DoD basic research discovers new spectroscopic signatures from the 'Stuff of Life'

Physics professor Elliott Brown and graduate student Anna Lukawska work in the lab on nanobiological characterizations.

There is hardly a greater discovery during the past century than DNAdeoxyribonucleic acidthe biomolecular material in every cell of the human body. DNA contains the genetic information necessary for cell replication, protein synthesis and reproduction.

Naturally, DNA sensing and identification has become a very important technology in such areas as biology, medicine and law enforcement. But positive identification without ambiguity is difficult because DNA is so sparse in the human organism and because it shares many of the same chemical bonds as other more common biomoleculesproteins and polysaccharides.

So traditional spectroscopic methods, such as infrared transmission, cannot distinguish DNA from these other molecules. More elaborate techniques are necessary, such as polymerase chain reaction (PCR) followed by gel electrophoresis, which are expensive and time-consuming.

Fortunately, the large size of DNA molecules makes them amenable to other spectroscopic methods in the THz region of the electromagnetic spectruma region well below the infrared in frequency but well above common radio and radar frequencies.

Wright State University researchers led by physics professor Elliott Brown have been investigating these unique THz DNA signatures through a Multidisciplinary University Research Initiative (MURI) funded by the U.S. Army Research Office. Their multi-year $600,000 grant has recently identified several unique and surprisingly strong signatures from DNA molecules between 0.7 and 1.0 THz.

The surprise is that we have recently measured these DNA signatures under physiological conditions in which the DNA was suspended in an aqueous buffer solution very similar to that in living cells, Brown said. Previously, the strong THz absorption by liquid water was thought to be too strong to observe signatures from any suspended molecular species.

So far, Brown said, the signatures appear unique to the DNA molecule at hand, be it single-stranded or double-stranded DNA.

The caveat is that so far we have only observed relatively short DNA strands well under the length of the human genome, he said. But we are moving in that direction.

The research project is headed by the University of California-Irvine, and along with Wright State University has collaborators at Marshall University, Yale University and the University of Chicago. The MURI Grant funds the research for up to five years.

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DoD basic research discovers new spectroscopic signatures from the 'Stuff of Life'

The £25m IVF doctor: Clinic's profits fuel criticism of the 'human life industry'

By Neil Sears

PUBLISHED: 17:02 EST, 13 May 2012 | UPDATED: 03:14 EST, 14 May 2012

A controversial fertility doctor has raked in 25million in a single year.

Mohamed Taranissi and his wife received the colossal sum through their IVF clinic, giving fresh evidence to critics who say that the creation of human life has become a multi-million pound industry.

On Saturday the Daily Mail revealed that a human egg agency has offered thousands of Cambridge university students 750 to donate their eggs.

The 25m man: Mohamed Taranissi earned the vast sum as head of London's most successful fertility clinic

Mr Taranassi, 57, and his second wife Elly Fincham, 53, are the owners of the Assisted Reproduction and Gynaecology Centre fertility clinic in London. Rod Stewarts wife Penny Lancaster had their son Aiden after treatment there.

Its reputation has helped the couple build a fortune of 45million, including the newly published dividend of 25million they paid themselves in 2010.

Women pay 150 for an initial consultation and 2,500 for a course of IVF, with other procedures and drugs pushing the cost up higher. Customers are attracted by Mr Taranissis impressive listing at the top of pregnancy league tables for woman under 35 and over 40.

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The £25m IVF doctor: Clinic's profits fuel criticism of the 'human life industry'

The great sperm race? Study reveals chaotic reproductive journey

It isn't the most elegant of races.

In a study that attempts to elucidate one of the "central unsolved problems" in human reproduction what separates the tens of sperm cells that find an egg, from the millions of cells ejaculated? British researchers are reporting that sperm crawl, collide and crash head-on into the walls of the female reproductive tract in their frantic swim to the site of fertilization.

"Despite it being the thing that put all of us here, effectively, we still know almost nothing about how something so simple and key to life actually happens in the body," said Dr. Jackson Kirkman-Brown, a senior lecturer in reproductive sciences at the University of Birmingham in the U.K.

"Every time a woman gets or doesn't get pregnant, there is something going on where what to me is an incomprehensible number of sperm two hundred million get reduced to a countable amount, 10, maybe."

Popular wisdom holds that sperm follow each other in their swim through the female tract "rather like you or I might swim through a swimming pool," Kirkman-Brown said.

Instead, the researchers observed sperm travelling along walls, ceilings and particularly corners as they navigated the "narrow and convoluted channels" of the female tract, the team reports in the journal Proceedings of the National Academy of Sciences of the United States.

Sperm failing to get to the egg dooms fertility. "But equally some of the most common things in contraception are based on sperm motility," Kirkman-Brown said. Oral contraceptives the Pill work by thickening cervical mucous and stopping sperm from getting to the egg.

With ever more people undergoing fertility treatment and the pharmaceutical industry looking to develop new contraceptives, "There has been a lot more interest in sperm motility," he said.

To try to get a better handle on the "individual and group behaviours" that occur, the researchers watched sperm swimming not on slides or in petri dishes, but through tiny, hair-thin mini-mazes etched into silicone and barely visible to the naked eye.

The micro-channels were filled with fluid mimicking the viscosity of fluid within the female reproductive tract, giving sperm a more realistic environment. The mini mazes "have lots of different twists and turns, so we can see how sperm cope with swimming around these," Kirkman-Brown said.

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The great sperm race? Study reveals chaotic reproductive journey

Intrauterine devices provide the most effective emergency contraception

Public release date: 8-May-2012 [ | E-mail | Share ]

Contact: Emma Mason wordmason@mac.com European Society of Human Reproduction and Embryology

Intrauterine devices (IUDs) should be used routinely to provide emergency contraception, according to the authors of the first systematic review of all available data from the past 35 years. They found that IUDs had a failure rate of less than one per thousand and were a more effective form of emergency contraception than the "morning after pill". In addition, IUDs continued to protect women from unwanted pregnancy for many more years if they were left in place.

The research, which is published online in Europe's leading reproductive medicine journal Human Reproduction [1] today (Wednesday), analysed data from 42 studies carried out in six countries [2] between 1979 and 2011 and published in English or Chinese. IUD use in China is the highest in the world with 43% of women using them for contraception compared with 13% in the rest of the world, according to a 2006 report. The studies included eight different types of IUDs and 7034 women.

An IUD, sometimes known as a "coil" is a small plastic and copper device that is inserted into the womb by a trained doctor or nurse. It can be left in place for between five and ten years, depending on brand. In recent years, intrauterine systems (IUS) have been developed; these are small, plastic devices that release a very low dose of the hormone progesterone. The current study looked at IUDs only, which have been used for emergency contraception for at least 35 years.

The first author of the study, Ms Kelly Cleland, a staff researcher at the Office of Population Research at Princeton University, Princeton, USA, said: "Unintended pregnancies are a significant health problem worldwide. It is estimated that globally at least 36% of pregnancies are unintended. We already know from previous research that IUDs are very cost-effective forms of regular contraception. This study is the most comprehensive review to date of the efficacy of IUDs used for emergency contraception, and our results provide clear evidence that they are a highly effective method of emergency contraception, as nearly 100% of users overall did not become pregnant after unprotected sex when an IUD was inserted post-coitally. In contrast, failure rates are at least 10-20 times as high for emergency contraceptive pills such as ulipristal acetate and levonorgestrel. IUDs also offer very effective ongoing contraception. Therefore, we conclude that IUDs should be included routinely as an emergency contraceptive option whenever feasible and appropriate."

When IUDs are used for emergency contraception they normally should be inserted within about five days of unprotected intercourse. The maximum timeframe in the current review ranged between two and ten days or more. However, in the majority of the studies (74%) insertion occurred within five days.

Out of the 7034 post-coital IUD insertions, there was a total of 10 pregnancies: six occurred among 5629 women in China, and the remaining four pregnancies in 200 women in one Egyptian study.

The researchers believe the unusual and abnormal results in the Egyptian study made it an "outlier" study, probably due to the way the women were chosen and, therefore, should be ignored for the purposes of their review. "This high failure rate can possibly be explained by the fact that women were specifically selected if they had had intercourse around the time of ovulation; in any event Egypt is a clear outlier," write the authors. "If the unusual results from the Egypt study were excluded, the overall failure rate would be 0.09% . . .; this is our preferred estimate."

By comparison, the "morning after pill" ulipristal acetate is the next most effective with a failure rate of approximately 1-2%, followed by levonorgestrel with a failure rate of approximately 2-3%. Both ulipristal acetate and levonorgestrel become less effective with increasing body mass index (BMI), but the researchers say that IUDs do not lose their effectiveness with increasing BMI.

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Intrauterine devices provide the most effective emergency contraception

Birth Defect Rates Vary Depending on Fertility Treatment

Mother's arm cradles an hour-old baby girl.

By Steven Reinberg HealthDay Reporter

SATURDAY, May 5 (HealthDay News) -- Birth defects are more common after certain infertility treatments, but whether the cause is the assisted reproduction techniques themselves or the underlying biology preventing conception isn't clear, Australian researchers say.

"While treatments appear quite safe, we cannot ignore that there are significant risks that require urgent investigation with additional ongoing studies," said lead researcher Michael Davies, an associate professor at the Robinson Institute of the University of Adelaide.

For the study, published online May 5 in the New England Journal of Medicine, Davies and colleagues collected data on more than 6,100 births achieved using assisted reproductive technology in South Australia.

[Read: Can't Get Pregnant?How Stress May Be Causing Your Infertility.]

The investigators compared these births with a registry of more than 300,000 births, looking for the risk of birth defects associated with infertility treatments compared to unassisted pregnancies. "Spontaneous" pregnancies in women who previously had infertility treatments were also considered.

Overall, with assisted reproduction methods, the risk of any birth defect was 8.3 percent compared with 5.8 percent for unassisted pregnancies. These included cleft palate, and heart, gastrointestinal and esophageal defects.

For in vitro fertilization (IVF), the risk for birth defects was 7.2 percent. For intracytoplasmic sperm injection (ICSI), it was 9.9 percent. In IVF, eggs are retrieved from a woman's ovaries and fertilized by sperm in a lab before being returned to her uterus. With ICSI, a form of IVF, a single sperm is injected into the center of an egg cell to aid fertilization.

Women using clomiphene citrate at home to stimulate ovulation had triple the risk of birth defects, the researchers noted.

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Birth Defect Rates Vary Depending on Fertility Treatment

New study published on fertility awareness among American university students

Public release date: 7-May-2012 [ | E-mail | Share ]

Contact: Sheri Ledbetter sledbett@chapman.edu 714-289-3143 Chapman University

ORANGE, Calif. A groundbreaking study lead by Chapman University professor Brennan Peterson, Ph.D. on fertility awareness of American college students will be published in the May 5th edition of Human Reproductiona top-tier international journal in reproductive biology. It is the first such study on fertility awareness among American undergraduate university students. In the USA, the postponement of childbearing is reflective of contemporary social norms of delaying marriage, pursuing education and securing economic stability prior to having a baby. However the awareness of the impact of age on fertility among American college students is low.

Dr. Peterson, an expert in infertility, and the lead author on the study, notes, "The findings from this study show that while undergraduate university students in our sample believed they are educated about fertility issues, they consistently overestimate the ages at which fertility declines in women, as well as their chances of success if they used fertility treatments to achieve pregnancy. It is important that men and women are educated regarding fertility issues so they make informed reproductive decisions, rather than relying on inaccurate information which may ultimately result in involuntary childlessness."

Infertility or the inability to conceive or give birth to a child after one year of regular sexual relations without the use of contraceptives impacts between 80 million to 160 million people in the world today. In the United States, 4.3 million married couples (15%) have been diagnosed with infertility.

For women, fertility rapidly declines between ages 35 and 37. Couples who unknowingly delay pregnancy past a woman's window of fertility may be faced with involuntary childlessness and unexpected cope with the stresses of infertility. When a couple is diagnosed with infertility they are likely to experience unexpected stress, increased depression and changes to their social family networks. These stresses, coupled with the burdens of fertility treatments, can be an enormous challenge for couples which often takes years to resolve.

Infertility has many causes which are often not preventable (e.g., irregular ovulation, low sperm count). However, avoiding the decline in fertility associated with age is well within a person's control. Despite this, many young men and women are unaware of the exact nature of the relationship between fertility and age and new research conducted at Chapman University suggests American college students lack fundamental awareness of reproductive issues as well as the impact of age on fertilityoverestimating their chances to get pregnant at ages when pregnancy is unlikely. For example, young people see celebrities having children into their 40's and conclude that they can wait and "simply" get fertility treatment to get pregnant later in life.

###

The research, called Fertility awareness and parenting attitudes among American male and female undergraduate university students (HUMREP 11 1203.R1) is published in Human Reproduction doi:10.1093/humrep/des011. The online publication is attached. The article also appears in the May 5th version of the print journal.

Consistently ranked among the top universities in the West, Chapman University provides a uniquely personalized and interdisciplinary educational experience to highly qualified students. Our programs encourage innovation, creativity and collaboration, and focus on developing global citizen-leaders who are distinctively prepared to improve their community and their world. Visit http://www.chapman.edu.

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Students and Teachers Respond to "Don't Say Gay"

COLUMBIA - Missouri House Bill 2051 has been dubbed the "Don't Say Gay" bill.

If the bill passes, all discussion concerning sexual orientation of any kind would be disallowed in all public schools. The only exceptions would be human reproduction and students speaking with a counselor.

Adia German is an MU student and an ally. She is heterosexual but she empathizes with the LGBT community. She says she has gay friends and the thought of keeping them from being honest about who they are is completely unfair.

"In silencing them, it's discriminatory for one thing, but being gay isn't something we should be silencing. The more educated we get people, the better it's going to be for everyone."

As for the facutly facing the threat of silence, MU theater professor Suzanne Burgoyne says it's not only wrong, it's unconstitutional.

"It says you can't exercise your right to free speech. You can't talk about something you might want to talk about," Burgoyne said.

As a member of a play group dedicated to fostering discussion around social justice issues, Burgoyne says free speech is just as important to education as any other class subjects.

"We feel that to be able to talk about important issues of the day including issues of diversity is as important to your education as anything that you could learn in a class in terms of subject matter," she said.

A Rockbridge High Shool faculty member asking not to be mentioned by name, expressed bewilderment at the fact this topic is occupying time in the senate.

"I just think there are way more important things we could be dealing with in politics than oppressing people from expressing themselves. Especially people who are at an age where they are trying to find themselves."

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Students and Teachers Respond to "Don't Say Gay"

Missouri lawmaker announces he is gay, denounces school bill

JEFFERSON CITY A Republican lawmaker on Wednesday announced he is gay and called on his colleagues to drop a bill that would restrict discussions about sexual orientation in public schools.

The so-called "don't say gay" bill appears unlikely to pass this legislative session, but Rep. Zach Wyatt of Green Castle in northeastern Missouri said he wants supporters to withdraw the bill.

"I just couldn't be silent anymore," Wyatt said. "I really hope they step back and look at the whole situation."

The bill would prevent any class, classroom material or extracurricular activity from "discuss(ing) sexual orientation other than in scientific instruction concerning human reproduction."

Wyatt and other opponents say it would outlaw gay-straight alliance groups and send a negative message to confused teens.

The proposal has been skewered on cable television and it has left national gay rights activists questioning Missouri lawmakers' priorities.

Rep. Steve Cookson, a Republican from Fairdealing in southeast Missouri who is sponsoring the bill, gave no indication he would withdraw the measure. Cookson said detractors are distorting its "true intent."

"In a time when our public schools continue to struggle financially, we want their focus to be solely on core education issues such as math, science and reading; and not on topics that are better left for discussion in the home at the discretion of parents," he said in a statement.

He said the bill would not prevent kids who are struggling with their sexuality from speaking to school counselors in private.

"My bill does not target a particular sexual orientation but instead says instruction or materials related to any sexual orientation should not take place in our public schools," he said.

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Missouri lawmaker announces he is gay, denounces school bill

Signals of Natural Selection Found in Recent Human Evolution

By Elizabeth Pennisi, ScienceNOW

In a world where weve tamed our environment and largely protected ourselves from the vagaries of nature, we may think were immune to the forces of natural selection. But a new study finds that the process that drives evolution was still shaping us as recently as the 19th century.

The finding comes from an analysis of the birth, death, and marital records of 5,923 people born between 1760 and 1849 in four farming or fishing villages in Finland. Researchers led by evolutionary biologist Alexandre Courtiol of the Institute for Advanced Study Berlin picked this time period because agriculture was well established by then and there were strict rules against divorce and extramarital affairs. The team looked at four aspects of life that affect survival and reproduction, key signposts of natural selection: Who lived beyond age 15, who got married and who didnt, how many marriages each person had (second marriages were possible only if a spouse died), and how many children were born in each marriage. All these steps can influence the number of offspring you have, says Courtiol.

Natural selection was alive and well in all of the villages the researchers surveyed. Almost half of the people died before age 15, for example, suggesting that they had traits disfavored by natural selection, such as susceptibility to disease. As a result, they contributed none of their genes to the next generation. Of those that made it through childhood, 20 percent did not get married and had no children, again suggesting that some traits prevented individuals from obtaining mates and passing on their genes to the next generation.

The numbers were about the same for landed and landless individuals, indicating that wealth did not buffer the environment enough to prevent natural selection from culling or favoring individuals. Although there is agriculture and transmission of wealth, there is still as much room for evolution to proceed as in other animals, says Courtiol, whose team reports its findings online today in the Proceedings of the National Academy of Sciences.

The Finns were also subject to sexual selection, in that men who were able to attract new mates had more offspring. With one partner, the average was about five children; with four partners, that jumped to 7.5, Courtiol notes. Men benefited more than women in terms of begetting more children, most likely because they tended to remarry young women with good child-bearing potential. Thus sexual selection was more important in men than in women.

From the records they had, the researchers could not tell which traits were being selected for, but the variation in the number of offspringfrom zero to 17indicates there was a large opportunity for selection to occur. That variation is the grist for evolution.

The importance of sexual selection is well accepted in birds and fish, but this is the first time that sexual selection has been so well documented in humans, says Stephen Stearns, an evolutionary biologist at Yale University. As for showing natural selection, they are providing additional, confirmational evidence.

Without a doubt, natural selection occurs in modern humans, agrees Jacob Moorad, an evolutionary biologist at Duke University in Durham, North Carolina, who was not involved in the study. He thinks this work will inspire other researchers with large databases of data on humans to look at how selection operates in populations.

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Signals of Natural Selection Found in Recent Human Evolution

HRW investigates Tunisian justice system

Tunisian prosecutors need to show their full commitment to justice with the prosecution of former regime officials accused of torture, Human Right Watch said.

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TUNIS, Tunisia, May 3 (UPI) -- Tunisian prosecutors need to show their full commitment to justice with the prosecution of former regime officials accused of torture, Human Right Watch said.

Human Rights Watch said it was investigating the first torture case to go before the post-revolutionary judicial system in Tunisia.

Former Interior Minister Abdallah Kallel and three other former security officials faced prosecution for "using violence against others" in a 1991 incident involving military officials accused of plotting with Islamist party Ennahdha, now in control of the Tunisian government.

Eric Goldstein, deputy director of Middle East and North Africa programs at Human Rights Watch, said torture was "rampant" under the government of former President Zine el-Abidine Ben Ali. Human Rights Watch said it was investigating the post-revolutionary torture case after an appeals court in April reduced prison sentences for Kallel and his co-defendants.

"Effective prosecution of torture requires an adequate legal framework as well as political will to end impunity," Goldstein said

Human Right Watch said the case shows Tunisian authorities aren't serious about addressing past human rights abuses.

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HRW investigates Tunisian justice system

Okla. top court rejects embryo 'personhood'

The Oklahoma Supreme Court today unanimously struck down a proposed ballot measure that sought to amend the state Constitution to grant "personhood" rights to human embryos, thereby outlawing abortion and many forms of birth control.

The state's high court ruled that Initiative Petition No. 395, which supporters had hoped to put to voters in November, was "clearly unconstitutional" because if violated a 1992 U.S. Supreme Court decision that upheld a woman's right to an abortion, The Oklahoman says.

Here's what the amendment, also known as State Question No. 761, sought to do:

This measure adds a new section to the Oklahoma Constitution to reconcile recent scientific developments with the definition of a human being for the purpose of equal protection under the law. The proposed amendment expands the legal definition of humanity or "personhood" to include every human being, regardless of place of residence, race, gender, age, disability, health, level of function, condition of dependency, or method of reproduction, from the beginning of biological development to the end of natural life. The amendment applies the term "person" under the Oklahoma Constitution equally to every human being so defined and prohibits the intentional killing of any such "person" without due process of law.

Personhood Oklahoma, which initiated the petition, said the organization's attorneys would decide on how to proceed after reading the decision.

Opponents said the measure would ban all abortions, limit a woman's choice of contraception and jeopardize in vitro fertilization.

"In this case, the Oklahoma Constitution said it best: It is not acceptable to propose amendments that are 'repugnant to the Constitution of the United States," said Nancy Northup, the head of the Center for Reproductive Rights.

The court's ruling was the second major blow to the personhood movement in Oklahoma in the past few days. On Thursday, leaders of the state House refused to take up a Senate-passed measure that declared life begins at conception.

Elsewhere, a federal judge in Nevada has blocked a personhood ballot measure from the November ballot, The Hill notes.

Last year, Mississippians rejected such a constitutional change, and Colorado voters have defeated a similar measure twice.

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Okla. top court rejects embryo 'personhood'

The ESHRE PGD Consortium: 10 years of data collection

BACKGROUND

Since it was established in 1997, the ESHRE PGD Consortium has been collecting data from international preimplantation genetic diagnosis (PGD) centres. Ten papers have been published, including data from January 1997 to December 2007.

METHODS

The data collection originally used a hard-copy format, then an excel database and finally a FileMaker Pro database. The indications are divided into five categories: PGD for chromosome abnormalities, sexing for X-linked disease, PGD for single gene defects, preimplantation genetic screening (PGS) and PGD for social sexing. The main end-points are pregnancy outcome and follow-up of deliveries.

RESULTS

In data collection I, 16 centres contributed data, which increased to 57 centres by data X (average of 39 centres per data collection). These centres contributed data on over 27 000 cycles that reached oocyte retrieval. Of these cycles, 61% were for aneuploidy screening, 17% for single gene disorders, 16% for chromosomal abnormalities, 4% for sexing of X-linked disease and 2% for social sexing. Cumulatively, 5187 clinical pregnancies gave rise to 4140 deliveries and 5135 newborns (singletons: 3182, twins: 921, triplets: 37).

CONCLUSIONS

In this paper, we present an overview of the first 10 years of PGD data, highlighting trends. These include the introduction of laser-assisted biopsy, an increase in polar body and trophectoderm biopsy, new strategies, methodologies and technologies for diagnosis, including recently arrays, and the more frequent use of freezing biopsied embryos. The Consortium data reports represent a valuable resource for information about the practice of PGD.

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

Principles of phenomics in endometriosis

BACKGROUND

Endometriosis has been associated with specific morphometric characteristics and pigmentary traits. The purpose of this study was to systematically review prior publications dealing with this aspect in order to revisit phenotypic information in the context of phenomics principles.

METHODS

Comprehensive searches of Pubmed, Medline and Embase were conducted to identify studies, published from 1990 to 2011 in the English language literature, on the relationship between endometriosis and morphometric characteristics/pigmentary traits.

RESULTS

We identified 11 studies on the association between endometriosis and body mass index (BMI) in the adult population and 5 studies on the same association during early life. While a modest inverse correlation was found between endometriosis and adult BMI, a stronger association was consistently demonstrated between endometriosis and early life body size, even after adjusting for confounding factors such as age, birthweight, age at menarche, parity and oral contraceptive use. Four papers have been published on the association between endometriosis and cutaneous naevi and five on the association between the disease and specific pigmentary traits. A skin phenotype characterized by the presence of naevi and freckles and by a high sensitivity to sun exposure is represented more frequently in women with endometriosis.

CONCLUSIONS

Endometriosis appears to be associated with some phenotypic variations likely attributable to the strong effect of the environment on the expression and function of genes influencing the traits. Novel clues on endometriosis pathogenesis may derive from the analysis of the phenotypic traits associated with the disease.

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

Aetiology of hypospadias: a systematic review of genes and environment

BACKGROUND

Hypospadias is a common congenital malformation of the male external genitalia. Most cases have an unknown aetiology, which is probably a mix of monogenic and multifactorial forms, implicating both genes and environmental factors. This review summarizes current knowledge about the aetiology of hypospadias.

METHODS

Pubmed was used to identify studies on hypospadias aetiology published between January 1995 and February 2011. Reference lists of the selected manuscripts were also searched to identify additional studies, including those published before 1995.

RESULTS

The search provided 922 articles and 169 articles were selected for this review. Studies screening groups of patients with hypospadias for single gene defects found mutations in WT1, SF1, BMP4, BMP7, HOXA4, HOXB6, FGF8, FGFR2, AR, HSD3B2, SRD5A2, ATF3, MAMLD1, MID1 and BNC2. However, most investigators are convinced that single mutations do not cause the majority of isolated hypospadias cases. Indeed, associations were found with polymorphisms in FGF8, FGFR2, AR, HSD17B3, SRD5A2, ESR1, ESR2, ATF3, MAMLD1, DGKK, MID1, CYP1A1, GSTM1 and GSTT1. In addition, gene expression studies indentified CTGF, CYR61 and EGF as candidate genes. Environmental factors consistently implicated in hypospadias are low birthweight, maternal hypertension and pre-eclampsia, suggesting that placental insufficiency may play an important role in hypospadias aetiology. Exogenous endocrine-disrupting chemicals have the potential to induce hypospadias but it is unclear whether human exposure is high enough to exert this effect. Other environmental factors have also been associated with hypospadias but, for most, the results are inconsistent.

CONCLUSIONS

Although a number of contributors to the aetiology of hypospadias have been identified, the majority of risk factors remain unknown.

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

Aromatase inhibitors for PCOS: a systematic review and meta-analysis

BACKGROUND

The effectiveness of aromatase inhibitors (AIs) in the treatment of anovulatory polycystic ovary syndrome (PCOS) remains unclear. The objective was to determine whether AIs are effective in improving fertility outcomes in women with PCOS.

METHODS

Databases were searched until July 2011. Inclusion criteria were women with PCOS, who are infertile, receiving any type, dose and frequency of AI compared with placebo, no other treatment or other infertility treatment. Outcomes were rates of: ovulation, pregnancy, live birth, multiple pregnancies, miscarriage and adverse events, as well as quality of life and cost effectiveness. Data were extracted and risk of bias was assessed. A random-effects model was used for the meta-analyses, using odds ratios (ORs) and rate ratios (RRs).

RESULTS

The search returned 4981 articles, 78 articles addressed AIs and 13 randomized controlled trials (RCTs) met the inclusion criteria. No RCTs compared AIs versus placebo or no treatment, in therapy naïve women with PCOS. Meta-analyses of six RCTs comparing letrozole with clompihene citrate (CC) demonstrated that letrozole improved the ovulation rate per patient [OR 2.90 (95% confidence interval (CI) 1.72, 4.88), I2 = 0%, P < 0.0001]; however, there was no statistical difference for the ovulation rate per cycle or the pregnancy, live birth, multiple pregnancy or miscarriage rates. Letrozole also did not improve pregnancy or live birth rates compared with placebo or with CC plus metoformin in women with CC-resistant PCOS. Results of comparisons of letrozole and anastrozole in women with CC-resistant PCOS were conflicting in terms of ovulation and pregnancy rates.

CONCLUSIONS

In the absence of supportive high-quality evidence, AIs should not be recommended as the first-line pharmacological therapy for infertility in women with PCOS, and further research is needed.

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

Occupational exposure to chemical substances and time to pregnancy: a systematic review

BACKGROUND

Fertility problems are an important health issue, as 10–15% of couples have difficulties conceiving. Reproductive function is thought to be compromised by lifestyle behaviours, but environmental contaminants and work-related factors are also thought to play a role. The objective of this review was to systematically summarize the available evidence concerning the influence of occupational exposure to chemicals on time to pregnancy (TTP).

METHODS

A structured search on occupational exposure to chemicals and TTP was carried out in PubMed and Embase. Studies were included if TTP was used as outcome measure and exposure to chemicals at the job level was described. In total, 49 studies were included in this review.

RESULTS

Studies varied widely in characterization of exposure, hampering a meta-analytic approach across all studies. For lead, strong indications for adverse effects on TTP were present, supporting the mandatory provisions for pregnant women being exposed to lead in many countries. These indications were also found for pesticide exposure, and one could argue that couples working in agriculture or horticultural trades must be informed about the risks of pesticide exposure. Epidemiologic evidence on other chemicals, such as organic solvents, and other metals remains equivocal, hampering clear counselling of couples who are trying to become pregnant.

CONCLUSIONS

Despite some uncertainties in the evidence base, it may still be prudent to advise against lead and pesticide exposure at the workplace for couples trying to conceive. This review also identifies several priorities for future studies in the field of occupational epidemiology.

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

Balancing ovulation and anovulation: integration of the reproductive and energy balance axes by neuropeptides

BACKGROUND

Because of the substantial energy demands of reproduction, the brain must temper the fertility of individuals to match nutritional availability. Under-nutrition is associated with infertility in humans and animals. The brain uses adipose- and gut-derived hormones, such as leptin, insulin and ghrelin, to modulate the activity of the GnRH neuronal network that drives reproduction. It is becoming clear that there are both direct and indirect pathways acting on GnRH neurones.

METHODS

A PubMed search was performed using keywords associated with neuropeptides and metabolic hormones that are associated with reproductive and energy balance axes.

RESULTS

Evidence that neurones which produce galanin, galanin-like peptide, kisspeptin, alpha-melanocyte-stimulating hormone, neuropeptide Y and oxytocin convey metabolic information to the reproductive axis is presented. The extent to which these neurones express receptors for metabolic hormones is variable but interactions between them allows for complex intermingling of information. Available metabolic fuels modulate hormone input to these neurones, leading in turn to altered GnRH release and appropriate drive to the gonads. The consequent change in sex steroid production is likely to contribute to co-ordination of the network.

CONCLUSIONS

We hypothesize that the absence of an estrogenic milieu during anovulation compared with presence of estradiol during follicular maturation is important for the regulation of most of the neuropeptides. An improved understanding of the normal responses to energy deprivation may also help to identify novel therapeutic targets for infertility that often accompanies metabolic disorders, such as diabetes, obesity and polycystic ovary syndrome.

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

Involvement of the prostate and testis expression (PATE)-like proteins in sperm-oocyte interaction

BACKGROUND

The prostate and testis expression (PATE)-like family of proteins are expressed mainly in the male genital tract. They are localized in the sperm head and are homologous to SP-10, the acrosomal vesicle protein also named ACRV1. Our aim was to characterize the expression and functional role of three PATE-like proteins in the testis and ejaculated sperm.

METHODS

The expression and localization of PATE-like proteins in human testis biopsies (n= 95) and sperm cells were assessed by RT–PCR, immunohistochemistry and immunofluorescence staining (at least 600 sperm cells per specimen). The function of the PATE protein was tested by the hemizona assay and hamster egg penetration test (HEPT).

RESULTS

PATE and PATE-M genes and proteins were present almost exclusively in germ cells in the testis: immunoflourescence showed that the percentage of germ cells positive for PATE, PATE-M and PATE-B was 85, 50 and 2%, respectively. PATE and PATE-M proteins were localized in the equatorial segment of the sperm head, while PATE-B protein was localized in the post-acrosomal region. A polyclonal antibody (Ab, at 1:50 and 1:200 dilutions) against the PATE protein did not inhibit sperm–zona binding in the hemizona assay (hemizona index of 89.6 ± 10 and 87 ± 36%, respectively). However, there was inhibition of sperm–oolemma fusion and penetration in the HEPT (penetration index: without Ab 7 ± 3.9; Ab dilution of 1:100, 4 ± 3.5; Ab dilution of 1:20, 0.6 ± 1.2, P < 0.001).

CONCLUSIONS

Our data suggest that PATE protein is involved in sperm–oolemma fusion and penetration but not sperm–zona binding.

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

Is there an optimal pH for culture media used in clinical IVF?

BACKGROUND

Reducing environmental stress imposed upon gametes and embryos in the IVF laboratory is crucial in optimizing culture conditions and development. One environmental parameter of particular importance is external pH (pHe) of culture media. An optimal pHe has not been identified.

METHODS

Electronic searches were performed using keywords focused on pH and the embryo using PUBMED through August 2011, with no limits placed on a beginning time. Examples of keywords include CO2, bicarbonate and hydrogen ion. Relevant papers were then examined to obtain additional publications.

RESULTS

Determining optimal pHe is problematic due to difficulty in isolating pHe from other variables, such as CO2 and bicarbonate. Various commercial media companies recommend differing pHe ranges, most within the range of 7.2–7.4, with some companies recommending altering pHe based on the gamete or stage of the embryo. However, changing pHe during culture has not been experimentally shown to improve outcomes. Further complicating attempts to define an optimal pHe is that media components can impact intracellular pH (pHi). As a result, media with different concentrations of substances, such as lactate or amino acids, may have different pHi, despite being in the same pHe.

CONCLUSIONS

Due to the plasticity of embryos, a range of pHe's can support development, and defining an optimal pHe is difficult. It is unclear whether there is any benefit in changing pHe at various steps during IVF. The ideal pHe will likely vary from media to media and, until comparative studies have been performed isolating pHe, adherence to manufacturer recommendations and maintenance of a small acceptable pHe range are advisable.

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

Oocyte cryopreservation for age-related fertility loss

The recent introduction of oocyte vitrification has significantly advanced the outcome of oocyte cryopreservation, leading to clinical results comparable to those achieved in IVF using fresh oocytes, as reported by experienced centres. This has lead to new debate, both in the professional community and in society at large, about the acceptability of offering this technology to reproductively healthy women who want to cryopreserve their oocytes against the threat of time. Given the many demands calling for simultaneous realization in a relatively short period of their lives, many women who want to have children feel to be under considerable pressure. The option of oocyte cryopreservation may in fact give them more breathing space. In this document, it is concluded that the arguments against allowing this application of the technology are not convincing. The recommendations include the need for adequate information of women interested in oocyte cryopreservation, also in order to avoid raising false hopes. The message must remain that women's best chances of having a healthy child are through natural reproduction at a relative early age. Centres offering this service must have the necessary expertise to employ oocyte cryopreservation efficiently with the so far non-standardized protocols. As data about long-term safety is still lacking, centres also have a responsibility to contribute to the collection of these data.

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