Does stress contribute to Infertility?

Am I infertile because I am stressed?
Am I stressed because I am infertile?
Does cortisol level has something to do with infertility?
Can stress trigger NK cells?
Does cortisol trigger NK cells, T-cells, T helper1...?
In the past generation, APAS (anti-phospholipid antibody syndrome) is never heard. Why nowadays it is prevalent?

Our karyotype result

What a relief! Normal 46,xx and 46,xy. Thank God.

My delayed cytotoxic reaction on LIT

Delayed cytoxic reaction and delayed hypersentivity reaction is the same.  It takes 2 to 3 days to develop. This explains why my LIT sites started to reduce its swelling and rebounded back after the third day.

This reminds me of my tetanus skin test. I did not react to the skin test within 15 minutes. My rashes developed few hours after the intramuscular injection. What is delayed type hypersensitivity mean on my previous tetanus toxoid skin test? I never had tetanus antibody, therefore no antibody to react with the tetanus toxoid yet? Or I have other immunologic factor?  I will ask again this issue to my immunologist.

I remembered he mentioned about th1/th2 balance. My Th1 is high. Hmmm... Haha next time I propose pro-histamine to induce th2 pathway. high th1 + high th2 = balanced th1/th2 ^.^ What if my wicked proposal is valid? Yeah, I dont have to worry about tnf-alpha... Tnf-alpha will be counted by il-10. Haha I can proceed with IVF,  no need for another round of LIT ^.^  just kidding...

Poor me, my obgyne asked how many sessions of LIT do I need? I replied I don't know. If I heard it right, my immunologist said in the past, I need four sessions of LIT. But my last consultation, he said he needs to evaluate again after my next LIT. Delayed cytotoxic reaction involves th1- it is problematic for him.

https://www.boundless.com/microbiology/immunology-applications/immunity-disorders-hypersensitivity/type-iv-delayed-cell-mediated-reactions/
"Type IV hypersensitivity is often called delayed type hypersensitivity as the reaction takes two to three days to develop. Unlike the other types, it is not antibody mediated but rather is a type of cell-mediated response. CD4+ helper T cells recognize antigen in a complex with Class 2 major histocompatibility complex. The antigen-presenting cells in this case are macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ Th1 cells. CD4+ T cells secrete IL-2 and interferon gamma, further inducing the release of other Th1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells."

LIT injection site and CMV issue

I met someone, who had LIT with another doctor in the past. They got shocked to see my 16 giant mosquito bites. She said she just had 2 mosquito bites with her paternal lymphocyte immunization.

With the protocol of our doctor, four donor at a time. Each donors are extracted with 70 mL blood. After processing, the lymphocyte was just below 1/3 mL. We did intradermal injection, 4x per donor.

The other doctor's protocol, 500 ml were extracted from her husband. She said the lymphocytes were injected on the skin also. I guess the lymphocyte collected was about 2~3ml. I guess they did subcutaneous injection because they had two giant mosquito bites only.

One more difference is the CMV cytomegalovirus seronegativity issue. My first immunologist doesn't care about CMV. My current immunologist only allows CMV- donor for CMV- recipient.

What is efficacy of intradermal vs subcutaneous LIT? I am really curious why she had implantation failure.  Next time, I will ask her Th1/Th2 ratio and other immune issues.

http://humrep.oxfordjournals.org/content/21/2/429.full
http://www.transfusion.com.au/blood_products/components/modified_blood/cmv_seronegative

TH1/TH2 - the untested new theory

http://www.autoimmunemom.com/immune-system/autoimmunity-th1-th2-cells.html
"The medical community is divided over whether achieving this balance is really a key part of restoring and maintaining health in the face of autoimmune disease."

"It is thought that an overactive TH1 system needs to be balanced by stimulating the TH2 pathway, and vice versa. Since the former is involved mainly in cellular infections, one approach involves increasing TH2 levels via deliberate allergic stimuli.  Conversely, down-regulating the TH2 response might possibly involve intentional infection (as with vaccines) with microbes in order to increase TH1 response and therefore restore balance."

Wahaha, sounds logical and interesting. I will ask my immunologist about this!
I have experienced uveitis, that was triggered by tetanus toxoid vaccine. Doctor said overproduction of T-cell, th1 pathway... Who knows,

- beer is the cure for uveitis attack.
- half bottle of red wine before IUI.
- two shot of Tequila before IVF.

I am allergic to alcoholic beverage- a possible trigger for my Th2 pathway. Simple problem gets simple solution.

My current supplements: calcitrol, fish oil, L-glutathione, L-carnitine, coQ10
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http://www.altmedrev.com/publications/8/3/223.pdf
http://autoimmune-paleo.com/what-is-the-role-of-th1-and-th2-in-autoimmune-disease/
http://www.rue309.com/book/autoimmune_disorders.shtml
http://www.precisionnutrition.com/rr-green-tea-hazards

My first LIT - reaction and interpretation

My consultation with immunologist was cancelled last week.  Today is 10th day after my LIT. Luckily, I photographed the first 5 days after my LIT.

1. My forearm is wrapped with bandage for four days to protect from UV light. UV light weakens the lymphocyte reaction.

2. The pustules are dead lymphocytes. The strong reaction means I am strongly capable of stimulating my immune cells. Good news, I did not react much to my husband's lymphocyte. 

3. Normally in two days, the inflammation should start to subside.  And it should continue to subside until the inflammation is out.

4. In my case, I had a delayed cytotoxic hypersensitivity reaction. 

After my macrophage has detected the foreign lymphocyte and engulfed it.  Macrophages have broken down these substances and present the smaller proteins to the T lymphocytes.  Then, my t-cells duplicate and attack the dead foreign lymphocyte again. There was also subcutaneous blood leak and swollen peripheral tissues. I thought because I did not have a good rest. Doctor said my T helper cell 1 is not balanced. My Th1/Th2 ratio is high.

 5. After learning that tetanus toxoid has triggered uveitis, I was afraid that LIT may cause uveitis. I complained I had tight eye muscle. Luckily, no uveitis. Doctor said LIT should alleviate the autoimmune disease because we are working to lower the Th1/Th2 ratio.

Polyps < 1cm

Small polyps (polyps <1 cm) may regress on their own. OBGYNE1 said she has a patient, who had large polyps. The patient got pregnant before the scheduled polypectomy. There is no need to remove my polyp. Am I spotting between periods? My left fallopian tube is not blocked. My main problems are immunology and husband's sperm count.

She feels I am so stubborn. I showed her my LIT marks to prove that I am following her advice.

Back to square one

I wish to go to OBGYNE1 on my luteal phase to let her check the 1 cm thing. I hope that 1cm thing is just imaginary.

I never discussed with OBGYNE1 the factors for my infertility.
- male factor (OATS- yes)
- fallopian tube (L- blocked?)(recheck?)
- ovulation, pcos
- endocrine hormones
- autoimmune (working on...)
- adenomyosis

- karyotype (rechecked)



- what else?

ovulating side: JAN (L), FEB (L), MARCH(L), APRIL (R), MAY(L)


I hope we are not limiting ourselves to the immunology perspective. Aside from my autoimmune disorder, are any other problems?

The robotics surgery hype- laparoscopy + hysteroscopy

My Fairy Godmother told me in March 2014 that I have polyps. If I remember it right, she said it measures 1 cm. Based on her experience, patients easily get pregnant after polypectomy. Where is my polyp located? In the uterine cavity. Where again? In the uterine cavity. It affects the implantation success. After 5th IUI, she will have to remove the polyp.  I was conditioned to believe that I need polypectomy the sooner the better. After my 6th failed IUI, she asked me to have laparoscopy + hysteroscopy guided polypectomy.

I asked My Fairy Godmother what is her indication for laparoscopy? Is it endometriosis? If I am asymptomatic and I never feel pelvic pain, what is her basis for suspecting that I have endometriosis? She said I have polyp and adenomyosis. Polyp, adenomyosis and endometriosis are correlated. These three are related to my autoimmune problem as well. I can skip laparoscopy for the meantime. I just scheduled the hysteroscopy. After all, there is no basis for me to refuse hysteroscopy. Hysteroscopy is the gold standard for polyp detection and polypectomy.

But why did OBGYNE1 never mention to me that I have polyp? In the span of two months, my polyp had became bigger? It was not noticeable in ultrasound before and now it is visible? Where is my polyp again? Sorry, I really have poor skills in visualization. Should I go back to OBGYNE1? Yes, I should satisfy my curiosity! Ooops, should I do that? It is an irony. I seek second opinion from my first doctor! Whatever!

I went to see OBGYNE1. I asked whether I have polyp or not. She said I have polyp. I asked what is the measurement of my polyp? She replied: "What is the indication for removing my polyp? Do I experience spotting between periods?" The reality is my polyp cannot be seen with transvaginal ultrasound. She explained she needed to infuse a saline solution for a better contrast. The procedure is called SIS- saline infusion sonography. My polyp measures 0.3cm.

Join the robotics surgery hype? Prior to robotics surgery era, how do doctors detect polyps? Is SIS obsolete? SIS became obsolete for some reasons? Should I or should I not? I cancelled my hysteroscopy.  Robotics surgery ... ai.. no comment. On other perspective, D&C is cheap. Why is there a need to do the hysteroscopy? Only time can tell. I keep my big mouth shut for now!

If I don't believe in immunology, what is next? We need to think out of the box possibilities. If I believe in immunology, I need to have LIT. I will put aside the polyp polyp issue! Wait and see!

Location of polyp may effect pregnancy rate after removal
http://www.ncbi.nlm.nih.gov/pubmed/17889854

Polyps <2cm do not decrease pregnancy rate, but may increase miscarriage http://www.ncbi.nlm.nih.gov/pubmed/10478319

https://sites.google.com/site/miscarriageresearch/polyps-and-fertility 

Karyotyping- another two approach

What shall we do if my husband has confirmed mosaicism. Two schools of thought from Taiwan IVF doctors.
1.[Conservative] First doctor asked me to retest the chromosome in another lab. PGS is expensive. There is no need to do PGS, if chromosome translocation is not confirmed.
2. [Aggressive] Second doctor said if our second karyotype does not show any abnormality, he will put me on maximum stimulation. He will believe in the first karyotype report. He wants to extract as many eggs as he can. Because he feels only a handful few will develop into good embryo. We will have frozen embryo transfer because all the embryos will be subjected to pre implantation genetic screening.

I am polycystic and my anti-mullerian hormone is 5.2.

I am afraid of OHSS. Who shall I choose? Doctor 1 or 2? Success is also a big consideration.

Karyotype - two perspective

Two perspective: OBGYNE1 vs MyFairy Godmother.
Obgyne1- reproductive endocrinologist vs My Fairy Godmother- reproductive endocrinologist (ivf specialist)

OBGYNE1 believes in the survival of the fittest. Nature has its own way of extricating abnormal chromosome. Don't worry on the 1% morphology. Abnormal sperm can't fertilize egg. Healthy motile sperm will grab the opportunity first. Chromosome study is just a waste of money.

My Fairy Godmother [ivf doctor] requested the karyotyping study. Her basis for that study is OATS, I guess. Oligoasthenoteratozooapermia (low motility, low concentration, low morphology). I am clueless on why we did not have further chromosome study afterwards. Maybe I made a wrong comment... I said I want frozen embryo transfer, I want PGS. PGS is banned in Philippines.

Back in my mind, I was thinking could the karyotype result be wrong? Why the abnormal cell of my husband is 1 out of 30 cells? Is there a mutation? Is there a difference if the abnormal cell is 2/30, 3/30... 30/30? I wished to check with another lab- but where? Question: What if the second test says: no problem, then which shall I believe? Geneticist to the rescue.

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Reading material
Chromosome Segragation Analysis [Yilmaz]
What is mosaicism?
http://ghr.nlm.nih.gov/handbook/illustrations/mosaicism

What is chromosome translocation?
http://arbl.cvmbs.colostate.edu/hbooks/genetics/medgen/chromo/translocations.html

Genetic causes for miscarriage

and there is lot of people complaining chromosome related miscarriage in forums http://community.babycenter.com/post/a24342903/four_consecutive_chromosomal_miscarriages

Aneuploidy frequencies in semen fractions from ten oligoasthenoteratozoospermic patients donating sperm from intracytoplasmic sperm injection.[Pfeffer]
- conclusion: OAT may increase risk of aneuploidy offspring.

Chromosome Segragation Analysis in Human Embryos Obtained from Couples Involving Male Carriers of Reciprocal or Robertsonian Translocation[Yilmaz]
- conclusion: Clinical pregnancy Robertsonian vs Reciprocal: 62.5% vs 19.2%

Relationship between embryo quality and aneuploidies [Baltaci] 

-Obesrvation: Many high grade embryo based on morphologic evaluation were detected to have chromosomal abnormality.

Of eccentricity... And mosquito bites

As for eccentricity, nobody beats my immunologist. He holds clinic til midnight and sometimes even til morning. I received a confirmation on Thursday that I will have a consultation slot on Friday or Saturday. It changed the ball game. I am now an "ON CALL" patient.

Ooopss... I am not complaining. I am learning to embrace eccentricity.  I am appreciating his good deeds and skills as well.  I got a number 7 slot today. For the mean time, I guess I should have a dinner date first, watch a movie and sleep tight. Who knows, I may receive the secretary's phone call at midnight.

Somebody touted that he is a vampire because he holds clinic in the evening. In his polite reply, he said most of his pregnant patients appreciate it. There are less people in the hospital during the late evening. Immuno compromised patients will have less chance to catch infection.  Nice alibi.

My Giant mosquito bites are very itchy. Some part of the surrounding skinned turned yellowish discoloration. Perhaps it had little faded hematoma? Luckily there is no pus anymore. I don't have any idea on what should be the ideal reaction of those giant mosquito bites.

Just playing my guessing game....
If there is no reaction, then it means I am not producing antibody against the donors HLA- NK cell very active?or immunologic dysfunction? If there is pus, my T-cells are over reactive. I just feel:  Dumb I do, dumb I don't.

Interesting blog- conceivable solutions

http://conceivablesolutions.wordpress.com

This is great site. It was written by a Ph.D. in Immunology mom.
Pro-inflammatory foods to avoid, how to avoid bruises from heparin injections and etc...

I quoted from some of her interesting lines.
- Don't ignore your little voice and intuition.
- "Don’t be trapped by dogma — which is living with the results of other people’s thinking. Don’t let the noise of others’ opinions drown out your own inner voice. And most important, have the courage to follow your heart and intuition.” (Steven Jobs).

I had this experience as well. I left OBGYNE1 and put all my hopes in My Fairy Godmother. My Fairy Godmother believes immunology is a second cause of infertility. Her magical potions: Heparin and aspirin. Voila! Bruises! Unfortunately, nothing magical happened. There was a time, I had cancelled my IUI and refused to consult with her. I was in my state of confusion- clashes in beliefs. There was also a time when I would always bring up immunology topic. I played dumb on my inner voice. But after each IUI failure, my inner voice got noisier and noisier until I ended up having my lymphocyte immunization therapy.

My Th1/th2 issue

My Tnf-alpha:il-10 is above border. I don't believe this issue needs to be addressed. It is just slightly higher than the maximum anyway. 

Simple problem needs simple solution. If my TNF-a is high, why not use a TNF-a inhibitor or TNF-a blocker? Why should I put all my hopes on LIT? LIT is a broad spectrum treatment.  To the older generations, LIT is crazy! Injecting white blood cells for fertility? But, why my circle of friends know this? My classmate, cousin-in-law, my neighbor's friend and godsister has APAS. I hope we are not having an LIT fad. Immunologist2 also asked for APAS screening test for husband. Ouch! Follow the trend!

Why not use Humira? Immunologist1 said she is concerned about its safely. She will never use it.

Immunologist3 will infuse IVIG 2 weeks before IUI or IVF, if I refuse LIT. Winger EE article was a wake up call to me. And I found the sad fate of a patient who underwent IVIG prior to embryo transfer. Zarpar8 complained the efficacy of IVIG in a forum.http://www.fertilethoughts.com/forums/immune-issues/300813-where-do-i-start.html I guess Th1/th2 is the missing puzzle. Oh my god, if I refuse LIT, IVIG alone might not be the solution.  I will respond to low dose IvIg only- according the the Chicago lab. My resistance to LIT is futile.

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Reading materials
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http://www.repro-med.net/th1-th2-assay

Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF

http://humrep.oxfordjournals.org/content/18/4/767.full.pdf+html

Treatment with adalimumab (Humira) and intravenous immunoglobulin improves pregnancy rates in women undergoing IVF.

http://www.ncbi.nlm.nih.gov/pubmed/19055656

Humira website. Pls read the risk warning
www.humira.com

The controversial dangerous blood therapy

controversial-dangerous-blood-therapy
"LIT is fast becoming a last resort for couples for whom IVF and natural conception has failed... "

Ouch! "last resort"

How does LIT work?

Injections are not painful. It is just like being bitten by mosquito. I have been using the word "mosquito" for a thousand times already. I though LIT is just like being bitten by giant mosquito! Ei... it is now swollen and itchy. (24 hours passed LIT). 

What is the mechanism of action of LIT? What attacks what? 

What produces anti-HLA?

How the CD19 and CD56 counts will decrease?

What will cause TNF-a to drop and how?

Do I need to let those giant mosquitoes bite til they drop? Until one day I get used to their sting?

I am interested to have a visualization of how t-cell, b-cell, macrophages and etc work. Curiosity killed the cat. I will end up in psychiatric ward first before I understand those. 

Any idea why LIT should be administered intradermally? "...The skin is an organ of immune defense it contains remarkable numbers of dendritic cells [roughly 10^4/μl (McLellan et al.,1998)] which are the most effective antigen-presenting cells to elicit a primary T-cell response. In blood their concentration is lower (0.1% of leukocytes, i.e. 10/μl)."

Now, I am one step closer to the psychiatric ward.

My First LIT (lymphocyte immunization therapy)

I just a month break from my fertility work up. I feel so relax, even though I am terribly busy at work. Back-to-school season is our peak season. Why I am so stressed these few months? Am I stressed because I am infertile? I am infertile because I am stressed?

Ai... Not all aspects of life are smooth sailing. My journey to fertility is like sailing against the current. If I don't advance, I will be swept downstream. I am racing against time. I exert all my effort to keep sailing forward. This afternoon, I bit the bullet as I tried the lymphocyte immunization therapy (LIT).

8 hours past, since I had the LIT. Yucks, the giant mosquito bites turned red. And it seems to me these are pustules. I afraid these pustules will get worsen in no time.

The first column was from my husband's lymphocyte. The other three columns were from the donors.The first column has the least reaction. Oh my god! I just realized what my immunologist was saying about genetic closeness. So, I developed little blocking antibody to my husband's lymphocyte? If I don't develop blocking antibody against my husband HLA, I will create antibody against my fetus. I cannot absorb what he was saying before because I was resisting to believe. I have created HLA antibody from the "donor HLA". This is my aha moment! Brilliant! That is called as the borrowed HLA. (^.^) Immunology is now an interesting.

17 hours past LIT, I am still restless. I cannot sleep while my immune armies are busily attacking these 16 giant mosquito bites. The surrounding area has also swollen. Is this what immunologist refer to as the wonder of immunology?

My left forearm is now bigger than my right forearm. I hope my left forearm circumference will not be as big as my arm when I wake up. Grrr... I really can't sleep. Is it because of the oolong tea? Is there a switch to turn off my immune response? Wahaha I want to sleep! It is 6:30 am already. I get a little throbbing pain on my left eye. I pray this is not a uveitis attack. My left forearm has a little throbbing pain also.

My paradigm shift: believing in immunology as the reason for my infertility

NK Assay Full Panel
	IVIG
dilution	0 mg	6.25mg/ml	12.5 mg/ml
50:1	12.3	4.9	5.9
25:1	7.5	5.5	5.2
12.5:1	3.6	-	-
			range
CD3%	65.5		60~85
CD19%	19.2		2~12
CD56%	14.6		2~12
CD19+CD5+	8.8		5~10
	TH1/TH2 Intracellular Cytokine
TNF-a:IL-10	31.3		13.2~30.6
IFN-g:IL-10	1.7		5.8~20.5

The effect of IvIg is non linear. I think there is an error on the flow cytometry. Take a look at 50:1 dilution, if 6.25mg/ml IvIg is able to kill 4.9 cells, I bet 12.5mg/ml should be able to suppress even more! Sorry me! Immunologist2 said IvIg never worked in linearly. It sometimes work in paradox. Why on the 25:1 concentration, if at 6/25 mg/ml IvIg the killed cells is 5.5, why increasing the dosage to 12.5mg/ml does not have a significant suppression? It was just 5.2. I am recommended to have low dose IvIg only.

I do not believe that I need to have to undergo an immunologic treatment. My NK cell count CD56% is just above the border. Quantitatively I have the count, qualitatively it has no killing power. I thought I will be the first patient to escape LIT. If this happens, I will publish my good news on the headline of our local newspaper. Immunologist2 said I have if I have category 5 problem only, he will not suggest any LIT at all. But I have compound problem. Category1,2,4 and 5. Therefore, I need lymphocyte immunization therapy. Good alibi.

CD19% is high. But other two immunologist said it has no effect on fertility. Immunologist2 said. CD19 is antibody producing cell. No wonder I have anti-sperm antibody. It is also likely that I will produce anti-progesterone antibody.

I will have my IVF first. I don't believe much in immunology. He said my eggs will be surrounded by TNF-a... Grrr....

What can I still say? I concede! Ooopss... I forgot to ask the mechanism of Lymphocyte Immunization Therapy (LIT). Oh never mind! I will get crazy. ^.^

Is LIT safe?

Is LIT (lymphocyte immunization therapy) safe? I went to the clinic this afternoon for the LIT. I was asked to sign a waiver form. In the waiver form, it says there is a risk of graft-versus-host-disease (GVHD), although it is rare. This a condition wherein the immune cells of the donor (or the graft) recognizes the recipient (or the host) as "foreign". Do I need to Google it? Wow! I don't care much. This is truly my leap of faith.

The LIT process was like being bitten by a giant mosquito for 16 times. The white blood cell inject from each donors is just 0.2 ml. Thanks to my 4 donors. I was warned that I may develop intense itch or pus in 24 hours and fever perhaps. I am just wondering on the efficacy of these 16 giant mosquito bites. Can this solve my immunologic problem? Wow! This is the true definition of faith!

Come what may! If it triggered my uveitis, so be it. Steriods to the rescue anyway. I will see my immunologist after 2 to 3 days.

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Adverse effects of intradermal allogeneic lymphocyte immunotherapy: acute reactions and role of autoimmunity http://humrep.oxfordjournals.org/content/21/2/429.full.pdf+html

The incidence of autoimmune disease was 0.1%. This is one in a thousand. I am not the unluckiest person in this planet. I am not a risk of GVHD (graft versus host disease) also. This usually occurs on consanguinous donors. Conclusion: The incidence of side effects are low therefore LIT treatment is justified.

Do I need LIT (lymphocyte immunization therapy)?

"The highest form of ignorance is when you reject something you don't know anything about." - Wayne Dyer quotes from BrainyQuote.com

I met someone in my immunologist clinic. She did a paternal lymphocyte immunization therapy with other doctor. Her PRA had shot up to 100%.  Unfortunately, her ivf failed. What was the cause? Polyp, endometriosis, chromosome or immunology?  Perhaps, she needed an in depth examination of her immunology. Good luck friend. I trust you are now in good hands. She said she will be trying an endometrial scratching days prior to embryo transfer.

Do I need LIT? Refusing LIT does not increase my pregnancy chance. But LIT does not guarantee pregnancy success either. My answer: What am I to lose if I did an unnecessary LIT? I am volunteering myself as a guinea pig. I hope the corrected category 1 and 5 shall increase my pregnancy chance. Give immunology a try!

After 6 failed IUI, Now, I concede to immunology. My immunologist is a bit reserved to use HUmira. But, I feel Ivig and LIT are broad spectrum solution, it may or may not address the th1/th2 thing.

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Treatment with adalimumab (Humira) and intravenous immunoglobulin improves pregnancy rates in women undergoing IVF http://www.ncbi.nlm.nih.gov/pubmed/19055656.

Leap of Faith- LIT

Where are my inhibitions? It seems I have amnesia. Vaccination and Immunization do not ring a bell to me anymore. Am I hypnotized?

I had anti-tetanus vaccine in the past, and it had triggered uveitis. Immunologist2 explained that my immune system reacted with the tetanus toxoid. The overproduction of T-cell had triggered my autoimmune response.  For this, I should consider anti-tentanus antibody instead of tetanus toxoid. I am not supposed to receive any form of vaccine. Yes! Well said. I developed an anti-LIT sentiment after my first consultation. 

In Lymphocyte Immunization Therapy (LIT), the white blood cells of donors are injected intradermally to my forearm. HLA (human leukocyte antigen) is a protein coating on the surface of the white blood cell. Each person has unique HLA. My immune system will be triggered to produce HLA antibody to donor's white blood cell. The overproduction of T-cells again can cause me another round of autoimmune response? I should opt to use IvIg (intravenous immunoglobulin) instead! But according to the NK cell cytotoxicity result, I will respond to low dose IvIg only.

I forgot to ask Immunologist2: whether LIT will trigger my autoimmune response or not.  It was 11:45 o’oclock in the evening and I was groggy already. But...What if I don’t have Rubella antibody? I am lucky enough to get pregnant after LIT and IVF, unfortunately I acquired measles during my pregnancy. Vaccination sometimes is really inevitable.

As I look back, I have autoimmune disorder. Yet, I insisted there was no probable cause to suspect immunology is the reason for my infertility. I hated Immunologist2 for scaring me over NK cells. Anyway, the NK cell scare was effective. I was challenged to take the test. Thank you Doctor. I acted stupid and funny in my effort to resist immunology. Now, I surrender to immunology. 

Courage never exists, if there is no fear. I decided to take my leap of faith. I will have LIT tomorrow. Come what may.

Fear of Failure

I have my own timeline. After 5 unsuccessful IUI, I will move on to IVF. IVF is my last string of hope.  If possible, I don’t want to reach that point. My 5^th IUI is a make or break. I backed-out from my first 5^th IUI attempt. I was tempted to try the immunologic work-up first. Was I just trying to delay the 5^th IUI? 

I wished to try the LIT (lymphocyte immunization therapy). LIT is my silver bullet. Does silver bullet exist? But, in the end, I just spent 4 months in refusing LIT.

Fairies are not alchemist. My Fairy Godmother does not have a crystal ball to see when I will get pregnant. The best advise I got was "to try again". Yes, I will try LIT and I will try IVF afterwards.

Why did I develop an intense fear of failure? My reasons were overshadowed with fear. I was fear of what? Haha, I don’t know. I failed my 5^th IUI, so what? What is the dread consequence? 

It is not easy to embrace LIT. I turned my back against immunology. Now, I returned. I bet I am not the only one who did so. Wait, where are my inhibitions on LIT? ^.^

Refusing LIT

To me, I don't believe LIT is a first line of treatment for unexplained infertility. I was exploring all other possible causes of my infertility.  I don't believe much in crossmatch PRA 100% as the pre-requisite for pregnancy. I spent 4 months in refusing LIT. But, I don't regret it. I don't even consider it as wasting my precious time.

I was worried about allergy and acquiring new autoimmune disease. I am also afraid that LIT will trigger my autoimmune response. LIT produces desirable antibody as well as the undesirable antibodies. I don't want to undergo unnecessary LIT. But, I was also open to understand immunology and its alternative.

Sad to say, the alternative to LIT is also a blood product- IvIg. The main difference between the two is IvIg is already IgG antibodies. With LIT, my body needs to react with donors' white blood cell in order to produce IgG antibody. Can I still refuse IvIg?

Well, intralipid and steroid are also alternative. For steroid, I don't know how long should I be using it? On my first consultation with Immunologist1, she ordered me to use it on day6 til next menstruation. Would this mean I have one week off from steroid every month as I try to conceive? I don't know if this would be too taxing for my body. I was just guessing... I don't have any idea on her management style. The second time I consulted her, I said I don't like LIT and IvIg but I surrender. I asked for her recommendation. She said if patient refuses LIT, she uses intralipid and steroid. I have no idea how many intralipid my body can accommodate, before my cholesterol shoots up. She asked me to retest my immunodeficiency panel two weeks before any planned procedure. She will prescribe steroid, again? Why doesn't she make her firm stand on LIT?

My Fairy Godmother said IvIg is expensive. She said I cried over heparin, what more, if I had IvIg and our IUI was not successful? She suggested that I have my IvIg infusion only after a confirmed pregnancy. I never got two lines in the pregnancy kit. Therefore, I never had any immunologic treatment. But, I have been very busy consulting immunologist after immunologist. This led to the impression that my immunologic factor is already covered.

I somewhat conceded to immunology. Here I am again, trying to postpone LIT this Wednesday. Do I need to wait for karyotype result first to do LIT? What if my husband is confirmed to have mosaicism of 46xy normal and 46xy balance translocation? I am indecisive again as I write this blog. Few minutes back, I said I replied the geneticist, I will still try IVF even if we have chromosomal abnormality. Grr... I will have my LIT on Wednesday!

Karyotyping again

The geneticist was not convinced in the accuracy of my husband's karyotype result. She asked to increase the cell samples and to study the possibility of mosaicism. She said if 46xy translocation is true, our pregnancy chance is just 10%.

She asked why My Fairy Godmother did not ask me to do my karyotype? I replied: Chromosomal abnormality will not stop me from doing my fertility work-up. Its detection is useless to me.
My fingers are crossed as I wait for the result.

She also asked why my brother-in-law is infertile? Why the other brother-in-law just had 1 child only? Oh my god! Is it a battle of the family size? My mom has 4 married offsprings and has 7 grandchildren. My father-in-law has 3 married offsprings and 1 grandchild. Why is my husband side has small family size? There maybe problem with my husband's chromosome.

Insanity or perserverance

Insanity according to Einstein is doing the same thing over and over again and expecting different result. Proverb says try and try until you succeed. Am I a loyal follower of Sun Yat-sen? Is perseverance a key to success or is it an act of insanity? After first batch and second batch (with heparin and aspirin) failed, what is next? IUI again? I want to give immunology a try or immediately proceed to IVF?

What if I had LIT and yet I fail my IVF? I heard somebody had 100% PRA but her IVF failed. What if I have my IVF first? I also heard many people had IVF but they knew they have immunologic problem only in the second trimester. 

Since, I doubted my immunology as the culprit of my infertility and I had suspected that I had a miscarriage on my 5th IUI, it is about time to follow my instinct. Refusing LIT will not increase the pregnancy chance. Another counter question is: will LIT increase my pregnancy chance?

After my long merry go round ride, I choose Immunologist2. I have lowered my resistance against LIT. I am volunteering myself as a guinea pig. If I join a combat, I will bring an amulet. Sad to say, there is no scientific evidence on the efficacy of amulet in winning a war. LIT is my amulet. LIT is banned in America because its efficacy is unproven. I will do hysterocopy (polypectomy) if it will increase my pregnancy chance. I will do endometrial scratching, if there is a need. I will wear lucky panty. (Just a hyperbole.)

I hope my crazy ideas is not a manifestation of insanity. According to Einstein, doing the same IUI procedure and strategy over and over again is a true manifestation of insanity. What is my next step?

Keep on trying! Maybe one day my perseverance can move the heavens. I may have success on my eleventh IUI attempt. If that happens, this will be my best Christmas gift ever! Go Sun Yat-Sen! Fight! Ooopss... I knew nothing about history!

I will keep my fighting spirit alive. I will have my LIT then polypectomy and then IVF. Come what may! I need to get a clearance and pregnancy go signal from my immunologist first. My husband karyotype result is annoying. I wished to check it out again as well.

6th IUI and second consultation to Immunologist2

I don't like to do IUI again. But since My Fairy Godmother extended one more IUI, I just complied. I have pending anti-sperm antibody result. It was withheld for quite sometime, because they need to check my husband's blood first before releasing it. The result was just release one day before our scheduled IUI.

On day12 past ovulation, I was able to schedule a consultation with Immunologist2. I told him, I want to have IVF first, before going back to see him again. He said my eggs will be swimming with TNF-a (tumor necrosis factor- alpha). It is a pro-imflammatory cytokine. At the time of harvest, my eggs will look great. However, after ICSI, the embryo development will be sluggish or poor development. I admire Immunologist2 for his exercising his maximum patience on pesky stubborn patients like me.

I don't believe in LAT (cross match test). Some people can get pregnant despite of 0% PRA. I believe fetal rejection occurs only during second trimester, I am safe for now. His reply: any damage to the placenta is irrepairable. Second trimester is the payback time.

At the end of the lengthy consultation,  I confessed that I had my 6th IUI. I will know the result within 2 days. I told him My Fairy Godmother said anti-sperm antibody can be circumvented with sperm washing. Crinone is a progesterone. It can take care of my uterine NK cells. He said my CD19 is high. CD19 is an antibody producing cell. No wonder I had developed an anti-sperm antibody. No doubt I may also develop anti-progesterone antibody.

After 3 days, I went back to My Fairy Godmother. My menstruation was delayed. Unfortunately, that evening, my period came. I had collected the large blood clot discharge and brought it to My Fairy Godmother. The discharge was crinone and some blood tissue. I also told her our discussion with Immunologist2. My Fairy Godmother asked me to have LIT. Did I hear this correctly? I thought she said LIT is banned in America.

I want to have LIT. I want to give immunologist a chance. After all, I was the one who suspected my autoimmune disorder as the main reason for my infertility. I refuse LIT mainly because of my cowardice!

I like take immunologist2's track record as his promise. He said he has 85% success rate.


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Immunology category5 problem

Eeny meeny miny moe

My Fairy Godmother's patient, who had born a 100% chromosome normal baby, had a Robertsonian translocation. It has 50% success rate. Most of the translocation, I saw in the web, is Robertsonian 45xy tranlocation. My husband has 46xy translocation.

PGS (pre-implantation genetic screening) is not allowed in the Philippines. Does good morphology mean normal chromosome? I guess not. I saw from the web ICSI results in 40% abnormal chromosome. I better consult a geneticist. I saw in the internet the pregnancy chance from 46xy balanced translocation carrier is less than 25%.

Imagine, I successfully retrieved 10 eggs, and 10 eggs were fertilized. What if only 7 are chromosomally normal. How does an embryologist decide which to implant?  Eeny meeny miny moe... Which is the fairest embryo of them all? Two embryo transfer? Quantitative analysis comes into play.What is the chance of picking implanting 2 good embryo? Combin(7,2)/combin(10,2). I almost failed in quantitative analysis back in college. I don't want to scratch my brains and I hate the eeny meeny miny moe!

In reality, the embryologist will be playing an eeny meeny miny moe on my embryo if we don't do PGS. I hope that embryologist is not the one, who did the crappy semen analysis. What if on the first few embryo transfer, all the transfered embryos are with chromosomal abnormalities? It will be a devastating experience for me.

If I do the IVF in the Philippines, can I freeze all the embryo and send samples abroad for testing?  

Not so fast, My Fairy Godmother said she wanted another IUI first before moving on to IVF. IUI again! Why? Grrr... She believed my husband sperm motility and morphology improved a lot. Was that a reverse psychology? I was afraid to have IVF before because I am afraid of OHSS ovarian hyperstimulation syndrome. Now, I am so eager to have ivf, then she wanted to try another round of IUI.

5th IUI part2

After consulting Immunologist2, I feel immunology is an intangible branch of medicine. I don't believe in those extra terrestial and unidentified flying objects. To me aliens and immunology are just fiction. I went to back to My Fairy Godmother after consulting with Immunologist2. It was day20 already. I regret I missed the IUI. She did a transvaginal ultrasound to check my Luteal phase endometrium. I told her I will believe in immunology only after I experience a miscarriage. I ignored my inner voice at that moment.

I told her my scary experience with Immunologist2. Nobody leaves his clinic without immunologic problem. Everyone needs LIT. I told her I retracted my request of having an immunologist. She asked me to consult Immunogist3. Either ways, I feel I cannot escape immunology. After more 10 days of resisting Immunologist2, I did all blood works requested by Immunologist2.

I was not able to visit My Fairy Godmother on day2. On day5, she said my follicle was too big for day5. Maybe it was a carried over effect of previous cycle's GonlF. This was not an ideal cycle for IUI to start with. She asked me to go back to her clinic 4 days after. I have no idea on what she was planning, I just followed her instruction. I was hoping she would do the IUI this cycle. Surprise! Good news: I was ovulating on the right side. She asked me to have Pregnyl shot on Saturday 5am. She scheduled our IUI on Sunday. Hospitals and fertility lab are closed on Sundays. Luckily, one lab is open on Sundays (by special arrangement). Bad news: karyotype result was released already. I did not have the courage to ask her about the karyotype result yet. I was thinking of the survival of the fittest sperm. I also inquired two Taiwan hospitals if they do abortion on grounds of chromosomal abnormalities. I cried again. But, I accepted my fate- come what may!

I thought this was an answered prayer. My husband's sperms were very motile and the morphology had jumped to 7%. This was a miracle.

The next day after the IUI, I went to My Fairy Godmother's clinic to check whether my follicle ruptured or not. Then, she shared her bad news about the karyotype. It is about my perspective, how I would see a glass as half empty or half full. She sees it as half full. She had a patient with chromosomal translocation who delivered a 100% normal baby. She extended one more IUI before we do IVF. She said my husband's sperms have improved a lot. I did not want to contest her. I was afraid she will blame me again for being pessimistic. I don't like another sermon. But, I gained enough courage to tell her that I really cannot accept the semen analysis result. How come the sum of motile and non-motile sperm exceeded 100%? For this reason, I don't believe in any of that lab's report. I don't believe in the 7% morphology.

After 14 days of waiting, I had spotting. I went back to My fairy Godmother the next day. She said my endometrium was thick and this was not a menstruation. She suspected pregnancy. I told her I have just passed large chunks of blood that morning. She asked me to come back 2 days after I experience larger blood flow.

Did I just experience a miscarriage?  Was it because of chromosomal abnormality? I guess not...  Why did she get mad when I asked if I had miscarriage? My stupidity, I did not use pregnancy kit. That product drives me crazy!  I felt guilty because I was just shopping for immunologist. I was not having any immunologic treatment. I doubted my immunology has cause the miscarriage. Did I have a miscarriage?

My first consultation with Immunologist2

I was scared by Immunology2 jumps to conclusion style of deduction and his leading questions. I wish I have brought a lawyer to defend me. I feel everybody who walks into his clinic has Immunologic problem!  After the consultation, I refuse to believe in immunology as the reason for my infertility. I regret of making a wild non-sense guess to my OBGYNE1 in trying to link an autoimmune disease (HLA-B27 spondyloarthropathy and uveitis) to infertility. 

I told him that if I failed in LAT (crossmatch test) PRA=0%, it doesn't automatically mean that I have immunologic problem. Somebody who never had blood transfusion, organ transplant and sex will have zero PRA (panel reactive antibody). Consider surrogacy case... a virgin... If we do an IUI on her, it doesn't mean she will not produce anti-blocking antibody.  I argued that my husband has erectile dysfunction. Limited semen exposure produced limited HLA antibody. No wonder my PRA is zero and my reaction code is 2 and 2.

I argued my CD56 NK cell count is just above the border. My result was 22.43 while St. Luke’s cut-off is 21. Immunologist2 argued that my NK cell is high. This is the reason why I seldom get sick. Grrr.. I am not as healthy as what he imagines. I complain he is using a cannon to kill a mosquito. What he is doing is really an overkill. He should make sure his cannon ball will hit the mosquito. Otherwise, it will be a laughing stock.

I asked if there are other factors aside from NK cells which contribute to my infertility? I have autoimmune disease, am I at higher risk compared to his other patients? He said I need to test Th1/Th2 ratio. (T helper cell 1 and 2 ratio).  Pro-inflammatory vs anti-inflammatory cytokine ratio. What the heck is this?

Since my NK cells are VERY HIGH and VERY ACTIVE, I need to test my NK cell Cytotoxicity. After 10 days of resistance, I had my blood sent abroad for testing. 

I can kill a mosquito with a swatter. I don't need to use a cannon. Btw, Why should I be resisting, after all it was just a blood test? (APR 2014)


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Reading material
Leukocyte antibody
Immunology category1 problem

5th IUI part1

My fifth IUI was a make or break. I had consulted an immunologist for the first time. I was prescribed with prednisone 10mg from day6 til next menstral period. I was also advised to have LIT (lymphocyte immunization therapy) 3 weeks after the IUI. What should go first IUI or LIT? I can read between the lines. I became undecisive because friends said they did LIT first. Is there any difference between third week after IUI and first week of next cycle? I felt Immunologist1 actions were biased. I did not get straight forward answer because she did not want to offend the referring doctor.

What would you prefer: IUI with NK cell highly active or IUI after NK cells are subdued? I prefer the latter. I cling on to hope that LIT is my silver bullet. LIT should be done first.

I called My Fairy Godmother to tell her I wished to cancel my IUI this cycle. But I was requested to see her at her clinic on day10. I went to her clinic as instructed. I also felt she and my immunologist had opposing opinion. I cried in her clinic as I told her my frustrations. Ooops... I made a white lie to cover up something. My Fairy Godmother was mad at my immunologist. I told My Fairy Godmother that I never confirmed the LIT, I was waiting for her go signal. My Fairy Godmother said LIT and IUI can be done simultaneously in one cycle.

I did not know who to trust. After a lengthy conversation, I agreed to proceed with IUI. She gave me a GonalF shot. Two schools of thoughts, either ways I can reach my goal. I chose to trust My Fairy Godmother. Then, I remembered OBGYNE1 last statement: no iui or ivf shall succeed if I have immunologic problem- this became the voice of my conscience. Grr... the voice my conscience is very noisy.

What should I do? There might be several other factors for my infertility. I was not absolute that my ultimate cause for infertility is immunology. Ah! Call my godsister- she is also a physician. If she did the LIT, ergo LIT must be safe. I will just follow her footsteps.

I cancelled the fifth IUI. No pressure, I can have my IUI again next cycle. The sad thing is : I just have offended My Fairy Godmother.

4th IUI

My Fairy Godmother's plan: 2 IUI first before IVF.

She believes immunologic factor is a secondary cause of infertility. She had requested my husband to have chromosome karyotyping because he has OATS oligoasthenoteratozoospermia. Hormones for husband and me...LH, FSH, Prolactin, Estradiol, etc...

Anti-mullerian, etc... For me. The only proven treatment for APAS (anti-phospholipid antibody) and ACA (anti-cardiolipin antibody) is heparin and aspirin. 

It was one day prior to ovulation when I had my first consultation with My Fairy godmother. We did the IUI the next day. I love about her aggressiveness. She suggested a double collection. Double insemination. But unfortunately, we never tried it.

I had a delayed period. I thought this was my fairy tale pregnancy! After I had endured the pain and bruises brought by heparin, but there was no reward. It was devastating to learn  that my endometrium did not get thicker after 2 weeks. 

Don't question why heparin... Heparin injection can be done after confirmed pregnancy but she prefers it to be injected immediately after IUI. She wants to improve pregnancy chance.  

I ovulated on the left. I suspect my left fallopian tube is blocked. I hope my problem was fallopian tube not immunology. I did my HSG with OBGYNE1. She believes my fallopian tubes are not blocked. Because she did the procedure but the radiology report shows otherwise. OBGYNE1's statement still reverberates at the back of my mind. No iui or ivf shall be successful if I have immunologic problem. For this, I requested My Fairy Godmother to hand me over to a reproductive immunologist. I just have the feeling she played blind on my LAT.