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The Right Environment for Your Baby from Day 1 – Part 1

Tuesday, June 28th, 2011
Dr. Carolyn Givens worked with thousands of in vitro fertilization patients over the last decade using a combination of attentive, personal care and advanced medical technology.
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We all know that people that are not particularly health-conscious can conceive, many times easily or even unintentionally. However, conception is a much more common event when the involved parties are young, and eggs and sperm are much more likely to be genetically normal. It may also be that the reproductive system has not been subjected to years of accumulated age-related, environmental damage. Successful conception does not just involve eggs and sperm and the reproductive tract. Just as in all other areas of human physiology, the reproductive system works best when the entire organism is healthy and balanced. This includes not just physical health, but mental health and sexual health. 

It makes sense that healthy people are more likely to have healthier babies, and this may be especially true in the later reproductive years. For example, a woman in her forties with mild high blood pressure is going to have a safer pregnancy when she keeps her weight down and consistently takes her medications for blood pressure. Similarly, the liver function may be negatively affected by the cumulative effects of drinking alcohol over many years and the liver is crucial to clearing toxins from the body.

The feeling of lack of control is one of the main issues for women and men facing the challenge of infertility. No one can know exactly when they are going to conceive, but for infertility patients undergoing fertility treatments, even the how of conception is being determined by medical factors that again are out of their control. One way to gain back some control is to take charge of our health and nutrition. Eating healthy and living healthy can only help one’s chances for successful conception. Furthermore, when a pregnancy is achieved, the habits set prior to conception and continued during gestation will provide for the best physical environment to nurture the developing fetus. In this issue, we present information about nutritional needs during pre-conception and early pregnancy. The goal of pre-conception nutrition is to promote the health of the gametes (eggs and sperm) and to set the nutritional habits that will carry on into pregnancy and breast feeding.

Certainly the most important component in eggs and sperm is the DNA, which carries the genetic material from the parents to the embryo. DNA molecules are long linear chains of nucleic acids, sugars and proteins. Damage to and degradation of DNA is a consequence of living.  The energy packets in all our body’s cells, including sperm and eggs, are called mitochondria. Mitochondria contain DNA and produce important enzymes for metabolism and energy production. Molecular by-products of metabolism, oxygen free radicals and nitric oxide species, are constantly forming in our bodies .These free radicals can damage both nuclear and mitochondrial DNA. All living organisms have developed many mechanisms to protect their DNA from the environmental damage of excessive nitric oxide and oxygen free radicals. Anti-oxidant nutrients and vitamins are essential to support these protective mechanisms. Truth be told, we all should be ingesting anti-oxidants throughout our lives to protect our DNA and all our tissues from assaults from the outer (and inner) world, but no time is more crucial for the next generation than at conception and fetal development. There are known substances and chemicals in the modern world that can overwhelm our highly evolved physiologic protective processes. Just one well-known example is phthalate ester, a chemical used to soften plastics such as in disposable water bottles, which leaches into the water it contains. These phthalates have been shown to have toxic effects in animal studies on the reproductive system1 and have been found in urine and breast milk of pregnant and lactating women2. Unfortunately, phthalates are only one of many, many chemicals we are exposed to on a regular basis. So, there are substances to avoid, when possible, but can we really avoid every harmful chemical? Not likely. What we can do, beyond avoiding these chemicals,  is make sure we are getting the nutrients, vitamins and minerals that help our own enzymes and proteins to protect our DNA.

There are numerous books on nutrition for pre-pregnancy and pregnancy. It is not possible to cover this topic exhaustively in this series of two articles. Suffice it to say that there is no one diet that has been conclusively shown to promote fertility. It is common sense that nutritionally empty diets, especially those that promote obesity, are clearly harmful to conception. Diets lacking in essential vitamins and minerals can have consequences beyond infertility, such as very poor pregnancy outcomes and malnourished babies. One recent article from the Netherlands2 looked at the diets of women undergoing IVF. They measured blood levels and follicular fluid levels of some essential vitamins and minerals in these women. To paraphrase their findings: In women, two dietary patterns were identified. The “health conscious–low processed” dietary pattern was characterized by high intakes of fruits, vegetables, fish, and whole grains and low intakes of snacks, meats, and mayonnaise, and positively correlated with red blood cell folate (β = 0.07). The “Mediterranean” dietary pattern that is, high intakes of vegetable oils, vegetables, fish, and legumes and low intakes of snacks, was positively correlated with red blood cell folate (β = 0.13), and vitamin B6 in blood (β = 0.09) and follicular fluid (β = 0.18). High adherence to the “Mediterranean” diet increased the probability of pregnancy by 40%. Their conclusion was “A preconception “Mediterranean” diet by couples undergoing IVF/ICSI treatment contributes to the success of achieving pregnancy.”

So avoiding environmental toxins and eating a healthy (possibly “Mediterranean”) diet may be helpful for general health, fertility and pregnancy, but what are the specifics? What to avoid? What to include? For some very general guidelines, see the side bar to this article. For more comprehensive help, I recommend the book “Fertility and Conception” but Dr. Karen Trewinnard3, listed in the References. Please also look for PART 2 to this article next month for more nutrition and health advice and information.

References:

1. Phthalates: toxicogenomics and inferred human diseases. Genomics. 2011 Mar;97(3):148-57. Epub 2010 Dec 13. Singh S, Li SS Department of Life Science, College of Science, National Taiwan Normal University, Taipei 116, Taiwan. sher@ntnu.edu.tw
2. Phthalate exposure in pregnant women and their children in central Taiwan. Lin S, Ku HY, Su PH, Chen JW, Huang PC, Angerer J, Wang SL. Chemosphere. 2011 Feb;82(7):947-55. Epub 2010 Nov 13
 
3.  The preconception Mediterranean dietary pattern in couples undergoing in vitro fertilization/intracytoplasmic sperm injection treatment increases the chance of pregnancy. Fertility and Sterility Volume 94, Issue 6 , Pages 2096-2101, November 2010. Marijana Vujkovic, B.Sc. Jeanne H. de Vries, Ph.D. Jan Lindemans, Ph.D. Nick S. Macklon, Ph.D. Peter J. van der Spek, Ph.D.  Eric A.P. Steegers, Ph.D. ,Régine P.M. Steegers-Theunissen, Ph.D.
 
3. Fertility and Conception – The essential guide to natural ways to boost your fertility and conceive a healthy baby – from learning your fertility signals to adopting a healthier lifestyle.  By Dr. Karen Trewinnard BM FFSRH, Carroll and Brown Publishers, Ltd.

 

SIDEBAR: 

What to Avoid (a much-abbreviated list):

  1. Drinking from plastic water bottles.
  2. Microwaving food in plastic (and especially stryofoam!) containers
  3. Pesticides and herbicides – whenever possible, buy organic, when not possible, wash fruits and vegetables well.
  4. Heavy metals such as lead (soldering, stripping old paint from walls), mercury (in high-food chain fish) and cadmium (cigarettes, solder materials, pesticides)
  5. White foods: too much white bread, refined sugar, white rice, potatoes 
  6. Too much salt and butter, fried foods
  7. Caffeine – it’s a blood vessel constrictor
  8. Alcohol – more on this next issue.

What to Include (somewhat abbreviated):

  1. Olive oil rather than butter
  2. Fish that do not contain mercury (e.g. salmon, most shellfish, halibut, flounder)
  3. Organically-grown fresh fruit and vegetables
  4. Whole grains
  5. Omega-3 Fish oils
  6. Anti-oxidants such as blueberries, cranberries, tomatoes (lycopene)
  7. Pre-natal vitamins containing at least 800 mcg folic acid and 2000 IU of Vitamin D3 (for a more thorough discussion of the essential vitamins and minerals, see the website www.essbeg.com)

PFC Achieves High Pregnancy Rates While Lowering Risks

Wednesday, August 11th, 2010
The PFC Staff, as a unified team, is guided by the highest ethical standards. We provide our patients with the best quality, individualized, compassionate fertility care.
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Every year thousands of families are created with the assistance of in-vitro fertilization. Many of those newborns are twins. While some may see this as a double blessing, it is important to understand that there are many potential risks associated with multiple gestation. Statistics show that a higher percentage of twins are born prematurely compared to singleton pregnancies. Premature birth can cause complications resulting in physical impairment, learning disabilities, and even death. In addition to the increased risk to the children born from a multiple pregnancy, there is also an increased risk for the pregnant woman of complications associated with carrying multiples.

Pacific Fertility Center (PFC) has been taking steps to minimize the risk of multiple gestation for several years. “We have worked actively to increase pregnancy rates and decrease the number of multiples,” comments Carolyn Givens, M.D. “Balancing high pregnancy rates with low pregnancy risk improves pregnancy outcomes. Our goal is to achieve this balance and reduce the risk of multiple gestation.”

PFC recently completed the analysis of our Elective Single Embryo Transfer (eSET) program for 2009. The twin rate was significantly lower, and, triplets were eliminated entirely. 79 patients underwent an embryo transfer procedure where they elected to transfer only one embryo created from their own eggs; these 79 transfers resulted in 38 pregnancies, two of which were identical twin pregnancies (the embryo split from one into two) and NO triplets. Compare this statistic to patients choosing to transfer two embryos: 159 patients, with embryos derived from their own eggs, transferred two embryos resulting in 80 pregnancies, of which 31% were non-identical twins and two triplet pregnancies (again from one of the embryos splitting).

Patients that choose eSET have excellent pregnancy rates with a single embryo. eSET embryos are grown for 5 days in the lab to the blastocyst stage, which allows for selection of the healthiest embryos for transfer. The transfer of fewer embryos provides for the healthiest outcomes; eSET produces high pregnancy rates while minimizing the risk of multiple pregnancy. “For many patients, there is no advantage to transferring more than one embryo. It is all about educating our patients. Given this information, these numbers and the potential risks of twin pregnancies, many will choose to transfer only one embryo,” says Carolyn Givens, M.D.

At PFC, careful consideration is given to the number of embryos transferred to each patient. Our goal is to create healthy singleton pregnancies. Utilizing advanced embryo culture techniques, the highest quality embryos can be selected for transfer. Special environmental conditions, advanced culture media, and the delicate handling of gametes and embryos is required; these efforts result in better embryos, with higher implantation and pregnancy rates.

In addition, PFC has developed an outstanding and robust program for freezing embryos not transferred in the fresh cycle. Using a technology called vitrification, we have been able to achieve pregnancy rates with frozen embryos that are very similar to those using fresh embryos. “The outstanding success of our freezing program has allowed us to be confident in transferring just one embryo at a time, which all but eliminates the risk of triplets or higher pregnancy,” says Dr. Joe Conaghan, PFC Lab Director. He adds, “We have been so successful with embryo freezing over the last 3 years that our embryologists are in high demand to provide training across the country and around the world. Our goal is to help our patients overcome infertility and build their family; one healthy baby at a time.”

Conception and Body Weight

Tuesday, May 22nd, 2007
Dr. Carolyn Givens worked with thousands of in vitro fertilization patients over the last decade using a combination of attentive, personal care and advanced medical technology.
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Many women are aware that very low body weight and low percentages of body fat can compromise ovulation and chances for successful conception. What many don’t realize is that excess body fat can also affect one’s chances.

A review of the literature shows that the majority of studies published report decreased chances of conceiving with in vitro fertilization (IVF) if a woman in significantly overweight. IVF data is useful to study this issue because all the women undergo similar treatments and because follow-up data on pregnancies is usually readily accessible to researchers. It may also be true that excess body weight is a negative factor in spontaneous conception and non-IVF treatment as well.

How much of a factor is weight in decreasing conception? One study from the Netherlands reported a higher cycle cancellation rate due to poor response to stimulation and lower fertilization rates1 than normal weight women. Another study from Norway reported higher requirements for stimulation medications and a higher miscarriage rate in the first 6 weeks of pregnancy2. One of the largest studies was from Cornell and reported on 960 women undergoing IVF. Although they did not find a statistically significant decrease in clinical pregnancy rates, rates of cycle cancellation were higher and gonadotropin dose requirements were greater in the obese patients3. Another large study from Iowa (1,293 patients) looked at outcomes in women who were obese and morbidly obese. Again, this study found that clinical pregnancy rates per egg retrieval were similar to normal-weight women but cancellation rates and gonadotropin dose requirements were much higher in the obese women. Furthermore, rates of pregnancy complications such as preeclampsia, gestational diabetes and cesarean section were higher in the obese women4.

How much weight is significant for this effect? Most studies calculate weight as Body Mass Index, or BMI. This calculation takes in weight vs. height. To calculate your BMI, many websites such as the one at the Centers for Disease Control ( www.cdc.gov/nccdphp/dnpa/bmi/index.htm) can provide a calculator. There is also a chart at the federal government’s website www.consumer.gov/weightloss/bmi.htm. You just need to know your height in feet and inches and weight in pounds. A normal BMI is between 18.5 and 24 and overweight is a BMI of 25 to 30. A BMI of 30 or more is considered obese and 40 or more is considered morbidly obese.

In general, it appears that excessive body weight can negatively impact a woman’s chances for conception and for a healthy, uncomplicated pregnancy and birth. It makes sense that being a normal body weight and in good shape is a good idea and should be a goal for aiding successful conception.

Carolyn Givens, MD

References

1. Gynecol Obstet Invest. 2005;59(4):220-4. Epub 2005 Mar 7. Obesity and Clomiphene Challenge Test as predictors of outcome of in vitro fertilization and intracytoplasmic sperm injection.van Swieten EC, van der Leeuw-Harmsen L, Badings EA, van der Linden PJ.

2. Hum Reprod. 2004 Nov;19(11):2523-8. Epub 2004 Aug 19. Impact of overweight and underweight on assisted reproduction treatment. Fedorcsak P, Dale PO, Storeng R, Ertzeid G, Bjercke S, Oldereid N, Omland AK, Abyholm T, Tanbo T.

3. J Reprod Med. 2004 Dec;49(12):973-7 Obesity and in vitro fertilization: negative influences on outcome. Spandorfer SD, Kump L, Goldschlag D, Brodkin T, Davis OK, Rosenwaks Z.

4. Obstet Gynecol. 2006 Jul;108(1):61-9. Obstetric outcomes after in vitro fertilization in obese and morbidly obese women. Dokras A, Baredziak L, Blaine J, Syrop C, VanVoorhis BJ, Sparks A.

Ask The Experts – Addicted to Caffeine

Sunday, November 5th, 2006
Dr. Eldon Schriock has been at the forefront of assisted reproductive technology since 1981. He was a member of the medical team that performed the first in-vitro fertilization treatment in Northern California.
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Question: I’m a heavy coffee drinker, consuming five cups per day. I’m concerned that my addiction to caffeine will hurt my chances of getting pregnant. How much caffeine is acceptable?

Answer: Moderate caffeine intake for women trying to conceive is acceptable. As a general guideline, women trying to conceive should limit intake to 3 cups of coffee (or 300 mg of caffeine) per day (Organization of Teratology Information Services (OTIS) 2001). Results from large published studies have not demonstrated that moderate caffeine intake adversely affects fertility (International Food Information Council (IFIC) August 2002). Furthermore, caffeine consumption has not shown to have an impact on fertility or birth defects for the male partner or sperm donor (OTIS 2001).

For women who are pregnant, there have been several studies analyzing the affect of caffeine and pregnancy with the conclusions of those individual studies being mixed (IFIC August 2002). Keep in mind that if you are pregnant or breastfeeding, the caffeine you consume may transfer to the infant. As such, guidelines for caffeine intake of pregnant or breastfeeding women are a little more rigid. The recommendation by OTIS and Motherisk is that consuming less than 1½ cups of coffee (or 150 mg of caffeine) per day is not likely to increase the chances of miscarriage or a low birth weight baby. The American Academy of Pediatrics states that: “no harm is likely to occur in a nursing child whose mother drinks one cup of coffee a day.”

For more information on the affect of caffeine on fertility, visit the National Toxicology Program-Department of Health and Human Services website. The website provides a more detailed look at some of the clinical studies referenced above. Additionally it provides a chart showing the levels of caffeine in certain food and drinks. This information is available at: http://cerhr.niehs.nih.gov/common/caffeine.html.

– Eldon Schriock, MD

Ask The Experts – Frequency of Intercourse

Friday, March 10th, 2006
Dr. Carolyn Givens worked with thousands of in vitro fertilization patients over the last decade using a combination of attentive, personal care and advanced medical technology.
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Question: I’m confused about how often to have intercourse around the time of ovulation. Some things I have read say it should be not more than every other day while my doctor tells me it should be daily. What is the right answer?

Answer: There may be no exact right answer for everyone. Indeed, there might be a slight decrease in sperm concentration on the second or third straight day of ejaculation. However, for most men, there are still millions of active sperm present on the second or third day. As such, it may be better to have more sperm available in the reproductive tract during the window of fertilization for the egg.

My bias is to have intercourse as frequently as possible when you know you are soon to be, or in the process of, ovulating. The best method to detect when this is occurring is to use an ovulation predictor kit such as Ovu-Quick or Clear Blue Easy. When the kit detects the surge, have intercourse on that day and the next day. Beyond that, it is probably too late. If you don’t want to get that technical, subtract 16 days from your usual cycle length and start having intercourse daily from that day of the cycle for the next 3-4 days. For example, if your usual cycle length is 30 days, begin having intercourse on about day 14 and continue to day 16 or 17.

– Carolyn Givens, MD

Exercise and Infertility

Wednesday, January 11th, 2006
Dr. Philip Chenette is rated as one of the “Best Doctors in America”, recognized by the Consumers’ Checkbook “Guide to Top Doctors” and is featured in America’s Guide to American’s Top Obstetricians and Gynecologists.
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Exercise and diet improvements are excellent enhancements to fertility therapy. There is evidence of a reduced risk of diabetes, high blood pressure, and pre-eclampsia in women who exercise in pregnancy. Some reports have identified a greater sense of well-being, shorter labor and fewer obstetric interventions in physically well-conditioned women. The standard recommendation by the Centers for Disease Control and Prevention, as well as the American College of Sports Medicine suggests that a minimum 30 minutes or more of moderate exercise per day, every day of the week, is ideal for pregnant women. The American Academy of Family Physicians and the American College of Obstetricians and Gynecologists (ACOG) endorse this 30 minutes per day recommendation.

In addition to physical benefits, gentle to moderate exercise is a healthy way to control the stress related to dealing with infertility diagnosis and treatment, but not all exercise is beneficial.

Level of Exercise
Everyone has a different level of exercise at which point it interferes with fertility. There is risk that the biological stress associated with exercise may induce ovulation problems and can, at times, increase the risks associated with fertility treatment. Maintaining or initiating a well balanced diet is important. This includes diverse nutrients (complex carbohydrates, balanced protein, low fat), a vitamin supplement and adequate hydration, especially during periods of exercise. Weight should be monitored: if weight loss occurs, intake should be increased; if weight gain occurs, intake should be evaluated and revised accordingly. Rapid weight gain or loss is not recommended.

Extreme exercise may affect fertility in both men and women. Serious athletes may have to add more calories to ward off fertility problems. Individual evaluation by a physician is recommended for those who are in a rigorous exercise program and concerned about their fertility.

If a woman has an established exercise program prior to treatment, that level of activity may be maintained and continued with some minor modifications and reasonable precautions.

If a woman has not begun an exercise program prior to treatment, a gentle start is advised such as walking or swimming 15 to 30 minutes, three days a week. A slow and steady increase in duration and frequency can be accomplished over a period of several weeks. A good guideline to follow is if it is difficult to carry on a conversation, slow down. For those starting a new program and can afford the luxury of a professional trainer, working with one who has expertise in exercise during pregnancy is a great way to begin.

Heavy exercise spurts followed by long periods of no activity is not recommended. Gentle to moderate, regular exercise is best.

Modifications to Exercise During Infertility Care
Generally, it is safe to assume that if an activity is uncomfortable, don’t do it, especially when considering discomfort in the region of the ovaries. Near the end of an IVF cycle and for a month after, avoid jostling tender ovaries and activities where even slight injury to the abdomen may occur. Ovaries are enlarged and may be uncomfortable when being jostled. Aside from causing discomfort, there is an increased risk of ovarian torsion, particularly after 5-7 days of gonadotropins. Bouncing exercises to avoid include vigorous step aerobics and running. Less traumatic, low impact exercises, such as walking, yoga, Pilates, swimming, are preferred.

A general rule of thumb is to aim for a target heart rate of 120-130 from stimulation day 8 to one week post transfer.

Contact sports or other activities that may increase the chance of bumping or hitting the abdomen or increase the risk of a fall such as horseback riding, vigorous racquet sports and downhill skiing should be avoided.

Avoid overheating especially during exercise; this includes hot tubs, hot yoga and exercising during very hot days.

Avoid conditions that limit oxygen availability especially during aerobic exercise; hiking up to a 6000 feet altitude is an acceptable limit.

Scuba diving is absolutely not recommended.

These are general guidelines, however, everyone’s level of comfort and physical condition is unique. It is always recommended patients discuss their exercise regimen with their physician.

– Philip Chenette, MD

Day 3 vs. Day 5 Transfer

Friday, January 6th, 2006
Dr. Carolyn Givens worked with thousands of in vitro fertilization patients over the last decade using a combination of attentive, personal care and advanced medical technology.
More about Dr. Givens · Read Other Posts

The field of assisted reproduction is continually changing and this is a good thing because, for the most part, these changes have been for the better. Better medications, improved treatment strategies and a better understanding of laboratory techniques are resulting in constantly improving embryo implantation rates. This will allow us to transfer fewer embryos, reducing the risks for twins or triplets, which will result in better obstetrical outcomes for our patients. Our goal in assisted reproduction is to do all we can to ensure that chromosomally normal embryos have the opportunity to result in a healthy pregnancy.

More and more, Pacific Fertility Center is utilizing the day-5 embryo transfer procedure. The benefits of this are to 1) improve implantation and pregnancy rates and 2) lower the number of embryos transferred. Allowing embryos to remain in the laboratory for 5 days after egg retrieval (as opposed to the more standard 3 days) gives us an opportunity to choose those embryos most likely to carry normal chromosomes and those most likely to keep developing in the womb after embryo transfer. PFC utilizes low oxygen incubators almost exclusively. As such, we are seeing an improvement in the percentage of embryos that are developing well in the lab environment, as evidenced by their continued progression from a cleavage stage embryo to a blastocyst stage embryo.

Although Day-5 embryo transfer has been around for a while, we have been hesitant to use it exclusively for our patients. Clinical data suggests that unless a woman has a good number of nice looking embryos on day 3, the risks of having no well developed embryos on day 5 is fairly high. Therefore, the patient choosing to attempt a day-5 transfer might end up with virtually no embryos to transfer. One argument asserts that this is what would probably occur within the uterine lining anyway. However, there are studies suggesting that pregnancy rates in women with less than three or four nice 8-cell embryos on day 3 will have a higher chance of pregnancy with a day-3 transfer as compared to women with less than three or four nice 8-cell embryos who have a day-5 transfer. We are noticing that, with the use of our new low oxygen incubators, we are getting better developed embryos on day 3. These embryos, in turn, have a greater chance of being a nice embryo on day 5.

We are also seeing a small but growing number of couples interested in the transfer of only one embryo because they wish to avoid the risks of having a twin pregnancy. Although the over-whelming majority of babies born as a twin do well, there is a measurable increase in the incidence of perinatal death and cerebral palsy in twins as compared to babies born as a singleton. Also, we have many patients returning to us for baby #2 or #3 and they would like to avoid a multiple gestation. This has been particularly true for our patients using donor egg-derived embryos. Last year, we saw a 50% pregnancy rate in women electively transferring one embryo in the donor egg program. We will definitely support any patient that wishes to transfer only one embryo at a time, and we will likely encourage day-5 transfers to better select the one embryo most likely to implant.

One potential downside of attempting day-5 transfer is the question of whether or not we will increase the number of pregnancies in the fresh IVF cycle at the expense of additional attempts with frozen embryos. This is because embryos frozen at a cleavage stage [day 3] have historically done better with freezing and thawing as compared to day-5 embryos.

Pacific Fertility Center has always had a strong freezing program with excellent success rates with frozen embryo transfers, mostly at the day-3 stage of freezing and thawing. Many patients have asked us why we do not freeze some embryos at day 3 and culture some to day 5. One reason is that when we freeze some embryos at day 3, we are taking them out of contention for fresh embryo transfer and therefore, we may be losing some of the selective advantage of doing a day-5 transfer. With patients that have a very large number of embryos on day 3 that look good (say 15 or more), this may still be a viable strategy. Most patients don’t have many good quality cleavage stage embryos, however. So when we are planning to attempt a day-5 transfer, we will usually plan to culture all embryos to day 5 and select the best one or two for transfer and freeze the remainder as a day-5 embryo. As a result, we are now seeing a larger number of our patients returning for frozen embryo transfer with their day-5 frozen embryos. Our laboratory director, Dr. Joe Conaghan is currently reviewing the data on implantation rates from frozen-thawed day-5 embryos from 2005.

Listed below are some of the situations for which we are more likely to recommend a day 5 transfer. These include:

1. Any woman undergoing transfer with donor egg-derived embryos (anonymous donors)
2. Any woman less than 40 with a large number of eggs/embryos/good quality day 3 embryos
3. Any woman that has had poor success with freezing and thawing on day 3 in prior ART cycles
4. Any patient considering transferring only one embryo
5. Any patient with a history of multiple ectopic pregnancies (one recent abstract from the ASRM
meeting suggested a decrease in the ectopic rate after IVF with a day 5 vs. day 3 embryo transfer).
6. Any woman with unexplained IVF implantation failures with day-3 transfer.

– Carolyn Givens, MD

Related Posts:

Low O2 Incubators
Stages of Embryo Development
From Egg to Blastocyst
Day 3 vs. Day 5 Transfer – Photos

Safe Lubrication

Tuesday, December 13th, 2005
Dr. Carolyn Givens worked with thousands of in vitro fertilization patients over the last decade using a combination of attentive, personal care and advanced medical technology.
More about Dr. Givens · Read Other Posts

It has been known for quite some time that many lubricants used to facilitate intercourse or as an aid in masturbation for sperm collection may actually be toxic to sperm. A new study presented at the American Society for Reproductive Medicine 2005 conference confirmed this through a more rigorous study analyzing sperm motility and DNA damage after exposure to four brands: FemGlide, Replens, Astroglide and Pre-Seed.

Although no single product left the sperm completely free of damage, the research identified the Pre-Seed product as causing considerably less motility and DNA damage than the others.

The company that distributes this product claims that Pre-Seed is of the same osmolarity (salt density) and pH as seminal fluid. They further claim that it contains a plant sugar that acts as an anti-oxidant.

The study was jointly conducted without funding from any of the lubricant companies by researchers at Cleveland Clinic Foundation in Cleveland, Ohio; South Dakota State University in Brookings, South Dakota; and Washington State University in Spokane, Washington.

In the first experiment, sperm from 13 different donors was analyzed for progressive motility after 30 minutes of exposure to each lubricant while compared to a control batch from the same sperm donors with no lubricant exposure.

The results showed that sperm activity ranged from a high of 66 percent in untreated sperm, followed by 64 percent with sperm treated with Pre-Seed, followed by 51 percent with FemGlide and 25 percent with Replens. The lowest reported sperm motility was 2 percent in a solution containing Astroglide.

In a second experiment, spermatozoa was exposed for 4 hours and then evaluated for sperm chromatin integrity and then analyzed for percentage of DNA fragmentation, and then compared to non-exposed sperm. Again, the results indicated that Pre-Seed was associated with the smallest amount of sperm DNA damage at 7 percent more than untreated sperm, followed by KY at 10 percent and FemGlide at 15 percent.

Besides the brands tested, it is also thought that KY Jelly, Vaseline, and even saliva can have a negative impact on sperm. (One of the least toxic substances is pure mineral oil but it is generally not advised that women use lipid-based products in the vagina. Mineral oil remains an excellent choice for lubrication for masturbation.)

We welcome the news that a product that is backed by independent laboratory analysis is now available that can make vaginal intercourse more comfortable as well as acting as a promoter of fertility.

– Carolyn Givens, MD

Sperm Boosters: Fact or Fiction?

Friday, June 17th, 2005
Dr. Carolyn Givens worked with thousands of in vitro fertilization patients over the last decade using a combination of attentive, personal care and advanced medical technology.
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In the last ten years or so in the U.S., we have seen an explosion in the number of over-the-counter dietary supplements for all manner of ailments as well as for the promotion of general health. Some are vitamins with well-known beneficial properties. Some are herbal supplements with a history of traditional Chinese medicine yet with little in the way of Western scientific studies to substantiate their use. Many other supplements contain elements and substances with very little known benefit.

Now there are several preparations being marketed to promote fertility. In this article, I chose to review three of the major products being actively marketed for the purposes of improving sperm.

The oldest supplement is ProXeed™. ProXeed™ is a citrus-flavored powder and can be dissolved in juice or other cold beverages. It is recommended by the manufacturer to be taken twice a day. The active ingredients in Proxeed™ are L-carnitine, L-acetyl carnitine and fructose. The cost is approximately $335.00 per 3-month supply.

Fertile One® is a pill that contains L-carnitine, anti-oxidant vitamins (ferulic acid, vitamins C and E, garlic, co-enzyme Q10 and selenium), ginseng root, zinc and B-complex vitamins (B-6, B-12, B-9 and folic acid). Cost is approximately $273.00 per 3-month supply.

FertilityBlend® for Men is a supplement containing L-carnitine, ferulic acid, vitamins E, B6, B12, and the elements selenium and zinc. The cost is only about $80.00 per 3-month supply.

Several studies have shown that the amino acid L-carnitine may promote sperm development. In a recent clinical trial1, 102 men with low sperm motility were treated with L-carnitine and acetyl L-carnitine. There was a significant correlation between higher levels of carnitine in the seminal (sperm) fluid and better sperm concentration, total sperm count, sperm total motility, rapid forward progression, live sperm count, membrane function, nuclear DNA integrity, capacity for cervical mucus penetration, linearity of spermatic movement, and amplitude of lateral sperm head movement after 3 and 6 months of L-carnitine/acetyl L-carnitine treatment. Another high quality study, a randomized, placebo-controlled trial of L-carnitine and acetyl L-carnitine showed that after 6 months of treatment increases were seen in all sperm parameters and the most significant improvement in sperm motility was present in patients who had lower initial absolute values of motile sperm (<4 million forward or <5 million total motile spermatozoa per ejaculate)2. There are no published randomized controlled trials looking at pregnancy rates on L-carnitine.

Several studies on the B Vitamins have been published showing anti-oxidant effects and virtually all find some benefit to the addition of this group to a daily vitamin regimen.

Ferulic acid is found in various medicinal herbs, has recently been shown to scavenge oxygen free radicals and increase the intracellular cAMP and cGMP (energy molecules). The only published article on ferulic acid involved adding this substance to previously ejaculated sperm specimens where it was shown to improve sperm motility3. A medline search did not reveal any studies on sperm after ingestion of ferulic acid.

It is interesting that Fertile One® contains garlic; at least one study has reported an inhibitory effect on garlic on sperm motility and survival in human and mouse sperm4 and crude extracts of garlic bulbs have been shown to immobilize ram sperm and are being investigated as a potential male contraceptive5.

Selenium is a trace mineral that is incorporated into several anti-oxidant proteins. It has been shown to improve human sperm parameters6 and fertility improved slightly when selenium-deficient mice were treated with it 7. What is not clear is whether most men with a normal diet would be selenium-deficient.

Folic acid supplementation may also be beneficial, especially for men who smoke Cigarettes8. Treatment of men with folic acid and 5 mg zinc improved sperm counts by 60% and also improved morphology (shape)9. Vitamin E has also been shown to improve sperm parameters and sperm-egg binding10. Co-enzyme Q10 has been shown in one small uncontrolled study to improve sperm motility in males11 but studies of men with a varicocele (dilated scrotal veins) suggest that high levels of seminal fluid Co-enzyme Q10 are found with men with the lowest sperm motility, suggesting that Co-enzyme Q10 would not be beneficial for men with a varicocele12.

Considering all these studies, there does seem to be a beneficial role for dietary supplementation for men with low sperm counts and low motility. The supplement marketed as FertilityBlend® for Men has almost all of the most well studied ingredients and is considerably less expensive than the others. Avoidance of garlic extracts and further supplementation with folic acid may also be beneficial.

– Carolyn Givens, MD

References:
1. Correlation between seminal carnitine and functional spermatozoal characteristics in men with semen dysfunction of various origins. De Rosa M, Boggia B, Amalfi B, Zarrilli S, Vita A, Colao A, Lombardi G. Drugs R D. 2005;6(1):1-9.

2. A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia. Lenzi A, Sgro P, Salacone P, Paoli D, Gilio B, Lombardo F, Santulli M, Agarwal A, Gandini L. Fertil Steril. 2004 Jun;81(6):1578-84.

3. Effects of ferulic acid on fertile and asthenozoospermic infertile human sperm motility, viability, lipid peroxidation, and cyclic nucleotides. Zheng RL, Zhang H. Free Radic Biol Med. 1997;22(4):581-6.

4. Spermicidal effect in vitro by the active principle of garlic. Qian YX, Shen PJ, Xu RY, Liu GM, Yang HQ, Lu YS, Sun P, Zhang RW, Qi LM, Lu QH. Contraception. 1986 Sep;34(3):295-302.

5. Sperm immobilization activity of Allium sativum L. and other plant extracts. Chakrabarti K, Pal S, Bhattacharyya AK. Asian J Androl. 2003 Sep;5(3):230.

6. Male fertility is linked to the selenoprotein phospholipid hydroperoxide glutathione peroxidase. Foresta C, Flohe L, Garolla A, Roveri A, Ursini F, Maiorino M. Biol Reprod. 2002 Sep;67(3):967-71.

7. Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Keskes-Ammar L, Feki-Chakroun N, Rebai T, Sahnoun Z, Ghozzi H, Hammami S, Zghal K, Fki H, Damak J, Bahloul A. Arch Androl. 2003 Mar-Apr;49(2):83-94.

8. Low seminal plasma folate concentrations are associated with low sperm density and count in male smokers and nonsmokers. Wallock LM, Tamura T, Mayr CA, Johnston KE, Ames BN, Jacob RA. Fertil Steril. 2001 Feb;75(2):252-9.

9. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP. Fertil Steril. 2002 Mar;77(3):491-8.

10. A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility. Kessopoulou E, Powers HJ, Sharma KK, Pearson MJ, Russell JM, Cooke ID, Barratt CL. Fertil Steril. 1995 Oct;64(4):825-31.

11. Coenzyme Q(10) supplementation in infertile men with idiopathic asthenozoospermia: an open, uncontrolled pilot study. Balercia G, Mosca F, Mantero F, Boscaro M, Mancini A, Ricciardo-Lamonica G, Littarru G. Fertil Steril. 2004 Jan;81(1):93-8.

12. Coenzyme Q10: another biochemical alteration linked to infertility in varicocele patients? Mancini A, Milardi D, Conte G, Bianchi A, Balercia G, De Marinis L, Littarru GP. Metabolism. 2003 Apr;52(4):402-

Ask the Experts – Fibroids: To Keep or Remove?

Sunday, February 13th, 2005
Dr. Isabelle Ryan is an experienced infertility specialist provider of fertility care who offers patients a combination of excellent clinical expertise, strong research experience and warm personal care.
More about Dr. Ryan · Read Other Posts

Q.
I sought our physician’s opinion about how my fibroids might impact our desire to get pregnant. Eight doctor opinions later, we are no closer to a decision. About half of the experts advise surgical removal; and the other half tell us to try to get pregnant despite them. Why is the medical community divided on this?

A.
Fibroid(s) of the uterus, also known as leiomyomas or just myomas, are benign growths that may be located on the exterior of or within the muscle layer of the uterus, or may be growing within the lining of the uterus. For the vast majority of women, fibroids do not cause significant health problems.

A few women who desire pregnancy may need to have their fibroids removed (myomectomy) prior to conceiving if the fibroids are very large (greater than 6 cm) and/or if they impinge upon and distort the uterine cavity.

Various surgical approaches to removal are further described on PFC’s web site, along with a more in depth summary of the factors that our physicians consider when counseling a patient to undergo a myomectomy.

You probably received different opinions because the impact of fibroids as related to pregnancy chances depends on the size and location of the fibroids. Other issues to consider are that fibroids are dependent on estrogen to grow, and high levels of estrogen produced during pregnancy can lead to rapid growth of the fibroid(s). If the fibroid is on the outer surface of the uterus, this may present little problem. If the fibroid is located within the uterus muscle wall or nearer the uterine cavity where the fetus is growing, a patient may be at higher risk for various pregnancy complications (miscarriage, preterm labor…).

In rare cases, the fibroid may grow so rapidly during pregnancy that it outgrows its blood supply and starts degenerating, which can be painful and sometimes lead to pregnancy complications. Also uncommon but of significance is the fact that some fibroids may block the lower portion of the uterus, prohibiting the baby’s head to descend into the birth canal, making cesarean delivery necessary. However, it is important to keep in mind that the majority of patients with fibroids experience no problems during pregnancy.

What is the impact of fibroids on pregnancy chances? It is unclear that there is any negative impact, if the fibroids are small and not growing within or distorting the uterine cavity.

 
Welcome to InfertilityDoctor.com, blog of Pacific Fertility Center. Located in San Francisco, California, PFC is the leading Bay Area infertility clinic specializing in PGD: preimplantation genetic diagnosis, IVF: in vitro fertilization, egg donor programs, embryo freezing, ICSI & IVF as well as other advanced female and male infertility treatment solutions. Our office is conveniently located near the Bay Bridge and is accessible to those traveling from Bay Area communities such as the East Bay (Berkeley, Oakland, and Walnut Creek), North Bay (Marin and Santa Rosa), Peninsula (San Mateo), and South Bay (San Jose). Our office is also less than an hour-and-a-half from Northern California communities such as Sacramento and Stockton.
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