Requesting Any Advice From Those Who Have Had All Successful Pregnancies & Then M/C

[MPTTC3]

M/C ment., child. ment.

Hi Ladies. I was a frequent visitor on this board a couple years ago when I was pregnant with my twins. Ally, the BC, totally helped me through all my questions, and I really appreciated that. Hoping someone can hold my hand again.

I'm 37 y/o with four children (one conceived naturally after a year of trying, one conceived via IUI, and my twins were conceived via IVF). They're all 5 years old and under. In my 30s, I found myself wanting a big family overnight, but my husband and I faced infertility issues with bilateral varicoceles and variable low sperm motility. During our family-building journey, I had an ectopic after an IUI that required an emergency surgery on my right tube.

We did an IVF in July to conceive our last baby (or babies) to complete our family. We transferred three 8-cell high-grade embryos on day 3. I'm currently 8 weeks pregnant with a non-viable pregnancy, and I'm devastated. I've never miscarried before. From the beginning, my HCGs were initially high but were not doubling appropriately, and I was concerned. At my 5 week scan, there was one sac measuring on time. At 5.5 weeks, 2 sacs, one meausuring on time with a yolk. At 6 weeks, one had a heart beat within normal limits, measuring on time. At 7 weeks, two had very weak, irregular heart beats in the 70s, and a very small THIRD gestational sac with a yolk sac showed up! Today at my last scan, Baby A & Baby B's heart beats have tragically stopped. I've opted not to do a D&C because I'm worried about scarring. I'm going to take Misoprostol tomorrow morning. I was going to try to catch the products of conception for karyotyping, but I found out my insurance doesn't cover it. It's a lot of money, and I'd rather save our $$ for a future cycle.

This has been my only m/c. From this IVF cycle, we had 8 embryos. Three were transferred (that I'm miscarrying now), 3 didn't make it to blast, and 2 good-quality blasts are currently frozen.

Do you think this miscarriage is happening because of my age (bad eggs), and therefore are my remaining two frozen embryos bad? I'm baffled as to why ALL THREE embryos that implanted are m/c'ing, especially since two of them had heart beats. Remember, I have four healthy children right now that I conceived between 31-35 years old.

After my ectopic emergency surgery in Oct. ’07, I developed chronic hives which I still have to this day. Some called my hives "allergic" and some called it "immune-related". I've had an immune work-up in 10/07 when I was newly pregnant with my twins, and it showed:

*IgE = 1025 (normal < 80)
*NK 36:1 = 15.7
*NK 25:1 = 7.4
*NK 12:5:1
*%CD3 = 79.2
*%CD19=14.0
*%CD56=7.2
*% of CD19+ cells, CD5+ = 4.3

*TH1:TH2 Cytokine Ratio:
*TNF IL-10 CD3+CD4+ = 36.4
*IFN IL-10 CD3+CD4+=10.6
*ANA Screen = Negative
*ANA Titer = None
*Antiphospholipid Antibody - borderline positive)
*Antithyroid Antibody Tests = Negative

Clotting:
*Serum Homocysteine Level = Normal
*Leiden Factor V= Negative
*Prothrombin Gene= Negative
*PAI-1 Heterozygous = Positive
*Factor x111 Heterozygous = Positive
*Heterozygous Positive (1 copy) for MTHRFR C677T Mutation= Positive

Of course, my NKs and cytokines fluctuated throughout. I was taking IVIG & prednisone until 25 weeks gestation, and I was taking Lovenox & baby aspirin only through the first trimester. I was under the care of an RI for the first half of my pregnancy. Eventually I transferred to a maternal-fetal medicine doctor who said those meds were unnecessary, and he discontinued them without incident. The high-risk doc said that IVIG was unfounded anyway and it was probably a waste of money. Due to financial issues, I could not afford IVIG this time and will not be able to do it for a subsequent pregnancy. The best I could probably do is intralipids.

Do you think that not treating my possible underlying immune issue could be a reason why I'm currently miscarrying? My maternal-fetal medicine doc had me convinced that I didn't have an immune issue and that they were just hives. I never had an immune issue with my first two pregnancies and never tested for it before the hives. My chronic hives started after my ectopic surgery and I’ve had them ever since. He had me thinking that I wasted all my money on IVIG, and that IVIG wasn't doing anything for the pregnancy. Since I had quit the IVIG & was weaned off Prednisone at 25 weeks and went on to deliver big, healthy twin boys at 39 weeks, I forgot all about my "immune issue".......until now.

I consulted my RE yesterday. She found it hard to believe that all 3 embryos are miscarrying d/t chromosomal issues, especially because I've had four live births before this. I am still considering doing CGH (very expensive) for our next cycle. Then again, I'm just not sure why I'm miscarrying. She said she may prophylatically put me on lovenox & baby aspirin next time. I requested at least Prednisone too, and she wasn't a fan of that idea.

So, I'm asking ...... is my current (only) miscarriage because of a bad egg situation where something was genetically wrong with the embryos or was it an immune issue that I didn’t treat with IVIG & blood thinners this time? Or, was it something else?????

I also consulted a fertility specialist on allexperts.com with my history and current situation, and because I've had live births and no m/c's up to this point, and because there were two heart beats involved in this pregnancy, he was not leaning toward a chromosomal cause. He said that I should have a full RPL workup. He said, for instance, having been instrumented so many times, it may be important to rule out endometritis (infection). Sperm DNA abnormalities can develop over time, and some of them may predict IVF failure/miscarriage. So, we may want to get that testing. Thoughts? I just don't want this to happen again, nor do I have the time to waste on my biological clock.

My RE couldn't offer much help other than karyotyping. In addition to it not being covered on our insurance and being very expensive, I just don't think my history warrants it.

Based off of my history, can anyone recommend what kind of testing to have done before our next cycle (which I want to do ASAP)? Do I need to repeat all the immune tests - are the results fixed or variable over time? For example, I know NKs fluctuate, but does a Factor V change over time? Any tests for hubby since he had the varicocele problem to begin with? Never had a real HSG.....only a saline test. Would that be helpful to see if anything is going on in-utero? Any other blood tests? I just want to get to the bottom of why we're miscarrying, and most importantly, treat any cause so it doesn't happen again.

Thanks so much for reading this VERY LONG post. I'm in a tough spot right now and desperately want another baby and I DO NOT want to miscarry again. Thank you so much!

[poohbear]

So sorry you are going through this! Gentle Hugs. Things can change and 37 is really not old! I delivered my last at 37. I'm kind of in the same boat as you as far as having two successful pg. and 2 m/c since and eggs definitely can have issues as we age. I've done a RPL protocol 2 times and had one early m/c and a BFN. I have done intralipids and if you have high nk's I would say go for it and forego the IVIG. If you are carrying 3 babies I wouldn't do miso and hard to believe a doctor would suggest it. Some end up having a d&c anyway. Just my friendly two cents but if you are going to go through with the miso make sure you get some painkillers. I have heard through friends it can be very painful. I opted and my OB said d&c. If you have done saline I wouldn't bother with HSG unless there are tubal issues. I would say if you have a d&c have the testing to rule out chromosonal or immune before repeating expensive b/w. If you do lovenox, baby aspirin, and intralipids you are pretty much covering everything except extra folate which you should be on if you have mthfr. The only thing I do question is the hives. I get rashes always post O even on the intralipids but not as bad. I haven't been able to get a definitive answer. Center for A. Beers website may have more info. HUGS

[MPTTC3]

Poohbear, Have you been trying since 37 (since you delivered your last)? I'm not sure how old you are, but if you haven't been able to conceive since 37, I'm getting a bit nervous about my own situation. As you know, I'm 37 and am going through this m/c now. Realistically, I won't be able to cycle again until probably the January time-frame.

You said that I'd cover all my immune bases if I did Folgard, baby aspirin, lovenox, prednisone, and intralipids, correct? Maybe I should make an appt. with Dr. Coulam's office. I saw Dr. Kwak-Kim for my successful twin pregnancy up until 25 weeks and she had me on IVIG that whole time (every 3 weeks). $30,000 later, we were drained and couldn't afford it anymore. LIke I said, I gave birth to big healthy twin boys at 39 weeks. It was the best outcome, but I just can't afford IVIG this time. So, I hope intralipids will help me if they find my NKs are elevated. Kwak-Kim only treats with IVIG as far as I know; so seeing her this time is not an option. After I'm back to baseline (after my current m/c), for the next cycle I'll probably do all the immune meds (including intralipids) and possibly CGH for chromosomal testing. Do you think that will cover all bases? Or, is there another cause, test, or treatment that I'm not thinking about? Thanks for your input, Poohbear.

You said you did an RPL protocol twice and had a BFN and an early m/c. What exactly is an RPL protocol?

Thanks!

[poohbear]

Child/Loss Ment.
Hi,
My story is I had my last at 37 and tied my tubes and had them reversed when I was 39. We ttc naturally for a year and I got pg. on my 2nd IUI cycle at 41 when we went back into tx. After I had my loss at 8 weeks (twin loss) I couldn't get pg. I did all the immune testing and mostly it was very high nk activity and + for anti-cardiolipins. My old RE didn't believe in the nk theory. I switched this past April to a new RE and they did the new protocol. My first cycle after intralipids I got an early BFP but betas went down fast. My last cycle was a BFN but I didn't have a good stim response probably due to the fact my meds were cut down because I had 10 follicles for my IUI and had mild OHSS. I am hoping to do IVF in 2010 and at 43 yea I know my chances are low. You are still young. My b/g twins are 10 conceived with IUI and my youngest is 6 who was a natural miracle, no drugs. My fsh has stayed low but that has nothing to do with quality. If you cando the CGH I would say do it. IVIG is used for other issues than nk activity. If nk activity is the main thing intralipids can replace IVIG. There are some people that have other factors that nk won't address so it depends on your situation. I have e-mailed and posted to Coulam in the ****** bb several times. Had I not been able to find a RE local to treat me I would have gone to her. The RPL protocol for my RE is baby aspirin, lovenox, progesterone, intralipids and hcg boosters. I didn't do the boosters this last time as I really think that is what made the OHSS worse. I didn't do prednisone but you wouldn't for an IUI cycle anyway. I believe they use something like that in the IVF tx. I wish you success. I understand your frustration. I always will wonder what if I had done the intralipids would I have still had my loss in 07. HUGS