05) than patients who had a single embryo transfer. Patients with concomitant high-quality embryo transfer were more likely to achieve a clinical pregnancy compared to those without high-quality embryo transfer (HR = 1.917, 95%CI 1.225-1.863, p < 0.05). Not receiving an ERA, having >3 previous implantation failures, using single embryo transfer and not transferring quality embryos are predictors for clinical pregnancy in patients with RIF. Having>3 previous implantation failures and using single embryo transfer were predictors for live birth in patients with RIF.

Anti-Müllerian Hormone: A Predictor of Successful Intrauterine Insemination.

The anti-Müllerian hormone (AMH) produced by the granulosa cells of ovarian follicles has been shown to correlate with ovarian reserve and is often measured for fertility therapies. In this study, we evaluated the relationship between serum AMH values and the clinical pregnancy (CP) rates of female partners with unexplained infertility undergoing intrauterine insemination utilizing varying ovarian simulation protocols. This is a retrospective cohort study conducted among couples who underwent intrauterine insemination therapy over a period of four years at Charleston Area Medical Center, a tertiary care medical center in West Virginia, USA.Logistic regression was used to determine the best predictor of CP. A total of 509 intrauterine inseminations resulting in81 (15.9%) Cps were analyzed. The cycles with a CPhad higher mean AMH values (3.7+3.5 vs. 2.2+2.1; p<0.001).The majority of patients were nulliparous (77.0%) with a mean age of 33.6+5.0 years.After including only patients with unexplained infertility (the predominate infertility diagnosis; n=255 (50.1% of the cycles)) and stimulation cycles >10, the final sample size for the analysis was 245/509=48.1%.Following a receiver operating characteristic (ROC) curve analysis, the optimal AMH cut-off point was 2.1 ng/mL with an area under the curve (AUC) equal to 0.61 and 95% confidence intervals (CIs) of 0.55- 0.67 (p=0.002). The CP rate was significantly higher with the AMH >2.1 ng/mL (20.0%) compared to <2.1 ng/mL (10.0%; p=0.041). With Clomid/human gonadotropins/human chorionic gonadotropin (hCG) trigger treatment, the CP rate quadrupled (odds ratio (OR): 4.6; 95% CI: 2.1-9.7; p<0.001). This study indicates that higher AMH levels and a more aggressive ovarian stimulation protocol for intrauterine insemination therapy (IUI) have a better probability of resulting in CP.

Human chorionic gonadotropin levels after ovulation triggering as predictors of clinical pregnancy after intracytoplasmic sperm injection: a prospective cohort study

ABSTRACT This study aimed to assess the correlation between human chorionic gonadotropin (HCG) levels after ovulation triggering and clinical pregnancy following intracytoplasmic sperm injection (ICSI), affected by HCG formulation and dose. The study was a prospective cohort study of 100 women who underwent ICSI and controlled ovarian stimulation (COS) using a fixed gonadotropin-releasing hormone (GnRH) antagonist protocol. Women were divided according to the type of ovulation triggering into three groups: (1) urinary HCG (uHCG) group (n = 33); (2) recombinant HCG (rHCG) group (n = 33); and (3) dual trigger group (n = 34). The three groups were compared to each other taking into consideration the HCG levels and their correlations to clinical pregnancy following ICSI. Clinical pregnancy could be predicted by serum HCG levels 34 h after ovulation triggering by uHCG, rHCG and dual trigger at cutoff levels of 73.72, 57.35 and 22.37 mIU/ml, respectively, with sensitivities of 95%, 94.7% and 87%, and specificities of 76.9%, 92.9% and 90.9%, respectively. Follicular fluid (FF) HCG levels could predict clinical pregnancy after ovulation triggering by uHCG, rHCG and dual trigger at cutoff levels of 21.58 mIU/ml, 20.82 mIU/ml and 8.66 mIU/ml, respectively, with sensitivities of 95%, 94.7% and 91.3%, and specificities of 92.3%, 92.9% and 90.9%, respectively. In conclusion, serum and FF HCG levels after ovulation triggering could predict clinical pregnancy following ICSI at variable cutoff levels according to HCG formulation and dose.

P-183 Blastocyst speed versus blastocyst look: Which is the better predictor of clinical pregnancy and live birth following time-lapse culture and single blastocyst transfer?

Abstract Study question To compare predictive value for pregnancy and live birth of morphological versus morphokinetic assessment of blastocysts after time-lapse culture and single blastocyst transfer. Summary answer Blastocyst morphokinetic assessment was not superior in predicting pregnancy and live birth compared to blastocyst morphology, but provides additional information, particularly for morphologically poorer-quality blastocysts. What is known already Blastocyst culture with time-lapse technology enables evaluation of both morphokinetic developmental speed and classical morphology including Gardner scoring of the blastocyst. One approach to assess the developmental speed of blastocysts is to use the morphokinetic classification proposed by Campbell, Fishel, et al., based on time to start of blastulation (tSB) and the duration of forming the blastocyst (dB). However, beyond the advantages of undisturbed embryo culture, the value of the kinetic data from time-lapse is debated. Study design, size, duration EDCOS (Embryo Developmental profiles from Controlled Ovarian Stimulation cycles using follitropin alfa) is a multicentre, prospective cohort study of patients undergoing IVF/ICSI whose embryos were cultured in time-lapse incubator devices in 10 ART centres throughout Denmark and Sweden. Patients undergoing IVF/ICSI (including donor oocyte cycles) who had ovarian stimulation with follitropin alfa (Bemfola®) and had zygotes and embryos available for monitoring in the EmbryoScope™ time-lapse incubator device (Vitrolife) were invited to join this study. Participants/materials, setting, methods Morphological and morphokinetic prognostic classifications for single blastocyst transfers (SET) were determined for three study subpopulations: fresh autologous SET (311 women), frozen autologous SET (246 women; 345 transfers) and frozen donor SET (38 women; 59 transfers). All blastocysts were graded morphologically in five grades from Amorph (best) to Emorph (worst) based on their Gardner score and morphokinetically in three grades from Akin (best) to Ckin (worst) based on tSB and dB. Main results and the role of chance Overall ongoing pregnancy and live birth rates (OPR/LBR) for morphokinetic classifications Akin, Bkin and Ckin were 36.1%, 30.0% and 16.3% (P = 0.021) and 30.4%, 21.8% and 9.1% (P = 0.000), respectively. OPR and LBR for morphological classifications Amorph, Bmorph, Cmorph, Dmorph and Emorph were 41.9%, 37.8%, 30.8%, 19.0% and 15.6% (P = 0.000) and 36.6%, 29.1%, 15.6%, 16.5% and 8.3% (P = 0.002), respectively. For Dmorph blastocysts, OPR and LBR for morphokinetic classifications Akin, Bkin and Ckin were 50%, 21.4% and 7.1% (P = 0.009) and 33.3%, 10.8% and 0% (P = 0.003), respectively. Receiver operating characteristic curve analyses achieved areas under the curve for fresh autologous SET of 55.7%, 58.9% and 67.2% for the morphokinetic, morphological and combined classifications, respectively; and 53.4%, 64.0% and 65.6%, respectively, for frozen autologous SET. Limitations, reasons for caution This was an observational study with no control group, conducted under usual clinical practice. Data were collected prospectively, although clinics could deselect and rank blastocysts according to their own procedures. However, the outcome of subsequent frozen blastocyst transfer cycles was also analysed. Wider implications of the findings Selection of a blastocyst for transfer based on morphokinetic assessment at the blastocyst stage was not superior to classical blastocyst morphological assessment after time-lapse culture but is a viable option. Combining morphokinetic and morphological evaluation provides additional supporting information to guide in blastocyst selection, especially for morphologically poorer-quality blastocysts. Trial registration number Not applicable

P-544 Biochemical markers as a predictor of clinical pregnancy on day 6 after embryo transfer

Abstract Study question Is it possible to predict clinical pregnancy using Machine Learning models on day 6 after embryo transfer to an acceptable degree of certainty? Summary answer Using selected biochemical markers it is possible to build a machine learning model to predict clinical pregnancy. What is known already Human chorionic gonadotropin (β-hCG) is considered the main early predictor of pregnancy. Due to the fact that the highest percentage of spontaneous abortions occurs in the first trimester predicting clinical pregnancy outcomes at the early stages of pregnancy is particularly difficult. The level of B-hcg measured at the early stages of implantation and the dynamics of its increase can help predict clinical pregnancy and predict its further development. However, the specific cut-off points at which pregnancy can be determined vary from study to study, and a different factor is often suggested to increase the certainty of β-hCG-based predictions. Study design, size, duration 1474 single frozen embryo transfers (1205 patients between 23 and 47 years of age), January 2019 -December 2022 were used for data modelling and statistical testing. The dataset consisted of endocrinal markers:β-hCG, PRG (progesterone), E (estradiol) measured on the 6th day after ET and other practitioner-chosen data: age, PGD results, embryo quality status, RIF or RPL history, embryo maturation days as well as pregnancy outcomes. Exclusion criteria were: PRG &amp;gt; 50ng/ml, β-hCG &amp;gt;70 mIU/ml. Participants/materials, setting, methods A machine learning model for predicting clinical pregnancy was trained using the gradient boosting technique. The model used 100 decision trees with 8 leaves, maximal depth of 2 nodes and a learning rate of 0.1. The performance of the model was measured using the accuracy score metric and area under ROC (AUC). Feature importance was based on Shapley values. Additional analysis was performed using statistical testing using a two-sided Student’s t-test. Main results and the role of chance A Machine Learning naive model employed chosen variables to predict clinical pregnancy. The most important variables turned out to be the serum level of β-hCG and PRG on day 6 after embryo-transfer. The final model, limited to those variables, performs with an accuracy of around 83 % (accuracy score = 0.834), the area under ROC (AUC) was 0.927. Based on Shapley values, β-hCG followed by PRG are the most relevant for the model’s predictions. Low PRG concentrations increased the chances of clinical pregnancy. The findings were confirmed by additional statistical analysis. Observations were divided into two groups for which the cut-off point was the level of PRG of 24 ng/ml – the median for the whole group. The probability of clinical pregnancy is higher in the group where the serum PRG is below 24 ng/ml even if β-hCG levels are the same. A statistically significant difference between these groups regarding β-hCG (P value &amp;lt; 0.001) was noticed. In order for serum β-hCG to be used as a more accurate clinical pregnancy predictor its level should be interpreted in the context of PRG serum levels. Limitations, reasons for caution Since in the dataset, only data regarding frozen embryo transfers were included, fresh ETs need to be explored further. The model was based on endocrinal markers as measured on day six after ET hence it cannot be used to interpret those markers as measured on any other date. Wider implications of the findings In order to most accurately inform patients regarding the possible outcomes of embryo-transfers, practitioners should not limit themselves to monitoring β-hCG serum levels but also include PRG as an important prognostic of clinical pregnancy. Trial registration number Not Applicable

Improved pregnancy outcomes of cyclosporine A on patients with unexplained repeated implantation failure in IVF/ICSI cycles: A retrospective cohort study.

Repeated implantation failure (RIF) is a daunting obstacle restricting the further improvement of embryo implantation rate (IR) and live birth rate (LBR). The beneficial effect of cyclosporine A (CsA) on reproductive outcomes of unexplained RIF(URIF) was explored after de novo embryo transfer (ET). A retrospective cohort study was conducted, comparing pregnancy outcomes of 146 cycles (CsA group, n=62; control group, n=84) at the IVF center of Suzhou Municipal Hospital from April 2016 to March 2020. Baseline and transfer cycle characteristics of participants were comparable between groups. Overall, CsA exerted obvious improvement on IR (51.16% vs 31.97%, P=.006), clinical pregnancy rate (CPR) (58.06% vs 38.10%, P=.017), and LBR (48.39% vs 32.14%, P=.047). Especially, CsA showed remarkably enhancement on IR (41.38% vs 14.63%, P=.012), CPR (47.62% vs 17.24%, P=.021) of non-high quality embryos. No difference in obstetric and pediatric complications was observed, and no birth defects were reported under CsA application. CsA was found to be a predictor of clinical pregnancy [fine adjusted OR 2.360, 95 % CI 1.165-4.781; P=.017] and live birth [fine adjusted OR 2.339, 95% CI 1.124-4.867; P=.023] for multivariate logistic regression. Not surprisingly, the number of high quality embryos should also be considered as an independent predictor for clinical pregnancy [fine adjusted OR 1.637,95%CI 1.027-2.609; P=.038] and live birth [fine adjusted OR 1.890, 95% CI 1.165-3.068; P=.010]. CsA application in patients with URIF promotes the pregnancy outcomes and does not increase the risk of obstetric and pediatric complications.

The Value of Anti-Müllerian Hormone in the Prediction of Spontaneous Pregnancy: A Systematic Review and Meta-Analysis.

ObjectiveTo determine whether serum anti-Müllerian hormone (AMH) level is a predictor of clinical pregnancy in women trying to achieve a natural conception.MethodsThe PubMed, Embase, and Cochrane Library databases were searched for articles published until August 2020. Studies that met the inclusion and exclusion criteria were included in the meta-analysis; no language limitations were imposed. Quality was appraised using the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. Heterogeneity due to the threshold effect was identified; thus, we plotted a summary receiver operating characteristic curve and calculated its area under the summary receiver operating characteristic curve (AUC) and Cochran’s Q index to assess whether AMH level is a predictor of spontaneous pregnancy. Publication bias and sensitivity were also assessed.ResultsEleven studies (4,388 women) were ultimately included in this meta-analysis. The AUC and Cochran’s Q indices were 0.5932 and 0.5702, respectively. For women younger than 35 years, the AUC was 0.6355 and the Q index was 0.6025. For those older than 35 years, the AUC was 0.5536 and the Q index was 0.5403. Subgroup analyses by study type and population characteristics showed results similar to the overall outcome. No publication bias was identified, and the sensitivity analysis confirmed the robustness of the final result.ConclusionsSerum AMH levels have poor predictive value for natural pregnancy. The predictive value of AMH was poor in the younger and older subgroups. Our findings suggest that low serum AMH levels are not associated with reduced fertility.IntroductionThis study investigated the predictive value of anti-Müllerian hormone (AMH) level for natural pregnancy. Other than age, few factors can predict the chances of natural fertility. AMH is an established biomarker of ovarian reserve that is widely used to predict oocyte yield in cases of in vitro fertilization (IVF) and menopause. In clinical practice, the applications of AMH are increasing. However, its predictive value for natural conception remains controversial. In this study, since AMH is closely related with ovarian reserve, we evaluated whether it has predictive value for natural pregnancy. Our findings will fine-tune the clinical application of AMH in pre-pregnancy counseling. The topic should be of wide interest to investigators in the reproductive endocrinology and gynecology fields.Systematic Review RegistrationPROSPERO 2020 CRD42020216265, Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020216265.

PREDICTABILITY OF OVARIAN SENSITIVITY INDEX FOR ANTAGONIST-PROTOCOL ICSI CYCLE OUTCOMES

This retrospective cohort study aims to revisit the generalizability and determine the predictability of the ovarian sensitivity index (OSI) for ICSI cycle outcomes. Women for ICSI in tertiary ART unit from January 2016 through 2020 were screened. Women were eligible if they had oocyte retrieval in fresh antagonist FSH/hMG stimulated cycles. OSI is calculated as oocytes retrieved × 1000/total gonadotropin dose. OSI standards determined by Huber et al. (1) were utilized to categorize women with OSI <1.69, 1.69-10.07, and >10.07 to poor-, normal-, and high-responders, respectively. For discriminative analysis, predictive and validation analytic models were constructed from total sample (n=622) by randomization in a 1:2 ratio, respectively. The OSI cutoffs, based on ROC analysis with Youden index that predicted clinical pregnancy (CP) and live birth (LB) in the predictive model, were further validated in the validation cohort. Multivariate bootstrapped logistic regression was done for the predictability of OSI for cycle outcomes, adjusted for other covariates. 622 cycles were eligible for analysis. Women had a median (IQR) age of 30 (6) years, BMI of 28 (5.5) kg/m2, and AMH of 2.1(2.3) ng/ml. CP and LB rates per retrieval were 36.2% and 27.7%, respectively. Based on Huber’s OSI, the cohort included poor (18.8%), normal (71.2 %) and high (10%) responders with a mean OSI of 1.04±0.41, 4.89±2.25, and 13.05±2.90, P< .001, respectively. High-responders had a higher CP (58.1% vs 36.4% vs 23.2%, P< .001), LB (50% vs 28% vs 14.5%, P<.001) and top-quality embryos (TQE) formation (87.1% vs 53.5% vs 2.6%, P<.001) rates compared to normal and poor responders, respectively. In the discriminative analysis, the predictive model (n=208) showed that OSI ≥ 3.6 was a predictor for CP and LB (OR 95% CI: 2.26, 1.25-4.08, P=.007 ; 3.00, 1.49-6.05,P=.002, respectively). Also, the selected cutoff has AUC, sensitivity and specificity of 0.60, 70.9 and 49.1 for CP, and 0.64, 75.4, and 48.9 for LB. In the validation cohort (n=414), women with OSI ≥ 3.6 had higher CP, LB, and TQE formation rates compared to their counterparts. The highest predictability of OSI ≥ 3.6 was for TQE production (OR 15.8, 95%CI 9.6-26.0) (r coefficient= .61) (AUC=0.86) compared to CP (OR 2.32, 95% CI 1.52-3.56) (r coefficient=.19) (AUC=0.65) and LB (OR 3.22, 95% CI 1.96-5.27) (r coefficient=.24) (AUC=0.68) with P< .001 for all. Similar predictability trend for TQE formation was also yielded by Huber’s OSIs. In polynomial regression curves, pregnant women yielded more oocytes when compared to non-pregnant receiving the same gonadotropins dose with reduced oocyte yield at doses of ≥2250 and 3000 for the pregnant and non-pregnant cohorts, respectively. In adjusted multivariate regression, AMH and OSI ≥ 3.6 were the only predictors for CP and LB. The gonadotropins requirement per oocyte retrieved is superior to other cycle parameters for predicting outcomes in antagonist cycles, specifically the potentiality to have TQE.

Dynamics of the urinary microbiome in pregnancy and the coincidental predictive value of the microbiota for IVF/IVF–ICSI outcome

Research questionWhat is the impact of clinical pregnancy on the composition of the urinary microbiota? DesignEighty-five women receiving IVF, without or with intracytoplasmic sperm injection (ICSI) treatment were enrolled in a prospective observational study performed in 2008. Approximately 14 weeks before the start of hormonal treatment and embryo transfer, a midstream urine sample was obtained, followed by an additional sample 16 weeks after embryo transfer. The microbial composition was determined by polymerase chain reaction of the V1–V3 regions of the 16S rRNA bacterial gene. Clinical pregnancy data were collected after the first IVF/IVF–ICSI cycle and 1 year later. ResultsA significant decrease in the abundance of Lactobacillus species as well as a significant increase in that of Staphylococcus species was observed in women who became pregnant after IVF/IVF–ICSI treatment (both P < 0.0001). In addition, based on the composition of the pretreatment microbiome it was possible to identify women with a lower likelihood of achieving clinical pregnancy after IVF/IVF–ICSI treatment. The resulting prediction model was validated in another 27 women who did not become pregnant during the first cycle and received additional IVF/IVF–ICSI cycle(s) or frozen embryo transfer(s). The model predicted the women with no clinical pregnancy after IVF/IVF–ICSI treatment with a sensitivity of 0.42 and a specificity of 1.00. ConclusionsThe data primarily showed that clinical pregnancy results in significant changes in the abundance and diversity of the urinary microbiota. Coincidentally, it was discovered that the urinary microbiome composition before IVF/IVF–ICSI treatment can potentially be used as a predictor of clinical pregnancy.

Trophectoderm morphology is a better predictor of clinical pregnancy in blastocyst transfers

In assisted reproduction, a successful outcome is closely associated with the selection of potentially implantable. culture has its own merits that it can possibly eliminate the selection of non-viable embryos, can mimic physiology with better embryo-uterine and the extended culture can also assess the embryos post-embryonic activation. Scoring of characteristics can also aid in single embryo transfers (SET), reducing the risks of multiple pregnancies. The morphological assessment can serve as a non-invasive tool for better prediction of the outcome in IVF. The two important morphological parameters of grading the inner cell mass (ICM) and the (TE) other than the expansion of the cavity. Various groups reported the importance of either characteristic predicting implantation, pregnancy and live birth. In this retrospective study, we have evaluated which one of these parameters possess the predictive ability of implantation and pregnancy. The embryos frozen as following morphological scoring in the stimulated cycles were replaced in subsequent cycles. The transferred with known implantation were grouped into four different combinations of grades of ICM and TE and analyzed for the association with the clinical pregnancy and the findings were statistically validated. This study demonstrates there is a significant correlation between the grades of TE cells and the clinical pregnancy, so TE grade possibly is a better predictor of in transfers. The grades of embryo can be used as a selection tool for a better IVF outcome.

Systemic oxidative stress as a possible mechanism underlying the pathogenesis of mild endometriosis-related infertility.

Does systemic oxidative stress occur during the early follicular phase of the menstrual cycle in infertile women with minimal (stage I) or mild (stage II) endometriosis? Are serum oxidative stress markers during the early follicular phase of the menstrual cycle good predictors of successful gestation in these women who undergo ovarian stimulation for intracytoplasmic sperm injection (ICSI)? A pilot study (prospective case-control study) was conducted in a University Hospital. Serum samples were obtained during the early follicular phase of the natural cycle preceding ovarian stimulation for ICSI of infertile women (with and without stage I and II endometriosis, the latter having male factor infertility). Total hydroperoxides (FOX1), malondialdehyde, advanced oxidation protein products, reduced glutathione, superoxide dismutase, total antioxidant capacity (TAC), 8-hydroxy-2'-deoxyguanosine (8OHdG) and vitamin E were analysed in serum from 35 women with stage I or II endometriosis and 60 control women. The accuracy of oxidative stress markers for predicting clinical pregnancy and live births was determined by receiver operator characteristic curves. Women with stage I and II endometriosis showed lower serum 8OHdG concentrations (16.02 ng/ml) compared with the control group (22.08 ng/ml). The best predictor for clinical pregnancy and live births was TAC, whereas FOX1 was the best predictor of clinical pregnancy in the control group. Infertile women with stage I and II endometriosis present systemic oxidative stress during the early follicular phase of the menstrual cycle. Some oxidative stress markers were good predictors of clinical pregnancy and live births after ICSI. Serum TAC was predictive of clinical pregnancy and live births after ICSI in women with stage I or II endometriosis.

Presence of the vitamin D inactivating enzyme CYP24A1 in human sperm and prediction of the success of intrauterine insemination: A prospective study

Male fertility is routinely evaluated by semen analysis, although semen quality variables such as; sperm count, motility and morphology have low predictive value for spontaneous pregnancies and fertility treatment outcomes. Vitamin D has been suggested to be beneficial for male reproduction. The vitamin D receptor and the vitamin D inactivating enzyme CYP24A1 are co-expressed in high quality sperm. Presence of CYP24A1 at the annulus of human sperm can distinguish between sperm from healthy and infertile men with high specificity and is positively correlated with semen quality. The high expression level in the testis of FAM57B2, which is activated by 24,25OH2D3, indicates an uncharacterized biological role for CYP24A1 in male reproduction. Moreover, activated vitamin D has been shown to induce sperm motility and promote fertilization in vitro. Here, we prospectively investigated whether the fraction of CYP24A1 positive sperm was a better predictor of clinical pregnancy than semen analysis by including 240 fertility treatments (169 couples) from a single fertility centre in Denmark. ROC-curve based analysis showed that the percentage of sperm expressing CYP24A1 was a better predictor of successful pregnancy outcome after intrauterine inseminations (IUI) than both sperm concentration and motility (p < 0.05). Interestingly, samples with CYP24A1 staining >67% of the sperm increased the likelihood of achieving pregnancy 4-fold after IUI compared with samples having fewer sperm with detectable CYP24A1 (p < 0.05). Neither CYP24A1 nor any of the other assessed semen quality variables were predictive for the treatment outcome of the more invasive assisted reproductive techniques (IVF and ICSI). In conclusion, our results provide proof of principle for a CYP24A1-based sperm test to improve fertility outcome for infertile patients referred for IUI and supports a role for vitamin D metabolites during fertilization.

Serum Albumin Level Adjusted Progesterone Level on the Trigger Day is Not a Significant Predictor of Clinical Pregnancy

Objective: We aimed to assess the effect of serum albumin level adjusted progesterone levels on the trigger day on clinical pregnancy rate in ICSI cycles.Study Design: A total of 100 women undergoing ICSI cycles due to poor ovarian reserve or tubal factor infertility were included in this study. Serum progesterone and albumin levels on the trigger day were utilized to predict clinical pregnancy among normal and poor responders.Results: There were significant differences between groups with and without successful clinical pregnancy in terms of serum albumin (4.6 vs. 4.3 g/dl), progesterone levels (0.5 ng/mL vs. 0.7 ng/mL) on the trigger day and endometrial thickness (11.5 mm vs. 9.3 mm) (p&lt;0.05, p&lt;0.05 and p&lt;0.05, respectively). In ROC analyses, progesterone level on the trigger day was found to be a significant predictor of clinical pregnancy (AUC=0.652, p=0.015). An optimal cut-off value of 0.55 ng/mL was obtained with 65% sensitivity and 57% specificity. Albumin level adjusted progesterone concentrations on the trigger day were 0.67 ng/mL versus 0.64 ng/mL, but this difference was not statistically significant (p&gt;0.05). Conclusion: Albumin adjusted progesterone concentrations may be utilized to determine cases for a freeze-all policy.

Predictive value of antral follicle count and serum anti-Müllerian hormone: Which is better for live birth prediction in patients aged over 40 with their first IVF treatment?

ObjectiveTo evaluate clinical utility of antral follicle count (AFC) and anti-Müllerian hormone (AMH) in predicting in vitro fertilization (IVF) outcomes among the patients over 40 years old in their first IVF cycles. Study designTotal 219 patients aged 40 or older who underwent their first IVF with gonadotropin-releasing hormone antagonist protocol from January 2013 to September 2014 in CHA Gangnam fertility center were retrospectively analyzed. AFC and serum samples were measured prior to IVF treatment. The main outcomes were clinical pregnancy rate and live birth. Results36 out of 219 patients achieved clinical pregnancy (16.4%) and 27 out of 219 patients delivered (12.3%). The receiver operating characteristic curve analysis to predict clinical pregnancy showed that both age and AFC equally had higher accuracy by area under the curve (AUC = 0.657, P < 0.01) than serum AMH (AUC 0.613, P = 0.03). The optimum cut-off value of age was ≤41 and that of AFC was >3 to predict clinical pregnancy. For the prediction of live birth, AFC had the highest accuracy (AUC 0.698, P < 0.01), followed by age (AUC 0.674, P < 0.01) and the number of total retrieved oocytes (AUC 0.620, P = 0.02). The optimum cut-off value of age was ≤41, that of AFC was >3 and that of the number of total retrieved oocytes were >6. With multivariate regression analysis, age and AMH were significantly correlated with clinical pregnancy (age, odds ratio [OR] 0.53, P < 0.01; AMH, OR 1.31, P = 0.04), whereas age and AFC were association with live birth significantly (age, OR 0.41, P < 0.01; AFC, OR 1.10, P = 0.02). ConclusionIn patients aged over 40, AFC and AMH were shown to be good biomarkers for the prediction of clinical pregnancy and live birth. Although AMH was positively correlated with clinical pregnancy and had no association with live birth, the predictive value of AFC and AMH were similar for both clinical pregnancy and live birth. To predict the live birth, age ≤41, AFC >3 and total retrieved oocytes >6 appeared to be meaningful. This study demonstrated the significance of AMH and AFC as predictors of clinical pregnancy and live birth for old aged women at their first IVF cycle with gonadotropin-releasing hormone antagonist protocol.

The Impact of laparoscopic surgery of peritoneal endometriosis and endometrioma on the outcome of ICSI cycles

ABSTRACTOur objective was to assess the role of laparoscopic removal of ovarian endometriomas and ablation of peritoneal endometriosis on the outcome of intracytoplasmic sperm injection (ICSI) - Embryo Transfer cycles by comparing with the results of patients with untreated endometriomas and tubal factor without underlying endometriosis confirmed by laparoscopy. For this purpose, between 2002 and 2015, outcomes of 257 ICSI cycles of 150 patients, including 91 cycles of 48 patients in minimal endometriosis, 57 cycles of 25 patients in endometrioma removal, 65 cycles of 53 patients in non-operated endometrioma, and 44 cycles of 24 patients in tubal factor groups were retrospectively analyzed. Basal ovarian reserve was significantly lower, mean starting and total gonadotropin consumption was significantly higher, and mean serum E2 on the day of hCG injection, number of dominant follicles, number of retrieved total, and MII oocytes were all significantly lower in the endometrioma cystectomy group. Fertilization and embryo cleavage rates were also significantly the lowest in the endometrioma cystectomy group, whereas clinical pregnancy and live birth rates were comparable among all groups. The number of transferred embryos and duration of infertility were the most significant predictors of clinical pregnancy and live birth. Basal antral follicle count was also significant in predicting live birth.

Retrospective analysis of GnRH antagonist cycles to assess ovarian reserve parameters as the predictors of clinical pregnancy

Aim: The present study aims to correlate AMH and AFC, with the number of retrieved oocytes , number of Grade1 embryos and clinical pregnancy in IVF/ICSI cycles stimulated with GnRH-antagonist protocol.Materials and Methods: 49 women who underwent grade 1 cleavage stage fresh embryo transfer from May to August 2017 were included. Primary end point was clinical pregnancy i.e. positive cardiac activity at 6 weeks. Pearson’s correlation coefficient was calculated and stepwise regression analysis was done to identify the best predictor.Results: Out of 49 patients 21 patients (42.9%) were pregnant. Serum AMH and AFC significantly correlated with the number of oocytes obtained (P=0.00, P=0.00). A positive correlation of serum AMH and AFC was seen with number of grade 1 embryos , but it was not significant. AFC had a stronger correlation with number of oocytes and grade 1 embryos than AMH . Stepwise regression analysis indicated that number of grade 1 embryos was an independent predictor for clinical pregnancy (P= 0.19) with an overall accuracy of 63%.Conclusion: Counselling of patients regarding outcome of IVF cycle should be based on the number of grade1 embryos.

The meaning of anti-Müllerian hormone levels in patients at a high risk of poor ovarian response

Measurements of ovarian reserve play an important role in predicting the clinical results of assisted reproductive technology (ART). The ideal markers of ovarian reserve for clinical applications should have high specificity in order to determine genuine poor responders. Basal follicle-stimulating hormone levels, antral follicle count, and serum anti-Müllerian hormone (AMH) levels have been suggested as ovarian reserve tests that may fulfill this requirement, with serum AMH levels being the most promising parameter. Serum AMH levels have been suggested to be a predictor of clinical pregnancy in ART for older women, who are at a high risk for decreased ovarian response. We reviewed the prognostic significance of ovarian reserve tests for patients undergoing ART treatment, with a particular focus on the significance of serum AMH levels in patients at a high risk of poor ovarian response.

Motile sperm organelle morphology examination (MSOME) can predict outcomes of conventional in vitro fertilization: A prospective pilot diagnostic study

The objective of this prospective diagnostic study was to explore the relationships between the morphological indices of sperm using motile sperm organelle morphology examination (MSOME) and the clinical outcome of in vitro fertilization (IVF). A total of 291 couples were included in this study. The female patients exhibited tubal and pelvic factors, and their partners’ gametes were tested prospectively by MSOME. Spearman correlation analysis was used to identify the relationship between MSOME and IVF rates and conventional sperm parameters. The effect of MSOME characteristics on pregnancy outcome was analyzed by multivariate logistic regression. MSOME characteristics showed statistical relationships with sperm concentration (R = 0.130, P = 0.025), progressive motility (R = 0.260, P < 0.001), and strict normal morphology (P = 0.648, R < 0.001). The percentage of sperm with normal morphology and vacuolation in the anterior head of the sperm, as observed by MSOME, was highly correlated with the IVF fertilization rate (R = 0.176, P = 0.002; P = − 0.230, P < 0.001 respectively). The combined incidence of morphologically normal sperm and posterior vacuolation of the sperm head, as assessed by MSOME, was a predictor of clinical pregnancy (CP) after IVF (sensitivity, 92.9%; specificity, 42.47; and area under the ROC curve, 76.59%). The percentage of normal morphology of sperm by MSOME (OR 3.52, 95% CI 2.05–6.05, P < 0.001) and the posterior part vacuolated sperm (OR 0.65, 95% CI 0.52–0.82, P < 0.001) were significant predictors of successful CP. The MSOME index was significantly correlated with fertilization rates and CP after IVF, and testing with MSOME could constitute a valid diagnostic predictor of IVF outcome.