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Biomedical subjects

T C Li

Publications and source records attributed to T C Li.

At least 127 records · Page 7Linked to original sources

The techniques and complications of out-patient uterine washing in the assessment of endometrial function.

The complications of a consecutive series of 90 uterine washings performed among 52 women were studied. The amount of discomfort was significantly less than that of endometrial biopsy but greater than that of cervical smear or blood sampling. Incomplete recovery of fluid (< 8 ml from 10 ml flushing fluid) was reported in only 3% of cases. Vaginal bleeding, pelvic infection and delayed abdominal pain were not encountered. The techniques of uterine washing are simple and may have important implications in the study of endometrial function.

Adult↗

Is the measurement of oestradiol/progesterone ratios in the peri-implantation period of any value in predicting endometrial development?

To examine the value of the measurement of oestradiol/progesterone ratios in the peri-implantation period, three different types of cycle were studied; natural cycles (n = 13), cycles treated with anti-oestrogens (n = 19), and artificial cycles (n = 41) produced by six different hormone replacement regimens. Normal endometrial development was found to occur across a wide range of oestradiol/progesterone ratios. There was no significant correlation between the oestradiol/progesterone ratios and results of endometrial dating. The results suggest that oestradiol/progesterone ratios are of limited value in predicting endometrial development at the time of implantation.

Embryo Implantation↗

The fine structure of the human endometrial glandular epithelium in cases of unexplained infertility: a morphometric study.

In the present study attempts have been made to express in quantitative terms the fine structure of the endometrial glandular epithelium in well-timed biopsies from fertile women during the early luteal phase. Biopsies from women with unexplained infertility have also been examined. Certain abnormalities of glandular maturation were found in these women. The nuclear channel system was not present at day luteinizing hormone (LH) + 4 in the infertile group while at LH + 6 there were more cells containing this feature than seen in the fertile group. There also seem to be abnormalities associated with intracellular deposits of glycogen-rich material and mitochondrial elaboration in the infertile women. Changes in the secretory apparatus and rough endoplasmic reticulum were observed. The evidence from the present study suggests that the endometria in the examined group of infertile women is responsive to steroidal stimulation. This response however, may be delayed or inadequate.

Cell Nucleus↗

The production of placental protein 14 and interleukin 6 by human endometrial cells in culture.

Epithelial and stromal cells prepared from endometrium taken at different times in the menstrual cycle were grown in primary culture and the production of placental protein 14 (PP14) and interleukin-6 (IL6) measured. Only the epithelial cells produced PP14. Epithelial cells from endometrium in the late secretory phase produced significantly greater amounts of PP14 (42 +/- 5.8 ng/24 h) compared with that produced by cells from early secretory and proliferative endometrium (16 +/- 1.7 and 11 +/- 1.9 ng/24 h respectively). PP14 production by cells from endometrium at all stages in the cycle was increased by progesterone, or progesterone and oestradiol together, while oestradiol alone had no effect on PP14 production. The greatest stimulation was seen during the early secretory phase when stimulated levels of PP14 reached those obtained during the late secretory phase. IL6 production by epithelial cells also varied depending on the phase of the menstrual cycle. More IL6 was produced by the cells prepared from the endometrium in the proliferative phase (10.9 +/- 0.56 ng/24 h) compared with that produced by cells from early and late secretory endometrium (2.5 +/- 0.19 and 1.45 +/- 0.09 ng/24 h respectively). Addition of steroids to the media stimulated the production of IL6 by cells from proliferative and early secretory endometrium but decreased IL6 production from cells in the late secretory phase. IL6 was also produced by stromal cells but could only be detected in supernatants of cells prepared from late secretory endometrium, and the amounts produced (0.8 +/- 0.09 ng/24 h) were less than that produced by epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Uterine flushing: a method to recover spermatozoa and leukocytes.

The process of sperm transport from the cervix, where a leukocytic reaction is initiated, through the uterus to gain access to the site of fertilization is very poorly understood. This preliminary study was designed to utilize a uterine flushing technique to determine firstly, the number of spermatozoa that can be recovered from the uterine cavity at 4 h post-insemination, around the time of ovulation, and secondly, to establish whether the spermatozoa initiate a leukocytic response while present. Uterine flushing was carried out in 10 potentially fertile women at 4 h post-insemination with donor semen, 24-36 h after the onset of the luteinizing hormone (LH) surge. The flush fluid was analysed for the numbers of spermatozoa and leukocytes present. In 8/10 women spermatozoa were retrieved from the uterus, in consistently low numbers (median 46, range 3-415). In 5/5 women leukocytes were recovered (median, 2.75 x 10(8)/l, range 2.0 x 10(8)-12.7 x 10(8)/l) from an origin other than peripheral blood contamination. These results suggest firstly that the flushing technique was a consistent method for retrieving spermatozoa and leukocytes from the uterine cavity, secondly that only low numbers of spermatozoa can be retrieved on flushing and thirdly that the leukocytic reaction to spermatozoa extends to the uterine cavity.

Female↗

Is endometrial development in the peri-implantation period influenced by high concentrations of luteinizing hormone in the follicular phase?

A retrospective study was designed to examine the relationship between luteinizing hormone (LH) concentrations in the follicular phase and endometrial development in the luteal phase of natural and artificial cycles. Two types of cycle were studied: natural cycles (n = 51) in subjects with unexplained infertility were divided into two subgroups, depending on whether LH measurements in the late follicular phase were based on urine (n = 24) or plasma (n = 27) samples; and artificial cycles (n = 17), produced by the administration of a standard hormone replacement therapy, in two subgroups of women, those with premature ovarian failure (n = 10) in whom plasma LH concentrations were high, and those with unexplained infertility (n = 7) who had their hypothalamic pituitary-ovarian axis down-regulated and in whom plasma LH concentrations were low. The correlation between plasma or urine concentrations of LH in the follicular phase and the results of endometrial biopsy obtained in the luteal phase was calculated. In natural cycles, LH concentrations were similar in those with normal or retarded endometrium, and there was no significant correlation between high LH concentration and retarded endometrial development. In artificial cycles, endometrial development was not different between those with low LH concentrations (down-regulated by Zoladex) and those with high LH concentrations (premature ovarian failure). Endometrial development in the peri-implantation period does not appear to be influenced by LH concentration in the follicular phase. The reported association between high LH concentration and poor reproductive performance cannot therefore be explained by abnormal implantation consequent upon retarded endometrial development.

Adult↗

A study of endometrial morphology in women who failed to conceive in a donor insemination programme.

OBJECTIVE: To examine the morphology of endometrium in women who failed to conceive after nine or more cycles of donor insemination treatment. DESIGN: Prospective study. SETTING: Jessop Hospital for Women, Sheffield. SUBJECTS: Two groups: twenty-six infertile women and a control group of eight fertile women. INTERVENTION: Endometrial biopsy specimens were obtained in the mid-luteal phase, timed precisely by the luteinising hormone surge. MAIN OUTCOME MEASURE: Morphological study of endometrial biopsy specimens by the use of traditional dating criteria and established morphometric techniques. RESULTS: Twelve biopsy specimens (42%) were found to be retarded. In addition, morphometric analysis revealed significant differences in the glandular component of the endometrium between the infertile and fertile groups. CONCLUSION: Endometrial defect leading to implantation failure may be an important underlying cause of failure to conceive after repeated attempts at donor insemination. The endometrium should be investigated in this group of women, and further attempts at donor insemination treatment should be offered only in conjunction with attempts to restore the normality of the endometrium.

Adult↗

Concentration of endometrial protein PP14 in uterine flushings throughout the menstrual cycle in normal, fertile women.

OBJECTIVE: To determine the variation in concentration of endometrial protein PP14 in uterine flushings throughout the menstrual cycle comparing this to concentrations in plasma samples. DESIGN: Precise timing of all samples by the luteinising hormone surge. SETTING: Jessop Hospital for Women, Sheffield. SUBJECTS: Twenty-three regularly cycling, previously fertile volunteer women. INTERVENTIONS: Observational study; 10 ml of physiological saline was used to flush the uterine cavity once or serially in the cycle of the study. MAIN OUTCOME MEASURES: The measurement of PP14 levels by radioimmunoassay in uterine flushings and plasma samples. RESULTS: In uterine flushing, PP14 levels were not detectable in significant amounts in the proliferative phase and the early luteal phase; after day LH + 6, the concentration rises rapidly with a doubling time of only 6.6 to 14.6 h in the midluteal phase. In the late luteal phase, the concentrations in uterine flushing were over a hundred times higher than the corresponding plasma samples. CONCLUSIONS: The measurement of PP14 in uterine flushings is likely to be of greater value than the measurement in plasma samples; it may provide a valuable alternative to the evaluation of endometrial function.

Adult↗

The endometrial biopsy as a predictive factor of pregnancy rate in women with unexplained infertility.

To investigate whether or not there is any relation between endometrial morphology and subsequent pregnancy rate, 47 couples with unexplained infertility were followed up for 3 years after they had had an endometrial biopsy. Each woman had an LH-timed endometrial biopsy performed in the luteal phase of the cycle. The biopsy was dated chronologically according to the luteinizing hormone (LH) surge and histologically using morphometric criteria. None of the women received any form of treatment in the endometrial biopsy cycle. Of 47 women with unexplained infertility, 36 (76.6%) (Group I) had 'in phase' endometrial development and 11 (23.4%) (Group II) had retarded endometrium. Women with normal endometrial development had a higher pregnancy rate than women with retarded endometrial development (50% vs. 9%; P less than 0.02). The fecundability during treatment cycles was higher in Group I than in Group II (0.051 vs. 0.008; P less than 0.05). In women with 'in phase' endometrium, treatment increased the monthly probability of conception (0.051 vs. 0.006; P less than 0.001). A precisely timed endometrial biopsy should be considered as part of the investigations for women with unexplained reproductive failure, to help determine prognosis.

Adult↗

Endometrial lymphoid tissue in the timed endometrial biopsy: morphometric and immunohistochemical aspects.

OBJECTIVES: The purpose of this study was to provide a morphometric profile of endometrial granulated lymphocytes and to investigate qualitative and quantitative differences in leukocyte subsets in precisely timed luteal phase endometrial biopsies. STUDY DESIGN: Endometrial biopsies were obtained from 24 normal fertile women at 4, 7, 10, and 13 days after the luteinizing hormone surge. Endometrial granulated lymphocytes were assessed morphometrically in 2 microns resin sections. Eleven monoclonal antibodies were used to characterize leukocytes in frozen sections. Semiquantitation was performed with a Quantimet 970 image analyzer. Data were analyzed with one-way analysis of variance. RESULTS: CD8+ (T suppressor-cytotoxic) cells increased significantly from 4 to 7 days after the luteinizing hormone surge, whereas CD68+ macrophages increased from days 10 to 13. Lymphocytes with an unusual phenotype (CD56+, CD38+, CD2+) increased dramatically after 7 days. The volume fraction of endometrium occupied by the nuclei of endometrial granulated lymphocytes did not alter, but their mean nuclear diameter and axial ratio decreased from days 7 to 13. CONCLUSION: The morphometric findings indicate in situ proliferation of endometrial granulated lymphocytes rather than migration from the peripheral circulation. T lymphocytes, macrophages, and endometrial granulated lymphocytes increase significantly between certain stages of the luteal phase.

Adult↗

An analysis of the variation of plasma concentrations of placental protein 14 in artificial cycles.

OBJECTIVE: To analyze the factors affecting the variation of plasma concentration of placental protein 14 (PP14) in artificial cycles. DESIGN: The effects of different hormone replacement therapy (HRT) regimens were examined in a crossover design. SETTING: Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Eighteen women with premature ovarian failure: 6 associated with Turner's syndrome and 12 with idiopathic premature ovarian failure. INTERVENTIONS: Four different HRT regimens; 36 study cycles. MAIN OUTCOME MEASURES: Plasma PP14 concentrations on days 1, 15, 19, and 29 of the artificial cycles. RESULTS: In cycles treated with a standard HRT, the levels were similar to those of the natural cycle. Subjects with Turner's syndrome did not have elevated PP14 levels, whereas the majority (9/12 [75%]) of those with idiopathic premature ovarian failure had elevated levels on day 29 of the cycle. Levels of PP14 were reduced when either the doses of estradiol valerate were reduced to 1/3 or the doses of progesterone (P) were reduced to 1/5 of the standard HRT. CONCLUSIONS: Plasma levels of PP14 are dependent not only on P stimulation but also on adequate estrogen priming.

Adult↗

How well does ultrasonographic measurement of endometrial thickness predict the results of histological dating?

In this study, transabdominal ultrasonographic measurement of endometrial thickness was performed prior to sampling of the endometrium for histological examination in regularly cycling women. In the natural cycles, the results of ultrasonography and histological dating were significantly correlated (r = 0.76, P less than 0.0001, n = 63). Endometrial histology was likely to be proliferative if the thickness was less than 8 mm, and likely to be secretory if the thickness was greater than 9 mm. However, for a given endometrial thickness, the stage of endometrial development appeared to vary widely, suggesting that ultrasonographic measurement of endometrial thickness cannot accurately predict the results of histological dating. In the second part of the study, endometrial thickness at a defined stage of histological development (results of histological dating between days LH + 4 and LH + 6) was compared in three types of cycles: natural (n = 13), clomiphene-stimulated (n = 12) and artificial (n = 22) cycles. The endometrial thickness (mean +/- standard deviation) in artificial cycles (9.9 +/- 1.3 mm) was significantly smaller than that in natural (11.3 +/- 1.4 mm) or clomiphene-stimulated (11.2 +/- 1.3 mm) cycles, but there was no difference in endometrial thickness between the latter two types of cycle. Our observations suggest that it is unlikely that ultrasonographic measurement of endometrial thickness can replace histological examination of the endometrium in the evaluation of the luteal phase.

Adult↗

A prospective, randomised, cross-over study comparing the effects of clomiphene citrate and cyclofenil on endometrial morphology in the luteal phase of normal, fertile women.

OBJECTIVE: To examine the effect of two anti-oestrogens, clomiphene citrate and cyclofenil, on endometrial morphology in the luteal phase. DESIGN: A prospective, randomised, cross-over study. SETTING: Jessop Hospital for Women, Sheffield, UK. SUBJECTS: 10 women who were previously fertile and regularly cycling. INTERVENTION: The administration of clomiphene citrate or cyclofenil in the treatment cycles. A LH timed endometrial biopsy was taken on day LH + 6. MAIN OUTCOME MEASURES: Histological dating and morphometric analysis of the endometrial sample. RESULTS: Only one out of 10 subjects had abnormal endometrium. There was no difference in the results between cycles treated with clomiphene citrate and cyclofenil. CONCLUSIONS: Clomiphene citrate or cyclofenil does not have a major adverse effect on endometrial morphology in the luteal phase of normal fertile subjects. The possible adverse effects of anti-oestrogens on endometrium may have been previously overestimated.

Adult↗

Endometrial responses in artificial cycles: a prospective, randomized study comparing three different progesterone dosages.

OBJECTIVE: To examine the endometrial response to three different regimens of progesterone. DESIGN: A prospective, randomized study. SETTING: The Jessop Hospital for Women, Sheffield. SUBJECTS: 14 women with premature ovarian failure divided into two equal groups. INTERVENTIONS: Three different regimens of hormone replacement therapy containing standard, high and low progesterone dosages. One group received the standard regimen in one cycle and high dosage regimen in another cycle. The second group received the standard regimen in one cycle and low dosage regimen in another cycle. The order of the two dosage regimens was randomized by lottery. MAIN OUTCOME MEASURES: Ultrasonographic measurement of endometrial thickness and morphological study of endometrial biopsy specimens taken on day 19 of the cycle using the traditional dating criteria and morphometric techniques. RESULTS: Compared with standard regimen cycles, the endometrial response in cycles treated with the low dosage regimen showed significant retardation of overall endometrial development and changes in a number of morphometric measurements. The response of endometrial glands to the high dosage regimen was similar to that of the standard regimen, although the stromal cell diameter was increased. CONCLUSIONS: In women receiving hormone replacement therapy normal endometrial development depends on an adequate dosage of progesterone, but increased dosage above our standard regimen does not produce any further change in the glandular component of the endometrium.

Adult↗

Endometrial responses in artificial cycles: a prospective study comparing four different oestrogen dosages.

OBJECTIVE: To examine the endometrial response to four different regimens of oestrogen. DESIGN: A prospective, randomized cross-over study. SETTING: Jessop Hospital for Women, Sheffield. SUBJECTS: Twenty one women with premature ovarian failure divided into three equal groups. INTERVENTIONS: Four different regimens of hormone replacement therapy: variable, fixed 1 mg, fixed 2 mg and fixed 4 mg oestrogen dosages. Each woman received the variable dosage regimen in one cycle and crossed over to receive one of the three fixed dose regimens (1 mg, Group 1; 2 mg, Group 2; 4 mg Group 3) in another cycle. MAIN OUTCOME MEASURE: Ultrasonographic measurement of endometrial thickness and outpatient endometrial biopsy on day 19 of the artificial cycle; analysis of endometrial specimens by three separate methods: traditional histological criteria, morphometry and immunohistochemistry. RESULTS: The endometrial response was similar in those treated with the variable and the fixed 2 mg or 4 mg dosage regimens. The response was suboptimal in those treated with the fixed 1 mg dosage regimen. CONCLUSIONS: Normal endometrial development requires adequate priming of the endometrium by oestrogen, which may be administered in a sequential, variable dosage fashion, or simply by a fixed daily dosage regimen. However, the minimum daily dose required is likely to be 2 mg of oestradiol valerate. No adverse effect on the endometrium was observed at a daily dose of 4 mg oestradiol valerate, which produced plasma levels of oestradiol above the reference ranges of the natural cycle.

Adult↗

Uterine factors in infertility.

Uterine factors contributing to infertility include abnormalities in the myometrium and in the endometrium. Recent studies have mainly addressed endometrial factors. Several methods have been developed to evaluate endometrial function, including quantitative histology, electron microscopy, histochemistry and immunohistochemistry, hysteroscopy, measurement of endometrial protein levels in plasma or endometrial washings, and ultrasonography. The relationship between endometrial abnormality and types of infertility has been explored by various investigators, as has endometrial receptivity in women over 40 years of age, with interesting results. Unfortunately, the best treatment for endometrial defect is still unknown. A better understanding of the precise nature of the abnormality should lead to effective treatment.

Age Factors↗

The variation of endometrial protein PP14 in different parts of the human endometrium.

The levels of the endometrial protein PP14 were shown to vary greatly in different sites in the endometrium (coefficient of variation ranged from 55% to 92%, mean = 73%). The variation was found to have no consistent pattern in the seven subjects studied and was unlikely to be the result of problems related to tissue sampling, processing or assay (intra-assay coefficient of variation of the PP14 assay used was less than 10%). Such a large variation in results suggests that the measurement of PP14 concentration in endometrial tissue may be of limited diagnostic value.

Biopsy↗

The effects of the antiprogesterone RU486 (Mifepristone) on an endometrial secretory glycan: an immunocytochemical study.

OBJECTIVE: To examine the effects of progesterone (P) receptor blockade by RU486 (Mifepristone; Roussel-Uclaf, Paris, France) on a secretory endometrial glycan recognized by monoclonal antibody D9B1. DESIGN: Retrospective comparison of endometrial biopsies from treated and untreated women from 2 to 8 days after the luteinizing peak (LH) peak. SETTING: Infertility clinic, Jessop Hospital for Women, Sheffield. PATIENTS: Twenty-two normal fertile women received the RU486. A control group of 44 normal fertile women were also assessed. INTERVENTIONS: RU486 was administered to 22 normal women during the first half of the luteal phase and an endometrial biopsy examined 3 days later. MAIN OUTCOME MEASURES: Immunohistochemistry was used to assess the production and secretion of the D9B1 epitope. RESULTS: When the drug was given 2 days after the LH peak, it prevented appearance of the epitope. When RU486 was administered 5 days after the LH peak, epitope already present in gland cells was subsequently secreted. CONCLUSIONS: These data suggest that production of the sialo-oligosaccharide is P-dependent, but secretion through established intracellular pathways is P-independent.

Adult↗