Time Of Embryo Transfer Research Articles

What is the optimal timing of embryo transfer when there are only up to two embryos at cleavage stage?

Not only has there been a debate whether embryo transfer should be performed at the cleavage stage or at the blastocyst stage but there is also uncertainty regarding when to transfer if there are only one or two embryos at the cleavage stage. The aim of this study was to compare the pregnancy rate of day 3 transfers vs. blastocyst stage transfers in patients who had only one or two embryos at the cleavage stage on day 3.

Preliminary study for pregnancy rate according to developmental stages of vitrified-warmed blastocyst

Purpose: To examine the pregnancy rate according to developmental stages of vitrified-warmed human blastocyst at the time of embryo transfer (ET). Materials and Methods: Retrospectively, the outcomes of total 140 elective frozen thawed blastocyst transfers were analyzed regarding the embryo developmental stage of the thawed blastocysts at the time of transfer. Group 1 included only expanding blastocysts, group 2 included an expanding blastocyst and a hatching blastocyst, and group 3 included only hatching blastocysts. Results: Implantation rate, clinical pregnancy rate, and ongoing pregnancy rate were significantly higher in group 3 than group 1 and 2. Implantation rates were 32.6% (group 1), 56.6% (group 2), and 77.2% (group 3) (p p p Conclusions: Pregnancy rate was higher in transfer of hatching blastocysts than in expanding blastocysts.

Gonadotropin-Releasing Hormone-Agonist Triggering and a Freeze-All Approach: The Final Step in Eliminating Ovarian Hyperstimulation Syndrome?

In vitro fertilization (IVF) has evolved dramatically in recent decades; however, clinical practices have been slow to adopt these advancements, particularly regarding final oocyte maturation and the timing of embryo transfer. Concerns still exist over the ability of gonadotropin-releasing hormone (GnRH) agonists and elective embryo cryopreservation to reduce the risk of ovarian hyperstimulation syndrome (OHSS) without compromising pregnancy outcomes. This review investigates IVF outcomes associated with GnRH-agonist triggering and elective embryo cryopreservation. The safety and efficacy of GnRH-agonist triggering are compared with conventional human chorionic gonadotropin triggering, and frozen embryo transfers are weighed against fresh transfers. A literature search was conducted using OVID (MEDLINE) and PubMed databases. The search strategy included keywords such as "ovarian hyperstimulation syndrome or OHSS," "GnRH-agonist triggering," "cryopreservation or freeze-all," and "IVF outcomes." A total of 214 articles were considered for review. Gonadotropin-releasing hormone agonist triggering reduces OHSS incidence without compromising oocyte retrieval and fertilization rates in donor and autologous cycles. However, GnRH-agonist triggering causes a luteal phase deficiency in autologous cycles, deleteriously compromising pregnancy rates. Elective embryo cryopreservation overcomes this deficiency, reducing the risk of OHSS and may improve neonatal and obstetric outcomes. Gonadotropin-releasing hormone agonist triggering should be considered in all donor cycles. It should also be selectively considered in autologous cycles in combination with elective cryopreservation of all viable embryos.

Embryo transfer: timing and techniques.

Since the first successful human in vitro fertilization (IVF) pregnancy nearly 40 years ago, remarkable progress has been made in assisted reproductive technology (ART). Improvements in oocyte retrieval, embryo culture, genetic screening, and embryo selection have contributed to dramatic improvements in IVF outcomes. A more robust understanding of embryologic development has driven innovation in not only the timing of embryo transfer but also the number of embryos to transfer. Additionally, overcoming the technical hurdle of embryo vitrification has given both physicians and patients several benefits including the flexibility to mitigate effects of superovulation on the endometrium, limit the number of embryos transferred, afforded an opportunity to screen the quality of embryos both by evaluating in vitro development as well as preimplantation genetic testing. Within this review, we highlight in a stepwise fashion the considerations for embryo transfer timing and technique that physicians and patients alike must consider when undergoing an IVF cycle.

Laser Acupuncture Before and After Embryo Transfer Improves In Vitro Fertilization Outcomes: A Four-Armed Randomized Controlled Trial

Objective: The objective was to perform a large, well-powered trial to assess the benefit of laser acupuncture (LA) on in vitro fertilization (IVF) success. Utilization of LA as a treatment allowed improvement of control groups used in prior studies, because there was no possibility of the potentially confounding effect of acupressure, noted in prior studies with blunt-tip controls. Materials and Methods: This was a four-arm, randomized controlled trial conducted at two private-practice fertility centers on couples who were attempting conception through IVF between June 2005 and January 2008. Following ovarian stimulation and oocyte retrieval, patients were randomized to needle acupuncture (NA), LA, sham LA (SLA), and no treatment (NT) groups. Main Outcome Measures: The primary outcome measure was implantation rate (IR). Secondary outcomes included clinical pregnancy rate (CPR) and live birth rate (LBR). Results: LA resulted in the highest IR among the 4 randomization groups (LA: 33.7% versus NA: 28.9% versus SLA: 26.8% versus NT: 24.9%; P = 0.02). When compared directly to SLA, LA resulted in a significantly higher IR (odds ratio: 1.38; 95% confidence interval: 1.05–1.81; P = 0.02). There were no significant differences among the groups for CPR or LBR, although the study was not powered to detect these differences. Conclusions: LA at the time of embryo transfer improves IR. This was the first trial evaluating the use of LA in the context of IVF. Utilization of LA allowed the unique opportunity to examine the benefits of acupuncture in IVF against a truly inert control group.

Transferring embryos on day 2 versus day 3 in women with low fertilization rates does not affect pregnancy and implantation rates

The timing of embryo transfer on day 2 (D2) or day 3 (D3) has been a topic of controversy. Studies on preferential embryo transfer on D2 versus D3 in women with a high yield of fertilized oocytes, comparing pregnancy and implantation rates, have led to conflicting results [1]. However, the potential difference in outcomes of D2 versus D3 embryo transfer in women with a low yield of fertilized oocytes has not been looked at thoroughly. To evaluate the differences, if any, in pregnancy and implantation rates when embryo transfer occurs on D2 versus D3. Design: Retrospective cohort. Setting: Academic fertility center. Interventions: A total of 94 IVF cycles from 87 women were analyzed. Women with a low yield of fertilized oocytes (≤2 2PN stage zygotes) who had their embryo transfer on D2 or D3 were included in the study. Exclusion criteria included: Donor oocyte, pre-implantation genetic testing, and gestational carrier cycles, as well as women who yielded >2 fertilized oocytes. Cycles were categorized into two groups: cycles during which embryo transfer had occurred on D2 (Group 1) or D3 (Group 2). Positive pregnancy test (serum β-hCG concentration >6 IU/L) per IVF cycle (PPT), clinical pregnancy rate (CPR) and implantation rate (number of sacs seen on US over the number of embryos transferred in cycles with β-hCG>6). Mann-Whitney U-test and χ2-test were used as appropriate. P<0.05 was considered significant. Table 1 summarizes the baseline and cycle characteristics of the two groups. Patients having their embryo transfer on D2, when compared to those who had a D3 embryo transfer, experienced similar PPT (31.9 vs. 29.8%, p=0.82; respectively). Most importantly, CPR (23.4 vs. 23.4%, p=1.00; respectively) and implantation rate (46.7 vs. 50.0%, p=0.81; respectively) were comparable between the two groups (Figure 1A-B). Our findings suggest that transferring embryos on D2 versus D3 in women with a low fertilization rate does not seem to affect CPR or implantation rates. These results indicate that there can be some flexibility in scheduling the day of transfer at the convenience of both the patient and the center.

Characterizing the endometrial microbiome by analyzing the ultra-low bacteria from embryo transfer catheter tips in IVF cycles: Next generation sequencing (NGS) analysis of the 16S ribosomal gene

There is growing interest in the microbiome of the reproductive tract. The vaginal and placental microbiome has been partially characterized and shown to be related to obstetric outcomes. In this study, we developed a sensitive method to analyze 16S ribosomal RNA profiling from ultra-low bacteria counts, then studied the endometrial microbial environment by analyzing catheter tips after embryo transfers during in vitro fertilization (IVF). An extensive validation was performed on extracted DNA and culture lysates without DNA isolation from the single- or poly-microbial samples of Escherichia coli, Proteus vulgaris, Staphylococcus epidermidis, and Bacillus cereus by Illumina 16S V4 metagenomics workflows. The direct lysis method can reliably detect the genus or species taxonomic level for both single- and poly-microbial samples when there were more than 60 bacterial cells in the culture lysates. Over 99% total operational taxonomic units (OTUs) were assigned to correct genus or species. The endometrial microbiome at the time of embryo transfer was characterized by analyzing catheter tips with Illumina V4 metagenomics for 70 patients who underwent IVF cycles. Lactobacillus spp. were detected in all 70 samples. Other vaginal bacteria (Corynebacterium, Bifidobacterium, Staphylococcus, and Streptococcus) were also detected. The Illumina V4 metagenomics workflow with preamplification provided a rapid and sensitive method for the identification of bacterial genus or species in single- or poly-microbial samples and clinical embryo transfer specimens. Ongoing work will illuminate the relationship between endometrial microbiome and reproductive success.

Patients experience of viewing time-lapse sequences: A prospective survey study

The use of time-lapse monitoring in ART is spreading rapidly and is already considered an important part of treatment in many centers internationally, but studies are lacking on patients experience of using this technology. We consider it important not to forget patient-oriented aspects of new technologies. The study question was therefore; how do patients value the chance to view time-lapse sequences of their embryos at the time of embryo transfer? We performed a prospective, observational questionnaire study at three of IVF Sweden`s centers, including 242 patients. We report the results from self-evaluated scores of patient´s experience which were reported anonymously. Participants in the study were patients who were offered to view time-lapse sequences of embryos at the time of embryo transfer. A 5-grade Likert-scale instrument was used for assessing patient’s experience. A majority of the patients found viewing the sequences to be a relevant and important aspect of their treatments. Patients felt increased participation in, and increased satisfaction with the treatment. There was a clear interest in obtaining a copy of the time-lapse sequence but only if the treatment resulted in a pregnancy. If time-lapse technology is available in a clinic it could be an additive value to share the sequences with the patients as deepened information about their treatment. If a copy of the sequences is made available to the patients we recommend to delay the time for that at least until there is a verified ongoing pregnancy.

Ovarian activity and embryo yield in relation to the postpartum period in superovulated dairy cows

The aim of this study was to evaluate superovulation response in cows at various postpartum periods (early postpartum period up to 3.5 months; middle postpartum period 3.7–7 months; later postpartum period above 7.5 months after calving). The data included observation of 55 Holstein cows superovulated at one farm in the Czech Republic during the years 2010 and 2013. Reproduction traits (dependent variable) were represented as number of the corpora lutea, number of transferable embryos, morulae, blastocysts, total number of embryos and embryo recovery. For statistical evaluation we used the PROC GLM of SAS® with fixed effect - breeding value of milk production. The study results show significant differences (P &lt; 0.05–0.01) in the three postpartum periods (early, middle, and later postpartum periods) and the number of corpora lutea (4.6; 7.4; 10.8), number of total embryos (3.2; 2.9; 6.5) and transferable embryos (1.8; 1.7; 4.4). Effective timing of embryo transfer in the later postpartum period resulted in greater ovarian activity and embryo yield compared to early lactation periods.

Therapeutic effect of acupuncture on the outcomes of in vitro fertilization: a systematic review and meta-analysis.

Controversial results have been reported concerning the effect of acupuncture on in vitro fertilization (IVF) outcomes. The current review was conducted to systematically review published studies of the effects of acupuncture on IVF outcomes. Women undergoing IVF in randomized controlled trials (RCTs) were evaluated for the effects of acupuncture on IVF outcomes. The treatment groups involved traditional, electrical, laser, auricular, and other acupuncture techniques. The control groups consisted of no, sham, and placebo acupuncture. The PubMed, Embase, and Web of Science databases were searched. The pregnancy outcomes data are expressed as odds ratios (ORs) with 95% confidence intervals (CIs) based on a fixed model or random model depending on the heterogeneity determined by the Q test and I2 statistic. The major outcomes were biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), live birth rate (LBR), and ongoing pregnancy rate (OPR). Heterogeneity of the therapeutic effect was evaluated by a forest plot analysis, and publication bias was assessed by a funnel plot analysis. Thirty trials (a total of 6344 participants) were included in this review. CPR data showed a significant difference between the acupuncture and control groups (OR 1.26, 95% CI 1.06-1.50, p=0.01), but there was significant statistical heterogeneity among the studies (p=0.0002). When the studies were restricted to Asian or non-Asian area trials with a sensitivity analysis, the results significantly benefited the CPR in Asian group (OR 1.51, 95% CI 1.04-2.20, p=0.03). Based on the area subgroup analysis, we found that in the Asian group, the IVF outcomes from the EA groups were all significantly higher than those from the control groups (CPR: OR 1.81, 95% CI 1.20-2.72, p=0.005; BPR: OR 1.84, 95% CI 1.12-3.02, p=0.02; LBR: OR 2.36, 95% CI 1.44-3.88, p=0.0007; OPR: OR 1.94, 95% CI 1.03-3.64, p=0.04). Meanwhile, compared with other acupuncture time, the IVF outcome results were significantly superior in the acupuncture group when acupuncture was conducted during controlled ovarian hyperstimulation (COH) (CPR: OR 1.71, 95% CI 1.27-2.29, p=0.0004; LBR: OR 2.41, 95% CI 1.54-3.78, p=0.0001; BPR: OR 1.50, 95% CI 1.02-2.20, p=0.04; OPR: OR 1.88, 95% CI 1.06-3.34, p=0.03). However, when acupuncture was conducted at the time of embryo transfer, the BPR and OPR from the acupuncture groups were significantly lower than those of the controls in the Asian group (BPR: OR 0.67, 95% CI 0.48-0.92, p=0.01; OPR: OR 0.68, 95% CI 0.49-0.96, p=0.03). Based on an analysis of the studies, acupuncture improves the CPR among women undergoing IVF. When the studies were restricted to Asian or non-Asian area patients, compared with traditional acupuncture and other methods, electrical acupuncture yielded better IVF outcomes. Optimal positive effects could be expected using acupuncture in IVF during COH, especially in Asian area. However, as a limitation of this review, most of the included studies did not mention the number of embryos transferred.

100 FACTORS AFFECTING PREGNANCY RATES IN THE TRANSFER OF IN VITRO-PRODUCED JAPANESE BLACK CATTLE EMBRYOS

Despite the rapid expansion of in vitro embryo production (IVP) technology for genetic improvement in the cattle industry in the last decades, pregnancy rates by the transfer of IVP embryos are still lower than those derived from in vivo-produced embryos. The objective of this study was to analyse factors affecting pregnancy rates after the transfer of IVP Japanese Black cattle embryos under farm conditions. Holstein heifers (n = 4,475) and cows (n = 8,541) were selected as recipients. Most cows (80%) were managed in tie-stall barns and most heifers (80%) were managed in pens. Embryo transfers were performed for 9 years, from 2004 to 2012. The embryos were produced from oocytes derived from a local abattoir and semen from 14 proven bulls by the Livestock Improvement Association of Japan (Hamano and Kuwayama 1993 Theriogelogy 39, 703–712). The fresh IVP embryos (quality; IETS code 1) that reached the blastocyst stage after 7 to 8 days (insemination = Day 0) were transported by an airplane (2 h) and subsequently by a car (1.5 h). Embryos were non-surgically transferred to each recipient on Day 7 to 9 of their natural oestrous cycle on farms. Pregnancy was diagnosed on Day 40 to 60 after oestrus. Pregnancy results were statistically analysed using the GLM procedures of SAS. The following variables were included in the model: recipient parity (0, 1, 2, or 3), day (7, 8, or 9) of the oestrous cycle at the time of embryo transfer, oestrus behaviour (increased activity observed by farmers), presence of mucus at oestrus, presence of blood after oestrus, and year (1, 2, 3, 4, 5, 6, 7, 8, or 9) and season (April–June as spring, July–September as summer, October–December as fall, or January–March as winter) of embryo transfer. The Bonferroni correction was used to counteract the problem of multiple comparisons. Heifers had significantly higher pregnancy rates than cows (51.0% v. 37.9%, respectively; P &lt; 0.01), and first parity cows had higher pregnancy rates than third parity cows (42.9% v. 35.7%, respectively; P &lt; 0.01). Pregnancy rates were significantly higher in recipients that received an embryo transfer on Day 8 of their oestrous cycle, than on Day 7 (46.6% v. 42.4%, respectively; P &lt; 0.01). Recipients without oestrus behaviour had higher pregnancy rates than those with oestrus behaviour (46.3% v. 43.4%, respectively; P &lt; 0.01). The presence of mucus and/or blood after oestrus and the season of transfer were not found to significantly affect pregnancy rates. The results of this study indicated that performing IVP embryo transfers on Day 8 of a recipient’s oestrous cycle will improve the pregnancy rate, season does not have an effect on pregnancy rate, and the detection of oestrus by monitoring increased activity is not always reliable and instead should be determined by multiple symptoms on farm conditions.

What are the benefits and harms of intrauterine administration of human chorionic gonadotropin around the time of embryo transfer in subfertile women undergoing assisted reproduction?

What are the benefits and harms of intrauterine administration of human chorionic gonadotropin around the time of embryo transfer in subfertile women undergoing assisted reproduction?

Integrins β1 and β3 are biomarkers of uterine condition for embryo transfer.

BackgroundClinical ovulation induction induces blood estrogen (E2) in excess of physiological levels, which can hinder uterine receptivity. In contrast, progesterone produces the opposite clinical effect, suggesting that it might be capable of recovering the lost receptivity resulting from exposure to high estrogen levels. Integrins are the most widely used biological markers for monitoring uterine conditions. We studied progesterone-induced changes in integrin β expression patterns as biomarkers for changes in uterine receptivity in response to increased estrogen levels.MethodsEndometrial biopsy samples from patients were screened for their estrogen (E2) and progesterone (P4) content and expressing levels of integrin β1 and β3. Uterine receptivity was evaluated using human endometrial adenocarcinoma cells in an embryo attachment model. The respective and concatenated effects of embryo attachment and changes in the integrin β1 and β3 expression patterns on the adenocarcinoma cell plasma membranes in response to 100 nM concentrations of E2 and P4 were evaluated.ResultsIncreased blood E2 concentrations were associated with significantly decreased the levels of integrin β3 expression in uterine biopsy samples. In vitro experiments revealed that a 100 nM E2 concentration inhibited the distribution of integrin β3 on the plasma membranes of human endometrial adenocarcinoma cells used in the embryo attachment model, and resulted in decreased rates of embryo attachment. In contrast, P4 enhanced the expression of integrin β1 and promoted its distribution on the plasma membranes. Furthermore, P4 recovered the embryo attachment efficiency that was lost by exposure to 100 nM E2.ConclusionsBlood E2 and P4 levels and integrin β3 and β1 expression levels in uterine biopsy samples should be considered as biomarkers for evaluating uterine receptivity and determining the optimal time for embryo transfer. Trial registration Trial number: ChiCTR-TRC-13003777; Name of registry: Chinese Clinical Trial Registry; Date of registration: 4 September 2013; Date of enrollment of the first study participant: 15 October 2013Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1052-0) contains supplementary material, which is available to authorized users.

Timing of embryo transfer after hysteroscopic polypectomy does not effect pregnancy rates

Timing of embryo transfer after hysteroscopic polypectomy does not effect pregnancy rates

Risk factors for abnormal umbilical cord insertions among term singleton art pregnancies

The placenta with velamentous umbilical cord insertion (VCI) is a rare pathologic condition that is supposed to increase the risk of perinatal complications. The reported adverse outcomes include fetal growth restriction, non-reassuring fetal status requiring emergency Cesarean section, fetal exsanguination due to the rupture of vasa previa, and cerebral palsy. We reported on a study, emphasizing a higher incidence of the placenta accompanied by VCI in ART pregnancies when compared with non-ART cases, at the 70th ASRM Annual Meeting. In this research, we examined the ART-conceived cases closely for the purpose of identifying the ART-associated risk factors that might affect the incidence of the placenta with VCI. Retrospective cohort study and comparative analysis. We reviewed the records of 427 consecutive singleton, term labor and delivery ART-conceived cases from January 2011 to April 2016. Information about maternal age, obstetric history, details of ART treatment, mode of delivery, and insertion site of the umbilical cord was all collected from their medical records. Our study population was divided into two categories as follows: cases with VCI (Group A: n=23), and cases without VCI (Group B: n=404). Odds ratios for VCI, 95% confidence intervals (CI), and significance of the odds ratio were calculated according to ART-related variables (i.e., fertilization method (conventional-IVF vs. ICSI), type of embryo (fresh vs. frozen-thawed), embryo transfer timing (day 2-3 early-cleavage stage embryo vs. day 5-6 blastocyst), and fetal sex), using multivariate logistic regression. Maternal basal characteristics and odds ratios were shown in the table below. The incidence of VCI in our study population was 5.4% (23/427). The rate of delivery necessitating emergency C-section or operative vaginal delivery in Group A (14/23, 61%) was much higher than in Group B (138/404, 34%). Blastocyst transfer and female fetus significantly increased the likelihood of developing the placenta with VCI. Fertilization method and type of embryo did not affect the incidence of the placenta with VCI.Tabled 1Baseline characteristics and adjusted odds ratio(aOR) for velamentous umbilical cord insertionGroup A (cases with VCI: n=23)Group B (cases without VCI: n=404)aOR for VCI (95% CI, P value)Maternal age35.9±3.835.5±3.61.03 (0.91 - 1.16, 0.66)Parity (primipara / multipara)20 / 3302 / 1021.00 (reference) / 0.40 (0.09 - 1.23, 0.15)c-IVF / ICSI5 / 18143 / 2611.00 / 1.96 (0.76 - 6.05, 0.19)Fresh / Frozen-thawed7 / 16136 / 2681.00 / 1.25 (0.52 - 3.34, 0.63)Early cleavage / Blastocyst1 / 22117 / 2871.00 / 10.23 (2.09 - 184.78, 0.02*)Male / Female5 / 18200 / 2041.00 / 3.48 (1.35 - 10.71, 0.02*)[Note of the table above: Data are mean±SD or number of subjects. Odds ratios were all adjusted for maternal age and parity. *: P<0.05 was considered statistically significant.] Open table in a new tab [Note of the table above: Data are mean±SD or number of subjects. Odds ratios were all adjusted for maternal age and parity. *: P<0.05 was considered statistically significant.] As VCI often brings about serious obstetric complications, ART pregnancies achieved by blastocyst transfer and/or of female fetus are optimal candidates for checking up on and identifying the umbilical cord insertion site more proactively during routine obstetric ultrasound examinations.

Application of flunixin meglumine at the time of embryo transfer and the effect on the fertility

The presence of Neon in terrestrial planet mantles may be attributed to the implantation of solar wind in planetary precursors or to the dissolution of primordial solar gases captured from the accretionary disk into an early magma ocean. This is suggested by the Neon isotopic ratio similar to those of the Sun observed in the Earth mantle. Here, we evaluate the second hypothesis. We use general considerations of planetary accretion and atmospheric science. Using current models of terrestrial planet formation, we study the evolution of standard planetary embryos with masses in a range of 0.1–0.2 MEarth, where MEarth is the Earth’s mass, in an annular region at distances between 0.5 and 1.5 Astronomical Units from the star. We determine the characteristics of atmospheres that can be captured by such embryos for a wide range of parameters and calculate the maximum amount of Neon that can be dissolved in the planet. Our calculations may be directly transposed to any other planet. However, we only know of the amount of Neon in the Earth’s solid mantle. Thus we use Earth to discuss our results. We find that the amount of dissolved Neon is too small to account for the present-day Neon contents of the Earth’s mantle, if the nebular gas disk completely disappears before the largest planetary embryos grow to be ∼0.2 MEarth. This leaves solar irradiation as the most likely source of Neon in terrestrial planets for the most standard case of planetary formation models.

A High-Throughput Assay for the Detection of α-Dystroglycan N-Terminus in Human Uterine Fluid to Determine Uterine Receptivity

Embryo implantation requires a healthy embryo and a receptive uterus. In women, the uterus remains a hostile environment and must undergo functional changes to convert to a receptive state for embryo implantation. Determining uterine receptivity is vital in IVF treatment, as the timing of embryo transfer needs to be synchronized with uterine receptivity. However, to date, no reliable biochemical tests are available to determine uterine receptivity. We recently established that removal of α-dystroglycan N-terminus (α-DG-N) from the uterine surface plays an important role in the establishment of uterine receptivity. Importantly, the α-DG-N removed from the uterine tissue enters into the uterine fluid, and the levels correlate with the tissue status of receptivity. Detection of α-DG-N in uterine fluid may therefore provide a nonsurgical approach to assess uterine receptivity. In this study, we first validated three monoclonal antibodies raised against α-DG-N in our system, and then established a sandwich ELISA suitable for the detection of α-DG-N in human uterine fluid. This ELISA detected significantly higher concentrations of α-DG-N in uterine fluid of women in the receptive phase. We believe this newly established α-DG-N ELISA may provide an important tool in the development of noninvasive strategies to detect uterine receptivity in women.

Assessment of the embryo flash position and migration with 3D ultrasound within 60 min of embryo transfer.

Does the air bubble (embryo flash) position and migration as visualized with 3D ultrasound (US) within 60 min of embryo transfer correlate with clinical outcome following fresh ART transfer cycles? The location of the embryo flash and the direction of its movement at 60 min, but not at 1 or 5 min after transfer, are associated with clinical pregnancy. Studies assessing the relation between the pregnancy rate and the position of the catheter tip and/or the position of the air bubbles following embryo transfer show conflicting results to date. This was a prospective cohort study including 277 infertile women undergoing ART between July 2011 and August 2013. Good prognosis patients undergoing fresh ART cycles within a single tertiary University unit were assessed by 3D US at 1, 5 and 60 min after embryo transfer. The distance of the embryo flash from the fundus was measured at these time points, along with the direction of the embryo flash movement within 60 min of transfer. Within 60 min of embryo transfer, 76.4% (198/259) of the embryo flashes migrated towards the fundus, 12.4% (32/259) migrated towards the cervix and 11.2% (29/259) remained static. There was no significant association between the embryo position or movement and the pregnancy rate at 1 and 5 min. At 60 min, however, the pregnancy and implantation rates among subjects with embryo flashes located <15 mm from the fundus was significantly higher than those with embryo flashes located >15 mm from the fundus (46.5 and 32.8% versus 25.8 and 18.2%, respectively; P < 0.05). The pregnancy and implantation rates when the embryo flash was seen moving towards the cervix (25.0 and 15.0%) was significantly lower (P < 0.05 and P < 0.01, respectively) compared with those remaining static (55.2 and 37.7%) or moving towards the fundus (45.5 and 32.8%). Although the air bubbles seen at the time of embryo transfer are thought to represent the position of the embryo, they are in fact a surrogate marker of the embryo itself, as this cannot be directly visualized by US. Following embryo transfer the majority, but not all, embryo flashes undergo significant migration towards the fundus. The location of the embryo flash and the direction of its movement at 60 min, but not at 1 or 5 min after transfer, is associated with clinical outcome. These findings may challenge the traditional notion that the exact position of the embryo flash immediately following embryo transfer is related to clinical outcome. The authors have no relevant funding or conflicts of interest to disclose.

Improvement of pregnancy rate by intrauterine administration of dexamethasone and recombinant human leukemia inhibitory factor at the time of embryo transfer in cattle.

Bovine embryos (day 5) were cultured to day 10 with or without 100 ng/mL PGF2α in medium supplemented with control; 100 nM Dex; 1,000 U/mL recombinant human leukemia inhibitory factor (rhLIF); or Dex+rhLIF. Although the rates to development to the blastocyst were not significantly different among groups, the hatching rate after additional culture with Dex +/or rhLIF was significantly higher in all supplemented groups than the control (p < 0.05). In the presence of PGF2α, the hatching rate was significantly restored in all supplemented groups relative to the group treated with only PGF2α and the control (p < 0.05). Embryo transfer (ET) was performed with blastocysts (day 7). PGF2α levels of control recipient cows were significantly higher in the circulatory blood samples collected 60 min after ET than in samples collected 60 min before ET (p < 0.005), and were decreased in cows injected with loading medium supplemented with Dex+rhLIF (p < 0.005). Pregnancy rate was significantly higher in the ET group that received supplemented embryo-loading medium than in the non-supplemented control (p < 0.05). The intrauterine administration of Dex and rhLIF at ET prevented increased PGF2α in circulatory blood and resulted in enhanced pregnancy rate.

Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit.

Characterization of the human microbiome has become more precise with the application of powerful molecular tools utilizing the unique 16S ribosomal subunit's hypervariable regions to greatly increase sensitivity. The microbiome of the lower genital tract can prognosticate obstetrical outcome while the upper reproductive tract remains poorly characterized. Here, the endometrial microbiome at the time of single embryo transfer (SET) is characterized by reproductive outcome. Consecutive patients undergoing euploid, SET was included in the analysis. After embryo transfer, performed as per routine, the most distal 5-mm portion of the transfer catheter was sterilely placed in a DNA free PCR tube. Next-generation sequencing of the bacteria specific 16S ribosome gene was performed, allowing genus and species calls for microorganisms. Taxonomy assignments were made on 35 samples from 33 patients and 2 Escherichia coli controls. Of the 33 patients, 18 had ongoing pregnancies and 15 did not. There were a total of 278 different genus calls present across patient samples. The microbiome at time of transfer for those patients with ongoing pregnancy vs. those without ongoing pregnancy was characterized by top genera by sum fraction. Lactobacillus was the top species call for both outcomes. The data presented here show the microbiome at the time of embryo transfer can successfully be characterized without altering standard clinical practice. This novel approach, both in specimen collection and analysis, is the first step toward the goal of determining physiologic from pathophysiologic microbiota. Further studies will help delineate if differences in the microbiome at the time of embryo transfer have a reliable impact on pregnancy outcome.