Photos provided by 3DbabyVu

A first glimpse of a baby in the womb, especially for women who have faced an arduous route to pregnancy, is perhaps as euphoric a moment as the “You’re Pregnant!” announcement. It is only natural for parents to want a visual connection with the infant as early as possible.

Seizing on this yearning, a new crop of commercial ultrasound studios has mushroomed all over the country, offering parents a chance to have a first look via an elaborate 3D and even 4D video ultrasound. At least three such businesses are in the Bay Area. Yet new parents contemplating a nonmedical 3D ultrasound simply for novelty or posterity should be fully aware of this technology in a rapidly evolving marketplace.

The safety of common medical ultrasounds is undisputed. For over 35 years, ob-gyns have used 2D ultrasound technology as standard practice to medically diagnose the health of a weeks-old fetus, enjoying an early glimpse of its emerging shape, major organ development, tissue and blood flow and when desired, the gender. The ultrasound repertoire is so common; over 80 million procedures are now performed in the US each year, reports one clinic.

Nevertheless, the Food and Drug Administration (FDA) and the primary medical association that oversees ultrasonography – the American Institute of Ultrasound Medicine (AIUM), have thus far refused to endorse 3D and 4D ultrasounds offered by commercial studios. The concern is less about the technology itself, and more about how it is applied. While the sound wave levels used for a 2D and a 3D/4D are reportedly of the same frequency, (it’s the computer diagnosis that creates the image differentiation), there is more built-in oversight in the medical community performing diagnostic ultrasounds.

For instance, is the person performing the commercial fetal portrait properly trained? Right now, it is up to the 3D studio to make sure that the person controlling the knobs and holding the transducer has undergone the same training standards required for ultrasonography at an ob-gyn office. Professional (non-physician) ultrasound practitioners undergo nearly three years of training, including 12-18 months for didactic and 12-18 months of clinical practice in order to gain the key certification from the American Registry of Diagnostic Medical Sonographers (ARDMS).

Moreover, there is concern that a commercial portrait ultrasound will reveal a developmental problem with the fetus that should be observed and discussed only through a physician/patient relationship. Another concern is that enthusiastic parents will forego a routine medical ultrasound after obtaining an elaborate portraiture one. In response, many commercial ultrasound studios are requiring patients to bring proof of a prior medical diagnostic ultrasound.

Finally, knowing a bit about the technology helps parents make an informed decision. In the medical community, the standard is to expose the fetus to the lowest possible exposure level for the shortest amount of time, usually 10 minutes or so. Because frequent ultrasonography at higher levels can produce a heating effect in bone and tissue, the aim is to minimize exposure. Yet some commercial fetal portrait studios offer deluxe packages involving a 45 minute video ultrasound.

A spokesperson from 3DBabyVu insists that the potential for physical damage to the fetus via a wrong decimal level setting is literally and virtually not possible, at least with the standard GE Voluson machines, which provide a cap to the frequency level. Yet he admitted that the same machines have two other settings for cardiac mode and vascular mode to examine more robust adult tissue. If patients choose to purchase a dynamic 3D or 4D image package offered by one of these enterprising studios, we strongly recommend that you learn as much as possible and even consult with your ob-gyn if you are at all confused. Also, it is best to confirm that the sonographer at the commercial studio is ARDM certified. Because the practice of fetal portraiture imaging is self-regulated, it is the patient’s responsibility to be aware of current research and be as informed as possible prior to using this new technology.

More and more patients undergoing fertility treatment ask about incorporating acupuncture and Chinese herbal medicine treatment with their IVF cycle. Some patients are especially inquisitive after reading Lifang Liang’s recently published book Acupuncture and IVF: Increase IVF Success by 40-60%. For most patients going through the struggle of infertility, this title proposes a provocative and enticing claim.

While acupuncture is based on an ancient medical tradition, current studies are trying to clarify the physiological basis for treatment results. Some indicate that the benefits of acupuncture may be mediated by opioid-types of proteins in the central nervous system. Some of the proteins affect gonadotropin secretion from the pituitary (brain), and therefore could impact menstrual cyclicity to help regulate ovulation. Others propose that blood flow to the pelvic organs may be improved through mechanisms other than the central nervous system therefore improving fertility. And yet others propose there might be a psychosomatic benefit.

While all these theories are intriguing, a true understanding of the benefit of acupuncture and its impact on fertility will not be elucidated until the execution of several well designed studies (large numbers of patients, randomized controlled trials).

To date, there is only one such study (Paulus et al, Fertil Steril. 2002 Apr;77(4):721-4), which was conducted in Germany. While this study revealed an improvement in pregnancy rates, there are a number of issues with the study itself, which calls for cautious interpretation of the final results (an improvement in pregnancy rates from 26% to 42% – 61.5% improvement rate). For instance, the study was weakened by a low baseline pregnancy rate (26.3%) in a young patient population (early 30yo). Statistically, it is much easier to show an improvement in pregnancy rate, when the baseline pregnancy rate is so low. This finding may not hold true if this study was performed in an IVF center where the pregnancy rates in young patients was closer to 50% (which is what we expect for patients in their early 30s). More importantly, when studying such complex questions, a clear understanding will not be obtained, and claims of improvement cannot be made, until a number of well designed studies are performed and the majority of results echo a similar theme (either positive or negative).

In her book, Lifang Liang presents a nice overview of the theories behind Chinese Medicine, as well as various herbal treatments available for fertility patients, and their proposed effects. She then presents a number of “Case Histories”, illustrating the use of both herbal therapies and acupuncture. While these are quite interesting, they are anecdotal stories, and do not represent a scientific study to evaluate the role of acupuncture and infertility. The above study by Paulus et al is mentioned in the book, and seems to be the basis for the claim of a 40-60% increase in IVF success rates. As mentioned, this claim should be taken with caution.

All of us who serve patients with fertility treatment, whether trained in Western or Chinese medicine, are looking for the best possible outcome for our patients. It would be wonderful if indeed there was a combination of various treatment approaches which, when practiced together, could provide the best “cocktail”. However, the exact role that acupuncture plays is currently an unanswered question, until more well-designed studies are performed. We look forward to such studies, to better define the role of acupuncture and herbal remedies in the treatment of infertility.

What might a mindful career-oriented 36-year-old woman have in common with a 22-year-old just diagnosed with an unusual cancer and scheduled for radiation or chemotherapy treatment?

• Both may want to carefully chart their course of family planning.
• Both face the loss of their ovarian egg reserves: one from the damaging chemotherapy, the other from age.
• Both may be considering oocyte (egg) freezing.

The idea that a woman can undergo a standard IVF procedure and then freeze individual eggs, instead of having her oocytes inseminated and then frozen as an embryo, is a notion that is capturing the imagination of grandmothers, women and doctors alike. So much so, dozens of infertility clinics are boasting egg cryopreservation as a new service even though most qualify it as “experimental”. Indeed, egg freezing is simply too new, and it has not shown the success rates necessary for widespread marketplace acceptance. This procedure is not a panacea or an insurance certificate for everybody. However, it can be a viable option for women who are aware of its limitations.

What is most important is a patient’s absolute understanding of the challenges of egg cryopreservation. To say women’s oocytes are much more difficult to freeze than male sperm is an understatement. A good quality female egg is essentially a pin head-sized globule of fluid plus the necessary DNA to carry new life into being. It is this sac of liquid that must be carefully drained and then filled with anti-freeze to help the egg freeze and thaw. Accomplishing this without damaging the microcosm of genetic material, as delicate as a spider web, is the main hurdle. When egg quality is compromised, a myriad of problems ensue: failure to fertilize or implant, miscarriage and birth defects.

The race to offer egg cryopreservation was initially fueled by favorable research results from a study that used subjects in their early 20s, and which resulted in >50% chance of a live birth. Yet with only 7 subjects, that study is not statistically significant. In subsequent studies that used women in their early 30s, the success rate dropped below 25%. Currently, most U.S. clinics pioneering this procedure predict only an 8-10% chance of live birth. Also, a side effect of freezing is the hardening of the egg’s outer membrane, known as the zona pellucida, making sperm penetration difficult. However, this is overcome by using ICSI (intracytoplasmic sperm injection).

Those requesting this service need to have all of the facts before making a choice. In particular women in their mid- to late-30s, who tend to be the most enthusiastic candidates, need to weigh other options with higher proven success rates. We at PFC share an understanding with much of the medical community that this procedure may be the right choice for the right person, but only with a full understanding of its limitations. This will be our approach when we start offering egg cryopreservation to our patients later in 2004.

The marketplace offers a dizzying selection of devices to help women predict ovulation to increase their odds of conceiving. Collectively, these products are called ovulation predictor kits (OPKs) or fertility monitoring devices.

They are broadly grouped into two main types: those that gauge a woman’s Luteinizing hormone (LH) surge and those that monitor one’s estrogen level. The LH surge is tracked with urine testing strips, which are then discarded. Estrogen can be tracked with longer-use fertility monitoring devices that check saliva or other bodily fluids.

When under-going artificial insemination (AI) and intrauterine insemination (IUI), women need a very precise measurement of ovulation. Single-use OPKs that require urine testing first thing in the morning or after 2-4 hours of “holding it” are ideal for this. They react when a woman’s pituitary gland sends out an LH surge, directing the egg to leave the ovary in 24-36 hours, like clockwork. The egg then spends the next 6-12 hours sliding down the fallopian tube where it must be fertilized before implanting into the uterus. This critical window requires sperm to be on the spot, ready to fertilize.

For LH testing, PFC recommends ClearPlan/ClearBlue Easy and Ovu-Kit One-Step because, in our experience, they tend to give the most unambiguous results. The kits that are not as highly recommended are Answer, First Response and generics; they appear to be more prone to false negative results.

For couples timing pregnancy to the LH surge, natural intercourse is recommended both on the day that the kit changes, and the next day. If a couple is going through IUI with fresh sperm, the insemination will be timed the day after the kit shows ovulation. If frozen sperm is being used, many times two inseminations take place: one on the day of change and another the following day.

The longer-use ovulation monitors that use saliva to measure estrogen levels typically identify a 72 hour peak “zone” of fertility. Tracking estrogen levels can be a fascinating process, although patients may need additional time to train their eye to spot the critical pattern that appears in saliva with elevated estrogen. Curiously, the salt content in body fluids increases with a rise in estrogen. Once dried in a magnified setting, the saliva reveals a distinct crystallization, or “ferning” from the salt level (see illustration on left), similar to ice patterns on a frosty window.

Some name brands include Fertile Focus, the Donna and Lady-Q. These devices are useful if couples can have frequent intercourse during their 3-6 day zone of fertility.

A brand new product that also tracks ovulation via estrogen levels uses a wrist watch-like calculator that must be worn every night. This device makes direct contact with one’s skin, and uses a sensor that contains a non-allergenic gel released to detect one’s estrogen from the moisture released off the wrist.

Since PFC has not reviewed the estrogen-monitoring products and their efficacy, patients are strongly advised to do their own research.

*Reproduced with permission: www.maybeit.com

Stress reduction through mindful well being… while this may sound like a new age mantra, the medical community is growing in consensus about a mind/body connection that can positively impact a patient’s health. No other physician has probed the mind/body infertility correlation deeper than Alice D. Domar, Ph.D., who has written extensively on health and stress, conducted research and designed a comprehensive workshop series. Included in these mind/body and mindfulness health and wellness programs are relaxation techniques involving controlled breathing and posture awareness; yoga, meditation, journaling, neuro-linguistic programming, and joining a support network. Dr. Domar’s techniques are designed to help women treat their own stress responses so their bodies might have a higher chance of conceiving. Pacific Fertility Center’s team has examined the scientific, medical and anecdotal information surrounding the topic of stress and infertility. And because various relaxation inducing/stress reducing techniques are likely to have an overall positive impact on a patients’ general health, PFC is offering classes modeled around Dr. Domar’s mind/body practice (see Mind/Body@PFC) Indeed, infertility clinics all over the country are offering similar programs despite the lack of scientific consensus about how stress affects fertility. Skeptics point out that millions of people under extremely stressful circumstances, even kidnap and rape victims, regularly get pregnant. But some facts are clear: Ongoing chronic stress can affect menstrual function; change hormone levels; alter blood sugar; increase heart rate and change a person’s immune response. Mind/body therapies are frequently initiated for groups with serious medical conditions, from lupus to multiple sclerosis to major heart disease. It is only natural that the more serious an illness, the more anxiety it can induce in a patient, thus potentially bringing on accelerated and aggravated symptoms. This vicious stress/body cycle, when broken through stress reduction techniques, can provide overall improvement in health. Dr. Domar’s initiated one of the few controlled studies funded by the National Institute of Mental Health on this topic. Results of the research showed an improvement in pregnancy rates using either relaxation techniques or though the psychological support of joining a group. With so much growing attention into the mind/body stress reduction methodologies, there is bound to be a greater body of critical scientific knowledge gathered. Meanwhile, take a deep breath and consider your own stress response strategy.

– Carolyn Givens, M.D. and Isabelle Ryan, M.D. contributed to this article

Despite the overwhelming success of In Vitro Fertilization (IVF) in helping couples to conceive in the past 25 years, there remains a group of women for whom there is no obvious explanation for repeated IVF failures. This has led to hundreds of theories, most debated and subsequently discarded, to explain these inexplicable, yet relatively uncommon embryo implantation failures.

One popular theory that lingers is that the implantation process is facilitated in part by the maternal immune system, acting at the contact point of the uterine lining and the normal embryo. While there is little doubt that many biological processes are likely at work here, the exact mechanisms of embryo implantation remain poorly understood. More basic research is underway to further understanding of this complex process.

Taking off on this theory that some abnormality in the immune system is responsible for implantation failures, some IVF practitioners will run a battery of tests for antibodies to phospholipid molecules on their IVF patients. These phospholipids are everywhere on cell surfaces. At high levels, such as with some auto-immune diseases, the presence of antibodies to phospholipids can lead to clotting disorders and sometimes repeated, mostly second trimester pregnancy losses. Much more controversial is the question of whether or not anti-phospholipid antibodies play any direct role in inhibiting embryo implantation. Approximately 9% of normal fertile women can be found to have anti-phospholipid antibodies in their blood.

A well designed study from 1997 by Denis and colleagues found that in a large number of patients undergoing IVF, the presence or absence of these anti-phospholipid antibodies prior to treatment had no effect on IVF outcome. This is why the majority of reproductive endocrinology and infertility specialists, including Pacific Fertility Center, do not run anti-phospholipid antibody tests on their infertility patients. But some IVF practitioners routinely run these tests and, based on the presence of any positive titers of antibodies, will prescribe a regimen of twice daily injections of heparin and a tablet of children’s aspirin daily. Heparin is a blood thinner and is known to inhibit the binding of anti-phospholipid antibodies to phospholipids on cell membranes.

Prior studies examining heparin use have resulted in conflicting findings, some studies showing amazing benefits and others finding none at all. Most of the prior studies had design limitations that made it difficult to form firm conclusions. This conflict, coupled with the inherent potential risks of heparin use, have limited the use of this controversial therapy to a very small number of centers.

A new study, recently published in the August issue of Fertility and Sterility (an official professional journal) may finally put the debate to rest. The study was designed as a randomized, double-blind, placebo-controlled trial of heparin and aspirin for women with prior in vitro fertilization failure, and with positive signs of anti-phospholipid antibodies or anti-nuclear antibodies. This study protocol is considered the “gold standard” design for a clinical trial and when performed as designed, the results are very hard to dispute.

Basically, some of the women, all of whom had had at least 10 embryos transferred over several prior IVF cycles and who had no known explanation for the implantation failure, were randomly assigned to receive either heparin and aspirin or a placebo (blank) during their IVF or frozen embryo transfer cycle. Neither the researchers nor the patients were aware whether or not the patient was receiving the active drug until the study was completed, to eliminate any potential study biases.

For the women receiving heparin and aspirin, a total of 296 embryos were transferred. This resulted in 20 cases with positive fetal heartbeats on early ultrasound (7%). For the placebo group, 259 total embryos were transferred and there were 22 positive fetal heartbeats (8%). Keep in mind that these patients had been through several prior IVF attempts so their overall chances for success would be low to start with. The live birth rate for the heparin and aspirin group was 6% and was 7% for the placebo group. There was no statistical difference in these numbers.

The bottom line on this study is that even with positive anti-phospholipid antibody tests, women with repeated IVF failures were no more likely to conceive if they received a treatment regimen with heparin and aspirin or with nothing at all. This study provides Class A medical evidence that recommendations to use heparin for infertility must be viewed very cautiously, as heparin’s effect on certain patients can be even detrimental to their overall health. For more information regarding the use of low-dose aspirin while attempting conception, please see our Sept. ’03 issue of Fertility Flash.

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.