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D B Seifer

Publications and source records attributed to D B Seifer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Activin A stimulates meiotic maturation of human oocytes and modulates granulosa cell steroidogenesis in vitro.

OBJECTIVE: To test the hypothesis that activin A promotes in vitro human oocyte meiotic maturation while inhibiting steroid secretion by nonluteinized antral granulosa cells. DESIGN: Prospective randomized controlled study. SETTING: A university medical center. PATIENT(S): Nine women ranging in age from 31-44 years who were undergoing oophorectomy for nonovarian pathology. INTERVENTION(S): Analysis of meiotic maturation of oocytes and steroid secretion by granulosa cells cultured in the presence or absence of activin A. MAIN OUTCOME MEASURE(S): Germinal vesicle breakdown (GVBD) and attainment of metaphase II (MII) in oocytes, and progesterone and E2 secretion by granulosa cells. RESULT(S): Activin A significantly enhanced GVBD (91% vs. 65%) for control and maturation to MII (56% vs. 35% for control) of immature oocytes. Activin A significantly suppressed basal, and inhibin A-and FSH-stimulated progesterone and E2 secretion by nonluteinized granulosa cells. CONCLUSION(S): Activin A is a promoter of oocyte maturation in vitro and a modulator of granulosa cell steroidogenesis in culture.

Activins↗
PubMed1998

Predicting probabilities of pregnancy and multiple gestation from in vitro fertilization--a new model.

OBJECTIVE: To develop a statistical model that adjusts for variation between patients and adequately predicts the observed distribution of pregnancies among singletons and multiple gestations of various orders. METHODS: All in vitro fertilization (IVF) cycles from the inception of the IVF program at Women and Infants' Hospital on May 26, 1988, until December 31, 1993, were evaluated using logistic regression in selected subsets. RESULTS: A new cycle-one specific model uses three different probabilities: P1, the probability of pregnancy (predicted by age and total embryo score); P2/P1, the conditional probability of finding a second implantation in those who had become pregnant with at least one (predicted by total embryo score); and P3/P2, the conditional probability of finding a third implantation in those who had become pregnant with at least two (with no significant predictors). This is the first model to use these three adjusted probabilities. CONCLUSION: P1 increases with increasing total embryo score but decreases with increasing age. P2/P1 increases with increasing total embryo score but does not depend on age. Embryo scoring is useful because the total embryo score is a better predictor of P1 and P2/P1 than the number of embryos alone. By using patient-specific information (age and total embryo score) and cycle-specific tables, an estimate of the probability of pregnancy and multiple gestation can be provided before embryo transfer.

Adult↗
PubMed1997

Multiple immunoreactive inhibin proteins in serum from postmenopausal women with epithelial ovarian cancer.

Inhibin is an ovarian protein previously shown, using a nonspecific assay, to be elevated in serum of women with ovarian cancer. However, inhibin is secreted in multiple biochemical forms, including dimeric inhibin A and B and alpha inhibin precursors (pro-alphaC), each of which can now be specifically measured. We have examined the secretion of inhibin B and pro-alphaC inhibin in serum from women with epithelial ovarian cancer (EOC) for the first time, and have compared these analytes to inhibin A and total inhibin (inhibin A + B + pro-alphaC) as potential serum markers for EOC in postmenopausal women. Of all the immunoreactive inhibin proteins studied, the best serum marker was pro-alphaC, with 22% of women with EOC having levels that exceeded the range of values in women without EOC. Since CA 125 and pro-alphaC levels were not significantly correlated, combination of these markers resulted in 87% of EOC cases having elevated preoperative serum levels, a 9% increase over CA 125 alone. These data suggest that alpha inhibin secretion, especially pro-alphaC, may be useful in addition to CA 125 as a serum marker for EOC in postmenopausal women.

Aged↗
PubMed1997

Follicular fluid vascular endothelial growth factor concentrations are elevated in women of advanced reproductive age undergoing ovulation induction.

OBJECTIVE(S): To determine whether follicular fluid (FF) from women of advanced reproductive age had a relative deficiency of the angiogenic cytokine vascular endothelial growth factor/vascular permeability factor. Furthermore, we sought to determine whether luteinized granulosa cells secrete vascular endothelial growth factor/vascular permeability factor in response to hypoxia. DESIGN: Retrospective cohort study. SETTING: University teaching hospital. PATIENTS: Women undergoing follicular aspiration after superovulation in preparation for IVF-ET. Women of advanced reproductive age consisted of 21 women > or = 38 years old (range, 38 to 46 years); 15 subjects < or = 30 years served as the control population. INTERVENTION(S): Granulosa cells and FF were collected by transvaginal aspiration 35 hours after hCG. Granulosa cells from two women were cultured for 24 and 48 hours in M199 + 10% fetal bovine serum in 1% O2-5% CO2-94% N2 (hypoxic) or 95% air-5% CO2 (normoxic) without or with 0.1 mol/L cobalt chloride. MAIN OUTCOME MEASURE(S): Pooled FF vascular endothelial growth factor/vascular permeability factor concentrations and media vascular endothelial growth factor/vascular permeability factor accumulation at 24 and 48 hours were determined. RESULT(S): Follicular fluid vascular endothelial growth factor/vascular permeability factor concentrations were higher in advanced reproductive age women compared with younger women (3,735 +/- 2,155 versus 2,205 +/- 952 pg/mL, mean +/- SD). Accumulation of vascular endothelial growth factor/vascular permeability factor at 24 and 48 hours was 391 +/- 54 and 744 +/- 2 pg/mL in media maintained in 5% CO2 and air. Cobalt chloride induced a marked increase in vascular endothelial growth factor/vascular permeability factor (2,008 +/- 52 pg/mL at 24 hours and 3,630 +/- 519 pg/mL at 48 hours). An intermediate but significant increase in vascular endothelial growth factor/vascular permeability factor (733 +/- 35 pg/mL at 24 hours and 2,675 +/- 864 pg/mL at 48 hours) was observed with 1% O2 compared with normoxic controls. CONCLUSION(S): After hMG and hCG administration the FF from women of advanced reproductive age showed increased vascular endothelial growth factor/vascular permeability factor concentrations compared with younger women. Increased vascular endothelial growth factor/vascular permeability factor concentrations could be consistent with a hypoxic environment within follicles of older women.

Adult↗
PubMed1997

The impact of hydrosalpinx on successful pregnancy in tubal factor infertility treated by in vitro fertilization.

OBJECTIVE: To determine the impact of hydrosalpinx on pregnancy rates in patients undergoing IVF for infertility caused by tubal disease. DESIGN: Review of the records of all patients who had undergone IVF for tubal factor infertility at our institution between May 1988 and October 1994. SETTING: A university-sponsored, hospital-based IVF facility. PATIENT(S): Two hundred fifty patients were identified with infertility due to tubal disease; 67 of these had at least one documented hydrosalpinx whereas the remaining 183 did not. MAIN OUTCOME MEASURE(S): Numbers of oocytes retrieved and fertilized, the number of embryos transferred and implanting, and resulting pregnancy rates. RESULT(S): The groups were similar in age and cycle cancellation rates. The patients with hydrosalpinx had greater numbers of oocytes retrieved per cycle (15.0 versus 11.6) and embryos transferred per cycle then those without hydrosalpinges (4.21 versus 3.98). The hydrosalpinx group also undertook more cycles per patient (2.31 versus 1.96). Fertilization rates between the two groups were similar, but implantation rates were decreased in those with hydrosalpinx (8.5% versus 11.2%). CONCLUSION(S): Hydrosalpinx did not result in impaired ovarian stimulation or decreased oocyte fertilization. It did, however, interfere with implantation and reduce to some degree the success of IVF in achieving an ongoing pregnancy. The validity of routine salpingectomy for hydrosalpinx is debatable, but its use in selected individuals may well be appropriate.

Abortion, Spontaneous↗
PubMed1997

Day 3 serum inhibin-B is predictive of assisted reproductive technologies outcome.

OBJECTIVE: To determine if women with day 3 serum inhibin-B concentrations < 45 pg/mL (conversion factor to SI unit, 1.00) demonstrate a poorer response to ovulation induction and assisted reproductive technologies outcome relative to women with inhibin-B values > or = 45 pg/mL. DESIGN: Analysis of inhibin-B, FSH, and E2 concentrations in day 3 serum samples. SETTING: Academic clinical practice. PATIENT(S): One hundred fifty-six women who underwent 178 assisted reproductive technology (ART) cycles with luteal phase GnRH agonist suppression plus hMG and urofollitropin stimulation. MAIN OUTCOME MEASURE(S): Serum E2 on day of hCG, number of oocytes retrieved per patient, fertilization rate, cleavage rate, clinical pregnancy rate (PR) per initiated cycle, cancellation rate per initiated cycle, and spontaneous abortion rate. RESULT(S): Women with day 3 serum inhibin-B < 45 pg/mL demonstrated 70% of the E2 response, had 66.6% of the number of oocytes retrieved per patient, with 28% of the clinical PR per initiated cycle, and three times the cancellation rate per initiated cycle than women with day 3 inhibin-B > or = 45 pg/mL. After controlling for age, day 3 serum FSH, day 3 serum E2, patient cycle number, and method of ART, day 3 serum inhibin-B > or = 45 pg/mL was noted to be prognostic of the number of oocytes retrieved and clinical PR. The adjusted odds ratio of clinical pregnancy for those with day 3 serum inhibin-B > or = 45 pg/mL versus those with inhibin-B < 45 pg/mL was 6.8 (95% confidence interval 1.8 to 25.6). CONCLUSION(S): Women with low day 3 serum inhibin-B concentrations demonstrate a poorer response to ovulation induction and are less likely to conceive a clinical pregnancy through ART relative to women with high day 3 inhibin-B.

Adult↗
PubMed1996

Effects of fetal number and multifetal reduction on length of in vitro fertilization pregnancies.

OBJECTIVE: To determine the effects of multifetal reduction and other variables on the duration of gestation of in vitro fertilization (IVF) pregnancies. METHODS: All 274 IVF pregnancies from the inception of the Women and Infants' Hospital IVF Program on May 26, 1988, until December 31, 1993, were evaluated. RESULTS: Spontaneous reduction occurred in ten pregnancies, and multifetal reduction was elected in 28 multiple gestations. Among 260 pregnancies that remained viable beyond 20 weeks, 162 singletons (37.9 +/- 0.29 weeks; mean +/- standard error) had a longer mean gestation than did 64 twins (34.6 +/- 0.61 weeks), 25 pregnancies reduced to twins (33.4 +/- 1.0 weeks), or nine triplets (29.7 +/- 1.9 weeks). Triplets delivered 4.9 weeks earlier than nonreduced twins (P < .05) and 3.7 weeks before twins resulting from multifetal pregnancy reduction (P < .05). Regression analysis showed that at the 8-week ultrasound, each viable fetus could be expected to reduce the duration of the gestation by about 3.6 weeks, and each fetus reduced medically or as a result of natural causes could be expected to prolong the gestation by approximately 3.0 weeks. Only 14% of triplet pregnancies underwent spontaneous multifetal reduction. CONCLUSION: Multifetal reduction of pregnancies with three or more fetuses was beneficial and increased the duration of gestation.

Female↗
PubMed1996

Relaxin secretion in in vitro fertilization pregnancies.

OBJECTIVE: This study was designed to determine whether the late luteal functional status of the corpora lutea in in vitro fertilization cycles alters the secretion of relaxin during pregnancy. STUDY DESIGN: Analysis of serum relaxin, human chorionic gonadotropin, and steroid concentrations in sera of women with pregnancies viable beyond the twelfth week as a result of in vitro fertilization treatment was performed. RESULTS: The serum estradiol and progesterone concentrations decreased 5.5- and 4-fold from days 5 to 6 after human chorionic gonadotropin to days 11 to 13 after human chorionic gonadotropin, respectively. The serum relaxin concentration increased 8-fold between the 11- to 15-day interval and the 16- to 50-day interval after human chorionic gonadotropin and another 6-fold to the 51- to 90-day interval after human chorionic gonadotropin (all p < 0.01). Multiple linear regression analysis showed that the serum estradiol level 11 to 13 days after human chorionic gonadotropin and the serum human chorionic gonadotropin level 11 to 15 days after human chorionic gonadotropin were the most powerful paired predictors of the concentration of serum relaxin measured in the 11- to 15-day interval after human chorionic gonadotropin interval (R2 = 0.39, n = 50), the 16- to 50-day interval (R2 = 0.61, n = 51), and the 51- to 90-day interval (R2 = 0.55, n = 39). CONCLUSION: Secretion of relaxin is determined by an interaction of the late luteal functional status of the corpora lutea and the human chorionic gonadotropin secreted by the implanting pregnancy. These data allow for the hypothesis that inducing functional luteolysis by substituting one or more injections of luteinizing hormone for the human chorionic gonadotropin injection may decrease secretion of steroids, relaxin, and other factors from the corpora lutea during pregnancy, decreasing the risk of premature delivery in multiple gestations and the ovarian hyperstimulation syndrome.

Chorionic Gonadotropin↗
PubMed1996

Apoptosis as a function of ovarian reserve in women undergoing in vitro fertilization.

OBJECTIVE: To test the hypothesis that preovulatory follicles from women with diminished ovarian reserve contain fewer numbers of luteinized granulosa cells and have a greater percentage of cells undergoing apoptosis as compared with women with uncompromised ovarian reserve undergoing superovulation for IVF-ET. DESIGN: Comparative study. SETTING: Academic clinical practice. PATIENTS: Luteinized granulosa cell counts were determined from follicular aspirates harvested from 19 women with day 3 serum FSH < or = 6 mIU/mL (conversion factor to SI unit, 1.00) and from 15 women with FSH levels > or = 10 mIU/mL. The second part examined the percent of proliferating and apoptotic cells harvested from nine women with day 3 serum FSH < or = 6 mIU/ mL and from eight women with FSH levels > or = 10 mIU/mL. MAIN OUTCOME MEASURES: Cell counts by hemacytometer and percent of proliferating and of apoptotic granulosa cells by flow cytometry. RESULTS: The mean number of viable cells isolated per follicle were 2.7 x 10(5) (95% confidence interval [CI] 2.3 to 3.1 x 10(5) from the low FSH group and 1.8 x 10(5) (95% CI 1.4 to 2.3 x 10(5) from the high FSH group. Although the percentage of proliferating cells was the same, the mean percentage of apoptotic cells was 0.5% (95% CI 0.2% to 1.4%) from the low group and 2.0% (95% CI 1.1% to 3.7%) from the high group. CONCLUSIONS: Women undergoing IVF with day 3 serum FSH > or = 10 mIU/mL have preovulatory follicles with fewer luteinized granulosa cells and an increase in the percentage of cells undergoing apoptosis as compared with women with day 3 serum FSH < or = 6 mIU/mL.

Adult↗
PubMed1996

A combined cytogenetic and molecular approach for diagnosing delayed puberty.

A phenotypic female aged 15 4/12 years was referred because of delayed puberty and short stature. Chromosomal analysis of peripheral blood leukocytes revealed two subpopulations of cells. The modal cell line was hypodiploid with a missing X chromosome while the other cell line was diploid with one X chromosome and a G-sized chromosome that resembled a Y chromosome in morphology. Subsequent fluorescent in situ hybridization yielded results consistent with the above conventional cytogenetic studies. To provide unequivocal evidence of the Y-chromosome material, molecular analyses using the polymerase chain reaction and various primers were carried out which identified an intact short arm and centromere of the Y chromosome and structurally altered long arms. A laparoscopic bilateral gonadectomy, performed because of the risk of neoplasia, also yielded cells with both 45,X and 46,XY karyotypes. The present report thus illustrates the usefulness of a combined approach for diagnosing delayed puberty.

Adolescent↗
PubMed1996

Differential secretion of dimeric inhibin in cultured luteinized granulosa cells as a function of ovarian reserve.

Day 3 serum FSH is an indirect assessment of ovarian reserve and has been shown to be prognostic of outcome in ovulation induction and assisted reproductive technology programs. The precise physiologic basis for day 3 serum FSH screening is unknown. We tested the hypothesis that dimeric inhibin is differentially secreted from luteinized granulosa cells collected from women in preparation for in vitro fertilization with low vs. high day 3 serum FSH levels. This prospective study consisted of luteinized granulosa cells harvested from 7 women with low day 3 serum FSH levels (< or = 6 IU/L) and from 8 women with high FSH levels (> or = 10 IU/L) in preparation for in vitro fertilization-embryo transfer. Following retrieval, cells were isolated and then pooled within each individual patient and plated at 50,000 cells per well. Media was removed at 24 and 48 h and analyzed for dimeric and total inhibin concentrations by immunoassay as well as estradiol and progesterone concentrations by RIA. Dimeric inhibin was secreted at 2-fold higher concentrations in the low FSH group 43.2 pg/ml (30.8-60.6) (geometric mean and 95% confidence interval) compared with the high FSH group, 21.0 pg/ml (15.0-29.6), P < 0.004. Total inhibin was secreted at 1.8-fold higher concentrations in the low FSH group, 1148.2 pg/ml (931.1-1415.8) compared with the high FSH group, 639.7 pg/ml (428.5-955.0), P < 0.013. No significant differences in either estradiol or progesterone concentrations were noted. These data suggest that day 3 serum FSH is an indirect bioassay of dimeric inhibin production at the granulosa cell level. Thus, these data provide a potential physiological basis for day 3 serum FSH screening in ovulation induction and ART programs.

Cells, Cultured↗
PubMed1996

Autologous granulosa cell coculture demonstrates zygote suppression of granulosa cell steroidogenesis.

OBJECTIVE: To determine if embryos can modulate steroid hormone production by luteinized granulosa cells. DESIGN: Granulosa cells obtained from follicular aspirates were cultured alone or in the presence of a two-pronuclear zygote. The production of E2 and P by these cultures was evaluated by RIA. SETTING: In Vitro Fertilization Unit in an academic research environment. PATIENTS: Sixteen women undergoing IVF. INTERVENTIONS: Standard IVF-ET treatment cycle using leuprolide acetate for pituitary desensitization before hMG or urofollitropin for ovarian stimulation. MAIN OUTCOME MEASURES: Estradiol and P concentration in culture media of luteinized granulosa cells alone or granulosa cells cocultured with a two-pronuclear embryo. RESULTS: Both E2 and P production by luteinized granulosa cells was reduced when cultured in the presence of an embryo. CONCLUSIONS: Human embryos secrete a factor that regulates granulosa cell steroidogenesis.

Adult↗
PubMed1996

Serum inhibin levels are lower in ectopic than intrauterine spontaneously conceived pregnancies.

OBJECTIVE: To determine if serum inhibin concentrations are lower in ectopic (EP) versus intrauterine pregnancies (IUPs) that are conceived spontaneously. DESIGN: Case-control study. SETTING: Academic clinical practice. PATIENTS: Serum samples were obtained from 19 women who had EP confirmed at surgery and by pathology. For comparison, serum samples were collected from 24 women of similar chronological and gestational age with sonographic evidence of an IUP. MAIN OUTCOME MEASURE: Serum dimeric inhibin-A, total inhibin, P, and hCG. RESULTS: Serum total and dimeric inhibin concentrations in women with EP were < 60% of the concentrations for women with single IUPs. Total inhibin, but not dimeric inhibin-A, was elevated in maternal serum before week 8 of gestation relative to normal menstrual cycle levels. CONCLUSIONS: Serum inhibin concentrations are lower in EP as compared with IUPs that are spontaneously conceived and the relative amounts of dimeric inhibin-A, B, and alpha inhibin subunit in maternal serum may change throughout gestation.

Case-Control Studies↗
PubMed1995

Maternal and neonatal morbidity associated with in vitro fertilization.

OBJECTIVE: The purpose of this case-control study was to examine the maternal and neonatal morbidities associated with in vitro fertilization (IVF) in a single large teaching hospital. It was hypothesized that IVF mothers would have more perinatal complications and IVF infants would have higher mortality and morbidity rates than non-IVF control subjects. METHODS: One hundred forty-three gestations resulting from 101 IVF pregnancies, which included singletons (n = 62), twins (n = 72), and triplets (n = 9), were compared with equal numbers of non-IVF control subjects. Each pregnancy was matched by maternal age, race, insurance type, neonatal gender, order of gestation, order in delivery, and date of delivery (+/- 6 months). Among the 143 matched gestations, six IVF and seven control infants died, leaving 137 IVF and 136 control neonates for comparison. RESULTS: The IVF mothers had more pregnancy-induced hypertension (21% vs 4%), premature labor (44% vs 22%), labor induction (25% vs 1%), and preterm delivery (37% vs 21%). The IVF infant survivors had a lower mean (+/- SD) birth weight (2623 +/- 857 gm vs 3006 +/- 797 gm), more frequent occurrence of low birth weight (42% vs 27%), and shorter gestations (37 +/- 4 vs 38 +/- 3 weeks). The IVF infants had longer hospitalizations, more days of oxygen therapy, more days of continuous positive airway pressure, and increased prevalence of respiratory distress syndrome, patent ductus arteriosus, and sepsis. CONCLUSIONS: Couples who undergo IVF appear to be at increased risk of having low birth weight and preterm infants, and multiple gestations account for most of the neonatal morbidities. Both the mothers who conceive multiple gestations by means of IVF and their neonates are at an increased risk of having multiple morbidities.

Adult↗
PubMed1995

Laparoscopic-assisted tubal anastomosis.

STUDY OBJECTIVE: To determine the length of procedure, length of hospital stay, complications, and postoperative pregnancy rates of traditional tubal anastomosis (TA) and laparoscopic-assisted TA (LATA). DESIGN: A comparison of 8 women undergoing LATA with 11 patients operated on by the same surgeon during a similar time period who were not candidates for, or did not desire, a laparoscopic approach. SETTING: Academic practice tertiary care setting. PATIENTS: Women requesting reversal of tubal ligation. INTERVENTIONS: Tubal anastomosis by laparoscopy or laparotomy. MEASUREMENTS AND MAIN RESULTS: Patients undergoing the two procedures did not differ by age or parity, although those selected for LATA had a lower body mass index (23.2 +/- 1.4 vs 30.8 +/- 2.0 kg/m2, p = 0.01). Although the LATA took longer (251 +/- 14 vs 194 +/- 10 min, p = 0.004), hospital stay was significantly shorter than for traditional TA (1.8 +/- 0.3 vs 3.0 +/- 0.1 days, p = 0.004). Of the eight LATAs, six were completed and two were converted to laparotomy. For all patients with follow-up, clinical pregnancy rates were 43% and 29% (NS) for TA and LATA, respectively, with 100% of the former and 80% (NS) of the latter group who did not conceive having at least one patent tube on hysterosalpingogram. CONCLUSIONS: Laparoscopic-assisted TA is a possible alternative to the traditional TA performed by laparotomy. Ideal candidates for LATA appear to be women without obesity and with proximal tubal segments of 3 cm or greater. Larger studies with longer follow-up will define appropriate candidates and identify long-term results.

Adult↗
PubMed1995

Follicular fluid insulin-like growth factor-I and insulin-like growth factor-II concentrations vary as a function of day 3 serum follicle stimulating hormone.

We determined follicular fluid concentrations of insulin-like growth factor (IGF)-I, IGF-II and inhibin as a function of day 3 serum follicle stimulating hormone (FSH) in 16 women undergoing follicular fluid aspiration in preparation for in-vitro fertilization and embryo transfer. Follicular fluid concentrations of IGF-I and IGF-II were significantly less in the 'low' FSH group as compared to the 'high' FSH group. The mean IGF-I concentration was 67.6 ng/ml [confidence intervals (CI) 51.6-92.5] in the 'low' FSH group compared to 87.1 ng/ml (CI 72.8-104.2; P < 0.025) in the 'high' FSH group. Mean IGF-II concentrations were 354.8 ng/ml (CI 297.8-422.9) in the 'low' FSH group compared to 489.8 ng/ml (CI 384.6-624.5; P < 0.05) in the 'high' FSH group. Follicular fluid inhibin concentrations did not differ between groups. These differences in follicular fluid IGF as a function of day 3 FSH may raise questions regarding the role growth factors play in the physiological processes of the ageing follicle.

Adult↗