Egyptian Fails One Fresh & One Frozen IVF Cycle: Advice On How To Improve Lining Thickness

Question:

Hi, I am 28 years old, married since 3 years, trying to get pregnant since 2 years. I had ectopic pregnancy since 15 months which ended by right laparoscopic salpingectomy. Then I tried clomid for 3 cycles, HMG induction for 2 cycles and I tried fresh IVF (in vitro fertilization) with long protocol.

I took 1 amp menogone , 1 amp fostimon 75 mg, 1 amp fostimon 150 mg/d. there was 36 mature follicles , all fertilized well, then 4 good embryos were transferred on 3rd day but ended badly on 5th week by blighted ovum.

Then I tried frozen embryo transfer by thawing the embryos and let them grow to the blastocyst stage. We got 14 good blastocyst from 19 embryos, then 2 hatched blastocysts were transferred. I took estrogen valereate 6 tab/d till endometrium thickness 8cm, then progesterone supp 800 mg/ d , aspirin 75 mg/d. but again a negative BHCG on due time.

Some history:

a) semen analysis is good with no abnormal forms or motlity
b) patent left tube by hysterosalpigogram
c) history of endometriosis discovered during laparoscopic salpingectomy.
d) good hormonal profile FSH, LH, TSH, prolactin, anti-phospholipid tests

Now I am planning to repeat but I still have 12 frozen blastocysts, but I need your advise because we thawed the 3rd day embryos from the first ivf , then let them grow till the blastocyst stage , then did the transfer the last time , then refreezed them again.

My question:

I am undergoing a new frozen cycle now. I take 6 tablets oral estrogen valereate/ day, 200mg sildenafil (viagra) vaginally/ day and vitamin e, aspirin, and after the endometrium reached 8.5 mm thickness on the 10th day stimulation, it decreased on the 13th day to 6 mm although I still take the same dose with no discontinuation, sure of the expiry date.

What is your explanation please, and what can I do to prevent cancellation of the cycle? If I continued the same dose is there any hope for restoration the thickness?

Please answer me because I am frustrated and breakhearted.

N. from Egypt

Answer:

 Hello N. from Egypt,

This is a protocol question, which I do not answer because protocols can vary widely and there is not only one way to do things. That being said, there is some general information that I can provide.

First, keep in mind that you have been pregnant with IVF and so can get pregnant again. IVF only gives you the opportunity to become pregnant, it cannot make you pregnant because there are still some natural steps that must occur on their own. Studies have shown that if you have gotten pregnant in the past, your chances of getting pregnant with IVF are higher. Also keep in mind that, just like trying to get pregnant on your own each month, it does not always work. Sometimes it can take several attempts before it is successful.

Second, it is well documented by studies that the best way to deliver hormones for IVF is either by injection, by patches or by vaginal delivery. Oral tablets can be used vaginally (you just push them to the very back). This helps with maximum absorption of the hormone and delivery to the uterus. Oral intake has been shown to be the worst way to give hormones for IVF because most of it is lost when it passes through the liver. I personally use patches, which most US doctors use, but tablets used vaginally is also a good option.

I would not necessarily cancel the cycle, because time can be taken to develop the endometrial lining further. It is only finalized once the progesterone is started. That is what determines the timing of the transfer, which for a blastocyst, should be on the 6th day after starting the progesterone. If you have not started the progesterone yet, you can keep using an increased amount of estrogen to get the lining to 9 mms.

Good Luck,

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

"The Menopause Map": A New Tool To Help Women Who Suffer From Menopause

Although I focus primarily on infertility in this blog, I also wish to expand on other women's issues, such as menopause. A recent article appearing on PBS online, "A New Online Tool Helps Women Track Menopause" caught my eye today. An online interactive tool has been developed by The Endocrine Society called the "Menopause Map". It was developed with the goal of aiding women who suffer from the symptoms of menopause, including hot flashes, sweating, insomnia, mood swings, fatigue, depression and vaginal dryness, among others. As a practicing gynecologist as well as an infertility specialist, I frequently treat women who come to me desperate for help with these sometimes debilitating symptoms. Hormone replacement therapy remains one of the most effective means of controlling and sometimes eliminating these symptoms. According to the guidelines set by my specialty (ACOG), a common treatment may include taking HRT commencing when symptoms begin (typically when women are in their late 40's early 50's) and continuing on this regimen for as short a period as possible.

In my mind, the benefits from HRT are many and worth considering. I have had years of feedback from my patients saying how it has helped them tremendously, not only with their mood swings, but also with their energy levels and their intimacy with their partner. I also believe that Estrogen, the main hormone in HRT, is essential to a woman's body.  There are benefits beyond the symptoms of menopause such as a reduction of heart disease, osteoporosis, vaginal dryness and thinning, emotional ability and Alzheimer's. Women are the most healthy during the years that they have lots of Estrogen aboard.  It only makes sense that they will remain healthier if they continue to have estrogen in my belief and experience.  So, despite ACOG's recommendations, I explain to my patients that there is no study or data that says "when" HRT is to be stopped and because of increasing longevity, they should continue it indefinitely. 

The Endocrine Society has released the results of a poll they recently conducted revealing that an astounding 72% of women do not seek assistance or therapy for their menopausal symptoms! One big reason for this lies in the repercussions of the Women's Health Initiative study of 2002. The NIH sponsored Women's Health Initiative (WHI) was done to evaluate the impact of HRT on heart disease but instead came out  condemming the use of hormone replacement therapy for women who are suffering from menopause because of a statistically insignificant increase in breast cancer, only in women who had taken a combined estrogen-progesterone drug called Prempro.

The WHI has since been refuted many, many times and shown to have been flawed in part by focusing on women in their 60's and 70's, long after menopause has ceased to be an issue. The beneficial aspects of HRT for women in their 50's were not considered as part of the study. According to Dr. Cynthia Stuenkel, an endocrinologist who specializes in menopause and one of the creators of this new tool, "Our current thinking is that for healthy women in their 50s -- women who have not had breast cancer or a history of blood clots -- and have been experiencing the symptoms of menopause for less than 10 years, hormone therapy can be very effective for symptom relief and overall is quite safe."  Other recent studies have in fact shown beneficial effects to heart disease and other long term problems, mentioned above, if the replacement starts within 5 years of the onset of menopausal symptoms.  Patients not requiring the progesterone component, because they don't have a uterus, and who take only estrogen, have been shown to have a decrease in breast cancer incidence.  The media seems to focus on an anti-HRT program when in fact, medically, the many benefits HRT provides continues to be proven with newer and newer studies.


I am pleased to see PBS Newshour bucking the trend and instead, promoting awareness in this very important issue to women both in the United States and all over the world.

Young Canadian With Hydrosalpinx And Endometriosis Complicating IVF Cycle

Question:
Hello Dr. Ramirez,

I am 27 years old and last year stage 4 endometriosis was discovered and I had 2 large cysts removed from both my ovaries, one was 12cm and and the other was 5cm. My left ovary is almost completely gone and both my tubes are not functional. My hormones as far as I know it are normal and my antral follicle count is 8.

My first IVF with ICSI (my husband has blood in his semen due to unknown reasons) was last November with an antagonist estrogen priming protocol. I had 10 eggs retrieved, 5 mature, 3 fertilized, and ended up with 1 good quality day 3 embryo to put back. The cycle ended with a chemical pregnancy. I was on 400 puregon and 75 repronex.

I did my second IVF cycle with ICSI this month on the exact same protocol. They saw 11 follicles before my retrieval and 6 was retrieved, but none fertilized at all. My RE said that egg quality was very poor and may not suggest another cycle for me.

My questions are:
1. Is my endo the cause of bad eggs?

2. Will changing the protocol help better egg quality?

3. They noticed 2 small cysts on a recent ultrasound, and also a hydrosalphinx on the left. Would it help to have another surgery?

4. Do I have any hope in becoming pregnant with my own eggs?
Thank you so much for your information!

Thanks... A. from Canada

Answer:

Hello A. from Canada (Ontario),

I don't think that endometriosis is causing the egg problem, but that is certainly debatable. There are some studies showing better results if the IVF cycle is preceded by 3 months of Lupron depot in stage 3 and 4 endometriosis. There is definitely an effect if there are endometriomas that are penetrated at the time of egg retrieval. These endometriosis debris has been found to be detrimental to egg quality. Because of that, I am very careful to avoid the endometrioma at the time of retrieval, or if it is penetrated, I replace the needle and tubing before continuing.

In terms of protocol, you certainly seem to be stimulating well, which is the goal of the protocol and there are many variations that can be used. Each doctor has their own preferences. There is not one protocol that is better than another. However, I would probably use a stronger protocol if you were my patient (you are currently using a 475 combination protocol# such as a 600 IU combination protocol #450 FSH + 150 FSH/LH (Menopur)). Changing the protocol will not improve egg quality, but having more eggs may help with getting more embryos to work with.

If you have a hydrosalpinx, you definitely need to have that surgically removed or excised from the uterus. Numerous studies have shown a reduction in pregnancy rates with IVF by 50% if a hydrosalpinx is present. In the U.S. it is now considered the standard of care. The cysts are not an issue.

I am always hopeful for my patients, in terms of your last question, even those that have a minimal chance because they are way too old. I see exceptions all the time and believe in miracles.You are only 27 years old. Your chances should be much much better and I am leery of the results you have had thus far. Frankly, it doesn't make sense to me, but I would have to review your medical records to see what might be going on. At your age, you should not have an egg quality issue and fertilization should be at least 60%. In my clinic, your age group has a 76% chance of pregnancy per attempt. That makes me worried about the quality of the clinic you are going to. You may want to seek a second opinion.

Good luck and don't hesitate to keep me updated,

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.

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/

IVF Protocol For High FSH

Question:

Dear Dr. Ramirez,
I am 39 years old in 2 weeks and about to undergo my first ivf (in vitro fertilization). I have only one fallopian tube, which an hsg has shown to be blocked, probably by adhesions (my other tube was removed due to damage from extensive adhesions - a reaction to previous surgery to remove a dermoid cyst on my left ovary).


My FSH level was 14 in March. Two weeks ago my FSH dropped to 8 and my AMH level was 7.42. An ultrasound scan and follicle count showed 9 follicles on my right ovary and 3 on my left (the ovary which the cyst was removed from).

My consultant has suggested the long protocol, as he thinks I will respond ok. I have read much about the short protocol being better for my age group, and if fsh has been high. I am anxious to get the correct protocol from the outset. What do you think my response might be, based on my levels? Do you think a short protocol would be better in my case? Many thanks, R. from the U.K.

Answer:

Hello R. from the U.K.,

The worst thing you can do is try to second guess your doctor, especially with information that you read on the internet. You are not an expert and don't have sufficient knowledge to make a proper decision. However, it is good to be educated regarding what you will be going through, and certainly, I have the knowledge to answer questions, so you can trust my input. But, given that you are not my patient, I don't have all your medical information and am not doing the procedure, the answers I give you have to be generalities and cannot be specific.

I personally don't criticize "protocol" questions because there is not one way or best way to do IVF. There are many different protocols and usually the specific protocol is based on the training and experience of your doctor. They all have the possibility to work. Some doctors stimulate less, some more, some use only pure FSh, some use mixed protocols, some use the long Lupron protocol, some use the antagonist protocol and some use the micro-dose flare protocol. There is not way to predict how any one will respond to any given protocol. But studies have shown no benefit to the micro-dose flare protocol (short protocol) in comparison to any other protocol, just as there is no study that shows that the long protocol is better than the antagonist protocol. I prefer the antagonist protocol because there are less injections in comparison to the long protocol.

Because you have had an elevated FSh level, despite it being lower more recently, you would still be considered a poor responder (or at least have the potential of being a low responder). For that reason, my preference would be to NOT inhibit your ovaries with Lupron in the stimulation phase, and only begin ovarian suppression once the lead follicles are at least 16 mms. This is the technique used in the antagonist protocol. With the long protocol, your ovaries are suppressed by the lupron starting from the previous cycles and may not respond as well. Before the antagonist protocol was developed, the micro-dose protocol was developed to reduce that suppression phase. Without criticizing your doctor's choice of protocols, my personal choice would have been different. But that is what makes Infertility doctors and clinics different and gives them different pregnancy rates.

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/

35 Year Old Responds Well To Low Dose Clomid IUI Cycle: NOT A Low Responder!

Question:

Dr. Ramirez,

My husband and I have been infertile for more than 2 years now. We have gone through a wide variety of tests. I have had a polyp removed through operative hysteroscopy and we were asked to try on our own for 3 months afterwards (unsuccessfully). I am 35 years with borderline bad FSH (around 10 on day 3). I have a low antral follicle count (usually around 7 if they can see both ovaries during the ultrasound). We have tried 1 IUI (negative for pregnancy) and I was prescribed 50 mg Clomid on days 3 - 7 for the IUI. I ovulated 3 eggs with this dose and was triggered with an HCG shot when the 3 follicles were between 1.7 - 2.0 and IUI took place approximately 24 and 48 hours after this injection.

I have 2 questions:

1. Is the fact that I developed 3 eggs on Clomid a good or bad sign? My doctor says I will likely be what he calls a poor responder to medications because of my low antral follicle count and IVF may not be more worthwhile than IUI because of this. Does the fact that I got 3 with Clomid mean I might do better with injections then he thinks or are the 2 medications so different that my response to Clomid doesn't indicate anything?

2. What is the purpose of a blood test the day of my second IUI? I have a lot of problems with all the blood work that is required for monitoring due to bad veins (day 3 plus 4 more days of blood tests/ultrasounds before my IUI). I thought when I was triggered that would be my last blood test, but I was told I needed another blood test/ultrasound the day of my second IUI (48 hours post trigger). I asked the nurse if the blood test was essential and she said yes and it is part of the cycle monitoring that all fertility clinics require it so I forced another blood test through my already bruised veins. I understand the ultrasound was to show if the follicles released, but what would the purpose of this blood test be and is it really as essential as they say it is? (I was also on progesterone suppositories 200 mg twice a day following the IUI so I don't think it was to measure progesterone since those were prescribed regardless of the blood results).

I really appreciate you providing this service and if we do decide to travel for treatment, California will be our choice. Thanks again, A. from British Columbia

Answer:

Hello A. from Canada (British Columbia),

The fact that you responded well to low dose Clomid is very, very reassuring and I completely disagree with your doctor's opinion. FSH levels and Antral counts are indirect measures of ovarian response but not absolute. In other words, studies have shown that these numbers can vary from cycle to cycle and so the response can vary from cycle to cycle. Besides, an FSH level of 10 is not necessarily that bad. Sure, we prefer the level to be 7 or less, but it is much better than a level of 12 or greater, which I often see. Even these patients do respond to stimulation albeit only a few follicles.

So, considering that you responded well to Clomid, low dose Clomid no less, is more of an indication that you are NOT a low responder. A low responder would have only one follicle despite high dose (250mg) of Clomid. One thing these two levels do tell you, however, is that you may not have as much time to work with as you would have thought. You will need to use your time wisely and strongly consider a more aggressive approach (such as IVF). I would not recommend more than 4 IUI attempts. If that does no work (which is the number where most patients will be pregnant), then you have to go to IVF.

In terms of your second question regarding the blood test, I have absolutely no idea why it is being done. It must be something specific to your doctor. You will have to ask him. Now, I do an ultrasound after each IUI so that I can see if ovulation has occurred. That way I know that the timing was good. Since I don't know what test they did or what it could be, I can't try to explain why they would do it. It can't or shouldn't be a progesterone level, which is what we often use to determine if ovulation occurred, but that test is not valid if progesterone supplementation is given.

Thank you for your question and consideration...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.