Frequently Asked Questions
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IVF
Why are some embryos transferred on day three, but others on day five after egg retrieval?
OTHER
Is letrozole better than clomiphene?
ANSWERS
Why are some embryos transferred on day three, but others on day five after egg retrieval?
The choice of day on which to transfer embryos reflects a balance between several factors:
- For most patients, embryos are better off in their uterus as opposed to in the laboratory. As careful as we are to maintain the right conditions in the lab for embryos to divide and grow, the woman’s own body usually is a better environment for embryo development.
- A day five embryo that appears to be developing normally is more likely to implant (and lead to the birth of a child) than a good looking day three embryo. This is because not every day three embryo continues to grow normally over the course of the fourth and fifth day.
- The goal of embryo transfer is to maximize the chance of a singleton pregnancy. No doubt, we consider a cycle which does not result in pregnancy to be a failure. However, the consequences of a multiple pregnancy (especially triplets of more) can be worse than failure to conceive. Multiple gestations (twins, triplets, etc.) are much more likely to result in premature delivery (at eight, seven or even six months of pregnancy) than a single pregnancy. Babies born premature can suffer lifelong problems, for example, learning disabilities, as a result of being born early.
Thus, for each individual patient we choose the number of embryos and the day on which to transfer them with the intention of maximizing the chance of pregnancy but minimizing the chance of m ultiples. Let’s consider some examples:
Patient A is 26 years old. IVF is done to achieve a pregnancy because her husband’s sperm count too low to allow pregnancy through other means. Ten high quality embryos are obtained. We intend to replace one embryo now and freeze the rest. (Extensive international experience has taught us that one embryo is the right number for a woman who is less than 32 years old.) We will wait until day 5 so that we may select a single embryo with the highest chance of implanting (leading to the birth of a child).
You may be wondering why we don’t wait until day 7, or week three, for that matter before transferring our embryos. True, an embryo that “makes it” to 3 weeks has shown itself to be more likely to be normal than any old day five embryo. However, issues of morality aside, the window of opportunity for returning an embryo to the uterus closes around day five or six. Embryos won’t stick if replaced later.
Patient B is 38 years old, having IVF because of extensive scar tissue in her pelvis. We obtain 8 eggs, but only 3 of them fertilize and develop normally. It is our plan to transfer 3 embryos. At age 38 each embryo has, perhaps, an 18% chance of “making it”. We must take some risk of triplets to maintain a reasonable chance of any success. By day 3 we are already able to identify which embryos we will transfer. There is nothing to be gained by waiting until day 5. Patient B will have a day 3 transfer.
The most important factors in selecting the number of embryos for transfer are age, age and age. The appearance of the embryos, the cause of the fertility problem, the number of failed cycle, the cost and the patient’s degree of desperation, while important, should not unduly influence our decision-making.
Is letrozole better than clomiphene?
Many of our patients are treated with fertility pills. These medications can enable a woman who does not normally ovulate to release eggs. Fertility pills are also used for controlled overstimulation of ovulation. The chances for conception may be increased when two or three eggs are released instead of the usual one per cycle. Fertilization and implantation may be more likely to occur in the presence of higher hormone levels stimulated by fertility medication.
Clomiphene citrate (Clomid, Serophene) is the most common fertility medication. It is approved by the FDA (government) for use as a fertility medication. It has been used for 40 years. Among women who don’t ovulate on their own, it is said that 80% will ovulate and 50% conceive, thanks to clomiphene. On the other hand clomiphene can have some unpleasant side effects: hot flashes, nervous tension/mood change, headache, etc. Moreover, because it is eliminated slowly from the body, clomiphene can have some lingering negative effects on a woman’s fertility: dry cervical mucus which prevents sperm from swimming to the egg and thin lining of the uterus which may make it harder for a fertilized egg to attach to the uterus. The bottom line is that not every woman can take or will be successful with clomiphene.
That is where letrozole comes in. At the outset it is important to state that letrozole, while approved for other uses, is not approved by the FDA as a fertility drug. In fact, the company who makes it, seeking to avoid the possibility of a malpractice claim, advises that the medication should not be used as a fertility medication. Letrozole’s lack of FDA approval as a fertility drug will be enough reason for some fertility doctors and patients not to use the medication. Please be aware that it is perfectly legitimate for doctors to use medications for indications not specified by the FDA so long as the medication is approved for another use.
The use of letrozole is not experimental. It is used throughout the world, both inside the U.S. and abroad. Much has been published attesting that the medication is safe and effective. In particular, letrozole does not cause birth defects so long as the patient is not already pregnant when she takes the medicine.
So why use letrozole? First, there are a few patients (usually having the diagnosis of PCO, polycystic ovarian disease) who don’t respond (ovulate) to clomiphene but do respond to letrozole. Given the alternative of moving on to expensive, complicated injectible medication, letrozole is worth a try in some PCO clomiphene non-responders.
Second, while similar in nature, the side effects of letrozole are usually less intense than those with clomiphene. Third, letrozole seems to have less negative effects on cervical mucus and uterine lining.
We are happy to have letrozole as a treatment option. Given a properly informed patient with the appropriate medical condition, letrozole may be the answer we seek.
