A New Direction: Donor Embryos

The outcome of this fourth Neupogen cycle is yet to be seen, but last night I hit a gigantic rock solid wall: we have too many obstacles to overcome for this to ever work. I am doctorless now because of some new policies with my specialist in NY who will no longer monitor patients out of state.  My husband's sperm fragmentation is sky high (24%) and the most recent studies are showing that a live birth with this kind of fragmentation, even with IVF, is slim to none, especially given my aging and limited eggs.  My body is clashing with his genetics with our 6 HLA matches, and even if we can overcome that with medicine/Neupogen, we can't clear the other obstacles.  What hit me last night was the truth I've been running from for these 3 loooooong years of infertility: we are NEVER going to make a healthy baby between us.  It's as if the universe is sending me a message...and I am finally able to hear it: 6 miscarriages, 5 failed medicated cycles, and 32 more failed natural cycles later.  I assumed though, that my husband, who has been so negative about alternatives to natural conception for so long (eg adoption, sperm donors, IVF, etc.), would never go for what seems like the only option left to us. In fact, his unwillingness almost lead to a divorce just 2 years ago until I gave in and dropped the whole subject. 

But tonight, I took a deep breath, said a prayer, and gave him my reasons for wanting to move on to embryo "adoption" (okay, that's not the legal term, but it makes intuitive sense)...basically to have healthy donor embryos transferred into my healthy uterus. I am completely humbled and in awe by my husband's reaction after I made my case...he said, "I love you and I want you to be happy and so yes, let's look into this."   I pressed him a bit more, somewhat in shock, and learned that he agrees with me and is actually excited about it too,  and he is willing for us to sign up and start looking at potential matches right away! We even agreed on a clinic and program in California.  To say that I am elated and on Cloud 9 would be a huge understatement: I started crying the most joyful tears imaginable  as we held each other a long time on the couch.  He is my new hero and I am falling in love with him all over again.  He amazes me...just when I think I "know" what he will do and say, he catches me off guard and shows me a side I didn't know was there. And I know it's a huge leap for him: the sadness of never having a biological child of his own...and yet, he is able to see past this. 

This is an amazing, momentous night, and I am going to look back on this day, July 31st, with deep joy, because tonight we begin the journey of a thousand steps that I truly believe will finally lead us to the miracle I've been praying for, for these many years.  The fact that my husband's heart has been changed to accept this new path is a miracle in and of itself, for which I thank God. 

And I never, never want to forget what this decision, his love, and this night means to me. This is our new direction, this is the way forward, and I am not going to look back with regret ever.  

Third Cycle on Neupogen/Lovenox/Intralipids

I am nearing the end of my third cycle on this medical protocol to theoretically fix/calm our allo-immune problems. This cycle is a BFN despite great BD timing though. On my second cycle our timing was so-so, but I had a flood of strong pregnancy symptoms early on and sky high temps that disappeared during the implantation window. I was really crushed because it feels like the protocol didn't work, although I know it could have just been a bad egg/sperm issue too.

We are thinking we may give it just 3 more cycles for a total of 6 months to try this protocol and if that doesn't work, we have will have hit the wall, officially. We have tried everything short of IVF, which we can't afford and with my few and aging eggs, probably wouldn't work.

I have been thinking a lot about whether we should pursue adoption or simply stop trying to give my daughter a sibling. It is a gut wrenching decision to be faced with and I have been hopeful, only to have my hopes crushed so many times, that I just don't know how much more I can take.  The fear of an adoption falling through puts me into feelings of absolute fear and trembling. It seems like nothing has worked out and nothing will.  I know that hope is that last thing to die...and mine seems to be on life support. 

Neupogen/Intralipids/Lovenox Cycle #1

Lord have mercy. I think this cycle is a bust.  We jumped the gun and thought I had ovulated, only to realize I ovulated later, so our BD timing was off by about 2-3 days.  Still in the fertile window, but not great timing.  A BFN today on 10DPO, so I think I'm out because I am just not feelin it and my temps have been on the low side since ovulating.

So, here is what I experienced for side effects on this first round:

Intralipids: Nothing other than a bit tired/headachey afterward. The worst part was just sitting there for over 2 hours with the dang needle. Really a breeze overall.

Neupogen: I have felt a bit achey in my joints all cycle long and the day after my first injection I felt some bone aches. Nothing much though, it's practically side-effect free!

Lovenox: I think this gave me some bloating, gas, and a lot of crampy/twingy sensations in my abdomen. The main problem with this drug is injecting it! The med stings like mad during the injection and locally at the site for about 20 minutes afterward, like a burning sensation. It leaves bruises every time at the site, most of them are not too bad, but I have one GIANT bruise the size of an orange on my abdomen. Seriously looks like I was beaten. The other problem is that a few times the injection site leaked, and leaked, and leaked blood...over 15 hours once, right through my clothing at work twice. I contacted the doctor but they just said this was not that uncommon. If it had continued I would have needed to get my platelets checked.  Argh.

So...I'm anxious to get on to a new cycle already. Now I wait for ages for Aunt Flow, who never shows until 17 freakin DPO with my long luteal phases. Had a good cry this morning, I always get so depressed around this time on BFN cycles.  Infertility SUCKS major sour pickles.  

Affordable Neupogen and Intralipids

I just put this together for the ladies on Fertility Friend on the immunology board by request, so I'm posting it here to for anyone searching! These are sometimes prescribed for women suffering from immune related loss/infertility. I have elevated Natural Killer Cells and alloimmune issues (6 HLA matches with my husband).

Affordable Intralipid Infusions

Prices may vary by region in the US, but the best price I've seen and used was by hiring the Walgreens Infusion Service to come to my home for an Intralipid Infusion: 20% IV, 100 ml, infused over 2 hours. (This was going to cost $300 at a local office with a private doctor.)

As self-pay, I paid:

$80 for Infusion Nurse
$50 for the Intralipids
$15 for Supplies
=$155.00

Affordable Neupogen
Most insurance companies (not all, so check!) will not cover Neupogen for pregnancy. I priced Neupogen from many sources, pharmacies, etc. One of the challenges with Neupogen is that it must be refrigerated/kept cold and cannot be jostled/shaken, which makes ordering it in the mail from outside one's country very difficult.

The best price I found was by purchasing a Walgreens "Prescription Club Membership" for $20 (individuals) or $35 (families) a year. By having that membership, one can save almost $100 a vial on Neupogen as well as many other medications.

At this time, the biggest savings is to purchase the 300mcg/1 ml vial of Neupgoen (not prefilled!!) and not the 480mcg/1.5ml. If you purchase it in bulk, you save a little more money too. 1 vial=$249.99 or in bulk (3+) 1 vial=$246.

My cost as of of May 2012:

4 vials of Neupogen, 300mcg/1ml = $246 a vial ($984 total)
with the Walgreens Prescription Club Membership

Neupogen is prescribed based on body weight, so it will vary a bit based on what you weigh. I am able to get a little more than 5 doses out of each 300mcg/1ml vial. It is taken starting at ovulation, so assuming I take it for 11 days each TTC cycle, it costs $492 in a BFN cycle. In a pregnancy cycle, taking it for a full 30 days, it will cost $1476 per month. It is taken for the first nine weeks, so for a pregnancy it would cost $3444 (in my case).

To me, this is reasonable given the cost of IVIG or LIT as alternatives to Neupogen. IVIG is usually about $3000 per infusion and multiple infusions are generally needed. Getting LIT involves travel to Mexico at this time, so that adds up over several visits.

A New Diagnosis: 6 HLA Matches and Absolute DQ Alpha Match

After 3 years with no helpful answers, I feel like I'm finally getting the answers we've been searching for. Not only did we discover and treat the Asherman's, but we finally had a full immune panel done with Dr. Braverman of NY, who specializes in recurrent loss and reproductive immunology.  Most of my bloodwork came out normally although I have slightly elevated risk for blood clots due to heterozygous mutations for both ACE I/D and PAI-1 (4G/5G) genes which will be treated with Lovenox. 

However, the really BIG finding is that my husband and I share way too many HLA genes! We actually share 6 genes but 3 of them are homozygous on DH's side, so that means our embryos are going to constantly look too much like me genetically (eg altered self) instead of an embryo (eg non-self).  When the body sees what appears to be altered self (like cancer), the immune system launches an all out attack. This is actually the opposite problem with organ transplants where HLA genes need to be the similar...in pregnancy they need to be different!  This may explain why my NK Cells are slightly elevated too: my immune system has been attacking our pregnancies over and over again. I am officially at 6 consecutive losses but I know there have been more that were lost so early that we couldn't get to a positive beta/HPT.  Dr. Braverman says that 5 or more matches are significant, with certain matches being more important than others. One of the discoveries is that we have an "absolute DQ Alpha" match of 4.1 (05) which is the worst possible gene because it most resembles cancer to the immune system according to Dr. Alan Beere. 

Here's our HLA gene panel:

Me:

DQ Alpha: 1.3, 4.1 
DQ Beta: 03,06
HLA A: 02, 24
HLA B: 33, 51
HLA C: 01, 05
HLA DRB1: 11, 13
HLA DRB3: 01, 02 
DRB4, DRB5

DH:

DQ Alpha: 4.1, 4.1
DQ Beta: 03, 03 
HLA A: 02, 32
HLA B: 15, 51
HLA C: 07, 14
HLA DRB1: 11, 12
HLA DRB3: 02, 02 
DRB4, DRB5

I highlighted all our matches....6 total but more like 9 with 3 of them being homozygous (the same) on DH's side. The only gene without a match is HLA C. Who knew we were so much alike? It's so weird!!

Some RE's say there is no treatment for this kind of genetic match and that a woman must use a surrogate to ever have a baby with her husband because the interaction is between her body and her husband (not her eggs). Others treat this with heavy doses of IVIG (super expensive) and steroids/prednisone and/or LIT (injecting the husband/partner's leukocytes into the woman's body...only done in Mexico at this time since it was outlawed in the US).  However, Dr. Braverman is treating this problem with success using Neupogen. Neupogen seems to be a miracle drug for this issue and while it's expensive, it's nowhere near as expensive as routine IVIG or flying to Mexico over and over again for LIT. 

Neupogen deserves a post of it's own, so for now I will list my treatment plan, which I started this cycle under Dr. Braverman's monitoring:

-Intralipid Infusion for elevated NK Cells (before ovulation, after a BFP)

-Lovenox for clotting risks at ovulation

-Neupogen at ovulation for the HLA matches

Here's a funny site describing why HLA genes need to be different in partners...apparently they match people up by analyzing their DNA!
http://www.genepartner.com/index.php/science

Wish me luck! Prayers accepted!  We're trusting God and utilizing science. :)

I Beat Asherman's :)

I am here to tell you that all is not lost if you develop Asherman's. I completely freaked out when I was diagnosed and I had a moderate case, but after 1 surgery with the right surgeon, all scarring was removed and did not return. Sometimes, it will take more than one procedure, but it can be beat. On my follow up hysteroscopy (after surgery) that was done here locally by a different RE, we were amazed that absolutely no scarring had come back and so no further cutting was required.

The KEY to beating Asherman's is not only prevention (avoid a D & C if at all possible!!), but having it treated by only experienced Asherman's surgeons. I cannot emphasize this enough because most OB's and RE's are not trained or experienced to handle AS despite what they say.  An experienced surgeon will NOT make AS worse (which many doctors do inadvertently) and they can do in 1 or just a few surgeries what it can take others many procedures to accomplish.  Basically, if treating AS is not something a doctor does every week, then don't have them treat you.

I have an HMO but found out that one of the top AS surgeons was in network. My surgery was totally covered but I did have to fly to Boston to have it done. In the end, the only expense was airfare and a one night hotel stay. Not bad for getting my uterus back in perfect shape!

The timeline was:

January 2012: diagnosed with Asherman's with an HSG at my request after 2 years of no diagnosis despite my complaints to doctors of a lighter/shorter period since my D & C's

February 2012: Asherman's hysteroscopic surgery to remove scarring followed by a round of estrogen. I treated myself with enzyme therapy (Medizym V), Red Rasberry tea and Castor Oil packs during recovery.

March 2012: Follow up hysteroscopy showed no return scarring.

April 2012: Cleared to try and conceive again!

Asherman's Syndrome: I Have It :(

Okay...I am devastated. I am going back and forth between crying, raging, being despondent, and being in denial.  My "questionable" HSG has become very definite: I have a very serious case of Asherman's Syndrome, eg intrauterine adhesions and scarring from my D & C's following 2 miscarriages. I emailed my image (above) to an Asherman's specialist in CA and he confirmed what I knew after seeing my films...there is significant scarring throughout my uterus that requires surgery. The uterus should be a solid white triangle shape without any blank space. Instead the stupid balloon is floating around in the center of my uterus (bad radiologist move) and large adhesions can be clearly seen all along the right side and in the top left near the tube of my uterus. I think I see a tiny bit more scarring near the right tube too.  My cervix and my tubes are open though...you can see the contrast flowing through them on either side.

My emotions are ALL over the place.  This looks really, really bad to me and I don't know what my chances are with surgery for full recovery.  I cannot believe that 2 RE's and 2 OBGYNs missed this over the span of 2 years. All the lost time, wasted money, the terrible grief and heartache of infertility and 3 more early miscarriages because of this...and I never had a snowball's chance in hell of having a healthy pregnancy with a broken uterus like this. I'm almost out of eggs and have lost 2 years of trying fruitlessly.

The scarring/Asherman's was caused by the 2 D & C's I had back in 2010.  It's possible that I have some retained placenta too and if I do, that's really bad news. 90% of Asherman's is caused by a D & C..some are caused by other uterine surgeries (like removing fibroids and polyps), C sections, or infections. The severity of it determines the liklihood of treating it succesfully...the statistics are low, maybe 30% when it is severe, 40% over all, but pretty good when it is mild at 80%.  I think my case is pretty severe though. Tomorrow I will see another RE who deals with Asherman's and find out what he says. Asherman's is way more common than people think and not only is it undereported but it often goes undiagnosed (like it would have for me had I not PUSHED for an HSG despite being told I didn't need one). I read that up to 40% of women can develop Asherman's when they've had more than one D & C. 

I am so furious with the OB who caused this, with the RE who missed it back in 2010 when I had a hysteroscopy, and most especially with my current RE who not only missed it on an SHG just weeks ago, but went on to tell me to "ignore the HSG" results and continue with the injectable cycle anyway.  He actually refused to order an HSG for me when I requested it previously. If I had listened to him, I would be trying fruitlessly, perhaps doing failed IVF's, until I hit menopause! Or worse, concieved only to lose a baby again, perhaps later, because Asherman's can cause second and third trimester losses.  Talk about medical negligence!  A total lack of medical ethics and terrible advice that would have put me and a baby at terrible risk. He is FIRED from ever being my RE again.

Asherman's can also cause ectopic pregnancies because when an embryo finds the uterus inhospitable, it will move back into the tubes to find a better implantation site.  No surprise now, but my suspected ectopic was in my right tube...obviously due to the inhospitable right side of my uterus covered in scar tissue.

What I don't know is if the Asherman's is THE cause of my subsequent losses or if there are still some immune issues going on.  At any rate, the first item on my list is surgery to get this repaired as much as possible. I am flying into to Boston to see one of the best Asherman's doctors, an "A list" RE on February 27th. I so hope he can help me.  If you are ever diagnosed with Asherman's...make sure you see someone very experienced with Asherman surgeries!  Most OB's and RE's can make it worse or just don't treat it succesfully. You can learn more and join the Asherman's support group at ashermans.org. 

Just wanted to report that I told me first RE that I feared I had Asherman's after my second D & C because my period changed from being 5 days of heavy/medium flow to barely 3 days of medium/light flow. Any change in a period can be a symptom following a D & C. Of course....he STILL missed it. I don't know what one must do to get a correct diagnosis for Pete's sake.

I don't know how many surgeries I will need now or how long this battle is going to last or even if there is any hope for me. I may be at the end of my long and painful journey to have another child.  I hope not.

I'm so scared...so angry...so sad.