Comprehensive Chromosomal Screening

[Jocalvin]

Hi Dr Roseff,

I'm a few weeks away from starting up for my last attempt at IVF. I have a great RE who I like and trust very much but there is another clinic in my area (RMA CT) that's doing this comprehensive chromosomal testing and it sounds very intriguing. Here is an article I found online about it http://www.medpagetoday.com/MeetingCoverage/ASRM/22987 I went in and had a consult with the RE there yesterday and he was really singing it's praises and thinks it's would be the right next step for me - I'm age 41, with many prior IVF's and pregnancies..all ended in m/c. My diagnosis is unexp. infertility and I've had several RPL work ups that have found nothing...

My question to you is this, is this CCS testing really the big breakthrough RMA is claiming it is? I plan on discussing it with my own RE soon, but I really would be interested in an unbiased medical opinion about it. It will add a good amount to the cost of the IVF and I don't want to spend the money if it wouldn't be worth it in the long run and I'm concerned that biopsing the embryos could damage them as is the case with day 3 PGD. The RMA doctor said it's much less risky than PGD but it's hard to know if that's really the case.

Thanks as always for your help!

JoAnn

[Scott Roseff MD]

Hi JoAnn,

The data suggesting this is beneficial are preliminary and largely unproven to date. One has to remember that centers offering this technique usually gain financially by offering it, so one has to be aware that the cost/benefit ratio may be unproven to date.

The article lists CCS increased success as "preliminary".

A 41 year old who hasn't beeen successful does NOT have unexplained infertility -- The pregnancy rate over age 40 is typically fairly low, and the loss rate over age 40 is generally quite high, due to genetic abnormailities in eggs/embryos in women of that age group. The overall IVF success rate in 41 year olds was just under 22% in 2008 at the center you quoted. What was your latest AMH?

Hope this helps,
Dr. Roseff in FL

[Jocalvin]

Thanks Dr Roseff. My diagnosis was from several years ago when I started treatment with my current RE. I know the realities of my age but still want to try IVF one more time since I cannot come to terms with the idea of using a donor egg (and really can't afford it). I've never had my AMH tested, but this new RE wants to test it when my next cycle begins along with FSH, which I will definitely do. He said if the AMH is too low and the FSH too high, he won't even let me do IVF, which makes total sense. My last FSH in 8/09 was only 2.3 on CD2, not bad for being 39 at the time...it's never gone higher than 6.9 as far as I know, but hasn't been tested in over a year so I have no idea what it is now. This new RE at RMA was saying that doing this CCS testing would let me know for certain if my age is indeed the problem b/c we would know if the embryos were abnormal before transfer. If they test normal and I still miscarry, then we'd know something else is going on. I just really wonder if this testing is as definitive as they claim, and if it poses any risk to embryos. They are saying it's very reliable and safe, but I know they are biased since they developed it. It's very hard to know what to do :o(

[Scott Roseff MD]

Hi,

There WILL be a high degree of chromosome abnormalities in the embryos at your age. We don't need PGS or CCS to tell us that... Many articles have been published demonstrating a high percentage of chromosome abnormalities in eggs/embryos from women over 40 - It's just a fact of life I'm afraid.

Good luck - Let me know how it goes if you decide to do it.
Healthy New Year,
Dr. Roseff in Florida

[Jocalvin]

Yes, you're absolutely right, but this RE's point was that with CCS they could select only normal embryos for transfer (if I'm lucky enough to have any) and if I miscarry those then we'd know it wasn't due to aneuploidy (sp?) at least, and if they're all abnormal, well, then I'll know it's time to give up . This does make sense to me to do this if the test is as reliable as they say...if it's not then I don't want to spend the money for it. It's hard to know what to do, sigh..

I will let you know what I decide and how things turn out though. Thanks again for taking the time to answer all these emails. It's so kind of you to do and unbelievable helpful to people like me!!!

Happy New Year!

JoAnn

[Scott Roseff MD]

OK, JoAnn - Let me know what you decide. Here's a message/abstract I sent all my patients recently:
Dr. Roseff
==========================
Hi All,

I frequently see patients over the age of 39 who believe they have other factors underlying their fertility problems (getting and/or staying pregnant) aside from age. They tell me, "My day 3 FSH and other hormone tests are normal, so my eggs must be OK". Or, they say, "I underwent an IVF cycle elsewhere, and they said my eggs or embryos looked great", so it must be something else aside from my age/eggs/embryos standing in my way of a successful pregnancy.

I want my patients to understand that there's an age-related decline in pregnancy success that is independent of blood test results and egg/embryo appearance under a microscope. Egg quality typically declines as a woman's age increases, and no matter how "perfect" the hormone levels may be in the blood, or irrespective of how "great" the eggs or embryos looked under the microscope, the quality of the egg may be poor if someone is over age 37 (and especially over the age of 39). The eggs/embryos may look good on the outside, but they may be suffering on the inside. And, if eggs or embryos aren't good on the inside (via their DNA), then pregnancy may not occur, or a miscarriage may take place if the pregnancy does indeed implant. This is also why the risk of aneuploidy (chromosome abnormalities, such as Down Syndrome) rises with maternal age...

I copied/pasted an abstract from a well-done publication appearing in "Fertility and Sterility", below. It highlights the age-related decrease in fertility associated with the increase in genetically abnormal eggs seen in women as they age. Chromosome abnormalities were seen in 96% of women aged 40 and above!

If you have any questions or comments regarding this important information, please feel free to get in touch with me.

All my best, always,
Dr. Roseff
==============================================
From: http://www.fertstert.org/article/S00...513-0/abstract

Volume 68, Issue 2, Pages 265-271 (August 1997)

Age-related decline in fertility: A link to degenerative oocytes?
Alvin S.T. Lim, B.S., Maurine F.H. Tsakok, M.D., Ph.D.

Received 8 October 1996; received in revised form 27 March 1997; accepted 27 March 1997.

Abstract
Objective: To determine whether the age-related decline in fertility is due to degenerative oocytes or to aneuploidy.

Design: Retrospective.

Setting: Fertility center of a public and tertiary institution.

Patient(s): One hundred fifty-one women (ages 24 to 44 years) undergoing 158 cycles of conventional IVF or IVF with intracytoplasmic sperm injection (ICSI) between January 1993 and December 1995 were divided into three age groups (group 1, = 34 years; group 2, between 35 and 39 years; and group 3, >- 40 years). They were selected on the basis of available oocytes that remained unfertilized after IVF and that had analyzable chromosomes.

Intervention(s): Standard pituitary down-regulation and ovarian stimulation with FSH and hMG were done for both IVF and ICSI patients. In addition, all patients were given luteal phase support with P, administered orally, via pessaries, or by IM injections from the day of transfer.

Main Outcome Measure(s): Fertilization rates and pregnancy rates (PRs), and cytogenetic analyses of unfertilized oocytes.

Result(s): Although fertilization rates were not different among women in groups 1, 2, and 3 (50.9%, 49.3%, and 37.9%, respectively), PRs were significantly lower between groups 1 and 3 (43.2% versus 14.3%). A total of 383 oocytes were examined, of which 287 (75%) could be karyotyped. Of these, 201 oocytes showed a normal 23,X karyotype (70%), 40 (13.9%) were aneuploid, 24 (8.4%) were diploid, 12 (4.2%) had structural aberrations, and 13 (4.5%) had single chromatids only. No increase in the aneuploidy rate was detected between groups 1 and 2 (14.8% versus 12.4%). However, highly significant differences in the rate of oocyte chromosome degeneration, characterized by chromosomes splitting into unassociated chromatids, were observed with increasing age (group 1, 23.7%; group 2, 52.0%; and group 3, 95.8%).

Conclusion(s): It seems that the age-related decline in fertility may be due more to degenerative oocytes than to aneuploidy. A decline in the number of oocytes retrieved with age may be of less importance than the decline in oocyte quality. Women in the older age group have a higher chance of achieving pregnancy from ovum-donation programs than by persisting in using their own aged oocytes, which have a very poor prognosis for success.

Department of Obstetrics and Gynecology, Singapore General Hospital, Singapore
Reprint requests: Alvin S. T. Lim, B.S., Department of Obstetrics and Gynecology, Singapore General Hospital, Block 6, Level 7, Outram Road, Singapore 169608 (FAX: 65-2253464).

[Jocalvin]

Thank you for the information Dr Roseff. Believe me, I am well aware that my chances of success are low due to my age. I've thought long and hard about donor egg for many months and cannot find any peace with it and really can't afford it anyway as it's almost triple what this last IVF will cost. I prefer to try one last IVF before I move on, esp since I have more than enough leftover meds that will be expiring soon. I know it must sound foolish to many to do this again, but some women do still get pregnant and have healthy babies at my age, so I want to give it one last try. It's the CCS that I'm unsure about doing. The RE at RMA is really pushing for it but I realize he is biased and I'm trying to figure out if it's worth it for me to do. I will let you know what I decide.

Thanks,

JoAnn

[tkuzin]

JoAnn, were you able to find out the cost of CCS?

JoAnn, were you able to find out how much your IVF clinic would charge for CCS? As Dr. Roseff pointed out, CCS is definitely a new IVF technology and only a handful of IVF clinics in the world offer it. I personally know of two clinics in the States. Nevertheless, the clinics which are currently running trials report very high live birth rates (75-85%).

[Jocalvin]

Yes, I know the fee...if you would like the clinics info you can private message me and I won't mind sharing

[Jocalvin]

Update

Hi Dr Roseff, Just to let you know I did not switch clinics and therefore will not be doing the CCS testing, it was just out of our reach financially and it wouldn't really "fix" egg quality issues anyways. I just started meds for my 5th and last IVF, but the protocol I'm on is something I've never heard about before and I can't find much on the internet on it. It's called the NETA (aygestin) protocol. I'm on this because my cycle was very late (probably due to an 18lb weight loss since Nov.) and it appears it was the only one that would fit my RE's IVF schedule for February (he does all his IVFs in bunches one week out of every month). I just started Lupron on Wed, 20 units daily for 8 days along with 5 mgs of Aygestin 2x/day for one week. On Friday 2/4 I drop Lupron to 5 units and start stimming with 375 of Follistim with 1 vial of Menopur once a day...

Can you tell me what you think of this protocol for someone who is 41? I'd just like more info since I can't find much online about it. My RE says is no better or worse than the previous protocols I did (MDL 3x and ganirelix 1x) and I do trust him, but I'd be happier if I could learn more about it.

Thanks as always for your help...

JoAnn

[Scott Roseff MD]

Hi JoAnn,

I generally like MDL or ganirelix protocols for my 41 year olds... It sounds like you've described a Lupron down-regulation protocol, and I don't typically down-reg my 41 year olds with Lupron as it's often difficult to subsequently get them out of the basement.

Aygestin is a synthetic progesterone derivative. I frankly don't see the purpose of using progesterone along with Lupron in a down-regulation cycle. You should ask your RE what he/she has in mind.

Good luck!
Dr. Roseff in Florida

[Jocalvin]

Huh, I though with a Lupron down regulation cycle that Lupron is started during the luteal phase, is that not correct? and isn't the woman on Lupron for longer than 8 days with that protocol? I started it on CD2 and will only be on it for 8 days at 20 units. My RE told me that the Aygestin will stop the pituitary gland from producing hormones and will prevent cysts from developing. I'm only on that for 7days. I will have to ask more about this when I go back next week. I do trust my doctor and believe he knows what he's doing, but it would be easier for me to relax if I understood what he's doing myself...

Thanks again,

JoAnn

[Scott Roseff MD]

You'll have to let me know. Perhaps you're on a flare protocol rather than a down-reg??? You should not let a doc pat you on the head and just tell you what to do -- ASK questions!

Dr. Roseff in Florida

[Jocalvin]

Maybe...and don't worry, I ask a lot of questions LOL, the problem is I usually come up with many more after I leave the RE's office...I will find out more next week.

Thanks for your help...

JoAnn

[Jocalvin]

Updaye

Hi Dr Roseff,

Well the IVF was a success...I'm 5w4d pregnant today, and scared to death of another miscarriage. My HCG levels are OK, at 14dpo it was 170 (prog 41.4), 16 dpo - 313 (prog 48) and 21dpo -1422 (prog 78.7). The levels didn't quite double in 48 hrs but my nurse said it's rising high enough and they are not concerned. I'm very worried though because I was having some mild breast tenderness on and off last week that peaked on Thursday but nothing at all since, in fact I feel physically great. Is it common for symptoms to come and go like this? I also am curious about why my progesterone levels have been so high and spiked at 21dpo. With my previous cycles, it was never above 35 with progesterone injections, and I'm doing the same dose again this cycle, 1cc each night. I'm hoping the fact that it jumped is promising, but would like to know your thoughts...is it possible that my ovaries are making progeterone this cycle on their own? I thought that wasn't possible since I used Lupron.

Anything you can tell me that's reassuring would be appreciated. I go for my first ultrasound Tuesday and may go insane with worrying if I don't get any symptoms beforehand...

Thanks for your help...

JoAnn