Fertility Basics: Your Questions Answered

Q: What do we need to do first?

According to Dr. Wahl, there are three fundamental questions that need to be answered for a woman trying to conceive.

1. How effectively is she ovulating (which is related to the quality of her eggs)?
2. Are her tubes functioning (you cannot conceive naturally if they are blocked)?
3. Is the semen quality good?

A woman purchasing sperm can be reasonably sure of good quality (see page 66). A woman using a known donor, on the other hand, will want to have it evaluated by semen analysis.

The other two important questions will need to be explored at the start with a doctor, especially for the single woman who doesn't have many options for trial and error, as married couples do who can attempt to conceive via intercourse for a year before seeing if there is a problem.

Wahl: In the basic fertility work-up, ovulation can be evaluated by serum levels of FSH, estrogen, progesterone and Mullerian Inhibiting Substance. For the latter, elevated levels are roughly correlated with growing ovarian follicles, suggesting positive ovulation potential. Tubal patency is determined by an HSG test.

Although sophisticated technology gives us many options, it should be an adjunct to a relaxed and confident attitude. I never underestimate the power of positive thinking.

Q: How do I find out if my eggs have the quantity and quality required?

Singleton: There are three main factors to look at when evaluating a woman's ovarian reserve, or her ability to produce eggs.

1. Age, because we know as we age that we have fewer eggs available and the quality of these eggs and their ability to function when mixing your DNA is reduced. That decline increases after age 35 and especially after age 37.
2. We also look at the size of the ovaries. An ovary that is not producing eggs will be smaller than one that is producing more eggs. A basal antral follicle count, by ultrasound, shows us the follicles. These are the fluid-filled pockets within the ovaries that have the potential to produce eggs. If we look at that and see numerous follicles, that's more reassuring than an ovary that has fewer.
3. We also look at hormones, specifically follicle stimulating hormone or FSH. We know that in a normal cycle for a woman, her pituitary gland produces FSH, which stimulates those ovarian follicles to grow. The more help her body needs to produce eggs, the higher her FSH production will be.

Willman: Perhaps the best method we have of testing the ovarian reserve is obtaining the FSH level on the second or third day of the menstrual cycle. This measurement may be very important in evaluating how aggressively to treat women, especially those who are approaching the age of 40, and also to give that woman a realistic idea of her chance for a successful pregnancy. Generally a level of less than 10 is good, 10-14 borderline, and 15+ suggests a very low chance for successful pregnancy with fertility treatment with a woman's own eggs. A single elevated FSH level predicts a poor prognosis even when subsequent FSH levels are normal.

Measuring an estradiol level in the blood at the same time as the FSH also is helpful. There is evidence that if the estradiol level at this time in the cycle is above 75, then even with a normal FSH level the ovarian reserve is compromised. The estradiol level, however, does not seem to be as predictive as the FSH level.

The Clomiphene Challenge Test seems to be more sensitive in picking up diminished ovarian reserve, particularly as women get close to 40 years old. For this test, an FSH and estradiol level is measured on the third day of the cycle, and then the medication Clomiphene is taken (100 mg. on cycle day 5 - 9). An FSH level is measured on day 10. It seems as though the full Clomiphene Challenge Test is more important as women get closer to age 40. An abnormal Clomiphene test predicts that a successful pregnancy will be achieved only about 5 percent of the time.

Studies are being done to evaluate other ways to test ovarian reserve. Possibilities include measurement of blood levels of Inhibin B, and ultrasound measurement of the number of small follicles on the ovaries early on in the cycle. However not as much predictive information about these tests is currently available.

Schoolcraft: A newer test, known as anti-Mullerian hormone, or AMH, can also be drawn in the blood and is a reflection of the quantity of eggs the patient has available.

Q: If my FSH level is high, what does this mean?

Note that testing FSH on day 3 of a woman's cycle, give or take one day, is crucial.

Licciardi: If the ovary has many eggs, the FSH in a woman's blood is low because the body doesn't need to work hard to get a normal ovulation. If the egg number is low, the body needs to work harder to get ovulation, so it increases the amount of FSH in an effort to push the ovaries. A high FSH means the egg number is reduced, sometimes to levels so low that pregnancy is not possible. What is a good level? That depends on each individual lab and IVF program. For most centers, anything over 12 is considered not so good. In fact, some centers will not give fertility treatment to those over 12 because the odds of pregnancy become very low (but are not always impossible).

Some doctors say once there is one elevated FSH, it's over. This is not true. FSH levels go up and down from cycle to cycle (could be by a few points), so one elevation, along with other levels that are in the normal range, does not mean sterility. Therefore, I always repeat levels when the first reading is high. Repeatedly high levels are a very bad sign and should not be ignored.

Redmond: FSH testing is tricky because it can appear normal even when egg quality is compromised. That's because of the prolonged period of time in every woman's life when her egg quality is severely compromised but her day 3 FSH level is still normal. It is not uncommon to have a patient come to you at age 38 with all testing, including the FSH normal, but no pregnancy happens. Then at age 40 her FSH finally becomes elevated.

How long is the interval of infertility until the FSH is high? Impossible to know. Can it be longer than a few years? Maybe. Can it be less time than that? Maybe. You just can't know because you can't check the eggs.

However, whenever a woman over age 35 sees me with infertility and all other testing is normal, the hidden problem may be many things, but it is most likely an egg quality issue. Over age 38 it is highly probable, over age 40 it is pretty much a certainty. It is much trickier with women coming for donor sperm, as usually they do not present with a pre-existing history of infertility. If their FSH is normal, all they can do is try and see. Some will conceive, some will not, and you cannot pick off the successful ones, or the unsuccessful ones in advance. All you can quote them is the group statistic. So normal testing cannot be interpreted as 'it's okay, you're fertile.' We can only say that if the FSH is high, 'it's not okay, you're unlikely to be fertile.'

It is often a bit confusing to patients. Normal testing does not infer normal fertility, because our testing cannot test many important things, like egg quality. Only the reverse is true: blocked tubes, high FSH, no ovulation and so on infer impaired fertility. No one can ever be reassured, before proceeding with donor sperm insemination, that it will work. You can only warn the ones who have testing results that pretty much tell you it will not work.

Willman: In practical terms, an abnormal FSH level usually, but not always, predicts a poor response to fertility medication. More importantly it predicts a low chance for a successful pregnancy with fertility medication or IVF.

A recently reported study from the large IVF program at Saint Barnabas in New Jersey reported on the outcome of IVF cycles in more than 1,000 patients with abnormal FSH levels. The pregnancy rate with IVF in these patients was less than 3 percent, and more than two-thirds of these pregnancies miscarried, resulting in a delivery rate of less than 1 percent. Women who get pregnant with an elevated FSH level have a high likelihood of miscarrying. Some studies have suggested that an abnormal FSH level is associated with a high percentage of genetically abnormal embryos. It is important to note, however, that abnormal FSH levels are not absolutely predictive of no possibility for a successful pregnancy. All of us in the field have had patients with markedly abnormal FSH levels who have gone on to deliver healthy babies. These situations are however, uncommon.

Q: What are some of the reasons my ovarian reserve might not be adequate for conception?

Ashby: In real estate, people talk about location, location, location. For fertility, it's age, age, age.

After the natural ovarian aging that goes with age, there are autoimmune diseases that can affect the ovaries. Lifestyle factors such as smoking, drug treatments and chemotherapy have an impact. Smoking alone reduces a woman's fertility by 50 percent, and that's not necessarily reversible after she quits. Extreme levels of exercise and being underweight can affect your ovarian reserve, as can being overweight. Research shows that being overweight and having polycystic ovaries reduces fertility. Being overweight only is an uncertain risk factor, we don't know if it reduces fertility.

Kim: Everyone ages at a different rate. Your ovarian function starts to decline well before you have any menopausal symptoms. You lose eggs all throughout your life, even if you're on the birth control pill and not ovulating. Ovaries usually become inadequate for fertility well before you get pre-menopausal symptoms and you're having abnormal cycles. By the time your FSH is high, it's not an early sign of reproductive aging, but rather a sign that the ovarian reserve is already diminished.

Willman: Risk factors for early loss of ovarian reserve include smoking, family history of early menopause, and previous ovarian surgery. A woman approaching 40 years of age should be evaluated over a period of one month, rather than spreading it over a number of cycles. Any abnormalities that are uncovered in the basic evaluation should be corrected promptly. If the evaluation is normal, or if abnormalities have been corrected and the patient still does not conceive in a short period of time, aggressive therapy is indicated.

A patient with an FSH level of 10 to 12 might be best directed promptly to an IVF cycle, with the understanding that the chance for a successful pregnancy is reduced. Patients with a day 3 FSH greater than 14 should be offered egg donation as the best medical option.

Success rates with any fertility treatment are very much age-related. Since live birth rates from IVF in women who are over 43 years old are less than 5 percent, and probably less than 1 percent in women over the age of 45, these patients may want to consider egg donation even if they have normal FSH levels.

On the other hand a woman who is 35 years old with a borderline FSH level would certainly want to consider a trial of IVF with her own eggs before moving on to egg donation. There is some evidence that pregnancy rates with IVF are good in younger women (under 35) even if they do not produce many eggs.

Q: I have a regular period and have never had endometriosis or fibroids. Does this mean I will not have fertility challenges?

Ashby: No, this does not mean you won't have fertility problems. There are so many different ways you can have fertility problems. Although it is certainly a possibility that you will not, having regular periods and no obvious signs of fertility issues does not guarantee that you will not have fertility problems.

Q: Do you have an opinion on Fertell(R), the new at-home fertility test?

Most doctors we talked to about this new product do not recommend it - even those who are not in the business of providing fertility tests. Neither for women trying to get a quick peek into whether they might have fertility issues, nor for men who might agree to be their donor.

Sims: I strongly feel that these tests are sufficiently unreliable that there is serious danger in relying on them. For a woman who is under the age of 35, healthy and has regular menstrual cycles with no history of infertility, her fertility should be assumed.

Whether the concern is male or female infertility or sub-fertility, I strongly recommend seeing a qualified specialist. Much valuable time can be lost. The causes are numerous and each potential cause needs to be considered. This begins with a careful medical history and physical examination before leaping into testing. If you think you may have a problem, get help from a qualified medical expert. Self diagnosis has no place here.

Schoolcraft: The Fertell(R) at-home fertility test is not very helpful. If it is normal but you are not getting pregnant, you still need to visit a doctor to have a blood FSH level and other fertility tests. If it is abnormal the same is true. You would still want to consult your physician to have more accurate blood testing.

Ashby: At-home fertility products are generally not good because they have no counseling and are not as accurate as clinic testing. In addition, one sperm count does not determine what a man's fertility is.

Wisot: My concerns are not about the accuracy of the tests but revolve around the interpretation of them. Fertility potential involves much more than a motile sperm count and a good FSH level. Normal results may give false reassurance and therefore delay needed treatment.

For example, for men, the test does not measure sperm morphology, a very important component in sperm potency. For women, it does not provide a confirmatory estradiol level to show that the test was performed at the proper time in her cycle. Also, many women with diminished ovarian reserve will start follicle production early and by day 3 have an elevated estradiol which can result in a false "normal" FSH level.

These tests are not meant for the serious person who should be seeking guidance from a qualified professional.