ICSI/AH/PGD? at 40
10 Replies
Sherri - March 26

First IVF coming up....age 40.25

Get preggo fast naturally but 4 losses (1 known trisomy) and 2 living children (3.5 yoa and 9 months). Clotting/immune stuff negative. On the cycle I got my 9 month old we did IUI/injects with Gonal-F (150IUs 3 days, then 75IUs 3 days, then 1 day 37IUs) and I made 15 follies above 11mm...probably 6 mature. One singleton pregnancy. My FSH was 2.8 then. I decided to go to IVF now b/c my FSH is now 6.8 and I don't want to waste time. RE did a trial IUI/inject cycle last month but I O'd prematurely on my own after 5 days of stimms (11 follies over 11mm on 150IUs Gonal-F). So now here we go IVF.

My question. RE says due to my good response to meds we should consider PGD. So.....

1) Can we still do AH and ICSI? I thought I needed these things due to my age-but how could the embies take PGD too?

2) How do you make the decision to do PGD? Can you give me some scenarios to help....like if I have a certain amount of embies on day 3 of certain quality maybe a try at PGD is doable? How do embryologists make the decision to let embies go to day 5? Can you look at an embie on day 3 and guess that it might survive PGD and/or a few extra days?


Dr Smith - March 27

If you have PGD, ICSI will automatically be performed to avoid DNA contamination from supernumary sperm attached to the zona pellucida (protein coat that surrounds the egg). Assisted hatching is performed when the embryo is biopsied. In order to remove a cell from the embryo for analysis, a rather large hole must be made in the protein coat. This hole is equivalent to the the hole made for assisted hatching.

Recurrent miscarriage (3 or more) is considered an indication for PGD. In your case, I would suggest PGD no matter how many embryos are available for biopsy on Day 3. The genetic analysis usually takes 24 hours, so the embryos will be cultured at least to Day 4 because of the PGD. Being the big fan of blastocyst transfer, I would suggest waiting to see if the "normal" embryos make it to the blastocyst stage prior to transfer. At least then you can be sure that the "normal" embryos are capable of attachement and implantation. Just because they are considered "normal" by PGD doesn't automatically make them capable of reaching the blastocyst stage. The contrary is also true.

In most practices, the RE, not the embryologist, makes the decision to culture to the blastocyst stage. This is based on several factors (most of them non-scientific). See http://sharedjourney.com/a

is impossible to determine, with any degree of confidence, which Day 3 embryos will continue to the blastocyst stage. Only time will tell.


Sherri - April 23

Thanks, me again. Would like your thoughts. Just got my fertilization report and worried. I know that my age and history make me a good candidate for zero normals via PGD, but I expected better fertilization b/c of the ease with which we get preggo naturally.

Here's the scoop. I am not PCOS by the way. I was put on Long Lupron Protocol, and after 9 days of stims I had 36 follicles, e2=3300, and lead follies 20mm, so triggered after 9 days of stims. 48 eggs retrieved.

Half were ICSI'd even though dh's sperm is stellar (I asked for this) and half fert. microdrop. Out of 24 ICSI'd, 20 were mature and 11 fertilized. Out of the 24 microdropped, 10 fertilized. This seems like a bad omen right out of the gate. It doesn't appear to be improper timing of hcg as a lot of ocytes seem to be mature. Is it just bad eggs? Would stimming longer help-more than 9 days? Geez I was on a low dose of meds (150IU Gonal-F and 75 Menopur).

I already know I have bad eggs due to 4 losses and age, but I always thought even bad eggs fertilized well.


Sherri - April 24

I guess what I'm wondering the most is...does the reduced fertilization imply I've got a bad cycle going here already? In this case, I'd avoid the PGD (get my money back) and just do a day 3 transfer, and then maybe try one more IVF in hopes of getting a good cycle for PGD. The PGD adds a lot of cost as you know....and I want to make sure I write that check on a good cycle.


Sherri - April 24

Okay, update. It's day 2, and lab told me everything looks great so far...all good news. She said all 21 are dividing and are 2, 3, 4, and 6 cells. She said 2 had minimal fragmentation but "they look like we want them to look." She said she had no bad news for me today. She said we will definitely have enough to do PGD on tomorrow. What do you think Dr. Smith?


Sherri - April 25

I went ahead with PGD today, day 3.

20 were biopsied (1 was a 4-cell which was left to culture further)


also know that fragmentation was as follows:
4 had 0-5%
9 had 20%
6 had 21-40%
1 had 41%

I know that I have zero chance with anything beyond 20%, but are the 20% frag ones in bad shape too?

I'm trying to do the odds here....if the 0-5% frag embies are only viable ones I have, then chance is small that one of them will be PGD normal.

I wonder why the lab biopsied the ones higher than 20% frag and didn't discard them. I forgot to ask.


Dr Smith - April 25

Its not hard and fast. Embryos with around 20% could go either way. I think you should consider those embryos as borderline and not rule them out yet. Wait for the PGD results. You may be surprised to find that a couple/few of them are "normal" by PGD. Whether or not they make it to the blastocyst stage is another matter, assuming they are going to wait until Day 5-6 to transfer the embryos. All bets are off if they bail out and transfer them on Day 4. I think they biopsied all the embryos for the sake of completness. I'd do the same.


Sherri - April 25

1)Thanks. So if any of the 20% frags make it to blast, and that is all I have, would you put in more on day 5 (we're going to day 5) b/c of reduced implantation related to fragmentation?

2)If they reach the blast stage does their fragmented history become less important?

3)Is my age the reason for reduced fertilization and higher fragmentation? If you would try another time, what might you change?


Dr Smith - April 26

A1. Not necessarily. If the "normal" embryos make it to the blastocyst stage and are of good quality (in spite of the early fragmentation), then the age-appropriate number of embryos for transfer should be considered the upper limit. If the quality of the "normal" blastocysts are less-than-stellar, then increase by one.

A2. At the blastocyst stage, the fragments are pushed to periphery of the embryo and left behind in the protein coat when the blastocyst hatches out. At that point, they are of no consequence.

A3. Age plays a role as does the mangement/mismagement of the ovarian stimulation. Sometimes changing the stimulation protocol to fit the patient will improve fertilization and reduce embryo fragmentation.


Sherri - May 7

Last questions....sorry.

This is what happened...and you were right by the way to wait for the PGD results.

PGD and transfer information below:
20 embryos biopsied for PGD (7 were normal on the 9 chromosomes tested but not all arrived at blast stage on day 5)

12 total blastocysts on day 5 (4 were normal)

4 normal blastocysts on day 5:
1) One at hatching stage (advanced stage)
2) One beginning to hatch (relatively advanced stage)
3) One cavitating (early developmental stage)
4) One early cavitating (early developmental stage)

3 normal embryos not quite at blast stage on day 5

***Transferred top 3 blasts (1,2, & 3)***

At transfer, 5dpo, (e2=2800 & progesterone=200)
Two days after transfer, hospitalized for severe/critical OHSS...3 liters fluid drained from pelvic cavity, and following blood tests abnormal (hematocrit, electrolytes, white blood cells, liver, kidney) I know you may not have time to reread the previous posts but I was on Gonal-F 150IUs, Menopur 75IUs for 8days, then triggered, 48 eggs retrieved...roughly 40 mature....50% fert. rate even with ICSI, 20% frag. on a lot of embies.

Day after transfer none of sufficient quality to freeze

1) I know I have better chance with donor egg....but
2) If you would say try one more time what would you make sure to change here? Can you troubleshoot the cycle a little? I know you can't talk about the medical stuff, but from the embryos point of view. I'm going to be evaluated for PCOS next cycle even though I have no other symptoms except for responding like someone who has it. Have you ever seen patients' embryo quality improve on Metformin? Do your patients with with severe/critical OHSS during implantation period show reduced success?


Dr Smith - May 9

You sound like a "closet" PCOS. They may also call you a "hyperresponder" or "multicystic". No matter what you call it, too many follicles develop on the stimulating cycle resulting in decreased fertilization and compromised embryo development. HOWEVER, you didn't do so bad and I think your chance of success is pretty good based on your post. There have been a few studies on pre-treatment with Metformin before IVF. The results of these studies are mixed, but none of them found that Metformin pre-treatment improved egg quality per se. OHSS does not interfere with implantation, but implantation interferes with OHSS. If implantation occurs, OHSS symptoms can be more pronounced and take longer to resolve.

Good news / Bad news: Yer pregnant, but you feel like crap for two weeks and may have to be drained more than once.



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