Considering prenatal diagnosis once pregnancy is achieved is an important and complex decision. Although there are a wide variety of screening options available, prenatal diagnosis is the most accurate method for detecting chromosome abnormalities, such as Down syndrome. Diseases like cystic fibrosis, Tay-Sachs, sickle cell anemia, and thalassemias can be tested for if the parents are known to be carriers for these genetic diseases. Because prenatal diagnostic testing allows genetic experts to test placental cells directly, the results are diagnostic and specific for the fetus.

There are two different prenatal diagnostic tests, chorionic villus sampling (CVS) and amniocentesis. CVS is a procedure in which a small amount of tissue (chorionic villi) is obtained from the developing placenta at approximately 10-13 weeks of pregnancy. The tissue is then evaluated for chromosome abnormalities, and if indicated, specific genetic diseases. The primary advantage to CVS is that this test can be performed much earlier in pregnancy than amniocentesis. However, CVS does not detect neural tube defects (spina bifida, meningomyelocele or anencephaly). Therefore, patients who opt to pursue CVS undergo an AFP blood test and a high-resolution ultrasound later in pregnancy to screen for these defects. Also, approximately one percent of all CVS results will show a mixture of normal and abnormal chromosomes, which is called mosaicism. The majority of the fetuses in these pregnancies are normal, however additional testing, including amniocentesis, may be indicated.

CVS can be performed one of two ways depending on the location of the placenta within the uterus. The transcervical method is performed by inserting a thin catheter, guided by ultrasound, through the vagina and cervix to reach the chorionic villi. The transabdominal method is similar to amniocentesis. Using ultrasound, a thin needle is inserted through the mother’s abdominal wall to obtain a small amount of tissue. In either case, this placental tissue is then sent for analysis.

Amniocentesis is typically performed between 16-20 weeks of pregnancy. Under ultrasound guidance, a thin needle is inserted through the mother’s abdominal wall into the amniotic fluid surrounding the fetus. A small amount of fluid is then taken and analyzed for chromosome abnormalities, neural tube defects, and if indicated, specified genetic diseases. The main benefit to amniocentesis is that although it is performed later in pregnancy, it is possible to test for genetic disorders, including chromosome abnormalities and specific genetic diseases, AND neural tube defects, such as spina bifida, all at once.

Whether patients choose CVS or amniocentesis, it is possible to obtain the same information with either procedure. However for patients who choose CVS, it is necessary to do a follow up blood test and detailed ultrasound in the second trimester to rule out neural tube defects. It should be noted that the results from this blood test and ultrasound are not as conclusive on neural tube defects as the results from an amniocentesis. Because both procedures are considered invasive, meaning that it is necessary to enter the womb with either a needle or a catheter in order to obtain cells, there is a small risk of miscarriage due to the procedures. The risk for either CVS or amniocentesis is approximately 1/200. Diagnostic results from either procedure take about ten days to be completed.

Regardless of whether you are considering CVS or amniocentesis, genetic counseling is an important step in your overall decision-making process and in assessing your risk factors for genetic disorders. Genetic counselors are available to discuss in further detail the benefits, limitations, and risks for prenatal diagnostic testing in order for you to make the best decision for you and your family.

– Kendall Glynn, MS, CGC, Certified Genetic Counselor, California Pacific Medical Center

The trend towards using more laptop computers in public places and airports will continue to grow as wireless internet access “hot spots” proliferate. This year laptop use in the U.S. is projected to grow to 60 million users. Additionally, laptops are also increasing their heat output with ever-faster processing power. Which begs the question: are we staring at a potential cause of male infertility without even knowing it?

It is well known that healthy sperm are produced ideally at a testicular temperature of 2 – 4 ºC below body temperature. Established studies have revealed a considerable decline in healthy sperm production – up to 40 % – resulting from scrotal or testicular temperature increases as small as 1 ºC. A long-term decline in sperm quality over several decades has also been identified by at least seven research studies, although definitive causes have yet to be determined. Given this, it was only a matter of time before the connection between laptops and infertility would be examined.

As reported in Human Reproduction, Vol.2, 2005, a group of scientists at State University of New York, Stony Brook embarked upon a research study monitoring the scrotal temperature change in 29 healthy male volunteers, median age 24, from laptop computer use. The researchers used two different types of laptop computers and randomly measured their thermal effect on the scrotum by using right and left scrotal temperature gauges in two separate 60 minute sessions.

They recorded scrotal temperature increases averaging 2.6 – 2.8º C.

The heat emitted by the laptops appears to be a factor, but curiously not the solo factor. The researchers also directed the study participants to sit upright without the laptop, but with their knees tightly pressed together. After sitting this way for an hour, researchers recorded their scrotal temperature, which increased on average 2.1 ºC.

This initial study may prompt further research seeking a more definitive link between laptop use and infertility, or it simply may be added to the myriad considerations of exogenous scrotal heat exposure related to lifestyle. In this same category are prolonged driving and sedentary sitting. Naturally this study calls for prudent use of laptops by men trying to become fathers while weighing in on how modern life in all of its ramifications might be boosting scrotal temperature and causing an overall decline in sperm count.

A woman trying to get pregnant doesn’t need the added stress of wondering if her breast milk carries any toxic synthetic chemical residues from everyday items or environmental pollution.

Besides methylmercury in fish, there are chemical residues found in fire retardants in the foam of that gorgeous new couch, organochlorines in common garden pesticides and anti-wrinkle agents in new clothes. Some residues are benign, and wash through the body; others linger, and through persistent exposure, can show up in blood, fatty tissue and breast milk.

Although the cumulative effects of these so-called bioaccumulators are actively being studied, there are good reasons not to panic. First, not all chemicals that enter a woman’s body persist. Many residues are attracted to water rather than fat, and will exit the body through urination.

Second, there is a global movement of activists and scientists working to recognize that women and their children have a fundamental right to clean breast milk. The most problematic pollutants have already been identified, and health activists are determined to stop exposure. In August 2003, they were victorious when California legislators passed a law to ban a class of chemicals used in common fire retardants known as PBDEs that were showing up in large amounts in breast milk.

Finally, some experts concur that the health benefits of breast feeding outweigh the potential negative impacts of low-level lingering chemicals in the breast milk. Some studies have even shown that breast milk can reverse some of the negative effects of low-level fetal exposure to toxic chemicals.

If you are inclined to get more involved in this topic, keep abreast of California State Senator Deborah Ortiz’s legislative initiative SB1168 Biomonitoring Program. This pilot program would enable target women to be tested for the presence of harmful chemicals, and it would represent the first statewide initiative of its kind.

Many women of child bearing age are wondering which fish to buy to get those beneficial omega-3 fatty acids without poisoning themselves or eating the last of some endangered species.

Higher intakes of the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), appear to decrease the risk for hypertension, atherosclerosis, type 2 diabetes, and some inflammatory diseases. DHA decreases the likelihood of premature birth, and is key to normal brain, retinal and possibly testicular development in fetuses.

Mackerel, herring, salmon, halibut and tuna have the greatest amounts of EPA and DHA, but caution is advised.

Some seafood contains significant amounts of methylmercury (meHg), which is toxic to the nervous system and may negate the cardiac benefits of fish. Large scale mercury poisonings 30-40 years ago in Japan and Iraq resulted in infants with cerebral palsy, mental retardation, developmental delay, seizures, blindness, and hearing impairment. While some mothers of affected infants were asymptomatic others showed toxic effects including fatigue, muscle and joint pain, headaches, hair loss, impaired memory and concentration, numbness, loss of peripheral vision, blindness, decreased coordination, difficulty walking, kidney failure, and death.

Research in monkeys has revealed that the reproductive effects of meHg include sperm toxicity, decreased pregnancy rates and increased miscarriages and stillbirths. Human studies describe higher mercury levels in couples experiencing infertility than in fertile couples. In ongoing studies, measurable decreases in intelligence and evidence of learning disabilities have been tied to methylmercury in children of some, but not all fish eating populations.

Toxic amounts of mercury rain down from skies polluted by the burning of coal and leach into waterways from old gold and mercury mines, including one in Marin near Tomales Bay. Bacteria convert the inorganic mercury to meHg, which then increases in concentration in organisms as it moves up the food chain. The human intestine absorbs 95% of ingested meHg, and then the body slowly excretes it over a period of months. Unfortunately, ingested methylmercury can show up in breast milk.

In 2000 the National Academy of Sciences (NAS) set the maximum acceptable daily meHg intake at 0.1 mcg/kg of body weight although some scientists have proposed an even lower threshold. Others have used a weekly or monthly intake guideline, which permits higher intake on any individual day, but limits the amount of fish eaten per week.

The San Francisco Chronicle recently sponsored an analysis of locally purchased fish, which revealed that a 120 lb. person could easily ingest 4 to 40 times her daily allowable intake of meHg by choosing popular fish including swordfish, halibut, Chilean sea bass, and ahi tuna. In separate tests white albacore tuna exceeded the NAS standard by 11 fold and chunk light by 3 to 4 fold.

Consistent with these findings is the report published last year by San Francisco physician Jane Hightower. She found that 66 of her female patients had an average blood meHg level three times the maximum recommended by the National Academy of Sciences (NAS). Many were symptomatic as were some of the children she studied. Agreement on what constitutes “safe” levels of exposure for pregnant women is still pending the outcome of ongoing studies. New data indicate that blood mercury concentrations are higher in the umbilical cord than in the mother and consequently, that 16% of infants are exposed to excessive mercury levels before birth. At an EPA conference in January a new maximum daily meHg intake for pregnant women of 0.07 mcg/kg was proposed.

The FDA has issued a warning that women who might become pregnant should avoid shark, swordfish, king mackerel and tilefish and PFC would add white albacore tuna. By not eating swordfish, shark and tuna, you’re not only protecting yourself but also these threatened species (www.montereybayaquarium.org). Also, many fish from Northern California waterways should not be eaten by women of childbearing age because of mercury or PCB contamination (www.oehha.ca.gov/fish.html).

Beth Schriock, MD, a pediatric endocrinologist, is PFC’s Clinical Research Coordinator. She has a keen interest in the environment’s impact on human health.

Q:
It’s the New Year and my husband and I plan to get serious about exercising and shed 10 pounds. Since I am trying to get pregnant, is there anything we should know?

A:
Before you jump on that bicycle, be aware that there is considerable debate about the impact of exercise on fertility. A sudden and extreme change in your diet or work out regimen can have hidden consequences. Too strenuous exercise can lower estrogen levels and suppress the hypothalamus and pituitary gland, leading to irregular ovulation. Some women who exercise vigorously cease menstruating and ovulating all together.

In fact, because the research on even moderate exercise has been inconclusive, some reproductive endocrinologists advise their female patients to avoid all exercise that brings the heart rate above 110 beats per minute. This pretty much rules out jogging, aerobics and biking but not necessarily yoga and weight lifting.

Both women and men need some body fat in order to reproduce. (Although overweight women experience more hormonal imbalances because excess weight can cause excessive production of estrogen.) Body Mass Index measures the ideal level. Women who have a BMI of between 20 and 25 are most fertile.

As far as the male factor, the most important thing to remember is that sperm are very sensitive to heat. Taking saunas and hot tubs are enjoyable side benefits at many exercise clubs, but these heated conditions can greatly diminish healthy sperm counts. Bicycling is the main sport that is best avoided by men who want to maintain optimal conditions for reproduction.

Each year Pacific Fertility Center® sends a delegation to the annual meeting of the ASRM the American Society for Reproductive Medicine. This prestigious conference draws researchers and practitioners from around the world, and this past event in San Antonio in October 2003 was no exception. Over 6,000 people attended from 32 different countries.

We have provided this summary of highlights to share with Fertility Flash readers. This tiny sampling by no means reflects the scope and depth of the 1800 scientific research papers that were presented. Human Nuclear Transfer From a popular press’s point of view, the most talked-about paper was Dr. Jamie Grifo’s research on human nuclear transfer. Each day of the conference, a new headline appeared with the world “clone” or “clone-like” even though Grifo and his Chinese colleagues, who reportedly tried the process unsuccessfully, insist that the process is not cloning. They fused the DNA from the oocyte of an infertile woman with a donor oocyte from which the DNA had been removed, and then fertilized the “reconstituted egg” with sperm. This experimental procedure has not yet produced a live birth, and the FDA prohibits this type of research in the U.S. It was recently banned in China as well. It is an incredibly complex procedure that is not likely to ever be commercialized due to the fact that so many embryos are rendered non-viable. OK to Go Patients who have just undergone Embryo Transfer after IVF are no less or more likely to conceive if they immediately go to the restroom. A study revealed that there was no difference in pregnancy rates between those women who had to go immediately and those who waited. Relax about SSRIs Women undergoing infertility treatment who take prescription medications in the category of Selective Serotonin Reuptake Inhibitors (Zoloft, Prozac, Paxil, etc.) have less to worry about. Children conceived by women on SSRI medication were no more or less likely to have problems. 911 Decline Infertility patients from New York treated in the midst of the September 11, 2001 tragedy suffered from a higher rate of pregnancy loss than those treated prior. The results of nearly 400 patients who underwent an IVF procedure before and after September 11 were examined. Individuals placed in the “before” or “after” groups showed no significant differences in age, number of eggs retrieved, or number of embryos transferred. Clinical pregnancy rates were also comparable between the two groups. However, there was a nearly 25% lower delivery rate for the patients with a pregnancy test after September 11. This study again points to the significance of psychological factors that impact outcomes of infertility therapy.

Telomeres Predict Poor Prognosis Scientists are noticing a correlation between short telomeres and egg quality. Telomeres are small pieces of DNA at the ends of chromosomes, that shorten naturally as we age. Telomere length could someday be used as a test of fertility potential.

Joe Conaghan, PhD	Eldon Schriock, MD

Drs. Joe Conaghan, PhD and Eldon Schriock, MD along with other PFC professionals attended the ASRM meeting and are committed to continually evaluating the latest research and using proven treatments to improve patient care.

Alcohol and pregnancy don’t mix.

This article includes contributions from Isabelle Ryan, MD and Beth Schriock, MD

Studies have tied alcohol consumption during pregnancy to increased risk for stillbirth and first trimester miscarriage. Indeed – alcohol abuse by women who are expecting is the number one cause of birth defects, premature births, low birth weight and mental retardation. A shocking 12,000 babies each year are born with Fetal Alcohol Syndrome (FAS) and at least twice that many with the milder Fetal Alcohol Effects (FAE) associated with learning disabilities and lower alcohol intakes.

While the tragedy of FAS is well established, less certain is whether casual consumption of alcohol while trying to conceive either hinders or helps a woman’s chances. Past published studies have been mixed as to whether there is an association between moderate alcohol consumption and waiting time to pregnancy. One study did show decreased probability of conception in women imbibing 1-5 drinks per week. Another study saw no effect of 7 or more drinks per week in younger woman but women over 30 were more likely to be infertile. None of these studies have stratified the data to see if any type of alcohol might benefit or hinder. Yet a recent study drew a mildly positive correlation between moderate wine drinking and pregnancy.

The study, published in the September Journal of Human Reproduction was conducted at the Danish Epidemiology Science Center in Copenhagen by Mette Juhl, who had already researched the impact of moderate alcohol consumption on conception. Her past survey work concluded that moderate consumption of alcohol (up to 7 glasses per week) does not reduce a woman’s chances of purposefully getting pregnant.

For this study, the researcher set out to take a closer look at specific types of alcohol consumed by the 29,844 pregnant women who had participated in the first survey. Researchers discovered that wine drinkers had a nearly 30 percent greater chance than nondrinkers of getting pregnant within one year of trying. Woman who exclusively drank wine became pregnant sooner than those that drank only beer or hard liquor (spirits). Interestingly, drinking all three types of alcohol was associated with the shortest time to pregnancy.

Again, the study confirmed that heavy drinking of spirits actually decreases conception chances. Women who drank more than seven shots per week were 240 percent less likely to conceive. However, it is important to note that many of these women also had other risk factors for subfertility (smoking, greater incidence of pelvic infections or abdominal surgeries).

Ms. Juhl is cautious to point out that it may not be wine consumption per se, causing the increase or decrease in pregnancy success, but rather other lifestyle influences that may go along with wine drinking. For instance, some oenophiles enjoy healthier food than nondrinkers and beer or liquor drinkers. They also are more likely to be of average weight, and practice healthier lifestyle habits. The wine drinkers were less likely to smoke; smoking has been shown to prolong time to conception. Other confounding factors such as caffeine consumption, partner’s age and frequency of intercourse were not evaluated. She cautioned against drinking alcohol specifically to try to conceive, since this benefit was quite mild.

As little as one drink per day in pregnant women has been linked to decreased cognitive performance in their infants. Alcohol can have detrimental effects on the fetus as early as three weeks gestation – before a woman even knows she is pregnant. The “safe” amount of alcohol intake for pregnant women has not been established. Given that wine drinking could just be a proxy for a healthier lifestyle and the known negative effects of alcohol on the fetus, it is premature to encourage the consumption of wine to enhance conception.

For now we at PFC endorse the positions of the Centers of Disease Control (www.cdc.gov/ncbddd) and the American Academy of Pediatrics (www.AAP.org) advising that women attempting pregnancy should abstain from alcohol.

References:

American Academy of Pediatrics: Preventing Fetal Alcohol Syndrome. www.aap.org/advocacy/chm98pre.htm

CDC: Alcohol Use and Pregnancy. www.cdc.gov/ncbddd

National Institute on Alcohol Abuse and Alcoholism: Fetal Alcohol Exposure and the Brain. www.niaaa.nih.gov/publications/aa50.htm

Barefoot JC, Gronbaek M, Feaganes JR, McPherson RS, Williams RB, Siegler IC. Alcoholic beverage preference, diet, and health habits in the UNC Alumni Heart Study. American J of Clinical Nutrition 2002;76 (2): 466-472.

Bolumar F, Olsen J, Boldsen J. Smoking reduces fecundity: a European multicenter study on infertility and subfecundity. The European Study Group on Infertility and Subfecundity. Am J Epidemiol. 1996; 143 (6): 578-87.

Bolumar F, Olsen J, Rebagliato M, Bisanti L. Caffeine intake and delayed conception: a European multicenter study on infertility and subfecundity. The European Study Group on Infertility and Subfecundity. Am J Epidemiol. 1997; 145 (4): 324-34.

Jacobson JL, Jacobson SW, Sokol RJ, Martier SS, Ager JW, Kaplan-Estrin MG. Teratogenic effects of alcohol on infant development. Alcohol Clin Exp Res. 1993; 17 (1): 174-83.

Jensen TK, Hjollund NH, Henriksen TB, Scheike T, Kolstad H, Giwercman A, Ernst E, Bonde JP, Skakkebaek NE, Olsen J. Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy. BMJ. 1998; 317: 505-510.

Juhl M, Andersen AM, Gronbaek M, Olsen J. Moderate alcohol consumption and waiting time to pregnancy. Human Reproduction. 2001; 16 ( 12) 2705-2709.

Juhl M, Olsen J, Andersen AM, Gronbaek M. Intake of wine, beer, and spirits and waiting time to pregnancy. Human Reproduction. 2003; 19 (9): 1967-1971.

Kesmodel U, Wisborg K, Olsen SF, Henriksen TB, Secher NJ. Moderate alcohol intake during pregnancy and the risk of stillbirth and death in the first year of life. Am J Epidemiol. 2002; 155 (4): 305-12.

Kesmodel U, Wisborg K, Olsen SF, Henriksen TB, Secher NJ. Moderate alcohol intake in pregnancy and the risk of spontaneous abortion. Alcohol Alcohol. 2002; 37 (1): 87-92.

Rosenberg A. Brain Damage Caused by Prenatal Alcohol Exposure. Scientific American. July/August 1996; 42-51

A new study, just published in the British Medical Journal has received quite a bit of press attention. This study, conducted at Kaiser Permanente in Northern California, suggests there may be a relationship between the use of aspirin and aspirin- like medications (called non-steroidal anti-inflammatory drugs, or NSAIDs) and first trimester miscarriage. We at PFC took a closer look at the study and determined that it has severe shortcomings.

NSAIDs, including aspirin, ibuprofen, naproxen and others, have not as yet been strictly forbidden during pregnancy, although most doctors, PFC physicians included, recommend acetominophen (Tylenol) if needed for headaches and other minor ailments during pregnancy.

Research has long established the impact of aspirin on women trying to get pregnant. At low doses (e.g. 81 mg), aspirin has markedly different effects on such things as platelet function as compared to higher doses (325-1000 mg). At low doses, some studies have suggested that aspirin may improve uterine blood flow and enhance embryo implantation. At higher doses, NSAIDs may inhibit prostaglandins, substances important for ovulation and implantation. This is the basis upon which we, at PFC, have designed our medication treatment protocol. We suggest patients not take drugs such as ibuprofen and naproxen during treatment, yet we do recommend patients undergoing infertility treatment take a daily baby aspirin.

This recent study surveyed 1055 women immediately after their pregnancy was diagnosed, and the women were followed up to 20 weeks of pregnancy. Only 53 women reported using NSAIDs around the time of conception or during pregnancy (5% of those surveyed). Of these, 15 (25%) miscarried. Of the 980 women who reportedly did not use NSAIDs, 149 (15%) miscarried. The 95% confidence interval was 1.0-3.2. When the 95% confidence interval is less than 1.0, the results are not considered statistically significant. Therefore, these results just barely achieved statistical significance. If the study had been able to find more women who had used NSAIDs, it might be more conclusive.

With so few women reporting NSAID use, and with results barely in the statistically significant range, more questions than answers are raised. It is disappointing that the authors did not include the average age of the mothers in their data presentation. Miscarriage is strongly associated with maternal age, as more embryos are genetically abnormal and will likely miscarry, as the mother is older at conception. Is there a possibility that the average age of the women using NSAIDs was greater, by chance or not? The study did not specify the maternal ages or how the data was adjusted to eliminate this potential important bias.

However cautiously we must review these results, PFC will continue to recommend a daily dose of baby aspirin to our patients undergoing infertility treatment. At such a low dose, baby aspirin improves uterine blood flow and this study does not warrant alarm. The primary conclusion from this Kaiser study strongly suggests that further research is needed.

An almost universal piece of advice from woman-to-woman trying to conceive is to take a daily dose of folic acid, also called folate. Folic acid is a B-vitamin that decreases neural tube birth defects by a dramatic 70%. Women who take 400 micrograms per day of folic acid on top of a healthy diet while attempting to get pregnant often assume that this is adequate.

At Pacific Fertility Center, we go one step further, and recommend a prenatal vitamin supplement for our patients undergoing fertility enhancement procedures. Besides the essential dose of folate, prenatals also contain other critical ingredients, such as iron and calcium.Additional iron is important as uterine blood volume builds up. Calcium is needed for a developing fetus, as well as to offset the iron, which impacts calcium absorption.

Some women complain of nausea from swallowing prenatal vitamins, which is usually caused by the iron concentration irritating the stomach lining. One way to overcome this queasiness is to take the pill with a full meal, or in half doses, twice a day. (Best to avoid dairy products, however.) Chewing ginger or sipping ginger tea also helps prevent digestive unease. And as a last resort, you may be a candidate for slow fe, which is an iron supplement designed for extremely slow absorption.

With so many over the counter vitamins available, some may wonder how these differ from prescription-based prenatals. In most cases, prescriptions are written so that insurance companies will cover the cost – there is generally no substantial difference in quality.

Also, it may be overwhelming to determine how prenatal vitamins differ in quality, given the sheer volume of products in the marketplace. Some women prefer vitamins with the least amount of flavoring and coloring additives; with fewer ingredients, absorption may be enhanced. If you would like to double check whether your prenatal supplement has what you need, you can compare the label with this list of important ingredients:

Folic acid 400 micrograms (mcg)
Calcium 250 mg
Iron 30 mg
Magnesium 320 mg
Vitamin A 800 mcg (8,000 I.U.)
B6 2.2 mcg
Vitamin C 65 mg
Vitamin D 10 mcg
Vitamin E 10 mcg
Zinc 15 mg

Supplementing your diet with a prenatal vitamin containing these basic ingredients helps create the building blocks for a successful pregnancy. Please don’t hesitate to ask your PFC physician if you have any questions.