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A1. Your chances of success are based on two things. The number of eggs produced during a stimulated cycle and the quality (genetic potential) of the eggs. Your highish (if that's a word) FSH is indicative of a diminishing ovarian reserve which is a way of saying that, compared to other women your age, you will produce fewer eggs on a stimulated cycle. The developmental potential of your eggs is closely associated with your age. Although you are older, you are not old. At 35, about 30-40% of your eggs will be genetically normal. So your chances are not too bad. It will be a numbers game - the more eggs you produce, the better your chances.

A2. Different labs grade embryos differently, so its a bit subjective (one lab's grade 3 is another lab's grade 4 and so on). Although they had significant fragmentation (hence grade 4), they still proceded to the blastocyst stage and were considered worthy of cryopreservation. So they must be O.K. I'd say your chances of success from the FET of two blastocyst stage embryos would be around 30%. Do an FET before considering another cycle.

A3. Increased intra-abdominal pressure (like from coughing or vomiting) is not a good thing during the attachment phase of implantation. It could have contributed to the failure, but it is unlikely that it was the only cause. Don't beat yourself up about it.

A4. This question is out of my field of expertise. To the best of my knowledge, only one program is using the mini-hCG protocol. I have no personal experience with the mini-hCG protocol. Sorry.

A5. Reproductive autoimmune testing is expensive and must be justified. In my opinion, the chemical pregnancy was more likely caused by a genetically abnormal embryo, rather than an autoimmune reaction. The second failure was likely just the luck of the draw.

A6. I am unaware of any association between high FSH and making the Day 3 versus Day 5 decision, so I'm not sure why they said that. As you are probably aware from my posts, I'm a proponent of blastocyst transfer and I believe there are several advantages to waiting until Day 5. You have a history of embryos reaching the blastocyst stage in vitro, so I don't see any reason why you shouldn't have a Day 5 transfer.

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Dr. Smith,
Since my last posting to you, I went through the FET cycle and unfortunately, it is another failed cycle. I would appreciate your opinion on a few issues.

I have two 5 days old blastocysts that thawed beautifully. The embryologist told us that one was fully expanded and the other was 80% expanded. We asked about why assisted hatching was not done on the blastocysts and was told that they don't do assisted hatching on blastocysts. What is your opinion on this?

For this cycle, it took 24 days for my linings to get to 8.3mm. The doctor told me that this is fine and that they give a window of 28 days for the linings to grow to acceptable range (which is atleast 8mm). Do you think the linings is still too thin and whether the length of time it takes the linings to grow contribute to the failed cycle?

Given my track record of failed cycles, would you recommend for me to try again? I am beginning to lose hope since all the cycles seems to produce good quality embryos but yet, none of the embryos want to take. The last 2 cycles have not even produced a chemical pregnancy.

Is there anything that you would recommend I should do differently should I try again? Your recommendation is very much appreciated.

Thanks,
Loanne

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We routinely hatch all frozen-thawed blastocyst stage embryos prior to transfer. The rationale for this is as follows: it is the time when hatching occurs naturally, so the timing is appropriate (as compared to Day 3 hatching which may be premature); there is some evidence to suggest that the freezing and thawing process "hardens" the zona pellucida and makes it more difficult for the embryo to hatch by itself. I guess the results of not hatching are reflected in their implantation rate (i.e. percentage of embryos that implant after transfer - this is distinctly different from pregnancy rate, which is an all-or-none outcome). Unforunately, there's not way to get at the numbers as they are not published with the othere CDC data. I know that our implantation rate went up 22% as a result of hatching blastocyst stage embryos.

I'm finding more and more that people don't know how to hatch blastocyst stage embryos, even though the protocol was published several years ago. It surprised me, as many programs have adopted routine hatching of Day 3 embryos, so why not blastocysts? Don't know.

In terms of thickness, your endometrium was within the "good" range of 8-10mm. The length of time required for endometrial development also seem appropriate. No problem there.

In your case, its a numbers game. You do not produce a large number of eggs on any given cycle (as predicted by your FSH lelve) and, at 35, your age is coming into play in terms of egg quality. Because there are fewer egg and their quality is decreasing with age, you may need more attempts that other women your age. I recommend that you do not give up. I also recommend that all subsequent transfers be performed at the blastocyst stage. That way, you can be sure that the transferred embryos are capable of attachment and implantation. No more "Your embryos look great!" Day 3 transfers that result in disappointment.

You may also want to investigate immunological factors such as increased NK cell levels or increased NK cell activation. I have recently posted some information sources regarding immune testing. The chemical pregnancy followed by 2X implantation failure with "good" embryos is suspicous...

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Dr. Smith,
I really appreciate your recommendation and the information you have provided. I got more answers and explanations from you than from all the doctors that I have been seeing put together.

Your forum has provided me with invaluable information and hope.

Thank you!
Loanne

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Dr. Smith,
I am 34 years old and have been diagnosed with diminished ovarian reserve, I have an FSH of 13.9 and my day 3 E2 levels were 41. I have had 2 IUI cycles on clomid but neither have been sucessful. The second cycle my RE had me on clomid 150 mg and I produced 2 follicles which she acted like she was pleased about. Since then I have done research on the internet and found conflicting information including much that says I should just get a donor egg. I do have a child already that is 2 yrs old, so I don't think I have any other fertility problems. Would your suggestion be to move on to injectables or is it simply unrealistic for me to expect to ever have another baby on my own? My FSH was 11.5 and then I did a couple rounds of clomid and a round of letrozole at my ob/gyn before I had the FSH of 13.9, could that have caused an increase in the FSH? Thank you so much for your help.

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