Tuesday, January 27, 2009

Just Before Blastocyst: The Morlula

So what happens after day 3? Two days later we would like it to be a blastocyst. The day before it becomes a blastocyst, it should be a morula. A morula forms when the 8 cell embryo divides further, and at the same time the cells become very close to each other. Here it’s difficult to see the borders of the cells, so the morula looks like one big blob. It ‘s solid in the middle. It’s still inside the shell. There are about 12-30 cells in a morula.
Here are some pictures:

Here is a nice looking morula.





Here are a few others . The top right looks nice, the others look OK, the bottom right looks the worst.







Most morulas (some write the pleural morulae, but most write it morulas) look about the same, so we don’t give them a number or a grade. We may say “nice” for a good one, but that’s about it.
Is it ok to transfer a morula? If your doctor wants to transfer your embryos on day 4, you will probably have morulas, but it will be hard for you to get a handle on quality. Most programs transfer day 3 or day 5. Day 4 transfer is ok, but most of us would say if you are waiting till day 4, just wait till day 5 so that the embryos have more time to grow, and quality can be better assessed.
What if on day 5 you are told the best embryos are morulas, not blastocysts? Not so good. I have had patients get back 2 morulas and become pregnant with twins. However the chances of pregnancy are much higher if you have blastocysts.
If there are morulas on day 5, isn’t it better to wait another day until they are blastocysts? No, because even if they become blasts on day 6 they are still a day behind. Rarely, we transfer on day 6. This may happen if , for example, there are 4 morulas and we want to give them, one more day to see which ones, if any, develop a little more.
Can we do anything to make the embryos grow faster? The same answer as last time. We try to change things up a bit next cycle, but there is no special drug protocol for slow embryos. Its just a matter of trying again and hoping for a better outcome.
Thanks again,
Dr. Licciardi

21 Comments:

Anonymous Anonymous said...

This is my first IVF cycle. ET was ironically the same day as your morula post.

Age 34 yrs. On day 3, I had nine embryos with four 8 cell embryos (Grade 1 best quality). RE decided for a 5 day transfer. By day 5, the best two were "advanced morula" that were transferred. If another cycle is needed, would it be best to transfer on day 3? How can you tell if its egg quality or lab technique if the embryos don't reach the blastocyst stage? RE previously mentioned 25% of their patients do a 5 day transfer. Is this a low percentage?

2:13 PM  
Anonymous mina said...

I just love your blog. I wrote to you sometime in Nov about having high FSH numbers when Im only 34. Your next post about high FSH gave me hope, and here I am doing my first IVF cycle. Tomorrow is my ER, and although I only have 5follicles due to my dr's decision to keep on me very low stims (a decision I really didnt appreciate)Im hopeful that atleast 2 will fertilize. I also did my research and found that many 5 day transfers have a better chance of positive pregnancies than a 3 day transfer. But again, my Dr has decided before even knowing what the number of eggs that will get fertilized, on a 2 day transfer!!!So really I doubt this cycle of IVF will succeed for me. Just being a realist. Any thoughts? Oh and reason they put me on very low stims is the fact that I weigh about 90lbs. Is that a viable reason? Again looking forward for your reply, so I know what to tell the Dr on my next IVF cycle.

2:50 PM  
Anonymous Anonymous said...

Dear Dr Licciardi,

My name is Ava and I am 29 and desperate (husband is 30). I am so frustrated with the indifference of the medical professionals with whom I have consulted.

I have been trying to conceive for about 18 months now. I had a chemical pregnancy 6 months ago. That was my only pregnancy thus far (no meds).

I have had all the regular hormonal tests done- normal TSH (high normal, I think it was around 2.2), normal free testosterone and testosterone, Day 3 FSH was 5.2, Day 3 LH 8, E2 normal. Day 21 of 24 day cycle P4 was 9 (not so great?), cholesterol & sugar are very good, not anemic (low end of normal hematocrit).

I have been checked for PCOS through blood tests and ultrasounds and am negative for that. I was worried because, though I am slender, I do have acne, oily skin and some hairiness (which could be justified by my mediterranean heritage). I had an antral follicle estimate done and I was told I had about 10-12 antral follicles per ovary, which I was assured was good?

My RE thinks that my husband's semen analysis was good. He had a high sperm count (over 200 million total) but his motility and morphology were both on the lower end (30% and 21%). The doctor seemed to think it was not an issue because the total sperm count was high enough to offset those numbers.

I have been using a sperm friendly lubricant (pre-conceive), no idea if it works and this month I took Robitussin. However, there has been no test to see if the sperm is capable of fertilising an ovum. How common is it to perform a human zona penetration test? Is it very costly?

I should add that we are both thin and healthy. We don't drink, do any drugs or smoke, or drink much caffeine (I have cut out caffeine all together)

The doctor put me on Clomid, despite the fact that I ovulate every month (verified with blood tests, BBT charts, fertility monitor and ultrasound). I have had an HSG and have clear tubes and normal uterus. This was my second month on Clomid, my endometrial lining showed 3 distinct layers and measured 11 mm thick on cycle day 13. I had 4-6 mature follicles (ranging from 22mm to 16 mm) and I am on 50 mg days 5-9. My day 13 E2 was 900. My day 21 P4 was 23. My luteal cycle is 14 days long (was about 12 to 13 before Clomid but I had 4-5 days of cramps and spotting before menstruation).

I have not done IUI yet because I thought I would try a couple of months naturally. I asked about having a post-coital test done and was informed that it was archaic technology- their answer is IUI.
I don't feel IUI is going to be the answer after all this time.
I really don't think I have ovulation issues, so why am I on Clomid?

Most of the tests I've had done were because I specifically requested them. Sometimes I feel like I know more about infertility than the doctors who treat me!
Can you please do a little write- up on FASIAR and mini-IVF? Are there other less expensive alternatives to IVF? How commonly practiced are these procedures and are there drawbacks? I live in NY state, so IVF is not covered by insurance.

I have not been checked for endometriosis. My cycles have become about a week shorter in the last 2 years (used to be 27-30 days, now 24-27 days but at one point they were 20-21 days) and I started to have bad PMS type symptoms which caused me to think I had elevated prostaglandins (have not had this checked).

I'm sorry to be writing all of this but I can't get in for a follow up consulation with my RE for another 6 weeks and I need to know what to do next. I am 10 days past ovulation right now and not feeling very hopeful for this month. Are there other bloodtests that can be done?

1:33 PM  
Anonymous Northwesterner said...

I'm wondering if you think that male factor issues can cause slow/arrested embryo development, especially after day 3? I just finished my first-negative-ivf cycle with exactly the scenario you described, only morlulas on day 5 (my clinic prefers to do only 5 day transfers), so I had 3 of them transferred with no success. I'm 38 but am doing ivf for severe male factor infertility--very low everything (< 1 mil. count, 10% motility, 12% normal morph.). The cycle started well--26eggs/19 mature/13 fertilized w/ ICSI, and the embryologist said that most of the embryos looked good on day 3. She said that this is usually a sign of decent quality eggs, so her theory is that the poor development after that was more likely a sperm than an egg quaility issue (I doubt it's the lab since they have some of the best success rates anywhere, in all categories). Do you think donor sperm is advisable at this point, or would you give ivf/icsi another try? Would you recommend ivf with donor sperm vs. a few months of iuis, simply because of the age issue?

Thanks. Your blog is wonderful!

12:41 PM  
Blogger ruth said...

Hi, my name is Ruth and I'm wondering if you can answer some questions for me. I'm 30 and have been ttc for 8 cycles. My periods are between 21-28 days over the last 15 months, usually 23-24 days. I've taken my basal temp for the last three and think my luteal phase is about 10 days (temp changes from around 97.6 pre ov to 98.2 post ov). I have antibodies for hashimotos and had thyroiditis a year ago but my TSH now is 1.42 and I don't take any meds. I was also diagnosed with a L sided 1 inch blood filled ovarian cyst last week. My PCP wants to put me on progesterone to see if it resolves. My ferritin is 35. He thinks it's premature to check any of my other hormone levels. What do you think? Do you think I need to see a gynecologist or fertility doc and if so would one be better than the other at his point? Thanks for your time!

6:54 PM  
Anonymous T2 said...

Thanks for your blog. Always very helpful.

I have a question about blastocysts - how often are they expanded on day 5? I get blastocysts on day 5 but they are never expanded. (I have one daughter from my first cycle of IVF and have just miscarried at nine weeks with my sixth IVF cycle - all fresh cycles). I do have two blasts that were frozen on day 6 that are expanded.

I suspect that it will be in your next post anyway, but it would be great to know a little bit more about the different blastocyst stages.

8:48 PM  
Anonymous Anonymous said...

Hi Doctor,
It's Ava again. I was just wondering if you could remove my post. I did not realize I would not be able to delete it.

5:35 PM  
Anonymous Campbell said...

Thanks so much for the blog - it's so helpful and encouraging. My question is about a steep decline in follicles from one cycle to the next (13 vs. 6). Can cycles vary widely from one to the next or does a drop indicate a decline that will likely continue? I'm 39 and had a successful first IVF last year - I became pregnant with twins but sadly lost them at 23 weeks due to PPROM. I was on 450 iu Gonal-F and 150 iu Menopur. We got 13 follicles, 7 eggs, 6 fertilized, 3 blasts, transferred 2 of them on day 5. In this cycle (10 months later) we got 6 follicles, 4 eggs, 3 fert, only 5 cells each on day 3, transferred an "average" blast on day 6, cycle failed. This was after they upped Gonal-F to 600 iu on Day 5 and gave me 2 extra days on meds. My FSH is 3.4 - but my MIS is low (2.8). Numbers have not changed at all since last year. Only thing doc mentioned was that estradiol was lower this time. For next cycle they want to add Clomid for first 5 days in addition to the injectables. Could my ovarian reserve have declined that much in 10 months?

2:53 PM  
Blogger Courtney said...

Dr. L- Thanks for your advice! We went ahead with injectibles (Menopur 150u daily--had to stim for about a week)...much better response and a thicker lining...and we are pregnant! I would love to hear you weigh in on the octuplets ivf controversy and the way the media has covered this story. Thanks for all that you do for us!

3:29 PM  
Anonymous BostonT said...

I am about to start my 3rd IVF cycle. I'm 30 years old and my husband is 31. We were diagnosed with mfi. My first cycle I was on gonal-f 350 (also lupron) for 4 days and during that cycle I only got 4 eggs and a lot of follicles. My e2 levels were in the 4,000 range. We ended up with two perfect embryos and transferred one, and froze the other. That cycle didn't work. For IVF #2, we lowerd my dose of Gonal-F to 150 (also lupron) and also added luveris, 75 starting on day 1 of stimms, until trigger. This time my e2 levels were in the 2000 range. I had about 24 follies. They retrieved 6 eggs, 4 fertilized with icsi, and we transfer 2 perfect embryos. The other two arrested. I did get pregnant with a singleton, but sadly m/c at 7 weeks 6 days.
So for this cycle my RE wants to lower my dose of Goanl-f to 112, use luvers, also use lupron again. Does this make sense to you? She said that my body has a set number of eggs that it want to make and the eggs that I do make create really good embryos. Thank you for your input and for taking the time to do this blog.

11:03 AM  
Blogger Stacy said...

Hi Dr. L, Looking forward to your next post. just wondering what you think the chances of a FET of 6 embryos resulting in 8 Babies, is. So much has been in the news about this, and I'd love to hear my favorite doctors perspective.

Thanks,
Stacy (former patient, and Mother to Maya/Thomas 3 years)

10:30 PM  
Anonymous Karen said...

Interesting and timely series of posts.

I am 33 years old, PCOS (and now a blocked left fallopian tube, but that's new) with 17 month old IUI triplets. Being, admittedly, slightly off my rocker, I'd like at least one more baby. ONE at a time, not THREE (not, heaven forbid, eight, either).

My RE and I agreed that though I'm not *quite* the "ideal" patient for eSET, this was the only acceptable route to take (my perinatologist advised that even a twin pregnancy would be an unacceptable outcome for me).

I had a surprisingly disappointing stim cycle (20units lupron, no drop when starting stims, 125-150IU Follistim, and 37.5 units Luveris - I ended up with a lead follicle) and they expected to retrieve only 4-6 eggs, but luckily retrieved 10... 9 mature, all fertilized.

On Day 3, had I been any other patient, he'd have recommended transferring 2 of my slow-growing 2-4 celled embryos, but that wasn't an option for either of us.

By Day 5, I had 4 morulas and some other even slower growing embryos. No blasts. I got moved to a Day 6 transfer to find that one elusive blast who would scream "pick me! pick me!". By Day 6, I had a couple "early" blasts of mid-grade quality, one of which was clearly the best of the crop, so I definitely see the advantage of having pushed to Day 6 in my case.

I am now waiting for my beta next week.

At any rate, I found this discussion of embryos/morulas/blastocysts fascinating and enlightening, and I really appreciate you having elaborated on the topic. Thanks!

9:49 AM  
Blogger Parenthood For Me said...

Hello,
I am reaching out to my fellow bloggers to spread the word about my non profit, Parenthood for Me, Inc. Our mission is to provide financial and emotional support to those starting families through adoption or medical intervention. I am an adoptive mom who underwent ART for four years.
We will be awarding grants to people all over the US. Maybe your patients would be interested in visiting our website.
Please visit our our blog http://parenthoodforme.blogspot.com
Pass the link on.

Sincerely,

Erica Walther Schlaefer
President
Parenthood for Me, Inc.
www.parenthoodforme.org

8:55 PM  
Blogger Gia said...

How big is the Morula? Thanks for this blog! Its a great resource.

11:53 PM  
Blogger minerva1822 said...

Just starting reading through your blog and it is great!!..thank you so much for the information so much of us out there are confused about. Alot of us women and their husbands trying to conceive and/or having difficult pregnancies need a resource that is informative without sounding like greek..lol...so once again thanks...i'll follow and keep reading!

6:54 PM  
Blogger Jesus, My Best Friend said...

hi... i asked you a question awhile back. i am the girl who had just found out she had a unicornuate uterus. i have been on meds for the past 3 months... 1 of which no eggs were produced on my good side. my doctor switched me to a total injectible cycle of 150 mg of hmg daily for 10 days. anyway... i went for my first ultrasound after 6 days of stims and i had 3-4 eggs on my good side with a few on the other side. this was cycle day 9. they checked my estradiol level and it was 62 which they said was a little low. my question is what does that mean exactly?

7:23 PM  
Anonymous Anonymous said...

i just found your amazing blog. we are struggling with infertility too.my husband has low sperm count and low motility. but there are always high level of leukocytes in his sperm. we didn't get right answer so far why is this happening. do you have some explanation maybe? thanks in advance!

11:26 AM  
Anonymous Anonymous said...

i just found your amazing blog. we are struggling with infertility too.my husband has low sperm count and low motility. but there are always high level of leukocytes in his sperm. we didn't get right answer so far why is this happening. do you have some explanation maybe? thanks in advance!

11:26 AM  
Blogger Jen said...

Dr. Licciardi -

This comment goes into the "topic request" category. A few posts ago (Stories of Persistence) you described a patient with high FSH who underwent a round of IVF after waiting until a month when her FSH level happened to be normal (despite what appeared from your description to be several prior months of high FSH levels).

You've written a couple posts about high FSH, but this topic in particular hasn't been addressed. Under what circumstances do you believe it is worth trying IVF in a high FSH patient? Are there studies or your own clinic's results that contradict the conventional wisdom that a single high FSH reading signals doom?

If an otherwise high FSH patient has one month with a low FSH reading, is there reason to believe any eggs produced that month are of better quality and/or suitable for a round of IVF? To what extent does the age of the high-FSH patient impact the determination that IVF might be appropriate in one of these normal-FSH months? Any thoughts, insights or experiences here would be so welcome.

I really appreciate the time you take to write this blog.

5:19 PM  
Blogger Kami said...

I had a similar scenario as Northwesterner. Very poor quality / quantity of sperm. After being successful with an IUI (miracle conception followed by a miracle neonatal death) we had 4 failed IVF cycles from 38.0 to 39.5 years old - one with half donor sperm (3 pregnancies - 2 early miscarriages and one chemical). We had between 8 and 20 eggs and always had one top grade blast to transfer.

We switched to DE. We had three top grade blasts to transfer and transferred all three, one implanted and grew into a full term, healthy baby. Was it my eggs or older eggs not handling poor sperm well or just luck? I will likely never know, but am glad to be parenting.

It is also interesting about your thoughts on day 5 vs day 6 transfers. Mine have all been day 6 transfers (except for one cycle we opted for a day 3), including the DE cycle. My clinic has rates comparable to CCRM. My RE believes the 6 day transfer does not decrease pg rates and helps better select the best embryos. He basis his beliefs on the work of Richard Scott. But then that was a couple of years ago, more recent research may have turned him back toward the day 5 transfers.

Thank you for the interesting blog. I very much enjoy reading it.

3:04 PM  
Blogger Chrissy said...

I have a question Dr. I recently underwent a HSG, which was incredibly painful. The doctor told me even despite tremendous pressure, the dye did not seem to fully flow into my tubes. He recommended we go straight to IVF. I'm not ready for that right now, so we asked for an alternative. I am scheduled to go in for a laprascopy to find the source of my blockage. What are your thoughts? I'm a 32 year old healthly female. I await your response.

4:33 AM  

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