Monthly Archives: February 2009

Study Examines Genetic Factors Associated With Spontaneous Pre-Term Births Among African-Americans

Pre-term births are a leading cause of neonatal morbidity and mortality in the U.S., where they occur in about 12% to 13% of all pregnancies and about 17% to 18% of pregnancies among African-American women. Family history is a known risk factor of pre-term birth, suggesting that genetics might affect the likelihood of pre-term birth. The disparity in pre-term birth rates between African-American and white women also suggests that genetic variants contribute to pre-term birth susceptibility. However, it is highly unlikely that a single gene mutation causes this complex event, according to the researchers. The study attempts to further understanding of the genetic predisposition for pre-term birth and investigate the high rate among African-American women through a large-scale gene association analysis focusing on an African-American population.

Methods

Digna Velez of the Miami Institute of Human Genomics and the Department of Human Genetics at the University of Miami and colleagues analyzed maternal and fetal DNA from birth events among African-American women ages 18 to 40, who were recruited between September 2003 and December 2006 at Centennial Medical Center in Nashville, Tenn. The study included 76 African-American women who experienced pre-term birth with no rupture of membranes and 191 African-American women in the control group, as well as 65 fetal cases and 183 fetal controls. Pre-term birth was defined as having two contractions per 10 minutes followed by delivery at less than 36 weeks’ gestation, and controls were identified by normal labor and delivery after at least 37 weeks’ gestation. The researchers used questionnaires and medical records to obtain demographic and clinical data about the women, and also performed single locus association and haplotype analyses on 1,432 single nucleotide polymorphisms from 130 candidate genes to identify genetic factors associated with spontaneous pre-term birth.

Results

The researchers observed significant differences between cases and controls for gestational age, birthweight, one-minute Apgar scores and five-minute Apgar scores. There were no differences between cases and controls for other demographic factors, including socioeconomic measures. In addition, the researchers identified 96 single nucleotide polymorphisms with statistically significant associations for either allelic or genotypic tests among maternal samples and 126 among fetal samples. They found the most significant associations in the maternal interleukin (IL)-15 and the fetal IL-2 receptor. Overall, fetal samples had more significant allelic associations with pre-term birth than did maternal samples. The researchers also determined that the largest number of significant associations with pre-term birth occurred in genes related to infection and inflammation.

Discussion

The data collected in the study indicate that “no single gene” accounts for pre-term birth, “but rather locus heterogeneity appears to exist for multiple genes from this pathway.” In addition, the “unexpectedly large number of associations” found between fetal genotypes and pre-term birth suggests “that the fetal genetic contribution to pre-term birth exceeds the maternal contribution” among African-Americans, the researchers write. They continue that the study’s finding that infection- and inflammation-related pathways have the most significant association with pre-term birth among African-American women is “very promising,” particularly because it is “consistent with documented elevated rates of infection” among African-American women. The researchers recommend further study on this topic to determine whether the type of infection is an important factor.

Source: American Journal of Obstetrics and Gynecology, February 2009.

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Travel Allowances Trimmed

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Welcome To India

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Your Menstrual Cycle And Insulin : Watch For Changes

A woman’s monthly hormone cycle can change the amount of insulin she needs. Don’t be surprised — or caught without as much medicine as your body requires.

Many women find they need more insulin in the days just before they start to menstruate, and that their insulin needs go back to normal when their periods begin. This ebb and flow is completely normal. Estrogen levels rise just before a woman’s period begins, and estrogen increases insulin needs. That doesn’t mean you can simply boost your dose a set amount. Everyone is different. Your menstrual cycle might have a tremendous effect on your glucose levels or it might have none at all. The fluctuation tends to be most dramatic in young women, for example.

Women should be encouraged to use available self-monitoring technology to identify possible cyclical variations in blood glucose that might require clinician review and insulin dosage adjustments. The menstrual cycle can be challenging for most women, but particularly to women with diabetes, and this is because the hormonal fluctuations that occur during the menstrual cycle do affect blood sugar levels.

What is typically see in clinical practice is that the week before a woman starts to menstruate, these hormonal changes increase what we call ‘insulin resistance,’ and so, the insulin that either the woman makes or that she takes by injection doesn’t work quite as well. Then, when menstruation begins, the blood sugar levels tend to drop a little bit.

So, there are a variety of strategies that women can use to improve blood glucose control during the pre-menstrual period. If a woman is not taking insulin, she could try a greater emphasis on diet to control blood glucose levels or even more exercise, which also can relieve some other pre-menstrual symptoms. If a woman is on insulin,  she can take a little bit more of the basal, or background insulin during that pre-menstrual week, to help control blood glucose levels. And, of course, if a woman wants to change her therapy, she should consult her primary care provider or her diabetes care provider and present the pattern of symptoms and of blood sugar levels that she’s experiencing that are related to her menstrual cycle.

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Reproducing Makes You Famous

People like Nadya Suleman, the IVF junkie mother of 14, and Alfie Patten,picture-11the 13-year-old father from England, are getting famous just for reproducing. It’s a pretty gross trend. Probably the most troubling thing of all is how greedily we’ve slopped all this stuff up. But after making celebrity baby covers the biggest sellers for the likes of Us, People and OK!, we get the freakshow news we deserve. Still hungry for more and more babies, we’ve turned to the circus disaster that is regular lives made alien and shocking when bad choices mixed with a few bits of bad luck and stories were born. Maybe it comes from exhaustion with all the other media. First it was scripted television shows, and then their high-concept reality descendants. And now we’ve sifted through every last layer of story until we’ve gone and found a low, universal denominator. People come out of other people’s vaginas sometimes. The more that come out of the same one or the younger the owners of the necessary body parts are, the more we’re interested. 220 channels and nothing else was on, so we’ve settled on the baby zoo currently on display on TLC or sitting in a dimly-lit room across from Ann Curry. While Suleman’s desire to go and get herself knocked up with octuplets when she was already a cash-strapped mother of six probably had far more to do with some murky and deep-seated emotional cataclysms than it did with a desire for fame, the end result has been a raft of high profile TV appearances, implied hopes for a reality series, and a website asking fans or followers or whomever to donate money to this Elephantitis-suffering family. Ms. Suleman has become a rickety celebrity simply by making the wreckless decision to bring many children into this world for whom she had no way of caring. Good for us! Little Mister Patten may not have been courting fame when he got his young girlfriend pregnant, but now he’s likely being paid exclusivity fees by the Sun. And, in the wake of the media frenzy surrounding the unsettling story, two more boyspicture-2 have come forward, claiming paternity of 15-year-old Chantelle Steadman’s daughter. There are posed photos of the two boys, aged 14 and 16, on Splash, the photo agency where I find many of the silly celebrity pictures I use for Open Caption. It had become fairly routine for celebrities to profit off the act of procreation, what with the big glossy magazine industry and whatnot. But now common folks are saying “me too!” and the troubling thing is, if you don’t already have a certain degree of popularity, you have to make your babymaking pretty sensational to get any attention. And what’s sensational is often ugly. Again these folks probably didn’t enter into reproduction with designs on tabloid notoriety, but once the first publicist calls or newspaper camera flashes… Well, the Siren call is tough to resist. Though humanity has its limits, and the public outcry against Nadya Suleman—and the sad revulsion expressed over the Patten thing—suggests that maybe there is a limit to this mayhem. But we don’t suspect it will die down quickly. Prepare yourselves for other strange stories, for other curious and unpleasant parlor tricks of the body. After all, while everything’s being torn down around it, Coney Island still has its sideshow.

-Richard @ gawker.com

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Ethical Issues Related to Birth of IVF Octuplets : Not a Cause for Celebration, Doctors Warn

 

Two newspapers recently published two opinion pieces examining the ethical issues surrounding the recent birth of octuplets to a California woman, Nadya Suleman, who reportedly underwent fertility treatments. Summaries appear below.

 


~ Arthur Caplan, Philadelphia Inquirer: “Something has gone terribly wrong when a 33-year-old single woman — who has no home of her own, no job and a mother who worries her daughter is ‘obsessed’ with having children — winds up with 14 of them,” Caplan, director of the University of Pennsylvania Center for Bioethics, writes in an opinion piece. “Examining what exactly went wrong may shed some light on what ought to be done,” Caplan says, adding, “If doctors cannot prevent such shambles from recurring, then society must.” Caplan reports that Suleman became pregnant with all of her 14 children through in vitro fertilization. He writes that the “most obvious questions raised by this sad saga include: How did Nadya Suleman become a fertility patient? And how did she get eight embryos implanted when she already had six young children to care for in a tiny house, with no partner and no income?” Although “[s]ome fertility doctors would answer that it’s not their job to decide how many children a person can have,” Caplan writes that the “idea that doctors should not set limits on who can use reproductive technology to make babies is ethically bonkers.” He continues, “Society needs to discourage mega-multiple births. And it is clear what needs to be done to accomplish that.” Government “needs to get involved,” Caplan says, concluding, “Other nations, such as Britain, keep a regulatory eye on reproductive technologies and those who wish to use them, knowing their use can put kids at risk in ways that nature never envisioned. We owe the same to children born here” (Caplan, Philadelphia Inquirer, 2/6).



~ Ellen Goodman, Miami Herald:  The medical team that delivered the octuplets “expected kudos and high fives,” but “instead of smiles, they saw jaws drop,” syndicated columnist Goodman writes. She continues, “Attention turned from the doctors to the mom, from her courage to her judgment, from the medical success of this delivery team to the ethical failures of fertility treatment.” Questions about whether anyone has “a right to tell anyone else how many kids to have” and whether only women with husbands or certain income levels should have children are “questions that make us feel queasy when we are talking about old-fashioned families,” Goodman writes. She adds, “But they take on a new flavor in the unregulated wild west of fertility technology.” According to Goodman, the “heart of this case” is that “it turns out there are no laws in this country limiting the number of embryos that can be implanted in one womb.” She adds that it is “against all guidelines to implant more than one or two embryos in a woman under 35. Given our experience with the extraordinary high risk of multiple pregnancies for mothers and babies, those who endanger patients ought to lose their licenses.” Goodman also writes that the infants will need “at least $1 million in neonatal care and more if they have the typical range of disabilities for premature babies.” A “reproductive business that generates so much controversy has produced a remarkable consensus,” she says, concluding, “Infertility treatment for an unemployed, single mother of six? Eight embryos in one womb? There must be a proper word in the medical literature to describe this achievement. I think the word is ‘nuts'” (Goodman, Miami Herald, 2/6).

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First the Biopsy, then The Baby

picture-42picture-32A common medical procedure may be the key to helping couples who’ve had no luck with artificial insemination and IVF. Could a common uterine biopsy make pregnancy “stick” for women having trouble conceiving? A small but growing number of couples are embracing an unusual use of biopsies during infertility treatments in the belief that they may help increase the chances of a successful pregnancy. In a handful of small studies, biopsies of the endometrium, the lining of the uterus, which are usually performed as a diagnostic tool to sample tissue and test for infections, disease or other problems, have been found to boost the pregnancy rates of women who had tried in-vitro fertilization and failed to become pregnant. One Toronto couple credits the procedure with the first successful pregnancy in 10 years of trying. After 11 artificial inseminations and two IVFs proved fruitless, Roslyn and Howard Kaman had experienced the gamut of failure, from miscarriages to ectopic pregnancies. They had opted to try adoption when they read an article about a lecture at Toronto’s Weizmann Science Canada by an Israeli researcher, Nava Dekel. In 2003, Dr. Dekel found that 45 women who had undergone a uterine biopsy during the menstrual cycle before undergoing IVF had almost twice the rate of pregnancies and births compared with a control group of 89 women. In 27.7 per cent of the women in the biopsy group, the embryo transfer was successful. The IVF worked for just 14.2 per cent of the control group. The Kamans wrote to Dr. Dekel, and she connected them with the fertility clinic in Israel that had performed the procedures. Doctors there sent the couple a detailed protocol, which involved three separate biopsies on particular days in the cycle just before an IVF treatment. The Kamans’ Toronto fertility specialist, Fay Weisberg, agreed to try it. Ms. Kaman became pregnant on the first IVF cycle after the procedure and baby Hannah is now three months old. “I still can’t believe it. I think I will go through my whole life and not believe we were successful,” says Ms. Kaman, 41. While broader research is being conducted to confirm the role these biopsies may be playing, anecdotal evidence is starting to mount suggesting that the disruption of the uterus somehow leads to the successful implantation of an embryo. Some practitioners say they’ll wait for randomized trial results before they start offering biopsies to IVF patients. Togas Tulandi, a McGill University medical researcher, is hoping to figure out what role the biopsies might play, if any, in the successful pregnancies of women like Ms. Kaman. He is in the midst of conducting a large randomized study (he hasn’t yet reached his goal of 162 participants) and says that if the biopsies are working, the mechanism may be akin to tilling the soil before you plant a tulip bulb. “Maybe this slight injury to the endometrium makes the environment for implantation better,” he says. “If we can prove that it works, we can do it routinely.” Since the procedure carries little risk, other than discomfort and a very small chance of infection or injury to the uterus, many fertility doctors are already incorporating it into their practices. While it is not listed on her menu of services at the First Steps Fertility clinic where she is medical partner, Dr. Weisberg says she now offers it to most of her patients who have failed to conceive with IVF and for most patients before they undergo a frozen embryo transfer. “I suspect that it will probably soon be a routine for all patients undergoing IVF.” The only reason it’s not routine is a paucity of large studies and the fact that it’s painful and uncomfortable for most women, she says. Although she can’t unequivocally say whether the biopsies are effective – “the women end up being their own control” – Dr. Weisberg has a hunch that they work. It could have something to do with increased blood flow, or the way in which the proteins in the uterus heal, she says. “I do believe something changes deep down.” And she’s not worried about a stampede for the procedure on the part of desperate couples. “Not to be cavalier, but this is a procedure already being done on younger women for bleeding of the uterus and other problems,” she says. “It’s easy, quick, but painful. There’s no anesthetic. You can go right back to work.” Other specialists take a more cautious approach. Fertility expert Arthur Leader does not offer it to patients at the Ottawa Fertility Centre where he practises. Until a randomized study such as Dr. Tulandi’s can prove that women undergoing these biopsies have a better chance of getting and staying pregnant, “the precautionary principle should apply,” he says. “You shouldn’t do it until a benefit has been shown.” He points out that there have been many other treatments, including low-dose Aspirin, a blood protein called albumin and a diabetes drug called metformin, that were believed to help women conceive and were routinely prescribed but which, after much study, proved either to do harm or have no effect. And, as far as Dr. Leader is concerned, “No good is harm.” For couples who end up with a healthy pregnancy after uterine biopsies, it’s hard not to credit the procedure for their little bundles of joy. Still, Ms. Kaman says that even though she suspects the treatment did work, there may have been some luck involved. When she imagines trying for a second IVF baby, “part of me thinks lightning’s not going to strike twice with us.” Anatomy of a biopsy An endometrial biopsy is performed by inserting a suction catheter through the vagina and cervix, into the uterus. The end is pressed up against the uterine wall where it cuts away a small sample of the lining tissue. Because of any number of factors, an embryo may not be able to attach itself to the cells that make up the lining of the uterus. After the biopsy is taken, some researchers and fertility experts believe that the slight damage caused to the wall of the uterus makes it a better environment for implantation, whether because of increased blood flow, the healing process or some other factor.

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