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Biomedical subjects

R T Scott

Publications and source records attributed to R T Scott.

At least 37 records · Page 2Linked to original sources

Antiphospholipid antibodies and pregnancy rates and outcome in in vitro fertilization patients.

OBJECTIVE: To determine the relationship between antiphospholipid antibodies and pregnancy rates (PRs) and outcome among IVF patients. DESIGN: Prospective collection of all serum samples with assays for immunoglobulin G (IgG), IgA, and IgM antibodies for anticardiolipin, antiphosphatidyl serine, antiphosphatidyl ethanolamine, antiphosphatidyl choline, antiphosphatidyl inositol, antiphosphatidyl glycerol, and antiphosphatidic acid being done following completion of all treatment cycles. SETTING: A tertiary care teaching hospital. PATIENT(S): Seven hundred ninety-three patients attempting to conceive through IVF. MAIN OUTCOME MEASURE(S): Pregnancy rates (PRs) and pregnancy loss rates relative to each of the various antiphospholipid antibodies that were measured. RESULT(S): There were 528 pregnancies for an overall PR of 66%. Pregnancy rates were equal among patients with positive and negative antiphospholipid antibodies for each of the 21 measured antibodies. Use of receiver operator characteristic curves and logistic regression further confirmed that there was no relationship between PRs or outcome based on antiphospholipid antibodies for any definable threshold value. CONCLUSION(S): Elevated antiphospholipid antibody levels are not associated with any change in PRs or pregnancy loss rates in patients attempting to conceive through IVF.

Adult↗

Cryopreservation of single human spermatozoa.

A procedure is described that allows cryopreservation and efficient post-thaw recovery of either a single or a small group of human spermatozoa. This is achieved by injecting them into cell-free human, mouse or hamster zonae pellucidae before the addition of cryoprotectant. The method involves a combination of physical micromanipulation procedures and glycerol-mediated cryoprotection. Zonae were tracked by positioning them in straws between two small air bubbles prior to freezing. Spermatozoa from poor specimens were cryopreserved and their fertilizing ability after thawing was compared with that of fresh spermatozoa from fertile men. Human eggs used for fertilization testing were either 1 day old or in-vitro matured. Only 2% of the frozen zonae were lost and >75% of spermatozoa cryopreserved in this manner were recovered and prepared for intracytoplasmic sperm injection. The feasibility of cryopreserving a single spermatozoon was assessed. Fifteen motile spermatozoa were frozen in 15 zonae, of which 14 were recovered after thawing. Ten were injected into spare eggs, of which eight became fertilized. Spermatozoa recovered mechanically from human zonae fertilized the same proportion of oocytes as fresh fertile control spermatozoa. The recovery and fertilization rates with spermatozoa frozen in animal zonae were 87 and 78% respectively. The fertilization rate was marginally higher (P < 0.05) than that for spermatozoa frozen in human zonae, perhaps because the latter may have acrosome reacted more frequently. The zona pellucida appears to be an ideally suited sterile vehicle for storage of single spermatozoa.

Animals↗

Efficacy of selection criteria for ovarian reserve screening using the clomiphene citrate challenge test in a tertiary fertility center population.

OBJECTIVE: To examine selection criteria for ovarian reserve screening. DESIGN: Retrospective study. PATIENTS: Two hundred nineteen women underwent testing for ovarian reserve for woman's age > 35 years, any age with unexplained infertility, one ovary, or a poor response to hMG. INTERVENTIONS: Clomiphene citrate challenge test. MAIN OUTCOME MEASURES: Frequency of abnormal ovarian reserve screening, menstrual cycle parameters, response to hMG, and pregnancy outcome by screening criteria. RESULTS: One hundred eighty-four (84.0%) women had a normal ovarian reserve screening test; 35 (16.0%) had an abnormal ovarian reserve screening test. Twenty-six had abnormal ovarian reserve screening when screened by age, 14 for unexplained infertility, 5 for poor response to hMG, and 6 for one ovary. Fifteen women with abnormal ovarian reserve screening had more than one indication for screening. For women attempting pregnancy (n = 182), 49 of 148 (33.1%) with normal ovarian reserve screening became pregnant compared with 2 of 34 (5.9%) with abnormal ovarian reserve screening. Within each screening category, women with abnormal ovarian reserve had menstrual cycle parameters associated with a short follicular phase, required more hMG, and responded poorly to hMG. CONCLUSIONS: One of six women undergoing ovarian reserve screening had an abnormal test, which was associated a poor reproductive outcome. Age was the most important single criteria. Selected ovarian reserve screening is simple and inexpensive and should be offered to all fertility patients meeting the specific screening criteria listed above.

Adult↗

Endometrial thickness is predictive of histologic endometrial maturation in women undergoing hormone replacement for ovum donation.

OBJECTIVE: To determine if ultrasonographic endometrial pattern or thickness is predictive of histologic endometrial maturation in women undergoing hormone replacement for ovum donation. DESIGN: Ultrasonographic endometrial thickness and pattern were determined and compared with histologic assessment of endometrial maturation. PATIENTS: Forty-six women underwent 52 preparatory cycles for ovum donation. Transvaginal ultrasound (US) was performed after 14 days of E2 replacement and, after 12 days of P, an endometrial biopsy was performed. In 12 cycles, a continuous dose of 2 mg/d E2 was administered. In cycles with out-of-phase biopsies (dated earlier than day 24) and in the last 34 cycles, all women received an escalating dose of E2 before initiation of P. Additionally, the 46 women underwent 55 ETs with USs performed on cycle day 15. RESULTS: Six women had abnormal biopsies in their first preparatory cycle on the continuous E2 protocol, which normalized with the escalating protocol. All other women had normal biopsies. Women with abnormal biopsies had significantly thinner endometrium (< or = 6 mm) but similar endometrial patterns compared with women with normal biopsies. In women having US in preparatory and transfer cycles, there were no differences in endometrial thickness or pattern between examinations. CONCLUSIONS: Endometrial thickness > or = 7 mm in hormone replacement cycles predicts in phase endometrial histology and can replace the endometrial biopsy.

Biopsy↗

Premature luteinization during controlled ovarian hyperstimulation for in vitro fertilization-embryo transfer has no impact on pregnancy outcome.

OBJECTIVE: To determine if elevated serum P concentration on the day of hCG administration or P area under the curve (AUC) impacts on pregnancy rates (PRs) in IVF-ET cycles. DESIGN: Retrospective study. PATIENT(S): One hundred thirty-three couples underwent IVF-ET using luteal GnRH-agonist suppression followed by hyperstimulation with gonadotropins. Patient cycles were controlled for female age, ovarian reserve, male factor with intracytoplasmic sperm injection (ICSI), endometrial thickness and pattern, number of embryos, and number of high-quality embryos transferred, and cell stage at transfer. Pregnancy was defined as an ongoing pregnancy > 20 weeks. RESULT(S): Patients and cycle parameters did not differ significantly based on the control parameters. Similar numbers of severe male factors treated by ICSI were in each group with similar PRs. Pregnancy rates and implantation rates did not differ based on P levels < or = 0.9, < or = 1.1, and < or = 1.4 ng/mL (conversion factor to SI unit, 3.18). Serum P concentrations per total eggs retrieved or per mature egg retrieved did not influence pregnancy outcome. Efficiency curves for serum P levels and P AUC did not demonstrate any differences in PR. At very high serum P (P > 2.0 ng/mL) samples size limits the ability of these data to rule out a negative effect. CONCLUSION(S): Serum P levels (and P AUC) commonly encountered during cycles of IVF-ET have no impact on pregnancy outcome.

Adult↗

Evaluation and treatment of low responders.

Identification and treatment of low responders to ovulation induction is one of the most frustrating challenges in reproductive medicine. Because complex ovulation induction is required so frequently and is so expensive, efficient diagnosis of hyporesponders is critical. At present, the best techniques of evaluating ovarian reserve are basal follicle-stimulating hormone/Estradiol levels early in the proliferative phase and the clomiphene citrate challenge test. When poor responders are identified, strong consideration should be given to adjunctive approaches such as gonadotropin-releasing hormone analog and microdose flare or possibly, embryo hatching in those women undergoing in vitro fertilization.

Adult↗

In-vitro fertilization outcome in women with hydrosalpinx.

Recent studies have suggested that the presence of hydrosalpinx has a negative effect on in-vitro fertilization (IVF) outcome, with markedly diminished implantation and pregnancy rates, and increased early pregnancy loss. We evaluated the impact of hydrosalpinx on IVF outcome in a large population with tubal factor infertility: 63 patients with hydrosalpinx and 60 without hydrosalpinx (no hydrosalpinx) underwent 103 and 89 IVF cycles respectively. Hydrosalpinx was diagnosed by hysterosalpingography and/or laparoscopy prior to IVF. Patients were further subdivided into those with or without elevated quantitative serum Chlamydia trachomatis IgG antibody (Ab) titres. All couples with elevated serum Ab titres (l: 16 or more) were treated with doxycycline (100 mg bid.) 10 days prior to the first IVF cycle. In all, 88 women (71.5%) had elevated C. trachomatis Ab: 47 women (74.6%) with hydrosalpinx had elevated titres, compared to 41 (68.3%) in the no hydrosalpinx group. There were no significant differences in mean age, number of mature oocytes obtained, and number of embryos transferred between the two groups. There was a trend for a higher implantation rate and ongoing pregnancy rate in the no hydrosalpinx group compared to the hydrosalpinx group (12.6 versus 9.8%, and 33.7 versus 24.8% respectively); however, this did not reach statistical significance. The incidence of early pregnancy loss was similar in the two groups. Two ectopic pregnancies were noted in the hydrosalpinx group compared to none in the no hydrosalpinx group. As expected, the prevalence of elevated titres of C. trachomatis IgG Ab in patients with tubal factor infertility presenting for assisted reproductive treatment was high. In contrast to recently published reports, our study did not confirm a negative effect of hydrosalpinx on IVF outcome when antibiotic treatment was given prior to assisted reproductive treatment. Prospective multicentre studies evaluating the effect of hydrosalpinx and its treatment on IVF outcome are needed.

Adult↗

Intraobserver, interobserver variation of sperm critical morphology: comparison of examiner and computer-assisted analysis.

OBJECTIVE: To examine intraobservational and interobservational variation in sperm critical morphology analysis between trained andrologists and a computer over the range of 0% to 15% normal forms. DESIGN: Retrospective. SETTING: Fertility center. PATIENTS: Twenty-four semen specimen slides were read five times in a randomized, blinded fashion by two andrologists and a computerized semen analyzer. Twenty-five samples were analyzed using a different stain and a centrifugation step. MAIN OUTCOME MEASURE: Sperm strict morphology. RESULTS: Mean average intraobserver deviation of normal forms was small (1.3% to 2.7%). Intraobserver deviation did not differ between andrologists, but both differed from the computer. Interobserver deviation for percent normal forms was similar for andrologists and computer. Mean average deviations were small over the variation was independent of the initial percent normal forms. The computer frequently evaluated significantly fewer cells than the andrologists. Updated software increased the number of cells read by the computer requiring more time than the andrologist. CONCLUSIONS: Trained andrologists and a computer determine sperm critical morphology similarly over the range of 0% to 15% normal forms. A single evaluation is highly predictive of multiple evaluations. Improvements in the speed of computer assessment are still necessary.

Diagnosis, Computer-Assisted↗

Characteristics of gonadotropin response, follicular development, and endometrial growth and maturation across consecutive cycles of clomiphene citrate treatment.

OBJECTIVE: To examine the patterns of gonadotropin response, follicular development, and endometrial growth and maturation across consecutive cycles of clomiphene citrate (CC) treatment. DESIGN: Prospective analysis of cycle characteristics. SETTING: Academic tertiary medical center. PATIENTS: Nineteen consenting anovulatory infertile women receiving standardized, cyclic, incremental treatment with CC (50 to 150 mg/d, cycle days 5 to 9) for ovulation induction. INTERVENTIONS: In each of up to six consecutive treatment cycles, urinary LH was monitored twice daily from cycle day 10 until detection of the LH surge or day 21; blood samples and transvaginal ultrasound (US) examination were obtained on cycle days 3, 10, and every 1 to 3 days thereafter until collapse of the dominant follicle. Endometrial biopsy was performed 11 to 13 days after the LH surge in the first, third, and sixth ovulatory cycle. RESULTS: Follicular phase duration, peak follicular diameter, the number of preovulatory follicles, and peak endometrial thickness and echo pattern remained consistent across consecutive ovulatory (n = 55) and anovulatory (n = 23) treatment cycles. Endometrial dating was > or = 3 days out of phase in 2 of 31 (6%) cycles sampled. Peak serum E2 and P concentrations did not vary with cycle number or correlate with endometrial thickness or echo pattern. Cycle day 10 FSH levels were significantly higher in ovulatory subjects than in anovulatory subjects. CONCLUSIONS: Patterns of gonadotropin response, follicular development, and endometrial growth and maturation remain consistent across consecutive cycles of CC treatment.

Adult↗

Evaluation of the reproductive performance of women with elevated day 10 progesterone levels during ovarian reserve screening.

OBJECTIVES: To evaluate the relationship of elevated day 10 P levels (> or = 1.1 ng/mL, conversion factor to SI unit, 3.18) during ovarian reserve screening and reproductive performance. DESIGN: Prospective screening with longitudinal follow-up. INTERVENTIONS: One hundred seven women underwent ovarian reserve screening with a clomiphene citrate challenge test. MAIN OUTCOME MEASURES: Serum FSH, LH, and E2 levels were determined on cycle day 3 and FSH, LH, and P levels were determined on day 10. A fertility evaluation was completed and a treatment plan was instituted. RESULTS: Twenty-two of 107 (20.6%) women had day 10 P levels > or = 1.1 ng/mL. Women with elevated day 10 P levels were similar in age to women with normal day 10 P levels (< or = 0.9 ng/mL) but had significantly shorter menstrual cycles, higher day 3 and day 10 FSH levels, higher day 3 E2 levels, and higher day 10 LH levels than women with normal day 10 P levels. During ovarian hyperstimulation, women with elevated day 10 P levels required more ampules of hMG, had lower peak E2 levels, and had fewer mature follicles than women with a normal day 10 P level. Sixteen of 85 (18.8%) women with normal day 10 P levels became pregnant, but none of the 22 women with elevated day 10 P levels became pregnant. The incidence of diminished ovarian reserve was higher in women with elevated day 10 P levels (13/22; 59%) when compared with women with a normal day 10 P levels (9/85; 10.6%). CONCLUSIONS: Elevated day 10 P levels (> or = 1.1 ng/mL) during ovarian reserve screening is associated with diminished ovarian reserve and correlates with menstrual cycle parameters associated with a short follicular phase and poor reproductive performance.

Adult↗

Relationship between circulating human chorionic gonadotropin levels and premature luteinization in cycles of controlled ovarian hyperstimulation.

OBJECTIVE: To determine if premature luteinization (serum P levels > 1.1 ng/mL on or before the day of hCG administration) during controlled ovarian hyperstimulation (COH) is associated with elevated levels of serum hCG. SETTING: Tertiary fertility center. DESIGN: Retrospective evaluation of ovum donors undergoing COH. PATIENTS: Forty-four women underwent COH. Comparisons of serum hCG levels and hormonal and cycle characteristics were made between cycles with premature luteinization (group I) and without premature luteinization (group II). RESULTS: Group I (16 women) were similar to women in group II in age, amount of hMG, and the ratio of FSH:hMG received. Both groups received hCG on similar days, but women in group I had higher peak E2 levels. Serum hCG levels increased and correlated with serum P levels in group I only and were higher on the day of hCG administration (group I 1.8 +/- 0.9 mIU/mL versus group II 1.2 +/- 0.45 mIU/mL; conversion factor to SI unit, 1.00). Peak E2 and LH levels, ampules of hMG and the FSH:LH ratio, and day of hCG administration did not correlate with hCG levels. Human chorionic gonadotropin exposure, as measured by area under the curve, was significantly higher in group I compared with group II. CONCLUSION: Higher serum levels of hCG and integrated hCG exposure are found in COH cycles with premature luteinization compared with cycles without premature luteinization. Higher hCG levels may be due to decreased clearance of hCG from the circulation and/or the hCG content of hMG.

Adult↗

Evaluation of the impact of concurrent gonadotropin-releasing hormone (GnRH) antagonist administration on GnRH agonist-induced gonadotrope desensitization.

OBJECTIVE: To evaluate the impact of chronic GnRH antagonist therapy on the extent of GnRH agonist-induced gonadotrope desensitization. DESIGN: Prospective and controlled. SETTING: Primate Research Center. PARTICIPANTS: Six reproductive age cycling female baboons (Papio cyanocephalus anubis). INTERVENTIONS: The animals were divided into two groups. Group A received a total of 19 pulses of 0.83 microgram/kg leuprolide acetate (LA) on a 12-hour dosing schedule. Group B received Nal-Lys (3 mg/kg then 1 mg/kg every other day) for 1 week and then added an identical 19 pulses of LA while continuing Nal-Lys therapy. MAIN OUTCOME MEASURES: Characterization of the gonadotropin response was done by collecting serum samples at -15, 0, 15, 30, 60, 90, 120, 240, and 480 minutes relative to the injection of the LA. RESULTS: After equivalent baseline responses, the baboons pretreated with Na-Lys had an increased LH and FSH response to the administration of the LA. After a total of 19 pulses of the LA, the Nal-Lys-treated animals had an increased FSH response in comparison to the untreated controls. This indicates that the extent of gonadotrope desensitization was reduced in the presence of the GnRH antagonist. CONCLUSIONS: The presence of GnRH antagonist reduces the extent of gonadotrope desensitization in response to the administration of repetitive pulses of GnRH agonist.

Animals↗

Life table analysis of pregnancy rates in a general infertility population relative to ovarian reserve and patient age.

This study evaluated the impact of age and ovarian reserve status on cumulative pregnancy rates. Approximately 1200 women from a general infertile population underwent ovarian reserve screening with the clomiphene citrate challenge test in the first few months of their initial evaluation. All patients then underwent a thorough infertility evaluation with therapy appropriate for their specific diagnoses. Patients with evidence of tubal disease, peritoneal adhesive disease, or male factor were eliminated. The 588 remaining patients were evaluated based on their age and ovarian reserve status, and their long-term pregnancy rates were compared using life table analyses. There was a dramatic decrease in pregnancy rates associated with an abnormal clomiphene citrate challenge test which was uniformly poor independent of age. Patients with normal ovarian reserve had much higher pregnancy rates, but a significant age-related decline in pregnancy rates was clearly identified. We conclude that women with evidence of diminished ovarian reserve have uniformly poor pregnancy rates independent of their age, but that age remains an important prognostic factor among those with a normal ovarian reserve. The combined use of maternal age and ovarian reserve screening should be used when counselling individual patients regarding their long-term prognoses for conception.

Adult↗

Evaluation of the Tru-Trax cervical mucus penetration test in predicting fertilization and pregnancy rates in in-vitro fertilization.

To evaluate the role of the Tru-Trax cervical mucus penetration testing of prognosis of patient performance in in-vitro fertilization (IVF) and to examine its use as a possible screening test prior to IVF, 133 couples presenting with infertility prospectively underwent in-vitro cervical mucus penetration testing. Of these, 66 couples subsequently underwent IVF. The penetration distance of the vanguard spermatozoa in both human and bovine mucus was compared to the fertilization and pregnancy rates during IVF. The fertilization rates in couples with normal human mucus penetration (n = 42, 80.6%) were higher than those with abnormal scores (n = 24, 49.6%; P < 0.001). Similarly, the fertilization rates in those couples with normal bovine mucus penetration (n = 50, 77.5%) were higher than those with abnormal results (n = 16, 40.0%; P < 0.001). Fertilization rates and penetration scores were highly correlated for both human (r = 0.66; P < 0.0001) and bovine (r = 0.66; P < 0.0001) mucus. However, the predictive value of an abnormal result for failed fertilization was poor for both human and bovine penetration, since 83.33 and 81.25% fertilized respectively. Pregnancy rates did not differ among couples with normal and abnormal penetrations. In conclusion, in-vitro cervical mucus penetration testing was highly correlated with fertilization rates in IVF. However, the poor predictive value of an abnormal result may limit the value of this test for generalized pretreatment screening.

Animals↗

Use of the GnRH agonist stimulation test in the diagnosis of ovarian remnant syndrome. A report of three cases.

Ovarian remnant syndrome is an uncommon problem that may follow bilateral oophorectomy. These patients may present with chronic pelvic pain or pelvic masses and may require surgery to confirm or exclude the diagnosis. In this report we describe the successful use of the gonadotropin releasing hormone agonist (GnRH-a) stimulation test to identify the presence of functioning ovarian tissue in three women with ovarian remnant syndrome who presented for evaluation of persistent chronic pelvic pain. In these cases the endogenous gonadotropin flare was able to stimulate the production of significant quantities of estradiol to confirm the diagnosis. The GnRH-a stimulation test may be a useful adjunct in the evaluation of women at risk for ovarian remnant syndrome prior to proceeding with surgery.

Adult↗

Prognostic assessment of ovarian reserve.

OBJECTIVE: To review the literature regarding diminished ovarian reserve, the screening techniques that are currently available, and their appropriate application in clinical practice. DATA RESOURCES: Directed Medline searches. RESULTS: Ovarian reserve screening identifies women with greatly diminished chances of achieving pregnancy. The screening techniques include the clomiphene citrate challenge test, basal day 3 FSH measurements, and the GnRH agonist stimulation test. All have been evaluated in assisted reproduction programs and the predictive values of an abnormal test for failing to conceive is very high. When abnormal, these tests allow physicians to counsel patients that their prognosis for conception is poor. Although the presence of a normal result does indicate better long-term chances for conception, an age-related decline in fecundity remains and patient age should still be considered when counseling patients with normal screening results. Clinicians are urged to validate the threshold values with the assay system used in their own laboratory before the application of these tests. CONCLUSION: The literature consistently demonstrates the value of diminished ovarian reserve screening.

Adult↗