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Biomedical subjects

P Dockery

Publications and source records attributed to P Dockery.

At least 37 records · Page 2Linked to original sources

Effects of male accessory sex glands on fertilization, polyspermy and morphometry of early embryos in the golden hamster.

Preimplantation embryos sired by hamsters without accessory sex glands (ASG) were found to have a higher mortality rate and a slower cleavage rate than those sired by sham-operated males at 72 h post coitum (p.c.). A time-course study of fertilization in vivo was conducted to determine whether this effect was due to delayed fertilization. Ultrastructural morphometry of 48 h embryos was also undertaken to establish the earliest manifestation of developmental anomalies. Compared to sham-operated controls (SH), ablation of all the ASG (TX), or just the ventral prostate (VPX) or ampullary gland (AGX) had no effect on the timing of sperm penetration, extrusion of the second polar body and pronuclear formation. Females mated with AGX males tended to have more polyspermic embryos (9.7%; p < 0.05). The volumes, volume fractions (VV) of the blastomere nuclei, mitochondria and yolk material of the four-cell embryos sired by these same groups of males were assessed using point counting techniques. No difference in the VV of yolk and mitochondria could be observed between groups. However, the SH group did have a significantly larger proportion of the cell occupied by the nucleus (p < 0.05), and the TX group had a higher proportion of the nucleus occupied by nucleoli when compared with the SH group (p < 0.01). Smaller nuclei and larger nucleoli in the TX group was interpreted as an early manifestation of a slower division rate of the blastomeres.

Animals↗

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 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 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↗

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↗

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↗

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↗

An endometrial factor in unexplained infertility.

OBJECTIVE: To study a group of women with unexplained infertility to see whether they have a defect that is intrinsic to the endometrium. DESIGN: Evaluation of the functional response of the endometrium by examining endometrial biopsy specimens using immunohistochemical methods in a group of women with unexplained infertility and in a control group of women with normal fertility. PATIENTS: 27 Women with unexplained infertility (average age 33.2); median duration of infertility five years. A control group of 44 women with normal fertility (average age 33.8) who were requesting sterilisation or reversal of sterilisation. SETTING: Infertility clinic, Jessop Hospital for Women, Sheffield. INTERVENTION: Secretory phase endometrial biopsy specimens were taken, with informed consent, as an outpatient procedure. MAIN OUTCOME MEASURES: Immunohistochemistry with monoclonal antibody D9B1, was used to assess the production and secretion of an oligosaccharide epitope produced by endometrial gland cells between two and seven days after the luteinising hormone surge. A reflected light measuring system was used to assess the amount of epitope within the gland cells, and in the gland lumen. RESULTS: In the control group of women, mean reflected light measurements at the cell base and cell apex peaked at three and five days after the luteinising hormone surge respectively, and in the gland lumen the epitope accumulated rapidly from three days, reaching a peak at seven days. In the women with infertility the peaks of epitope at the cell base and cell apex were lower, broader, and delayed in onset, and the build up of epitope in the gland lumen was retarded. The synthesis and secretion of the epitope in the women with infertility was therefore significantly reduced and delayed, even in the presence of normal concentrations of circulating progesterone. CONCLUSIONS: The results suggest that a primary dysfunction of the endometrium might be associated with hitherto unexplained infertility.

Adult↗

Ultrastructural abnormalities of myelinated fibres in the tibial nerve of streptozotocin-diabetic rats.

In this paper we have examined the ultrastructural changes in myelinated fibre structure after the administration of streptozotocin to Sprague-Dawley rats which had passed the rapid growth period. Myelinated fibre size in the tibial nerve was found to be less in diabetic animals 4 and 6 months after the induction of diabetes, when compared to age-matched controls, but not less than onset. The relative contributions of axon and myelin to this reduction in fibre dimensions were examined. When myelin area was plotted against axon area (derived from perimeter) it showed that the pathological insult of diabetes had a greater effect on the rate of myelin production. The incidence of axonal glycogenosomes was also assessed. These results are discussed in detail.

Analysis of Variance↗

A morphometric study of the human endometrial stroma during the peri-implantation period.

In this study we have examined the human endometrial stromal cell population in well-timed biopsies during the peri-implantation period, using traditional stereological techniques. This paper reports data obtained from 16 women of known fertility who underwent endometrial biopsies at known times after the luteinizing hormone (LH) surge (four each at LH + 2, LH + 4, LH + 6 and LH + 8). The average stromal cell nuclear diameter increased in size throughout the period of study (P less than 0.01), with a significant decrease (P less than 0.05) in the nuclear profile axial ratio. This suggests that the nuclei were increasing in size and becoming more rounded. There was a dramatic increase (P less than 0.01) in the packing density between LH + 2 and LH + 6; this is likely to be due, at least in part, to the glands filling up with secretory products and so compressing the intervening stroma. A substantial decrease (P less than 0.01) was seen in the packing density between LH + 6 and LH + 8. This corresponds to the time when stromal oedema is thought to be maximal.

Adult↗

A morphometric study of the human endometrial stroma during the peri-implantation period.

In this study we have examined the human endometrial stromal cell population in well-timed biopsies during the peri-implantation period, using traditional stereological techniques. This paper reports data obtained from 16 women of known fertility who underwent endometrial biopsies at known times after the luteinizing hormone (LH) surge (four each at LH + 2, LH + 4, LH + 6 and LH + 8). The average stromal cell nuclear diameter increased in size throughout the period of study (P less than 0.01), with a significant decrease (P less than 0.05) in the nuclear profile axial ratio. This suggests that the nuclei were increasing in size and becoming more rounded. There was a dramatic increase (P less than 0.01) in the rounded. There was a dramatic increase (P less than 0.01) in the packing density between LH + 2 and LH + 6; this is likely to be due, at least in part, to the glands filling up with secretory products and so compressing the intervening stroma. A substantial decrease (P less than 0.01) was seen in the packing density between LH + 6 and LH + 8. This corresponds to the time when stromal oedema is thought to be maximal.

Adult↗

A comparison of some clinical and endocrinological features between cycles with normal and defective luteal phases in women with unexplained infertility.

The luteal phase in a group of women (n = 49) with unexplained infertility was evaluated by improved methods, including the use of the LH surge for precise timing of measurements, quantitative techniques for histological dating of endometrial biopsy and determination of the integrated progesterone concentration in the luteal phase. Overall, 10 out of 49 (20%) women were considered to have a retarded endometrium. The prevalence of retarded endometrium in women with primary infertility (10/37, 27%) was found to be significantly higher (P less than 0.05) than in women with secondary infertility (0/12, 0%). Women with retarded endometrial development had a significantly (P less than 0.01) lower integrated P concentration than those with normal endometrial development; however, of the 10 cases with retarded endometrium, only four were associated with an integrated P concentration below the normal range, whereas the remaining six were associated with an integrated P concentration within the normal reference range, suggesting that an abnormal response of the endometrium is a likely cause of abnormality in these latter cases. There was no difference in age, duration of infertility, follicular phase length, magnitude of the oestrogen surge, magnitude of the LH surge, maximum follicular diameter and luteal phase length between women with a normal or defective luteal phase, defined either by endometrial morphology or integrated progesterone concentration.

Endometrium↗

A quantitative study of endometrial development in the luteal phase: comparison between women with unexplained infertility and normal fertility.

This study compared endometrial development in the luteal phase of women with unexplained infertility (n = 30) with that in women with normal fertility (n = 70) by the use of quantitative histological techniques (morphometric analysis) on endometrial specimens which were precisely timed from the luteinizing hormone surge. When overall endometrial development (histological dating) was considered, the proportion of women with unexplained infertility who had retarded endometrial development (20%) was found to be significantly higher than for women with normal fertility (3%) (P less than 0.01). When individual histological features were considered, women with unexplained infertility were found to have significant deviation from the normal range established from fertile women in only five of the 14 histological features measured. All of these five features related to the glandular but not to the stromal component of the endometrium; four of these five features are related to glandular secretory activity.

Adult↗

How precise is histologic dating of endometrium using the standard dating criteria?

Sixty-three endometrial biopsies were dated histologically by using the standard criteria on two separate occasions by the same observer. Overall, it was found that exact agreement occurred in 15 (24%), but disagreement of more than 2 days occurred in 6 (10%). The proportion of exact agreement in the first half of the luteal phase (32%) was found to be significantly higher (P less than 0.05) than that in the second half of the luteal phase (9%). In a separate part of the study, 27 women had two endometrial biopsies, each performed in a separate cycle. The within-subject between-cycle variation of the results of endometrial dating (exact agreement: 4%, disagreement of more than 2 days: 41%) was found to be significantly different from intraobserver variation (P less than 0.01 for both). The amount of intraobserver variation suggests that the traditional dating criteria are not precise enough to quantify corpus luteum function in the second half of the luteal phase, whereas the amount of within-subject between-cycle variation implies that the result of endometrial dating in one cycle cannot be used reliably to predict that of another cycle.

Adult↗

The effects of steroids on the fine structure of the endometrium.

This brief review illustrates the lack of ultrastructural studies on human endometrium, particularly on well-dated material from normal, fertile women. The glandular epithelium, with its triad of unusual organelles in the early luteal phase, poses fascinating problems in cell biology and, probably for this reason, has attracted the most work. Many problems in reproductive biology, in uterine pathology and in the study of unexplained infertility are crying out for detailed study of the luminal epithelium, the stroma and the blood vessels. If this review, by highlighting the gaps in our knowledge, stimulates research into these areas, it will have been successful.

Endometrium↗