The International Council on Infertility Information Dissemination, Inc

SIRM Shares new Egg Freezing Breakthroughs

Freezing the Biological Clock

 

The proverbial “biological clock” is not just a myth. 

A woman’s fertility begins to decline around age 27.   In fact, even in her late 20’s and early 30’s, more than half of a woman’s eggs are chromosomally abnormal.  Egg quality declines with age so that in the early 40’s, the percentage of “competent” eggs decreases to less than 5% on average.  This is an irrevocable fact.

Though we can’t change the rate at which a woman’s reproductive system ages, we are now much closer to stopping the biological clock via another route: egg freezing and banking. 

There are numerous reasons for a woman to preserve her fertility through egg freezing/banking.  These include fertility-threatening cancer treatment, postponement of child bearing for career purposes, lack of a suitable partner, and various other issues of timing and choice. 

 

Obstacles to Successful Egg Freezing

Women seeking viable options for fertility preservation have long faced a difficult barrier due to the poor success rates for egg freezing.  Pregnancy rates for women using frozen/thawed eggs have historically been less than 4% for each individual egg frozen.  This is due to several factors:

First, at least 60% of eggs frozen are chromosomally abnormal from the outset and therefore cannot produce a normal embryo.  Second, traditional (slow) egg freezing techniques cause ice crystal formation within the structure of the egg, reducing viability or destroying the egg in the process. 

 

The Solution

A recent breakthrough by researchers at the Sher Institutes for Reproductive Medicine (SIRM) and its affiliate, ReproCure Genetics, addresses both of these issues, yielding a promising advance in the viability of egg freezing/banking. 

First, using a proprietary process known as CGH (Comparative Genomic Hybridization), each egg is tested for its chromosomal integrity prior to freezing, ensuring that only the “competent” ones are frozen. 

Second, a new method of ultra-rapid freezing (modified by ReproCure) called Vitrification is used, allowing much more successful freezing without ice crystal formation. 

The combination of chromosome analysis through CGH and Vitrification to preserve the eggs has resulted in post-thaw pregnancy rates that are more than 8 times higher per egg stored than previously reported methods. Initial studies at SIRM/ReproCure have already resulted in many births from frozen eggs using this technique.  These exciting breakthroughs promise to finally open the door to viable fertility preservation for women.

Do you have more questions about egg freezing and how it might relate to the way eggs are fertilized and to IVF?  Come over to the INCIID Community Forums where Dr. Saleh (a reproductive endocrinologist) who will answer your questions online daily.

 

Overcoming Infertility and Blocked Fallopian Tubes

This article is part of the October 2006 INCIID Insights Newsletter

Overcoming Infertility and Blocked Fallopian Tubes

Written by Jacqueline Schuld as told by Theresa Tieszen

 

Infertility is a lonely road to walk down. My husband and I tried for eight years to have a child. Every time we received a friend’s birth announcement or invitation to a baby shower, we were painfully reminded of our own struggles and felt isolated from our friends’ joy.

When my husband and I suspected we had fertility problems, we decided to speak with a doctor. We had to skip around from doctor to doctor at first because we moved from Minnesota to New Hampshire. As a result, we were never able to spend much time with one doctor.  We felt they were quick to make decisions or never understood the whole picture of our medical history.

We finally settled with an endocrinologist in New Hampshire who suggested I have a hysterosalpingogram (HSG) to see if my fallopian tubers were blocked. I was very hesitant at first, but I finally decided to go through with the procedure. We didn’t expect anything to be wrong. Yet, the results showed that both of my tubes were blocked.

The endocrinologist suggested we proceed with laparoscopic surgery to attempt to open my tubes. If the surgery did not work, we could consider IVF or adoption.

I wasn’t comfortable with having surgery and IVF wasn’t an option for us because of personal and financial reasons, but adoption had always been in the back of our minds. We had even been accepted as parents at an adoption agency.

However, we still didn’t feel ready to make a decision. We were live-in caregivers for my grandparents at the time and under a lot of stress. We needed more time to think and pray about our options. We decided to put everything on hold for six months.

A few months later, my husband and I settled into the couch to watch the nightly news at 5pm – a time we seldom watched. A report about Clear Passage TherapiesÒ, a clinic that had success relieving pain and increasing chances of fertility, aired on the news. They reported that the treatment used manual (hands-on) therapy, without drugs or surgery.

My husband and I were both intrigued, so I asked him to watch the news again at 6pm – the time we normally watched the news. When the news report did not come on at 6pm, we knew it wasn’t a coincidence that we had sat down early to watch the news.

I sent my information to Clear Passage and was excited when they approved me for treatment. We made arrangements to stay with a family from a local church while I underwent ten hours of treatment within one week.

The first day of treatment I felt nervous and uneasy. However, my anxiety dissipated when I met my therapists. They were so warm, friendly, and natural with me that I felt comfortable and relaxed.

 

By the end of the week, my entire body felt healthier and I headed home to try and become pregnant. After six months, we still had no success. The therapists told me that most of their patients experienced success after 20 hours of treatment, so I decided to return for ten more hours.

I was excited for my second round of treatment. It was comforting to be back in the relaxing atmosphere with encouraging therapists. Following the treatment we waited another 6 months and then decided to have another HSG to see if my fallopian tubes had been opened.

My husband and I went to the hospital together for the procedure. We held hands as we actually watched the dye go through my tubes – both of my tubes were clear! Tears of joy ran down my face and we couldn’t wait to tell Clear Passage.

However, we still hadn’t become pregnant yet. Because my tubes were open, the endocrinologist suggested we try Clomid (a hormonal drug) with an intrauterine insemination (IUI). Although I was nervous about the entire process, my husband and I decided to try it.

A few weeks after my IUI, I woke up in the middle of the night and decided to take an early pregnancy test. It showed I was pregnant! I woke up my husband excited, “The test is positive! It’s positive!” Because it was only 3am, he groggily asked, “What test? You took what? What is it?” I finally calmed down enough to explain I was pregnant.

That afternoon we had a blood test that confirmed my pregnancy. We were overwhelmed with joy. After eight agonizing years of infertility, we were finally going to experience pregnancy and parenthood.

Now, our beautiful baby girl is almost a year old. We are so grateful that the Lord led us to Clear Passage TherapiesÒ and for the doctors who helped us overcome infertility.

For more detailed information about this therapy, the Wurn TechniqueÒ, please visit www.clearpassage.com. Clear Passage currently has clinics in Florida, New York, California, and Iowa, with plans to open in Arizona this summer and other metropolitan locations soon. 

Please feel free to post your questions on the INCIID forum, “Physical Therapy for Infertility and Pelvic Pain,” (http://inciid.org/forum). Belinda Wurn, PT, Director of Services, Clear Passage TherapiesÒ, and Larry Wurn, LMT, Director of Clinical Studies, Clear Passage TherapiesÒ, moderate the forum.

 

 

INCIID Insights is sponsored by Sher Institutes for Reproductive Medicine.

 

Assessing Information on the Internet

Assessing Infertility Information on the Internet: Challenges and Possible Solutions

 

  by Yakov M. Epstein, Ph.D.[a] [b]  and Helane S. Rosenberg [c]

 

Capsule:

Patients visiting consumer-related internet sites often have no clear way to evaluate content within these sites.  This article reviews the problem and offers suggestions to remedy the situation.

 

Abstract

Although patients frequently visit consumer-related internet sites to help them make informed decisions about treatment, there is no clear way for these consumers to evaluate content within these sites.  This article reviews the problem and offers suggestions to remedy the situation.

 

 

            Over the past decade, there has been rapid growth in the use of the internet by American adults. Around 1997,  the proportion of the U.S. adult population, (22.1%) accessing the internet became substantial. Since 1997 the proportion of adult internet users in the U.S. has increased markedly:  22% in 1997, 40% in 2000, 59% in 2002, and 78% in 2003. (1-2).

Around 1997, when internet usage began to approach one quarter of the US adult population, concern about the quality of health information available on the internet  was voiced and became the subject of numerous publications. In 1997 the editor of JAMA and colleagues published an editorial raising these concerns and advocating the creation of procedures that would enable users to ascertain the quality of online information in a manner comparable to ascertaining the quality of print information (3).  This call for action was followed by the publication of AMA guidelines in 2000 (4) .  These guidelines offer principles in 4 areas: content, advertising/sponsorship, privacy/confidentiality, and e-commerce. 

In this paper, we want to concentrate on the first of these areas – content.  In our view, as internet access has become more widespread and more frequent, consumers have become much more sophisticated in their understanding of potential dangers associated with loss of privacy, unethical use of advertising or unlawful e-commerce schemes – the other 3 areas addressed by the AMA guidelines.  So though the AMA concern about addressing these matters is laudable, it is not nearly as timely as it was when the guidelines were established.  Concerns about content, on the other hand, are more important than ever as more and more people turn to the internet to find this information.

The Huang group (5) studied private practice websites which they compared with hospital/university affiliated sites.  Interestingly, most consumers do not go to either of these types of venues when looking for infertility information or support.  A Google search on the term “infertility” conducted in mid September, 2004, reveals that of the top ten sites located only 1 was to a hospital related site and 1 was to private practice website.(6) The rest were to organizations such as the International Council on Infertility Information Dissemination (INCIID), RESOLVE, the American Infertility Association (AIA) and similar consumer-related sites.

The AMA guidelines for content highlight 8 areas of concern. (4)  Curiously, only one of these 8, “quality of editorial content,” goes to the heart of the issue of information which might confuse or mislead a consumer. The other 7 (site ownership, site viewing, view access payment and privacy, funding and sponsorship, linking, intersite navigation, downloading files, and navigation of content) are issues which most consumers can handle on their own without having to rely on the AMA’s assistance to ensure that they have a high quality experience.  When it comes to awarding value to an online health resource, content is truly king.

The problem, however, is that the AMA guidelines offer no practical way for consumers to know which content to cherish and which to discard. For example, the AMA recommends and we agree that the posted content should have been reviewed. But how is a consumer to know whether it has been reviewed and if it has been reviewed how credible is the review panel?

Huang et al used the AMA criteria to evaluate private and hospital-affiliated infertility websites and reported that “the overall quality fails to meet the American Medical Association (AMA) Internet health information guidelines.” (5)  To ascertain the ideal of how a website should be constructed and how quality content should be made available, we visited the AMA web site (http://www.ama-assn.org/).  We navigated to the patient section and then to the MEDEM patient information resource where we visited the “Life Stages” section and then, more specifically, the “women’s health” section and finally the “pregnancy and fertility issues” section.  We then applied Huang et al’s criteria to evaluate this site. (5) We invite readers to try this themselves, perhaps using one of the other patient areas of MEDEM.

Ownership and affiliations could be found by clicking on “About Medem (1 point). Copyright information was present (1 point.)  Restrictions on access to content were available by clicking “terms of service” (1 point). There was information about “secure pay” (1 point).  Privacy notices were easy to find (1 point). Funding information is ambiguous.  The FAQ states “Revenue for Medem comes from traditional sponsorships, e-commerce, licensing subscriptions and transaction fees” but it does not indicate whether the content that appeared had any particular sponsor. As to the final criteria, ability to distinguish content from advertising, Huang’s guidelines did not permit us to enter a score of 1 or 0.  There were several ads on the content page such as “click here to order Family Health Supplies.”  We had no way to know whether a consumer would believe this was part of or separate from the content.  Overall, however, the site earned a good score for this area (5 or 6 out of 7).

A second area that Huang’s group evaluated was navigation. (5)  Navigating the site was easy.  There was no information about the optimal browser or platform. The internal links all worked (1 point) as did the external links (1 point.). Medem permitted us to return to previously viewed sites (1 point) and did not redirect us to unintended sites (1 point.)   There was no information about PDF software but neither were any of the documents in PDF format.  Do we award a point or not? The Huang group offered no guidance on this matter. There was a site map (1 point) and an FAQ page (1 point). There was a “contact us” link to provide feedback (1 point).  There was no specific customer service mechanism (but we might possibly award a point because we could contact the site so it was not clear whether 1 or 2 points should be awarded.) There was a search engine (1 point).  All in all navigation would earn a good score (at least 8, although it would be hard to enter this score into a statistical analysis since Huang’s criteria for evaluation described in his paper were too ambiguous to award a distinct score.)

The real difficulty for consumers, however, involved an evaluation of content. The site had relatively little information and none of it dealt with fertility issues.  There was no information about peer review for the posted content. Language was not complex (1 point). There was no description of the editorial process.  There were no posted names of staff members responsible for content. There was no date for the posting of this content. There were no author bylines or organizational affiliations indicated. No financial disclosure information was posted.  Finally, no references were cited. Using the Huang group’s criteria, the AMA’s own consumer information site earned a poor score, a score of  1 out of 8 for editorial content.

Of greater concern, however, was the fact that nowhere on the page of this organization which published guidelines, was there any information about how a consumer could evaluate the quality of the content she found there.  Near the bottom of the page, in typically small print was a heading called “medical disclaimer.”  When we clicked on it we saw the following warning: Rely at Your Own Risk: RELIANCE ON ANY INFORMATION ON THIS WEB SITE IS SOLELY AT YOUR OWN RISK. Hardly a guideline to help consumers assess the quality of the content on this site!

Thus using the Huang group’s criteria, the AMA earns good scores for ownership and affiliation and for ease of navigation but a failing grade for evaluating the content posted. This is not at all surprising nor does it reflect a failing on the part of the AMA.  It is easy to evaluate navigation and information about privacy and ownership.  It is a much more difficult and complex problem to evaluate content.  But evaluation of content and not ease of navigation is how these sites should be judged.

Even more to the point, the AMA guidelines don’t deal with an even more problematic issue of online access: discussion groups.  In 1998, we conducted a survey of internet consumers looking for information and support on the internet.(7)  The 589 respondents we studied spent approximately 1½  hours/day searching for information and support in various interactive internet forums.  Some of these venues were moderated by physicians but others involved only lay participation. Some of the information imparted by physicians was most likely accurate but it is difficult to know how accurate the information posted by lay participants was.  Nonetheless, these consumers considered the information they received extremely valuable. Approximately  45% believed they got valuable medical information and 40% reported that this information helped them deal better with their physicians. Nearly 1 in 4 said their participation influenced them to switch from an OB/GYN to an RE.  Approximately 1 in 5 stated that they decided to ask for a test or procedure they had never had before because of the views of participants in these forums. We have no way of ascertaining how good the information was that influenced these decisions or whether the decisions were appropriate or helpful in each case. On the other hand, we do know of a patient whom we counsel at the Fertility and Gynecology Center where we consult who insisted on pursuing a course of action contrary to what the physicians told her based solely on poor advice she received from members of a discussion group.  Following their advice she had a poor cycle outcome and later on lamented her decision to follow the forum advice rather than the counsel of her doctors.

There probably is no way to develop a system to evaluate these discussion forums. One could state that a forum moderated by a physician is superior to a lay run group.  Discussion group guidelines similar to those which the AMA created would be welcomed and probably even more important than they are for static content.  We should know whether a group is moderated by a physician, the physician’s background and training, experience with various procedures, information about privacy and how to contact the physician to share information the patient does not want to share with the public, whether the physician has any financial relationship with the organization sponsoring the discussion group or any links to a pharmaceutical group that might influence the suggestion of a particular medication.

One possible mechanism for enhancing interactive information would be to have ASRM sponsorship of discussion groups operated from the ASRM website using a rotating group of moderators.  Physicians could volunteer to moderate these sites and their qualifications could be ensured by an ASRM group who would evaluate their credentials.

As to the evaluation of static content, numerous articles have attested to the difficulty of creating any reliable evaluation tool that could be used by a consumer to evaluate the content of a site.(8,9,10,11)  In the UK, the NHS has funded the DISCERN project which developed an instrument designed to enable consumers to judge the quality of written health information.(12) Extensive testing of this instrument revealed that it could be used reliably by health professionals but consumers were unable to use it effectively. It was suggested that perhaps if consumers received special training they could use this instrument but we believe such an approach is impractical.  

Evaluating static content can be done through filtering.  Two approaches are possible: downstream filtering and upstream filtering. (8)  Downstream filtering is the process by which consumers use criteria suggested by experts to evaluate the content themselves.  As the DISCERN project has demonstrated, this approach is unlikely to work. Upstream filtering, on the other hand has experts reviewing the content and evaluating it. The result of such an approach which has been suggested by several people could be the creation of a “trustmark” mechanism.(13) This mechanism would amount to a seal indicating that the material meets certain standards of accuracy and appropriateness that have been established by this ASRM group of professionals.  Rather than placing the onus on a layperson to evaluate the content of a site, the consumer could simply look to see whether the content has earned an ASRM trustmark.  An ASRM assembled group could be charged with assigning trustmarks to content. Persons wishing to have the ASRM trustmark associated with some item of content would submit the material to this group for evaluation and the award of the trustmark. 

While trustmarking could help, it would still be an imperfect solution.  It is difficult to know, for example, in what context the user encounters information.  Some information, if read out of context can be misleading. (8)  Ultimately, there is no substitute for consumer education provided by physicians. The time is ripe for the ASRM, perhaps in partnership with consumer organizations such as RESOLVE, INCIID, and AIA to launch a task force to study the problem of managing infertility information on the internet and proposing useful solutions.

 

References

1.         Newburger E. Computer Use in the United States. U.S. Census Bureau 1997;PPL-114:1-11.

2.         US-Department-of-Commerce. A Nation Online: How Americans Are Expanding Their Use of the Internet, 2002 Available at www.ntia.doc.gov/ntiahome/dri/index.htm

3.         Silberg WM, Lundberg GD, Musacchio RA. Assessing, Controlling, and Assuring the Quality of Medical Information on the Internet: Caveant Lector et Viewor-Let the Reader and Viewer Beware. JAMA 1997;277:1244-1245.

4.         Winkler MA, Flanagin A, Chi-Lum B, et al. Guidelines for medical and Health Information Sites on the Internet: Principles Governing AMA Web Sites. JAMA 2000;283:1600-1606.

5.         Huang JYJ, Discepola F, Al-Fozan H, Tulandi T. Quality of fertility clinic web sites. Fertility and Sterility 2004.

6.         Google. available at www.google.com  Accessed on September 12, 2004

7.         Epstein Y, Rosenberg H, Grant T, Hemenway N. Use of the internet as the only outlet for talking about infertility. Fertility and Sterility 2002;78:507-514.

8.         Eysenbach G, Diepgen TL. Towards quality management of medical information on the internet: evaluation, labeling, and filtering of information. BMJ: British Medical Journal 1998;317:1496-502.

9.         Eysenbach G, Powell J, Kuss O, Ra E-R. Empirical studies assessing the quality of health information for consumers on the Word Wide Web. JAMA 2002;287:2691-2715.

10.       Gagliardi A, Jadad AR. Examination of instruments used to rate quality of health information on the internet: chronicle of a voyage with an unclear destination. BMJ: British Medical Journal 2002;324:569-573.

11.       Kim P, Eng TR, Deering MJ, Maxfield A. Published criteria for evaluating health related web sites: review. BMJ: British Medical Journal 1999;318:647-649.

12.       Charnock D, Shepperd S, Needhan G, Gann R. DISCERN: an instrument for judging the quality of written consumer health information on treatment choices. Journal of Epidemiology & Community Health 1999;53:105-111.

13.       Sheldon T. Trust mark launched as a guarantee of safety in the Netherlands. BMJ: British Medical Journal 2002;324:567.

 

 

[a]  Center for Mathematics, Science, and Computer Education, Rutgers – The State University of New Jersey, Piscataway, NJ

[b]  Correspondence: Center for Mathematics, Science, and Computer Education, Rutgers – The State University, 118 Frelinghuysen Rd. Piscataway, NJ 08854-8019  email: yepstein@rci.rutgers.edu

[c]  IVF New Jersey Fertility and Gynecology Center, Somerset, NJ

Semen Analysis: Normal Ranges

 

Normal Ranges for a Semen Analysis*

Parameter

Normal Ranges

Color

Gray/Transluscent

Coagulate?

Yes

Liquify?

Yes

  If yes, time in minutes

Less than or equal to 30

Volume (mL)

2 to 6

Viscosity (1,2,3,4)

1

pH

7.5 to 8.1

% Motility

Greater than or equal to 50%

% of 3-4 + Forward Motile Sperm

Greater than or equal to 50%

Sperm Concentration (x 1 Million per mL)

20-200

Total Sperm Count (x 1 Million per mL)

Greater than or equal to 40

Total Motile Sperm (x 1 Million per mL)

Greater than or equal to 20

White Blood Cells (x 1 Million per mL)

Less than or equal to 1

Agglutination (0,1,2,3)

 

  Clumping of sperm to sperm

0

  Clumping of sperm to round cells

0

% Normal Morphology

Greater than or equal to 30%

Penetrak Score (mm)

Greater than or equal to 30

 

mL = milliliter

mm=millimeter

   

Based on World Heath Organization criteria, 1992. Table excerpted from Berger, G.S., Goldstein, M., and Fuerst, M. (1995). The Couple's Guide to Fertility. New York: Doubleday.

Q & A for Injectable Infertility Medications

Buy it on Amazon

 

The term "injectables" describes a group of medications frequently used in the treatment of infertility. Oral drugs such as Clomid stimulate the ovaries indirectly by tricking the brain into thinking there is less estrogen in the body than there actually is. As a result, the body produces more "follicle stimulating hormone" (FSH) which in turn stimulates follicle production on the ovaries. In contrast, injectables actually contain FSH, so they stimulate the ovaries directly.

The term injectables generally does not include injected medications that are used for purposes other than ovulatory stimulation. Examples of these medications include GnRH agonists (e.g., Lupron) and hCG (e.g., Profasi, Pregnyl).

Why does my doctor want me to take injectables?
Most commonly, doctors recommend injectables after unsuccessful use of Clomid. In some cases, Clomid induces ovulation, but simply never results in pregnancy. Some women experience uterine lining thinning and/or cervical mucus hostility as a result of Clomid. Both of these side effects can actually prevent a successful pregnancy, and injectables do not have these side effects. Other patients, for various physiological reasons, simply do not respond to Clomid.

Injectables are also most doctors' ovulatory stimulant of choice for in vitro fertilization cycles, because their use will generally lead to a larger number of follicles than Clomid.

What are the different kinds of injectables?
Upon first encounter, the different types of injectables can seem quite overwhelming. However, many of these drugs are actually just different brand names of what is essentially the same drug. If the different brand names are all grouped together, we end up with only four general categories of injectables.

  • Humegon, Pergonal, and Repronex - These injectables consist of equal amounts of FSH and another substance, known as luteinizing hormone (LH). These medications are normally injected intramuscularly in the hip or thigh, using a 1.5 inch needle. The shot is similar to many routine vaccinations.
  • Metrodin - This drug contains FSH and no LH. It is also normally injected intramuscularly.
  • Fertinex - Fertinex is also FSH with no LH; however in addition, it is highly purified. As a result, it can often be given subcutaneously rather than intramuscularly. Subcutaneous shots are given directly beneath the skin, using 1/2 or 5/8 inch needles. These shots are similar to those used by diabetics to inject insulin.

The drugs in these first three of categories are refined from the urine of post-menopausal women. The drugs in the remaining category drugs are manufactured in the laboratory.

  • Follistim and Gonal-F - These drugs are highly pure FSH and are normally given subcutaneously. Outside of the United States, Follistim is called "Puregon."

Injectable dosages are most commonly described in terms of ampules ("amps") or vials. Ampules are all glass, and the top is snapped off in order to access the medication. Vials are glass containers with a rubber membrane in the top. The medication is accessed by pushing a needle through the membrane.

Why would I take one drug versus another?
In recent years, the drugs that are subcutaneously injected have come into favor. Many women find it difficult to give injections to themselves in the hip. Subcutaneous injections are easier to administer; as a result, individuals are able to give the shots to themselves, which increases the flexibility of the medication schedule. The more purified nature of the subcutaneous injectables is also viewed favorably.

Polycystic ovarian syndrome can play a role the type of injectable selected. Because women with this disorder frequently already have elevated LH levels, one of the newer FSH-only drugs is often the injectable of choice.

There is still a place, however, for the original LH-containing intramuscular drugs. Some individuals simply respond to these drugs more strongly than the pure-FSH drugs. Evidence has also emerged that a small amount of LH may be desirable for individuals who do not already have high LH levels. This issue can be especially relevant in IVF patients, whose own LH is normally suppressed by Lupron or another GnRH agonist.

How much will I take and for how long?
The answer is contingent upon age, ovarian responsiveness, and a number of other variables. Patients with highly responsive ovaries who are doing IUI may take as little as one amp or vial per day; on the other hand, poor responders going through IVF make take as many as 6-8 amps or vials per day. Younger patients who are not on Lupron may take injectables for as few as 4-8 days; women on IVF and those being stimulated at a conservative rate may use injectables for 8-12 days or sometimes even more.

Aren't injectables expensive?
There is no way around it - yes, they are. Depending on the medication and the place of purchase, prices can easily approach $60-$70 per vial/amp. Over the course of an entire cycle, these amounts do add up. Adding to the difficulty is the fact that many people's insurance policies do not cover injectables.
The best way to cut expenses for injectables is to order by mail. Many of the pharmacies specializing in infertility drugs have prices that are substantially lower than local drug stores. Additionally, doctors who are at larger research institutions will sometimes offer free or reduced medications as incentive to participate in a research study.

Are there risks in taking injectables?
The primary risks of injectables are multiple births and ovarian hyperstimulation syndrome (OHSS). However, the risks for both are sharply reduced with appropriate monitoring and sound decision-making on the part of the physician and the patient.

In fact, despite all the emphasis placed on choosing one drug over the other, the most important determinant of efficacy and safety for many patients taking injectables is the monitoring. Correct monitoring of follicle size, via ultrasound, and serum estradiol levels will reduce the risk of adverse side effects and will increase the chances of success.

The Impact of Maternal Age and Ovarian Age on Fertility by Steven D. Spandorfer, M.D.

The Impact of Maternal Age and Ovarian Age on Fertility
By Steven D. Spandorfer, MD

 

INTRODUCTION

 

     Age is the most important single variable influencing outcome in assisted reproduction.  The effect of advancing age on clinical infertility is manifested not only in the pattern of ovarian response to superovulation, but also in reduced implantation efficiency and an increased spontaneous abortion rate. In this article, we will explore the physiologic mechanisms behind this reduced implantation efficiency and its effect on infertility outcomes.

 

EPIDEMILOGY OF INFERTILITY

 

            Infertility is evolving.  As the overall health and wealth of the United States has improved there has been a dramatic decrease in the birth rate.  One of the prevailing theories to explain this phenomenon has been that women are more often entering the work force, thereby delaying marriage and childbearing.  The modern development of oral contraception has allowed the working woman to delay her childbearing and therefore, the impact of maternal aging on fertility has become an increasingly important issue.  Attempting pregnancy at 40 is far different than that at 25 years of age.  Fecundability (ability to conceive) decreases and the spontaneous miscarriage rate increases with increasing maternal age.  Therefore, advancing maternal age has become a very important issue for modern fertility.

 

MATERNAL AGE, REDUCED FERTILITY AND OVARIAN RESERVE  

 

     A physiologic decrease in fecundity as maternal age increases has been observed.  In the 1950's, a comprehensive analysis of the fertility rates of the Hutterite sect of the western United States and Canada was undertaken1. This sect originated in Switzerland in 1528, and practically all of the living Hutterites came to South Dakota in the 1870’s.  Because contraception is prohibited and the communal nature of this sect removes economic burdens, there is no incentive to limit the size of families.  Furthermore, sexually transmitted diseases were almost non-existent.  As a result, the birth rate of the Hutterites is one of the highest on record, with an average of 11 live births per married woman.  Only 5 of 209 women studied had no children, for an infertility rate of 2.4%.  There was a definite decrease in fertility with advancing age; 11% of women bore no children after the age of 34, 33% of women had no children after the age of 40, and 87% of women were infertile by the age of 45.  The average age of the last pregnancy was 40.9 years.  This analysis highlights the enormous decline in fecundity after the age of 40 years.

     Although there is an apparent decrease in the frequency of sexual intercourse with advancing age, this does not fully account for the decline in female fertility.  A French study of couples treated with donor insemination for isolated male factor infertility, has revealed that the per cycle pregnancy rate declines with advancing age2.  The cumulative pregnancy rate for women under 30 was 73% after 12 insemination cycles.  In women between the ages of 31 and 35, the cumulative pregnancy rate was 62% over the same time period, whereas women ages 36 to 40 had achieved only a 54% cumulative pregnancy rate.  Therefore, a measurable decline in female fecundity appears to occur at least 15 years before the climacteric.  This decline is independent of frequency of sexual intercourse and is most dependent on maternal age.

     Why does this age-dependent decline in female fertility occur?  Unlike their male partners, women are endowed with a finite and nonreplenishable complement of germ cells.  The maximum number of germ cells actually occurs at midgestation during fetal life, at which time a total of 6-7 million oogonia are present.  Thereafter, the germ cell content irretrievably decreases and no further de novo gametogenesis occurs. Apoptosis and degeneration occur continuously decreasing the total oocyte number.  By birth, a woman is thought to only have 1/6 of her initial oocyte complement (1 million oocytes).  At the onset of puberty, the germ cell mass has already been reduced to approximately 300,000 oogonia.  In other words, before a woman has sufficiently matured physiologically where she can utilize her oocytes, she has already lost almost 95% of her initial complement of gametes.  Thereafter, during the reproductive years, a number of oocytes are stimulated each month with only one or a few becoming dominant while the others undergo atresia.  The absolute number of oocytes therefore continues to diminish with age. 

            At the age of 37 to 38, there is usually an acceleration of follicular loss.  This occurs when the number of follicles reaches approximately 25,0003.  This accelerated loss correlates with a subtle increase in serum follicle-stimulating hormone (FSH) concentration and a decrease in inhibin production.  These hormonal measurements during the early follicular phase of a menstrual cycle (usually on cycle day 3) have allowed clinicains to estimate a woman’s “ovarian reserve”.   The functional capacity of the remaining follicles and germ cells has been termed the "ovarian reserve", or ovarian age.  The functional ovarian age may be discordant with chronologic age, when accelerated follicular loss and/or diminished functional capacity of the remaining follicles occurs at an earlier age than expected.  The subtle changes, which indicate diminished ovarian reserve, are associated with a markedly reduced fertility potential, often without apparent changes in clinically identifiable characteristics or major alterations in menstrual cyclicity.  In other words, while in a population based study, measurable changes of a rising FSH and a falling Inhibin level occur around age 37 years, for the individual this can occur many years earlier.  Importantly, no clinical characteristics absolutely suggest the presence of this phenomenon of a “poor ovarian reserve” despite a relative youthful age.

           

AGE AND IVF OUTCOME

     Older women have a poorer prognosis for success after IVF.  An analysis of our results at The Center for Reproductive Medicine and Infertility of The New York Hospital-Cornell Medical Center has revealed that the mean peak estradiol (E2) level on the day of human chorionic gonadotropin (hCG) declines steadily with advancing age.  This decline in the serum E2 concentration is paralleled with a concomitant decrease in the mean number of oocytes retrieved per cycle.  The delivery rate per embryo transfer procedure in our series drops from around 60% in women 30 years of age or younger to 5.2% for women 44 years of age or older. 

            An examination of the embryo implantation rate (as assessed by the presence of a fetal heart beat per embryo transferred) reveals a decline from 33.5% in women under 34 years to 5.9% in women at age 44.  Thus, a single given embryos has only a 16% chance of implanting when from a woman of 44 years of age as compared to her younger counterpart under the age of 34 years.

            We have analyzed 1621 consecutive cycles of IVF for implantation efficiency as a function of age (June 1995 – October 1996).  In this study we found an overall implantation rate of 23.3%.  Table 1 demonstrates the implantation and delivery rates per embryo transfer throughout this study period.  Implantation was noted to remain almost constant until the age of 35, and then decreased in a significant linear fashion by approximately 2.77% per year (R2 = 0.975; p < 0.0001).  Even when analyzing the sub-group of women with pure male infertility and no identifiable female factor, this same response of diminished implantation efficiency with advancing maternal age was noted.

 

OOCYTE DONATION AS A MODEL OF IMPLANTATION EFFECIENCY

            Oocyte donation serves as a useful in vivo model to further understand the impaired implantation efficiency seen in older women.  Several authors have suggested that the successful implementation of oocyte donation in women older than 40 years suggests that the endometrium of older women retains normal receptivity.7,8 One investigative team failed to show a decrease in the implantation rate per transferred embryo in women older than 40 years undergoing donor oocyte transfer compared to younger recipients9. In a subsequent report, pregnancy outcomes in younger IVF donors were compared with those in their respective older recipients who shared oocytes from the same cohort10.  There was no statistically significant difference in clinical pregnancy and delivery rates between the donors (33% and 23%, respectively) and recipients (40% and 30%, respectively).  These data suggest that oocyte quality, rather than uterine factors, is the primary determinant of human implantation efficiency.

     However, other investigators have suggested that uterine factors may also play a role in the age-related decline in fecundity.  It has been reported that there may be a slight reduction in the embryo implantation rate in women older than 40 years undergoing oocyte donation, which can be offset by doubling the dosage of exogenous progesterone11.  We have also examined the issue of implantation efficiency in older women at our donor oocyte program.  Twenty-four IVF patients who donated half of their oocytes were studied along with their respective recipients. The mean age of donors and recipients was 32.3 and 40.0 years, respectively.  Although the ongoing pregnancy rate for donors (62.5%) and recipients (58.3%) was similar, there was a statistically significant decrease in the per embryo implantation rate in the recipients (25.6%) compared with the donors (42.5%).  These data taken together suggest that there is a subtle decrease in implantation efficiency in older donor oocyte recipients, which may be overcome by performing multiple embryo transfers or by manipulating the hormonal milieu.  Thus, although oocyte quality appears to be the major factor associated with the reduction in fecundity with advancing age, uterine factors and reduced endometrial receptivity may also play a role.

 

 

MATERNAL AGING AND SPONTANEOUS MISCARRIAGES

 

            Maternal age is also a significant factor in determining the miscarriage rate in after successful implantation (as defined as a positive fetal heart).  We have reviewed 2346 consecutive IVF clinical pregnancies (1991-95) and analyzed the pregnancy loss rate by maternal age. The overall pregnancy loss rate after demonstrating a FH during a 7 week U/S was 11.31%.  A highly significant trend demonstrated an increase in fetal loss when comparing the four age groups ( < 30 yrs = 4.95% vs. 31-34 yrs = 9.46% vs. 35-39 yrs = 11.57 % vs. > 40 yrs = 21.28%; P < 0.0001). 91.3% of the losses in women over the age of 40 were chromosomally abnormal as compared to 71.1% of the losses in women under the age of 40 years. Thus, there exists a highly significant increase in pregnancy loss after demonstrating a FH during a 7 week U/S with increasing maternal age. The overwhelming explanation for these losses appears to be chromosomal in nature with almost 80% having an abnormal chromosomal composition.

 

OVARIAN RESERVE

 

            Determining basal FSH and E2 concentrations early in the follicular phase can assess ovarian reserve.  Serum FSH concentrations in the early follicular phase appear to rise several years before the menopause.  It is hypothesized that elevated levels of FSH may result from the reduced secretion of inhibin from the germ-cell depleted ovaries.  These subtle elevations, signaling a decline in the ovarian reserve even in women with regular menstrual cycles, have been typically associated with poor responses to gonadotropin stimulation.  An elevated FSH concentration of greater than 20 mIU/Ml (the ansolute number of FSH elevation depends on the assay utilized and should be individualized by lab) on day 3 of the menstrual cycle has predicted a markedly diminished chance for success after IVF and related assisted reproductive therapies.(12,13)  We have recently demonstrated that elevated E2 levels in the early follicular phase also represent a poor prognostic sign for IVF outcome.  There were very few successful pregnancies in women with elevated E2 levels (>75 pg/mL) on day 3 of the menstrual cycle.  It is theorized that elevated FSH concentrations in the late luteal phase of the preceding cycle may cause latter aberration.

     We have further examined the relationship between basal day 3 hormonal values and IVF outcome.  An analysis of 1249 gonadotropin-stimulated cycles in 782 women treated at Cornell without gonadotropin-releasing hormone agonist (GnRHa) down-regulation, where basal day 3 FSH and E2 were determined concomitantly in the cycle of stimulation, reveals that both influence IVF outcome14.  The ongoing pregnancy rate per retrieval in this series in women with day 3 FSH levels of >20 mIU/mL was one-half of that in women with day 3 FSH concentration <10 mIU/mL.  The same was true for the embryo implantation rate as well.  In this series, the ongoing pregnancy rate per retrieval fell by more than one-half when the day 3 E2 was >75 pg/mL  as compared to when the E2 level was <30 pg/mL. Women with a high basal E2 level rarely exhibit a concomitant elevation in FSH, due to feedback inhibition.  In short, meaningful interpretation of basal hormonal values in the assessment of ovarian reserve requires the simultaneous determination of FSH and E2 on day 3 of the menstrual cycle.  Both have been shown to impact IVF outcome as measured by pregnancy rates and embryo implantation rates. Low early follicular phase inhibin-B concentrations may complement FSH and E2 as markers of ovarian reserve.  As this assay becomes more clinically available, it too can be added as a prognostic assessment of a woman’s “ovarian reserve”.  Finally, a number of provocative tests have been devised to assess ovarian reserve indirectly.  The clomiphene challenge test and the early E2 response to leuprolide acetate administered during a flare protocol have both been reported to be useful tests of ovarian reserve. 

 

SUMMARY

 

      Advanced maternal age is associated with a decrease in fecundity potential.  Diminutions in implantation and pregnancy rates are generally seen after the age of 35, and diminish significantly after the age of 40.  Oocyte factors are felt to be primarily responsible; however, uterine factors may also play a role.  Hormonal assessments of FSH and E2 levels on day 3 of the menstrual cycle are reliable measures of diminished ovarian reserve and the anticipated response to ovulation induction.  A similar decrease in implantation rates and pregnancy rates are seen in older women undergoing assisted reproductive techniques, including IVF.  The decrease in implantation efficiency seen in older women undergoing IVF appears to be independent of the magnitude of stimulation response.  Maternal aging appears to be the single most important factor in predicting fertility outcome.

 

Steven Spandorfer, M.D. can be reached at The Center for Reproductive Medicine and Infertility, The New York Presbyterian Hospital - Cornell University Medical Center, New York, New York

Phone: (212)746-1762

Email: IVF@nyp.org

Website: http://www.ivf.org



 

REFERENCES    

1.         Tietze C:  Reproductive span and rate of reproduction among Hutterite women.  Fertil Steril 1957; 8:89-97.

2.         Federation CECOS, Schwartz D, Mayaux JM:  Female fecundity as a function of age: results of artificial insemination in 2193 nulliparous women with azoospermic husbands.  New Engl J Med 1982; 306:404-406.

3.                  Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF: Accelerated disappearance of ovarian follicles in midlife: implications for forecasting menopause.  Hum Reprod 1992; 7:1342-1346.

4.     Munne S, Alikani M, Tomkin G, Grifo J. Embryo morphology,developmental rates and maternal age are correlated with chromosomal abnormalities. Fertil Steril 1995; 64:382-91. 

5.         Lim AST, Tsakok MFH. Age related decline in fertility: a link to degenerative oocytes? Fertil Steril 1997; 68:265-71. 

6.         Fujino,Y, Ozaki K, Yamamasu S, et al. DNA fragmentation of oocytes in aged mice. Hum Reprod 1996; 11:1480-83. 

7.         Sauer MV, Paulson RJ, Lobo RA:  Reversing the natural decline in human fertility. An extended clinical trial of oocyte donation to women of advanced reproductive age.  J Am Med Assoc 1992; 268:1275-1279.

8.         Antinori S, Versaci C, Gholami GH, Panci C, Caffa B: Oocyte donation in menopausal women. Hum Reprod 1993; 8:1487-1490.

9.         Sauer MV, Paulson RJ, Lobo RA:  Preliminary report on oocyte donation extending reproductive potential to women over 40.  N Engl J Med 1990; 323:1157-1160.

10.       Navot D, Bergh PA, Williams MA, Garrisi GJ, Guzman I, Sandler B, Grunfeld L: Poor oocyte quality rather than implantation failure as a cause of age-related decline in female fertility.  Lancet 1991; 337:1375-1377.

11.       Meldrum DR: Female reproductive aging-ovarian and uterine factors.  Fertil Steril 1993; 9: 1-5.

12.       Muasher SJ, Oehninger S, Simonetti S, Matta J, Ellis LM, Liu H-C, Jones GS, Rosenwaks Z: The value of basal and/or stimulated serum gonadotropin levels in prediction of stimulation response and in vitro fertilization outcome.  Fertil Steril 1988; 50:298-307.

13.       Toner JP, Philput C, Jones GS, Muasher SJ: Basal follicle stimulating hormone (FSH) level is a better predictor of in vitro fertilization (IVF) performance than age.  Fertil Steril 1991; 55:784-791.

14.       Licciardi FL, Liu H-C, Rosenwaks Z:  Day 3 estradiol serum concentrations as prognosticators of stimulation response and pregnancy outcome in patients undergoing in vitro fertilization.  Fertil Steril 1995; 64:991-994.

15.     Cohen J, Alikani M, Trowbridge J, Rosenwaks Z. Implantation efficiency by selective assissted hatching using zona drilling of human embryos with poor prognosis.  Hum Reprod 1992; 7:685-91.

 

Age

Number

Implantation Rate (%)

Delivery/
Transfer (%)

< 25

28

24.4

50.0

26

13

28.9

53.8

27

20

32.7

65.0

28

28

37.5

50.0

29

48

31.9

62.5

30

57

35.4

57.9

31

89

33.0

60.7

32

69

33.0

52.2

33

92

36.8

65.2

34

113

29.5

54.0

35

133

31.0

 

51.1

36

125

28.2

44.8

37

138

23.8

49.3

38

150

18.9

40.0

39

121

18.8

38.8

40

108

16.3

36.8

41

111

14.0

29.7

42

77

9.9

22.1

43

71

5.1

15.5

44

19

5.9

5.8

>44 44

11

2.3

0

History of Data Collection and Statistics and IVF

FACT SHEET:
IVF CONSUMER DATA HISTORY

1984
The Society for Assisted Reproductive Technology (SART) is established at a meeting of the American Fertility Society. At the time, it is named the "IVF Special Interest Group" in order to report only pooled data of its membership (no clinic-specific data) for inclusion in the IVF Registry

1985
In response to complaints regarding exploitation and unscrupulous practices in the area of infertility, and IVF in particular, the United States Congress starts hearings under the auspices of the Office of Technology Assessment (OT A) to address
consumer concerns.

1989
Office of Technology Assessment (OT A) proceedings and conclusions published in the "Wyden Report". Congress subsequently mandates -- under threat of prosecution -- that all IVF programs in the United States report their ART outcome statistics for 1987. The first report of clinic-specific ART outcome statistics in the U.S. is published.

1992
Congress passes the "IVF Success Rate Certification Act of 1992" -- which is implemented in 1997 -- to compel honest disclosure of IVF success rates and quality assurance in all IVF programs

1994
SART gives tacit support to introduction of an "audit" of all its member programs. Peat, Marwick & Company engaged to develop and implement a clinic-specific-IVFoutcome based reporting process. This is abandoned before year-end.

Subsequent gestures to introduce alternative methods for appropriate verification of IVF outcome reporting lead to current "Self-Reporting Process" with "token" random and sporadically conducted onsite reviews

2002
SART sends letter to all IVF Program Directors in the U.S. stating that as a result of "lack of financial and human resources," random onsite reviews of outcome data would not be done for 2002. Instead, IVF facility Medical Directors to perform a "self-review" of medical and laboratory records of ten (10) pre-selected IVF clinic cases. Upon receipt, the center would pass certification and the programs' total, selfgenerated IVF outcome date for the year 2000 would be published on the Center for Disease Control's (CDC) website.

Good Eggs, FSH levels and Ovarian Reserve: The Egg Factor by David Sable, MD

Good Eggs, FSH levels and Ovarian Reserve: 
The Egg Factor 
by David Sable, MD

The concept I describe most frequently to anyone interested in fertility is that of ovarian reserve, or the "egg factor." As of this writing we are quite capable of bypassing the problems of poor quality sperm or low sperm count or problems stemming from dysfunction or disease of the female reproductive system such as endometriosis or tubal disease.

Still vexing though are women in the reproductive age group whose eggs do not seem to respond to the tools that we have available. Eggs are not replaceable. Women are born with all of the eggs they will ever have, and the number of eggs rapidly depletes as women age. Even before a first menstrual period, the number has shrunk from the millions present just before birth to the hundreds of thousands, and many more are lost monthly. Each menstrual cycle sees hundreds of eggs start the journey to maturity, a journey that only one or two will successfully complete. Each woman's ovaries have their own rate of egg depletion, a sort of ovarian career that lasts from puberty to sometime before menopause.

Over time, the chance of conceiving in any particular month drops. For years we debated whether this decline was a result of the aging ovaries or the aging uterus, but the discovery that a woman's reproductive potential could be greatly increased by the use of donated eggs demonstrated that the eggs, and not the uterus, were the cause of the decreased fertility.

Why would that be so? Think about what an egg is and what it does. Compare an egg to a sperm cell, which is essentially a DNA-filled ziplock bag with a tail. Its job is to deliver DNA to the egg and safely usher it inside. A good sperm cell contains normal DNA and has an effective way to gain entry into the egg. This process is so inefficient that nature sends millions of sperm cells out for each egg, to insure that one individual sperm cell gets the job done. Once the sperm has delivered the male DNA, however, the egg itself has to do the important work. It must provide an environment for the effective combining and replication of the now combined male and female DNA, and must split again and again in an equal fashion.

Looking for Good Eggs
A "good egg" has two functions: it must have good normal chromosomes and it must let those chromosomes combine with those from a sperm cell and subsequently divide in an efficient fashion. Eggs with abnormal chromosomes or eggs with cytoplasm (the non-DNA containing portion of the egg, in a simplified but not entirely accurate view) that cannot foster the effective distribution of chromosomes as it splits are the cause of the difficulty women experience as they age.

Unfortunately, egg quality is not easy to judge. Although egg quality declines as women get older, going by a woman's age is not enough. Two women at the same age can have vastly different possibilities of conceiving on any given month. Differences seem particular wide in the 36-41 year old age group. And while we can easily look at sperm, look at its shape and watch it swim, we can directly view eggs only after they have been somehow removed from the ovaries in an unnatural way.

FSH: The cruelest number
We have to look for our clues to egg quality in indirect ways. One possible way is by observing the menstrual pattern. As women age, their cycles shorten. Unfortunately this is such a late phenomenon in a woman's reproductive career and most women's cycles vary somewhat month to month that observing menstrual patterns is a very imprecise method of determining egg quality. So too are measurements of estrogen levels or follicle sizes on ultrasound scans.

So far, the best simple test we have been able to come up with is an early cycle FSH level. FSH stands for follicle stimulating hormone, and is one of the more important ways in which the brain talks to the ovaries. Simply, the brain releases FSH when it wants the ovaries to mature an egg; as the ovaries choose and mature the egg, hormone products from the ovaries signal the brain to decrease the release of FSH. This is an example of a feedback loop. An important concept to recognize is that the communication between the brain and the ovaries seems to be controlled by the eggs themselves, or by the cells that surround the egg and if the communication seems to be poor, it is an indication that there may be a problem with the eggs themselves. We are not sure what the exact nature of these problems are, whether they are in the DNA or the cytoplasm or just in the eggs' ability to respond to stimulation, but we know that a breakdown in the communication between the eggs and the brain correlates with very poor pregnancy rates in infertility treatment.

The FSH test is the simplest method we know of in 1998 to test the ability of the eggs to talk back to the brain. If the system is functioning the way it should, then the FSH level early in the cycle should be on the lower end of the scale. How low? That depends on the laboratory doing the testing. Each lab, by nature of the way the test is done there, will report a different level for a given test. One of the great confusions regarding FSH testing is that a similar level means very different things at different places. Also, some clinics characterize their tests very carefully; others less so. FSH is reported in "units" and results from 2 units to 7 are probably normal in just about any lab. Levels above 25 are probably abnormal. The area between 9-24 may represent normal or abnormal levels, depending on how the test is performed.

Adding to the confusion is that FSH bounces around quite a bit. One month the result may be a 7 and the next month may be a 13. For a while we thought that it might be possible to wait for a month with a better level and improve the odds that a given cycle would work. Unfortunately we learned that the intermittent high FSH is as bad a prognostic sign in months where the FSH is normal as in months where it is high.

Pregnant with decreased reserve
Now I know someone, somewhere is reading this and saying, "Wait a minute-I know someone who got pregnant after being told she had a high FSH." Yes, you can get pregnant with a high FSH. But we are virtually incapable of bringing it about. Almost all of the tools we use in infertility care in 1997 need the ovaries to respond to extra stimulation: make extra eggs, higher hormone levels at the least. Ovaries with diminished reserve still have eggs that can turn into a pregnancy; unfortunately those ovaries respond to the most aggressive stimulations we know of by responding at a baseline level only. One of my colleagues compares the situation to a car that runs perfectly well at 30 miles per hour, and when you push the gas pedal all the way down, it goes…… 30 miles per hour.

Further, the eggs produced by ovaries with diminished reserve seem quite fragile. The tools we use, particularly HMG and IVF are often too much of a stress on these fragile eggs. Many fail to mature at all, many quickly move from immaturity to postmaturity (a sort of over cooking) and the few that withstand fertilization outside of the body rapidly dissolve away into numerous fragments since the ability of the resulting embryo to foster even cell division is compromised. The body, when left on its own, can still gently nurture some of these fragile eggs towards maturity in an effective way, and pregnancy is still feasible (although not nearly as common as we would like). When we bombard these same eggs with FSH or FSH and Lupron, or try to develop them in the in vitro environment, they do very poorly.

In these circumstances we are left with two polar extreme choices to offer patients: either to try on your own and hope that one of the infrequent natural pregnancies occur, or do IVF using a donor's eggs. In the unfortunate cases where there are blocked tubes or a severe male factor, where a natural pregnancy is extremely unlikely even if a perfect egg were matured and released, the only real option, as of early 1998 anyway, is oocyte donation.

Returning to the subject of testing, I mentioned earlier that the FSH bounces in and out of the abnormal range during the diminished reserve period and that waiting for a "good month" is not helpful, that once the level starts appearing in the high range the ovaries as a whole can be considered unresponsive and the eggs more fragile. This leaves open the possibility of being misled by a normal value when the FSH is on the downswing of its variability. Are there ways to avoid this? Actually there are two. Recall that a finely tuned communication between the ovary and the brain will result in a low FSH value on days 2,3, or 4 of the cycle. We have noted that the same fine tuning results in a low estradiol (estrogen) level at the same time. Further, an abnormally high estradiol level can artificially decrease the FSH and lull us into a false sense of security about the ovarian reserve. For these reasons we usually look at the estradiol (a.k.a. E2) level when testing FSH. And while there is no specific E2 level that precludes successful infertility treatment the way FSH levels can, E2 levels that are high (above 100 is a good benchmark) are good indications to look beyond just one FSH level for reassurance that the ovarian reserve is ok. How do we look beyond the one FSH level? One way is just to repeat the day 3 tests several months in a row, but this is obviously inconvenient and wastes a lot of time. A quicker way is by using the second method of extended ovarian reserve testing, called the clomiphene citrate challenge test (a.k.a. CCCT).

Clomiphene citrate challenge test:
Day 3: FSH and E2 level 
Day 5-9: clomiphene citrate 100 mg (2 tablets) 
Day 10: FSH and E2 level 
The basis for this test is that the FSH level should be lower on day 10 than on day 3. Using clomiphene citrate (a.k.a. Clomid or Serophene) on days 5 to 9, the FSH will actually rise on day 10 in women whose ovaries lack the ability to properly signal the brain. A high FSH level on day 10 is as bad as a high level on day 3, and can keep us from mistaking the bottom part of a bouncing FSH curve for false reassurance on the state of the ovaries.

I hate all of these tests. They are nothing but bad news. A bad level is always bad, good levels might still be bad and I can't fix the underlying problem. And while oocyte donation offers many couples an excellent and fulfilling way to bypass the problem of diminished ovarian reserve, FSH testing is a constant reminder that we are still unable to help one of the largest groups of people who seek us out to help them conceive. Hopefully, advances in our ability to either rejuvenate the eggs in these women or to better separate the genetic from the growth components of eggs (and then use donor eggs with a woman's own chromosomes) will change this scenario. Cytoplasm transfer is an important step in this direction; others are coming. I look forward to using FSH testing to help choose the right tools, rather than having them tell me I have none. 

SEE the Video Web Cast with Geoff Sher, MD: New Breakthrough in IVF. Study Doubles IVF Success

NEW STUDY --- Doubles the IVF Success Rates -- Geoffrey Sher will be coming to INCIID to chat about this breakthrough
You will need Windows Media Player to view this audio/video webcast.
Download the free media player here.

 

(SEE THE VIDEO OF THE WEBCAST  ---- CLICK HERE)

A process that could markedly improve pregnancy rates from In Vitro-Fertilization (IVF) was reported in a
study published in the prestigious medical journal Fertility and Sterility (F&S). 
This was presented on Feb. 15, 2007 - 9:30 PM ET

 

      "This very exciting breakthrough could more than double IVF pregnancy success rates while reducing the risk of multiple births. We are now much closer to the goal of one IVF attempt, one egg, and one embryo, yielding one healthy baby," said Dr. Geoffrey Sher, who along with Levent Keskintepe PhD , both of ReproCure, LLC and the Sher Institutes for Reproductive Medicine(SM) (SIRM) developed the process and conducted the study.

Dr. Geoffrey Sher will come back to INCIID and do a follow up chat with us. TBA  

Start sending your questions ahead of time, please email them "WebCast" using the INCIID Contact Form
Subject of your email should be IVF Breakthrough Question
Check back here for time and date of this chat.

 

Press Release: Class Action Law Suit Filed Against Blue Cross Blue Shield of California

October 26, 2007

PRESS RELEASE

[For Immediate Release]

 

A lawsuit charging Blue Cross of California with failing to offer infertility benefits required by California law was certified as a class action on Tuesday.  This will allow the class representative and her attorneys to seek an injunction directing Blue Cross to offer much broader infertility coverage to group health plans covering employees of governmental entities and many religious institutions.  Blue Cross currently offers only a limited benefit of $2,500 a year, and requires plan members to pay 50% co-pays.

According to attorney Mark F. Didak of Los Angeles, who represents the class, California Health & Safety Code and Insurance Code require health plans to offer infertility coverage on the same terms as they cover other health conditions, without lower coverage limits or higher co-pays.  “The benefit should cover all infertility diagnosis and treatment services ‘consistent with established medical practices,’” Didak said, “except that health plan providers are not required to offer coverage for the actual laboratory procedures involved in in vitro fertilization.”  The last part is important, says Didak, because health insurers typically refuse to pay for anything associated with in vitro fertilization, which can cost anywhere from $10,000 to $25,000 per cycle.  “The law only allows them to not offer coverage for the lab procedures, which usually cost between a few hundred dollars and $1,500.”  Didak hopes to persuade the court to issue an injunction that might serve as an example to the health insurance industry by clarifying what infertility benefits must be offered and which ones they can choose not to offer.

The lawsuit was filed in 2006 by plaintiff Deborah Dunn Yeager and is pending before Judge Victoria Chaney of the Los Angeles Superior Court.  Prof. Dunn Yeager, who teaches communications at Westmont College in Santa Barbara, enrolled in a Blue Cross plan at work believing it covered infertility problems, only to have her benefits claim denied.  Her college, she discovered, had not been offered infertility coverage on the terms required byCalifornia law.  The statutes, Health & Safety Code section 1374.55 and Insurance Code section 10119.6, also mandate that “every plan shall communicate the availability of that coverage to all group contractholders and to all prospective group contractholders with whom they are negotiating.”

Up to 15% of all couples of child-bearing age suffer problems conceiving.  The problems are often treatable, many times with relatively inexpensive methods.  “When the California Legislature passed the law requiring health plans to offer this coverage in 1989, they found that infertility ‘affects millions of Californians,’” said Mr. Didak. “The Legislature also found that ‘[i]f properly treated, successful pregnancies can result in 70 percent of [infertility] cases,’ but that ‘[i]nsurance coverage for infertility is uneven, inconsistent, and frequently subject to arbitrary decisions which are not based on legitimate medical considerations.’”

Mr. Didak continued, “what’s clear is that if infertility coverage is always offered as the law requires, it will be sold more often, solving the problems the Legislature was trying to address.  It will also bring the price of coverage down as more and more groups purchase it.  Blue Cross will no longer be able to deny necessary medical treatment to people who want the chance to start a family or have another child.  It’s one of the most fundamental rights any person has.”

 

[For more information, please contact class counsel Mark F. Didak at (310) 689-7022 or mdidak@selmanbreitman.com.]

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