What blood tests/consult during immune treatment - HLA C match & Hizentra questions

chirish

1 Posts
Reply Posted on: May 26, 2017 at 10:05pm
Hi Dr Braverman

I would like to thank you for your very information posts and time which I have learned a lot from.I am putting together an application for finance from our pension fund as the last resort to pay for our very very last and desperate attempt to be parents. I have posted our long fertility journey below which I can safely say has been nothing more but heartbreaking. I have asked my FS to refer me to Dr Sacks (your partner in Australia) however I will not see him until after our application has been submitted. What blood tests will we need to include in our application to get from Reprosource in Aug-Sept 2017 to determine if our immune treatment (LIT x 2 and IL x 4 starting July) has worked or not? I will need to get quotes now from Reprosource for these exact tests (including international blood courier) so that these expenses are included in our application for finance. I won’t see Dr Sacks until after the application for finance is submitted so can you please provide a list of the actual blood tests Dr Sacks may request in Aug 2017 so that we will have the funds to support them.

Our RI says that we have a ‘partial’ match but I think we have a 100% match – He has recommended immune treatment starting in July 2017 for our last egg donor cycle in Sept 2017. This treatment includes LIT x 2 doses, IVIg (1-2 doses), Intralipid (6 infusions given 2 weeks apart July-Sept, and Neupogen injection 60mcg 5 days per week starting in Sept 1 week before the transfer.

Me

HLA-ABC

HLA-A 01,02

HLA-B 08,35

HLA-C 04,07

HLA-DRB1: 03,11 - HLA DRB3 present, DRB4 Absent, DRB5 Absent

DQ Alpha 0501, 0505 (4.1, 4.1)

DQ Beta 02, 03

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Husband

HLA-ABC

HLA-A 02,24

HLA-B 41,44

HLA-C 05,07

HLA-DRB1: 13,16 - HLA DRB3 present, DRB4 Absent, DRB5 Present

DQ Alpha 0505, 0505 (4.1, 4.1)

DQ Beta 03, 03

Our donor will also be HLA tested to ensure there isn’t a match to us. However my husband has duplicate DQs so whatever way we look at it, all his embryos will match me. Our RI has recommended paternal LIT. Should we also ask him for donor LIT (similar HLAs) or will this make any difference?

Thanks to your posts about HLA C matching embryos and uNK activation because now we have included PGD HLA typing on day 5 blasts to prevent transferring blasts with matching HLA C 07.

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NK Assay full panel

50:1 - 19.1% (10.0 - 40.0)

25:1 - 15.8% (5.0 - 30)

12:51 - 13.7% (3.0 - 20.0)

IVIG 12.5mg 50:1 - 15.2%** 25:1 - 14.9%**

IVIG 6.25 mg 50:1 - 17.2%** 25:1 - 13.3%**

%CD3 90.7% (h) out of range (60 - 85)

%CD19 - 3.7% (2.0 - 12.0)

%CD56 4.7% (2.0 - 12.0)

%CD19 + cells CD5 1.5 (L) (5.0-10.0)

>10% reduction in killing at each effector/target ratio

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Our RI has recommended IVIg x 1-2 doses which is very expensive treatment ($3,000 each infusion at hospital) - I read your posts about Hizentra 20% (CSL Behring) as an alternative to IVIg. In previous pregnancies all (egg donors) I have always MC exactly at 5w 1d. I will be receiving Intralipids every 2 weeks starting 3 months before transfer and my first IVIg will be just before I depart Australia. We will be overseas for approx. 4-5 weeks so if an IVIg is needed I wouldn’t be able to get this until we get back to Australia so I may need Hizentra 20% (CSL Behring) when I’m still overseas. Your post recommended Hizentra 20% (CSL Behring) every 3 weeks of pregnancy – up to what stage in pregnancy do you take this treatment and what dose do you recommend so that I can at least include this medication in my application for finance so that it’s covered should I need more IVIg and could use the cheaper alternative instead.

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LAD Panel

Flowcytometry Negative

(T cells) IgM+ 18.3 % IgG+ 10.5%

(B Cells) IgM+ 1.0 IgG+ 29.4

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Thyroid Antibodies

Past history Graves Disease (2005 resolved).

TG less than 20 reference less thsn 41

Sept 2015: TPO 1300

Latest April 2017: TPO 292 (H) reference less than 60

Thyroid function tests normal within range

APA negative

ANA negative

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Cell Surface Markers - lymphocyte subsets

Absolute Lymphocyte count 2.8 (1.0-4.0)

CD19 (B Cell) 6% 0.17 (0.04-0.50)

CD3 (pan T cells) 86 2.41 (0.90-2.10)

CD4 (T helper) 65 1.82 (0.60 - 1.70)

CD8 (T suppressor) 21 0.59 (0.40-1.00)

CD3-/CD16+CD56+(NK) 7 0.20

Th:Ts (CD4/CD8) Ratio 3.1 (1.20 - 3.00)

CD3-/CD16+(NK) 6 0.17

CD3-/CD56+(NK) 5 0.14

CD3+/CD16+ 1 0.03

CD3+/CD56+ 1 0.03

CD57 5 0.14

CD57/CD8 1 0.03

CD4+/CD25+ 5 0.14

CD200+ 5 0.14

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MTHFR (A1298C) Heterozygous – will be taking methy-folate

Karotyping tests both husband and I are normal

Celiac disease – negative

Lupus –negative

2015: Uterine septum removed - Mild endometriosis (silent)–found removed

2016: Laparoscopy – no endometriosis found------------------------------

FERTILITY HISTORY

2004: cone biopsy for CIN III – regular normal paps since then

Migraines with aura taking Estrogen based BCP – moved to implanon

2005: diagnosed with Graves Disease – resolved in 2005 – regular Thyroid function tests normal – not taking any thyroid medication

2009 – implanon removed - all my fertility tests including HyCosy were reported as normal – timed cycles resulting in no pregnancies

2010: male factor diagnosis– I was age 39 and my husband was 31 at this time - IVF ISCI recommended

2010 – 2014: 7 x full IVF cycles using my own eggs - (4 IVF 1 x d3 embryo transferred and 3 IVF 1 x D5 early blasts BB grade transferred– embryos started to arrest from d3 with none to freeze) – cold like symptoms and cramping week after transfer – all cycles using own eggs BFN – egg donor overseas recommended due to age (no longer eligible for IVF program in Australia)

Donor IVF ISCI #1 overseas using vitrified donor eggs – USS at overseas clinic diagnosed a uterine septum 1-2cm that had been missed in all fertility scans in Australia 2009-2014 – (progesterone, estrofem, aspirin, metformin), week after transfer cold like symptoms, light cramping and elevated BP) – first ever BFP which ended in MC at 5w 1 d – a uterine septum 2 cm was confirmed and removed in early 2015 and mild silent endometriosis in cul de sac was found and removed

Donor IVF ISCI #2 using a different egg donor synced fresh cycle (clexane 40, dexamethasone, melatonin 6mg nightly, progesterone, estrofem, aspirin, metformin, labetalol) – BFP - scan at 5 weeks showed 1 gest sac - sharp drop in BHCG the next day at 5w 1 d with light spotting –5w 4 d scan showed sac had just disappeared - ended in MC (like normal period)

Hysteroscopy: polyp removed – uterine biopsy - uNK elevated

IVF FET #3 using same donor eggs as previous cycle - received HLA matching results from Chicago at this time too late for any pre-immune treatment – TPO was 1300 which had lowered to 256 after 1 x pre- transfer IL, clexane 40, prednisolone increased from 20mg to 30 mg daily after transfer, Neupogen (60 mcg injections 5 days on 2 days off per week starting week before transfer, labetalol, metformin, aspirin, progesterone in oil 2cc and 800mg pessaries daily, estrofem) – 2 x grade 4AB blasts transferred (1 blast from husband and 2nd blast double donor), BFP BHCG 51 at 6dp5dt – scan at 5 w 1d showed 2 x gest sacs 1 measuring 4w 5d and 1 at 5w 1d – light spotting/no cramping - BHCG results later that day showed sharp drop in BHCG – told possible vanishing twin and was put on bed rest – scan at 5w 4 d showed both sacs had disappeared – ending in MC both twins

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Husband

Semen analysis: Male factor 2014 – triple defects

2017: Recent semen analysis: huge improvements (borderline normal results)

Semen defragmentation: Index: 15% (excellent DNA integrity) - normal DNA stainability 2.1%

Dr. Braverman

2026 Posts
RE: What blood tests/consult during immune treatment - HLA C match & Hizentra questions Posted on: May 27, 2017 at 5:13am
I dont think I see the indication here for IVIG, the workup is not complete nor is the analysis. HLA C matching is still in a questionable area of significance. I do not see any need for LIT at all. I would not proceed with HLA typing at this point. I think the issues here are more with the underlying diagnosis of endometriosis and its associated conditions and these should be addressed first. Feel free to call me (fill out consult form on website) and we can go over all my thoughts in detail. Its a free consult.
Dr. Jeffrey Braverman MD FACOG
Medical Director
Braverman Reproductive Immunology P.C.