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Irene’s testing came back with a positive result, for a test called Lupus Anti-Coagulant (LAC). Instead of being depressed about having something abnormal, she was actually happy, especially when she learned that there was a way to address this problem.

The name, Lupus Anticoagulant, is paradoxically misleading. Most women with Lupus don’t have a positive LAC. Most women with a positive LAC don’t have lupus. Furthermore, it’s not truly an anti-coagulant. In fact, the miscarriage issues stem from it being a PRO-coagulant, meaning it causes excessive blood clotting. One way to think of this is that Irene’s immune system is overachieving. Instead of merely attacking germs and foreign substance invaders to her body, the immune system is also attacking her own cells, leading to unpredictable outcomes, one of which is recurrent pregnancy loss. The important thing to remember is this. Patient with a history of recurrent miscarriage and a positive LAC would most likely benefit from some form of true anticoagulation.

With a focus on the practical implications, we now had a plan. The next time Irene got pregnant, we would give her something to counteract the harmful effects of the positive LAC.

Irene now had the following concrete game plan. She would call us as soon as she missed a period and come in for a pregnancy test. If it was positive, then we would put her on heparin, a blood thinner. We had to also have a backup plan. In case she wasn’t pregnant within six months, we would re-evaluate to see if she would like us to do something to speed things up.

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Irene bravely finished sharing the stories behind her previous four miscarriages. She gathered herself together and we began going down the list of possibilities, searching for a reason to explain her many pregnancy losses, and more importantly, hoping to figure out the right interventions to minimize the chance of a fifth one.

In no particular order, we started by discussing ANATOMICAL causes. A baby needs a certain type of safe environment in which to grow. If the uterine cavity is an abnormal shape, is an abnormal size or if it contains a mass pushing in on it, this can create a suboptimal site of implantation, thereby increasing the odds of miscarriage. In general, for patients with anatomical factors, I've seen more pregnancy losses later on in the pregnancy, rather than in the very early first trimester, as Irene's had been.

Next, we discussed GENETIC causes. Sometimes, a husband or a wife who looks normal, carries what's called a translocation in their genes. This leads to an increased risk of miscarriage, so that rather than the usual 15% risk of miscarriage for average couples, the couple in question will have over a 60% risk of miscarriage. There is no cure for it, but there are solutions, such as IVF with PGD to help pick the normal embryos. Another choice which is rarely taken is to use someone else's sperm or egg (depending on which spouse carries the translocation). The strategy I see adopted the most by these couple is just to get pregnant frequently and often so that despite many miscarriages, eventually one will take.

We then discussed INFECTIOUS causes. Some women don't realize they have a low-level chronic infection that is causing them to have trouble getting pregnant and/or sustaining pregnancies.

We also discussed AUTOIMMUNE / BLOOD CLOTTING issues. I put these two broad areas together in one category, because their treatments are similar. Some people have abnormalities with how their blood clots. If the blood clots TOO easily, then the blood supply to the baby will be compromised as the vessels clot up.

Finally, there are HORMONAL issues. This, too, is a general category as there are many different hormonal abnormalities that can affect miscarriage risk. Not every patients should have all these investigated. There are costs and risks associated with every action, so we need to customize the plan according to what's best for each individual. The following are the specific conclusions we reached and the decisions we made as a result.

ANATOMICAL: Irene's regular ultrasound exam looked perfectly normal. I performed it myself. This means there are no whopping obvious anatomical problems. However, in order to see more subtle anatomical lesions, one needs to do either an HSG or a saline-contrast ultrasound, tests which involve putting liquid into the uterus in order to see a clearer contrasting view. So should we get one of those tests? It always depends. Irene's insurance did not cover the test, which can run anywhere from $500 to 1000 dollars or so depending on the part of the country and the specific radiological facility. Our decision to put off this test was based on the fact that we found something else positive. If we had nothing abnormal in any of the other categories, or if her regular ultrasound had been suspicious, or if it was free for her to get an HSG, then she would have more likely chosen to get it.

GENETIC: This category is tested by getting a karyotype on each partner. This is also an expensive test and wasn't covered by her insurance. The main reason we did not do this test was because there was nothing we could do if the results came back positive. Irene and Harold were opposed to using donor sperm nor donor eggs, in case one of them came back as having a translocation. They also could not afford to do IVF with PGD at this point. Therefore, we decided not to do a karyotype yet.

INFECTIOUS: Instead of testing for a chronic infection, it turns out to be more practical to just give antibiotics to both partners. First of all the cultures are not very sensitive, so it's possible for someone to have an infection and for the test to wrongly suggest that they are negative for it. Also, the test turns out to be more expensive than the antibiotics. I prescribed doxycycline 100mg twice daily for both partners. The downside is potential stomach upset for both partners and and potential yeast infection for Irene. There is also the bigger ecological downside of introducing more antibiotic resistance to the world's bacteria. However, Irene and Harold decided there were perfectly fine with this option.

AUTOIMMUNE / BLOOD CLOTTING: We ordered some tests. Specifically, we checked Lupus Anticoagulant and Anti-Cardiolipin Antibodies. There are the two most common tests. There are other ones such as factor V Leiden, Activated Protein C Resistance, a fasting Homocysteine level and Factor II, but for cost reasons, we held off on those for now.

HORMONAL: After reviewing Irene's history, we did not order any hormonal tests. For example, if she would have admitted to feeling tired or low-energy, I would have checked her thyroid. If she had evidence of PCOS, I would have checked her for insulin resistance. She did not have anything in her history that warranted any other tests. Irene was scheduled to come back and discuss the results with me in two weeks, by which time everything should be back.

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Irene and Harold are here for help because all four of their pregnancies so far have ended in miscarriage.

We talked and elicited more information. Irene worked as a nurse. She liked her job and described it as being moderately stressful only. She did not work with any radiation or chemotherapy. Harold owned his own painting business. He described his stress level as an 8 out of 10. He clarified that he didn’t have much contact with the actual paint and chemicals, but rather did management. They lived in their own condo with Harold’s parents.

Their first pregnancy was conceived on their wedding night. It came as a surprise that it happened so easily. Irene, who had previously been regular, every 28 days, missed her first period a week after the honeymoon. She did a home pregnancy test and it was positive. Two weeks later, she noted some spotting, which progressed to moderate flow with cramping. By the time, she went to see her doctor, she was bleeding like a period. She remembers that her blood test was positive, but the values proceeded to drop. She wound up not getting a D&C, but rather just passing everything naturally. Harold attributed the miscarriage to the stresses of the honeymoon and the initial moving-in process.

Seven months later, Irene was pregnant again. She went to her OB immediately and her pregnancy was indeed confirmed with a blood test. The numbers went up initially, but then she had bleeding again. When she went back for another exam, her cervix was open and the pregnancy was once again lost. No D&C was done. Her doctor had examined her uterus and found it to be normal size. There was no further testing done and Irene felt confused and depressed. Being a nurse, she tried to read up on miscarriages, but did not know what to do. Their doctor told them to avoid getting pregnant for three months, so they completely abstained from sexual intercourse.

After the three months were over, they hesitatingly started trying again. They were more fearful than excited when Irene was pregnant again in two months. Per Harold’s mother’s instructions, Irene cut her work hours significantly and avoided lifting anything. She also drank a daily concoction of herbal tea that her mother-in-law made for her. Things were more promising as she didn’t have any bleeding for two months. Then, one night, Irene was having a bad headache. Their neighbors were throwing some sort of party and the music was blaring. After lying down and trying to block the sound with pillows, Irene’s stress level built and she wound up sending Harold to tell them to please turn down the music. A mild confrontation ensued and things were eventually resolved by having the police come and talk to the neighbors. Meanwhile, the stress mounted and Irene felt panicked. All of a sudden, she started bleeding. They rushed to the emergency room. An ultrasound was done, which showed a sac in the uterus, but no fetus. Because of the heavy bleeding, Irene underwent a D&C. This time, her OB ordered some testing, which consisted of chromosome tests on Irene, but not on Harold. The test was normal. Before Irene could tell me about her fourth pregnancy, we took a break. She was tearing up too much for us to continue.

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When I met Harold and Irene, I quickly learned that their story was different from those of other patients.  Unlike other couples who had trouble getting pregnant, Harold and Irene had gotten pregnant easily on their own four times in the past three years. Their problem was pregnancy losses.

Irene was 31 years old and Harold was 35. They were Korean, but had grown up for most of their lives in the US. After getting married three years ago, they immediately got pregnant. They lost that pregnancy and got pregnant again seven months later with similar results. In their second year of marriage, they once again had two pregnancies and losses. After a lot of frustration, their OB referred them to me.

We started by reviewing the concept of miscarriage. I explained that miscarriage was a very common part of life, with about 1 out of 6 pregnancies ending in miscarriage. So having ONE miscarriage was not anything unusual, sort of like getting into a minor car accident. However, if it gets to be a pattern, then it’s time to step back and see what’s wrong. Again, if someone gets into a minor traffic accident, you don’t make a big fuss, but if someone gets into four accidents in two years, then that raises many questions regarding their vision, judgment or driving ability. With four consecutive pregnancies all resulting in losses and not a single healthy baby born, it was definitely long overdue to explore the medical issues of this couple's problem.

As you know, I like to structure all problem-solving in an organized fashion. For infertile couples, I divide the problems into issues of sperm, of eggs and of anatomy, as you can tell from our previous case stories. For recurrent miscarriage, I divide the problems into those of anatomy, genetics, hormones, blood clotting antibodies and infectious causes.

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Summary: Caroline returns today for her second prenatal ultrasound. The first one was done at around 6 weeks and showed two gestational sacs.

Today, Caroline is 8 weeks pregnant. Her last ultrasound showed two gestational sacs, but heart motion was not yet seen. She chose this particular day for her ultrasound because her husband was able to get time off from work today to be with her.

This is what we saw: 

First, I did a general scan to look at the big picture. Right away, I saw two sacs, but something was wrong. One of the sacs was normal in size and contained a healthy-looking baby with positive fetal heart motion. The second sac was much smaller and contained what appeared to be a small yolk sac. However there was no sign of a fetal pole and there no motion of any sort detected within the sac. Just a look at the disparity between the sizes of the two gestational sacs made it clear that something was different between the two. Even Caroline and Darryl were able to tell.

Sac A, seen here on the left contained a fetus with positive fetal heart motion. Sac B, seen here on the right is much smaller and just more "shriveled" in appearance. There does look like there's something in there, but it appears to be a yolk sac only. The actual fetal pole is too small to be seen and there is no fetal heart motion.

I then focused on visualizing sac A from a different angle. This second picture shows the same baby as the one seen on the left in the first picture. The measurement of the baby from head to butt is known as the Crown Rump Length. According to the table of average fetal sizes, it was expected to be about 16mm today and when I measured it, it was indeed 16mm. The yolk sac ( not seen in this picture) was measured to be a very small 3mm, which was good news, as we don't like it at this early gestational age if the yolk sac is very enlarged, as that can lead to a higher risk of miscarriage or fetal abnormality.

You can visualize the very early outline of a baby as the head tilts downwards and to the left. The circular area with blackness inside is the baby's head, with normal fluid seen inside it. You can see what look like two little angel wings. Those represent the arm buds. In this angle you can't see the leg buds, but there are there.

So, I explained to Caroline that one baby was super healthy and looking as perfect as it could, but the other one had ceased to grow and was no longer living. When a woman becomes pregnant with twins, or triplets or more, there is always the possibility of something happening to ONE baby, but not to the others. Most of the time, this is because something is genetically not quite right with that specific one. This is a source of mixed feelings that can be very confusing. On one hand, if you told Caroline last month that she would be carrying a single healthy baby, she would given anything for that to come true. However, it's normal human nature that once that notion of twin babies enters your imagination, then anything less feels like a loss. Fortunately, Darryl was there to comfort her.

The next challenge is to stay positive while awaiting the next ultrasound. It is a common, rational fear after losing one baby, that the next ultrasound could reveal similar devastating news. Caroline dried her tears and she and Darryl left the office holding hands with ultrasound pictures of their baby in the other hand.

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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.

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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.

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June's story has spilled over a bit into July

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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.

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June's story has spilled over a bit into July

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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