South African Had Surgery for Stage 4 Endometriosis - Now What?

Question:

Hi, doc, I'm 30yrs old and recently had laparascopic surgery. I was diagnosed with stage iv endometriosis, most of it was removed. My fiance also has fertility issues. He was diagnosed with anti sperm antibodies. We are desperate to conceive and will meet our doctor next week to discuss our options. I would love your opinion on this matter?

Thank you, Regards from South Africa.

Answer:

Dear M. from South Africa,

Stage IV endometriosis is the worst stage that you can have. This has definitely been shown to impair fertility via natural means. The problem is that the endometriosis has now impaired the pelvis and this is the path that the egg must take in order to reach the tube. Both the scar tissue formed from the endometriosis and surgery, and the inflammation caused by the endometriosis will interfere with the egg.

Most women with stage III or IV will not get pregnant naturally and will need to go directly to IVF. To these women I first recommend trying naturally after surgery for a 6 month period. You can either try on your own or with IUI, it doesn't really make that much of a difference. Most RE's would treat with Lupron or Letrozole after the laparoscopy for three months to remove any residual endometriosis prior to starting with a treatment.

Since your problem is combined with your partner's problem, then you have two major strikes against you. That would definitely make me strongly recommend IVF as the treatment of choice. That is not to say that you could not get pregnant without IVF. I have had a patient with stage four endometriosis that became pregnant spontaneously. However, the statistical chances of pregnancy is 1% or less.

Thank you for your question and good luck!

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com

OHSS: Ovarian Hyperstimulation Syndrome and the PCOS Patient

On Wednesday, February 24th, at 6pm EST, I will be interviewed by Sasha Ottey on her radio show. The subject: "The Real Deal about PCOS and Your Fertility" Join us at http://blogtalkradio.com/pcoschallenge.

Prior to my blog radio interview, I would like to publish a question from last year regarding OHSS, ovarian hyperstimulation syndrome, in a PCOS patient. In this year's January cycle I had a patient with PCOS at my clinic who had undergone IVF last year at another clinic in the Bay Area. There she developed severe, life-threatening OHSS, was admitted to the hospital and stayed there for seven days. Needless to say, that cycle failed. She returned to the same clinic to do a frozen embryo transfer, which also failed. She then came to me. I put her on my standard protocol for PCO patients, low dose stimulation (Lupron/Ganerelix) and carefully monitored her. I'm proud to report that this patient had no adverse reactions and is now pregnant after only her first cycle with us.

Typically, signs and symptoms of OHSS appear within the first 10 days after a gonadotropin injection, when the ovarian blood vessels have an abnormal reaction to the hormone and begin to leak fluid. This fluid fills the follicles, swells the ovaries and sometimes moves into the abdomen in large amounts. Fewer than 2% of women develop the most severe form of OHSS.

Here is a link to the Mayo Clinic's informative website regarding OHSS, definition and symptoms http://bit.ly/bYGk1R .

Question:

Dear Dr. Ramirez,

First I would like to give you some background information. I have PCOS and have been undergoing infertility treatment for apx. 2 years. First, I tried using drugs like Clomid and Follistem. After about 1 1/2 yrs of it not working, we decided to go the route of IVF.

On June 23 I had my egg retrieval. They retrieved 15. After the retrieval they recommended not doing the transfer due to the risk of over stimulation (OHSS). I ended up being admitted to the hospital on June 29 with severe OHSS and on July 1, they drained a little over a liter of fluid. I was sent home on July 2. I had my period on July 5. I went back on July 7 and still had a little fluid around my lungs and my left ovary was still swollen. They were able to freeze 7 fertilized eggs. How long should I wait to do the transfer and can I develop OHSS again with the transfer?

Thanks! I am from Missouri.

Answer:

Hello,

It is unfortunate that you developed OHSS with this cycle. It should have been expected and could have been prevented. There are measures/protocols an RE can take to reduce the chances of developing OHSS such as "coasting" using "antagonist + Lupron to trigger" and lowering the dosage of stimulation.

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. 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.

I have not had a case of OHSS in over 10 years by taking these precautions. In any case, you should not do the transfer until your ovaries have returned to normal. Pregnancy can exacerbate the OHSS. Once this resolves then you can go through the frozen embryo transfer cycle. You will not undergo ovarian stimulation with an FET. Only the uterine lining needs to be prepared. For that reason, you are not at risk of OHSS.

Good luck,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com

PCOS & Insulin Resistance Syndrome Trying IUI for the Fourth Time

Question:

Hi, I am 37yrs old soon to be 38. I have PCOS and Insulin Resistance Syndrome. I did three cycles of IUI (intra uterine inseminations) with 150mg of clomid. When it came time for the IUI I received the first one then was given the Ovidrel (HCG) shot then had the second IUI the next day. No success at all.

For my fourth cycle, my RE put me on Bravelle 150 for 4 days then 225 for two days. I was told to take the ovidrel shot the evening before the IUI. I am wondering if my RE is having me take the triggers too late? Everything I read says 24-36 hours later. I asked my nurse during the clomid cycles why get the trigger after the first IUI and not before? She said to make sure I have definitely O'd (ovulated) for the second insemination. I am using Donor sperm.

Thank you. N. from U.S.A.

Answer:

Hello N. from the U.S.,

I am greatly dismayed by the treatment regimen you have received! Is the doctor you are seeing really an RE? Does he/she do IVF? The usual protocol for IUI is to follow the follicular development by ultrasound, just as is done in an IVF cycle, and when the lead follicle reaches 18 mm to 22 mms, the HCG (human chorionic gonadotropin) trigger is given, stimulating the release of the egg, or ovulation. The IUI is then done at approximately 36 hours (if only 1 IUI per cycle protocol) or at 24 and 48 hrs (if 2 IUI per cycle protocol). Neither cycles that you have gone through makes much sense to me, and may be a waste of your time and money (I know how expensive donor sperm is).

My other question is at your age, one or two IUI's might be advised but not more than three. Is it something that you insisted on? Certainly there is a chance of pregnancy with IUI at your age, I have had patients that were successful up to the age of 41, but the chances are only about 5% per cycle, whereas, with IVF you have a 60% chance of pregnancy per month.

I would recommend that you give that option some thought.

Good Luck,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com

33 Yr. Old Low Responder Trying For A 5th IVF Cycle, One Stillbirth But Not Ready For Donor Eggs Yet

Question:

Dear Dr. Ramirez:

I've just recently gone through my 5th IVF Cycle. Yesterday at retrieval they got 11 eggs but said that 6 of them were empty. The embryologist called today to say that none of the eggs fertilized and they are not sure what is going on. To give you a brief synopsis of my history:I'm 33, my husband is 46. We have been together for 6+ years. I was first diagnosed with blocked tubes back in 2005. I had bilateral tubal repair which successfully opened both tubes. Since I did not get pregnant we moved to IUI, which most of those got cancelled due to relationship difficulties. In 2008 I had a chemical pregnancy using donor sperm. My RE didn't count it because my AF started the next day after the beta. We then found out that my husband had a low sperm count. He was not tested prior to this because he has a child from a previous relationship years ago.

We did our first IVF in May 2008 with the transfer of 3 day 3 embryos. I conceived on this first attempt. However, my son was stillborn when I was 25 weeks along. We don't know the reason why because an autopsy was not performed. All I know is that I had an amnio at about 19 weeks and things were never quite the same after that. After meeting with my RE a month later he said we could try again soon because I have a high FSH which normally measures around 10 or so. The last two cycles my FSH was 9.9 and 8.8. We have done 4 IVF cycles in 2009 and all have failed.

1/09--bcp for 1 week, lupron, follistim 450, and menopur 150. 5 Eggs retrieved, 3 fertilized only one made it to day 3 transfer. Result=BFN3/09--same protocal as above, retrieved around the same amount of eggs but none fertilized.

4/09--bcp, follistim 450, menopur 150, and ganirelix towards the end of stimulation. 7 eggs retrieved, 5 were mature, 4 fertilized, and 2 made it to day 5 transfer. My RE said the day 5 transfer was of morulas (by day 5 they should be blastocyst so they were lagging behind in thier development). Result=BFN. My RE did a hysterosonogram and indicated that my uterus looks fine.

6/09--At this point we've decided to go for a 5th try, although it is now out of pocket as I've maxed out on insurance benefits for IVF. This time around my RE starts me on stimulation day 2 of my cycle with 450 follistim, and 150 menopur. No suppression. I produced more follicles than in my previous cycles. What puzzles me is that as of last Friday I had 16 follicles measuring between 14mm - 18mm and a few that were below 12mm and a few that were less than 10mm. When they did the retrieval yesterday I was a bit surprised that they only got 11 and then more than half of those were empty. The trigger shot I take is two shots of Ovidrel, one on each side. The first cycle when I got pregnant the trigger I took was Novidrel in the butt.

During all of this, after I lost my son with the stillbirth last year, the only person that did any thorough testing on me was my hematologist to find a clue as to what happened. In May 2009 he did an entire work up and discovered I had a Protein S deficiency and something else that may cause my blood to clot along with a positive PPA which he indicated could cause congestive heart failure in a fetus. His recommendation to my RE was that I should be on 81mg of baby aspirin daily and once I conceive I should be placed on Lovenox. Of course this didn't seem like a big deal of concern to my RE. His take is lets get you pregnant first.

My question is, given what I've described above, is there any change in protocol that would be recommended? I'm 33 and not ready for donor eggs but can't afford the cost of more failed cycles. Are there questions I should be asking my RE that I'm not focusing on?

Answer:

Hello,

Boy, you have gone through quite an ordeal, and I'm sorry to hear it. At least you know that you can get pregnant. Despite the fact that you are a poor responder (high FSH), your chances should still be good at your age. I am very surprised that it has failed so many times.

The stimulation protocol that you used recently (Follistim 450/Menopur 150) is my highest protocol as well. I use ganerelix (GnRH antagonist) for 1-3 days prior to retrieval to prevent spontaneous ovulation. I also use Ovidrel to trigger (only 1 shot however). Your stimulation was very good. I am very shocked that there were "empty" eggs. I presumed that meant empty cumulus, not eggs. That is something that we usually only see in Older patients (over 40). That is highly suspicious.

My protocol for patients that fail two IVF cycle is to add the following:

1. Aspirin 81 mg daily beginning at the start of the cycle continue through the pregnancy.

2. Low Dose heparin 2000 units twice per day or Lovenox 30 mg per day starting at the beginning of the cycle. Continue until 10 weeks pregnancy.

3. Medrol 16 mg per day until embryo transfer then decrease to 8 mg per day until the pregnancy test then stop.

4. Both injectable progesterone 50 mg per day beginning after the retrieval and vaginal Endometrin 100 mg vaginally twice per day beginning after the transfer.

I NEVER take low responder patients to blastocyst. I do not believe the blastocyst culturing is perfected and there is still a high embryo loss rate. I only take high responder young patients to blastocyst to decrease the number of embryos to choose from. In most cases, I transfer at day 3.

I don't know if your RE will accept some of these things because they are not well established in studies. But when my patients fail, I pull out all the plugs. The medications are not harmful or dangerous and can only help. The aspirin, heparin and medrol help to decrease the immune response AND decrease the micro clot formation in the early blood vessels going to the implantation site.

Despite all the IVF cycles you have done, at your age I would still want you to continue to try, but certainly donor eggs would be the next option. If you have implantation failure, however, and don't use the above protocol, then even donor eggs might fail. One other option would be to consider trying a different clinic because success rates are highly variable among clinics and doctors within a clinic.

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

South African Husband Concerned: Is Wife's Abnormal Bleeding Caused By Cystourethrocele?

Question:

Good day, I am writing from South Africa. My spouse has recently been having blood discharge and discomfort after intercourse. After consulting a local gynae, he advised that her bladder muscles seem to have collapsed pushing the bladder more into her vagina. He has recommended constructive surgery by insertion of some sutures.

Could you please advise what causes this (she works long period as a scrub sister in theatre), possible treatments? Also, please advise what effects having intercourse would have before the surgery is performed. Thanks. J.

Answer:

Hello J. from South Africa,

I understand the problem that your wife's gynecologist identified. It is called a cystourethrocele. It is a condition whereby the upper vagina becomes weakened and the bladder sags into the vagina. It is usually a result of childbearing, which causes the muscles to stretch out, and they never return to their normal tensile strength. The upper vagina supports the base of the bladder.

However, although this may be an identified problem, I am not sure that this is the reason for the post-coital/intercourse bleeding. Cystoceles don't usually bleed, unless over vigorous intercourse causes the vaginal skin to tear, which is hard to do. The other possibility is if your wife is menopausal, the vaginal tissues can become thinned and brittle and intercourse can cause an abrasion, leading to some bleeding. In any case, an evaluation needs to be done to identify the cause of the post-coital bleeding. The most common source of bleeding is from the cervix or uterine cavity. Disorders such as cervical polyps, endocervical polyps, cervical lesions/cancer, endometrial lesions/cancer, can cause post-coital bleeding. I would not assume that it is from the cystocele if these things have not been evaluated.

Cystoceles are repaired by opening the vaginal layer, pushing the bladder up and bringing the muscle back together to hold the bladder up, then closing the vaginal skin. The formal name for it is anterior vaginal repair or anterior colporrhaphy. If there is bladder leakage, called stress urinary incontinence, this procedure can also be combined with a bladder neck suspension to lift the bladder neck with sutures on either side.

Please have your wife evaluated further for some of the possible disorders I named above if she hasn't been already before proceeding further.

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.

41 Year Old With High FSH, High Estradiol - Can I Still Get Pregnant?

Question:

Dear Dr. Ramirez,

I am forty-one year old professional woman living in OH, and I desperately want another child (I have a 16 year-old and a five year-old that were conceived with no problem at all). Before trying to conceive this time, my dr. ran day 3 FSH and estradiol testing, with an FSH result of 15.9 and an estradiol result of 207.

What does all of this mean for me? I've heard that I should take Clomid to stimulate ovulation, but since Clomid raises the FSH, isn't that counterproductive? How does Femara work? Is there any hope for me without donor eggs?

Thank you so much, M.

Answer:

Hello M. from Ohio,

First of all, thank you for your questions. They have relevancy with a topic which I have addressed lately, which is how to approach infertility at +40 and beyond.

So, how does Femara work? Well, FSH stands for Follicle Stimulating Hormone. It is the hormone that the pituitary (brain) produces to stimulate the ovary to grow and ovulate an egg. Think of the ovary as a ball with lots of holes in it (sort of like a practice golf wiffle ball). Imagine this ball at the end of your blood vessel and the holes let the FSH in. When the FSH reaches the inside, the ovulatory process is stimulated. Now, imagine the same ball with much less holes because over time the holes have blocked off. So now less of the FSH is entering the ball and stays in the blood stream. That is your cycle day# 2 or 3 level. If the ovary is picking up a lot of the fSH, the level is low, but if it is picking up less, the fSH is high. When then level reaches 20, that signifies that the ovary is not picking up the fSH anymore, which is menopause. From a fertility point of view, we want the fSH to be less than 10. When it is higher than 10, that signifies "ovarian resistance", which simply means that if we stimulated the ovary with fSH (fertility medications), the ovary will not respond very well i.e. not increase the number of eggs that it ovulates.

The main purpose of fertility drugs, in someone who is ovulatory, is to increase the number of eggs that are ovulated in order to increase the chances that one egg will find and get into the tube to be fertilized, etc. So if the ovary is "resistant" to being stimulated, then more eggs will not be ovulated or available to be retrieved (as in IVF). When the fSH level is 15 or above, as yours is, that is significant ovarian resistance and very close to menopause. It is very, very unlikely that we would get more than one egg, if any at all, which means that the IVF cycle would be wasted. Here's the catch: That doesn't mean it won't work, after all, it only takes one good egg and one good embryo to become pregnant (and I have had several of these types of patients), but merely that the chances are less. For this reason, many IVF clinics use an fSH of 15 as their cutoff for a patient to use their own egg. However, it is not an absolute and the choice is ultimately yours.

Regarding your question re Clomid/Femara. Clomid and Femara work by stimulating the ovary indirectly. They are both estrogen receptor blockers, and in doing so, trick the brain into thinking that it is not producing enough estrogen (which occurs from the ovulation process in the ovary). As a result, the brain increases the amount of fSH in the blood to stimulate the ovary. As you can see, if you have ovarian resistance already, meaning that the ovary will not pick up more fSH anyways, then using Clomid or Femara will not help. In fact, using high dose injectable fSH won't do much either. Finally, the way that IVF helps with the age factor, what I call the "age related egg factor", is by stimulating the ovary to get lots of eggs out at a time. The assumption is that there are still some good eggs left in the ovary. By taking many, many eggs out at a time, we are hoping that we will have a good egg in that group, and thereby increase the chances of pregnancy. We do not have the technology to make eggs better. If we can't get a lot of eggs out at a time, then then IVF is helping a little more than trying naturally but not by much. I still think that IVF is better, however, than trying naturally because more of the process required to become pregnant is accomplished with IVF, whereas your natural process is less exact.

I have had and have patients will high FSH levels, such as yours, attempting IVF. Again, it is your choice, and my role is to be your advisor, not your parent. Most patients want to try at least once, to convince themselves that they gave their best effort. Also, as I mentioned previously, I have had some successes with only one egg. One can make a good argument for not using fertility stimulation in these cases, since a natural cycle will produce one egg on its own if the ovary is still functioning normally, however, we can't know that until we try, so I still use high dose stimulation. By the way, having such a high estradiol level on cycle day#3 does not make sense. The estradiol should be at its lowest level. Having a high level like that means that something else is producing estrogen, such as a cyst, or that the timing of the test is wrong. Therefore, I would recommend that you repeat the test after another natural cycle.

I know this is a long answer, but I hope it gave you some relevant information.

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.

Follow-up comment: Thank you so much for your honest and clear answer. You did not have to put so much time into answering by question, and I truly appreciate it that my question was important enough to you for you to do so.

44 Year Old Woman Has Faith That She Will Conceive - Fact or Fiction?

Recently on the All Expert's site, I had an interesting comment from 44 year old woman who feels that RE's are unfairly pessimistic towards "older women" who come to them for infertility evaluations and treatment. I want to publish her point of view because it is a valid one and to point out that there is reason for optimism. It also brings to mind the recent publicity on 41 year old Celine Dion, the feature article in People magazine (Feb. 10, 2010) and her appearance on the Oprah Winfrey show. Celine has admitted publicly that she will not give up despite her age, four failed IVF cycles, and a recent miscarriage, championing the cause for those women like her who wish to conceive past the age of 40.

Comment:

I know what the stats say but I am a 44yr who went into an ivf specialist who did an iui and advised me even as he was doing it that it won't work nor will the ivf if I tried and advised me to just get a donor egg. Well, I did get pregnant on the first try even if I miscarried. I am now trying iui with injectables since I was advised by the new specialist it would work better than an ivf at this point. All my labs each time are consistent with that of a younger woman of childbearing years. Why are you guys so pessimistic for older women? Why do you suppose I got pregnant right away the first time?

I started my period at fourteen and I don't know if it has anything to do with it. I think that sometimes IVF clinics tend to cherry pick their cases to increase the level of "success" stories they can tell. I think it only fair that you fight just as hard for older patients before nudging us to donor eggs..after all the whole point of my husband and me trying to conceive is to see a by product of the two of us, otherwise we can as well adopt. I am just as confident that this cycle will work too, but when I read what you say, it's easy to loose hope but I am a faith filled woman. Pls let older folks out there know their situation is not as hopeless as stats make it sound, at least that has not been the case for me thus far.

Answer:

Thank you for your letter, although it is not a question for me to answer.

I am sorry that your RE was so pessimistic with you. However, there are two sides to this. First, we base our recommendations on statistical chances. Our purpose, as your consultant, is to give you the best and most accurate advice that we can. We cannot predict outcomes, only give you the "statistical" chances. Because IUI is a "natural" procedure, the chances of pregnancy are based on your natural pregnancy rates, which is less than 0.5% per month in your age group. That is NOT a 0% rate, so there are some 44 year olds that get pregnant naturally and with IUI and IVF. It is just a reflection of the possibilities. Part of that decreased pregnancy rate is a very high risk of miscarriage, as you experienced. That is due to old eggs leading to abnormal embryos. Nature (your body) realizes that it is an abnormal embryo and thus stops the pregnancy leading to a miscarriage. Despite the fact that you became pregnant, you need to be prepared to possibly undergo several miscarriages before being successful.

But you are correct. There are always exceptions to the rule. In fact, in November 2009, the New York Post reported a case of a woman who was 49 years old, the doctor using an egg that was retrieved & frozen from her at 48 and who successfully delivered the child conceived by IVF (Dr. Zhang of NYC see related link: http://bit.ly/5PX4k9). It took her two years of many, many IVF cycles, but her perseverance paid off. She is now the oldest woman to conceive with IVF using her own eggs, and I am sure that she was advised to use donor eggs all along the way.

Now the other side of why we advise, as we do, is because we want you to have success, NOT because we want higher statistics or make more money. I'm sure there are doctors who are unscrupulous, but most of us are not. Our mission is to help our patients get pregnant, and for you to have the highest chances of having a successful pregnancy. In addition, we also get criticized by patients, and the press, when we let patients do lower level treatments, such as IUI, for several tries and they are unsuccessful. We are then scolded for allowing the patient to attempt a procedure that would not have worked so that time was wasted. We should have "urged" or "made" the patient go directly to IVF, these patients say. Then they say that "they were not told" that the success rates were too low and that we let them try that procedure because we just wanted to take their money. I have read about MANY such cases in print and on the internet.

In general, we are NOT advising that the case is hopeless, and I know that patients don't want to hear that as well. We are advising what would give the patient the highest success rate, so that they don't get disappointed, which takes its emotional, as well as, financial toll. In my practice, I have let patients as old as 47 years old try both IUI and IVF, with very clear counseling regarding their chances for success. I do not tell them what to do. I let them choose, just as you have done. You became pregnant in your first IUI cycle, which is a triumph. That means that you still have good ovarian function, a key component to getting pregnant. The goal is to get a good egg so that you can have a successful pregnancy. IVF is more suited to this because we are able to get lots of eggs out at one time. That is why it is suited for the "age related egg factor." In an IUI cycle, you are not stimulated to the maximum point (for good reason), so the chances of getting a good egg are reduced (3-5 eggs). Whereas, with IVF, if you respond well, we can get 10-20 eggs out at a time, increasing the chances that we will find a "good" egg in that group.

If, despite all the information and knowledge you have acquired, you feel that IUI is the best route for you to take, then GO FOR IT and give it your best shot. Feel comfortable with this decision and don't doubt or regret it because you made the decision you thought was best for you. Each and every infertility patient has to do this as well.

I wish you the best of luck,

Sincerely,Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com