Rolling the Dice, Fingers Crossed

After much discussion, some tears, and a whole lot of wallowing in self pity, E and I have cleared our heads, discussed our different options and decided to roll the dice. Beginning with my next period, we are going to be attempting IUI.

We went with this incredibly scary decision for a number of reasons.

Success. For starters, this is our best chance. People with Fragile X Premutation infertility don't respond well to the stimulation hormones required for IVF, so I am unlikely to produce many eggs for PGD testing. Most have better luck getting pregnant naturally, or with IUI as long as their ovaries are still functioning. I'm not entirely sure why this is. With the extra methylation of my CGG repeats, it could be that the protein necessary for ovarian stimulation is being used up by extra mRNA :/  My FMR1 gene is still functioning just fine since I don't have Fragile X, I have normal brain develop and am intellectually normal, but there's definitely some deficiency in my ovaries.  I'm hoping that since I'm still ovulating without assistance that my ovaries will oblige me and respond at least decently to the IUI drugs.

Cost. It feels horrible to be basing fertility decisions on money, but there's no way to get around the cost of IVF. Given my likely poor response to stimulation, we'd probably have to do IVF, or at least mini IVF, several times. Although Kaiser will cover PGD, it will still run us 20-30k per cycle.  Mini IVF would be less expensive, but we'd only get 1-2 eggs per attempt and 50% of them would probably be positive for Fragile X. Kaiser will cover unlimited IUI attempts for us, although the national average is about 4 attempts per pregnancy and most people don't try more than 6 times if they're unsuccessful. If IUI produces no results after several attempts, we will still have IVF in our back pocket and USC Fertility will give us a 20% discount because we're Kaiser members.

Information. Even if IUI doesn't work, I'll be taking the drug Menopur which is also used for IVF. Given that it takes awhile to figure out the right combination of hormones to stimulate ovarian production, IUI will give us a lot of information on how my body responds. Although we're only trying to stimulate one or two eggs with IUI, it would be nice to know if my body can be stimulated to make more so we'd have more for PGD.

(source)

On the flip side, we're taking a very big risk with IUI. We have a 50% chance that if it works, our baby would have Fragile X and we would have to terminate. Since we won't be able to do any testing on the embryos beforehand, we'd have to rely on CVS testing at 10-11 weeks. The cells would then have to be cultured, which could take up to two weeks, and then tested which could add another week. We probably wouldn't have an answer until 14 weeks and then we'd either get good news or bad news. Our RE has suggested that we schedule a termination in advance to make sure we wouldn't have to wait even longer in case the news was bad.

The notion of terminating a desperately wanted baby is terrifying. I'm a strong supporter of women's rights and fiercely pro-choice, but I never thought I'd be in a position where I'd have to make this decision. We spent so many years carefully trying to avoid pregnancy, and if we'd been 16 and stupid I think we would have terminated without guilt because it would have been the right decision. At this point in our lives I naively assumed that we'd be taking home any baby we got pregnant with, when the reality is that 50% of the time we won't be.

I'm also not sure how many terminations I could endure. I know other carriers of horrible diseases often undergo several terminations for medical reasons, but if IUI works and we have to terminate the baby, I'm not sure if I could try IUI again. It would still be our best chance for getting pregnant but I just don't know if I could take that chance again. I really hope we won't have to.

Options: IVF with PGD or IUI

People in my situation have two not so fabulous but viable options for having a healthy genetically related baby.

Option A: IVF with PGD, my eggs and donor sperm
Option B: IUI, my eggs and donor sperm

Option A is quite expensive. It would involve doing IVF which would run us about $20-$30k. I am unlikely to respond well to stimulation so we aren't likely to get very many eggs, no matter how many hormones they throw at me. Any eggs we did get would be fertilized with donor sperm and biopsied on day 5 for PGD testing.  Luckily, Kaiser will cover PGD which will save us about $8,000 but it can be hard on the embryos and not all will make it. If we were lucky enough to have healthy embryos, we would do a FET, or frozen embryo transfer and hope that they take. We may potentially need to do IVF several times to get healthy, viable embryos.

Option B is essentially a roll of the dice with 50/50 odds. We would do an insemination with donor sperm and hopefully get pregnant. We would then do CVS testing as soon as possible, probably around 11 weeks, and then wait with everything crossed for the results to come back. If they come back negative, we get to have a healthy baby. If they come back positive, we would need to terminate the pregnancy. Kaiser will cover unlimited IUIs for us, so the bulk of the expense would be donor sperm, about $4,000 for 5 vials, but we would have to endure a 50% chance of terminating a desperately wanted pregnancy at around 14-15 weeks. I don't know how I'm going to cope with that.

(Source)

Our other options for a baby would be using an egg donor and sperm donor, adopting left over embryos, or adopting a baby.

I was originally leaning heavily towards IVF with PGD but IUI may potentially yield better results. People with FXPOI have a better chance of getting pregnant naturally or via IUI since we respond so poorly to fertility drugs. E is on board with either decision, though he would strongly prefer the option that doesn't bankrupt us.

Fragile X Premutation

You might recall from my last infertility post that the genetic counselor decided to test me for Fragile X as a last attempt to explain my ovarian failure. Since my family has no history of Fragile X, any type of Mental Retardation or even Autism, I didn't think much about it. As it turns out, this was a bad move on my part.

As I hung up from a very successful conference call for work, my cell rang again in my hand. I didn't recognize the number, but since I'd been talking to three different states, I assumed it was work related and picked up without much thought.  Instead of my web developer, it was the genetic counselor from Kaiser. In a voice too cheerful for the subject matter, she gently explained that my results came back positive for a Fragile X premutation. Normal people have between 0 and 54 trinucleotide repeats in their FMR1 gene on their X chromosomes, although some argue that there's another intermediate category between 45-54 repeats. Both of these repeat categories are stable, if mom or dad has 30 repeats, their kids will get 30 repeats and the allele will remain stable.  There might be the tiniest bit of growth in the 45-54 region, if mom has 47 her child might have 50, but the again it's fairly stable.

People with Fragile X have over 200 CCG repeats, leaving a murky grey area in between for carriers with a premutation, 55-200. My test came back with 99 CGG trinucleotide repeats, putting me squarely into the group of carriers. The problem with this category is that the larger the repeat size, the more unstable it becomes. Although my other X chromosome is normal, a repeat of 99 on my bad X has, on the lower end, an 80% chance of expanding to a full mutation if passed on. This means that if my child received my faulty X, they would likely have full blown Fragile X. This is absolutely devastating news.

In addition to the crushing fear that my child might inherit severe mental retardation, we finally have an explanation for my failing ovaries. About 20% of women with a Fragile X premutation have premature ovarian failure, FXPOF or FXPOI. Women with more than 80 repeats are supposed to be at a lower risk for POF than those with smaller repeat sizes, but apparently my body didn't get the memo. This means that all the lovely symptoms I've been complaining about for years, hello hot flashes, night sweats, and weight gain, were because my ovaries were shutting down and my hormones were tanking as they tend to do when you go through menopause. Apparently my ovaries may continue to shut off, or spaztically turn back on every so often if they feel like it and only 5-10% of women with FXPOF can have children. Thus far I still appear to be making eggs every month so we're crossing our fingers that all hope is not lost yet. As you might be able to tell, I don't feel particularly hopeful.

In addition, I have to watch out for FXTAS.  Although it tends to be a bigger problem for men with only one X chromosome, rather than women who have some protection from their good chromosome, FXTAS causes ataxia, tremors, memory loss, dementia, a loss of feeling and weakness in the lower legs, and even mental and behavioral changes.  Basically, another horrific possibility, even if it usually effects men.

If you've been following along thus far, let's take a look at our odds.

Me:
0.44% or 1 in 225 women have a Fragile X Premutation
20% of women with a premutation have POF, or 20% of 0.44% which is 0.088%

E:
0.033% - 0.05% of men have y chromosome infertility
10% of Y chromosome infertility involves a deletion in the b region, so 0.0033% -  0.005%

Can you imagine the odds of both of us having such catastrophic genetic infertility?

Seriously, what in the ever loving fuck universe.

What. The. Fuck.

Genetics Expanded

After waiting two months for an appointment with a genetic counselor, E and I finally got in to see one this morning. As expected, they had the results on E's second genetic screening which confirmed his diagnosis of Y chromosome infertility due to an AZFb microdeletion.

They were fascinated with E and the fact that he has any sperm at all. With his genetic profile, he shouldn't be able to produce any sperm but has still had counts as high as 23 million. I would have liked to talk about the particulars more, but ultimately the end result is same, 20 million or 2, his non-motile swimmers are not usable.

The counselor got more info on our families but couldn't really suss out why we both have fertility problems. For a multitude of reasons, both our families are fairly small, and with such a small sample size it's tough to draw good conclusions. We can assume that E's infertility occurred de novo, as a fluke, while mine is still unexplained. They're testing me for fragile x syndrome as a last ditch explanation, since my family consists of all girls for two generations, but it's fairly rare to have a completely silent carrier and I don't have any of the symptoms or markers for the disease aside from my lack of eggies. E was almost late for work so I couldn't get my labs drawn today and will have to go back.

The counselor was really analytical which I appreciate, I approached the situation in the same manner and it made it really easy to connect with him. He understood my desire to have 5 years of egg fertility data to look at before making a decision (sadly impossible) and suggested we come up with a wall sized algorithm to predict all possible choices.  We went over pretty much every situation from E's sperm and my egg to egg and sperm donors. I think we have a somewhat solid plan of action.

**The Plan!**
1. Get my labs done for Fragile X and possibly CMV antibody. CMV antibody status is important for picking a donor. Done!
2. Decide if E is going to have the stimulated semen analysis to confirm for sure that his sperm is unusable.
      a. If E's sperm can't be stimulated, we go with a donor
      b. If E's sperm can be stimulated and is usable, we begin proceedings for IVF with ICSI
          - If E's sperm is usable, we will gender select so as not to pass on the mutation
3. Assuming E's sperm is unusable, we need to pick the donor. I want this to be mostly E's choice. I'm thinking a local sperm bank would be best so we can order the day before it's needed and courier it over.
4. Purchase donor sperm. We need to decide how many vials we want and how many will be stored.
5. Decide whether we're doing a stimulated cycle to see how I respond and try to get a better idea of my egg reserve, or proceed directly to a medicated cycle and IUI
6. Proceed with a medicated IUI cycle
7. Hopefully get pregnant!

While I definitely still have that I might cry sensation at the back of my throat, I am feeling a little better and more prepared. My biggest concerns are that I might be pushing E and not allowing him enough time to grieve. I've been really waring with myself on what we should do next and how we can balance my time crunch with his coping and emotional well being. Today, the genetic counselor said something along the lines of "people take fertility for granted, like gravity. It's just something that's there. But the reality is that for many people it isn't". I talked about how, cost aside, I wished our rolls could be reversed because I don't care about being genetically related to my child but E does/did.

Although we already knew it, the counselor said that not being able to have biological children is horrible and devastating and may always hurt, but that's normal and okay. I think that really helped E to hear this since he's been struggling with the idea that he may never be 100% okay with not having  genetically related children. I think he understands now that it's okay for that to always hurt a little, but it doesn't have to prevent us from having a family and kids that are his in every way that matters. He doesn't have to be thrilled about it, he just has to be at peace with it. I told E the only things I need him to be 100% on are 1. That he still wants children and 2. The donor we pick. As long as he's sure about these two things, I think we'll be okay.

HSGs and Saline Ultrasounds

After much anticipation, I finally had the saline ultrasound and HSG this morning! And they weren't too bad.

The saline ultrasound was worse than the HSG, but the AFC/Exam portion of it was worse than the actual saline portion. I am definitely not a fan of the trans-vaginal ultrasounds, they are fast rising to the top of my things that suck list. The Dr. had a tough time counting follies on one side and had to press down on my stomach while pressing up with the wand which was really uncomfortable. She also had a tough time placing the catheter (speculum, dilate the cervix, thread the catheter through and up into the uterus) so it took awhile, but the saline injection itself wasn't too uncomfortable. All in all, I was really glad E was there holding my hand.

My ovaries looked fine, if rather empty, and my uterus looked fine too. The only concern was that she thinks she dislodged a piece of my endometrial lining when she put the catheter in but she was only 90% sure. If the little blob wasn't endometrial lining, it could have been a tiny polyp so she suggested I come back for another test, a Hysteroscopy. It sounds like an awful test (several needles to my uterus??? while I'm awake??) but she said if we're going to do IVF we might as well check everything :(

I'm still not sure how I feel about it, especially since I'm pretty darn sure it was just dislodged lining. She did a detailed ultrasound before inserting the catheter and it wasn't there until after she put the catheter in. If I go through with the test I'm supposed to start taking progesterone tonight which will thin out my lining and stop the 10.5mm follie she saw developing from maturing. I'm a week away from ovulating, from that little follie being ready to go. Logically I know DH and I have no chance of conceiving with 0 motility but actively preventing any chance just feels so wrong.

Since the RE had such a tough time getting the catheter in, she said she was going to leave it in so we could use it for my HSG. Then she accidentally pulled it out at the end, working on autopilot. Since she does these all day and the radiology department has less experience with cervixes, she put in a second one which was just soooo much fun -_- And as I'd read, you definitely leak saline afterwards, I didn't notice until it went down my leg, while I was still laying there and got my socks wet, ugh. I then got to get dressed with the catheter taped to my thigh, go down 4 floors, fill my prescription at the pharmacy, cross the street to another building, go up a floor and stand in the waiting room since I couldn't sit -_-

That was probably my least favorite part of the experience, the radiologist later asked me how I got there since I didn't have a wheelchair and you don't generally walk around with a catheter hanging out of your ladybits. I told her I took tiny steps lol.  After they wouldn't let E in, and the radiology tech tried to direct me into the wrong position, I was really glad that I'd had it put in by the RE, even if I had an uncomfortable walk. All the radiologist had to do was plug into the catheters IV port and inject the dye. Both tubes were nice and open, the dye shot through one side and after I tiled slightly, shot through the other, and not a single cramp from the dye, though it could have been that I was so uncomfy already I didn't notice.

All in all not too bad, a little uncomfortable but not awful by any stretch. 

SA Number 5, Christmas Hope??

We just got E's 5th semen analysis back and we are SO confused! I have been shoving supplements down E's throat  encouraging E to take FertilAid for Men, Count Boost for Men and Motility Boost for Men for the past few months and I can't believe they might actually be working. Keep in mind E's hormone levels have always been perfect, so its not like the supplements could correct something that wasn't broken, and we still don't have the results of his genetic testing yet, but look!

SA 1 at Lab A: 0.65 million, 0 motility
SA 2 at Lab B: 0
SA 3 at Lab C: 0
SA 4 at Lab C: 10 million, 0 motility
SA 5 at Lab C: 23 million, 0 motility

Again his doctor doesn't seem to be too enthused, he ordered another SA for him and said we should focus on my procedures tomorrow. The motility is still, and has always been, 0 and the morphology is always N/A, I think because they're don't grade them if they're not moving. We're trying not to get our hopes up since 23 million dead sperm are no more useful than 1 dead sperm, and they might still be genetically defective, but we're so so glad to see the number moving impossibly upwards!

Tomorrow is the HSG and saline ultrasound, I'm not expecting to see anything wrong on either test so hopefully our goodish news streak will continue. 

Merry Christmas Everyone!

Lab Results!

On Saturday we returned to the Kaiser lab for our multitude of tests. E submitted another semen sample and gave another 3 vials of blood, and I had the extreme pleasure of giving 11 vials of blood. The experience could have been horrible, but I got a wonderful tech who found the vein on the first try, even though she couldn't feel it. I'm so grateful for techs like her :)

Now that a couple days have gone by, the early results are starting to trickle in.  My TSH has come down to just below 2.5, which is still high for me but not as bad as we thought it was. It also turns out that I have the exact opposite blood type that I was told I have by Kaiser. In high school I donated blood at Kaiser for my grandmother's surgery, and a few days later was given a little card with my name and blood type on it. For over 10 years I've been living my life and telling doctors that I'm B- when, according to the newest test, I am actually A+. Mind blown. I'm not sure how a mistake could have been made at the blood bank, since I'm assuming my most recent test is accurate, but it will be nice to not need the RhoGam shot if/when we do get pregnant. I'm still waiting on the results of the other lab tests but they'll probably take a few weeks.

In even bigger news, we got E's 4th SA back and the results were totally startling! So far we've had a 0.65 million, a 0, another 0, and this last one showed 10 million! There was still no sign of any motility so we still don't know if we can obtain anything usable but the numbers were so shocking that E didn't believe them. Our doctor has suggested that its a one time fluke and we shouldn't get our hopes up but I've got my fingers crossed. We've been supplementing the crap out of his sperm with FertilAid for Men, Count Boost and Motile Boost and it would be great to know that they're actually working. His next SA, number 5, is on the 23rd and my tests are on the 26th so we're keeping our fingers crossed. 

New RE = More Tests

So after waiting over a month for the urology appointment, the Kaiser system worked a little faster and we were able to get in to see the RE on Black Friday. My overall impression of her was positive, she allowed us to share our story and explain where we are and agreed with most of our assumptions and concerns. For me, she ordered more lab work as well as a saline ultrasound and a hysterosalpingogram. For E, another couple lab tests. Once we begin the procedure for IVF, Kaiser will no longer cover anything so she would like to cover all our bases now.

I will have to go in for my labs on Monday and pick up a course of antibiotics for the hysterosalpingogram since E had to get to work on Friday and we didn't have time. The RE said she very rarely has a case where they can't find any reason at all for male infertility and thinks E might have a microdeletion on his Y chromosome. If he does, the location will play a big part in whether we're able to retrieve viable sperm. And, if we can get viable sperm that produces viable embryos, we will have to have PGD to select for female embryos since any male children will inherit the same deletion.

However, given the information we have thus far, it's likely that we're going to have to use a donor. The RE does agree that I have diminished ovarian reserve and is very concerned that we may have a rapidly closing window to retrieve viable eggs. There was also some confusion over my AFC, during the appointment the RE at the fertility clinic told me 3 and 4 follies for a total of 7. However, the paperwork he faxed over said 3 and 7 for a total of 10, which while it would be AMAZING, doesn't match up with my FSH or my memory. Regardless, the new RE is concerned that in a couple years I will not have any eggs left.

Given that prognosis, we need to think seriously about the IVF vs IUI decision. Kaiser would pay for an IUI, which would be much less invasive and inexpensive. If we were successful, it would probably be at least 2 years before we tried for a second child and by then I might be completely out of eggs. If I did still have high quality eggs left for siblings, we would need to store our donor of choice and do IUI again. If we do IVF now, it will be entirely out of pocket, more invasive and expensive, but will hopefully yield enough embryos that we can freeze some and use them for a second and/maybe third child. It would also mean we would have the same donor for all our children since the embryos would all be made at once.

We've been talking back and forth about it and have just started to casually look at donors online. We won't have DH's results for another month since they have to grow the genetic test in culture, but they probably won't be good. In the meantime, the RE wants me to take DHEA three times a day, keep taking a prenatal and see if I can get my thyroid levels down. While all my tests for the past 10 years have been below or around 1,  my last one was 3. Although it's still technically normal, numbers over 2.5 are associated with much higher rates of miscarriage so I'm going to need to do something about that.

E Update

After lots and lots of anxious waiting, E's results are in. His lab work was absolutely and completely normal, I'm actually pretty jealous of his FSH level, it was way way better than mine. Unfortunately, or fortunately? his third semen analysis came back at a zero. We aren't sure if this indicates a partial blockage, which would be fixable with microsurgery, or a genetic problem like a lack of the cells that produce sperm.

The next step is a biopsy to see if there are any viable sperm in there. You'd think since all the medical professionals agree on this course of action, that it wouldn't be too difficult to move forward. Unfortunately, you'd be wrong. E can't proceed with his biopsy with his current urologist, he needs a specialist in the urology department at a different Kaiser.  After E's results came in, his urologist said he was referring us to this new urologist. Then, he accidentally forgot to put through the referral before he went on vacation. In the two weeks it took E's urologist to get back from vacation, almost the entire month of November filled up :( We were expecting this so I had tried to schedule the appointment sooner, as both the current urologist's nurse and the new urologist's nurse knew the referral was supposed to be sent, but it was no good.

Now that the referral is finally in, the new urologist's office refused to schedule the appointment because our insurance still shows no infertility coverage. I had to explain that the new coverage is coming and argue with three different people before they agreed to make the appointment.
E has his next appointment on November 25^th, which also happens to be the day I have jury duty and we'll have guests from out of town >_< I expect it will be another consultation instead of the biopsy he's supposed to be having so at least it won't slow him too down too much.

We did get the good news that our new insurance should be in effect as of November 1st but it didn't come quite fast enough to stop the payments for our individual plans. I also called on the first to confirm the new plans and cancel the individual ones, and they had no record of the new ones. I'm assuming it takes a little while for all the paperwork to be processed on their end, but it sure isn't making things easy and the waiting is driving me nuts.

Urological Update

Today was E's urological consult with what turned out to be the director of the department. He was an excellent doctor, really down to earth and honest without being overly optimistic or depressing. E's physical exam was normal, as we had all expected, and the doctor ordered blood work and semen analysis number 3. We're waiting on the results of the blood work now and semen analysis number 3 will be on Monday.

More importantly, he advised us to manage our expectations. Don't get too high or too low. He said he has seen so many couples spend hundreds of thousands of dollars trying to get pregnant without success. That more often than not, people were not the exception to the rule and that he defined success as a baby in your arms, while most clinics define it as a positive test. That we shouldn't tie our self worth in with our ability to have biological children.

On the downside, he seemed to be laying the ground work for what sounded like inevitable bad news. He talked about friends who have wonderful adopted children. How the most important thing is E and I together as a couple, that we're here because we love each other and to not lose sight of that. I know that it's easy to do, that the stress of treatment, the hormones and failures can take its toll on your body and mind. That having a child can come to mean two different things to each partner and that even a strong relationship can be sorely tried.

The doctor said that if E's FSH results come back with a level like 40, we have no hope of having E's biological babies. Right now we're hoping for normal blood work to indicate a mechanical problem somewhere in the factory. Mechanical problems might be fixable, while high FSH, like my high FSH, can't really be fixed.  He said that if a mechanical problem is indicated, that a biopsy would be the next step. Since he agrees IVF is our only shot right now, if he found viable sperm while E was opened up, he would collect and preserve them for IVF.  I think this would save E a procedure, and potentially lots of money, since I don't think E can product viable sperm via ejaculate.

Overall, we were happy with E's new urologist. Now we just have more waiting, for lab work, for the SA, for some indication of what our next step is. We also need to determine whether we want to continue treatment with Kaiser and pursue their IVF clinic, out of pocket of course, or stick with the clinic we had our initial consult with. The urologist spoke highly of one of the IVF doctors in particular, and said he would introduce us, but I'm not sure they'd even be willing to treat me with my FSH as high as it is.

Another Blow

Yesterday the RE called and said that E's second semen analysis came back at 0. As in not One.Single.Sperm present, he might as well have poured water in the cup. This was after a one day hold, versus E's previous SA which was after a three day hold. 

While the RE had previously said he thought E's poor quality sperm was the result of genetics, he has now referred us to a urologist to rule out things like hormone imbalances and physical problems. I had asked about this during our initial consultation but he had tentatively ruled it out since E's first SA did show sperm present. It makes me really glad that we did another SA to confirm, since I was sure there had to be something more going on than just shitty genetics.

This morning, I called and set up an appointment with a urology specialist at Kaiser on the 10th. I'm not sure they are going to be able to do anything since we have no infertility coverage, but I figured it would pay to start with them before going directly to the outside specialist. The RE referred us to an excellent urologist who is one of the top in the country for male infertility problems, but he would be very pricey. Just in case, we called as got some info about him as well and he has an opening on the 17th if Kaiser is no help.  

We also have an appointment with a genetic counselor set up with Kaiser that I think they're going to cover, though the testing will likely be out of pocket. It will probably be a moot point anyway if we have to use a donor, but I am still proceeding with the intent of using E's sperm. I want to have our babies, not just a baby and I'm not ready to give up on that.