Title: The Fertile Kitchen Cookbook

Can diet influence fertility? Can altering your diet help you conceive? Is it true that you are what you eat (and so is your baby)?

At age 40 and after trying to conceive for over a year, Cindy Bailey and her husband Pierre Giauque were told that they were unlikely to conceive. With disconcerting medical test results and failure in conven tional treatment, alternative therapies seemed the best option. After trying a fertility-friendly diet, to their surprise, their son was conceived four months later.

The Fertile Kitchen is one couple’s story of overcoming the odds against conception while using common sense and easily executed measures to optimize health. Using fresh, high quality, organic ingredients, and reducing wheat and dairy; the couple developed a nutritional plan that they feel contributed to their success. These authors found that optimizing the basic ingredients for life, adjusting calories, carbohydrates, fats, and proteins into a regimen that has the potential to optimize pregnancy rates, should be considered in a given fertility plan.

Science is still catching up to medical concerns about fertility and diet. As an example of this emerging science, it is known that women with abnormal body fat levels, either high or low, suffer from lower pregnancy rates, and that improvement in body weight and body fat levels improves fertility rates…Certain types of animal protein are potentially problematic for fertility, whereas vegetable protein sources seem to carry less risk. Calorie source, simple sugar versus protein, makes a difference in treating anovulatory women. Irregular menstrual cycles can be optimized by changing diet. Omega-3 fatty acids are related to uterine artery perfusion pressures, and supplementation seems to provide some clinical improvement in these parameters. Studies are showing a role for B-complex vitamins, folic acid, and dietary fat in regulating ovulation.

It is unfortunate that some people have serious challenges to fertility that cannot be addressed with a change in diet. Diminished ovarian reserve, male factor, and tubal occlusion are problems that go beyond what can be remedied with diet alone. With that said, fertility treatment programs, regardless of the health issues, should include a healthy diet, as a good preventative measure for already healthy women wishing to conceive. The recipes in this book are easy to follow and the ingredients are amply available at most grocery stores.

Fertile Kitchen Media Kit (pdf)

— Philip Chenette, M.D.

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

Since Pacific Fertility Center came into existence in November of 1999, we have been offering genetic pre-screening of IVF embryos for couples with recurrent miscar- riage, repeated IVF implantation failure and sex selection for family balancing. For most of the last decade, a technology known as Fluorescent In-Situ Hybridization, or FISH has been used to screen embryos. FISH is employed to probe a cell removed from a Day 3 embryo to determine the chromosomal makeup for anywhere from three to twelve of the cell’s 23 pairs of chromosomes. With time, we, as well as everyone else in the reproductive genetic world, came to realize the serious limitations of this technology.

In the last 2-3 years, as the Human Genome Project has been completed and as more DNA-related biotechnologies have emerged to evaluate human genes, these methods are being utilized to analyze human embryos. The technology now available—the ability to analyze large numbers of genetic locations on each human chromosome, and quantify that genetic material, with the previously well-established techniques to amplify a single cell’s genetic material up to hundreds of thousands of copies—has allowed PGS to take a quantum leap forward. It is now possible to more accurately analyze all 23 chromosome pairs from a single embryo; not only to determine if the correct number of copies of each chromosome is present, but also to look at single gene mutations.

At the end of 2009, Pacific Fertility Center began working with a new biotech company called Gene Security Network, located in Redwood City (genesecurity.net). This company uses gene microarray technology to analyze amplified DNA from a single cell.

It then uses microchips to analyze 30,000 genetic loci in a quantitative manner. In addition, their unique technology allows us to compare the analysis of the embryos’ cells to the parent’s chromosomes to ensure that all the genes are being properly analyzed. It does appear that the error problems that plagued FISH technology have been overcome with this new, more sophisticated, method.

In October of 2009, Dr. Conaghan and I were invited to tour the GSN laboratory and see the technology in action. We met with David Johnson, the lead scientist at GSN, who explained the cell process; from the amplification of the DNA, to arranging the chromosomes on chips, to DNA analysis, to synthesizing the data generated with the parental genetic data to come up with a full analysis of that cell’s genome. In order to process the cells between the day of embryo biopsy (Day 3) and receive the results on the day of embryo transfer (Day 5), their technicians work around the clock in shifts. GSN has a very cold, clean room to replicate the single cells into multiple copies. They cannot allow any outside contamination, not even from a single cell. They videotape the cell duplicating process so if any errors subsequently arise, they have a video record of what the laboratory technician did. We found this to be very impressive. We also saw how the chips were coated with DNA and analyzed. We were shown the sophisticated software that generates the final report detailing the genetic makeup of each embryo from the cells in which they originated. All in all, the tour gave us great confidence in the quality control and scientific integrity at GSN.

Even with this 21st century technology, we continue to biopsy Day 3 embryos because it provides us with a 48 hours window to send the cells to the lab and complete the analysis in time for transfer. However, we have not yet found a way around the problem of mosa- icism. GSN and microarray technology appears to have largely solved the resolution error problem but it can only tell us what is in the chromosomal make-up of the single cell. It cannot tell us whether or not that cell represents what is truly going on with the rest of the embryo. We are currently looking at the possibility of biopsying Day 5 embryos. The set back would result in having to freeze these embryos due to the time constraint in analyzing the genetic material in time for fresh transfer. With all of the innovation occurring daily in the genetics field, we hope that this puzzle will be resolved.

— Carolyn Givens, M.D.

Previous Fertility Flash articles about PGS:
2 Methods of Gaining Info Prior to Implantation
PGD & PGS: Why Genetic Counseling is a Prerequisite
The Benefits and Pitfalls of PGS

These tests can be done by your primary care physician or gynecologist prior to consulting your Reproductive Endocrinologist:

• Day 3 FSH (follicle stimulating hormone) and Estradiol (Day 2-3 is acceptable)
• TSH (thyroid stimulating hormone)
• Prolactin
• Progesterone: 7 days prior to menses, this test is occasionally helpful
• Semen analysis

These tests may be useful based on each patient’s particular needs:

• Hysterosalpingogram (HSG) or documentation of tubal status
• Hysteroscopy
• Laparoscopy: The surgeon should be able to treat during this procedure, not just diagnosis.

The following treatments may be done, if indicated, for a limited number of cycles:

• IUI (intrauterine insemination)
• Clomiphene citrate (Clomid, Serophene)

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

These tests are best done through your Reproductive Endocrinologist (fertility specialist):

• Strict sperm morphology
  Strict morphology is a very specific method of evaluating the shape of sperm. Most laboratories do not use strict criteria thus potentially missing a sperm problem. Our laboratory is staffed with embryologists trained to analyze sperm with these strict criteria.
• Evaluation of ovarian reserve
  Evaluation of ovarian reserve includes family history, ultrasound to detect the antral follicle count (AFC), a cycle day 2-3 FSH and estradiol level (both must be done at the same time), Anti-mullerian Hormone AMH, and clinical and family history.  An REI can bring all of these assessments together into one consistent picture of a woman’s ovarian reserve.
• Ultrasound
  A pelvic ultrasound is a very useful test when it is done at the appropriate time in the menstrual cycle. A few days prior to ovulation an ultrasound can evaluate ovulation, follicle growth, endometrial thickness and pattern, polyps, and fibroids. During menses is the best time to evaluate the ovary for cysts and endometriosis.
• Genetic testing
  Genetic testing is important in women with premature menopause and multiple miscarriages and men with very low sperm counts.  Patients with a family history of a genetic disease can use genetic testing to determine if they are carriers of the disease.  Universal genetic testing (Counsyl, www.counsyl.com) can be used to assess risk for certain genetic illnesses that run in families. If detected, Preimplantation Genetic Diagnosis (PGD) can help prevent genetic illness in your child.
• Insulin
  Women who have irregular periods and have been told they have Polycystic Ovary Syndrome (PCOS) should be evaluated by an REI.  Testing can lead to more effective treatment.

Treatments by a fertility specialist

The advanced training of an REI is helpful to provide the most successful treatments for infertility.

Some of these treatments include:

• In vitro fertilization with embryo transfer (IVF, or IVF/ET),
• Fertility preservation
• Egg freezing
• Intracytoplasmic sperm injection (ICSI)
• Preimplantation genetic diagnosis (PGD)
• Ovulation induction
• Intrauterine insemination

A specialist is able to evaluate simpler treatments and finely tune them to make them more effective. For example, a specialist can monitor ovulation induction with clomiphene (Clomid) with ultrasound and blood tests. The vaginal ultrasound can be used to assess follicle development and endometrial pattern and thickness. Intrauterine inseminations can be done to bypass hostile mucus caused by clomiphene. The specialist can also help decide when to stop a particular treatment and/or proceed with more.

Alternative medications like letrozole (Femara) are just as effective as clomiphene but have fewer side effects.  Since letrozole is not approved by the FDA for marketing for fertility use, its use is generally restricted to specialty clinics, that is, REIs.

Gonadotropins, the injectable drugs, for example Follistim, Gonal-F, Bravelle, and Menopur, are potent stimulants to the ovary.  They are designed to produce multiple follicles, in order to improve pregnancy rates.  Due to the risk of multiple pregnancy and overstimulation of the ovaries, the medications should be used only by experts in the field.  Most of these treatments are performed by REIs in the United States.

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

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

Tune your radios to KGO 810 AM, tonight. Dr. Givens will be the featured guest on the Pat Thurston Show from 10 – 11 p.m. PST. Dr. Givens will be discussing many fertility issues including treatments, outcomes, and ethical issues. She will also be taking questions from callers. You may also stream the show live on the KGO website.

Title: Everything Conceivable
Subtitle: How Assisted Reproduction is Changing Men, Women and the World
Penguin Books, 2007. 343 pages, with 57 pages of footnotes and references.
By: Liza Mundy

This is a very interesting book about the current state of affairs in the world of assisted reproduction. It is comprehensive in its coverage of almost all the latest technologies and the author has been very thorough in researching the subject. On most topics, there are insightful observations on the societal implications of current technologies. In this regard, it is a thought-provoking book.

In the epilogue, the writer states, “It was my goal to help readers understand why certain changes in the family are taking place and what their likely consequences might be. Why there is so much demand for donor eggs, now. Why there are so many more triplet sets than there once were. What life is like for those triplet parents. How embryo research and embryo politics are influencing our thought on human life and its origins. What is the real, rather than the imagined impact of medicine and science on families and culture.”

I think this would be an excellent resource if one were a health care policy maker or if one were writing a term paper or thesis on the subject but I don’t really think it’s a book to inform the infertility patient about fertility options or what to expect with treatment. It really does not seem to be intended for fertility patients as the target audience.

However, the book does provide a lot of useful information in a somewhat scholarly fashion. Most of the facts are correct, with some of the usual journalistic license.

One of the biggest challenges we face as fertility medicine specialists is how to do more to help our least-likely-to-succeed patients. What I mean here is the 42-and-over age group, patients with high FSH levels (decreased ovarian reserve), patients with very low responses to fertility medications, or those with very poor quality eggs. Some patients have a combination of the above which leads to a really dim prospect of having a baby with their own eggs.

Some people get the impression that fertility clinics avoid these patients like they have a communicable disease. They get the impression that we try to cherry pick patients to keep success rates high and make the CDC stats look good.  My impression from talking to my colleagues across the country and certainly from our own practice is that we do not try to discourage patients with poor possibilities from making a consult appointment and discussing treatment options. We all have such patients. In fact, we have so many of them at PFC, I don’t think we would have many patients at all if we tried to pre-select our best prognosis patients for IVF. When it comes to treatment, although there are challenges and sometimes the rewards are few, we don’t just throw up our hands and give up. We try to come up with a strategy to achieve the goal, looking at the emotional reserves and financial resources we have to work with, and start by making a plan.

Sometimes that plan will be to try a couple of cycles of low-tech approach, like just intrauterine insemination or Clomid + insemination, or a mid-level approach, like injections of FSH along with  insemination. We would see how things go and play it by ear from there. Sometimes, the plan will be to blast ahead to the big guns, full steam ahead to IVF. Sometimes, it’s counseling with our marriage and family therapist to begin the discussion: are we ready to move on to donor eggs? Sometimes it’s a sequence of all of the above. There really is no one plan for any one person. It’s just too complex to say one size fits all.

A certain percentage, even of the-less-likely-to-succeed patients will get pregnant with their own eggs and go on to deliver a healthy baby. The remainder may be faced with a tough decision. Do we just stop here and live child-free?  There are certain perks to that plan (sleeping in on the weekends, eating in nicer restaurants, adult vacations to name just a couple) but most people want to have a family no matter what or how. So then there is the adoption vs. egg donation question. There is no right or wrong choice here, either: just choices.