Dq Alpha testing

[constance2]

Hello Ladies
I am new to this forum although not new to ivf and infertility.

I have had 20 IVF cycles and several miscarriages, Recently I was told I may have NK cells after a uterine biopsy so I recieved all the treatment for that, this included steroids, clexane and several other drugs with no luck.

After trying every protocol available I have recently had a consult with a US doctor who is suggesting my problem is DQ alpha matching. That is my dna and my husbands are so closely matched my body is killing off all the embryos.

Now I am in the process of sending my blood over to the US and having it tested since according to him there are no labs in AUstralia that can confirm this.

I was wondering if anybody has gone done this path or if they are aware of this particular alloimmune disorder.
thanks
Constance2

[buliej]

I'm sorry I don't know anything about this. I just googled DQ Alpha Matching to see what it is. I find it fascinating that 2 unrelated adults can have "matching" DNA - has anyone ever explained to you how this happens and what it means to be matching (how much has to match)? This may sound stupid, but given how they use DNA to solve crimes etc., I would have thought that there are always substantial differences except with relatives.

Have you done your own research to see if labs here can do it? I know there's a FS in Sydney who is the expert on NK cells - may be it's worth contacting him to see if he does or knows anyone in Oz who does the DQ Alpha Matching test or maybe who could coordinate with the US lab to instruct a local lab to do the tests.

[constance2]

Hi buliej

Yes it is not a common situation, unfortunately even relatives manage to conceive with each other, yet here we are definitely not related yet possibly sharing dna. That really is darned bad luck. This is what the immunologists refer to as alloimmune dysfunction.

I have seen both Dr Sacks and Dr Matthias, Dr Sacks (SYdney)at the time spoke to me about high nk levels and treating them with steroids. Mosty treating autoimmune dysfunction, Dr Matthias(Sydney) wanted to send my blood to the us as only 3-4 US labs have these particular tests. He also wanted me to do the DQ Alpha test. There are also a number of other tests related to immune issues they will test.

The DQ alpha test give you back two numbers each. In a normal pregnancy the father's DNA in the baby tells the mother's body to set up a protective reaction around the developing embryo. If the father's DNA is too closely matched to the mother's, there is a good chance that the embryo created by them is unable to differentiate itself from the mother's body. The mother's body then rejects the embryo because it cannot identify the embryo as a baby.

According to Dr Beers web site

"Each person gets two DQ numbers from their respective parents. Similarly, when couples try to have a baby, they also give DQ numbers to their fetus. These numbers are, for example, 1.1, 1.2, 1.3, 1.4, 2, 3 or 4".

I know that having this condition is quite difficult to treat so I wondered if anybody had any experiences with it. Currently trying to organise the logistics in flying my bloodwork to the US (Very costly exercise). But if I get an answer I can move forward knowing what the problem has been. There is nothing more frustrating as you all know than having perfect cycle after perfect cycle and getting great looking embryos with no explaination other than it must be your eggs.

Immune issues only make up such a small amount of the infertility world and nobody here is prepared to consider this. My FS kept telling me to keep trying and never suggested that there could be other tests or options to consider.

Although I have spoken to scientists at both MIVF and monash Ivf and both are working on studies looking at implantation failure they are now suggesting that imbalances of proteins /cytokines in the uterus can lead to implantation failure. Although a long way off from finding treatments.

Constance

[Loula]

Very interesting, sending you the very best wishes with your journy and that you will get an answer soon

[gab72]

Just bumping this up.

Constance, I'm wondering how you went with your blood test results from the US?

I've just sent my blood over to have the same testing as you, and will get my results in 2 weeks. The Dr thinks our problem is a DQ alpha match too. We've done 10 ivf cycles, with no hint of implantation ever.

I hope you've been able to get some direction now.

Gabbi

[constance2]

Hi Gabi
Good to hear from you!!
It was a nervous 2 weeks for me not knowing if my bloodwork was going to arrive in time for it to be tested. Unfortunately I was told some people from Australia have their test come back inconclusive because it does not get there in time. The lab still charges for the tests.

I only just got them back and surprise surprise no dq alpha match. I had 2 doctors tell me they thought it was this, Dr Matthias and Dr Sher. I had convinced myself this was definitely the problem.

The only thing they did confirm was I have Natural killer cells so they must be incredibly aggressive because they dont seem to respond to prednisolone. I have been on steroids for a year. So I think we might give the intralipids a shot. My doctor said he would call Dr Sher in the US and have a chat to him about my treatment. I dont think he has done this yet because I have not heard back.
But Dr Sher said to give the prednisolone and the intralipids a shot. I will let you know what my treatment actually is.

Good luck
constance

[gab72]

Thanks so much for replying Constance!

I have a sinking feeling my results will be much the same as yours - ie no DQ Alpha match. I too have been on steroids for the past 9 months, as well as clexane, for very very slightly raised uNK cells, but the prednisone does not seem to have made a difference.

Have you considered doing (or done) PGD? This is our next step. My Dr (Dr Sacks) believes that we will find an answer by doing it - I'm not convinced. I wonder given that you've had miscarriages, if there could be something that might be found with PGD?

Its good that your Dr is willing to consult with Dr Sher. Good luck with everything. I'll come back in and update you once I get my results.

[constance2]

Hi Gabbi
Did pgd 2-3 times, also to see if we could find answers, we had great embryos, always looked good anyway. No answers there. I then went to blastocyst where we always had at least 2 blastocysts.

So then I started thinking it must be me. Hence the NK cell discovery. The issue with NK cells is that not all of us respond the same way to steroids, so its about working out what does work for you. At least thats Dr Shers opinion.

I have also set up an appointment with Dr Mathias to see if he has any further ideas. Not sure what his treatment is for NK cells, unsure if he uses anything other than the standard steroid.
But happy to keep you updated with this also.
Let me know when you get your results.
good luck with them
Constance

[gab72]

Good luck with Dr Matthias. He's also on my list of people to consult. From what I understand he will administer iVIG and LIT (not that you would need that), so he may also do intralipids.

I'm so sorry that you've had such a long and tough journey so far. I really hope that something works for you very soon.

Please keep in touch and update me.

Gabbi

[Bengal]

Hi Ladies,

I stummbled across Dr Sher myself yesterday! I am also reading on a US site that Intrippids are quite common practice in the States, and will be very interested to hear you FS's opinions. I emailed my FS about the Intrippids yesterday, no response as yet.

Please keep us posted

[constance2]

Hi Ladies / Gabbi

Just a quick update.

Have not heard from my doctor yet, so I assume he has not been in touch with Dr Sher, I will follow up tomorrow.
I am also calling with Dr Matthias this afternoon by telephone for a 2nd opinion and I think given my nk cells and their lack of responsiveness to steroids I think I will need the works. I will be interested to see if he suggests IVIG or LIT. I always thought IVIG was impossible to get for fertility issues.

Gabbi let me know the outcome of your results when you get them
Constance

[constance2]

Hi Gabbi

Just wanted to drop a not and see if you got the results of your blood work?

Ive been having consultations with several doctors, Including Dr Matthias. Looks like I will be trying with intralipids and steroids. Hoping to start stimming this week.

Love to hear from you

Constance

[gab72]

Hi Constance,

I got the results of my blood tests just last week, and there was nothing! Not one little thing. Much like you, I was really hoping DQ Alpha matching was our problem. Anyway, Dr Sher has suggested doing a CGH cycle (with him of course!, but SIVF have just started doing CGH), and if that fails, he then suggests donor eggs.

I have an appointment with my Dr (Sacks) today, one with SIVF tomorrow and one with a Dr Lamaro next weeks who has a great reputation in dealing with women's 'issue's, particularly endo and laparoscopic surgery. I thought perhaps a fresh pair of eyes might be helpful.

So how is your cycle going to work with the intralipids - ie, will you fly up to Sydney to Dr Matthias to administer? and at what point in the cycle? A friend of mine who did a donor cycle with Dr Sher, also saw Dr Matthias for NK cell treatment, however she had IVIG. Thankfully for you, the intralipids are so much cheaper.

Do you mind me asking what other Dr's you've been talking to? Do they all agree with your course of action?

I wish you all the best of luck with this cycle, and I really hope the intralipids do the trick. Please stay in touch.

Gabbi

[constance2]

Hi Gabbi

I know how frustrating it is, just looking for a reason to understand constant failure. At least Sher suggested it could be the nk cells with me.
Did you have any indication of nk cell activity?

However having a dq alpha diagnosis would have explained the years of failure so much easier rather than nk cells. I guess nk cells is still hard to accept.

Doctors ive spoken to are my doctor at Monash, had a quick chat to a couple of scientists doing work on implantation failure. Gab Kovaks at monash is working on a study for this and Im thinking of letting them take a biopsy of my endometrium next pick up, at least I can contribute something to the world of infertility. Their theory is very simply, protein imbalances in the endometrium/uterine. Did not go into detail with them. Although the scientist I spoke to said they were making some major revelations. Long time before we see the results. When I told her about nk cells she implied that it was all related.

I also spoke with gamal matthias. He did a phone consult with me. He tweaked my protocol a little and suggested the intralipids between day 7-10. The plan is to fly to sydney or try and get it done here. I have not worked out the details yet.

Dr matthias suggested i switch to dexamethasone which is supposed to be a stronger steroid. He also has me on it earlier than normal. He said that since youve given prednisolone a try to try something new. My understanding is that dr sher used to use dexamethasone quite a lot before switching to prednisone.

I also had a consultation with Dr sacks who confirmed my nk cells but I never went back for treatment. The idea of flying to Sydney just for a steroid was not convincing enough. I think he only uses steroid treatment? That is prednisolone? Is that right??

Good luck with your appointment today, would love to hear if he sheds any further light on your situation.

Let me know if i could share anything else with you.
Constance

[gab72]

Hi Constance,

I had my appointment with Gavin last week. We are going to progress with PGD (what was to be my first pgd cycle was cancelled due to poor response last time), as Gavin believes and I agree, we really need to tick that box off - ie its the only thing we haven't done. We are also going to do the cycle without prednisolone this time, just to see whether perhaps it has been doing more harm than good. I only have slightly raised uNK cells, so the clexane may be enough. But to answer your question, yes he treats NK cells with prednisolone and clexane. I didn't realise that Dr Sher had switched to prednisone, I thought he still used dexamethasone. But yes, I think the dex is stronger.

I then saw SIVF the next day and spoke to them about CGH. Whilst it seems like great technology, and I was very tempted to go ahead with them, I got cold feet . It is still in very early stages, and also they biopsy on blasts rather than day 3 embryos, and I know Dr Sher, who pioneered CGH, believes that day 3 biopsy is better. At the end of the day, I think I also really wanted to give Gavin a go with PGD. We still may consider CGH down the track if we think its needed.

And lastly I saw Dr Lamaro yesterday who is interested to see if my implantation failure may be endo related. I had a lap 2 years ago where some endo was removed but there was some around my bowel that they couldn't get to, which Dr Lamaro was concerned about. So I had a blood test, and am going to have a pelvic ultrasounds and sonohystogram at the beginning of my next cycle. He said to still go ahead with my pgd cycle as planned, and if we need to we can do a lap in December.

So I've booked in my pgd cycle, epu will be 2nd November. I am not holding out hope of a pregnancy, and it seems backward to say this, but I hope that all the embryos are abnormal, so that maybe maybe I'll finally get my answer.

Doctors ive spoken to are my doctor at Monash, had a quick chat to a couple of scientists doing work on implantation failure. Gab Kovaks at monash is working on a study for this and Im thinking of letting them take a biopsy of my endometrium next pick up, at least I can contribute something to the world of infertility. Their theory is very simply, protein imbalances in the endometrium/uterine. Did not go into detail with them. Although the scientist I spoke to said they were making some major revelations. Long time before we see the results. When I told her about nk cells she implied that it was all related.

Gavin spoke to me about something similar but I don't think the same, but through someone in the UK, at my appointment with him last week, and I also volunteered to help/contribute when the time comes.

Have you started your next cycle yet?

Gabbi

[Loula]

just wondering how you two ladies have got on in the last few months? hope there is good news

also how do you do the DQ Alpha testing?

[gab72]

Hi Loula,

As far as I know, the DQ Alpha testing cannot be done in Australia. The Sher Institute in the USA does the testing. You would have to contact them, and then they send you a blood test request form (for a lab over there). You then call the lab and they send you out vials for the blood and forms etc. You then get the blood taken and FedEx it over. I am not sure whether you have to have a phone consult with a Dr first - I had one, but I don't know if you could request the testing first and then have the phone consult.


*** pg mentioned ***

While down regging for my PGD cycle (& 11th ICSI cycle), I discovered I was pg - naturally. To say that I was shocked is an understatement! I immediately stopped the lucrin and started Clexane and 400mg of p4 pessaries/day. I have had lots of bleeding, some very heavy, some only spotting, but always red. I am now 15 wks and there is still no apparent reason for the bleeding, but I've been lucky enough to have regular scans to ease my anxiety/nerves.


Constance, would love to know how you're going....

[Karen NJ]

Hi Ladies, Your post are very interesting and I am so glad I found them..
I am in a similar situation with 3 miscarriages (that I know of ) before going to Sher Institute (SIRM) in nj. I've done 2 cycles with PGD (all normal healthy cells) and ICSI.. and a 3rd cycle with no testing, resulting in 15-20 follicles and minium of 5 blasts each time. The last cycle (dec 09) I had a B1 blast and 2 B2 blasts with slight change in meds. ( blasts sis not take... My meds were, Dexamethasone, Lupron, Menapur, follistim, estradial, endometrim, Progesterone injections and now we are planning to do the DQ alpha testing as well as NK cell testing.. It's very costly to do the test and insurance doesn't cover it. ($1030 including shipping) If it's NK cells we will try the IV infusions they recommend and hope for the best, since this is our last oportunity to do IVF I want to the the most aggressive protocol possibly. We can not afford to go any further without insurance help. Each cycle has been about $22 thousand dollars.. (our portion has been a combined 10k out of pocket) My concern is, if there is a protocol to reduce NK cells, and prevent loss from matching genetic markers, will the embryos be healthy?
After 3 cycles at Sher Institute, and no emotional support or suggestions as to how to handle the hormone changes and psychological effect they have on me, I've become extremely depressed and am afraid to continue.. should I keep trying?? what if I do all these medical protocols, and have a baby with abnormalities or genetic problems because it just wans't supposed to happen??. I'm afraid..Is this nature'sway of warning me not to keep trying..

Thx for any support you may have...
Karen
NJ