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Analysis of intra-uterine cytokine concentration and matrix-metalloproteinase activity in women with recurrent failed embryo transfer.

BACKGROUND: In all IVF programmes, some patients fail to achieve an ongoing pregnancy, even after numerous embryo transfer procedures. An unfavourable environment within the uterus might be a contributory factor to such recurrent implantation failure. This question was addressed by measuring cytokine concentrations and matrix metalloproteinase activities in fluid derived from uterine irrigation of such patients. METHODS AND RESULTS: The uterine cavities of 22 patients who had previously undergone embryo transfer of at least 10 embryos without ongoing pregnancy were irrigated during the luteal phase. The resultant fluid was assayed for the concentration of interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, leukaemia inhibitory factor (LIF), IL-10 and matrix metalloproteinase (MMP) -2 and -9 activity. The results were compared with those of a control population of women known to be previously fertile (n = 16) and also with women with recurrent spontaneous abortion (n = 13). In the recurrent implantation failure group, the MMP score and IL-1beta concentration were significantly higher than those in the control group, whereas concentrations of IFN-gamma and IL-10 were significantly lower. CONCLUSIONS: In IVF patients with recurrent implantation failure, an altered pattern of intra-uterine cytokine concentration and MMP activity was observed.

Abortion, Habitual↗

Identification of Xenopus laevis sperm and egg envelope binding components on nitrocellulose membranes.

Interacting egg envelope and sperm surface components were identified for Xenopus laevis using blotting methods. Sperm were extracted with sodium dodecyl sulfate (SDS), the extracted proteins separated by gel electrophoresis and blotted, and the blots treated with 125I-labeled heat solubilized envelopes. The converse experiment was also performed where envelope components were separated by gel electrophoresis, blotted, and the blots treated with 125I-labeled sperm components. Blotted sperm components with apparent molecular weights of 14K, 19K, 25K, and 35K selectively bound the solubilized envelopes. All of the envelope binding components were found to be localized on the sperm surface by radioiodinating intact sperm using Iodo-Gen. The blotted egg envelope component with an apparent molecular weight of 37K selectively bound to solubilized sperm components, and this binding was due to the protein moiety of the glycoprotein. 125I-labeled heat solubilized envelopes from unfertilized and fertilized eggs showed the same pattern of binding to blotted sperm components. Selected sulfated carbohydrates (fucoidan, dextran sulfate, and heparin, but not chondroitin sulfate) inhibited fertilization and binding of 125I-labeled heat solubilized envelopes to blotted sperm extract. Thus, the binding of heat solubilized envelopes to electrophoretically separated and blotted sperm proteins may reflect cellular interactions.

Animals↗

Oocyte euploidy, pronuclear zygote morphology and embryo chromosomal complement.

BACKGROUND: Pronuclear morphology has been proposed as an indicator of embryo development and chromosomal complement. In this study, the morphology of pronuclear zygotes generated from euploid oocytes [diagnosed by first polar body (PB1) analysis] was evaluated and compared with the configurations observed in chromosomally normal embryos (diagnosed by blastomere analysis). MATERIALS AND METHODS: Group 1--238 patients underwent 273 assisted conception cycles in combination with the screening of aneuploidy on PB1 for the chromosomes 13, 15, 16, 18, 21 and 22. Only normal oocytes were inseminated. Group 2--218 patients underwent 318 assisted conception cycles with aneuploidy screening on day 3 embryos. In both groups, oocytes were checked for fertilization and pronuclear morphology at 16 h after insemination. RESULTS: Seventy-three percent of zygotes from Group 1 had the configurations with centralized and juxtaposed pronuclei, large-size aligned or scattered nucleoli and PB located in the longitudinal or perpendicular axis of pronuclei. In Group 2, these configurations corresponded to those with the highest proportion of chromosomally normal embryos. Accordingly, in both groups, these configurations had a higher implantation rate than all the others. CONCLUSIONS: These observations confirm that some patterns of pronuclear morphology are associated with a higher proportion of euploidy and implantation reaffirming the relevance of this scoring system for the prediction of zygote viability.

Adult↗

Uterine thermal balloon therapy for the treatment of menorrhagia: the first 300 patients from a multi-centre study. International Collaborative Uterine Thermal Balloon Working Group.

OBJECTIVE: To evaluate the safety and efficacy of thermal balloon therapy for menorrhagia. DESIGN: Prospective, observational study. SETTING: Fifteen centres in Canada and Europe. POPULATION: Two hundred and ninety-six eligible women for whom follow up data were available for three months or more. Eligible women included those for whom further fertility was not a concern, were not postmenopausal, suffered from intractable menorrhagia, had a normal uterine cavity, and who were fully informed regarding the investigational nature of uterine thermal balloon therapy. METHODS: Three hundred and twenty-one procedures of balloon endometrial ablation were performed using the same protocol between June 1994 and August 1996. Exclusion criteria included structural uterine abnormality or (pre) malignant lesions. Treatment entailed controlled heating of fluid in an intrauterine balloon. General anaesthesia was employed in the 61% of procedures while local anaesthesia with or without sedation was used in 39% of cases. ANALYSIS: Follow up data at 3 and/or 6, and/or 12 months were required for inclusion in the analysis. A paired t test, Wilcoxon signed-ranks test, and multiple and logistic regression analyses were used to evaluate the changes in bleeding and dysmenorrhoea patterns, and possible confounding variables, respectively. Success was defined as the subjective reduction of menses to eumenorrhoea or less. RESULTS: No intra-operative complications occurred, and post-operative morbidity was minimal. Success of the procedure was constant over the year (range 88%-91%). Treatment led to a significant decrease in the duration of menstrual flow and severity of pain (P < 0.0001). Increasing age, higher balloon pressure, smaller uterine cavity, and a lesser degree of pre-procedure menorrhagia were associated with significantly improved results. Pre-treatment with gonadotrophin releasing hormone agonists increased amenorrhoea and spotting rates (P = 0.03), but was only used in 5% of cases. CONCLUSION: Thermal balloon endometrial ablation appears to be safe, as well as effective in properly selected women with menorrhagia and is potentially an outpatient procedure.

Catheter Ablation↗

Breast cancer risk in relation to type of estrogen contained in oral contraceptives.

We report analyses designed to address the recent hypothesis that women who use combination-type OCs containing ethinylestradiol (EE) are at increased risk of breast cancer before age 45, if use of such OCs occurs prior to first term pregnancy (FTP). Our findings, based on data from 1679 cases and 1689 controls, 20-44 years of age, from the population-based Cancer and Steroid Hormone Study, are against the hypothesis. The relative risk of breast cancer by duration of exclusive use prior to FTP of OCs containing EE is estimated to be 1.0 (1-12 months EE use), 1.2 (13-48 months EE use), and 0.9 (49+ months EE use). There was no evidence of a latent effect. Among parous women with 49+ months exclusive use prior to FTP of EE-containing OCs, the relative risk of breast cancer was estimated as 0.9 (0-4 years after FTP) and 0.6 (5-9 years after FTP). Among nulliparous women with 49+ months exclusive use of EE-containing OCs, the relative risk of breast cancer was estimated as 1.0 (0-4 years since first use), 0.7 (5-9 years since first use), and 1.1 (10-14 years since first use). With regard to exclusive use of OCs containing mestranol, parous women who used such preparations long-term before their FTP showed no alteration of breast cancer risk, even 15 years or more after pregnancy. Nulliparous women with exclusive use of ME-containing OCs did show elevations in breast cancer risk, but the magnitude of risk in relation to duration of use and latent interval shows no pattern that suggests a cause-effect relationship.

Adult↗

Genetic differentiation in the soil-feeding termite Cubitermes sp. affinis subarquatus: occurrence of cryptic species revealed by nuclear and mitochondrial markers.

BACKGROUND: Soil-feeding termites are particularly interesting models for studying the effects of fragmentation, a natural or anthropic phenomenon described as promoting genetic differentiation. However, studying the link between fragmentation and genetics requires a method for identifying species unambiguously, especially when morphological diagnostic characters are lacking. In humivorous termites, which contribute to the fertility of tropical soils, molecular taxonomy and phylogenetic relationships are rarely studied, though mitochondrial and nuclear molecular markers are widely used in studies of pest termites. Here, we attempt to clarify the taxonomy of soil-feeding colonies collected throughout the naturally fragmented Lopé Reserve area (Gabon) and morphologically affiliated to Cubitermes sp. affinis subarquatus. The mitochondrial gene of cytochrome oxidase II (COII), the second nuclear rDNA internal transcribed spacer (ITS2) and five microsatellites were analyzed in 19 colonies. RESULTS: Bayesian Inference, Maximum Likelihood and Maximum Parsimony phylogenetic analyses, which were applied to the COII and ITS2 sequences, and Neighbor-Joining reconstructions, applied to the microsatellite data, reveal four major lineages in the Cubitermes sp. affinis subarquatus colonies. The concordant genealogical pattern of these unlinked markers strongly supports the existence of four cryptic species. Three are sympatric in the Reserve and are probably able to disperse within a mosaic of forests of variable ages and savannahs. One is limited to a very restricted gallery forest patch located in the North, outside the Reserve. CONCLUSION: Our survey highlights the value of combined mitochondrial and nuclear markers for exploring unknown groups such as soil-feeding termites, and their relevance for resolving the taxonomy of organisms with ambiguous morphological diagnostic characters.

Animals↗

Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome.

AIM: To study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome (KFS). METHODS: Blood and semen samples were collected from azoospermic patients with KFS (n = 14) and a control group of men of proven fertility (n = 13). Semen analysis was done according to World Health Organization (WHO) guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization (FISH) and measurement of plasma follicle stimulating hormone (FSH) by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction (PCR) of 16 sequence tagged sites (STS) and three genes (DFFRY, XKRY and RBM1Y) was performed on isolated genomic DNA. Testicular fine needle aspiration cytology (FNAC) was done in selected cases. RESULTS: Y chromosome microdeletions spanning the azoospermia factor (AZF)a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels. CONCLUSION: Patients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques.

Adolescent↗

Emergency contraception: preventing unintended pregnancy.

Approximately 60% of all pregnancies are unintended at the time of conception, either unwanted or mistimed. Emergency contraception (i.e., use of a birth control method after intercourse has occurred) is a preventive treatment that has been underutilized. Six brands of oral contraceptives have recently been found by the U.S. Food and Drug Administration to be safe and effective as emergency contraceptive pills. These pills have been shown to reduce the likelihood of pregnancy occurring by at least 74%. Treatment with emergency contraceptive pills should be initiated within 72 hours of unprotected intercourse. Adverse effects include nausea, vomiting headache, and a change in menstrual bleeding patterns. Postcoital insertion of an intrauterine device is also highly effective as a postcoital contraceptive, but only in a select group of patients at low risk for sexually transmitted diseases. Promotion of access to emergency contraception includes educating both patients and providers about the method and making emergency contraceptive pills available to patients even before the need arises.

Contraceptives, Postcoital↗

Factors associated with ex-nuptial birth.

The paper examines the background to 210 live exnuptial births studied in the first phase of the Christ-church Child Development Study. The results show: 1. That nearly half of the children had been conceived within cohabiting situations. 2. That nearly one in five ex-nuptial children was the result of a planned pregnancy. 3. Maternal reactions to the birth and pregnancy varied with the mother's situation: cohabiting mothers reported considerably less adverse reaction to the birth than did non-cohabiting mothers. 4. Overall, mothers of ex-nuptial children had a fairly sophisticated appreciation of contraceptive methods. 5. One quarter of unplanned ex-nuptial pregnancies were the result of contraceptive failure and three-quarters were the result of contraceptive non-usage. 6. In common with previous findings for nuptial pregnancies, about 35 percent of unplanned ex-nuptial pregnancies were ascribed to a breakdown in the mother's pattern of usage of the contraceptive pill.

Adolescent↗

Search for a male contraceptive: the effect of gossypol on sexual motivation and epididymal sperm.

Studies of men and animal models have reported informally that gossypol reduces fertility without behavioral disruptions. In the present research, we used an animal model and quantitative psychobiologic methods to examine the capacity of gossypol to suppress sperm reserves and to maintain both libido and performance. Sexually experienced male rats were exposed for 11 weeks to either 5, 10 or 20 mg gossypol/kg body weight, values representing the moderate to threshold dosages for induction of sterility. Behavioral changes over weeks of administration and reproductive physiology at necropsy were measured. Results showed that the expected dose-response reduction in gamete quantity and quality was accompanied by reductions in reproductive organ weights and copulatory performance, but the reductions were modest and principally with the higher dosages. On the other hand, there was the suggestion of a dose-response suppression of motivation, or interest in seeking and maintaining contact with a receptive female. Indeed, the characteristic pattern of a progressive loss of sperm motility and numbers with dose and time of exposure to gossypol closely paralleled the pattern of behavioral decrements. Implications of the data are that: 1.) gossypol may induce sterility in males at the expense of loss of motivation, and 2.) sexual performance and libido can vary in dependently. Future assessments of a substance under consideration as a contraceptive agent should consider quantitative measurement of both components of sexual behavior.

Animals↗

Visibility of the impact of environmental noise: a response to Kaitala and Ranta.

Based on simulation modelling, Kaitala and Ranta (2001 Proc. R. Soc. Lond. B 268, 1769-1774) have argued that detecting the statistical relationships between environmental variability and population fluctuations will be difficult. However, their study was limited in that only one pattern of density dependence and one detection method were used. Here, we show that their conclusion is in part a consequence of their choice of population model and in part a consequence of using relatively weak or inappropriate statistical methods. Other patterns of density dependence respond differently to environmental fluctuations, and the impact of the disturbance on these is clearly visible using their methods. For some patterns of population dynamics, environmental impacts are more readily detectable by correlating running-average environmental conditions with the population time-series or by correlating the first differences of the population time-series with environmental noise. When more appropriate statistical methods are used, environmental forcing is detectable in the majority of cases used by Kaitala and Ranta. The interplay between environmental stochasticity and density-dependent population growth means that there is no single best method to detect the influence of environmental forcing, even when population dynamics are approximately linear. But environmental forcing will often be detectable, contrary to Kaitala and Ranta's assertions.

Age Factors↗

Models of birth trajectories with certain patterns of variations in vital rates.

This article records experiments with a modified version of Lotka's stable population model. The traditional assumption of a set of unchanging net maternity rates as one of the preconditions has been replaced by allowing the rates to vary in certain ways while approaching or varying around a set of underlying constant rates. The integral equation assumes a different form but can be simplified and solved in the same old way. As a result, the birth trajectory does not necessarily attain a stable state. For certain patterns of mathematical functions the trajectory eventually becomes stable while for certain others it shows cyclical fluctuations. The variations in net maternity rates can also be postulated to follow the patterns of some measurable empirical functions which, like the mathematical functions, should be amenable to projections in the future. This information is needed for deriving the long-term solutions in additions to the information about the intrinsic rate of growth which is obtained from the traditional integral equation.

Birth Rate↗

Fetal pulse oximetry: a critical appraisal.

Despite 40 years of cumulative clinical experience, and a number of randomized clinical trials, electronic fetal heart rate monitoring is perceived by many obstetrical caregivers as a suboptimal method of intrapartum fetal assessment. Fetal pulse oximetry emerged 15 years ago as a promising new technology intended to improve assessment of fetal condition during labor. A large amount of physiologic data and one large randomized clinical trial have brought this technology into clinical practice. We know that fetal acidemia is rare when the arterial oxygen saturation is >30% but fetal pulse oximetry as currently understood and applied does not reduce the overall cesarean rate. Thus, many clinicians remain unconvinced of the benefit of this technology and its utilization has stalled in the US and Europe. We need to further understand if there is a way to use fetal pulse oximetry in the setting of labor dystocia and a non-reassuring fetal heart rate pattern. Although hypoxemia is an accepted mechanism of fetal brain injury, other potential mechanisms should be explored. Current controversies and fertile areas of research are presented.

Acid-Base Imbalance↗

Real-time sperm separation system: a review of Wang tubes and related technologies.

This paper discusses real-time sperm separation technology and the use of Wang tubes for isolating high-quality and fertile sperm. Several methods have been developed and used to prepare a better sperm specimen, including the conventional swim-up technique, Percoll discontinuous density gradient, Sephadex gel filtration, centrifugation, migration-sedimentation, albumin column, and Sperm-prep. However, none of these methods has the ability to isolate from the original ejaculum a large number of highly motile, morphologically normal, and normal-chromatin sperm, while retaining in an adequate volume of physiological medium, free of less-motile and nonmotile sperm, and free of microorganisms, cell debris, seminal plasma, leukocytes, and foreign bodies. These methods should be classified as incomplete techniques of sperm separation and are of only limited effectiveness in infertility treatment. They may also cause irreparable damage to the mother or fetus. Real-time sperm separation technology is based on the observations that nonpathological spermatozoa do not transfer organisms, that the motility pattern and swim-up capacity of pathological sperm are limited or disturbed, and that the movement of sperm differs from the passive motion of nonciliated microorganisms and the random active motion of ciliated microorganisms in terms of velocity and direction. Real-time sperm separation technology encompasses the Wang tube system, which has two main functions: to isolate organisms-free, normal-chromatin, morphologically normal, and highly motile spermatozoa that are suitable for use in infertility treatment, and to prevent sex-linked inherited diseases. The results of these evaluations indicate that real-time sperm separation technology is the most effective and precise method of isolating and decontaminating sperm to date.

Cell Separation↗

The varicocele and male infertility.

Varicocele is accepted as a common cause of male subfertility, even though many men with varicocele appear to have normal fertility. The pathophysiology of the varicocele effect on fertility remains unclear, but the association of varicocele with decreased testicular size, abnormal testicular histology, and abnormal semen parameters is clearly established. Because a small varicocele may impair fertility, it must be diligently sought, and the Doppler stethoscope may be helpful in establishing the diagnosis when a venous thrill is equivocal during the Valsalva maneuver in a standing patient. Abnormal semen parameters should be demonstrated in subfertile males with varicocele prior to advising varicocelectomy. Decreased sperm motility or a "stress pattern" in the semen should be documented; however a decreased sperm count may or may not be present. Various surgical approaches are available. When suprainguinal approaches have been used, failures have been shown to be attributable to secondarily incompetent cremasteric system veins. When high inguinal approaches are used, unsuccessful operations are probably secondary to a failure to identify one of the several venous tributaries that may be present at this level. The surgeon's approach should be based on available data, and his patients should be informed that failures are possible with any method of varicocelectomy until experience indicates otherwise. In most series, improvement in semen quality and pregnancy rates have been reported in a significant percentage of patients undergoing varicocelectomy for infertility. However, prior to subjection of the patient to varicocelectomy, the wife of the varicocele patient should be thoroughly studied (and treated when indicated).

Adolescent↗

Transmission factors of schistosomiasis japonica in the mountainous regions with type of plateau canyon and plateau basin.

OBJECTIVE: To provide the scientific basis for formulating the control strategies of schistosomiasis japonica in mountainous regions in China Schistosomiasis Control Programme. METHODS: We selected Chuanxing Village in Sichuan Province and Zhonghe Village in Yunnan Province as the two pilot areas for an epidemiological investigation according to their geographical and topographical characteristics, i.e. plateau canyon and plateau basin, respectively. Concentrated-egg hatching method in nylon tissue bag and Kato-Katz technique were used for the survey on prevalence rate and intensity of infection of man and domestic animals. Questionnaires were applied to investigating the infection sources, community behavior and the socioeconomic status. Snail survey and detection of cercaria-infested water bodies were conducted using routine techniques. RESULTS: The results showed that in the endemic areas with plateau canyon, the key infection source was cattle. The infection rate in women was higher than that in men. The pattern of water-pollution was wild feces and the pollution source was cattle feces. Snails and infectious snails were distributed over the rice fields and the resident was infected through production activities. In plateau basin, the key infection source was human beings. The infection rate in men was higher than that in women. The pattern of water pollution was fertilization. The pollution source was human feces. Snails and infectious snails were distributed over the canals and ditches and the resident was infected through production and daily activities. CONCLUSIONS: Therefore, it was suggested that the mountainous endemic areas should be divided into two sub-types, i.e., plateau basins and plateau canyons. The different control strategies should be formulated in accordance with the environmental situations and socioeconomic factors in the two kinds of endemic areas.

Adolescent↗