Probability Of Clinical Pregnancy Research Articles

Alteration of relative telomere length and telomerase reverse transcriptase expression in the granulosa cells of women during aging and assessment of in vitro fertilization outcomes.

Telomere attrition plays a critical role in the reproductive aging process in humans. Telomere length (TL) is typically regulated by telomerase, the main component of which is telomerase reverse transcriptase (TERT). The aim of the present study was to investigate the changes of relative TL (RTL) and TERT expression in granulosa cells (GCs) during aging and its association with reproduction. Clinical data on the frozen‑thawed embryo transfer cycles of older (>35year old) and younger (≤35year old) women from a single center over a 3‑year period were retrospectively analyzed. Preimplantation genetic testing for chromosome aneuploidies in older women during the same period was also analyzed. Following the analysis of the data, several biological characteristics of senescent GCs were explored. In addition, a total of 160women who were undergoing their first fresh cycle of invitro fertilization (IVF) or intracytoplasmic sperm injection were included in the study. GCs were collected from all participants. The changes of RTL and TERT expression in GCs during aging were investigated using quantitative PCR and western blotting. The associations of RTL and TERT with IVF outcomes were also assessed. The clinical data demonstrated that the pregnancy and live birth rates of women aged >35years were ~20% lower than those of women aged ≤35years, and the number of embryos with aneuploidy was 7‑fold of that without euploidy in the older age group. An aging‑induced change in follicle stimulating hormone receptor expression was observed. A shorter TL and increased TERT expression were detected in the older women. A significant inverse correlation between the expression levels of TERT and oocyte yield was identified. However, no association of RTL and TERT with blastocyst formation rate and the probability of clinical pregnancy was detected. It may be concluded that RTL and TERT alterations in GCs are potential determinants of ovarian aging. TERT expression in GCs appears to be a potential biomarker for the prediction of ovarian response, which provides a novel strategy for the assessment of female fertility.

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)

Follicular flushing increases the number of oocytes retrieved: a randomized controlled trial.

Does follicular flushing increase the number of cumulus-oocyte complexes (COCs) retrieved compared to single aspiration? Follicular flushing significantly increases the number of COCs retrieved compared to single aspiration. On the basis of published meta-analyses, follicular flushing does not seem to increase the number of oocytes retrieved, the probability of clinical pregnancy, or that of live birth and has been associated with an increase in the duration of oocyte retrieval. It should be noted, however, that all the eligible randomized controlled trials (RCTs) in these meta-analyses have randomized patients into either single aspiration or follicular flushing. This study design might not allow the detection of the true effect of follicular flushing. Despite randomization, this might still be obscured, to an extent, by heterogeneity in patients, stimulation characteristics, and differences in the oocyte retrieval procedure. A prospective, single centre, RCT, including 105 patients was performed between July and December 2022. Eligible patients were those undergoing oocyte retrieval for ICSI, aged <43 years, with BMI 18-35 kg/m2. Patients with all types of ovarian response (low-normal-high), as assessed on the day of triggering final oocyte maturation, were included. Random allocation of the ovaries of each patient to either single aspiration or follicular flushing was performed on the day of oocyte retrieval, using a computer-generated randomization list. Patients could enter the study only once. All follicles from ovaries allocated to either follicular flushing or single aspiration, were aspirated by the same 16G double lumen needle, with a constant aspiration pressure of 190 mmHg, resulting in flow rate of 0.42 ml/s. In the ovaries allocated to the follicular flushing group, if a COC was not recovered in the initial aspirate of each follicle, follicular flushing was performed until a COC was retrieved, up to a maximum of five times. The primary outcome measure was the number of COCs retrieved. Secondary outcomes were oocyte recovery rate, oocyte maturation rate, fertilization rate, and rate of good quality embryos on Day 2. Values are expressed as a median (inter-quartile range). Significantly more COCs were retrieved in the follicular flushing as compared to the single aspiration group in all patients [5 (7) vs 2 (3), P < 0.001, respectively], as well as in patients with high [9 (3) vs 5 (4), P < 0.001, respectively], normal [5 (2) vs 2 (3), P < 0.001, respectively] and low [1 (1) vs 1 (1), P < 0.001, respectively] ovarian response. In patients with low ovarian response, no COCs were retrieved in 5.7% of the ovaries in the flushing group vs 42.8% of the ovaries in the single aspiration group (P < 0.001). The oocyte retrieval rate was significantly higher in the follicular flushing vs the single aspiration group, in all patients [88.9% (25.0) vs 45.5% (37.5), P < 0.001, respectively], as well as in patients with high [81.8% (15.9) vs 45.5% (22.2), P < 0.001, respectively], normal [85.7% (28.6) vs 40.0% (30.0), P < 0.001, respectively], and low [100% (0) vs 50.0% (100), P < 0.001, respectively] ovarian response. No significant difference was observed regarding maturation rate [85.2% (30.8) vs 100% (33.3), P = 0.78], fertilization rate [76.4% (50) vs 83.3% (50) P = 0.42], and the proportion of good quality embryos on Day 2 [83.3% (40) vs 100% (50), P = 0.62]. Similarly, no differences in the above variables were observed in patients with different types of ovarian response. Follicular flushing as compared to single aspiration was associated with a significant increase in the duration of oocyte retrieval in all patients [248 s (332) vs 135 s (164), respectively], as well as in patients with high [464 s (225) vs 237 s (89), P < 0.001, respectively], normal [248 s (108) vs 141 s (95), P < 0.001, respectively], and low [64 s (59) vs 48 s (10), P < 0.001, respectively] ovarian response. Although the current study design allows for a more accurate evaluation of the true effect of follicular flushing on the number of COCs retrieved, it does not permit the evaluation of its role on the probability of pregnancy. This is the first RCT to suggest that follicular flushing increases the number of COCs retrieved compared to single aspiration, independently of ovarian response. This implies that follicular flushing plays an important role in the optimization of oocyte retrieval. These results, however, need to be confirmed in future studies, in which an equal flow rate should be used during oocyte retrieval. No external funding was obtained for this study. There are no conflicts of interest to declare. NCT05473455. 15 July 2022. 27 July 2022.

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

Elevated serum uric acid level is associated with adverse reproductive outcomes in women with polycystic ovary syndrome undergoing in vitro fertilization or intracytoplasmic sperm injection embryo transfer cycles: a retrospective cohort study

Serum uric acid levels are elevated in polycystic ovary syndrome, however, the relationship between serum uric acid level and reproductive outcomes in women with polycystic ovary syndrome remains unclear. This study aimed to investigate the association between serum uric acid level and the reproductive outcomes in women with polycystic ovary syndrome undergoing invitro fertilization or intracytoplasmic sperm injection embryo transfer cycles. This was a retrospective cohort study performed at a university-affiliated reproductive medicine center. A total of 1903 women with polycystic ovary syndrome undergoing their first invitro fertilization or intracytoplasmic sperm injection embryo transfer cycles between January 2010 and January 2021 were initially included. The trends for reproductive outcomes in polycystic ovary syndrome across quartiles of serum uric acid levels were assessed. A logistic regression analysis was performed to obtain the odds ratios for invitro fertilization outcomes based on the quartiles of serum uric acid with or without adjusting for potential confounding variables. Using generalized additive models, serum uric acid was further treated as its original continuous property to visualize its nonlinear relationship with invitro fertilization outcomes. The live birth rate was the main outcome. After exclusions, a total of 883 women with polycystic ovary syndrome with their first fresh-embryo transfer cycles were included. In quartiles of serum uric acid levels, there was a significant decreasing trend in the live birth rate from the lowest quartile (Q1: 61.8%) to the highest (Q4:45.9%) (Ptrend=.002). The percentage of low birthweight increased from Q1 (22.3%) to Q4 (31.7%) (Ptrend=.049). Compared with those in Q1, women in Q4 showed a significant lower probability of live birth and clinical pregnancy and a higher risk for low birthweight (all P<.05). Both the unadjusted and adjusted generalized additive models indicated that as the serum uric acid level increased, the probability of clinical pregnancy and the live birth rate exhibited an overall decreasing profile, and the risk for low birthweight showed an increasing profile. An elevated serum uric acid level is associated with decreased probabilities of live birth and clinical pregnancy and an increased risk for low birthweight in women with polycystic ovary syndrome. However, these associations may be confounded by other factors and more well-designed studies are needed to confirm these findings in the future.

P–716 The relationship of men’s adherence to the Mediterranean diet with sperm parameters and outcomes of assisted reproductive technologies

Abstract Study question Is men’s adherence to the Mediterranean diet (MD) associated with sperm parameters and couples’ outcomes of assisted reproductive technologies (ART)? Summary answer Higher men’s adherence to the MD was associated with an increased probability of clinical pregnancy and live birth among couples undergoing ART. What is known already There is growing literature supporting the hypothesis that some nutrients, foods, and dietary patterns may be related to sperm quality and fertility. However, no previous studies analyzed the relationship of men’s adherence to the Mediterranean diet with sperm parameters and ART outcomes in the same cohort. Study design, size, duration The Environmental and Reproductive Health (EARTH) Study is a prospective preconception cohort of couples seeking fertility treatment at the Massachusetts General Hospital Fertility Center (Boston, USA). This analysis includes 314 men and their female partner, who underwent 791 ART cycles (2007–2020). Diet intake was measured by a validated semi-quantitative food frequency questionnaire completed prior to ART. Men’s adherence to the MD was estimated using the Trichopoulou score. Participants/materials, setting, methods Primary outcomes included: conventional sperm parameters (volume, sperm count, concentration, motility, and morphology), and ART outcomes (implantation, clinical pregnancy, and live birth). We estimated the marginal means and 95% confidence interval (95%CI) for semen parameters and the probability of ART (95%CI) by employing generalized linear mixed models while adjusting for several potential confounders. Sensitivity analyses by changing the cut-off points of adherence to the MD were tested. Main results and the role of chance At baseline, men had a median (IQR) age of 35.6 (32.6, 38.8) years and a BMI of 26.7 (24.0, 29.4) kg/m2. Female partner age median (IQR) was 35.0 years (32.0, 38.0) and BMI 23.3 (21.3, 26.6) kg/m2. Couples were mostly white and had never smoked. Men’s adherence to the MD was not associated with seminal parameters in the multivariable-adjusted models but it was related to a higher probability of clinical pregnancy and live birth. The predicted marginal proportions and confidence intervals among men in the lowest compared with the highest quartile of adherence to the MD were 0.25 (0.14, 0.40), 0.55 (0.41, 0.68) for clinical pregnancy (P-trend=0.005), and 0.19 (0.10, 0.32), 0.42 (0.30, 0.55) for live birth (P-trend=0.014). Male partner MD dietary pattern scores were unrelated to the probability of implantation. Sensitivity analyses using tertiles and quintiles of men’s adherence to the MD showed similar associations. Limitations, reasons for caution Although we have adjusted our models by several potential confounding factors, residual confounding cannot be ruled out, and therefore our results should be interpreted with caution. The findings may not be generalizable to other populations or couples attempting conception without ART. Wider implications of the findings: According to our knowledge, this is the first study suggesting that adherence to MD could be suitable dietary guidance for men whose partners are undergoing infertility treatment. Trial registration number Not applicable

P–585 The influence of omega–3 fatty acids on female fertility in assisted reproductive technology

Abstract Study question Is there evidence that the intake of omega–3 fatty acids has a positive effect on probability of clinical pregnancy in women undergoing IVF/ICSI treatment? Summary answer No significant correlation was found between omega- 3 fatty acid intake (neither supplemental or as fish intake) and clinical pregnancy. What is known already: Omega–3 fatty acids are important substrates in metabolism and the supplement of omega–3 fatty acids have been thought to have a positive effect on semen quality in infertile men. Studies have shown that the intake of omega–3 fatty acids might also have a direct effect on oocytes, the quality of the embryos, and implantation of the embryo in the uterus at conception. However, the role of omega–3 fatty acids in female fertility still remains unclear as the relationship between omega–3 fatty acids and successful IVF treatment in women has shown conflicting results. Study design, size, duration Systematic review. Systematic literature research (PRISMA) on PubMed, Embase, and Cochrane identifying clinical studies focusing on omega–3 fatty acid intake amongst women receiving IVF treatment, using good scientific practice for literature search and management. 5 articles meeting inclusion criteria were found, with a total of 1.100 women undergoing IVF/ICSI treatment. Participants/materials, setting, methods: Population: women in fertility treatment Intervention: omega–3 fatty acid and/or fish intake Comparison: No/low intake of omega–3 fatty acid and/or fish intake Outcome: Primary: clinical pregnancy rate, Secondary: number of follicles, embryo quality, live birth rate Main results and the role of chance Number of follicles was found to be inversely associated to omega–3 intake in a single study. Higher levels of total omega–3 intake were found to be positively associated to embryo morphology scores, and thus quality, independent on energy intake. None of the four studies considering clinical pregnancy found any statistical significance in the association between fish intake and clinical pregnancy. Regarding live birth as an endpoint, fish intake, but not fish oil supplements, was seen to significantly increase the probability in one study with a dose-response relationship. A similar association was not found by the only other study also examining live birth. Limitations, reasons for caution: Only five studies were found to meet inclusion criteria. None of the included studies were randomized controlled trials. No meta-analysis was carried out due to the heterogeneity of the studies. Wider implications of the findings: The need for further studies, including randomized controlled trials of high quality with larger population sizes, is critical in order to thoroughly investigate and conclude any possible association of the beneficial effect of omega–3 fatty acids on female fertility in regard to IVF treatment. Trial registration number Not applicable

Adenomyosis: Impact on Fertility and Obstetric Outcomes.

In this commentary, we discuss the associations between adenomyosis, fertility, and obstetric outcomes. A recent meta-analysis on the impact of adenomyosis on reproductive outcomes found a 43% reduction in the odds ratio (OR) for clinical pregnancy and a threefold increase in the risk of miscarriage in women with adenomyosis compared with controls. Moreover, adenomyosis seems to be strongly associated with pre-eclampsia with an OR of almost 8. Also, the risk for small for gestational age was almost fourfold increased, whereas for preterm deliveries was threefold increased. The presence of deep infiltrating endometriosis and adenomyosis seems associated with particularly adverse obstetric outcomes, especially concerning natural conception. Some observations suggest that the probability of clinical pregnancy is considerably low in these cases, around 11.8%. Although several methodological drawbacks prevent definitive conclusions, all these elements should be considered in counseling women with adenomyosis seeking pregnancy, especially in cases of IVF.

Low dose hCG supplementation in a Gn-RH-agonist trigger protocol is associated with worse pregnancy outcomes: a retrospective cohort study

BackgroundA number of studies have looked at dual triggers with hCG and GnRH agonist (GnRHa) in varying doses, but the question remains: what is the optimal dose of hCG to minimize ovarian hyperstimulation syndrome (OHSS) and still offer adequate pregnancy rates? The purpose of this study was to compare pregnancy and OHSS rates following dual trigger for oocyte maturation with GnRHa and a low-dose hCG versus hCG alone. A secondary objective was the assess pregnancy outcomes in subsequent frozen cycles for the same population.MethodsA total of 963 women < 41 years old, with a BMI 18–40 kg/m2 and an AMH > 2 ng/mL who underwent fresh autologous in vitro fertilization (IVF) with GnRH antagonist protocol at a University-based fertility center were included in this retrospective cohort study. Those who received a low dose dual trigger with hCG (1000u) and GnRHa (2 mg) were compared to those who received hCG alone (10,000u hCG/250-500 μg Ovidrel). Differences in implantation rates, pregnancy, live birth, and OHSS were investigated.ResultsThe dual trigger group was younger (mean 33.6 vs 34.1 years), had a higher AMH (6.3 vs 4.9 ng/mL,) more oocytes retrieved (18.1 vs 14.9) and a higher fertilized oocyte rate (80% vs 77%) compared with the hCG only group. Yet, the dual trigger group had a lower probability of clinical pregnancy (gestational sac, 43.4% vs 52.8%) and live birth (33.4% vs 45.8%), all of which were statistically significant. There were 3 cases of OHSS, all in the hCG-only trigger group. In subsequent frozen cycles, pregnancy rates were comparable between the two groups.ConclusionsThe dual trigger group had a better prognosis based on age and AMH levels and had better stimulation outcomes, but significantly worse pregnancy outcomes, suggesting the low dose hCG (1000u) in the dual trigger may not have provided adequate luteal support, compared to an hCG-only trigger (10,000u hCG/250-500 μg Ovidrel). Interestingly, the pregnancy rates were comparable in subsequent frozen cycles, further supporting the hypothesis that the issue lies in inadequate luteal phase support, rather than embryo quality. Based on these findings, our program has changed the protocol to 1500u of hCG in a dual trigger.

The presence of cytoplasmic strings in human blastocysts is associated with the probability of clinical pregnancy with fetal heart.

Is the presence of cytoplasmic strings (CS) in human blastocysts associated with the probability of clinical pregnancy with fetal heart (CPFH) after transfer. This case-control study involved 300 single blastocyst transfers. 150 of these resulted in a CPFH (cases) while 150 did not (controls). All embryos were cultured in Embryoscope+ and AI software (IVY) was used to select the blastocyst with the highest score from the cohort for transfer. An embryologist, blind to the transfer outcome, recorded the CS number, location, and duration of their activity. There was a significant difference in the number of blastocysts that contained CS, with 97.3% of women's blastocysts resulting in +CPFH containing the CS compared to 88.7% of blastocysts in women who did not have a pregnancy (p = 0.007, OR; 4.67, CI 95% 1.5-14.2). CS appeared 2.4 h earlier in embryo development in the +CPFH group compared to their negative counterparts (p = 0.007). There was a significant difference in the average number of CS/blastocyst with a higher number being present in those that achieved a clinical pregnancy (mean: 6.2, SD 2.9) compared to those that did not (mean: 4.6, SD 3.0) (p ≤ 0.0001). There was a significant increase in the number of vesicles seen traveling along the CS with more seen in the blastocysts resulting in a +CPFH (mean: 4.3 SD 2.1) compared to those in the -CPFH group (mean: 3.1, SD 2.1). This study has shown that the presence of cytoplasmic strings in human blastocysts is associated with the probability of clinical pregnancy with fetal heart.

Progesterone protocol versus gonadotropin-releasing hormone antagonist protocol in women with polycystic ovarian syndrome undergoing in vitro fertilization treatments with frozen-thawed embryo transfer: a prospective randomized controlled trial.

BackgroundExogenous progestational agents have recently been introduced as an alternative pituitary modulator for the prevention of premature luteinizing hormone (LH) surges during in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments. There is increasing evidence that frozen-embryo transfer (FET) is associated with a lower risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovary syndrome (PCOS). Herein, we compared the clinical outcomes of the progesterone protocol with the gonadotropin releasing hormone antagonist (GnRH-ant) protocol in PCOS patients with a ‘‘freeze-all’’ strategy.MethodsIn this prospective single-central randomized controlled trial, a total of 120 PCOS patients undergoing their first IVF/ICSI treatment were randomly assigned to receive the progesterone protocol (study group) or GnRH-ant protocol (control group). The main outcome was the number of oocytes retrieved. Secondary outcomes included the incidence of premature LH rise/surge, the number of viable embryos, and pregnancy outcomes.ResultsThe number of retrieved oocytes (14.65±7.64 versus 12.8±8.57) and viable embryos (5.38±3.54 versus 5.03±3.92) in the study group were comparable to those in the control group (P>0.05). Similarly, no between-group differences were found in the number of mature oocytes, fertilized oocytes, cleaved embryos, and the viable embryo rate per oocyte retrieved (P>0.05). However, the oocyte retrieval rate (66.02%±19.63% versus 54.38%±26.39%) and fertilization rate (78.12%±18.41% versus 62.76%±23.32%) in the study group were significantly more than that in the control group (P<0.05). The mean serum LH value on day 6–7 was lower in the study group than that in the control group (7.47±0.97 versus 3.98±0.52 IU/L, P<0.05), and the incidence of premature LH rise was higher in the study group than in the control group, although no patients experienced premature LH surge. The clinical pregnancy rate [58.82% vs. 57.32%, RR 0.94 (95% CI: 0.508, 1.738), P>0.05] and implantation rate [43.21% vs. 41.4%, RR 0.929 (95% CI: 0.595, 1.448), P>0.05] were also similar between the two groups.ConclusionsThe progesterone protocol is comparable with the GnRH-ant protocol regarding oocyte/embryo yields and the probability of clinical pregnancy in PCOS patients, but the two regimens were distinct in the regulation of pituitary LH secretion.Trial registration numberChictr.org.cn: ChiCTR-IOR-15006633.

Impact of thawing-loading interval of frozen embryo on pregnancy outcome: retrospective analysis

Embryo transfer is a critical final step in the in vitro fertilization (IVF) cycle. Much attention has been paid to standardizing the procedures of embryo transfer to improve pregnancy outcome. Objective. To identify the impact of embryo thawing-loading interval (the time interval passing from thawing to loading of frozen embryo into the catheter) on pregnancy outcome. Results. The study was divided into quartiles according to thawing-loading interval in minutes (G I: &lt;60; G II: 60–119; G III: 120–239; G IV: 240 and above). Numerical variables are presented as median and interquartile range, and inter-group differences are compared using the Mann-Whitney U test. Categorical variables are presented as numbers and percentages, and differences are compared using the chi-square test for trend. After adjustment for the age of women, time of previous failed ICSI (Intracytoplasmic sperm injection) trials, number and maturity of transferred embryos, a thawing-loading interval between 60–119 minutes (adjusted odds ratio = 2.222, 95% CI = 1.370 to 3.603, p-value = 0.001) or between 120–239 minutes (adjusted odds ratio = 1.924, 95% CI = 1.172 to 3.161, p-value = 0.010) was independently associated with increased probability of clinical pregnancy compared with a thawing-loading interval of &lt;60 minutes. On the other hand, a thawing-loading interval of ≥240 minutes significantly decreased the probability of clinical pregnancy (adjusted odds ratio = 0.378, 95% CI 0.215 to 0.664, p-value = 0.001). Conclusion. After adjusting for potential confounders, this analysis found that a thawing-loading interval between 60–239 minutes was independently associated with better pregnancy outcomes compared with a thawing-loading interval of &lt;60 minutes. On the other hand, a thawing-loading interval of ≥240 minutes was significantly associated with a worse outcome. Key words: embryo transfer, IVF (in vitro fertilization), frozen embryo, thawing-loading interval

The Impact of Endocrine-Disrupting Chemicals on Female Fertility

Nowadays, infertility is a prevalent problem among couples. Exposure to endocrine-disrupting chemicals (EDCs) may influence the female reproductive outcomes through multiple mechanisms, being one of the important causes of infertility. These compounds may interfere with some fertility and fecundity markers, leading to increased time to pregnancy, increased risk of spontaneous abortion, shorter menstrual cycles, early age at menopause, anovulation or delayed ovulation, smaller preovulatory follicles, increased serum FSH, decreased synthesis of estradiol and progesterone, low plasma levels of anti-Mullerian hormone and decreased antral follicle count. Endocrine-disrupting chemicals may also impair in vitro fertilization outcomes, being responsible for: a lower probability of implantation, reduced fertilization rates, diminished probability of clinical pregnancy, and near term pregnancies after in vitro fertilization. Another mechanism of altering the female reproductive function is through the disorders induced by EDCs, such as polycystic ovary syndrome, uterine fibroids, and endometriosis. Those conditions may finally lead to infertility.

Is the probability of pregnancy after ovarian stimulation for IVF associated with serum estradiol levels on the day of triggering final oocyte maturation with hCG? A systematic review and meta-analysis.

The objective of this systematic review and metaanalysis was to examine if the probability of pregnancy after ovarian stimulation for in vitro fertilization (IVF), using GnRH analogues and gonadotrophins is associated with serum estradiol level (Ε2) on the day of triggering final oocyte maturation with human chorionic gonadotrophin (hCG). Twenty-one studies were eligible for this systematic review, including 19,598 IVF cycles, whereas three studies were eligible for metaanalysis, including 641 IVF cycles. The main outcome measure was achievement of ongoing pregnancy/live birth and, if not available, clinical pregnancy or biochemical pregnancy. Pooling of data showed no differences in the probability of clinical pregnancy between patients with high and low Ε2 levels on the day of triggering final oocyte maturation. The pooled effect sizes for the Ε2 thresholds groups constructed, regarding clinical pregnancy were 2000-3000pg/mL-OR 0.91, 95% CI 0.55 to 1.50, (fair quality/moderate risk of bias, n = 1 study), 3000-4000pg/mL-OR 0.89, 95% CI 0.46 to 1.70, (fair quality/moderate risk of bias, n = 1 study, good quality/no information on which to base a judgement about risk of bias n = 2 studies), 4000-5000pg/mL-OR 0.74, 95% CI 0.37 to 1.49 fair quality/moderate risk of bias, n = 1 study), 5000-6000pg/mL-OR 0.62, 95% CI 0.19 to 1.98, (fair quality/moderate risk of bias, n = 1 study). In addition, no difference was observed in the probability of ongoing pregnancy for the Ε2 threshold group of 3000-4000pg/mL OR 0.85, 95% CI 0.40 to 1.81(good quality/no information on which to base a judgement about risk of bias, n = 1 study). Currently, there is insufficient evidence to support or deny the presence of an association between the probability of pregnancy and serum Ε2 levels on the day of triggering final oocyte maturation with hCG in women undergoing ovarian stimulation for IVF.

23. SCORING METHOD TO ESTIMATE CLINICAL PREGNANCY USING ARTIFICIAL INTELLIGENCE MODEL

Introduction Clinical pregnancy represents success outcome in a PGT-a in cycle. It can be defined as the presence of sacs with fetal heart beats at 7-8 weeks. Main purpose of PGT-a study is to identify euploid embryos in order to be replaced to patient endometrium. Nevertheless, PGT-a cycles differs in relation with attributes related to patients as well cycle information. The main goal of the present study is to design an predictive model capable to give a probability of clinical pregnancy before embryo transfer takes place. Material & methods Dataset used included 1190 cycles that belong at New York University Fertility Center between 2012 and 2015. Patient id was encrypted with an alphanumeric code. The classifier implement was a Multilayer Perceptron. Feature engineering and standardization was carried out in the original variables. Algorithm was implemented using Python programing language.Model parameters was searched using grid search methodology. Classification performance was evaluated via 5-fold cross validation and area under the curve (AUC) Results Variables used as a predictor were: maternal age, biopsy specimen method, reason for referral and quantity of euploid and aneuploid embryos generated in the cycle. In order to evaluate normality distribution among the dependent variables selected D'Agostino's K2 test was performed as a goodness-of-fit measure. Results variables showed a non gaussian distribution (p>0.05). Lack of normality was due to presence of outliers. To mitigate it effects we employed a technique called feature engineering applying mathematical function to the original variables. In order to include categorical variables, it were coded using numerical encoding. Model implemented achieves an Area Under the Curve (AUC) of 80%. In other words, the sensitivity-specificity tradeoff in the classifier was of 80%. It is important to note that threshold selected was 0.5. It means that cases with an output after classification with values higher than the cut-off were classified as Pregnant. On the other hand cases with output lower than 0.5 were assigned as non pregnant. Furthermore, Sensitivity (True Positive / True Positive + False Negative) and Specificity (True Negative / True Negative + False Positive) were 82% and 69% respectively. Conclusions We are aware about the presence of an intrinsic bias closely related to the Fertility Center where the PGT-a cycles was performed. In order to overcome that we are developing a new algorithm capable to solve current limitation being capable to be adapted for a specific center. A scoring tool based on artificial intelligence can be helpful in selecting those patients with high probability to achieve clinical pregnancy during PGT-a cycle. Artificial neural networks is a robust estimator that allowed us to overcome multicollinearity between the original variables. Overall performance of the model was high (80%) giving strong evidence that the cycles can be accurately classified.

Exposure to phthalates in couples undergoing in vitro fertilization treatment and its association with oxidative stress and DNA damage

This prospective study of 599 couples seeking fertility treatment and who were recruited between 2015 and 2017 was conducted to (a) explore the associations between phthalate exposure and in vitro fertilization (IVF) outcomes; and (b) examine the implication of oxidative stress as a mediator of these. We measured eight phthalate metabolites in two spot urine samples; oxidative stress biomarkers such as malondialdehyde, 8-hydroxy-2-deoxyguanosine, hydrogen peroxide, catalase (CAT), and total antioxidant capacity in follicular fluid and seminal plasma. We also examined DNA damage in sperm and granulosa cells. Couples were exposed to a broad range of phthalate compounds and seven metabolites were detected in over 94% of the urine samples, whereas monobenzyl phthalate was found in only 24% of women and 26% of men. Our results showed high levels of seven urinary phthalate metabolites (except monobenzyl phthalate) and a notable increase in many oxidative stress markers in both follicular fluid and seminal plasma. However, their associations with exposure were rather limited. Multivariate binomial regression modeling showed higher levels of follicular CAT levels reduced the probability of fertilization rate (≤ 50%) [Adjusted relative risk (RRadj) = 0.52, p = 0.005] and unsuccessful live birth (RRadj = 0.592, p = 0.023). We observed a 46% decrease in the probability of clinical pregnancy in association with an elevated percentage of DNA in the tail (RRadj = 0.536, p = 0.04). There was a 32% and 22% increase in the probability of clinical pregnancy and unsuccessful live birth associated with higher levels of mono-(2-ethylhexyl) phthalate (RRadj = 1.32, p = 0.049) and monoethyl phthalate (RRadj = 1.22, p = 0.032) in women, respectively. In contrast, the probability of clinical pregnancy reduced by 20% with higher levels of mono-(2-ethyl-5-carboxypentyl) phthalate (RRadj = 0.797, p = 0.037) and 19.6% with mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) (RRadj = 0.804, p = 0.041) in men. Other oxidative stress biomarkers or urinary phthalate metabolites showed suggestive relationships with certain IVF outcomes. Lastly, our results demonstrated that elevated levels of CAT in follicular fluid might have a positive impact on fertilization rate ≥ 50% and successful live birth. CAT seems to play a potential role in mediating the relationship between the risk of poor fertilization rate and MEOHP and mono-isobutyl phthalate. Additional data are required to understand the clinical implications of oxidative stress and its contribution to the reproductive toxicity of phthalate exposure.

Decreased clinical pregnancy and live birth rates after short interval from delivery to subsequent assisted reproductive treatment cycle

Does the interval from delivery to initiation of a subsequent ART treatment cycle impact clinical pregnancy or live birth rates? An interval from delivery to treatment start of <6 months or ≥24 months is associated with decreased likelihood of clinical pregnancy and live birth. Short interpregnancy intervals are associated with poor obstetric outcomes in the naturally conceiving population prompting birth spacing recommendations of 18-24 months from international organizations. Deferring a subsequent pregnancy attempt means a woman will age in the interval with an attendant decline in her fertility. Retrospective analysis of the Society for Assisted Reproductive Technology Clinical Outcome Reporting System (SARTCORS) cohort containing 61 686 ART cycles from 2004 to 2013. The delivery-to-cycle interval (DCI) was calculated for patients from SARTCORS with a history of live birth from ART who returned to the same clinic for a first subsequent treatment cycle. Generalized linear models were fit to determine the risk of clinical pregnancy and live birth by DCI with subsequent adjustment for factors associated with outcomes of interest. Predicted probabilities of clinical pregnancy and live birth were generated from each model. A DCI of <6 months was associated with a 5.6% reduction in probability of clinical pregnancy (40.1 ± 1.9 versus 45.7 ± 0.6%, P = 0.009) and 6.8% reduction in live birth (31.6 ± 1.7 versus 38.4 ± 0.6%, P = 0.001) per cycle start compared to a DCI of 12 to <18 months. A DCI of ≥24 months was associated with a 5.1% reduction in probability of clinical pregnancy (40.6 ± 0.5 versus 45.7 ± 0.6%, P < 0.001) and 5.7% reduction in live birth (32.7 ± 0.5 versus 38.4 ± 0.6%, P < 0.001) compared to 12 to <18 months. The SART database is reliant upon self-report of many variables of interest including live birth. It remains unclear whether poorer outcomes are a result of residual confounding from factors inherent to the population with a very short or long DCI or the interval itself. Birth spacing recommendations for naturally conceiving populations may not be generally applicable to patients with a history of infertility. Patients planning ART treatment should wait a minimum of 6 months, but not more than 24 months, from a live birth for optimization of clinical pregnancy and live birth rates. National Center for Advancing Translational Sciences, National Institutes of Health, UCSF-CTSI Grant number UL1TR001872. The authors have no competing interests.

Donor TSH level is associated with clinical pregnancy among oocyte donation cycles.

The purpose of the study is to evaluate the association between donor TSH level (independent of recipient TSH level) and recipient pregnancy outcome among fresh donor oocyte IVF cycles. This is a retrospective cohort study investigating 232 consecutive fresh donor-recipient cycles (200 total oocyte donors) at an academic medical center. Main outcome measures include clinical pregnancy and live birth. Cycles were categorized into two groups based on donor TSH level (< 2.5 and ≥ 2.5mIU/L). After controlling for multiple donor and recipient characteristics, the probability of clinical pregnancy was significantly lower among donors with TSH levels ≥2.5mIU/L compared to those with TSH values <2.5mIU/L (43.1%, 95% CI 28.5-58.9, versus 66.7%, 95% CI 58.6-73.9, respectively, p = 0.01). The difference in live birth rates between the two groups did not achieve statistical significance (43.1%, 95% CI 28.8-58.6, versus 58.0%, 95% CI 50.0-65.6, respectively, p = 0.09). Donor TSH level, independent of recipient TSH level, is associated with recipient clinical pregnancy. These findings suggest that thyroid function may impact the likelihood of pregnancy at the level of the oocyte.

Probability of clinical pregnancy and live-birth in ART for women previously treated for ART-related ectopic pregnancy

Ectopic pregnancy is an undesired yet somewhat common outcome after ART therapy. Women may consider additional ART treatment after this outcome, yet little published evidence exists to guide them in this decision. Thus, we sought to evaluate predictors of pregnancy and live-birth (LB) for women undergoing ART after previous treatment for an ART-related ectopic.

The duration of pre-ovulatory serum progesterone elevation before hCG administration affects the outcome of IVF/ICSI cycles

During controlled ovarian stimulation (COS), does the duration of premature serum progesterone (P) elevation before administration of hCG affect the outcomes of IVF/ICSI embryo transfer (-ET) cycles? The duration of the premature serum P elevation is inversely related to the clinical pregnancy rate of IVF/ICSI-ET cycles. The majority of the previous studies only considered a single serum P measurement made on the day of hCG administration and the results of attempts to relate this to IVF/ICSI-ET outcomes were controversial. However, the effect of the duration of premature serum P elevation before the hCG administration on the outcomes of IVF/ICSI-ET cycles has not been studied well. Here we demonstrate that the duration of premature serum P elevation has a more significant inverse correlation than the absolute serum P concentration on the day of hCG administration with IVF/ICSI-ET outcomes. It is a retrospective, single-centre cohort study. A total of 1784 IVF and/or ICSI-ET cycles were included from October 2005 to June 2011. A total of 1784 patients underwent their IVF and/or ICSI-ET cycles in a university hospital IVF unit. The inclusion criteria include (i) age between 20 and 42 years and (ii) eligible indications for COS before IVF/ICSI. The duration of premature serum P elevation to >1 ng/ml is significantly inversely associated with the probability of clinical pregnancy (odds ratio = 0.773, 95% confidence interval: 0.660-0.891, P < 0.001), after adjustment for possible confounders with multivariate logistic regression analysis. However, the significance of inverse correlation between the absolute serum P concentration on the day of hCG administration with clinical pregnancy rate decreased after adjustment. The cutoff value we chose to define premature serum P elevation (P > 1.0 ng/ml) might not be able to be applied to different immunoassay kits and study population. The retrospective nature of this study inevitably might be influenced by some selection bias. Older patients (>42 years) are excluded from our study.