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Biomedical subjects

S S Thatcher

Publications and source records attributed to S S Thatcher.

At least 19 recordsLinked to original sources

Risk factors for low bone mineral density in individuals residing in a facility for the people with intellectual disability.

BACKGROUND: Individuals with intellectual disability (ID) are known to have a high prevalence of both low bone mineral density (BMD) and fractures with significant attendant morbidity. Effective strategies aimed at reducing fractures will be facilitated by the identification of predisposing risk factors. METHODS: Bone mineral density was measured by quantitative ultrasound of the calcaneus performed on 79 women and 132 men residing in a facility for adults with ID. Multiple variable logistic regression analysis was performed to determine the significance of risk factors for low BMD. RESULTS: Mobility impairment consistently appeared to be a significant risk factor for low BMD regardless of age or sex and especially for middle-aged men with profound ID. Further risk was identified for postmenopausal women taking enzyme inducing anticonvulsant medications and middle-aged men who were either smokers or tended to be short. Hispanic followed by Caucasian origin also put middle-aged males at a greater risk than their African-American counterparts. CONCLUSIONS: Specific risk factors for low BMD, some of which have potential for modification, were identified in the study population. Targeted strategies for risk factor reduction may result in a decrease in the high rate of fractures among these individuals.

Adult↗

Sex-selection of human spermatozoa: evolution of current techniques and applications.

Methods claiming to achieve sex selection by sperm sorting have existed for many years. Numerous applications for safe and effective selection procedures exist in current clinical practice, as sex-linked conditions could be theoretically eliminated by use of appropriate sperm for fertilization or insemination. Use of such techniques could also address the need to effect family balancing for some couples. Modern preconception sex-selection methods may be classified into two general types: those that attempt to segregate spermatozoa on the basis of subtle physical or kinetic features, and those that rely on distinctive nuclear characteristics unique either to X- or Y-chromosome bearing sperm. Laboratories providing sperm sexing using the former method have been available for some years, although the associated efficiency and reproducibility are controversial. Sex selection of spermatozoa by chromatin differences has been shown to achieve significant enrichment of X- or Y-chromosome bearing sperm, but clinical experience in humans is limited. The fundamental elements of the two approaches introduced here are reviewed and compared. Selected key historical concepts in sex selection by sperm sorting are outlined, followed by a summary of promising areas for future research.

Centrifugation, Density Gradient↗

Platelet activating factor enhances the acrosome reaction, fertilization in vitro by subzonal sperm injection and resulting embryonic development in the rabbit.

This study was conducted to investigate the effect of platelet activating factor (PAF) on the acrosome reaction and fertilizing capacity of spermatozoa, and development of the resulting embryos in the rabbit. Rabbit spermatozoa were exposed to PAF, lyso-PAF, or high ionic strength medium (HIS) prior to subzonal sperm injection (SUZI) into 326 mature oocytes, or morphological assessment of the acrosome reaction. The rates of fertilization and blastocyst formation were compared among the three treatment groups. Acrosome reaction was assessed by fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA) staining and electron microscopy. PAF-treated spermatozoa fertilized the oocytes at a significantly higher rate (56.1%) than did lyso-PAF-(36.8%, P < 0.01) or HIS- (38.2%, P < 0.05) treated spermatozoa. The embryos produced by PAF-treated spermatozoa showed significantly higher blastocyst formation rates (34.0%) than lyso-PAF- (8.6%, P < 0.05) or HIS-(8.8%, P < 0.05) treated spermatozoa. FITC-PSA staining demonstrated a significantly higher incidence of acrosome reaction in PAF-treated spermatozoa (45.8%) than in lyso-PAF- (28.0%, P < 0.01) or HIS- (34.9%, P < 0.01) treated spermatozoa. Acrosome reaction of PAF-treated spermatozoa was also confirmed by electron microscopy. PAF treatment of spermatozoa enhances fertilizing capacity for SUZI possibly by augmenting the acrosome reaction. Enhanced embryonic development was also found in the oocytes fertilized by SUZI of PAF-treated spermatozoa.

Acrosome↗

Influences of in vitro oocyte aging on microfertilization in the mouse with reference to zona hardening.

PURPOSE: Our purpose was to investigate the influence of in vitro oocyte aging on fertilization and subsequent embryonic development following subzonal sperm injection with reference to spontaneous zona hardening in the mouse. RESULTS: First cleavage rate was significantly higher in long vs short (69 vs 41%, P < 0.001). However, significantly higher blastocyst formation and hatching were observed in short than long (50 vs 7%, P < 0.001, and 86 vs 50%, P < 0.001, respectively). No significant differences were found for two pronuclei formation between short and long (30 vs 27%). Sham injection revealed a significantly higher parthenogenetic activation in long than short (19 vs 2%, P < 0.001). Zona digestion required a significantly longer time for long compared to short (trypsin--37 vs 29 min, P < 0.01; pronase--17 vs 14 min, P < 0.001). CONCLUSIONS: Prolonged culture of mature mouse oocytes in vitro alters the zona pellucida, increases the rate of parthenogenetic activation by subzonal sperm injection, and impairs subsequent embryonic development. Zona hardening appears to be an indicator of oocyte aging.

Animals↗

Baseline ovarian cysts do not affect clinical response to controlled ovarian hyperstimulation for in vitro fertilization.

OBJECTIVE: To evaluate the effect of baseline ovarian cysts at the onset of controlled ovarian hyperstimulation for in vitro fertilization (IVF) on cycle outcome. DESIGN, PATIENTS: A review of 82 IVF cycles in 29 women in which each patient served as her own control. The stimulation regimen for each patient remained constant over time. Each woman had at least one cycle in which an ovarian cyst measuring 14 to 53 mm was present at baseline and one cycle in which no such cyst was present. SETTING: The In Vitro Fertilization Program at Yale University School of Medicine. RESULTS: There was no statistically significant difference in cycle cancellation rates, baseline serum estradiol (E2), peak serum E2, number of follicles present at retrieval, number of oocytes retrieved, or fertilization rate between groups. Stimulation regimen, cyst size, and age were unrelated to outcome. The number of cysts present at baseline correlated positively with the number of follicles present at retrieval. CONCLUSION: Baseline ovarian cysts in the setting of a low baseline E2 level do not affect the clinical response to controlled ovarian hyperstimulation in IVF cycles.

Adult↗

Ovarian cysts decrease the success of controlled ovarian stimulation and in vitro fertilization.

Forty cystic structures, 16 to 60 mm, of probable ovarian origin were found in 126 cycles during an ultrasound scan on day 3 of a cycle in which in vitro fertilization was planned. The response of these patients to exogenous gonadotropin stimulation, oocyte capture, fertilization, cleavage, and pregnancy was studied. Patients with cystic change had significantly lower peak estradiol (E2) levels. Pregnancy rates were lower, but not significantly so. Those patients with structures 16 to 29 mm had more cycles canceled due to precipitous drops in E2, consistent with an untimely surge of luteinizing hormone. Patients with structures 30 to 60 mm had increased numbers of cycles with poor response to stimulation. The importance of an early follicular phase ultrasound scan is stressed, and the management of ovarian cysts in this patient population is discussed.

Estradiol↗

A critical assessment of the indications for in-vitro fertilization and embryo transfer.

In-vitro fertilization therapy (IVF-ET) should be considered an important and indispensable component of all comprehensive infertility treatment programmes. It is neither more, nor less important than operative laparoscopy, hysteroscopic diagnosis, a broad-based programme for ovarian stimulation and ovulation induction or even psychological counseling. Clearly, with today's technology, IVF-ET is not a panacea of infertility, but in selected cases it may provide a child where other forms of therapy have failed. However, what sets this therapy apart from all others is that it has heralded a new era in human biology that will not only enable us to treat, but also to understand the problem of infertility.

Embryo Transfer↗

Glucose phosphate isomerase activity in mouse and human eggs and pre-embryos.

We have measured the activity of glucose phosphate isomerase (GPI-1) in 12 unfertilized human eggs and five human pre-embryos relative to the GPI-1 activity in C57BL/OlaWs mouse eggs. The GPI-1 activity in the human eggs was approximately 6 times that in the C57BL mouse eggs. This implies that human eggs have approximately twice the activity per unit volume of the C57BL mouse eggs but no more than certain other strains of mice. The activity in five human pre-embryos, the most advanced of which was an early blastocyst, was similar to that seen in the human eggs. No change in GPI-1 activity was seen in mouse pre-embryos up to 2 1/2 days (8- to 12-cell stage) but the activity had declined by 3 1/2 days (compacted morula and early blastocyst stages). It seems that high levels of GPI-1 activity are maintained during the early preimplantation development of both species.

Animals↗

Pelvic trophoblastic implants after laparoscopic removal of a tubal pregnancy.

Laparoscopic removal of ectopic gestations is becoming increasingly popular. We present a case in which an early, unruptured ampullary ectopic pregnancy was identified clinically, removed during laparoscopy, and subsequently confirmed by pathology. The patient later presented with pain and with rising titers of beta-hCG. Laparotomy demonstrated multiple pelvic implants of trophoblastic tissue.

Adult↗

Anovulatory infertility. Causes and cures.

Disorders of ovulation rank with tuboperitoneal disease as the most common causes of female infertility. A proper diagnosis and selection of therapy can also make anovulation the most treatable form of infertility. A review provides a framework for understanding the various etiologies of anovulation, its detection and current treatment modalities.

Anovulation↗

Cocaine use and acute rupture of ectopic pregnancies.

The hemodynamic changes associated with ingestion of cocaine may precipitate rupture of ectopic pregnancy. Two cases are presented in which this association was suspected. We believe this to be the first report of this clinical entity, representing a risk factor that should be identified in patients with suspected ectopic pregnancy.

Adult↗

Superovulation with exogenous gonadotropins does not inhibit the luteinizing hormone surge.

The administration of human chorionic gonadotropin to women undergoing superovulation with exogenous gonadotropins was delayed in order to document the occurrence of a surge of luteinizing hormone (LH). An LH surge was seen to occur in 10 of 10 women receiving clomiphene citrate (CC) and pulsatile human menopausal gonadotropin (hMG); in 10 of 12 women treated with pulsatile hMG alone; and in 12 of 14 women treated with single daily injections of hMG without CC. The height of the surge was attenuated in all cycles and the timing of its onset was significantly earlier among women receiving single daily injections of hMG. Possible mechanisms for these findings are discussed.

Adult↗

The effects of clomiphene citrate on the histology of human endometrium in regularly cycling women undergoing in vitro fertilization.

Thirty-six women with histories of regular cycles undergoing elective laparoscopic sterilization volunteered to participate in a research program of endometrial biopsy, oocyte donation, and in vitro fertilization (IVF). One half of the volunteers received 5 days of 150 mg of clomiphene citrate (CC) ending 5 days before human chorionic gonadotropin injection and 6.5 days before laparoscopy and biopsy. The control patients were treated identically, except they received no CC. CC cycles were more uniform in duration and follicular response better, enabling a prescheduled IVF regimen. Control cycles were complicated by poor follicular response or untimely endogenous surges of luteinizing hormone (LH). The mean urinary estrone glucuronide excretion per follicle was the same in each group, and there was no evidence of a luteal defect by either luteal phase length or urinary pregnanediol excretion. Although there were minor differences in mitotic rate and basal vacuolation of glandular epithelium in biopsies, no specific deleterious effect of CC could be seen.

Adult↗

A comparison of dosages of norethisterone for synchronization of cycles in a fixed regimen of follicular augmentation and in vitro fertilization.

Twenty-four patients undergoing elective laparoscopic sterilization were randomized in a fixed schedule of follicular augmentation, oocyte recovery, and in vitro fertilization (IVF) using either 2.5 or 10 mg of norethisterone (NE) in the luteal phase of the previous cycle. The objectives of the study were to determine the effect of a synthetic progestin, given for 5 to 14 days beginning on day 21 of the cycle before the IVF cycle, on folliculogenesis, estrogen secretion, the luteinizing hormone (LH) surge, luteal function, and IVF success. It was found that this treatment was easy to administer and well tolerated by patients. At the 10-mg dose, patients uniformly had vaginal bleeding 2 to 4 days after NE, whereas 40% of patients using the 2.5-mg dose bled before NE was discontinued. Significantly lower estrone glucuronide excretion in the early follicular phase and lower luteal phase pregnanediol excretion in patients receiving 10 mg NE suggested a delay or reduction of developing follicles after luteal phase suppression. No spontaneous LH surges were found in the 10-mg group, compared with surges in 5 of the 13 cycles of the 2.5-mg group. There were no differences between regimens in cycle or luteal phase length. It is postulated that NE, by suppressing folliculogenesis in the luteal phase, may provide for a smaller, but more homogenous cohort of follicles available for exogenous stimulation and recovery.

Creatinine↗

Sexing whole human pre-embryos by in-situ hybridization with a Y-chromosome specific DNA probe.

We have used DNA-DNA in-situ hybridization with a DNA probe for the human Y-chromosome to distinguish between male and female human pre-embryos. Both biotinylated and tritiated Y-probes worked well on control cell cultures where 100 interphase nuclei were scored. Morphologically normal pre-embryos could be sexed with confidence with the tritiated Y-probe but the biotin results were less reliable (although only a few pre-embryos were analysed in this way). Early cleavage stage pre-embryos had large nuclei with relatively diffuse Y-bodies and were more difficult to score with the biotinylated Y-probe. Morphologically abnormal pre-embryos often had large nuclei with multiple Y-bodies (presumably polyploid nuclei) or small nuclei with no Y-bodies (possibly fragmenting nuclei). In all, 38 cleaving and two non-cleaving pre-embryos were analysed. The incidence of false positive and false negative cells seen after hybridization of tritiated Y-probes to control lymphocyte cultures suggests that it should normally be possible to distinguish morphologically normal male and female pre-embryos with samples of three to six interphase nuclei.

Blastocyst↗

Effects of preovulatory tamoxifen in regularly cycling women on folliculogenesis, oocyte recovery and luteal function.

Forty women undergoing elective sterilization and oocyte donation were randomized in a trial to study the effects of administration of 30 mg of tamoxifen 12 h before injection of human chorionic gonadotrophin and 48 h before oocyte capture. Cycles were regulated for advanced operative scheduling with norethisterone given in the luteal phase of the previous cycle and 150 mg of clomiphene given in the early follicular phase of the recovery cycle. Tamoxifen cycles showed a delay of peak urinary oestrone excretion by 2 days, associated with a slight decrease in total excretion. Tamoxifen administration lengthened treatment cycles by 0.5 days and the luteal phase by 0.4 days. The urinary excretion peak of pregnanediol was 3 days later than in controls. Total pregnanediol excretion was slightly elevated. There were no differences in oocyte recovery rate although cleavage rate was decreased (0.84 versus 0.65, not significant at P greater than or equal to 0.05). Intrafollicular oestradiol levels were similar (794 +/- 97 versus 735 +/- 102 ng/ml). Intrafollicular progesterone levels were marginally lower in tamoxifen cycles (3.5 +/- 0.5 versus 2.3 +/- 0.8 micrograms/ml).

Adult↗