Click here for episode 1

Summary: Caroline is now pregnant after doing an aggressive IUI cycle in which she had six mature-sized follicles. It was roughly estimated that she had close to a 40-50% chance of getting pregnant and close to a 1-2% chance of triplets. She was clearly informed and she chose to take the risk. Now that she is pregnant, we are not out of the woods yet. There is always the risk of miscarriage, ectopic or multiple gestation and the only way to detect this early is with close monitoring of the pregnancy. We talked at her first ultrasound.

ME: Congratulations! You know, you were right. You didn’t need an HSG after all.
CAROLINE: I told you about my dream, right? But before we talk, Darryl and I just want to thank you and your staff. We’re just in awe!
ME: You’re very welcome. Regarding your dream, yes, you told me that you knew your tubes were open because of the dream, but forgive me for not writing that into your medical chart. Haha. Anyway, I know that you and I haven’t spoken in person since you got the good news, so today, you can ask questions after we do the ultrasound. My staff have been keeping me up to date. I see that your beta-hCG values have been rising very strongly. That is certainly good news. And how have you been feeling?
CAROLINE: Honestly, I don’t feel anything different. Maybe a bit tired, but I was expecting bad morning sickness. Sometimes, I ask myself if I’m really pregnant.
ME: No, don’t worry. Most women do have some symptoms, but  there are some who have perfectly healthy pregnancies and yet, have no real symptoms. Today, you are 5 weeks and 5 days so we’re going to do your first ultrasound to count how many sacs you have. Are you nervous?
CAROLINE: No, not in a bad way. But I’ve very curious to see what we have.
ME: OK, let’s see then.

ULTRASOUND FINDINGS: There are two sacs seen! One measures 7mm in size and the other 5mm. They are both in the perfect location in the center of the uterine cavity. The ovaries are somewhat enlarged and measure about 5 cm each with multiple cysts seen. There are some faint yolk sacs in each gestational sac. No fetal heart motion is seen.

ME: Well, I see two sacs.
CAROLINE: That’s it? Only two?
ME: Only?
CAROLINE: I mean, whew. We were prepared for news of more, just in case, we braced ourselves for the possibility.
ME: Well, right now, there are two sacs. Now bear in mind that this doesn’t necessarily mean that both will survive. I try not to be negative, but I want to tell you the possibilities. Most likely, next visit, we will see two heartbeats, but anything is possible, including seeing no heartbeats. It’s sometimes even possible that a third sac will show up next week, although today I searched pretty thoroughly and I don’t see any evidence of a third sac. Sometimes, we see a small fluid pocket and have to wonder if that’s a small sac, but in your case, I don’t see anything other than those two big ones.
CAROLINE: Darryl will be relieved. And he is going to be so excited that we’re having twins.
ME: Well, remember, I caution you about telling too many people at this early stage. In fact, I wouldn’t necessarily tell casual friends about your pregnancy. You may tell your closest family members, but a lot could still happen at this point. And especially don’t tell them that you have twins yet. OK?
CAROLINE: (smiling with tears) I am just speechless.
ME: Do you have any questions?

I gave Caroline 10 minutes to call Darryl and returned to field her questions. Most of them were routine, concerning her progesterone, her activity limits and her dietary recommendations. She was on progesterone supplementation and was continued on her metformin. She was on prenatal vitamins and fish oil. I printed out three copies of the ultrasound pictures - one for the chart and two for Caroline. She was scheduled to come back in about a week.

Check here for episode 12 when published.

Click here for episode 1

I knew something was up. Even as I sat in my private office, going over patient charts and answering email, I could hear happy shouts coming from the outside my door. I looked at my schedule. We had just finished the last ultrasound of the morning and I was pretty sure the screams of joy were coming from my staff in response to the pregnancy tests that just rolled off the machine. The schedule showed six blood draws for pregnancy tests that day, four first time beta-hCG’s and two repeats. I sent an instant message to my staff and asked for the results. They replied quickly with each of the six results. Four of them were followed by a and the other two were followed by a . I saw that Caroline’s was one of the happy ones! Now there would be friendly negotiation between my staff to see who got to call the patients with the good news and who had to call the ones with the bad news.

Caroline’s beta-hCG value was 111 IU/L. This was twelve days after her IUI. For the first time ever in her life, she was pregnant. It has become our office policy that my staff are always the first to break the news, good or bad, to the patients. Within that same day or the next, I usually call back the negatives. I rarely call back the positives, even though that’s always a fun thing to do. Instead, I put my time to better use, consoling the negatives and preparing the detailed plans for the next step in their treatment. As per routine, Caroline was scheduled for a repeat beta-hCG in two days.

This is the standard way of doing things in our office after a positive pregnancy test. First we run a progesterone (P4) test for all the patients with positive pregnancy tests. Caroline’s P4 was 40 ng/ml, which was fine. She was already on progesterone supplementation via Crinone 8% gel, so she was kept on the same dose. If the value would have been low, we would have been alerted that this might be an abnormal pregnancy (miscarriage or ectopic) and we would watch her more carefully. We would also consider increasing her progesterone.

The next thing we always do is to repeat the hCG, usually two days later. In a healthy pregnancy, we usually expect the value to rise by at least 70%. If the rise is slower than that, we have to suspect a miscarriage or even worse, a tubal pregnancy. If the value drops instead of rises, then that’s even more suspicious for an impending miscarriage. Pregnancy losses happen in about 1 out of 6 pregnancies, whether they arise spontaneously and naturally, without a doctor’s help or whether they are with IUI or IVF. So at this point, Caroline still had a possibility of losing the pregnancy, just as anybody else would.

Two days later, we celebrated her repeat beta-hCG. It was a 378. It had more than doubled! This was excellent news. However, while we love it when the rise is very good, in Caroline’s case, in the back of my mind, I started to have a nagging concern about just how many babies she could have.

Before we go on, let’s review the standard terminology regarding how far along someone’s pregnancy is. As you may well know, the standard pregnancy lasts 40 weeks. Very few women deliver exactly on their due date. Most of the time, anyone delivering after 36 weeks has a pretty unremarkable outcome. Even though the baby is considered as having delivered earlier than their due date, they usually go home with the mother when they have made it that far and if they have no complications. When pregnancies go beyond 41 weeks, the OB’s get nervous and often induce, so as to lower the risk of something bad happening to the baby, so you rarely see pregnancies go beyond 42 weeks. The tricky part, which often gets patients confused is that we start counting the pregnancy dating by calling the day of ovulation as TWO WEEKS PREGNANT. Technically, the patient isn’t pregnant yet, because we won’t know the outcome until about two weeks after ovulation. However, at two weeks after ovulation, we refer to it as FOUR WEEKS PREGNANT. So, in Caroline’s case, even though it’s only two weeks after ovulation (after IUI), she is considered to be four weeks pregnant already.

We continued to check her beta-hCG levels. The next one was done four days after the 378 value and it came back at 1677. Again, an excellent rise because it was more than doubling every two days. For those of you who love math, I’ll try to explain the way we calculate beta-hCG rises. Those of you who get bored by semi-complex mathematics are free to skip the next section. I am proud to say that everyone in my office can now do this calculation in their sleep, from the newest medical assistant to my office manager. OK, I’m not sure if my billing manager can do this, but I wouldn’t be surprised if she could.

In order to calculate the rise in hCG from two consecutive values we need to know three things. We need to know the first value, the second value and the number of days in between the two. We always speak of the rise in terms of how many % it rose per TWO-DAY period. The reason we use this terminology is because we know for a fact that beta values that rise more than 70% or so every two days are a pretty good indicator of a healthy pregnancy.

Back to the calculations. This is how we get the rise value. We start with the later value, which of course should be higher than the earlier value and we divide it by the earlier value. This gives us the absolute rise. Let’s call this R. Next, we take the interval between the two tests (in number of days) and divide by two. This essentially tells us how many two-day-intervals are between the two values. Let’s call this value T. Then we pull up the calculator that comes with our Microsoft Windows or Vista. If you hit the VIEW button on the toolbar, it should give you a choice between STANDARD and SCIENTIFIC. You will want to choose the Scientific Calculator. We then enter the value we got as R, check off the box that says INV, hit the button that says x^y and then enter the value that we got as T. This will spit out a final answer like 1.29 or 1.86 or 2.89. If this final answer is greater than 2, we relax, because it tells us that the values are more than doubling. If the answer is something like 1.86, it tells us that there is a 86% rise every two days, which is fine. If we get an answer like 1.29, then that tells us that the rise is only 29% every two days and that’s very concerning and not good at all.

So let’s calculate Caroline’s rise for the last four days. We take R = 1677 / 378 = 4.44. We then calculate T by figuring that there were four days between the two tests and dividing by 2. So T = 4 / 2 = 2. We then enter 4.44    INV    x^y   2   =   2.10, which tells us that Caroline’s values are more than doubling every two days. Hurray!

Recently, I’ve been tutoring a few of my friends who are studying for the MCAT, so my mind is very much in calculation-teaching mode. For those of you who were bored silly with all these calculations, let’s just go back and celebrate that Caroline and Darryl are ecstatic at this point and looking forward to their first prenatal ultrasound, what we traditionally consider to be the "let’s count how many babies we have" ultrasound.

Click here for episode 11

June’s story has spilled over a bit into July

Click here for episode 1

Caroline is set to start her fifth attempted IUI cycle. Three previous cycles failed to result in pregnancy and one previous attempt was cancelled, never making it to the ovulation stage. My recommendation was to do an HSG to make sure her tubes are patent and her uterus was clean, because it would be a shame to have her keep making eggs if her tubes are blocked. Somehow, she felt confident her tubes were OK. Caroline strongly believed that the best thing for her is to do is to get some really good egg production, if possible.

As usual, we started her cycle by doing a baseline ultrasound on day 3. She had called us the day before to report that her period had started. Both her ovaries were quiet, meaning there were no cysts nor any early-growing follicles.

We had a discussion. I made it clear to Caroline that if we were not successful this month, we would not do any more IUI cycles, until and unless we checked her tubes and uterus. When I chose the starting dosage, I took into account that she grew 3 follicles on a starting dose of 225 IU and 2 follicles on a starting dose of 300 IU. I would have to really search my memory to recall the last time I put someone on 375 IU or higher for anything other than an IVF cycle. Another factor to consider was Caroline’s weight, which was now down to 221#. In none of her previous cycles was she ever this light. I warned Caroline about the possibility of overstimulating if we put her on 375 IU. She laughed it off. I repeated my warning a bit more seriously, reminding her that YES, I realized how she had stimulated on 225 IU and 300 IU, but that it was certainly possible to have a huge boost in response with just a small increase in dosage. She humored me this time and calmly acknowledged the risk. Logistical reasons (how quickly she could get the medication) led us to start her on Gonal-F instead of Bravelle and to start on day 4 instead of day 3. She took 375 IU of Gonal-F for four days and came back for an ultrasound. This is what we saw on day 8:

RIGHT OVARY: (15×12) (13×13) (11×11) (10×10)
LEFT OVARY: (7×7) (6×6) (6×6)
E2 = 329 pg/ml

Decision time. Do we lower her dosage or do we keep going with the same? If I lower the dosage and she comes back next time with no growth, we’ll be kicking ourselves. If I keep the same dose and she comes back hyperstimulated, we’ll be equally upset. Tough call, but I do know one thing. I’m not going to skimp on monitoring. Whatever I decide, she’ll be back to check again in 2 days. Frequent monitoring helps us adjust things more precisely. I decided to keep the dosage stable and bring her back in two days. Here is what we saw on day 10:

RIGHT OVARY: (18×17) (14×14) (13×13) (10×10) (10×10)
LEFT OVARY: (15×15) (13×13) (13×13) (11×11) (10×10)
E2 = 699 pg/ml
This was great! At this point, I was happy with keeping her on the same dose and not dropping it. She switched to the donated Bravelle and continued at 375IU. After two days, she came back on day 12 and this is what we saw:

RIGHT OVARY: (22×22) (19×19) (18×18) (16×16) (14×14)
LEFT OVARY: (18×18) (16×16) (13×13)
E2 = 1077 pg/ml

Decision time again. There are 6 mature follicles today, which is quite a lot. I reviewed the mathematics with Caroline. We don’t know exactly what the odds of pregnancy are PER EGG. However, if we assume a good-case scenario and a bad-case scenario, we come up with the following numbers.

Good case scenario: Each egg has a 20% chance of becoming a baby. Odds of at least one live-born baby = 74%!! Odds of triplets or more= 9.8%
Average case scenario: Each egg has a 10% chance of becoming a baby. Odds of at least one live-born baby = 47%. Odds of triplets or more = 1.6%
Bad case scenario: Each egg has a 3% chance of becoming a baby. Odds of at least one live-born baby = 17%. Odds of triplets or more = 0.001% = 1 out of 874
Worst-case scenario (ie tubes blocked): Each egg has 0% chance.

I estimated that if these eggs were each high probability (20% chance each), her risk of triplets could be as high as 8-10%!! Was that really acceptable to her? Even if this would give her a 70%+ chance of at least one baby.
And if things were more along the average case scenario (10% chance per egg), then she would have a decent 47% chance of a baby with just a 1.6% chance of triplets.
If she were the bad-case scenario (3% per egg), then her chances of triplets are very safe (1 out of 874), but then her chance of pregnancy would drop to 17%.
And of course, if her tubes were blocked, then all this would be a moot point.

With these numbers in our heads, it was a bit easier, but still difficult to make our decision. Caroline called Darryl to discuss it with him, and gave me the answer 20 minutes later. They would be willing to take the risk. They wished to go ahead.

The fact that the E2 was a little lower than expected given the number of follicles we see would tend to suggest that some of these follicles are not as mature as we would like. This further emboldens us because it lowers the pregnancy rate and the triplet rate.

The decision was final. We would launch her ovulation today and do an IUI in two days. She and her husband were taking the risk of triplets in exchange for a good chance at pregnant. The nice thing is that things go in parallel. If the real chance of pregnancy is low, then the real chance of triplets is low too. It goes hand in hand. A 9.8% chance of triplets would give her a 74% or pregnancy, although realistically, this combination is not likely to be the case. More likely, she has a situation closer to the combination of 47% chance of pregnancy and 1.6% of triplets or the lower combination of a 17% of pregnancy and a 0.0011% chance of triplets. Personally, this would be my favorite scenario.

Caroline was instructed to launch her ovulation at 5PM with 10000 IU of hCG. She was scheduled to come back in two days for her IUI.

Darryl’s sample was excellent and we were able to process it to get 20 million total motile sperm. The IUI was easy. Ultrasound done after the IUI confirmed that all the follicles had successfully released except for one and that the sperm was deeply placed in her cavity. Caroline was started on progesterone supplementation and scheduled for her pregnancy test. Everyone in the office came out to say goodbye to Caroline and to wish her the best. I also took the opportunity to congratulate her that her chances this time were pretty good, but if it didn’t take, then HSG was the next step.

Click her for episode 10

June’s story has spilled over a bit into July

Click here for episode 1

Caroline slumped in the phlebotomy chair and offered up her right arm. She had been here many times before and she no longer allowed herself to get too emotional. Her last cycle had consisted of 13 stressful days of mixing together 5 vials of medications and then taking the injection in the arm. She was just now coming to terms with the disappointing stimulation. Her dosage was the highest ever, and yet she made fewer follicles than before. Still, there was hope, all resting on two follicles. She left our office and awaited the results.

An hour later, we called her with the bad news. Her test was negative.

Right now, there are some of you wondering why Caroline doesn’t just give up. Well, many in her situation would do that. There are also some of you wondering why she doesn’t do IVF. Well, even assuming she has the financial means to do so, we are still facing the dilemma of making enough eggs.

As painful as it is for me, the physician, to face this disappointment, I always remind myself that it’s obviously much more painful for the patients themselves. So I take the time to collect my emotions before the next re-consultation with Caroline and Darryl, and then we began our discussion.

We have a 20 minute talk and resolve the following questions.

Do they wish to continue trying? YES, most definitely. As many setbacks as there have been, they still are not ready to give up.
Should they get an HSG now to check Caroline’s tubes? YES, it would be a very good idea. With all the eggs that Caroline has had cumulatively, it’s now worthwhile to check her tubes before doing any more cycles.
Do they wish to stimulate the ovaries and do another IUI in the same cycle as the HSG? No. They can’t afford another cycle right now. The last cycle had cost about $2000 for the Bravelle, because of the high doses that Caroline required. They now really have to save up before doing the next cycle. Meanwhile, she could do the HSG while otherwise taking this month off.

The course was set. Caroline would call with her period and we would schedule her HSG. We would hold off doing another treatment cycle until they save up enough for the medications. This was our solid plan, or so we thought.

A few days later, Caroline got her period and she called our office. Unexpectedly, she requested to speak directly to me. My staff did their job and tried their best to address her question, but Caroline, who had always been easy to deal with and reasonable, told them adamantly that she wanted to speak only to me, and she added a polite "please". I took the call.

ME: Caroline, how can I help you?
CAROLINE: OK, doctor, please don’t think I’m nuts, but I don’t want to do the HSG after all.
ME: I see. What is making you change your mind?
CAROLINE: I know you and I talked before about how much Darryl and I have been praying. Well we finally decided to stop keeping this all to ourselves and last night, we shared openly with our Bible study group regarding our infertility problems. We have a couples’ group that we meet with every week. They kind of knew our struggles in a vague way, but last night I shared with them every last detail and we all ended up crying. I asked for them to pray for us. It was a huge relief. Then I went home that night and I had a dream. I dreamed that my tubes were clear. It was very clear and very vivid.
ME: Are you sure you don’t want to do the HSG to confirm that they are clear? I understand what your saying, but with all due respect, do you really want to base your treatment decisions on a dream?
CAROLINE: Let me ask you this, doctor. Suppose I didn’t have any dream and I just wanted to do another cycle without the HSG. Is this possible?
ME: Well, let’s see. You’ve had about six total mature follicles in all your cycles put together, right? So that’s a pretty reasonable number to expect at least one pregnancy by now. Even though you don’t have any risk factors for tubal problems, do you really want to invest another $2000 in medications without having some assurance that your eggs are even getting to where they should?
CAROLINE: How about one more cycle then? Please?
ME: Caroline, you know you don’t have to plead with me. I’m just giving you my sound professional advice, but I also respect your wishes. What if we were to do agree that after one more cycle, if it fails, we will not go on without an HSG.
CAROLINE: It’s a deal! So the next thing I want to talk to you about is…
(While I’m at my desk talking with Caroline on the phone, an instant message from my nursing staff flashes across my computer screen)
ME: Caroline, I just got a message with some good news. We have some free medication for you.
CAROLINE: Really? (very excitedly) From where?
ME: Well, one of our patients had ordered extra medication for more than one cycle, but she got pregnant on the first cycle, and she just graduated today after making it to her 13th week of pregnancy. Apparently, she wanted to donate the extra medication she had left over and immediately we thought of you. So you now have about $1000 worth of Bravelle waiting. You just need to save up for the remainder.
CAROLINE: (silence)
ME: Hello? Are you there?
CAROLINE: (tearful sobbing) I was just about to tell you. One of the sisters in our Bible Study group recently found out that her father needed emergency surgery out East. She and her husband were having some temporary financial problems, so we all took up a collection to buy her a plane ticket, so she could fly out and be with her dad. Well, things changed and it turned out he got completely better and didn’t need surgery after all. So she asked everyone’s permission to take the airfare money and give it to me and Darryl instead. We really fought it, but they all insisted, so anyway….wow.
ME: Wow indeed. So I guess it’s your choice then. We can start a cycle whenever you are ready. When did your period start?
CAROLINE: Last night.
ME: Do you want to come in today? or tomorrow?
CAROLINE: Yes! Yes!
ME: OK. I’ll transfer you back up front and you can schedule an US

Click her for episode 9 when published.

Click here for episode 1

The pregnancy test was negative again. As sad as this is, let’s temporarily depart from the obvious emotional aspects of this failed cycle and tackle the decision process scientifically.

Caroline is 35 years old. She was presumed to not have ovulated regularly by virtue of her consistently negative ovulation tests. Her husband’s sperm looks fine. In the past few months, with the help of medication, she has been able to successfully ovulate. In three treatment cycles, she grew 0, 1 and 3 mature follicles, respectively. She still has not had an HSG to test her tubes.

What are our choices?

1. Give up and/or consider adoption.
2. Suspend treatment until another 20 pounds of weight loss
3. Move on to IVF
4. Get an HSG
5. Try another IUI cycle
6. Try homeopathic methods

Out of all these choices, my personal favorites  would be #2, #4 or #5 followed by #3. But a lot would depend on Caroline and Darryl’s personal preference.

Choice #1 would be understandable, but not recommended. Sure, they have been through a lot. They have spent a lot of money. They have spent a lot of time. Caroline has endured many injections. All this has resulted in no pregnancy. It HAS, however, resulted in progress. We now know that Caroline can ovulate. She has lost a lot of weight and is physically feeling better than ever. Caroline and Darryl made it clear to me that they had zero intention of giving up.

Choice #2 is reasonable. Caroline has shown evidence that she can get healthier. Whether or not the metformin gets the credit for her amazing weight loss is not the point. The point is, she is succeeding. So whether this is due to the medication or just to a new mental attitude, we are just happy that it’s going so well. Caroline and Darryl expressed that they wished to keep going without resting.

Choice #3 would be an even better idea if they had insurance coverage for IVF or if they had $13K in discretionary spending available. While I think that their chances of a successful IVF cycle are excellent, I am still optimistic of her chances with IUI, given that she has only failed with four eggs total so far. I would however, like some assurance that her tubes are patent and her uterus is normal.

Choice #4 is probably my top choice. An HSG will reassure us that Caroline’s tubes are open and that there are no polyps or fibroids in the uterus. If the test is normal, then we can return to do another IUI. Caroline, however, was very against this. Her reasoning, while not scientifically sound, was certainly understandable. She stated that she knew of three people who had excruciating pain with their HSG’s and she didn’t want to go through that at this time. I reminded her that those friends of her are clinically very different from her. In my experience, I’d say 1 out of 10 women have severe suffering during their HSG’s. I make it a point of surveying my patients after their HSG’s and the majority have mild discomfort only or no discomfort at all. In Caroline’s specific case, there are no risk factors for her having bad tubes. She has no history of a sexually transmitted disease. She has had no previous surgery. She does not have painful periods at all. In addition, after her IUI’s, I would do an ultrasound trying to see an image of her uterine cavity after it was distended by the IUI specimen. This allowed me a peek at her cavity and gave some additional evidence that it was normal. Because of all this, I gave in to Caroline’s request to postpone her HSG until after one more IUI cycle.

Choice #5 then becomes the most likely option.

Choice #6 is something that we’re already doing. By losing body fat and improving her overall wellness, Caroline is helping boost her chances of pregnancy, both naturally and with treatment. With regards to taking herbs or nutritional supplements, there is no proof at all that this would be worth the money.

After going over all the pros and cons, we decided to put off the HSG and do another IUI cycle. This time, we’re going to use 300 IU, which is a very high dose for an IUI cycle. However, everything we’ve learned from the previous failed cycles adds to the evidence that this is a good plan.

Day 3. Baseline scan shows no cysts. Caroline started on Bravelle 300 IU daily from day 3 to day 7.  Before we reveal what we actually saw, I should add that an ideal finding on this date would be 3-5 follicles of size 12-14mm. This is what we actually saw on day 8:

RIGHT OVARY: Not clearly seen
LEFT OVARY: (8×8) (7×7) (6×6) (7×6)
It’s only a little odd that we can’t see her right ovary clearly today when we’ve seen it easily in most of the previous scans. Sometimes things shift and move. The very fact that it’s hard to see suggests that there are no large follicles contained within it, and for all practical purposes, that’s all I need to know for today. This reassures me that we don’t need to drop her dosage for safety reasons. I keep her on the same dose for day 8 to day 11 and bring her back on day 12. This is what we saw.

RIGHT OVARY: (11×9)
LEFT OVARY: (13×11) (9×9)
Estradiol = 125 pg/ml

Yikes! This is extremely disappointing. Caroline is on her highest dose ever, and yet her stimulation is less than her previous cycle, when she was on a lower dose. Because the lead follicle on the left has made it to 13mm, we forge ahead, rather than cancel the cycle. I keep in mind that Caroline is still taking her injections in her arm, which is a little more brutal than the usual shots that go into the fat pad of the stomach area. She bravely continues 300 IU from day 12 to day 14 and this is what we see on day 15:

RIGHT OVARY: (12×11)
LEFT OVARY: (22×20) (17×17)
Today, there is some relief that we have not one, but two mature sized follicles. I give her 10,000 IU of hCG that afternoon and bring her back for an IUI in two days. We have a discussion about how it sometimes happens that a higher dose results in a lower stimulation. We also keep in mind that it only takes one follicle to get a pregnancy. I remind her that there have been times when patients fail to get pregnant with 5 follicles and 4 follicles in their first two cycles, only to get pregnant on a third cycle when there is only one follicle. Anything is possible.

Two days later, we inseminate with 27M total motile sperm, confirm that both follicles are gone and we begin the waiting game.

Click here for episode 8

Click here for episode 1

Caroline and Darryl have been trying to get pregnant for almost two years now. The most obvious problem is Caroline’s failure to ovulate. First, she was started on metformin to correct address her insulin resistance. Then she was tried on a combination cycle of Clomid and injectables. She didn’t grow a mature follicle. Next cycle, it took quite a bit of injectable medications, but Caroline ovulated. We even did an insemination to give that egg the best chance.

However, according to today’s blood test, Caroline was not pregnant.

It is very normal to have fleeting thoughts of giving up when things don’t go our way. Caroline had worked hard to lose weight (now down to 228#), spent hundreds of dollars on medications, endured the daily needle injections, had gotten her hopes up with the egg that we saw, only to have it all end with a negative pregnancy test.

We reconvened to talk about options.

ME: How are you feeling?
CAROLINE: Trying to see the bright side. (smiling) I really thought this was going to do it. I mean seeing that egg on ultrasound made my eyes tear up, with joy. I realize now that one egg isn’t guaranteed to give a baby and I’m prepared to get more eggs until one takes.
ME: Hmmm. You have a pretty good attitude. And you’re right. While it’s optimistic that you got the one egg last cycle, it’s not always enough just to have one. So now we have a few choices. We can do another cycle, with a high enough dose to get multiple eggs. We can check your tubes to make sure that they’re open. Or we can wait for you to get into better shape. You’re doing a great job of that, by the way.
CAROLINE: Well, Darryl and I discussed it. We want to try one more cycle. If it doesn’t work, we might take a break. So can we be aggressive?
ME: Of course. I’m going to start you on 225, because that’s what got you going last time. Remember we don’t want to give you too much, or else you’ll end up risking having TOO many babies.
CAROLINE: Honestly, I wouldn’t mind having triplets and just getting this all over with.
ME: A lot of women say that. Many of them don’t really mean it. Haha.
CAROLINE: I know. I know.

We started the cycle.

Day 3 baseline ultrasound:
RIGHT OVARY: Nothing.
LEFT OVARY: Nothing

Good start. From her friends and online friends, Caroline knew the disappointment of finding a cyst on the baseline scan. Luckily, this wasn’t one of those months. The next decision is what dosage to start her on. Last month, nothing really happened until we raised the dosage to 225 IU, so this month I decided to start her off with that. Another tweak is the decision to have Caroline take the injections into her arm IM. I’ve tried this in the past on women with a lot of abdominal body fat with mixed results. It was certainly worth a try. There just might be better absorption of medication when given this way. Caroline took 225 IU of hMG from day 3 to day 7 and returned on day 8. This is what we saw.

RIGHT OVARY: (9×9) (9×9)
LEFT OVARY: (10×10) (9×9) (8×8) (8×7)
Estradiol = 200 pg/ml

This was a great start! There appeared to be six promising follicles. If the estradiol level would have been a bit higher, I would have been tempted to drop her dosage. But I would have met with some great resistance from the patient. Caroline was stoked and eager to continue the same dose. I warned her that if all six grew and we wound up with some additional follicles, then she would be at big risk for twins or more. She acknowledged the risk and we trekked forward. On day 8 to day 11, Caroline took another 225 IU daily. This is what we say on day 12:

RIGHT OVARY: (21×17) (11×11)
LEFT OVARY: (19×18) (18×17) (9×9) (9×9)

I was very happy with the three mature follicles. Caroline was disappointed. She had wanted all six to grow. I reminded her that this was a great stimulation and furthermore, it was SAFE! She eventually cheered up, especially after we checked her weight and found out she was down to 226#.

I launched her ovulation with 10000 IU or hCG and brought her back in two days for an IUI.

Again, it was a great sperm sample (20M total motile sperm) and again, US showed that she did indeed ovulate everything. Caroline had a lot of questions right after the IUI. She wanted to know her restrictions on activity, like what she could eat, how much she could lift and how much stress she could permit herself to be exposed to at work with her students. After we covered all her questions, I added that if she didn’t get pregnant this cycle, I would give serious thought to getting an HSG to check her tubes.

Click her for episode 7

Click here for episode 1

UPDATE: Caroline and Darryl are infertile. Caroline has had regular periods, but her ovulation kits don’t turn positive, leading us to suspect an ovulation problem. She underwent one monitored cycle where she received medication to help her ovulate. In that cycle, she not only took Clomid, but also injectables. Sadly, she did not grow follicles well. She comes back to discuss the game plan for the next cycle.

It is helpful to discuss things in terms of options. One option is to give up and do no further treatment. That is always an option. If we were to take this path, Caroline would be banking on the hopes that she could someday ovulate on her own and get pregnant naturally. The odds of this are low, but might improve as long as she continues to lose weight. In any case, it would likely take a very long time to have good news, if any.

A second option is to increase the dosage and try again. The natural evolution of treatment choices would dictate giving injectables from the beginning rather than to start with Clomid.

A third option is to increase the dosage but to patiently wait until Caroline loses some significant weight. This is not a bad plan, with the only downside being the delay in treatment.

After some discussion, Caroline and Darryl opted to do another cycle immediately.

Carolyn came in on day #2 of her cycle for a baseline ultrasound. It showed that both ovaries were quiet and without activity. She then started taking 150 IU daily of Bravelle. We switched from Gonal-F to Bravelle this cycle for the simple reason that the company was running a special discount program. It was simple. Buy 20, get 10 free. Caroline would need it, because she was taking 2 x 75 IU amps daily ( 75 IU x 2 = 150 IU).

Caroline took 150 IU of Bravelle from day 3 to day 7. This is what we saw on day 8:
Right ovary: (7×7) (6×6)
Left ovary: (7×7)
Lining: 9mm triple layer
Estradiol = 82 pg/ml

At this point, it’s still uncertain how things will progress. We forged ahead with a dose increase to 225 IU daily from day 8 to day 10. This is what we saw on day 11:
Right ovary: Nothing
Left ovary: (14×12) (10×9)
Lining: 9mm triple layer
Estradiol = 95 pg/ml

Usually, when a follicle makes it to 14mm, that’s the point where it is likely that it will continue to grow, so as painstakingly slow as this was all going, there was hope. The daily injections were not painful, but the fact that it was costing over $100 in medication (not counting the discount) every day was emotionally painful. But if those two follicles would keep growing, then next visit we will start thinking about when to trigger the follicles for ovulation. The fact that the estradiol level barely went up didn’t make me too happy, but we kept going. Caroline took 225 IU of Bravelle from  day 11 to day 13. This is what we saw on day 14:
Right ovary: Nothing
Left ovary: (17×14) (11×11)
Lining: 11mm triple layer

This was it! The one follicle was almost at a mature size. I told Caroline to grow the follicle one more day with 225 IU of Bravelle and then I had her launch her ovulation with 10,000 IU of hCG at 5PM. She came back in two days for her IUI. Darryl’s sperm sample was excellent, with 28M total motile sperm injected. Ultrasound right after the IUI showed that the follicle was gone. Successful ovulation!

For once, maybe the first time in her life, Caroline had ovulated! We waited 12 days for her pregnancy test.

Click here for episode 6

Click here for episode 1

Summary: DARRYL and CAROLINE have been infertile for 19 months. The most likely cause is Caroline’s failure to ovulate. This was suspected because her ovulation testing always remained negative, despite the unexpected finding that she has fairly regular periods. Caroline’s ovulatory problem seems to be a result of PCOS and the effect of PCOS on Caroline’s body weight. We have a plan in place to tackle the problem from both directions. Caroline is actively losing weight, through diet, exercise and metformin. In addition, we are going to give her ovulation medication to further help her ovulate. Although she has already failed several cycles of Clomid with her OB, she requested to do one more Clomid cycle, in the belief that her decreased weight and her successfully being on metformin will give a different result this time.

I picked up the chart. We still defy the temptation of going to electronic medical records, and there are many good reasons for us to keep from doing so. I saw that Caroline had gotten her period five days ago and was here for her baseline scan. The purpose of today’s ultrasound is to make sure she doesn’t have any cysts at the moment. The presence of cysts would make it wise to wait another month before doing a cycle.

I walked into the room and Caroline greeted me enthusiastically, sharing that she had lost more weight and was now down to 234#. I congratulated her and proceeded to do the ultrasound. Both ovaries were quiet. The lining was thin. No real surprise. The results were exactly as we hoped for.

As I was about to leave the room, Caroline asked if she could talk to me. I told her I would have to do two more ultrasounds, but I would be available after that.  She dressed and met me later in the consultation room.

CAROLINE: Guess what! I’ve changed my mind about the Clomid.
ME: What do you mean?
CAROLINE: Remember you didn’t want me on just Clomid. I’m sick of not being pregnant. I want to move forward and be more aggressive.
ME: So do you want to start injectables today?
CAROLINE: Can we do the combination that you talked about?
ME: Absolutely. We’ll start you on 150mg of Clomid and then add injectables.
CAROLINE: Perfect!
ME: What made you change your mind?
CAROLINE: I never told you, but i have a cousin on the East Coast who is trying. She failed Clomid for four cycles, like me, but on her first cycle of injectables, she just got pregnant.
ME: Great for her! OK, let’s try and get good results.

So, DAY 6 to DAY 10, Caroline took 150mg of Clomid. Starting day 11, she took 150 IU of Gonal-F. On day 14, she returned for an ultrasound. This is what we saw:

RIGHT OVARY: Nothing
LEFT OVARY: 7mm follicle. 6mm follicle.
LINING: 11mm triple layer.

While this was disappointing, it was not surprising. There are many different things that we could have seen today. It was possible that she would have so many eggs that we would have to consider cancelling the cycle. She could also have had 3-5 promising follicles, which is what would have been ideal. Instead, she had two follicles, both of which were quite small. I checked an estradiol level on her. It was 122 pg/ml. This led me to give her a few more days. I increased the dosage to 187.5 IU per day. With the Gonal-F or Follistim pens, it’s possible to easily do intermediate dosage, rather than be limited to multiples of 75 such as 75-150-225-300. She continued on this for three more days and then checked again.

RIGHT OVARY: Nothing
LEFT OVARY: 7mm follicle. 6mm follicle.
LINING: 11mm triple layer
E2 = 145 pg/ml

It was time to cancel the cycle. Yes it was good that we did injectables this time, not because it did anything positive, but because we saved ourselves from wasting any more time.

Caroline wound up negotiating with me to try 2 more days of injection, since she had enough left in her remaining Gonal-F vial to do so. I gave in to her request. She continued on 187.5 IU for three more days and then returned for ultrasound.

This is what we saw.

RIGHT OVARY: Nothing
LEFT OVARY: 9mm follicle. 6mm follicle.
LINING: 11mm triple layer.
E2 = 170 pg/ml.

We sadly cancelled the cycle and waited for her to call with the next period.

Click her for episode 5

Click here for episode 1

There are many things I love about being an RE, one of which is the chance to participate in the transformation of peoples’ lives, as they go from having no baby to suddenly becoming happy parents. That one is pretty obvious. Besides that, there’s another thing that I like and that’s the daily suspense. You see, every day, we run pregnancy tests to see if our patients are pregnant or not. There is no way to predict ahead of time who is going to be positive and who is going to be negative. Often, patients whose cycles seem like sure things, end up not being pregnant. Other times, patients whose cycles offer small hope end up defying the odds and winding up pregnant. This daily feature of not knowing the results really keeps things fresh and interesting for me and my staff.

Another thing that keeps us in suspense is the metformin follow-up visit. I would estimate that about 3 out of 4 first-time metformin patients demonstrate some very positive changes in their lives with regards to weight loss, increase in energy level and sometimes even normalization of their periods together with spontaneous ovulation and pregnancy.

Three weeks earlier, when Caroline was first started on the metformin, we had checked her weight in the office. Initially, she wasn’t thrilled to be weighed, but eventually gave in. Her weight had been 245# on our scale. As I picked up her chart today, for her follow-up visit, I was pleased to see that her weight today was down to 240#. With that in mind, we began our conversation.

ME: So, Caroline, I’ve asked you back today to discuss how you are responding to the medication I gave you three weeks ago, the metformin. How have things been different since then?
CAROLINE: Well…I must admit you were right, when you said that it could help me lose weight. I saw that I’m 5 pounds less than the last time I was here. I feel it too.
ME: That is wonderful news. So if you had to say, what do you think are the reasons for this weight loss? Are you eating fewer carbs?
CAROLINE: Well, I definitely don’t crave carbs and sweets as much. I mean I’ll still have a little bit, which is still enjoyable, but then I no longer want to have much more.
ME: And any side effects?
CAROLINE: Hmm.. the first two days, I got bad diarrhea, just as you predicted, but it really was just for those first two days. I think I lost the most weight during those first two days, because I felt miserable and didn’t feel like eating anything. However, even after the diarrhea cleared up, I still continued to lose weight. So happy! Oh and you know what? I really noticed a difference. I don’t get so sleepy in the afternoons any more. It’s been wonderful.
ME: Good.
CAROLINE: But I still have a long way to go. I know you’re going to say that.
ME: Actually, I was going to talk with you regarding our options at this point. But first of all, are we in agreement that the metformin is doing well for you and that we should continue it?
CAROLINE: Definitely!
ME: Then the next question to ask ourselves is what to do regarding getting you pregnant. We still have the task of making sure you ovulate. Now one thing to keep in mind is that there might come a point where you lose so much weight that things start working right and you begin to ovulate regularly. Of course, if we had all the time in the world, this is definitely one option, just to keep you on the metformin, allow you to regulate your carb intake the way you have been doing so well and allow you to ramp up your exercise habits. Then we just sit back and watch the progress. However, for several reasons, we DON’T have all the time in the world. Therefore, I have a suggestion.
CAROLINE: I’m so glad you said that, and that we’re not just going to count on weight loss to solve our problem. I mean, I’m happy with these past three weeks, but look at me. I still have a lot of weight to lose. And I’m old.
ME: You’re not older than a lot of my patients, Caroline. Come on. But I’m with you in that we should be proactive. OK, let me share with you what we can do. One. We can give you gentle pills to try and help you ovulate, or we can give you more expensive, but more powerful injectable medications. It’s basically a choice between Clomid or injectables. Either choice is reasonable for you, although I’m a little more in favor of the injectables, because of the very fact that you have already failed Clomid.
CAROLINE: OK, doctor. If you will, let me tell you what Darryl and I discussed. We really feel that the metformin is doing something. Now let me ask you, is it possible that my body has now become more normal because of the metformin and that I might respond to the Clomid now even though I didn’t respond to it before?
ME: Hmmm, that’s the big question. It’s certainly possible, but again, I think the odds would be better with injectables, or at least a combination of Clomid and injectables.
CAROLINE: Well, how about this? I really was gung-ho and ready to be aggressive, but I want to try one cycle of Clomid. Is that OK? One cycle.
ME: It’s your choice, Caroline. We can be as conservative or aggressive as you like, within reason and doing one more cycle of Clomid falls in the range of what I consider within reason.
CAROLINE: Great.
ME: One suggestion is that we monitor it. That way, we at least know if you are ovulating or not.
CAROLINE and DARRYL look at each other and nod.

The plan was set. Caroline would call us with her next period and we would bring her in for a baseline ultrasound before starting her on a monitored cycle of Clomid. With the conclusion that the metformin was a success for her general health, I refilled it for another four months. In addition, I chose to repeat the liver test to confirm that she did not have any unusual hepatic reaction to the metformin. The couple left my office very encouraged.

Click here for episode 4

Click here for episode 1

Darryl and Caroline are here for their first consultation. After breaking the ice and warming up to each other, we tackled some of the potential problems that could be contributing to their infertility. One red flag was the fact that Caroline has never had a positive ovulation test, despite taking the tests properly for six months now. The ultrasound exam further supported the diagnosis of Polycystic Ovarian Syndrome. After the US exam, we went back to the consultation room and continued our discussion.

ME: Caroline, when we first started today, you had mentioned something about the experiences you had with other doctors. Do you want to fill me in on that?
CAROLINE (sighs): OK, but it’s not easy for me to talk about it. However, if it will help you…When the first year had gone by, I went to my family practice doctor. She basically told me that it was unhealthy for me to have a baby and I should not even think about it until I lose some weight. That clearly was not the type of help I was looking for, so I went to my OB. She too, said the same thing, only maybe not so bluntly. She did try and help me with some Clomid. I took that for three months maybe four but it was making me nauseous and it wasn’t making me pregnant.
ME: Were you monitored for those Clomid cycles? Do you know how many follicles you made?
CAROLINE: No. No monitoring. But I did do ovulation kits and still, they never turned positive.
ME: So what was your OB’s plan?
CAROLINE: Nothing. Just Clomid and telling me to lose weight. I wasn’t too happy, needless to say. So THEN, I saw an ad on the internet for a reproductive endocrinologist. I went to see him and right away, the first thing he wants to do is IVF. I was happy for once that someone didn’t give up on me just because of my weight.
ME: I see, so did you actually do IVF?
CAROLINE: I almost did. But something just didn’t feel right. Maybe you can explain it. (turning to Darryl)
DARRYL: Yeah.  He really didn’t bother to ask many questions. We almost got the feeling that he was just out to sell his IVF and we don’t have insurance coverage for it. I know a bad salesman when I see one.
CAROLINE: I felt the same way. And that’s when by God’s grace, I ran into my co-worker showing the office her new baby pictures and that’s when I started talking with her and decided that I should hold off on the IVF and come get your opinion first.
ME: Who was the doctor that you saw, if I may ask?
CAROLINE: Dr. ____. Do you know him?
ME: I do. Well, I actually know pretty much every RE in Southern California. We probably all know each other. The reason I asked is that there are many excellent RE’s out here and we often see each other’s patients for a second opinion. If one of the ones whom I trust says you need IVF, I would want to explore more why they would think that. But the one you saw is not one whom I know and trust very well, so I’m going to discount what they recommended for now. That’s not to say that we won’t be talking IVF someday, but there’s certainly a lot we can explore and try before going that route.
CAROLINE: Well, I’m glad that I did come see you. I feel very comfortable right now.
ME: Good. Well, let’s summarize what we know right now, OK?
CAROLINE and DARRYL nod in unison.
ME: You’ve been trying to get pregnant for a year and a half. The sperm looks fine. There is no obvious suspicion of a tubal problem (although we don’t know for sure yet that your tubes are open). The big suspicion is an ovulation problem. You’ve tried Clomid 3 or 4 months and didn’t get pregnant. Based on your ovulation kit testing, it doesn’t seem like you even ovulated. Therefore, it would make sense that our best strategy for now, would be to focus on helping you ovulate. Does that make sense?
CAROLINE (smiling and nodding): Completely.
ME: There are a few obvious things that we need to rule out, like thyroid disease, but I’m going to go over these records (pointing to the stack of papers they had brought) after we are done talking and see what’s been ordered in the past. I might get some more tests after seeing what’s missing. You said you never had a blood test in which you were given a sweet drink to drink, right? So we’re going to start with that.
CAROLINE: Doctor, you know what’s best, but if it’s OK with you, I’d rather not waste an entire morning getting this test. Can’t you just give me that medicine that you were talking about?
ME: Well, let’s talk about that. The medication is called metformin, or Glucophage. Have you heard of it?
CAROLINE shakes head no.
ME: It’s a medicine that is often given to diabetics and it’s quite safe compared to something like insulin, which is another medicine that diabetics take.

We spent 15 minutes discussing the side effects of metformin, as well as all of the possible benefits. Our plan was set. Caroline would have some blood tests drawn today to confirm the safety of taking the metformin. These were tests of her liver and kidney status. She was to try the metformin for three weeks, after which we would meet again to go over her progress.

Click here for episode 3