Saturday, September 25, 2010

"Nutritional Supplements" and Fertility

We've been seeing a lot of patients in the office recently on some kind of nutritional supplements, mostly to improve fertility, but some being taken (by men) as part of a regimen to increase strength or muscle-building. I think taking such supplements is unwise. Here's why:

Body-building supplements for men - Several of our patients with really low sperm counts (or even no sperm) admit to being on these supplements. Sometimes the guys say they are just using a "protein supplement" from the health food store; others admit they are getting something from a friend at the gym. We don't know just what's in these supplements, but some of them probably contain testosterone derivatives, which are well known to reduce sperm production. The good news is that sperm production usually comes back when the supplements are stopped, but it can take several months.

Fertility supplements for men and women - In my opinion, the use of nutritional supplements to improve fertility is mostly bogus. Nutritional supplement manufacturers are exempt from the rigorous regulations of pharmaceutical manufacturers. If you label your product as a nutritional supplement, you can pretty much make any claim about it you like. The "scientific proof" they hold up is nonexistent or quite flimsy. Although some fertility clinics recommend these products, in my opinion, they are a waste of money.

Friday, August 13, 2010

More about HSGs

I am sorry to report that the US manufacturer of Ethiodol, the oil-based hysterosalpingogram dye that promotes fertility, has ceased manufacture of the product. To my knowledge, this wasn't a safety issue, but rather a financial one. There is potential good news on the horizon, though, as the FDA has solicited an application from a French company that makes Ethiodol to begin selling it in this country. The FDA isn't particularly interested in having the product available for HSGs, but it turns out that Ethiodol is used by interventional radiologists to deliver targeted chemotherapy to inoperable liver tumors.

I did the last Ethiodol-HSG a month ago on a patient who had previously conceived after an HSG a few years back. She called the hospitals all over Birmingham until she found a vial. For now, we are stuck with doing HSGs with water-soluble dye, but as soon as the Ethiodol becomes available again, I plan to switch back. Stay tuned.

Thursday, April 15, 2010

More IVF questions: How many embryos to transfer? The "plus/minus rule"

Q: How many embryos do you transfer?

A: Short answer: "Usually two. Sometimes one or two more if you are an especially difficult patient."

Long answer: This is the second most common question IVF patients ask (#1 is "How much is it going to cost?" I'll answer that one another day). It's a tricky issue - who is really the "decider" in this setting: the couple? After all, it's their embryos; the IVF programs? they're the experts; the insurance company or the government? they may be paying for the cycle, as well as the medical care of any children conceived. In Belgium, for example, it's Hobson's choice if you're less than 35 years old doing your first IVF cycle - only one embryo can be transferred if you want to be reimbursed for the cost of the cycle. (On the other hand, the government will reimburse much of the cost of IVF for up to six cycles if you follow their rules. It's not a bad concept. You can do what you want, but you'll have to pay for the privilege.)

The more embryos you put back, the higher the chance of pregnancy. Don't believe what you may read elsewhere, that pregnancy rates fall when higher numbers of embryos are transferred, or some study somewhere (usually in Europe) showed that pregnancy rates weren't increased when extra embryo was transferred. The conclusion about lower pregnancy rates with higher embryo transfer numbers comes from the naive examination of national data sets like those compiled by SART or the CDC. Of course pregnancy rates are lower in women who are getting more embryos - IVF programs are putting more embryos back in those women because they know the chance of pregnancy is lower (because of advanced patient age, poor embryo quality, or repeated failure in previous IVF cycles), and they are trying to compensate for it. If they didn't do this, the outcomes might even be worse. Every viable embryo has some chance of implanting, and the more you put in, the greater the chance that one will turn into a pregnancy.

But the success rate may not increase all that much with additional embryos, and the more embryos you transfer, the greater the chance of multiple pregnancy. Now, many infertile couples welcome the idea of twins or even triplets ("that way we would be finished with all this" is what I often hear). I have twins myself, and they were healthy and a great joy to raise, but I would never wish twins on someone, as the risks of prematurity and its associated complications are higher with twins; and the risks are astronomically higher with triplets or quadruplets. It's best to bear one child at a time.

Thus, IVF programs and their patients balance the risk of no pregnancy versus the risk of multiple pregnancy when choosing how many embryos to put back. At AFS, we use the SART/ASRM guidelines as the starting point for deciding how many embryos to transfer (you can read these guidelines here: Basically, if you are under 35, it's your first IVF cycle, your embryos look good, and if you have extra embryos good enough to freeze, we recommend two embryos to transfer. If you don't meet one of those criteria, we recommend a third embryo (although if you had two really good looking embryos and the others weren't clearly worth freezing, I would still recommend just two). If you're forty or older, we'll usually recommend four embryos, as we have never had more than twins in that age group using their own eggs.

However, I am personally uncomfortable with this dictatorial approach to determining how many embryos to transfer. In virtually every other aspect of medicine, decisions for medical care are made cooperatively between patient and doctor. If you don't like a doctor's recommendation, you can always go find another doctor for a second opinion, but not when you have embryos sitting in the incubator (yes, you could choose to freeze them and find another program to transfer them, but let's not make this any more complicated than it already is). So I have developed my "plus/minus" rule: when we (meaning me, the IVF program director, with input from my staff) make a recommendation about how many embryos to transfer, the patient has the option to choose one more or one less. If we say "two embryos", you can choose 1, 2, or 3 embryos to have transferred. That way, the patient has a say in the decision, too.

More than 90% of patients go along with our recommended number, but our last frozen embryo pregnancy decided to have only one embryo transferred (she already had twins at home from her previous IVF cycle); our last set of triplets asked for that third embryo, even though she was young, was doing her first IVF cycle, and had good embryo quality. She thought she had a low chance of success because she had been trying to get pregnant for such a long time (this is not a prognostic factor for IVF success, but sometimes you just can't talk people out of a concept).

The system isn't perfect, but it works for us. We haven't had triplets in anyone who has followed our advice in quite a while. There are plenty of twins, though - 7 out of the last 29 births (24%) in the under-35 group were twins. Maybe when that good Belgian insurance coverage becomes available in Alabama, more patients will elect to transfer just one embryo.

Thursday, March 11, 2010

More IVF questions

Q: How many eggs do you retrieve in an IVF cycle?

A: As many as develop. We're happy if we get a dozen. We won't do the egg retrieval if we think we'll get only one or two.

The maximum number of eggs in the human ovaries is found at 20 weeks of intrauterine life. For reasons that remain unclear, some of the eggs atrophy, so that by birth only 1 to 2 million eggs remain. These primordial follicles (remember that a follicle is a cyst with an egg inside) remain in a state of suspended animation, but every day some of the follicles begin to develop, or mature. This maturation process is thought to take as long as one year, and once it begins, there is no going back - the follicle either winds up releasing the egg at the time of ovulation, or it stops developing and atrophies along the way. The mechanism regulating this process of follicular recruitment from the pool of primordial follicles is the "terra incognita" of reproductive physiology - if you figure it out, please let me know. We will quit our jobs and make some big money! Think of the possibilities if we could develop a pill that could stop this recruitment process. Not only would it be a very effective contraceptive, but we could postpone menopause indefinitely!

But I digress. At the very end of this maturation process, the developing follicles must see follicle stimulating hormone (FSH) for maturation to continue. At the start of the spontaneous menstrual cycle, one of the developing follicles gets ahead of the others and does something very sneaky - it revs up its cellular machinery to become more sensitive to FSH while sending a hormonal signal to the pituitary gland to decrease FSH production. (There are actually two hormonal signals that do this: estradiol and inhibin.) Thus, the dominant follicle continues to develop while its siblings starve from lack of FSH, and out of the many follicles that began to develop, only one completely matures to ovulate.

So, what can you do if you want more eggs to complete this maturation process? Simple, just give the woman FSH at the start of her menstrual cycle, subverting this process of follicle selection and dominance. This is why IVF patients take FSH injections (many IVF programs give luteinizing hormone (LH) as well, since LH also plays a role in follicle maturation). We typically retrieve about a dozen eggs in an IVF cycle, and sometimes many more (I think my personal record is 80 or so, but this isn't a record to be proud of, as women with too many eggs developing can get sick from ovarian hyperstimulation, and sometimes the quality of the eggs obtained isn't so good). If we see only one or two mature follicles, we will cancel the IVF cycle and treat the woman with a higher FSH dose in a subsequent cycle.

But sometimes even higher FSH doses don't result in more follicles developing. After all, FSH only rescues eggs that would have been lost before ovulation, and if only a few follicles are developing, there aren't many to rescue. As women get older, the number of follicles maturing at any one time declines until no follicles are left, and this process of follicle depletion occurs at different rates among women. Sometimes the reason for running out of eggs prematurely is obvious. Cancer chemotherapy, radiation treatment, and cigarette smoking can do it, as can ovarian surgery (like removing an ovarian cyst). Many times, though, there is no clear reason. I think some cases of unexplained infertility are due to accelerated follicular atresia, as the last eggs to mature seem to work the worst (although this concept is much debated among fertility specialists).

Tuesday, March 9, 2010

IVF Questions

There is a lot of information about in vitro fertilization (IVF) on the Web (including our own web site,, but I still get a lot of questions from patients about this procedure. I've decided to start posting some of the more common questions as preparation for including them in our IVF patient information booklet. If you have a question, please submit it, and I'll do my best to answer it, either right then, or at a later posting. (Keep in mind that if you send a question like "I'm 41 and my FSH is 9, should I do egg donor IVF?" it probably won't get answered. That's a question for your doctor.)

Q: Do I have to take shots to do IVF?

A: Yes. Although the first successful IVF treatment was performed by retrieving a single egg in a spontaneous cycle, the success rate is much higher if more eggs can be obtained. A variety of ovarian stimulants are used to achieve this. Most commonly, some form of follicle stimulating hormone (FSH) is used to rescue developing eggs that would be lost in a spontaneous cycle. (Thus, these drugs don't use up your eggs or hasten the onset of menopause.) And FSH (Follistim, Gonal-F, Bravelle, or Menopur) is given by injection (you give it to yourself, actually, although sometimes husbands seem to enjoy participating). We generally use Menopur (which has both FSH and LH) along with one of the pure FSH products. Other injections include leuprolide (Lupron), another injection used to prevent you from releasing the eggs before they can be retrieved; hCG, which is used to complete the maturation of the eggs; and progesterone, which begins on the day of the egg retrieval and continues until we see a heartbeat in your uterus for your Ob visit, or until you have a negative pregnancy test. Although vaginal progesterone preparations (Crinone, Endometrin) are available, we still recommend progesterone injections at least until the first pregnancy test, when we (usually)offer the option of vaginal progesterone. My partner Dr. Malizia trained at a program where vaginal progesterone was the standard, but she hasn't managed to convince me to abandon progesterone injections yet. By the way, the progesterone is intramuscular (with a 1.5 inch needle in the buttocks), but all the other injections (including the hCG) are subcutaneous, with a much smaller needle. You are looking at taking some sort of injection daily for the better part of five weeks during an IVF cycle, with about two or three weeks more if you get pregnant (unless you opt for the vaginal progesterone at that point).

Tuesday, January 19, 2010

Should I be abstain from sex during an IUI cycle?

Our patient info about intrauterine insemination doesn't have anything about this, but it probably should. If you are scheduled for an intrauterine insemination using your husband's sperm (IUI-H), there is no reason to abstain from having sex during that cycle except for the night before the insemination. In fact, it might be bad to abstain. I saw a recent presentation claiming that IUI pregnancy rates are lower in couples who abstain for many days before the insemination.