Woman With Endometriosis Failed IVF Cycle: Poor Egg Quality? Age Issue? PGS?

                                                                                                                                                    

Question:
I am 38 years old from Los Angeles. I just had a failed IVF cycle because my six embryos arrested on Day 5. On Day 3, five were Grade A and one was Grade B. They were 10, 8 and 6 cell. Doctor blames my age for the embryos arresting and basically said my eggs are poor quality. I find this confusing, since they were top ranked on Day 3. I've done one previous failed IVF last year at a different clinic (and still have a frozen Grade B blastocyst from that), but the doctor never blamed my egg quality. My AMH is 2 and other hormone numbers are normal. First IVF, they retrieved 27 eggs. This IVF, they retrieved 16 eggs.

I don't know my fertilization rate  for my most recent IVF because my doctor never told me how many of my eggs were immature, only answering that some of them were. For my first IVF about half the eggs were immature, and I had about a 50 percent fertilization rate. I have endometriosis, which has never been treated. It was discovered 2 1/2 years when I was having a myomectomy, but the doctor didn't remove it, only noting that I had significant ovarian endometriosis but no endometriomas. I've read that endo can affect egg quality or do you think the only issue here is my age, and I should just give up on IVF? My next step is to have a laparoscopy to remove the endometriosis.

Thanks for your time. N2N from California.

Answer:

Hello N2N from California USA,

I think that age has a significant effect on egg quality and that is the issue with age.  More and more eggs become less and less fertile.  There was a study recently that looked at IVF patients that were 37 years old and underwent PGS. PGS, or preimplantation genetic screening, is the proper term for testing for overall chromosomal normalcy in embryos. This involves removing a cell from an IVF embryo to test it for chromosomal abnormalities before transferring the embryo to the uterus.  Only 2 out of every 10 embryos were genetically normal.  So, even if they make it to blastocyst, there is still a chance that the treatment would fail because of abnormal embryos.  In general, there is debate as to whether endometriosis needs to be removed prior to IVF because of a potential effect on pregnancy rates, but there is no clear indication that endometriosis absolutely affects eggs unless there is an endometrioma present and/or the endometriotic fluid contaminates the fluid at retrieval.  If you want to be sure that it is not a factor, a laparoscopy followed by three months of Lupron should take care of that issue, but I'm not sure I would have you do it if you were my patient.  I think you are battling an age issue.

It is not unusual for good looking day #3 embryos to not make it to blastocyst.  In one of my patients recently, we had 12 embryos that were good quality (grade 1 or 2, 6-8 cells) on Day #3.  We cultured all of them and only 6 made it to blastocyst.  The rest arrested before Day #5.  So, your doctor is probably correct that this failure was due to egg quality.  That is what you are battling.  The bottom line is that IVF is trying to help you find the one or two good eggs that are still remaining in the ovary and it will just take time.  If you want it to go faster, then you need to move to donor eggs to improve the egg quality, but if you want a genetic child, then you need to resolve that it may take several attempts.  Unfortunately, there are no technologies yet, that can improve egg quality.  Only repetition is the option.  As long as your ovaries still respond well to stimulation, so that we can get a lot of eggs at retrieval, then you have a good chance of being successful if you hang in there.

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com 

Monterey, California, U.S.A.

40 Year Old UK Woman Trying IVF After Implantation Failures: Assisted Hatching & PGD?

PGD

QUESTION:
dear doctor ramirez, i am so glad to find you on this website and would very much appreciate your help. I will try to give you some background.

i have had 3 failed iui, then found problems with my fallopian tubes which led to bilateral salpingectomy, myomectomy, adhesiolysis and cornual tubal occlusion, left ovarian cystectomy, i also have fitz hugh curtis syndrome.


so then after recovery from the above op i had

one fresh ivf cycle - 18 follicles, 14 eggs collected, 8 fertilised, 3 day transfer of 2 embryos(8 cell, grade 2)on 18/10, started bleeding 30/10

fet - 19/3. 2 embryos transferred (5 cell grade 2 & 7 cell

grade 1-) Negative test 4/4

fet - 9/8. 2 embryos transfered (6 cell grade 3/3 & 3 cell grade 4/4) Negative test 24/8

on each occassion as you can see i had 2 embryos put back (blastacysts on the last fet) and all failed at implantation stage. these were in 2006 & 2007.

now in june 2012 i have started my ivf journey again. so far:

low amh result (i am 40 in october)

2 new fibroids found on ultrasound, advised to proceed anyway

down regulation extended 1 week as lining not thin enough

stim injections all went to plan

15 follicles (2 v large suspected to be cysts)

10 eggs retreived

7 fertilised

7 made it to blast but one left to perish as structure wasnt great.

2 fantastic blasts put back after using embryoscope which i was told had started collapsing which was explained as a very good development.

4 frozen.

so, 2 put back in and progesterone pessaries used one morning & 1 night.

day 5 post transfer sign of period.

evening of day 6 post transfer period definately started with heavy bleeding & clots, continued until today (day 9pt) flow seems to be slowing down.

negative test today 9dpt

clinic advised me to continue with pessaries and re-test on saturday (day 11 pt)
theres the background for you, so here are my questions:

1. why am i failing at implantation stage every time?

doctor says it just nature but i cannot help feeling something else could be wrong and i am running out of time

2. is there any kind of contraception or other medication that i could use to stop producing eggs, thus preserving the small reserve i have left?

3. what tests can i have done to rule out ANY other problems? ie immunology, uterine probs, endometrium probs?

4. fibroids-what should i do have them removed or is there any medication available that may shrink them before my next fet

5. assisted hatching-could this help?

6. pgd (preimplatation genetic diagnosis)?

7. having read my history but you advise i do????

if need be i will pay for any tests that they wont complete at my clinic. i feel if i can rule all other possible problems out then i can admit that yes it is in gods hands and just a matter of keep trying but at the moment i feel what if there is something else that is being overlooked?

many thanks for your help in advance doctor.

as you can see i am getting pretty desperate now!

lisa, uk

ANSWER:

Hello Lisa from the U.K.,

The term "Implantation failure" means that the last two steps of the reproductive process did not occur. These last two steps are natural steps and we do not have the technology to make them happen. That is why IVF is not a perfect technology. Once the embryo is placed into the uterus, the embryo has to hatch out of its shell and attach to the endometrial ining. Then the endometrial has to engulf the embryo (implantation). So either of these two steps could have been the source of failure. In addition, it is well know that pregnancy rates will vary from doctor to doctor and clinic to clinic because the transfer technique can play a significant role.

In your previous cycles, your embryo quality was poor. I am not surprised that they failed. In this last cycle, despite having good blastocysts, there is still a potential deficiency that they have. This is because of your age, or what I refer to as the "age related egg factor." We know that as the eggs age, the internal structures of the egg become more debilitated and so less likely to thrive. One of these deficits is the chromosomal structures are more brittle and can lead to chromosomal abnormalities as the cell is dividing. Without doing genetic testing, these cannot be detected. Even chromosomally abnormal embryos can turn into good looking embryos but not necessarily into pregnancies. That is another possible source of failure. IVF helps to overcome this problem by increasing the number of eggs retrieved and therefore, statistically, increases the chances of finding the perfect egg. But that does not occur every time. You will have to keep trying in the hopes of finding the perfect egg eventually. The good thing is that your ovaries are still very responsive (you don't have decreased ovarian reserve and stimulate well), which gives you a good chance.

In terms of your other questions, I would not do anything with the fibroids, any birth control pill can stop your ovaries from going through the ovulatory cycles and hopefully preserve your eggs and I can't think of any other testing. Without thoroughly reviewing your medical record, however, it is difficult for me to give you specific advice.

I would recommend assisted hatching as this has been shown to increase pregnancy rates in older patients. I would also recommend that you scrutinize your clinic, because of all the failures. Pregnancy rates can be very clinic and doctor dependent. You should try to find one that has good pregnancy rates for your age group. I am getting a 57% pregnancy rate in 40 year olds and many of the clinics in the U.S. are getting similar results. I would also recommend that you consider transferring more than two embryos (we allow up to 4 in 40 year olds).

You faith in God will help you through this, and eventually it will happen. You may have to change course at some point and look at a different approach, but your faith will get you to that dream of having a child. When I complete my embryo transfers, I say a prayer with each of my patients and ask God to bless my couple with fruit of the womb and grant their wish for a child. I am confident that he will do so as He wills it.

Good Luck

FOLLOW-UP QUESTION:
hi doctor

thank you so very much for your speedy and detailed response, it has set my mind at rest on a lot of points. it is interesting to be told that the quality of the embryos on our cycle a few years ago were of poor quality. although that is sad, at least now i can accept that maybe that is why we failed on those 3 occassions. i had been under the impression that the embryos were good quality, particularly on the first fresh cycle after egg collection.

i have read lots on assisted hatching and am glad you agree this may be a way forward for us.

can i please just take a few more minutes of your time to clarify my point on pgd & other test (point 3&6)

When you mention checking the quality of the eggs/embryos were you suggesting asking our clinic to go ahead with pgd for our next fet?

also what is your opinion on other testing such as Natural Killer cells, immunology, uterine/endo probs? Which of these or any other tests would you suggest i rule out before going ahead with our fet?

also you mention my ovarian reserve being good but i was under the impression that the AMH test i had done suggested i was on the bottom level in terms of my remaining eggs? this has confused me slightly?

thank you in advance.

many many many thanks for you time again. Lisa

FOLLOW-UP ANSWER:

Hello Again,

There are pros and cons about using PGS. It can help to identify embryos that are chromosomally abnormal so that you can be more selective in the ones that you transfer. The downside is that there is a decrease in pregnancy rates, probably because of the impact of the biopsy on the embryo.

I check certain immunologic testing on my patients that fail two or more IVF cycles. The tests I choose do not include natural killer cells because I don't believe in that concept as a source of implantation failure. Despite this testing, I also automatically place my patients on low dose aspirin, low dose heparin and medrol, as well as, increase the progesterone supplementation. The latter is the treatment for patients that have endometrial biopsy for beta integrins and find that they are deficient. I figure, why waste money on doing the test and just cover any ways, since increasing the progesterone is the treatment.

Remember that AMH is an "indirect" test for ovarian reserve and does not necessarily predict how you will respond. Your have already shown good response so it is not an issue.

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.com
Monterey, California, U.S.A.

How Can I Have A Year Of The Dragon Baby?

Question:
Dear Doctor,

We are a Chinese couple who would like to have a baby this year. We have been trying for many months in the natural way for timing the baby for the Dragon year but we are not successful so far. We are thinking that maybe we can make our chances better for a baby this year if we go see a baby specialist here in Hong Kong. My wife is 34 years old and I am 38 years old. We have been trying for six months now. If we try for test tube baby, can we choose for a boy or girl? What would you suggest would be the proper next step for us?

Thank you, you are very kind for your advice. L. from Hong Kong

Answer:

Dear L. from Hong Kong,

I appreciate the fact that many Chinese couples are looking forward to having a child in the Year of the Dragon. If you wish to time your wife's pregnancy for a delivery within this Chinese lunar year, you do not have much time to spare! In essence, since you have been trying to conceive already for six months, it may be time to look at alternatives. I will go over all your options, from least complicated to the most aggressive:

First option:

What I would suggest if you still choose to go the "natural way" for just this month, is that your wife begin taking prenatal vitamins that have at least 1 mg of Folic acid within it, and that you keep in mind that the actual fertile days are pretty narrow - 2-3 days. If your wife has regular and predictable cycles, you can predict ovulation by counting back 14 days from the period. That would show where ovulation probably occurred in the previous cycle and by counting from the first day of her period, gives you an idea of what cycle day ovulation occurred. Then with this information, you can use the calendar method by counting from the period the number of days where you can both expect ovulation to occur. You need to stop intercourse 5 days from that anticipated ovulatory day, then start intercourse two days prior and have intercourse daily, once per day, with having only one ejaculation per day for five days.

Second option:

I think that an IUI (intra uterine insemination or artificial insemination) is a better starting point and should be done right away, but you need to make sure that the appropriate treatment is being done to increase your chances. IUI's are better than trying naturally because the number of eggs ovulated are increased with fertility medications, timing is better known by ultrasound surveillance and the sperm is injected into the tubes to await the egg. Ideally, your wife should be ovulating 3 eggs per cycle, or have 3 eggs of ovulatory size (18-24 mms) so maximize the chances that an egg will find and get into a tube. You did not say if either one of you have been tested for infertility. In your age group (34yo), your chances of natural pregnancy are about 10% per month and with IUI, up to 24% per month.

At my center, typically, we do an hsg (hysterosalpingogram) to see if the woman's tubes are open and viable. We also do a semen analysis on her partner. A negative result in either of these tests would make it quite difficult for you to immediately succeed with either an IUI or naturally.

Third and probably best option:

Considering the fact that you do not have much time and that you are considering gender selection, then IVF (in vitro fertilization) or "test tube baby" may be the best choice if you wish to conceive within the next few months.

With IVF the woman can produce many follicles and as long as you get at least one good embryo, IVF has a better pregnancy chance than IUI because it is accomplishing 7 of the 9 steps your body goes through to achieve pregnancy (IUI only accomplishes one). The remainder have to be accomplished by your body. That is what gives IVF a pregnancy rate of 60-76% per cycle in your age group.

If you wish to do gender selection, then IVF with PGS (pre implantation genetic screening) is the only option you have. A microscopic biopsy of the trophectoderm (the outer cell layer of an embryo) is done by the embryologist and sent to a lab for analysis. Recently it has been shown that the pregnancy rates from a single PGS-selected euploid embryo were 58% and 60.7% compared to 42% and 40.7%, respectively, from a morphologically comparable but non-PGS-selected embryo. Interestingly, the miscarriage rates were seen to decrease to 6% and 6.3% from 12% and 12.5%, respectively. With transfer of one embryo, the risk of multiple gestation is essentially eliminated.

I know that in China, Korea and Japan, genetic screening for gender selection is not allowed. Here in California it is, though. We have had Asian patients come to us who have chosen to have PGS for gender selection and succeeded. Your chances would be reasonable if normal embryos were obtained and transferred. You can choose to freeze or vitrify some embryos and transfer one fresh (vitrification is a method of rapid cooling of embryos that minimizes ice crystal formation which has further improved success). If one is transferred and it takes (implants), I would expect that there would not be any abnormalities in the fetus or child.

I wish you luck in the Year of the Dragon and hope that you will find a good physician in Hong Kong or abroad that will be willing to work with you and help you succeed in your quest for a child this year.

I hope all this information is helpful.

Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
http://www.montereybayivf.com/
Monterey, California, U.S.A.

Grading Of Embryos At Blastocyst: How Does It Reflect Implantation Rates?

Question:

My husband and I recently went through our first IVF. We have been trying for 2.5 years to get pregnant and have done 6 failed IUIs. We have stage 2 endometriosis that was cleared out by a laparoscopy last Fall. Aside from that we are unexplained infertility. We retrieved 10 eggs and 9 fertilized naturally. We transferred 2 blastocysts on Day 5 that were graded 2BB and 3BB at transfer. We had 5 others that made it to freeze on day 6.

I have been a little stressed out about the quality of the blastocysts. I know that 4AA is the highest. Will our blastocyst quality impact implantation rates? R. from the U.S.

Answer:

Hello R. from the U.S.,

The answer to your question is yes and no. It is ambiguous because grading does not necessarily predict whether implantation, pregnancy or a successful delivery will take place. I have often been surprised when I get a pregnancy from embryos that are "graded" as poor quality. I have also seen cases where when we do genetic testing called PGS (preimplantation genetic screening) the test results reveal that the good quality embryos are abnormal and the real bad one is normal! So I don't think you can say that the way your blastocyst are graded will necessarily have any impact on their ability to implant.

At this point in time, we do not have the technology to evaluate embryos fully to know which ones will implant and which ones won't. As far as I'm concerned, all embryos have the potential to implant and lead to a successful pregnancy. In my opinion, only God knows for sure. It is a good sign that you had embryos to transfer and freeze...Good luck with your transfer results!

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

http://www.montereybayivf.com/

Monterey, California, U.S.A.