38 Year Old Has Five Failed Fresh IVF Cycles But Has Frozen Embies: Should She Try FET?

Question:

Hello - I have been reading you blogs for some time now and am so thankful that you take the time you do with such thoughtful answers.

I am 38 and husband is 41. My history is as follows: 2009 wasted time on clomid prescribed by my obstetrician, 2010 saw RE (reproductive endocrinologist) and began the real journey. Major issue is male factor morphology but I suspect with my age quality may be issue too.

In 2010 we had 2 Fresh IVF (in vitro fertilization) cycles, first was a failure 3 eggs collected, thankfully 3 fertilized and implanted 2 (1 frozen) but no pregnancy, cycle 2 doubled my stim meds to 300 gonal f and 150 repronex, collected 13 eggs but transferred 2 "decent" but beta was very low around 70 the pregnancy continued to around 11 weeks saw heartbeat but clearly there was issues as the size kept loosing ground until miscarriage and D&E. Cycle 3 same meds, 13 eggs, transferred 2 on day 5 and then arrived my beautiful baby girl delivered 12/29/2011.  Fast forward to 2013 where I have done two more fresh cycles same protocol, birth control, 10 lupron, to 5 lupron when stimming, retrievals after 9-10 days of stims. Cycle 4 resulted in collecting 20 eggs, 2 "decent" transferred on day 5 (blastocyst and morula) very low beta resulted in loss about a week later.  Cycle 5 same protocol except menopur instead of repronex, collected 18 eggs, 14 fertilized and transferred 2 blastocysts on day 5. This was a negative. BTW all cycles are ICSI and included medrol, baby aspirin, antibiotics, vivelle patches and  progesterone in oil injections. 

My question is what are your thoughts on FET (frozen embryo transfer).  I have 4 frozen embryos 1 from cycle 1, 1 from cycle 4 and 2 from cycle 5. RE and hubby think I should take a break and try for FET. I and concerned as I don't want to "waste" a cycle insurance will cover on the lower cost option but the meds did really affect me this time and see their point about giving my body a rest. I am at a very reputable clinic in Boston and doc said 4 frozen is a lot due to their strict freezing criteria so am optimistic although obviously embyro age has no advantage. Would FET also be something you would recommend at this point? Fresh cycles are a big logistical challenge as my husband travels 70% of the time.

Also if I go back to fresh cycle is there anything significantly different you would do (btw I am also doing acupuncture). Thank -you in advance for your time. I also want to say I am very grateful for my daughter and don't want to seem selfish but I would really like her to grow up with a sibling. 

J. from Boston

Answer:

Hello J. from the U.S. (Boston),

It sounds like you are in good hands.  Your clinic has accomplished several pregnancies, which is an IVF success.  Keep in mind that IVF can only give you the "opportunity" to become pregnant.  It can't make you pregnant because the last three steps (embryo hatching from its shell, attachment to the endometrial lining, and lining growing around the embryo are natural processes that are in God's hands.  That fact that you got a pregnancy (positive bHCG) shows that those steps occurred.  Continuation of the pregnancy is then based on pregnancy factors and not IVF factors.  Because of your age, your chances of a miscarriage are high due to abnormal embryos.  You've shown that you can get pregnant, and your ovaries stimulate very well.  Now it is just a matter of finding the perfect egg/embryo which will then lead to a successful pregnancy.  I wish all my 38 year olds responded as you do.  So hang in there!

I think I would advise proceeding with the FET cycle before another fresh cycle.  It is a much easier cycle on your body, and some newer studies are showing better pregnancy rates than fresh, probably because of the lack of overstimulation of the endometrial lining.  I don't completely agree that FET is "better" but it certainly gives a good chance.  If they fail, you can certainly try fresh cycles again.  I would advise two FET cycles consecutively.  In fact, I always advise my patients to do an FET cycle, if they have frozens, before trying a fresh cycle again.  You never know. . . the frozen might work.
In terms of additional protocol changes, you are doing everything that I have my patients do in terms of supplemental medications, but I also add low dose heparin (2000 U per day).  Not all RE's agree with this protocol, but it is an accepted protocol for recurrent pregnancy loss so you might want to ask your RE.

Thanks for following my Blog.

Good Luck,

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

www.montereybayivf.com

Monterey, California, U.S.A.

Comment: Thank you much for the quick and thoughtful answer. I have several time contemplated seeking a more aggressive clinic despite my comfort level. Your response puts many of my worries at ease. You are truly a huge help to those of us in a constant state of limbo. Thanks again.

 

Canadian IVF Cycle Fails: Husband Asks, Try Again?

Question:

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

Answer:

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 Programwww.montereybayivf.com

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

 

A Step By Step Guide To The IVF Process: Step Five -- Fertilization

Dear Readers:

This is the fifth part in the series I have begun to help answer what In Vitro Fertilization (IVF) is and how it works with my world-wide Blog audience. What you read here is what I also provide my patients with on a daily basis. I plan on going into some detail but in a way that is understandable to the normal (lay) audience, and not the medical or scientific one. I also hope that this will not only clarify what you will go through, but explain why things are done a certain way and what the goals of each step are. I also want to convey that IVF is actually a replacement for some of the “natural” steps required to get pregnant and not some miraculous high tech fertility treatment that gets patients pregnant artificially, as many think it is. It is somewhat of a miracle that we can do as much as we can, but there are still lots of things/steps that we cannot do or influence. I hope this discussion will benefit you. This series will continue to be posted over the next few weeks in installments. (For earlier installments in correct order scroll down to the beginning of July 2012.)

STEP FIVE: FERTILIZATION

In the previous step, the eggs were aspirated and retrieved from the ovaries, the equivalent of ovulation in the natural process. These eggs have been collected and the embryologist now isolates each egg within a petri dish. The eggs are prepared for the fertilization step. In the natural cycle, after ovulation, the egg needs to pass through the culdesac of the pelvis to find the fimbria of one the tubes. In the normal anatomical position, the fimbria of the tubes are lying within the culdesac. If there is scar tissue within the culdesac or the anatomical positions of the tubes are altered, then this “pickup” step may not occur. This would be an indication to do IVF. If this does not occur, then that is the end of the process in that cycle. If it does find the tube, it is then brought into the tube and through peristalsis (muscular motion) within the tube it is pushed to a portion of the tube where the sperm need to be waiting to accomplish fertilization. Again, if the sperm are not there, then fertilization will not take place and the cycle ends at that point. If the sperm is in the correct position at the correct time, then sperm attach to the egg and one sperm penetrates the egg to accomplish fertilization. In IVF, these two steps are accomplished by laboratory means, so there is little chance that those steps will not be accomplished. This is another step that IVF accomplishes for your body, thereby enhancing your chances of success. It is not left to chance as in the natural process.

At this point, there are two ways to accomplish fertilization. It can be allowed to occur by natural means, meaning the sperm can be added and the egg-sperm interaction allowed to happen on its own, or it can be assisted, also known as ICSI or "intracytoplasmic sperm injection". In order for the fertilization process to occur, a sperm needs to penetrate the outer lining (shell) and enter the egg and then there is an elaborate process within the egg whereby the nucleus of the egg and the nucleus of the sperm unite. This latter process is the actual process of fertilization. Just putting a sperm into the egg is NOT fertilization. The second part of the process, a natural step, has to occur on its own. In other words, just doing ICSI is not fertilizing the egg and does not guarantee fertilization. ICSI is just putting the sperm within the egg so that fertilization has the possibility of happening.

If natural fertilization is going to be done, the egg and sperm are put together and the sperm is allowed to penetrate the egg on its own. But if injection of the sperm is going to be done, then the embryologist removes the filmy lining of the egg, called the cumulus. This will also allow evaluation of the maturity of the egg. Only mature eggs, in Meiosis stage II, can be fertilized. Eggs can be in either Meiosis stage II (M2), Meiosis stage I (M1) or Germinal Vesicle (GV) stages at the time of retrieval. As explained previously, the follicles, and the eggs within, don’t all mature at the same rate. That leads to some larger follicles and some smaller follicles. The larger follicles have the matured eggs, eggs that have had the time to mature, and the smaller follicles have immature eggs. As a result, eggs in the various stages can be retrieved, but only the mature ones will fertilize. In the case of Meiosis stage I eggs, these can be left in culture and allowed to mature, if the clinic has an egg maturation program and the proper media in place, or in some cases, just waiting will allow the egg time to mature to the mature Meiosis stage II. They can then be fertilized at that time. So with ICSI, an anatomically normal appearing and swimming sperm is identified and aspirated into a glass needle. This needle is then inserted into the egg and the sperm is then injected within. All of this procedure is done microscopically. ICSI essentially assists the step whereby the sperm enters the egg. This procedure is done mostly in cases where there is an abnormality of the semen analysis, since it is known that with abnormal semen analysis, there is a high possibility of a functional problem i.e. that the sperm cannot fertilize the egg. Also, it is recommended in older patients (>37 years old) because the shell of the egg is thicker and sperm have a more difficult time penetrating the shell normally. In some cases, patients will choose to have ICSI because they don’t want to take the risk of fertilization not taking place (fertilization failure), which will essentially end the cycle at that point. Without fertilization, embryos are not formed, and no embryos means there will be nothing to transfer.

Once the eggs are put with the sperm, the petri dishes are placed into an incubator. Fertilization will take a minimum of 12 hours to occur so most clinics will re-evaluate the eggs the next morning for fertilization. It is expected that some eggs will fertilize normally, called a 2PN stage, some will not fertilize and some will fertilize abnormally (1PN or 3PN). Because of this, there will be another reduction in the number of eggs available to use. With fertilization, the egg is now referred to as an embryo. A typical threshold to evaluate fertilization is to expect a minimum of 50% of the available (mature) eggs to fertilize. If that threshold is not reached, it could be because of egg quality, sperm quality or lab quality. Only the fertilized embryos can be cultured to develop into embryos that can be transferred back into the womb, so this number essentially establishes how many might be available for transfer. Fertilized embryos are now transferred into a new culture media and placed in incubators that have a specific gas content and temperature to allow them to grow.

We will continue this discussion soon with the next installment, "Step Six: Embryo Development". Thank you for joining me today!

Edward J. Ramirez, M.D. F.A.C.O.G.
Medical Director, Monterey Bay IVF
Monterey, CA
http://www.montereybayivf.com/

A Step By Step Guide To The IVF Process: Overview

Dear Readers,
I get many  many questions regarding what In Vitro Fertilization (IVF) is and how it works that I thought I would share the information with my world-wide Blog audience. What you read here is what I also provide my patients with on a daily basis. I plan on going into some detail but in a way that is understandable to the normal (lay) audience, and not the medical or scientific one. I hope that this will not only clarify what you will go through, but explain why things are done a certain way and what the goals of each step are. I also want to convey that IVF is actually a replacement for some of the “natural” steps required to get pregnant and not some miraculous high tech fertility treatment that gets patients pregnant artificially, as many think it is. It is somewhat of a miracle that we can do as much as we can, but there are still lots of things/steps that we cannot do or influence. I hope this discussion will benefit you. This series will be posted over the next few weeks in installments.

OVERVIEW:
Before I begin explaining each step, let me give you an overview of IVF. As I mentioned earlier, IVF or "In Vitro Fertilization" is actually a replacement for the natural steps your body would go through in order to get pregnant, and it still relies on many of those natural steps to occur before you become pregnant. “In Vitro” means in the laboratory versus “In Vivo” which means in the body. As I’ll explain, IVF is not all done in the lab. Some parts of the process still are required to be in the body, so in actuality, it is both an “In Vitro” and “In Vivo” procedure.

There are basically nine steps that your body goes through in order to achieve a pregnancy:

(1) Your brain (hypothalamus and pituitary) sends a signal to the ovaries to stimulate the growth of a follicle and maturation of the egg within.

(2) The designated follicle grows, and the egg matures, until it reaches a critical size, whereby there is an LH surge to induce ovulation.

(3) The follicle surface ruptures and an egg is expelled with the rush of fluid within (ovulation) and enters a space behind the uterus called the culdesac, the lowest point in your abdomen.

(4) Through fluid motion (this part is not exactly known so it is my personal belief that this is how it happens), the egg contacts one or the other fimbria of the tube, which is hanging into the culdesac in its natural position, and now lies within this puddle of fluid. The egg is then brought into the tube by the fimbria and tubal motility.

(5) The egg moves into a part of the tube where, hopefully, the live sperm are waiting to attach to the egg, and then fertilization occurs.

(6) The fertilized egg slowly moves down the tube, dividing and forming into a blastocyst.

(7) The blastocyst then enters into the uterine cavity and settles there.

(8) The inner portion of the blastocyst then hatches out of the shell and attaches to the uterine lining.

(9) The uterine lining then engulfs the embryo, which is known as implantation and at this point bHCG begins to be produced.

These are the steps that your body goes through to get pregnant, but does not do it exactly or perfectly each month. That is why it may take several months before a human woman gets pregnant. IVF is basically accomplishing most of these steps for you, NOT doing some artificial process. Yes, it is not within your body, or at least some of it is not, but the same processes have to occur. If you know and understand IVF you can see that IVF basically accomplishes steps 1-7. Two steps then have to occur naturally for pregnancy to occur. So as you can see, IVF is still basically a “natural” process because it still relies on natural processes within your body.

In other words, we give fertility drugs to stimulate the ovaries to grow and mature eggs but the ovaries still have to pick up and process these hormones on their own, and growth and maturation of the eggs still have to occur naturally. We can put the egg and sperm together but fertilization still has to occur by itself. Even ICSI (intra cytoplasmic sperm injection) is only putting the sperm into the egg. The actual fertilization process, the merging of the egg nucleus and sperm nucleus, among other processes; still have to occur on their own. We cannot make that happen. We can put a grown embryo into the uterus but we cannot make it hatch out of its shell, attach to the uterine lining or make the lining engulf the embryo (implant). All of these steps are left up to nature or, as I tell my patients, are in God’s hands and the way He reminds me that I am but His humble servant. This keeps my head and ego from becoming too big!

Many patients are devastated when an IVF cycle fails, because they have the false belief that it is the ultimate and perfected technological way to become pregnant, and therefore works every time. It is certainly more technological but not even close to being the ultimate or perfect method, and it doesn’t work every time. For that reason we cannot achieve 100% pregnancy rates, and much research and technological advances still need to be developed before we will get there. Make no mistake, however, we have improved greatly since the first IVF success with Louise Brown, but that took years to occur as well.

Sixteen years ago when my wife and I did IVF, she was 37 years old, and her statistical chances were about 12-15% but now a 37 year old in my center has a 65% chance of pregnancy per cycle. We have improved greatly and come a long way. We can now help a couple acheive a pregnancy where previously there would have been no other option but adoption. IVF is certainly better than trying naturally because more steps are accomplished, whereas in natural cycles, the body does not always do each and every step correctly. For example, ovulation may occur but the egg may never find the fimbria so that month pregnancy will not occur. Just to put things in perspective, a 37 year old has a 5% chance of pregnancy per month of trying by natural means. When trying naturally, women have to keep trying for several months before a pregnancy occurs. In fact it will take 85% of women under 30 years old 8 to 12 months to achieve a pregnancy. In the same way, because IVF is just replicating the process, it can take several attempts before the body does its part of the process correctly. In my center 55% of patients (not adjusted for age), achieve pregnancy in their first attempt. Most patients will be pregnant by three attempts rather than the 12 months it may take to achieve a pregnancy naturally.

We will continue this discussion soon with the next installment, "Step One: Stimulation".

Thank you for joining me today!

Edward J. Ramirez, M.D. F.A.C.O.G.
Medical Director, Monterey Bay IVF
Monterey, CA
http://www.montereybayivf.com/

Fourth IVF Cycle Ends In A Chemical Pregnancy: What Can Be Done?

Question:

Hi Dr. Ramirez,

I have been on a rollercoaster ride for the past week and I am hoping that you can offer me your opinion.


I received a positive beta after my 4th IVF on Monday (11dp3dt). It was 14.3 and my RE said that it was quite low. I held out hope as I am convinced that I tend to implant a little later than others. In a previous cycle I had a negative beta 12dp3dt and found out that I was pregnant a couple of weeks later. I tested 3 days later and my beta was up to 52.8. I was so excited and felt so much better about things. I am scheduled to go back on Sunday morning for another beta.

I am currently taking Crinone 2xday. For the past week, I have had dark brown Crinone gunk(sorry for TMI). Last night and this morning there was some red blood on the applicator tip. At 1st I thought it was just irritation but for the past couple of hours, when I wipe there has been more red blood. I am also getting some minor cramping.

I am freaking out and I am so worried that things are moving in the wrong direction. I called my clinic and they said that they cant know anything until Sundays beta. They said it could be start of a miscarriage given the low beta #'s or it could be irritation from the Crinone or even pregnancy spotting.

I was hoping that you could offer some advice as I remember in the past that you prescribe Crinone to your patients.

Is RED spotting normal? How much spotting is normal? Was I foolish to be hopeful after my #'s doubled? Do you think its likely that this will end in miscarriage?

Any insight would be greatly appreciated. I dont know if i can hold out until Sunday's beta.

Thank you,

D. from Boston, Mass.

Answer:

Hello D. from the U.S.(Massachusetts),

The advice that your doctor gave you is completely correct. It could be from the Crinone, and I have seen an increased incidence of spotting in my patients using Crinone), it could be implantation spotting or pregnancy spotting or it could be indicating an abnormal pregnancy. There is no way to know which of these is the correct diagnosis. In general, I reassure my patients not to worry about spotting. I only worry if the bleeding is bright red flow like a period with accompanying cramping. The only way to determine the fate of this pregnancy at this point is to continue to follow the bHCG's every other day. This trend will then give you a better idea of how the pregnancy is doing. AS long as the bHCG is rising, then you can be reassured. If it plateaus or drops, then that is not a good sign.

Follow-Up Question #1:

 Dr. Ramirez,


Thank you for getting back to me. Unfortunately, my beta level dropped on Saturday so it looks like I will be having another chemical pregnancy. I am devastated of course. I was hoping that you might be able to provide me with some insight as to an explanation as to why this keeps happening.

A little history:

Me: 31 years old- normal FSH but AMH is .8

Husband: Very low morphology (less than 1%)

This was our 4th IVF cycle and 3rd chemical pregnancy. I have had tons of testing... RPL work-up, HSG, genetic testing, uterine biopsy and all came back normal.

I am a low responder and in previous cycles have had poor egg quality. I just switched REs and had a better response with an Estrogen Priming Antagonist protocol. He used a low dose HCG with Gonal F. Quality and ICSI fertilization rate was much better so I was hopeful that this was it.

My RE said that it was likely a chromosomal issue with the embryo and probably because of poor egg quality and we just need to keep trying and hopefully will get that “one” good egg. I don’t know if I am comfortable with that answer. We only have 2 insurance tries left and I want to make sure we are exploring all options before proceeding again. What would you recommend for your patients at this point? Do you think that it is worth doing a Sperm DNA fragmentation test?

What could be the reason for all of these chemical pregnancies?

Any insight is greatly appreciated.

Follow-Up Answer #1 :

Hello Again,

The exact reason cannot be known, of course but the most common reason for chemical pregnancies are a genetic abnormality in the embryo. With poor morphology in the semen analysis and your young age, definitely the genetic weakness could be from the sperm. I don't recommend the sperm DNA fragmentation test because it only gives the indication for the batch of sperm that it tests and not the sperm as a whole. In addition, the treatment recommendation is to use ICSI, which I presume you are doing already. So you won't gain anything from that test. If we suspect the sperm, other than ICSI you have the choice of either using donor sperm the next time or maybe try using a supplement for three months before doing IVF again. The supplements that your husband can try, which might help with sperm quality, are either Proxeed or Fertility Blend (vitamins) and CoQ10 600 mg per day. He will have to wait three months because sperm are on a 90 day cycle #the sperm made today won't be expressed for 90 days.

The only other options I could give are what I would do with my patients who have recurrent miscarriages (which is what you have even if it is a chemical pregnancy). Studies have shown the benefit of these meds and it is standard of practice to use these with recurrent miscarriages.

I would add: aspirin 81 mg per day, Medrol 15 mg per day until transfer then decrease to 8 mg per day, Heparin 2000 units twice per day and CoQ10 600 mg per day, all starting with the start of the cycle (CD#2). The Aspirin and Heparin are withheld from the day of HCG trigger until the day after the retrieval. The only other option you might want to consider is genetic testing of the embryos prior to transfer, called preimplantation genetic screening (PGS). That way you will know if the embryos are normal genetically or not. The downside of using PGS is I have observed and some studies have shown a drop in pregnancy rates after this. Some of my colleagues say that if it is done by a very experienced embryologist who does lots of these procedures, the pregnancy rate does not drop.

You'll have to discuss these options with your doc. I'm afraid there are no exact answers to your dilemma. But, studies on patients with recurrent pregnancies have shown that eventually these patients are successful. So, hang in there, even if your insurance coverage expires.

Follow-Up Question #2:

Thank you so much for your thorough response. I really appreciate it.

I am only 31 years old but I do have a low AMH (only .8) so along with that and the fact that I am a low responder, my RE suspects that I may have a diminished ovarian reserve. So, unfortunately, both my husband and I seem to have issues.

Do you think that the low AMH and dimished ovarian reserve contribute to the repeat miscarriages? Or do you think it is likely a sperm issue?

Is there any way to tell who is main contributor to this issue? We are not ready to talk about donors at this point and will continue to try with our own eggs/sperm for now but in the event that we need to explore other options, it would be helpful to know if we would be more likely to succeed using donor egg or donor sperm.

My RE has given us the impression that it is more a egg issue but hasn't given us any explanation of why.

Any help with this would be hugely appreciated.

Follow Up Answer #2:

Hello Agian,

There is no way to know what the exact cause of the recurrent miscarriages is. It could be egg or sperm derived since the genetics of the embryo come from both. Considering that you are ONLY 31 years old, I would suspect that it is NOT an egg issue but there is no way to be sure.

It is definitely not related to AMH or low ovarian reserve. The AMH is a measure of follicle availability and low ovarian reserve is a description of ovarian response to stimulation.

Good Luck,

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

Can I Thicken Endometrium With Estrogen?

Question:

Dear Dr. Ramirez,

I´m 35 years old (will be 36 in Feb). I have been trying to get pregnant for 2 years (had a miscarriage a year ago). After going to a reproductive clinic, I´ve tried Clomid for 2 cycles with no success, an it really thinned up my endometrium, which usually wasn´t very thick (7-8mm). So my RE recommended to change to Menopur in the next cycle and do a IUI (My husband´s Kruger morphology is 5% - lab reference 4% all the rest is good). This current cycle (no meds) she did an sonogram on me on day 12 (my last period, which followed the Clomid treatment, was only 21 days longer and she wanted to check me for cysts). I had a 20mm follicle and several smaller ones, but my endometrium although trilaminar was only 7mm. For all I have been reading 7mm is not optimal thickness, although my doctor seems to think it´s ok and there´s no need to do anything.

So I was wondering how can I prime it before ovulation? Will taking estrogen help? Will it interfere with ovulation? What are the cycle days you normally recommend your patients to take it and what is the dosage?

Thanks for your time. I really appreciate it. C. from Brazil

Answer:

Hello C. from Brazil,

Yes, you can use estrogen in addition to the Menopur. I use it as an estrogen patch (Climara 0.2 mg per week up to 0.4 mg) or vaginal tablet (FemHRT, Estrace 1 mg up to 4 mg per day). As the follicles grow, they produce more and more estrogen so that should help as well. 7 mm is the minimum size needed, but ideally it should be 9 mms.

In terms of treatment, keep in mind that you have three problems going on. My opinion is that the more problems there are, the higher the treatment level you need to use. The problems identified are: (1) thin endometrial lining, (2) age factor (going on 36yo) and (3) severe male factor. Because of the age and SEVERE male factor, I would advise IVF with ICSI as the treatment of choice. The sperm may not have the ability to fertilize the egg naturally and so ICSI is required. This can only be done with IVF. IVF is also the only treatment that helps to increase pregnancy rates related to age, which is an egg problem, by increasing the number of eggs available to fertilize.

Follow-Up Question:

Thanks for answering my question, Dr. Ramirez.

When would I start taking the estradiol, cd1 and go up to ovulation? I´d like to know so I can talk to my doctor about it.

Also, now I am really concerned about the severe male factor. Is a 5% Kruger morphology that bad even if the sperm concentration is high (85 million/ml) and they show good motility (>70%)? For the IUI procedure, after swim up test and washes, can the doctor choose only the sperm that have good morphology? I´ve read that some doctors think that the Kruger method is really too strict and based on it, most males would be called fertile. What´s your opinion on that? Is there any treatment for sperm morphology (my husband is 37yo)?Thanks again for your valuable time and input! C. from Brazil

Follow-Up Answer:

Hello Again,

1. The estradiol patch or vaginal suppository would begin with CD#1 or 2.

2. If only 5% of the sperm are anatomically normal (morphology), even with an 85 Million count that means only 3.2 Million are available to actually fertilize the sperm (85 Million x 75% motility = 63.75 Million motile x 5% = 3.2 Million). This is inadequate for natural fertility. In addition, when there are sperm abnormalities, there is a high chance that there could be a defect in its ability to fertilize, and there is no test for that other than with IVF. For that reason ICSI is recommended. The embryologist will only take anatomically normal forward swimming sperm for the ICSI (if they are good embryologists).

3. I somewhat agree with the opinion regarding Kruger, but the decision has to be made based on the information that you have. Even 5% normal morphology is pretty low using Kruger.4. Unfortunately, other than ICSI there is no good treatment methods available to change morphology. There are two products that he can try, which are basically vitamins, called Proxeed and Fertility Blend. These can be purchased via the internet. He would need to use them for 3 months minimum. He can then repeat the semen analysis and see if this helps at all.

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.

Comment: Thank you again Dr. Ramirez. I wish I was still living in the US to go to your clinic :)

After 11 IUI's, Canadian Fails 1st IVF cycle: Poor Embryos, Bleeding Or Implantation Failure?

Question:

Dear Dr. Ramirez,

I'm writing to you from Toronto, Canada. Thank you in advance for your answer!

My husband and I are both 37 years old. I was diagnosed with mild PCOS due to the shape of my ovary (pearl-like follicles) and irregular cycle (28-36 days), and as result was prescribed Metformin. My husband has low sperm count and motility. Last year I was pregnant after 5 attempts of IUI (intra uterine insemination), but unfortunately ended up in miscarriage due to chromosome abnormality. The protocols include Letrozole Femara on its own, Letrozole Femara in combination with Gonal-f and Hcg Ovidrel, and one unstimulated cycle. In all cycles, we only worked with 1 follicle. My husband's sperm ranged from 1-5 million after washed during those cycles. During our pregnant cycle, Letrozole Femara in combination with Gonal-f and Hcg Ovidrel were used, his sperm was 1.6 million after washed.

Three months after the miscarriage we tried again, with 6 rounds of IUI with similar protocols as before, but also include doubling Letrozole Femara with Gonal-f and Orgalutron, as well as Gonal-f injection only but none resulted in pregnancy. With the exception of 1 cycle where we worked with 2 follicles, the rest we only worked with 1 follicle. My husband's sperm ranged from 1-7 million after washed during those cycles.

Recently we went through an unsuccessful round of IVF-ICSI (in vitro fertilization with intra cytoplasmic sperm injection), with 5 days transfer. Protocols include Gonal-f, Repronex, Orgalutron, and Hcg Ovidrel. I was also put on a birth control pill the cycle prior to IVF cycle, and had an endometrium biopsy during the luteal phase of the birth control cycle. Post retrieval include antibiotics and vaginal natural progesterone 100mg in the morning and 200mg in the evening. Post transfer include vaginal natural progesterone 200mg in the morning and 200mg in the evening, and 81 mg aspirin daily.15 eggs were retrieved with 11 matured. 3 were IVF and 8 were ICSI. 1 out of the 3 IVF fertilized, and 4 out of the 8 ICSI fertilized. Since more than 3 eggs fertilized, the clinic's policy is to do 5 days transfer. By day 3 the quality of the 5 embryos were as follows: 10-12 cells grade 2 (good), 8 cells grade 1 (excellent), 8 cells grade 1 (excellent), 8 cells grade 2 (good), and 6 cells grade 2 (good).Unfortunately only 1 of the 8 cells (ICSI) turned into a blastocyst (with quality "not bad" according to my doctor).

The day 5 transfer include the only blastocyst we have and the 10-12 cells embryo. We ended up having no embryos to freeze. I started bleeding 7 days after the transfer.

Sorry for the long background story, my questions are as follows:

What should we do to ensure successful IVF next time? Failing the IVF, do I have an implantation problem?

What could have been done to prevent the early bleeding, could the progesterone injection prevent it? I didn't seem to have luteal phase defect in the past since my period normally come 14-16 days after ovulation.

What would have caused the poor embryo development after day 3? My doctor mentioned about possible sperm DNA fragmentation issue although this still need to be tested. Are there any other tests we should do?

What could have caused sperm DNA fragmentation, my husband doesn't smoke or drink, or exposed to any chemical environment in his day to day.

What protocol would you suggest for an IUI? Just want to mention that I didn't respond well to clomid and therefore my doctor prescribed letrozole. Why did IUI work for us last year and the last 6 attempts didn't? Also, I started taking Chinese herbs subsequent to miscarriage, therefore for the first 5 attempts out of the 6 IUI attempts I was also taking Chinese herbs at the same time, would that be why the IUI's failed?

I very much appreciate your time and help.Yours sincerely, E. from Canada

Answer:

Hello E. from Canada,

Thank you for all the information, it helps a great deal. Let me get to your questions directly.

1. Unfortunately, I don't comment on specific protocols because each doctor, clinic and country use different protocols. There is no right one or wrong one. These variations will often determine pregnancy success, however, and is the reason why some clinics are more successful than others. So, despite what I might advise you as to protocols, inevitably it will be your doctor's opinion, based on his training, knowledge and experience, that determines what protocols you use. Given that, it looks like you stimulated well, had a good number of eggs and embryos formed. The only changes I might suggest, which you have control over is (1) ICSI ALL eggs to allow for maximum fertilization and embryo number, (2) DO NOT PROGRESS TO BLASTOCYST CULTURE without at least 5 8-cell grade 1 or 2 embryos.There is an inherent attrition rate from day#3 embryos to blastocyst that may have nothing to do with inherent embryo quality. Based on preimplantation genetic testing data, sometimes even genetically normal and healthy embryos may not make it to blastocyst. Keep in mind that blastocyst culturing is still in its early development stages and not perfect. If you don't have enough embryos to lose, don't do it.

2. The bleeding after embryo transfer is very very common. I would refer you to my blog where that particular topic is the most often viewed. There is more information to this than I can give in this forum. Basically, however, it is not clear why or where this bleeding is from and how to prevent it. The good thing is that in many, if not most cases, it is of no consequence.

3. As mentioned above, the lack of embryo development does not necessarily have to be due to poor embryo quality. But, embryo quality can certainly affect the ability of an embryo to develop to blastocyst. The sperm fragmentation part . . . I'm not sure I would agree with that. Your age affects egg quality and therefore embryo quality more significantly.

4. Unknown what causes sperm fragmentation.

5. If you were going to return to IUI (which is an option but you have to consider that you will be lowering your chances of pregnancy) I would probably go to injectables only stimulation and not a combination protocol. The goal would be for you to have three to four ovulatory sized follicles (n0t one like you have been having), which will increase your chances of a successful pregnancy. The fact that you have gotten pregnant in the past is an indication that your reproductive system works but you have to overcome the sperm factors and the age factor. For these two, I would probably recommend IVF.

I would caution against adding herbal regimens. These are just un-purified pharmaceuticals. They could certainly have adverse affects.

Follow-Up Question:

Thank you so much for your reply.

In reading your blog on early bleeding, I mentioned to my doctor about using injectable progesterone. She wasn't on board and she still recommends vaginal progesterone. She explained that based on numerous researches, the vaginal progesterone is as effective as injectable, and the injectable create much discomfort. Instead for the next IVF, she will add estrogen patch. Should I insist on the injectable, I'm worried that I won't have enough progesterone support for implantation. Is it possible that's what might have caused the early period bleeding in my last IVF (7 days post 5 days transfer)?

Lastly, could the miscarriage that happened last year after IUI was also caused by lack of progesterone? That cycle I was only prescribed 100mg vaginal progesterone daily. However there was no bleeding whatsoever and after the fetal heartbeat stopped at 2.5 months pregnancy, I had a D&C done.

We will be doing another IVF 2 months later, in these 2 months, 1st month will be natural cycle and the 2nd month will be birth control cycle. Will doing the next IVF this early affect the eggs quality (the quality will be worse) and therefore reduce the pregnancy chance? Best regards, E.

Follow Up Answer:

Hello Again, Your doctor is correct in that studies have shown that vaginal progesterone is just as effective as injectable, and doesn't have the discomfort of the injection (Injectable progesterone has to be given intramuscularly). Injectable progesterone is still the gold standard, however, and if that is the form that you want, I don't see why your doctor can't change. But these kinds of things are what make each doctor different. Extra progesterone does not hurt, so why not? You could continue to argue with her but it sounds like she has her preferred way and will stand by it. The estrogen is a different hormone. I don't see any benefit to that for the bleeding but I certainly supplement with estrogen in my protocols.

Remember, I said that you cannot compare protocols because there is no one way, right way or wrong way. Protocols differ between doctors and clinics and that is okay.In the IUI pregnancy, which found a heart beat, progesterone was definitely not the cause. The lack of progesterone will result in very early pregnancy loss. Way before the placenta develops to produce its own progesterone. After that point, losses are usually due to abnormal pregnancies or fetal development.

The answer to your last question is NO. One can do an IVF cycle as quickly as every other month. Each cycle is different and unique and the eggs retrieved are unique. They can be good eggs or bad eggs, which is already predetermined prior to the IVF cycle depending on the state that the egg is in prior to stimulation.

Good Luck,

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 Yr Old Austrian Doing 2nd IVF: Use PICSI Or "Embryo Glue"? Antibiotics OK?

QUESTION:

Dear Dr. Ramirez, my name is J. from Austria. I am 40 years old, have a failed 1.IVF (in vitro fertilization) this year (6 eggs, 4 fertilized, only 2 were transferred, because the other 2 arrested development before the transfer) , FSH of 10.6 mIU/mL, AMH of 0.8 ng/mL. My husband has anti-sperm antibody. So, we used ICSI (intra cytoplasmic sperm injection). I want to try the 2.IVF.

An IVF-clinic in Austria offers PICSI or "embryo glue". Are PICSI and embryo glue useful? They also use Prednisolon 5mg to avoid immune system reaction and Aspirin 100 and Lovenox 40 to to make blood more liquid/avoid congestion problem during embryo implantation. Are Prednisolon, Aspirin and Lovenox really helpful? All of these things I did not have at my last IVF.

Do you think that antibiotic taken before egg collection is recommendable? Thank you for your time. Best wishes! J.

ANSWER:

Hello J. from Austria,

Failing the first IVF is not that uncommon. The chances of pregnancy in the first try is 60% That means that 40% have to try more than once. That is because IVF is not a perfect technology. It mimics the natural cycle. There are 9 steps the body goes through to achieve a pregnancy. IVF accomplishes 7 of those 9 steps. The problem is that the last two steps are still natural steps and despite the best embryos and circumstances, it does not always occur.

I would not recommend PICSI or embryo glue. Embryo glue is a total fallacy and has never been proven to help. Implantation is an endometrial lining process, NOT the embryo just attaching to the wall. I do use aspirin, Lovenox and Prednisolone in my patients. They do help. I recommend low dose aspirin 81mg, Lovenox 40 is fine, and Prednisolone (Medrol) 16 mg then decreased to 8 mg after the transfer. Antibiotic should not be given prior to the egg collection but is started on the day of the egg collection.

You have two very big problems: your age and your decreased ovarian function. Age affects the quality of the eggs. The elevated FSH, which is an indication of ovarian function, shows that the ovaries will not stimulate well and so you won't get a lot of eggs. The only way to overcome the age factor is to get a lot of eggs in the hope that a good egg will be found. Because of this, it may take you multiple IVF attempts. You have to be persistent. There is nothing that can reverse the age factor.

Good Luck,

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.

37 Yr Old Failed Two IVF Cycles, Has Frozen Embies And Husband With Slow Swimmers: What Would You Suggest?

Question:

I just failed my second IVF (in vitro fertilization) procedure. I am 37 years old living in the Bay Area. My husband has slow swimmers and not great morphology either. We used ICSI (intra cytoplasmic sperm injection) with both IVF procedures.

The first cycle I had 8 eggs, 6 fertilized and only two made it for transfer. The second cycle I had nine retrieved, 8 fertilized and we transferred two embryos on day 3, one an 8 cell and one a nine cell. We were able to freeze 3 embryos, not of as high quality. I believe the frozen embryos are 5 and 6 cells. I am planning to use the frozen embryos, but it seems like a lost cause as the quality of the embryos are not as good as the fresh ones that were transferred. I am doing acupuncture treatments as well.

Any advice would be most helpful. L. from San Francisco, California

Answer:

Hello L. from the U.S.,

I am sorry to hear of your failures, but IVF is certainly the best treatment for you based on your husband's problem and your age.

Without reviewing your IVF records, I cannot give you any specific information regarding your cycles or chances. Keep in mind that each IVF center uses different protocols and methods and pregnancy rates vary. For example, my pregnancy rate in your age group with ICSI is 56% per attempt with 41% continuing pregnancies. Pregnancy rates are very dependent on the stimulation, how many mature eggs are retrieved, embryo development and transfer technique. In addition, in your age group, having failed one IVF cycle already, I would have placed back all four embryos, even though the lesser celled ones were not as good quality. There is no utility to freezing them, and the prognosis with those embryos is not good as you already know. The success rate of a frozen embryo transfer cycles with good embryos is approximately 30%. Your best chance, once you have tried with the frozens if you choose, is to keep trying with fresh embryos.

In my protocol, I would probably place you at the max stimulation protocol, add low dose aspirin, low dose heparin, medrol and increased progesterone with the next cycle. Acupuncture certainly does not hurt and I would recommend that you continue it. On a side note, when my wife & I went through IVF she was 37 like you. We also did ICSI. She had 14 eggs retrieved, eight fertilized, and we ended up with one nine cell, one eight cell and the other two 5 cell. After conferring with her RE, (she was under the care of my colleague at the time) we decided to transfer all four. She became pregnant with a singleton, our daughter, who is now a healthy young teenager (her baby picture is on the Doctor's Background page of my blog). Needless to say, we did not regret our decision :)

Good Luck on your journey, I will keep my fingers crossed for you both!

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.K. Patient Concerned About ICSI And Husband's Diabetes: Will There Be Abnormal Embryos?

Question:
Dear Dr. Ramirez,

My husband had a semen analysis result and he had Moderate Oligospermia and Severe Asthenospermia (only 4% normal progressive). It has been suggested that we would require ICSI IVF, however my husband also has Type 1 diabetes. I have read that his sperm cells might have DNA damage and to use such sperm in ICSI could result in an unhealthy child prone to cancer. None of the professionals I have spoken to in this early stage have made any reference to the implications of my husband being diabetic and it is causing me concern.

I was hoping that you could clarify how sperm are tested for DNA damage and if it could be used in conjunction with ICSI. Also, does non-ICSI IVF avoid the risks of DNA damaged sperm cells? Would they be filtered out by natural processes? Thanks, L. from the U.K.

Answer:

Hello L. from the U.K.,

Sperm can only undergo DNA testing apart from IVF/ICSI because the sperm tested are essentially destroyed. There is not method to test the sperm prior to ICSI at the time of IVF. There is also no way to test the resultant embryos from DNA damage, but testing for genetics is possible.

There have been some studies, mainly out of Europe and using small homogeneous numbers (homogeneous meaning that everyone tested was of the same racial type such as Sweden), that showed the possibility of fetal abnormalities with ICSI. However, that has been unproven and IVF with ICSI has been around for almost 20 years. In the U.S., where the population is more diverse, studies have not shown any type of abnormalities, so the tests that were done previously in Europe might have some type of population/genetic weakness.

The fact that your husband has diabetes might explain why his semen analysis was abnormal (due to reduced blood flow in the testicles). This should not affect the embryos formed with ICSI, however. In general, the embryologist performing ICSI chooses the healthiest swimming and formed sperm for injection. There should be plenty to choose from. The embryos that might be abnormal generally do not progress, and therefore are not implanted.

Hope this helps to set your mind at ease!

Good Luck,

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.

Comment: Thank you for your response. It has really put my mind at ease. It is very difficult to find a small amount of information that could have a massive impact on your children and it not seeming to be acknowledged. Regards, L.

TTC For Seven Years & Dealing With Male Factor Infertility: Do We Do IUI or IVF?

Question:

My hubby and I have been trying to conceive for 7 yrs. One specialist told us only IVF (in vitro fertilization)would work, but a second opinion told us IUI (intra uterine insemination) would work.

He has a count of 9mill and motility of 60%. I'm perfectly fine, my eggs and tubes are good all blood work came back good, and I have conceived in the past and have a son.What are our chances with conceiving using IUI and how many attempts do you think will be needed? Any additional advice would be greatly appreciated. Thanks, S. from the U.S.

Answer:

Hello S. from the U.S.,

If you are under the age of 35 years old, then I think that IUI would be an option for you. The sperm findings are abnormal, but there is a small chance. Your chances of pregnancy under the age of 35 would be 20-24% per cycle, and I would not recommend more than 4 attempts. Your best option is IVF with ICSI (intra cytoplasmic sperm injection). In general, if the count is less than 10 million, ICSI/IVF is the recommendation. You have to bear in mind that only 60% of the 9 million are sperm that can fertilize the egg (3.6 million). That is way lower than the normal required for natural pregnancy (20 million is required).

In most cases where the semen analysis is abnormal, that is an indication that there is a problem with sperm function. After all, it only takes one good sperm to achieve fertilization but for some reason, studies have shown that if there is a severe abnormality in the semen analysis, the sperm have difficulty or lack the ability to fertilize the egg. That is how & why ICSI was developed (see my website for further explanation http://bit.ly/9AdrJc ) . So far, over 10,000 babies have been born with this technique from men who were otherwise considered hopelessly sterile, whose sperm are weak or too few to effectively fertilize an egg. These ICSI/IVF babies have long been proven to be physically, mentally and genetically completely normal, no matter how poor the sperm of the father. If I were your doc, I would have recommended IVF/ICSI as your best treatment option, but would allow a trial of IUI if that is what you wanted to do.

Good Luck,

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.

Prometrium Vs. Endometrim For Luteal Phase Support In IVF

Question:

Dear Dr. Ramirez,

I've written to you before about luteal phase bleeding. We've tried 3 IUI's, but my husband's morphology has been consistently 0%, so we are moving on to IVF with ICSI.

My RE has me on a long protocol (BCP, Synarel, Puregon, Repronex). My main concern is luteal phase support. My RE plans to have me on 200mg of Prometrium PV TID starting the evening of retrieval... During my last natural cycle I tried this dose of Prometrium and I still had some breakthrough bleeding (but not everyday). Do you think that this is sufficient luteal phase support for someone with a history of luteal bleeding? My RE is doing a hysteroscopy next week to rule out other causes.

Thank-you for your time, L. from Canada

29yo, secondary infertility

Answer:

Hello L. from Canada,

The dosage of prometrium that your doctor has prescribed is certainly adequate for luteal phase support but is not the mainstay with IVF treatments. The gold standard is injectable progesterone 50 mg per day starting on the day of the retrieval. The alternatives that have been studied with IVF are Endometrin 100 mg vaginally three times per day or Crinone 8%/Prochieve 8% vaginally each morning. I double up and use the progesterone injection and the Endometrin or Crinone together to make sure that I have adequate progesterone coverage. So, prometrium can be used but is not the medication of choice with IVF. It is the cheapest alternative however.

Good Luck,

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.

Comment: Thank-you Dr. Ramirez! My RE has given me the option of using Endometrin (just recently approved in Canada) so I will use your advice.

Male Factor Infertility -- IVF Cycle FET Positive But Ended With Miscarriage: Should I Seek A Second Opinion?

Question:

Dr. Ramirez,

My husband and I are a 29yo healthy couple with male factor infertility. Motility is less than 1%, morphology is about 25-30%, and count is pretty low-normal. There are no female issues. We have done 2 IVF/ICSI cycles and one FET (frozen embryo transfer). The first IVF (in vitro fertilization) cycle, I was mildly hyperstimmed. The egg quality wasn't great, and we had about a 50% fertilization rate. We transferred 2 grade A embryos that did not result in pregnancy. No embryos made it to day 5. IVF #2 was much better and had an 80% fertilization rate. 2 day-3 grade A embryos were transferred, but there was no implantation. There were 2 day-6 blasts that were frozen. Both were starting to hatch upon thawing, and the FET resulted in a singleton pregnancy with a heartbeat at about 7 weeks. Unfortunately, I miscarried (no heartbeat) at 8 weeks.

My question to you is when should I seek a second opinion? We had planned on obtaining a 2nd opinion if the FET was unsuccessful, but we feel like technically it was successful. We like the place we go to right now and feel that they are familiar with us. We are planning to do IVF #3 in the near future and are torn as to whether we should stay here or move on. If we stay with the current practice, we will not be changing the protocol since it was successful last time. Although it has been suggested, we are not ready to use donor sperm since we were able to grow 2 blasts and achieve a pregnancy. We are located in Missouri.

Thanks in advance for your time.

Answer:

Hello L. from Missouri,

I agree with your statement that technically the FET was successful. In fact, the FET cycle WAS successful. Remember, IVF can only give you the opportunity to become pregnant. It cannot MAKE you pregnant because the last two steps in the natural process, embryo hatching and implantation, are NATURAL steps and we don't have the technology to make that happen. So, the fact that an embryo did those two steps and the pregnancy went to 7 weeks is a success. And, it is a very good sign because it now shows that what you are doing can work!

I would not give up on that clinic yet. In fact, pregnancy rates with FET are lower than fresh cycles, so a success with an FET is good. They deserve the credit. Now that they have stimulated you twice, know how you react, etc., they are hopefully in a good position to build on that the next cycle. You have to give them some credit for that.

Overall, I would hang in there. You've proven that it can work. Whether or not the pregnancy continues is solely and completely dependent on the embryo. It was probably an abnormal embryo. Now, you just need to get a good one there and you'll go all the way. Don't look back, just look forward. You should now be more encouraged than before because you know that it can work. It is just a matter of time!

On a personal note, I have a patient that I was able to get pregnant on her first try at the age of 36 and she had a beautiful child. She just came back to me for her second child at 39 (worse chances statistically) and became pregnant again, but it was an abnormal pregnancy and ended in a miscarriage. I found out today, that she is planning to transfer to another clinic because they have a "special" research program going on that gives patients a significant discount. You can't believe how heart broken and how I feel rejected by this. I put my heart and soul into my patients, and they get the best care that they can receive. I know that logically the cost is a significant issue, and this is what is driving the patient, but having gotten so close to a success, when we have been successful before, is difficult for me. That is what your clinic will think too. They'll ask themselves, "why is she leaving when we were successful under less odds?"

Good Luck,

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.

Twitter with me at @montereybayivf, and follow me on Facebook at http://bit.ly/9Iw9oV

Comment: Dr. Ramirez clearly stated his opinion and seemed to have genuine answers. I appreciate his advice and his providing this service

Husband Has Prostate Cancer & Has Banked Sperm: How Many "Straws" Of Sperm Are Needed For IVF?

Question:

My husband has prostate cancer and was referred for sperm banking. He's ready to start hormone treatment but the lab techs don't know if he's stored enough sperm. They said to ask our doctor, but as we're not under a fertillity specialist yet no one seems to know.

He has 43 or 48 straws stored from 3 banks (can't remember which they said). Is this enough? How many cycles of IVF might this equate to? I think motility was lower than average.

Thanks. S. From Germany

Answer:

Hello S. from Germany,

Only one "straw" of sperm is required per IVF cycle, and I would doubt that you would need to do IVF 43-48 times. It is safe to say you have banked enough sperm.

Sperm is usually washed and frozen in alloquats of 0.3-0.5 ml each. I presume that is what your sperm bank did. With that amount, you will have to do ICSI with your IVF cycle and so you would only need enough sperm for the number of eggs that are retrieved.

Good Luck to you and your husband,

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.

Husband Has Severe Varicocele: Surgery or IVF?

Question:

My husband has a severe varicocele on the left. The sperm count is 0.8 million in total and has 5% motility after 1 hour. What should be our first option: should we do varicocele repair first or should we go for IVF/ICSI?

Thank you for your help in advance. S. from Illinois.

Answer:

Hello S. from Illinois,

The severely decreased sperm count is probably not from the varicocele but other factors. Several studies have shown that removing the varicocele make little difference, and so nowadays it is not recommended. Many Urologists will recommend it and do the procedure because that is the only treatment they can offer. I think most infertility centers will recommend proceeding directly to IVF/ICSI. That is what I recommend. Besides, if your husband goes through this surgery and the semen analysis is still abnormal, you will still have to go to IVF with ICSI.

Why not go to your infertility clinic directly and get pregnant? :)

Good Luck,

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.

Young PCO Austrian Had 5 IVF Cycles Over 3 Years And Is Ready To Give Up - Short Protocol, CGH Advised & Keep Trying!

Dear Dr. Ramirez,

Thanks for taking the time to do this, I have read several of your previous answers on the website and I am looking forward to hear your thoughts on our case. I am writing from Austria. Both my husband and I are 30, we have been doing IVF/ICSI for the past 3 years (5 cycles) with no success. My husband has the CF gene and no vas deferens (0 count). Everything is fine with me (blood work, hormones, etc). I had a laparoscopy/hysteroscopy in 2006 (prior to the treatments) where an endometrial cyst was removed from one ovary, as well as one polyp from the uterus and some adhesions from the tubes. I have been getting continuously checked since then and my uterus, ovaries are clear from anything. My husband has had 3 TESE procedures, and good looking sperm was found each time and lots of it has been frozen.

We had 2 treatments in 2007, 1 in 2008, and 2 in 2009. In the first cycle (with fresh sperm) I had 14 eggs, 3 fertilized, and 2 grade A embryos were transferred. In my second and 3rd cycle I had 20 eggs (different protocols used in each of the treatments) and none fertilized. I hyperstimulated severely in cycle # 2 and ended up in the hospital. I was told we had an egg issue and to try with donor eggs. We took a year off to think about it and switched clinics. In 2009, cycle # 4, we had 15 eggs (frozen sperm), 3 fertilized and 2 grade A embryos were transferred on day 3. In cycle #5, we had 15 eggs again (frozen sperm), 7 fertilized, and we had 2 morulas transferred. We have a lot of trust in our doctor and clinic used for the past 2 treatments, and have a great relationship. The clinic is a stat of the art building with all new technology. This doctor does not think I have egg quality issues since I had good embryos (although very few of them) in the last two cycles, and thinks we should keep trying. However, we know it is not normal that within our age group we have not succeeded yet. It is hard to not think that there is something wrong with us. I stimulate very well in terms of numbers, and the protocol has been decreased (amount of drugs) with each treatment (always yielding a high number of eggs). We have tried acupuncture, yoga, bed rest, no bed rest, and all kinds of things. We do have a possibility to try one treatment in the US (due to the expenses), but are not sure of what we should do.

Any thoughts would be appreciated. What do you think of my egg quality issue? Would a US clinic suggest donor eggs? I would really like to try with mine...Best regards from Austria.

ANSWER:

Hello S. from Austria,

Based on the history you have given me, it sounds like you may be a PCO-type ovarian stimulator. That is why you have so many eggs, and had hyperstimulation syndrome. The good part of that is that you yield lots of eggs. There have been some studies that show a decrease pregnancy rate in PCO patients, however, and it is thought that it is because they stimulate too much. This leads to unequal maturation of the eggs within. Certainly, you seem to have had good quality (albeit external quality) embryos in the latter two cycles. At your age, I would have expected a pregnancy, easily. One concern is whether the sperm is contributing to poor embryos (again internal quality/genetically), because of your husband's CF gene. The embryo could still look good but be genetically abnormal. The only way to know this is to do preimplantation genetic screening, preferably by polar body biopsy and CGH, to verify that only normal embryos are transferred. CGH, or "comparitive genomic hybridization" is a genetic test that analyzes the chromosomal integrity of an egg or embryo. In IVF, it is ideally done in women under the age of 39 who have more than 6 healthy embryos after fertilization. They can be her own or donor eggs.

I would not recommend that you give up yet. If you give up, you certainly will fail. Since your ovary stimulates so well, and you are young, I think your chances of pregnancy are still high. The alternative to the above genetic testing on the embryos, would be to go to donor sperm, rather that donor eggs, in order to eliminate that paternal genetic factor. I know that you husband would probably prefer a genetic child, however, so in that case, you just have to keep trying.

If you came to me or any other clinic in the U.S., I don't think we would be ready to give up with your eggs. I think we would continue to encourage you to keep trying with your own eggs. I recently had a patient, similar to you that seemed to have poor embryo quality in another clinic. They did three IVF cycles there and then were recommended to use donor eggs. Fortunately, her husband got transferred to my locale and they came to me for consultation. I encouraged them to try at least one more time with her own eggs, again since her ovaries stimulated well. They decided to go with my recommendation and in their first attempt, became pregnant.

Follow-Up Question:

Thank you Dr. Ramirez for your answer.

In the meantime, I just had a hysteroscopy 3 days ago and a polyp removed from the uterine wall, this polyp was not showing up on ultrasounds. Could you please elaborate on why you think I have PCO? I do ovulate every month, no diabetes issues, no acne, no absence of menstruation, none of the signs I have read are present in me, but since it is the first time I hear that, please explain me how I could have it and how does it affect stimulation? How is it better to deal with it?

I forgot to mention that in the last two treatments (with 2 embryos/morulas transferred each time) we did polar biopsy of the eggs and only the 2 perfect/healthy ones were transferred each time, still no success. My doctor recommends that we continue to do this polar biopsy and we will. What kind of stimulation would you recommend for me? What could have caused this polyp I just had removed? Could it be the same stimulation drugs (estrogen), which is given to me as part of the treatments that made my uterine tissue grown into a polyp? (it was a long, flat polyp, not the regular ones that can be seen by ultrasound).

With regards to the couple you mention in the last paragraph, what did you do different from their 3 previous treatments that could have led to success? Is it just a matter of numbers/attempts, that we need to keep trying? The more one fails, the harder it is to believe it could happen....and I know mental power can do lots for either direction.

We might try one more treatment here (much more affordable) and then have a final treatment in the States. We are definitely not ready to give up! Thanks again!

Follow-Up Answer:

Hello Again,

There are many variations of PCO. Not all fit the classic descriptions. In your case, what makes me think that you have a PCO tendency is the fact that you overstimulated and developed hyperstimulation syndrome. I have had many patients that have surprised me in the same way. They are thin, have regular menstrual cycles, don't have any other PCO-type tendencies, yet they stimulate like a PCO patient. That is, their ovaries are very sensitive to the fertility medications. Since you don't have any of the other PCO findings, the only thing to keep in mind is that your ovaries are very sensitive to stimulation, so that the next time, a low dose protocol will be used and you don't develop hyperstimulation syndrome.

In terms of stimulation protocols, with my PCO patients I use a "step-up" protocol. Patients start at a low dose of Follistim 150IU for three days then the estradiol level is checked for response. If there is not a high response then I step up the dosage to Follistim 150IU + Menopur 75. We continue the same pattern of checking and adjusting the dosage as needed. I don't use Lupron agonist suppression (long protocol), but instead use the Antagonist Ganerelix. When the follicles are appropriate sized, I trigger with Lupron 0.5 mg instead of Ovidrel. This combination and protocol has been shown to be effective in preventing hyperstimulation syndrome.

Polyps are normal. It is very common and is due to an overgrowth of endometrial tissue. The finding is probably not significant in terms of pregnancy chances, but we prefer to remove them anyway so that they can't potentially interfere.

In terms of my couple, I used a completely different protocol than what she used previously, and some additional medications. Different clinics have different success rates because of differences in their protocols and techniques. "Failing" is when you stop trying. As long as you continue to try, you have a chance of success and that is what you have to focus on. Focus on the goal, not the pathway.

Good Luck,

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.

***See continuing follow up to this question on May 16th, 2010...