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Biomedical subjects

D R Abramovich

Publications and source records attributed to D R Abramovich.

At least 19 recordsLinked to original sources

Ponderal index is a poor predictor of in utero growth retardation.

OBJECTIVE: To evaluate the usefulness of ponderal index (PI) and related indices of weight and length in identifying asymmetric growth, body thinness and organ asymmetry associated with IUGR. DESIGN: Cross sectional study. SETTING: Aberdeen Maternity Hospital. POPULATION: The population includes term (>/=37 weeks) singleton live births (n= 53,934) between 1986 and 1996, ultrasound measurements in 2522 pregnancies, 712 unselected term pregnancies in 1979/1980 and stillbirths (24-36 weeks) between 1986 and 1995 where the fetus was diagnosed as suffering from acute (n= 73) or chronic (n= 30) anoxic death. METHODS: The strength of association between direct measures of IUGR and various indices of weight and length was determined by linear and multiple stepwise linear regression. MAIN OUTCOME MEASURES: Weight, length, PI and skinfold thicknesses (triceps, biceps, flank thighs, back) were measured at birth. Abdominal circumference, biparietal diameter and femur length were measured by ultrasound at >/=37 weeks. Ratio of liver, heart and kidney to brain were measured in stillbirths. RESULTS: Weight alone was a better predictor of skinfold thickness, abdominal circumference and the ratio of abdominal circumference to biparietal diameter than weight divided by length raised to the power 1, 2, 3 (PI), 4 or 5. The inclusion of gestational age made little difference to the predictive ability of weight for these full term births. Weight, but not PI, was significantly different between the two groups of stillborn fetuses (chronic and acute), which had significantly different (P < 0.001) organ ratios. CONCLUSION: Body weight alone was a better predictor of anthropometric ratios, organ asymmetry and measures of thinness at birth thought to be associated with IUGR than the PI. The inclusion of a length term generally reduced the predictive ability with the highest powers resulting in the poorest prediction.

Body Weight↗

Placental nutrient transfer capacity and fetal growth.

The objective of this study was to determine whether the ability of the human placenta to transfer glucose and fatty acids is related to normal fetal growth. The intrinsic nutrient transport capacity of the placenta was measured under standardized conditions during in vitro perfusion of 30 human term placentas and related to birth weight (range 2640-4640g), birth weight centile (8th-99th), ponderal index (2.43-3.69), placental weight (418-1030g) and placental:fetal weight (0.14-0.31). There was no statistically significant change in the rate of nutrient transfer per placenta or per kg fetal weight, with birth weight, birth weight centile, ponderal index, placental weight and placental:fetal weight. There was a weak but significant relationship (P=0.020, r(2)=9 per cent) between the ratio of glucose to fatty acid transport and birth weight centile, largely due to the high ratio found in the lowest birth weight quartile where the babies are thinnest. This study provides no evidence that placental nutrient transport capacity limits fetal growth across a wide range of birth weights in normal pregnancies. It is proposed that the fetus itself may regulate placental nutrient transport in vivo via the fetal cardiac output and the rate of fetal nutrient utilization.

Adult↗

The effect of maternal smoking and ethanol on fatty acid transport by the human placenta.

The role of the placenta in controlling the supply of fatty acids to the fetus was investigated in term placentas from non-smokers (n 5), smokers (>ten cigarettes/d; n 5) and after addition of ethanol at 2 mg/ml (n 4). The maternal side was of the placenta was perfused ex vivo for 90 min with a physiological mixture of fatty acids and fatty acid:human albumin ratio. There was no effect of smoking on the transfer of linoleic (LA, 18: 2 n-6), alpha-linolenic (alphaLN, 18: 3 n-3), arachidonic (AA, 20: 4 n-6) or docosahexaenoic acid (DHA, 22: 6 n-3), expressed per perfused area (calculated from H2(18)O exchange). However, the presence of ethanol in the perfusate at a concentration of 2 mg/ml significantly reduced (P<0.01) the absolute rate of transfer of the two n-3 polyunsaturated fatty acids, alphaLN and DHA. This specific effect of ethanol on alphaLN and DHA also resulted in an altered selectivity for transfer of individual fatty acids. In the non-smoking control group the placenta selectively transferred polyunsaturated fatty acids to the fetus in the order DHA > AA > alphaLN > LA. The order of selectivity was unaltered in placentas from smokers, but the addition of ethanol to the perfusion medium altered the order of selectivity to AA > alphaLN > LA > DHA. The presence of ethanol in the perfusate was also associated with a significant reduction (P<0.05) in the clearance of H2(18)O. These results suggest that the presence of ethanol at a concentration of 2mg/ml may reduce the availability of polyunsaturated fatty acids to the developing fetus.

Arachidonic Acid↗

Characterization of an antibody to the human melatonin mt1 receptor.

Melatonin acts via high affinity, G-protein coupled, seven transmembrane domain receptors. To precisely localize these receptors, antibodies were raised in chickens against a 15 amino acid fragment at the intracellular C-terminal region of the human melatonin receptor subtype mt1 (DSSNDVADRVKWKPS, mt(1338-352)). A chimeric form of the receptor with a hydrophilic Flag peptide (DYKDDDDK) in sequence with the extracellular N-terminus (Flag-mt1) was generated by polymerase chain reaction and expressed in mammalian cell lines. An IgY antibody (Y31), which gave high antibody titres by enzyme-linked immunosorbent assay, was used to localize Flag-mt1 in stably transfected cells by immunofluoresence. Flag-mt1 localization with Y31 was identical to that obtained with the M5 antibody directed against the Flag epitope and was mainly localized to the Golgi apparatus with some staining at the cell surface. No staining was seen in untransfected cells with either antibody. Y31 staining was abolished using antibody preabsorbed with peptide antigen. Y31 immunofluorescence in fetal human kidney sections was restricted to nephrogenic regions and matched that of 2-((125)I)iodomelatonin binding and mt1 gene expression by in situ hybridization. Y31 was used to immunoprecipitate biotinylated membrane proteins from Flag-mt1 stably transfected and untransfected CHO cells. Western blotting of immunoprecipitated proteins revealed two major bands specific to stably transfected cells, one at 63 kDa and one at 86 kDa. The first band almost certainly corresponds to the glycosylated form of Flag-mt1 and the second band to receptor dimers. Thus, Y31 antibody is suitable for use in detecting the human mt1 receptor subtype in tissues and in transfected cells.

Amino Acid Sequence↗

Leptin secretion to both the maternal and fetal circulation in the ex vivo perfused human term placenta.

The contribution of placental leptin, if any, to both the fetal and maternal circulation and its role in pregnancy remains to be determined. In an experiment to investigate this, 27 placentae from term pregnancies were perfused ex vivo (gestational age=39.5 s.d. 1.2; range=38-42 weeks: fetal weight=3285 s.d. 482; range=2480-4420; birthweight centile range=4th to the 98th) at both the maternal and fetal interface. Placental leptin was exported into both the maternal and fetal circulations. The log leptin production by the maternal side of the placenta was significantly greater (P=0.001) than that for the fetal side (5.193 s.d.1.049 versus 4.387 s.d. 0.768 ng/placenta/min). There was no significant relationship between maternal and fetal log leptin production and maternal body mass index, birthweight, birthweight centile, ponderal index or gestational age or with cord blood pO(2), pCO(2) and pH. There was however, a significant increase in the maternal log leptin production with increasing fetal to placental weight ratio (P=0.017; r(2)=20.7 per cent) but no corresponding relationship for fetal leptin production. It is proposed that such a mechanism would allow the placenta to modulate fat supply to the fetus in response to the fetal demand relative to placental supply.

Body Mass Index↗

Endocrine disrupting chemicals: effects on human male reproductive health.

There is now considerable evidence that male reproductive function is declining in human and wildlife populations. This is coincident with the increasing use and prevalence of man-made chemicals in the environment over the last fifty years. Certain chemicals have subsequently been shown to disturb the developing fetal endocrine system of laboratory animals in utero. In these experiments, treatment caused similar male reproductive problems in offspring as those already observed in wildlife and human populations. In addition, both the human DES data and rodent studies have shown that there are specific windows of gestation when the developing fetal gonad is highly sensitive to small endocrine changes. Animal in vivo and human in vitro studies have identified EDC sensitive genes. Consequently, hypotheses are being generated concerning mechanism of action e.g. disturbed testicular apoptosis and altered hepatic biotransformation of steroids. While animal studies provide us with valuable insights into the range of effects that can be attributed to in utero EDC exposure, varying maternal doses employed by different research groups make relation of the results to human observations difficult. The EDC concentration representative of fetal exposure levels is uncertain. Confounding factors include: (a) the vast number of chemicals termed EDCs, (b) the ability of chemicals to bioaccumulate in body lipid, (c) the metabolism of body lipid during pregnancy releasing the mothers lifetime EDC legacy into circulation and (d) the poorly understood kinetics of EDC transfer across the placenta. Thus, the level of fetal exposure can only be crudely estimated at present. This highlights the need for large animal models of EDC in utero exposure where the partitioning of EDCs between the mother and fetus and transfer across the placenta can be studied in detail. Despite considerable effort the mechanisms by which these endocrine disrupting chemicals exert their effects are still largely unknown. Further studies of the mechanism of action, and consequences, of EDCs in fetal development must be done in order to elucidate how EDCs exert their effects. This can only be achieved using a combined approach whereby animal models are used in combination with in vitro human studies. In conclusion however, there are now sufficient animal model data to prove that EDCs can adversely affect reproductive development and function in the male. Our further understanding of the mechanisms involved may allow intervention strategies whereby we can at least prevent a further decline in male as well as female reproductive health.

Animals↗

Maternal cigarette smoking and oxygen diffusion across the placenta.

The aim of this study was to test whether or not adaptations in partial, total and specific oxygen diffusive conductances occur in the placentae of women who smoke cigarettes during pregnancy and help to compensate for intrauterine fetal hypoxic stress. Tissue sections were randomly sampled from human term placentae divided into two groups (non-smokers and smokers) according to maternal smoking status. In smokers, status was expressed as either declared smoking rate or level of plasma cotinine (the major metabolite of nicotine). Sections were analysed stereologically to estimate key structural quantities (vascular volumes, exchange surface areas, tissue diffusion distances). These were combined with previously-published physicochemical quantities (oxygen-haemoglobin reaction rates and tissue oxygen diffusion coefficients) in order to estimate the partial conductances of six tissue compartments of the oxygen pathway: maternal erythrocytes and plasma, villous trophoblast, villous stroma (including fetal capillary wall), fetal plasma and erythrocytes. From partial conductances and birthweights, total and specific conductances were calculated for each placenta. Results were assessed statistically by analyses of variance and t -tests. Despite apparent improvements in the partial conductances of the maternal erythrocytes and plasma, total and specific conductances did not alter significantly in smoking groups. However, the relative biases affecting these estimates may be different in smokers and non-smokers. We conclude that total conductance does not increase in placentae associated with maternal smoking. However, given that the fetus suffers chronic hypoxic stress as a consequence of smoking (evidenced here by elevated haematocrits), even a constant diffusive conductance implies a reduced transplacental partial pressure gradient. This could be a contributory factor to the reduced birthweight.

Adult↗

Human fetal testis: second trimester proliferative and steroidogenic capacities.

The period of Leydig cell hyperplasia (14-18 weeks gestation) in human fetal testis is crucial for normal gonad development. We have studied the spatio-temporal distribution of key developmental and functional markers in human fetal testis between 13-19 weeks gestation. Proliferating cell nuclear antigen-positive cells were immunolocalized to both interstitium and tubules. Image analysis confirmed an increase in positive interstitial cells during Leydig cell hyperplasia (P: < 0.05). c-Myc was localized to the interstitium with no gestational changes. The steroidogenic enzymes 3beta-hydroxysteroid dehydrogenase (protein) and cytochrome P450 17alpha-hydroxylase/C(17-20)-lyase (P450c17; messenger ribonucleic acid and protein) were confined to the Leydig cells. The number of immunopositive cells increased between 13 and 19 weeks (P: < 0.001). P450c17 mRNA (in situ hybridization) and protein were localized to the same population of interstitial Leydig cells. Androgen receptor and Bcl-2 protein (anti-apoptotic) were gradually restricted to the peritubular myoid cells as gestation progressed. Conversely, Bax protein (pro-apoptotic) was predominantly localized to the tubule Sertoli cells, whereas the germ cells were Bax immunonegative. In conclusion, human fetal Leydig cell hyperplasia is characterized by increasing numbers of proliferating cells and increased expression of steroidogenic enzymes. The Bcl-2-positive, Bax-negative status of the peritubular myoid cells may be a strategy for cell survival.

3-Hydroxysteroid Dehydrogenases↗

Variable inhibition of placental IgG transfer in vitro with commercial IVgG preparations.

Maternal administration of high-dose intravenous immunoglobulin (IVIgG) for treating fetal RhD haemolytic disease and alloimmune thrombocytopenias may be beneficial. Treatment failures, even when IVIgG is used optimally, may result from product differences. Using an in vitro placental perfusion model there was significant inhibition of placental anti-D IgG transfer with three commercial IVIgG preparations where circulating maternal IgG concentrations were > 20 g/l. One IVIgG product, which was not inhibitory, had lower circulating IgG levels (16.5 +/- 0.9 g/l) and significantly reduced placental transfer of total IgG, suggesting that the reduced functional activity of IgG from IVIgG preparations may correlate with poor clinical efficacy.

Erythroblastosis, Fetal↗

Effect of maternal polyunsaturated fatty acid concentration on transport by the human placenta.

The role of the placenta in controlling the supply of fatty acids to the fetus was investigated in term placentas (n = 5) from normal pregnancies. The maternal side was perfused ex vivo for 90 min with a modified Krebs Ringer solution containing a physiological mixture of fatty acids - designed to mimic the composition of non-esterified fatty acids (NEFA) measured in the last trimester of pregnancy (n = 10) - and ratio of fatty acid to human albumin. The selectivity for alpha-linolenic acid (alphaLN) transfer to the fetal circulation was not significantly different from that observed when using the triglyceride (TG) composition (1.21 +/- 0.04), but significantly different for AA (1.43 +/- 0.12; p < 0.001) and docosahexaenoic acid (DHA; 2.02 +/- 0.09; p = 0.048). The absolute rate of transfer (nmol. ml-1) compared to that using the TG maternal perfusate composition was significantly different for LA (0.562 +/- 0.038; p = 0.50), alphaLN (0.130 +/- 0.009; p < 0.001), arachidonic acid (AA; 0.218 +/- 0.022; p = 0.001) and DHA (0.383 +/- 0.04; p < 0.001). Thus, placental selectivity for alphaLN and DHA appears to be relatively unresponsive to changes in the mixture of fatty acids in the maternal circulation but the selectivity for AA increased with the increase in the maternal AA concentration. For an 8-fold increase in the concentration of DHA in the maternal circulation there was a 13-fold increase in the transfer of DHA to the fetal circulation. For a 2-fold increase in the concentration of AA, transfer was increased 8-fold. For a 1.3-fold increase in the concentration of alphaLN, transfer was increased 2.1-fold. These results suggest that the maternal concentration of individual fatty acids, and hence the composition of the maternal diet, can have large effects on polyunsaturated/long-chain polyunsaturated fatty acids delivery to the fetus.

Adult↗

Admission-discharge policies for hysteroscopic surgery: a randomised comparison of day case with in-patient admission.

OBJECTIVE: To study the effectiveness and acceptability of day case hysteroscopic surgery. DESIGN: Prospective randomised controlled trial. SETTING: Aberdeen Royal Infirmary. SUBJECTS: One hundred and ninety four consecutive women who underwent hysteroscopic endometrial ablation. INTERVENTION: Seventy three women were allocated to day case surgery and 37 to inpatient admission; 84 women though otherwise fit for day case surgery were scheduled for in-patient admission as they lived more than 20 miles away. All women completed a questionnaire 24 h after their operations. Readmission rates were obtained from case notes. Satisfaction rates 12 months after the operation were recorded by means of a follow-up questionnaire. RESULTS: Post-operative pain was absent or slight in 48 (75%) of the women in the day case group 27 (84%) of women in the in-patient group, and 55 (82%) in the non-randomised in-patient group. Post-operative analgesia was necessary in 34 (52%) women in the day case group, 24 (75%) women in the in-patient group and 36 (53%) women in the non-randomised in-patient group. Hospital costs were significantly less in the day case group. Satisfaction with stay 92% in the day case group, and 100% in the other two groups. CONCLUSION: In this setting, day care is a safe acceptable and less expensive alternative to in-patient care for hysteroscopic endometrial ablation.

Adult↗

Dietary intake and tissue concentration of fatty acids in omnivore, vegetarian and diabetic pregnancy.

The aim of this study was to determine the effect of fatty acid intake and insulin dependent diabetes on the fatty acid composition of maternal erythrocytes, the placenta and cord. Fatty acid intake (from food frequency questionnaire) and the fatty acid composition of maternal erythrocytes, the placenta and cord from pregnant vegetarians (n = 4) and insulin dependent diabetics (n = 5) was compared with pregnant omnivores (n = 10). There was a significantly lower intake of n-6 long chain polyunsaturated fatty acid (LCPUFA) (-75% P < 0.01) and n-3 LCPUFA (-92% P < 0.01) and increased ratio of n-6/n-3 LCPUFA in the vegetarians (103%; P < 0.001). The concentrations of 22:4 n-6 (+28%; P < 0.05) and 22:5 n-3 (+40%; P < 0.05) were higher in vegetarian erythrocytes. Placental 18:2 n-6 (+26.9%; P < 0.05) 18:3 n-3 (+139%; P < 0.05) and 22:5 n-3 (+24%; P < 0.05) were increased while 20:5 n-3 (-36%; P < 0.05), 22:6 n-3 (-16%; P = 0.059), and the ratios of 20:4 n-6/18:2 n-6 (P < 0.01) and 22:6 n-3/18:3 n-3 were reduced. 22:6 n-6 (-49%; P < 0.05) and total n-3 LCPUFA (-11%; P < 0.01) were reduced in vegetarian cord. For the diabetic mothers, all of the n-6 LCPUFA and n-3 LCPUFA were reduced in the maternal erythrocytes; 22:4 n-6 (-42%; P < 0.05), 22:5 n-6 (-46%; P < 0.05) and 22:6 n-3 (-41%; P < 0.05). For the diabetic placenta and cord the general pattern of n-3 LCPUFA was the same as that in the vegetarians. In the vegetarian mothers, the PUFA profiles in the maternal erythrocytes, placenta and cord are consistent with an elevation in the rate of LCPUFA synthesis in order to make up the relative deficit in LCPUFA intake. However, it may be that the higher level of desaturase activity is not able to overcome the dietary deficit of 22-6 n-3 and 22:6 n-6. Despite the fact that the dietary LCPUFA intake in the pregnant diabetic was comparable with that in the pregnant 'normal' omnivore mothers, the pattern of PUFA in the tissues resembled that of the vegetarian mothers.

Diabetes Mellitus, Type 1↗

Melatonin receptors in the human fetal kidney: 2-[125I]iodomelatonin binding sites correlated with expression of Mel1a and Mel1b receptor genes.

Melatonin receptors in the human fetal kidney were identified and characterized by quantitative in vitro autoradiography using the melatonin agonist, 2-[125I]iodomelatonin. Specific binding was localized to cells in the nephrogenic region at the outer perimeter of the developing kidney and was time-dependent, saturable and inhibited in the presence of guanosine 5'-0-(3-thiotriphosphate) indicative of a G protein-coupled receptor. Expression of the Mel1a and Mel1b melatonin receptors in human fetal kidney was determined using RT-PCR. In situ hybridization confirmed the localization of the Mel1a mRNA transcripts. A role for melatonin in development of the human fetal kidney is postulated.

Autoradiography↗

The role of melatonin in the human fetus (review).

Melatonin, an indole amine, primarily derived from the pineal gland is secreted during the hours of darkness. Melatonin acts as a hormonal transduction of photoperiod influencing the timing of seasonal and daily (circadian) physiological rhythms. Maternal melatonin crosses the placenta and enters the fetal circulation providing photoperiodic information to the fetus influencing the subsequent circadian and seasonal rhythms of the offspring. The function of melatonin in humans is more obscure. However, melatonin has attained prominence as a treatment for disturbed circadian rhythms and sleep patterns which occur as a result of transmeridian travel, shift work or blindness. The biological clock, the hypothalamic suprachiasmatic nuclei (SCN), possesses melatonin receptors, in both the adult and fetal human. This concurs with the reported influence of melatonin on human circadian rhythmicity and indicates that this influence may begin in utero. Melatonin receptors are widespread in the human fetus and occur in both central and peripheral tissue from early in fetal development. Thus, the influence of melatonin on the developing human fetus may not be limited to entraining circadian rhythmicity. Considering the transplacental availability of melatonin to the fetus the ingestion of melatonin by pregnant women may be inadvisable.

Fetus↗

Identification and characterisation of 2-[125I]iodomelatonin binding and Mel1a melatonin receptor expression in the human fetal leptomeninges.

Melatonin binding sites were identified over the leptomeninges surrounding the human fetal brain using quantitative in vitro autoradiography and the melatonin agonist, 2-[125I]iodomelatonin. Binding was found to be saturable and of high affinity (dissociation constant (Kd) = 54 pM and maximal theoretical binding (Bmax) = 13 fmol/mg protein), and inhibited by guanosine-5'-o-(3-thiotriphosphate) (GTPgammaS) suggesting that these binding sites represent G protein-coupled melatonin receptors. RT-PCR performed on mRNA isolated from the human fetal leptomeninges detected expression of the G protein-coupled melatonin receptor Mel1a, but not Mel1b. In situ hybridisation confirmed the localisation of Mel1a mRNA transcripts over the leptomeninges of the fetal brain. The identification of 2-[125I]iodomelatonin and Mel1a melatonin receptor expression in the fetal leptomeninges implies that melatonin may play a role in the early growth and development of the human brain.

Fetus↗

Long-chain polyunsaturated fatty acid transport across the perfused human placenta.

The role of the placenta in controlling the supply of fatty acids to the fetus was investigated in term placentae (n = 9) from normal pregnancies. The maternal side was perfused ex vivo for 90 min with a modified Krebs Ringer solution containing a physiological mixture of fatty acids and ratio of fatty acid to human albumin. There was no evidence of chain elongation and desaturation of the essential fatty acids. Relative to the value for oleic acid, the rate of transfer to the fetal circulation was: 1.30 +/- 0.02 (P < 0.001) for linoleic acid, 1.61 +/- 0.09 (P = 0.002) for alpha-linolenic acid, 0.67 +/- 0.10 (P = 0.033) for arachidonic acid and 2.10 +/- 0.16 (P = 0.003) for docosahexaenoic acid. For tissue accumulation the values were 1.47 +/- 0.39 (P < 0.001) for linoleic acid, 2.24 +/- 0.37 (P = 0.027) for alpha-linolenic acid, 9.84 +/- 1.03 (P = 0.001) for arachidonic acid, and 3.01 +/- 0.79 (P = 0.064) for docosahexaenoic acid. The order of selectivity for transfer from the maternal to the fetal circulation was docosahexaenoic > alpha-linolenic > linoleic > oleic > arachidonic acid. Such a mechanism would allow the preferential transfer of docosahexaenoic acid and the essential fatty acids to the fetal circulation, thereby protecting the polyunsaturated fatty acid supply to the fetus during a critical period of development.

Adult↗

Transfer of anti-D antibodies across the isolated perfused human placental lobule and inhibition by high-dose intravenous immunoglobulin: a possible mechanism of action.

Using an in vitro perfusion model, therapeutic intravenous immunoglobulin (IVIgG) and IgG anti-D have been shown to cross the placenta from the maternal circuit to the fetal circuit. The transfer of all IgG species was linear with respect to time, and the amount of IgG transferred was proportional to the concentration of IgG in the maternal circuit ([IgG]m), but reached saturation at upper limits. With total [IgG]m at 6.5 g/l, 11.1 g/l or 26.2 g/l the increase in the fetal concentration of total IgG was 4.6 mg/l/h. 8.9 mg/l/h and 9.9 mg/l/h respectively. The rate of transfer of specific anti-D antibody to the fetal circuit was 0.026 IU/ml/h at a concentration of 38 IU/ml in the maternal circuit ([anti-D]m). High-dose therapeutic IVIgG added to the maternal circuit (total [IgG]m 29.2 g/l) significantly inhibited (P < 0.001) anti-D transfer to 0.004 IU/ml/n. Addition of the same IVIgG at a lower concentration (total [IgG]m 11.1 g/l) also reduced anti-D transfer, but only to 0.015 IU/l/h. The inhibitory effect of IVIgG does not appear to be mediated by anti-idiotypic or non-specific complexing with the anti-D, but may be the result of competition with IgG anti-D for placental Fc gamma receptors involved in the endocytotic uptake of IgG. The efficacy of IVIgG in this model suggests that it may be clinically useful in preventing HDN and other immune cytopenias, provided a sufficiently high dose is given.

Female↗

A pragmatic randomised comparison of transcervical resection of the endometrium with endometrial laser ablation for the treatment of menorrhagia.

OBJECTIVE: To compare endometrial laser ablation (ELA) with transcervical resection of the endometrium (TCRE) in the treatment of menorrhagia. DESIGN: Randomised controlled trial. SETTING: Gynaecology department of a large teaching hospital. PARTICIPANTS: Women with menorrhagia due to dysfunctional uterine bleeding (n = 372) were randomly allocated to ELA (n = 188) or TCRE (n = 184). MAIN OUTCOME MEASURES: Operative complications, post-operative recovery, relief of menstrual and other symptoms, need for further surgical treatment, satisfaction with treatment after 6 and 12 months, and differential resource use. RESULTS: TCRE was significantly quicker, with lower rates of fluid overload. Perioperative morbidity was low and similar in both groups. Outcome at 12 months was also similar: 72 women (45%) had either amenorrhoea or brown discharge in the ELA group compared with 71 (49%) in the TCRE group; 79 (49%) versus 68 (46%) had lighter periods. Thirty (16%) versus 36 (20%) had received further surgical treatment: 9 (5%) compared with 25 (14%) had had a hysterectomy and 21 (11%) versus 11 (6%) had received repeat ablation. Anxiety and depression, dysmenorrhoea and pre-menstrual symptoms were improved by both procedures and bladder symptoms were affected by neither. At 12 months 148 (90%) women in the ELA group and 140 (91%) women in the TCRE group were satisfied with their treatment. The estimated additional cost of ELA was Pound 145 per procedure. CONCLUSIONS: At one year there was no clear difference in clinical outcome between ELA and TCRE. Both procedures were associated with low morbidity. ELA was the more costly procedure. Despite the need for further surgery for about one in six women, satisfaction rates were high following both ELA and TCRE.

Adult↗