Tuesday, July 26, 2011

40 Yr Old German Woman With Great Ovarian Stim Fails IVF: Likely Abnormal Embryos, Try Again!



Question:

Dear Dr. Ramirez,

My name is A. from Germany, 40 years old, never pregnant before. I had 2 failed IVF this year (1 in March, 1 in June). My FSH=10.6, AMH=0.8. progesterone level is normal.

The 1.IVF had 6 eggs (2 embryos were transferred: 1 grade 1 and 1 grade 2) and 2.IVF had 7 eggs (3 embryos with grade 1 were transferred in July).

The 2.IVF was done in North Cyprus. Do you think the failure was caused by taking airplane back home on the 2.day after transfer? It was just about 3.5 hours flight.I will try the 3.IVF this year.

How long should I take a break before trying the 3.IVF? Because I heard that the hormone level, uterus lining and ovary need time to get back to normal. Are these correct? I have also read an answer of yours regarding implantation failure.

You wrote in March this year:

"My approach to patients with implantation failure is to add the following medications:
1. Aspirin 81 mg per day beginning at the start of the cycle.
2. Heparin 2000 units twice per day beginning at the start of the cycle.
3. Medrol 16 mg daily until transfer then 8 mg from that point until positive pregnancy, then stop.
4. Increase progesterone to 50 mg injection plus Endometrin 100 mg twice per day vaginally. The injections starts on the day of the retrieval and the suppositories start the day after the transfer. "

My questions are:

1.what for an effect is the heparin in the case of repeated failure? I did not have this in the last 2 IVF. Do I need this, even I do not have thrombosis problem?

2. Do I need to increase my progesterone level even I have a normal level?

3. I will do an autoimmune test next month. Which tests should I do in addition?Thank you very much for your time. Best Wishes. A.

Answer:

Hello A. from Germany,

I was impressed to see that your ovary stimulated well and gave you an adequate number of embryos despite your age and elevated FSH levels. One thing to keep in mind is that despite having a good IVF cycle with reasonable embryos, IVF is not a perfect technology. The last two steps, embryo hatching and attaching to the endometrium and implantation, must occur naturally. This does not always happen. Also the embryos have to be completely genetically and otherwise normal. There is a higher chance of abnormal embryos with increasing age. That is what is called the "Age factor."

What that means for older women (35 years and older) is that it may take a lot more attempts to achieve a pregnancy, but as long as the ovaries still respond and put out eggs and embryos, then you have a good chance. Also keep in mind that pregnancy rates are highly variable among clinics so the clinic you go to is very important.

With multiple failed attempts, I add the protocol that you cited. There is a saying in the U.S. called "throwing in the kitchen sink" which basically means doing everything you can possibly do. That is the reason for this protocol. These medications are mainly used in patients that have recurrent miscarriages. But in IVF failure patients, it seems to work as well.

The Heparin and aspirin are at low doses so they are mainly targeting very small clots that occur in the micro-vessels that feed the implantation site. It is not enough to prevent a large clot in your vasculature. At that level they also have an anti-immune action to prevent failure due to an increased immune response from your body. That is also the reason for the Medrol or prednisone. It is an anti-immune drug. Some women are found to have an increased immune system when an antiphospholipid antibody screen in done (21 points). Finally, the increased progesterone is to insure that adequate progesterone is reaching the endometrium because this hormone is vital to implantation and survival of the pregnancy.

Travel is not an issue. I have many patients that come to me from far away places, yet they have been successful. Studies have shown that travel has no impact on pregnancy rates. What is more important is finding a good IVF center that uses state of the art techniques and has good pregnancy rates in your age group. I have many patients that come from Europe so that is always an option as well.

Good Luck,

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

Saturday, July 23, 2011

Calendar Method Vs. OPK? It's All In The Timing...



Question:

So my husband and I are trying for our first child. We've trying for about 3 months with no luck yet. i was thinking of trying the ovulation test but i'm not sure if its worth it. I've read online that they can help but i figure it would never hurt to ask. Do you know much about them and if there worth the money or should i just track my temp every morning.Thanks for the help! S. from Canada

Answer:

Hello S. from Canada,

An ovulation predictor kit (OPK) does not help any more than timing it well. I don't recommend it to my patients. Instead, I recommend the calendar timing method. It goes like this:

CD#1 The day your period starts. Mark you calendar then count each day. For instance the next day is cycle day #2, then cycle day #3 etc.

CD#10 Stop having intercourse. You can have regular intercourse until that day but you have to stop on that day.

CD#13-17 Assuming you have normal regular cycles, this is your fertile period. You should have intercourse each day, only once per day and only one ejaculation per episode. After cycle day #17 you can resume your normal frequency.

Keep in mind that 85% of women under the age of 30 take 8-12 months to achieve pregnancy so you have not yet been trying long enough. Hopefully this method will help.

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.

Comment: Ok thank you so much for the advice! I'm going to try the calendar method.

Thursday, July 21, 2011

Failed IVF Cycle With Drop in Estrogen & Progesterone Levels & PCO Type Response: Might Benefit From Adjustment In Protocol




Question:

HI, I have a question regarding spotting 5 days post transfer with full period bleed on 6 days post transfer. Here is our history:-I am 32 and my husband is 41. He has a daughter from a previous relationship.-I was diagnosed with diminished ovarian reserve in January, and also stage III endometriosis in June with a laparoscopy. They were able to clean out almost all of the endometriosis except for some on the colon because I did have some bowel in my colon and they didn't wan to rip it. They also found a polyp in my uterus that they removed. Also, I have a luteal phase defect as I always would spot around 9dpo and would have an 11 day luteal phase with 24-26 day cycles.

- January/February 2011 - First treatment cycle. Letrozol with monitoring and intercourse and prometrium 50mg 1x a day. Luteal phase increased to 14 days with 29 day cycle. Negative.


-February/March - An ovulatory cycle - went in on day 3 and never came down to baseline. Ovulated day 8 (which has never happened) so couldn't do meds. Prometrium again, but only 11 day luteal phase, obviously negative.


-March/April. Anther cycle on Letrozol and prometrium - same as first cycle but negative.


-April/May - Moved to injections. Follistim 150mg and then decreased to 75 due to good response and high estrogen. Ganirelex 3-4 days prior to IUI. HCG trigger with 6 follicles developed and 1 mature. IUI with crinone (prometrium was causing depression). Luteal phase 14 days with 28 day cycle - negative.-Laproscopy in June.


-IVF June/July - Long protocol - BCP, 10mg Lupron for 10 days, Follistim 150mg day's 3-6, increase to 175 day 7-9 (estrogen at 840 after this). Decrease to 150mg days 10-11(estrogen shot up to 3400) Decrease Follistim to 75mg day 11-12 (estrogen 6000). All along with 5mg Lupron. HCG shotday 13(only half dose b/c estrogen so high. Retrieval on day 15. Starteg Crinone that day. 15 eggs retrieved with 14 fertilizing without assistance (husbands sper is great quality). Day 5 transfer, 1 blastocyst very good quality. All other embryo's taken to day 6 to freeze, but all but 1 poor quality so couldn't freeze. The 1 completely hatched so couldn't freeze and they didn't want to disrupt other embryo by transferring it. I had a follow up on day 5 post transfer to just check me for OHSS and they took my levels and my progesterone was 3 and estrogen 60 (at baseline they have never seen it below 72).


I knew something was wrong b/c I started spotting that day and a full period started that night. It is very heavy bleed which I usually don't have, but not nearly as much pain as I have had int he past, most likley from the endo surgery. I am taking a little while off, but it sounds like they think I have a true luteal phase as they never see this response to IVF. I want to be as edcuated as possible when I meet with my doctor.


What would your suggestion be for a luteal phase protocol to address this? I am nervous about the shots. The nurse said possibly estrogen patch, prometrium, and crinone or something along those lines with 2 progeteron meds. I have also asked to have my levels monitored during the next luteal phase. I am taking a cycle or two off before jumping into the next cycle. I am lucky to have the flexibility b/c my insurance covers this. I appreciate your feedback on this.


Thank you! K. from New York

Answer:

Hello K. from the U.S. (New York),

You had an awkward IVF cycle to say the least, was my first impression. There were several interesting moments in your cycle. First, your response was very characteristic of a PCO-type response, very sensitive ovaries. I don't know if your doctor was expecting this or not, but hitting an estrogen level of 6000 put you at very high risk of OHSS. Despite this, your doctor continued the cycle and triggered with HCG, which further increases the risk. I think you are lucky to not have developed full blown OHSS.

Second, I found the up and down of your meds to be unusual.

Third, a PCO type response would explain the decrease in embryo quality. When the ovaries are hyperstimulated they often lead to a deficit in embryo development or quality. That would explain why there were so few embryos to freeze. If they had to culture to day#6 that means that the embryos had not reached blastocyst stage by day#5, which is not necessarily a good sign. For the one that did, I was surprised it wasn't just frozen at day#5 so there would not have been a hatching problem. Why did they wait an extra day?

Finally, the abrupt drop in estrogen and progesterone levels was sure curious. I have never seen such a precipitous drop in a patient that is receiving supplementation. Surely, the problem with serum (blood) hormone levels is that they don't accurately reflect the levels within the endometrium, but there will be some levels and there are minimum levels in the blood that we know usually mean there is adequate levels in the endometrium. Neither of your levels met these minimum levels, but there should have been hormone in the blood because of the medications you were taking. You were taking medications weren't you? I would be very surprised if they didn't supplement you. Basically the bleeding that you had was the onset of your period because the hormone levels had dropped so precipitously. That is how it works in a natural cycle.

Certainly in the next cycle, I would recommend that you take progesterone injections (50mg) per day beginning with the retrieval, then add vaginal progesterone (Crinone or Endometrin) after the embryo transfer (because it is messy and interferes with the transfer), I also would add estrogen supplementation by patch starting with the transfer as well, but in your case, your levels should have been high from the hyperstimulation. I'm still thinking of possible causes for the drop. . . did you not stop the lupron?

Protocols are highly different between centers and there is not one protocol that is necessarily better than another. These are just suggestions. Your doctor may want to do something entirely different. Also, because you had a PCO-type response, I would recommend that you not use the long protocol and instead use an antagonist protocol with Lupron 0.5 mg as the trigger instead of HCG. This will reduce your chances of developing OHSS.

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.

Friday, July 15, 2011

Inadequate Luteal Phase Support In IVF Cycle Can Cause Bleeding & Failure



Hello Dr. Edward,

Thank you in advance for your answer! I'm from Paraguay. I just went through my second IVF-ICSI and both times I started bleeding 7-8 days after day 3 transfer, just when implantation should be occurring. Do I have an implantation problem? Are there any tests I should do? What should be done to prevent this early bleeding? I'll appreciate your expert opinion on this!

Here are the details of the case:

He: 38, had testicular cancer 6 years ago (unilateral orchiectomy and radiotherapy), very low count, morphology and motility. Now healthy, treated autoinmune hypothyroidism, BMI 26.

She: 34, no known fertility concerns, healthy, BMI 27.

Went directly for IVF-ICSI due to male factor.1st IVF/ICSI: 12 eggs, 6 fertilized, 3 transfered (day 3, 2x 8 cell + 1x 7 cell, fair quality), none to freeze. Long agonist protocol: suppressed with BCP + Lupron, stimulated with Menopur + Puregon, triggered with HCG, after ER Dostinex (8 days), anti-inflammatories and antibiotics (3 days), luteal support with Prometrium. Early bleeding 8dp3dt: BFN.2nd IVF/ICSI: 14 eggs, 8 fertilized, 3 transferred (day 3, 1x 9 cell + 1x 8 cell + 1x 7 cell, good quality), 4 frozen. Same protocol, added Estrace and more Prometrium for luteal support. Early bleeding 7dp3dt: BFN. Thank you!

Answer:

Hello E. from Paraguay,

Thanks for the information. You don't mention how much Prometrium you used in your cycles but I think that may be the problem. I think you may have inadequate luteal phase support i.e not enough progesterone. Certainly prometrium should be adequate to cover the luteal phase, and many studies have shown that vaginal progesterone only is adequate, but the dosage has to be adequate as well. I think the minimum used should be 100mg three times per day. In my practice, because I don't want patients to not get pregnant or lose a pregnancy because of inadequate progesterone, I use both injectable progesterone 50mg per day and vaginal progesterone (I use Endometrin) 100 mg per day. That is what I would recommend for you. You should not be having bleeding that soon after embryo transfer.

Protocols and technique are what distinguishes IVF centers and their respective pregnancy rates. So, that is what you need to carefully evaluate.


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.

Wednesday, July 6, 2011

Jamaican Woman Doing 1st IVF Confused About Meds: Possible PCOS Misdiagnosis



Question:

I am about to do my first ivf with a clinic and I got a lsit of medications that I will have to use/purchase. I am a litte uncertain about one of them - menopur. The list has over 40 vials of 75iu. I am certain that this is a mistake.

I will of course be asking the clinic but I wanted to be certain. I have had two iui - failed previously. one on clomid with three follicles gretaer than 10mm and one with menopur 150 with about 4 or 5 follicles. This is why I am uncertain about the quantity of menopur on the list.This medication represents the most expensive item on the list and I wouldn't want to order this many at once.

Again, I will be clarifying but I needed additional research/opinion. I have pcos and was diagnosed with endo, had a laporoscopy, ovarian drilling, suppression after lap etc etc

Thank you. KL from Jamaica

Answer:

Hello KL from Jamaica,

I cannot tell you if this is the right dose or not because it depends on the protocol your doctor has you on. But I can make the following comments:

1. PCOS patients tend to be very sensitive to medication and therefore require less medication to stimulate. For that reason alone, I would be skeptical, as you are, of the amount of medication ordered.

2. Menopur is NOT a good medication for PCO patients (if that is a correct diagnosis) because PCO patients already tend to have an increase LH level and the additional LH in Menopur is not needed and will lead to the risk of ovarian hyperstimulation syndrome (OHSS). I will usually either use only Follistim or will use a very low dose of Menopur less than or equal to 75IU. However, given that you only had 4-5 follicles with Menopur 150IU before, I wonder if maybe the PCO diagnosis is not correct?

You definitely need to ask your doctor regarding these concerns.

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.

Sunday, July 3, 2011

4 Weeks Pregnant, Hypothyroid, At 43 After Clomid Cycle: How Are My Levels? What To Do If I Miscarry?




Question:
Hello, I’m in California.

I just found out I’m pregnant, about 4weeks 4days. I had my first beta; it was only 18 at 14 dpo and 24 at 15 dpo. I took another yesterday at 17 dpo, but I won’t know the results until tomorrow. Either way, a very poor prognosis for a viable pregnancy.

I know I should just wait until tomorrow, but I want another opinion. This is an agonizing waiting period – I feel like I don’t know if I’m coming or going. This is the 5th or 6th time I’ve been pregnant, but I’ve never had a pregnancy like this, where I have no symptoms whatsoever. I can unhappily handle a miscarriage, but I do NOT want it to turn out to be ectopic, which is what I fear the lack of symptoms means.

Question 1:
I am on Crinone 8% 1/day. Would that “mask” a miscarriage? I know it won’t stop a miscarriage, but what I’m trying to find out is if the progesterone will stop the bleeding I would have if I were to miscarry? Will I not start bleeding until I stop using the Crinone? (Which I’m not going to do until I find out for sure what’s going on.)

It turns out that my TSH is high, about 5.7. And from what I understand, that number may actually have been higher prior to pregnancy. I should have been medicated for this problem before getting pregnant, but the multitude of doctors I’ve been to never had me get this test done, as a matter of a fact, I actually added this test to the beta lab slip myself.

Question 2:
I have been told that the rate of early miscarriage is high in women with untreated hypothyroidism – IF they can get pregnant at all. Do you have any information on this?

I am going to ask to be put on thyroid medication tomorrow at my appointment. Is there a specific medication that I should be on while trying to get pregnant that is more effective for fertility and safer for a growing fetus?

I am assuming an upcoming miscarriage (I’m a realist). I am also 43, so I literally do not have a second to spare. I got pregnant on my first round of 50mg Clomid (I also added Soy Isoflavones and Black Cohosh), which says to me that I was either previously not ovulating – or my follicles were not rupturing (exact 30 day cycles). If/when I miscarry I will immediately begin trying again.

Question 3:
Should I try the Clomid again because it worked, or try something a bit stronger, injectables with an IUI perhaps?

Question 4:
Can I use fertility drugs immediately after miscarrying, i.e. before I get another period? I know that often a woman will conceive immediately after a miscarriage.

Thank you so much for your help. I wish you weren’t so far away, it would take me about three hours each way to get to you! J. from California


Answer:

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

The reason you are not feeling any pregnancy symptoms at this time is because the bHCG levels are still very low. The symptoms may come on if the levels risk over time but not all patients have pregnancy symptoms even with normal pregnancies.

The fact that the levels are increasing is a good sign. They cannot be interpreted in less than 48 hr intervals so I don't know why your doctor ordered them that way. Basically the bHCG should increase by 80% in 48 hrs. If the next level is still going up, I would continue to follow them. I caution against drawing any conclusions based on these results. They are a guide only.

Your TSH level is indeed elevated and is an indication of hypothyroidism. That means that you need thyroid supplementation. I would recommend that you see an endocrinologist or reproductive endocrinologist to have this done.

The fact that you got pregnant on Clomid is a very, very good sign! It shows that you have the ability to get pregnant! However, your obstacle is the "age factor" i.e. decreased egg quality and viability due to age. You certainly got very lucky on your first Clomid cycle but I would not expect that each time. Your natural chances of pregnancy per month (Clomid, injectables and IUI fall into this category) is approximately 0.2% per month. Using fertility medications to increase the number of eggs that you ovulate is the only way to increase your chances per month. If you are determined to continue the natural pathway, then I would strongly recommend injectables with a closely monitored cycle. Ideally, you should be going directly to IVF to give you the highest chances per attempt of 33%.

You will not be able to go directly into another ovulation inductions cycle after the miscarriage. You will need the miscarriage to resolve completely, as determined by following the bHCG's. Once this has resolved, then you can induce ovulation.

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.

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