Andrew W. Rogers

A new method of histologic dating of human endometrium in the luteal phase

Morphometric analysis was performed on 70 endometrial biopsy specimens collected from a population of fertile women. Of the 17 morphometric measurements that were performed on each endometrial biopsy, only 5 were required to achieve a highly significant correlation with chronologic dating based on luteinizing hormone surge (R = 0.99). The result of histologic dating, based on morphometric analysis of endometrial biopsies collected from a separate, unbiased population, correlated strongly and significantly with chronologic dating (r = 0.98, P less than 0.0001). The correlation was better than that achieved when histologic dating was performed according to the conventional dating criteria (r = 0.88, P less than 0.001).

A comparison between two methods of chronological dating of human endometrial biopsies during the luteal phase, and their correlation with histologic dating

This prospective study was performed on 61 infertile women to examine the correlation between histologic dating using the same criteria by two independent observers and chronological dating by two different methods: (1) determination of luteinizing hormone (LH) peak by daily LH assay, (2) calculation based on the onset of the next menstrual period (NMP). The correlation between histologic dating and chronological dating was found to be significantly better if the LH peak was used to determine the chronological date than if the NMP was used (r = 0.70 and 0.37, respectively).

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.

The effects of progesterone receptor blockade in the luteal phase of normal fertile women

The effects of a single, variable dose (5 to 200 mg) of RU38486 (RU486) (Roussel-Uclaf, Paris, France) in the first half of the luteal phase of the menstrual cycle were studied in 30 normal fertile volunteers. Quantitative histologic techniques were employed, and the results were compared with normal ranges derived from a separate, normal, fertile population. It was found that RU486 inhibited glandular secretory activity, accelerated degenerative changes, induced various vascular changes, increased stromal but not glandular mitotic activity, and did not affect the predecidual reaction. The superiority of morphometric analysis over traditional dating criteria was demonstrated in this study of endometrial responses to an exogenously administered agent. In addition, it was found that temperature drop occurred in 56%, menstrual induction in 43%, luteolysis in 24%, mood change in 23%, and thirst sensation in 3% of women studied. Both menstrual induction and changes in hypothalamic function after the administration of RU486 occurred independently of luteolysis and so were likely to be the direct result of progesterone receptor blockade in these organs. Menstrual induction was significantly related to the dose given and the day on which RU486 was administered. Mood change was significantly related to the day on which RU486 was given. Most of the effects of RU486 occurred around 48 hours after its administration.

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.

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

Summary. 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<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.

The relation between daily salivary progesterone profile and endometrial development in the luteal phase of fertile and infertile women

Summary. This study analysed the relation between daily salivary progesterone profiles in the luteal phase and endometrial development as assessed by morphometric studies of endometrial biopsies that were timed by luteinizing hormone surge. Among 34 fertile women studied, a threshold relation was noted between cumulative salivary progesterone concentration and 11 of the 17 morphometric features measured, as well as the results of the histological dating. Above the observed threshold, a significant linear correlation was found between cumulative salivary progesterone and the results of histological dating. Among 55 women, the progesterone profile in the first half of the luteal phase, but not the second half, was found to be significantly lower in those with retarded endometrial development than in those with normal development. Overall, 50% of retarded endometrial development was associated with a subnormal progesterone profile, but the other 50% was associated with a normal progesterone profile, in keeping with an abnormal response of the endometrium due to progesterone receptor deficiency. Retarded endometrial development was more likely to be associated with a subnormal progesterone profile in the first half of the luteal phase than in the second half.

Why does RU486 fail to prevent implantation despite success in inducing menstruation

The administration of RU38486 (RU486) in the luteal phase may induce menstruation, but it may not be associated with shedding of the functional layer of the endometrium. This provides an explanation why, in some cases of successful menstrual induction by RU486, pregnancy continues undisturbed. The ability of RU486 to interrupt a very early pregnancy is more likely to be related to its ability to cause shedding of the endometrium than its ability to induce menstruation.

Prevention of Negative Chemography in Phenylenediamine Stained Autoradiographs of Plastic Semithin Sections

Negative chemography is the loss of latent image during autoradiographic exposure, due to reactive groups in the specimen. Tissue fixed with glutaraldehyde and osmium tetroxide, block stained with p-phenylenediamine and embedded in Epon for light microscope sections causes intense negative chemography when autoradiographed by dipping in Ilford K2 emulsion: this cannot be completely prevented by separating section from emulsion by means of a layer of evaporated carbon. Chemical treatment of the sections before autoradiography may reduce the chemography. Treatment with 1% hydrogen peroxide for 15 min reduced it to such an extent that subsequent coating with 5 nm carbon abolished it. Material block stained in this way gave excellent contrast, both for light and electron microscopy.

Selective logging in tropical forests decreases the robustness of liana–tree interaction networks to the loss of host tree species

Selective logging is one of the major drivers of tropical forest degradation, causing important shifts in species composition. Whether such changes modify interactions between species and the networks in which they are embedded remain fundamental questions to assess the ‘health’ and ecosystem functionality of logged forests. We focus on interactions between lianas and their tree hosts within primary and selectively logged forests in the biodiversity hotspot of Malaysian Borneo. We found that lianas were more abundant, had higher species richness, and different species compositions in logged than in primary forests. Logged forests showed heavier liana loads disparately affecting slow-growing tree species, which could exacerbate the loss of timber value and carbon storage already associated with logging. Moreover, simulation scenarios of host tree local species loss indicated that logging might decrease the robustness of liana–tree interaction networks if heavily infested trees (i.e. the most connected ones) were more likely to disappear. This effect is partially mitigated in the short term by the colonization of host trees by a greater diversity of liana species within logged forests, yet this might not compensate for the loss of preferred tree hosts in the long term. As a consequence, species interaction networks may show a lagged response to disturbance, which may trigger sudden collapses in species richness and ecosystem function in response to additional disturbances, representing a new type of ‘extinction debt’.