Sustained Implantation Rate Research Articles

Sequential versus Monophasic Media Impact Trial (SuMMIT): a paired randomized controlled trial comparing a sequential media system to a monophasic medium

To determine whether sequential or monophasic media is the more optimal formulation for blastocyst development and sustained implantation rates (SIR) in IVF. Paired randomized controlled trials. Academic. Infertile couples (N = 192) with female partner ≤42years old and normal ovarian reserve. Fertilized zygotes from each patient were randomly divided into two groups: [1] cultured in sequential media and [2] cultured in monophasic medium. Sequential media consisted of Quinn's Advantage Cleavage Medium (SAGE) followed by Blast Assist (Origio). The monophasic medium used was Continuous Single Culture (Irvine Scientific). Paired ETs were accomplished by transferring the best euploid blastocyst from each media group. DNA fingerprinting was used to link outcomes. The primary outcome measure was the proportion of blastocysts suitable for clinical use. Secondary outcome measures included timing of blastulation, aneuploidy rates, and SIR. Sustained implantation rate is defined as the number fetal heart beats at 8-9weeks of gestation, divided by the number of embryos transferred. A total of 192 patients had their 2PN embryos (N = 2,257) randomized to each culture system. Sequential media had higher blastulation rate than monophasic medium (55.2% vs. 46.9%). No differences were found in the day of blastulation or aneuploidy rate. Of the 168 patients who had euploid blastocysts suitable for transfer, 126 completed a paired ET. Among the double ETs, there was no difference in implantation between groups. This is the first randomized controlled trial to examine paired euploid transfers of sibling zygotes cultured in sequential versus monophasic media. This study demonstrates that the usable blastocyst rate is greatest after culture in the sequential media tested in comparison with the monophasic formulation selected for study. However, no difference exists in timing of blastulation, aneuploidy, or SIR. Whether these observations are generalizable to other media systems remains to be determined. NCT01917240.

A prospective, blinded, non-selection study to determine the predictive value of ploidy results using a novel method of targeted amplification based Next generation sequencing (NGS) for comprehensive chromosome screening (CCS)

NGS technologies are now being utilized for CCS with promises to increase throughput and decrease costs. Unfortunately, these technologies have not been validated clinically. Most concerning is the lack of data documenting the false abnormal rate, defined as the proportion of embryos labeled as aneuploid through NGS but which would have delivered a healthy infant had they not been discarded. This study utilizes a non-selection design where embryos are transferred without knowledge of the NGS CCS result to determine the predictive value of both aneuploid and euploid results. Prospective, blinded, non-selection study. Patients with normal ovarian reserve ≤ 42 years of age were recruited. Following routine IVF care, trophectoderm biopsy was performed. Embryos were subsequently selected for transfer per routine. No NGS CCS analysis was done prior to transfer. A novel targeted amplification method of NGS based CCS which does not require whole genome amplification was then performed. The outcome for each transferred embryo was compared to the NGS screening result to determine the predictive value of that result. In the case of a two embryo transfer, DNA fingerprinting was utilized to ensure that the embryo responsible for the pregnancy was identified correctly. Implantation rates were compared between embryos designated euploid, aneuploid, and for the population as a whole. 117 patients had 187 blastocysts transferred. Of the 41 embryos assigned an aneuploid karyotype, none sustained implantation yielding a predictive value of an aneuploid result of 100%. 97 of 146 embryos designated as euploid implanted and progressed to delivery yielding a predictive value for a euploid result of 66.0%. No embryo designated as euploid subsequently developed into an aneuploid gestation. Euploid embryos had a higher sustained implantation rate than the population as a whole (50.8%, p<0.0001) and those designated aneuploid (0%, p<0.0001). This study represents the first prospective clinical evaluation of the predictive values of both a euploid and an aneuploid result when using NGS based CCS. This targeted amplification NGS CCS paradigm has a high degree of precision and provides excellent predictive values for actual clinical outcomes.

Endometrial disruption does not improve implantation in patients who have failed the transfer of euploid blastocysts.

PurposeTo assess the impact of single pass outpatient endometrial biopsy in patients at the highest risk for an endometrial cause for failed implantation; those that have failed to conceive despite the transfer of morphologically normal euploid embryos.MethodsThis is a retrospective cohort study consisting of all patients less than 42 years old who failed their first euploid blastocyst transfer and subsequently completed a second transfer cycle of euploid blastocysts. Cycles were analyzed to determine if a single pass endometrial biopsy, termed 'endometrial disruption', was performed in a cycle preceding their second embryo transfer. Transfer outcomes were analyzed and implantation rates calculated. Data analysis was performed to compare outcomes between patients who had endometrial disruption performed versus those that did not.ResultsTwo hundred ninety patients failed their first euploid embryo transfer and subsequently completed a second euploid embryo transfer and were included. Thirty-nine patients underwent endometrial disruption and 251 did not. There were no statistical differences in clinical implantation rate or sustained implantation rate between the group with endometrial disruption and subjects without any intervention (Clinical IR, 43.6 % vs. 55.0 %, p = 0.13; 38.5 % vs. 42.6 %, p = 0.60). When controlling for transfer order there was no statistical difference noted in implantation rates.ConclusionsSingle pass endometrial biopsy has no impact on endometrial receptivity in the highest risk subgroup- patient's that have failed to sustain the transfer of morphologically normal euploid embryos- as evidenced by equivalent implantation rates. It is possible that variations in technique may alter outcomes and randomized trials are needed to answer this question.

Endometrial infusion of human chorionic gonadotropin at the time of blastocyst embryo transfer does not impact clinical outcomes: a randomized, double-blind, placebo-controlled trial

To determine whether endometrial hCG infusion at the time of human blastocyst transfer impacts implantation rates. Randomized double-blinded placebo-controlled trial. Academic. Infertile couples with the female partner less than 43 years old (n = 300) undergoing fresh or frozen ET of one or two blastocysts. Patients undergoing ET were randomized into either a treatment or a control group. The treatment group received an infusion of 500 IU of hCG diluted in ET media. The control group received a sham infusion of ET media. Infusions were done using a separate catheter less than 3 minutes before actual ET. Sustained implantation rate: ongoing viable gestation (primary outcome) and ongoing pregnancy rate (secondary outcome). A total of 473 blastocysts were transferred into 300 patients. There were no differences between the two groups in sustained implantation rate (48.1% in the hCG group, 44.2% in the control group) or ongoing pregnancy rate (58.8% in the hCG group, 52.0% in the control group). Endometrial infusion of hCG at the time of blastocyst ET does not improve sustained implantation rates. NCT01643993.

Cohort aneuploidy rates are not predictive of sustained implantation rate of euploid blastocysts: give that blastocyst a chance!

Comprehensive chromosome screening (CCS) enhances pregnancy rates and outcomes by allowing for the selection of euploid embryos. While implantation rates (IR) are dramatically improved, factors beyond aneuploidy are involved in reproductive competence as a substantial number of euploid embryos fail to implant. This can make patient counseling complex, especially when the prevalence of aneuploidy is particularly high or low. This study aims to determine if the overall aneuploidy rate (AR) exerts a cohort effect on the implantation rate of euploid blastocysts selected for transfer, thus impacting implantation rate.

Comprehensive chromosome screening (CCS) of previously cryopreserved embryos results in excellent ongoing pregnancy rates

Comprehensive chromosome screening (CCS) of previously cryopreserved embryos results in excellent ongoing pregnancy rates

First pregnancies after blastocyst biopsy and rapid 24 chromosome aneuploidy screening allowing a fresh transfer within four hours of biopsy

OBJECTIVE: Trophectoderm (TE) biopsy on blastocysts may represent a safer and more reliable time to perform embryo biopsy. TE biopsies include only extraembryonic cells, involve a reduction in the fraction of the embryo biopsied, and provide multiple cells which improves precision in most analyses. To attain these putative advantages, it has previously been necessary to cryopreserve the blastocysts after biopsy to accommodate the prolonged time interval needed for microarray or CGH based 24 chromosome aneuploidy screening (24chr-AS). This study describes the initial clinical experience of the first 24chr-AS technology rapid enough to allow for TE analysis with fresh transfer within 4 hours of biopsy. DESIGN: Prospective observational. MATERIALS AND METHODS: Patients with recurrent loss, advanced maternal age, or recurrent implantation failure were recruited. All embryos underwent TE biopsy on day 5 of culture. Real-time PCR based 24chr-AS was performed. This technology displayed >98% accuracy in preclinical validation. Results were available within 4 hours. A karyotype was assigned to each embryo. The best morphologic embryos designated as euploid were selected for transfer. RESULTS: Eighty blastocysts from 15 patients (age=36.7+4.5 years) were evaluated. The overall aneuploidy rate was 46%. Embryos from 2 patients' were all aneuploid (2/15; 13%) and were not transferred. The biochemical pregnancy rate was 87% (13/15) or 100% per transfer. The ongoing clinical pregnancy rate was 53% (8/15) for all patients and 62% per transfer (8/13). Of 20 embryos transferred (mean 1.5 per patient), 12 have ongoing development (sustained implantation rate of 60%). CONCLUSION: It is possible to perform rapid 24chr-AS on TE biopsies and have results quickly enough to allow a fresh transfer. The high implantation and pregnancy rates in a difficult population were encouraging. A prospective randomized clinical trial will be necessary to definitively demonstrate that TE biopsy results are superior to those attained following day 3 biopsy.