Monday, September 19, 2016

Three IVF Cycles With Immature Eggs: PCOS and HCG Trigger?


QUESTION:
Dear Dr. Ramirez,
I'm 39 years old and have done 3 IVFs (in vitro fertilization cycles). During the first two IVFs, half of my eggs were immature. I had 25 retrieved (age 37) the first time, and 16 retrieved (age 38) the next time with 50 percent maturity in both cases. However, I just had an egg retrieval where 15 were retrieved and only 2 eggs were mature. They used generic HCG in this case, and the doc seems to want me to try the transfer the pretty crappy embryos that resulted from this retrieval. He is offering no answers as to why just 2 eggs were mature upon retrieval and the embryo quality was my worst yet.

Does the kind of HCG trigger make a difference? For the second retrieval, I didn't use generic HCG but Novarel. I think I used Ovidrel for the first trigger. Do you think I have a genetic defect and should be tested? I also think I have some of the signs of PCOS (acne and some sideburn hair that I remove), but doctors don't think I have PCOS because I have regular periods and am not overweight. Yet, I've heard many PCOS (polycystic ovarian syndrome) women produce immature eggs. Also think I may be insulin resistant and have heard a connection between this and immature eggs as well.

Would appreciate your insight.  Emma from California

ANSWER:
Hello Emma from the U.S. (California),

Egg maturity at the time of retrieval is based on two things: (1) the size of the follicle when triggered and (2) adequate HCG stimulation. 

First, let me answer the HCG question.  If the HCG is an inadequate dosage or not a quality product, then it is possible that the follicle and consequently the egg within, will not get adequate hormonal stimulation to go through the final maturation phase.  Sometimes the egg will not release from the wall and so no egg will be retrieved but otherwise, it would not be mature.  In terms of follicle size, it is usually a requirement that the follicle reach a minimum of 16 mm to insure that the egg within has matured.  Physiologically, as the follicle grows from FSH stimulation, the egg grows toward maturity.  When it reached mature size, the final act is for the HCG or LH which is the physiologic trigger, causes the egg to go through the final phase of maturation and release from the wall.  If the follicle is less than 16 mm, an egg could still be retrieved but it would not be mature.  This is where the "art" and experience of the physician comes into play.  It is his/her decision as to when the optimal time to trigger is.  The goal, or what should be the goal, is to trigger when the majority of follicles are of mature size but not let it go on so long that you begin losing the larger follicles.  That balance is the key.  In my case, I use 50% maturity as my baseline measure, since follicles tend to grow at different rates.  That is to say, that I strive to have at least 50% of the retrieved eggs to be mature.  In most cases it is much more than that.

You are correct that PCOD patients tend to have a lot of immature eggs but that is because they have so many follicles that result from stimulation.  Where a normal woman might produce 15-20 follicles, a PCOD patient will often produce 30-40 follicles.  Since they develop at different rates, that leads to different maturity levels.  In terms of medication, I favor Ovidrel.  In my experience (22 years), I have had cases where the eggs don't mature as a result of Novarel or Generic HCG, so I abandoned them.  In addition, Ovidrel is a subcutaneous injection whereas the HCG is intramuscular so, it hurts more. 

Good Luck,

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

---------- FOLLOW-UP QUESTION ----------

QUESTION:
Thank you, Dr. Ramirez. There was one more piece of information I forgot to include. Before I started this last cycle, I had been on a three-month dose of lupron. I began stimming exactly three months to the day of my lupron injection, even though I still had hot flashes and only had six follicles to start. Follicles grew from 6 to 8 to 12 the day of the trigger. Normally my number of follicles are in the teens at the beginning of the cycle. I even mentioned this to the doctor and told him that I was still having hot flashes as well. Is it possible that my ovaries were over-suppressed, which resulted in just two immature eggs out of 15?

Thank You,

Emma

Answer:

Hello Again,

Usually the stimulation, if given in adequate dosage, is enough to overcome the Lupton suppression, but I think that your thinking may be right, and that your ovaries may have been suppressed enough so as to not perform as well in the last cycle and the stimulation was not enough to overcome that suppression.

Good Luck,

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

Monterey, California, U.S.A.
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
Monterey, California, U.S.A.

Wednesday, November 4, 2015

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

Monterey, California, U.S.A.



Tuesday, August 18, 2015

History of Miscarriages, Now 9 Weeks Pregnant: Continue Progesterone Supplement (Crinone) ?

Question:

I'm from the U.S. After a long struggle with secondary infertility and 2 miscarriages, I am pregnant again, 9 weeks along. I'm on supplemental progesterone, Crinone 8% once a day. When can I feel okay about stopping the Crinone? I was supposed to see my doctor in 2 days, but he experienced a family tragedy, and I'm not sure when he'll be back. I think he had talked about stopping the Crinone at 9 or 10 weeks, but I was going to confirm that with him at my appointment, and I have no way of asking now.
Thank you for your time. M. from the U.S.

Answer:
Hello M. from the U.S.,

With your history of two miscarriages, I will usually be very conservative and continue the progesterone until 12 weeks gestational age.  However, medically, it would be okay to stop at 10 weeks.  By then, the placenta should be fully functional and providing all the hormone necessary to maintain the pregnancy.

Good luck!

Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program

Monterey, California, U.S.A.
 
**For my readers who are unfamiliar with the use of progesterone to support a pregnancy, here are some additional facts: "Progesterone is essential for the normal functioning of the reproductive system. After ovulation, the corpus luteum (which is the empty follicle from which the egg was released) produces progesterone, which acts on the womb lining and causes it to thicken in preparation for a fertilized egg to implant. This is known as the luteal phase of the menstrual cycle. If an egg implants successfully into the womb, the corpus luteum continues to produce progesterone to maintain the pregnancy until the placenta develops fully. The placenta produces increasing amounts of progesterone until it is fully developed, when it then takes over the production of progesterone to continue to support the pregnancy.
In some women, insufficient progesterone is produced during the luteal phase and this causes problems with implantation of fertilized eggs into the womb lining and maintaining a pregnancy in the early stages. Crinone vaginal gel is used to treat this hormone deficiency. One applicatorful is inserted into the vagina every day, starting either one day after ovulation is known to have occurred, or on day 18 to 21 of the woman's cycle. (Day one is the first day of your period.) The gel is usually continued until the placenta is producing enough progesterone to support the pregnancy.
Crinone vaginal gel is also used to support pregnancy in women having in vitro fertilization (IVF). In this case the gel is used daily, starting after the embryo has been transferred into the womb, for the first 30 days of confirmed pregnancy."
www.netdoctor.co.uk/pregnancy/medicines/crinone.html
 

Wednesday, July 15, 2015

Conceiving After 45: IVF With Your Own Eggs Or Donor Eggs?


Question:

Dr Ramirez,
What are the chances of a 45 year old woman conceiving using IVF with her own eggs? Would it be worth trying or would you recommend using donor eggs? A. from the UK

Answer:
Hello A. from the UK,

There are always exceptions to the rule, however, the chances of pregnancy, even with IVF, are very slim.  In the 2012 National summary produced by our Centers for Disease Control (CDC), based on IVF reporting data, the national averages for women >44 years old is 5% pregnancy rate and 2% delivery rate.  This, of course, is an average and the statistics can be different for different centers.  There have been pregnancies over 44 years old but they are very few.  In my center, the oldest patient to get pregnant using her own eggs (as opposed to using donor eggs) was 44 years old.
I tell my patients that only God can determine who will be the exception to the rule, but if you don't try, then you have a 0% from the start.  However, if you decide to try, you have to go in with the understanding that your chances are slim.  Until you try, you won't know the outcome.  If you want a better chance, the donor eggs will be much better.

I have a 45 year old patient contemplating this now who is leaning toward trying at least once because she wants to reassure herself that she has done everything possible to have another child (she has one already).  I told her, and you should understand this too, that IVF is not a perfect technology even in young women, and like trying naturally, it can take several tries.  So if you want to be absolutely sure that you tried your very best with IVF, then you need to be prepared to try several times.

As to whether or not it is worth it, that is a totally individual decision.  The worthiness of something is defined by yourself.

Good Luck,
Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program

Monterey, California, U.S.A.
 

 

Tuesday, July 14, 2015

"How In Vitro Fertilization Works" Video from TED-Ed

Dear Readers,
I recently found this nicely animated video on In Vitro Fertilization created on the new TED-Ed platform. You might find this a good way to not only inform yourself but also friends and family who might have trouble understanding the fertilization process. 

"Infertility affects 1 in 8 couples worldwide. But in the last 40 years, more than 5 million babies have been born using in vitro fertilization (IVF). How does it work? Nassim Assefi and Brian A. Levine detail the science behind making a baby in a lab."

Lesson by Nassim Assefi and Brian A. Levine, animation by Kozmonot Animation Studio.


 
 
 
As always, I am open to questions regarding this complex but important assisted reproductive technology, IVF.
 
 
Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program

Monterey, California, U.S.A.



Thursday, October 2, 2014

Upcoming Frozen Embryo Transfer #4: Do I Transfer 1, 2 or 3????


Question:

Hello,
I have a son via FET. I have now had three cycles of FET total. The first did not work, the second we got my son, and this last one worked- however I had a miscarriage at 6.5 weeks pregnant. I now have 4 embryos left frozen and am starting my next IVF cycle. They are frozen in vials of 2 each. I am so concerned if only one survives: do I only implant only one and pray it works, or do I thaw the last two we have and implant all 3? I obviously want the ultimate outcome: a pregnancy. 
 
My doctor is NO help when I ask what he recommends.  I am scared to only implant one.  Yet I am scared to use all of them in this one last attempt we have.  Is only implanting one pointless? Can you give me a recommendation on what is best if this situation were to happen on the day of transfer? The transfer is only a couple weeks away so I am so nervous.
 
Thank-you so much.
 
S. from Illinois. Nervous mom!!!!!!!

Answer:

Hello S. from the U.S. (Illinois),

Since you haven't given me your age, I can't give you specific recommendations but will have to answer your question in more general terms.  Also, another significant piece that would help answer the question is whether your embryos were frozen on day#3 (cleaved) or day#5 (blastocyst).

We always consider age when counseling patients on the number to transfer because this affects the quality of the embryos and therefore their chances of implantation.  Of course, the younger you are, the higher your chances of implantation and pregnancy per embryo.  Because the technology has gotten so much better over the years, pregnancy rates have gone up and we have realized a problem; namely, an increase in multiples, especially those over twins.  As a consequence, every IVF Physician is wary of putting to many back for fear of getting too many in return.  As a result, the American Society for Reproductive medicine and the Society for Assisted reproduction, its subgroup, have produced recommendations or guidelines for transfer.  these of course are dependent on the age and the stage of development.  Their recommendations are as follows:

 Cleaved embryos:   
                             35    35-37    38-40  40 years old
   Favorable         1-2       2         3        5+
   Unfavorable        2        3         4        5+

 Blastocyst         

   Favorable          1        2         2        3
   Unfavorable      2        2         3        3

I have my patient sign a counseling for that they have been informed regarding these guidelines and either choose to follow them or choose a different number.  I do let my patients decide within reason.  Because you have gotten pregnant with these embryos before, that would be an additional piece of information making me more cautious.

So here's the decision.  Unless you are over 35, I would recommend no more than 2 if they are blastocysts.  If these are cleaved embryos, then I would recommend 2-3.  But, the risk is of getting multiple implantations leading to at least twins.  With blastocysts and transferring 2, my twin rate is 56%.  With cleaved and transferring 3, my twin rate is 35%.  Are you willing to take the risk of having twins?  The pregnancy is harder and there is an increased risk of fetal loss.  If you are not willing to take the risk of twins then you would only transfer 1 no matter what stage.  If you are not willing to take the risk of triplets, then you would not transfer more than 2.  I do not recommend triplets.  The fetal loss rate can be as high as 50%.  The down side of transferring less than 2 is a decrease in pregnancy rates per cycle, but not necessarily over all.  It make take more attempts to get pregnant doing single embryo transfer.

I hope this gives you the information you needed to help with the decision.

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program

Monterey, California, U.S.A.

 

Thursday, August 21, 2014

Recurrent Miscarriages: Is It A Hormonal Issue?


Question:

Dear Dr. Ramirez,

I am writing from Pennsylvania. In 2006, I had two or three miscarriages.  After that, I went to a fertility clinic and had TSH, prolactin, DRVV, and anti-cardiolipin antibodies tested.  All were normal.  I also had progesterone level checked at the very beginning of one of the pregnancies as well as a non-pregnant menstrual cycle after ovulation.  Both were normal.  I had irregular cycles that were anywhere from six to ten weeks apart.  I knew when I ovulated because I got pain in whichever ovary released the egg and always had a luteal phase of 14 days. I also conceived easily.  
 
The doctor felt the lining of my uterus was getting too old to sustain a pregnancy since so much time elapsed between cycles. In February 2007, I conceived on one round of Clomid and carried that child full-term.  I then had two more children in 2009 and 2011 with no help despite still having the same irregular cycles.  My cycles are a little better now and usually five to six weeks apart, but I have had three miscarriages again in September 2012, December 2013 and June 2014.  All the miscarriages I ever had were missed abortions with embryo development ending between week 5 and 6 with the exception of the most recent which ended at 11 weeks 5 days despite fetus having a strong heartbeat and normal looking development.  Since a drop in progesterone causes shedding of the lining of the uterus, is it safe to assume that since my miscarriages were not spontaneous that progesterone was not an issue?  Could other hormones be issues or was chromosomal defect the likely issue all these times? 

Thank you for your time. Sincerely, M. from Pennsylvania

Answer:

Hello M. from the U.S. (Pennsylvania),

There are basically five known causes of recurrent miscarriages from the following abnormalities: genetic, anatomic, immunologic, hormonal and infectious.  When a woman has had two or three miscarriages, she automatically has earned the diagnosis of "recurrent pregnancy loss" and as such, needs to undergo a thorough evaluation of these elements.  The most common cause of miscarriages is genetic abnormalities and is responsible for 85% of miscarriages in women over 35 years old.  A recent study showed this cause to be less in younger women.  Genetic abnormalities can be caused from an inherited disorder or a spontaneous disorder, whereby the egg makes a genetic error when it is dividing leading to an abnormal embryo.  Most of these pregnancies will end before 12 weeks gestational age.

The recommended testing is as follows:

Genetic: wife and husband chromosomal analysis, saliva DNA analysis

Anatomic: diagnostic hysteroscopy, pelvic ultrasound, end cycle endometrial biopsy for dating and b-Integrin

Immunologic: Complete antiphospholipid antibodies, natural killer cells, Factor V Leiden, MTHFR, Antinuclear antibodies, Lupus anticoagulant, anti-Thyroid antibodies

Hormonal: FSH, LH, TSH, Prolactin, Estradiol, Mid-luteal Progesterone

Infectious: GC, Chlamydia, Ureaplasma/Mycoplasma, Toxoplasmosis

Age is probably the most common major cause which leads to an increase in genetic abnormalities.  Since you don't mention your age, that could be part of the problem if you are over 35 years old.  The good news is that most women with recurrent miscarriage will eventually have a successful pregnancy.

Good Luck,

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

 

LinkWithin

Related Posts with Thumbnails