IVF for Dummies (Part 2)

The stimulation part of the IVF cycle can be the most problematic. If patient is prescribed too little medication then she can get cancelled for a poor response. Give a patient too much and she can develop OHSS which really sucks (as was pointed out in a comment recently by one of my 5 regular readers-my Mom not included). How do we pick the protocol? Well first of all I consult my Magic 8 Ball toy that I bought on Ebay…then I spin a big wheel in my office and then I review it with Dr DiMattina, my partner, who usually changes the dose all around reminding me that he has been doing IVF since before I was in college and didn’t I read the latest paper in Fertility and Sterility. Actually, Mike and I usually agree on protocols although I really like the stop Lupron protocol for low responders and he is not a believer and uses MDL flare (which I also like…). If these comments make absolutely no sense to you, then don’t panic. If you agree or disagree with them and can cite the latest journal articles to support the thesis then you are really much too involved in your own care and are probably driving your spouse/partner over the edge.

But seriously, I review past stimulations, look at the appearance of the ovaries on sonogram and check the FSH level. From these I make my best estimate as to how to stimulate the patient. Usually we are on target. We average 11 eggs/retrieval here and that I think is ideal. Not too many…not too few..

So onto Part 2 of IVF for Dummies. Maybe I should call it something more PC but you may want to check out the book sales for those Dummies books. Not too shabby.


50. What is IVF and how is it performed?


PHASE 2: OOCYTE RETRIEVAL
Many physicians perform IVF as an office-based procedure, whereas others utilize a free-standing surgery center. Some programs are located within a hospital. There are advantages and disadvantages to each of these. We prefer to perform the egg collection within our office, as the location and staff are familiar to the patients undergoing the IVF process. We also find that the location of the IVF lab within the office encourages continuous communication between patient, physician, and embryology staff. However, clearly many successful programs utilize a surgery center or a hospital. The use of a hospital setting may allow patients with significant medical conditions (cardiac disease, severe pulmonary disease) to undergo IVF, whereas such patients would be considered an anesthesia risk in the office setting.

Although many patients are nervous about the oocyte retrieval, in fact the vast majority of women find it to be less uncomfortable than some of the screening tests leading up to IVF. The egg collection is performed under light conscious intravenous sedation using a vaginal ultrasound probe with a special needle guide adapter. The needle passes through the side of the vagina into the ovary, and the follicles are easily aspirated. The fluid containing the eggs is then inspected by the embryologist using a microscope. Both the eggs and the sperm are then placed together in small plastic dishes containing media and incubated for the next 3 to 5 days. If there is a significant male factor, then ICSI is performed several hours after the egg collection.

Read More

IVF for Dummies (Part 1)

Clearly Reproductive Medicine changed forever after the birth of Louise Brown in 1978. The first US IVF baby did not arrive until 1980 with the birth of Elizabeth Carr. I was up on Capitol Hill a few years ago on a committee promoting insurance coverage for fertility care and Elizabeth was on the panel with me. I asked her why her Mom had remained in the hospital in Virginia for the entire pregnancy and why they had come down from Massachusetts. She explained that IVF was not available in Massachusetts at the time and may have even been illegal. Wow, how times have changed given that Massachusetts has mandated statewide fertility benefits now….But why not go home after the pregnancy was established? She told me that there were so many death threats against her parents that for their safety they stayed in the hospital under an assumed name. Hard to believe. I only rarely use an assumed name and usually it is while I am cruising websites to see how badly I am being bashed in cyberspace. Hey, in Hollywood people read their own reviews don’t they???

Over the next few blog posts let’s review IVF and discuss some hot topics. First we will start at the beginning with the basics. I will break this into 3 posts so those with short-attention spans will not be distracted like Dori in Finding Nemo. So as our book slowly rises in the Amazon.com ratings here is the Question of the Day from 100 Questions and Answers about Infertility…

50. What is IVF and how is it performed?


In vitro fertilization (IVF) was first successfully performed in Oldham, England, in 1978, resulting in the birth of Louise Brown. Since then, more than 1 million children have been born using IVF. The introduction of this technique completely changed—and greatly improved—our ability to treat even the most difficult cases of infertility, many of which were previously untreatable. Although it is clearly not a “cure-all” for infertility, IVF has revolutionized our approach to, and understanding of, the disease called infertility. IVF literally means “the fertilization of eggs with sperm in the laboratory.” An IVF cycle consists of several discrete phases, as detailed in the sections that follow.

PHASE 1: OVARIAN STIMULATION
A woman’s ovaries contain thousands of fluid-filled sacs called follicles. Inside each follicle is an egg (or ovum). In a normal reproductive cycle, only a single follicle (and egg) reaches maturity. Although Louise Brown (the world’s first IVF baby) was produced in a natural cycle from a single follicle, this form of IVF is less efficient because it often leads to cancelled cycles as a result of premature ovulation prior to the egg collection or the failure to retrieve the single egg that is produced. The introduction of injectable gonadotropin drugs enabled physicians to increase the efficiency of IVF through the production of multiple mature follicles. Two forms of these medications are used: (1) drugs containing equal parts of the pituitary hormones follicle-stimulating hormone (FSH) or luteinizing hormone (LH) [Menopur] or (2) drugs containing only FSH (Bravelle, Gonal-F, Follistim). Both kinds of medications induce the growth of multiple ovarian follicles, so it is important to monitor the woman’s response to them carefully with ultrasound and blood hormone testing.

Estrogen is produced within each of the developing follicles and induces the growth of the lining of the uterus (endometrium). Unfortunately, the rise in estrogen can also induce the pituitary gland to prematurely trigger ovulation, resulting in the cancellation of an IVF cycle. Two other classes of drugs are used to reduce the chance of this problem occurring during an IVF stimulation: (1) GnRH agonists (such as Lupron and Synarel) and (2) GnRH antagonists (such as Centrotide and Antagon) . Lupron (or Synarel) is usually started 1 week prior to the woman’s anticipated next menstrual cycle. Given that a patient may have spontaneously conceived during this cycle, all women beginning Lupron are recommended to use a barrier form of contraception. Approximately 1 week after starting Lupron, the woman should experience a normal menstrual period. An ultrasound exam is performed at the start of this menstrual cycle to examine the ovaries and measure any existing cysts. In some cases, empty follicles from a previous cycle will persist and may influence the response to FSH. If the baseline ultrasound and blood tests are normal, then the patient receives instructions that afternoon as to when and what dose of medication she should take and when she should report back to the office for repeat ultrasound and blood tests.

Patients remain on Lupron to prevent the premature release of the eggs until the end of the stimulation phase. During a typical treatment cycle, they take daily injections for 9 to 12 days before the follicles reach maturity based on their ultra- sound results and blood hormone levels. Once the follicles reach a 20- to 24-mm diameter, the woman receives a final injection of human chorionic gonadotropin (HCG; Pregnyl, Profasi) at a precise time. This hormone serves as a trigger to incite the final maturation and release of the egg (ovulation). Ovulation typically occurs about 40 hours after this shot, so the egg collection procedure is scheduled for 34–36 hours after the HCG injection.

Cycles using GnRH antagonists are somewhat different. GnRH antagonists are started several days following the start of ovarian stimulation with gonadotropins. Most clinics add the GnRH antagonist once the largest follicle reaches a diameter of 14 mm. This medication effectively prevents the release of LH from the pituitary within hours of administration. Although many clinics have used GnRH antagonists successfully as part of their IVF stimulation protocols, some studies have demonstrated a trend towards decreased implantation rates in IVF cycles using this class of medications.

Read More

Are Babies from IVF Normal?

The astute reader of this blog may come to the conclusion that Dr Gordon is not normal. I mean the guy likes Monty Python, couldn’t get a date in high school, tells bad jokes and yet somehow managed to convince a PhD in Engineering to marry him and reproduce with him. Go figure. What really does it mean to be normal? I banged my head on the kitchen counter this morning when I saw that the Red Sox lead over the Yankees was down to 2 and a half games. Is that normal behavior? Well, for a Sox fan it is but that is besides the point.

So many questions arise when considering the normalcy of children after IVF. Are they normal? Will they get 2400 on the new SAT? Will they cheer for the Red Sox against the evil empire? Who knows. However, a lot of attention has been focused on the issue of birth defects after IVF so here is today’s Question of the Day from 100 Questions and Answers about Infertility.


53. Are the children born after IVF normal?


The question of the health of children born after advanced fertility treatments is one that has great importance both to the parents and to fertility physicians. In general, the data regarding the outcomes for children born after IVF, either with or without the use of ICSI, have been extremely reassuring. The problem with these studies remains the identification of an appropriate control group with which to compare the rate of problems found in the children conceived with advanced fertility techniques. Overall, most studies suggest a background risk of birth defects in naturally conceived children of approximately 4% to 5%. However, these couples tend to be younger than the couples undergoing IVF and, by definition, do not suffer from infertility. Although the vast majority of studies suggest no increased risk of anomalies in children conceived after IVF, none of these studies have looked at the rate of congenital anomalies in children conceived naturally but born to parents who suffered infertility that spontaneously resolved without treatment. This group of patients would clearly represent a more appropriate control group with which to compare with patients who seek out advanced fertility treatments.

One recent study from Australia (Hansen, M et al, Human Reproduction 20 (2):328-338, 2005) was a systematic review of all studies that had previously examined the possible increased risk to children conceived after treatment with IVF and/or ICSI. However, many of these studies compare the rate of congenital abnormalities in children conceived spontaneously with the rate in children who were born to older couples undergoing IVF and/or ICSI. In many studies the rate of congenital anomalies in the control group have been around 4%, whereas the rate of congenital anomalies in the group of couples undergoing IVF and ICSI have been 6% or greater. The difference between 4% and 6% is statistically significant and suggests that there may be an increased risk to children conceived through the use of advanced reproductive techniques. However, the question remains as to whether this is a problem related to IVF itself or to the underlying infertility that leads to the use of IVF. In any case, most patients accept an increased absolute risk of 2% as being reasonable, especially given that their options for spontaneous conception may be significantly limited. The greatest risk to the children conceived after fertility treatment is that of prematurity related to multiple pregnancy.

Several strategies are used to reduce the rate of multiple gestations (see Question 54, which deals with how many embryos to transfer in IVF). The risks of prematurity are significant and should not be discounted quickly, especially given that 50% of twins deliver a month or more before their due date. In addition, the question has been raised as to whether even
IVF singleton pregnancies are at higher risk for low birth weight and prematurity. If true, the cause of this increased risk may be difficult to determine.

Patients undergoing IVF suffer from infertility, so that any increased rate of adverse pregnancy outcome might not be so much a result of the IVF process as it is related to the couple’s underlying problem ofinfertility. Several studies have suggested that women who conceive spontaneously, but who have a preceding history of infertility, have a significantly increased rate of prematurity and pregnancy-related complications such as placenta previa, abruption, and low-birth-weight infants. Another way to look at the question of whether any risk is related to the process of IVF itself versus the patient who is undergoing IVF is to examine the pregnancy outcomes in women who undergo IVF and then use a gestational carrier (carriers usually have an excellent reproductive history). A study of these pregnancies found there was no increased risk of prematurity or low birth weight in the children conceived and carried in this way. This reassuring outcome would suggest that the problem lies not so much with the IVF process but, unfortunately, with the patients who require IVF to conceive.

The impact of new and emerging technologies on the rate of congenital anomalies in children born after fertility treatment remains a subject of ongoing debate. The potential risks inherent in micromanipulation of the embryo prior to embryo transfer—like that required for preimplantation genetic diagnosis (PGD)—remain unknown. Although more than 4 million IVF babies have been delivered worldwide to date, only a relatively small number of children have been delivered after the use of PGD or another emerging technology (such as egg freezing) or following unusual situations such as performing rescue ICSI on the day following egg collection because of unanticipated failed fertilization. When considering such novel treatments, the physician needs to inform the patient /couple of any known or suspected risks. Currently, several studies are under way in this country and throughout the world to continue to monitor the health of those children delivered following advanced fertility treatments.

Read More

Sex, Drugs, Rock and Roll....

Back in high school I was the well-behaved, straight A student, Eagle Scout, nice boy who would never do drugs or drink…so of course, no girl would give me the time of day. My wife believes that the real cause of my high school social isolation was the fact that I was a science fiction fan who went to science fiction conventions and had dinner with noted authors like Hal Clement (my high school chemistry teacher), Larry Niven, Isaac Asimov to name drop a bit… She reminds me that this part of my history was kept concealed along with the Monty Python memorization issue until well after we were married. Right now my old high school (Milton Academy) has been in the news because of a sex scandal involving hockey players, a young girl and well….you can guess the rest (or check out the book now available about the whole mess: www.washingtonpost.com). Needless to say this was not my experience at Milton Academy.

So are drugs always bad? Yes, as far as my teenage son is concerned but for fertility patients drugs can be very helpful. Although we can perform IVF without medications (Natural Cycle IVF) most programs use fertility medications to increase the odds of success. The same is true for cycles of IUI (intrauterine inseminaton). Here then is today’s Question of the Day from 100 Questions and Answers about Infertility the book that contains no information about the Milton Academy sex scandal.


42. Which fertility drugs are used with IUI, and why are they used if I already have normal periods?


IUI can produce fair success rates when combined with fertility drugs. Many studies show superior pregnancy rates when IUI is combined with either Clomid or injectable gonadotropins, as compared to using these medications alone. For this reason, most infertility experts will recommend IUI to their patients when treating them with fertility drugs. In women who fail to ovulate regularly, the goal of drug therapy is to induce the growth and release of a single mature egg. This treatment is known as ovulation induction. In contrast, the treatment goal for women with regular menstrual cycles is to induce the growth of multiple follicles with the subsequent release of multiple eggs. Hence the term superovulation (also called controlled ovarian hyperstimulation) is used to describe this situation. During a cycle of superovulation and IUI, the goal is to develop 3 to 5 mature follicles, whereas the goal in an IVF cycle is 10 to 15 mature eggs. Clomid is the fertility drug of first choice for both ovulation induction and superovulation with IUI. Women who fail to respond to Clomid or who fail to conceive may be candidates for treatment with injectable fertility medications (gonadotropins) combined with IUI. In some cases, it is best to skip the treatment with Clomid and instead proceed directly with gonadotropin therapy; this decision depends on the severity of the couple’s infertility situation. In women who have normal, regular ovulation and menstrual cycles, it would appear on the surface that IUI alone without fertility drugs would be as successful as IUI with fertility drugs. Unfortunately, this simply is not the case. Instead, the combination of IUI and fertility drugs to induce superovulation yields a synergistic benefit over either treatment alone.

Read More

Is there any hope?

We are often asked the difficult question of whether there is any hope when the beta levels are not rising appropriately. The short answer is that there is always hope and yet I wish that I could know the outcome as soon as possible so that I could spare patients that roller coster ride of emotions when things are not going according to the textbooks. However, I have become very cautious about writing off pregnancies too early. There are several patients who love to write at the bottom of their Christmas cards little reminders like “The little boy in the reindeer sweater is the pregnancy that you thought was never going to end well.”

Hey, I am only human and you can only take so much abuse from your patients before you learn to keep your mouth shut and just let it ride…

So given today’s question on the INCIID bulletin board here is the Question of the Day from 100 Questions and Answers about Infertility, the book that has not yet been featured on MSNBC unlike that other book 100 Questions and Answers about Cancer and Fertility…Oh well, that is a good book too.


80. My beta­HCG levels are as follows: 260 mIU/mL 14 days after a day­3 embryo transfer, 500 mIU/mL 16 days post transfer, 900 mIU/mL 18 days post transfer, and 1900 mIU/mL 20 days post transfer. Is there any hope for this pregnancy?

In a normal early pregnancy, regardless of the method of conception, the woman’s blood beta-HCG levels will roughly double every 48 hours. Failure of the beta-HCG levels to double suggests an abnormal intrauterine pregnancy or an ectopic pregnancy. Given that biologic variation can occur in both normal and abnormal pregnancies, however, we cannot assume that a pregnancy is in jeopardy simply because the beta-HCG levels fail to perfectly double. In the case described in the question, the woman’s beta-HCG levels did not double, but she could have either a normal intrauterine pregnancy, an abnormal intrauterine pregnancy, or an ectopic pregnancy. This determination can be made only by performing a transvaginal ultrasound examination. Even then, the results may be inconclusive. In our practice, we have seen several cases in which patients had dramatically abnormal beta-HCG levels associated with a first sonogram, suggesting an early blighted ovum pregnancy, only to discover later that the pregnancy was completely normal. Another common cause for abnormal increases in the beta- HCG level is multiple pregnancy. When patients undergo transfer of two or more embryos, a multiple gestational pregnancy may occur. In roughly 40% of these pregnancies, spontaneous fetal reduction of the extra implanted sacs occurs, resulting in a sudden drop in the beta-HCG level. Initially this decrease might be falsely interpreted as an apparent problem with the pregnancy when, in fact, one surviving embryo is completely healthy. For all these reasons, the blood beta- HCG doubling effect must be viewed as a guide, and not as absolute proof of the woman’s condition and future outcome of her pregnancy.

Read More

You say tow-mah-tow and I say tow-may-tow

I agree that the medical profession has too many abbreviations and that it is hard to know how to act knowledgeable in front of your RE. So here are some helpful hints about how we on the other side of the desk pronounce various abbreviations:

RE (reproductive endocrinologist): are-ee
IVF (in vitro fertilization): eye-vee-eff
GIFT (gamete intrafallopian transfer): gift NOT gee-eye-eff-tea
ZIFT (zygote intrafallopian transfer): zift NOT zee-eye-eff-tea
FET (frozen embryo transfer): eff-ee-tea NOT fete
ICSI (intracytoplasmic sperm injection): ick-see NOT eye-see-ess-eye
POF (premature ovarian failure): pee-oh-eff NOT poff
PCOS (polcystic ovarian syndrome): pee-see-oh-ess NOT pee-cos
PGD (preimplantation genetic diagnosis): pee-gee-dee
ASRM (American Society of Reproductive Medicine): as-ram OR ay-ess-are-em

If there are other abbreviations that anyone needs help with just post a comment and we will discuss it.... But don't stress out just read the post below...


86. What role does stress play in causing infertility?


Not surprisingly, dealing with infertility can itself be very stressful. And stress—both physical and psychological—can significantly affect a woman’s ability to conceive. A recent study examining the role of psychological stress in successful pregnancy showed a one-third decrease in pregnancy rates in those women undergoing IVF who perceived themselves to be overly stressed. Most of these women were lawyers whose stress was perceived to be job related. Excessive physical stress can also be detrimental to a woman’s ability to conceive. Studies show that women who run more than 20 miles per week may begin to experience abnormalities in their menstrual cycle, which may in turn affect their fertility potential. Women who run marathons or compete at a very high physical level, for example, commonly have ovulatory dysfunction and infertility. There are many different ways to decrease the stress inherently present with infertility and its treatment—for example, decreasing work hours or changing jobs, exercise, meditation, yoga, acupuncture, getting a new hobby, or simply setting aside some time for oneself. Many patients are able to reduce their infertility-related stress by simply becoming more knowledgeable about the subject of infertility. In addition to providing physician counseling, we ask our own patients to read and become more educated about their infertility, thereby empowering them to take control of it. Excellent and reliable information is available at the American Society of Reproductive Medicine website (www.ASRM.org).

Read More

Labor Day at Dominion

Labor Day is not a real funny holiday for fertility patients. It is really an obstetrical holiday and having worked a fair number of Labor Days during my residency everyone thought that it was so clever to quip about being in labor on Labor Day…yup, a real yuck fest.

Of course, for REs the funny holiday is Easter. Not for the religious significance but of course, for all the Easter egg jokes. Same phenomenon of really bad jokes occurs as patients who undergo egg collection on Easter are participating in an “egg hunt” of sorts.

Hey, I don’t make this stuff up, I just pass it on..you know, life is not like an episode of Scrubs.

So back to our introductory questions on infertility. Clearly infertility is a common disorder as you can read below. In the Gordon household we did not deal with infertility per se, but had the emotional distress of dealing with recurrent pregnancy loss instead. My 16 year old son Seth wished we had infertility. When we announced that we were pregnant, Seth looked at me and asked quite seriously: “Dad, how did this happen?” I replied “What do you mean?” Seth, at that time age 12, fired back “I mean did you take Mom to your office or what?” “No," I replied, "this was the old-fashioned way.” And that was way too much information and Seth wanted to hear not another word on the subject of his parents procreative activity.

Without further ado, here is the Question of the Day:


3. How common is infertility?


Infertility is an extraordinarily common disorder. An estimated 25% of all women will experience an episode of infertility during their lifetime. Infertility currently affects about 6.1 million women and their partners in the United States. The percentage of reproductive-age women who report problems successfully conceiving and delivering a pregnancy varies with age. In the youngest segment of the population, approximately 10% to 15% are affected by this problem. Among women older than age 35, however, more than one-third report diminished fertility. The rates of pregnancy loss are also related to a woman’s age, with the rate of miscarriage exceeding 50% in women older than age 40.

Read More