Tuesday, September 29, 2009

Multiple Failed IVF cycles


Question:
Dear Dr Ramirez

Welcome back from your holiday ! I’m Australian but am writing to you from sunny Singapore, one degree north of the equator, which is where I work and where I am now having IVF (after 6 failed cycles in Australia).

I had metastatic cancer (melanoma) at 35 so had no choice but to stop trying for a baby back then, and I received the "all clear" to try again just before my 41st birthday (this would be my first/only). I tried 3 IUI cycles (because my hormone levels were apparently great) but when they failed, I went to IVF with ICSI and assisted hatching. I am now 43 and trying for what will probably be my last (or next to last) attempt. I very much want to try with my own eggs (my medical history makes me ineligible to adopt).

I wasn’t told, but have recently discovered, that I have what appears to be very high E2 levels (I’ve discovered that from the web sites I’ve visited…..my first clinic just told me I was "too old"). My D2 bloods this month were similar to every other non-stim month: FSH 6.5, LH 5.6, E2 168.8, P4 .76 and Prolactin 12.8. Those numbers have changed little since my first tracking cycle in Jan 06 and it’s common for me – at ovulation – to have E2 levels of 900-1800 on unstimulated cycles. On stimulated cycles (I’m using 250IU Puregon with Nafarelin/buserelin as downregulation) I’m getting E2 at trigger of 9000-21 000 (21000 was on a flare protocol). I get good response usually (10-17 eggs so far, with about 70% mature and about 75% of those fertilise) but apart from one chemical pregnancy, no good outcomes despite some AA grade blasts last year. I usually get mild OHSS but last cycle, it was so bad I had trouble breathing (due to the abdo swelling….it made it hard to expand my lungs).

The only other significant background I can think of is that my periods became light to non-existant (spotting only some months) after the first IVF cycle and despite the excellent efforts of my naturopath and acupuncurist who work together and work with my new clinic), they’re still really light. Even after the chemical pregnancy ended, there was no bleeding. I had some spotting as the HCG hit 500 but then as the numbers went down, nothing. I just ovulated again 2 weeks later (confirmed with a P4 blood test) and it seems to me you can hardly expect a pregnancy with minimal endometrium. I’m otherwise really healthy – normal weight, and work out 3 times a week with a personal trainer.
 
My questions are
1. If I have such high E2, why aremy periods so light ? My P4 at 14 days post transfer is usually 40 (with crinone pessaries) but is that too low in view of the high E2 ?
2. My new doctor has suggested birth control pills (Gynera: gestone + estradiol) for a month to quieten down my ovaries and then a long downreg to try and suppress the E2 level. His plan is that if E2 becomes too high, we can just freeze any embryos and transfer later but I don’t expect that to do much more than kill any embryos, so any suggestions you have for controlling the high E2 would be great. (not sure if there is a particular type of BCP/downregulation that’s better than others ?) 3. What protocol would you suggest for someone with that profile ?
Thanks for any help you can suggest. I realise we’re going through a lot in the hope of "one good egg" but I want to make sure I’ve tried everything possible before I give up. I’ve been reading your previous responses (to make sure I don’t ask something you’ve already answered !) and have been quite cheered up by your "20% chance of success" stats. That’s more than I’d expected and a little under the chance I was given of surviving 5 years from metastatic cancer, so I hope to be "queen of the small percentages" one more time ;) Thank you so much for volunteering your time for this – I guess you can tell that it’s enormously appreciated.

Warmly

Alison

Answer:
Hello Allison,

Thank you for all the information. You are certainly in a tough spot because you are trying to "beat the odds", but since your ovaries respond so well to stimulation, there is certainly hope. The major obstacle for you at this point is the age related changes to your eggs. This passage of time has rendered them quite debilitated, and therein is the problem. Finding that one good egg will be difficult and make take many more attempts. Fortunately, you provide your clinic with lots of eggs to work with and that increases your chances.

It is curious that your baseline estradiol is elevated, and certainly not normal. I am surprised your doctor has not tried to find the source of that elevation. It is not normal, and something has to be producing the estrogen. In most cases it is an ovarian cyst, but that would easily be seen by ultrasound. Ovarian tumors can do the same. That certainly needs to be followed up in an unstimulated cycle. If your doc is going to proceed anyway, I would definitely recommend suppression with the birth control pill for at least three weeks prior to the start of the cycle. That, hopefully, will suppress the estrogen and it should be under 100 at the start of the cycle. If it starts out elevated, how can the clinic know exactly what your real estradiol level is to make decisions. By the way an estradiol of 21,000 is the highest I have ever seen. I watch my patients very very carefully to prevent hyperstimulation syndrome, which is the most dangerous complication of IVF, so I have never had a patient get so high.

In term of protocol suggestions, other than the BCP, I can't think of any specific protocols for your situation except the following:
1. Your doctor might want to consider using an antagonist instead of the "long protocol" with Naferelin (a GnRH agonist) such as Ganerelix or Cetrotide. This uses less medication, and is used extensively in European protocols, but the major advantage, and the reason I use it in high stimulators, is that Lupron can be used to trigger, instead of HCG. Since Lupron has a shorter half-life, there is a significantly decreased incidence of hyperstimulation syndrome. Lupron is a GnRH agonist so it can't be used when you are already on one.
2. I would recommend post-retrieval day # 3 transfer and NOT blastocyst transfer. I am not confident that culturing to blastocyst is entirely perfected yet and your good embryos may not make it to the point. There is not change in pregnancy rates between the two transfer dates, but you lose more embryos going to blastocyst. In addition, I don't know if they allow it in Singapore, but they should put back up to 8 embryos to give you the best chances. The chance of a super-multiple (>2) is low at your age.
3. Because of your age, you are at an increased chance of miscarriage, which includes chemical pregnancies, due to spontaneous chromosomal breakages. That is part of the age factor. You'll have to be prepared for that if you use your own eggs.
4. Because you have gotten pregnant before, that is a big positive on your side. That means that if you can get a good embryo into your uterus, you have a good chance of having a successful pregnancy. That is the hard part. Instead of adoption, have you ever considered using donor eggs? Is it allowed where you are. I think that if you switch to donor eggs, and this can be done at any age because the uterus does not age, you would have an excellent chance of pregnancy. In our center the pregnancy rate is 62% per cycle with donor eggs. It would be genetically your husband's and biologically yours, since you would be pregnant, nurture it in utero and deliver the child. No one would ever dispute that it isn't your genetic child. It is a better alternative to adoption, and would give you the highest chances of success. It is an alternative that you should keep in mind.

I hope this helps,
 
Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
Monterey, California, U.S.A.

check me out on Facebook and twitter with me at @montereybayivf

Monday, September 28, 2009

Blocked Fallopian tubes and Disabled sperm?


Question:
Hi Edward,

I have two quick questions for you.....
  
The first is, how likely is it for Fallopian tubes to block for no reason? I fell pregnant November 07 but miscarried in January 08 and have been trying to fall pregnant since but to no avail. I am currently attending a fertility Clinic in ireland and despite 3 IUI's and 4 months on Clomid with a very good response to meds each time and my husbands's samples being good I have still failed to fall pregnant and was wondering could it be possible that one or both of my tubes are blocked? I had a lap and dye done but that was back in March 07 before I fell pregnant.

My second question is this, myself and my husband are now going down the IVF route - I am starting on the meds on 29th September. My husband in the past has used Viagra on occasion to help with producing samples. At the time the fertility clinic had no problem with him using Viagra but over the past few weeks I did a bit of research re the use of Viagra when trying to conceive and there are some findings just recently saying that Viagra can actually have a negative impact when trying to conceive as it can prevent the sperm from penetrating the egg successfully.....do you know if this is the case? The reason I ask is because you are based in the States and normally the States are one step ahead of Europe in terms of medical findings, research, etc. and having the most up to date info. I would hate for my husband to use Viagra to produce his sample during our IVF procedure only to find that the swimmers cannot penetrate any of the eggs. It's a very expensive procedure as you know so don't want to take any chances. Any advice greatly appreciated.

Answer:
Hello Katie from Ireland,
  
Tubes don't usually get blocked without a reason. Something has to block them. I would recommend you consider doing an HSG (hysterosalpingogram) to check them out. Sometimes a woman can develop mucous plugs in the tubes. The HSG can be used as a treatment for this and the pressure can push the plugs out, resulting in pregnancy thereafter.
 
I have not seen any research in our fertility journals stating that Viagra disables the sperm. However, if this is a concern, then you have the option of requesting that ICSI be performed to be sure that the sperm penetrate the egg, rather than doing natural fertilization where the risk is that fertilization does not occur. Most of my patients will elect this anyway, because they would hate to have a cycle fail because fertilization did not occur. ICSI is where individual sperm is taken and injected into each egg.

I hope this helps,

Sincerely,

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

for additional information check out my blog at http://womenshealthandfertility.blogspot.com/ check me out on facebook and twitter with me at @montereybayivf.

Sunday, September 27, 2009

Cystic Fibrosis Carrier and Infertility

Question:

I am a carrier of the Cystic Fibrosis gene. How does this affect my chances of becoming pregnant? I am 33 yrs old and am taking 5mg of folic acid to prepare my body. My husband and I definitely want a child, but we were for waiting at least until next year before trying. I have a very strong fear that conceiving is not going to be straight forward. Can you advise me on this issue? I have been advised to have children sooner rather than later.

Answer:
Hello Sharon,
Thank you for your question. First, I do advise sooner than later, especially after the age of 30. As you know, your fertility rate is decreasing with time. For instance, at 30, the pregnancy rate is 60% per year. At 35 it is 30% per year. You're in-between that rate. I wouldn't put it off.

In terms of your cystic fibrosis gene, it has no bearing on your pregnancy chances. It only impacts on the fetus, if and only if, your husband is also a carrier. In that case, you have a 50% chance of the fetus having cystic fibrosis, which is a fatal disease in children. If your husband is a carrier, and he should be tested if he has not, then you should undergo IVF with PGD (preimplantation genetic diagnosis) to exclude the embryos with the cystic fibrosis gene.

I hope this answers your question.

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.
Check me out on Facebook and twitter with me at @montereybayivf.

Saturday, September 19, 2009

No Menstruation

Question:

I am 26 and have two children. I am about 5'7.5" tall. My last spontaneous menses was April 6, 2005. After this, I became pregnant with my first child. After her birth, I dropped from 168 pounds (the same weight as prepregnancy, but since I stopped drinking alcohol and eating unhealthily and started walking daily, I maintained healthily) to 113 pounds in 10 months while breastfeeding and walking. I stopped breastfeeding and walking to try and gain weight to get pregnant with my second, but even after gaining 20 pounds, taking progestin and estrogen, there was no menses. After estrogen therapy plus clomid, I menstruated, took Clomid again, and got pregnant with #2. After her birth, my weight fell from 171 at her birth to 113 with breastfeeding and running. I never menstruated. She was born March 1, 2008.

Four months ago, I was prescribed the NuvaRing for amenorrhea after progestin again failed to produce a period. I have had four successful withdrawal bleeds. After this month, however, I have to stop; we cannot afford my taking it and pills make me sick.

I am currently training for a half marathon and run 50 miles per week. I am about 117 pounds now. I don't want to have more children but am concerned that after all of this time I won't be able to get my period back. I will cut back my running after my October 3 race, but what do I do to get my period back? CAN I get my period back? After gaining weight in late 2006/early 2007 there was no menses. There are no blockages or anything abnormal, though I may have mild subclinical hyperthyroidism as a byproduct of my running; my follicles are just dormant.

I want to be normal and healthy. I MISS my period, however odd that may sound to some. How can I get this back?

Answer:
Hello Bethany from the U.S.,

The problem that you have is more long-term than short term. The fact that you are not having periods is a sign that your ovaries are not functioning an therefore not ovulating. Because of that, you are NOT producing the essential female hormones, Estrogen and Progesterone. Without estrogen, you will be at long term risk for osteoporosis, heart disease, vaginal dryness and shrinkage. Once these occur, they are not reversible.

It is most likely that you have a disorder called "hypogonadotropic hypogonadism" which is a lack of hypothalamic stimulation to produce the hormones that the pituitary produces to stimulate the ovaries. The thyroid is one of those hormones that the pituitary stimulates as well. You need to see a Reproductive endocrinologist or Gynecologist to solve this problem. It is not so much that you need to have a period, that is just the monthly shedding of the uterine lining if you don't become pregnant, but the lack of hormone is worst. You need to be evaluated to make sure that you don't have some other underlying cause, other than your weight and decreased body mass.

In terms of replacing hormones, the birth control pill is the best because it has both estrogen and progesterone in it. If you can't tolerate the pill because of gastric side effects, then you can consider the patch. A progesterone only contraceptive of any type is NOT adequate. You need estrogen.

Sincerely,

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

Monterey, California, U.S.A.

Friday, September 18, 2009

Pregnancy after endometrial ablation?

Question:
Is there any possible way of conceiving after an endometrial ablation? Is there any way of repairing the uterine lining?

Answer:
Hello Leah from Canada,
 
If the endometrial ablation was performed correctly, which destroys and scars the endometrial lining/cavity, pregnancy is not possible. However, sometimes pregnancies occur where some area of the endometrium has not been ablated, which is an error in technique. In these cases, the patient will usually continue to have menstrual cycles. There is absolutely no way to repair the uterine lining. The only option would be to use a surrogate if pregnancy were desired and the ovaries were still functioning.

Sincerely,

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.

for additional information check out my blog at http://womenshealthandfertility.blogspot.com check me out on facebook and twitter with me at @montereybayivf.

Thursday, September 17, 2009

Lupron trigger instead of HCG

Question:
My RE gave me a lupron trigger instead of my usual HCG or ovidrel trigger. It concerns me because when I read about lupron it is a ovulation suppressor. Did I ovulate? I took two lupron shots 12 hrs a part. I am now on progesterone supp. and patch along with a estrogen pill 3 x daily.
 
I was on 150 gonal-f for 9 days and then 75 for day 10. I also used ganarelix starting day 5 of stim. My E2 was higher than my RE liked and he wsa worried about OHSS. It was an IUI cycle. I OHSS in 2004 when I got preg. with my twins.
  
I love my RE, but I just can not find much info on lupron trigger so I am a little concerned.

Answer:
Hello Michelle from the U.S.,
  
The Lupron trigger has been used extensively and written about extensively in Europe. It is better than HCG with hyperstimulation because it has a shorter duration, reducing the chances of developing OHSS. I use it with my PCO patients who have a tendency to hyperstimulate and are at higher risk of OHSS. As a result, I have not had a patient with OHSS in years. I only given one injection, not two. Lupron used daily or in the higher doses can certainly suppress the ovary. It works indirectly but has the same effect as the Ganerelix. In low doses, it mimics HCG and triggers ovulation. I love the Ganerelix-Lupron protocol.
 
My biggest concern with your story is why you are following an IVF protocol for an IUI cycle? You are getting stimulated way too much. With IUI, we only want up to 3 ovulatory sized follicles. If you ovulate more than that, you will be at high risk of a super-multiple pregnancy (not good). Also, if you stimulated so much that your RE would be worried about hyperstimulation then you should not be completing the cycle. It should be cancelled, again because of the high risk of a super-multiple. OHSS occurs when the Estradiol level is greater than 4000 and you have more than 20 follicles. that's way too much for an IUI cycle!!! 
 
I think you have good reason to be concerned.
  
Sincerely,
  
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.

Check me out on Facebook and twitter with me at @montereybayivf.

Wednesday, September 16, 2009

D and C or not for miscarriage.

Question:

I wrote to you several months back and took your advice on seeing a fertility specialist since I was approaching and now am 41 years of age (as of late July 2009). In mid-July I went through the pre-testing treatment, including the estrodiol day 3 levels and hsg to check for fallopian tube blockage. My estrodial was 9.6, which was ok, and my tubes were not blocked, per my doctor's review of the testing results. Well, found out that I did get pregnant just after the hsg test, and today at 8 weeks pregnant found out by ultrasound that there is no fetal heartbeat/viable pregnancy. Not sure what to do. It looks like the development stopped around week 6, and at 8 weeks my body has not registered the loss. Should I go for a DNC in a week or so or wait for a natural miscarriage. I would like to do what is best for trying to conceive as soon as possible again. Does a DNC cause extra recovery period than a natural miscarriage? I had a DNC about 3 years ago and it took me about 6 cycles to conceive at the age of 38 (which I had a beautiful girl). Now at 41 there seems to be less time, so any advice would be very appreciated. My ob/gyn told me to come to her office in a week to discuss my options - especially if I have not naturally started to miscarry in a week. Should I head back to the fertility specialist after this time and start treatment? Ultimately my question is whether a DNC has a longer recovery than a natural miscarriage? Thanks, Kim

Answer:

Hello Kim from the U.S.,
 
At this point you have three options:
 
1. Await natural miscarriage.
PROS: It is the most natural method.
CONS: It could take up to 4 weeks, it will be painful and lots of bleeding, it is unpredictable, and you may still need a D&C if all the tissue does not pass.
 
2. Medical induction of miscarriage (vaginal tablets)
PROS: Onset of miscarriage is within 24 hours, easy to use medication
CONS: Just like natural miscarriages except no waiting.
 
3. D&C (Dilation and Curettage)
PROS: Over quickly, scheduled procedure, done under anesthesia so you won't feel anything
CONS: Surgical procedure with surgical risks (infection, perforation, bleeding, anesthesia)
 
With all miscarriages, it will take time for the ovaries to reset so that you can get pregnant. This will take 6-8 weeks. Because of the inflammation caused by the D&C, you need to wait at least 6 weeks.
 
Because of your age, you are at increased risk of miscarriages due to spontaneous chromosomal abnormalities, and, yes, you time is running short. You might want to consider a more aggressive treatment method such as IVF, rather than the natural methods you are using now. IVf increases your chances of a successful pregnancy better than any other method. Otherwise, be prepared for more miscarriages before you are finally successful. Your infertility specialist should have explained exactly what your chances for pregnancy are with each method. If not, then ask.
 
I hope this helps,
 
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.

for additional information check out my blog at http://womenshealthandfertility.blogspot.com check me out on facebook and twitter with me at @montereybayivf.

Sunday, September 13, 2009

TTC And Using Ovulation Kit

Here is a fairly common question that I get on the All Experts site having to do with ovulation kits...

Hi Doc,

I have a 25 day cycle and my period usually lasts 3 to 4 days. When do you think I would ovulate? When should I start testing with the ovulation kit?

Thanks in advance.

Hello,

Thank you for your question. Generally the second half of the cycle is the most constant. It is 14 days from the onset of menses. So, if your cycles are 25 days, then you are most likely ovulating around cycle day #11. Your fertile period would then be CD# 9-13. Those are the days I would recommend intercourse. You should stop intercourse on CD#7 and wait until CD#9 to start. Have intercourse once per day on those days, only one ejaculation per day. Start using your ovulation kit on CD #9 (counting back 16 days from the end of your average cycle).

Hope this helps and good luck!

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

Check me out on Facebook http://www.facebook.com/home.php#/ejramirez1?ref=profile and Twitter with me at @montereybayivf.

Friday, September 11, 2009

Carbon Monoxide Poisoning in Pregnancy

Question:

Hi, Dr:

I am a little over 9 weeks pregnant. Over the last 3 weeks or so, I have been suffering with severe nausea and vomiting, and was diagnosed with hyperemesis gravidarum. At one point I needed to go to the ER for IV fluids, and my doctor started my on an anti-nausea medication called Zofran. Even with use of the medication, I have continued to feel very 'queasy' and there are days when I still vomit.
I recently moved to a new apartment and wanted to use the oven yesterday for the first time. When I turned it on, there was a strange smell emanating from it, so I went into the bedroom to watch some TV. About 20 minutes later, I began to feel very lightheaded and developed a headache. Concerned, I evacuated the building and called my local gas company to inspect for a gas leak. When they arrived and checked out the premises, they informed me that there was no gas leak, but that there was carbon monoxide coming out of the oven vents and this was likely responsible for my symptoms.
After sitting outside for a few minutes and getting some fresh air, I began to feel much better. The problem is that since this incident, I have not been feeling my usual "nausea and vomiting" symptoms. In fact, last evening for the first time I was actually able to eat dinner! I'm no longer feeling that constant nausea and my appetite has returned full force. I spoke to my doctor's office and they were very dismissive of what happened, telling me that the baby and I are probably fine. I have a nagging suspicion that the carbon monoxide exposure has had an ill effect of my baby. What should I do?


Answer:
Hello T from the U.S.,
 
Carbon monoxide is a toxic gas that can lead to death if not treated quickly. By getting out into the fresh air, you treated the problem, and allowed oxygen to get into your system. the CO works by blocking the oxygen uptake in the red blood cell. Usually you cannot smell CO, which is what makes it so deadly. You basically "suffocate" to death.
 
The CO should not have any affect on your baby or pregnancy since you treated it quickly. Again the worry would be the lack of oxygen delivery to the baby. It is possible that the reason your N/V resolved is because you have advanced in your pregnancy. It will often cease after a period of time that is variable from pregnancy to pregnancy.
 
I think if you need further reassurance that everything is proceeding well, then you should schedule to see your doctor and have an ultrasound done. This way they can verify that the baby/ pregnancy is proceeding well. Of course if there are any effects on the baby itself, that cannot be detected unless it is catastrophic, but there is a blood-placental barrier that keeps toxic chemicals away from the baby.
 
Sincerely,
 
Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
http://www.blogger.com/www.montereybayivf.com
 
Monterey, California, U.S.A.
 
for additional information check out my blog at http://womenshealthandfertility.blogspot.com/ check me out on facebook and twitter with me at @montereybayivf.

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