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Biomedical subjects

R N Clarke

Publications and source records attributed to R N Clarke.

At least 19 recordsLinked to original sources

The prognostic value of age and follicle-stimulating hormone levels in women over forty years of age undergoing in vitro fertilization.

PURPOSE: Basal follicle-stimulating hormone (FSH) and age are predictors of successful outcome in in vitro fertilization (IVF). More recently, the clomiphene citrate challenge test (CCCT) has been proposed as a better way to predict IVF outcome than FSH alone. The purpose of this study was to determine which indicator of ovarian reserve--basal (day 3) FSH or the CCCT--is the better predictor of IVF success in the critical age group of women over the age of 40. METHODS: In this retrospective study, basal FSH and clomiphene-stimulated FSH levels from 104 women who underwent 175 cycles of IVF were analyzed. RESULTS: Neither basal FSH level nor stimulated FSH level alone were statistically significant predictors of IVF success; however, no patient with a day 3 FSH level > 11.1 mIU/ml or a stimulated day 10 FSH level > 13.5 mIU/ml conceived and carried a pregnancy. All ongoing pregnancies occurred in the first two cycles of IVF. CONCLUSIONS: Clear prognostic cutoff values were found to predict IVF success in women over age 40. IVF programs should consider limiting the number of cycles of IVF in women above age 40.

Adult↗

Power frequency electromagnetic fields and health. Where's the evidence?

Twenty years ago concerns were raised that exposure to power frequency (or extremely low frequency (ELF)) electromagnetic fields (EMFs) may be associated with an increased risk of cancer or other health hazards. Subsequently no associations have been shown between laboratory magnetic field exposures and carcinogenesis in either animal or cellular models. Indeed, studies have demonstrated that magnetic fields are not associated with cancer. However, the puzzle remains that the results of some epidemiological studies may be interpreted as suggesting that living close to high-voltage transmission (HVT) lines appears to increase slightly the risk of childhood leukaemia. Alternatively, these results could result from small biases and errors in individual studies, which might not necessarily be the same in each study. The nature of the epidemiological studies (power-line, wire code, magnetic field or appliance based) appears to determine whether and how the EMFs associated with HVT lines might be a risk factor. It is possible that a simple association with either magnetic or electric field exposure may not be the whole answer, and an alternative mechanism is always a possibility. Although the interpretation of the available evidence by most expert bodies has led them to conclude that exposure to power frequency electric and magnetic fields is not a human health hazard, a working group under the auspices of the US National Institute of Environmental Health Sciences (NIEHS) concluded that there was a possible low risk associated with certain exposures to ELF magnetic fields. NIEHS itself interpreted the finding as insufficient to warrant aggressive regulatory concern but stated that, because virtually everyone is routinely exposed to ELF EMFs, passive regulatory action is warranted, such as a continued emphasis on educating both the public and the regulated community on means aimed at reducing exposures. These analyses, conclusions and advice are not contradicted by subsequent studies, and therefore the conclusion of the World Health Organisation that further research is needed seems valid.

Electromagnetic Fields↗

The Graafian follicle is a site of L-ascorbate accumulation.

PURPOSE: Our purpose was to evaluate the L-ascorbate level in human preovulatory follicular fluid and to quantify the blood/follicle gradient for vitamin C. The effect of smoking on the follicular L-ascorbate concentration was studied. The correlations were tested between follicular L-ascorbate and follicle size and oocyte maturity. METHODS: In 65 women undergoing in vitro fertilization, samples of follicular fluid and blood serum were collected. Biochemical analyses included L-ascorbate determinations by a colorimetric method and cotinine measurements by a radioimmunoassay. RESULTS: The average follicular fluid:serum ratio for L-ascorbate was 1:68. Ascorbate levels in follicular fluid and serum were significantly correlated. The follicular L-ascorbate level did not correlate with the follicle size and the oocyte maturity grade. Insignificantly lowered follicular L-ascorbate levels were observed in smokers. CONCLUSIONS: The extracellular compartment of the Graafian follicle is a site of an ascorbate accumulation. Exposure to tobacco smoke does not significantly diminish the intrafollicular pool of L-ascorbate.

Adult↗

Relationship between psychological stress and semen quality among in-vitro fertilization patients.

The purpose of this study was to determine the relationship between psychological stress and semen quality among men undergoing in-vitro fertilization (IVF). We assessed psychological variables, including self-reported stress, and sperm parameters in a group of 40 men undergoing IVF for the first time at a pre-IVF sampling period (T1) and at the time of egg retrieval (T2). Thirty-one patients completed the study. Results indicated that total and motile sperm concentration, total motile spermatozoa, and lateral head displacement decreased significantly from T1 to T2 in a high percentage of participants. In addition, the perceived importance of producing a semen specimen increased significantly (P = 0.001) from T1 to T2, and this change was significantly correlated (P < 0.05) with diminished semen quality at the time of oocyte retrieval. No decline in the semen quality or increase in perceived stress at egg retrieval was observed at T2 in male factor patients (n = 7). This study provides evidence for a significant decline in semen quality of male IVF patients at egg retrieval and demonstrates an inverse relationship between semen quality and specific aspects of psychological stress.

Anxiety↗

Multinucleation in normally fertilized embryos is associated with an accelerated ovulation induction response and lower implantation and pregnancy rates in in vitro fertilization-embryo transfer cycles.

OBJECTIVE: To determine if multinucleation in normally fertilized embryos is indicative of poor developmental or clinical pregnancy prognosis and to examine the ovulation induction characteristics associated with multinucleation. DESIGN: Retrospective review. SETTING: A tertiary care institution. PATIENT(S): Patients undergoing IVF-ET cycles (exclusive of other assisted reproductive technologies). MAIN OUTCOME MEASURE(S): Cycles in which embryos had at least 1 multinucleated blastomere were compared with cycles in which all blastomeres exhibited no nucleus or a single nucleus (control). RESULT(S): When >50% of transferred embryos contained multinucleated blastomeres there was a significant reduction in implantation (3.4% vs. 14.7%), clinical pregnancy (9.1% vs. 29.1%), and live birth rates (7.5% vs. 27.6%) when compared with transfers of control embryos. In conjunction with this finding, multinucleate cycles had higher E2 levels and more follicles on the day of hCG administration, a higher number of oocytes retrieved, a higher fertilization rate, and more embryos transferred per patient than did the cycles that produced control embryos. When multinucleated embryos were present, but not transferred, the developmental capacity of the sibling embryo was reduced. CONCLUSION(S): The evaluation of nuclear status using simple light microscopy is predictive of embryo developmental capacity and should be included in the embryo scoring system. The presence of multinucleated blastomeres in normally fertilized embryos is associated with a more effusive response to gonadotropin therapy and is indicative of a poor developmental outcome and lower clinical pregnancy rates.

Adult↗

Effects of endometriomas on ooccyte quality, embryo quality, and pregnancy rates in in vitro fertilization cycles: a prospective, case-controlled study.

PURPOSE: The effect of endometriomas on oocyte quality, embryo quality, and pregnancy rates in in vitro fertilization (IVF) cycles was evaluated. METHODS: Forty-five women had "chocolate" cysts aspirated at the time of oocyte retrieval, and cyst fluid CA 125 levels were measured to ascertain presence of "true" endometriomas. Fifty-seven women without any complex cysts at the time of oocyte retrieval served as controls. IVF cycle outcome parameters were compared between the two groups. RESULTS: Women with endometriomas experienced a significantly higher rate of early pregnancy loss compared to controls (47 vs 14%). There was also a trend toward fewer oocytes retrieved and fewer embryos reaching at least the four-cell stage 48 hr after retrieval in patients with true endometriomas vs controls. CONCLUSIONS: The presence of endometriomas at the time of oocyte retrieval is associated with increased rates of early pregnancy losses. The number of oocytes retrieved and the embryo quality may also be affected adversely in the presence of endometriomas.

CA-125 Antigen↗

A low dielectric constant customized phantom design to measure RF coil nonuniformity.

The selection of a suitable low dielectric constant liquid for radiofrequency coil nonuniformity measurements is described. Measurements of dielectric constant (relative permittivity) were made on a range of candidate liquids. After excluding liquids that were too inflammable or too viscous, Esso Bayol 82 oil (dielectric constant epsilon' = 2.37) was chosen. At 1.5 T, a 27 cm diameter cylindrical phantom (test object) filled with Bayol 82 has a maximum nonuniformity of 1.9% arising from radiofrequency standing waves. The maximum diameter cylinder that can be used without the nonuniformity exceeding 2% is given for a range of liquids and field strengths. The construction of customized containers that fit closely inside a radiofrequency head coil from glass fiber reinforced resin ("fiberglass") is described. Thermal expansion of the liquid takes place without a rise in the internal pressure in the container.

Dimethylpolysiloxanes↗

A randomized clinical trial to evaluate the clinical effects of split- versus single-dose human menopausal gonadotropins in an assisted reproductive technology program.

OBJECTIVE: To compare the effect of twice (split) versus once (single) daily administration of hMG on assisted reproductive technology (ART) cycle parameters. DESIGN: A randomized clinical trial. SETTING: Hospital-based academic ART program. PATIENTS: A total of 171 patients undergoing their initial ART cycle were enrolled. All patients received one of two hMG regimens and were excluded from the study if they were receiving medications other than leuprolide acetate (LA) and hMG for ovulation induction. INTERVENTIONS: Subjects were randomized to receive an initial dose of 300 IU/d of hMG in either split-dose (i.e., 150 IU twice daily) or single-dose fashion for four successive days after down-regulation with LA. Thereafter, their daily dose was individualized, maintaining a split-or single-dose schedule. All cycles were managed in accordance with our standard ART protocols. MAIN OUTCOME MEASURES: Cancellation rate, total hMG requirements, number of days treated with hMG, E2 and P responses, oocyte yield and maturity, fertilization rate, total number of embryos, embryo quality, number of embryos transferred, implantation rate, clinical and ongoing-delivered pregnancy rates. RESULTS: Split-dose hMG administration resulted in a significantly higher implantation rate, but significantly lower normal and polyspermic fertilization rates than single-dose hMG administration. No significant differences were noted between the two dosage protocols with respect to the other outcome measures. CONCLUSIONS: Split-dose hMG administration may be associated with significantly higher implantation rates; single-dose hMG with significantly higher fertilization rates. Although our data also demonstrate a trend toward higher clinical and ongoing-delivered pregnancy rates with split-dose therapy, demonstration of a significant difference would require a multicenter trial. Based on our data, clinicians may want to consider split-dose therapy for patients with repeated implantation failures.

Adult↗

Antioxidative capacity of preimplantation embryo culture medium declines following the incubation of poor quality embryos.

Total antioxidative capacity (TAC), a measure of overall free-radical scavenging potential, was determined by enhanced chemiluminescence in preimplantation embryo culture medium (PECM; pre-equilibrated Ham's F-10 medium supplemented with 7.5% patient's serum). Changes were evaluated in PECM TAC following a 24 h incubation of 66 single human embryos, as was TAC of patient's serum alone. The PECM TAC averaged 8.1% of the same patient's blood serum TAC. The percentage decline of PECM TAC over an incubation period of 24 h ranged from 0.9 to 41.7%, with a median of 5.5%. The decline in PECM TAC in different embryo quality groups was also studied. Embryos were categorized as 'good', 'fair' or 'poor' according to a scoring system based on an assessment of both the morphological appearance and developmental speed of the embryos. Incubation of poor quality embryos was associated with a decline in TAC, which was significantly higher than that observed in 'good' and 'fair' embryos. The findings suggest that impaired embryo development may be associated with an increased generation of reactive oxygen species by the embryo.

Adult↗

Screening of maternal sera using a mouse embryo culture assay is not predictive of human embryo development or IVF outcome.

PURPOSE: Maternal serum is commonly added to media used for human IVF but can vary widely in its ability to support the development of human embryos in vitro. The objective of this study was to determine if the screening of maternal serum with a mouse one-cell embryo culture assay would be useful in predicting human embryo development and clinical outcome following IVF. METHODS: Twenty-two individual serum samples from IVF patients were used as a supplement (7.5%) to Ham's F-10 media for culturing human embryos. All embryos were evaluated at the time of transfer for stage of development and embryo quality. Each serum sample was also tested for its ability to support mouse embryo development. One-cell embryos were recovered from superovulated female mice and cultured in serum-supplemented media. Mouse blastocyst development was assessed after 96 h of incubation. RESULTS: No correlation was found between mouse blastocyst formation and human embryo development in media supplemented with maternal sera. Similarly, there was no association between the development of mouse blastocysts and clinical outcome following IVF. A subanalysis of patients whose sera tested poorly on the mouse assay again revealed no association between mouse and human embryo development. CONCLUSION: Mouse embryo development in media containing human serum did not predict development of human embryos in vitro or clinical outcome following IVF. There would be little benefit to screening maternal sera using a mouse embryo culture system for determining its suitability for use in human IVF.

Animals↗

A self-programmable in vitro fertilization/gamete intrafallopian transfer patient database management system for MacIntosh computers.

PURPOSE: Our purpose was to develop a data processing system for a large in Vitro Fertilization/Gamete Intrafallopian Transfer (IVF/GIFT) practice which would (1) require minimal data entry time, (2) be easy to operate, (3) be simple to construct (no knowledge of procedural language or programming necessary), and (4) quickly collate and reduce data. RESULTS: A database management system was successfully constructed on an Apple MacIntosh computer which met the above criteria. The key elements of this database were its user-friendly features (MacIntosh-based system), adaptability (user was constantly able to update and revise the program as informational needs changed), and ability to perform complex searches and data analyses imposed by the individual operators. CONCLUSIONS: The software and hardware described in this report were found to be highly effective in meeting the ever-changing administrative and clinical needs of our IVF/GIFT program.

Database Management Systems↗

The appearance of one-pronuclear human oocytes is associated with a better ovulation-induction response and successful pregnancy outcome.

OBJECTIVE: To study the relationship between the presence of one-pronuclear oocytes in in vitro fertilization (IVF) patients and ovulation-induction response, oocyte and embryo development, and clinical outcome. DESIGN: Retrospective analysis of 535 consecutive IVF retrievals. Retrievals in which one or more oocytes exhibited one pronucleus were compared with retrievals in which no one-pronuclear oocytes (control) were observed. The following one-pronuclear versus control subgroups were also examined: leuprolide acetate/human menopausal gonadotropin (LA/hMG) ovulation inductions, high estradiol (E2) response cases, and retrievals in which a large number of oocytes (greater than or equal to 15) were recovered. SETTING: Brigham and Women's Hospital, a tertiary care, university-affiliated hospital. PATIENTS: Three hundred forty-six IVF patients were treated between January 1989 and May 1991. MAIN OUTCOME MEASURES: Parameters examined included E2 concentration and number of follicles with maximum diameter greater than or equal to 12 mm on day of human chorionic gonadotropin administration; number of total and mature oocytes retrieved; total fertilization rates; number of embryos; and percent per retrieval of embryo transfers (ETs), clinical pregnancies, and ongoing-livebirths. RESULTS: The one-pronuclear patients had higher E2 levels and larger number of follicles, yielded significantly more total and mature oocytes, had a higher overall fertilization rate, produced more embryos, and had higher ET, clinical pregnancy and ongoing-livebirth rates per retrieval than did the control patients. Analysis of the subgroup populations revealed no significant differences in the majority of the main outcome measures studied; however, the one-pronuclear patients yielded significantly more total and mature oocytes per retrieval. CONCLUSIONS: Although there was an increase in the clinical and ongoing-livebirth pregnancy rates (PRs) in one-pronuclear patients, this was probably associated with an improved ovulation-induction response in the one-pronuclear patients. They achieved significantly higher E2 levels, recruited a larger number of follicles, and yielded more oocytes and embryos per retrieval than the control patients. When only the LA/hMG, E2 greater than or equal to 1,500 pg/mL, or the greater than or equal to 15 oocytes/case retrievals were analyzed, the PRs were no longer different; however, the one-pronuclear patients still yielded significantly more total and mature oocytes per retrieval than the controls. Therefore, the appearance of one-pronuclear oocytes is probably associated with the maturation stage of the oocytes obtained and is indicative of an ovulation induction in which a large number of preovulatory, metaphase II oocytes have been recruited.

Cell Nucleus↗

Sperm DNA and sex chromosome differences between two geographical populations of the creeping vole, Microtus oregoni.

The relative DNA content of the "O" and Y chromosome-bearing sperm is presented for the creeping vole, Microtus oregoni. The animals had been trapped in Oregon and in Washington State. The two populations had very similar autosomal chromosome relationships but differed greatly in the size of their X chromosome (which is not carried by vole sperm) and in their Y chromosome. The greater size and banding differences of the Y chromosome of the Washington State vole compared to the Oregon vole paralleled the greater differences in sperm DNA between the Y-bearing sperm and the sperm carrying no sex chromosome (O). The actual DNA differences between O and Y sperm was 12.5% for the sperm from the Washington State voles and 9.1% for sperm from the Oregon voles. The difference in sperm DNA content (12.5%) for Washington State voles was far greater than the difference shown for other voles or other mammals.

Animals↗

Development of a noninvasive ultramicrofluorometric method for measuring net uptake of glutamine by single preimplantation mouse embryos.

A noninvasive ultramicrofluorometric method for measuring net uptake of glutamine by single preimplantation mouse embryos is described. A linear relationship was found between fluorescence intensity of NADH produced and glutamine concentration (R2 = 0.985). Single embryos were placed in 20 nl drops of medium containing 0.5 mM glutamine, and the medium was sampled after 2 hr incubation at 37 degrees C. Changes in net glutamine uptake were determined in one-cell, two-cell, and eight-cell embryos and blastocysts incubated in medium containing no energy substrates (glucose, pyruvate, and lactate). The median glutamine uptake increased significantly from 0.480 and 0.270 pmoles/embryo/2 hr at the one-cell and two-cell stages, respectively, to 1.610 pmoles/embryo/2 hr at the blastocyst stage. Mean glutamine uptake was compared in the presence or absence of energy substrates at several developmental stages. A highly significant reduction of glutamine uptake in the presence of substrates was observed at the one-cell and two-cell stages of development. At the eight-cell stage, glutamine uptake was only marginally reduced in the presence of substrates, and no effect was found at the blastocyst stage. These data may partially explain the beneficial effect of glutamine on the culture of early mouse embryos through the two-cell block of development.

Animals↗