Publications

Publications

  • The developmental competence of human metaphase I oocytes with delayed maturation in vitro. Fertility and sterility Moon, J. H., Zhao, Q., Zhang, J., Reddy, V., Han, J., Cheng, Y., Zhang, N., Dasig, J., Nel-Themaat, L., Behr, B., Yu, B. 2022

    Abstract

    To evaluate if metaphase I (MI) oocytes completing maturation in vitro to metaphase II ("MI-MII oocytes") have similar developmental competence as the sibling metaphase II (MII) oocytes that reached maturity in vivo.Retrospective cohort study.A total of 1124 intracytoplasmic sperm injection (ICSI) cycles from 800 patients at a single academic center between April 2016 and Dec 2020 with at least one MII oocyte immediately after retrieval and at least one sibling "MI-MII oocyte" that was retrieved as MI and matured to MII in culture before ICSI were included in the study.A total of 7865 MII and 2369 sibling MI-MII retrieved from the same individuals were compared for fertilization and blastocyst formation rates. For patients undergoing single euploid blastocyst transfers (n=406), the clinical pregnancy, spontaneous pregnancy loss rate and live birth rate were compared between the two groups.The fertilization rate was significantly higher in MII oocytes than delayed matured MI-MII oocytes (75.9% vs 56.1%, p<0.001). Similarly, the blastocyst formation rate was higher in embryos derived from MII oocytes as compared to those from MI-MII oocytes (53.8% vs 23.9%; p<0.001). The percentage of euploid embryos derived from MII oocytes was significantly higher than those from MI-MII oocytes (49.2% vs 34.7%; p<0.001). Paired comparison of sibling oocytes within the same cycle showed higher developmental competence of the MII oocytes than MI-MII oocytes. However, the pregnancy, spontaneous pregnancy loss and live birth rate after a single euploid blastocyst transfer showed no statistically significant difference between the two groups (65.7% vs 74.1%: 6.4% vs 5.0%: 61.5% vs 70.0%, respectively, MII vs MI-MII group, p>0.05).Compared to oocytes that matured in vivo and were retrieved as MII, the oocytes that were retrieved as MI and matured to MII in vitro before ICSI showed lower developmental competence, including lower fertilization, blastocyst formation, and euploidy rates. However, euploid blastocysts from either cohort resulted in similar live birth rates, indicating the MI oocytes with delayed maturation can still be useful even though the overall developmental competence was lower than their in vivo matured counterparts.

    View details for DOI 10.1016/j.fertnstert.2022.12.033

    View details for PubMedID 36567036

  • Single-cell analysis of transcriptome and DNA methylome in human oocyte maturation. PloS one Yu, B. n., Doni Jayavelu, N. n., Battle, S. L., Mar, J. C., Schimmel, T. n., Cohen, J. n., Hawkins, R. D. 2020; 15 (11): e0241698

    Abstract

    Oocyte maturation is a coordinated process that is tightly linked to reproductive potential. A better understanding of gene regulation during human oocyte maturation will not only answer an important question in biology, but also facilitate the development of in vitro maturation technology as a fertility treatment. We generated single-cell transcriptome and used our previously published single-cell methylome data from human oocytes at different maturation stages to investigate how genes are regulated during oocyte maturation, focusing on the potential regulatory role of non-CpG methylation. DNMT3B, a gene encoding a key non-CpG methylation enzyme, is one of the 1,077 genes upregulated in mature oocytes, which may be at least partially responsible for the increased non-CpG methylation as oocytes mature. Non-CpG differentially methylated regions (DMRs) between mature and immature oocytes have multiple binding motifs for transcription factors, some of which bind with DNMT3B and may be important regulators of oocyte maturation through non-CpG methylation. Over 98% of non-CpG DMRs locate in transposable elements, and these DMRs are correlated with expression changes of the nearby genes. Taken together, this data indicates that global non-CpG hypermethylation during oocyte maturation may play an active role in gene expression regulation, potentially through the interaction with transcription factors.

    View details for DOI 10.1371/journal.pone.0241698

    View details for PubMedID 33152014

    View details for PubMedCentralID PMC7643955

  • Superovulation alters global DNA methylation in early mouse embryo development. Epigenetics Yu, B. n., Smith, T. H., Battle, S. L., Ferrell, S. n., Hawkins, R. D. 2019; 14 (8): 780–90

    Abstract

    Assisted reproductive technologies are known to alter the developmental environment of gametes and early embryos during the most dynamic period of establishing the epigenome. This may result in the introduction of errors during active DNA methylation reprogramming. Controlled ovarian hyperstimulation, or superovulation, is a ubiquitously used intervention which has been demonstrated to alter the methylation of certain imprinted genes. The objective of this study was to investigate whether ovarian hyperstimulation results in genome-wide DNA methylation changes in mouse early embryos. Ovarian hyperstimulation was induced by treating mice with either low doses (5 IU) or high doses (10 IU) of PMSG and hCG. Natural mating (NM) control mice received no treatment. Zygotes and 8-cell embryos were collected from each group and DNA methylomes were generated by whole-genome bisulfite sequencing. In the NM group, mean CpG methylation levels slightly decreased from zygote to 8-cell stage, whereas a large decrease in mean CpG methylation level was observed in both superovulated groups. A separate analysis of the mean CpG methylation levels within each developmental stage confirmed that significant genome-wide erasure of CpG methylation from the zygote to 8-cell stage only occurred in the superovulation groups. Our results suggest that superovulation alters the genome-wide DNA methylation erasure process in mouse early pre-implantation embryos. It is not clear whether these changes are transient or persistent. Further studies are ongoing to investigate the impact of ovarian hyperstimulation on DNA methylation re-establishment in later stages of embryo development.

    View details for DOI 10.1080/15592294.2019.1615353

    View details for PubMedID 31060426

    View details for PubMedCentralID PMC6615540

  • Genome-wide, Single-Cell DNA Methylomics Reveals Increased Non-CpG Methylation during Human Oocyte Maturation. Stem cell reports Yu, B., Dong, X., Gravina, S., Kartal, Ö., Schimmel, T., Cohen, J., Tortoriello, D., Zody, R., Hawkins, R. D., Vijg, J. 2017; 9 (1): 397-407

    Abstract

    The establishment of DNA methylation patterns in oocytes is a highly dynamic process marking gene-regulatory events during fertilization, embryonic development, and adulthood. However, after epigenetic reprogramming in primordial germ cells, how and when DNA methylation is re-established in developing human oocytes remains to be characterized. Here, using single-cell whole-genome bisulfite sequencing, we describe DNA methylation patterns in three different maturation stages of human oocytes. We found that while broad-scale patterns of CpG methylation have been largely established by the immature germinal vesicle stage, localized changes continue into later development. Non-CpG methylation, on the other hand, undergoes a large-scale, generalized remodeling through the final stage of maturation, with the net overall result being the accumulation of methylation as oocytes mature. The role of the genome-wide, non-CpG methylation remodeling in the final stage of oocyte maturation deserves further investigation.

    View details for DOI 10.1016/j.stemcr.2017.05.026

    View details for PubMedID 28648898

    View details for PubMedCentralID PMC5511109

  • DNA methylome and transcriptome sequencing in human ovarian granulosa cells links age-related changes in gene expression to gene body methylation and 3'-end GC density. Oncotarget Yu, B., Russanova, V. R., Gravina, S., Hartley, S., Mullikin, J. C., Ignezweski, A., Graham, J., Segars, J. H., DeCherney, A. H., Howard, B. H. 2015; 6 (6): 3627-43

    Abstract

    Diminished ovarian function occurs early and is a primary cause for age-related decline in female fertility; however, its underlying mechanism remains unclear. This study investigated the roles that genome and epigenome structure play in age-related changes in gene expression and ovarian function, using human ovarian granulosa cells as an experimental system. DNA methylomes were compared between two groups of women with distinct age-related differences in ovarian functions, using both Methylated DNA Capture followed by Next Generation Sequencing (MethylCap-seq) and Reduced Representation Bisulfite Sequencing (RRBS); their transcriptomes were investigated using mRNA-seq. Significant, non-random changes in transcriptome and DNA methylome features are observed in human ovarian granulosa cells as women age and their ovarian functions deteriorate. The strongest correlations between methylation and the age-related changes in gene expression are not confined to the promoter region; rather, high densities of hypomethylated CpG-rich regions spanning the gene body are preferentially associated with gene down-regulation. This association is further enhanced where CpG regions are localized near the 3'-end of the gene. Such features characterize several genes crucial in age-related decline in ovarian function, most notably the AMH (Anti-Müllerian Hormone) gene. The genome-wide correlation between the density of hypomethylated intragenic and 3'-end regions and gene expression suggests previously unexplored mechanisms linking epigenome structure to age-related physiology and pathology.

    View details for DOI 10.18632/oncotarget.2875

    View details for PubMedID 25682867

    View details for PubMedCentralID PMC4414142

  • Changes in markers of ovarian reserve and endocrine function in young women with breast cancer undergoing adjuvant chemotherapy. Cancer Yu, B., Douglas, N., Ferin, M. J., Nakhuda, G. S., Crew, K., Lobo, R. A., Hershman, D. L. 2010; 116 (9): 2099-105

    Abstract

    Premenopausal women undergoing chemotherapy are at risk for amenorrhea and impaired fertility. The objective of the current study was to assess levels of mullerian inhibitory substance (MIS), estradiol (E2), follicle-stimulating hormone (FSH), and menstrual status, in women undergoing chemotherapy.A nested prospective cohort study was conducted in women aged <40 years with breast cancer (BC) who were undergoing adjuvant chemotherapy (n = 26). Serum MIS, FSH, and E2 were measured before chemotherapy (baseline) and at Weeks 6, 12, 36, and 52. Controls were 134 age-matched women with known fertility. Hormone levels were compared between the cases and controls at baseline. Differences between amenorrhea and age subgroups were tested using the nonparametric Wilcoxon 2-sample test using a 2-sided alpha of 0.05.Subjects with BC and age-matched controls had similar baseline MIS levels (median, 0.94 ng/mL vs 0.86 ng/mL;, P > .05). Serum MIS decreased significantly at 6 weeks and remained suppressed for 52 weeks. E2 levels decreased, and FSH levels increased during chemotherapy; however, at 52 weeks, the levels returned to baseline. At 52 weeks, only 1 patient had MIS above the lower normal range, 15 had return of menstrual function, 11 had premenopausal levels of FSH, and 13 had follicular phase levels of E2. In women aged <35 years, 25% remained amenorrheic, whereas in women aged >35 years, 50% were amenorrheic. Amenorrheic and menstruating women were found to have similar MIS values at baseline and follow-up.In young women with BC, chemotherapy decreases MIS rapidly and dramatically. Rapid reductions in MIS do not appear to be predictive of subsequent menstrual function. Ovarian reserve and endocrine function may be affected differently by chemotherapy.

    View details for DOI 10.1002/cncr.25037

    View details for PubMedID 20187091

    View details for PubMedCentralID PMC3625425

  • Congenital male genital malformations and paternal health: an analysis of US claims data. Andrology Yu, B., Zhang, C. A., Chen, T., Mulloy, E., Shaw, G. M., Eisenberg, M. L. 2023

    Abstract

    OBJECTIVE: To investigate the potential association between paternal health and male genital malformations in the offspring.MATERIALS AND METHODS: We analyzed data from 2007 to 2016 derived from the IBM MarketScan Research database, which reports on reimbursed private healthcare claims in the United States. The association between paternal comorbidities (defined as individual and combined measures) and genital malformations in male offspring was analyzed.RESULTS: Of 376,362 male births, 22% of fathers had at least one component of the metabolic syndrome (MetS ≥1) prior to conception. Totals of 2880 cases of cryptorchidism (0.77%) and 2651 cases of hypospadias (0.70%) were identified at birth. While 0.76% of sons born to fathers with no MetS components were diagnosed with cryptorchidism, 0.82% of sons with fathers with multiple MetS components had cryptorchidism. Similarly, 0.69% vs 0.88% of sons had hypospadias when fathers had 0 or 2+ components of MetS. After adjusting for maternal and paternal factors, the odds of a son diagnosed with hypospadias increased with two or more paternal MetS components (Odds ratio [95% confidence interval]: 1.27 [1.10 - 1.47]). Specific components of paternal MetS were not generally more associated with a son's genital malformations. When we performed a subgroup analysis where genital malformations were defined based on surgical correction, the association with hypospadias persisted.CONCLUSIONS: Fathers with multiple components of the metabolic syndrome in the preconception period were observed to be at increased risks for having sons born with hypospadias. The results support the association between a man's andrological and overall health. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/andr.13404

    View details for PubMedID 36727635

  • Pregnancy outcomes in women with sickle cell disease in California. American journal of hematology Adesina, O. O., Brunson, A., Fisch, S. C., Yu, B., Mahajan, A., Willen, S. M., Keegan, T. H., Wun, T. 2023

    Abstract

    Adverse pregnancy outcomes occur frequently in women with sickle cell disease (SCD) across the globe. In the United States, Black women experience disproportionately worse maternal health outcomes than all other racial groups. To better understand how social determinants of health impact SCD maternal morbidity, we used California's Department of Health Care Access and Information data (1991-2019) to estimate the cumulative incidence of pregnancy outcomes in Black women with and without SCD-adjusted for age, insurance status, and Distressed Community Index (DCI) scores. Black pregnant women with SCD were more likely to deliver at a younger age, use government insurance, and live in at-risk or distressed neighborhoods, compared to those without SCD. They also experienced higher stillbirths (26.8, 95% confidence interval [CI]: 17.5-36.1 vs. 12.4 [CI: 12.1-12.7], per 1,000 births) and inpatient maternal mortality (344.5 [CI: 337.6-682.2] vs. 6.1 [CI: 2.3-8.4], per 100,000 live births). Multivariate logistic regression models showed Black pregnant women with SCD had significantly higher odds ratios (OR) for sepsis (OR 14.89, CI: 10.81, 20.52), venous thromboembolism (OR 13.60, CI: 9.16, 20.20), and postpartum hemorrhage (OR 2.25, CI 1,79-2.82), with peak onset in the 2nd trimester, 3rd trimester, and 6weeks postpartum, respectively. Despite adjusting for sociodemographic factors, Black women with SCD still experienced significantly worse pregnancy outcomes than those without SCD. We need additional studies to determine if early introduction to reproductive health education, continuation of SCD-modifying therapies during pregnancy, and increasing access to multidisciplinary perinatal care can reduce morbidity in pregnant women with SCD. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/ajh.26818

    View details for PubMedID 36594168

  • Preconception paternal comorbidities and offspring birth defects: Analysis of a large national data set. Birth defects research Yu, B., Zhang, C. A., Li, S., Chen, T., Mulloy, E., Shaw, G. M., Eisenberg, M. L. 2022

    Abstract

    BACKGROUND: Despite the fact that the father contributes half the genome to a child, associations between paternal factors and birth defects are poorly understood.OBJECTIVES: To investigate the association between preconception paternal health and birth defects in the offspring.MATERIALS AND METHODS: We conducted analysis of a national cohort study utilizing the IBM Marketscan Research Database, which includes data on reimbursed private healthcare claims in the United States from 2007 to 2016. The potential association between paternal comorbidities, as measured by the components of metabolic syndrome (MetS), and any birth defect in the offspring was analyzed.RESULTS: Of the 712,774 live births identified, 21.2% of children were born to fathers with at least one component of the metabolic syndrome (MetS ≥1) prior to conception. Compared to infants born to fathers with no components of the metabolic syndrome, a modestly higher percentage of infants with cardiac birth defects were born to fathers with more components of MetS (MetS=1, OR [95% CI]: 1.07 [1.01-1.13]; MetS ≥2, 1.17 [1.08-1.26], in comparison to MetS=0) after adjusting for maternal and paternal factors. Similarly, a higher percentage of infants with respiratory defects were born to fathers with two or more components of metabolic syndrome (MetS ≥2, OR [95% CI]: 1.45 [1.22-1.71]).DISCUSSION AND CONCLUSION: In this private insurance claims-based study, we found that fathers with metabolic syndrome-related diseases before conception were at increased risk for having a child affected by birth defects, especially cardiac and respiratory defects, and this association was not influenced by paternal age or assessed maternal factors.

    View details for DOI 10.1002/bdr2.2082

    View details for PubMedID 36106720

  • Pregnancy Outcomes in Women with Sickle Cell Disease in California: A Retrospective Cohort Study Fisch, S. C., Brunson, A. M., Mahajan, A., Keegan, T., Yu, B., Wun, T., Adesina, O. O. AMER SOC HEMATOLOGY. 2021
  • Severe ovarian hyperstimulation syndrome associated with long-acting GnRH agonist in oncofertility patients. Journal of assisted reproduction and genetics Christ, J., Herndon, C. N., Yu, B. 2021

    Abstract

    To report three cases of severe ovarian hyperstimulation syndrome (OHSS) among oncofertility patients receiving a long-acting GnRH agonist for ovarian suppression after controlled ovarian hyperstimulation (COH) with a GnRH antagonist protocol METHODS: Chart abstraction was completed for three patients at a single academic medical center. Patients included were undergoing fertility preservation prior to gonadotoxic chemotherapy. All patients underwent COH with GnRH antagonist protocol and embryo cryopreservation immediately followed by ovarian suppression with long-acting GnRH agonist. Main outcome measure was development of OHSS.Despite using GnRH agonist trigger and freezing all embryos, patients developed ascites, intermittent hyponatremia and hemoconcentration consistent with severe early-onset OHSS after receiving long-acting GnRH agonist immediately following oocyte retrieval for ovarian preservation.Risk of severe OHSS may be increased when a long-acting GnRH agonist is used for ovarian suppression immediately following oocyte retrieval. A delay in initiating long-acting GnRH agonist after oocyte retrieval in patients at high risk for developing OHSS should be considered.

    View details for DOI 10.1007/s10815-020-02051-7

    View details for PubMedID 33471229

  • Dissociation of Pubertal Development Abnormality and Gonadal Dysfunction in Childhood Cancer Survivors JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY Yu, B., Fritz, R., Vega, M., Merino, M. 2020; 9 (4): 490–95

    Abstract

    Purpose: To determine the relationship between pubertal development and postpubertal gonadal function in childhood cancer survivors. Methods: Childhood cancer survivors (≥10 years of age) who received follow-up care in a pediatric oncology group in an academic medical center during the period from January 1, 1985, to July 1, 2010 were included in this case series. Their pubertal development and gonadal function were evaluated. Results: The cohort consists of 39 males (age 10-21 years) and 35 females (age 10-29 years) with a variety of cancer diagnosis and treatments. The average age at diagnosis was ∼7.5 years. The average age at the time of the study was 16 and 16.7 years in males and females, respectively, representing a mean follow-up interval of ∼9 years. Despite the fact that 60% of survivors received cyclophosphamide equivalents and 16.2% received cranial radiation or brain tumor resection, the majority of survivors (68%) presented with both normal puberty and normal gonadal functions at the time of follow-up. In 27% of survivors, puberty development did not predict gonadal function in early adulthood: 20% of survivors had normal puberty, but abnormal gonadal function; 7% of survivors had abnormal puberty, but gonadal function remained normal as young adults. Conclusions: Most childhood cancer survivors had normal puberty and gonadal function despite a variety of cancer treatment modalities. However, normal puberty did not predict normal gonadal function later in life in many survivors. Therefore, close follow-up with gonadal function in adolescent and early adulthood years is essential.

    View details for DOI 10.1089/jayao.2019.0138

    View details for Web of Science ID 000524993500001

    View details for PubMedID 32186962

    View details for PubMedCentralID PMC7415869

  • Gonadotropin-Releasing Hormone (GnRH) Agonists for Fertility Preservation: Is POEMS the Final Verse? Journal of the National Cancer Institute Yu, B., Davidson, N. E. 2019; 111 (2): 107-108

    View details for DOI 10.1093/jnci/djy188

    View details for PubMedID 30371813

    View details for PubMedCentralID PMC6376902

  • The impact of using donor sperm in assisted reproductive technology cycles on perinatal outcomes. Fertility and sterility Yu, B., Fritz, R., Xie, X., Negassa, A., Jindal, S., Vega, M., Buyuk, E. 2018; 110 (7): 1285-1289

    Abstract

    To assess the impact of using donor sperm in assisted reproductive technology (ART) cycles on perinatal outcomes.Historical cohort study.US national database from the Society of Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 2012 to 2013.Patients undergoing the first fresh autologous ART cycle using either donor or partner sperm.None.Miscarriage, preterm birth, low birthweight rates.A total of 134,710 fresh autologous ART cycles were evaluated from the SART CORS database. Following exclusion criteria and after restricting to the first cycle, 2,123 donor sperm and 42,799 partner sperm ART cycles were included in the final analyses. After adjusting for all confounding variables (including maternal age, race, body mass index, smoking status, gravidity, history of preterm birth, highest follicle stimulating hormone count, blastocyst transfer percentage, total embryo transferred, and etiology of infertility), no statistically significant differences in miscarriage rates, preterm births, very preterm births, low birthweight, and very low birthweight were observed. Birthweight was significantly lower in the partner sperm group than in the donor sperm group (3,292 ± 601 and 3,233 ± 592 g in donor and partner sperm groups, respectively, adjusted P value 0.003); however, this small absolute difference (adjusted effect estimate 42 g, 95% CI 14.7-70.9) does not carry clinical significance.The use of donor sperm in fresh autologous ART cycles was not associated with increased miscarriage, preterm births, or low birthweights, as compared to cycles using partner sperm. This information can be used in patient counseling to reassure patients using donor sperm in ART cycles.

    View details for DOI 10.1016/j.fertnstert.2018.08.012

    View details for PubMedID 30503127

    View details for PubMedCentralID PMC7605214

  • Comparison of perinatal outcomes following frozen embryo transfer cycles using autologous versus donor oocytes in women 40 to 43 years old: analysis of SART CORS data. Journal of assisted reproduction and genetics Yu, B., Vega, M., Zaghi, S., Fritz, R., Jindal, S., Buyuk, E. 2018; 35 (11): 2025-2029

    Abstract

    To study the differences in perinatal outcomes after frozen embryo transfer cycles using autologous or donor oocytes in women of advanced maternal age.Historical cohort study.US national database from the Society of Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 2009 to 2013.Women at 40-43 years of age undergoing autologous frozen embryo transfers (a-FET) or donor oocyte frozen embryo transfers (d-FET) resulting in singleton pregnancies that were entered in the SART CORS database from 2009 to 2013.a-FET resulted in 4402 singleton live births whereas d-FET resulted in 2703 singleton live births. d-FET resulted in a higher risk of preterm births (< 37 weeks), with adjusted odds ratio (aOR) 1.33 (95% CI 1.02-1.75), but similar risk of small for gestational age (SGA), with aOR 1.75 (95% CI 0.85-3.7), when compared to a-FET. However, when only single blastocyst transfer cycles are considered, d-FET and a-FET showed no difference in preterm births or other adverse perinatal outcomes.Singletons resulting from d-FET are at increased risk for perinatal morbidity. However, the risk was diminished in single blastocyst transfer cycles. Our study supports the current American Society for Reproductive Medicine (ASRM) guidelines of transferring a single blastocyst in d-FET cycles.

    View details for DOI 10.1007/s10815-018-1287-1

    View details for PubMedID 30128819

    View details for PubMedCentralID PMC6240548

  • Single-cell genome-wide bisulfite sequencing uncovers extensive heterogeneity in the mouse liver methylome. Genome biology Gravina, S., Dong, X., Yu, B., Vijg, J. 2016; 17 (1): 150

    Abstract

    Transmission fidelity of CpG DNA methylation patterns is not foolproof, with error rates from less than 1 to well over 10 % per CpG site, dependent on preservation of the methylated or unmethylated state and the type of sequence. This suggests a fairly high chance of errors. However, the consequences of such errors in terms of cell-to-cell variation have never been demonstrated by experimentally measuring intra-tissue heterogeneity in an adult organism.We employ single-cell DNA methylomics to analyze heterogeneity of genome-wide 5-methylcytosine (5mC) patterns within mouse liver. Our results indicate a surprisingly high level of heterogeneity, corresponding to an average epivariation frequency of approximately 3.3 %, with regions containing H3K4me1 being the most variable and promoters and CpG islands the most stable. Our data also indicate that the level of 5mC heterogeneity is dependent on genomic features. We find that non-functional sites such as repeat elements and introns are mostly unstable and potentially functional sites such as gene promoters are mostly stable.By employing a protocol for whole-genome bisulfite sequencing of single cells, we show that the liver epigenome is highly unstable with an epivariation frequency in DNA methylation patterns of at least two orders of magnitude higher than somatic mutation frequencies.

    View details for DOI 10.1186/s13059-016-1011-3

    View details for PubMedID 27380908

    View details for PubMedCentralID PMC4934005

  • Cost-effectiveness analysis comparing continuation of assisted reproductive technology with conversion to intrauterine insemination in patients with low follicle numbers. Fertility and sterility Yu, B., Mumford, S., Royster, G. D., Segars, J., Armstrong, A. Y. 2014; 102 (2): 435-9

    Abstract

    To compare the cost effectiveness of proceeding with oocyte retrieval vs. converting to intrauterine insemination (IUI) in patients with ≤4 mature follicles during assisted reproductive technology (ART) cycles.Probabilistic decision analysis. The cost effectiveness of completing ART cycles in poor responders was compared to that for converting the cycles to IUI.Not applicable.Not applicable.Cost-effectiveness analysis.Cost effectiveness, which was defined as the average direct medical costs per ongoing pregnancy.In patients with 1-3 mature follicles, completing ART was more cost effective if the cost of a single ART cycle was between

  • The prevalence of genuine empty follicle syndrome. Fertility and sterility Mesen, T. B., Yu, B., Richter, K. S., Widra, E., DeCherney, A. H., Segars, J. H. 2011; 96 (6): 1375-7

    Abstract

    To describe the prevalence of "genuine" empty follicle syndrome (EFS) and "false" EFS at assisted reproductive technology (ART).Retrospective cohort.Large private fertility center.A total of 12,359 patients who underwent ART between 2004 and 2009.None.The failure to recover an oocyte during oocyte retrieval at ART, with and without a detectable serum β-hCG on the day of retrieval.Two cases of genuine EFS and nine cases of false EFS were identified in the cohort examined. The prevalence of genuine EFS was 0.016%, and the prevalence of false EFS was 0.072%. Only two out of 11 cases of EFS were considered genuine.Genuine EFS is a rare occurrence. Because this syndrome tends to recur with dismal pregnancy rates at ART, continued identification and further investigation of the syndrome are needed.

    View details for DOI 10.1016/j.fertnstert.2011.09.047

    View details for PubMedID 22130102

    View details for PubMedCentralID PMC3576020

  • Subclinical elevations of thyroid-stimulating hormone and assisted reproductive technology outcomes. Fertility and sterility Michalakis, K. G., Mesen, T. B., Brayboy, L. M., Yu, B., Richter, K. S., Levy, M., Widra, E., Segars, J. H. 2011; 95 (8): 2634-7

    Abstract

    The prevalence of moderately elevated TSH levels consistent with subclinical hypothyroidism (2.5-4.0 μIU/mL) was 23% in a cohort of 1,231 women pursuing assisted reproductive technologies. Preconception elevated levels of TSH were associated with diminished ovarian reserve but were not associated with adverse assisted reproductive technology or pregnancy outcomes.

    View details for DOI 10.1016/j.fertnstert.2011.02.056

    View details for PubMedID 21457968

    View details for PubMedCentralID PMC3124612

  • The role of peripheral gonadotropin-releasing hormone receptors in female reproduction. Fertility and sterility Yu, B., Ruman, J., Christman, G. 2011; 95 (2): 465-73

    Abstract

    To review the physiologic functions and clinical significance of peripheral GnRH receptors.Literature review. All peer-reviewed journal articles published before 2010 on peripheral GnRH receptors were searched for in the Pubmed database, and relevant findings were summarized.Peripheral GnRH/GnRH receptor systems may serve as regulators of hCG synthesis and implantation, and play crucial roles in antiproliferation and apoptosis. Currently, GnRH agonists have been used in cancer treatment and ovary protection during chemotherapy, taking advantage of the local direct effect mediated by peripheral GnRH receptors.The ubiquitous GnRH/GnRH receptor system in human tissues has been shown to have some important physiologic functions. Further research to clarify functions of these peripheral GnRH receptors may lead to discovery of new therapeutic options.

    View details for DOI 10.1016/j.fertnstert.2010.08.045

    View details for PubMedID 20888559