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The success rate for ICSI with fresh or frozen thawed sperm is the same. Since ICSI is going to be used to achieve fertilization (anyway), the morphology is not severe enough the affect outcome. No worries.

Yeah, there are some recent papers suggesting that all sperm parameters decline with age (including morphology). This goes against the (male researcher biased) dogma that men remain fertile for life. Although this may be true, it may be harder (wink, wink) for an older man (60's+) to achieve a pregnancy with his young trophy wife. Justice is served.

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Dear Dr. Smith:

thanks so ever much for your responses.

Liked the sense of humor too!

Turns out after bloodwork today, the retrieval is Monday now. So here's to hoping third time is a charm.

Cheers, Diana

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Dr. Smith,

I'm butting into Diana's conversation with you to ask what you mean by the "success rate for ICSI". Is that just fertilization rate? Or is it live birth rate? (Obviously it doesn't matter much if frozen sperm is as good at achieving fertilization, but is not as good at getting to a live birth. Something you once said gave me the impression that freezing sperm compromises the chromosomes.)

Thanks.

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I was referring to live birth rate. All things being equal, its the same for frozen-thawed and fresh sperm. In cases where frozen-thawed donor sperm is necessary, the live birth rate can actually be higher because the husband's sperm is of such poor quality.

I am not aware of any study that demonstrates that cryopreservation of sperm alters their genetic potential (chromosomes). This is probably because, in mature ejaculated sperm, the genetic material (DNA) is very tighly packaged and crammed into the head of the sperm. The DNA in mature sperm is inaccessable to most chemicals, including those used to cryopreserve sperm (i.e. glycerol).

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I now remember what you had said that made me think that freezing might damage the genetic components of the sperm. I had asked you a question about re-freezing sperm and you said that it wasn't a good idea because not very many would survive the second thaw. And I said that that didn't seem to me a very good reason not to refreeze, since ICSI would require only that maybe 10 out of millions survive the second thaw. You then said that even if the sperm survive, they might be too damaged to result in a successful pregnancy. What are the data on this?

Thanks, as always.

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Dr. SMith:

well, it may not be the most scientific....but here I am as a pratical subject matter on this topic of fresh vs. frozen

Back in Jan, the IVF cycle resulted in 11 eggs, 3 immatrue, 8 ICSI'ed, 6 fertilized and 5 transferred (8,8,7,7 4 divisions and looked non-fragmented as far as I could tell) and one made a pregnancy (then MC at WK8). This was with fresh sperm.

This cycle results in 11 eggs, 3 immature, 8 ICSI'ed and 4 fertilized. This is with frozen sperm. I believe all 4 embroyos will be transferred this Thursday. I'll see the picture of the embroyos then.

So most other variables held constant: me same (same food, exercise, etc), partner same....almost the same protocol of stims, except one day longer...I could tell that my right ovary was not a productive this time....only 3 follicles...Jan cycle had a good balance between the ovaries.... So the only variable I can think that really changed was his sperm from fresh to frozen....but again I am sure there are other factors outside of my pervue.....I aged 5 months for example... Just thought I would share my results since the starting point of 11 eggs /follicles was the same.

QQ if I may....(or kindly direct me to Dr. Jacobs)...when they do the aspiration of the follicles....it seems to be a long thin needle "poking" through from point A to ovary....I've seen the pictures, but forgot the terms....does the "hole" from the poking....self-heal?? Or do I leak???

Thanks so ever much for your understanding! Wishing you a terrific Tuesday! Diana

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Answer for teri-chan (BTW are you Japanese? The "chan" suffix is commonly used in Japan by friends and family members. The reason I know this is because my wife is from Kyoto, "Kiku-chan").

About 50% of the sperm die outright upon thawing the first time. Re-freezing and thawing again will result in even fewer surviving sperm. In my previous post, the term "damage" refered to their motility. Frozen-thawed sperm sustain damage to their tail that can result in weak motility. In other words, they swim slowly and, in many cases, around in circles. So the sperm that do survive are also be compromised.

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Answer for DianaEvans2:

The 5 months difference in age wouldn't have made a big difference. However, the big cycle-to-cycle variable is that every batch of eggs is different. You can have cycles with mostly "good" eggs and cycles with mostly "bad" eggs. That's probably the reason fewer fertilized on the second cycle. The fact that the sperm had be frozen and thawed did not come into play. As long as the sperm was viable at the time of ICSI, it can do its job. The reason an egg doesn't activate and initiate development after ICSI is that there is something inherently wrong with the egg. It does not respond to the injection procedure and/or presence of the sperm in the cytoplasm - a dud, as it were. Looks like you had more "bad" eggs on the second cycle. Look on the bright side, you have 4 embryos and there's still a chance.

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Dr. Smith,

Yes, I'm Japanese. Half. And that's in essence why I have the question about refreezing sperm.

Here's the story. I'm 42 years old, and I have no insurance coverage for IVF, so it makes the most sense for me to use an egg donor. But it's pretty much impossible for me to find a local egg donor who is like me. (To tell you the truth, it's hard to find any half Japanese and half Caucasian egg donors anywhere. Well, unless you and your wife have a daughter who'd want to help our cause!) Since my husband is Caucasian, and it's easy enough to find Caucasian egg donors locally, we decided to look for an egg donor who is like him and a sperm donor who is like me. We found a sperm donor, but he had only three vials of sperm available. One got wasted on a donor cycle that went very badly (14 eggs retrieved, only 3 mature, only 1 fertilized, none made it to blastocyst). To make up for the bad cycle, my clinic is giving me my next donor cycle "free" (not including my meds and certain lab tests). That's why I'm interested in the possibility of re-freezing sperm. (My other characteristics are also very hard to match, so I think that the chance of finding another sperm donor that matches me is vanishingly small. I keep looking, but so far, no luck. Again, unless you and your wife have a son who wants to help with our cause!)

So, given all this, and given that ICSI would require only a VERY VERY SMALL percentage of sperm to survive the re-thaw, does it make sense for us at least to try refreezing the sperm? (I don't suppose there's any way to thaw just part of the sperm, is there?)

Thanks.

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Dr. Smith: thanks so ever much for clarifying the two reasons why a greater percentage of my eggs this cycle were duds...That makes sense. I read your posts before about duds but forgot the reasons... As you say....I still have a chance-THANKS YOU! (albeit statistically more remote than I was hoping for this cycle....but as Gloria Gaynor sings...."I will survive"....I am talking about my embryos)

Back to my slightly silly question (why would I even think of it now after having the procedure done...well, I was describing it to a foreign friend who looked perplexed and that got me to thinking....)

QQ if I may....(or kindly direct me to Dr. Jacobs)...when they do the aspiration of the follicles....it seems to be a long thin needle "poking" through from point A to ovary for the follicle aspirations...I've seen the pictures, but forgot the terms....does the "hole" from the poking....self-heal?? Or do I leak???

Aside: Teri-Chan: very interesting set of matching questions you have...you have my empathy....I can only share that I have one Caucasian/Japanese female friend (half Danish actually)....but she's 32, deathly afraid of needles and have moved back to Scotland recently. Her father was a Danish sea-captain and the mother Japanese.....any donor potentials that are children of US servicemen in Okinawa....I think there is still an Army or something base there....probably not me being helpful here....so I'll stop...

Wishing everyone a wonderful Wednesday!

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Answer for Teri-chan:

Yes, I guess you could always try to re-freeze the sperm. What harm could it do? Worst case, they would have to thaw another vial.

Sorry, no daughter. Two sons, 13 and 15. I'm not sure they want to be fathers just yet. So far, I've try to discourage them from attempting...

I would suggest sperm banks on the west coast (i.e. California Cryobank) for the best chance of a match. Too bad there is no sperm bank in Hawaii. Many, many "haapa" (Hawaiian slang for half and half) people there. A match would not be difficult.

Just as an aside. My older son cleary looks "haapa", but my longer son looks 90% caucasion. Hard to tell he's Japanese at all. He looks a lot like my father (not me!) Go figure. Genetics is a funny thing.

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Answer to DiannaEvans2:

Sorry, I forgot to answer your second question in your first post. Yes, the hole in the follicular wall is self healing. In a natural cycle, the follicle wall ruptures to release the egg. So, its a natural process. However, during an aspiration, the needle pokes through ovarian tissue to get to the follicle (not a natural process). There is usally some bleeding from the poking around, but the blood clots at the puncture site. Some blood accumulates in the cul-de-sac (a pouch-like area behind the vagina), which get resorbed in time.

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To Dr. Smith:

The sperm donor we found was from California Cryobank. He's 100% Japanese instead of happa, but since he matched my other characteristics unbelievably well, we went with him. As you say, genetics is a funny thing, and we feel confident that it's funny enough that if we had a child by this donor, it would not be obvious that the child was not ours genetically. (I have a friend whose children are half Japanese and half Caucasian, and like your children, one of his looks like a mix and the other looks pretty much Caucasian. In my own family, one of my brothers looks more Japanese than I do and the other more Caucasian.)

I do keep checking at California Cryobank (and also at Fairfax), but so far no more luck.

Do you know anything about the feasibility of my searching Japanese sperm banks? Is sperm shipped internationally?

Just by the way, I did check into egg donors in Hawaii. But I didn't find one who felt like a good match. There are also logistical issues. It's just a lot easier to use a local egg donor.

Here's what you had said previously about the issue of refreezing sperm--the stuff that made me think that it was an issue more of genetic damage than motility. "As long as you have the other two vials as back up, you could re-freeze the frozen-thawed sperm. You're right that when ICSi is performed, only a few sperm are needed. However, there have been a few publications from independent labs demonstrating that cryopreservation induces DNA damage in the sperm. In addition to ending up with a very few viable sperm, they may contain damaged DNA. They will look normal on the outside, but if used for fertilization, can cause embryonic arrest - usually before the blastocyst stage. I would consider this risk seriously."

To DianaEvans2:

Too bad your friend is afraid of needles! Interesting that you should mention Okinawa. I lived there when I was a child. I hope your four embryos are still developing and that all make it to your Day 3 transfer.

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I appear to be contradicting myself. Let me try to explain.

In one post I said that I knew of no publications that demonstrated that cryopreservation damaged the chomosomes. As far as I'm aware, cryopreservation does not damage the chromosmes directly or not effect the number chromosomes. Using frozen-thawed sperm (frozen-thawed once) seems to be safe. That is, no observed increase in early misacarriage or birth defects that would be associated with chromosomal abnormalities.

However, a couple of recent publications (one in the boar, one in the human) suggest that cryopreservation may induce damage to the DNA (see references below). Although chomosomes are made of DNA, there is a functional difference between the two. DNA damage may occur, but that doesn't necessarily affect the function of the chromosome as a whole. Does that clear up the apparent contradiction? It looks like cryopreservation may cause the DNA to become fragmented and we know that embryos derived from sperm with excessive DNA fragmentation can arrest prior to reaching the blastocyst stage.

My cautionary point was, although you might be able to get away with freezing and thawing once with some minimal DNA damage, freezing and thawing twice may be pushing it. No one has studied the effect of freezing and thawing sperm twice on DNA integrity, but it stands to reason if once causes damage, twice will cause more. It is something to consider. I think that the individual sperm that do survive being frozen-thawed twice [i]may[/i] be OK to use for ICSI. The egg has some capacity to repair the DNA fragmentation in the sperm. Its all a matter of degree and how much risk you want to take.

References:

Effects of freezing-thawing on DNA integrity of boar spermatozoa assessed by the neutral comet assay.
Fraser L, Strzezek J.

"The results of this study show that the freezing-thawing process affects the DNA integrity of boar spermatozoa..."


Evaluation of chromatin integrity in human sperm using acridine orange staining with different fixatives and after cryopreservation.
Chohan KR, Griffin JT, Carrell DT.

"...cryopreservation increased damage to the sperm DNA. Present data also showed that spermatozoa from some individuals are more prone to DNA damage after freezing and thawing procedures than others."

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Yep, that clears it up. Thanks so much!

So, I'd like your thoughts about the following plan, which assumes that we can come up with the money for three egg donor cycles (and any associated thaw cycles). I realize that this is a matter for individual judgment, but your judgment is appreciated.

Cycle 1:
Use one of the two "original" vials of donor sperm. Refreeze what we can.

If Cycle 1 (and any associated thaw cycles) doesn't result in a live birth, move to Cycle 2:
Use the second of the two "original" vials of donor sperm. Refreeze what we can.

If Cycle 2 (and any associated thaw cycles) doesn't result in a live birth, move to Cycle 3:
If we haven't found another sperm donor who is a really good match for me, then use one or both of the "refrozen" vials of donor sperm. (In this case, we would have as back-up, sperm from some donor who though not a REALLY GOOD match for me is at least not a bad match. We could use this if not enough of the re-thawed sperm were in good enough shape for ICSI.)

Does it ever happen that a vial of sperm from a reputable cryobank is a complete dud with not enough sperm survivng one thaw for ICSI?

As always, thanks.

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Yes, I think this is an excellent plan.

I have never thawed a vial of frozen donor sperm that did not contain at least enough sperm for ICSI. Most banks guarantee, if you use their thawing protocol, somewhere between 10-12 million motile sperm post thaw. That shouldn't be a concern.

Best of luck.

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