Sunday, December 14, 2008

The Road to Blastocyst: Eggs and Embryos






This is the first installment of blastocyst blog; but it's a bit of a pre-requisite. To give you a feel of where we are going, I will start with pictures of eggs and embryos and then blastocysts.




This is an egg. I doesn't really look like an egg. Part of the reason for this is that in this picture there are hundreds of cells, but just one that is an egg. The dark circle in the center is the egg. You can see how big eggs are compared to the rest of our cells. The surrounding specs are granulosa cells. These are the ovarian cells that line the inside of the follicle. Prior to ovulation, the egg's position in the follicle is along the edge, so the granulosa cells that are growing along the inside of the follicle surround the egg. When the egg ovulates, it carries some of these cells along. When an egg is retrieved during IVF, it is also surrounded by granulosa cells.
The granulosa cells make the estrogen (estradiol). So as the follicle grows, more granulosa cells form, and estrogen rises. In an IVF cycle, the more eggs there are, usually the higher the estrogen levels.





This is a picture of an egg a few hours after retrieval, after the granulosa cells have been removed.
In the case of IVF using ICSI, the embryologist needs to remove the granulosa cells a few hours after retrieval. This is necessary so she can see the egg and to properly inject the sperm. If ICSI is not necessary, we can mix the eggs and sperm together, and the sperm will swim through the granulosa cells to get to the egg.
The little round object on the top is the first polar body, and this is an indication that the egg is mature. The first polar body contains chromosomes, as does the larger egg cell. For the egg to accept the DNA of the sperm, it needs to dump some of its own DNA, otherwise there will be too much. So the egg unloads some of the DNA into the polar body, which just withers away. Sometimes testing the DNA of the polar body can tell us about genetic diseases in the egg. For the most part, we can not use an egg that is not mature. There is some encouraging research looking at maturing eggs in the lab, but so far the process of maturing eggs in culture has not been widely accepted.



This is what we call a 2 pn zygote (or 2 pn embryo). The picture was taken one day after the retrieval. You can see a few granulosa cells still hanging around.
The halo around the embryo is the zona pellucida. It's the shell of the egg. It has the consistency of a thin vitamin E capsule. Inside is the egg (or oocyte). In the middle of the egg, you can see 2 little round objects, and these are the pronuclei (pn). One contains the genetic material from the egg, the other from the sperm. In some animals we can tell which came from where, but not in the human, although as our microscopes improve, I suspect we will very soon be able to tell. So if we expose eggs to sperm, and look the next day, and do not see 2 polar bodies, fertilization has not occurred. Sometimes we see one, and this means fertilization possibly occurred. In this case we may or may not see 2 later in the day. The 2 pn will combine to complete the fertilization process.
Dr. Licciardi

23 Comments:

Blogger Niki said...

Thanks Dr. L! I love it that you are doing a mini-biology lesson! I'm a biologist and feel that too many women suffering from IF don't understand reproductive biology let alone embryology, so it's great that you are teaching them! Again thank you for sharing your wealth of knowledge with the IF blogworld and Happy Holidays to you and yours!

11:16 AM  
Blogger Mo and Will said...

This is a great and helpful post, thank you! Am hoping that in your next installment of "on the road to blastocyst" you will write about embryo quality - and specifically the significance of embryo fragmentation (even on embryo fragmentation removal if that's something NYU does). I am at another large academic medical clinic in NYC and am in the two week wait following the transfer of 3 day embryos that were fairly fragmented. I got so upset about the way they looked, I even blogged about it (http://lifeandloveinthepetridish.blogspot.com/2008/12/pictures-from-petri-dish-dont-judge.html).

Would love to read more on embryo quality and development and the prognostic significance of this.

Thank you! You do a great service for infertile couples everywhere.

Mo
www.lifeandloveinthepetridish.blogspot.com

9:27 PM  
Anonymous Anonymous said...

Dr. L - I don't know if you are answering more questions but if you are, here goes: I am 34, trying for 15 months, did 3 clomid/iui cycles, first was neg, second was biochem, 3rd was early mc at 5 weeks. Since then I have been taking baby aspirin, prescription folic acid, Endometrin suppositories (2 am, 2pm) and vivelle patches. I have done that by itself for 2 cycles. Should I keep doing that and trying naturally and if so, for how long? Are injectibles the next step?

7:11 PM  
Blogger Laura said...

Awesome! This is very informative, but easy to understand. You have great pictures also. Thank you for doing this. You are truly a blessing to the world.

8:21 PM  
Anonymous Anonymous said...

Do you think there is anything to the idea that bisphenol a (BPA) could affect implantation? I've had two failed IVFs (with lovely embryos/blasts), and I'm wondering if it was because I drank from an old Nalgene bottle all the time and ate lots of canned vegetables (BPA leeches out of the liner in the cans). I know some research about BPA was presented at ASRM recently - do you think it's something to consider?

3:58 PM  
Blogger newenglander2 said...

Hello, Dr. Licciardi:
thank you for taking the time to write this blog. It's immensely helpful!
My husband and I are a particularly challenging case. He has been diagnosed with severe oligospermia. At the time of diagnosis, his count was 0 (or fluctuating to 400K) with little to no motility, borderline low testosterone. He is 41 yo, healthy, normal genetic testing. He's been on clomid for 6 months now, count has gone up to 800K, much improved motility and good testosterone level. ICSI is the way to go for us.
I'm 34 yo healthy female, normal genetic testing, however I respond poorly to IVF. First cycle was estrogen patch/antagon (gonal F 450, repronex 150), 4 follicles, 3 eggs retrieved, 1 fertilized (at the time husband was not "optimized"). Second cycle (3 months ago) was estrogen priming/antagon (same dosages), I had 5 follicles, but ovulated prematurely. Now I'm on my 3rd cycle: went right ahead with flare up, cetrotide on day 7 and on. Only 3 follicles on Day 8: an 18, a 15 and a 9.
When I see the number of follicles, my hopes just sink. Any thoughts, hopes, success stories?

1:53 PM  
Anonymous ASABgirl said...

If you are taking questions, I have one:

My husband has good sperm quality. I check out great on everything except I have a pretty bad case of antisperm antibodies. The only time I have ever been able to get pregnant was unexpectedly eight years ago when I was taking codeine cough syrup for a bad cold. I theorize the codeine suppressed by immune system enough to allow conception. I've tried regular cough syrup with guafenesin and it doesn't work.

Any suggestions for me outside of IVF, such as how to suppress the ASAB? Thank you!

8:54 PM  
Blogger Lorraine said...

This is fascinating - thanks for explaining it all so clearly. The only thing I don't understand is in the last paragraph - are the pronuclei also polar bodies? Do they wither away? At what point does the mix of genetic material become permanent?

Of course, I should probably just wait for the next installment...

3:59 AM  
Blogger Lisa said...

Dr. L - I am new to your blog - thanks for your posts - they are so helpful.

I will toss a question out to you as well...

I am 34 years old and did two IVF cycles last year and an additional one that was canceled after four days on stims. My husband had a vasectomy 10 plus years ago and we are doing PESAs. All my numbers are ideal and I look like a dream on paper first antral count of follies was 10 but after my suppression checks I had 16 and 17 follies. My protocol has been roughly the same - long lupron with 300 units gonal f and 75 of menopur. The first IVF - I responded with a few eggs growing very rapidly and the rest not doing much of anything - three eggs retrieved, one fertilized, perfect 8 cell transferred on day 3, biochemical pregnancy. For #2, they got 9 eggs - I responded well - 4 fertilized, transferred two nice 6 cells on day 3, biochemical pregnancy again and the other two did not make it to blast. IVF# 3 - same response as IVF#1 and we canceled. Oh, my lining both times has been at 16.

There is some question whether we have a sperm or egg issue and I have always been worried about the thickness of my lining - too thick?

We are going to try again - my RE said she would use less lupron even though there is not much to prove it has a result ovarian response and a more aggressive stim protocol. What are your thoughts for getting more eggs and my lining? Thank you in advance if you are able to respond.

2:23 PM  
Blogger carrie b said...

Thank you so much Dr. L for your blog! It is very informative and i have passed it on to all my friends on Ovusoft.com and it was listed now as a FAQ :)
We have one daughter, 18 months concieved naturally. Now, we have been struggling for #2 for 8 months. I am currently on clomid 100mg cd 3-7 to improve a lutel phase defect..I start spotting 10 days past ovualation. All my bloodwork has come back normal and i am normal weight and healthy. My husbands sperm analysis came back as 39 Million, 41% motility and 0% Morphology. He does have a hydrocele though. We are concerned about the morphology and wondering what your thoughts are on this subject. Thanks!!

1:35 PM  
Anonymous Anonymous said...

Hi Dr L,
What do you think of the OV Watch or being able to tell from a chemical being sensed through the skin for ovulation?

My husband has had one good not great count/motility and the next 5 have shown low count and low motility, the uroglist told him his prostate was a little enlarged and put him on antibotic for 6 weeks not much improvement. He also told him it was good that he did it more that once during intercourse.
AL

A

5:56 PM  
Blogger Jenn said...

Dr. Licciardi:
This has nothing to do with blastocysts (unless I miraculously conceive!). I've posted a couple times before here.

In brief summary - in March of '07, my first lap revealed stage 3 endo. In November of '07, a repeat lap showed that the endo had regrown significantly worse than before. Due to previous hormone intolerance, we chose not to use Lupron. I was put on a trial of a combination of Femara (letrazole), 3mg/day and low-dose birth control for four months. I have since done five (unsuccessful) treatment cycles.

I just had a repeat laparoscopy last week due to increasing pain and symptoms. The surgery revealed very minimal endometriosis regrowth. The vast majority of problems were due to adhesions, and a couple large (9 and 11cm) cysts. One half of one ovary was removed, and large quantities of Intercede were used to try and prevent future adhesions.

Just thought you'd want to know that while it's not a cure, the femara treatment did apparently significanly inhibit endometriosis regrowth.

4:24 AM  
Blogger Jenn said...

Dr. Licciardi:
I just had my post op. I already commented once on this post regarding the apparent success of the letrazole (Femara) treatment. In comparison to the last laparoscopy, there was LESS endometriosis now, at the START of surgery, than there was before after she removed as much as she safely could. This is definately a major step in the right direction.

10:42 PM  
Blogger Florecita said...

Oh! It is my first time in this blog, and it is amusing to think that one day I was a little blastocyst like the one in the picture :-)
Biology is wonderful!

Happy New Year ;-)

12:12 AM  
Blogger Lisa DG said...

I heard of a procedure where the nucleaus from the dna of a mother can be combined with that of an egg donor to be used in IVF. In this case, it takes 3 to make a baby. Is this still being researched? What have the findings been? Is this process available to the public?

8:01 PM  
Blogger KellyAnne said...

Hello Dr. Licciardi. I am fortunate to be a patient of yours, however I am currently on a break from treatment following an early miscarriage at 5 weeks.

While on break from treatment my endocrinologist discovered I have Hashimoto's Thryoiditis. How exactly does this effect fertility, how successful is pregnancy with this disease and is it possible to have Hashimoto's for a while before it is detected?
I also have PCOS and Endometriosis. My problem is, I ovulate late, I do have a normal luteal phase, but my progesterone while on supplements was only 21, does the thryoid affect progesterone?

With all these fertility issues would jumping into IVF serve me better? I do respond to Clomid, and did get pregnant on clomid/IUI cycle. I was just wondering if IVF would reduce the chances of miscarriage? How does Endometriosis, PCOS and Hashimotos effect the outcome of IVF success rates?

11:56 PM  
Anonymous Laura said...

Happy New Year Dr Licciardi!

I was wondering if you could do a post later this year about vitamines and supplements to help count, motility and/or morphology? Are we just buying into dreams?

Thank you,

Laura

3:07 PM  
Anonymous Anonymous said...

HI there,

Forgive me if you've heard this question already. Not sure if my last question posted properly.

This August, when I was still 37, my husband and I did a round of IVF with ICSI. I made 21 eggs, 13 of which fertilized. We transferred one fresh embryo that did not result in a pregnancy.

I have an FSH of 4 and I have remarkably regular periods. My uterine lining was fine. My HSG was normal.

We froze the remaining twelve embryos, two of which are of excellent quality (four are good, four are average, two are less than good).

My questions are these: Are we decreasing our chances of getting pregnant if we wait until December 2009 to transfer four frozen embryos? My doctor says that age of RETRIEVAL is most important, and has told me to exhale a bit, but I am worried...I'll be 39 when we finally do the FET...should we do it now instead and not wait? Would 13 months make that much of a difference? Is maternal age a factor in implantation as well as retrieval? I've just turned 38.

Thanks for your time,

Anonymous

12:00 PM  
Blogger Me said...

Thanks Dr. L for your site. It's great that you are sharing much coveted information with us.
I would love your thoughts on my situation.
I am 39 and have had four pregnancies without medical intervention:
Preg #1(age 19)miscarriage <6 wks
Preg #2(age 20) healthy girl
Preg #3(age 21) healthy boy
Preg #4(age 24) healthy boy
My husband had a vasectomy when he was 28 and I was 24.
My husband had his vasectomy reversed when he was 39 and I was 35. His reversal was done by a specialist in Florida. DE's counts are great and have been since the reversal.
This month we are starting our fourth year of TTC. I have very regular 26-28 day cycles. I have EWCM every cycle varying from day 12-16.
The only thing my RE can find wrong is my progesterone is low. Very low - my day 22 progesterone levels are usually 2 or 4. I have tried Prometrium without success and progesterone suppositores without success. The only type of progesterone that would raise my levels was PIO. But after several unsuccessful cycles of TTC using PIO we decided to take a break.
I don't understand why two people can be fertile - in fact very fertile together and then not. Did our 11 year break mess things up that much?
Thanks for your insight.

6:22 PM  
Anonymous Anonymous said...

Dr.L-
I have a question regarding PCOS. I have not had an "official" diagnois of PCOS but all factors seem to point to this. Recently, I have been following a low sugar, low refined carb diet. This has caused my typically 6-10 cycles to be regular 28-30 day cycles. However, through daily temp. readings and also a few progest. blood tests after day 21 I have not ovulated in the last six months. My question is, if I am not ovulating why have my cycles become regular? Is this an indiciation that I could possibly ovulate naturally at some point if I continue with this diet?
Thanks!

9:24 PM  
Anonymous Anonymous said...

Dr. Licciardi, I love your blog, thanks! I recently had an IVF with the estrogen priming protocol. I had 5 eggs. 2 were immature and out of the remaining 3 only 1 fertilized. It took and I became pregnant but I had a very early miscarriage. Is there anything else I can do to increase egg yield? I know you say you don't use DHEA, but do you think it can hurt? Getting desperate.

3:33 PM  
Anonymous Anonymous said...

This is for these women with low egg count...

I'm 39 now and have been trying to get pregnant for the past 3 and half years. I did 5 unsuccessful IUI cycles and 1 IVF cycle before the one this month. All resulted in a very low egg production. Usually I had just one mature egg after follistim injections (we went up to the highest possible medication level: 300IU follistim and 150 Menopur). Then I have read on internet about DHEA (over the counter pills) that might increase the egg production. Well, it has worked for me. We retrieved 9 eggs, 6 were mature, all fertilized and I just had 2 beautiful blastocysts transfered yesterday.

Please check with your doctor about DHEA (you need to be taking it for at least 3 months) as well as the injectible growth hormone. It made a huge difference for me.

Good luck!

3:28 PM  
Anonymous Anonymous said...

Hi Dr. L.! I affirm your commitment to this field of medicine that you are in. Reading your blogs, I am encouraged to continue hoping. I am 34 and so is DH. I had 2 pregnancies (IUI without Clomid and IUI with Clomid), both pregnancies did not have heartbeat on U/S at 6 weeks. We did a couple more Clomid with IUI cycles but without success then proceeded to have IVF in 8/2008. 13 eggs retrieved and had 6 blasts. Transferred 2 and was unsuccessful and in 1/09 transferred 2 frozen blasts, again, unsuccessful. We have 2 frozen blasts left and I am apprehensive as to whether we should start with a fresh cycle or transfer the two frozen knowing the first four in the batch did not take. I would appreciate your input. Thanks and God bless you!

9:35 PM  

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