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Background: Hyperglycosylated human chorionic gonadotropin, the predominant human chorionic gonadotropin variant secreted following implantation, is associated with trophoblast invasion., Objective: To determine whether the initial serum hyperglycosylated human chorionic gonadotropin differs between ongoing and failed pregnancies, and to compare it to total serum human chorionic gonadotropin as a predictor of ongoing pregnancy., Materials and Methods: Women undergoing fresh/frozen in vitro fertilization cycles at a university-based infertility clinic with an autologous day 5 single embryo transfer resulting in serum human chorionic gonadotropin >3 mIU/mL (n = 115) were included. Human chorionic gonadotropin was measured 11 days after embryo transfer in a single laboratory (coefficient of variation <6%). Surplus frozen serum (-80 o C) was shipped to Quest Laboratories for measurement of hyperglycosylated human chorionic gonadotropin (coefficient of variation <9.1%). Linear regression analyses adjusted for oocyte age a priori were used to compare human chorionic gonadotropin and hyperglycosylated human chorionic gonadotropin in ongoing pregnancies (>8 weeks of gestation) and failed pregnancies (clinical pregnancy loss, biochemical and ectopic pregnancies)., Results: A total of 85 pregnancies (73.9%) were ongoing. Hyperglycosylated human chorionic gonadotropin and human chorionic gonadotropin values were highly correlated (Pearson correlation coefficient 92.14, P < .0001), and mean values of both were positively correlated with blastocyst expansion score (P value test for trend < .0004). Mean human chorionic gonadotropin and hyperglycosylated human chorionic gonadotropin were significantly higher in ongoing vs failed pregnancies. Among ongoing pregnancies vs clinical losses, mean hyperglycosylated human chorionic gonadotropin, but not human chorionic gonadotropin, was significantly higher (19.0 vs 12.2 ng/mL, β -8.1, 95% confidence interval -13.0 to -3.2), and hyperglycosylated human chorionic gonadotropin comprised a higher proportion of total human chorionic gonadotropin (4.6% vs 4.1%; risk ratio, 0.79; 95% confidence interval, 0.66-0.94)., Conclusion: Measured 11 days after single blastocyst transfer, hyperglycosylated human chorionic gonadotropin and human chorionic gonadotropin values were highly correlated, but only mean hyperglycosylated human chorionic gonadotropin and its ratio to total human chorionic gonadotropin were significantly higher in ongoing pregnancies vs clinical pregnancy losses. Further evaluation of hyperglycosylated human chorionic gonadotropin, including in multiple embryo transfers and multiple pregnancy, and using serial measurements, is required., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study is to investigate whether abnormal hCG trends occur at a higher incidence among women conceiving singleton pregnancies following transfer of multiple (two or more) embryos (MET), as compared to those having a single embryo transfer (SET)., Methods: Retrospective cohort study was performed of women who conceived singleton pregnancies following fresh or frozen autologous IVF/ICSI cycles with day 3 or day 5 embryo transfers between 2007 and 2014 at a single academic medical center. Cycles resulting in one gestational sac on ultrasound followed by singleton live birth beyond 24 weeks of gestation were included. Logistic regression models adjusted a priori for patient age at oocyte retrieval and day of embryo transfer were used to estimate the Odds Ratio of having an abnormal hCG rise (defined as a rise or < 66% in 2 days) following SET as compared to MET., Results: Among patients receiving two or more embryos, 6.1% (n = 84) had abnormal hCG rises between the first and second measurements, compared to 2.7% (n = 17) of patients undergoing SET (OR 2.16, 95% CI 1.26-3.71). Among patients with initially abnormal hCG rises who had a third level checked (89%), three-quarters had normal hCG rises between the second and third measurements., Conclusions: Patients who deliver singletons following MET were more likely to have suboptimal initial hCG rises, potentially due to transient implantation of other non-viable embryo(s). While useful for counseling, these findings should not change standard management of abnormal hCG rises following IVF. The third hCG measurements may clarify pregnancy prognosis.

Objective: To compare serum hCG levels after transfer of a single fresh cleavage embryo and of a single fresh blastocyst embryo and to determine the predictive value of serum hCG levels for pregnancy outcomes., Design: A single center retrospective cohort study., Setting: Tertiary university health center., Patient(s): All fresh single ETs between December 2008 and December 2013., Intervention(s): None., Main Outcome Measure(s): Mean serum hCG levels on day 16 after oocyte collection, after the transfer of a fresh single cleavage embryo and a fresh single blastocyst embryo were compared. Multivariable regression analysis was performed to determine the association of potential factors on hCG value and a clinical pregnancy., Result(s): One thousand twenty-six fresh single ETs were analyzed, 801 (638 pregnancies) from a single blastocyst transfer and 225 (167 pregnancies) from a single cleavage ET. The mean hCG levels resulting from a single fresh blastocyst transfer (299 ± 204 IU/L) were significantly higher than those from a cleavage transfer (245 ± 204 IU/L). This difference remained after adjusting for confounding variables. The threshold value predicting a clinical pregnancy for a cleavage embryo was 100 IU/L, and for a blastocyst transfer, 133 IU/L., Conclusion(s): Our study suggests that initial serum hCG values are higher after the transfer of a single fresh blastocyst embryo compared with after a single fresh cleavage ET, even after adjusting for confounding variables., (Copyright © 2015. Published by Elsevier Inc.)

Background: Single embryo transfer (SET) is the most successful way to reduce the frequency of multiple pregnancies following in vitro fertilisation. However, selecting the embryo for SET with the highest chances of pregnancy remains a difficult challenge since morphological and kinetics criteria provide poor prediction of both developmental and implantation ability. Partly through the expression of specific genes, the oocyte-cumulus interaction helps the oocyte to acquire its developmental competence. Our aim was therefore to identify at the level of cumulus cells (CCs) genes related to oocyte developmental competence., Methodology/principal Findings: 197 individual CCs were collected from 106 patients undergoing an intra-cytoplasmic sperm injection procedure. Gene expression of CCs was studied using microarray according to the nuclear maturity of the oocyte (immature vs. mature oocyte) and to the developmental competence of the oocyte (ability to reach the blastocyst stage after fertilisation). Microarray study was followed by a meta-analysis of the behaviour of these genes in other datasets available in Gene Expression Omnibus which showed the consistency of this list of genes. Finally, 8 genes were selected according to oocyte developmental competence from the 308 differentially expressed genes (p<0.0001) for further validation by quantitative PCR (qPCR). Three of these 8 selected genes were validated as potential biomarkers (PLIN2, RGS2 and ANG). Experimental factors such as inter-patient and qPCR series variability were then assessed using the Generalised Linear Mixed Model procedure, and only the expression level of RGS2 was confirmed to be related to oocyte developmental competence. The link between biomarkers and pregnancy was finally evaluated and level of RGS2 expression was also correlated with clinical pregnancy., Conclusion/significance: RGS2, known as a regulator of G protein signalling, was the only gene among our 8 selected candidates biomarkers of oocyte competence to cover many factors of variability, including inter-patient factors and experimental conditions.

PurposeThis study investigated the relationship between the vitamin D [25(OH)D] level in individual follicles and oocyte developmental competence.MethodsA prospective cohort study in a private infertility center. Infertile women (N = 198) scheduled for intracytoplasmic sperm injection (ICSI) and a single embryo transfer (SET) provided serum samples and 322 follicular fluid (FF) specimens, each from a single follicle on the day of oocyte retrieval.ResultsFFs corresponding to successfully fertilized oocytes (following ICSI) contained significantly lower 25(OH)D level compared with those that were not fertilized (28.4 vs. 34.0 ng/ml, P = 0.001). Top quality embryos on the third day after fertilization, when compared to other available embryos, developed from oocytes collected from follicles containing significantly lower 25(OH)D levels (24.56 vs. 29.59 ng/ml, P = 0.007). Positive hCG, clinical pregnancy, and live birth rates were achieved from embryos derived from oocytes that grew in FF with significantly lower 25(OH)D levels than in follicles not associated with subsequent pregnancy. The concentration of 25(OH)D in FF in women with negative hCG was 32.23 ± 20.21 ng/ml, positive hCG 23.62 ± 6.09 ng/ml, clinical pregnancy 23.13 ± 6.09 ng/ml, and live birth 23.45 ± 6.11 ng/ml (P

Abstract Background The KIDScore™ Day 5 (KS-D5) model, version 3, is a general morphokinetic prediction model (Vitrolife, Sweden) for fetal heartbeat prediction after embryo transfer that was developed based on a large data set that included implantation results from a range of clinics with different patient populations, culture conditions and clinical practices. However, there was no study to comparing their pregnancy and live birth prediction ability among different maternal age. The aim of this study is to analyze the performance of KS-D5 in predicting pregnancy and live birth in various maternal age groups after single vitrified-warmed blastocyst transfer (SVBT). Methods A total of 2486 single vitrified-warmed blastocyst transfer (SVBT) cycles were analyzed retrospectively. Confirmed fetal heartbeat positive (FHB+) and live birth (LB+) rates were stratified by Society for Assisted Reproductive Technology (SART) maternal age criteria (

Summary: We report a series of 20 cases of heterotopic cesarean scar pregnancy in this study. The results show that transvaginal sonography offers highly accurate diagnoses of heterotopic cesarean scar pregnancy during the first trimester. Careful exclusion of cesarean scar pregnancy is of great clinical importance for patients with a history of cesarean section after in vitro fertilization‐embryo transfer, even when an intrauterine pregnancy has been detected. We recommend single embryo transfer for patients with a history of cesarean section. Expectant management may provide the opportunity for a live cesarean scar pregnancy to develop, albeit at high risks of placenta accreta and hemorrhage, and this needs further verification in the future. [ABSTRACT FROM AUTHOR]

Background: The KIDScore™ Day 5 (KS-D5) model, version 3, is a general morphokinetic prediction model (Vitrolife, Sweden) for fetal heartbeat prediction after embryo transfer that was developed based on a large data set that included implantation results from a range of clinics with different patient populations, culture conditions and clinical practices. However, there was no study to comparing their pregnancy and live birth prediction ability among different maternal age. The aim of this study is to analyze the performance of KS-D5 in predicting pregnancy and live birth in various maternal age groups after single vitrified-warmed blastocyst transfer (SVBT). Methods: A total of 2486 single vitrified-warmed blastocyst transfer (SVBT) cycles were analyzed retrospectively. Confirmed fetal heartbeat positive (FHB+) and live birth (LB+) rates were stratified by Society for Assisted Reproductive Technology (SART) maternal age criteria (< 35, 35–37, 38–40, 41–42 and ≥ 43 years of age). Within each age group, the performance of the prediction model was calculated using the AUC, and the results were compared across the age groups. Results: In all age groups, the FHB+ rates decreased as the KIDScore decreased (P < 0.05). Conversely, the AUCs increased as the maternal age increased. The AUC of the < 35 age group (0.589) was significantly lower than the AUCs of the 41–42 age group (0.673) and the ≥43 age group (0.737), respectively (P < 0.05). In all age groups, the LB+ rates decreased as the KIDScore decreased (P < 0.05). Conversely, the AUCs increased as the maternal age increased. The AUC of the ≥43 age group (0.768) was significantly higher than the AUCs of other age groups (P < 0.05; < 35 age group = 0.596, 35–37 age group = 0.640, 38–40 age group = 0.646, 41–42 age group = 0.679). Conclusions: In the present study, we determined that the KIDScore model worked well for prediction of pregnancy and live birth outcomes in advanced age patients. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of additional embryo transfer (ET) on pregnancy in young women, we used a natural-experiment approach. Patients and Methods: The design was based on the national policy of South Korea limiting the number of embryos transferred in vitro fertilization (IVF):≦2 embryos on day 2– 4 or one on day 5– 6 for patients aged < 35, with one extra embryo allowed for patients aged ≥ 35. Using the data from 1909 ET cycles of 1287 women aged ≥ 34 and ≤ 35, we calculated adjusted risk ratios (RRs) for pregnancy. Results: Half of cycles were undertaken by women aged 35, and additional ET was performed in 68.7% of them. Intrauterine pregnancy (45.2% vs 51.3%) and multiple gestation (30.5% vs 6.9%) were more common in women aged 35 than in those aged 34. The RR for intrauterine pregnancy was 1.34 (95% confidence interval: 1.12– 1.59) when comparing double ET to single ET in frozen day 5– 6 cycles. Conclusion: We observed no evidence of a higher probability of pregnancy with additional ET in fresh or frozen day 3– 4 ET, or in fresh day 5– 6 ET of women aged 35. Additional ET may not increase the successful pregnancy rate in the 35-year-old group, unless it is a frozen day 5– 6 ET cycle. [ABSTRACT FROM AUTHOR]

BackgroundThe scoring system for human blastocysts is traditionally based on morphology; however, there are controversies on the effect of morphology parameters on pregnancy outcomes. The aim of this study is to evaluate the predicting value of each morphology parameter on pregnancy outcomes in a setting of single embryo transfer.MethodsThis is a retrospective cohort study on patients undergoing frozen-thawed single blastocyst transfer at our center, between Jan. 2009 and Dec. 2018. A total of 10,482 cycles were analyzed. The blastocysts were scored according to the expansion and hatching status, morphology of inner cell mass (ICM), and cells of trophectoderm (TE). The primary outcome measure was live birth rate. One-way analysis of variance, chi-square test, and multiple logistic regression were used for statistical analysis.ResultsThe clinical pregnancy rate was lower in the blastocysts of stage 3 (48.15%), compared with those of stage 4 (56.15%), stage 5 (54.91%), and stage 6 (53.37%). The live birth rate was lower in the blastocysts of stage 3 (37.07%), compared with those of stage 4 (44.21%) and stage 5 (41.67%). The rates of clinical pregnancy (A: 66.60%, B: 53.25%, C: 39.33%) and live birth (A: 54.62%, B: 41.29%, C: 28.45%) were both decreased with decreasing grade of ICM morphology, and these differences were pairwise significant. The miscarriage rate of blastocysts with ICM grade A was lower, compared with ICM grade C (17.53 vs. 27.66%). Blastocysts with TE morphology of C had lower rates of clinical pregnancy (43.53%) and live birth (32.57%), compared with those with TE morphology of A and B (clinical pregnancy rate: 64.26% for A, 58.11% for B; live birth rate: 52.74% for A, 45.64% for B). There were no significant differences in rates of clinical pregnancy, live birth, and miscarriage between the blastocysts with TE grade A and B.ConclusionsThe blastocyst expansion stage, ICM grade, and TE grade are all associated with pregnancy outcomes. ICM grade is the strongest predictor of live birth. A blastocyst with stage 4–5, ICM grade A, and TE grade A/B should be given priority for single embryo transfer.

Background: The scoring system for human blastocysts is traditionally based on morphology; however, there are controversies on the effect of morphology parameters on pregnancy outcomes. The aim of this study is to evaluate the predicting value of each morphology parameter on pregnancy outcomes in a setting of single embryo transfer. Methods: This is a retrospective cohort study on patients undergoing frozen-thawed single blastocyst transfer at our center, between Jan. 2009 and Dec. 2018. A total of 10,482 cycles were analyzed. The blastocysts were scored according to the expansion and hatching status, morphology of inner cell mass (ICM), and cells of trophectoderm (TE). The primary outcome measure was live birth rate. One-way analysis of variance, chi-square test, and multiple logistic regression were used for statistical analysis. Results: The clinical pregnancy rate was lower in the blastocysts of stage 3 (48.15%), compared with those of stage 4 (56.15%), stage 5 (54.91%), and stage 6 (53.37%). The live birth rate was lower in the blastocysts of stage 3 (37.07%), compared with those of stage 4 (44.21%) and stage 5 (41.67%). The rates of clinical pregnancy (A: 66.60%, B: 53.25%, C: 39.33%) and live birth (A: 54.62%, B: 41.29%, C: 28.45%) were both decreased with decreasing grade of ICM morphology, and these differences were pairwise significant. The miscarriage rate of blastocysts with ICM grade A was lower, compared with ICM grade C (17.53 vs. 27.66%). Blastocysts with TE morphology of C had lower rates of clinical pregnancy (43.53%) and live birth (32.57%), compared with those with TE morphology of A and B (clinical pregnancy rate: 64.26% for A, 58.11% for B; live birth rate: 52.74% for A, 45.64% for B). There were no significant differences in rates of clinical pregnancy, live birth, and miscarriage between the blastocysts with TE grade A and B. Conclusions: The blastocyst expansion stage, ICM grade, and TE grade are all associated with pregnancy outcomes. ICM grade is the strongest predictor of live birth. A blastocyst with stage 4–5, ICM grade A, and TE grade A/B should be given priority for single embryo transfer. [ABSTRACT FROM AUTHOR]

As women age, the increasing rate of aneuploidy lead to an augmentation in the incidence of clinical miscarriages. It was anticipated that biochemical pregnancy rates would also rise with maternal age. However, no study has previously evaluated the effect of maternal age on biochemical pregnancy rates. A retrospective cohort study of 2177 subjects who underwent single embryo transfer (SET) as part of a fresh or thawed IVF cycle were recruited from 2008 through 2012, resulting in 952 pregnancies. Data was stratified for age and compared using analysis of variance (continuous data) and chi-squared tests (categorical data). The likelihood of a clinical miscarriage increased with age (p <.001). Surprisingly, advancing age had no effect on the biochemical pregnancy loss rate (p =.72) (Age 21–30 y: 10.7%, Age 31–35 y:9.8%, Age 36–40y:11.5%, Age 41–42 y:13.6%). Biochemical pregnancy loss rate did not increase as a function of age in women 21 to 42 years of age. [ABSTRACT FROM AUTHOR]

This study reports the results of a 2-year long IVF programme ('One by One') in which all patients (median age 40 years; range 27–45 years) were offered preimplantation genetic testing for aneuploidy (PGT-A) and had all blastocysts vitrified (freeze-only), followed later by single vitrified-warmed blastocyst transfer (vSET) in managed cycles. Between January 2016 and December 2017, a total of 155 patients started 222 treatment cycles and 99 (45%) cycles resulted in one or more vitrified blastocysts (untested or with normal copy number for all chromosomes) available for transfer. Seventeen patients (11%) aged ≤35 years opted out of PGT-A. Over this period, 85 vSETs in 74 patients resulted in an implantation rate of 80% (68/85) and a singleton clinical pregnancy rate of 66% (56/85). Cumulative live birth rates will not be known for 1–2 years. Nevertheless, these high success rates with vSET confirm larger studies using selected patients and are likely to deliver similar, if not higher, live birth rates per cycle started than rates typically reported in national registries with conventional IVF and transfer of one or more fresh and/or frozen embryos. [ABSTRACT FROM AUTHOR]

BackgroundIdentification of a non-invasive technique to assess embryo implantation potential in assisted reproduction would greatly increase success rates and lead more efficiently to single embryo transfer. Early studies suggested metabonomic analysis of spent culture media could improve embryo selection. The goal of this study is to assess if embryo implantation can be predicted based on proton nuclear magnetic resonance ((1)H NMR) profiles of spent embryo culture media from patients undergoing transfer of multiple embryos on cycle day 3.MethodWe conducted a retrospective study in an academic assisted reproduction technology (ART) program and analyzed the data in a university research center. Two hundred twenty-eight spent culture media samples originating from 108 patients were individually analyzed. Specifically, five distinct sets (1 to 5) of different types of spent media samples (volume ~14 μL) from embryos that resulted in clinical pregnancy (positive heart rate at 6 weeks gestation) (n (1) = 29; n (2) = 19; n (3) = 9; n (4) = 12; n (5) = 33; n (total) = 102) and from embryos that did not implant (n (1) = 28; n (2) = 29; n (3) = 18; n (4) = 15; n (5) = 36; n (total) = 126) were collected on day 3 of embryo growth. The media samples were profiled using (1)H NMR spectroscopy, and the NMR profiles of sets 1 to 5 were subject to standard uni- and multi-variate data analyses in order to evaluate potential correlation of profiles with implantation success.ResultsFor set 1 of the media samples, a borderline class separation of NMR profiles was obtained by use of principal component analysis (PCA) and logistic regression. This tentative class separation could not be repeated and validated in any of the other media sets 2 to 5.ConclusionsDespite the rigorous technical approach, (1)H NMR based profiling of spent culture media cannot predict success of implantation for day 3 human embryos.

Background and objectives: Most of previous studies are comparing the perinatal outcome on singleton babies. There has been no study evaluating the possible effect of singleton embryo transfer on the perinatal outcomes in initial singleton pregnancy resulting from fresh embryo transfer. The purpose of our study is to access the effect of embryo transfer number on obstetric and perinatal risks in order to examine the role of single embryo transfer on perinatal outcomes on initial singleton pregnancy. Materials and methods: This study is a retrospective cohort study and analyzed 6439 fresh embryo transfer women. 1647 initial singleton pregnancy patients were divided into one of the following three groups according to the embryo transfer number: group A (n = 94): single embryo transfer (SET); group B (n = 1321): double embryo transfer (DET); group C (n = 262): triple embryo transfer (TET). The miscarriage rate and the ectopic pregnancy rate was compared between group A and group B, group C. 1273 live birth patients were divided into three groups too. The obstetrics outcomes and perinatal outcomes between group A and group B, group C. Results: There were 94 singleton pregnancy patients in unselective single embryo transfer. Comparing with double embryo transfer, the early miscarriage rate was higher, but late miscarriage rate, ectopic rate, and live birth rate were comparable between two groups. The obstetrics outcomes were comparable between single embryo transfer and other two groups. Although there was no significant difference between group A and other two groups, preterm birth rate, extremely preterm birth rate, low-birth weight rate and very low-birth weight rate increased with the increase of embryo transfer number. The mean delivery weight was highest in singleton babies in single embryo transfer group. It is higher in group A comparing with group B (3440.4 versus 3320.7 g) and comparing with group C (3440.4 versus 3277.4 g). Conclusions: Single embryo transfer was associated with a better perinatal outcome such as preterm birth and low-birth weight in a singleton pregnancy. The mean birth weight was significantly higher in single embryo transfer group too. Single embryo transfer is a reasonable option to reach the goal of in vitro-fertilization – a healthy singleton neonate. [ABSTRACT FROM AUTHOR]

Objective: To assess whether receiving information about twin pregnancy in the form of oral presentation given by a physician could affect the acceptance of single embryo transfer (SET) by couples undergoing IVF. Study design: Prospective interventional study. Setting: University hospital IVF unit. Patients: One hundred and forty patients (70 couples) undergoing IVF. Interventions: A questionnaire to measure patients' emotions about twin pregnancy was administered to IVF patients just before and immediately after attending a slide presentation in which the risks of twin pregnancy were explained. Patients scored (1 to 6) ten adjectives linked either to positive or negative emotions; scores before and after presentation were compared. The patients' preference between double embryo transfer (DET) and SET was also registered before and after the presentation. Results: The presentation about twin pregnancy caused a significant (p < 0.001) shift of the score distribution toward lower values for positive adjectives referred to twin pregnancy and higher values for negative adjectives. Information impacted similarly on women and men. Despite the relevant change in the emotional attitude, after presentation, 45.7% of women and 48.6% of men were still favorable to DET, whereas 24.3% of women and 37.1% of men preferred SET. Conclusions: Oral information on the risks of twin pregnancy can affect the emotional attitude of patients toward twin pregnancy, but the wish of getting pregnant after fresh embryo transfer overcomes all rational consideration, and the majority of patients still prefer DET. [ABSTRACT FROM AUTHOR]

Summary: Vitrification is a highly efficient technique for the cryopreservation of the human embryo. The effect of delayed blastulation may be responsible for implantation failures and negatively affects in vitro fertilization (IVF) outcomes. The current literature displays discordant results; some studies have announced higher pregnancy rates after day 5 (D5) transfer compared with day 6 (D6) transfer, while others have shown equivalent outcomes. In the present study an investigation into the clinical implications of delayed blastulation (D5 versus D6) was carried out. We performed a retrospective study comparing clinical pregnancies and implantation rates following warmed single blastocyst transfer (WSBT). All patients coming for a programmed warmed transfer at Edinburgh Assisted Conception Programme, EFREC, Royal Infirmary of Edinburgh, were included in this study and divided in two groups according to the day of blastocyst vitrification: D5 (n = 1563) and D6 (n = 517). The overall survival rate was 95.0% (1976/2080) with no significant difference between the D5 and D6 groups: 95.3% (1489/1563) and 94.2% (487/517) respectively. WSBT of D6 blastocysts resulted in a lower implantation and clinical pregnancy compared with D5 embryos. The implantation rate (IPR) and clinical pregnancy rate (CPR) were respectively 49.4% and 42.6% for the D5 and 37.4% and 32.2% for the D6 embryos, which was statistically significant. The multiple pregnancy rate was 1.32% (1.14% for D5 vs 1.84% for D6). Although the transfer of D6 vitrified-warmed blastocyst remains a reasonable option, priority to a D5 embryo would reduce the time to successful pregnancy. [ABSTRACT FROM AUTHOR]

In this single-center matched-cohort study, women who underwent IVF/ICSI with donor oocytes between 2007 and 2014 (n = 259) were compared to women undergoing autologous cycles during the same time period (n = 515). The matching (1:2) took into consideration the women's age, type of treatment (IVF/ICSI), and year of embryo transfer. All women were healthy and below 40 years of age at the time of IVF/ICSI, and the treatments were performed using a strict policy of single embryo transfer. Multiple logistic regression analysis, adjusted for body mass index (BMI), smoking, and parity, showed a four times increased risk of gestational hypertensive disorders (adjusted odds ratio, AOR 4.25; 95% confidence interval (CI), 2.61–6.92) and pre-eclampsia (AOR 3.99; 95% CI 2.27–7.00) in pregnancies achieved with donor oocytes. There was also a higher rate of cesarean section in women who gave birth after oocyte donation (AOR 1.69; 95% CI 1.22–2.35) and a higher risk of postpartum hemorrhage >1000 mL (AOR 1.59; 95% CI, 1.11–2.27). After further adjustment for preeclampsia in the logistic regression analysis, no additional increased perinatal risks were found. The incidence of preterm delivery, low weight at birth, need of neonatal intensive care, Apgar scores, and incidence of perinatal death were also similar between the groups. [ABSTRACT FROM AUTHOR]

Purpose: Clinical pregnancy rate after IVF with eSET stagnates between 30 and 40%. In order to increase pregnancy and live birth rates, multiple embryo transfer is still common practice. Providing additional non-invasive tools to choose the competent embryo for transfer could avoid multiple pregnancy and improve time to pregnancy. Cumulus mRNA analysis with quantitative PCR (QPCR) is a non-invasive approach. However, so far, no gene sets have been validated in prospective interventional studies. Methods: A prospective interventional single-center pilot study with two matched controls (day-3 and day-5 eSET) was performed in 96 patients consenting to the analysis of the cumulus-corona of their oocytes. All patients were super-ovulated for ICSI and eSET at day 3. All oocytes were denuded individually and cumulus was analyzed by quantitative PCR using three predictive genes (EFNB2, SASH1, CAMK1D) and two housekeeping genes (UBC and β2M). Patients (n = 62) with 2 or more day-3 embryos (good or excellent morphology) had their embryo chosen following the normalized expression of the genes. Results: Corona testing significantly increased the clinical pregnancy and live births rates (63% and 55%) compared to single embryo transfer (eSET) on day 3 (27% and 23%: p < 0.001) and day 5 (43% and 39%: p = 0.022 and p = 0.050) fresh transfer cycle controls with morphology-only selection. Time-to-pregnancy was significantly reduced, regardless of the number of good-quality embryos available on day 3. Conclusion: Combining standard morphology scoring and cumulus/corona gene expression analysis increases day-3 eSET results and significantly reduces the time to pregnancy. Trial registration number: This is not an RCT study and was only registered by the ethical committee of the University Hospital UZBRUSSEL of the Vrije Universiteit Brussel VUB (BUN: 143201318000). [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of embryonic factors on serum beta human chorionic gonadotropin (β-hCG) levels in pregnancy and live birth resulting after a single fresh cleavage embryo and blastocyst transfer.Study Design: This was a retrospective cohort study conducted at a tertiary care hospital. All fresh single embryo transfers (sETs) between September 2011 and December 2016 were included. The correlation analysis was performed to determine the association of embryo morphological parameters on mean serum β-hCG levels on day 12 after the transfer of a fresh single cleavage embryo and a fresh single blastocyst embryo.Results: Out of a total of 455 fresh sETs, 60 positive β-hCG results after the transfer of a single fresh cleavage-stage embryo and 82 after the transfer of a single fresh blastocyst. The mean β-hCG level resulting from a single fresh blastocyst ET was 371.7 ± 52.7 IU/L, which was similar to the mean β-hCG level resulting from a cleavage ET (314.5 ± 36.9 IU/L) (p = .70). Interestingly, serum β-hCG levels resulting from a single fresh blastocyst ET showed a correlation with day 5 blastocoele expansion, trophectoderm cell number and blastocyst quality score in ongoing pregnancy (r = .33, p = .02; r = .29, p = .04; and r = .31, p = .03, respectively). Moreover, day 5 blastocoele expansion and blastocyst quality score showed a correlation with the serum β-hCG levels resulting from a single fresh blastocyst ET in live birth (r = .36, p = .02; r = .31, p = .04, respectively).Conclusion: Our study suggests that serum β-hCG levels resulting from a single fresh blastocyst ET showed a correlation with day 5 blastocoele expansion and blastocyst quality score in both ongoing pregnancy and live birth. [ABSTRACT FROM AUTHOR]

Study Question: Does transfer of multiple embryos affect perinatal outcomes of resulting singleton live births following ART?Summary Answer: There is a higher risk of preterm birth (PTB) and low birthweight (LBW) in singleton live births associated with spontaneous reduction of an initial multiple to singleton gestation following transfer of multiple embryos.What Is Known Already: Singleton pregnancies following ART are at a higher risk of adverse perinatal outcomes compared to spontaneous conceptions. Earlier studies have found an increased risk of PTB and LBW in singletons following transfer of multiple embryos versus single embryo transfer (SET). However, these studies did not address the specific role of vanishing twin, i.e. spontaneous reduction of an initial multiple to singleton gestation.Study Design, Size, Duration: Anonymised data on all ART cycles performed in the UK were obtained from the Human Fertilization and Embryology Authority. Data from 1991 to 2011 involving 508 410 fresh and 131 157 frozen autologous ART cycles resulting in 95 779 and 18 005 singleton live births, respectively, were analyzed.Participants/materials, Setting, Methods: Fresh and frozen ART cycles were analyzed separately to compare perinatal outcomes of PTB and LBW of singleton live births resulting from transfer of multiple (≥2) embryos versus SET. Logistic regression analysis was performed adjusting for confounders. Subgroup analyses were carried out for perinatal outcomes of singleton live births with initial multiple or initial single gestational sacs following transfer of multiple embryos versus singleton live births following SET.Main Results and the Role Of Chance: In fresh cycles, there was a significantly higher risk of PTB (adjusted odds ratio (aOR) 2.70, CI 2.37-3.05) and LBW (aOR 2.76, CI 2.44-3.13) in singleton live births with initial multiple gestational sacs but there was no significant difference in the risk of PTB (aOR 1.08, CI 1.00-1.16) or LBW (aOR 1.08, CI 1.00-1.16) in singleton live births with an initial single gestational sac following transfer of ≥2 embryos compared to those following SET. In frozen cycles, there was a significantly higher risk of PTB (aOR 2.13, CI: 1.55-2.93) and LBW (aOR 2.61, CI: 1.87-3.64) in singleton live births with initial multiple gestational sacs but there was no significant difference in the risk of PTB (aOR 1.02, CI: 0.88-1.18) or LBW (aOR 0.91, CI: 0.77-1.07) in the singleton live births with an initial single gestational sac following transfer of ≥2 embryos compared to those following SET.Limitations, Reasons For Caution: While the analysis was adjusted for a number of known confounders, the dataset had no information for confounders such as smoking, BMI, previous obstetric history and comorbid medical conditions during pregnancy. The lack of information about the timing of occurrence of the vanishing phenomenon is another limitation because poorer perinatal outcomes of a surviving twin have been reported following second trimester fetal demise compared to the first trimester.Wider Implications Of the Findings: The study results suggest that the vanishing twin phenomenon is associated with increased risk of PTB and LBW in the resulting singleton live births and there was no increased risk when there was a single gestational sac from the outset following transfer of multiple embryos.Study Funding/competing Interests: Nil. [ABSTRACT FROM AUTHOR]

Study Question: What is the prevalence of multiple pregnancy with zygotic splitting after single embryo transfer (SET)?Summary Answer: The prevalence of multiple pregnancy with zygotic splitting after SET was 1.36%.What Is Known Already: In 2008, the Japan Society of Obstetrics and Gynaecology (JSOG) recommended the adoption of SET to reduce multiple births. Since then, to improve the clinical pregnancy rate, elective SET using blastocyst transfer and frozen-warmed ET has increased. Blastocyst culture and zona pellucida manipulation, including ICSI and AH, have been widely reported as risk factors for monozygotic twinning. However, all these studies may have included cases with dizygotic pregnancies produced by a transferred embryo and a spontaneous conception.Study Design, Size, Duration: A retrospective observational study was performed, based on 937 848 SET cycles in registered ART data from the JSOG between 2007 and 2014. The study was approved by the Registration and Research Subcommittee of the JSOG and Juntendo University Ethics Committee.Participants/materials, Setting, Methods: To identify possible factors affecting the prevalence of zygotic splitting, we identified pregnancies, in which the number of foetuses exceeded the number of gestational sacs (GSs), to restrict our analysis to 'true' zygotic splitting. Multiple logistic regression analysis was performed using singleton pregnancy after SET, as control. P < 0.05 was considered statistically significant.Main Results and the Role Of Chance: Fresh and frozen-warmed SET produced 276 934 clinical pregnancies (29.5%/SET), including 4310 twins (1.56% of pregnancies) and 109 triplets (0.04% of pregnancies). Based on sex analysis of dichorionic twins after SET, the prevalence of multiple pregnancy with zygotic splitting was 1.36%. Statistical analysis revealed that compared to singleton pregnancies zygotic splitting pregnancies were associated with frozen-warmed ET cycles (odds ratio [OR] = 1.34; 95% CI: 1.16-1.55), blastocyst culture (OR = 1.79; 95% CI: 1.54-2.09) or AH (OR = 1.21; 95% CI: 1.08-1.35). In fresh ET cycles, the prevalence rate of zygotic splitting pregnancy after single blastocyst transfer was significantly higher than that after SET cycles with cleavage embryos (OR = 2.20; 95% CI: 1.83-2.66). However, no significant difference in ovarian stimulation and fertilization methods was recognized.Limitations, Reasons For Caution: In the current Japanese ART registry system, data regarding frozen-warmed ET do not include information about ovarian stimulation and fertilization methods. Registration for AH only began in 2010. There is no way of validating if data submitted by clinics is correct.Wider Implications Of the Findings: Clinicians should consider whether to counsel couples about the small increase in the risk of zygotic splitting associated with some embryo manipulations.Study Funding/competing Interest(s): No external funds were used for the study. The authors have no competing interests to declare.Trial Registration Number: None. [ABSTRACT FROM AUTHOR]

Study Question: Are trophectoderm biopsy or other pre-vitrification features or laboratory practices associated with differences in blastocyst post-warming behavior (degeneration, re-expansion and live birth after single embryo transfer (SET))?Summary Answer: Blastocyst morphology, day of full development and artificial shrinkage (either laser-assisted or biopsy-induced) are the pre-vitrification parameters/practices most strongly associated with post-warming behavior and implantation potential while there was no association with trophectoderm biopsy.What Is Known Already: Since the introduction of vitrification, the adoption of cycle segmentation, freeze-all and SET policies, as well of trophectoderm biopsy-based aneuploidy testing (i.e. pre-implantation genetic testing for aneuploidies (PGT-A)), the number of blastocysts vitrified worldwide has increased greatly. Previous studies already defined generally high blastocyst cryo-survival rates after vitrification-warming (>95%), along with a positive correlation between blastocyst re-expansion and morphology with implantation. Additionally, artificial shrinkage has been outlined as a potentially beneficial procedure, while the association between embryo cryo-survival and trophectoderm biopsy is still unclear.Study Design, Size, Duration: Cohort study conducted at two IVF centers (1 and 2). A total of 2129 consecutive SETs using vitrified-warmed blastocysts in either non-PGT or PGT-A cycles between June 2016 and August 2017 were included. A freeze-all strategy was in place and three main pre-vitrification practices were used: (i) no biopsy and no artificial shrinkage (Clinic 1); (ii) trophectoderm biopsy and vitrification of collapsed blastocyst within 30 min (Clinics 1 and 2); and (iii) no biopsy but laser-assisted artificial shrinkage (Clinic 2). The primary outcome was the blastocyst degeneration rate. Overall, 2108 surviving blastocysts were graded at 1.5 h after warming for degeneration (absent or partial) and re-expansion (full, partial or absent) grades and post-warming morphological quality. Logistic regression analyses were conducted to assess the association of any pre-vitrification feature with blastocyst post-warming behavior. The logistic regressions conducted upon live birth after either untested or euploid SET also included the post-warming characteristics.Participants/materials, Setting, Methods: Center 1 is a private IVF facility, while center 2 is the IVF facility of a University hospital. In non-PGT cycles, ICSI with blastocyst culture up to full-expansion and vitrification were performed. At center 1 the untested blastocysts were vitrified when still expanded, while at center 2 they underwent laser-assisted artificial shrinkage. In PGT-A cycles, in both clinics, trophectoderm biopsy (which involves laser-assisted shrinkage) was done without previous zona-opening on Day 3, and vitrification was performed within 30 min whilst the blastocyst remained collapsed. A qPCR-based chromosome analysis was conducted. Only SETs were performed (euploid-SET in case of PGT-A). Any cycle-, laboratory- and embryo-based feature which could impact blastocyst post-warming behavior was included in the analyses as putative confounder.Main Results and the Role Of Chance: The overall degeneration rate was 1% (N = 21/2129). The results were consistent among different vitrification/warming operators or kits used, as well as any other IVF laboratory-related parameter. Blastocyst artificial shrinkage (either laser-assisted or biopsy-induced) involved a lower risk of degeneration after warming (odds ratio (OR) [95% CI] = 0.26 [0.09-0.79]). Conversely, both poor morphological quality pre-vitrification and taking 7 days to reach full blastulation resulted in a significantly higher risk (OR [95% CI] = 11.67 [3.42-39.83] and 4.43 [1.10-20.55], respectively). Importantly, trophectoderm biopsy did not show any association with blastocyst cryo-survival/degeneration. Overall 2.5% (N = 53/2108) blastocysts failed to re-expand post-warming. The only parameters significantly associated with no blastocyst re-expansion post-warming were average (OR [95% CI] = 4.96 [2.20-11.21]) or poor (OR [95% CI] = 19.54 [8.39-45.50]) morphological quality and taking 7 days to reach full blastulation (OR [95% CI] = 3.19 [1.23-8.29]), as well as prevention of spontaneous hatching pre-vitrification (OR [95% CI] = 0.10 [0.01-0.85]). The post-warming features of the survived blastocyst (i.e. degeneration and re-expansion scores and morphological quality) showed no significant association with vitrified blastocyst competence (i.e. live birth) when corrected for pre-vitrification ones (i.e. morphological quality, day of full development and, for untested SET, maternal age at oocyte retrieval). Of note, poor-quality blastocysts pre-vitrification showed a high overall cryo-survival rate post-warming 92.8% (N = 116/125), but the live birth rates were only 2.1% (N = 1/48) and 7.3% (N = 5/68) after untested and euploid SET, respectively.Limitations, Reasons For Caution: This study is not randomized and the populations of patients undergoing either non-PGT or PGT-A cycles were different. Centers 1 and 2 adopted different pre-vitrification practices for non-biopsied blastocysts, according to their own laboratory policy. To this regard, multivariate logistic regression analyses were conducted for all outcomes under investigation.Wider Implications Of the Findings: Pre-vitrification features may be used to assist selection of competent embryos, moreover, these results allay concern that trophectoderm biopsy might be associated with impaired blastocyst quality or competence after vitrification/warming.Study Funding/competing Interest(s): None.Trial Registration Number: None. [ABSTRACT FROM AUTHOR]

Study Question: Does single cleavage-stage (Day 3) embryo transfer using a time-lapse (TL) hierarchical classification model achieve comparable ongoing pregnancy rates (OPR) to single blastocyst (Day 5) transfer by conventional morphological (CM) selection?Summary Answer: Day 3 single embryo transfer (SET) with a hierarchical classification model had a significantly lower OPR compared with Day 5 SET with CM selection.What Is Known Already: Cleavage-stage SET is an alternative to blastocyst SET. Time-lapse imaging assists better embryo selection, based on studies of pregnancy outcomes when adding time-lapse imaging to CM selection at the cleavage or blastocyst stage.Study Design, Size, Duration: This single-centre, randomized, open-label, active-controlled, non-inferiority study included 600 women between October 2015 and April 2017.Participants/materials, Setting, Methods: Eligible patients were Chinese females, aged ≤36 years, who were undergoing their first or second fresh IVF cycle using their own oocytes, and who had FSH levels ≤12 IU/mL on Day 3 of the cycle and 10 or more oocytes retrieved. Patients who had underlying uterine conditions, oocyte donation, recurrent pregnancy loss, abnormal oocytes or <6 normally fertilized embryos (2PN) were excluded from the study participation. Patients were randomized 1:1 to either the cleavage-stage SET with a time-lapse hierarchical classification model for selection (D3 + TL) or blastocyst SET with CM selection (D5 + CM). All normally fertilized zygotes were cultured in Primo Vision. The study was conducted at a tertiary IVF centre (CITIC-Xiangya) and OPR was the primary outcome.Main Results and the Role Of Chance: A total of 600 patients were randomized to the two groups, among which 585 (D3 + TL = 290, D5 + CM = 295) were included in the Modified-intention-to-treat (mITT) population and 517 (D3 + TL = 261, D5 + CM = 256) were included in the PP population. In the per protocol (PP) population, OPR was significantly lower in the D3 group (59.4%, 155/261) than in the D5 group (68.4%, 175/256) (difference: -9.0%, 95% CI: -17.1%, -0.7%, P = 0.03). Analysis in mITT population showed a marginally significant difference in the OPR between the D3 + TL and D5 + CM groups (56.6 versus 64.1%, difference: -7.5%, 95% CI: -15.4%, 0.4%, P = 0.06). The D3 + TL group resulted in a markedly lower implantation rate than the D5 + CM group (64.4 versus 77.0%; P = 0.002) in the PP analysis, however, the early miscarriage rate did not significantly differ between the two groups.Limitations, Reasons For Caution: The study lacked a direct comparison between time-lapse and CM selections at cleavage-stage SET and was statistically underpowered to detect non-inferiority. The subject's eligibility criteria favouring women with a good prognosis for IVF weakened the generalizability of the results.Wider Implications Of the Findings: The OPR from Day 3 cleavage-stage SET using hierarchical classification time-lapse selection was significantly lower compared with that from Day 5 blastocyst SET using conventional morphology, yet it appeared to be clinically acceptable in women underwent IVF.Study Funding/competing Interest(s): This study is supported by grants from Ferring Pharmaceuticals and the Program for New Century Excellent Talents in University, China.Trial Registration Number: ChiCTR-ICR-15006600.Trial Registration Date: 16 June 2015.Date Of First Patient’s Enrolment: 1 October 2015. [ABSTRACT FROM AUTHOR]