Finally, I would like to share my philosophy about my role as a fertility physician and the set of beliefs that guides me in my relationships with my patients.

1. Be honest. My number one role as a physician is to care for my patients. This sounds so obvious, but I, as I suspect is true of most doctors, went into medicine because I wanted a career where I could provide for the medical and the emotional needs of those I CARE for. My job is to provide the best information to my patients, based on sound medical evidence (i.e. research studies) so that they can make informed decisions about their own care. Sometimes, the information I provide is good news: your chances are good, we can help you. Sometimes, the news is not so good: your chances of conceiving are statistically very low and you may need to consider alternatives. Whatever the situation, my job is to provide this honest assessment in a compassionate manner and help my patients come to the right decision.
2.  Commit to the treatment. Once the patient and I have made a decision on the course of treatment based on the best information, I commit myself to this completely. We may modify the plan as we gain more information in the process, but I am fully committed when it comes to implementing the treatment plan.
3. Keep striving to be the best. This means attending meetings, reading journals, staying current with research studies and applying sound data to keep the treatments we prescribe grounded in the best medical information. If I don’t know the answer to a problem, I do my best to find it.
4. Use information wisely. I do not jump into the latest fad in fertility treatment. After 20 years in this field, I have seen a lot of hot ideas come and mostly go. What sounds so good on the surface often, under the careful scrutiny of well done studies, does not end up being the magic bullet everyone had hoped.  However, other promising ideas (e.g. ICSI, egg and embryo vitrification, microarray PGD) do turn out to be sound. The beauty of PFC is that as soon as we can verify a treatment to be sound, we can incorporate it into our practice.
5. Strive for the overall health of our patients and their family. My responsibility is to ensure that my patients’ treatment is safe as well as effective. This means not only the safety of the patient during treatment, but also the fetus and baby.  We are working very hard to minimize multiple gestations, even twins, because this is the one thing we can do that will directly impact the health of our patients’ children.
6. Live compassion. If a physician does not take the time to get to know his or her patients and their individual needs, how can there be treatment of the complete person?  In my scrapbook I have saved the thank you cards, baby announcements and yearly holiday greetings from my patients of the last 15 years, so one day I can look back with pleasure on my life’s work. But the greatest compliment comes from the patient who tried very hard to conceive and could not, despite their and my best efforts, and says to me “thank you for giving me all you could. I know you tried your best and I was well cared-for.” That means the world to me.

 -Carolyn Givens, M.D.

This past July, I had the opportunity to attend the 23^rd Annual In Vitro Fertilization and Embryo Transfer meeting in Santa Barbara, CA. This is an IVF meeting sponsored by UCLA.  It’s hard to believe that a meeting devoted solely to IVF has been presented annually for 23 years now.  I used to think of IVF as a brand new field, but it really has matured as a specialized area of medicine. This meeting is not considered a scientific meeting because it has more of a lecture/didactic course format rather than one of   presentations of new research by physicians and scientists.  However, this meeting is devoted to bringing various experts together with clinicians providing IVF care to discuss the latest theories and clinical practices. I had not attended this meeting in several years as it had not appeared to present much new information.  However, this years’ meeting was surprisingly thoughtful and relevant.

While not the sole focus of the lectures, a definite theme running through the meeting addressed the current interest in the fundamental health of sperm and eggs. There were several talks covering the data (or lack thereof) of stress and our modern chemical-laden environment on reproduction. There was some discussion of the role anti-oxidants and other nutritional supplements play in reproduction. Dr. David Meldrum from Southern California and Dr. Peter Schlegel from Cornell Medical Center touched on whether or not anti-oxidants may be useful in improving eggs and sperm, respectively. The preliminary data is intriguing, but much further study will likely be needed. However, because anti-oxidant nutritional substance show so many benefits in other aspects of human bodily function, there is hope they will also be shown to be beneficial for reproduction.

Dr. Sarah Berga, Professor and Chairman of the Obstetrics and Gynecology Department at Emory University Medical Center in Atlanta, gave several excellent talks. Dr. Berga’s area of research interest is in the effect of stress and diet on reproduction. She is a thinker and applies scientific evidence to the theories of hormones and stress. She is an excellent speaker and has always been an open, accessible and friendly colleague of mine.

One of Dr. Berga’s talks focused on the topic of “What is Stress?” She defined two aspects of stress: metabolic stress and psychogenic stress. These two different aspects of stress result in the same pathologic process potentially leading to impaired reproduction. She discussed psychological stress that emanates from a sense of the “lack of control” that many of us, but especially individuals suffering from infertility, feel when faced with this challenge. In some individuals, there may be overly high personal expectation of oneself and of others, which contributes to a sense of failure. With regards to physiologic or metabolic stress, a harmful result of stress may be hypothyroidism. That is, decreased levels of thyroxine (thyroid hormone) may be a result of psychological stress, leading to metabolic stress, and in severe cases can contribute further to infertility and increased risks of miscarriage. In turn, it becomes the quintessential vicious cycle. With regards to diet, normal and healthy caloric intake can lower cortisol levels, which is good. Cortisol, an important adrenal hormone produced in response to stress, also shortens telomeres – the pieces of DNA on the ends of chromosomes that protect our chromosomes from damage and slows the aging process. Dietary caloric restriction and an over-energized metabolism can result in a person becoming significantly underweight.   Potentially, this could further raise cortisol levels and, in women, may contribute to lack of ovulation and infertility. Thyroid hormone levels drop, trying to slow down metabolism and hang on to calories. Furthermore, for the pregnant woman, the only source of thyroid hormone for the baby comes from the mother, and hypothyroidism in pregnancy is a serious challenge for the developing fetus. Thus far, other than thyroid hormone replacement (a band-aid for the problem), a potential solution is to attempt to break this cycle. Cognitive Behavioral Therapy (CBT) and techniques such as conscious relaxation (Mind-Body training) have shown promise in reversing these trends.

Another interesting speaker at the conference was Dr. Douglas Carrell, PhD, Associate Professor of Surgery (Urology), Obstetrics and Gynecology, and Physiology, University of Utah School of Medicine. One of his talks concerned how to locate the best sperm to inseminate eggs at the time of IVF, especially in men with male factor infertility, but potentially for all men. He spoke about various tests that some scientists currently advocate for determining whether a man’s sperm is capable of producing healthy embryos and healthy babies, such as DNA fragmentation assays. His bottom line take on this is that no one test on one sperm sample is likely to predict that all sperm are bad all the time. He also addressed an area that has interested us at Pacific Fertility Center: Hyaluronic Acid (HA) binding test and the Annexin separation sperm quality test. The HA binding test uses the phenomenon of good sperm binding to hyaluron prior to selecting that sperm for egg injection (ICSI). The Annexin separation test uses a similar substance to select out sperm that are apoptotic (DNA heavily damaged). While intriguing, neither test has yet been put to a definitive randomized controlled-trial, which would be needed to show improvement in pregnancy rates.

These are just a few of the many topics covered at this very interesting and thought-provoking meeting. I am fortunate to be a part of a fertility center that believes in the value of attending and participating in meetings that allow us to share ideas and concepts.  This sharing of ideas will no doubt lead to the further understanding and treatment of problems in human reproduction.

-Carolyn Givens, M.D.

Soothing music is playing, breakfast is on the table and your two guides for the day, Allison and Peggy, are relaxing and joking with group members who arrived earlier. So begins a day spent with others who understand your feelings, share your concerns and plan for the same outcome as you, to be parents.

As the day progresses, amid much laughter and a few tears, you experience deep feelings of peace as you are gently led through visualizations that calm the body and mind. You learn mindfulness meditation and techniques for breathing that lower your oxygen consumption, lower your heart rate and allow for your stress to run backwards, calming your tense body, quieting your anxious mind.

One of the documented benefits of practicing mindfulness is learning the practice of “being in the moment.” This ability to bring our attention to the Now is one in which we become a witness to our thoughts as they are simply passing through, much as though you are standing behind a waterfall watching water as it cascades down. Our attention is no longer wrapped up in worry or desire. We are simply bringing our attention to the breath. It is this simple act of breathing in and out that provides a space of peace.

Lunch arrives and we lounge together and talk about how best to cope through this “ordeal of infertility.” We learn to manage our unruly thoughts through cognitive restructuring, a technique that sounds complicated but is quite simple to learn. We have discussions of what foods best support us, how much to exercise, how to talk with family and friends. Then spend more time relaxing. Then, before you know it, our time together is over. However, you have made new friends, you have felt less isolated and you have relaxed.

Here is a sample of feedback from other mind/body class attendees:

“It was really good to be able to share our concerns about our journey with other patients going through similar things.”

“Peggy and Allison are a good team and complement each other. They are genuine and I appreciate their sincerity and honesty delivered with compassionate care.”

“The relaxation was difficult at first, but after the opportunity to try so many techniques, I left the class feeling very relaxed and better prepared to go through my cycle.”Join us for our monthly Mind/Body Stress Reduction Classes. You will be glad you did.

-Peggy Orlin, M.S., M.F.T. & Allison Chamberlaine, RN

Last November, PFC embryologist Erin Fischer had the opportunity to travel to Cairo, Egypt for the 16th Annual Meeting of the Middle East Fertility Society (MEFS). At the meeting, she presented an abstract on our vitrification results at PFC and also assisted with a vitrification workshop. She met many remarkable embryologists from all over the Middle East while teaching the embryo vitrification and sharing the successes that PFC has had with vitrification.She also had the chance to visit three IVF clinics in Cairo during her stay. “Seeing other IVF labs was the highlight of my trip, I was impressed by the large number of cycles that these teams performed daily,” comments Erin. She adds,“Traveling to Egypt was an amazing experience. I was proud to represent PFC and appreciate our state of the art facility.“

Endometriosis was a puzzling disease when first described by pathologist Rokitansky in 1860. Though we now have a clearer understanding of some aspects of the biology of this disease, it still remains largely a mystery 150 years later.

Endometriosis affects about 5 million women in the U.S. Of women with infertility, approximately 25% are diagnosed with endometriosis. The symptoms fall into two categories: 1) pelvic pain, most significantly with menses, and 2) infertility. The definitive method to diagnose this disease is surgery. A laparoscopy is performed to obtain tissue biopsies of typical peritoneal lesions (peritoneum is the internal layer overlaying pelvic organs including the uterus, fallopian tubes and ovaries); and confirm the presence of endometrial glands in those biopsies. The American Fertility Society has created a classification scheme which grades the disease (Grade I-IV). It is important to understand that there is not necessarily a correlation between pelvic pain and the severity (or grade) of the disease. Another method for presumptively diagnosing endometriosis is with ultrasound, if the patient has endometriosis ovarian cysts (endometriomas), or with MRI if one there is endometriosis growth in the
uterine muscle layer (adenomyosis).

A diagnosis of even minimal to mild endometriosis (stage I and II) can have significant consequences on fertility success rates. A fertile 30 year old woman has about a 25% chance of pregnancy per month (fecundity rate). A patient diagnosed with minimal to mild endometriosis has about a 3% monthly fecundity rate (1, 2, 3). If surgery is performed to dissect and remove the visible endometriosis lesions, the fecundity rate improves to 6%; but this is still much lower than the 25% afforded a fertile 30 year old. If that same patient undergoes ovarian stimulation and insemination cycles, her monthly fecundity rate increases to 11% (4). If the combination of ovarian stimulation/IUI treatment is going to increase chances of pregnancy, results are usually seen within the first 3-4 treatment cycles. Undergoing additional IUI cycles is not typically beneficial, and proceeding to in-vitro fertilization (IVF) treatment would be the next step. For patients with severe endometriosis, gonadotropin/IUI therapy is of minimal assistance. Most patients with moderate to severe endometriosis (stage III and IV) will need to pursue IVF therapy (5).

IVF studies from the 80s and 90s indicate that patients with endometriosis have a slightly lower chance of achieving a pregnancy than patients with other infertility diagnoses (6). With current IVF laboratory techniques and current ovarian stimulation strategies, this difference will probably disappear—but up-to-date studies are needed as proof. When assessing if the lower pregnancy rate is because of a uterine or ovarian issue, it appears that the uterus of endometriosis patients is effective in providing a supportive environment for the embryo to attach (7). However, the oocytes (eggs) from endometriosis patients, particularly those with endometriomas, seem to have some compromised quality (8). This lower egg quality seems to lead to less healthy and effective embryos, and therefore overall lower pregnancy rates.

We clearly understand that strategies of suppressing endometriosis growth by using medications such as birth control pills, Danazol, Lupron or others, does not lead to improved pregnancy rates (9). The concept of a fertility “rebound” post-medical suppression has been proven false over-and-over again. These strategies only lose potentially precious time for the patient. Similar strategies of using medical suppression post surgical removal of endometriosis also fail to improve fecundity rates. The best approach is to move forward with an appropriate form of fertility treatment as soon as the patient desires fertility.

How to treat endometriomas has been debated, but we now have some studies to guide us. Collectively these studies indicate that patients who have undergone surgery for their endmetrioma(s) have the same IVF outcomes as those where the endometrioma(s) was left alone (10). We feel that the patient’s current clinical situation should be scrutinized carefully before recommending ovarian surgery for a patient who is seeking fertility. With surgical removal of an endometioma (ovarian cystectomy), we know that the ovary where surgery is performed will have fewer eggs and less normal ovarian tissue post surgery (11). This implies that we will have a lower chance of gathering eggs in an IVF cycle. Additionally, the patient will have a greater chance of having an elevated FSH after a cystectomy procedure, especially if she undergoes cystectomies of both ovaries (11). The risk of premature ovarian failure (POF or premature menopause) for a patient undergoing cystectomies of both ovaries for endometriomas is about 2% (12).

Historically the strategy for treating endometriosis has been to surgically remove or hormonally suppress its growth with various medications. As we better understand the biology of this disease, we can use more targeted therapies which interrupt the biochemical pathways that promote the growth of endometriosis lesions: aromatase inhibitors, estrogen and progesterone receptor blockers, angiogenesis inhibitors, etc. All of these types of medications are being studied in endometriosis patients. The future may hold some promising new medical options.

In summary, endometriosis clearly affects fecundity rates, even with minimal and mild disease. Using hormonal medications to suppress endometriosis provides no improvement in pregnancy rates, and surgical intervention provides minimal improvement. Most patients will need to pursue fertility treatment. For patients with moderate to severe disease, they most often will need to pursue IVF. For patients with endometriomas, careful consideration has to be given to all factors (age, assessment of egg quality, prior fertility treatment, etc.). The patient needs to be fully counseled prior to surgery, including risk of diminished ovarian quality (DOR) and premature menopause (POF). Patients with adenomyosis seem to have impaired implantation rates, and those with severe adenomyosis may need to consider a gestational carrier. Having a clear understanding of endometriosis as it impacts fertility, and having realistic expectations with each treatment type is most important when choosing fertility treatment options.

– Isabelle Ryan, M.D.

References

1. Jansen RP, Fertil Steril 1986; 46:141-3
2. Marcoux et al, NEJM 1997; Jul 24; 337(4):269-70
3. Parazzini, Hum Reprod 1999; 14(5):1332-4
4. Tummon et al, Fertil Streil 1997; 68(1):8-12
5. Dmowsky et al, Fertil Steril 78:750 2002
6. Barnhart et al, Fertil Steril 2002; 77:1148-1155
7. Diaz et al, Fertil Steril 2000; 74:31-34
8. Simon et al, Hum Reprod 1994; 9, 725-9
9. Hughes et al, Cochrane Database Syst Rev 2007; 3:CD000155
10. Tsoumpou et al, Fertil Steril 2009; 92, 75-87
11. Li et al, Fertil Steril 2009; 92(4):1428-35
12. Busacca et al, Obstet Gynecol 2006; (195), 4

A Reproductive Endocrinologist (REI) is a specialist in Reproductive Endocrinology and Infertility, a medical doctor with advanced training in the science of fertility and its evaluation and treatment.  An REI focuses on the hormones and mechanics of conception with advanced knowledge of sperm, eggs, male anatomy, female anatomy, and the complex interactions between pituitary and reproductive hormones.  An REI will be trained in evaluating the problems that can interfere with conception, and has in depth knowledge of the treatments for fixing these problems.

An REI starts training after medical school in a 4 or 5 year residency in obstetrics and gynecology.  Specialty training in reproduction after residency requires 2-3 years at an advanced educational and research institute.  The fellow in REI works side-by-side with experts in the field, developing clinical expertise in evaluation and treatment of fertility, and researching new areas of reproduction.  The REI will be trained in laboratory and clinical research techniques, the mechanics and hormones of fertility, and in maintaining a lifelong love of the pursuit of advancing knowledge of fertility.

After completing the fellowship, an REI is “board eligible”. To be “board certified,” an REI must publish a thesis in a peer-reviewed journal. The REI must pass an in-depth written exam and then appear before experts in the field for an oral exam to test their depth of knowledge, defend their thesis, and demonstrate reasoning in solving fertility problems.  If they pass the exams, they are then “board certified”. This certification is the highest level of achievement in the field of infertility.

All REIs certified since 1990 are required to maintain their certification every year (a few are grandfathered in).  This involves reading and evaluating peer-reviewed journal articles on current advances in the field, and a written exam every year.  New standards require demonstration of clinical knowledge and a commitment to advancing standards of clinical care, the Maintenance of Certification (MOC) process.

While there is no formal requirement, most REIs will maintain membership in national and international fertility societies, such as the Society for Reproductive Endocrinology and Infertility (SREI).  The Society for Assisted Reproduction (SART), devoted to in vitro fertilization and its variants, does not require REI certification.  The American Society for Reproductive Medicine (ASRM) is the umbrella organization supervising these specialized societies.  Most anyone with a professional interest in fertility can join ASRM, but SREI requires board certification.

At Pacific Fertility Center, we bring a complete team of specialists together to focus on your fertility situation. With extensive backgrounds as REI specialists, embryologists, nurses, marriage and family therapists and financial counselors, we develop a single, integrated solution to your medical, psychological and financial needs.

Please use our Ask the Experts resource if you have further questions.

– Philip Chenette, MD

Spring, a time for celebrating Mothers and Fathers, can be a particularly difficult time for infertility patients. Because dealing with these two holidays can be a challenge, I have some suggestions for ways to develop some good coping skills. To cope is to “develop the ability to manage in a difficult situation.”

Here are a few suggestions:

1. Give up any and all feelings of guilt for how you are feeling! There is no right or wrong way to experience Mother or Father’s Day.
2. Know your limits and stick with them. If attending a family gathering is too painful, then don’t. You can still write a caring letter to your parent letting them know how you feel about them. If you do feel comfortable attending a family gathering, then do.
3. Plan to do something that is unrelated to parenting.
4. Attend religious services if you are comfortable knowing that the focus may be on mother’s or fathers. Perhaps you can ask your religious leader to say a prayer for those who have not yet achieved parenthood or are dealing with some other sort of crisis.
5. Plan for how you will answer uninvited questions about how you are feeling. Remember, you are not required to tell them your entire “story!”
6. Communicate with your partner to let him/her know of your feelings. Even if you and your partner are feeling differently about Mother’s or Father’s Day, it may help to share. If you are single, call a friend with whom you feel safe to share your feelings.
7. If you think it might be helpful, please call the clinic and set up an appointment with me, at no charge. Our number is 415-834-3000.

– Peggy Orlin, MS, MFT

Microarray Preimplantation Diagnosis (MA-PGD) created much excitement and interest at three recent meetings attended by Dr. Schriock; Pacific Coast Reproductive Society, The Midwest Reproductive Symposium, and the IVF Comprehensive Update.

PGD is a technique used to diagnosis genetic disorders by performing a biopsy of the embryo on day 3 or 5. PGD can diagnose single gene or chromosomal defects. PFC has been doing embryo biopsy for over 10 years. During this time the major method of diagnosing chromosomal disorders has been fluorescent in situ hybridization, FISH. FISH uses a fluorescent color to label individual chromosomes. This technique lacks accuracy and is now seldom used to screen embryos for the presence of missing or extra chromosomes. (refer to Fertility Flash Vol. 5 Issue 2). This technique, however, is still valid for identifying the gender of the embryo. MA-PGD uses a new technology, Single Nucleotide Polymorphisms (SNPs). SNPs are single bases, the building blocks of DNA, which can be in a different sequence in different individuals. Six to ten million SNPs have been characterized. This is the technology used in DNA fingerprinting in criminal or forensic work. Compared to FISH, where only one color marker identifies the chromosome, SNPs havethousands of markers per chromosome.

FISH can only identify 8-12 of the 24 unique chromosomes; MA-PGD will identify all 24 chromosomes, similar to amniocentesis. Identifying both single gene defects and chromosome abnormalities from one embryo cell was not possible with the older techniques, but can be done with MA-PGD. MA-PGD will identify whether the abnormal chromosome came from the mother or father. If from the mother, it will determine if the error was in meiosis I or II, or mitosis. In other words, it can identify in which stage of early cell division the genetic error occurred. Using MA-PGD, it may be possible to determine which embryo produced the baby when more than one embryo is transferred. The most important advance, however, will be the accuracy of the result. New research using MA-PGD shows that FISH is inaccurate over 40% of the time. MA-PGD appears to be nearly 100% accurate in diagnosing abnormal embryos.

This new technology is also helping to answer scientific questions. 50 – 70% of embryos with one missing or extra chromosome still develop to a healthy-looking day 5 blastocyst. This helps explain why beautiful blastocysts do not always turn into healthy pregnancies. MA-PGD will also raise new questions: Only 55% of chromosomally normal embryos turn into successful pregnancies in 30-year-olds, only 25% in 40-year-olds. Why do these embryos with a normal number of chromosomes fail? There is more to the embryo than chromosomes and more research is needed to determine what factors allow an embryo to develop into a healthy baby. Current areas of investigation include RNA production (transcriptomics), protein production (proteomics), and metabolic by products (metabolomics).

We will continue to update readers on PFC’s experience with MA-PGD in future Fertility Flash issues.

On May 15th, we were fortunate to have Dr. Daoshing Ni, D.O.M, L.AC., Ph.D., a Licensed Acupuncturist in the State of California, a Diplomat of Chinese Herbology, and a 76th generation acupuncturist come to speak at PFC about the benefits of combining acupuncture and ART.

Dr. Ni spoke about some of his own research studies on acupuncture and ART and also discussed some of the issues with the current protocols that are being used today. He emphasized that the Paulus protocol is a good guideline when doing embryo transfers, and he encouraged the addition of other supportive acupuncture points. He also strongly encouraged that patients be treated with Chinese medicine for at least 3 months before their ART cycle begins. Dr. Ni also spoke about how the use of Chinese herbs contribute to improving egg quality.

This outstanding program was attended by PFC’s acupuncturists, physicians, and staff. In addition, area wide acupuncturists were invited to hear Dr. Ni’s presentation, meet one another, and share ideas.

We are excited to introduce a new website FertilityWire, http://fertilitywire.com.  This site is separate from our current website www.pacificfertilitycenter.com.

FertilityWire will provide access to a wealth of fertility information, news, and social content. Please take a moment to check out this exciting new resource. You can let us know what you think in the comments section.

Enjoy!

-Robb Mayberry, Director of Development