Budget signals death knell for public appointments commission

OTTAWA The Conservative government is putting an end to an agency it created to oversee public-sector appointments, another focused on assisted human reproduction, and a Trudeau-era educational program designed to build national unity.

The cuts to agencies, boards and Crown corporations announced in the federal budget amount to hundreds of millions of dollars in savings over three years.

The Conservatives created the public appointments commission soon after coming to office in 2006. Its goal was to oversee the process of appointing Canadians to boards and agencies, such as the Employment Insurance Board of Referees, and avoid political involvement in the process.

However, opposition parties raised concerns and ultimately blocked the appointment of a commissioner five years ago, and the commission has sat silent ever since.

The government argued in its budget that the commission is no longer needed because it has "strengthened the rigour and accessibility" of the appointments system, even though the NDP has raised concerns about Tory backers receiving patronage appointments.

Eliminating the commission is expected to yield $1.1 million in savings.

The government also said it plans to eliminate Katimavik, a Trudeau-era program that had French- and English-Canadian students learn in each other's provinces, a nation-building exercise during an era of fierce divides between nationalists and separatists in Quebec.

"It reaches a relatively small number of participants annually at a relatively high cost per participant, due to the nature and duration of the experience," the government wrote in its budget. "Canadian Heritage will continue to invest in youth programming and provide opportunities for more youth to learn about their country."

The Canada Council for the Arts, the National Gallery of Canada and national museums will not see any budget reductions. The National Film Board will see its budget cut by $6.7 million over the next three years, while Telefilm Canada will see a $10.6 million budgetary reduction.

Three of Canada's research councils will see a combined budgetary loss of $60.3 million over three years, while the Canada Mortgage and Housing Corporation will have its budget cut by $102.4 million, with the bulk of that cut coming in the 2014-15 fiscal year.

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Budget signals death knell for public appointments commission

German hermaphrodites push for human rights

Courtesy Of Fackeltraeger Verlag / Courtesy of Fackeltraeger Verlag

Christiane Voelling is a 52-year-old intersexual who lives in Dusseldorf, Germany and has fought for greater rights for people like herself whose sexual gender is indeterminate.

By Andy Eckardt , NBC News Producer

MAINZ, Germany Pink? Or blue? For most parents this is the paramount question when it comes to organizing a baby shower or choosing a color for a newborn's room.

But, what happens if the exact gender of the child cannot be determined? It is estimated that in Germany alone approximately 80,000 people are intersexual, so-called hermaphrodites, who have physical features such as chromosomes, hormones, gonads and outer sexual organs which cannot be unambiguously attributed to just one gender.

Christiane Voelling, 52,is an intersexual.

She is a nurse living in Dsseldorf who was born without defining gender characteristics.

Because German law requires that a newborn's personal data including gender specification is registered within a week, Christiane was proclaimed a boy at birth and called Thomas after a midwife supposedly mistook her enlarged clitoris for a penis.

In Voelling's case, it was later diagnosed that her indeterminate external genitalia were the result of a rare genetic disorder of the adrenal gland, the so-called congenital adrenal hyperplasia, or CAH.

"My childhood and teenage development was often agonizing because I did not really know what was wrong with me and where I belonged," Voelling said in a recent interview with NBC News.

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German hermaphrodites push for human rights

Value Subjectivism and Monetary Instability

By Ron Hera

2012 Hera Research, LLC

Subjectivism is the philosophy that reality is what we perceive to be real and that no underlying, true reality exists independent of human perception. In other words, the nature of reality for an individual person is dependent on that individuals own consciousness. It follows that each person experiences their own reality that is not shared with others. What is true and what seems moral to one person may not be true or moral for another person, i.e., truth and morality are relative. In contrast, objectivism is the philosophy that reality exists independent of human consciousness; that human beings have direct contact with reality through sense perception; and that objective knowledge of reality can be obtained through perception, evidence and logic, e.g., through scientific methods.

A subjectivist might view the stock market as a perpetual bubble floating on the hopes and dreams of entrepreneurs and investors who invest in stocks in the same way that gamblers place chips on a craps table in a casino, without any concept of an objective economic reality outside of the game. A subjectivist might view technical analysis, which is based purely on trading activity in the stock market, as the ideal tool to understand financial markets, despite the fact that is has no direct connection to the objective economic realities of the companies that stocks represent. In contrast, an objectivist might view the stock market as a venue for participation in business ownership where stocks have value as a function of the particular businesses that they represent and because of the goods and services that the businesses provide in the objective world. A subjectivist might say that everything is relative (although the statement is self contradictory), while an objectivist might say that they believe in justification, not by faith, but by verification (Thomas H. Huxley 1825-1895). Although they may not know it, Keynesian economists, bankers and day traders are often philosophical subjectivists while Austrian economists, advocates of the gold standard and value investors are often philosophical objectivists.

An objectivist interpretation of morality is that morality flows naturally from people pursuing their own interests and that immorality results from coercion. For the vast majority of individuals, self interest includes supporting their own family and community, simply because human beings are social animals. Parents naturally care for their own children, for example. Morality is a natural phenomenon, not a product of coercion. Human beings naturally live peacefully together in communities and the vast majority of individuals experience empathy. Both charity and resistance to coercion occur naturally and voluntarily in human communities. Those who do not experience empathy (sociopaths) and who disregard the interests of their fellow human beings or act in ways that harm the community are extremely rare. Philosopher Ayn Rand wrote Force and mind are opposites; morality ends where a gun begins. Human beings do not act morally because they are being watched by police or because a gun is held to their heads. In all cultures and at all times and places throughout recorded history, and certainly before, what is immoral is initiating violent force or coercion without cause, most especially when it harms the community. Although particular rules vary from one culture to another, morality is neither subjective nor relative.

Ironically, the objectivist view of morality has been widely misconstrued as a sanction for selfishness. Selfishness typically results in the deprivation or coercion of others. In contrast, pursuing their own self interest is what human beings naturally and voluntarily do in the absence of coercion. In fact, the idea that what is moral arises in a natural way based on the freedom to pursue ones own self interest, i.e., freedom from coercion, is precisely the moral doctrine of the 1776 American Declaration of Independence:

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Value Subjectivism and Monetary Instability

Dutch man seeks child with father's sperm

London, March 24 (IANS) A childless man in the Netherlands has turned to his father for his sperm after having failed to conceive with his wife despite three years of their marriage.

The couple has found a clinic which will honour their unusual request, the Daily Mail reported.

According to researchers in the journal Human Reproduction, while such arrangements have potential advantages over using donations from strangers, they do bring their own set of complications, such as confusion over the child's actual parent.

In this case, the child produced from this union of egg and sperm will have a "father" who is his biological half-brother and a "grandfather" who is his biological father.

There are varying views on the issue. But most experts agree so-called intra-familial assisted reproduction should not necessarily be banned.

"I don't know that laws should encompass forbidding intra-familial donation," said Adrienne Asch, director of the Centre for Ethics at Yeshiva University in New York City.

But couples who request it "should be very carefully counselled about the psychological pitfalls that could await them", said Asch.

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Dutch man seeks child with father's sperm

Fertility treatment centre plans overseas expansion

Home business Fertility treatment centre plans overseas expansion

THE NATION March 24, 2012 1:00 am

Sarayuth Assamakorn, chief operating officer, said Superior ART's pregnancy success rate was at international levels, and its reproduction technology among the most advanced in Southeast Asia. Foreigners make up 80 per cent of its clients.

This year, the company plans to maintain that proportion, and to open new centres both in Thailand and overseas, with Udon Thani and Burma among the targeted locations. Central to the firm's business is its "management chain" process of managing advanced assisted reproduction technology.

"Superior ART was set up more than five years ago. It has the most advanced assisted reproduction technology laboratories and has achieved international success rates in pre-implantation genetic diagnosis," Sarayuth said.

"Superior ART will expand into the global market using the 'management chain' approach. Our know-how is differentiated by high technology.

"For example, our controlled pregnancy environment - at 37 degrees Celsius - is similar to that of the human body. It features controlled light, similar to that in the uterus, and embryo feeding until the fifth day before being returned into the uterus - compared with the usual three days."

The aim of the firm's marketing strategy is to educate physicians and the public about its use of PGD-PCR (pre-implantation genetic diagnosis and polymerase chain reaction) technology for embryo screening to ensure freedom from congenital diseases, Sarayuth said.

One of the most common inherited disorders among Thais is the blood disease thalassaemia, which according to one report is carried by 25 per cent of Thais.

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Fertility treatment centre plans overseas expansion

Tackling burden in ART: an integrated approach for medical staff

Discontinuation is a problem in fertility clinics. Many couples discontinue assisted reproductive technologies (ART) without achieving a live birth for reasons other than poor prognosis or the cost of treatment. Discontinuation has been attributed to the burden of treatment. The causes of burden can be broadly classified according to whether they originate in the patient, clinic or treatment. Interventions to alleviate these burdens include provision of comprehensive educational material, screening to identify highly distressed patients, provision of tailored coping tools and improvements in the clinic environment and medical interventions. Practical interventions to reduce the different causes of burden in ART exist, but further development and evaluation of the efficacy of these interventions requires more precise definition of terms and theory. In this paper, we propose a general integrated approach to cover different perspectives in dealing with burden in ART clinics. We firstly describe the integrated approach and present common sources of burden. We then describe interventions that could help reduce the burden in ART. Our paper is aimed at fertility clinic staff because of their day-to-day involvement with patients. However, this discussion should also be relevant to companies that develop treatments and to psychosocial experts. Reducing the burden of treatment should lead to improved outcomes, namely better quality of life during treatment and lower discontinuation rates.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Survey shows Kanawha County parents want sex education in schools

Although a majority of Kanawha County parents with school-aged children say sexual education should be taught in schools, a quarter say they're not even sure they're child is learning anything about human reproduction.

The findings are a result of a Public Policy Polling survey conducted in July 2011. The poll surveyed 260 parents via telephone. Sixty-eight percent of respondents said sex education should be taught in West Virginia schools, while 25 percent said no and 7 percent said they weren't sure. Of those surveyed, 53 percent said sex education was taught in their school district while 21 percent said no and 25 percent said they weren't sure.

"Public support for sex education in public schools is very strong," said Kira Miskimmin, public affairs coordinator for Planned Parenthood Health Systems West Virginia. "we know that sexual health education is critical to our young people. It's critical to helping them lead healthy lives and critical to helping them make informed decisions that will allow them to chart the course of their livesto get an education, choose their careers, to plan a family, you name it."

Miskimmin pointed out that some people view sex education in schools as inappropriate or controversial. However, she pointed out that medical and evidence-based sexual education curriculum is informative and helps teens make better decisions about their sex lives.

"The fact is, the vast majority of Americans support teaching medically-accurate, age appropriate sexual health education to young people in schools," she said.

In addition to the Kanawha County poll, nationally-conducted polls also show that parents want their children to learn about sex in schools.

The poll comes at a time when West Virginia is experiencing the highest teen birth rate in the country. According to a Centers for Disease Control and Prevention study released last fall, West Virginia was the only state to see an increase in the teen birth rate. Between 2007 and 2009, the birth rate among 15 to 17-year-olds shot up 17 percent, according to that survey.

"Lack of access to health care information and services, high rates of teen and unplanned pregnancy and poor sexual health have very real and often long-term consequences for individuals and communities as well," Miskimmin said. "Unfortunately, West Virginia is not immune to these issues or the social and economic costs that go along with this issue."

Miskimmin called the CDC study "absolutely alarming," but pointed out that more people and groups, such as Planned Parenthood and West Virginia Free, are more tuned in to the issue and ready and willing to do something about it. The federal government has provided a new funding stream to provide sexual health education and programs to reduce teen pregnancy.

"When you think about all of that, we do have a lot of opportunity before us," she said. "We have the opportunity to come together, to educate our teens and give them the tools they need to really chart their futures."

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Survey shows Kanawha County parents want sex education in schools

Father-to-son sperm donation: 'Too bizarre'?

After three years of trying to conceive, a married couple in the Netherlands in their early 30s learned they could not have a child because the husband produced no sperm. They did not want to use sperm donated from a stranger, partly because this would mean the child would not share genes with the husband's side of the family. But because the husband had no brothers to donate, the couple seemed at a loss on how to pass on his gene pool.

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They use archery, swiftness and brute strength to compete against each other but, luckily, the participants in these games -- which take place at a gym in New York -- will still be alive at the end of the day.

Then the couple thought of an unconventional solution: Use sperm from the husband's father. The child produced from this union of egg and sperm would have a "father" who was his biological half- brother, and a "grandfather" who was his biological father.

As all parties were comfortable with the decision, the couple went to a fertility clinic with their request. After much deliberation, including a discussion with the hospital ethics committee, the clinic eventually decided to honor the couple's wishes.

Though not common, donations of sperm, egg or womb from family members to couples trying to conceive are not technically illegal, and do happen. Such arrangements have potential advantages over using donations from strangers, but they bring their own set of complications, including potential confusion regarding who the child's parent is, say researchers who detail these complexities in a case report of the Netherlands' couple published online March 7 in the journal Human Reproduction. Experts have varying views on the issue, but most agree so-called intrafamilial assisted reproduction should not necessarily be banned, and can perhaps work in some circumstances. However, any couples who decided to enter this territory should tread carefully, say experts.

"I dont know that laws should encompass forbidding intrafamilial donation," said Adrienne Asch, director of the Center for Ethics at Yeshiva University in New York City. But couples who request it "should be very carefully counseled about the psychological pitfalls that could await them," Asch said.

Ethical problems

Couples may turn to family members to assist with reproduction for many reasons. Some, like the couple in the Netherlands, want to have a genetic tie with their child. Others may wish to cut down on the time and money needed for the procedure, according to a position statement from the American Society for Reproductive Medicine (ASRM).

However, one concern in these situations is that the person who donates will want to act as a parent to the child. In the case of the couple from the Netherlands, the "grandfather" may find it hard to resist inserting himself into the family, said Arthur Caplan, bioethicist at the University of Pennsylvania.

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Father-to-son sperm donation: 'Too bizarre'?

Assisted reproductive technology in Europe, 2007: results generated from European registers by ESHRE

BACKGROUND

This 11th European IVF-monitoring report presents the results of assisted reproductive technology (ART) treatments initiated in Europe during 2007.

METHODS

From 33 countries, 1029 clinics reported 493 184 treatment cycles: IVF (120 761), ICSI (256 642), frozen embryo replacement (91 145), egg donation (15 731), preimplantation genetic diagnosis/preimplantation genetic screening (4638), in vitro maturation (660) and frozen oocytes replacements (3607). Overall, this represents a 7.6% increase since 2006, mostly related to an increase in all registers. IUI using husband/partner's (IUI-H) and donor (IUI-D) semen was reported from 23 countries: 142 609 IUI-H (+6.2%) and 26 088 IUI-D (+7.2%).

RESULTS

In 18 countries where all clinics reported, 376 971 ART cycles were performed in a population of 425.6million (886 cycles per million). The clinical pregnancy rates per aspiration and per transfer were 29.1 and 32.8% for IVF, and 28.6 and 33.0% for ICSI. Delivery rate after IUI-H was 10.2% in women aged < 40 years. In IVF/ICSI cycles, 1, 2, 3 and ≥4 embryos were transferred in 21.4, 53.4, 22.7 and 2.5% of cycles, with no decline in the number of embryos per transfer since 2006. The proportion of multiple deliveries (22.3: 21.3% twin and 1.0% triplet), did not decrease compared with 2006 (20.8%) and 2005 (21.8%). In women < 40 years undergoing IUI-H, twin deliveries occurred in 11.7% and triplets in 0.5%.

CONCLUSIONS

In comparison with previous years, the reported number of ART cycles in Europe increased in 2007; pregnancy rates increased marginally, but the earlier decline in the number of embryos transferred and multiple births did not continue.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Seminal vesicles ultrasound features in a cohort of infertility patients

OBJECTIVES

Previous studies concerning ultrasound evaluation of the seminal vesicles (SV) were performed on a limited series of subjects, and considered few parameters, often only before ejaculation and without assessing the patients' sexual abstinence. The aim of this study was to evaluate the volume and the emptying characteristics of the SV and their possible correlations with scrotal and transrectal ultrasound features.

METHODS

The SV of 368 men seeking medical care for couple infertility were evaluated by ultrasound. All patients underwent, during the same ultrasound session, scrotal and transrectal evaluation, before and after ejaculation, and the ejaculate was subjected to semen analysis. A new parameter, SV ejection fraction, calculated as: [(SV volume before ejaculation – SV volume after ejaculation)/SV volume before ejaculation] x 100, was evaluated.

RESULTS

After adjusting for sexual abstinence and age, both pre-ejaculatory SV volume and SV ejection fraction were positively associated with ejaculate volume. As assessed by receiver operating characteristic curve, a cut-off for SV ejection fraction of 21.6% discriminates subjects with normal ejaculate volume (≥1.5 ml) and pH (≥7.2 ml) with both sensitivity and specificity equal to 75%. Subjects with SV ejection fraction of <21.6% more often had a higher post-ejaculatory SV volume and ejaculatory duct abnormalities. Furthermore, a higher post-ejaculatory SV volume was associated with a higher prostate volume and SV abnormalities. Higher epididymal and deferential diameters were also detected in subjects with a higher post-ejaculatory SV volume or reduced SV ejection fraction. No association between SV and testis ultrasound features or sperm parameters was observed. Associations with SV ejection fraction were confirmed in nested 1:1 case–control analysis.

CONCLUSIONS

The SV contribute significantly to the ejaculate volume. A new parameter, SV ejection fraction, could be useful in assessing SV emptying. A SV ejection fraction of <21.6% was associated with prostate–vesicular and epididymal ultrasound abnormalities.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Human papillomavirus sperm infection and assisted reproduction: a dangerous hazard with a possible safe solution

BACKGROUND

Human papillomavirus (HPV) infection has been demonstrated in the sperm of a large percentage of sexually active males and is associated with an impairment of sperm parameters, with a particular negative impact on sperm motility, suggesting a possible role in male infertility. Conventional sperm selection techniques have a low efficiency in removing HPV.

METHODS

Evaluation of sperm parameters, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling test to evaluate DNA fragmentation and fluorescence in situ hybridization or immunohistochemistry for HPV were performed on semen samples from infected patients (n= 22), control subjects (n= 13) and on pooled control sperm samples incubated with HPV16-L1 (HPV capsid), before and after direct swim-up and modified swim-up (with added Heparinase-III). Moreover, cytofluorimetry for HPV detection was performed in pooled sperm pre- and post-incubation with HPV 16-L1 before and after direct and modified swim-up. Statistical analysis was performed with a two-tailed Student's t-test.

RESULTS

Direct swim-up reduces the number of HPV-infected sperm by ~24% (P< 0.01), while modified swim-up is able to remove completely HPV DNA both from naturally and artificially infected sperm. Enzymatic treatment with Heparinase-III tended to decrease sperm motility, viability and DNA integrity but the effects were not significant.

CONCLUSIONS

This study shows that Heparinase-III treatment seems not to affect spermatozoa in vitro and suggests that this treatment should be investigated further as a means of preparing sperm from patients who are infected with HPV in order to reduce the risk of HPV infection when using assisted reproduction techniques.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

A novel application of cell-free seminal mRNA: non-invasive identification of the presence of germ cells or complete obstruction in men with azoospermia

BACKGROUND

Cell-free seminal mRNA (cfs-mRNA) exists in human ejaculate at high concentrations and with high stability, and contains many tissue-specific transcripts secreted from the male reproductive system. Owing to the sensitivity of RNA technology, cfs-mRNAs are ideal candidates for non-invasive biomarkers of physiopathological conditions. This study applied cfs-mRNA in identifying the presence of either germ cells or complete obstruction in men with azoospermia.

METHODS

RT–PCR was performed to amplify the germ cell-specific (DDX4), seminal vesicle-specific (SEMG1) and prostate-specific (TGM4) mRNAs from cfs-mRNAs, which were isolated from the seminal plasma of men with non-obstructive azoospermia (NOA) or obstructive azoospermia (OA). The 39 patients with NOA, diagnosed by testicular biopsy, included 8 men with maturation arrest (MA), 3 men with incomplete sertoli cell only (iSCO) syndrome and 28 men with complete SCO (cSCO). The 29 patients with OA, confirmed by the presence of sperm in the testis or epididymis, included 8 men with congenital bilateral absence of the vas deferens (CBAVD) and 21 men with non-CBAVD. Healthy individuals and vasectomized men were enrolled as controls.

RESULTS

TGM4 was detected in all participants. Consistent with their diagnosis, DDX4 was detected in all patients with MA or iSCO but was absent in most cases of cSCO (n = 21, 75.0%) or non-CBAVD (n = 18, 85.7%), and in all men with vasectomy or CBAVD. The presence of DDX4 in the other seven men with cSCO and three patients with non-CBAVD suggests the presence of germ cells in the testis, and incomplete obstruction, respectively. SEMG1 was undetectable in three patients with CBAVD with bilateral absence of the seminal vesicles, and in two non-CBAVD cases with low ejaculate volume.

CONCLUSIONS

These results suggest that, with high sensitivity and representativity, cfs-mRNA could be non-invasive biomarkers for identifying the presence of germ cells or complete obstruction in azoospermia.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Failure of a combined clinical- and hormonal-based strategy to detect early spermatogenesis and retrieve spermatogonial stem cells in 47,XXY boys by single testicular biopsy

BACKGROUND

Although germ cells in boys with Klinefelter syndrome (KS) are reduced in number as early as infancy, a severe germ cell loss occurs during mid-puberty. Therefore, we wanted to detect spermatogenesis at an early stage and investigate the strategy of preserving spermatozoa and/or testicular spermatogonial stem cells in adolescents with KS when signs of deteriorating spermatogenesis are observed.

METHODS

Tanner staging, testicular size, serum inhibin B and spermaturia were assessed every 4 months before the attempt to procure gametogenic cells in seven non-mosaic 47,XXY adolescents, aged between 10 and 16 years.

RESULTS

Despite an increasing testis volume in the youngest and a Tanner staging of more than three in the oldest patients, no spermaturia was observed. In two patients serum inhibin B increased gradually, while in all others a rather rapid but variable decline was observed at different ages. No spermatozoa were observed after electroejaculation. No spermatocytes or spermatids were found at microscopic examination of single biopsies, while spermatogonia were identified in four subjects, three of whom had measurable serum inhibin B. Massive fibrosis and hyalinization were observed in all biopsies.

CONCLUSION

No spermatogenesis was documented in non-mosaic 47,XXY adolescents either by spermaturia, electroejaculation or testicular biopsy. Neither clinical nor hormonal parameters were of value in determining the timing for optimal spermatogonial stem cell retrieval. More data are needed to elucidate the potential role of testicular tissue cryopreservation in adolescents with KS. Therefore, at present, the cryopreservation of testes tissue for clinical reasons should not be recommended.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Unconjugated bisphenol A cord blood levels in boys with descended or undescended testes

BACKGROUND

Human toxicity of bisphenol A (BPA), a weak estrogenic environmental endocrine disrupting compound, widely used in plastics, baby bottles, cans and dental sealants, is under investigation. Fetal or perinatal exposure in rodents is associated with programmed adult reproductive diseases. Human epidemiological studies remain scarce, especially concerning testicular development. We have investigated the relationship between fetal exposure to BPA and cryptorchidism.

METHODS

Using a radioimmunoassay performed after extraction, validated by high-performance liquid chromatography and mass spectrometry, active levels of unconjugated BPA (uBPA) in cord blood (CB) were measured in 152 boys born after 34 weeks gestation, with cryptorchid or descended testes.

RESULTS

Active uBPA was detectable in all CB samples, with values in the control group (n = 106) of 0.14–4.76 ng/ml, median: 0.9 ng/ml; mean ± SD: 1.12 ng/ml ± 0.86 ng/ml, which did not differ from cryptorchid boys (n = 46, 1.26 ± 1.13 ng/ml, P = 0.38). uBPA in controls correlated with CB inhibin B (P < 0.01) and total testosterone (P < 0.05), and with maternal milk polychlorinated bisphenyl 138 (P < 0.03). uBPA did not correlate with clinical maternal or fetal parameters or with other steroid or polypeptide CB hormones assessed.

CONCLUSIONS

The presence of uBPA in all CB samples suggests placental transfer and fetal exposure. Similar uBPA levels in the control and cryptorchid groups make the participation of fetal exposure to uBPA in the physiopathology of undescended testes unlikely. However, the observed nanomolar uBPA concentrations support assessment of epidemiological relationships between CB uBPA and other human diseases.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Endocrine-disrupting chemicals in human follicular fluid impair in vitro oocyte developmental competence

BACKGROUND

Increased global industrial activity has exposed humans to a wide variety of chemical substances some of which, called ‘endocrine-disrupting chemicals’ (EDCs) or ‘endocrine disruptors’, can disrupt the endocrine system in the body. The ovarian follicle is a very fragile micro-environment where interactions between hormones, growth factors, the oocyte and its surrounding somatic cells are essential to generate a fully competent oocyte. In vitro experiments suggest that EDCs can disturb this finely tuned balance, but very scarse in vivo data are available to confirm this assumption. Therefore, we have investigated if the presence of EDCs in human follicular fluid is a risk factor for the developmental competence of an in vivo exposed oocyte. Furthermore, because of the limited access to human follicular fluid, we verified if follicular fluid contamination can be predicted based on EDC levels in serum.

METHODS

Follicular fluid (n = 40) and serum (n = 20) samples from women undergoing assisted reproductive technology (ART) were analyzed by means of gas chromatography combined with mass spectrometry to examine the presence of different EDCs, such as polychlorinated biphenyls, polybrominated diphenyl ethers and organochlorine pesticides. Statistical models were used to investigate the relation between the characteristics and ART results of the patients and the contamination status of their follicular fluid and to assess the capacity of serum samples to predict follicular fluid contamination.

RESULTS

Chlorinated biphenyl 153 (72 ± 44 and 201 ± 106 pg/ml) and p,p'-DDE (392 ± 348 and 622 ± 406 pg/ml) were the compounds found in the highest concentrations in follicular fluid and serum samples, respectively. A new variable principal component 1, representing the overall contamination status of the follicular fluid samples, is strongly associated with fertilization rate (P < 0.00001) and the proportion of high-quality embryos relative to the amount of retrieved oocytes (P < 0.05), even when the analysis is adjusted for age, estradiol concentration, BMI, fertilization procedure and male subfertility as explanatory variables. The strong correlations between the EDC concentrations in serum and follicular fluid (r ≥ 0.93) allowed us to build regression models, which accurately predict EDC concentrations in the follicular fluid based on serum samples.

CONCLUSIONS

An overall higher EDC contamination in the follicular micro-environment was associated with a decreased fertilization rate and consequently with a lower chance of an oocyte to develop into a high-quality embryo. In addition, EDC concentrations in serum were reliable predictors of the contamination status of the follicular micro-environment.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Glycodelin-A interferes with IL-2/IL-2R signalling to induce cell growth arrest, loss of effector functions and apoptosis in T-lymphocytes

BACKGROUND

The progesterone-regulated glycoprotein glycodelin-A (GdA), secreted by the decidualized endometrium at high concentrations in primates, inhibits the maternal immune response against fetal antigens and thereby contributes to the tolerance of the semi-allogenic fetus during a normal pregnancy. Our earlier studies demonstrated the ability of GdA to induce an intrinsic apoptotic cascade in CD4+ T-lymphocytes and suppress the cytolytic effector function of CD8+ T-lymphocytes. In this report, we investigated further into the mechanism of action of GdA controlling perforin and granzyme B expression in CD8+ T-lymphocytes and the mechanism of action of GdA leading to lymphocyte death.

METHODS

Flow cytometry analysis was performed to check for the surface expression of interleukin-2 receptor α (IL-2Rα) and intracellular eomesodermin (Eomes) in activated T-lymphocytes, whereas quantitative RT–PCR analysis was used to find out their mRNA profile upon GdA treatment. Western analysis was carried out to confirm the protein level of Bax and Bcl-2.

RESULTS

GdA reduces the surface expression of the high-affinity IL-2R complex by down-regulating the synthesis of IL-2Rα (CD25). This disturbs the optimal IL-2 signalling and decreases the Eomes expression, which along with IL-2 directly regulates perforin and granzymes expression. Consequently, the CD8+ T-lymphocytes undergo growth arrest and are unable to mature into competent cytotoxic T-lymphocytes. In the CD4+ T-lymphocytes, growth factor IL-2 deprivation leads to proliferation inhibition, decreased Bcl-2/enhanced Bax expression, culminating in mitochondrial stress and cell death.

CONCLUSIONS

GdA spurs cell cycle arrest, loss of effector functions and apoptosis in different T-cell subsets by making T-lymphocytes unable to respond to IL-2.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Heated spermatozoa: effects on embryonic development and epigenetics

BACKGROUND

Sperm chromatin is highly condensed and relatively resistant to chemical and physical treatments. The purpose of this study was to explore the highest temperature that sperm can tolerate and still produce live offspring.

METHODS

Mouse sperm were heated in a water bath at 50, 65, 80 or 95°C for 30 min before they were microinjected into mouse oocytes. Fertilization, embryo development and 1-cell embryo karyotypes were evaluated. Epigenetic reprogramming including DNA methylation and histone H3K4-trimethylation were evaluated by immunofluorescent staining.

RESULTS

The ability of mouse sperm to activate the egg after ICSI was heat sensitive; only 20% of eggs were activated by sperm that had been heated to 50°C and none was activated by sperm heated to 80°C. However, if eggs were activated artificially, mouse sperm subjected to 80°C for 30 min were able to produce live offspring, while 95°C treatment disabled sperm decondensation after ICSI. Once the heat-treated sperm nucleus had developed into a pronucleus, sperm chromatin was able to undergo normal active DNA demethylation and histone methylation. Aberrant chromosome rates increased from 16.3 to 100% when the temperature was raised from 50 to 95°C.

CONCLUSIONS

Heat treatment destroys integrity of sperm chromatin in a temperature-dependent manner. Eighty degree Celsius was the highest temperature that mouse sperm could withstand and still produce live offspring.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Tailored expectant management: a nationwide survey to quantify patients’ and professionals’ barriers and facilitators

BACKGROUND

Prognostic models for natural conception help to identify subfertile couples with high chances of natural conception, who do not need fertility treatment yet. The use of such models and subsequent tailored expectant management (TEM) is not always practiced. Previous qualitative research has identified barriers and facilitators of TEM among patients and professionals. The aim of this study was to assess the prevalence of those barriers and facilitators and to evaluate which factors predict patients' appreciation of TEM and professionals' adherence to TEM.

METHODS

We performed a nationwide survey. Based on the previously identified barriers and facilitators two questionnaires were developed and sent to 195 couples and 167 professionals. Multivariate analysis was performed to evaluate which factors predicted patients' appreciation of TEM and professional adherence to TEM.

RESULTS

In total, 118 (61%) couples and 117 (70%) professionals responded and 96 couples and 117 professionals were included in the analysis. Patients' mean appreciation of TEM was 5.7, on a 10-point Likert scale. Patients with a lower appreciation of TEM had a higher need for patient information (P = 0.047). The professionals reported a mean adherence to TEM of 63%. Adherence to TEM was higher when professionals were fertility doctors (P = 0.041). Facilitators in the clinical domain were associated with a higher adherence to TEM (P = 0.091). Barriers in the professional domain had a negative impact on adherence to TEM (P = 0.008).

CONCLUSIONS

The limited implementation of TEM is caused by both patient and professional-related factors. This study provides practical tools to improve the implementation of TEM.

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http://humrep.oxfordjournals.org/rss/current.xml

Cumulative pregnancy rate after ICSI-IVF in patients with colorectal endometriosis: results of a multicentre study

BACKGROUND

There is currently no consensus about indications for surgery for infertility associated with colorectal endometriosis. The aim of this study was to evaluate cumulative pregnancy rates (CPRs) after ICSI–IVF cycles in patients with colorectal endometriosis and to identify determinant factors of fertility outcome.

METHODS

Prospective longitudinal multicentre study from January 2005 to June 2011. We included 75 patients with colorectal endometriosis and proved infertility without prior surgery for deep infiltrating endometriosis. Univariable analysis was used to identify determinant factors of pregnancy rate. CPR was calculated using cumulative-incidence methods from log-rank test and Kaplan–Meier curves. For multivariable analysis, Cox proportional hazards model was used.

RESULTS

For CPR per patient analysis, the total number of cycles was 113 and the median number of cycles per patient was 1 (range: 1–3). In the whole population the CPR per patient after three ICSI–IVF cycles was 68.6%. The CPR for patients with or without associated adenomyosis was 19 and 82.4%, respectively (P= 0.01). In addition, a patient age over 35 years (P= 0.02) and anti-Mullerian hormone serum level under 2 ng/ml (P= 0.02) were associated with a decreased CPR per patient. At multivariable analysis, adenomyosis [HR = 0.34, 95% CI (0.12–0.99), P= 0.49] was associated with a decreased CPR.

CONCLUSIONS

Our data confirm that ICSI–IVF offers a high CPR per patient. However, determinant factors of CPR should be taken into account when informing couples of their options.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

A short exposure to polychlorinated biphenyls deregulates cellular autophagy in mammalian blastocyst in vitro

BACKGROUND

Polychlorinated biphenyls (PCBs) are common environmental contaminants that represent an important risk factor of reproductive disorders in chronically exposed human populations. However, it is not known whether a short accidental exposure of embryos to PCBs before implantation might influence their further development and whether the effect might be reversible.

METHODS AND RESULTS

To this aim, in vitro-matured sheep blastocysts were incubated with 2 or 4 µg/ml Aroclor 1254 (A1254), a mixture of 60 PCB congeners for 48h after which blastocyst proliferation and ability for outgrowth in vitro were assessed. Blastocysts exposed to A1254 showed: (i) reduced proliferation and cell number (particularly in the inner cell mass compartment); (ii) accumulation of vacuoles and lipid droplets, diffused mitochondrial damage and up-regulation of autophagy markers (ATG6 and LC3), all signs indicative of deregulated autophagy, and (iii) massive cell death. Although exposed embryos resumed growth following A1254 removal, their subsequent development remained severely perturbed.

CONCLUSIONS

These findings indicate that short exposure of blastocysts to PCBs leads to its damage characterized by deregulated autophagy and subsequent cell death.

Source:
http://humrep.oxfordjournals.org/rss/current.xml