Hormone-Replacement Therapy: Could Estrogen Have Saved 50,000 Lives?

2013-07-22

By Alexandra Sifferlin @acsifferlin

For more than a decade, doctors have cautioned women about the risks associated with hormone-replacement therapy. But those warnings may have put one group of women at increased risk of dying early, according to the latest study.

Researchers at Yale University say nearly 50,000 women may have died prematurely after they stopped taking hormone-replacement therapy (HRT) to treat menopause symptoms, following a much publicized 2002 study that revealed the treatment increased risk of heart disease and breast cancer.

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What to Drink While Expecting: Study Says Moderate Booze OK

2013-06-20

By Alexandra Sifferlin

Alcohol isn’t generally the first drink that moms-to-be reach for, but if they do, they may not be doing as much harm to their children as previously thought.

According to a British study, children born to mothers who drank moderately while pregnant did not show signs of balance problems when they were 10; trouble with balance is a good indicator of problems with brain development in utero, the authors say.

The researchers, who published their results in the journal BMJ Open, studied nearly 7,000 ten-year-olds enrolled in the Avon Longitudinal Study of Parents and Children who were born between 1991 and 1992. The children were given three different balance tests, including walking on a balance beam and standing still on one leg with their eyes closed. Those whose mothers reported drinking three to seven alcoholic beverages a week during their 18th week of pregnancy were more likely to fall into the top 25% of performers on the balance exercises compared to those whose moms abstained.

These findings support those of a previous study out of Denmark that reported light to moderate drinking early in pregnancy was not associated with declines in intelligence, attention or self-control in children at age 5. But this study did caution that heavy drinking was linked to negative developmental effects.

Despite the fact that better balance is an indicator of healthy brain development in the womb, the current results don’t necessarily mean that it’s time to rethink the advice that pregnant women shouldn’t drink. Research has shown that drinking can cause physical deformities as well as behavioral and cognitive symptoms in babies, including fetal alcohol syndrome. The scientists in the UK study accounted for other factors that might explain the results of the balance test, including the mothers’ age, smoking and previous pregnancies, and they found that the moderate drinkers tended to have more education and more comfortable socioeconomic backgrounds. These environmental effects, they say, could explain the improved balance results among their children as the youngsters may have benefited from more education, physical activity training and other opportunities that made up for any potential cognitive deficits caused by the alcohol.

The researchers also say that the majority of the mothers in the study (70%) did not drink at all while expecting and only about 25% drank rarely to moderately. About 5% drank seven or more alcoholic beverages a week, and one in seven of these women regularly consumed four or more drinks in one sitting, which the scientists considered binge drinking.

Adding to the possibility that the children’s education and socioeconomic status were compensating for any potential harms from the alcohol, the scientists also studied women who possessed genes that prevented them enjoying alcohol as much. If alcohol had a positive effect on brain development and enhanced balance, these children would be expected to do worse on balance tests, but they performed as well as the other youngsters.

The study doesn’t suggest whether there is a safe level of alcohol consumption for pregnant women, so most experts say the current recommendation that moms-to-be avoid alcohol while expecting is still good advice; there’s no evidence yet that wine is good for the womb.

Timeline: The Battle For Plan B

2013-06-12

By Alexandra Sifferlin

On Monday, the Obama administration announced it is ending its fight to keep age restrictions on the morning-after pill. The Department of Justice will no longer appeal the ruling by Judge Edward Korman of the District Court of Eastern New York that overturned Health and Human Services (HHS) Secretary Kathleen Sebelius’ decision to keep the age limit of 17 on obtaining Plan B without a prescription.

Instead, it plans to move forward on making the morning-after pill available to girls of all ages, over-the-counter and without a prescription.

For over a decade, reproductive rights advocates, politicians, the FDA, and Plan B manufacturers have clashed in a back and forth of regulation and restriction with advocates for the pill pushing for the greater availability and opponents arguing for limiting access for girls considered by some to be too young to understand the risks.

Here is a timeline of the key legal moments in the battle to get Plan B over-the-counter:

1999: The FDA approves Teva Pharmaceutical Industries Ltd to market the emergency contraceptive drug levonorgestrel as Plan B, and offer it as a prescription-only drug. At the time, Plan B was two tablets. The first tablet was taken within 72 hours of unprotected sex and another was taken 12 hours later.

2001: The Center for Reproductive Rights and over 70 other public-health groups file a citizen petition to make Plan B available over-the-counter and without a prescription.

2003: Teva files an FDA application to make the drug available over-the-counter. This spurred political conflict over wether the drug should be easily accessible to minors.

2005: The Center for Reproductive Rights files a lawsuit in Brooklyn federal court to force the FDA to respond to their petition. They argue the FDA is holding Plan B to stricter standards compared to other drugs and not embracing evidence.

2006: The FDA denies the Center for Reproductive Rights’ citizen petition. But a few months later, the federal agency gives the OK for  Plan B to be sold without a prescription to women ages 18 years and older. Minors still need a prescription.

2009: U.S. District Judge Edward Korman in Brooklyn rules that FDA acted without good faith in denying the petition, and orders morning-after drugs to be made available to women 17 and older. Korman says the FDA should think about lowering the age and access restrictions.

The FDA also approves Plan B One-Step, which allows women to take only one pill instead of two pills.

August 28, 2009: The FDA approves Next Choice, a generic version of Plan B. Next Choice is also available over-the-counter for women ages 17 and older and with a prescription for anyone younger.

February 2011: Teva files an application with the FDA to move Plan B from “dual label” status–which requires it to be sold under over-the-counter and prescription-drug regulations– to a full over-the-counter status without age limits. This would make the drug easier to buy off the shelves, like condoms and other medications. The FDA has until Dec. 7 to make a decision.

December 7, 2011: After reviewing Teva’s application and available research, the FDA‘s Center for Drug Evaluation and Research (CDER) determined the drug was safe and effective for girls of all ages, and concluded that adolescents were capable of using and understanding the risks of Plan B without their doctor’s aid. In a statement, FDA commissioner Margaret Hamburg says there is adequate evidence that the morning-after pill is for “all females of child-bearing potential.”

But, the FDA ultimately rejects Teva’s application after receiving a memorandum from Sebelius that overruled the recommendation, saying TEVA failed to provide research showing that young girls could use the drug safely. President Obama, backed up Sebelius’ decision, saying, “As I understand it, the reason Kathleen made this decision was she could not be confident that a 10-year-old or an 11-year-old going into a drugstore should be able — alongside bubble gum or batteries — be able to buy a medication that potentially, if not used properly, could end up having an adverse effect.  And I think most parents would probably feel the same way,” according to the New York Times.

December 12, 2011: The FDA dismisses the Center for Reproductive Rights’ citizen petition again [PDF], stating that there is still not enough research on whether users comprehend labeling and usage for the two-dose Plan B version.

February 2012: The Center for Reproductive Rights re-opens their lawsuit against the FDA for its restrictions against morning-after drugs. This time, they also add Sebelius as a defendant for her overruling on the FDA’s decision to make Plan B available over-the-counter in 2011.

April 5, 2013: Judge Korman overturns Sebelius’ decision to have age limits for getting Plan B without a prescription. Korman says the ruling was made in “bad faith and improper political influence.” Writing in his decision he states that, “it is hardly clear that the Secretary had the power to issue the order, and if she did have that authority, her decision was arbitrary, capricious, and unreasonable.”

April 30, 2013: FDA announces that the Plan B morning-after pill will move out from behind the counter and be available for girls ages 15 and older without a prescription. The FDA says the new approval was independent of Judge Korman’s April 5 order, and was for an already pending application from Teva that requested its product be made available over-the-counter for women aged 15 or older. A spokesperson for the HHS told TIME that Commissioner Hamburg briefed Sebelius about the review process and the amended Teva application, and Sebelius felt the new decision met her concerns.

May 1, 2013: The Obama administration announces it is appealing Koman’s order to lift all age limits on buying Plan B without a prescription.

June 5, 2013: The 2nd U.S. Circuit Court of Appeals in Manhattan permits girls of all ages to purchase generic versions of morning-after drugs without a prescription.

June 10, 2013: The Department of Justice announces it will no longer seek an appeal. The federal group alerted Judge Korman that it plans to submit a compliance plan and if the judge he approves it, the Department of Justice will drop its appeal.

Frontiers of Fertility

2013-06-10

By Jeffrey Kluger and Alice Park

Making babies ought to be the easiest thing you’ll ever do—indeed, it ought to be a hard thing not to do. The evolutionary game is rigged so that it’s fun, the kind of fun you want to have even when offspring aren’t on your mind. Our body cycles make parenthood a constant possibility: women are ready to conceive every month, and men are pretty much ready to go any second. And the product of all that happy activity—a chubby, cuddly, cooing baby—is something we’re hardwired to find irresistible.

But things, of course, aren’t always so simple. The human reproductive system may be a prolific thing, but it’s also a very fragile thing, and there is a lot that can go wrong with it. In the U.S. alone, more than 7 million women have received treatment for infertility, spending more than an estimated $5 billion per year. For the past 10 years, the average billed cost for a single in vitro fertilization (IVF) cycle is $12,400—something infertile couples must pony up on their own since most insurance companies don’t cover infertility treatments—and just one cycle is usually not enough. According to the U.S. Centers for Disease Control and Prevention, only 42% of assisted-reproduction cycles lead to a live birth when the woman is younger than 35. The figure drops to 22% by age 40, 12% by 42 and just 5% by 44. Outside the U.S., the odds are no better, and the number of people who need help is far greater: an estimated 48.5 million couples worldwide are unable to conceive after five years of trying, according to figures released last year by the World Health Organization.

Given the powerful, primal hold baby-making has on us, the inability to perform so straightforward a genetic job can be deeply painful. “My husband and I would look around, and everyone we knew was having kids,” says Cindy Flynn, 35, an IT worker at a Sacramento nonprofit. “We struggled so hard to get pregnant. Building a family should not be so difficult.”

For now, it still is, but the outlook is getting decidedly brighter. Scientists are steadily refining and improving assisted-reproduction techniques. They’re harvesting better eggs, using fewer drugs to do it and selecting more vigorous sperm that have a better chance of producing a baby. They’re monitoring embryos while they’re still in the lab in ways that were impossible before. Perhaps most tantalizing, they are working to engineer human stem cells so that eggs and sperm can be produced in the lab using raw cellular material taken from the parents. This would lead to a baby that was entirely, genetically theirs, the product of an ordinary union of egg and sperm—nothing short of a last-ditch miracle for people who, without this help, might have been unable to produce any healthy egg or sperm at all.

“Twenty years ago I would often tell a patient, ‘I am sorry. There is nothing we can do,’” says Dr. Craig Niederberger, head of the department of urology at the University of Illinois at Chicago College of Medicine. “Fifteen years ago I would have been saying, ‘There is something I can do, but it’s very experimental.’ Today I can often say, ‘There is at least a 2-out-of-3 chance you are going to have a baby out of this process.’ It is becoming the most exciting field, with the most gratifying outcomes you can imagine.”

Boosting the Odds
Improving the outlook for fertility patients starts with improving the art of IVF, which is not just expensive and less than reliable but a true physical grind. Women must first endure a month’s worth of hormonal dosings, including two or three shots a day in the final stretch, all of which can lead to headaches, restlessness, irritability and hot flushing. The dosing pushes the ovaries to hyperovulate, producing up to a dozen ova at once, which are retrieved via laparoscope through an incision in the pelvis. Even after all that, there’s no guarantee the eggs will be viable; many immature ones that the ovaries would never have released on their own are shoved out prematurely by the drugs.

“Every time a patient goes through conventional IVF, the number of eggs designated as waste is about 90%,” says Dr. John Zhang, founder and director of the New Hope Fertility Center in New York City.

What does your birthday have to do with immune disorders?

2013-04-16

By Alexandra Sifferlin, TIME.com

The month in which babies are born can affect how their immune systems develop, and even how vulnerable they are to autoimmune diseases.

Scientists studying the neurological disorder multiple sclerosis, in which the body’s own immune cells destroy the protective coating around nerves and can lead to paralysis and loss of other functions, have long been puzzled by the “birth month effect.” Many patients with MS are born in the spring, and rates of the disease are lowest for those born in November.

Some have speculated that insufficient levels of vitamin D, which the skin produces when exposed to sunlight, on the mom’s part could play a role, since babies born in May are gestated during the colder, darker months, while winter babies are in utero during the spring and summer.

Now a study published in JAMA Neurology shows that this hunch may be correct, and suggests a mechanism for how the vitamin might be driving immune system development.

Researchers in the UK studied 50 babies born in London in May and 50 babies born in November between 2009 and 2010. They sampled blood from the newborns’ umbilical chords and recorded levels of vitamin D and a specific type of immune cell known as autoreactive T-cells.

T-cells are the white blood cells that battle pathogens like bacteria and viruses, but autoreactive T-cells are aberrant versions that mistake the body’s own cells as foreign and attack them as they would an unwanted infection.

The researchers found that babies born in May had vitamin D levels that were 20% lower than those in babies born in November, and almost double the amount of autoreactive T-cells. They speculate that vitamin D may be important in some way in educating T cells about how to recognize self cells; this occurs in the thymus, and errors in the training could lead to higher levels of the destructive T cells.

The connection between vitamin D and immune disorders first emerged from population studies that showed people who lived further away from the equator, in places with less sunlight, were at higher risk of developing MS. But the researchers caution that their results still don’t suggest that lower levels of the vitamin cause autoimmune disorders like MS.

So it’s not clear yet whether supplements of vitamin D could help to lower rates of the disease — especially for those conceived in July and born in May. In fact, experts continue to debate how much vitamin D is appropriate for otherwise healthy people when it comes to preventing disease, since studies on the subject are conflicting. The Institute of Medicine currently recommends that adults get about 600 IU daily.

More research is needed to figure out whether pregnant women might need to take more vitamin D in order to strengthen their babies’ immune systems, but doctors now have a better understanding of what birth months have to do with how the immune system develops.

This article was originally published on TIME.com

Hope for Infertility Treatments: Scientists Make New Eggs from Mouse Stem Cells

2012-10-10

Japanese researchers have produced mouse eggs from stem cells that bred healthy offspring, a breakthrough that may one day help treat human infertility.

Researcher Mitinori Saitou and his team from Kyoto University in Japan used two different types of stem cells during their research: embryonic stem cells — a controversial technique since scientists must destroy embryos to cultivate them — and induced pluripotent stem (iPS) cells, which are adult cells, such as skin cells, that are reprogrammed to an embryonic-like state. Producing healthy eggs from iPS cells is potentially even more exciting than using embryonic stem cells, since iPS cells sidestep the ethical issues that plague those derived from embryos and because the resulting eggs would contain the same DNA as their donors.

Stem cell experts greeted the work with praise. “They’ve gotten to what was our Holy Grail, which is making eggs,” George Daley, a leading stem-cell scientist at Harvard, told NPR. “It’s like cellular alchemy. I mean, they can turn lead into gold here. They can turn skin cells or blood cells into eggs.”

(MORE: Ovary Stem Cells Can Produce New Human Eggs, Scientists Say)

In previous efforts, scientists — including the current group — have been able to create sperm and egg cells in the lab, but they weren’t able to produce healthy offspring from those cells. In the current study, published in the journal Science, the researchers first added growth factors and proteins to the stem cells to turn them into primordial germ cells. These cells were then combined with somatic cells from mouse ovaries to make “reconstituted ovaries,” which they transplanted into the mice. Four weeks later, the scientists removed them again, isolated immature egg cells from the ovaries and allowed them to mature in a dish. The mature eggs were fertilized with mouse sperm in a test tube and the resulting embryos were transferred into female mice, leading to the birth of healthy, fertile pups that went on to reproduce themselves.

It’s not at all clear whether the procedure would work similarly in humans, but the researchers if it does, it could revolutionize treatment for infertile couples and for older women who want children. “Now is the time for society to think about this,” Amander Clark, a stem cell scientist at UCLA, told the Los Angeles Times. “If we want to use stem cells to treat women who are older, we have to decide what the parameters are. Should this be available for women who are 40 to 50 years old? How about 50 and above? These shouldn’t be questions for scientists to decide alone.”

Indeed, such an advance would lead to a thicket of ethical questions: would you allow the use of tissues from a dead person to create new life, for example?

(MORE: Scientists Restore Fertility in Mice Using Lab-Generated Sperm)

The researchers said the lab-created egg cells led to healthy pups less frequently than did natural mouse eggs, which were also fertilized and transferred to female mice in a control group. Mice impregnated with embryos created via in-vitro fertilization with natural eggs produced healthy offspring 13% of the time, compared with 3.9% for eggs created from embryonic stem cells and 1.8% for eggs made using iPS cells.

Nevertheless, the advance sheds light on how precursor cells eventually develop into sperm or egg cells, a scientific understanding that could in itself aid infertility treatments. That’s encouraging for the many women who struggle with fertility: according to the U.S. Centers for Disease Control and Prevention, about 10% of America women have problems getting pregnant or staying pregnant.

Infertility Too Much Coffee Could Hurt Women’s Chances of IVF Success

2012-07-05

Women who drank five or more cups of coffee a day were about 50% less likely to get pregnant through in-vitro fertilization (IVF) than non-drinkers, according to a recent Danish study.

“Although we were not surprised that coffee consumption appears to affect pregnancy rates in IVF, we were surprised at the magnitude of the effect,” said lead researcher Dr. Ulrik Schiøler Kesmodel of the Fertility Clinic of Aarhus University Hospital, in Denmark, in a statement.

For the study, presented at the annual meeting of the European Society of Human Reproduction and Embryology in Istanbul, Kesmodel and his colleagues followed nearly 4,000 women receiving IVF or intracytoplasmic sperm injection (ICSI) treatments in a large Danish fertility clinic. The women reported their coffee consumption at the start of treatment and at the start of each cycle. The researchers controlled for a variety of factors: the women’s age, smoking and alcohol consumption, the cause of their infertility, weight, ovarian stimulation and number of retrieved embryos.

Their findings showed that the relative chances of pregnancy were cut in half for women who drank more than five cups of coffee per day — “comparable to the detrimental effect of smoking” the authors noted — but there was no effect in women who drank less coffee.

(MORE: Coffee: Drink More Live Longer?)

“There is limited evidence about coffee in the literature, so we would not wish to worry IVF patients unnecessarily,” said Kesmodel in a statement. ”But it does seem reasonable, based on our results and the evidence we have about coffee consumption during pregnancy, that women should not drink more than five cups of coffee a day when having IVF.”

The assumption is that it’s the caffeine in coffee that may interfere with IVF success, but as Kesmodel told the BBC, there are so many substances in coffee, it’s hard to know for sure. However, researchers have long sought to understand whether caffeine affects fertility, and previous studies have found mixed results. Some data suggest that coffee drinkers are more likely to miscarry, while others have found the opposite. Some studies have also linked high caffeine consumption with lower odds of pregnancy, low birthweight and preterm birth, but a 2009 Cochrane review of gold-standard trials couldn’t confirm any benefits of avoiding caffeine during pregnancy.

Women who enjoy a cup-o-joe in the morning shouldn’t fret. “The fact that we found no harmful effects of coffee at lower levels of intake is well in line with previous studies on time-to-pregnancy and miscarriage, which also suggest that, if coffee does have a clinically relevant effect, it is likely to be upwards from a level of four-to-six cups a day,” said Dr. Kesmodel.