Friday, February 22, 2013

Canadian IVF Cycle Fails: Husband Asks, Try Again?


Hello Dr. Ramirez and thank you so much for answering these questions.
My wife and I just completed our first IVF (although there was no transfer).  A previous attempt was cancelled due to only a couple follicles (150 Gonal F/150 Menopur).  We had done 2 previous IUIs with Clomid (3 follicles).

My wife is 37 and has very low AMH (0.40), FSH that ranges from 7 to 14 and an AFC of 6 to 14.  My analysis has been normal but we were recommended ICSI as it was unlikely we would get many follicles.  The clinic said they generally like to aim for 2 good ones.

To bring down FSH, my wife used an estrogen patch before her period and had 3 Ganirelix injections.  She then started 300 Gonal F & 150 Menopur on Cycle Day 2.  From Day 9 to 15 she also used Ganirelix. She was told to change the patch every other day and on cycle day 4 stop changing the patch (but it would last 7 days so would still have medication until cycle day 10).

She was slow to respond, not developing any measurable follicles (greater than 1.0) until after 7 nights of stims, but in the end, used the same Gonal/Menopur dosages for 15 nights.  Her AFC had been 14 and when she triggered (with 10,000IU HCG) on night 15 she had 7 follicles (2.2, 3 at 2.0, 1.6, 1.4, 1.0).  On trigger night her e2 was just over 2,500 (I have converted this to the U.S. value - pg/nl). 
35 1/2 hours later was retrieval.  They got 4 eggs and had to skip a few on one ovary due to blood vessels. The next day the embryologist called and said they had been able to ICSI 3 of the 4 and as of that morning (day after retrieval) only 1 of the 3 remained.  The next morning (2 days after retrieval) they called to say that embryo failed to divide.  It was the same the next day so there was no transfer.  They didn't have a definite answer as to why but said one of the eggs was soft and they weren't all smooth so it is probably egg quality issues.

Also - up until day 11 of stims her lining had been building well daily (to 1.2 cm).  Over the next 3 consecutive days it got thinner each day (even though e2 was rising) and was 0.9 the day of trigger.  Her lining has never been a problem in any other cycle (natural or medicated - even on Clomid).

We are trying to decide if it is worth it to do another cycle.  Could this be a fluke?  Could the long stim period have compromised egg quality (in addition to her age/FSH/AMH?)  Could ICSI have damaged the eggs at all if they were soft?  Will the blood vessels mean some follicles have to be left in one ovary at every retrieval?

Did the thinning lining indicate anything - coincidentally - when the lining started thinning her own e2 was raising daily quite a bit, but this was the same time the medication from her final estrogen patch would have worn off.  She had a bit of bleeding a few hours before the trigger shot on night 15 and was put on 8 mg/day of estrace the day of retrieval in addition to progesterone because of that. 

I would appreciate your advice.  We would like to try again but I don't want my wife to have to go through another cycle of injections/monitoring/retrieval, etc. if our results would be the same.  She had 12 days of blood tests & ultrasounds between day 2 & 15 and the 12 blood tests made it really hard to find a vein for IV at retrieval which took a couple tries.

We would like to at least make it to transfer before considering other options, but if we can't develop embryos in a lab, we're not sure if we should try again.
Thank you,

T. from Ontario, Canada

Hello T.  from Canada,

A lot of the answers you seek are due to technical quality issues and I cannot address that.  Without a thorough review and evaluation of your wife's medical records, I cannot evaluate if I would have done things the same or differently, and whether or not that will make a difference.  Suffice it to say that I am saddened by your results, but at the same time, I am a little leery about some of the embryology outcomes.

Let me just give some information that might help you in your review. 

1.  The dosage of 350/150 is NOT the highest stimulation protocol.  Your wife could go up to the max dosage of 450/150 which might make a difference in the number of follicles recruited. 
2.  Based on the number of follicles formed, she actually stimulated well so the AFC, AMH and FSH may not be valid in predicting her decreased ovarian reserve (which does not predict fertility).

3.  I have not heard of the failure to retrieve due to "veins" or "blood vessels".  There are techniques that can be used to move and manipulate the ovaries to avoid those problems.  I have, however, had patients where I could not retrieve completely because the ovaries moved too much and deep into the pelvis.

4.  I think that ICSI in a 37 year old woman is appropriate and would concur with doing that procedure.  Keep in mind that ICSI is a procedure and "technique and skill" are critical to preventing damage/injury to the embryo.  It has been shown that ICSI done by an embryologist without adequate experience and skill can reduce embryo survival.  That could possibly have been a problem, but certainly inherent egg quality can influence that as well.

5.  Embryo quality (based on external features) are certainly based on inherent egg quality and that decreases with age.  However, that does not mean that all the eggs are bad.  Studies have shown that at 37 years old, 2 of 10 embryos formed will be normal.  The trick is to find the two good ones.  That may take several attempts or you would have the option of moving to donor eggs.  Since you have never completed an IVF cycle, you certainly have not tested whether or not it will work.

6.  Finally, I don't think I have ever had a patient that needed 12 blood tests during an IVF cycle.  The maximum I've had was 7.  Keep in mind that IVF success rates are highly variable between clinics and doctors.  Even in the U.S., rates are highly variable as compiled by the CDC.  I'm sure they vary greatly in Canada as well.  Based on what you have told me in your review, I can't help but be a little skeptical of the level of care you are receiving, but again, I can't draw any conclusions without a careful review of your records.
Good Luck,
Dr. Edward J. Ramirez, M.D. F.A.C.O.G.
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program

Comment: Thank you very much for your quick and helpful response.

Saturday, February 16, 2013

Off The Pill After 12 Years, No Period: Trying To Conceive, What Can I Do?


Dr. Ramirez,
I was on the pill for 12 years, and stopped taking it back in September of 2012 to try and conceive. I did not have a period for over 3 months, so I went to the doctor who gave me a progesterone injection. About a week later, I had light bleeding for one day. A month later, I had the same light bleeding for one day. Five weeks later, I had nothing.

I went back to the doctor and got another injection. Two days later I had light spotting and nothing else. Is this considered a cycle? I am suppose to start Clomid on day five, but I am worried that the progesterone is not working for me and that the absence of my period is something else. Also, is there any difference in results if I were to take Provera instead? I am 30 years old, and really want to start having children. Should I try the Provera or just go on to an infertility specialist? I am so impatient and ready to get started, but very frustrated. Please help! L. from Tennessee


Hi Lisa from the U.S. (Tennessee),

Obviously your current doctor is wasting your time (and has done so three times), so I would recommend that you go see a fertility specialist. Not only will you have an appropriate evaluation done to see why your ovaries are not working, but you'll get the appropriate treatment and get pregnant in the shortest time period.

Basically, progesterone injections and Provera (progesterone) accomplish the same thing, which is to induce a withdrawal bleed. So, using Provera won't make any difference. The reason the bleed wasn't much is because you probably did not have much of an endometrial lining formed. In that case, the light bleed would be the first day of the cycle and the counting of the cycle days would start from then. However, before starting the Clomid, a baseline ultrasound is usually done to confirm that you are on your period, as evidenced by a thinned lining, and that there are no cysts in the ovaries that might prevent ovulation. Having a cyst in the ovary is a contraindication to using Clomid or any other fertility drug.

Good Luck,

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

Tuesday, February 5, 2013

42 Year Old TTC With Endometriomas And Low Antral Follicle Count

Hi Dr. Ramirez,
Not sure what to do.  I met the love of my life later in life and we just started trying to conceive, I am 42 years old.  We really want to have a child, but not so sure about donor eggs .  I have never been pregnant or attempted to get pregnant before. Six months ago my AFC=3, FSH=6.3, E2=117.  My results today were AFC=0, FSH=1.4, and E2=252 and two endometriomas that appear to be growing.  Could the endometriomas have caused the change in numbers?  If so, would removing them increase my chances of becoming pregnant?  I've read that surgery reduces the ovarian reserve which is not a good thing so I'm confused as to what to do.  I've also had a hard time figuring out which doctors would be gentle/skillful and not remove any unnecessary ovarian reserve, this could be crucial in my situation.  I would like to do IVF (in vitro fertilization) but the clinic I've gone to is not willing to discuss it due to the change in numbers.  Are there any clinics that will work with my numbers and the endometriomas?  We want to give it our best shot, it would mean so much for us to have a baby together.

My pelvic transvaginal ultrasound results were: 

FINDINGS: The uterus is normal in size measuring 7.9 x 3.9 x 4.6 cm.  No fibroids or other myometrial abnormalities are visualized.  The double layer endometrial thickness is normal measuring 7mm. No focal endometrial abnormality or endometrial cavity fluid is seen.

Right ovary is enlarged.  The right ovary measures 6.1 x 4.4 x 6.1 cm.  Homogeneous hypoechoic structure in the right ovary measures 5.1 x 3.9 x 5.7 cm previously 3.9 x 2.6 x 3.8 cm (on 18Nov2012 ultrasound).  The left ovary measures 4.2 x 2.5 x 3.9 cm. Hypoechoic structure in the left ovary measures 3.6 x 2.5 x 3.2 cm previously 2.0 x 2.0 x 2.4 cm (on 18Nov2012 ultrasound). No abnormal free fluid is seen.

IMPRESSION:  Normal uterus. No uterine fibroids are seen.  Homogeneous hypoechoic structures in both ovaries, increased in size since 18Nov2012.  Findings most likely represent endometriomas.

Thank you so much for any advice you can give us. L. from Virginia


Hello L. from Virginia,

First, I think that your blood testing is incorrect.  The reason is that the FSH test is only valid if done right at the beginning of the cycle, generally cycle day#2 or 3.  I suspect that the test was not correct because your estradiol was above 100 in both tests. This shows that the ovaries were not at rest i.e. not in the early phase.

Second, I am sure that you can find a clinic or doctor that is compassionate enough to allow you to try IVF (in vitro fertilization) with your own eggs, but that will be with a complete understanding of your chances.  For example, I don't have a blanket policy to not allow patients to try as long as they understand the risks and chances.

Third, you have to understand the major problems you are facing and the impact that has on your chances.  The first major problem is your age.  This is what we call the "age related egg factor".  This basically means that because of a woman's age, the quality of her eggs decreases so that the majority are no longer viable.  As a result, the pregnancy rate decreases and the risk of miscarriage due to genetic abnormalities increases. Even with IVF your chances will be decreased, BUT they will much better than trying naturally! The second major problem is Stage IV Endometriosis.  When you have endometriomas, that automatically makes it stage four, which is severe endometriosis.  As a consequence, IVF is the treatment of choice.  You can, and probably should, try to find a very good gynecologist to remove the endometriomas laparoscopically, with specific instructions to NOT remove any ovarian capsule tissue (that is the layer that has the eggs).  That will help to give you the best chances of pregnancy.  However, it is not an absolute necessity. Third, you have a decreased antral follicle count (AFC), which is supposed to represent the number of follicles available, but frankly, I don't rely on that too much.

You can achieve pregnancy if you go about it with an open mind and choose a good clinic. For more information on endometriosis and infertility, as well as other age-related factors please see these pages: “Endometriosis” and “Age Factors” in my website’s section on Understanding Infertility.

Good Luck,

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


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