Start here with Episode #1

I called Terra early in the morning and had her get Miles on the other line, preparing them for the good news about their embryos. To review, we retreived 15 eggs. Out of those, 11 were mature. Out of those, all 11 successfully fertilized. Today this is what we had:
(10cA) (9cA) (9cA) (8cA) (8cA) (8cAB) (6cB) (8cB) (8cB) (degenerate) (degenerate)

Just as different schools have different grading systems ( A / B+ / C- / F vs 100% / 95% / 45% vs High-Honor / Honor / Pass / Fail ) so different embryology labs have different scoring systems. The embryo grading system we use in this particular lab (for Day 3 embryos) is as follows. The # refers to how many cells are present. The letter is a grade representing how fragmented the embryos is. A is excellent, meaning there is no fragmentation. AB is like A-, meaning it’s not quite as fragmented as a B, but is also not as perfect as an A.

The reason we grade embryos is to help us estimate the odds of getting a baby from them. If we have High-Chance embryos, then we wouldn’t want to put in as many, for worry about twins or triplets. If we have Low-Chance embryos, then we can safely put more in. In fact, with Low-Chance embryos, we SHOULD put more in so as to have a higher of success. I coined the simple terms Low-Chance and High-Chance and use this terminology the way other people use the terms Low-Quality Embryo and High-Quality Embryo. I prefer this terminology to avoid the incorrect perception that a baby that comes from a Low-Quality embryo is someone less healthy than one from a High-Quality embryo.

The three factors that determine if a day 3 embryo is High-Chance vs Low-Chance are as follows:|

• CELL NUMBER: When a sperm fertilizes an egg, a 1-cell embryo is created. The cells then begin to individually divide. One cell splits into two. Then each of the two new ones will split into two more each. Because the splitting does not all happen exactly at the same time, we aren’t restricted to seeing 1/2/4/8/16 cell embryos. That’s why you can sometimes have a 7-cell. In that case, you have a 4-cell embryo and 3 of them split, while the 4th has yet to split. In general, embryos that are 6 cells or greater by day 3 have a much higher chance of becoming a baby than embryos which are less than 5 cells. There are some more subtle factors to consider, such as time-of-day (a 5-cell early in morning might be a 7-cell by the afternoon), but in general, six-cell to ten-cell embryos are what we are happiest with at transfer time.
• DEGREE OF FRAGMENTATION: The more cells that are broken into little chunks, the lower the chance of success. Perfect grade-A embryos have classic perfectly round, unfragmented cells.
• FROM WHOM DID THE EMBRYOS COME: This is a very important factor. An 8cA embryo from a 43-year old with 2 previous failed IVF cycles has a much lower chance of successful implantation as compared to a 6cB from a 27-year-old egg donor with 3 previous pregnancies.

So, of Terra’s original 11 embryos, 3 looked pretty good, 6 looked great and 2 were dead (degnerated).
So taking all this into account, an 8cA embryo from Terra, a healthy 30-year-old with no previous IVF failures would be considered High-Chance. My best guess was that each of those had perhaps a 40-50% chance of becoming a baby and my recommendation was to transfer two. If she absolutely refused to consider having twins, we could always just transfer one. If she wanted to take a risk of triplets, but boost her odds of success, we could transfer three. If we were in Europe, we would have no choice as the government controls how many embryos can be transferred with different countries having different guidelines. However, in the US, we have the freedom of choice to use our best medical judgment. Terra and Miles opted to be aggressive, against my recommendation and transfer three. Had they asked me to put in 4, I would have strongly advised against it and most likely, I would have even refused. But transferring three would give them less than a 5% chance of triplets in my estimate based on their entire clinical picture. Different RE’s have different preferences. I have known other RE’s who would not have transferred three, while I’ve known still others who would have transferred 6 without hesitation!

In Terra’s case, there was yet another possibility. We could wait 2 more days and see how each of those nine surviving embryos looked then. Sometimes an embryo that looks great at day 3 can look worse on day 5 and one that looks mediocre on day 3 can look amazing on day 5. This is the whole idea between doing a day 5 blastocyst transfer vs a day 3 transfer. The advantage of doing this is the opportunity to better tell which embryos are High-Chance and which are Low-Chance. The disadvantage is that some embryos that would have made a baby had you put it safely into the mom on day 3, might die in the lab before making it to day 5. This is controversial, because some RE’s believe that any embryo that grows poorly in the lab to day 5 would have not survived anyway had you transferred into the uterus on day 3. In my opinion, this is often true, but not 100% true.

Our final decision was to stick to a D3 transfer and to transfer three embryos. The exact rationale for this decision would require a long detailed explanation. Suffice it say that the optimal choice varies greater from laboratory to laboratory. (During this particular year, the D3 results for this lab were as good as the D5 results).

I should add that we have the unique advantage of having two laboratories that we work with. I am blessed with having exclusive dual access to two of the top embryology labs in our area. I share access to one lab with 5 other RE’s and I share access to the second lab with 3 other different RE’s. A lot of my decisions on which lab to use, how many embryos to transfer and whether to day 3 or day 5 transfers depend on factors that are always changing from lab to lab and from year to year. I believe that each lab has its specific strengths and weaknesses. So the best strategy is to individualize all decisions. One obvious strategy for patients who fail a cycle at one lab is to have them try the other lab, because although one is not necessarily better than the other, one might be better for THAT particular patient. Brand A tennis racket might not be better than Brand B, but a player that doesn’t do well with racket A might excel with racket B, just as a player who doesn’t do well with racket B might excel with racket A.

In any case, I went along with Terra and Miles in their slightly more aggressive choice and I put back three embryos with a careful ultrasound-guided transfer.

I realize that just because the result is a good one doesn’t mean the decision was necessarily the best. However, Terra wound up 12 days later with a positive pregnancy!

To fast forward, two and a half weeks after that, we saw two heartbeats on ultrasound. Two weeks after that, one of the heartbeats had stopped. Fortunately, however, Terra went on to deliver a single baby boy. Of the remaining embryos, 4 survived to blastocyst and were frozen on day 5. Three years later, Terra returned for transfer of two of those frozen embryos and went on to get pregnant again, and have another boy. They still have two embryos safely frozen in liquid nitrogen awaiting their chance in another few years.

We still don’t know why Terra and Miles get pregnant so easily with IVF and yet don’t get pregnant on their own or even with IUI. However, this is the case for many infertile couples, for whom we don’t have a diagnosis other than unexplained infertility, but yet, we can often provide an effective cure without knowing the exact cause .

I have nicknamed Andrea, one of my medical assistants, "The Empath".

 Before most of us were born, the original old old Star Trek series had an episode about a mysterious mute woman from another world. She had the power to absorb other people’s pain and injuries and transfer them to herself. She alleviated their suffering by taking the pain onto herself and enduring it. (If you have 50 minutes to spare, follow the link to the episode. You will see how different TV was back then. Great ideas + cheesy dialogue + laughable special effects. Compared to today’s lame concepts + lame dialogue + fancy special effects)

Our patients come to us having suffered through infertility, sometimes for years and years. The curative process itself of getting a baby is fraught with stress and pain, both mental and physical. It’s natural for patients to subconsciously look for an escape valve to shoot off their negative emotions. So often, they vent it onto their spouses, which is definitely not a good thing for the marital relationship. Other times, they vent it onto myself or more often, onto my staff since they are in the direct line of fire. I’m very proud of my staff as they have gotten very disciplined at recognizing this in certain patients and handling it very professionally and compassionately. Bear in mind not all patients need it as much, as many have a natural tendency to bring their own private supply of optimism and good cheer. But for those who have the need to vent, we are ready.

Often, patients just need someone to listen and validate that what they’re feeling is normal. However, every once in a while, sad to say, they can get outright MEAN. I’ve seen patients bring in their box of medications and scream at my staff for failing to order a certain drug, when all along it was in the box right in front of them. I’ve seen patients accuse our staff of scheduling their appointment on the wrong day, but when we all looked at the appointment slip they pulled out of their pocket, the date WAS correct all along. This confusing phenomenon represents the subconscious channeling of their anger onto the closest outlet, and occurs more commonly than most people realize. While we set limits on this if it really gets out of hand, we also have a high threshold for being willing to tolerate quite a bit when it is of benefit to our patients.

All our MA’s are kind and patient, but Andrea, in particular seems to be a magnet for the many hurricanes of emotional venting we encounter. I’ve witnessed her skillfully juggle being an attentive listener, balanced with the need to cut the visit short when necessary so she could attend to other patients who are waiting. Patients love her because they feel much better after talking with her. The patients feel better, but Andrea oftens comes away looking sad and drained. When I pointed out to her what was happening and called her an EMPATH, one of the other MA’s joked, "Andrea draws the pain from the patients onto herself and then vents it to the rest of us." So apparently our office has evolved into a mutually supportive, efficient tag-team empath system.

This compassion is something that is not easily taught, but is the exact thing that medical schools strive for when selecting the students of the future. We’re proud that nine of our former staff have left us to go on to prestigious universities for medical school, PA school or graduate studies in genetic counseling. I have no doubt that Andrea will join them some day.

Willingness to sacrifice ones own comfort and to suffer on another’s behalf is the truest display of love and compassion. With the recent passage of Easter, we are reminded of the world’s greatest example of such a sacrifice.

Start here with Episode #1

Thirty minutes after her egg retrieval, Terra was still groggy from the anesthesia. Knowing she might have just a faint memory of this conversation, I turned to her husband, who had just been allowed to come join her in the recovery room, and reported the good news to him.
"15 eggs"
"That’s better than we expected," he beamed.

An IVF cycle has the variability of a sporting event. Most of the time, the high scoring teams will score well. Most of the time, the low scoring teams will score poorly. Occassionally, upsets and surprises happen, but usually, not.
For Terra, we saw about 11 mature follicles on ultrasound in her last scan prior to the retrieval. With that, it would be no surprise if she got anywhere between 6 to16 eggs. Anything way above or below that would be quite a shock, although things like that HAVE happened. In this case, the outcome was good. It’s obviously good to have results that are better than expected.

As per my routine, as I drive from the surgery center back to my office, I used the time to dictate the operative report via my BlueTooth.

The next morning, I received the fertilization report. First of all, I should tell you that we had made the decision ahead of time to do ICSI with all the eggs. There are two ways to do IVF — the standard way and ICSI (Intracytoplasmic sperm injection). Standard IVF involves layering the sperm over the eggs and letting them do their thing on their own. The advantage to this is that natural selection is allowed to come into play as the strongest individual sperm with the best fertilizing ability are the ones that end up in the egg. With ICSI, the embryologist chooses the best-LOOKING one, based on how well it looks and how well it moves and then injects it into the egg.

I love to do standard IVF as much as possible and I probably do it in up to 25% of my cases. My colleagues, on the other hand, tend to do ICSI on 100% of their cases. The advantage of their strategy is that they don’t have to think about the risk of failed fertilization. If you choose to do standard IVF rather than ICSI, you might come back the next morning and find that all the eggs are sitting in the dish with a lot of sperm swimming around them, but with none successfully fertilized and that would be a horrible feeling. You are then forced to do second-day ICSI, which still has SOME hope, but is much much worse at getting you a pregnancy than if you would have done ICSI on the first day.

Then, why not play it safe and always do ICSI? Because, when you let survival of the fittest come into play, there is the belief that the embryos are "stronger" and result in a higher chance of pregnancy. It also saves the patient money, usually $1000-1500, depending on the lab. There is no evidence that the standard IVF babies are cuter, stronger, or better at math than "ICSI" babies, but whenever I feel it is safe, I will prefer recommending standard IVF over ICSI, because I believe in the principal of natural selection.

For which patients do I recommend ICSI?

• Cases in which the sperm is the suspected problem.
• Cases in which the husband has never proved that he can fertilize, meaning he has never initiated any pregnancies in his life.
• Cases when we use frozen sperm.
• Cases in which we don’t have a lot of eggs.
• Cases in patients who had poor fertilization in the past.

For which patients do I sometimes recommend standard IVF?

• Cases in which the sperm is almost for sure not the problem and the husband has a proven record of fertilization in the past (either naturally or through IVF).
• Cases in which the sperm is PROBABLY not the problem, but the husband has no proven fertility AND we have a lot of eggs to play around with. In these cases, I will consider taking some of the eggs and doing standard IVF and then doing ICSI on the rest, just to be safe.

I will only do this if the patient is well aware of the risk involved. A lot of times we do this mixed strategy and find that the ICSI group fertilizes fine, but the standard IVF embryos all failed to fertilize. In this case, we learned a big lesson about how bad the sperm functions. Fortunately, it’s not TOO costly a lesson as we can then get a pregnancy from the successful ICSI embryos. Other times, we might come back the next day and find equal or even BETTER fertilization in the standard IVF group. In these cases we will take into account this fact when we choose which embryos to transfer. We’ll still pick the better looking ones to transfer, but if it’s a tie, then we lean towards using the non-ICSI ones. In the future, if this couple does IVF again, then we would likely have the confidence to NOT do ICSI.

For Terra and Miles, since Miles had never fertilized any pregnancies before and Terra made a lot of eggs, we could have chosen to do the mixed strategy, but they decided to play it super safe and just do all ICSI. Their results were excellent. 11 embryos out of 11 injected. Recall that they had 15 eggs. Well, 11 of them were mature and normal enough to undergo ICSI and to our pleasant surprise all of them fertilized normally. This is usually not the case, just like hitting 11 out of 11 free throws is not usually the case for a basketball player. But when it does happen, everyone is feeling good (except maybe for the opposing team).

We’re going to let these embryos incubate for two days and reevaluate our next strategy on how many embryos to transfer and when to transfer them.

Click here for episode 9

Start here with Episode #1

For Terra who was now undergoing her first IVF cycle, the anticipation and uncertainty of starting something new was offset by the excitement and hope that maybe finally, her years of sadness were soon to be over.

"If you would like, let’s review the big picture for you two," I said to Miles and Terra on the day of their trial transfer. "You came to see me because of three years of failing to get pregnant on your own. We did your basic testing and found no obvious problems, except maybe for the issue with the cervical mucus. We started off conservatively by trying IUI. We tried it twice and failed both times. Now, as I said before, most couples try three cycles of IUI and can expect about a 50% chance of success overall. You two have done only two IUI cycles, but have chosen to skip the third and go ahead with IVF. Is this correct?"  They both nodded enthusiastically.

I went on. "Today, we’re going to do something that hopefully turns out to be unnecessary. I’m going to map out your cervix in anticipation of the day when I will be transferring your precious embryos for implantation. Of course, we have no embryos today, but we are going to go through the motions. If we get surprised by a cervix that is too tight, we will try and loosen up the scar tissue. If we find a cervix that is too twisted, we will map out each turn for future reference."

What followed was one of the easiest trial transfers I did that week. Terra’s cervix was readily accessible. The catheter went in smoothly with a 12:00 curve (directly upwards) and no resistance. I used ultrasound, visualized the exact tip of my catheter and took a picture. "Your actual transfer is most likely going to be a breeze", I said.

The next step was to ultrasound her ovaries to see if there were any cysts. You would think that by taking birth control pills, we could prevent any cysts from forming, but it’s not that perfect. True, taking birth control pills ahead of time, as part of the IVF protocol can MINIMIZE the chance of cyst formation. However, it is not 100% foolproof. Fortunately for Terra, it worked and she had no cysts. Everything was perfect to go and she was started on Lupron with instructions to quit taking the birth control pills according to her schedule.

Without going into extreme detail, Lupron is a drug used to start most IVF cycles. The Lupron shuts down the ovaries and gives us full control over the stimulation. By continuing the Lupron until we are ready to harvest the eggs, we protect Terra from the risk of premature ovulation. Terra got her period about a week after starting the Lupron, so we were all set to go.

Just as she did with her 2 IUI cycles, Terra faithfully gave herself the ovulation medication. By doing ultrasounds and checking the estradiol level every 2-3 days we were able to track the progress and adjust her doasge accordingly. After 10 days of stimluation, this is what we saw.

Right ovary: (22×15) (19×14) (17×17) (16×15)
Left ovary: (22×20) (22×19) (17×15) (17×12) (21×13) (18×16) (24×18)
The lining was a beautiful triple layer appearance, measuring 8mm.
Estradiol = 3402. Progesterone = 1.2.

"This is it perfect!", I exclaimed. "The follicles are at their optimal size. The lining is fantastic. Your blood tests are good. Today, you stop the ovarian stimulation. We’re all done with that. Tonight you will take the most important injection of the cycle. You will take your shot of hCG at a precise time exactly 35 hours before your egg retrieval surgery in 2 days."

After my nursing staff reviewed the exact instructions with Terra, I came back to answer any final questions. There were none. The next time I would see her would be two days from now for the big day of her egg retrieval.

Click here for Episode #8

Last week, Spring arrived. Those of you who have been basking in the sunlight, enjoying the smell of cut grass and daffodils while planting next year’s azaleas will appreciate my comparison of planting flowers with doing In-Vitro-Fertilization.
What makes for a successful planting of flowers? Three things. You need good soil. You need healthy bulbs to plant. You need to use good planting technique.
What makes for a successful IVF cycle? Three things. You need a good uterus. You need quality embryos. You need to use proper transfer technique to implant the embryos gently into the optimal location. We’ll discuss uterine factors and embryo factors another time. Today, we focus on the art of embryo transfers.

What’s so difficult about transferring embryos?
    Doing a perfect embryo transfer is a challenge for many reasons. Not every uterus is the same. Some tip forwards. Some tip backwards. Some are longer. Some are shorter. Some women have a cervix that is so tight that it will require some forceful dilation to open up. Some have a twisting cervical canal that will require tricky navigation to traverse.  The name of the game is to place the embryos in the right place, as gently as possible, without taking too long and without touching the fundus (the top of the uterus).
    Imagine taking an empty non-transparent bottle, laying it on its side and blindly poking a pair of tweezers into the mouth of it, with the hopes of dropping a grain of rice into a spot exactly 2 cm away from the bottom of the can. Now imagine doing this without being able to see the entire bottle and without knowing the exact size and shape of the bottle. You can only see the opening and once your tweezers pass through it, your view is obscured and you can only operate by touch. One more rule: You get penalized if you go too far and make contact with the bottom of the bottle.
    Let’s make it harder. Imagine that you have to do this for dozens of different bottles, of different sizes and shapes.  Also, every once in a while, you will run into a bottle whose neck is so tight that you can’t easily fit your tweezers in. Also, every once in a while, you will run into a bottle whose neck is so twisted that you can’t get the tweezers in without first going up and then turning left at just the exact spot and then twisting back to the right and then down, like some bad puzzle or combination lock.
Now you have a better idea of what it’s like to do embryo transfer.

Why is it so important to do a good transfer?
    The transfer can make the difference between a successful cycle and a failed one. The more kindly you treat the cervix and uterus on the day of the transfer, the more receptive the womb will be to good implantation. The more you rough up the uterus, the more irritable it will be and the more likely it will be to contract and slosh the embryo fluid around into the wrong places, possibly even spitting the embryos out completely (although not that likely). The more precisely you transfer the embryos into the optimal site, the better the chance of good implantation. Most will agree that transfer technique is the most important variable related to physician skill and experience in determining the outcome of an IVF cycle and the #3 most important factor overall. (The #1 and #2 factors are the characteristics of the patient and the characteristics of the laboratory). In my program, I don’t try to cherry-pick for the easiest patients. By offering reduced pricing to patients who have failed IVF in the past, I end up attracting the more difficult patients.  How likely is it that a patient who has failed elsewhere will get pregnant with my help? Think back to the flower analogy. A lot depends on which of the three factors is the main reason for her past failures. Was it bad soil, bad bulbs or bad planting technique? I’m usually very optimistic about patients who failed IVF in the past due to a previously undetected bad uterine environment. After I fix the uterine problem, I can usually expect a better outcome. I’m also very optimistic about patients who failed IVF in the past with great embryos, but had a bad transfer. There are many tricks I have available to improve embryo transfers and I can usually offer these patients a much better chance at pregnancy. However, for patients who failed IVF in the past because of bad embryos, I’m much less optimistic that anything I can do will make that big a difference in their outcome.

Why is doing a practice transfer beneficial?
    Surprises are nice on your birthday or when you play the lottery. But they are not fun when you are doing something critical. We want our medical procedures to be safe, routine and boring with no surprises.
For example, some patients will surprise you with a cervix that is too stenotic (too tight). This is NOT something that you want to discover for the first time on the all-important day of the transfer, especially if the embryos are already in the room, waiting to be transferred, all-the-while being exposed to the random temperature and air mixture of the exam room, rather than being in the tightly-regulated safety of the incubator. It is greatly preferred to learn of this problem well ahead of time, under controlled conditions, so that you can take the necessary steps to address the problem and not have to struggle on transfer day.
    I have a consistent policy of doing a practice embryo transfer on every single IVF patient. I’d say that over 90% of the time, we find out to that it was unnecessary, as the transfer ends up smooth and easy. However, in a small, but significant % of patients, it will make a world of difference between having an easy, worry-free transfer vs struggling through a sweating-bullets, cursing-to-yourself transfer which in turn can make the difference between a successful pregnancy vs a failed cycle. Are you one of those people who when faced with the most important job interview of your life will make the effort of driving to the location a week beforehand, assessing the traffic, gauging the travel time and scoping out the parking, so that the actual day will be as stress-free as possible? If so, you would understand the concept of doing practice transfers ahead of time. However, if instead, you are the carefree just-wing-it type, then you will do fine 90% of the time. But 10% of the time, you’ll end up getting lost or unexpectedly delayed, arriving late for the interview and blowing your chances of making a good impression, thereby costing you that job you wanted so badly.

What are some important things you can discover during a practice transfer?
As I mentioned earlier, some patients have a cervix that is so stenotic (tight) that it becomes impossible to do a transfer. There is a RE from whom I’ve inherited many failed patients, several of whom had transfers that were so difficult that they had to be put under general anesthesia. This is something that I’ve almost never heard of anyone else doing, except for this particular doctor. The majority of those patients have wound up getting pregnant with my help. There are many tactics of getting around the problem of a really difficult cervix.

• Dilatation. By using a set of increasingly large dilators, the cervix can be made more accommodating. I repeat that this is something that you want to do ahead of time – not on the day of the transfer. True, sometimes, you dilate the heck out of the cervix and it still creates a bit of a struggle on the day of the real transfer, because it shrinks back. However, this still beats being caught fully by surprise.
• Tension suture. One trick I rarely use is to place a suture on the cervix. This is helpful for a cervix that is too sharply bent. By pulling on the suture, I can straighten out the cervix and help pass the catheter more easily. In the US pictures below, you see that the canal is just slightly curved. However, some patients have a cervix that is so sharply curved that it makes a 90 degree angle.  Now you don’t want to place the stitch on the day of the transfer because that hurts a lot and it angers the uterus. By anticipating this problem, I can place the stitch at the time of the patient’s egg retrieval while she is under anesthesia. Then, on the day of the transfer, I have a painless handle by which to straighten out the cervix. After the transfer, I cut the suture and remove it.
• Laminaria. This is a commonly used gynecological device, although technically it’s more of a biological entity rather than a device. It’s a little stick-like thing that is harvested from a particular type of sea creature. When you put it into the cervix, it will absorb water and get really fat overnight. This is a very safe, gradual way of dilating the cervix. Again, this is of no use if you wait until the day of the transfer to find out that the cervix is too tight.
• Proper mapping. Sometimes, the cervix is not too tight, but rather, too twisted. If you have a cervix shaped like an S, for example, you have to map it out so you know when to turn up and when to turn down, when to turn left and when to turn right, like in that Kenny Rogers song.
• Giving up on the cervix. There is that one in a 1000 women whose cervix is completely impassable. I had a patient whose cervix made a 180 degree hairpin turn. I did a saline-contrast ultrasound and a hysteroscopy on her to confirm this. I consulted many of my colleagues and mentors who were all stumped. I eventually wound up doing an old procedure called GIFT (Gamete IntraFallopian Transfer), in which I didn’t even bother trying to pass through the cervix, choosing instead to put the eggs and sperm into her tubes. She got pregnant in what is likely the last GIFT I will ever do, so I might be able to retire with a 100% batting average there. One other option for these patients is to try a transmyometrial transfer in which you push a needle THROUGH the wall of the uterus. I’ve never done that, but I hear from those who have tried it that the success rate is low. The last resort would be to use a surrogate, ie use some OTHER woman’s uterus to carry it.

    There are a few other tricks that I’ve learned over the years, but a lot comes from practice and taking advantage of a whole armamentarium of different catheters.

What is an ultrasound-guided transfer?
    In the past, all transfers were done blindly. Some RE’s still do their transfers blindly to this day. I can’t understand why. Think back to the model I described earlier of blindly putting a grain of rice into a bottle. Now how much easier do you think it would it be if you had a special camera that could show you exactly where you are at all times. Well we do have such a magical device and it’s called ultrasound.

In these pictures, we see the uterus. We come in with our cathether from the cervix at the top left (red arrow) and we are hoping to land at the sweet spot designated by the X. This is where the embryos want to go. The brown line shows the outline of the uterus.

Every step of the way, as I slowly advance the catheter, I can see where I am and where I want to be.

Ultrasound-guided transfers are not some fancy gimmick. While I can’t prove yet that the location I choose is immensely better than another spot a half centimeter deeper or shallower, I can guarantee that the embryos are not being pushed too deep into the wall of the uterus. I can guarantee that they are not being put too shallow into the lower uterine segment. I can guarantee that the catheter is not curling around and coming back to spit the embryos into the cervix. My own IVF success rates went up after adopting this technique several years ago. (Last year saw 59 pregnancies out of 100 transfers for me) as did those of my colleagues who adopted this technique. I apologize if this is sounding too self-congratulatory, but I have a very strong opinion on the huge advantages of doing things this way and I wanted to provide some convincing evidence.

Why doesn’t everyone do their transfers under US-guidance?
    You would have to ask them. I wonder that myself. I have some theories. One is that it’s hard to change old habits. There have been people around who were doing IVF before I was in high school and they will claim that they can do a transfer blindly as well as I can do one under US visualization. Who am I to argue with them?
    Now, some people try to do them under ABDOMINAL ultrasound-guidance. This is still better than doing it blindly, but it has a few disadvantages. One is that it requires an additional set of hands to hold the ultrasound and you’re at the mercy of a technician or nurse who may or may not be that good at it. The other big disadvantage of doing it under abdominal ultrasound guidance is the need to have the bladder uncomfortably full, which can eventually progress to inhumanely full, according to some patients who have had it before. In case I didn’t mention it specifically, I advocate doing the transfers under VAGINAL ultrasound-guidance. In general, you get a much clearer picture and for two types of patients (those with a retroverted uterus and those who are obese), the vaginal approach just blows the abdominal approach right out of the water.
    This brings us to the main reason why not everyone does it this way. It’s not that easy to master (at first, anyway). Before I first started using this technique about seven years ago, I was intrigued to hear about it. How can you fit a speculum, an embryo catheter and an ultrasound transducer all in the vagina at the same time? It didn’t sound possible. However, with a lot of practice, I can now do an ultrasound-guided transfer in close to the same time that it takes someone to do a blind transfer.  Maybe it consumes an extra 2 minutes of my time for each transfer, but again, the extra effort is well worth it to the patient.
    The last answer to why not everyone does US-guided transfers is this. More and more people ARE doing them. My closest colleagues all do some sort of US guidance, although many still like the abdominal approach. So in reality, I would guess that more than half of all RE’s in the US ARE using US-guidance. I will be happy to hear some day that all of them are doing it, but to this day, I know of some who are still doing things blindly.

How does one get better at doing embryo transfers?
When I first wanted to learn US-guided transfers, I practiced by doing ultrasound guided IUI’s. The difference between an IUI and an embryo transfer is like the difference between dropping a grain of rice into a precise spot in the bottle vs shooting a syringe full of water into the bottle. IUI’s don’t need to be precisely placed to be successful. But for quite some time, whenever I did an IUI, I would do it under US-guidance just for the practice. To this day, this is how I train RE fellows and interested residents how to do US-guided transfers. In fact, for some patients with difficult IUI’s, I will, at their request, do the IUI under US-guidance. As I said, it takes me an extra 2 minutes, but the extra hard work is well worth it. I point out the story of Steve Nash. Most of you will know him as a very hard-working NBA basketball player who in 2002, made 49 consecutive free throws without missing. He also made 47 straight in 2003. Those who laughed at me for so tediously practicing transfers are the same type of people who laughed at Steve Nash for staying late after basketball practice and shooting 100 free throws every day. A waste of time? Think what you want.

Start here with Episode #1

Terra arrived for the pregnancy test for her 2nd IUI cycle. She had fought the temptation to test on her own and came in with an open mind, although she confessed she felt a little more bloated this cycle than last, for whatever that means. When the blood test results rolled off the machine, we were all saddened again. Another negative. She and her husband requested a face-to-face meeting the next day.

This is what I told Terra and Miles. "Our goal is to help you get pregnant in the easiest way possible. For someone of your age and your situation, most likely you will get pregnant with either IUI or IVF. Whether it will happen easily with just IUI or require the power of IVF is unknown. However, each unsuccessful IUI cycle leans us closer towards choosing IVF. Also, each successful IUI cycle reinforces our confidence in IUI. For example, prior to doing any treatment, I would strongly urge trying IUI first. Let’s pretend that you did get pregnant on the first IUI cycle, but had a miscarriage. Then I would be more persistent about sticking with IUI, even if the next two didn’t work, because we now know that you CAN get pregnant with just IUI. On the other hand, let’s say as an extreme example, that you did six IUI’s and they all failed, and let’s say that you made more than six eggs each time, then it would be pretty convincing that it was time to move on to IVF, because it would mean that something else was wrong, something that wasn’t being helped enough by the IUI procedure. Maybe the sperm is totally incapable of penetrating the eggs. Maybe the eggs are just not getting picked up properly by the tubes, or they are surviving poorly because of something like endometriosis."

So based on the two failed IUI cycles, I still felt that the evidence pointed towards trying one last IUI cycle. Many patients have failed 2 IUI’s and then got pregnant on the third IUI. However, if they wanted to move on to IVF, I wouldn’t dissuade them at this point. We spent the next half hour going over the details of an IVF procedure including the pros and cons, the risks and the benefits and all the variations of decisions. I did a baseline ultrasound and my staff gave them the medication instructions for both IUI and IVF. They were to go home and discuss it tonight. If they wanted to start IUI #3, they would take the medications again. If they wanted to do IVF, Terra would start taking birth control pills.

Miles called the next day and said they were ready to proceed with IVF. I generated a schedule for them and had them to come back in two weeks for the next step — the trial transfer. Meanwhile, Terra continued to take the birth control pills.

Click here for episode 7

On my older blog, I shared a story about a woman who got tired of waiting to meet Mr. Right and instead chose to become a single-mother-by-choice through donor insemination. Hers was an especially happy story, because not only did she have a wonderful baby, she later wound up meeting a man, getting married and having another child with him.

I recently came across an article that tells a different story of another woman who also decided to become a single-mother-by-choice rather than settle for any of the guys she dated, because none of them were quite perfect enough. In her article, she openly wonders if she might have been better off just "settling".

I sent this article to a lot of my single friends, and not to any surprise, most of them disagreed with it (as did I). It’s still a consensus that no matter how strong of an argument is presented for people not to be so picky, there will still be a strong resistance to stubbornly hold out for Mr. Right. By the way, for one of my friends, she liked the article because it made her more appreciative of her current boyfriend, who although not everything she always dreamed, is a very solid guy. She’s going to give the relationship every chance to work, instead of restlessly looking for something "better".

So for all you married women undergoing fertility treatment, be thankful that you have at least found the man of your dreams father of your future baby

Start here with Episode #1

For eleven days, coming down from the high of a highly optimistic first IUI cycle, Terra was full of anticipation for her pregnancy test. She was so anxious that she did a home pregnancy test the day before coming to our office. I saw her look of devastation when she confessed to having tested. It had been negative. She was not the first patient to "cheat" in this manner and I told her the truth. If the test would have been positive, that would have been great news, because that means the blood test would confirm the pregnancy. However, a negative urine test USUALLY, but not always means a negative blood test. There have been some memorable times when a patient came in despondent from a negative home urine test, but was surprised to find out that the blood test was positive, signaling the beginning of a nine-month healthy pregnancy. In Terra’s case however, her blood test came back the same as her urine test - a big negative.

We had a long conversation over the phone later that day. The good news had been that she had stimulated very well and the sperm sample had been very good. But, understandably, that doesn’t mean all that much when the result is a negative. At this point, we made the decision to do a second cycle, knowing that about 50% of patients will get pregnant with this treatment approach (ovarian stimulation and IUI) within three cycles. Three failed cycles would tell us something, that it’s probably time to move on to IVF. But ONE failed cycle does not tell us that at all.

Her Day 03 ultrasound showed three large cysts (over 25mm) left over from this past cycle. This was not a huge surprise. Many times, after a vigorous stimulation, there are cysts left over. Because of the cysts, we could not do a cycle right away this month. At least this gave Terra a one-month break to try on her own again. She called a month later with her period.

Taking what we learned from the first cycle, we modified things a bit in this second cycle.

Day 03 Right ovary clear. Left ovary two 6mm cysts.
Day 08 After 2 days on 225 IU and 3 days on 150 IU of injectable gonadotropins. Right ovary (15×13) (10×10) (9×9) (7×7). Left ovary (12×10) (11×11) (11×11) (10×10) (10×7) (9×7). Lining 8mm triple layer.
Day 11 After another 2 days on 150 IU. Right ovary (17×13) (15×15) (8×8) (8×7) (7×7). Left ovary (19×15) (24×18) (18×14) (14×14) (15×13). Lining 10mm triple layer.
Day 13 After 2 more days on 150 IU. Right ovary (19×17) (17×17) (10×10) (11×10) (12×11). Left ovary (21×19) (27×21) (21×16) (16×16) (16×16) (13×12). Lining 10mm TL.
Day 14 After 1 more day of 150 IU. Launch ovulation at 2PM with 10000 IU of hCG.
Day 16 IUI #1 with 25 MILLION total motile sperm. Right ovary (23×19) (21×21) (13×11). Left ovary (22×22) (40×28)CL (23×21) (20×16) (19×19) (13×12). Lining 10mm TL.
Day 17 IUI #2 with 20 MILLION total motile sperm. Right ovary (24×24)CL. Left ovary (39×32)CL. Lining 12mm TL.

COMMENTARY:
    Immediately after her first cycle, Terra had 3 large cysts on day 03. They were well over the cutoff size, so it was an easy decision to postpone things and wait a month. When she came back a month later, she had two tiny cysts, which were so small as to be of no consequence, so finally we could proceed with cycle #2. As per our discussion, we would be a tad bit more aggressive, but not much more. We started with a higher dose for the first 2 days to try and recruit more follicles. Her day 08 US showed a good response but nothing too vigorous, so we continued the same dose.
    By day 11, there were 2 maturing follicles on the right and five on the left. However 2 of those 5 were still at an immature size. Then, by day 13, we had 2 mature ones on the right and 3 clearly mature-sized follicles on the left. Remembering that there were a few unpopped follicles last cycle, I told Terra that normally, I would trigger ovulation now. But because of what happened last cycle, I would grow her out one extra day this time. We would also give the hCG a few hours earlier to give the eggs more time to release before the IUI. We used the full 10000 IU of hCG. A lot of times, with this many eggs, it is safer to give just 5000 IU to lower the risk of hyperstimulation syndrome. However, in Terra’s first cycle, she had no bloating at all and surprisingly, no indication of hyperstimulation.
    Despite all our attempts at adjusting the duration of stimulation and the time of hCG, when Terra came back for her IUI, most of the follicles STILL were not ovulated. The only one that might have done something was the very large corpus luteum on the left. So mildly frustrated, we scheduled another IUI the next day. True to form, Miles gave another excellent sperm sample.
    The next day, there was great news. Almost everything was now ovulated! There were two CL’s left, one on each ovary. The rest of the follicles were gone, meaning that the eggs had released and were somewhere outside the ovary now. Hopefully, they were in the tube. We were once again optimistic. This cycle was definitely better than the first in that we had more follicles and the ovulation was more definitive. Of course, with a total of seven follicles, we were also facing the opposite problem, the risk of twins or triplets. For many patients, this cycle would have been managed more gently or cancelled all together. However, Terra and Miles clearly stated that they were aware of the risks and wanted to aggressively go forward with it.

Again, the long waiting period began, leading to the day when we would once again do a pregnancy test.

Click here for Episode 6

Start here with Episode #1

Miles and Terra have nothing wrong with their fertility. Nothing other than for the fact that they haven’t gotten pregnant in three years. The most abnormal finding, after all their testing, was cervical mucus that was not the best. I’m not totally convinced that this is the real problem, but if it is, then insemination should solve it most readily.

Terra called with her period and came in for a baseline ultrasound. This is a necessary step prior to starting the ovulation medications to stimulate Terra’s ovaries. In the event that a large cyst was seen, we would have to postpone her cycle. This is something that happens in about 1 out of 10 cycles. Well, Terra was very unlucky. There was a cyst on her right ovary measuring 16mm, well above the usual 12mm-13mm cutoff. I explained to her that she would have to wait another month before starting stimulation. However, the good news was this. Most likely, the cyst would go away on its own by next month. Also, this meant they would have another month to try to concieve naturally. Many times, couples who have to take a month off due to cysts somehow end up getting pregnant naturally. Whether this is just coincidence or not is still unclear. There is the thought that a cyst somehow rotates the ovary and changes its position so that it could end up in a more strategic location to have the released egg get captured by the tube. In any case, this did not happen for Terra. A month later, she called with her next period and came in, eager to start her IUI cycle.

Baseline scan showed both ovaries clear. The cyst was gone. Hooray! Sometimes, with really bad luck, the cyst is gone, but then a new cyst is seen in the opposite ovary. Fortunately, this was not the case and we were clear to start. The next decision was what stimulation protocol to use. We could do anything from a natural cycle with no medications all the way to straight injectables. The progression goes something like this:

No medication
Clomid only
Clomid followed by injectables
Straight Injectables (moderate dose)
Straight injectables (higher dose)

On one end you have greater safety from twins (or triplets or more), lower cost and less medication. On the other end, you have a higher chance of pregnancy. After careful deliberation, Terra and I agreed to go with straight injectables, moderate dose. She was started on 150 IU’s of injectable gonodotropin. In a first time cycle, the choice of brand of medication (for example, Bravelle vs Repronex vs Gonal-F vs Follistim) is based a lot on cost. Certain patients might have certain insurances that ally themselves with one drug company or another. There are other factors to consider, such as ease of administration and flexibility of dosing. In any case, we chose a brand and monitored her progress with ultrasound.

Day 03 Both ovaries clear.
Day 08 After 5 days of injections. Righ ovary (15×14) (12×12). Left ovary (13×10) (14×13)
Day 12 After 4 more days of injections on the same dose. Right ovary (18×15) (18×14) (12×12) (12×11) (12×11). Left ovary (19×15) (17×15) (11×11).
Day 13 Ovulation triggered with 10,000 IU of hCG at 5PM.
Day 15 IUI performed at 8AM. Sperm sample 15 MILLION total motile sperm. Ultrasound after IUI confirms deep passage of specimen into the uterine cavity. Lining 10mm triple layer. Right ovary (31×24) (22×17) (18×15) (17×17). Left ovary (23×21) (22×17) (14×13). Minimal free fluid.
Day 16 Another IUI performed at 9AM. 12 MILLION total motile sperm. Lining 10mm triple layer. Right ovary (30×26) (28×22) (24×20)CL. Left ovary (32×25)CL (12×11)

COMMENTARY:
    When a woman takes ovulation medication for the very first time, the results are a lot like Forrest Gump’s box of chocolates. You never know what you’re gonna get. Sure, just knowing Terra’s age and the dosage of medication, I could guess that she would possibly have 2-3 eggs, but I would not have been totally shocked had she made zero nor would I have been shocked had she made 8 eggs. After her first US on day 08, the largest follicles was the 15×14, followed by the 14×13. The other two were smaller and more likely to stop growing. In general, we like them to grow to about 18mm. On the next visit on day 12, four mature follicles emerged as the leaders (they are highlighted in BOLD lettering). The other four are smaller and not likely to result in pregnancy. On that day, I could have chosen to trigger her ovulation, but instead, I decided to wait one more day before triggering, just to allow those four to grow a smidgen more. So she continued with another 150 IU of medication that night, before taking a different medicine, the hCG, on the night of Day 13.
    The hCG is a medication that is given to trigger ovulation. It is also the same hormone that is tested in a pregnancy test. Therefore, if you were to do a pregnancy test too soon after taking the hCG shot, it would give you a false positive pregnancy test. In general, for a first cycle, I time the hCG shot about 40 hours prior to the insemination.
    On the day of the IUI, I did another ultrasound, right after putting the sperm in. This enables me to confirm that it went into the cavity. Sometimes, if the volume of IUI specimen is high enough, it can distend the uterine cavity and give me a free peek to make sure there are no polyps or fibroids in it. I also use the ultrasound to see if the follicles have ovulated. In Terra’s situation, none of her follicles had ovulated. This was evident, because all the big follicles were still there. In fact, they each had gotten quite a bit bigger. Also, there was not a lot of free fluid seen behind the uterus. If the follicles would have ovulated and released their fluid, one would expect more free fluid to be seen. Many times, the patient also reports a lot of pain right near the time of ovulation.
    It would not have been wrong to stop there. Even though the follicles had not ovulated, at least some of them were expected to do so shortly. However, Terra was in an extra-diligent mood and when I offered her an optional second insemination the next day, she and Miles clearly stated that they wanted it. Miles was confident he could produce another stellar sperm sample, and it turns out he did.
    On Day 16, after the second IUI, it was clear that at least one follicle had successfully ovulated on the left, seeing how there was only one large one remaining, when previously there had been two. In addition, some of the follicles, even though they were still there, were filled with echogenic shadows, suggesting that they had already ovulated, but just refilled with blood. This is called a CORPUS LUTEUM and is what’s left over of a follicle after ovulation. So it was clear that we had successful ovulation.
    So optimistically, Terra was routinely started on progesterone to help support the lining and we waited for the scheduled pregnancy test in about 11 days. With about four mature follicles, her expected chances of pregnancy were good, while still maintaining a pretty safe threshold against having twins or triplets. On paper, this had been a great cycle. Terra and Miles eagerly awaited some good news on the day of the pregnancy test.

Click here for episode 5

Today is the day that about 35000 medical students around the country find out what the rest of their lives are going to be like. Sort of. This morning, these graduating medical students were notified of which specialties they will be going into and at which program they will be working geographically for the next 3-4 years or more. For the past year, they have been completing applications, visiting programs and undergoing interviews. Then each program ranks in order the applicants that they want most. The students, likewise, rank in order the programs they want most. Then a computer sorts it all out. The formula is not TOO complicated other than for a little tweaking that has to occur for students who "couples-match". This involves spouses or almost-spouses who wish to stipulate their preferences jointly so that they will end up in programs that are geographically matched, thereby preventing them from being in a long-distance relationship for the next 3-4 years.

Among the students whom I know personally, all got near their top choices, even the ones who couples-matched! But that’s not always the case.

Each year, many applicants fail to match in the specialty of their choice, forcing them either to take a different specialty or find some other way, either by scrambling for a spot or reapplying next year.

As Dr. Reece points out in his blog, the most competitive residency spots to get include Dermatology, Plastic Surgery, Orthopedic Surgery, ENT, Radiation Oncology and OB-Gyn with fewer than 90% of applicants getting accepted in 2007. Dermatology was the toughest, with only 61% of applicants getting their wish. Internal medicine and family medicine, on the other hand, was successfully matched by 98%+ of the applicants. Many of these internal medicine physicians will some day transition to a more lucrative subspecialty, such as cardiology. Infertility is also a two-step process, with applicants first completing a general OB-Gyn residency before applying later for a Reproductive Endocrinology / Infertility fellowship position.

After my lectures, I ask my 3rd-year medical students what factors they take into account when choosing specialties and the answer is overwhelming - LIFESTYLE, which some of them defined as "the best salary for the least hassle". Doctors do not differ from engineers, lawyers or plumbers in this respect. Human motivation for optimizing ones state does not necessarily rule out a place for personal integrity and compassion. In fact, in a free-market environment (which we don’t have) the hardest-working, most ethical, most compassionate, most caring doctors would be the most attractive to patients and command the most favorable compensation. Sadly, in the artificial model we have today, only the most idealistic souls would enthusiastically embrace a career in primary care, and it’s arguable how long their idealism will sustain them after facing a few years or even a few months of reality. If economics holds true, what will happen eventually is a severe shortage of primary care doctors (already happening) and then a cyclical increase in demand as people suddenly become willing to pay what’s reasonable in order to have access to the sparse pool of good primary care doctors. However, medicine does not follow normal economic models the way it’s set up now.

I repeat what has been said many times already by others, but falling on deaf ears. The way our medical system is headed, some day soon, we will be facing a severe shortage of primary care doctors.