Good Prognosis Patients Research Articles

Elective single embryo transfer (ESET) versus double embryo transfer (DET) following failed mandatory single embryo transfer (MSET)

To compare live birth and multiple birth rates among women who underwent eSET versus DET in the first frozen embryo transfer (FET) cycle following a failed fresh mSET. Retrospective cohort study. All patients at our institution from 1/1/2012-9/14/2017 who met criteria for mSET (age <38, good quality blastocyst, and no previous failed fresh cycle), did not have a live birth following their first fresh transfer, had at least 2 remaining cryopreserved blastocysts, and subsequently underwent FET were included. Primary outcomes were live birth per transfer and multiple birth per delivery. Secondary outcomes were clinical pregnancy rate, miscarriage rate, ectopic pregnancy rate, term vs. preterm delivery, vaginal delivery vs. cesarean section, and infant birth weight. Exclusion criteria were preimplantation genetic testing (PGT) cycles, FET cycles in which only 1 embryo survived the thaw process, mSET due to maternal condition (e.g. unicornuate uterus), cycles in which birth data were not available, and donor oocyte cycles. Chi-squared tests and t-tests were used to compare demographic, cycle characteristics, and outcome data between groups. Medians with interquartile ranges, means with standard deviation, or percentages are presented. Of the 731 patients who underwent an initial mSET and had outcome data available, 450 had a live birth (61.5%). Of the 281 that failed their fresh mSET, 218 of these went on to have a FET within our time frame (77.6%). Of those, 54 patients were excluded due to no outcome data available (n=9), <2 blastocysts frozen (n=15), only 1 surviving embryo available to transfer after warming (n=27), or mSET due to maternal condition (n=3). This left 164 patients, of which 88 (53.7%) chose to transfer 1 embryo and 76 (46.3%) chose to transfer 2 embryos in their FET. Demographic and cycle characteristics were similar between eSET and DET patients (Table 1). DET patients had a significantly higher live birth rate and clinical pregnancy rate than eSET patients. However, DET patients also had a significantly higher multiple birth rate, C-section rate, and lower birth weight (Table 1). There was no other differences in outcomes seen between groups. In a group of good prognosis patients with an unsuccessful mandatory single embryo transfer, DET in the subsequent cycle resulted in a higher live birth rate than SET, but also was associated with a much higher multiple birth rate. When deciding on the number of embryos to transfer in this group, patients and providers should consider both the higher pregnancy rate and the significant risk of multiples with DET vs. SET.Tabled 1Demographic and Cycle CharacteristicsceSET (n=88)DET (n=76)pAge31 (29-34)32 (29-34)0.248BMI26.7 (21.9-31.5)25.4 (22.6-32.7)0.618Number of oocytes retreived18 (13-25)18 (13-30)0.377Number of blastocysts cryopreserved3 (2-6)4 (2-7)0.345Parity0 (0-0)0 (0-1)0.586Live birth39 (44.3%)52 (68.4%)0.002Multiple birth1 (2.6%)19 (35.8%)<0.001Clinical pregnancy53 (60.2%)57 (75.0%)0.045Preterm delivery5 (12.8%)13 (25.0%)0.149C-section13 (33.3%)29 (55.8%)0.034Birth weight (grams)3540 (3090-3720)3090 (2584-3443)0.003 Open table in a new tab

Sperm quality can affect the embryo kinetic and the embryo development

Time lapse technology is offering a multitude data about kinetics of embryonic development, but few have studied influence of the male gamete in embryonic kinetics. Our main objective is to determine if the seminal quality can affect the morphokinetic variables of human embryos. Retrospective study in which were included 118 oocyte donation cycles. Two groups of patients were compared. 80 of them (863 oocytes and 719 embryos) were good prognosis patients sperm samples (more than 15 million/ml, more than 30% of motility and more than 4% of normal forms) (group A) and 38 cycles (427 oocytes and 303 embryos) coming from sperm samples from poor prognosis patients (less than 5 million/ml, less than 5% of motility and less than 1% of normal forms) (group B). This oocyte donation cycles were incubated in embryoscope. Cellular events studied in this work were described by Meseguer, M. et al 2011, including all cellular divisions until blastocyst stage, appearance and fading of some cellular structures and two cellular events described as cc2 (difference in hours between first and second cellular cleavage) and S2 (difference in hours between second and third cellular cleavage). Data were exported from the embryo viewer data base. SPSS statistical software was used on data analysis. We found significant differences respecting the time of cell division between our two groups under study (A and B) only in the time of PN appearance, shorter in A group, and longer T9 and TM (morula formation) in A group. Besides, the duration of the third and fourth cell cycles (CC3 and CC4) are shorter in the B group, then, in the B group, the embryos have less time to complete a right interphase and mitosis. We didn’t find significant differences when we compared the classical embryo morphology in D2 and D3 of development in both groups, but we found significant differences in the blastocyst expansion in D5 and D6, being higher in the A group. We also found significant differences when we apply the time lapse algorithms that we used in our lab for implantation forecast in D3 and D5 of development, being in a greater degree the A group embryos. Moreover, we subdivided groups A and B into two subgroups respectively. The first subgroup consists of transferred and frozen embryos, and the second consists of discarded embryos. We found statistically significant association in most of the times of cell division, when we compared the two subgroups of the A group, and the two subgroups of the B group, observing a development delay in discarded embryos. Finally when we compared the viable embryos between A and B group, we found significant differences in the T9 (shorter in A group), and in the duration of CC3 and especially CC4, taking more time to complete it in the viable embryos of A group. The bad sperm sample quality may induce a lower T9, that point out the beginning of the fourth cell cycle, lower TM that point out, in this study, the beginning of cell compaction, and shorter third and fourth cell cycles, if we compare to embryos coming from good sperm samples quality.

PO-516 Genes of infiltrated immune cells are prognosis biomarkers in specific subtypes of colorectal cancer

IntroductionColorectal tumours are composed of mixed tissues, including tumoral and stromal cell types. The functional communication between these cell entities defines the biology of the tumours and eventually influences disease progression and patients’ prognosis. Recently, the first bona fide consensus molecular subtypes of colorectal cancer have been defined, each of them showing a specific immune-cell composition. CMS1 comprises hypermutant tumours with better prognosis associated to a higher immune infiltration. CMS2 tumours are characterised by a high CIN and strong WNT/MYC pathways activation. CMS3 have activated pathways related to metabolism. CMS4 tumours are more stromatic and showed the worst survival. In this work, we aim to assess the immune cell infiltration in the tumour as a prognosis indicator for colorectal cancer as well as to understand the molecular biology behind this crosstalk, while stratifying tumours by molecular subtype.Material and methodsOur discovery series includes 100 paired normal and stage II MSS tumour samples. For validation purposes, public GSE39582 and TCGA series have been used. Using gene expression data, tumours have been classified into CMS subtypes using CMSclassifier R package. We were estimating tumour immune cell infiltration (R library MCPcounter) and calculating the immunephenoscores. GSEA has been performed to make a functional enrichment analysis. To assess the utility as prognosis biomarkers of genes expressed in the immune compartment, a cox model were fitted.Results and discussionsWe corroborate that CMS1 and CMS4 subtypes showed higher levels of immune and stromal infiltration than CMS2-3 subtypes. Several CD molecules have been found to be under-expressed in tumour vs. normal tissues that have a protective effect. Interestingly, when stratifying by subtypes, they showed the better accuracy discriminating between good and poor prognosis patients in the CMS4 subtype. Significant functions associated with higher expression of those molecules are IGA production, IL12 pathway, TCR pathway and PD1 signalling among others; thus suggesting an immune modulation of the microenvironment that leads to a better prognosis.ConclusionThe CMS4 subtype has usually higher risk of relapse comparing to other subtypes. However, segregating the group using specific immune biomarkers is able to identify patients with the significantly better survival.

Chromosomal mosaicism in human blastocysts: the ultimate challenge of preimplantation genetic testing?

To what extent does a trophectoderm (TE) biopsy reliably reflect the chromosomal constitution of the inner cell mass (ICM) in human blastocysts? Concordance between TE and ICM was established in 62.1% of the embryos analysed. Next generation sequencing (NGS) platforms have recently been optimised for preimplantation genetic testing for aneuploidies (PGT-A). However, higher sensitivity has led to an increase in reports of chromosomal mosaicism within a single TE biopsy. This has raised substantial controversy surrounding the prevalence of mosaicism in human blastocysts and the clinical implications of heterogeneity between the TE and ICM. To define the distribution and rate of mosaicism in human blastocysts, we assessed chromosomal profiles of the ICM and multiple TE portions obtained from the same embryo. We evaluated donated embryos with an unknown chromosomal profile (n = 34), as well as PGT-A blastocysts, previously diagnosed as abnormal or mosaic (n = 24). Our intra-embryo comparison included a total of 232 samples, obtained from 58 embryos. Four embryo samples, including the ICM and three distinct TE portions, were acquired from good quality blastocysts by micromanipulation. Whole genome amplification (WGA), followed by NGS was performed on all embryo segments. Profiles were compared between samples from the same embryo, while the results from pretested blastocysts were further correlated to the original report. The embryos investigated in our untested group were obtained from good prognosis patients (n = 25), with maternal age ranging from 23 to 39 years. For the pretested embryo group, maternal age ranged from 23 to 40 years (n = 18). We uncover chromosomal mosaicism, involving both numerical and structural aberrations, in up to 37.9% of the blastocysts analysed. Within the untested group, the overall concordance between the ICM and all TE portions was 55.9%. A normal ICM was detected in 20.6% of blastocysts for which at least one TE portion showed a chromosomal aberration. Conversely, 17.6% of embryos presented with mosaic or uniform abnormalities within the ICM, while showing normal or mosaic TE profiles. For the pretested blastocysts, the overall concordance between the ICM and all TE samples was 70.8%. However, 50% of embryos previously diagnosed with mosaicism did not confirm the original diagnosis. Notably, 31.3% of embryos with a mosaic aberration reported in the original TE biopsy, revealed a euploid profile in the ICM and all three TE samples. Taken together, concordance between the ICM and all TE portions was established in 62.1% of blastocysts, across both embryo groups. Finally, we could not observe a significant effect of age on embryo mosaicism (P = 0.101 untested group; P = 0.7309 pretested group). Similarly, ICM and TE quality were not found to affect the occurrence of chromosomal mosaicism (P = 0.718 and P = 0.462 untested group; P = 1.000 and P = 0.2885 pretested group). All data that support the findings of this study are available online in Vivar (http://cmgg.be/vivar) upon request. Evaluating biological variation in some instances remains challenging. The technological limitations of sampling mitotic errors that lead to mosaicism, as well as WGA artefacts, warrant careful interpretation. Our results highlight the complex nature of genetic (in)stability during early ontogenesis and indicate that blastocysts harbour a higher rate of chromosomal mosaicism than may have been anticipated. Moreover, our findings reveal an overall high diagnostic sensitivity and relatively low specificity in the context of PGT-A. This suggests that a considerable proportion of embryos are potentially being classified as clinically unsuitable. Ultimately, more precise quantification will benefit the clinical management of embryo mosaicism. M.P. is supported by the Special Research Fund, Bijzonder Onderzoeksfonds (BOF01D08114). J.T. and L.D. are supported by the agency for innovation through science (131673, 141441). B.H. and this research are supported by the Special Research Fund, Bijzonder Onderzoeksfonds (BOF15/GOA/011). The authors declare no competing interests. Not applicable.

Does the endometrial receptivity array really provide personalized embryo transfer?

The aim of the present study was to determine the percentage of infertility patients who are diagnosed with a non-receptive endometrium according to the endometrial receptivity array (ERA) test and to examine whether adjusting the embryo transfer day according to the proposed shift in the window of implantation improves the pregnancy rate compared to non-ERA-tested patients. A single-center retrospective cohort study, including 53 consecutive good prognosis patients (0-2 previous frozen embryo transfers) admitted to our IVF unit for a mock cycle prior to their frozen day-5 embryo (blastocyst) transfer cycle. The mock cycle included an endometrial biopsy for both the ERA test and histological assessment by the Noyes criteria (study group). The next cycle frozen embryo transfer (FET) in the study group was adjusted according to the ERA results. The control group consisted of patients who underwent FET cycles at our clinic during the same period, without performing the endometrial biopsy and ERA testing. During the study period, 503 patients (control group) underwent FET cycles without performing the ERA testing and 41 patients had FET following an ERA test. There were no between-group differences in patients' age, number of previous transfers, endometrial thickness, number of transferred embryos, and ongoing pregnancy rates (35.2 vs. 39%, respectively, p= NS). Out of the 53 patients who performed the ERA test before their first or second FET, five endometrial samples (9.4%) were found to be post-receptive, 29 (54.7%) pre-receptive, and only 19 samples (35.8%) were receptive. Women in the study group with pre- or post-receptive endometrium on ERA testing, the appropriate adjustment in timing of FET according to the ERA test resulted in a 33.3% pregnancy rate, which is comparable to the 35.2% background ongoing pregnancy rate of the control group. Performing the ERA test in a mock cycle prior to a FET does not seem to improve the ongoing pregnancy rate in good prognosis patients. Further large prospective studies are needed to elucidate the role of ERA testing in both good prognosis patients and in patients with recurrent implantation failure.

The likelihood of transferring a euploid embryo after PGD-aneuploidy cycles depends not only on female age but also on the number of oocytes collected

Introduction: Aneuploidy is the most common type of chromosome abnormality and the leading cause of implantation failure, miscarriage and congenital abnormalities. Three RCTs have already demonstrated higher clinical pregnancy rates in young good prognosis patients with single embryo transfer, but investigations in other groups are limited to observational studies. Although scientific principles of comprehensive aneuploidy screening are widely accepted, controversy remains about the clinical and, particularly, economic effectiveness of this approach (Lee et al., 2014). Thus, patients and especially advanced maternal age cases need to be informed properly regarding their realistic chances of producing euploid embryos in different clinical scenarios.

IGG practice guidelines on germ cell tumor in adult male patients.

Germ cell tumors are rare neoplasms that affect young males. Nearly 99% of patients with localized stage I disease and nearly 80% of patients with metastatic disease can be cured. Even patients who relapse following chemotherapy can achieve a long-term survival in approximately 30-40% of cases. The main objective in early stages and in good prognosis patients has changed in recent years, and it has become of major importance to reduce treatment-related morbidity without compromising the excellent long-term survival rate. In poor prognosis patients, there is a correlation between the experience of the treating institution and the long-term clinical outcome of the patients, particularly when the most sophisticated therapies are needed. So far, of utmost importance is the information from updated practice guidelines for the diagnosis and treatment of germ cell tumors. The Italian Germ cell cancer Group (IGG) has developed the following clinical recommendations, which identify the current standards in diagnosis and treatment of germ cell tumors in adult males.

Equivalency of In vitro fertilization Success Rates in Elective Single Blastocyst Transfer and Elective Double Blastocyst Transfer: An Example of Equivalence Methodology in Clinical Reproductive Health.

Context:When comparing success rates between treatments, it is more appropriate to structure analyses in terms of equivalence rather than traditional analyses that assess differences. Unfortunately, no studies of elective single blastocyst transfer (eSBT) have been conducted in this manner.Aims:The objective of this study was to assess clinical equivalence of in vitro fertilization success rates among patients undergoing eSBT.Settings and Design:A historical prospective study was conducted at a private fertility center.Methods:Medical records were reviewed to identify patients eligible for eSBT. Equivalency of success rates, defined as no more than a 10% difference based on 95% confidence intervals (CIs), was compared between eSBT (n = 125) and eDBT (n = 213) groups.Results:Using traditional analysis techniques, no differences in pregnancy or live-birth rates were seen (eSBT: 84.6% vs. eDBT: 84.5%, P = 0.99; eSBT: 65.3% vs. eDBT: 72.3%, P = 0.23). The 95% CI around the difference in pregnancy rates ranged from –7.9 to 8.1, suggesting clinically equivalent pregnancy rates. Clinical equivalence was not established for live-births (95% CI = −18.5–4.5).Conclusions:Findings suggest comparable pregnancy rates can be achieved in a clinical setting when utilizing eSBT in good-prognosis patients. Although live-birth rate equivalence was not demonstrated, it is thought the additional complications associated with multiple gestations outweigh the potentially higher live-birth rate. The present study highlights the importance of utilizing equivalence analyses when making statements regarding the similarity of two treatments in reproductive health, rather than relying on superiority analyses alone.

Systematic review and survival meta-analysis of real world evidence on first-line pazopanib for metastatic renal cell carcinoma.

A systematic review was conducted to identify real world studies reporting outcomes after first-line pazopanib in patients with metastatic renal cell carcinoma. Studies had to be observational and report survival data in terms of progression-free survival and overall survival in order to conduct meta-analysis techniques. These real-world data were compared to those obtained in the phase II and III randomized controlled trials of pazopanib. Real world evidence showed that the clinical and safety outcomes were consistent with those observed in the clinical trials despite the inclusion of unselected patients with a wide spectrum of prognostic features and comorbidities. Similarly to the results of the pivotal studies, good prognosis patients had the most benefit from pazopanib. Further investigation is needed to complement evidence from clinical trials, in particular focused on patient-centered outcomes.

Dynamic visualization of multi-level molecular data: The Director package in R

Background and objective: High-throughput measurement technologies have triggered a rise in large-scale cancer studies containing multiple levels of molecular data. While there are a number of efficient methods to analyze individual data types, there are far less that enhance data interpretation after analysis. We present the R package Director, a dynamic visualization approach to linking and interrogating multiple levels of molecular data after analysis for clinically meaningful, actionable insights.Methods: Sankey diagrams are traditionally used to represent quantitative flows through multiple, distinct events. Regulation can be interpreted as a flow of biological information through a series of molecular interactions. Functions in Director introduce novel drawing capabilities to make Sankey diagrams robust to a wide range of quantitative measures and to depict molecular interactions as regulatory cascades. The package streamlines creation of diagrams using as input quantitative measurements identifying nodes as molecules of interest and paths as the interaction strength between two molecules.Results: Director’s utility is demonstrated with quantitative measurements of candidate microRNA-gene networks identified in an ovarian cancer dataset. A recent study reported eight miRNAs as master regulators of signature genes in epithelial-mesenchymal transition (EMT). The Sankey diagrams generated with data from this study furthers interpretation of the miRNAs’ roles by revealing potential co-regulatory behavior in the extracellular matrix (ECM). An additional analysis identified 32 genes differentially expressed between good and poor prognosis patients in four significant pathways (FDR ≤ 0.1), three of which support a complementary role of the ECM in ovarian cancer. The resulting diagram created with Director suggest elevated levels of COL11A1, INHBA, and THBS2 — a signature feature of metastasis [1] — and decreased levels of their targeting miRNAs define poor prognosis.Conclusion: We have demonstrated a visualization approach suitable for implementation in an analysis workflow, linking multiple levels of molecular data to gain novel perspective on candidate biomarkers in a complex disease. The diagrams are dynamic, easily replicable, and rendered locally as HTML files to facilitate sharing. The R package Director is simple to use and widely available on all operating systems through Bioconductor (http://bioconductor.org/packages/Director) and GitHub (http://kzouchka.github.io/Director).

Impact of patient preference on rate of double embryo transfer and resultant twin gestation

Significant strides have been made in the United States to encourage single embryo transfer and minimize the occurrence and resultant risks associated with twin gestations. While the medical community has recognized the need for refinement and demonstrated the success of single embryo transfer, patient choice and education remains a significant factor in reproductive medicine and resultant obstetrical outcomes. This study aims to assess the impact of patient choice on number of embryo transfer and resultant twin gestation. Patients undergoing in vitro fertilization (IVF) between 2013 and 2016 at Mayo Clinic, Rochester were reviewed. Patients under 35 who received a double embryo transfer, which resulted in a twin pregnancy, were included in this review. The embryo transfer consent forms and transfer reports were reviewed. The planned number of embryos transferred, actual number of embryos transferred and embryo grade were assessed. Consent forms for number of embryos to transfer are signed prior to starting an IVF cycle. Our practice is to encourage good prognosis patients to consent to transfer 1-2 embryos, allowing the final decision on whether to transfer one or two embryos to be made by the embryology and physician team after assessment of embryo quality on day of transfer. If grade A blastocysts are in culture, a single embryo is transferred. Subsequent clinical pregnancy rate, including number of fetal heart beats, was calculated. 129 fresh and 75 frozen cycles were analyzed. In patients undergoing fresh double embryo transfers who were less than 30, there was a 55% clinical pregnancy rate and a 42% twin rate. In patients between age 30 and 35, there was a 50% clinical pregnancy rate with a 40% twin rate. 28 fresh double embryo transfers resulted in twin pregnancies. Among these, 21 (75%) had requested the transfer of 2 day 5 embryos despite our recommendations. Seven patients (25%) had requested the transfer of 1-2 day 5 embryos. In patients undergoing frozen double embryo transfers who were less than 30, there was a 67% clinical pregnancy rate and 0% twin rate. Patients aged 30-35 who underwent frozen double embryo transfer had a 44% clinical pregnancy rate and 46% twin rate. 13 frozen double embryo transfers resulted in twin pregnancies. Among these, 11 (85%) had requested the transfer of 2 day 5 embryos despite our recommendations and 2 (15%) patients had requested the transfer of 1-2 embryos. The majority of twin pregnancies that occur after IVF from good prognosis patients are from patients who request that two embryos are transferred despite our recommendations to consider single embryo transfer. This observational study identifies the significant impact of patient choice on number of embryos transferred and resultant rates of multiple gestations.

Prognostic roles of tetrahydroxy bile acids in infantile intrahepatic cholestasis

Tetrahydroxy bile acids (THBAs) are hydrophilic and are present at minimal or undetectable levels in healthy human adults, but are present at high levels in bile salt export pump (abcb11)-knockout mice. The roles of THBAs in human cholestatic diseases are unclear. We aimed to investigate the presence of THBAs in patients with infantile intrahepatic cholestasis and its correlation with outcome. Urinary bile acids (BAs) were analyzed by GC-MS. Data were compared between good (n = 21) (disease-free before 1 year old) and poor prognosis groups (n = 19). Good prognosis patients had a higher urinary THBA proportion than poor prognosis patients [25.89% (3.45-76.73%) vs. 1.93% (0.05-48.90%)]. A urinary THBA proportion >7.23% predicted good prognosis with high sensitivity (95.24%), specificity (84.21%), and area under the curve (0.91) (P < 0.0001). A THBA proportion 7.23% was an independent factor for decreased transplant-free survival (hazard ratio = 7.16, confidence interval: 1.24-41.31, P = 0.028). Patients with a confirmed ABCB11 or tight junction protein 2 gene mutation (n = 7) had a minimally detectable THBA proportion (0.23-2.99% of total BAs). Three patients with an ATP8B1 mutation had an elevated THBA proportion (7.51-37.26%). In conclusion, in addition to disease entity as a major determinant of outcome, a high THBA level was associated with good outcome in the infantile intrahepatic cholestasis patients.

Metastatic surgery in testis cancer.

In testis cancer, prognosis is excellent even in metastatic disease. Treatment and timing of patients with multiple metastatic deposits can be challenging. This review was performed to underline the current guideline recommendations. Depending on the primary histology, the indication of further surgical resections differ. In seminoma, resídual tumor resections are performed according to the results of a flouoro-deoxy-D-glucose-PET. Positive results must be considered critically, and to recent results it is advisable to first repeat flouoro-deoxy-D-glucose-PET to avoid overtreatment. In nonseminomatous germ cell cancer, complete remissions in good prognosis patients are followed and can be spared from surgery. All other patients still need to undergo postchemotherapy retroperitoneal lymph node dissection. In bone metastases, significant histology is found in 80% so that one should go for complete resection. In liver metastases, resections can be performed according to the histology in the retroperitoneum. Both resections, including vessel replacement, are usually performed in one session underlining the complex multidisciplinary approach. Pulmonal metastases, at least in one lobe, need to be resected. Brain metastases are rare with no standard treatment recommendation. Every patient should be presented in a multidisciplinary tumor board. Surgical interventions should be done in tertiary referral centers to achieve the best oncologic outcome and reduced morbidity.

Can affordability and access to care be enhanced by minimal stimulation IVF (MS-IVF) and single embryo transfer (SET)?

To analyze cumulative live birth/ongoing pregnancy rates and potential cost savings associated with MS-IVF and single embryo transfer (SET) in good prognosis patients. A retrospective analysis comparing outcomes and costs of MS-IVF and traditional IVF in good prognosis patients. 137 good prognosis patients (defined as age <35, AMH>2.4, AFC>10, BMI <35, with diagnoses of PCOS, stage I-II endometriosis, tubal factor, and/or mild to moderate male factor) underwent MS-IVF or traditional IVF based on patient/physician preferences. FSH/low dose hcg/antagonist protocols were utilized. MS-IVF included 5 days of clomiphene 100mg prior to initiation of 150u FSH. Traditional IVF cycles had a mean starting FSH of 244u FSH. Cycle outcomes and cost analyses of the two groups included all fresh and frozen transfers. The two groups were comparable in age, basal FSH, BMI, and mean embryos transferred, with SET in all but one fresh transfer and all but one frozen transfer. The MS-IVF group was more likely to have a fresh transfer, contributing to cost reduction. 5 MS-IVF cycles were canceled due to low response; this was not statistically significant. There were significant differences in mean total gonadotropins, oocytes retrieved, blastocysts formed, and fresh transfers. SET was utilized to decrease multiple pregnancies while resulting in delivered, ongoing, and cumulative pregnancies higher than U.S. averages (SART 2014). Ongoing fresh, FET, and cumulative pregnancy rates achieved from one stimulation cycle were not statistically different between the two groups. Overall costs were 27% less in the MS-IVF group, while a 24% cost reduction was found on a per live birth/ongoing pregnancy basis. Greater affordability should result in enhanced access to IVF care by offering lower cost MS-IVF to good prognosis patients without sacrificing success. SET can dramatically reduce downstream costs associated with multiple gestation. We propose that MS-IVF combined with SET could be an appealing aspect of fertility benefits for employers and insurers who desire greater subscriber access to affordable IVF care.Tabled 1MS-IVF and Traditional IVF Outcome and Cost ComparisonMS-IVFTraditional IVFp ValueNumber of Stimulation Cycles8354Mean Total FSH Dose (IU's)12092168p<0.01Mean Total Oocytes15.724.1p<0.01Mean Blastocysts7.511.7p<0.01Fresh Transfers/Retrieval53/78 (68%)25/54 (45%)p<0.04Ongoing Pregnancies/Fresh transfer - N (%)33/53 (62%)17/25 (68%)NSOngoing Pregnancies/Frozen Transfer - N (%)28/45 (62%)29/44 (66%)NSOngoing Cumulative Pregnancies/Stimulation Cycle - N (%)61/83 (73%)46/54 (85%)NSMean Number of Transfers to Ongoing Pregnancy1.21.3NSMean Cycle Cost/Stimulation Cycle$14,088.80$19,345.54p<0.01Mean Cost/Live Birth or Ongoing Pregnancy$15,265.91$20,131.72p<0.01 Open table in a new tab

The disruption of genes involved in oogenesis is significantly associated with longer time or failure to achieve live birth in patients undergoing IVF

It can be a challenge for fertility specialists when good prognosis patients fail treatment for unexplained reasons. Conversely, poor prognosis patients often beat the odds and achieve live birth (LB). The aim of our study was to uncover subclinical, genetic factors that may help better stratify patients ahead of treatment decisions.

Modified natural cycle IVF increases value and access to care over traditional IVF for good prognosis patients: a decision analytic model and cost effectiveness analysis

Modified natural cycle IVF increases value and access to care over traditional IVF for good prognosis patients: a decision analytic model and cost effectiveness analysis

Single blastocyst transfer: does PGS improve outcome? comparison of single thawed euploid embryo transfers (STEET) with fresh (FSET) and frozen (ZSET) morphology-based single embryo transfers in good prognosis patients (GPP)

One ASRM 2015 prize abstract [1] suggested that STEET in young GPP was equivalent to FSET. We extended this analysis to assess if embryo selection using chromosome screening was superior, inferior, or equivalent to FSET and/or ZSET. Retrospective cohort study of STEET, FSET and ZSET procedures performed in women age < 41y who had at least 3 Gardner’s Stage 2BC or 2CB blastocysts or better at a single, large university-based center from 2008 to 2015. We compared 131 STEET (median age: 35 y, IQR: 32-37 y) vs. 207 FSET (median age: 33, IQR: 31-36 y) vs. 95 ZSET (median age 33 y, IQR: 30-35 y) in GPP. Data was mined for: implantation rate (IR), live birth / ongoing pregnancy rate (LBR), and spontaneous abortion rate (SABR). Exclusion criteria included: age > 40 y; > 2 prior ART procedures; > 2 prior spontaneous abortions; endometrial thickness < 6 mm at progesterone start, or uterine pathology (fibroids or synechiae). Fisher’s exact test (two-tailed) was used for statistical analysis. When grouping all cycles of women age < 41y, IRs for STEET, FSET, and ZSET were 82/131 (63%), 126/207 (61%), and 50/95 (53%) respectively; p=NS. LBRs were 73/131 (56%), 99/207 (48%), and 39/95 (41%), respectively (LBR was significantly higher with STEET vs. ZSET; p=0.03 but vs. not FSET). SABRs were 8/82 (10%), 24/126 (19%), and 11/50 (22%), respectively; p=NS. The Table divides the data by age. For women age < 35 y, no differences in IR or LBR were noted. In women age 35-37 y, IR and LBR were significantly higher with STEET and FSET vs. ZSET. For women age 38-40 y, IR was not different, but LBR was significantly higher with STEET vs. FSET. SABRs were not statistically different within any of the age groups. In younger (age < 35 y) GPP, FSET and ZSET appear equally beneficial to STEET, but as female age advances (38-40 y), STEET may have the advantage of producing a higher chance for live birth. While the SABR is not statistically lower with STEET in this data set, it is in others [2], and the lack of statistical significance here may be due to small sample size, especially in the older age groups. The financial costs, emotional burden, and time of storage and transfer of abnormal embryos, miscarriage, and pregnancy termination of chromosomally abnormal fetuses need to be considered when choosing not to perform STEET, especially in older patients, and GPP should be counseled accordingly. We will continue to collect data.Tabled 1STEET vs. FSET vs. ZSET by age. n = number of patients (pt), embryo transfers (ET).IRLBRSABR< 35 y: STEET (n=43 pt, 57 ET)34/57 (60%)28/57 (49%)5/34 (15%)< 35 y: FSET (n=131 pt, 133 ET)79/133 (59%)63/133 (47%)14/79 (18%)< 35 y: ZSET (n=60 pt, 70 ET)40/70 (57%)32/70 (46%)8/40 (20%)35-37 y: STEET (n=36 pt, 43 ET)28/36 (78%)a27/36 (75%)d1/28 (4%)35-37 y: FSET (n=49 pt, 49 ET)36/49 (73%)b29/49 (59%)e6/36 (17%)35-37 y: ZSET (n=16 pt, 18 ET)7/18 (39%)c5/18 (28%)f2/7 (29%)38-40 y: STEET (n=25 pt, 31 ET)20/31 (65%)18/31 (58%)g2/20 (10%)38-40 y: FSET (n=24 pt, 25 ET)11/25 (44%)7/25 (28%)h4/11 (36%)38-40 y: ZSET (n=7 pt, 7 ET)3/7 (43%)2/7 (29%)1/3 (33%)P values: a-c <0.01, b-c 0.02, d-f <0.01, e-f 0.03, g-h 0.03, other comparisons: NS Open table in a new tab

Selection of single blastocysts for transfer via time-lapse monitoring alone and with next-generation sequencing to reduce multiple pregnancies: a randomized pilot study

Recent advances in time-lapse monitoring and next-generation sequencing (NGS) have provided new methods for selecting competent embryos for transfer in IVF treatments. The present study aimed to investigate the effects of time-lapse monitoring and NGS testing on clinical and ongoing pregnancy outcomes of single embryo transfer for good prognosis patients to reduce multiple pregnancies.

Different effectiveness of closed embryo culture system with time-lapse imaging (EmbryoScopeTM) in comparison to standard manual embryology in good and poor prognosis patients: a prospectively randomized pilot study

BackgroundPreviously manual human embryology in many in vitro fertilization (IVF) centers is rapidly being replaced by closed embryo incubation systems with time-lapse imaging. Whether such systems perform comparably to manual embryology in different IVF patient populations has, however, never before been investigated.We, therefore, prospectively compared embryo quality following closed system culture with time-lapse photography (EmbryoScope™) and standard embryology.We performed a two-part prospectively randomized study in IVF (clinical trial # NCT92256309). Part A involved 31 infertile poor prognosis patients prospectively randomized to EmbryoScope™ and standard embryology. Part B involved embryos from 17 egg donor-recipient cycles resulting in large egg/embryo numbers, thus permitting prospectively alternative embryo assignments to EmbryoScope™ and standard embryology.We then compared pregnancy rates and embryo quality on day-3 after fertilization and embryologist time utilized per processed embryo.ResultsPart A revealed in poor prognosis patients no differences in day-3 embryo scores, implantation and clinical pregnancy rates between EmbryoScope™ and standard embryology. The EmbryoScope™, however, more than doubled embryology staff time (P < 0.0001). In Part B, embryos grown in the EmbyoScope™ demonstrated significantly poorer day-3 quality (depending on embryo parameter between P = 0.005 and P = 0.01). Suspicion that conical culture dishes of the EmbryoScope™ (EmbryoSlide™) may be the cause was disproven when standard culture dishes demonstrated no outcome difference in standard incubation.ConclusionsThough due to small patient numbers preliminary, this study raises concerns about the mostly uncontrolled introduction of closed incubation systems with time lapse imaging into routine clinical embryology. Appropriately designed and powered prospectively randomized studies appear urgently needed in well-defined patient populations before the uncontrolled utilization of these instruments further expands.Trial registrationNCT02246309 Registered September 18, 2014.

In Estimated Good Prognosis Patients Could Unexpected "Hyporesponse" to Controlled Ovarian Stimulation be Related to Genetic Polymorphisms of FSH Receptor?

It has been reported that 10% to 15% of young normogonadotrophic women show suboptimal response to standard gonadotropin-releasing hormone-a long protocol. These patients require higher doses of exogenous follicle-stimulating hormone (FSH). This phenomenon could be associated with genetic characteristics. In this study, FSH receptor polymorphism was retrospectively evaluated in 42 normoresponder young women undergoing an in vitro fertilization/intracytoplasmic sperm injection cycle; patients were stratified according to recombinant human FSH (r-hFSH) consumption. We selected 17 normoresponder young patients who required a cumulative dose of recombinant FSH (rFSH) >2500 UI (group A). A control group was randomly selected among patients who required a cumulative dose of rFSH <2500 UI (group B). Follicle-stimulating hormone receptor (FSH-R) 307Ala and 680Ser variants were analyzed in all our patients. Our results show that the mean number of rFSH vials (36.3 ± 7.5 vs 28.6 ± 4.5, P = .0001) and days of stimulation (12.7 ± 2.4 vs 10.8 ± 2.8, P = .03) were significantly lower in group B, whereas the number of oocytes retrieved (7.1 ± 1.5 vs 9.6 ± 2.4; P = .0005) and the average number of embryos transferred (2.1 ± 0.7 vs 2.7 ± 0.4; P = .001) were significantly lower in group A. Estradiol serum levels on the human chorionic gonadotrophin day were significantly lower in group A (997.8 ± 384.9 pg/mL vs 1749.1 ± 644.4; P = .0001). The incidence of the Ser/Ser genotype was higher in patients with higher r-hFSH consumption (group A; P = .02). Based on our results, we hypothesize an association between the FSH-R polymorphisms and a "hyporesponse" to exogenous FSH.