Issue Contents:
 

Pacific Fertility Center

55 Francisco Street,
Suite 500
San Francisco,
CA 94133
TEL: 888-834-3095
FAX: 415-834-3080
www.InfertilityDoctor.com
[email protected]



Our Promise

As a unified team, guided by the highest ethical standards, we provide our patients with the best quality, individualized, compassionate fertility care.
SCIENCE PULSE    A Closer Look at Letrozole

Infertility and OBGYN professionals across the U.S. and Canada appear to be united in agreeing that there is an undue amount of fear and controversy concerning the use of letrozole (under the trade name Femara) for fertility treatment. Letrozole is a drug that is used for the prevention of recurrence of estrogen-receptor positive breast cancer. Its “off-label” use for ovulation induction is increasingly common, although not approved by the FDA for this application.

In late 2005, Novartis Pharmaceuticals, the Swiss company that developed letrozole for treatment of breast cancer reacted to a single study that showed higher than normal adverse reactions. Novartis sent out a warning letter to infertility clinics asserting that the company does not advocate the use of this medication for infertility treatment. Despite the drug’s successful track record as an alternative to clomid for ovulation induction, at least one Canadian clinic has stopped using it.

As for the background, it started with the presentation of a study conducted by the Montreal Fertility Clinic at the 2005 annual meeting of the American Society for Reproductive Medicine (ASRM). The study reported a much higher rate of serious fetal abnormalities among patients who had been prescribed letrozole. The author’s analysis of only 150 babies born after letrozole therapy revealed a 4.7% rate of major anomalies. This rate was compared to the 1.8% rate of a “control group” of more than 36,000 babies born at a nearby hospital.

Our reading of this study leaves us skeptical about forming any conclusion that letrozole causes an increase in birth defects. First, it is generally agreed that within an unselected population, the background rate of birth defects is 3% for major anomalies and 6% when including minor anomalies. So the background rate in the “control” population seems low. Second, the comparisons between these groups are not indicative of a true controlled study whereby patients of like demographics and health are provided the same treatment protocol, ideally through a double-blind placebo study.

Common sense would remind us that infertility centers treat a higher percentage of women who have delayed childbirth and their older status is typically associated with higher rates of birth defects. The control group in the letrozole study of 36,000 women at a standard hospital would likely include a high percentage of younger women who, by nature, and backed by statistics, have fewer births with congenital anomalies. Indeed, in this study, the mean age of the women treated with letrozole was 35.2 years and the mean age in the control population was 30.5 years. Further, there may be “ascertainment bias” as there may have been under-reporting of defects in the “control” population. Comparing these two groups and drawing a conclusion that sends such alarm through the infertility community is questionable. Lastly, the limited size of the study makes drawing any conclusion very premature.

Novartis has not led any independent studies of its drug with applicability as an infertility medication. But it took the opportunity to analyze its own database with regard to safety. The company claims there were 13 cases involving “adverse reactions” involving letrozole and congenital birth anomalies.

No control groups or comparison to the background rates of congenital anomalies were made. Given this day and age of class action lawsuits, it is understandable for a pharmaceutical company to issue a warning at the hint of any trouble. In light of this, it has been up to the professional associations and communities of medical professionals handling infertility cases to sort through the data carefully, make up their own minds and provide full disclosure to patients.

Just this month, a new study on this subject is appearing in the primary infertility journal of the U.S., Fertility and Sterility. Again from Canada, researchers from Toronto reported on 911 babies conceived with the assistance of either letrozole or clomiphene. In this study, 14 of 514 newborns (2.4%) in the letrozole group and 19 of 397 newborns (4.8%) in the clomiphene group were found to have any congenital anomaly.

For major malformations, the rates were 6/514 (1.2%) for letrozole and 12/397 (3.0%) in the clomiphene group. These rates were not statistically significantly different, and were felt by the authors to be similar to rates of congenital anomalies seen in the general population.

In the field of medicine, there are hundreds of medications that were originally discovered to treat one condition and are subsequently found to be useful for other conditions. Once a drug is approved for a specific indication, most pharmaceutical companies will not go through the trouble and expense to have their drug officially approved for another indication. We at Pacific Fertility have carefully reviewed the data and circumstances around the controversy and we continue to believe that the use of letrozole is appropriate in certain circumstances and with full disclosure. Hundreds of infertility centers and OBGYN clinics worldwide are doing the same.

Although no broad scientific studies have yet established the efficacy of letrozole as the first course standard treatment for treating ovulatory problems, preliminary studies have shown letrozole to be useful, especially for women whose uterine lining may be thinned out by clomiphene (Clomid).

Please see the sidebar to learn more about how letrozole works. The only other alternative to clomiphene for ovulation induction is the use of injectable fertility medications (gonadotropins). Use of these drugs in anovulatory women can be tricky, as it is often difficult to induce just one or two eggs to mature with these powerful drugs. So the risks of ovarian hyperstimulation and multiple gestation are significantly higher in anovulatory women on gonadotropins.

We at Pacific Fertility Center carefully explain to those women who might benefit from its treatment the controversy as well as the potential for adverse reactions. Letrozole is generally prescribed to be taken from days 3-7 of the menstrual cycle and has a short life span in the body. There are no traces of the medication in the body by the time an embryo will be implanting.

  Carolyn Givens, MD was the first in San Francisco to successfully initiate a pregnancy using intracytoplasmic sperm injection (ICSI). She currently co-directs Bay Area Pre-Implantation Genetic Diagnosis Program (PGD) and is director of PFC's PGD program. Dr. Givens' excellent care and over 12 years of experience is recognized by her peers who repeatedly single her out as a �Best Doctor� in national surveys.

               
Back to Top

SCIENCE PULSE EXTRA    How Letrozole Works

Infertility clinics around the country as well as OB/GYN centers are reporting favorable results from letrozole for extremely specific treatment options for a small percentage of patients. It is by no means a medication that is or will become standard until more studies are conducted.

   Both clomiphene citrate (marketed as Clomid) and letrozole (marketed as Femara) are oral medications used to stimulate ovulation. Letrozole was originally developed for breast cancer treatment, as certain types of breast cancer cells slow their growth in response to decreasing estrogen levels. Letrozole falls in the category of drugs known as non-steroidal aromatase inhibitors, meaning it is highly specific in suppressing estrogen synthesis. Aromatase is an important enzyme prompting the creation of estrogen. If the body makes less estrogen at the start of the cycle, a woman's FSH level increases and ovulation is stimulated or enhanced. Letrozole is considered as an alternative to Clomid for women undergoing ovulation induction especially for women whose uterine lining may be thinned out by Clomid. As an anti-estrogen, Clomid can limit the development of the endometrial lining making it difficult for an embryo to implant. For reasons that are not yet quite clear, letrozole appears less likely to affect the uterine lining, perhaps because of a short half-life and therefore, a shorter effect on estrogen production. Letrozole has a short life span in the body whereas Clomid can last for 4-6 weeks following an oral dose. • Carolyn Givens, MD

               
Back to Top

CRITICAL REVIEW    At Home Sperm Testing

The laboratory team here at Pacific Fertility Center tested the over the counter Male Fertility Test from Baby Start. The test, also marketed by Embryotech as “FertilMARQ”, comes with everything needed to test two separate semen samples. We found the instructions easy to follow and we used semen samples from several men to run our tests on the kits.

The kit is FDA approved and readily available from major drugstores and through the Internet. It claims to tell you if you have a normal sperm count, which according to the World Health Organization (WHO) is having > 20 million sperm per milliliter of semen. The test does not measure any other parameters of the semen sample such as sperm motility (how many are swimming) or sperm morphology (size and shape).

We ran the test multiple times using kits that the manufacturer had supplied and asked us to test. We used a variety of semen samples with different sperm counts.

The kit contains a small test strip with 4 “wells” labeled A through D, and it looks similar to a home pregnancy or ovulation predictor test. Two of the wells (A and C) are controls and are a blue green color. The other 2 wells (B and D) are used for testing the semen samples and these change color depending on how many sperm are in the test sample. If the color is as dark as or darker than the control well, you have sperm. If the color is lighter than the control well, you have little or no sperm.

To perform a test, a fresh semen sample is collected either into the supplied cup or condom. If collected with the condom, this is simply emptied into the cup, which contains some small flakes of a dried enzyme. The enzyme helps to liquefy the sample over a period of at least 15 minutes and then the semen is ready to be tested. One drop of semen is added to a test well, followed by 2 drops of “blue solution” 1 minute later. After another minute, 2 drops of “clear solution” are added to the test well. The color of the test well is then compared to the control to determine if normal sperm numbers are present in the sample.

The kit comes with everything that is needed to perform the tests. All you will need to supply is a clock or timer. The instructions are clear and simple with helpful diagrams for guidance. The rules for when you should test are acceptable: no more than 3 days since your last ejaculation before you run the first test, and 3-7 days abstinence before running the second test. The instructions also contain common questions, with answers that might arise when you are doing the test. We also found a good and helpful frequently asked question page at http://www.webwomb.com/fertilmarq_faq.htm.

In our trials, the test easily distinguished between samples with normal sperm counts and those with little or no sperm. Clear positive results were obtained with sperm counts of 99, 73.5 and 32.6 million sperm/ml. Clear negatives were obtained with samples that we counted as 0, 3 and 4.4 million sperm/ml.

Only when we analyzed samples close to the test threshold did we find any discrepancies (a sample counted at 18 million sperm/ml came up positive).

The kit is no substitute for testing in a clinical laboratory. The main shortcomings are that the test only looks at sperm number and not other parameters in the semen sample that are equally important for fertility diagnosis and treatment. If you have sperm, but they are not swimming, you would pass this test. Also, individuals with sperm counts that are slightly below normal can pass the test perhaps giving certain men a false sense of security. For these reasons, your fertility physician may order a more detailed sperm analysis.

In general, the test is easy to perform, readily available and inexpensive. The test kits that we received were part of a batch being shipped overseas, perhaps to a location where good clinical testing is not as accessible as it is in the US. And men that are too shy or embarrassed to go to their doctor for a semen analysis now have a better alternative.

  Two of the wells (A and C) are controls and are a light blue green color. The other 2 wells (B and D) are used for testing the semen. Wells B and D change color depending on how many sperm are in the test sample. If the color is as dark as or darker than the control well, you have sperm.

• Joe Conaghan, PhD

               
Back to Top

PFC SPOTLIGHT    My Passion Followed Pain

  As many of us do, I began a career in one area and discovered my true passion along the way. I began as a teacher in Long Island. After working for several years as a teacher for students in special education, I moved to San Francisco in 1978.

During my early years in California, I continued to teach adolescents with special needs. I soon realized that what I enjoyed most of all was not teaching the classes, but the informal counseling and group sessions that happened outside of the normal classroom experience. This motivated me to return to the classroom for a Marriage and Family Therapist's (MFT) degree.

Once I was licensed in 1984, I worked for a few more years in the school system as a counselor for Special Education students. Concomitantly, I began a private practice counseling women and couples. Both counseling settings were rewarding.

By the early 1990's, after being inspired by work I did with another therapist, I left the school system and began training other counselors. It was exciting and a stimulating change of pace.

During this time I was going through some personal challenges. My husband and I had difficulty conceiving and subsequently underwent infertility treatments. Finally we became parents through adoption, a wonderful family building solution!

After the adoption, I took some time off from work to enjoy our daughter. Our daughter, adopted at birth, is a never-ending source of joy for both of us.

My passion followed my pain. During our trials with infertility we learned of Resolve and joined a support group. This greatly diminished our feeling of isolation. I went on to do adoption home studies, join the Board of Resolve of Northern California and lead support groups. Eventually, through word of mouth and referrals from Resolve, I began counseling infertility couples.

I have remained active in Resolve, coordinating their support services while on the board, speaking at conferences and agreeing to be the Keynote speaker in 1995. This year, 2006, I have been asked to sit on Resolve's National Mental Health Advisory Board.

My career at Pacific Fertility Center began over 8 years ago with a referral from a colleague who knew of my work with infertility patients.

About that same time I began attending the ASRM Mental Health Professional Group (ASRM-MHPG) conferences. In 2001 I became co-chair of Internet Integration Task Force to organize a worldwide online community of therapists for the group (ASRM-MHPG).

I find the topics tackled by this professional group fascinating. It assists in developing guidelines for the infertility industry, especially on the many ethical issues surrounding egg donation as well as guidelines and protocols for protecting the donors and the recipients. As an active member of the MHPG community, I have served as secretary/treasurer, newsletter editor, program chair for the mental health portion of the ASRM conference in 2005 and am in the 3rd year sitting on the executive committee. I am looking forward to my new responsibilities as the 2006-7 chair of ASRM's MHPG.

In general, this group allows me to learn from the mostly PhD/research oriented group and communicate with therapists dealing with infertility issues from all over the world.

My involvement with this research oriented group has piqued my interest in developing a study at Pacific Fertility Center which would further our understanding of stress as it relates to infertility.

• Peggy Orlin, MFT

               
Back to Top

FROM US TO YOU    2005 IVF Statistics

Pacific Fertility Center is pleased to provide its final IVF laboratory statistics for 2005. (This is the most recent data from our clinic and has not yet been reported to CDC/SART. This data includes undelivered pregnancies. The pregnancies counted as positive include all pregnancies with a clear gestational sac on ultrasound examination. We urge caution when comparing these statistics to that of another center. Be advised that a comparison of clinic success rates may not be meaningful because patient medical characteristics and treatment approaches may vary from clinic to clinic.)

Comparing IVF programs by published statistics requires some insight into why programs may or may not be different. We have listed some key points to facilitate your understanding of our statistics.

Some factors associated with Pacific Fertility Center statistics:
  1. Pacific Fertility Center does not restrict IVF to only those patients most likely to succeed (a practice which often leads to higher pregnancy rates). Our less restrictive approach is confirmed by our high percentage of DOR patients as described in point #2.
  2. Over the years, PFC has treated a substantial number of IVF patients diagnosed with Decreased Ovarian Reserve, DOR (a basal FSH level of 10 mIU/mL or higher). As reported by SART/CDC, in 2003 and 2004, 28% and 22% of PFC patients, respectively, were diagnosed with DOR.
  3. PFC performs a substantial volume of IVF and ovum donor cycles. This allows for better statistical accuracy of our data, (the fewer number of patients - the less statistically significant the rates become). We feel it keeps all of us well-attuned to the practice of ART.
  4. PFC's non-donor egg success rates with frozen embryo transfers approaches that of fresh embryo transfers. We have had a very strong embryo freezing program for many years and are proud of this. Our patients can avoid high order multiple pregnancies by transferring fewer fresh embryos and successfully freezing the remaining embryos. They may also increase the odds of having more than one pregnancy from a single IVF cycle.

FRESH EMBRYO TRANSFER CYCLES
Table 1: IVF with Own Eggs
Patient Age <35 35-37 38-40 41-42 >42
Number of cycles 158 154 166 104 71
% Embryo Transfers
Resulting in Pregnancy
39 42 27 16 7

Table 2: IVF with Ovum Donor
Patient Age  
Number of cycles 192
%Embryo Transfers
Resulting in Pregnancy
60


FROZEN EMBRYO TRANSFER CYCLES
Table 3: IVF with Own Eggs/Frozen Embryo Transfers
Patient Age <35 35-37 38-40 41-42 >42
Number of cycles 115 74 47 17 7
% Embryo Transfers
Resulting in Pregnancy
33 43 26 24 29


Table 4: IVF with Ovum Donor
Patient Age  
Number of cycles 145
%Embryo Transfers
Resulting in Pregnancy
29

An individual's chances for success are based on a variety of factors including age, diagnosis and choice of treatment. We will be happy to discuss any questions you may have and estimate your individual chances of success.


               
Back to Top


Thank you for your interest in subscribing to Pacific Fertility Center's free monthly newsletter. In order to better protect your privacy, we have a new secure subscription/log in form. We respect your privacy: Your email remains confidential and will not be shared or sold. Please click here to change your subscription preferences.

-- Best regards from all of us at Pacific Fertility Center.


Copyright © 2006 Pacific Fertility Center and Its Licensors. All rights reserved.