STUDY QUESTION

Are there any links between the length measurements of sperm components (head, midpiece, flagellum, total sperm length and the flagellum:head ratio) and data obtained during semen analysis?

SUMMARY ANSWER

Both the mean measurement and the variation in the lengths of sperm components are related to characteristics of semen.

WHAT IS KNOWN ALREADY

Studies in non-human species have shown that sperm morphology (size and shape) is associated with testes productivity and the consistency of sperm manufacture. However, no study to date has investigated whether there are relationships between the size and consistency of human sperm components, and measures of semen characteristics, including sperm numbers and how well they swim.

STUDY DESIGN, SIZE AND DURATION

A retrospective laboratory study of the semen provided by 103 randomly selected men from a 500-man cohort who enrolled into the study between April and December 2006.

PARTICIPANTS AND SETTING

Men attending Sheffield Teaching Hospital NHS Foundation Trust for semen analysis as part of investigations for infertility and whose ejaculates were found to contain sperm.

MAIN RESULTS AND THE ROLE OF CHANCE

The mean flagellum length and the mean total sperm length were positively associated with semen characteristics measured manually, but were not associated with the sperm swimming speed measured by computer-aided sperm analysis. Ejaculates with a lower variation in the length of sperm components contained sperm that were more likely to be motile. The mean sperm length components accounted for up to 9% of the variance in semen characteristics, while the coefficient of variation accounted for up to 21%.

LIMITATIONS AND REASONS FOR CAUTION

The sperm examined were obtained from men undergoing fertility investigations and so these results may not reflect men in the general population.

WIDER IMPLICATIONS OF THE FINDINGS

Sperm length measurements may provide a useful insight into testis function and the efficiency of spermatogenesis.

STUDY FUNDING AND COMPETING INTERESTS

This study was supported by funding from the University of Sheffield. The authors declare no conflicts of interest.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/22?rss=1

STUDY QUESTION

Is there a need for a specific guide addressing studies of seminal quality?

SUMMARY ANSWER

The proposed guidelines for the appraisal of SEMinal QUAlity studies (SEMQUA) reflect the need for improvement in methodology and research on semen quality.

WHAT IS KNOWN ALREADY

From an examination of other instruments used to assess the quality of diagnostic studies, there was no guideline on studies of seminal quality.

STUDY DESIGN, SIZE AND DURATION

Through systematic bibliographic search, potential items were identified and grouped into four blocks: participants, analytical methods, statistical methods and results.

PARTICIPANTS/MATERIALS, SETTING AND METHODS

Our findings were presented to a panel of experts who were asked to identify opportunities for improvement. Then, a checklist was designed containing the questions generated by the items that summarize the essential points that need to be considered for the successful outcome of a SEMQUA.

MAIN RESULTS AND THE ROLE OF CHANCE

Eighteen items were identified, from which 19 questions, grouped into four blocks, were generated to constitute the final checklist. An explanation for the inclusion of each item was provided and some examples found in the bibliographic search were cited.

LIMITATIONS AND REASONS FOR CAUTION

We consider that not all items are equally applicable to all study designs, and so the hypothetical results are not comparable. For that reason, a score would not be fair to critically appraise a study. This checklist is presented as an instrument for appraising SEMQUAs and therefore remains open to constructive criticism. It will be further developed in the future, in parallel with the continuing evolution of SEMQUAs.

WIDER IMPLICATIONS OF THE FINDINGS

The final configuration of the SEMQUA is in the form of a checklist, and includes the items generally considered to be essential for the proper development of a SEMQUA. The final checklist produced has various areas of application; for example, it would be useful for designing and constructing a SEMQUA, for reviewing a paper on the question, for educational purposes or as an instrument for appraising the quality of research articles in this field.

STUDY FUNDING/COMPETING INTEREST(S)

None.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/10?rss=1

STUDY QUESTION

Does the seminal plasma proteomic profile and functional enrichment of gene ontology terms change after microsurgical varicocelectomy? Are there any potential targets for diagnosis or therapeutic intervention in varicocele?

SUMMARY ANSWER

A shift in state from a responsive-to-stress condition before varicocele correction to a responsive-to-environment condition after varicocelectomy was observed in enriched proteomic pathways.

WHAT IS KNOWN ALREADY

Varicocele may lead to many adverse effects, including failure of testicular growth and development, and is associated with decreased semen quality and increased semen oxidative stress. Varicocelectomy is the treatment of choice, and is associated with improved semen quality, but little is known regarding the underlying molecular mechanisms and post-genomic pathways following intervention.

STUDY DESIGN, SIZE, DURATION

A prospective study was carried out including 18 adult men with varicocele. These patients provided one semen sample before they were submitted for bilateral varicocele repair through microsurgical varicocelectomy, and one other semen sample 90 days after the surgery.

PARTICIPANTS/MATERIALS, SETTING, METHODS

An aliquot of each semen sample was used for unbiased proteomics analysis by a label-free quantitative approach (2D nanoUPLC-ESI-MS^E). Samples were pooled according to group (normalized to protein content) and run in quadruplicate. These quadruplicate runs provided degrees of freedom in order to compare groups using a non-parametric Mann–Whitney test for quantified proteins.

MAIN RESULTS AND THE ROLE OF CHANCE

A total of 316 proteins were quantified or identified, of which 91 were exclusively identified or quantified in one of the groups (53 in the pre- and 38 in the post-varicocelectomy group), and 68 were quantified in both groups and submitted to statistical analysis, of which 5 were overrepresented in the pre-varicocelectomy group (P < 0.05). In enriched functional analysis, binding and response to stimulus functions were enriched in a common cluster (present in both groups), nitric oxide metabolism and tetratricopeptide repeat domain-binding functions were enriched in the pre-varicocelectomy group, and response to reactive oxygen species, gluconeogenesis, nicotinamide adenine dinucleotide-binding and protein stabilization were enriched in the post-varicocelectomy.

LIMITATIONS, REASONS FOR CAUTION

Because a shotgun proteomics analysis was chosen in order to generate a list of putative biomarkers, a targeted follow-up study should be performed to confirm these biomarkers.

WIDER IMPLICATIONS OF THE FINDINGS

The proteins found in both groups possess functions usually found in human semen. The enriched function analysis demonstrated a shift back to homeostasis after varicocelectomy, suggesting that varicocele correction promotes return of semen to a physiological state.

STUDY FUNDING/COMPETING INTEREST(S)

The funding for this project was received from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) as a scholarship for Ms Camargo. There was no conflict of interest.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/33?rss=1

STUDY QUESTION

Does adjudin disrupt chloride ion (Cl^–) ion transport function in human sperm and impede sperm capacitation and fertilizing ability in vitro?

SUMMARY ANSWER

In this study the results indicate that adjudin is a potent blocker of Cl^– channels: disrupting Cl^– ion transport function results in a decline in sperm capacitation and fertilizing ability in humans in vitro.

WHAT IS KNOWN ALREADY

Although our previous studies have demonstrated that adjudin exerts its effect by disrupting sertoli-germ cell adhesion junctions, most notably apical ectoplasmic specialization by targeting testin and actin filament bundles that disrupts the actin-based cytoskeleton in sertoli cells, it remains unclear whether adjudin impedes Cl^– ion transport function in the human sperm.

STUDY DESIGIN, SIZE AND DURATION

Semen samples were obtained from 45 fertile men (aged 25–32). Spermatozoa were isolated from the semen in the human tube fluid (HTF) medium by centrifugation through a discontinuous Percoll gradient, and incubated with adjudin at 10 nM–10 µM and/or other reagents under capacitating conditions for 0–5 h.

PARTICIPANTS/MATERIALS, SETTING, METHODS

We evaluated the effect of adjudin and different reagents on sperm functions with which they were incubated at 37°C. Sperm motility and hyperactivation were analyzed by a computer-assisted sperm analysis (CASA) system. Sperm capacitation and the acrosome reaction were assessed by chlortetracycline fluorescence staining. Sperm fertilizing ability was evaluated by sperm penetration of zona-free hamster egg assay, and cellular cAMP levels in spermatozoa were quantified by the EIA kit. The proteins tyrosine, serine and threonine phosphorylation in the presence or absence of adjudin were analyzed by means of a immunodetection of spermatozoa, especially, compared the effect of adjudin on sperm hyperactivation and capacitation in the complete HTF medium with the Cl^–-deficient HTF medium as well as the various Cl^– channel blockers.

MAIN RESULTS AND THE ROLE OF CHANCE

Adjudin significantly inhibited sperm hyperactivation but not sperm motility. Adjudin-induced inhibition of sperm capacitation was reversible, and it was found to block the rhuZP₃β- and progesterone-induced acrosome reaction in a dose-dependent manner. Adjudin also blocked sperm penetration of zona-free hamster eggs, and significantly inhibited both forskolin-activated transmembrane adenylyl cyclase and soluble adenylyl cyclase activities leading to a significant decline in the cellular cAMP levels in human spermatozoa. Adjudin failed to reduce sperm protein tyrosine phosphorylation but it did prevent sperm serine and threonine protein phosphorylation. Interestingly, adjudin was found to exert its inhibitory effects on sperm capacitation and capacitation-associated events only in the complete Cl^–-HTF medium but not Cl^–-deficient medium, illustrating the likely involvement of Cl^–. Adjudin inhibits the fertility capacity of human sperm is mediated by disrupting chloride ion and its transport function.

LIMITATIONS, REASONS FOR CAUTION

This study has examined the effect of adjudin only on human sperm capacitation and fertilizing ability in vitro and thus has some limitations. Further investigations in vivo are needed to confirm adjudin is a potent male contraceptive.

WIDER IMPLICATIONS OF THE FINDINGS

Our studies demonstrated that adjudin inhibition of capacitation is reversible and its toxicity is low, opening the door for the examination of adjudin as a mediator of male fertility control. Adjudin may be a safe, efficient and reversible male antifertility agent and applicable to initial clinical trials of adjudin as a male antifertility agent in humans.

STUDING FUNDING/COMPETING INTEREST(S)

This work was supported by the National Basic Research Program of China (2006CB504002), the Nature Science Foundation of China (Nos. 81000244 and 81170554), Zhejiang Project of Science and Technology (2011C23046), the Nature Science Fund of Zhejiang province (Nos.Y2100058 and Y2090236), the key Science and Technology Innovation Team of Zhejiang Province (No.2012R10048-07) and the National Institutes of Health (NICHD U54 HD029990 project 5), USA. The authors declare no conflict of interest.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/47?rss=1

STUDY QUESTION

What is the treatment success rate of systemic methotrexate (MTX) compared with expectant management in women with an ectopic pregnancy or a pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations?

SUMMARY ANSWER

In women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations, expectant management is an alternative to medical treatment with single-dose systemic MTX.

WHAT IS KNOWN AND WHAT THIS PAPER ADDS

MTX is often used in asymptomatic women with an ectopic pregnancy or a PUL with low and plateauing serum hCG concentrations. These pregnancies may be self-limiting and watchful waiting is suggested as an alternative, but evidence from RCTs is lacking. The results of this RCT show that expectant management is an alternative to treatment with systemic MTX in a single-dose regimen in these women.

STUDY DESIGN, SIZE, DURATION

A multicentre RCT women were assigned to systemic MTX (single dose) treatment or expectant management, using a web-based randomization program, block randomization with stratification for hospital and serum hCG concentration (<1000 versus 1000–2000 IU/l). The primary outcome measure was an uneventful decline of serum hCG to an undetectable level (<2 IU/l) by the initial intervention strategy. Secondary outcome measures included additional treatment, side effects and serum hCG clearance time.

PARTICIPANTS, SETTING, METHODS

From April 2007 to January 2012, we performed a multicentre study in The Netherlands. All haemodynamically stable women >18 years old with both an ectopic pregnancy visible on transvaginal sonography and a plateauing serum hCG concentration <1500 IU/l or with a PUL and a plateauing serum hCG concentration <2000 IU/l were eligible for the trial.

MAIN RESULTS

We included 73 women of whom 41 were allocated to single-dose MTX and 32 to expectant management. There was no difference in primary treatment success rate of single-dose MTX versus expectant management, 31/41 (76%) and 19/32 (59%), respectively [relative risk (RR) 1.3 95% confidence interval (CI) 0.9–1.8]. In nine women (22%), additional MTX injections were needed, compared with nine women (28%) in whom systemic MTX was administered after initial expectant management (RR 0.8; 95% CI 0.4–1.7). One woman (2%) from the MTX group underwent surgery compared with four women (13%) in the expectant management group (RR 0.2; 95% CI 0.02–1.7), all after experiencing abdominal pain within the first week of follow-up. In the MTX group, nine women reported side effects versus none in the expectant management group. No serious adverse events were reported. Single-dose systemic MTX does not have a larger treatment effect compared with expectant management in women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations.

WIDER IMPLICATIONS OF THE FINDINGS

Sixty percent of women after expectant management had an uneventful clinical course with steadily declining serum hCG levels without any intervention, which means that MTX, a potentially harmful drug, can be withheld in these women.

BIAS, LIMITATION AND GENERALISABILITY

A limitation of this RCT is that it was an open (not placebo controlled) trial. Nevertheless, introduction of bias was probably limited by the strict criteria to be fulfilled for treatment with MTX.

STUDY FUNDING

This trial is supported by a grant of the Netherlands Organization for Health Research and Development (ZonMw Clinical fellow grant 90700154).

TRIAL REGISTRATION

ISRCTN 48210491.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/60?rss=1

STUDY QUESTION

What is the performance of a simple scoring system to predict whether women will have an ongoing viable intrauterine pregnancy beyond the first trimester?

SUMMARY ANSWER

A simple scoring system using demographic and initial ultrasound variables accurately predicts pregnancy viability beyond the first trimester with an area under the curve (AUC) in a receiver operating characteristic curve of 0.924 [95% confidence interval (CI) 0.900–0.947] on an independent test set.

WHAT IS KNOWN ALREADY

Individual demographic and ultrasound factors, such as maternal age, vaginal bleeding and gestational sac size, are strong predictors of miscarriage. Previous mathematical models have combined individual risk factors with reasonable performance. A simple scoring system derived from a mathematical model that can be easily implemented in clinical practice has not previously been described for the prediction of ongoing viability.

STUDY DESIGN, SIZE AND DURATION

This was a prospective observational study in a single early pregnancy assessment centre during a 9-month period.

PARTICIPANTS/MATERIALS, SETTING AND METHODS

A cohort of 1881 consecutive women undergoing transvaginal ultrasound scan at a gestational age <84 days were included. Women were excluded if the first trimester outcome was not known. Demographic features, symptoms and ultrasound variables were tested for their influence on ongoing viability. Logistic regression was used to determine the influence on first trimester viability from demographics and symptoms alone, ultrasound findings alone and then from all the variables combined. Each model was developed on a training data set, and a simple scoring system was derived from this. This scoring system was tested on an independent test data set.

MAIN RESULTS AND THE ROLE OF CHANCE

The final outcome based on a total of 1435 participants was an ongoing viable pregnancy in 885 (61.7%) and early pregnancy loss in 550 (38.3%) women. The scoring system using significant demographic variables alone (maternal age and amount of bleeding) to predict ongoing viability gave an AUC of 0.724 (95% CI = 0.692–0.756) in the training set and 0.729 (95% CI = 0.684–0.774) in the test set. The scoring system using significant ultrasound variables alone (mean gestation sac diameter, mean yolk sac diameter and the presence of fetal heart beat) gave an AUC of 0.873 (95% CI = 0.850–0.897) and 0.900 (95% CI = 0.871–0.928) in the training and the test sets, respectively. The final scoring system using demographic and ultrasound variables together gave an AUC of 0.901 (95% CI = 0.881–0.920) and 0.924 (CI = 0.900–0.947) in the training and the test sets, respectively. After defining the cut-off at which the sensitivity is 0.90 on the training set, this model performed with a sensitivity of 0.92, specificity of 0.73, positive predictive value of 84.7% and negative predictive value of 85.4% in the test set.

LIMITATIONS, REASONS FOR CAUTION

BMI and smoking variables were a potential omission in the data collection and might further improve the model performance if included. A further limitation is the absence of information on either bleeding or pain in 18% of women. Caution should be exercised before implementation of this scoring system prior to further external validation studies

WIDER IMPLICATIONS OF THE FINDINGS

This simple scoring system incorporates readily available data that are routinely collected in clinical practice and does not rely on complex data entry. As such it could, unlike most mathematical models, be easily incorporated into normal early pregnancy care, where women may appreciate an individualized calculation of the likelihood of ongoing pregnancy viability.

STUDY FUNDING/COMPETING INTEREST(S)

Research by V.V.B. supported by Research Council KUL: GOA MaNet, PFV/10/002 (OPTEC), several PhD/postdoc & fellow grants; IWT: TBM070706-IOTA3, PhD Grants; IBBT; Belgian Federal Science Policy Office: IUAP P7/(DYSCO, `Dynamical systems, control and optimization', 2012–2017). T.B. is supported by the Imperial Healthcare NHS Trust NIHR Biomedical Research Centre.

TRIAL REGISTRATION NUMBER

Not applicable.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/68?rss=1

STUDY QUESTION

Are maternal progesterone levels in early pregnancy associated with fetal birthweight?

SUMMARY ANSWER

Low levels of first-trimester maternal progesterone are significantly associated with a reduction in birthweight in girls, but not boys.

WHAT IS ALREADY KNOWN

Progesterone in the third trimester of pregnancy has previously been related to birthweight in humans.

STUDY DESIGN, SIZE, DURATION

Pregnant women between gestational weeks 4 and 12 were recruited by 99 obstetricians in private practice and enrolled in a prospective cohort study. A follow-up took place at birth. Women younger than 18 years, who had undergone fertility treatments or were diagnosed with infectious diseases, were excluded from the study. A subgroup of 906 participants in whom progesterone had been measured was then selected retrospectively based on the following criteria: no miscarriages, elective abortions or pregnancy complications, infections or multiple births. Data from the follow-up were available for 623 women, who were included in the analyses.

PARTICIPANTS/MATERIALS, SETTING, METHODS

The study was coordinated at the Charité University Medicine in Berlin, Germany. Anthropometric, medical and psychosocial information were collected and serum progesterone and estradiol levels were measured in women during the first trimester of pregnancy, followed by the documentation of the pregnancy outcome at birth. Univariable and multivariable regression analyses were performed to identify maternal markers, among them progesterone, affecting birthweight and to determine environmental and maternal factors that are associated with maternal progesterone levels during pregnancy.

MAIN RESULTS AND THE ROLE OF CHANCE

In the multivariable regression model, each increase in maternal progesterone by 1 ng/ml during the first trimester increased girls' birthweight by 10.17 g (95% CI: 2.03–18.31 g). If the mother carried a boy, maternal smoking and perceived worries during early pregnancy predicted a reduced birthweight, irrespective of progesterone levels. Maternal body mass index over 25 and maternal age <21 years significantly correlated with the reduced levels of progesterone. Correlations between environmental challenges and maternal progesterone did not reach levels of significance. Since the analyses were exploratory, the likelihood that results may be due to chance is increased.

LIMITATIONS, REASONS FOR CAUTION

Due to the exploratory nature of the analyses, results need to be independently confirmed in a larger sample. Furthermore, our findings pertain to pregnant women without pregnancy complications or fertility treatments.

WIDER IMPLICATIONS OF THE FINDINGS

Maternal progesterone during early pregnancy is an indicator of subsequent fetal development in female children. Future studies should confirm this relationship and determine whether maternal progesterone is a useful tool in predicting pregnancies at risk resulting in the birth of a girl with low birthweight. Detailed identification of environmental factors modulating maternal progesterone levels should be addressed in future studies.

STUDY FUNDING/POTENTIAL COMPETING INTERESTS

Financial support was provided by the Alexander von Humboldt Foundation, Excellence Initiative of the Hamburg Foundation for Research and the Association for Prevention and Information for Allergy and Asthma (Pina e.V.). The authors have no conflict of interest.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/77?rss=1

STUDY QUESTION

Does calcium oscillatory pattern analysis following heterologous intra-cytoplasmic sperm injection (ICSI) of human sperm into mouse oocytes lead to diagnostic and prognostic information for patients suffering from ICSI fertilization failure?

SUMMARY ANSWER

We found that calcium oscillatory pattern analysis following heterologous ICSI has the strength to reveal, for the individual patient, the most probable underlying reason for low or failed fertilization after conventional ICSI.

WHAT IS KNOWN ALREADY

Fertilization failure occurs in 1–3% of the couples undergoing conventional ICSI, for whom the mouse oocyte activation test (MOAT) or a similar heterologous ICSI model is the only diagnostic test available to evaluate the oocyte-activating capacity of human sperm cells. The MOAT classifies the patients into three groups: a low (group 1), an intermediate (group 2) and a high (group 3) activating group. In MOAT group 1 patients, a sperm-related deficiency is likely to be the cause of previous fertilization failures, while in MOAT group 3 patients a sperm-related deficiency can most probably be refuted. For MOAT group 2 patients, the result is called inconclusive; hence, both sperm and oocyte deficiencies may still contribute to the previous ICSI fertilization failure.

STUDY DESIGN, SIZE, DURATION

The calcium-releasing ability of sperm from 26 MOAT patients with a history of zero or low fertilization following conventional ICSI was compared with the calcium-releasing ability of sperm from 4 control patients, with proven oocyte activation potential. Per case an average of 19 mouse oocytes were injected. Calcium imaging started within 5–10 min after ICSI and continued for 2 h.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Human sperm were demembranated with 0.02% lysolecithin for 1 min immediately before heterologous piezo-driven ICSI. For calcium imaging, metaphase II oocytes from B6D2/F1 mice were loaded with fura-2 acetoxymethyl ester. The calcium oscillatory patterns following heterologous ICSI were scored per oocyte and per patient individually based on the presence of calcium spikes and their frequency and amplitude.

MAIN RESULTS AND THE ROLE OF CHANCE

For patients with low or high MOAT activating capacity (MOAT group 1 or 3, respectively), calcium analysis confirmed the MOAT result. For patients with a former inconclusive intermediate MOAT activating capacity result (MOAT group 2), no or strongly dissimilar calcium oscillatory patterns were seen, with significantly lower amplitude and frequency compared with control sperm. When the product of the amplitude and the frequency of the calcium traces was compared between the groups, MOAT group 1 and 2 cases differed significantly from MOAT group 3 cases and the control sperm (P < 0.01).

LIMITATIONS, REASONS FOR CAUTION

The results of the calcium analysis in mouse oocytes should not be directly extrapolated to human oocytes, since it is well known that human spermatozoa exhibit a greater activating potency in mouse oocytes compared with mouse spermatozoa. Furthermore, not much is known yet about the influence of aberrant calcium oscillatory patterns, such as found in MOAT group 2 patients, on pre- and post-implantation embryo development in the human.

WIDER IMPLICATIONS OF THE FINDINGS

Based on the current calcium oscillatory pattern analysis, we found that the product of calcium spike amplitude with its frequency allowed us to create a new threshold value, which can assist in confirming or refuting, on a single patient base, a sperm-borne activation deficiency. The latter is especially interesting for patients with a former intermediate inconclusive MOAT result (MOAT group 2 patients), for whom calcium oscillatory pattern analysis should be considered.

STUDY FUNDING/COMPETING INTEREST(S)

F.V.M. is holder of an aspirant clinical research mandate by the Flemish foundation of Scientific Research (FWO-Vlaanderen). B.H. is supported by a Ghent University grant (KAN-BOF E/01321/01). P.D.S. is holder of a fundamental clinical research mandate by the same Flemish foundation of Scientific Research (FWO-Vlaanderen).

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/87?rss=1

STUDY QUESTION

Is the occurrence of pelvic pain in women with ovarian endometrioma associated with coexisting peritoneal lesions (PLs)?

SUMMARY ANSWER

Pelvic pain in women with ovarian endometrioma is usually associated with coexisting PLs. An increased tissue inflammatory reaction with elevated prostaglandin (PG) production may be responsible for the generation of pain.

WHAT IS KNOWN ALREADY

Severe pelvic pain in women with ovarian endometrioma is reported to be associated with deeply infiltrating endometriosis. However, information on pelvic pain in women with ovarian endometriosis with and without coexistent peritoneal superficial lesions is limited.

STUDY DESIGN, SIZE AND DURATION

Retrospective clinical study with case-controlled biological research using prospectively collected tissue samples derived from women with and without endometriosis and their retrospective evaluation.

PARTICIPANTS/MATERIALS, SETTING, METHODS

We performed a retrospective cohort study conducted in 2988 cases who had laparoscopic surgery for indications of ectopic pregnancy, tubal infertility and other benign gynecologic diseases. We analyzed the occurrence of pelvic pain in the cases with ovarian endometrioma according to the distribution of coexisting PLs and pattern of intrapelvic adhesions. Inflammatory reaction of eutopic and ectopic endometria was measured by immunoreaction to macrophage marker, CD68. The tissue expression of cyclooxygenase (COX) 2 was examined by immunohistochemistry and tissue concentrations of PG F2α were measured by ELISA.

MAIN RESULTS AND THE ROLE OF CHANCE

Among the 2988 surgical cases, 350 (11.7%) were found to have ovarian endometrioma at laparoscopy. Coexisting PLs were present in 269 of these women and in this group 85.4% of cases experienced pelvic pain and 14.6% had no pain. In contrast, among the 81 women with ovarian endometrioma only, 38.3% cases experienced pelvic pain and 61.7% cases had no pain and the difference between the groups was statistically significant (P < 0.01). The infiltration of CD68-immunoreactive macrophages was significantly higher in the eutopic and ectopic endometria of women with peritoneal endometriosis than in ovarian endometrioma. The tissue expression of COX2 and levels of PGF2α were significantly higher in both the eutopic and ectopic endometria derived from women with peritoneal endometriosis than in similar tissues derived from women with ovarian endometrioma.

LIMITATIONS, REASONS FOR CAUTIONS

Lack of evaluation in the detection of general or disseminated deeply infiltrating endometriosis in the pelvic cavity could be a bias or limitation in this study. Further multicenter prospective studies are needed to strengthen our current findings.

WIDER IMPLICATIONS OF THE FINDINGS

Our findings may provide some new insights to understand the physiopathology of pelvic pain in women with ovarian cystic endometriosis and may hint at proper surgical manipulation to prevent the recurrence of pelvic pain in these women.

STUDY FUNDING/COMPETING INTEREST(S)

This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology of Japan. There is no conflict of interest related to this study.

TRIAL REGISTRATION NUMBER

Not applicable.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/109?rss=1

STUDY QUESTION

Is endometriosis associated with changes in CD4⁺ CD25⁺ FOXP3⁺ regulatory T cells (Treg cells)?

SUMMARY ANSWER

Endometriosis is associated with disturbed compartmentalization of CD25^high FOXP3⁺ Treg cells.

WHAT IS KNOWN ALREADY

Endometriosis is associated with an abrogated immune response and displays some features of an autoimmune disorder. Treg cells play a part in the development of autoimmune reactions; however, their role in pathogenesis of endometriosis is still poorly recognized.

STUDY DESIGN, SIZE AND DURATION

Case–control study comparing 17 women with laparoscopically and histopathologically confirmed ovarian endometriosis with 15 control women without visible endometriosis foci, pelvic inflammation or related pathology who were subjected to laparoscopic surgery between 2010 and 2011.

PARTICIPANTS/MATERIALS, SETTING AND METHODS

Peripheral blood and peritoneal fluid were collected during laparoscopy and T cell subpopulations were analysed by flow cytometry using specific monoclonal antibodies recognizing CD4⁺, CD25⁺ and FOXP3⁺ markers.

MAIN RESULTS

The percentage of CD25^high FOXP3⁺ Treg cells was significantly decreased in the peripheral blood of women with ovarian endometriosis compared with control women. On the other hand, the proportion of these cells was significantly increased in the peritoneal fluid of women with endometriosis.

LIMITATIONS, REASONS FOR CAUTION

The present study is limited to patients with ovarian endometrioma and further investigations are needed, including patients with lower grade of endometriosis.

WIDER IMPLICATIONS OF THE FINDINGS

The present results suggest that Treg cells may play a part in immunopathogenesis of endometriosis being responsible for abrogated local cellular immune responses and facilitation and development of autoimmune reactions. Treg cells may be thus a potential target in the treatment of endometriosis.

STUDY FUNDING/COMPETING INTEREST(S)

This study was supported by 1M15/N/2011 and NK1W grants from the I Faculty of Medicine, Warsaw Medical University. None of the authors has any competing interests to declare.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/119?rss=1

STUDY QUESTION

What are the characteristics of the pregnancy outcomes in women undergoing robot-assisted laparoscopic myomectomy (RALM) for symptomatic leiomyomata uteri?

SUMMARY ANSWER

Despite a high prevalence of women with advanced maternal age, obesity and multiple pregnancy in our cohort, the outcomes are comparable with those reported in the literature for laparoscopic myomectomy.

WHAT IS KNOWN ALREADY

Reproductive outcomes after traditional laparoscopic myomectomy are well documented. However, reproductive outcomes following robotic myomectomy are not well studied. This paper describes the pregnancy outcomes for a large cohort of women after robotic myomectomy.

STUDY DESIGN, SIZE, DURATION

This is a retrospective cohort of women who became pregnant after robot-assisted myomectomy at three centers. Of the 872 women who underwent robotic myomectomy during the period October 2005–November 2010, 107 subsequently conceived resulting in 127 pregnancies and 92 deliveries through 2011.

PARTICIPANTS/MATERIAL, SETTING, METHODS

Women of reproductive age with fibroids who wanted a minimally invasive treatment option and desired uterine preservation were recruited. We conducted a multicentre study with three centers, two in a private practice and one in an academic setting. Pregnancy outcomes and their relationship to myoma characteristics were analyzed.

MAIN RESULTS AND ROLE OF CHANCE

Mean ± SD age at myomectomy was 34.8 ± 4.5 years and 57.4% [95% confidence interval (CI) 48.0, 66.3] of women were overweight or obese. The mean number of myomas removed was 3.9 ± 3.2 with a mean size of 7.5 ± 3.0 cm and mean weight of 191.7 ± 144.8 g. Entry of the myoma into the endometrial cavity occurred in 20.6% (95% CI 15.0, 27.7) of patients. The mean time to conception was 12.9 ± 11.5 months. Assisted reproduction techniques were employed in 39.4% (95% CI 32.6, 46.7) of these women. Seven twin pregnancies and two triplet pregnancies occurred, for a multiple pregnancy birth rate of 9.8% (95% CI 5.0, 17.8). Spontaneous abortions occurred in 18.9% (95% CI 13.0, 26.6). Preterm delivery prior to 35 weeks of gestational age occurred in 17.4% (95% CI 10.9, 26.5). One uterine rupture (1.1%; 95% CI 0.3, 4.7) was documented. Pelvic adhesions were discovered in 11.4% (95% CI 7.0, 18.0) of patients delivered by Cesarean section. Higher preterm delivery rates were significantly associated with a greater number of myomas removed and anterior location of the largest incision (compared with all other sites) in logistic regression analyses (P = 0.01). None of the myoma characteristics were related to spontaneous abortion.

BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION

Given the retrospective nature of the data collection, some pregnancies may not have been captured. In addition, owing to the high prevalence of infertility patients in this cohort, the data cannot be used to counsel women who are undergoing RALM about fertility rates after surgery.

GENERALIZABILITY TO OTHER POPULATIONS

Prospective studies are needed to determine if the results shown in our cohort are generalizable to all women seeking a minimally invasive option for the conservative treatment of symptomatic fibroids with pregnancy as a desired outcome.

STUDY FUNDING/COMPETING INTEREST(S)

There was no funding source for this study.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/99?rss=1

STUDY QUESTION

Does the use of a digital home ovulation test have any effect on the level of stress in women seeking to conceive?

SUMMARY ANSWER

No difference was found in levels of stress between women using digital ovulation tests to time intercourse compared with women who were trying to conceive without any additional aids: in addition, their use did not negatively impact time to conception in users but may provide additional benefits, including an increased understanding of the menstrual cycle, reassurance and confidence in focusing conception attempts to the correct time in the cycle.

WHAT IS KNOWN ALREADY

It has been suggested that timing of intercourse in such a way that it coincides with ovulation by using ovulation tests can lead to emotional distress; however, no study has been conducted to investigate this hypothesis specifically, until now.

STUDY DESIGN, SIZE AND DURATION

The study was performed over two complete menstrual cycles as a prospective, randomized, controlled trial including quantitative and qualitative methods. The intervention (test) group were given digital ovulation tests to time intercourse to the most fertile time of the cycle and the control group were provided with the current National Institute for Health and Clinical Excellence guidelines for increasing the chances of conception (intercourse every 2–3 days) and asked not to use any additional methods to time when ovulation occurs.

PARTICIPANTS/MATERIALS, SETTING AND METHODS

A total of 210 women who were seeking to conceive were recruited from the general UK population. A total of 115 women were randomized to the test group and 95 to the control group through block randomization. The positive and negative affect schedule (PANAS) and the Perceived Stress Scale (PSS) were used to measure subjective stress levels, the Short-Form 12 health survey was used as a measure of general health and well-being and urine samples were measured for biochemical markers of stress including urinary cortisol. Qualitative data were collected in the form of a telephone interview upon study completion.

MAIN RESULTS AND THE ROLE OF CHANCE

There was no evidence for a difference either in total stress as measured using the PSS or in total positive or negative affect using the PANAS questionnaire between the test and control groups at any time point for the duration of the study. During cycle 1, for example, on Day 6, the difference in total stress score (test–control) was –0.62 [95% confidence interval (CI) –2.47 to 1.24] and on the day of the LH surge, it was 0.53 (95% CI –1.38 to 2.44). In addition, no correlation was observed between time trying to conceive and levels of stress, or between age and levels of stress, and no evidence was found to show that stress affected whether or not a pregnancy was achieved. There is also no evidence that the biochemistry measurements are related to whether a pregnancy was achieved or of a difference in biochemistry between the treatment groups. The use of digital ovulation tests did not negatively affect time to conception and with an adequately sized study, could potentially show improvement. To ensure that the results of this study were not affected by chance, we used a number of different methods for measuring stress, each of which had been independently validated.

LIMITATIONS AND REASONS FOR CAUTION

Randomization occurred before the start of the study because of the need to provide the ovulation tests in readiness for Day 6 of the first cycle. As a consequence, a number of women fell pregnant during this period (22 and 13 in the test and control groups, respectively). A further 15 women were either lost to follow-up or withdrew consent prior to study start. Pregnancy rate was higher overall in the test group, so to ensure that there were sufficient data from women who failed to become pregnant in the test group, we implemented an additional biased recruitment. This second cohort may have been different from the first, although no significant differences were observed between the two phases of recruitment for any of the information collected upon admission to the study.

WIDER IMPLICATIONS OF THE FINDINGS

Women who seek medical advice while trying to conceive should not be discouraged by health care professionals from using digital ovulation tests in order to time intercourse. The cohort of women recruited to this study initially had no evidence of infertility and were looking to conceive in a non-medical setting. A separate study to assess the impact of home ovulation tests in a subfertile population would be of interest and complementary to the present study.

STUDY FUNDING/COMPETING INTERESTS

This study was funded by SPD Swiss Precision Diagnostics, GmbH, manufacturer of Clearblue^® pregnancy and ovulation tests. SPD Development Company Ltd is a wholly owned subsidiary of SPD Swiss Precision Diagnostics GmbH; together referred to as SPD.

TRIAL REGISTRATION NUMBER

NCT01084304 (http://www.clinicaltrials.gov).

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/138?rss=1

STUDY QUESTION

Are there factors predicting the number of total and mature oocytes retrieved after controlled ovarian hyperstimulation (COH) utilizing a gonadotropin-releasing hormone (GnRH) antagonist protocol and a GnRH agonist (GnRHa) to induce oocyte maturation?

SUMMARY ANSWER

Peak estradiol (E₂) level, post-trigger LH and progesterone and the magnitude of LH rise are independent predictors of the total number of oocytes and mature oocytes retrieved.

WHAT IS KNOWN ALREADY

Despite multiple follicular development in high responders, oocyte retrieval after a GnRHa trigger in a small subset of patients fails to obtain a substantial number of total oocytes or mature oocytes.

STUDY DESIGN, SIZE AND DURATION

A retrospective chart review of all autologous and oocyte donation cycles utilizing a GnRHa antagonist protocol where GnRHa was used for the induction of oocyte maturation between 1 April 2003 and 31 December 2011.

PARTICIPANTS/MATERIALS, SETTING AND METHODS

A total of 508 autologous and donor IVF/ICSI cycles utilizing a GnRH antagonist protocol for COH and GnRHa for the induction of oocyte maturation at a university-based tertiary fertility center.

MAIN RESULTS AND THE ROLE OF CHANCE

Peak E₂ on the day of trigger (r = 0.19, P < 0.001), post-trigger LH (r = 0.12, P = 0.009) and progesterone (r = 0.47, P < 001) and LH rise (r = 0.18, P < 0.001) all positively correlated with the number of total and mature oocytes retrieved. The true incidence of empty follicle syndrome was 1.4% (7/508). There was no post-trigger LH or progesterone cut-off value for the prediction of oocyte yield. However, all cases of empty follicle syndrome occurred in patients with post-trigger LH <15 IU/l and P ≤ 3.5 ng/ml. The findings of this study may also be due to chance since it was a retrospective study and not prospectively designed.

LIMITATION, REASONS FOR CAUTION

This is a retrospective chart review and therefore subject to bias. Serum hormone measurements were performed between 8 and 12 h after GnRHa trigger rather than a standardized time period following trigger administration. Therefore, peak levels of LH may have been missed due to the short ascending limb of LH rise lasting approximately 4 h after GnRHa trigger.

WIDER IMPLICATIONS OF THE FINDINGS

The results of this study can be generalized to high responders utilizing a GnRH antagonist protocol for COH and a GnRHa for the induction of oocyte maturation. The use of alternative stimulation regimens or medications will limit the ability to generalize the results of this study to other populations.

STUDY FUNDING/COMPETING INTEREST(S)

This study was not funded, and there are no conflicts of interest.

TRIAL REGISTRATION NUMBER

n/a

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/152?rss=1

STUDY QUESTION

Do women who conceive without treatment after a long time to pregnancy (TTP) have an increased risk of preterm birth compared with women in the general obstetric population?

SUMMARY ANSWER

Based on this meta-analyses of 14 studies, women with a long TTP are at an increased risk of preterm birth: pooled crude odds ratio (OR): 1.38 (95% CI: 1.25–1.54).

WHAT IS KNOWN ALREADY

Several studies have shown that women who conceive without treatment after >12 months of trying have an elevated risk of poor pregnancy outcomes. To date, no systematic review or meta-analysis of this evidence has been published.

STUDY DESIGN, SIZE, DURATION

This systematic review identified literature from Embase, Medline and Popline published between January 1974 and October 2011, on the association between infertility in a non-treated population and the risk of preterm birth, low birthweight (LBW), small-for-gestational age and birthweight deficits.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Two authors independently conducted the searches, selected the studies and abstracted the data. A total of 89 full-text articles were assessed for eligibility and 17 met the inclusion criteria. The pooled analysis of the primary outcome led to a total sample size of 1 269 758 births: 19 983 in the exposed/infertile group and 1 249 775 in the unexposed/fertile group. There were a total 68 885 preterm births in the overall sample: 1644 (8.2%) and 67 241 (5.4%) among the infertile and reference groups, respectively.

MAIN RESULTS AND THE ROLE OF CHANCE

A moderate increase in the risk of preterm birth persisted irrespective of the type of pooling. The common OR of the pooled crude preterm birth data compared with the pooled regression-adjusted analysis was modestly attenuated: from 1.38 (95% CI: 1.25, 1.54) to 1.31 (95% CI: 1.21, 1.42), with I² decreasing from 53.2 to 3.9% in the crude to adjusted results, respectively. An association of a similar magnitude was seen between infertility and LBW, due in part to overlapping of outcomes.

LIMITATIONS, REASONS FOR CAUTION

Consistency of the estimates across various types of pooling, including the more restricted sensitivity analyses of higher quality studies, is reassuring. While it is possible that systematic error may have been present through misclassification of exposure and confounding, these findings suggest that it would need to be of the same magnitude across diverse studies, which seems unlikely.

WIDER IMPLICATIONS OF THE FINDINGS

A long TTP is only a symptom, research is needed to assess whether specific groups of infertile couples are at increased risk of adverse outcome, or whether the increased risk is due to characteristics common to most infertile couples. As long as the contribution of infertility is not clarified, the risks due to assisted reproductive technologies cannot be properly assessed.

STUDY FUNDING/COMPETING INTEREST(S)

C.M. was supported by a Canadian Institutes of Health Research doctoral research award at the time of this study. No competing interests are declared.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/125?rss=1

STUDY QUESTION

What is the current literature on the safety and efficacy of selective serotonin reuptake inhibitor (SSRI) use in infertile women?

SUMMARY ANSWER

There is little evidence that infertile women benefit from taking an SSRI, therefore they should be counseled appropriately about the risks and be advised to consider alternate safer treatments to treat depressive symptoms.

WHAT IS KNOWN ALREADY

SSRI use is associated with possible reduced infertility treatment efficacy as well as higher rates of pregnancy loss, preterm birth, pregnancy complications, neonatal issues and long-term neurobehavioral abnormalities in offspring.

STUDY DESIGN, SIZE, DURATION

Review of existing literature.

PARTICIPANTS/MATERIALS, SETTING, METHODS

We conducted a review of all published studies that evaluate females with depressive symptoms who are taking antidepressant medications and who are experiencing infertility.

MAIN RESULTS AND THE ROLE OF CHANCE

Antidepressant use during pregnancy is associated with increased risks of miscarriage, birth defects, preterm birth, newborn behavioral syndrome, persistent pulmonary hypertension of the newborn and possible longer term neurobehavioral effects. There is no evidence of improved pregnancy outcomes with antidepressant use. There is some evidence that psychotherapy, including cognitive-behavioral therapy as well as physical exercise, is associated with significant decreases in depressive symptoms in the general population; research indicates that some forms of counseling are effective in treating depressive symptoms in infertile women.

LIMITATIONS, REASONS FOR CAUTION

Our findings are limited by the availability of published studies in the field, which are often retrospective and of small size.

WIDER IMPLICATIONS OF THE FINDINGS

Practitioners who care for infertility patients should have a thorough understanding of the published literature so that they can adequately counsel their patients.

STUDY FUNDING/COMPETING INTEREST(S)

None.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/160?rss=1

STUDY QUESTION

Is thin endometrium unresponsive to standard treatments expandable by intrauterine perfusion with granulocyte colony-stimulating factor (G-CSF)?

SUMMARY ANSWER

This cohort study is supportive of the effectiveness of G-CSF in expanding chronically unresponsive endometria.

WHAT IS KNOWN ALREADY

In a previous small case series, we reported the successful off-label use of G-CSF in four consecutive patients, who had previously failed to expand their endometria beyond 6.9 mm with the use of standard treatments.

STUDY DESIGN, SIZE AND DURATION

In a prospective observational cohort pilot study over 18 months, we described 21 consecutive infertile women with endometria <7 mm on the day of hCG administration in their first IVF cycles at our center. All previous cycles using traditional treatments with estradiol, sildenafil citrate (Viagra™) and/or beta-blockers had been unsuccessful. G-CSF (Nupogen™) was administered per intrauterine catheter by slow infusion before noon on the day of hCG administration. If the endometrium had not reached at least a 7-mm within 48h, a second infusion was given following oocyte retrieval. Primary and secondary main outcomes were an increase in endometrial thickness and clinical pregnancy, respectively. Endometrial thickness was assessed by vaginal ultrasound at the most expanded area of the endometrial stripe.

PARTICIPANTS/MATERIALS, SETTINGS AND METHOD

This study was uncontrolled, each patient serving as her own control in a prospective evaluation of endometrial thickness. The mean ± SD age of the cohort was 40.5 ± 6.6 years, gravidity was 1.8 ± 2.1 (range 0–7) and parity was 0.4 ± 1.1 (range 0–4); 76.2% of women had, based on age-specific FSH and anti-Müllerian hormone, an objective diagnosis of diminished ovarian reserve and had failed 2.0 ± 2.1 prior IVF cycles elsewhere.

MAIN RESULTS AND THE ROLE OF CHANCE

With 5.2 ± 1.9 days between G-CSF perfusions and embryo transfers, endometrial thickness increased from 6.4 ± 1.4 to 9.3 ± 2.1 mm (P < 0.001). The in change was 2.9 ± 2.0 mm, and did not vary between conception and non-conception cycles. A 19.1% ongoing clinical pregnancy rate was observed, excluding one ectopic pregnancy.

LIMITATIONS AND REASONS FOR CAUTION

Small sample size (but a highly selected patient population) in an uncontrolled cohort study and in unselected first IVF cycles at our center.

WIDER IMPLICATIONS OF THE FINDINGS

This pilot study supports the utility of G-CSF in the treatment of chronically thin endometrium and suggests that such treatment will, in very adversely affected patients, result in low but very reasonable clinical pregnancy rates.

STUDY FUNDING/COMPETING INTEREST(S)

This work was supported by the Foundation for Reproductive Medicine, New York, New York, USA, a not-for-profit research foundation and intramural grants from the Center for Human Reproduction (CHR)—New York. N.G. and D.H.B. are members of the board of the Foundation for Reproductive Medicine. N.G. is owner of CHR-New York, where the study was conducted. N.G. and D.H.B. have been recipients of research awards, travel grants and speaker honoraria from various pharmaceutical and medical device companies. None of these companies was, however, in any way associated with the materials and the manuscript presented here. N.G. and D.H.B. are listed as co-inventors on a number of awarded and still pending U.S. patents, none related to the materials presented here. N.G. is on the board of a medically related company, not in any way associated with the data presented here.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/172?rss=1

The conditions in the environment are subject to large fluctuations. In Germany, for instance, temperatures can range from a freezing minus 20 degrees Celsius in the winter to a hot 40 degrees Celsius in the summer. Organisms that are unable to adapt to such temperature changes will not survive and thus will not pass on their genetic information to the next generation. In a world in which we are confronted with constantly rising average temperatures due to global warming, we must ask ourselves: How do organisms react to changing temperatures? What molecular mechanisms do they use?Decades of research have shown that different organisms respond very similarly to temperature changes. When organisms are exposed to heat, their cells cease to grow, they shut down the production of housekeeping proteins that are required for growth and reproduction. Instead, they start to produce proteins that protect the cells from heat-related damage. In other words, the cell factory changes its protein production. However, it is not known how cells recognize heat stress and which mechanisms trigger the production change.

"In yeast, we were able to identify one critical protein, Ded1p, which changes its structure upon heat stress and then reprograms the cell machinery. In the laboratory, we simulated the behavior of Ded1p with purified components and observed the following: Under normal conditions, Ded1p is evenly distributed in the cytoplasm of cells, but when the temperature rises, it assembles into dense structures, using the process of phase separation," explains Christiane Iserman, the lead author of the study. "The fact that Ded1p is able to sense temperature suggests that this protein is a kind of thermometer inside the cell."

Furthermore, the scientists have investigated the consequences for the cell when Ded1p forms these dense structures. "They are telling the cell to downregulate the production of housekeeping proteins, and to ensure that the production of stress-protective proteins is upregulated," explains Chrisitine Desroches Altamirano, second author of the study.

Alberti: However, our discovery may have an even more general relevance: We have discovered a mechanism within the cell that helps the organism to deal with a variety of changes in the environment, not just heat stress. Cells seem to be able to deal with a wide variety of environmental signals by using proteins that phase separate to run different gene expression programs. In further studies, we want to determine whether this mechanism can help us understand human diseases - primarily those in which our cells do not process certain stress situations properly, as it appears to be the case in age-related neurodegenerative diseases".

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Link:
Who Takes the Temperature in Our Cells? - Technology Networks

Do you know your blood type? Even though blood type tests are simple and accessible, many people are not aware of their blood types.There are four blood groups A, B, AB and O. These blood groups refer to the presence of different antigens on the red blood cell. Those whose blood group is AB have both and B antigens on their red blood cells. If you have blood group O, you have neither A or B antigens.Theres an additional antigen, D. People with this antigen are Rhesus D positive. Those who lack the D antigen are said to be RhD negative. The suffix (such as A+ or B-) in blood types usually indicates the presence or absence of the D antigen.1. Blood transfusionBlood transfusions with the wrong blood type can be catastrophic or even fatal. Receiving incompatible blood type can cause the recipients blood to clump, which can quickly become fatal. Therefore, testing the blood type of recipients and donors cant be over-emphasised.But other than transfusion, your blood group has other implications on your health. Although the medical community used to dismiss the idea, recent studies have shown that there could be a link between blood groups and certain health conditions.

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Explainer: Why you need to know your blood group - Standard Digital

STUDY QUESTION

Can resveratrol and epigallocatechin-3-gallate (EGCG) inhibit the growth and survival of endometriotic-like lesions in vivo in a BALB/c model of endometriosis, and in vitro in primary cultures of human endometrial epithelial cells (EECs)?

SUMMARY ANSWER

Resveratrol and EGCG exerted a potent inhibitory effect on the development of endometriosis in a BALB/c murine model and on the survival of EECs.

WHAT IS KNOWN ALREADY

Endometriosis is a common condition associated with infertility and pelvic pain in women of reproductive age. Resveratrol and EGCG are two polyphenols with anticarcinogenic and antioxidant properties that have been proposed as natural therapies to treat endometriosis.

STUDY DESIGN, SIZE, DURATION

Fifty-six 2-month-old female BALB/c mice underwent surgical induction of endometriosis. Treatments with resveratrol or EGCG started 15 days post-surgery and continued for 4 weeks. Human biopsies were taken with a metal Novak curette from the posterior uterine wall from 16 patients with untreated endometriosis and 15 controls who underwent diagnostic laparoscopy for infertility.

MATERIALS, SETTING, METHODS

After the treatments, animals were sacrificed and lesions were counted, measured, excised and fixed. Immunohistochemistry for proliferating cell nuclear antigen and CD34 was performed for cell proliferation and vascularization assessment in the lesions. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) technique was performed for apoptosis evaluation. Peritoneal fluid was collected to analyze vascular endothelial growth factor levels. Human EECs were purified from proliferative-phase endometrial biopsies and cultured. The effect of both polyphenols on cell proliferation was determined by a colorimetric assay using the CellTiter 96^®AQueous One Solution Cell Proliferation Assay kit and on apoptosis by the TUNEL technique, using an In Situ Cell Death Detection Kit with Fluorescein.

MAIN RESULTS

In the mouse model, both treatments significantly reduced the mean number (P < 0.05 versus control) and the volume of established lesions (P < 0.05 versus control). Treatments consistently statistically significantly diminished cell proliferation (resveratrol P < 0.01 and EGCG P < 0.05, versus control), reduced vascular density (resveratrol P < 0.01 and EGCG P < 0.001, versus control) and increased apoptosis within the lesions (resveratrol P < 0.01 and EGCG P < 0.05, versus control). Both compounds induced reduction in human EEC proliferation (P < 0.05 versus basal) and increased apoptosis (P < 0.05 versus basal) in primary cultures.

LIMITATIONS

In vitro studies were only carried out in epithelial cells from human eutopic endometrium.

WIDER IMPLICATIONS OF THE FINDINGS

The present findings are promising and will assist the development of novel natural treatments for endometriosis.

STUDY FUNDING

This study was supported by ANPCYT (PICT 6384 BID 1201 OC-AR) and CONICET (PIP 5471), Argentina. None of the authors has any conflict of interest to declare.

Source:
http://humrep.oxfordjournals.org/cgi/content/short/28/1/178?rss=1

Abstinence First-Teen Birth Control and Human Reproduction.mp4
For use with Chapter 10 of Love Notes v2.0 this dvd includes both abstinence/birth control and human reproduction content.From:TheDibbleInstituteViews:0 0ratingsTime:02:22More inEducation

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Abstinence First-Teen Birth Control and Human Reproduction.mp4 - Video