The public’s appetite for promising pills that purportedly slow down the aging process is stronger than ever. Sensationalized claims revolving around Dehydroepiandrosterone (DHEA), a natural steroid hormone produced from cholesterol by the adrenal glands, has followed this trend.

DHEA is a hormone secreted by the adrenal gland whose level in the body peak at early adulthood and then decline with age. As the most abundant steroid in the body, DHEA is chemically similar to testosterone and estrogen.

Because low DHEA levels brought on by aging also correlate with age-related diseases, DHEA supplements are openly marketed to prevent the effects of aging. Because a woman’s fertility declines with her age, it is no surprise that DHEA has been associated as a “promising” drug to offset age-related infertility. Yet there have been no scientific studies or evidence revealing that adjusting DHEA levels changes the development of age-related diseases. Nor has there been evidence that DHEA slows down the decline in fertility. Simply stated, there is no evidence that increasing DHEA slows down, stops, or reverses the aging process.

Some past rodent studies indicated DHEA was effective in controlling obesity, and prevented cancer, arteriosclerosis and diabetes. As a result, DHEA was quickly promoted as a miracle weight-loss drug. Yet no human studies have duplicated these results.

Nevertheless, DHEA has received considerable acclaim, with some authors touting it as a “superhormone” or “the youth and health hormone.” Articles on DHEA abound. In fact, DHEA received over 850 citations in a Medline search and 52 publications come up on an Amazon.com search.

A search of serious scientific research examining DHEA’s impact on fertility is scanty. There are less than a handful of scientific presentations or papers on the topic. Just last year a study (Fertil Steril. 2005; 84(3):756) conducted at the Albert Einstein College of Medicine announced: Increased oocyte production after treatment with dehydroepiandrosterone. This paper focused only on one 42 year old woman, whose number of oocytes retrieved increased after undergoing eight IVF cycles over the course of a year with DHEA supplementation. Not only did she take a DHEA dietary supplement, she also underwent acupuncture. Since she froze her embryos, it is not reported whether any of her eggs led to a successful pregnancy.

To date, no sound or controlled scientific studies have been designed to examine whether DHEA is able to reverse the results of aging on ovarian reserves.

A research paper was presented at the 2005 ASRM conference (O-101 by D. H. Barad and N. Gleicher). This retrospective cohort study examined 45 women previously diagnosed with decreased ovarian reserve who were treated with 25 mg DHEA for 4-48 weeks before undergoing ovulation induction for IVF. The study concludes that DHEA increased oocyte production and quality. Yet no pregnancy or live birth outcomes were reported. Both Drs. Barad and Gleicher are already offering “DHEA Therapy” in their practice.

Very little of the encouragement to self-administer DHEA is coming from the physician community, especially those who are initiating viable scientific research. Elizabeth Barrett-Connor, MD, professor and chair, department of family and preventive medicine at University of California, San Diego calls DHEA “a modern day snake oil”. Her initial research revealed that higher natural levels of DHEA in older men may help protect them against heart disease yet she recognizes the need for more studies.

Self-medicating by using DHEA supplements is a form of testosterone therapy. It is not likely to affect each individual in the same way due to variable existing androgen levels in the body and a lack of consensus on what are normal or benchmark levels. Increasing DHEA (and thus testosterone) may well lead to additional facial hair and possibly acne for women. Until more is known, taking DHEA is a risky gamble based on insubstantial evidence.

The hype about DHEA as a way to improve fertility will only continue as the public seeks information that they want to hear. An entire chapter is devoted to DHEA in an online book called “Mothers over 40”. If there were such an easy panacea to reverse the impacts of aging on infertility, the benefits would have been known much sooner.

– Eldon Schriock, MD

Question:
What is my fertility physician looking for in conducting an antral follicle count?

Answer:
Women are born with all of the eggs (oocytes) that they will ever have. This is a set number, which is determined before birth. This pool of eggs is never replenished. A female fetus will have the greatest number of eggs around 16-20 weeks of pregnancy (6-7 million); at birth this number decreases to about 2 million; and by puberty to about 300,000. This constant and dynamic process of decline continues until menopause and is not interrupted by birth control pills, pregnancy, or ovulation. From this reservoir of eggs, fewer than 500 eggs will ovulate during a woman’s reproductive life.

There is a continuous process occurring in the ovaries, where eggs are constantly being prepared for the maturation process. It takes 3-6 months for eggs to develop and mature. As the eggs are developing, they transition from a primordial, to preantral, to then antral follicle. Antral follicles are visible by vaginal ultrasound. Antral follicles therefore represent the reserve of eggs in our ovaries and those that are candidates for selection and growth by fertility stimulation medications (gonadotropins).

When assessing one’s ovarian reserve (potential for a successful pregnancy), a number of parameters are evaluated. One of these is called the “antral follicle count” (AFC). An antral follicle count is typically done during the 2nd-4th days of menstrual flow, though it can probably be as accurately done during other times of the menstrual cycle. Studies show that the AFC is predictive of the expected ovarian response to gonadotropins. An AFC less than 6 total (between both ovaries), predicts a poor stimulation response. For those undergoing IVF, a similarly low AFC will be associated with a higher cancellation rate. As women approach their 40s, and as day-3 FSH results rise above 10 mIU/ml, this typically correlates with fewer eggs overall in our ovaries, and therefore a low AFC. Indirectly, a low AFC can correlate with diminished ovarian reserve.

In the same way that there can be monthly variability in day-3 FSH test results, there can be monthly variability in the AFC. More variability is observed in the AFC of young infertile women than in older women. However, overall a single AFC is still quite predictive of ovarian response under gonadotropin stimulation, and there is fairly good agreement between repeated AFC over consecutive cycles. In conclusion, doing an AFC is an adjunct to the day 3-FSH test to predict ovarian reserve and ovarian response to fertility medications.

– Isabelle Ryan, MD

Q.
I’ve noticed that there are FSH urine test kits for sale over-the-counter to help women confirm the onset of menopause. Since FSH testing is involved in determining fertility reserve, can I use this over-the-counter FSH test to help realize my fertility potential?

A.
It appears as if a fair number of over-the-counter FSH test kits are indeed sold in drug stores and over the Internet. I am not going to comment on their efficacy for measuring hormonal changes that the pre menopausal body starts to undergo. But I can answer your question. These test kits are not useful tools to help you determine your fertility potential.

By way of background, human follicle stimulating hormone (FSH) produced by the pituitary gland stimulates primordial follicular growth and estrogen production by the emerging follicle that will mature into an egg.

The urine test kits provide a black or white – yes or no answer, not a glimpse of your FSH level in the context of a gray scale range of indicators. For accurate fertility potential diagnosis, we analyze FSH level in much more detail. On day two or day three of your cycle (following menses) we test your FSH level in conjunction with other tests including estradiol (E2) and an antral follicle count.

Most home urine tests, such as for pregnancy tests and ovulation predictor tests, use a threshold level of the hormone in the urine to detect a positive. With FSH test kits, only when the level reaches menopausal levels of FSH, equivalent to around 40-50 mIU/mL or higher in the bloodstream, will the test turn “positive.” For most women interested in testing for ovarian reserve, we would be looking for levels equivalent to 5-20 mIU/mL. So the sensitivity of the testing is set for menopausal and post-menopausal levels, not the levels seen in women with regular menstrual cycles. By the same token, they will not be able to discriminate normal from decreased ovarian reserve.

– Carolyn Givens, MD

Q.
My grandmother had a daughter (my mother) pretty late in her life – I believe she was 42! Can I count on being fertile at this late age?

A.
Aging of the egg is a complex event. It is possible that the eggs of mothers and daughters age similarly, and that some of what we see as age-related infertility may be genetically determined. We have not identified any definitive research, but there is suggestive evidence that late age fecundity is passed from one female generation to another.

It is clear that the age at menopause runs in families. The average age at menopause is 49, but a few women enter menopause in their 20s or 30s and some in their 50s or 60s. The strongest predictor of a woman’s age at menopause is her mother’s age at menopause.

In certain population clusters there are women that show very high natural fecundity. In these groups, the women are closely related, and they continue to attempt conception into later years. Very high natural fertility rates can occur into the late forties.

There are some chromosomal abnormalities that can cause premature menopause that can be inherited. An example is a Turner’s mosaic, where a woman is missing a piece of her X-chromosome. This problem is associated with premature menopause, and can be passed from mother to daughter.

Many non-genetic factors determine late-life fertility, such as use of birth control, degree of sexual activity, and medical problems that affect the uterus and ovaries. Some of these factors are determined by personal choice, and some are events that occur naturally. Many are not genetically determined.

The determinants of fertility are complex; many factors play a role in fecundity. Until dedicated research studies examine the question of whether late life fertility is heritable, we would have to say that we are not sure of the strength of the genetic relationship. There likely is a genetic determinant, but not necessarily one on which you can depend.

– Philip Chenette, MD

After four years of trying to have children we were beginning to lose hope. At 36 and 48 years of age we knew we didn’t have unlimited time to keep trying.

Our journey began with high tech ovulation monitors, hoping for the best every 28 days. We lost faith more than once, struggling through the monthly disappointments. Eventually we went for fertility testing – sperm count and motility for him, ovary and uterine health for me. Everything looked fine. Still no results.

Next we sought out a Naturopath. More tests plus a daily regime of herbal remedies. No luck. Then we turned to our trusted OB for a round of IUI – what we affectionately called the “turkey baster”. Still no results. Next we looked to Eastern medicine and engaged an acupuncturist specializing in infertility. More herbs. Every day. No results. Finally, in the summer of 2004, we began researching Bay Area fertility clinics. We assumed it would be the last step in our journey, either way.

In September 2004 we began working with PFC and embarked on our first round of IVF. Scott learned to give shots, and Cara dutifully produced five eggs of various sizes, only two of which turned into embryos, both of very low quality. We hoped for the best but knew the chances were minimal. The pregnancy test ten days later confirmed we weren’t pregnant. It was disappointing, to say the least.

We met with Dr. Ryan and discussed what to expect for our second round. If we had a similar experience in round two, which was likely, we needed to consider the alternative of an egg donor. This was not good news. To learn that IVF may not allow us to have our own children was extremely discouraging. We took several months off to prepare for the second round. We felt it might be our “last chance” of having a baby that was biologically ours.

In January 2005 we started our second round at PFC with a modified stimulation protocol. This time Cara produced eight eggs, two of which became “viable” embryos and a third that was marginal. Even though the two viable embryos were “Grade 2” and were only six or seven cells, they were at least considered “reasonable.” We hoped, prayed, and tried to remain calm and positive.

Then the “magic” began. Within a few days of the egg retrieval Cara had a dream we would have twin babies – a girl and a boy. And a week before our first pregnancy test a close friend dreamt we were pregnant. Then his wife announced she had a premonition we were going to have twins. We stayed hopeful.

After ten days of waiting we received the results of our pregnancy test, and it was positive! Plus Cara’s hCG level was high enough to indicate there could be more than one “bun in the oven.” At our 6 week ultrasound we announced to Dr. Ryan that we had twins (before the ultrasound). When she found two embryos (7mm and 9mm long) with two happy heartbeats, it was as if we were being told something we already felt we knew.

We are now entering our 4th month of pregnancy. Every day we envision our babies being born healthy and happy. We are so grateful to Dr. Ryan, the entire PFC staff, and the many people that have supported our journey. We remain in awe of both medical technology and the magic of the universe for helping us to create two new lives.

– Cara and Scott France, Pacifica, CA

Q.
I’m strongly considering an IVF cycle. Is there any way to know how productive my ovaries are likely to be besides blood tests? I’m 38 years old.

A.
There is no reliable screening test that peeks into your ovaries to determine your “ovarian reserve”, that is, how many eggs you might have available for fertilization. However, one good measuring method that we use is to count your antral follicles, which are tiny resting sacs containing immature eggs that are waiting to develop.

Active ovaries continuously form these follicles – they bubble up or percolate from microscopic immature eggs to the antral follicles that are visible on ultrasound. As ovaries age, fewer of these antral follicles are visible. The antral follicle count is a powerful method of predicting the numbers of eggs; it is not quite so good at predicting embryo quality.

The test is usually done early in the menstrual cycle. Ideally, we like to see 6-8 follicles per ovary, although women have been known to get pregnant even with low antral follicle counts.

After three failed IVF attempts, my partner, whom I’ll call “Sam”, and I decided to go the egg donor route. The choice actually reduced the degree of frenetic attention we had been paying to our “baby project”. All along, we had been racing against my biological clock as I went from age 38 to 41 with only disappointing results, including one early miscarriage. Curiously, our decision to use a donor evoked a peculiar calmness as I realized that as long as we chose a young egg donor, I could be almost any age!

We then spent some time looking at the various donor databases, yet weren’t truly happy with any of the candidates. Not that we could define the perfect donor profile, but none of the women felt just right. So I let our “baby project” sit on the back burner as life moved on, thinking autumn would be a good time to resume.

Given that the entire process can take up to three months, this past July, without too much expectation, I casually made a 2nd appointment to view PFC’s binders, which contain photos and essays of each egg donor. I was fully prepared to go through the motions and leave without finding the “right one” but one particular donor’s profile just leapt out.

Her photographs revealed a woman who just beamed with exuberance and yet seemed grounded. Other positive indicators included a completed college degree and a job in a field that interests me. Her intelligence, focus and motivation were good signals. I also noticed we shared the same favorite color, and had both played the flute and piano at one point.

A second woman, with a closer ethnic background also emerged as a good candidate. At age 21 she already had a child but no college whatsoever. I decided to return home with both profiles so that Sam could have some buy-in on our choice, although I had quietly decided on my favorite.

When Sam wholeheartedly chose my favorite, I felt an enormous wave of relief. The process started feeling less like an abstraction and I posted her portraits on my bulletin board and looked at her face on a daily basis. Her smile was actually encouraging and I grew increasingly comfortable with the notion of using her eggs and having her genetic material in my body and baby. After all, I am in a sense fusing with her.

We then had to decide whether to meet our donor. Sam opted out but I reluctantly decided yes. No doubt, the meeting would be awkward and my biggest fear was that I might change my mind after discovering an undesirable trait!

But the mediated 45-minute meeting went well and felt relatively natural even though there was a drastic limitation to our conversation. Imagine making small talk and not being able to say much about work, home and so forth! Her quiet and reserved demeanor offset my nervous energy, and she just let me babble on. I enjoyed hearing her mention a few anecdotal points about her own childhood, giving me a good sense of her family past. We agreed that it would be a good idea to meet again at some far-off point, if a child indeed developed. I definitely got the impression that she would respect boundaries and she affirmed this.

Soon we’ll know if our donor relationship is truly successful and results in a pregnancy. Sam and I have high expectations. He likes the favorable odds and I like the donor, so we hope for the best.

– JMT / San Francisco (name withheld upon author’s request)

Q:
I am a 49 year old man considering becoming a father again. Should I be concerned that my age has an impact on sperm quality?

A:
Although there is no strong evidence that sperm suffer the same age related degradation as women’s eggs undergo, older sperm do cause their fair share of genetic problems, albeit in a much different way.

In contrast to females, who are born with all their eggs, men have no sperm when they are born. They don’t make any sperm until they reach puberty, when a prolific and persistent production begins. The average man makes about 250 million sperm a day: that’s about 6,000 sperm every time his heart beats. As a man ages, sperm production continues unabated, and there is no strong clinical or scientific evidence that production decreases significantly even in 70 and 80 year old men.

Since sperm production is so high, a man has to keep copying his DNA over and over again to make sperm. All this DNA copying leads to small mistakes, called mutations. If you remember that at its most basic level, DNA is a series of letters that make up recipes called genes. If the recipe is copied millions of times a day, mistakes inevitably happen.

Imagine having a cake recipe that has 3 cups of flour as part of the text. You photocopy the recipe for a friend. She photocopies your photocopy for a friend and so on. After multiple copies, your 3 cups of flour might start to look like 2 cups of flour, and suddenly your cake recipe doesn’t work any more.

These subtle copying defects cause a long list of diseases in the children of older fathers. Lesch Nyhan Syndrome, Polycystic kidney disease and Hemophilia A are among the most well known. For fathers over age 40, the risk of having a child with a disease-causing mutation is similar to the risk the mother has for a child with Down syndrome.

The biology of eggs and the aging of ovarian reserves are relatively well understood phenomena. As people gain a better understanding of how aging sperm can contribute to fertility complications, older couples will have better tools for planning their families.

Our 7 year old daughter sneers when we joke about why she is a fanatic about ice cream: “Because you were a frozen embryo for 9 months.” To our 4 year old twin boys, also conceived by ICSI/IVF, we sometimes say, “double trouble – we wanted one more boy, and we got two!” They, along with our adopted Korean son, don’t realize that they are true miracles, particularly since the most recent IVF attempt was given a 2-5% chance of success by Dr. Schriock, because “age was an issue,” and to our dismay Emily’s FSH level had tripled since our prior successful IVF cycle.

Never as a couple did we predict that we would be challenged with unexplained infertility. Emily took for granted that she would some day have children, having put career and studying as a top priority throughout her second decade. But as a pediatrician and geneticist, we too became part of the Bay Area epidemic of infertility as we struggled to start a family. Each day at work Emily became ever-so-more aware of the challenge as she counseled pregnant women about genetic testing. I myself, a psychiatrist, became concerned about the emotional roller coaster, because Emily seemed obsessed with the goal of having a child.

Despite the lack of control we felt, now that we have completed our quest to be parents, we are truly appreciative of the expertise, wisdom, and compassion of PFC doctors and staff.

We feel blessed by what we have learned:

1. We never take our children for granted;
2. Each child, no matter how he/she came into the family, is loved equally for the joy each one brings – adoption is just as much of a gift as a pregnancy;
3. There are some advantages to raising twins;
4. Our lives are enriched from the relationships we formed with health care providers and friends;
5. Life is precious – we more deeply cherish our own lives and value friendships, hobbies, nature, family time;
6. We have more sensitivity towards others who have similar struggles.

We are also compelled to share what we learned:

1. Don’t hesitate to ask questions or seek multiple consultations;
2. It is useful to record all notes in a journal to help think of questions, and to feel more knowledgeable and in control;
3. Take advantage of scientific journals on infertility, RESOLVE and their resources;
4. Start therapy and counseling if needed;
5. Use the internet to research and read the many available books, but also keep in mind that some information is not substantiated by good, sound data;
6. The field of infertility advances quickly, and given new choices – there is always hope;
7. Look into other options, even though at times it may seem there is no light at the end of the tunnel. Adoption does not have to be a last resort;

Don’t forget, after the challenge of infertility, there is perhaps an even greater challenge – parenting!!!!

– John and Emily, San Francisco

Q:
I am 40 years old and have been experiencing unexplained infertility for about 2 years. I have been reading that PGD may help to improve my chances of success with IVF. Is this true?

A:
PGD, or Pre-implantation Genetic Diagnosis is a technique, when used in combination with IVF, that can help to determine if the embryos have what it takes to successfully establish a pregnancy. As women get older, there are more errors in the chromosomal make-up of eggs. The most well-known of these defects is Down Syndrome or Trisomy 21, a condition in which the fetus or baby has an extra chromosome number 21. Having a missing or an extra chromosome may make the embryo unable to develop much past a few days of life or may result in a first trimester miscarriage. PGD uses a DNA-binding technique to determine if there are a correct number of chromosomes in the embryo. To do this, embryos on Day 3 of culture (5-10 cells) undergo a biopsy to remove a single cell. The rest of the embryo remains in culture in the IVF laboratory. The biopsy cell is analyzed for the correct number of chromosomes. Currently, PFC with its cytogenetic partner, St. Barnabas Medical Center, tests for 9 chromosome pairs which represent the most common abnormalities seen and some of the most serious in terms of a potential birth defect. As this technology continues to evolve, we expect to be able to assess all 23 pairs. IVF with PGD cannot correct defects in chromosomes. It can only diagnose whether an embryo is abnormal for these 9 chromosomes. The embryo could still be abnormal for one of the other 14 pairs. PGD may decrease the possibility of a miscarriage due to abnormal chromosomes. It may allow for the selection of the embryos most likely to implant and cause a normal pregnancy. If a woman has a good number of fertilized eggs to work with, it may eliminate having an excess number of embryos returned to the uterus at any one time and may eliminate having frozen embryos that really are not genetically normal. Because the embryos will have been screened for some of the major chromosomal abnormalities, theoretically, the remaining embryos should provide a patient who is older a better chance at a viable pregnancy. Some studies have shown that the implantation rates (chance that any one embryo will successfully implant) can be doubled with IVF/PGD. Also, miscarriage rates have been reduced by one-half and the delivered pregnancy rate is increased. Women or couples interested in this procedure should discuss it with their Reproductive Endocrinologist. At PFC, we also refer our PGD patients for a special genetic counseling session in preparation for this process.