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Biomedical subjects

T C Li

Publications and source records attributed to T C Li.

At least 19 recordsLinked to original sources

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

A morphometric study of the uterine glandular epithelium in women with premature ovarian failure undergoing hormone replacement therapy.

In this study we examined the fine structure of the human glandular epithelium in women with idiopathic ovarian failure in artificial cycles produced by two different types of hormone replacement therapy (oestradiol valerate orally and either intramuscular injection of progesterone or progesterone via vaginal pessary), both of which had been claimed to be capable of supporting successful implantation. Biopsies were performed on day 19 of the artificial cycle. A variety of sterological probes were used to quantify the structural characteristics of these cells and the results obtained were compared with those from normal fertile subjects biopsied on days 2 and 5 after the luteinizing hormone (LH) surge. The glandular epithelial cells from the vaginal group had a less elaborate secretory apparatus when compared with the intramuscular group or with LH + 5 controls. Many of the features of the vaginal group suggested a continued oestrogenic influence, while the intramuscular group seemed to be more advanced than LH + 5.

Cell Nucleus

Endometrial development in the luteal phase of women with various types of infertility: comparison with women of normal fertility.

In this study, the prevalence of retarded endometrial development in the luteal phase of an infertile population (20/142 = 14%) was found to be significantly higher (P less than 0.05) than in that of a control, fertile population (3/68 = 4.4%). However, when the infertile subjects were subdivided into groups of different aetiology, it was found that women with endometriosis and unexplained infertility had a significantly higher prevalence of retarded endometrium (6/21 = 29%, 10/48 = 21% respectively; P less than 0.01 in both cases) than women with normal fertility; whereas the prevalence in women with tubal or male infertility (1/34 = 2.9% and 3/39 = 7.7%, respectively) was not significantly different from that in the fertile subjects. There were no significant differences in the progesterone profiles of the four groups of infertile subjects and the group of fertile subjects. Of the 15 cases of retarded endometrial development with known progesterone profile, two were associated with subnormal progesterone whereas the remaining 13 were associated with normal progesterone, the latter suggesting an abnormal response of the endometrium to a normal amount of progesterone. The findings suggest that further morphological study of the endometrium should be aimed at subjects whose infertility is unexplained or associated with endometriosis, in whom the prevalence of abnormal endometrium is increased.

Adult

Evaluation of the luteal phase.

The values of various methods used to evaluate the luteal phase, including basal body temperature, measurement of progesterone (P), endometrial biopsy, ultrasonographic measurement of endometrial thickness, and measurement of endometrial proteins, are reviewed. Luteal phase defect (LPD) is a controversial entity. The diagnosis of this condition is best based on a histological study of the endometrium. Methods to improve the accuracy of the diagnosis are discussed. LPD is more likely to be a result of an abnormal response of the endometrium to P, than to a subnormal production of P by the corpus luteum. Many methods of treatment for LPD have been proposed but none is based on a properly controlled clinical trial. Treatment designed to improve the response of the endometrium to P may be more rewarding than P supplementation.

Biopsy

Effect of exogenous progesterone administration on the morphology of normally developing endometrium in the pre-implantation period.

The effects on endometrial morphology of a single, intramuscular dose of 100 mg of progesterone administered in the early luteal phase, between days LH + 1 and LH + 6, were studied in a group (n = 8) of normal, fertile subjects by morphometric techniques and transmission electron microscopy. While the dose of progesterone administered consistently resulted in an increase of salivary progesterone concentration to above the upper limit of the reference range, no significant effect on endometrial development was observed; in particular, endometrial development was not advanced.

Embryonic Development

A review of 254 ectopic pregnancies in a teaching hospital in the Trent Region, 1977-1990.

A total of 254 cases of ectopic pregnancy were reviewed in a teaching hospital in Sheffield, in three defined periods: I, 1977-9; II, 1985-7 and III, 1988-90. A previous history of infertility was noted in 37% of cases. Overall, the presenting symptoms, clinical, laboratory, operative as well as histological findings, are in broad agreement with other series. The incidence increased steadily from 8.6 per 1000 total births in period I to 16.5 per 1000 total births in period III. A number of changes noted in recent years include: (1) the diagnosis of ectopic pregnancy was made significantly (P less than 0.05) earlier; (2) a significantly (P less than 0.05) greater proportion of ectopic pregnancies had an association with the following factors: previous tubal surgery, the diagnosis established with ultrasonography, laparotomy preceded by laparoscopy and treatment by conservative surgery; and (3) a significantly (P less than 0.05) smaller proportion of ectopic pregnancies had the diagnosis based on pelvic tenderness or pelvic mass. During the period 1988-90 a total of 126 laparoscopies were performed for suspected ectopic pregnancy, of which 82 (65%) were confirmed to have ectopic pregnancy and 44 (35%) were thought to have no evidence of ectopic pregnancy on laparoscopy. However, two of the latter cases were subsequently found to have an ectopic pregnancy within 2 weeks. The clinical implications of these findings are discussed.

Adolescent

An analysis of factors influencing the outcome of 232 consecutive tubal microsurgery cases.

A consecutive series of 232 tubal microsurgical operations performed at the Jessop Hospital for Women, Sheffield, between 1983 and 1989, was analysed. The various contributory factors to tuboperitoneal damage were reviewed. Eighty patients (35%) conceived, resulting in 66 (29%) live births and 14 (6%) miscarriages. A further 12 (5%) had ectopic pregnancies. The overall cumulative conception rate (CCR) was 40% at the end of 50 months. Microsurgery has been most successful in the adhesiolysis group (n = 78) with a CCR of 46% at the end of 50 months. The terminal salpingostomy group (n = 97) had a CCR of 40% at the end of 36 months. There was a significant reduction in the live birth rate for the group with hydrosalpinx greater than 20 mm in diameter compared with the group with less than 20 mm (P = 0.05). The proximal anastomosis group (n = 27) had a CCR of 33%. No pregnancy was reported following reconstructive surgery for multiple occlusion sites. Overall, the extent of pelvic adhesions had a significant influence on the outcome (P = 0.02). The likelihood of conception was significantly influenced by the duration of infertility (P = 0.02) but not affected by the aetiology of tuboperitoneal damage, parity or age of the patient. In our hands, tubomicrosurgery is more cost-effective than in-vitro-fertilization as a primary treatment of infertility due to tubal diseases.

Abortion, Spontaneous

The variation of endometrial response to a standard hormone replacement therapy in women with premature ovarian failure. An ultrasonographic and histological study.

The endometrial response to a standard hormone replacement therapy in 18 women with premature ovarian failure was examined by serial ultrasonographic measurement of endometrial thickness and histological study of endometrial biopsy taken on day 19 of the cycle. Women with idiopathic ovarian failure (n = 10) had significantly better response than women with Turner's syndrome (n = 4), whereas women with premature ovarian failure associated with previous chemotherapy (n = 4) had an intermediate response. These observations suggest that the endometria of women with Turner's syndrome responded suboptimally to steroid hormones. However, all endometrial biopsies studied revealed secretory changes. Overall, the results of histological dating of endometrial biopsy were found to be positively correlated with endometrial thickness on day 19 of the cycle (r = 0.72, P less than 0.01). The plasma concentration of oestradiol on days 15, 19 and 29 of the artificial cycle were found to be significantly higher than those on the corresponding days of the natural cycle.

Endometrium

The obstetric and neonatal outcome of pregnancy in women with a previous history of infertility: a prospective study.

OBJECTIVE: To compare the frequency of common antenatal problems, the amount of antenatal surveillance and the obstetric and neonatal outcome in women with and without a history of infertility. DESIGN: A prospective cohort study with age and parity matched controls. SETTING: A single consultant unit at the Jessop Hospital for Women, Sheffield, over a 22-month period. SUBJECTS: 114 women with a history of infertility who reached 16 weeks gestation with a singleton live fetus and 114 control women matched for age and parity. MAIN OUTCOME MEASURES: Frequency of antepartum complications, amount of antepartum surveillance, obstetric and neonatal outcome. RESULTS: Common antenatal complications were not increased. In the infertility compared with the control group, the relative risk of requiring an emergency caesarean section was 2.43 (95% CI 1.05-5.63). There was no difference in birthweight. CONCLUSION: Many of the previously observed differences in outcome of pregnancy in women after infertility compared with those without are associated with age and parity but these characteristics do not explain the increased frequency of emergency caesarean section.

Body Height