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David B Seifer

Publications and source records attributed to David B Seifer.

15 recordsLinked to original sources
PubMed2007

Serum müllerian-inhibiting substance in Down's syndrome pregnancies.

BACKGROUND: To examine whether maternal serum levels of müllerian-inhibiting substance (MIS) differ in Down's syndrome and unaffected pregnancies. METHODS: Case-control study was conducted using stored serum from an antenatal screening programme. Sera from 25 Down's syndrome pregnancies were retrieved from -20 degrees C storage together with 125 unaffected controls individually matched for maternal age, weeks of gestation and duration of storage. Results were expressed in multiples of the gestation-specific median value (MoM) in controls. RESULTS: The median value in Down's syndrome pregnancies was 0.83 MoM (P = 0.77, two-tail Wilcoxon rank sum test). Among unaffected pregnancies, there was a statistically significant correlation between MIS and pregnancy-associated plasma protein-A (P < 0.05). MIS levels were elevated in pregnancies where assisted reproduction techniques had been used. CONCLUSION: There is no evidence for a substantial reduction in maternal serum MIS levels in Down's syndrome pregnancies. This study provides useful information regarding serum MIS levels in pregnancy.

Adult↗
PubMed2006

Immunocytochemical evidence for the presence and location of the neurotrophin-Trk receptor family in adult human preovulatory ovarian follicles.

OBJECTIVE: This study was undertaken to evaluate the presence or absence of neurotrophins and their respective receptors within adult human preovulatory follicles. STUDY DESIGN: Prospective study of neurotrophins and their receptors in follicular cells and unfertilized oocytes from women undergoing aspiration for in vitro fertilization/intracytoplasmic sperm injection. Cells (mural and cumulus granulosa cells, unfertilized oocytes) were examined for immunocytochemical staining of neurotrophin and receptor proteins. RESULTS: Mural and cumulus granulosa cells were positive for BDNF, NT-4/5, NT-3, and NGF, as well as for Trk B, Trk C, and Trk A receptors. Unfertilized oocytes were positive for Trk B, Trk C, and Trk A receptors. CONCLUSION: Neurotrophins and their respective receptor proteins are present within the mural and cumulus granulosa cells of adult human preovulatory follicles. Neurotrophin receptors are present in human unfertilized oocytes. The location of the neurotrophins and their receptors suggest both an autocrine and paracrine function within the adult human ovarian follicle.

Adult↗
PubMed2006

Effects of HIV infection and its treatment on self-reported menstrual abnormalities in women.

OBJECTIVE: To describe menstrual abnormalities among women with HIV. METHODS: Women in a multicenter prospective cohort study of HIV natural history reported menstrual abnormalities every 6-months between October 1994 and September 2002. Logistic regression and Cox proportional-hazards models were applied. RESULTS: The prevalence and incidence of menstrual abnormalities were <20%. HIV serostatus was not associated with prevalent menstrual abnormalities, but in HIV-seropositive women, higher CD4 counts were associated with fewer problems: compared with women with CD4 counts <200/mm3, in women with counts 200-500/mm3, odds ratio (OR) for amenorrhea was 0.55, p = 0.02, and for oligomenorrhea was 0.54, p = 0.0003; for women with counts >500/mm3, OR for amenorrhea was 0.67, p = 0.14, and for oligomenorrhea was 0.55, p = 0.001. HIV serostatus was not associated with incident abnormalities. Highly active anti-retroviral therapy (HAART) use was not associated with prevalent abnormalities, but both HAART use and higher CD4 counts were linked to lower rates of incident menstrual problems. CONCLUSIONS: Compared with seronegative women, HIV-seropositive women are at increased risk for some menstrual changes, although the absolute frequency of most abnormalities is low. Higher CD4 counts and HAART protect against incident abnormalities.

Adult↗
PubMed2005

Metformin reduces serum mullerian-inhibiting substance levels in women with polycystic ovary syndrome after protracted treatment.

OBJECTIVE: Assessment of ovarian responses to metformin treatment in obese women with polycystic ovary syndrome (PCOS). DESIGN: Prospective treatment with randomization to two doses of metformin. SETTING: University teaching hospital. PATIENT(S): Obese women (n = 82) with PCOS. INTERVENTION(S): Markers of ovarian function were assessed after 4 and 8 months. MAIN OUTCOME MEASURE(S): Hormone (androgens and mullerian-inhibiting substance [MIS]) changes over time. RESULT(S): There was no difference in the reproductive hormone changes between the doses of metformin, and data were combined for further analyses. Significant responses to treatment were recorded for menstrual frequency and androstenedione (A) (reduction) within the first 4 months of treatment. However, suppression of the elevated circulating MIS concentrations required protracted treatment, because no change was observed in the first 4 months-only in the second 4-month assessment period. CONCLUSION(S): Metformin treatment of PCOS leads to rapid suppression of A and improved menstrual frequency. Suppression of MIS is a delayed response that may be secondary to the development of a cohort of follicles that underwent initial recruitment in an environment of reduced insulin stimulation.

Adult↗
PubMed2004

Impact of retained embryos on the outcome of assisted reproductive technologies.

OBJECTIVE: To assess the impact of embryo retention in the embryo transfer catheter followed by "immediate" retransfer on pregnancy outcome in women undergoing assisted reproduction. DESIGN: Retrospective analysis of embryo transfer following in vitro fertilization. SETTING: Assisted reproductive technology practice in a university in vitro fertilization program. PATIENT(S): In vitro fertilization charts for 1,812 embryo transfer cycles representing 1,139 patients between January 1997 and March 2002 were reviewed. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy rate, implantation rate, delivery rate. RESULT(S): Three embryo transfer cycles were excluded from analysis because of missing data, leaving 1,364 embryo transfers during oocyte recovery cycles and 445 embryo transfer cycles using thawed embryos. Seventy-one embryo transfers (3.9% of all transfers) were complicated by finding retained embryos after the initial embryo transfer-all retained embryos were immediately retransferred. There was no difference in the frequency of retained embryos during oocyte retrieval versus thawed embryo cycles. The pregnancy, implantation, and delivery rates per embryo transfer were not negatively affected by embryo(s) retained in the transfer catheter. Age, fresh versus frozen embryo, use of ultrasound during the procedure, or transferring physician did not influence pregnancy outcome. CONCLUSION(S): Immediate retransfer of embryos retained in the catheter following the initial transfer attempt did not have an adverse effect on pregnancy outcome.

Biomarkers↗
PubMed2004

Serum antimüllerian hormone/müllerian-inhibiting substance appears to be a more discriminatory marker of assisted reproductive technology outcome than follicle-stimulating hormone, inhibin B, or estradiol.

OBJECTIVE: To test the hypothesis that the concentration of early follicular phase serum antimullerian hormone (AMH) or mullerian-inhibiting substance (MIS) is a useful marker of ovarian response and assisted reproductive technology (ART) outcome. DESIGN: Retrospective analysis of day 3 serum samples drawn before treatment. SETTING: Private ART program. PATIENT(S): One hundred nine consecutive serum samples from women younger than 42 years of age who were undergoing ovulation induction for IVF. INTERVENTION(S): Follicular aspiration for IVF after ovarian stimulation with FSH in a down-regulated cycle using GnRH-a treatment. MAIN OUTCOME MEASURE(S): Correlations between day 3 serum AMH/MIS, E2, FSH, inhibin B levels, and IVF outcome (i.e., number of retrieved mature oocytes, number and quality of embryos obtained, ongoing clinical pregnancy rates). Multivariate regression analysis on categorical data was performed to describe a predictive model of clinical pregnancy outcome. RESULT(S): Mean serum AMH/MIS value for clinical pregnancy (n = 38) was 2.4 ng/mL, in comparison to 1.1 ng/mL for those who did not become pregnant (n = 71). No differences were noted in mean values for day 3 FSH, inhibin B, or E2 between groups. Multivariate regression analysis demonstrated that day 3 serum AMH/MIS had the greatest independent contribution in predicting pregnancy outcomes. CONCLUSION(S): These data demonstrate a strong association between day 3 serum AMH/MIS level and IVF outcome in women younger than 42 years of age. Higher AMH/MIS concentrations are associated with a greater number of mature oocytes, a greater number of embryos, and ultimately a higher clinical pregnancy rate. Furthermore, AMH/MIS may offer greater prognostic value than other currently available serum markers of ART outcome.

Adult↗
PubMed2003

In vitro fertilization in the older patient.

In vitro fertilization (IVF) in the older patient presents a significant challenge to the clinician. Older IVF patients have higher cancellation rates, lower oocyte yields, lower pregnancy rates, and higher miscarriage rates, despite significant improvements in IVF success rates in the past decade. Markers of diminished ovarian reserve, including basal follicle-stimulating hormone and estradiol levels, clomiphene citrate challenge test, inhibin B, müllerian-inhibiting substance, ovarian volume, and antral follicle counts, can be useful in counseling patients. Alterations in the stimulation protocol, such as changing the gonadotropin or gonadotropin-releasing hormone (GnRH) agonist dose, use of the agonist flare or microdose flare protocols, or use of a GnRH antagonist have met with varying degrees of success in improving outcomes.

Adult↗
PubMed2002

Early follicular serum müllerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles.

OBJECTIVE: To test the hypothesis that the concentration of early follicular phase serum müllerian-inhibiting substance (MIS) is associated with ovarian response in women undergoing ovulation induction in preparation for assisted reproductive technology (ART). DESIGN: Retrospective analysis of frozen day 3 serum samples. SETTING: Academic ART program. PATIENT(S): One sample of frozen day 3 serum from women with < or = 6 retrieved oocytes (n = 28) compared with women with > or = 11 oocytes retrieved (n = 79) in preparation for IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Comparison of day 3 serum MIS levels between two groups of women. Other comparisons included maximum serum E(2) concentrations, number of retrieved oocytes, and percentage of mature oocytes between groups. RESULT(S): Mean serum MIS concentrations were 1.0 +/- 0.4 ng/mL compared with 2.5 +/- 0.3 ng/mL, or more than a 2.5-fold greater serum concentration of MIS in the group with > or = 11 oocytes retrieved compared with in the group with < or = 6 retrieved oocytes. CONCLUSION(S): These data demonstrate an association between early follicular phase serum MIS and the number of retrieved oocytes. Higher day 3 serum MIS concentrations were associated with greater number of retrieved oocytes.

Adult↗
PubMed2002

DNA microarray analysis of the expression profiles of luteinized granulosa cells as a function of ovarian reserve.

OBJECTIVE: To examine the expression profiles of luteinized granulosa cells isolated from women with normal or diminished ovarian reserve undergoing in vitro fertilization. DESIGN: Expression profiling by complementary DNA microarray analysis. SETTING: Women undergoing in vitro fertilization-embryo transfer in a university-based fertility clinic. PATIENT(S): Eighteen women with normal or decreased ovarian reserve. INTERVENTION(S): All patients were given gonadotropin stimulation in preparation for IVF with granulosa cells isolated at the time of follicular aspiration. MAIN OUTCOME MEASURE(S): Expression profiles of luteinized granulosa cells isolated from each woman were determined by using DNA microarray analysis. RESULT(S): Changes in patterns of gene expression in granulosa cells were observed between women with normal and diminished ovarian reserve. These genes included several anonymous expressed sequence tags and also expressed sequence tags that correspond to known genes. CONCLUSION(S): Expression profiling of granulosa cells by DNA microarray may yield signature patterns that reflect the status of ovarian reserve and the competence of granulosa cells.

Adult↗
PubMed2002

Mitochondrial deletions in luteinized granulosa cells as a function of age in women undergoing in vitro fertilization.

OBJECTIVE: To test the hypothesis that mitochondrial DNA (mtDNA) deletions are more prevalent in granulosa cells from women of advanced reproductive age than from younger women undergoing IVF. DESIGN: Granulosa cells screened for presence or absence of the 4977-bp deletion in human mtDNA. SETTING: University-based fertility clinic. PATIENT(S): Twenty-four women divided equally between two groups: </=34 years old and >/=38 years old. INTERVENTION(S): Patients were given gonadotropin stimulation in preparation for IVF with granulosa cells isolated at the time of follicular aspiration. MAIN OUTCOME MEASURE(S): Presence or absence of the 4977-bp deletion in human mtDNA. RESULT(S): Seven out of 12 women analyzed who were <38 years old and 0 out of 12 women who were >38 years old had normal mtDNA as indicated by the presence of the 4977-bp fragment. CONCLUSION(S): These data suggest that women over the age of 38 have granulosa cells that contain a substantial decrease in the level of normal mitochondria as compared with women </=34 years.

Adult↗
PubMed2002

Practice patterns among board-certified reproductive endocrinologists regarding high-order multiple gestations: a united states national survey.

OBJECTIVE: To assess current practice management, attitudes, and strategies of reproductive endocrinologists in the United States regarding high-order (at least three) multiple gestations. METHODS: Questionnaires were mailed to 768 board-certified reproductive endocrinologists of whom 722 were eligible for the study. The questionnaires addressed topics such as practitioner demographics, management strategies, and attitudes regarding high-order multiple gestations. RESULTS: The survey response rate was 52%. Most physicians performed 100-300 cycles of each ovulation induction with intrauterine insemination and in vitro fertilization in 1998 and 1999. The most commonly reported incidence of high-order multiple gestations resulting from each ovulation induction with intrauterine insemination and in vitro fertilization was 2-5% in 1998 and 1999. Strategies used to decrease the rate of high-order multiple gestations varied among practitioners. Informed consent regarding high-order multiple gestations was provided by 99.5% of practitioners. Information regarding selective reduction was provided by 98.3% of respondents. Over 90% of practitioners believed it is worthwhile to attempt to decrease the risk of high-order pregnancies at the risk of decreasing their group's overall pregnancy rates. CONCLUSION: Most reproductive endocrinologists reported concern over the rising risk of high-order multiple gestations resulting from therapies such as superovulation with intrauterine insemination or in vitro fertilization. However, the ways in which patients are counseled regarding such events, their sequelae, and methods to avoid them greatly differ among respondents. Given the inconsistent practice patterns, a multifaceted educational approach may provide an opportunity to reduce the incidence of high-order multiple gestations and their sequelae.

Counseling↗
PubMed2002

Neurotrophin-4/5 and neurotrophin-3 are present within the human ovarian follicle but appear to have different paracrine/autocrine functions.

Neurotrophins are a family of soluble polypeptide growth factors widely recognized for their role in the mammalian nervous system. We first reported the unique presence of one neurotrophin, brain-derived neurotrophic factor (BDNF), in the follicular fluid of the human ovarian follicle. The BDNF receptor, Trk B, was identified in mouse oocytes, and BDNF accelerated first polar body extrusion in vitro. In the present study, we examined human follicular fluid and mouse immature oocytes to determine whether another Trk B ligand, neurotrophin-4/5 (NT-4/5), is present within the ovarian follicle and if so, whether it demonstrates activity similar to that of BDNF. We also examined whether a non-Trk B neurotrophin ligand, neurotrophin-3 (NT-3), is present within the follicle and has a possible role in oocyte maturation. NT-4/5 and NT-3 were noted to be present in all human follicular fluid samples aspirated from follicles of women undergoing in vitro fertilization. NT-4/5, but not NT-3, significantly promoted mouse oocyte polar body extrusion. Trk C receptors were not noted to be present in mouse oocytes. This study demonstrates for the first time that NT-4/5 and NT-3 are present in the follicular fluid of the human ovary. These data suggest that NT-4/5, like BDNF, promotes oocyte nuclear maturation. In contrast, NT-3 does not promote oocyte maturation but may contribute to follicle-oocyte maturation by mechanisms not yet identified.

Adult↗
PubMed2002

Brain-derived neurotrophic factor: a novel human ovarian follicular protein.

Neurotrophins are a family of soluble polypeptide growth factors widely recognized for their roles in the mammalian nervous system. One such neurotrophin, brain-derived neurotrophic factor (BDNF) was originally described in the nervous system but has now been shown to be expressed in a variety of nonneuronal tissues including endocrine tissues. We examined the human ovarian follicle for its possible secretion of BDNF and further studied mouse oocytes to determine BDNF's possible influence upon oocyte maturation. In a series of experiments derived from human specimens from in vitro fertilization following oocyte retrieval, BDNF was detected in human follicular fluid. To define the source of BDNF, cumulus granulosa cells (the cells that immediately surround the developing oocyte) were grown in cell culture for 1-2 d. BDNF protein increased over 24 h in the culture medium. Moreover, the release of BDNF was enhanced upon stimulation with cAMP or forskolin, an activator of cAMP. In contrast, mural granulosa (cells lining the follicle), oocytes, and embryos did not release appreciable quantities of BDNF. To examine possible targets of BDNF, mouse studies were used to localize the BDNF receptor, Trk B, immunocytochemically. The receptor was present on the surface of isolated oocytes. Moreover, BDNF promoted mouse oocyte maturation in culture. These experiments demonstrate for the first time the presence and secretion of BDNF from follicular cells in the human ovary and suggest a possible role for BDNF in the regulation and modulation of oocyte maturation.

8-Bromo Cyclic Adenosine Monophosphate↗