Failed five - immune issue?
7 Replies
WDTP - December 11

Hi Doctor Smith,

Don't you get sick of all sometimes? You really appear to have the patience of a saint and the expertise worthy of the title. Thank you!

TTC for three years. We have been through five failed cycles, all on Gonal 150 (lucrin 15mg), aged 35 and originally no known cause from me or my partner although following cycle three, endo was confirmed and removed from both ovaries. Previous tests over the past few years suggested i ovulate well with good oestrogen levels. No family history of infertility and generally i feel great and healthy even with the IVFs. (Yes I do have quite a few cramps and aches but i assume that is all to be expected and pretty normal.)

I have detailed my cycles below but to save you itme and get to the punchline my question is. Is this an immune issue?

From what I gather from your incredibly helpful replies and what i have read on this forum, my response is in range and pretty ok so I wondering if it is an immune issue as out of five attempts i have not even succeeded with implantation. Sigh.

My RE maintains it is all about numbers and immune testing isn't on the radar as yet. (Also a great beliver in endo as the symptom and not the cause of infertility and i think that sounds rather wise). How much should we push immune testing or is it better just to keep going on the basis that the best way to raise our chances of conception is IVF? I am dong ok and getting increasingly philosophical about what the future holds -yes a bit demoralised at this stage and really trying to make the right decisions so I hope you can help.

Bit more b'ground below if you have time to read it:

Cycle one was fresh with oestrogen levels of 12,000 (you've converted these levels before for me and reckoned they were ok) and pick up on day 13. Nine occytes and seven fertilised. One transfer on day three, grade two four cell. The remainder were frozen but the second frozen cycle had poor thawing results, two were replaced but no luck.
My third cycle was also a fresh cycle, oestrogen levels got to 14,000 by pick up on day 14 - there were fewer follicles than expected in ultrasounds so as I understand it my doctor was hoping to catch a few mature but not over sized. They got 8 follicles, varying in size from 18mmm to 28 mm. Five fertilized and they replace two, two grade two four cell. None were frozen as I asked them to only freeze good quality and there were two grade three that survived.

Subsequently I have had my first laparoscopy and removal of endo growth on both ovaries which wasn't properly discovered until post my third cycle.

My fourth cycle appeared to go well with nine eggs, all 9 of which (or whom!) fertilised. Three made it to blast on day six and were frozen and two were transferred on day five one was a good blast (no more info) and the other was compacted morula but looked good. Result no implantation.

Our fifth attempt yielded seven eggs, (not so good) six fertilised and by day five only one was looking good (but a compacted morula) so was transferred along with a frozen (well yes thawed) day six blast. As it transpired another made it to day 6 blast and was frozen but the embryologist wasn't too enthusiatic about it. So neither am I.
Result - no implantation.

Thanks Doc I look forward to your reply!


Dr Smith - December 13

I'm going to forward your post to Dr. Jane Miller, the RE I work with. She will give you the full poop on immune testing.

There are a few of red flags in your history that would point towards immune problems (Dr Miller will explain). I would push for immune testing. It is not surprising that your RE thinks that immune problems are not in the picture. The contribution of immune factors to implantation failure is controversial. You are either a "believer" or not. At our program, we are believers. This is because we are not usually the patient's first stop. Most of our patients have been to one of the super-sized programs in NYC, but without success. Because of our patient population (the "tough" cases), we have to be better "detectives". That leads us to think outside the box and try different approaches.


Dr Jane - December 13

My goodness - you've been through so many cycles. There are several things that concern me: 1) why was the laparoscopy done after 3 failed cycles?I believe in diagnosis first and then treating the patient. Endometriosis may affect the outcome of an IVF cycle. It may compromise egg quality. It may prevent implantation - so I do not agree with your doc that it was noncontributory. I note some follicle dyssynchrony in your stimulations. I would use a GnRh agonist - we use Lupron - concommitantly with the gonotropins in hopes of ultimately retrieving more mature eggs. As far as the immune issues: I definitely think that you should have testing for antiphospolipid antibodies as well as natural killer cells. The fact that you have not even had a chemical pregnancy is highly suggestive of an "implantation factor". If your endometrium is proliferating well (triple pattern, at least 8mm) then there may be an autoimmune problem preventing embryo attachment. As Dr. Smith wrote, we see many cases of patients with immunologic factors that have not been discovered previously.It is true that this is a controversial area but we have seen and successfully treated for implantation problems time and time again.
Good luck,
Dr. Jane


WDTP - December 14

Dear Dr Smith and Dr Jane

Thank you both so much for your replies. It is difficult to properly communicate what an impact the assistance that you offer has on the lives of people like me and so many others. It is almost hard to believe that you are there adding to our picture as you do.

Re your questions Dr Jane:
1. A suspicion of endo was noted during the first cycle but not followed through (spotted during ultrasound). It was actually I who insisted that we pursue the lap after cycle three. I hadn't really presented with it until then as I think I was so accustomed to managing the pain. Certainly previous bloodtests and ultrasounds hadn't picked it up. It was only when I priorised actually registering the pain, rather than trying to get on with life, that I realised i had quite a bit of it! Not great but we are where we are.

Yes my endometrium lining appears fine. It has been between 11 and 13 cm throughout each of the cycles so again all looks fine on paper.

2. Could you please explain what you mean by follicle dyssynchrony in the stimulations? Is it that there is a variance between cyles where a different protocol might assist with greater quality control?

3. Similarly I don't understand what you mean about the GnRh agonist and what it is. Again is it that the addition of another drug might assist with egg maturation or locating the good ones (assuming they are there)?

Finally what you both say about immune issues makes perfect sense. I certainly feel that I am heading towards the tough cases basket. I will pursue immune testing with verve, not sure what options are open to me in Australia but I'll keep trucking and keep you posted.

Sincere thanks


WDTP - December 19

Sorry Dr Jane (or Dr Smith but I think these are for Dr Miller)
I fear my reponse and accompanying questions may have gotten lost in the mix. Perhaps not as I know how busy you must be it may just be one on your long list but I'd be grateful if you could reply to my questions (above) when you get a moment.

Many thanks


Dr Smith - December 19

A2. Follicular dysynchrony means that within a given stimulated cycle there are some big (mature) follicles and some small (immature follicles). Usually about half anf half. When there is a great deal of dysynchrony, there may be only a few mature follicles at the time of hCG. At the time of the egg retrieval, only a small number of the eggs are mature (presumably from the larger follicles). Follicular dysynchrony can be lessen by the use of a GnRH agonist (more about that in the next answer) to prevent the pituitary gland from secreting your own FSH which jump starts the growth of some of the follicles at the begining of the cycle.

A3. The most common GnRH (Gonadotropin Releasing Hormone) agonist is marketed in the US under the brand name Lupron. I don't what its called in Australia, but I'm sure its available under some brand name. In a standard stimulation protocol, it is used during the last part of the preceding cycle and during the stimulation phase of the IVF cycle to prevent the pituitary gland from secreting FSH and LH. In this way, all FSH and LH comes from the stimulation medications. When Lupron is used, follicular growth can be more tightly controlled and, to some degree, synchronized. The follicles will mature at approximately the same rate and (hopefully) more mature eggs will be available at the time of egg retrieval. This standard "down regulation" protocol is not always the best approach, especially in cases of low ovarian reserve and advanced maternal age.


WDTP - December 20

Many thanks Dr Smith as always for this exceedingly helpful reply. If we are ever to be successful, much of it will be attributed to you and this site. If not then you have been equally helpful albeit in a different way!

Merry Christmas!


Dr Smith - December 21

Thanks (blush). Happy Hollidays.



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