Question: I’m confused about how often to have intercourse around the time of ovulation. Some things I have read say it should be not more than every other day while my doctor tells me it should be daily. What is the right answer?

Answer: There may be no exact right answer for everyone. Indeed, there might be a slight decrease in sperm concentration on the second or third straight day of ejaculation. However, for most men, there are still millions of active sperm present on the second or third day. As such, it may be better to have more sperm available in the reproductive tract during the window of fertilization for the egg.

My bias is to have intercourse as frequently as possible when you know you are soon to be, or in the process of, ovulating. The best method to detect when this is occurring is to use an ovulation predictor kit such as Ovu-Quick or Clear Blue Easy. When the kit detects the surge, have intercourse on that day and the next day. Beyond that, it is probably too late. If you don’t want to get that technical, subtract 16 days from your usual cycle length and start having intercourse daily from that day of the cycle for the next 3-4 days. For example, if your usual cycle length is 30 days, begin having intercourse on about day 14 and continue to day 16 or 17.

– Carolyn Givens, MD

Question:
Which insurance company has the most favorable coverage for infertility treatment?

Answer:
The package of insurance coverage for infertility treatment is not up to the insurance company, per se. It is typically up to an employer to determine the scope of coverage that is offered by its insurance company, and whether that package includes compensation simply for diagnosis of infertility, or whether it also covers treatment.

Moreover, one cannot assume that coverage will be the same from one employer to another even if that company uses the same insurer. For instance, an employee of Bank of America with Kaiser coverage might have a completely different insurance package for infertility as compared to an employee of Wells Fargo who also has Kaiser insurance. Through negotiation, an employer may choose an insurance plan with more or less infertility coverage than the average plan.

Another caveat has to do with state regulations. A total of 12 states in the United States have passed laws mandating infertility insurance coverage. However much of this regulation is considered a “soft mandate” meaning the insurers only have to offer it to employers who can choose to take it or leave it. California has a soft mandate so companies here are not legally obligated to purchase coverage for its employees.

A more forceful “hard mandate” requires a company to actually provide it, not just offer it. Massachusetts and Illinois are two states that have this hard mandate.

An exception to this is when a company is self-insured and is not legally required to follow state mandates. Because the majority of people with employer-sponsored health insurance policies are “self-insured”, the mandates do not apply to the majority of people, even in states with mandates.

Obviously, people who are self-employed and therefore pay for their own insurance might have a greater motivation to research those insurance companies that might have more comprehensive infertility coverage. Watch for subsequent articles in Fertility Flash that address this question for people who purchase insurance directly from insurance companies. In addition, the financial consultants at Pacific Fertility Center are available to work with our patients so they receive the benefits their insurance company provides. Click here for more Insurance Information.

– PFC Financial Consultants

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.
Clomid did not work for me. My physician is offering letrozole or she says I should go directly to the injectables. What do you think?

A.
Both clomiphene citrate (marketed as Clomid), and letrozole (marketed as Femara) are oral medications used to stimulate ovulation. Letrozole is emerging as a viable alternative to Clomid for women undergoing ovulation induction, although no broad scientific studies have yet established the drug’s efficacy as the first course standard treatment. Several preliminary studies have shown letrozole to be useful for anovulatory women, and provides few side effects, especially for women whose uterine lining may be thinned out by Clomid. As to its exact mechanism, letrozole falls in the category of drugs known as nonsteroidal aromatase inhibitors, meaning it is highly specific in suppressing estrogen synthesis. Aromatase is an important enzyme prompting the creation of estrogen. If the body makes less estrogen, FSH level increases and ovulation is stimulated. Letrozole was originally developed for breast cancer treatment, as certain types of breast cancer cells slow their growth in response to decreasing estrogen levels. Letrozole has shown to be particularly helpful for a subset of anovulatory women whose endometrial lining may be thinned out while taking Clomid. As an anti-estrogen, Clomid can limit the development of the endometrial lining, making it difficult for an embryo to implant. For reasons that aren’t quite yet clear, letrozole appears less likely to affect the uterine lining. Furthermore, letrozole has a short life span in the body whereas Clomid can last for 4-6 weeks following an oral dose. Overall, we’re pleased with what we’ve seen so far with the medication and we look forward to seeing the outcome of studies that are underway to further assess its efficacy as standard treatment.

– Philip Chenette, MD

Q.
We recently had PGD performed, and it revealed that two abnormal embryos were developing beautifully and two genetically normal embryos had ceased developing. Why would the genetically normal embryos not develop in comparison to the genetically abnormal embryos? Would this be due to egg quality? Would the same results be expected for a future PGD procedure? Is it unlikely that a six-cell embryo that had not developed in two days would result in a pregnancy?

A.
I don’t have all the information needed to give you a complete answer but I’m going to assume that you are a typical IVF patient (in your late 30′s) and were doing PGD to eliminate embryos with chromosomal abnormalities or aneuploidy. During your IVF cycle the eggs that were harvested from your ovaries were inseminated and those that fertilized and continued to develop were analyzed genetically. Depending on your (maternal) age, somewhere around 50% of your eggs would have been genetically abnormal. The genetically abnormal embryos look and behave in the same way as normal embryos.

Most genetic abnormalities cause an embryo to fail at the time of implantation (5 or 6 days old) or cause a pregnancy to fail early (miscarriage). When we look at embryos under the microscope in the days leading up to transfer, there is no way of knowing which are genetically normal or abnormal. Both types of embryos grow and develop similarly. In fact, some embryos that we know are abnormal (e.g. resulting from an egg that is fertilized by 2 sperm) often develop faster and look more beautiful than normally fertilized embryos.

The egg is a very large cell and when it is released from the ovary it has already been programmed to develop for 3 or more days after fertilization. Mom pre-loads her eggs with the necessary information for this early development. In most cells, including sperm, there are internal checks to make sure that the cell is functioning normally and that it is genetically normal. Cells that are abnormal, commit suicide in a process that we call apoptosis. Eggs however, seem to have a very poor internal surveillance mechanism, and even those that are grossly abnormal (e.g. with a whole extra chromosome) can fertilize and develop even to the point of giving you a live child. Down syndrome is the classic example, although at least 75% of embryos affected with this condition miscarry early in pregnancy.

So, eggs are endowed at ovulation with the necessary information to keep them going and looking normal for days, regardless of their genetic constitution. There is no relationship between their genetic status and how beautiful they look in our petri dish. If there were, we wouldn’t need to do PGD. We can keep embryos alive in the laboratory for 5 or 6 days and some of the abnormal embryos might stop developing by that time. However, our experience with PGD over the years tells us that about 50% of the genetically abnormal embryos will still look beautiful on their 5th day of life.

The pattern of development that we see with human embryos, regardless of their genetic status, is extremely variable. As you have witnessed first hand, normal embryos often arrest for reasons that we don’t always understand. This is true, regardless of whether the embryos are growing inside of you or in our lab, and this leads to a very inefficient process of reproduction in human females because she only ovulates one egg per month. We do know that the younger a woman is, the better the chance that the embryo will continue to grow. Embryos are more likely to fail in older women. In very young women, over 50% of embryos will implant in the uterus, but in women over age 40 less than 10% will implant. Although we can’t fully explain this phenomenon, a major contributing factor is egg age. Since women have all the eggs they will ever have when they are born, a 40-year-old woman is trying to get pregnant with a 40-year-old egg. And 40-year-old eggs just don’t perform as well as younger eggs.

Are PGD results consistent from one cycle to the next? The PGD technicians tell me that they get similar results for a patient 2 out of every 3 times.

Any embryo that has not developed in 2 days will not get you pregnant. If an embryo is to be ready for implantation, it must be alive and increasing its cell number every day. We expect a full round of cell division (e.g. from 4 to 8 cells) every 16 hours. Further, an embryo transferred to your uterus on day 4 or day 5, following your PGD analysis, should have enough cells to begin forming a placenta. It sounds like your embryo had arrested (i.e. it was dead).

Human reproduction is a very complex undertaking, and often patients feel like they’re left with more questions than answers after their fertility treatment. Don’t be afraid to ask your questions, no matter how simple or complicated they might be. Chances are, we’ve encountered your situation before.

– Joe Conaghan, PhD, HCLD

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

Q.
Can you give me some advice about choosing and buying donor sperm?

A.
When it comes to finding a sperm bank (check with our New Patient Guides for a list of recommended banks) and choosing a donor, you will have plenty of options. Typically, individuals have very specific ideas about the physical, intellectual and sporting abilities they would like in a donor and the sperm banks do a very good job of providing a wide variety of donors. They also ensure that the donors are healthy, disease free and have good quality sperm, though some banks have better quality sperm samples than others. All of this information will be made available to you, ensuring an informed choice.

Unfortunately, we do not see patients making donor choices based primarily on sperm quality. From a medical standpoint this is an important factor. You would be wise to choose a donor with high numbers of sperm with good motility. Motility tells you how many of the sperm are alive. Unfortunately human sperm samples contain a lot of dead sperm and freezing those samples will kill even more sperm. After thawing, most sperm banks will guarantee that at least 35-40% of the sperm will be alive, but it’s worth taking the trouble to find samples that will thaw with motility of 50% or more. To calculate the total number of live sperm that you are buying, multiply the sperm count by the motility. We expect this number to be at least 20 million sperm, but the more the better. This is especially important when choosing donor sperm for intrauterine insemination (IUI) as sperm are quickly attacked and killed by white blood cells (the foot soldiers of the immune system) when placed inside a woman’s body. So the more live sperm we have, the greater the chance that one will make it to fertilize the egg.

Once you have chosen your donor, and are satisfied that he has great sperm, your final decision will be whether to buy the sperm processed or unprocessed. If a fresh sperm sample is frozen without being processed, it will be cheaper for you to buy, and easy for you to take home to do your own vaginal insemination. This type of sample is usually referred to as Intra Cervical Insemination (ICI) prepared, and it is essentially neat semen to which they have added cryoprotectant. Sperm banks will also offer IUI prepared sperm at a higher price. This refers to specimens that have the dead sperm and seminal fluid removed before freezing. You would typically only buy this type of sperm if you were having your Physician perform your insemination. Your Physician will place the sperm directly into your uterus and thus closer to the site of fertilization. It is important to understand that ICI prepared sperm cannot be placed in the uterus as the seminal fluid may cause contractions that could be painful and also counterproductive to the sperm trying to swim up to reach an egg.

When buying donor sperm for an In Vitro Fertilization (IVF) cycle, we suggest buying ICI prepared sperm. It is less expensive and our laboratory will have to process the sample regardless if it is ICI or IUI prepared sperm for use in IVF.

If a sperm sample thaws with less live sperm than guaranteed by the bank, (an event that we occasionally see) we will give you a report that you can take to the sperm bank for a refund. Their liability however, is limited to the amount you paid for the sample. We therefore recommend that you buy more than one vial of sperm at a time, and suggest that you buy sperm that was frozen on different dates. This will minimize the chance that you will end up with sub-optimal sperm on the day of your insemination. Couples undergoing IVF with donor sperm should always have a minimum of 2 vials on hand for their cycle, even though we usually only need one.

If you have sperm left over after your cycle, you cannot return it to the sperm bank for a refund. You can continue to store it at PFC and you will be billed annually for the cost of storage (currently $400 regardless of how many vials you have stored). The sperm banks will also store the sperm for about the same storage fee, or you can ask for it to be discarded if you no longer need it. Bear in mind however, that the same donor may not be available the next time you want to get pregnant. If you are hoping to have two or more children that will be true genetic siblings, you may want to stockpile some sperm from your favorite donor.

Q.
My friend was tested with a high FSH of 10 and she still got pregnant, naturally! Now I’m confused – I have a low FSH of 7 and have not been able to conceive, even with IVF.

A.
It is true that the follicle stimulating hormone (FSH) test can be a useful indicator of a woman’s ovarian reserve (egg quality/quantity) but it is by no means a perfect screening for egg quality and/or quantity.

FSH, a hormone produced by the pituitary gland in the brain, is released into the bloodstream and travels to the ovary where it stimulates immature follicles containing microscopic oocytes to eventually develop a mature oocyte (egg). Early in the menstrual cycle, if the blood level of FSH is high, it indicates that the pituitary is working hard to stimulate the ovaries, therefore, the number and perhaps quality of the remaining eggs is decreased.

FSH is tested on day 2 or 3 of your cycle to provide a baseline measurement. An elevated FSH level above 8 might suggest that a woman is starting to experience the loss of her ovarian reserve. Menopausal women show FSH levels that are above 40. However, there are several variables, and as with many issues surrounding infertility, it has much to do with age.

Proper interpretation of FSH levels requires a simultaneous measurement of blood estrogen (estradiol) levels. Estradiol is made by the ovary, enters the blood stream and travels back to the brain (pituitary) to help regulate FSH release. Early in the cycle, day 2 or 3, it should be less than 60. A high level of estradiol, above 80, indicates that estradiol is suppressing the pituitary and providing an inaccurate FSH reading.

Several studies have set out to determine whether women with elevated basal FSH levels should be excluded from fertility treatment. A comprehensive study in the United Kingdom analyzed over 2000 patients for four years undergoing IVF treatment. Although it found no significant correlation between FSH levels and fertilization rates or miscarriage rates, the pregnancy rates and live birth rates were lower among women with higher FSH levels. Elevated FSH levels were also associated with more frequent cycle cancellation, need for larger amounts of stimulation medication, and lower numbers of eggs and embryos with fewer embryos transferred. However younger women, even with high FSH levels, had significantly greater live birth rates compared to older women with normal FSH levels. Again, age matters, despite a normal FSH value.

A normal FSH reading, although reassuring, may be indicative of egg quantity but not necessarily quality. The follicles may be producing mature eggs, however, the quality of those eggs may not be adequate. This is especially true for women over 40 years old.

Another caveat is that most women have variable FSH readings from one cycle to another. The best indicator of treatment response, however, is typically the highest FSH reading. There is no benefit, therefore, in repeated testing of FSH over several cycles and choosing to undergo an IVF cycle when the FSH is normal.

Q.
I sought our physician’s opinion about how my fibroids might impact our desire to get pregnant. Eight doctor opinions later, we are no closer to a decision. About half of the experts advise surgical removal; and the other half tell us to try to get pregnant despite them. Why is the medical community divided on this?

A.
Fibroid(s) of the uterus, also known as leiomyomas or just myomas, are benign growths that may be located on the exterior of or within the muscle layer of the uterus, or may be growing within the lining of the uterus. For the vast majority of women, fibroids do not cause significant health problems.

A few women who desire pregnancy may need to have their fibroids removed (myomectomy) prior to conceiving if the fibroids are very large (greater than 6 cm) and/or if they impinge upon and distort the uterine cavity.

Various surgical approaches to removal are further described on PFC’s web site, along with a more in depth summary of the factors that our physicians consider when counseling a patient to undergo a myomectomy.

You probably received different opinions because the impact of fibroids as related to pregnancy chances depends on the size and location of the fibroids. Other issues to consider are that fibroids are dependent on estrogen to grow, and high levels of estrogen produced during pregnancy can lead to rapid growth of the fibroid(s). If the fibroid is on the outer surface of the uterus, this may present little problem. If the fibroid is located within the uterus muscle wall or nearer the uterine cavity where the fetus is growing, a patient may be at higher risk for various pregnancy complications (miscarriage, preterm labor…).

In rare cases, the fibroid may grow so rapidly during pregnancy that it outgrows its blood supply and starts degenerating, which can be painful and sometimes lead to pregnancy complications. Also uncommon but of significance is the fact that some fibroids may block the lower portion of the uterus, prohibiting the baby’s head to descend into the birth canal, making cesarean delivery necessary. However, it is important to keep in mind that the majority of patients with fibroids experience no problems during pregnancy.

What is the impact of fibroids on pregnancy chances? It is unclear that there is any negative impact, if the fibroids are small and not growing within or distorting the uterine cavity.