GIVF Fertility eNews
August 2008

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World-renowned for its pioneering work in infertility and genetics, GIVF developed or perfected many of the treatments and techniques used today in other centers. 

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Olympics and Infertility 

Everyone who watched the 2008 Beijing Olympics marveled at the three silver medals won by Dara Torres, 41, the oldest American swimmer on the team. She first competed in the Olympics in 1984 at the age of eighteen. Torres competed in an unprecedented fifth Olympic games after foregoing eight years of competition. Her recent medals raise her career Olympic total to twelve (four gold, four silver and four bronze).
 
What viewers of the Olympics might not know is that Torres' daughter, Tessa Grace, was conceived through IVF. Torres' story highlights the little known occurrence of infertility in female athletes who perform at the highest levels of competition.
 
Olympic Medal Winners 

Exercise is a well-recognized approach to the enhancement of general health and well-being. In contradistinction to the beneficial effects of exercise, there is increasing evidence that heavy exercise may have detrimental consequences in female athletes. When exercise is started during adolescence, athletes have increased ovulatory dysfunction reflected as menstrual irregularity. It is well recognized that long distance runners, swimmers, dancers and other competitive female athletes have varying degrees of menstrual dysfunction. Menarche (onset of menses) may be delayed by as much as 3 years and these women have more menstrual abnormalities in adulthood than their non-athlete peers. Menstrual dysfunction is usually a reflection of abnormal folliculogenesis and ovulation. Consequently, female athletes and others engaging in heavy physical exercise are often subfertile.

Female participation in high school athletics has increased 800% in the last thirty years. Menstrual abnormalities have subsequently increased. One study evaluating cross country runners found that twenty-three percent of these women reported irregular menstrual cycles. Interestingly, nineteen percent of these cross country runners reported previous eating disorders. As many as forty percent of female triathletes have menstrual dysfunction. As many as two thirds of runners who have menstrual periods have short luteal phases or are anovulatory. The extent to which exercise-related infertility exists has been underestimated because of a lack of attention to anovulatory cycles in female athletes.

Although the pathophysisology of exercise-induced amenorrhea and infertility remains to be elucidated, some common themes have emerged. The preponderance of the evidence indicates that the condition is influenced by modulators of the hypothalamic-pituitary-ovarian axis. Gonadotropin releasing hormone (GnRH) is a peptide hormone that is synthesized and released by the hypothalamic portion of the brain. GnRH causes the release of both follicle stimulating hormone (FSH) and luteinizing hormones (LH) from the anterior pituitary gland. FSH and LH are the primary hormones that control ovarian function. Disturbances within the hypothalamic-pituitary-ovarian axis alter the pattern and quantity of FSH and LH release resulting in abnormal ovarian function often reflected as abnormal menses. Central inhibition of GnRH can be discerned in some female athletes even before there is perceptible evidence of menstrual irregularity. This is a very important observation in view of the fact that not all of these athletes will exhibit overt menstrual irregularities. There appear to be three primary modulators of exercise-induced infertility: a critical level of body fat, energy expenditure, and stress.

Both body weight and the proportion of body fat must be maintained above a critical level for the onset of menses to occur and for normal menstrual function to be sustained. A loss of body weight in the range of 10 to 15% of normal weight for height represents a loss of about one third of body fat which will result in abnormal menstrual function (Falsetti et. al., 1992). This concept is recognized as the "critical weight hypothesis" (Frisch 1985). The proportion of body fat is also very important to maintain normal menstrual function. It has been estimated that approximately 22% body fat is necessary to maintain normal menstrual function. This body fat criterion is not completely accurate; nevertheless, the concept is valid and remains useful to illustrate the concept. Competitive female athletes have about 50% less body fat than the non-competitor and less than the 22% required for normal menstrual function. Fat is converted to lean body mass during exercise. As a result, there may be no discernible change in total body weight in the athlete. Competitive female athletes generally have less than the 22% body fat required for normal menstrual function since these women have about 50% less body weight than those who exercise less. There may be no significant change in total body weight in the athlete since fat is converted to lean body mass during exercise (Frisch et. al., 1993).

Energy availability is defined as dietary energy intake minus energy expenditure. Low energy availability appears to be the factor that impairs reproductive function. Restrictive eating behaviors practiced by girls and women in sports or physical activities that emphasize leanness are of special concern. Differential physiological mechanisms controlling energy balance are closely linked to fertility. Metabolic status is transmitted to the brain via peripheral (e.g. leptin, insulin, and ghrelin) and central (e.g. neuropeptide Y., melanocortin, and orexins) metabolic fuel detectors. When oxidizable fuel is scarce, these detectors function to inhibit the release of gonadotropin releasing hormone and luteinizing hormone, thereby prompting alteration of ovarian function and reproductive cyclicity.

Infertility can result when resources are abundant, but food intake fails to compensate for increased energy demands. Examples of these conditions in women include anorexia nervosa and exercise-induced amenorrhea. Caloric restriction caused by under-nutrition or over-exercise is increasingly common, and has significant health consequences such as hypothalamic amenorrhea and infertility. Several observations provide further evidence of the tight association between energy balance and reproduction. For example, fifty-three percent of female triathletes were found to be in caloric deficit, forty-seven percent had a fat deficit, forty percent had a protein deficit in one study. These findings highlight the importance of metabolic imbalance in female athletes.

Exercise represents a physical stress that challenges homeostasis. Stress and stress hormones play a profound role in the etiology of the onset of menstrual dysfunction in female athletes. Adrenocorticotrophic hormone (ACTH), corticotrophin releasing hormone (CRH), adrenal steroids and cathecholamines are increased in female athletes. Endogenous opiates are thought to decrease GnRH secretion and, thus, the release of LH and FSH for ovarian stimulation. Abnormal luteinizing hormone pulse frequency has been observed in high performance female athletes. When the stressor (heavy exercise) is removed, menstrual function returns to normal. For example, dancers experience the return of normal menstrual function during periods of rest. This observation implies that abnormal ovarian function associated with the stress of exercise is a reversible endocrine metabolic phenomenon. The degree of reversibility is unknown, although general experience indicates that the majority of women regained ovulation upon decreasing the stress of exercise and correction of caloric intake.

Historical and physical evidence should lead the clinician to suspect exercise or dietary related ovulatory dysfunction in patients with a history of heavy exercise. Abnormal ovulatory function associated with heavy exercise is usually reversible, providing that there are no other underlying neuroendocrine causes for the problem. The prognosis for return of normal menstrual function and pregnancy is excellent with early recognition, and simple weight gain will often reverse the state of amenorrhea. Nutritional counseling should be an integral part of the treatment plan. Full weight recovery and restoration of metabolic balance can lead to reversal of ovulatory dysfunction. A multidisciplinary treatment team should include the physician or other health care professional, a registered dietitian, and, for athletes with eating disorders, a mental health practitioner. When pregnancy is desired, reduction in the amount of exercise and weight gain should be recommended, or induction of ovulation may be pursued. It is important for the clinician to realize that suboptimal ovulatory function may exist in female athletes with regular menstrual cycles and that routine hormone testing may not detect subtle changes in the patterns of hormone secretion. Advanced assisted reproductive techniques may be necessary depending on the severity of the patient's ovulatory dysfunction.

What's New at GIVF


 
GIVF DONOR EGG IVF SUCCESS RATES CONTINUE TO SHINE. Since January 1, 2008 GIVF has recorded a donor egg clinical pregnancy rate of 75%. For additional information visit www.givf.com or call (888) 834-2229 for an appointment.
 
GIVF ANNOUNCES AFFORDABLE SPLIT CYCLE DONOR EGG IVF PROGRAM. Effective September 1, GIVF is introducing a new split cycle option for sharing a fresh Donor Egg IVF cycle with another recipient. A Split Cycle means that two recipient couples are matched with one donor, cycles are synchronized and the eggs retrieved from this donor are shared or "split" between both recipients. This allows patients to attempt pregnancy through the use of donor eggs and still experience the same high pregnancy rates, while decreasing their overall costs. Please ask your GIVF physician if this program is right for you.  
 
GIVF VITRIFICATION PROGRAM FEATURED IN WASHINGTON POST. GIVF's Director of Embryology, Andrew Dorfmann, discusses the Institute's Vitrification program in this recent article appearing in the Washington Post. For more information and to read the full article, click here
  
GIVF HOSTS RECEPTION FOR WASHINGTON AREA WOMEN'S FOUNDATION. Genetics & IVF Institute will host a luncheon to spotlight volunteer opportunities with Grantee Partners of the Washington Area Women's Foundation at GIVF's headquarters in Fairfax, VA on Tuesday, September 30, 12:00 pm to 1:30 pm. Please click here to register for the luncheon and find out how you can help women and girls through these programs.
 
AATB. Stephen H. Pool, PhD, Director of Fairfax Cryobank and Cryogenic Laboratories, Inc., which are divisions of GIVF, has been voted Chairman of the Reproductive Council of the American Association of Tissue Banks (AATB). The American Association of Tissue Banks is dedicated to ensuring that human tissues intended for transplantation are safe and free of infectious disease, of uniform high quality, and available in quantities sufficient to meet national needs. The Reproductive Council provides promotional and educational programs regarding safe collection, processing and handling of reproductive tissue including, sperm, oocytes, and embryos.
 
GIVF BLOG. GIVF is now sponsoring a blog, "Infertility Bits," to provide a more frequent and informal discussion about infertility and reproductive issues. For additional information, please visit the blog at www.givf.com/blog
 
 
 
 
Ask a Question  
 
Are babies born through IVF at an elevated risk for birth defects?
 
Determining if babies born after IVF are at any elevated risks for birth defects or other conditions is very important. Many studies have evaluated birth outcome data, and overall, most babies born after IVF are found to be healthy. Specifically, studies have examined obstetrical outcomes such as birth weight, prematurity, and hypertension in pregnancy. Some studies have looked at the rate of sex chromosome abnormalities, like Klinefelter syndrome,  following ICSI  (intracytoplasmic sperm injection). A small amount of data suggests a possible connection between rare genetic disorders and IVF, however the data are quite limited.   
 
Many of the studies showing risks associated with IVF are criticized because they compare babies born following assisted reproductive technologies (ART) to babies of the general population. Most studies have not accounted for the fact that couples with infertility or couples of advanced reproductive age may have a higher chance for certain conditions with or without the use of ART.  While additional research is needed in this area, the current consensus in the medical community is that the benefits to be gained from the use of ART outweigh any potential increased risks above that found in the general population.    
 
If you have more questions about this topic, please contact your Reproductive Endocrinologist. The ASRM also provides information for patients on this topic on their website.
Does Acupuncture Improve IVF Outcomes?
 
Laurence C. Udoff, MD, FACOG
 
 
Dr. UdoffCan acupuncture, which has been utilized in China for centuries to regulate the female reproductive system, really improve success rates for patients undergoing IVF, one of today's modern medical miracles? This is what many patients and doctors are asking as numerous reports have appeared in well respected, prestigious medical journals suggesting that patients who complement IVF with acupuncture have a better pregnancy rate than patients who have IVF alone.
 
Acupuncture is part of Traditional Chinese Medicine (TCM) which is based on the view that everything is created and ruled by two principle energy forces called "yin" and "yang". Balance and free flow of these energies are critical to the health of our body and mind. Too little, too much or a blockage of the free flow of the energy are common examples of illness, according to TCM.
 
Generally speaking, acupuncture is given in two forms: a fixed protocol which composes predetermined acupuncture points and frequency of treatment; and an individualized treatment approach where points change with each patient, following a TCM diagnosis. Besides the choice of the acupuncture points, the way the acupuncture needles are manipulated, such as rotating the needles in a certain direction, or in conjunction with electrostimulation, are components of the treatment. These manipulations are believed to enhance the effect of the needles in balancing the energy, or opening the energetic pathways.
 
Despite centuries of use, only recently have modern investigative methods been used to evaluate claims that acupuncture can improve the chances for pregnancy. The earliest reports focused on the use of acupuncture to treat women who do not ovulate regularly. Studies by Gerhard et al (1992), Chen et al (1997) and Stener-Victorin et al. (2000) concluded that acupuncture could be considered as an alternative or adjunct to traditional ovulation induction with medications such as clomiphene. Studies also were published that indicated that acupuncture was effective peri-operative anesthesia for egg retrieval. One of these trials (Stener-Victorin 1999) also found that the pregnancy rate in those patients receiving acupuncture for peri-operative anesthesia was significantly higher. Though this was not confirmed in subsequent trials by this and other groups, interest increased in the possibility that acupuncture could improve success rates in IVF patients.
 
To study the impact of acupuncture on IVF outcomes more conclusively, a randomized controlled clinical trial would be needed to take into account the many variables that can impact success rates with IVF. In a randomized study, patients are assigned to a treatment group or a control group (no treatment) by random selection (like a flip of a coin). This helps to ensure that factors such as age, egg quality, and sperm quality are evenly distributed between the groups. In a study where patients are free to choose whether or not they get acupuncture, it is possible that patients with a poorer prognosis would be more likely to choose acupuncture as a means of doing anything they can to improve their chances for success. Conversely, patients who believe they have a good prognosis may not want to do anything that is not proven fearing it may lessen their chances for success. In this scenario, the impact of acupuncture could not be accurately assessed.
 
The first randomized clinical trial investigating the impact of acupuncture on IVF outcomes was reported by Paulus et al. (2002). In this study, conducted in Germany, 160 IVF patients were randomly assigned to acupuncture (treatment twenty-five minutes before and after embryo transfer) or no acupuncture. The clinical pregnancy rate in the acupuncture group was 42.5% vs. 26.3% in the control group. This represented a statistically significant difference, meaning that it was very unlikely these results occurred by chance. This rather dramatic increase in pregnancy rate caught the attention of patients, clinicians and researchers around the world and stimulated great interest in the use of acupuncture as an adjunctive treatment to enhance pregnancy rates in infertility patients undergoing IVF.
 
Like any good study, the report by Paulus et al. generated more questions than answers. Chief among them was the possibility that the results represented a placebo effect rather than a true impact of TCM/acupuncture. To answer this question, many critics called for studies that included a placebo control group where patients would be randomized to "real" acupuncture or to treatment that seems like real acupuncture, but actually uses needles placed in non-acupuncture points and too shallowly to produce the desired effect. Others have stated that a placebo control group is not really possible in an acupuncture study as there are people who are very sensitive to any manipulation and this could cause a treatment-like effect. Others have stated that a placebo control is only needed for studies with a subjective outcome (e.g. pain relief studies) not when there is an objective outcome like pregnancy.
 
In the years that followed the study be Paulus et al., numerous articles appeared in the literature reporting the results from randomized clinical trials (some with placebo controls and some with just "no treatment" controls) studying the impact of acupuncture on IVF pregnancy rates. The results were mixed, with some studies showing a statistically significant improvement in pregnancy rates and some studies showing no difference. Only one of the eight randomized studies reported so far has found a lower pregnancy rate in the acupuncture group. The investigators in this study have not yet explained why the results of their trial are so different from previous studies. They did note that in their study patients sometimes had to travel significant distances to get acupuncture treatment before and after embryo transfer.
 
In an attempt to clarify the situation, a group at the University of Maryland Center for Integrative Medicine reported the results of a meta-analysis (Manheimer 2008). This commonly used method combines data from many smaller studies (which may not have had enough patients to reach a statistically significant result) into a single analysis that may be more likely to find a statistically significant difference between treatment and no treatment (or placebo) groups. In fact, this study concluded that complementing the embryo transfer process with acupuncture was associated with a 65% increase in the clinical pregnancy rate. The study also noted that this effect was not seen in the studies where the no treatment or placebo group had higher (or more average) success rates. More studies with larger patient numbers were suggested to more definitively answer this question.
 
In summary, to date, more than twenty research studies have been performed to examine the impact of acupuncture on patients undergoing IVF for the treatment of infertility. Thus far, the results have been mainly positive, though not all studies have found a benefit and one trial suggested a lower pregnancy rate with acupuncture. Larger studies are needed to address the many questions raised, including the possibility of a placebo effect and a plateau effect (i.e. may only help increase the pregnancy rate to a certain level and if the patient's expected IVF pregnancy rate is at that level or beyond, the intervention has no benefit). There is also the question of lack of a biologically plausible mechanism (i.e. how does acupuncture increase the pregnancy rate?). Several hypotheses have been proposed, but none are proven, including a positive affect of acupuncture on blood flow to the uterus and ovaries, a reduction in stress levels, and mediation through beta-endorphin levels (the purported mechanism by which acupuncture reduces pain). It is hoped that future studies will adequately address these issues and give patients the information they need to make a better informed decision about whether to include acupuncture as part of their IVF protocol. For now, the most sensible approach for physicians is to keep an open mind and not to discourage patients who may wish to add acupuncture treatment to their IVF cycle. Certainly, it will be interesting for all of us to see what future studies may prove.
 

Copyright 2008 Genetics & IVF Institute