Cue tears

I started Lupron on Sunday.

I had thought I was done with Lupron after moving to an estrogen priming/antagonist protocol for IVF 3 and 4.

But Dr. Sh.er uses an agonist/antagonist conversion protocol, which starts with a week of tiny Lupron doses (10 IU once a day for 4 days, then 5 IU a day for 3 days).

Apparently, that's not tiny enough - Lupron tears started last night.

I was irritable and sensitive all day, and finally at night I reacted poorly to a funny comment by my husband, and he said 'are you pmsing', and I said 'no I'm on Lupron', and we realized that was behind the whole day of emotional muck.

Oh, and yesterday was my birthday. :D We actually celebrated it over the weekend, when we went up to Sonoma, and we had a fabulous dinner on Sunday night with my husband's sister and her husband, as her birthday is 3 days before mine. And we'll celebrate with my family next weekend.

I am glad to be starting meds for IVF 5.1 - I much prefer the feeling of making forward progress to the feeling of waiting around for things to happen. And even though this is just going to be one of three small milestones on the way to December/January, and even though I have to figure out what we're doing about the DQ Alpha match (I emailed Dr. Sh.er with some followup questions but haven't heard back yet), moving forward is good.

Oh, and I'm extremely happy that Dr. Sh.er lets me do the subcutaneous shots anywhere I want. Upper thigh happens to be really easy for me, and it's nice to give my tummy a break.

Lupron this week, then Cetrotide and estradiol valerate next week.

Hope everything had a nice Memorial Day weekend!

Not the type of surprise I like

(Warning, this is going to be a long, detailed, post.)

I had my followup phone call with Dr. Sh.er yesterday. (He does this after every phone consult, whether or not you're doing a cycle with him.)

Remember that in our first phone consult he wanted us to get tested for a possible DQ Alpha match; although he thought it was unlikely, he wanted to rule it out?

Well, we didn't rule it out. We have a partial DQ Alpha match. Dr. Sh.er believes this, not my endometriosis, explains my elevated NK cell levels and TH1:Th2 issues. We thought we were dealing with diminished ovarian reserve and immunological issues that were manageable. Instead we're dealing with diminished ovarian reserve, and a ~50% chance per embryo that I can carry it to term, even with managing the immunological issues.

My understanding in layman's terms is that the DQ Alpha gene from the paternal side sends a signal to the mother when the embryo is trying to implant, telling the mother to recognize this embryo as "safe" (e.g. don't have your immune system attack it). If the DQ Alpha gene happens to match the mother, then this signal gets confused. With a partial match, 1 out of 2 embryos will match (there are 2 genes that provide this signal, and one gets used in the sperm contribution to the embryo). With a complete match, 2 out of 2 embryos will match. Matching embryos are very unlikely to survive to birth - the NK cell activity gets higher and higher, and eventually Intralipids can't control it.

Since I'm not a doctor, and that's just my understanding of how this all works, here's a link to Dr. Sh.er's recent blog about this topic: Understanding Immunologic Implantation Disfunction"

What this means for us is that a CGH normal embryo will still have only a 50% chance of being compatible with me. And because the match is between the sperm and the uterus, not the sperm and the egg, it means donor eggs aren't a solution - I'd still have a 50% chance for each embryo.

So... in the short term this doesn't affect anything regarding our three planned retrievals. But... once we figure out how many CGH normal embryos we have, we're going to have some difficult decisions about what to do with them.

The safest path would be to use a gestational carrier (who is screened to make sure she doesn't have a partial DQ Alpha match with my husband). That would give each CGH normal embryo the 72% live birth rate chance that Dr. Sh.er expects.

But... I really want to be pregnant. But... the idea of another miscarriage is daunting.

I don't know yet what the chance of success with a matched embryo is - it's not 0%, but it's low. And I don't know how quickly we'd know that it's a problem embryo. (He only transfers one embryo at a time in cases of a DQ Alpha match, so that a problem embryo doesn't lead to miscarrying a normal embryo as well.)

Since I don't expect to have very many CGH normal embryos, I'm not sure I can risk them in my body.

Which is devastating.

I really didn't expect this - our two miscarriages were missed miscarriages, with chromosomal issues. And my pregnancies, short-lived though they were, were easy.

It makes me very sad. And I feel (again) betrayed by my body.

We could choose to use a gestational carrier for our embryos, since we're likely to have only a few. Or maybe use a GC for the first one, and then risk the others in my body. Or use GC for our embryos, and risk donor egg embryos in my body since we're likely to have many more to work with. It's a whole set of options I didn't think I had to face, and it's deeply upsetting to have that all turned upside down.

All that said, I'm glad to know. I would much rather make an informed decision, weighing the risks, than to transfer CGH normal embryos in my body and wonder why they either a) don't take, or b) keeping miscarrying.

If you're feeling supportive tonight, please also visit Augusta who got some devastating news today.

IVF 5.1

It's crazy to write IVF 5. How have I possibly ended up here? It doesn't depress me, it's just shocking that I've gone through that much in the past 15 months.

I'm defining IVF 5 to consist of IVF 5.1 (retrieval in June), IVF 5.2 (retrieval in August), IVF 5.3 (retrieval in October), and then IVF 5 finishes with transfer in December or January (assuming we have good embryos to transfer, which is what I'm doing).

So. Last Wednesday morning my husband and I went to have blood drawn for the DQ Alpha testing. That got sent off, and results should be back in a few weeks, although even if we do have a partial match (which no one really suspects), it won't matter until transfer time.

I also had my nurse consult last Wednesday, just to talk through the medications and pre-cycle testing that I need to redo. Since most tests are good for 18 months, we didn't have to redo them when we started IVF last year, but now they're too old. This is going to be a very different protocol than any of the ones I've done before (micro dose lupron flare, which I should never have been on, and estrogen priming/antagonist which worked reasonably well).

For the gory details, read on...

I'm on birth control pills now - at the end of May I have a week of Lupron in the morning (10 units while overlapping with BCP, and then 5 units for 3 days after that). Then I do a half dose of Cetrotide (like Ganirelix) for about a week, with estradiol valerate injections twice during that week. The following week (when I'm on my trip in Mexico), I start estradiol suppositories in the evenings, start Gonal F at a super high dose in the mornings, along with a full dose of Cetrotide, and twice-weekly estradiol valerate shots continuing. I also start Luveris that week. Then I fly to Vegas and we find out what all those meds are doing to my follicles.

Whew!

I picked up the cheaper meds this week at my local compounding pharmacy (lupron, estradiol valerate, my Novarel trigger, and the estradiol suppositories). The 7 (!!) Gonal F pens, Cetrotide, and Luveris will be coming week after next from Freedom Pharmacy.

The bloodwork I had to have redone was TSH, prolactin and rubella. I also have to have a physical done (form for my local doc to fill out, which will happen on Friday morning) and I may need to get my pap smear done since it's slightly more than 12 months old. I also faxed the forms to my ob/gyn and previous RE to have my records sent to Dr. Sh.er.

I'm happy to have a plan and very curious to see how I respond to this vastly different protocol. I booked our flights to Vegas, and am working on the hotel - since my husband will be working remotely, and we'll be there a whole week, we're going to stay somewhere that has kitchens/laundry. Also booked us to see a Cirque du Soleil show that we haven't seen yet (since they keep opening new ones there.)

I've decided to largely stay off twitter for the rest of this year (e.g. not checking it multiple times a day). I'm not going to have "progress" for 7 months, and it's too hard to see BFPs and pregnancies progressing while I'm in limbo (for a good reason, but still in limbo). I'm still reading and commenting on blogs, and I'll be on twitter more around my retrievals when I have interesting info to share, but I'm focusing on the blog for now.

Not my favorite day

This is my fourth Mother's Day since starting our journey. And I know there will be at least one more Mother's Day childless since the earliest our transfer could be is December or January, making next August-September the earliest we could actually have a baby.

And last week was one year since our first miscarriage.

So it's been a rough day. I went to brunch with my family/grandmother/aunt/cousins, and then spent the rest of the day with my family. Of that group only my immediate family knows about the miscarriage(s) and none of them realized it's been a year.

*sigh*

And my husband just left for five days on a business trip. (On the bright side it's much easier to have him leave this year than it was this time last year... I don't recommend being solo a week after a miscarriage/D&C...)

I'm happy to have a plan for this year and happy to be working with Dr. Sh.er and try a change in protocol. But it's been a long journey and right now it feels like there's still a long journey ahead.

I have a post about my chat with Dr. Sh.er's nurse with more details about my impending retrieval cycle. But I think I'll post that separately in the next day or two.

Gulp

I just paid my deposit to cycle with Dr. Sher in Las Vegas starting with the June 20 cycle.

I also just emailed my current RE, letting him know we were going to do this last-ditch effort with my eggs with Dr. Sher. I had some stress about that, since we are very grateful to him *and* if my eggs don't work out, would like to work with him for donor eggs. But he sent a nice note back hoping that don't need to do donor eggs. Phew.

I have a nurse consult on Wednesday to talk through scheduling and meds and stuff.

Today is CD 2 - my body had a perfectly normal, 32-day cycle last month, which was a relief. I haven't had a natural cycle (e.g. not recovering from a D&C) since last September, and that was the first one since January 2010.

My husband has been very supportive of my investigating Dr. Sher, and trusts my research and my instinct on what the best option for us is. The financial aspect isn't actually very different (3 cycle embryo banking with Dr. Sher costs about the same as two regular IVF cycles with my current RE), but the medications will be more expensive (estimate is $8-10k of meds per cycle - up from about $5k per cycle now), and thinking about it as one big lump sum is intimidating. (Email me privately if you're interested in the specific numbers.)

Traveling to Vegas will add to the cost - flights are about $150 roundtrip right now on Southwest, and hotel will be $100/night. For this first cycle, my husband will spend the entire time with me in Vegas (working remotely), but for future cycles we're likely to have him just fly in at the end for his contribution. :)

One interesting facet of the embryo banking plan is that I can start with a 2 cycle embryo banking plan, and up to my first egg retrieval, can upgrade it to a 3 cycle plan. I strongly suspect we'll want to do 3 retrievals, but if I happened to have tons of eggs, I might consider doing just 2. Anyway, it's nice to have some flexibility there.

Someone asked last time in the comments about why we're doing CGH and why I'll be on the estradiol. The estradiol is to prime my follicles so they're more responsive to the stimulation medications. With diminished ovarian reserve, estrogen priming is a trick they use to increase results. CGH is our choice - having had two miscarriages that would have been avoided if we'd done genetic screening, I can tell you I would pay ANYTHING to avoid going through that again. The physical and emotional cost of a miscarriage, not to mention the delay while you're pregnant find out it's not good, recover from the D&C, etc., is awful. Even if we end up doing donor eggs, I suspect I'll want to test the embryos to make sure we're only putting back good ones.

I'll post again after the nurse consult on Wednesday, but I think I"ll be starting medications in about 3 weeks.

Thanks for all your input!

Second opinion

Yesterday afternoon I had a long phone conversation with Dr. Sh.er. I was interested in his opinion of how to treat my immunology and diminished ovarian reserve, as he's expert in both areas.

He gave me a lot to think about.

Much of the call was a professor-style lecture on how natural killer cells work, and how they interfere with implantation. He'd looked at my records before the call (although some things I pointed out during the call, which I don't mind - I sent a LOT of records). We were on the phone for over an hour.

For my immune system stuff, he would not use Humira, which he doesn't believe is helpful. He does use Intralipids, and also uses prednisone. He would (and in fact is sending me a lab order to) test me and my husband for a DQ alpha match (which interestingly, is now treated with Intralipids, vs. the blood-based treatment they used to do out of the country). He thinks it's quite unlikely we are a partial or complete match, but since the protocol would change dramatically, it's important to rule it out.

For my protocol, he would use an agonist - antagonist - agonist approach. Birth control pills, overlapped with lupron, then 1/2 dose ganirelix, then estrogen priming with estradiol shots every other day, then start gonal f at a very high dose while continuing estradiol twice per week. After 5 days of gonal f, the dose drops a bit, and then he uses luveris until 2 follicles are over 18mm and 50% of follicles are over 15mm.

He doesn't believe baby aspirin is helpful, so I'd just be on Lovenox for the clotting issue.

Probably the most important factor is that he strongly encourages that we do embryo banking. Meaning we would do 3 back to back retrieval cycles, then send all the biopsies off for CGH, then transfer after the results come in. That way we a) collect as many eggs as possible while they're 36 years old (I turn 36 at the end of May) so that we have a chance at a second genetic child, and b) only pay for CGH once instead of multiple times. If we didn't bank embryos, by the time I'm pregnant, have a baby, and finish nursing, my eggs would be 2-3 years older, harder to get given my diminished ovarian reserve, and less likely to be normal.

That would mean doing retrievals in June, August and October, and then a transfer in December.

While I'm not in love with the idea of not being possibly pregnant until December, we do want to have more than one child, and I think this is our best chance of doing so with both our genes. And it would make this year very predictable schedule-wise (the clinic times cycles, so I'd know ahead of time when I'd need to be in Vegas). And I wouldn't be doing immune treatment until November in prep for a December transfer.

With a CGH normal embryo, and a uterus that's normal immunologically, he's getting a 73% live birth rate per embryo.

What I found fascinating (and scary) is that a FISH-normal embryo (where they test 9 chromosomes) is only CGH-normal 55% of the time (CGH tests all the chromosomes). So in IVF4, the FISH-normal embryo that we transferred, given it didn't implant, was very likely not actually a normal embryo. Argh!

Now 3 cycles of retrieval doesn't mean we'll have a ton of embryos. Typically we get 2-3 per cycle. But that would still mean going into testing with 6-9, even if his protocol doesn't improve our rates.

I'm talking with his office manager today to find out how much this will cost, and to learn more about the timing of each cycle.

I'm thinking of this as our last ditch effort to use my eggs. I think working with Dr. Sher would give a sense that we've tried everything we can to make it work. And if come December we don't have any normal embryos, or don't get pregnant using the ones we do get, it will be easier to move on to donor eggs. If we stay with our current doctor, I think it's harder to draw a finish line and move on.

So lots to think about. Retrievals in Vegas would mean being in Vegas from Day 7 until retrieval, every other month. Which is a pain, but manageable. It's only a 90 minute flight from Northern California.

Would love to hear from anyone who's worked with Dr. Sh.er, or anyone who decided NOT to work with him.

Update:

I got the pricing info. a 3-cycle embryo banking package + FET package works out to about the cost of 2 cycle with our current RE. I think meds will be higher, since I'd be on higher doses. It's scary to think about this much money, but it's what we'd likely be spending anyway. And it gives us the chance to have something to freeze. I also got scheduling info - the June cycle is June 20, and that's when I'd have to be in Vegas. Miraculously, this should work perfectly with my vacation to Mexico the week prior, although I'll be doing shots while I'm there.

It is completely terrifying to think about the amount of money we'll be spending if this *doesn't* work and we move on to egg donors. Easily this much money again. *gulp*

Still here

I'm still here -- just quiet because usually it's appointments and milestones that drive my blogging.

We had our WTF phone call today with our RE. He said what I've been thinking, which is this was the cruelest cycle. We had everything lined up, normal embryo and all, but it just didn't implant. (My beta was 1, so he doesn't think it even tried to implant.) Based on how the cycle went, there's nothing he would change -- we're just rolling the dice each time to try to get everything to line up.

Which is basically what I had concluded. It's frustrating, since it's $20k a pop now with PGS...

Speaking of which, I asked about any financial help -- e.g. a discount -- and he said they don't do that for fee-for-service. If we end up using a donor, we can do a shared risk plan based on her FSH (my FSH is the only thing preventing me from doing it). So this next cycle will take us to the $100k mark spent on IVF so far. Yikes.

The other thing we talked about is timing the next cycle around my vacations. We're going to do birth control pills immediately followed by estrace, which will do the estrogen priming while the birth control pills get out of my system. Hopefully that'll work.

The reason we're doing this is that I want to start stims on June 19, right after I get back from vacation #1 (which is active, so can't do it on a 2ww). With natural cycles, the timing is too unpredictable, and if we just did estrogen priming with my next cycle, we'd be doing stims in early June, which won't work.

So we're only pushing things about 3 weeks, and I can live with that. (Also, I really want to go on this vacation. :D) A little more time with my husband, injection- and hormone- free, is always good for our marriage.

I wish there was a silver bullet, but after 4 IVFs we have a pretty good idea of what worked. And this last cycle we just rolled the dice badly on implantation. We now know we can make a normal embryo, and my lining was good (as always) and my immunology numbers were great (aka normal).

I have a phone consult with Dr. Sher on Monday -- I'm most interested in what kind of protocol he'd use for me. Clearly the antagonist protocol works best, but I know he tweaks it to optimize for diminished ovarian reserve patients...

Not much more to report. Moodwise I'm ok. I generally pick myself up pretty fast and start aiming for the next cycle. I have nurse and financial consults for IVF5 the first week of May, and that'll give me my calendar for up to June 19.

Sending sticky thoughts to the big bunch of ladies in their 2ww's right now!