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Biomedical subjects

S A Daniel

Publications and source records attributed to S A Daniel.

At least 19 recordsLinked to original sources
PubMed1996

Future in vitro fertilization pregnancy potential of women with variably elevated day 3 follicle-stimulating hormone levels.

OBJECTIVE: To determine the IVF-ET pregnancy potential of women with variably elevated day 3 FSH. DESIGN: Cohort evaluation of 1,868 consecutive IVF-ET cycles January 1991 to December 1994. SETTING: University hospital infertility unit. PATIENTS: Four cohorts of couples were defined based on day 3 FSH determinations with an arbitrary threshold of 20 mIU/mL, only > or = 20 mIU/mL, always < 20 mIU/mL, current < 20 mIU/mL but one previous > or = 20 mIU/mL, and current < 20 mIU/mL but two or more previous > or = 20 mIU/mL (conversion factor to SI unit, 1.00). INTERVENTION: In vitro fertilization-embryo transfer. MAIN OUTCOME MEASURE: Fetal heart activity on luteal day 40 transvaginal ultrasound. RESULTS: No pregnancies occurred in 53 cycles with day 3 FSH only > or = 20 mIU/mL. In 1,750 women whose day 3 FSH levels were always < 20 mIU/mL, the pregnancy rate (PR) per cycle was 16.5%. In 54 cycles in which day 3 FSH was > or = 20 one time only, but < 20 mIU/mL during the treatment cycle, the PR was 5.6%. In 11 cycles where two or more previous FSH determinations were > or = 20 mIU/mL but with a current day 3 FSH < 20 mIU/mL, no pregnancies occurred. CONCLUSION: Our data leads us to the conclusion that day 3 FSH determination precede every IVF cycle and that cycles with FSH > or = 20 mIU/mL be canceled. It also suggests that women with two previous elevations of day 3 FSH be discouraged from future IVF cycles. The 5.6% pregnancy per cycle with one previously elevated FSH warrants extreme pessimism in discussion of further cycles.

Chorionic Gonadotropin↗
PubMed1995

Confounding variables affecting in vitro fertilization success: a decade of experience.

PURPOSE: To evaluate etiology of infertility, female age, ovarian response and stimulation protocol in affecting in vitro fertilization (IVF) success. METHODS: Retrospective analysis was used. Computer records of all 5209 cycles initiated in 2391 couples from February 1, 1984 to December 31, 1993 were analyzed. RESULTS: There were 644 intrauterine, 24 solely ectopic and 7 heterotopic pregnancies. Pregnancy rates increased with number of embryos transferred with a significant increase still found between transfer of three or four embryos. Multiple gestations also increased in association with an increasing number of embryos transferred. Pregnancy rates per cycle did not decline with repeated cycles. Reduced pregnancy rates were associated with a primary diagnosis of male infertility. Covariates associated with a better pregnancy rate were younger age of the female partner or higher peak preovulatory serum estradiol. Routine administration of GnRH-agonist was associated with a reduced cycle cancellation rate, an increase in oocytes retrieved and an improved pregnancy rate. CONCLUSIONS: Couples with male infertility and increased female age should be counselled regarding the reduced prognosis for success.

Age Factors↗
PubMed1995

Epidermal growth factor (EGF) receptor localization in cultured human granulosa lutein cells and the stimulation of progesterone production by EGF and transforming growth factor-alpha (TGF-alpha).

PURPOSE: The purpose of this study was to investigate the expression of EGF receptor (EGF-R) in human granulosa cells undergoing luteinization and progesterone production by these cells in response to EGF an TGF-alpha alone or in combination with luteinizing hormone (LH). Granulosa cells were obtained from IF patients following oocyte retrieval 34 to 36 hr post-hCG injection. EGF receptor was localized in cells by means of immunoperoxidase staining using a polyclonal primary antibody directed against the human EGF-R. To assess progesterone production, cells were seeded overnight, washed, and cultured with the growth factors +/- LH. Medium and treatments were changed every 24 hr for 3 days. RESULTS: Specific EGF-R staining was observed in the cultured cells compared to those incubated with antibody that was preabsorbed with a 10-fold excess of EGF. Basal progesterone accumulation per 24-hr period was stimulated dose dependently on each day of culture, by both EGF (up to 3.5-fold at 5 or 50 ng/ml) and TGF-alpha (up to 4-fold at 50 ng/ml). The addition of LH alone also stimulated progesterone accumulation daily, and this effect was further enhanced dose dependently by cotreatment with EGF or TGF-alpha. Furthermore, tyrphostin, an EGF-R-specific tyrosine kinase inhibitor, inhibited both basal and growth factor-stimulated progesterone production. CONCLUSION: These data suggest an EGF receptor-mediated physiological role for EGF and TGF-alpha in human luteal function involving an autocrine and/or a paracrine stimulation of progesterone production.

Cells, Cultured↗
PubMed1995

Randomized trial of partial zona dissection for male infertility.

OBJECTIVES: To compare IVF rates using partial zona dissection versus zona intact insemination in couples with male infertility. To analyze pregnancy rates relative to sperm characteristics, fertilization rates, and treatment. DESIGN: Randomized prospective comparison of fertilization in sibling oocytes. Transfer of the three best quality embryos from one or both treatments. SETTING: Department of Gynaecology and Reproductive Medicine, University Hospital, London, Ontario, Canada. PARTICIPANTS: Thirty-two couples undergoing IVF with a principal diagnosis of male infertility. INTERVENTION: Treatment with partial zona dissection. MAIN OUTCOME MEASURES: Fertilization and pregnancy. RESULTS: Fertilization rates were 26% and 9% after partial zona dissection and IVF, respectively. Polyspermy was < 1% in each treatment. There were five singleton pregnancies in 29 completed cycles, three in cycles with fertilization only by partial zona dissection and two in cycles with both partial zona dissection and IVF fertilization. There were no pregnancies after fertilization by IVF only. Stepwise logistic regression analysis indicated that pregnancy was related to partial zona dissection, initial sperm concentration, and total acrosin activity. CONCLUSION: Partial zona dissection was associated with minimal polyspermic fertilization and higher normal fertilization rates than sibling oocytes treated by modified IVF. Pregnancy occurred only after transfer of embryos from partial zona dissection or combined partial zona dissection and IVF.

Adult↗
PubMed1994

Transferring more embryos increases risk of heterotopic pregnancy.

OBJECTIVES: To analyze symptoms and signs that may distinguish heterotopic pregnancy from solely ectopic pregnancy (EP) after IVF. To determine if the number of embryos transferred is a risk factor for heterotopic compared with solely EP. DESIGN: Retrospective cohort of 587 IVF pregnancies, 328 with distorted tubal anatomy. SETTING: University Hospital, London, a referral center for Ontario provincial government-supported assisted reproductive technologies. PARTICIPANTS: Couples undergoing IVF. INTERVENTION: None. MAIN OUTCOME MEASURES: Heterotopic pregnancy, solely EP, intrauterine pregnancy, and distorted pelvic anatomy. RESULTS: Of 587 pregnancies, 7 were heterotopic pregnancies and 24 were solely EP, all in the subset of 328 women with distorted tubal anatomy. Symptoms, signs and time of diagnosis were not different between heterotopic and solely ectopic gestations. Compared with solely EP, heterotopic pregnancies were associated with transfer of more embryos. With four or more embryos transferred, the odds ratio for development of heterotopic versus solely ectopic gestation was 10.0. CONCLUSION: Heterotopic pregnancy occurred in 2% of gestations after IVF, all in women with distorted tubal anatomy. Transfer of four or more embryos was a risk factor for heterotopic pregnancy.

Adult↗
PubMed1993

Risk of repeated spontaneous luteinizing hormone surges in ovarian stimulation for in vitro fertilization.

Although spontaneous luteinizing hormone (LH) surges are preventable with gonadotropin releasing hormone agonist (GnRH-a) inclusion in ovarian stimulation protocols, GnRH-a-containing protocols are more expensive and associated with an increased risk of ovarian hyper-stimulation syndrome. The present study assessed whether spontaneous LH surges occur in predictable patterns, allowing GnRH-a to be utilized selectively. We assessed 1,103 patients receiving clomiphene citrate/human menopausal gonadotropin (CC/hMG) without GnRH-a for their first in vitro fertilization (IVF) cycle and observed spontaneous LH surges in 30.4%. When patients who demonstrated a spontaneous LH surge received a second CC/hMG stimulation protocol, 45.9% surged again. Of those patients who did not demonstrate a spontaneous LH surge in their initial CC/hMG cycle, only 23.0%, significantly less (P < .001), surged in their second cycle. Of those patients who did not surge in their first two cycles, only 15.7% had an LH surge in their third cycle (P < .001). Thus, if all patients received CC/hMG without GnRH-a as their first IVF stimulation protocol, GnRH-a could be reserved for patients who have demonstrated a spontaneous LH surge. By tailoring the treatment plan, the pregnancy rate would be optimized while decreasing cycle cancellations due to spontaneous LH surges in those patients susceptible to LH surges and limiting costs and inconvenience for patients unlikely to surge spontaneously.

Female↗
PubMed1992

Randomized, prospective comparison of luteal leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins in 408 first cycles of in vitro fertilization.

OBJECTIVE: To compare luteal phase leuprolide acetate (LA) initiated pituitary down regulation followed by human menopausal gonadotropins (hMG) versus clomiphene citrate (CC) and hMG for follicular recruitment and oocyte maturation before in vitro fertilization (IVF). DESIGN: Randomized, prospective comparison in first cycles of IVF. SETTING: University Hospital, a tertiary referral center offering assisted reproductive technologies. PARTICIPANTS: Participants were couples undergoing their first ever cycle of IVF and consenting to participation in the trial. RESULTS: Luteal phase initiated LA/hMG was associated with a lower probability of cycle cancellation, improved folliculogenesis, and a higher probability of embryo transfer (ET) compared with CC/hMG alone. Implantation rates were not different. CONCLUSION: A higher rate of ET with LA/hMG suggests that gonadotropin-releasing hormone agonist for the induction of folliculogenesis before IVF may be appropriate.

Clomiphene↗
PubMed1991

Total acrosin activity correlates with fertility potential after fertilization in vitro.

OBJECTIVE: To evaluate the possible relationship between total acrosin activity in spermatozoa and fertility potential after fertilization in vitro. DESIGN: Total acrosin activity of spermatozoa was measured in 101 in vitro fertilization (IVF) cases by an observer unaware of fertilization and cleavage results. SETTING: University Hospital is a tertiary referral center offering a government supported In Vitro Fertilization Programme. PARTICIPANTS: Participants were couples undergoing IVF. INTERVENTIONS: A miniature assay measured total acrosin activity in the semen sample used for IVF. OUTCOME MEASURES: The proportion of mature oocytes fertilized, the proportion of mature oocytes transferred, and fertilization of at least one mature oocyte were considered outcomes with fertility potential. RESULTS: Total acrosin activity correlated with both the proportion of mature oocytes fertilized and the proportion of mature oocytes that were transferred as cleaving embryos. Total acrosin activity was higher in cycles when one or more mature oocyte fertilized compared with cycles with failed fertilization of all mature oocytes. CONCLUSIONS: The likelihood ratio for subnormal results indicates that measurement of total acrosin activity is a fair test of the fertilizing capacity of sperm.

Acrosin↗
PubMed1990

Follicle-stimulating hormone and estradiol regulate antrum-like reorganization of granulosa cells in rat preantral follicle cultures.

Formation of a fluid-filled antrum results from the actions of FSH and estrogen on preantral ovarian follicles in most mammalian species. To investigate the novel proposal that hormone-regulated cell-cell interactions mediate antrum formation, we isolated preantral follicles from infant (10- or 11-day-old) Wistar rats and cultured them in a substratum-adherent manner in Minimum Essential Medium supplemented with 2 mM hypoxanthine, 3 mg/ml bovine serum albumin, 5 micrograms/ml insulin, 5 micrograms/ml transferrin, and 5 ng/ml selenium. Similar cultures were previously shown to support oocyte growth and acquisition of meiotic competence. In the absence of FSH, follicles attached to the plastic surface and granulosa cells spread-out uniformly around granulosa cell-enclosed oocytes. FSH treatment caused certain follicles to show an increase between culture days 3 and 7 in appearance of conspicuous antrum-like reorganization of the granulosa cells, but without forming a completely enclosed fluid-filled cavity. This response was biphasic over 10-500 ng/ml FSH, with an optimal concentration of 50 ng/ml resulting in a mean of 37.8 +/- 4.7% of follicles showing antrum-like reorganization for 3 similar experiments. Estradiol-17 beta alone at 10(-10)-10(-8) M was without effect on this response, but at 10(-10) and 10(-9) M, it significantly augmented the action of an optimal concentration of FSH by about 2-fold in 4 experiments. In these experiments, the effect of 10(-8) M estradiol was not significantly different from FSH alone, indicating that the response to estradiol was also biphasic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Maintenance of meiotic arrest in mouse oocytes by purines: modulation of cAMP levels and cAMP phosphodiesterase activity.

Hypoxanthine and adenosine are present in preparations of mouse ovarian follicular fluid, and these purines maintain mouse oocytes in meiotic arrest in vitro (Eppig et al.: Biology of Reproduction 33:1041-1049. 1985). The first hypothesis tested in this study is that purines which maintain meiotic arrest act by maintaining meiosis-arresting levels of cyclic adenosine monophosphate (cAMP) in the oocyte. Oocyte-cumulus cell complexes were incubated in control medium (no added purines), or medium containing 0.75 mM adenosine, 4 mM hypoxanthine, or both for 3 hr and the percentage of the oocytes that underwent germinal vesicle breakdown (GVB) and the cAMP content of the intact complexes and the oocytes were determined. Adenosine alone had little inhibitory effect on GVB at this time point but sustained higher levels of cAMP in the oocytes. Hypoxanthine maintained 80% of cumulus cell-enclosed oocytes in meiotic arrest and also sustained higher cAMP levels in the oocytes. The addition of adenosine to hypoxanthine-containing medium increased the percentage of oocytes maintained in meiotic arrest, and increased the amount of cAMP in the oocytes above that maintained by either hypoxanthine or adenosine alone. Neither hypoxanthine, adenosine, nor hypoxanthine plus adenosine altered the cAMP content of intact complexes when assayed after 3 hr culture. Microinjection of an inhibitor of the catalytic subunit of cAMP-dependent protein kinase induced GVB in denuded oocytes cultured in medium containing hypoxanthine. This purine, therefore, maintained meiotic arrest by sustaining elevated cAMP levels within the oocytes. The second hypothesis tested in this study is that purines maintain meiosis-arresting levels of cAMP, at least in part, by inhibiting cAMP phosphodiesterase activity. In descending order of potency, 3-isobutyl-1-methylxanthine (IBMX), guanosine, hypoxanthine, adenosine, and xanthosine inhibited cAMP phosphodiesterase in oocyte lysates. Moreover, like the potent phosphodiesterase inhibitor IBMX, hypoxanthine augmented the meiotic arrest and cAMP accumulation mediated by follicle-stimulating hormone (FSH) in intact complexes. Therefore, inhibition of oocyte phosphodiesterase appears to be one mechanism by which the purines could maintain meiosis-arresting levels of cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Growth and development of rat oocytes in vitro.

Rat oocytes from preantral follicles have been shown to grow and acquire meiotic competence in vitro. Follicles were isolated by enzymatic digestion of ovaries from infant (10- or 11-day-old) Wistar rats. Follicles were cultured for up to 20 days in Minimum Essential Medium (MEM) supplemented with 2 mM hypoxanthine to maintain meiotic arrest. When cultures were begun, oocytes were in midgrowth phase (40-45 microns diameter), and were incapable of undergoing meiotic maturation when placed in hypoxanthine-free MEM. Oocytes grew and acquired meiotic competence during culture for 20 days attaining mean diameters of 62.6 +/- 0.6 microns and 61.1 +/- 0.6 microns in two experiments. Germinal vesicle breakdown (GVB) occurred in 60-70% of oocytes when transferred to MEM without hypoxanthine. Concomitant with oocyte growth and maturation were spontaneous increases in follicular production of progestins, androgens and estrogens. When oocytes grown and matured in this system were inseminated in vitro with epididymal sperm, 36.1% and 25.8% were penetrated by one or more sperm in two experiments. However, fertilization was not generally normal with multiple penetrations and abnormal numbers of pronuclei (one or three) being common, suggesting that in these oocytes cytoplasmic maturation was incomplete or abnormal. In the two experiments, normal fertilization (two pronuclei and one sperm tail in the vitellus) occurred in 34.6% and 47.1% of penetrated oocytes with development of these apparently normal zygotes to two-cell embryos being 66.7% and 62.5%, respectively.

20-alpha-Dihydroprogesterone↗
PubMed1989

Preovulatory biosynthesis and granulosa cell secretion of immunoreactive oxytocin by goat ovaries.

Oestrous cycles of goats were synchronized hormonally. Immunoreactive oxytocin was undetectable (less than 0.1 ng/mg protein) in media from granulosa cells isolated before the LH surge for small (1-2 mm), medium (3-5 mm) and large (greater than 5 mm diameter) follicles when cultured for 24 h without or with added hormones. Granulosa cells from large and medium, but not small, follicles isolated 6-12 h after spontaneous preovulatory LH surges secreted high concentrations of oxytocin (4-12 ng/mg protein). Addition of PGE-2 (1 microgram/ml) caused a further significant (P less than 0.05) increase in oxytocin secretion by cultured granulosa cells, whereas PGF-2 alpha, FSH and LH were ineffective when added to culture media. Ovarian venous blood and granulosa cells were collected at 0, 6, 12 or 18 h after GnRH injection in hormonally synchronized goats. Peripheral serum LH values were increased significantly in all but 2 of 22 goats within 2 h of GnRH injection. At the earliest sampling time after GnRH (6 h), ovarian venous levels of oxytocin were increased significantly from basal levels of 0.4 pg/ml to 2.4 pg/ml. Oxytocin concentrations in follicular fluid increased from a basal value of 67 pg/ml to 155 pg/ml by 6 h and to 372 pg/ml by 18 h after GnRH injection. Oxytocin secretion by cultured granulosa cells was not increased significantly by 6 h (0.1 ng/mg protein) but rose to 1.4 and 3.5 ng/mg protein at 12 and 18 h, respectively. Approximately parallel increases occurred in progesterone in ovarian venous blood and granulosa cell culture media over the same time period. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Induction of maturation in cumulus cell-enclosed mouse oocytes by follicle-stimulating hormone and epidermal growth factor: evidence for a positive stimulus of somatic cell origin.

The efficacy of follicle-stimulating hormone (FSH), epidermal growth factor (EGF), and dibutyryl cGMP (dbcGMP) as inducers of germinal vesicle breakdown (GVBD) in cumulus cell-enclosed mouse oocytes was examined when meiotic arrest was maintained in vitro with purines, dibutyryl cAMP (dbcAMP), or the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). When FSH was added to hypoxanthine (HX)-containing medium, the effect on oocyte maturation was at first inhibitory and later stimulatory. EGF stimulated GVBD at all time points tested. FSH and EGF also induced GVBD when oocytes were arrested with dbcAMP, IBMX, or guanosine. Dibutyryl cGMP stimulated GVBD when meiotic arrest was maintained with HX, but not when oocytes were meiotically arrested with guanosine, and was inhibitory in dbcAMP-supplemented medium. FSH and dbcGMP produced a transient delay of oocyte maturation in control medium, but the FSH effect was much more pronounced. EGF had no effect on maturation kinetics. The actions of FSH and EGF required the presence of cumulus cells. Both agents significantly stimulated cAMP production in oocyte-cumulus cell complexes. A brief exposure of complexes to a high concentration of dbcAMP induced GVBD, suggesting that FSH and EGF may act via a cAMP-dependent process. The frequency of FSH- and EGF-induced GVBD in cumulus cell-enclosed oocytes was significantly higher than the frequency of GVBD when oocytes were cultured while denuded of cumulus cells. of maturation is apparently not mediated solely by oocyte-cumulus cell uncoupling and termination of the transfer of an inhibitory meiotic signal from cumulus cells to the oocyte. The data suggest the generation of a positive signal within cumulus cells in response to hormone treatment that acts upon the oocyte to stimulate GVBD in the continued presence of inhibitory factors.

Animals↗
PubMed1988

In vitro fertilization: diurnal and seasonal variation in luteinizing hormone surge onset and pregnancy rates.

The authors studied 740 consecutive in vitro fertilization (IVF) cycles over a 3-year period to compare the results of cycles in which an endogenous luteinizing hormone (LH) surge occurred with cycles in which human chorionic gonadotropin (hCG) was administered for induction of follicular maturation. Clomiphene citrate (100 to 150 mg daily on cycle days 5 to 9) and human menopausal gonadotropin (hMG; 75 to 150 IU daily from cycle day 6) were used for stimulation. Embryo transfer (ET) occurred in 164 (81.2%) of the LH surge cycles and 452 (84%; P = not significant [NS] of the hCG cycles. The first urinary rise in LH was detected in the 6 or 9 A.M. collections in 78 (47.3%) of the LH surge cycles, a greater number (P less than 0.01) than expected if LH surge onset was random. A total of 107 pregnancies was achieved, for an overall pregnancy rate of 17.4% per ET. The pregnancy rate in the hCG-stimulated cycles was 13.9% per ET (63/452) and, in spontaneous LH surge cycles, was 28.8% (44/166; P less than 0.001). The spontaneous abortion rate was 9.1% in LH surge cycles, compared with 25.4% in hCG-triggered cycles (P less than 0.001). The result was a 2.4 times increase in live births for LH surge cycles compared with cycles in which hCG was administered. In this program, occurrence of an LH surge is a favorable event, associated with higher pregnancy and live birth rates than hCG-stimulated cycles, and usually occurring in the early morning, allowing oocyte retrieval during normal working hours.

Adult↗
PubMed1987

Prostaglandin E2 enhances uterine stromal cell alkaline phosphatase activity in vitro.

Prostaglandins have been implicated in the process of uterine decidualization in vitro, but sites of action are uncertain. Since one of the earliest changes in endometrial stroma following induction of decidualization is an increase in alkaline phosphatase activity, we have investigated the effects of PGs on stromal cell alkaline phosphatase activity in vitro. Immature rats were pretreated with hormones to sensitize their uteri for the decidual cell reaction. Endometrial stromal cells were isolated and cultured for up to 4 days with PGE2 (0-10 micrograms/ml) or PGF2 (0-10 micrograms/ml). Analysis of variance revealed a highly significant interaction between day of culture and concentration of PGE2 in medium (P less than 0.01). Stromal cell alkaline phosphatase activity decreased significantly with increasing culture duration (P less than 0.01). In the presence of PGE2, alkaline phosphatase activity was significantly higher (P less than 0.01) regardless of day of culture. In contrast, PGF2 alpha had only a small and inconsistent effect. These data indicate that PGs, and in particular PGE2, can act directly upon stromal cells.

Alkaline Phosphatase↗
PubMed1987

In vitro fertilization: determination of follicular maturation for timing of human chorionic gonadotropin administration.

Hyperstimulation protocols for IVF require critical timing of hCG administration to complete follicular maturation. We studied 170 IVF cycles in 142 patients and retrospectively compared ultrasound and endocrine parameters in pregnancy cycles and spontaneous LH surge cycles with nonpregnancy, non-LH surge cycles. Twenty-six of the 170 cycles resulted in a pregnancy (15.2%). Oocytes were recovered from 27 of 31 cycles in which a spontaneous LH surge occurred, and 9 of these cycles produced a pregnancy (33%). Follicle number and serum E2 on the day of ultrasound (cycle day 12 or 13) was lower in the LH surge group and pregnancy group than in the nonpregnant, non-LH surge group. In contrast, on the day of hCG administration or LH surge, serum E2 concentration per follicle greater than 1 cm in diameter was higher in the combined LH surge/pregnancy group (1219 pmol/l) than in the nonpregnancy/non-LH surge group (932 pmol/l). Our data suggest that it may be possible to individualize hCG administration at midcycle by determining the number of follicles greater than 1 cm by ultrasound on cycle day 12 or 13 and giving hCG when serum E2 levels reach 1100 to 1200 pmol/l per follicle.

Adult↗