On the day when patients get their inseminations, many times, we have to face challenges with the scheduling. Aimee had called me the day before the insemination in a panic because she found out that Boyd had to leave town on a short road trip. This was for a baseball tournament for the team he coached. Fortunately, we were able to figure a way around this. So, Aimee showed up Saturday morning with a warm box of donuts for the office. We thanked her with a smile as we received the thoughtful gift. Even though we get more than our share of sweets, we still appreciated the kindness. One hour earlier, her husband, Boyd had dropped off something quite different, a specimen cup with the semen sample that he produced at home. He had gotten up early in the morning and had done his thing. One of my staff was kind enough to come early to open up the office and begin processing the specimen. This allowed Boyd to make it out of town on time. While Amy waited in the waiting room, we finished up processing the sample.
There are several ways to prepare sperm for an intrauterine insemination. Raw sperm can NOT be injected into the uterus safely. All the stories about people doing their own inseminations at home with the turkey baster involve putting the sperm into the vagina and NOT into the uterus. Nature never intended for the chemical substances in sperm (known as prostaglandins) to enter the uterus. Under natural conditions, when the sperm is deposited into the vagina during sex, the liquid, known as the seminal fluid, stays there until it eventually leaks out. It is only the actual sperm cells, the "swimmers", that leave the seminal fluid and make the long journey up into the uterus and tubes. The prostaglandins have the potent power to make smooth muscle contract violently, so if placed into the uterus, the uterus will get very angry and start cramping very hard.
I once got a call from a referring OB/Gyn who got it into his head to try doing inseminations on a patient for the very first time without learning how to do it properly. He had taken the husband’s sperm and drawn it up with a syringe and then injected it all into the uterus without doing any sort of wash. The patient was on the exam table howling with pain in the background as the panicked doctor asked me for help. He wound up giving her pain medications and had her ride it out. The next month, she was referred to us and we helped her get pregnant with a properly washed IUI. It did take a lot of talking on my part to convince her that this time it wouldn’t be painful.
Anyway, the three most common types of sperm prep are the simple wash, the Swim-Up and the Gradient Prep.
The simple wash is just that, a simple wash. The raw sperm is mixed with a special solution which is especially formulated to mimic natural Fallopian tube fluid. The ingredient list of nutrients that nourish the sperm during the insemination process reads like this:
Sodium Chloride
Potassium Chloride
Magnesium Sulfate, Anhydrous
Potassium Phosphate, Monobasic
Calcium Chloride, Anhydrous
Sodium Bicarbonate
HEPES
Glucose
Sodium Pyruvate
Sodium Lactate
Phenol Red
Bovine Albumin
These help provide the proper pH and osmolarity to keep the sperm happy and alive. Then, the mixture is centrifuged at speeds high enough to separate things, but not high enough to damage the sperm. All the sperm will get pulled into the bottom of the test tube, along with all the other solid stuff such as bacteria, dead sperm, white blood cells, red blood cells. All these particles form a visible pellet. The liquid that has all the prostaglandins in it stays at the top. We draw up this unwanted liquid (which has the prostaglandins in it) and discard it. With a simple prep, we take the pellets and dissolve it back in a little bit of fresh media before insemination into the patient. This is intuitively a bad way to do it, because you are not only putting in the good sperm, but you are also putting in the junk. It is safe because the prostaglandins have been removed, but Simple Wash IUI’s have been documented to result in pregnancy rates that are only half as good as when we use the other two prep methods. We almost never do a simple wash. The only times we have ever done it was either because the sperm sample was so poor that any processing would jeopardize losing all of the meager sperm that was present or because the patient is in a real hurry. In the first case (very poor specimen), this almost doesn’t matter, because it’s quite unlikely that patients will get pregnant when the sample is that poor. In the second case (time constraint), simple wash is a very fast method of prepping. For example, one patient wanted to do an insemination right before leaving for a vacation. It was a morning flight, so we had a very tight time window. Well, Murphy’s law dictated that her husband, who had no trouble producing the previous month, wound up having a hard time ejaculating that day. Eventually he succeeded, but two hours after we had originally planned. So we had no time to do anything other than a quick spin and wash.
The sperm prep method that we like the best is the Swim-Up. We start out with a simple wash first, spinning everything down into the pellet. Then we discard all the old liquid that is above the pellet and replace it with fresh media. Then, under controlled temperature and environment, the fresh media is allowed to settle above the pellet for an hour. What will happen is that the good swimmers in the pellet will break free from the pellet and swim up into the media, leaving all the dead sperm and debris behind. After giving it an hour, we will take the liquid only and leave the pellet behind. The liquid should contain clean media in addition to any of the champion swimmers that made it out of the pellet. We then take THIS and spin it down again, making a new pellet that is composed of just the most motile sperm.
The gradient prep is another method that results in a prep that is as good as the Swim-Up. It involves layering a test tube with special media that has been formulated to have different densities. It is specially formulated so that when spun, the good sperm will end up in a very specific segment of the column that can then be isolated and extracted.
Most reputable centers will do either the Swim Up or Gradient preps, although I do know of a very large center that as of the 1990′s, was still doing simple washes. Not suprisingly, there were long periods of time when their IUI pregnancy rates were less than 4%, in comparison to the general expectation of 5-15%.
We called Aimee in from the waiting room and then privately told her that the sperm prep was ready. I then explained to her what to expect for the IUI. Now, bear in mind that different patients react differently to the process, but the routine is fairly similar. It starts out very much like having a Pap smear. The speculum is inserted gently and the cervix is found. Then using a cathether attached to a syringe full of the finished sample, the sperm are injected into the uterus. We have custom tables that can be tilted gently to let gravity aid in the upward flow of the sperm. Some studies have shown that tilting the patient head down after IUI can improve success rates. Note that this is NOT true of regular sex. The difference is that with sex, the sperm is in the vagina, so tilting upside-down only results in the sperm pooling in the top part of the vagina.
In the diagram, point A represents the inside of the vagina. This is where sperm is deposited during sex. Almost of all it is will end up leaking downwards eventually. The cervix is just above point A and is the opening to the cervical canal that leads into the uterus. During an IUI, the sperm is deposited very deeply at point C. The triangle surrounding point C represents the uterine cavity. The top corners of the triangle are where the tubal openings reside. So when you do an IUI and then lie upside down, the sperm flow easily into the tubes. If you lie upside down after sex, the sperm pool in the upper regions of the vagina represented by point B. In medical terms, these areas are known as the vaginal fornices.
I completed the IUI, which was completely painless, according to Aimee. I then did another ultrasound and saw the following:
Right ovary: (30×21) (24×19) (18×18) (16×15) (14×14)
Left ovary: (22×18) (21×19) (20×20) (14×12)
Lining: 12mm triple layer with the IUI fluid seen distending the cavity.
Minimal free fluid seen.
Imagine seeing a room with one balloon in it. Pretend you go in and measure it to be 15 inches. You come back to the room two days later and see one balloon which measures 18 inches. Since you only have one balloon, it’s pretty easy to infer that this is the same balloon, but it has been inflated a little bit more. Now imagine a room full of red balloons of many different sizes. You can measure the size of each one and write it down, but there are also a bunch of tiny barely inflated baby-size balloons that are so small that they are not worth measuring. Then you come back two days later and see different balloons of many different sizes. Again, you measure the sizes of these. The problem is this. You have no way of matching the balloons seen on the first day to the ones seen on the second day. So, if one of the balloons from day one pops and is gone, you have no way to accurately track it, because you still see a bunch of balloons which might be the same one from two days before OR it might be one of the little unmeasured ones from two days before, but which has now grown big.
So, in Aimee’s case, I could guess that the huge 30×21 today was the 24×14 from Thursday. I’d probably be right, but I can’t be 100% sure. It’s very possible that the 24×14 from Thursday has popped! And the 30×21 today is actually the 16×14 from Thursday. I think you get the point. It appears that none of Aimee’s follicles have ovulated. What we are seeing today are the large ones from Thursday after they’ve all grown a bit more. We even see some extra ones, which most likely were the small, unmeasured follicles from before. Of course, if we looked today and saw that everything was gone, we could be confident that all the follicles had ovulated. As it stands, I told Aimee that most likely all of her follicles were still not ovulated. Sure, it’s possible that maybe one had ovulated, but we’re sure that most of them have not.
The fact that there was not a lot of free fluid seen supports the conclusion that nothing had ovulated. Imagine that these balloons were actually water balloons. If on the first day you see a bunch of balloons and on the second day you also see a bunch of balloons, what could you conclude if you also saw a whole lot of water on the floor? You can infer that some of the water balloons must have burst and relased the water onto the floor. But since Aimee had minimal fluid, this was probably just the small amount of regular physiological fluid that all women have in their pelvis and NOT any extra water from a popped follicle.
So what do we do now?
One choice would be to bring Aimee back tomorrow and do a second IUI. This could boost her odds of getting pregnant. BUT, we are already a little nervous at this point. Even though none of these follicles had ovulated, it is very likely that they will do so in a few more hours. And since there were so many of them and since this was her first cycle, we actually decided to be grateful that they hadn’t ovulated. We agreed not to do a second IUI tomorrow. Instead, I brought Aimee back in two days to do another ultrasound. This time, all the large follicles were gone! There were only a lot of medium sized ones 13mm and under. Also, as you can guess, there was a ton of free fluid seen. Aimee had ovulated.
Now bear in mind, had this been Aimee’s third insemination attempt, we might have gone aggressive and proceeded with a second IUI, but again, we always customize our decisions based on the specific circumstances and we shouldn’t treat patients with a cookie-cutter formula.
Aimee was started on progesterone supplemention. And the suspenseful waiting period began. We will return 10 days later when Aimee comes back for her pregnancy test.
