Hi
I found this site when i was searching google site for my questions.This
site is wonderful with good information.I too want to ask some questions.I
will explain my situations.
This is a very lengthy mail.Please make time to read this and answer my
questions.I will be very thankful to u.

MADHAVI
Helsinki, Finland

Dear Madhavi,

Thank you for sharing your story. Your doubt and disappointment are understandable. However, in my judgment, based only on what you have revealed, your chances of ever having a baby are quite good.

I will summarize what you’ve revealed to us so far, but bear in mind there are some key bits of information that you either left out completely or for which you have been vague. Email is not the optimal form of communication for this, but let’s try our best.

When I work on seeing the big picture for someone’s fertility, I focus on three areas which most of the regular readers already know and those are SPERM, EGGS and ANATOMY. You mention nothing of your husband’s sperm, but with the two pregnancies you have described, we might assume that the sperm is OK. Your eggs have produced two pregnancies (even if they were an ectopic and a biochemical), so that is promising. Your age is even more promising. This brings us to your big problem — your anatomy. From what you said, your HSG showed that your left tube was open. Can we assume you mean that your right tube is absent or blocked then? If, so that leaves you with a realistic chance of getting pregnant ONLY IF you ovulate from the good side.

Now going back to the ovulation issue, your periods are not every 28 days on your own. The fact that naturally, they are every 32-35 days means you will have fewer ovulations per year than average. Also, half of your ovulations are essentially wasted because they will be on the right side where the tube is blocked / absent / disconnected. We don’t know for sure whether or not you ovulate on your own. We do know that you have ovulated at least twice using a combination of Clomid and hCG (Pregnyl and Pubergen are both hCG. Just different brands). Your descriptions of your ultrasound findings are very good. It seems everything went as expected with respect to the sizes of the follicles.

Now let’s look at your specific questions:
1.As i got Ectopic Pregnancy once will i be able to have normal pregnancy
again?
A woman who has at least one open tube can usually still have a normal pregnancy. Most pregnancies that occur are normal rather than ectopic. This is true even for women who already had an ectopic.
2.In my case will egg releases only if i take that injection? Without that
is it not possible??
This question is not answerable, because I have no way of knowing, without doing further monitoring whether you can release an egg on your own or not. I would venture to guess that you CAN ovulate on your own without the trigger injection, but the chances of ovulation are MORE CONSISTENT if you take the injection. In other words, some months you might and some months you might not. But it is not that important anymore. Remember that the best questions to ask focus on WHAT DECISIONS TO MAKE, which is what we will discuss shortly.
3.Even if I take that injection i think my chances of getting pregnant is
good only if my left follicle gets matured. Am I right?
As I said earlier, if your right tube is truly blocked or missing, then the chances of pregnancy are terrible UNLESS you have ovulation on the good side (the left side), so I would agree with you there.
4.My doc is asking to try one more cycle of clomid and then start the
injections treatment.Shall I do that or shall I start injections treatment
in this cycle itself?
This is the type of question I find most practical. You have many choices. You can try naturally, on your own. You can try Clomid again. You can move up to taking injectables. With each advancement, costs go up, but chances also go up. So the choice is individualized depending on the balance between how great your sense of urgency vs how great is your preference to save money. I always thought medical care was free in Scandinavia. Isn’t it? If so, have you considered just going on to IVF?
5.I am very depressed thinking about this all the time I have a big doubt
that will I become pregnant and have a baby?
Your feelings are very normal. However, don’t forget that with IVF, your chances of getting pregnant should be very very high.
6.Please suggest me which treatment is better based on ur opinion in my
case.
This is best discussed with your doctor. I still have incompletely information. Some things that would be considered in making the decision are as follows:
What exactly does the HSG film show? Is the uterine cavity normal? Is it confirmed that the left tube is open and the right tube is not? How brisk is the spillage from the left side. Is it just a small trickle? Or is there a large amount of dye spillage?
What other ovuations problems might you have? Do you have a healthy BMI (below 25)?
How much will it cost you to do IVF? How much will it cost you to do IUI?

For most couples in your situation, I would probably offer at least one aggressive IUI cycle with injectable stimulation, trying to get 2 or 3 eggs to grow on the good side. (It doesn’t matter how many grow on the bad side). Then, if there is still no pregnancy, I would give serious consideration to going on to IVF. Your age is on your side and gives you many options. If you were 40, I’d probably suggest IVF sooner than later.

Thanks for sharing your story. We all wish you the best. Feel free to give us an update on your progress!

Click here for episode 1

Six days after her IUI, we got a phone call from Aimee.

"I think something is wrong", she said. "I feel pretty bad, with a lot of cramping and my stomach is really swollen. Is it normal to feel this way?"

My staff transferred the call back to me. It was possible that Aimee was suffering from Ovarian Hyperstimulation Syndrome (OHSS).

OHSS is a condition that sometimes occurs after stimulation of the ovaries. It can sometimes happen with Clomid and has even been reported in people who are taking no ovulation drugs at all. However, most of the time that it occurs, it’s a reaction to injectable ovulation medication.

ME: Tell me what’s going on, Aimee.
AIMEE: Dr, after the IUI, I felt OK. Very mild cramping only. But the past few days, my stomach has gotten quite large and I feel so bloated.
ME: I see. Tell me this. Are you able to eat OK and drink OK?
AIMEE: So far.
ME: Have you been going to work?
AIMEE: I worked yesterday, but was tempted to clock out early. I didn’t, though.
ME: OK, have you been peeing a lot?
AIMEE: Tons.
ME: That’s good. Do you have any idea what your weight is doing?
AIMEE: Actually, I do. After the IUI, I realized I was at 157# when normally I’m usually around 155#. I think those injections made me gain 2 pounds. Then the past few days, I found myself at 158#, but today, I’m back at 157#.
ME: How do you feel today compared to yesterday? By the way, it’s very smart of you to weigh yourself everyday like that. That information is helpful.
AIMEE: Hmmm. About the same. Maybe a little better.
ME: How are you breathing? Also, do you have any swelling or pain in your calf?
AIMEE: No trouble breathing. No, my calves are fine.
ME: Aimee, I don’t think you have hyperstimulation, but if you don’t feel a lot better by tomorrow, I might have you get some blood tests drawn. I’m possibly going to check your blood to see if it is overly concentrated. I also want to confirm that your kidney function is good. However, I’m reassured that you’re peeing a lot and losing weight from yesterday. It means your body is getting rid of the excess water. If you don’t feel better by tomorrow, come on in and I’ll examine you, but otherwise, you may work. You’re a nurse, right? We’ll see what happens with your pregnancy test next week.
AIMEE: OK, thanks for answering my questions. Yeah, I think I can work. I just feel blah.
ME: Do you want me call your husband and tell him to be extra nice to you?
AIMEE: Haha. No, he’s been good. I guess I’ll survive. I sure hope I don’t have to do this again.
ME: Me neither. Me neither. Let’s hope for some great news next week.

ONE WEEK LATER…

"Aimee is here for her beta today", said my staff member. "I think she cheated, because she looked really really happy."
I had just gotten to work and was passing by the blood-draw station.
"Aww, Aimee, did you cheat?" I smiled.
Aimee’s expression alternated back and forth, at times looking like a kid who snuck a cookie from the cookie jar and at times looking like a new fiancee about to burst with happiness showing off her ring. "You know me. I couldn’t wait! I did a home preg four days ago and was so sad when it was negative. But then I did one yesterday and it was faintly positive and today it was very very positive!"
"That sounds pretty promising. We still have to wait for the blood test"

Aimee was correct. She was pregnant. Her hCG was 46. In two days, it was 84. A few weeks later, she had one sac seen on ultrasound with a fast heartbeat. She graduated at 12 weeks gestation, went on to her OB and eventually delivered little baby Raymond at term!

Your site is fantastic. I have searched many infertility sites and there is nothing else like it. I have a question that I would respect your opinion on, please.
Recently, i found out that my FSH is high (20.4). My fertility doctor says that this is the reason for my infertility and it means my eggs are getting bad.  I also went to see a Chinese medicine specialist. She says I need to get a full evaluation and then she can come up with a formula of herbs that will definitely lower my FSH. I don’t really trust her. She’s not even Asian! What can I do to lower my FSH? Is there no hope for me?

Angel
Larkspur CA

Dear Angel,
I’m sorry to hear about the bad news that your doctor gave you. Since I don’t even know some very basic and crucial pieces of information, such as your age, I don’t have enough clues to directly comment about your specific situation. However, you do bring up a very popular topic, namely that of FSH values, so I will be glad to tell a little story about the significance of FSH.

FSH is the abbreviation for FOLLICLE-STIMULATING HORMONE. It is a substance created from part of the brain called the pituitary gland. In a young, healthy woman, a small wave of FSH released at the beginning of the cycle will get her follicles to start developing for that month. Why only a small amount? Because a young fertile woman’s ovaries are very sensitive. They don’t need much to get them going. After getting just a tiny whiff of FSH, they will start to do their thing. As the follicles do their thing, they start to grow bigger AND they will produce another hormone called estradiol. The news that estradiol is rising goes back up to the pituitary and tells it the good news that "OK, things are moving along just fine. You can ease up on the FSH production. Thank you very much. Talk to you later." The FSH factory supervisor gets this message and tells the production crew to slow down, get some rest and wait until next cycle. In physiological terms, this is known as NEGATIVE FEEDBACK, which is not a bad thing here, unlike the way it is when you’re talking about your EBay rating.

In a woman who is 45, the follicles are few in number and poor in quality, so a different scene plays out. The story begins the same way. At the beginning of the cycle, the pituitary faithfully sends out pulses of FSH and waits for a negative feedback estradiol signal from the follicles that will tell the pituitary to rest again. However, because the follicles are bad, they won’t develop as vigorously, if they even develop at all. So while the follicles struggle to grow and develop in a healthy manner, they will not send out a strong estradiol signal. Meanwhile, the pituitary starts to get a little nervous. "Hmm, it’s been several days and we still haven’t heard back from the follicles. Maybe they need a little more juice." The pituitary then makes the decision to crank up the FSH production and the FSH level goes up a bit. If the follicles eventually respond to this new increase of FSH, then the estradiol signal will arrive and the pituitary crew will breathe a sigh of relief. However, in a worst case scenario (for example if the woman is completely menopausal or if her ovaries have both been surgically removed), then the pituitary is in for a big surprise. The estradiol signal will never come. So what happens is the pituitary will frantically shift into panic mode, going full power and pouring out tons of FSH. The FSH levels will skyrocket!

This second scenario doesn’t just happen in 45 year-olds. It can also happen in some younger women whose ovaries for some reason or other are behaving much older than they really are. This is a condition, known as diminished ovarian reserve or in an extreme situation where the follicles have completely shut down, it is known as PREMATURE OVARIAN FAILURE.

So when your RE checks your FSH level, he is screening to see if your pituitary is overworking itself. If the FSH level is high, it typically means that the follicles are fewer in number and/or lower in quality. The elevated FSH is the INDICATOR of the bad news. It is NOT THE CAUSE of the bad news.

So the concept of trying to lower your FSH, as that herbalist suggests, is downright silly. It won’t solve your problem. It’s actually easy to lower you FSH. Can you guess how? That’s right. If you just give someone a high dose of estrogen through pills, injections or a patch, that will give the pituitary the signal it has been waiting, albeit a fake signal. The pituitary will then ease up on the FSH production. But you haven’t achieved anything helpful. The follicles are still as poor as they always were.

Think of it like this. You are happily driving your car when all of a sudden, a bright red warning light starts flashing telling you that the engine is overheating. Trying to lower the FSH would be like taking a wire cutter and cutting the wire that powers the warning light. The light will go off and you will longer see the bad news. However, that doesn’t change the fact that something is very wrong with the engine.

In general, FSH levels over 10 IU/L are a little bit concerning. If they are over 12 IU/L, it’s definitely a predictor of poor follicle function. And if it’s over 20, it’s almost for sure that something is seriously wrong with the follicles. I will share that I’ve had patients with FSH levels over 20 who eventually got pregnant with their own eggs, but those cases are so rare that they are distinctly memorable. But it’s not entirely without hope.

So now that you understand this, I hope that you don’t let anyone mislead you. As for your Chinese medicine provider not being Asian, you shouldn’t let that alone prejudice you against her. I once took martial arts from a non-Asian master and he’s definitely someone not to mess with.

Click here for episode 1

On the day when patients get their inseminations, many times, we have to face challenges with the scheduling. Aimee had called me the day before the insemination in a panic because she found out that Boyd had to leave town on a short road trip. This was for a baseball tournament for the team he coached. Fortunately, we were able to figure a way around this. So, Aimee showed up Saturday morning with a warm box of donuts for the office. We thanked her with a smile as we received the thoughtful gift. Even though we get more than our share of sweets, we still appreciated the kindness. One hour earlier, her husband, Boyd had dropped off something quite different, a specimen cup with the semen sample that he produced at home. He had gotten up early in the morning and had done his thing. One of my staff was kind enough to come early to open up the office and begin processing the specimen. This allowed Boyd to make it out of town on time. While Amy waited in the waiting room, we finished up processing the sample.

There are several ways to prepare sperm for an intrauterine insemination. Raw sperm can NOT be injected into the uterus safely. All the stories about people doing their own inseminations at home with the turkey baster involve putting the sperm into the vagina and NOT into the uterus. Nature never intended for the chemical substances in sperm (known as prostaglandins) to enter the uterus. Under natural conditions, when the sperm is deposited into the vagina during sex, the liquid, known as the seminal fluid, stays there until it eventually leaks out. It is only the actual sperm cells, the "swimmers", that leave the seminal fluid and make the long journey up into the uterus and tubes. The prostaglandins have the potent power to make smooth muscle contract violently, so if placed into the uterus, the uterus will get very angry and start cramping very hard.

I once got a call from a referring OB/Gyn who got it into his head to try doing inseminations on a patient for the very first time without learning how to do it properly. He had taken the husband’s sperm and drawn it up with a syringe and then injected it all into the uterus without doing any sort of wash. The patient was on the exam table howling with pain in the background as the panicked doctor asked me for help. He wound up giving her pain medications and had her ride it out. The next month, she was referred to us and we helped her get pregnant with a properly washed IUI. It did take a lot of talking on my part to convince her that this time it wouldn’t be painful.

Anyway, the three most common types of sperm prep are the simple wash, the Swim-Up and the Gradient Prep.

The simple wash is just that, a simple wash. The raw sperm is mixed with a special solution which is especially formulated to mimic natural Fallopian tube fluid. The ingredient list of nutrients that nourish the sperm during the insemination process reads like this:

Sodium Chloride
Potassium Chloride
Magnesium Sulfate, Anhydrous
Potassium Phosphate, Monobasic
Calcium Chloride, Anhydrous
Sodium Bicarbonate
HEPES
Glucose
Sodium Pyruvate
Sodium Lactate
Phenol Red
Bovine Albumin

These help provide the proper pH and osmolarity to keep the sperm happy and alive. Then, the mixture is centrifuged at speeds high enough to separate things, but not high enough to damage the sperm. All the sperm will get pulled into the bottom of the test tube, along with all the other solid stuff such as bacteria, dead sperm, white blood cells, red blood cells. All these particles form a visible pellet. The liquid that has all the prostaglandins in it stays at the top. We draw up this unwanted liquid (which has the prostaglandins in it) and discard it. With a simple prep, we take the pellets and dissolve it back in a little bit of fresh media before insemination into the patient. This is intuitively a bad way to do it, because you are not only putting in the good sperm, but you are also putting in the junk. It is safe because the prostaglandins have been removed, but Simple Wash IUI’s have been documented to result in pregnancy rates that are only half as good as when we use the other two prep methods. We almost never do a simple wash. The only times we have ever done it was either because the sperm sample was so poor that any processing would jeopardize losing all of the meager sperm that was present or because the patient is in a real hurry. In the first case (very poor specimen), this almost doesn’t matter, because it’s quite unlikely that patients will get pregnant when the sample is that poor. In the second case (time constraint), simple wash is a very fast method of prepping. For example, one patient wanted to do an insemination right before leaving for a vacation. It was a morning flight, so we had a very tight time window. Well, Murphy’s law dictated that her husband, who had no trouble producing the previous month, wound up having a hard time ejaculating that day. Eventually he succeeded, but two hours after we had originally planned. So we had no time to do anything other than a quick spin and wash.

The sperm prep method that we like the best is the Swim-Up. We start out with a simple wash first, spinning everything down into the pellet. Then we discard all the old liquid that is above the pellet and replace it with fresh media. Then, under controlled temperature and environment, the fresh media is allowed to settle above the pellet for an hour. What will happen is that the good swimmers in the pellet will break free from the pellet and swim up into the media, leaving all the dead sperm and debris behind. After giving it an hour, we will take the liquid only and leave the pellet behind. The liquid should contain clean media in addition to any of the champion swimmers that made it out of the pellet. We then take THIS and spin it down again, making a new pellet that is composed of just the most motile sperm.

The gradient prep is another method that results in a prep that is as good as the Swim-Up. It involves layering a test tube with special media that has been formulated to have different densities. It is specially formulated so that when spun, the good sperm will end up in a very specific segment of the column that can then be isolated and extracted.

Most reputable centers will do either the Swim Up or Gradient preps, although I do know of a very large center that as of the 1990’s, was still doing simple washes. Not suprisingly, there were long periods of time when their IUI pregnancy rates were less than 4%, in comparison to the general expectation of 5-15%.

We called Aimee in from the waiting room and then privately told her that the sperm prep was ready. I then explained to her what to expect for the IUI. Now, bear in mind that different patients react differently to the process, but the routine is fairly similar. It starts out very much like having a Pap smear. The speculum is inserted gently and the cervix is found. Then using a cathether attached to a syringe full of the finished sample, the sperm are injected into the uterus. We have custom tables that can be tilted gently to let gravity aid in the upward flow of the sperm. Some studies have shown that tilting the patient head down after IUI can improve success rates. Note that this is NOT true of regular sex. The difference is that with sex, the sperm is in the vagina, so tilting upside-down only results in the sperm pooling in the top part of the vagina.

In the diagram, point A represents the inside of the vagina. This is where sperm is deposited during sex. Almost of all it is will end up leaking downwards eventually. The cervix is just above point A and is the opening to the cervical canal that leads into the uterus. During an IUI, the sperm is deposited very deeply at point C. The triangle surrounding point C represents the uterine cavity. The top corners of the triangle are where the tubal openings reside. So when you do an IUI and then lie upside down, the sperm flow easily into the tubes. If you lie upside down after sex, the sperm pool in the upper regions of the vagina represented by point B. In medical terms, these areas are known as the vaginal fornices.

I completed the IUI, which was completely painless, according to Aimee. I then did another ultrasound and saw the following:

Right ovary: (30×21) (24×19) (18×18) (16×15) (14×14)
Left ovary: (22×18) (21×19) (20×20) (14×12)
Lining: 12mm triple layer with the IUI fluid seen distending the cavity.
Minimal free fluid seen.

Imagine seeing a room with one balloon in it. Pretend you go in and measure it to be 15 inches. You come back to the room two days later and see one balloon which measures 18 inches. Since you only have one balloon, it’s pretty easy to infer that this is the same balloon, but it has been inflated a little bit more. Now imagine a room full of red balloons of many different sizes. You can measure the size of each one and write it down, but there are also a bunch of tiny barely inflated baby-size balloons that are so small that they are not worth measuring. Then you come back two days later and see different balloons of many different sizes. Again, you measure the sizes of these. The problem is this. You have no way of matching the balloons seen on the first day to the ones seen on the second day. So, if one of the balloons from day one pops and is gone, you have no way to accurately track it, because you still see a bunch of balloons which might be the same one from two days before OR it might be one of the little unmeasured ones from two days before, but which has now grown big.

So, in Aimee’s case, I could guess that the huge 30×21 today was the 24×14 from Thursday. I’d probably be right, but I can’t be 100% sure. It’s very possible that the 24×14 from Thursday has popped! And the 30×21 today is actually the 16×14 from Thursday. I think you get the point. It appears that none of Aimee’s follicles have ovulated. What we are seeing today are the large ones from Thursday after they’ve all grown a bit more. We even see some extra ones, which most likely were the small, unmeasured follicles from before. Of course, if we looked today and saw that everything was gone, we could be confident that all the follicles had ovulated. As it stands, I told Aimee that most likely all of her follicles were still not ovulated. Sure, it’s possible that maybe one had ovulated, but we’re sure that most of them have not.

The fact that there was not a lot of free fluid seen supports the conclusion that nothing had ovulated. Imagine that these balloons were actually water balloons. If on the first day you see a bunch of balloons and on the second day you also see a bunch of balloons, what could you conclude if you also saw a whole lot of water on the floor? You can infer that some of the water balloons must have burst and relased the water onto the floor. But since Aimee had minimal fluid, this was probably just the small amount of regular physiological fluid that all women have in their pelvis and NOT any extra water from a popped follicle.

So what do we do now?

One choice would be to bring Aimee back tomorrow and do a second IUI. This could boost her odds of getting pregnant. BUT, we are already a little nervous at this point. Even though none of these follicles had ovulated, it is very likely that they will do so in a few more hours. And since there were so many of them and since this was her first cycle, we actually decided to be grateful that they hadn’t ovulated. We agreed not to do a second IUI tomorrow. Instead, I brought Aimee back in two days to do another ultrasound. This time, all the large follicles were gone! There were only a lot of medium sized ones 13mm and under. Also, as you can guess, there was a ton of free fluid seen. Aimee had ovulated.

Now bear in mind, had this been Aimee’s third insemination attempt, we might have gone aggressive and proceeded with a second IUI, but again, we always customize our decisions based on the specific circumstances and we shouldn’t treat patients with a cookie-cutter formula.

Aimee was started on progesterone supplemention. And the suspenseful waiting period began. We will return 10 days later when Aimee comes back for her pregnancy test.

Click here for episode 7

I’ve heard of an orthopedic surgeon naming his dog Bones. I’ve heard of an ophthalmologist not naming his dog Spot, but instead naming it Macula, which is a "spot" on the retina.

One of my dogs is named Ixie, after ICSI, the procedure by which a sperm is injected into the egg as part of IVF.

Here is a video of my yorkie, Ixie, fighting with Brandy, my german shepherd.

Click here for episode 1

Despite her usual cheery nature, Aimee’s smile and chatter on the day of her ultrasound hid her underlying nervousness. This was the first monitoring visit after she started her stimulation medications. And although she went into this, optimistic about her chances of a good response, she had been properly warned about potential unpredictable outcomes as well.

Just as is the case with the majority of fertility patients, she was now quite accustomed to having the ultrasound probe placed internally. What was very strange and stressful the first time, was now second nature.

This is what we found:
Right ovary: (19×13) (12×12) (12×12) (11×11)
Left ovary: (14×14) (13×12) (8×7)
Lining: 8mm triple-layer

After four days of stimulation, this is a response that is above average, but certainly not out of the ordinary. The dominant follicle is the large one on the right. The large one on the left is not bad either. It is extremely likely that both will go on to mature in a few days. The rest of them may or may not, and herein lies the dilemma. If we continue at the same dosage, she may end up maturing all seven, which would make for a somewhat risky first cycle. If we drop the dosage too much, we might end up losing most or even losing all of them.

Again, the situation was explained to Aimee and just as I expected, she opted to proceed on the aggressive side. We continued her on 150 IU and saw her back in three days.

This is what we found:
Right ovary: (24×14) (17×16) (16×14) (13×13) (12×12)
Left ovary: (20×14) (19×15) (14×12) (11×10)
Lining: 9mm triple layer.

In general, follicles that are over 15mm in size have a reasonable chance of being mature. The optimal size that I personally like is close to 17-19mm. Different RE’s may have different preferences based on their own experiences and based on their own ultrasound measurement tendencies. For example, the same patient could experimentally get back-to-back ultrasounds from two different doctors and end up with measurements that differ by 2mm. The optimal follicle size may also differ from patient to patient. Some patients get pregnant with IUI and then 2 years later, get pregnant with IUI again. If they took three cycles each time to conceive, we have six cycles to look back on, 2 successful ones and 4 unsuccessful ones. If we see that the follicles were generally larger, like around 22mm in the successful cycles, then we might infer loosely that this patient tends to do better when her follicles are triggered at a size that is larger than average.

Because this was the first cycle ever for Aimee, we didn’t have the luxury of past information and have to make decisions based on our best judgment. She clearly has five follicles (highlighted in bold above) which are in the mature range. We might even be generous and call the 14×12 a potential as well, but that might be stretching things a bit. So with five mature follicles estimating that each has a 10-20% chance of becoming a baby, the chance of pregnancy is quite good, the risk of twins is moderately high and the risk of triplets is low, but possible. Aimee phoned Boyd and got his confirmation that they wished to proceed. Had this been a couple that told me that they really didn’t want twins, I would have counseled them to cancel this cycle and restart next month at a lower dose. But based on their wishes, Aimee was instructed on how to take an injection of hCG at 5PM later that afternoon.

Injecting hCG is like lighting a long fuse on a firecracker. Once you inject it, the countdown begins. In general, about 36-40 hours after the injection, the follicles will release the eggs in a process known as ovulation. This is an estimate only. Some patients might release them earlier and some might release them later. And as you can guess by now, the exact same patient might ovulate in different time frames from month to month.

Since this was on a Thursday, Aimee will come back in two days on Saturday for her first insemination. She was given a specimen cup to take home.

Click here for episode 6

I found your website from someone who posted about it on the bulleting boards and I can’t stop reading it!
I took Clomid once and it made me ovulate but not get pregnant. My doctors says that it was successful because before Clomid I didn’t even ovulate. She told me that the chance of getting pregnant each time I ovulate is 20%. Why is it only 20% and what can I do to make it 100%? Does that make sense?

ROBERTA, Alabama

Dear Roberta,

Clomid works its very best when it is given to women who normally do not ovulate on their own, but then end up ovulating while on the Clomid. It is not as helpful when given to women who already ovulate on their own. Remember that the average woman with normal fertility does not always get pregnant every single month. In fact, the monthly odds of getting pregnant are about 20-25%. If you are a woman who does NOT ovulate on your own, but is fortunate enough to respond to Clomid, then it is an approximate, but fair estimate that the Clomid now has converted you from having zero chance of pregnancy that month (had you not ovulated) to having a normal chance, provided that the sperm and tubes do not contribute any problems, and that normal chance is about 20-25% in most cases.

The question of why normal fertile women or women who respond to Clomid do not have a 100% chance of conceiving with each ovulation is a good one.

One way to look at it is to realize that few things in life are 100%. This is not purely a philosophical answer, but rather one based on reality. If you have normal vision, normal hand-eye coordination and normal arm strength, then you have the capability to wad up a piece of paper and throw it into the wastepaper basket across the room. You can probably succeed on a fairly regular basis, tossing it in every few tries, but you can NOT do it 100% of the time.

Now let’s consider what has to happen in order to get a successful conception. First of all, you must have ovulation. But even assuming that you do ovulate, the egg, which explodes out of the ovary into the general area of the Fallopian tube now has to be lucky enough to be scooped up by the tube. This does not always happen. On my old blog, I posted a description of how egg pickup by the tubes can be compared to the actions of a swimming pool sweeper. So, if the egg is successfully picked up, then it may or may not encounter a sperm. Even if sex occurs within the correct window period, the egg is microscopic and the few sperm that reach its general neighborhood may still not collide with it. Even if the sperm does hit the egg, it may not have the strength left, so to speak, to successfully fertilize it. And even if the sperm and egg do result in a fertilized embryo, that particular sperm or that particular egg may not have perfectly normal DNA. Without perfectly normal DNA, the embryo will stop growing and fail to implant. With all that can go wrong, it is a wonder that pregnancy occurs naturally at all, but it does. And it does so about 20-25% of the time.

Your doctor is on the right track. However, if you still don’t get pregnant after ovulating several times on the Clomid, then it’s time to look at stronger ways of getting the job done, such as IUI or even IVF. Remember that even though something is only 20% and not 100%, if it’s done enough times it will eventually succeed. Thank you for your question. 

Hello!  Your website is great.  It is so informative and helpful.  i was
wondering if you could give me some insight……

KIM, North Carolina

Dear Kim,

Let’s look at the big picture. It has been nine months since you went off the OCPs. While we would love it if you had regular ovulatory cycles, the harsh fact, based on the detailed information that you provide about your cycles,  is that you don’t , at least not on a consistent basis.  Your RE has chosen Clomid as the first line treatment for you. Let’s assume that you have had your thyroid and prolactin checked already. The goal is straighforward at present. GIVE CLOMID. MONITOR to see if ovulation occurs.

I have to admit I don’t quite understand what the 45 and 55 mean. I can’t imagine that your RE counted 45 and 55 small follicles in your ovaries. I’m wondering if you meant that he saw a very large 45mm follicle. That wouldn’t quite make sense either, because if you had 45mm and 55mm follicles, your E2 (estradiol) would be expected to be higher than 69 pg/ml. In any case, to answer your specific questions, some RE’s will start patients on Clomid and if there is no response, they will add injectables. I have never tried to give a higher dose of Clomid within the same cycle. It doesn’t mean that it won’t work, but time will tell. Again, it’s a good thing that you are being monitored so we will at least know what’s going on.

As for what the chances are that it will make you ovulate, at this point, the decision has already been made, so we should just be patient and see what the monitoring shows. After something is done and committed, I try to minimize thinking about what the chances are, but instead focus on carefully tracking what DOES happen. Having said that, I’ll venture a guess that someone who does nothing on Clomid 100mg, will probably not do much on Clomid 150mg givin within the same cycle.

As for whether or not you have PCOS, the smartest things would be to get more information before answering that. There are several questions I need to know before venturing an opinion. I will agree with you that you being so slender would make it atypical for you to have it. BUT there are exceptions. If you haven’t already read this story, you might find it interesting.

So what if Clomid doesn’t work? Your RE knows more about you than I do, so I would defer to him/her. My general approach is to start with some investigation into the causes of the poor ovulation. This starts out with better understading the patients lifestyle (nutrition, stress level, exercise, overall wellness). This might then include checking TSH, prolactin and insulin resistance. Another factor that influences the choice of letrozole vs injectables is the patient’s preference. Is this someone who begs to avoid needles if at all possible and wants to go as conservatively as she can? Or is this someone who is determined to get pregnant as quickly as possible? Most of my patients go on to injectables rather than try letrozole.

Thanks for the question. Feel free to leave a comment with an update on your story. Good luck!

Click here for episode 1

Even before starting their first IUI cycle, Aimee encountered disappointment. She has a cyst. She had called with the first day of her period and eagerly came in for the baseline ultrasound before starting her cycle. This ultrasound is important because prior to stimulating the ovaries, it is important to establish a baseline and confirm that the ovaries are in the early resting phase. Just as prior to a race, it is important to make sure all the participants are at the starting line without any who are already half way around the track, so it is important to make sure that no follicles are already developed at the time we are starting the cycle. I know that the terms, FOLLICLE, CYST and EGG are often used in a confusing interchanged manner. For clarification regarding these terms, please refer to this previous post.

So, on day 3 of her cycle, there was a cyst seen on ultrasound in her right ovary. We were hoping to see nothing or at the very least, only the smallest of cysts. This one was 15×13mm and was above the cutoff for what I judged to be optimal for Aimee this month. Now, medical care is best conducted with flexibility and individualization, not with a cookie-cutter approach. So while, I would still say that something this big prevents us from starting the cycle, under certain circumstances, I might have permitted her to proceed. For example, if this was her last chance at treatment before her husband was being deployed to Iraq for three years, then we might reconsider. But since we were not pressed for time, I told her again that we would be wise to wait a month when conditions are more perfect. This would at least give them another month to try on their own. After overcoming the initial disappointment, Aimee agreed to call next month with her period.

Not being able to do a cycle because of the presence of a cyst is something that happens in about 5-15% of initial baseline ultrasounds, so having cysts is not unusual. Often patients ask why they have a cyst. One answer is that the ovaries are just "out-of-sync" that month. The ovaries are counted on to grow follicles and release eggs with perfect timing month after month. For most women, most of the time, they do. However, just as a professional shortstop in baseball will make an occasional error, so do the ovaries. In patients with infertily problems, these errors might be more frequent.

When Aimee called with her NEXT period, it turned out that she and Boyd had Boyd’s cousin’s wedding to attend on the East Coast and the dates for it fell near the time when she would be ovulating, so we skipped yet another month, leaving them to try on their own once again.

Aimee called the following month. This time, there were no cysts and we finally were able to start her first treatment cycle.

Let’s review what’s going on. Today is day #3 of Aimee’s cycle. She is just finishing up the final portion of her menstrual flow. If we completely left her alone with no medical help this month, she would be predicted to grow ONE follicle. This would give her one chance to get pregnant. This is how it has always been for the past few years. Because this has not been working, we now have made the choice to help this couple "cheat" to get the odds more in their favor. One way to do this is to get more than just one egg.

In a previous post, I described how the odds of getting pregnant can be similar to the odds of drawing a winning card in poker. Aimee and Boyd’s deck of cards is clearly not normal. Instead of having a 25% chance of winning a baby each month, as a fertile couple would, they might only ahve a 2-3% chance. By doing an IUI and sending Boyd’s purified supercharged sperm sample deep into Aimee’s uterus, we hope to be boosting these odds to maybe 5-15% per egg. Not only that, we are hoping to get more than one egg. So the rules of the game change in their favor now. Instead of drawing one card out of a deck that has 2-3% winners, we hope to get them the opportunity to draw 3-4 cards from a deck that has 5-15% winners.

As we plan for this cycle, we have to decide on a starting dosage of stimulation medications. This is a very tricky task to do in a first-timer. It is impossible to predict with 100% accuracy how someone will respond to injectable medications on their first cycle. I can give the same dose to 4 different women. One could make no eggs. One could make two. One could make six. And the last one could make 20. However, I am not just wildly guessing. I do have some information, such as their age, their diagnosis and their body weight. If she overstimulates, we will have to cancel or subject ourselves to the risk of triplets. If she understimulates, then her chances of getting pregnant are not as good.

Imagine you are a bartender at a party, entrusted to making sure everyone is happy and slightly buzzed, but not excessively inebriated. If your guest does not feel a thing at all, then you fail. If your guest is so drunk that they are singing at the top of their lungs and knocking over furniture, then you also fail. So the first guest comes up to the bar. He is a boisterous 300-pound college football player and he’s wearing a Budweiser hat and a T-shirt that boasts "I only drink on days that end in Y". After careful consideration, you decide to serve him an extra large pitcher of beer and a shot of whiskey to start off with. The next guest is a young 104-pound woman whom you recall works as a librarian and teaches Sunday School. She tells you that she gets dizzy from taking strong cough medicine. You pour her a quarter glass of Chardonnay. As you can imagine, you probably can do a pretty good job of keeping everyone happy based on your clinical estimates of how much alcohol they can tolerate. However, in a party with 100 guests, there are bound to be some guests for whom you overestimate and some for whom you understimate. If this becomes a regular job for you that you will do week after week for the same crowd of guests, then you can keep records on each patron for whom you misjudge and do a much better job readjusting next time. However, without past performance as a guide, you will often misjudge the proper dosage during the guests’ first encounters.

So anyway, I decided to start Aimee on a daily dosage of 150 IU (International Units) of injectable gonadotropin. I could have chosen different brands of medication, such as Bravelle, Gonal-F or Follistim. For Aimee, there was no glaring differences between the three of these as far as the pharmocological properties. There are differences with respect to price and convenience of administration. I chose to go with a drug that is a little different from these — Menopur. The difference is that the first three are composed of nearly pure FSH and no LH. Menopur, on the other hand, contains a signficant amount of LH in addition to FSH. I could have just as easily chosen pure FSH for Aimee, but the Menopur is also a little less expensive for her.

After the baseline ultrasound was done, one of my nursing staff sat down with Aimee and Boyd and taught them how to do their own injections. After four days of injections they were scheduled to come back for their first follicle check. Bearing in mind that we never completely know what to expect, we are prepared for anything. We won’t be surprised to to see no follicles, three follicles or even eight follicles.

Check here for episode 5

I went for a one-day trip this weekend to catch part of the 2008 meeting of the Pacific Coast Reproductive Society. Those of us who do IVF have many meetings we can attend where we can exchange ideas with each other. For, example, this year, ESHRE is meeting in Barcelona. I’ve never been to ESHRE, but I’ve been to Spain and I sure would like to go back. The other big academic meeting is the ASRM meeting, which I will almost for sure be attending, as its location this year, San Francisco, is relatively close. These two meetings consist primarily of people presenting their research. There is another annual meeting that is more like an IVF review course, and that is held each year in Santa Barbara, sponsored by UCLA, my alma mater (well my infertility fellowship alma mater, anyway). Go Bruins!

PCRS is a much smaller meeting, but unique in how casual and non-pretentious it is. In the registration materials, there was an actual statement to the effect that “anybody who shows up in a suit and tie will be asked to go back to their room and change into something more fun”. The presidency of the society, which changes yearly, is a thankless position undertaken by an RE who while still attending to the daily duties of his/her own practice, must somehow manage to find an average of five hours a week to deal with the administrative matters of the position, most notably organizing this annual meeting.

It just so happens that this year’s PCRS president is a friend of mine and someone whom I greatly admire. We go way back, to the time when we were OB/Gyn interns together. We finished four years of grueling, but fun residency together before we went our separate ways to different RE fellowship programs. He then went on to build a small empire with two IVF centers in different states ( One in Reno, Nevada. One in Boise, Idaho ). That in itself is quite a feat, but doing so while still maintaining a pristine reputation as one of the nicest, easy-going guys around is not easy. He has also been happily married for close to twenty years, with so many kids that I’ve lost count. That is a rarity among RE’s, who ironically, for being doctors in such a family-oriented field, in general aren’t always known to have the most stable family lives themselves.

I also got to spend time at the meeting with another doctor whose story is pretty interesting. We first became friends when I had started my IVF practice for a few years and he was just about to start one himself. He likes to thank me for my helping in his getting set up, but I didn’t really do much. At the time, he was already an established general OB/Gyn and professor in Hawaii who was well known for his laparoscopy skills. He was with a group of doctors who had been doing IVF together for a long time. Like some of the other IVF doctors in his group, he was succefully getting IVF pregnancies without ever having done a formal RE Fellowship. In fact, his group was pretty much THE only IVF program in Hawaii at the time. (Hawaii is a cozy place). I still don’t know what kind of amazing ambition bug bit him, but he decided to go back and hit the schoolbooks to become a certified embryology lab director. For those of you who don’t know the difference, if RE’s are like pilots, then embryologists are like the engineers who build the planes we fly. There are a few amazing RE’s who are skilled at both. Imagine a pilot taking the time to go back and study engineering so that he can build a better plane and then to go on and fly that plane himself. So here’s a guy who did just that, and since then, he has branched out and built a new lab that because of the success rates, is now recognized by the “locals” in Hawaii, as the best IVF program, and over there, pretty much everybody is a local.

During the meeting, besides the scientific talks, I also heard a different type of lecture, one about practice management. A doctor from the East Coast spoke about being the single RE in a program that does an astounding 1000 IVF cycles per year! That is just insane to imagine. Logic would dictate that patients would not like it very much when they don’t get to see the doctor for more than a few seconds, but this guy has his PA’s, NP’s, RN’s and other staff trained so well that patients love it! He manages his 88 employees with principles learned from Ritz-Carlton, such as regular staff pep-sessions and daily motivational emails. Along with five-star treatment, patients enjoy a relaxed spa-like atmosphere complete with facials, foot massages and comfortable Pottery Barn furniture. This is a doctor whose employee management skills put many CEO’s with MBA’s to shame. I don’t know anything specific about the medical care there and I would guess it’s good, but I was amazed that such a thriving practice could be built primarly around customer service and it’s at least made me think a little about some new ideas for my own practice. However, I still don’t think we’ll be offering massages any time soon.

The medical talks I attended got me up to speed on the latest in PGD, embryology topics and some interesting controversial issues regarding the integration of IVF with Traditional Chinese Medicine and acupuncture. I hope to write more on this in future posts.

Palm Springs was relaxing, yet productive. I met some great people, learned a little medicine, touched bases with old friends and got caught up on the latest gossip of who is now working whom in the musical-chairs world of IVF practices. All in all, not bad for one day.

Click here for episode 1

RECAP: Aimee and Boyd have been infertile for three years. After completing some basic testing, we are ready to discuss treatment options.

When considering what treatments to do, what are some of the things that patients consider?
In my experience, patients care primarily about cost and effectiveness. Some other concerns include how much time is consumed, how much risk is involved and how much inconvenience, or even outright suffering is involved?

What choices do Aimee and Boyd have?

• NO TREATMENT: Starting with the simplest, let’s not forget that one choice is to do nothing, and just continue trying on their own. Given the facts of the case that we know so far, I would estimate that their chance of getting pregnant on their own is about 2% per month. It’s not entirely insignificant. If only we knew for sure that their monthly odds were truly 2% and would remain at 2%, then we could confidently tell them that they have about a 38% chance of getting pregnant naturally in the next 2 years. One problem is that if we guess wrong and they really have a zero % chance, then those two precious reproductive years are completely wasted. For many couples who choose not to see a doctor, this is what they choose to do. Some of them just keep trying, month after month (as long as they have the patience) and in two years, about a third of them will finally get pregnant. The other two thirds will then find themselves in a worse situation than they were in two years ago, because they will have aged.
• CLOMID ONLY: If a woman is clearly not ovulating on her own, and if Clomid works to get her to ovulate, then this becomes a great strategy with little cost. Clomid is very helpful in this setting. However, if someone is already ovulating, then Clomid is LESS helpful and in some cases, not helpful at all. There are certain scenarios in which one could argue that Clomid is harmful to ones fertility by its adverse effects on the cervical mucus and on the lining. So, two factors make this an unwise choice for Aimee and Boyd. First of all, we believe that she already ovulates on her own. She has regular periods and positive ovulation testing, so she is far from the ideal candidate for just purely taking Clomid. The second reason this would be a poor choice is that they have already tried it. I’m more enthusiastic about something that has not been tried before than I am about something that has been tried before and that has failed, especially six times.
• INJECTABLES ONLY: Taking injectable ovulation medications instead of Clomid is certainly an option, but I would suggest that they do it in conjunction with intrauterine insemination (IUI)
• INJECTABLES + IUI: This is my recommendation for this couple. We would give Aimee medications to make a greater number of eggs and she would have a higher quality chance of conceiving with each egg because of the overall better hormonal environment. On the perfect day, or sometimes at the perfect HOUR, we would introduce the sperm deep into the uterus with a relatively painless procedure. This greatly increases the number of sperm that have access to where the eggs should be
• IN-VITRO FERTILIZATION: There are definitely some aggressive RE’s who would push IVF on this couple. I have been the second-opinion consultant on many such cases. I will concede the fact that IVF stands to produce a higher chance of instant conception as compared to three cycles of IUI, but in general, it’s important to let the patients make the choice, after properly counseling them of course.

After listing the different options, I asked them if they had any questions. They had several, so we broke it down to a comparison of the two best choices, Injectables+IUI vs IVF.

• COST:
  An IVF cycle runs about $11K to $15K for everything. This include the medications, the anesthesia, the doctor’s fees, the blood tests, the embryology fees. That fee usually includes features such as ICSI and assisted hatching.
  An IUI cycle runs about $1K to $3K.
  Both of these can be less expensive or even free if a patient has insurance coverage for them, but most of my patients here in California don’t have any coverage.
• EFFICACY:
  I estimated, given our past track record, that they would have a 40-60% chance of pregnancy with a single cycle of IVF plus all the subsequent frozen embryo transfers that we could do until we ran out of embryos.
  A single IUI cycle has a 5-25% chance of success, but in general, they would have about a 40-50% cumulative chance of success with three cycles. Now, of course, we never have to commit to three cycles. We can just make the decision to do one cycle and hopefully, it will be the only cycle we need to do. However, if it fails, we still have the choice at that time to decide to move on to IVF rather than to do another 1-2 IUI cycles. Because they have never failed (or even tried) an IUI cycle before, their odds are at their best. Each time someone fails at something the predicted odds of success of the exact same treatment end up less.
  For example, imagine you know 100 people who are about to take their driver’s license exam. And you know that the passing rate is 90%. So if your friend is about to take the test and asks you what you think the odds are that he will pass, you might guess 90%. But if he fails the test and goes back to take it again, you might think his odds to be less than 90%. But what if he is allowed to take the test 15 times and he fails it every time. Then when he is contemplating taking attempt #16, you would certainly not estimate his odds of success at 90%. This is an important principle to consider in infertiltiy treatment. Had Aimee not done Clomid with her OB and had she wanted to do Clomid for the first time, I would have been fine with trying it at least once. But since she had already tried and failed six times, I told them that trying a 7th cycle of Clomid was a bad idea.
• RISK:
  The two biggest risks to consider are hyperstimulation and multiple gestation (twins or more). With IVF, we have much more control, because we take out all the eggs, make them into embryos and then CHOOSE how many to put back. With IUI, it’s totally uncontrolled. If a woman ovulates 20 eggs, we have to either cancel the cycle entirely (which is what we would do) or risk exposing all 20 eggs to a chance of conceiving. So in general, the risk of triplets would be higher with IUI. With regards to hyperstimulation, in an IUI, I would give a lower dose of medicine and that would minimize the risk. With IVF, we want to be more aggressive with the stimulation, so with higher doses, there comes a higher risk of Hyperstimulation Syndrome, a condition where the ovaries swell up with fluid leading to a lot of pain and potential serious medical issues. The overall chance of serious hyperstimulation is below 1%, but many patients may have a milder form.
• TIME COMMITMENT
  With an IUI cycle, Aimee could expect to come for about 4-6 office visits for ultrasound monitoring and for the actual insemination. This would be over a course of two weeks.
  IVF, was a little more extensive, but not much more. Over the course of 4-6 weeks, there would still be about 5-8 office visits, but there would also be the big day of the egg retrieval followed a few days later by the transfer and a day of bedrest.

Armed with all this information, Aimee and Boyd confidently left the office with the firm decision to do a cycle of IUI with injectable medications. Her instructions were to call us with the first day of her period. Aimee shared that she was going to be in a great mood at work this week, because she would be filled with excitement about her upcoming treatment. I told her that a good attitude was definitely helpful in all this.

Click here for episode 4