Denny Sakkas

Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

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Publications (195)703.25 Total impact

  • Human Reproduction Update 09/2015; DOI:10.1093/humupd/dmv043 · 10.17 Impact Factor
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    ABSTRACT: Purpose: The aim of this study is to evaluate the outcomes of in vitro fertilization (IVF), including cumulative live birth rate, among women <25 years, 25 to <30 years, and 30 to <35 years. Methods: A retrospective cohort study of all women 18 to <35 years of age at their first fresh-embryo, non-donor IVF cycle from January 1995 through December 2012 at a single center was conducted. A competing-risk regression model was used to estimate the cumulative probability and 95 % confidence interval (CI) of the first live birth in up to 6 cycles during the study period with IVF cycle number as the time metric. Results: Among 7243 women who underwent 16,792 cycles, there were 163 (2.3 %) women <25 years, 1691 (23.3 %) women 25 to <30 years, and 5389 (74.4 %) women 30 to <35 years. Women <25 years had the lowest cumulative live birth rate after each cycle, followed by women 30 to <35 years. In both groups, the cumulative live birth rate after 6 cycles was significantly lower than that of women 25 to <30 years; these rates were 58 % (95 % CI 0.51-0.66) among women <25 years, 69 % (95 % CI 0.67-0.71) among women 25 to <30 years, and 64 % (95 % CI 0.63-0.65) among women 30 to <35 years. Conclusions: Our findings are consistent with other reports of less favorable IVF treatment outcomes in women <25 years of age following their first IVF cycle. This indicates that there are underlying factors in couples with a female <25 years of age that should lead to different treatment counseling when they attempt IVF.
    Journal of Assisted Reproduction and Genetics 09/2015; DOI:10.1007/s10815-015-0570-7 · 1.72 Impact Factor
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    ABSTRACT: Objective: We conducted a systematic review to evaluate the influence of race and ethnicity on clinical pregnancy and live birth outcomes after in vitro fertilization. Data sources: We searched PubMed, EMBASE, Web of Science, CINAHL, POPLINE, and Cochrane Central, and hand-searched relevant articles published through July 22, 2015. Study appraisal and synthesis methods: Two reviewers independently evaluated abstracts to identify studies that compared clinical pregnancy rates and live birth rates for two or more racial and/or ethnic groups after non-donor IVF cycles. Results: Twenty-four studies were included. All five U.S. registry-based studies showed that black, Hispanic, and Asian women had lower clinical pregnancy rates and/or live birth rates after IVF, compared with white women. Similarly, most clinic-specific studies reported significant disparities in these primary outcomes, potentially attributable to differences in infertility diagnosis, spontaneous abortion, and obesity. Studies varied with respect to definitions of race/ethnicity, inclusion of first cycles vs. multiple cycles for individual women, and collected covariates. Most studies were limited by sample size, inadequate adjustment for confounding, selection bias, and extensive missing data. Conclusions: Although current evidence points to race and ethnicity, especially black race, as strong predictors of poorer outcomes after in vitro fertilization, the utility of results is constrained by the limitations described.
    American journal of obstetrics and gynecology 09/2015; DOI:10.1016/j.ajog.2015.09.002 · 4.70 Impact Factor
  • Fertility and Sterility 02/2015; 103(2):e38-e39. DOI:10.1016/j.fertnstert.2014.12.074 · 4.59 Impact Factor
  • P. Jarmuz · C.B. Barrett · D. Sakkas
    Fertility and Sterility 09/2014; 102(3):e133-e134. DOI:10.1016/j.fertnstert.2014.07.457 · 4.59 Impact Factor
  • Basak Balaban · Denny Sakkas · David K Gardner
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    ABSTRACT: Successful and consistent outcomes in human in vitro fertilization (IVF) can be readily achieved by all IVF clinics through consideration and optimization of each procedure associated with the collection and processing of gametes, culminating in the resultant culture and transfer of healthy embryos. Furthermore, understanding the interactions between the individual components of the IVF cycle will assist when trouble-shooting possible problems in a laboratory which could have an adverse effect on cycle outcome. This article will review handling of oocytes and embryo culture, preparation of gametes for insemination and microinjection, selection of the most viable gametes and embryos, cryopreservation, and successful embryo transfer from the laboratory perspective.
    Seminars in Reproductive Medicine 07/2014; 32(4):272-282. DOI:10.1055/s-0034-1375179 · 2.35 Impact Factor
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    ABSTRACT: During spermatogenesis, gene expression is regulated post-transcriptionally by modification of the poly-adenylation tail length of repressed mRNAs. In a previous study, we demonstrated that the expression of two mRNA binding proteins, embryonic poly(A)-binding protein (EPAB) and somatic cytoplasmic poly(A)-binding protein (PABPC1), is spatially and temporally controlled during male germ-cell development, suggesting that they may modulate gene expression in different spermatogenic cell types (Ozturk et al. 2012).We therefore evaluated the fertility of homozygous Epab knockout male mice (Epab-/-) to further define the importance of EPAB during spermatogenesis. Mol. Reprod. Dev. © 2014 Wiley Periodicals, Inc.
    Molecular Reproduction and Development 05/2014; 81(5). DOI:10.1002/mrd.22319 · 2.53 Impact Factor
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    ABSTRACT: Genes critical for fertility are highly conserved in mammals. Interspecies DNA sequence variation, resulting in amino-acid substitutions and post-transcriptional modifications, including alternative splicing, are a result of evolution and speciation. The mammalian Follicle Stimulating Hormone Receptor (FSHR) gene encodes distinct species-specific forms by alternative splicing. Skipping of exon 2 of the human FSHR was reported in women of North American origin and correlated with low response to ovarian stimulation with exogenous FSH. To determine whether this variant correlated with low response in women of different genetic backgrounds, we performed a blinded retrospective observational study in a Turkish cohort. Ovarian response was determined as low, intermediate or high according to retrieved oocyte numbers after classifying patients in 4 age groups (<35, 35-37, 38-40, >40). Cumulus cells collected from 96 women undergoing IVF/ICSI following controlled ovarian hyperstimulation revealed four alternatively spliced FSHR products in seven patients (8%): exon 2 deletion in four patients; exon 3 and exons 2+3 deletion in one patient each, and a retention of an intron 1 fragment in one patient. In all others (92%) splicing was intact. Alternative skipping of exons 2, 3 or 2+3 were exclusive to low responders and was independent of the use of agonist or antagonist. Interestingly, skipping of exon 3 occurs naturally in the ovaries of domestic cats - a good comparative model for human fertility. We tested the signaling potential of human and cat variants after transfection in HEK293 cells and FSH stimulation. None of the splicing variants initiated cAMP signaling despite high FSH doses, unlike full-length proteins. These data substantiate the occurrence of FSHR exon skipping in a subgroup of low responders and suggest that species-specific regulation of FSHR splicing plays diverse roles in mammalian ovarian function.
    Molecular Human Reproduction 03/2014; 20(7). DOI:10.1093/molehr/gau024 · 3.75 Impact Factor
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    ABSTRACT: What is the value of embryo selection by metabolomic profiling of culture medium with near-infrared (NIR) spectroscopy as an adjunct to morphology, compared with embryo selection by morphology alone, based on an individual patient data meta-analysis (IPD MA)? The IPD MA indicates that the live birth rate after embryo selection by NIR spectroscopy and morphology is not significantly different compared with the live birth rate after embryo selection by morphology alone. Retrospective proof of principle studies has consistently shown that high NIR viability scores are correlated with a high implantation potential of embryos. However, randomized controlled trials (RCTs) have generally shown no benefit of the NIR technology over embryo morphology, although there have been some conflicting results between pregnancy outcomes on different days of embryo transfer. This IPD MA included all existing RCTs (n = 4) in which embryo selection by morphology was compared with embryo selection by morphology and the use of NIR spectroscopy of spent embryo culture medium by the Viametrics-E(™). Searches of PubMed, the Cochrane Library and the WHO International Clinical Trials Registry were conducted and the sole manufacturer of the Viametrics-E(™) was consulted to identify clinics where an RCT comparing embryo selection by morphology to embryo selection by morphology and the use of the Viametrics-E(™) (NIR viability score) was performed. A total of 20 citations were potentially eligible for inclusion, two of which met the inclusion criteria. The manufacturer of the Viametrics-E(™) provided two additional clinical sites of use. In total, four RCTs were identified as eligible for inclusion. The IPD MA was based on a fixed effect model due to the lack of heterogeneity between included studies. Differences between study groups were tested and reported using logistic regression models adjusted for significant confounders. The pooled analysis of the primary outcome led to a total sample size of 924 patients: 484 patients in the control group (embryo selection by morphology alone) and 440 patients in the treatment group (embryo selection by morphology plus NIR spectroscopy). The live birth rates in the control group and the NIR group were 34.7% (168 of 484) and 33.2% (146 of 440), respectively. The pooled odds ratio (OR) was 0.98 [95% confidence interval (CI) 0.74-1.29], indicating no difference in live birth rates between the two study groups. The data of the four studies showed no significant heterogeneity (I(2) = 26.2% P = 0.26). The multivariate regression analysis including all confounders show that maternal age (OR 0.90, 95% CI 0.87-0.94) and the number of previous IVF cycles (OR 0.83, 95% CI 0.71-0.96) were significantly related to live birth. The study group (i.e. embryo selection by morphology or embryo selection by morphology plus NIR) was not related to live birth (OR 0.97, 95% CI 0.73-1.29). The availability of at least two similar best quality embryos as an inclusion criterion prior to transfer in the two largest RCTs might have caused a selection bias towards a better prognosis patient group. There is at present no evidence that NIR spectroscopy of spent embryo culture media in its current form can be used in daily practice to improve live birth rates.
    Human Reproduction 01/2014; 29(3). DOI:10.1093/humrep/det456 · 4.57 Impact Factor
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    ABSTRACT: To determine (a) the correlation between follicular sizes, oocyte maturity, normal fertilization rate, cleavage and embryo quality; and (b) to establish whether oocytes recovered with or without follicular flushing have different developmental competence. Prospective observational study. Academic medical center. Forty nine cycles (37 ICSI and 12 IVF). Measurement of 360 follicular diameters on the day of egg retrieval and classification into three groups Group A (mean diameter 12-14.5 mm.), group B (mean diameter 15-18 mm.) and group C (diameter >18.5 mm.). Correlation between follicular size at the time of retrieval and oocyte maturity, fertilization and cleavage rate in 226 oocytes (163 ICSI and 63 IVF). Developmental competence of oocytes retrieved with flushing versus non flushing. Almost all (99 %) of the oocytes recovered from follicles of group C were in metaphase II as opposed to 80 % in group A and 81 % in group B (p < 0.01). Overall there was a progressive and significant increase in fertilization rates from group A follicles to group C (47 % vs. 67 %, p 0.05). Overall 53 % of oocytes retrieved from group A follicles showed either no fertilization or abnormal fertilization versus 27 % in group C (p 0.05). The oocyte recovery rate with follicular flushing improved from group A to group B and to group C follicles (65 % vs. 49 % vs.37 % respectively p < 0.01). There were no differences in rates of immature oocyte, fertilization, abnormal or not fertilization and cleavage. The results of this study shows that: a) Follicles larger than 18 mm at retrieval have consistently mature oocytes with a higher rate of fertilization; b) Small size follicles are still capable of containing mature oocytes, but their rate of abnormal or no fertilization is high; c) Oocytes recovered with flushing are still able to produce embryos with full developmental competence.
    Journal of Assisted Reproduction and Genetics 11/2013; 31(1). DOI:10.1007/s10815-013-0124-9 · 1.72 Impact Factor
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    ABSTRACT: In mammalian species, acquisition of sperm fertilization competence is dependent on the phenomenon of sperm capacitation. One of the key elements of capacitation is protein tyrosine phosphorylation (TP) in various sperm membrane regions. In previous studies performed, the pattern of TP was examined in human sperm bound to zona pellucida of oocytes. In the present comparative study, TP patterns upon sperm binding to the zona pellucida or hyaluronic acid (HA) were investigated in spermatozoa arising from the same semen samples. Tyrosine phosphorylation, visualized by immunofluorescence, was localized within the acrosomal cap, equatorial head region, neck, and the principal piece. Tyrosine phosphorylation has increased in a time-related manner as capacitation progressed, and the phosphorylation pattern was identical within the principal piece and neck, regardless of the sperm bound to the zona pellucida or HA. Thus, the data demonstrated that the patterns of sperm activation-related TP were similar regardless of the spermatozoa bound to zona pellucida or HA. Further, sperm with incomplete development, as detected by excess cytoplasmic retention, failed to exhibit TP.
    Reproductive sciences (Thousand Oaks, Calif.) 09/2013; 21(5). DOI:10.1177/1933719113504467 · 2.23 Impact Factor
  • Fertility and Sterility 09/2013; 100(3):S486. DOI:10.1016/j.fertnstert.2013.07.326 · 4.59 Impact Factor
  • P. Jarmuz · B. Barrett · D. Sakkas
    Fertility and Sterility 09/2013; 100(3):S482. DOI:10.1016/j.fertnstert.2013.07.389 · 4.59 Impact Factor
  • A. Zimon · B. Lannon · S. Sheller · D. Sakkas · M. Ulrich · M. Alper
    Fertility and Sterility 09/2013; 100(3):S110. DOI:10.1016/j.fertnstert.2013.07.1677 · 4.59 Impact Factor
  • Fertility and Sterility 09/2013; 100(3):S224. DOI:10.1016/j.fertnstert.2013.07.1282 · 4.59 Impact Factor
  • Fertility and Sterility 09/2013; 100(3):S96. DOI:10.1016/j.fertnstert.2013.07.1724 · 4.59 Impact Factor
  • Fertility and Sterility 09/2013; 100(3):S274. DOI:10.1016/j.fertnstert.2013.07.1140 · 4.59 Impact Factor
  • Denny Sakkas · Emre Seli
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    ABSTRACT: Metabolomics is the systematic study of the dynamic inventory of metabolites, as small molecular biomarkers representing the functional phenotype in a biological system. Metabolomic analysis utilizes nonselective but specific spectroscopic analytical technologies to investigate complex metabolic profiles within a biological milieu. As such, metabolomic assessment has the potential to provide a fast, reliable, easy-to-use test for on-site embryo assessment in the IVF laboratory. Using NIR and Raman spectroscopic analysis, an association between embryo viability and the metabolomic profile of spent embryo culture medium has been determined. However, commercialization of this technology seems to have currently failed to develop a system to consistently predict viability when selecting a single embryo for transfer.
    Human Gametes and Preimplantation Embryos, 08/2013: pages 275-280; , ISBN: 978-1-4614-6650-5
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    ABSTRACT: Purpose: The aim of this study was to analyze the outcomes of IVF/ICSI cycles in women aged 43 and beyond. Methods: Retrospective analysis of clinical pregnancy and live birth rates in 168 fresh, non donor, ART cycles performed in two Connecticut university IVF programs. Results: In women of 43 and 44 years the overall clinical pregnancy and live birth rates were 8.3% and 5.3% per initiated cycle, respectively. There were no clinical pregnancies in women ≥45 years old. First cycle characteristics were not different from repeated cycles in terms of duration of ovulation induction, number of collected oocytes and transferred embryos (p > 0.05). Conclusions: Pregnancies can still be achieved with IVF/ICSI up to the age of 44. Since most pregnancies occurred within the first 3 cycles, another attempt may be a reasonable option before resorting to oocyte donation for patients who failed two previous cycles. Women 45 years and beyond do not benefit from ART procedures using their own oocytes.
    Journal of Assisted Reproduction and Genetics 03/2013; 30(5). DOI:10.1007/s10815-013-9981-5 · 1.72 Impact Factor
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    ABSTRACT: Metabolomics was introduced in human in vitro fertilization (IVF) for noninvasive identification of viable embryos with the highest developmental competence. To determine whether embryo selection using a commercial version of metabolomic analysis leads to increased implantation rates (IRs) with fetal cardiac activity (FCA) compared with morphology evaluation alone. Randomized controlled trial from April to December 2010 at a private IVF unit. The study was terminated prematurely due to the market withdrawal of the instrument. IVF patients ≥18 and ≤43 years with ≥4 × 2PN were randomly allocated to metabolomic analysis combined with embryo morphology (ViaMetrics-E; metabolomics + morphology group) or embryo morphology alone (morphology group). Cycles with frozen embryos, oocyte donations, or testicular biopsy were excluded. Categorical and continuous data were analyzed for statistical significance using 2-tailed Fisher's exact test and t-test, respectively. Statistical significance was accepted when P > 0.05. A total of 125 patients were included in the study; 39 patients were allocated to metabolomics + morphology group and 86 patients to morphology group. Patients were stratified according to the day of embryo transfer (Days 2, 3, or 5). IRs with FCA were similar for Days 2 and 3 transfers in both groups. For Day 5 transfers, IRs with FCA were significantly higher in the metabolomics + morphology group (46.8% vs. 28.9%; P = 0.041; 95% confidence intervalp [CI]: 1.09-34.18). Pregnancy and live births rates were similar for Days 2, 3, and 5 in both groups. The study was terminated early following the voluntary market withdrawal of ViaMetrics-E in December 2010. Metabolomic analysis using the commercial near-infrared (NIR) instrument does not appear to have a beneficial effect on pregnancy and live births, with improvement in IR with FCA for Day 5 transfers. However, no solid conclusions can be reached due to the lack of adequate study Identifier: NCT01490515.
    Journal of Human Reproductive Sciences 03/2013; 6(2):133-139. DOI:10.4103/0974-1208.117174

Publication Stats

7k Citations
703.25 Total Impact Points


  • 2015
    • Beth Israel Deaconess Medical Center
      Boston, Massachusetts, United States
  • 2013–2014
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
    • Ministério da Educação do Brasil
      Rio de Janeiro, Rio de Janeiro, Brazil
  • 2001–2014
    • Yale-New Haven Hospital
      • • Reproductive Endocrinology Services
      • • Department of Pathology
      New Haven, Connecticut, United States
  • 2000–2014
    • Yale University
      • • Department of Obstetrics, Gynecology and Reproductive Sciences
      • • School of Medicine
      New Haven, Connecticut, United States
  • 2003–2009
    • University of New Haven
      New Haven, Connecticut, United States
  • 2008
    • University of Crete
      • Department of Obstetrics and Gynaeocology
      Retimo, Crete, Greece
  • 1999–2000
    • University of Birmingham
      • School of Biosciences
      Birmingham, England, United Kingdom
  • 1993–1999
    • University of Geneva
      • Department of Obstetrics and Gynaecology
      Genève, Geneva, Switzerland
  • 1992
    • Monash University (Australia)
      Melbourne, Victoria, Australia