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lundi 28 mars 2011

Question 46: What is IVF, and how is it performed?

Posted on 10:31 by Unknown
Sometimes the first step is really the hardest in the entire journey. There is no doubt that IVF can be a roller coaster ride...physically, emotionally and psychologically. As physicians the best we can do is try to educate our patients so they can handle the ups and downs. Personally, I am really wimpy when it comes to riding roller coasters. At Universal Islands of Adventure my knees went weak at the site of the Hulk roller coaster and you can just forget any of the other big kid coasters. The best I can do is the little kid roller coaster as seen in this video. Those little girls thought it was so funny that I looked petrified but it's not my fault....it's my parents' fault for never taking me to Paragon Park in Nantasket Beach back in my formative years....



So as you consider the potential roller coaster ride of infertility treatment here is an overview of the IVF process from 100 Questions and Answers about Infertility, 2nd Edition.


46. 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 who was conceived using Natural Cycle IVF (NC-IVF). Since then, more than 4 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 glass” which translates to fertilization outside of the body in the laboratory. There are two types of IVF: 1) stimulated cycle IVF and 2) Natural Cycle IVF (NC IVF). We will focus on stimulated cycle IVF in this question but for more information on NC IVF please refer to many of the previous blog posts listed). 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. Louise Brown (the world’s first IVF baby) was produced in a natural cycle from a single follicle (NC IVF). Although a few clinics in the US (including our own) remain enthusisastic about NC IVF, most IVF in the USA is performed in a stimulated cycle using injectible fertility medications. The introduction of the medications (called gonadotropins) 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) and luteinizing hormone (LH) [Menopur] or (2) drugs containing only FSH (Bravelle, Gonal-F, Follistim) or LH (Luveris). 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, a 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 ultrasound results and blood hormone levels. Once the follicles reach a 20- to 24-mm diameter, the woman receives an injection of human chorionic gonadotropin (HCG; Pregnyl, Profasi, Novaryl) 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. Failure to take the hCG will result in an egg collection with apparently empty follicles as the eggs will not be ready for aspiration or eggs that are retrieved will be immature. Clearly, taking the hCG is absolutely critical which is why we check a blood test for hCG the morning after the shot to ensure that it was given correctly.

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. Some physicians use GnRH agonists (Lupron) instead of hCG to induce follicular maturation. This approach only works in patients who have not already been taking Lupron as part of their stimulation protocol.


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 egg collections at our office in a special procedure room, 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.

Phase 3: Embryo Culture
On the day following the egg collection, patients learn how many eggs were fertilized. Remember that although your RE measures all of the follicles during stimulation, mature eggs are usually found only in follicles with a diameter of more than 17 mm. In general, about 70% of the mature eggs will fertilize. Unfortunately, some attrition occurs at each point in an IVF cycle so the total number of healthy embryos is often much less than the original number of follicles or eggs.

Three days after the egg collection procedure, the embryos selected for embryo transfer will be identified. Allowing the embryos to grow for an additional 2-3 days in the laboratory may allow for enhanced embryo selection as some excellent appearing day 3 embryos will fail to continue to grow. Thus, implantation rates are usually higher for day 5-6 transfers because of this improved ability to select the best embryos. Additionally, there is some evidence that suggests waiting until day 5-6 may provide for improved synchronization of embryo and endometrium given that in nature the embryo usually doesn’t arrive in the uterus until day 5-6 after ovulation. On the day of embryo transfer your RE should review the quantity and quality of the embryos with the embryologist and then discuss with you his or her recommendations regarding the number of embryos to transfer.

Embryos that are not selected for transfer may still be of excellent quality, so they may be candidates for cryopreservation (freezing) with liquid nitrogen. These frozen embryos can then be replaced into the uterus during a future cycle, eliminating the need for the woman to undergo the entire IVF process of ovarian stimulation and egg collection. There is little benefit to freezing poor-quality embryos, however, because they are unlikely to result in a pregnancy and may not even survive the thawing process.


Phase 4: Embryo Transfer
Embryo transfer is one of the most critical aspects of an IVF cycle. During this phase, the embryos are transferred into the uterus by a procedure similar to an IUI. At our office, we perform our embryo transfers under abdominal ultrasound guidance to ensure the accurate placement of the embryos into the uterus. On the day of embryo transfer, patients are asked to drink 48 ounces of water and keep a full bladder to enable us to visualize the transfer of the embryos. No anesthesia is usually required for an embryo transfer and this step usually takes only 1-2 minutes to complete.

Phase 5: Post-Transfer and Pregnancy
During the 2 weeks after the embryo transfer, patients take supplemental progesterone (shots and/or suppositories). If a patient’s estrogen level drops significantly during the 2 weeks following embryo transfer, her physician may add supplemental estrogen as well.

Two weeks after the transfer, the woman typically undergoes a blood pregnancy test. Once a pregnancy test is positive, the physician may repeat the test every 2 days until the beta HCG level is high enough to visualize the pregnancy sac on transvaginal ultrasound (the beta HCG level should be more than 2000 IU around 3 to 4 weeks following embryo transfer). A follow-up ultrasound is then performed to confirm fetal cardiac activity. At this point, patients are usually referred back to their obstetrician/gynecologist for prenatal care.
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lundi 21 mars 2011

Question 45. How would I know when to pursue more advanced fertility treatments?

Posted on 11:16 by Unknown
In the Kenny Rogers song the gambler there is a very famous line "you gotta know when to hold them, know when to fold them, know when to walk away, know when to run...." Sometimes I think about that line when counseling patients, but fortunately for them I never break out into song during a consultation. Deciding when to move onto more advanced treatments is a common concern among most fertility patients. Even those that start with IVF have to consider moving to donor egg/embryo if success is eluding us. I wish that I had that crystal ball to provide a glimpse into the future. That way I could advise patients "Don't worry, I know the 3rd IUI will work or the second clomid cycle or the first IVF or the FET or whatever.....But I don't have that ability...and if I did I would have used it to play the Powerball lottery and then it would be "see-ya later."

In general, most successful treatments will occur in the first 3-4 cycles of whatever treatment has been chosen. It can be hard to hold my tongue when a patient describes 18 months of continuous clomiphene or 9 clomid / IUI cycles or 7 FSH /IUI cycles etc etc.

No one wants to be a professional fertility patient....there just isn't any money in it. But seriously, most couples/individuals can only take so much disappointment before they throw in the towel and consider alternative paths to parenting. So if you don't have a Magic Eight Ball handy....how do you know when to "fold 'em" and move on.....well that is the Question of the Day from the 2nd Edition of 100 Questions and Answers about Infertility.

P.S. Princeton lost to Kentucky by 2 points.....oh well.


45. How would I know when to pursue more advanced fertility treatments?

The decision to seek out more advanced fertility treatments is a complex question, and multiple factors must be considered when making it. For most couples undergoing treatment with IUI (either alone or with fertility drugs), the best chances for success usually occur within the first four treatment cycles. After that, the likelihood for pregnancy decreases. In many of our patients, we recommend only one or two IUI treatments. If these efforts are unsuccessful, we suggest that the couple proceed with other more aggressive treatments including both Natural Cycle IVF and traditional IVF using injectible fertility medications.

For some patients, IUI should rarely be utilized. For example, those couples with severe tubal disease, severe endometriosis, pelvic adhesions, or severe male factor infertility may do best by directly proceeding with IVF as their first treatment option. If an age factor is present or if the couple has prolonged infertility (infertility lasting more than 5 years), we often recommend IVF first, as well. Remember that IVF is the only treatment for which even a failed treatment cycle provides some insight into a couple’s fertility potential. IVF does allow us to make some assessment of egg quality, fertilization and embryo development. A failed IUI cycle yields no such information as we only know that the cycle failed but learn nothing about fertilization, embryo growth or embryo quality.
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mercredi 16 mars 2011

Princeton Beats Hahvahd (WARNING: This Post Has NOTHING to do with Infertility

Posted on 14:01 by Unknown
I know that world events have been so depressing lately.....from the unrest in the Middle East to the terrible earthquake and tsunami in Japan. It is hard to find something to cheer about and for a moment forget all the troubles and suffering that confront us on a daily basis. And then something completely meaningless (in the cosmic sense) and really quite silly can lift your spirits and make you grin from ear to ear.

Last Saturday afternoon I had just such an experience as I watched the Princeton Men's Basketball team battle Hahvahd in a one-game playoff to determine which team would go to the NCAA Tournament. Princeton battled back from a half-time deficit to finally pull even in the last few minutes. The teams traded baskets and then Princeton had the ball with 2.8 seconds on the clock under the Hahvahd basket but trailing by 1 point.

Here is the YouTube video of what happened next.





For those few moments I was transfixed watching the joy of the players and fans as they swarmed onto the court.

GO PRINCETON! BEAT KENTUCKY!

DrG
Princeton Class of 1985



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jeudi 10 mars 2011

Question 44. What complications can occur after IUI?

Posted on 08:36 by Unknown
Years ago in Long Island I had a patient experience an allergic reactions to an IUI. She got very bad hives and even began to have a bit of laryngospasm (throat tightening). She was taken to the ER and did fine with a dose of epinephrine and some steroids. Such reactions are really really rare but it was so surprising given the number of IUIs that I have done over years without any weird reactions. Clearly the more concerning complications after IUI are those of multiple pregnancy and OHSS. Both have plagued our specialty for years. However, the risk of both can be somewhat mitigated (but not eliminated) through judicious use of fertility medications.

First of all, no one ends up with a litter without seeing it coming. A patient does not have one follicle on Monday and 14 on Tuesday. Secondly, if there are more than 2 follicles > 15-16 mm at trigger then there can be more than 2 babies. It may be too risky to try an IUI when so many follicles can ovulate so often we discuss 3 major options to try to prevent the patient from having to deal with a pregnancy with > 3 babies or having to make a decision about performing a selective reduction. I do not view Jon and Kate plus 8 as a good outcome....

1. Cycle cancellation: stop the medications and let the follicles all regress and avoid intercourse for 2 weeks.

2. Follicle reduction: perform an IVF like egg collection but then just discard the extra eggs and go forward with the IUI leaving behind only 2-3 follicles. This option can be effective and egg collection would be scheduled like we do for IVF using an HCG trigger. I like to have the embryologists at least look at the fluid to tell be how many eggs I retrieved. If the eggs have already ovulated then this option will not be helpful as the "horse is out of the barn."

3. Convert to IVF: simply go for egg collection as if this had been the plan all along. Patients may experience an LH surge before HCG trigger so consideration can be given to using a GnRH antagonist as soon as the decision is made to convert to IVF. Personally, I have not had any patients surge in this setting but the chance of an LH surge is probably 20% so I may just have been lucky so far!

In spite of impeccable logic: "But Dr. Gordon I have a history of recurrent miscarriage and I am 37 years old and I failed IVF....so how is there any chance that I would end up with triplets???" I have ended up with just that in such cases.....Oh well. It's biology and not engineering.....So good luck and as I tell all my patients in these settings: "remember I don't babysit so let's not have any multiples!"

With that introduction, here is today's Question of the Day from 100 Questions and Answers about Infertility.

44. What complications can occur after IUI?


Complications related to the actual IUI procedure are very rare. IUI is a simple, in-office, nonsurgical procedure, usually performed by nurses. Occasionally patients may experience mild to moderate uterine cramps as the catheter is passed through the cervix into their uterus. These cramps usually last 10 to 15 minutes. Infection rarely occurs (its incidence is less than 1%). Many infertility specialists routinely obtain cervical cultures prior to initiating an IUI cycle, and the culture media used to prepare the IUI specimen commonly contains antibiotics. Occasionally, patients may note some light spotting after placement of the IUI catheter, but this is not an indication of a complication or a problem. Multiple pregnancy can occur in any situation when two or more mature follicles are present at the time of HCG. Your physician should discuss with you the risk of multiple pregnancy in cycles using fertility medication to induce the growth of multiple follicles. Similarly, patients with an excessive response to fertility medication can also be at risk for ovarian hyperstimulation synderome (OHSS). However, both multiple gestation and OHSS can result from the stimultion of the ovary with hormones regardless of whether an IUI is performed or not.
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lundi 7 mars 2011

Question 43. My doctor wants to use Lupron or Antagon during my IUI cycle. What are these drugs, and why do I need them? I thought they were only for

Posted on 11:28 by Unknown
The blue screen of death....or in the world of Mac computers...the gray screen of death with the question mark folder. These two phenomenon are terrifying for those of us dependent upon computers on a daily basis. Last week my college-aged son called us with the news that his MacBook Pro was giving him this problem. So naturally we all jumped into the mini-van and raced up Route 95 to his rescue! In our computer based world we are all on that razor's edge between happy computing and disaster!

In Natural Cycle IVF we are always on the razor's edge between wanting the follicle big enough to have a mature egg but not so big that there is an LH surge and the cycle gets canceled. In stimulated cycle IUI, an early LH surge is not such a big deal unless the follicles really were too small and the eggs immature. So what can one do about premature LH surge...well that is the topic of today's Question of the Day from 100 Questions and Answers about Infertility.

43. My doctor wants to use Lupron or Antagon during my IUI cycle. What are these drugs, and why do I need them? I thought they were only for IVF.

Lupron and Antagon are injectible medications that are used to prevent premature release of LH hormone during a stimulation cycle for IUI or IVF. These two medications work through different mechanisms to prevent the LH surge. Lupron usually requires at least 7 days to effectively prevent an LH surge whereas Antagon works within hours. This difference explains why the drug protocols that employ these two medications are so different. Premature ovulation during an IUI cycle can be dealt with by simply adjusting the timing of the IUI, so these medications are primarily used in patients undergoing IVF rather than IUI. For most patients undergoing treatment with IUI unless a patient repeatedly experiences a premature LH surge during the treatment cycle. In such cases, these medications can allow for a more optimal stimulation and larger follicle sizes.
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