Use of Ovidrel after BFP in an IVF cycle - Did It Cause My Miscarriage?

Question:
Good afternoon Dr Edward,

I'm 36yrs. I did IVF for the first time and it resulted in preg. Upon a positive pregnancy result, my doctor prescribed Ovidrel 250 iu inj to be taken immediately: This inj was given to me once a week thereafter. My dr also placed me on gestone 100mg(1 inj daily), progynova 2mg (1tab 3ce daily), folvite 5mg (1tab 2ce daily)& Ecosprin tab 75mg (1 tab daily). However, progesterone and estrogen test were not done on me.

I went for my ultrasound (U/S) on the 6th week and the sonologist said she could see a gestational sac (6x6mm), yolk sac but no embryo and no fetal heart beat. Another U/S by the 7th week revealed 2 gest sacs ( 11x11mm & 7x7mm) but no yolk sac, and embryo could not be visualised. Their prognosis was a missed abortion.

I did a search on Ovidrel and this revealed that Ovidrel is used for ovulation induction 36hrs before egg collection which was done in my case. The articles I read said women who became pregnant or think they may be pregnant after IVF treatment with Ovidrel must discontinue the use of the drug immediately because it may cause harm to an unborn baby, intrauterine death & impaired parturition!

My question is this, is it possible that Ovidrel could have caused the miscarriage I had? Secondly,under what condition should ovidrel be prescribed for a pregnant woman? I'll appreciate your honest opinion.

Thank you. O. from India.

Answer:

Hello O. from India,

I'm sorry to hear about your miscarriage. Indeed the primary indication for Ovidrel is to induce ovulation when a woman is undergoing ovulation induction with fertility medications. However, Ovidrel, which is HCG, can also be given after ovulation in order to help with implantation and support of the pregnancy. It is not used much for that indication, but some doctors will. The other medications used are also very commonly used in IVF cycles, again to support implantation and the early pregnancy. HCG has not been found to lead to birth defects or increase the risk of miscarriage. The pharmaceutical companies put that warning because of the risks of being sued in the U.S., but that is not clinically true.

At 7 weeks gestational age, the fetus should be nearly developed and will be clearly seen and with a heart beat, so your ultrasound showed that the fetus had not developed. The most common reason for this is that there was a chromosomal abnormality in the fetus, and so the fetus did not develop. At your age, you are at an increased risk of spontaneous chromosomal abnormalities because the chromosomes in eggs are more fragile in older women. This miscarriage was not due to the medications.

In the U.S., the medications you took are given as part of the IVF cycle, and many are started before or during the IVF cycle, rather than waiting until a pregnancy ensues. Most important: If they are going to help the pregnancy, and prevent a miscarriage, they need to be within the body prior to the pregnancy occurring. I don't use HCG in the manner that you were prescribed. I don't personally know any fertility specialist in the U.S. that does but I have read papers by doctors that do. HCG acts in the same way as progesterone does.

I think you just need to keep trying. The fact that you got pregnant on your first try is a very good sign and you will eventually be successful. If you don't trust the treatment or protocol that your doctor has used, then maybe you should find a different doctor to work with. Trust is of the utmost importance in a Doctor-Patient relationship.

I hope that answers your questions.

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

http://www.montereybayivf.com/

Interview on PCOS Challenge Talk Radio Part Two: Insulin Resistance, The Metformin Myth and Infertility

Again, it was a pleasure being interviewed by Sasha Ottey of http://www.pcoschallenge.com/ on her radio show. We covered a lot of ground, although I probably could have gone on for another hour since this is such an important subject for many of you PCOS sufferers out there. You can still listen to the show in it's entirety at http://www.blogtalkradio.com/rss/tag/pcos.rss. We left off in the last blog at defining the characteristics of a typical woman who suffers from polycystic ovarian syndrome. I would now like to touch upon one of the hot topics of the PCOS community:

Insulin Resistance In PCOS Patients

Sasha and I went over how PCOS treatment protocols need to be tailored to the specific individual. There is no "one size fits all" with this particular syndrome. One of the most important points that was brought up during the show was the question of insulin resistance in PCOS patients. There has been a lot of press coverage regarding "insulin resistance" as being the main cause of polycystic ovarian syndrome. This has led to many, many women being misdiagnosed and mismanaged. As a result, there has been a tendency to automatically prescribe Metformin (Glocophage). In reality, only 30-40% of these women have insulin resistance, and only those patients will have some response. Some will resume normal ovulatory function, and others will become more respondent to fertility medications. It will take 6-8 months to see if the medication works and a minimum dosage of 1500mg per day is required.

When is it appropriate to go this route with a patient? The patient must be evaluated for insulin resistance. This is going to be manifest by an elevated fasting insulin blood test, or abnormal glucose tolerance, that is, when the fasting glucose is elevated, a glucose tolerance test is positive or there is a diagnosis of diabetes. In these cases, the insulin level may be low or normal because the long-standing resistance has caused the pancreas to stop secreting insulin. If a patient is not insulin resistant then Metformin or similar medications are not indicated.

Non-Insulin Resistant PCOS Patients

For non-insulin resistant patients the treatment varies,depending on whether a patient is trying for pregnancy or not. For those who are not trying to get pregnant, the dominant male hormones have to be suppressed, female hormone needs to be increased and the patient needs to have regular cycles. This is done through the use of birth control pills because it does all of the above. My preference is a new pill called Yasmin or the lower dosage version, Yaz, because its progesterone, drospirenone, blocks testosterone receptors and so has a stronger effect in lowering the testosterone effects of PCOS. This also replaces the female hormone so that the person does not suffer the long-term effects from a lack of estrogen.

A Tough Journey To Pregnancy

For those women who have PCOS and want to get pregnant the journey gets a little tougher. My job, as an infertility specialist, is to try to get my PCOS patients pregnant. The goal is to get them to ovulate! We use fertility drugs for this purpose, but it varies as to how a patient responds to these medications. The "fertility drug" is actually stimulating the ovary to ovulate.

The first drug we use is Clomid, but it has to be used in higher dosages than normal because of the ovarian resistance that PCO patients have to Clomid. I use it from 150 mg to 250 mg. Another similar medication called Femara (Letrozole)can also be tried. Some Clomid resistant patients will respond to Letrozole. In the patients that do not respond to either of these medications, I use a combination protocol.

Briefly, it entails starting with Clomid or Femara then adding injectable fertility drugs like Follistim, Gonal-f or Bravelle. This "boosts" the Clomid or Femara effect to stimulate a few follicles to grow. The problem with going straight to the injectables is that most PCO ovaries will have a hyper or exaggerated response to the medication, because these ovaries are more sensitive to these drugs, causing the formation and/or ovulation of 10 or more follicles. When that happens the cycle is often converted to an IVF cycle in order to prevent a super-multiple pregnancy to occur, or the cycle is cancelled. With the combination protocol we are trying to give the patient the opportunity to get pregnant using a natural means such as intercourse or IUI. Of course it may take several attempts before pregnancy occurs, since the body has to go through many steps to become pregnant naturally. The medication is just trying to make the ovaries act like normal ovaries.

We have been pretty successful at getting some of our patients pregnant with this protocol. Keep in mind, most PCOS patients are young with fertile eggs. It can be merely a matter of persistance with them, of trial and error with their treatment until success is hopefully soon achieved. But, just like national statistics show that up to 80% of PCOS patients have to progress to IVF, we also see a high number of patients having to go in that direction. The combination protocol is just one option to try to achieve pregnancy through an easier means.

Lastly, Sasha asked me if patients come to me for "damage control"....not only for OHSS (as I blogged on February 20th) but for recurrent miscarriages. It is not really "damage control" but recurrent failures, or looking for a different option. I have seen many, many patients that have been put on Metformin and/or Clomid for long periods of time and not get pregnant. Many of these patients have just been given a prescription with multiple refills and told to take that for 6-8 months. They never get checked to see if they are even responding to that dosage. In some the dosage is slowly increased up to 150 mg but again they are not checked, by ultrasound, to see if they are responding. So, when they come to me, we have to take a more aggressive tact, and the patient gets to the protocol that will lead to success.

I hope with these last couple of blogs and through the radio show, that I was able to help clarify some of the issues regarding Polycystic Ovarian Syndrome, as well as debunk some of the myths surrounding this difficult illness.


Thank you!

Interview on PCOS Challenge Talk Radio Part One: What is PCOS & the Pathophysiology of PCOS

It was a pleasure being interviewed for the first time for on such an important topic, Polycystic Ovarian Sydrome. I would like to thank Sasha Ottey of www.pcoschallenge.com for giving me the opportunity to debunk many of the myths surrounding this syndrome as well as address the infertility issues surrounding PCOS. The title of the radio show was "The Real Deal About PCOS and Your Fertility". It can still be heard in it's entirety at: http://www.blogtalkradio.com/rss/tag/pcos.rss. I would like to take the opportunity over the next couple of blogs to discuss some of the more salient points that were brought up during the interview.

PCOS Is An Ovarian Dysfunction

Polycystic Ovarian Syndrome in a patient is a challenging problem that takes a certain amount of finesse on the physician's part to handle, especially in women who are trying to conceive. We began the interview with a discussion of the pathophysiology of this syndrome. I told Sasha that in my opinion, PCOS is not a very good name for this syndrome, that it is more a description of what the ovaries look like, because in reality it is an OVARIAN dysfunction. The real problem is that the ovaries are not processing the hormones correctly. This causes them to not ovulate and produce the female hormones correctly, and instead the hormone precursors are shifted to production of the male hormone testosterone. We don't know exactly what it is in the ovary that causes this dysfunction.

A Diagnosis Of Exclusion

I addressed the issue of correctly diagnosing PCOS, based on clinical findings. There is not a specific test that can be done. The physician must draw a clinical picture and look at a variety of factors in order to make this diagnosis. It is also a diagnosis of exclusion, which means that other causes such as other hormonal disorders, tumors and genetic abnormalities, must be investigated and ruled out first. The real name for this disorder is "idiopathic hyperandrogenism", which means increased male hormone.

There Is No Typical PCOS Woman

There are many types of women who fall into this PCOS category. In the past, the classic PCOS was a woman that was obese, had facial hair, thinning hairline and irregular menstrual cycles. Now we are finding more and more atypical women presenting with this syndrome, including patients that may be slim, for instance, and it is only when you look at their ovaries with the ultrasound, or see how they respond to ovarian stimulation, or look at their blood tests, that you find they are PCOS. There are even a few that have regular menstrual cycles, and are found to be PCOS when they hyperstimulate from injectable fertility drugs.

Key Indicators For PCOS

What are some of the key indicators? Well, visually, a patient might present with increased facial hair, acne, perhaps be overweight but not necessarily. Blood tests can be done to show an increase in insulin, glucose or testosterone. We can also observe, through ultrasound, how the ovaries look in their pre-ovulatory state where there are lots of small follicles. Also, in most cases, the patient will have irregular or infrequent menstrual cycles. Hormone testing will show a normal TSH, Prolactin, Estradiol, FSH and LH. In some patients there will be the characteristic elevation in LH/FSH ratio. That is the LH level will be significantly higher than the FSH level. In some, testosterone levels will be elevated, but most will be at the high end of normal. In the patients that do not have regular menstrual cycles, the mid luteal phase progesterone level will be decreased, with a level less than 10, indicating that ovulation did not occur. Because there is such deviation in presentations, in most cases only one or two of the criteria need to be present to make the diagnosis.

What happens after the diagnosis and what about insulin resistance? I will go into further detail in my next blog post!

Thank you!

Off Depo Provera But Still No Period, What's Wrong?

Question:

Hello, I am 30 years old and was on the Depo-Provera shot for 3 years during which time I did not have a single period. I had my last shot in January 2008 and still have not had a period. My husband and I would like to start a family in the next 2-3 years and I am getting increasingly worried that this will not be possible. I am also suffering from very bad vaginal dryness (could this be related?)

I am currently doing some voluntary work in Argentina now and it is difficult to see an English speaking doctor. Is there something I can do to help my self in the short-term or should I consider returning home to seek medical advice?

Answer:

Hello T. from Argentina,

I am surprised that you can't find an English speaking doctor in Argentina. Maybe you should look for a Reproductive specialist specifically as most of them do speak English. If you still can't find one, then you should return to the U.S. for consultation.

Certainly, something is not working correctly which is preventing the ovary from ovulating, hence no periods. This is not due to the Depo Provera, since it does not last this long. It can delay periods for 1-3 months but not usually longer. There is something else going on and you need to undergo evaluation. The vaginal dryness is because you are probably not producing estrogen, which occurs with ovulation, and the vaginal gland is estrogen dependent. You don't want this to go on much longer because the vagina will actually begin to shrink and intercourse will be difficult and painful.

In order to get pregnant, depending on the cause of the problem, you need a treatment that will get you ovulating again. There are various options, but it depends on the cause. In the meantime, you might want to consider going on the birth control pill in order to get you cycling again (it overrides the ovaries so is not correcting the problem), which will give you estrogen. Many parts of your body require estrogen. You should be able to get this from a non-English speaking doctor while you plan to return to the U.S. for consultation.

Thank you for writing and good luck!

Sincerely,

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

Premature Ovarian Failure in 38 Year Old - What Are Her Options?

Question:

Dear Dr. Ramirez, I am a 38 year old from Birmingham, UK. After experiencing irregular periods and sometimes having 3 to 4 month absences, my hormone levels were tested and showed my level as 20. I was told that either I was experiencing premature ovarian failure (POF) or an early menopause. The course of action I was given at that time to determine which I had was to take a months supply of hormone replacement therapy. Obviously the bleed at the end would not have accounted for anything but the idea was to see if my periods came back after that. My gyno told me was that sometimes the ovaries can shut down for whatever reason and because of this the pituitary gland is desperately sending out more and more fsh to try and spur the ovaries into action and they are not responding hence the high FSH.

I was told that by taking a month of HRT it will switch off the pituitary gland and give the ovaries a rest from this constant hammering and that sometimes after this rest the ovaries start working again on their own. They did come back for about 3 months and a day 21 progesterone test showed my level as 20 suggesting some kind of ovarian activity.

I was told if I was in POF or menopause the ovaries would not respond to this but because I did get my periods back after the hrt for about 3 months it showed that I had POF, not menopause. I was also told that if I didn't get my periods back then they would be able to confirm menopause with a laparoscopy. My gyno said that because the HRT brought back my periods it showed that I have eggs so I am not in menopause.

Does this make any more sense to you at all? I have now been advised to stay off HRT for 2 months and then just go and get my hormone levels tested again and if my levels show menopausal then go on hrt permanently. I sort of feel as though I was given false hope. Can I still get pregnant?

Answer:

Hello,

The elevated FSH level is definitely concerning. It needs to be confirmed and should have been done on cycle day #2 or 3 of the first available menstrual cycle. If you are not having periods any more, then a random FSH can be done (done at any time in the cycle). If that level is greater than 20, then your ovaries have shut down and you are menopausal. The only difference between that and premature ovarian failure, is POF occurs in women under the age of 40 (as in your case). Otherwise, the net effect is the same. The ovaries have shut down. In that case, you cannot conceive naturally. Having a period is not a sign of the lack of menopause. You can have breakthrough bleeding or dysfunctional bleeding, which are caused by a lack of hormones, not the result of ovulation.

The exact cause of POF is unknown. Most think that it is an autoimmune problem, whereby somehow the body is shutting down the ovary. However, pregnancies have occurred in POF patients from random spontaneous ovulation. The problem is that the ovary is not picking up the FSH so the levels are increased. Fertility medications work by "bombarding" the ovary with increased FSH. The pituitary does not do that. The pituitary sends FSH to the ovary to stimulate ovulation. If the ovary does not pick up the hormone from the blood stream, the level is increased. I tell my patients to think of the ovary as a ball with lots of holes in it. If the holes are plugged up, the FSH can't get into the ovary and hence the FSH levels in the blood stream are elevated. POF is NOT due to the lack of eggs. It is due to the lack of ovarian stimulation/function. In addition, laparoscopy CANNOT diagnose menopause. It is a purely clinical and hormonal diagnosis.

In order to have a period on HRT, you need to be cycled i.e. take estrogen and then progesterone. In a young woman, the best method for HRT and cycling is the birth control pill. DO NOT USE menopausal hormone replacement drugs. It is too low for a young woman and you won't get adequate estrogen replacement. If you are indeed in premature ovarian failure, then you need to take estrogen and progesterone because your ovaries are not making them. The lack of these hormones will have long term detrimental effects. Since you want to get pregnant, then you need to see a reproductive specialist as soon as possible. Sometimes, in the early evolution of POF, the ovary can still be stimulated with HIGH dose FSH, which can lead to pregnancy. You want to be doing the optimal treatment method for pregnancy to ensue if either of these occur. That optimal treatment method is IVF because it performs 7 of the 9 steps required to get pregnant and has the highest chances of pregnancy.

For that reason, I would definitely recommend that you proceed to IVF as soon as possible. As long as your ovaries stimulate and eggs can be obtained (you only need one or two good quality embryos), you would have a 50-70% chance of pregnancy per IVF cycle. There are some IVF programs that will not allow a patient to try with her own ovaries if the FSH level is above 12. I do not have that policy. I don't make decisions for my patients, I only counsel them thoroughly and let them decide what they want to do. In your case, I would encourage you to try with your own eggs as long as the ovaries can be stimulated.

I counsel patients who are POF to also consider freezing some of thier eggs. Egg freezing techniques have greatly improved over the years and can be an alternative method of extending your fertility. It takes approximately four to six weeks to complete the egg freezing cycle, which follows the same protocol as IVF. Two to four weeks of self-administered hormone injections along with birth control pills to temporarily turn off natural hormones. This is followed by ten to fourteen days of hormone injections to stimulate the ovaries and ripen multiple eggs. Once the eggs are retrieved they can be frozen using a slow-freeze method or the flash-freeze method known as vitrification. They then can be thawed, ICSI'd, and the resulting embryos transferred into the uterus. The egg freezing process should be carefully considered, as it is still classified as an experimental technique by the American Society for Reproductive Medicine (ASRM). We have begun to offer this as a service at our clinic.

If the ovaries don't stimulate well, that means your ovaries have shut down or are shutting down. Then your next alternative would be donor eggs, but I would recommend you give it the best try that you can right away. Make sure you choose an IVF clinic that has good pregnancy rates. You don't want to waste your eggs! Good Luck!

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

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

U.K. Patient with Inactive Pituitary and History of Bulimia Trying To Conceive

Question:

Dear Dr Ramirez,first of all I would like to thank you for taking the time to read my question. I'll give you a brief history of my problem. I have a history of anorexia/bulimia which became very serious when I was 18, I lost around 20 kilos of weight in under two months when I was 19 and since then have not had my periods. I am now 27 (will be turning 28 in three months). I also developed bilateral, simple, unilocular ovarian cysts that were removed through laporoscopy when I was 23.

I am 99.99% cured of my eating disorder now, my weight and BMI is normal, but my estradiol levels are extremely low (around 40 whereas they should be around 400 (?) at my age?). All other causes of secondary amenorrhea have been ruled out, I have been thoroughly checked and there is no problem with my ovaries, fallopian tubes or uterus, and the hormonal levels show an inactive/hypoactive pituitary.

It might help to add here, when I was about 24, I had an attack of ventricular fibrillation due to low potassium levels because of all the purgeing. The blood supply to my brain was compromised for about 5 - 10 minutes (if not more). I was wondering if that might have affected my pituitary in some way. I recently got a bone density scan done and I have developed osteopenia, because of the low estrogen levels for so long.

From age 19/20 to 25/26 I have been on and off of contraceptive pills, which were being prescribed to me first to deal with the ovarian cysts, and after the removal of the cysts, as HRT, but at that time my weight and BMI were below normal.I have recently brought my weight to normal (my BMI had been around 18 since last year, and I have brought it to 20 - 21 just recently after being told by my doctor to do so)and I have been put on Prempak C as HRT (one month ago) after being off of any contraceptive pills or anything for more than a year.

My questions are:

1) Will this HRT with Prempak C help awaken my pituitary? so that my periods might become regular on their own? Or will I be on HRT for life?

2) Will I regain my bone density with the help of this treatment?

3) I am married now and we are trying to conceive, could you please tell me what the risks involved would be? I mean will my low bone density be a problem? Will I be able to sustain the pregnancy with my inactive pituitary? Will my condition affect the health of my child?

Thank you so much for your time and consideration. Kindest Regards.

Answer:

I am glad to hear that you are almost cured of your eating disorder. As you know, the worst outcome is death from such a disorder.

The decreased oxygen insult could certainly have affected your pituitary, causing it to become inactive. We have seen similar cases after hemorrhage from childbirth. If that is the case, your FSH and LH levels will be almost 0. You would have what is called hypogonadotropic hypogonadism i.e. the ovarian function would be low because of low pituitary stimulation. In that case, you will need to receive pituitary hormones for the ovary, thyroid and adrenal in order to have a normal body function. If you have normal thyroid and adrenal function now, then you do not have this disorder, only an ovarian dysfunction. Female hormone levels must be checked on the 2nd or 3rd day of the menstrual cycle in order to find the baseline because the levels vary during the cycle. The estrogen level that you report is within the normal limits. 400 is not a normal findings unless you are undergoing fertility treatments. The peak estradiol level in the mid-cycle is around 200-250. If the anorexia was the cause of your lack of ovarian function, then with return of your body to normal, that should return your ovarian function. If it does not, then there could be an inherent ovarian dysfunction as well.

I do not believe in bone density tests. I have NEVER seen a woman have a normal test. Everyone, has osteopenia based on these tests, so I can't give a lot of credibility to the results. That being said, however (my bias#, if you have a lack of estrogen production, you can certainly develop osteoporosis, as well as other problems. For that reason, it is important to have estrogen replacement therapy if you are not producing it on your own. The easiest and best method for a young woman under 45 yo is to use the birth control pill. Menopausal hormone replacement therapy, like what you are taking, is NOT made for young woman and does not give sufficient estrogen for your increased metabolic requirements. The birth control pill is better because it has an increased amount of estrogen.

If you are trying for pregnancy, that is another issue and should take precedent. Of course, you cannot be on the birth control pill if you are trying for pregnancy. Getting your weight up to normal is a good start. If ovarian function does not return on its own, then you will need medication to induce ovulation. Without ovulation, you cannot get pregnant using your own eggs. In that case, you need to see a reproductive endocrinologist to diagnose what needs to be treated (pituitary or ovary) and place you on the correct regimen and hormonal supplementation. Once your pregnancy gets past 8 weeks gestational age, the placenta will produce the hormones that it needs, so you will no longer require the supplements. Your child's health and well being will be independent of this treatment.

I'm sorry for the long reply, and the short reply. I cannot cover all the topic in detail because it would take too much space. What you have is a complex issue, but easy to treat if you are in the right hands. Don't worry.

Follow-up Question:

Dear Dr Ramirez,

I'm extremely thankful for your detailed response, I feel very comforted as well that you understand my situation and also that I understand it better now myself too!

I just wanted to tell you that my FSH and LH is within normal range, so I'm glad it's not hypogonadotropic hypogonadism, which I guess is good news.

Secondly, I'm very happy that it's no big deal that my come density scan showed osteopenia as you say bone density scans are not accurate, but my aunt also got hers done, she's a young 53 yo and her scan showed normal come density. But I feel fine really, no bone pains or anything.

Could you please tell me further that with normal weight and normal eating habits, how long it might take for my normal cycles to start on their own? And if there is anything further that I can do or discuss with doctors here to help me get better?

Thank you very much again.

Follow-up Answer:

Hello Again,

Good to hear that your FSH and LH are normal. Then, we can assume it's an ovarian dysfunction. Normally, I would expect your periods to resume within 4-6 months of achieving a normal weight, but to speed things up, you could go directly to ovulation induction (if you're trying for pregnancy or the birth control pill for three months to kick start your ovary).

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.

Infertility Treated Without Appropriate Testing Equals One Confused Patient & Poor Results

Question:

Hello, I am writing from somewhere in the United States. My husband (35) and I (30) tried to get pregnant for about 13 months with no luck. After initial bloodwork where everything looked good except for slightly elevated testosterone, my doctor put me on Femara. I did day 3 bloodwork to check FSH, which was normal, and then took 2 pills a day for 5 days and checked my progesterone on day 21. It was 0.5. So we decide to do another round of Femara. Both times I had to take provera to start my period. After doing the exact same thing with this round, my progesterone was still 0.5. We discussed that injections would be the next option.

I guess my question is did I do enough before moving to injections? And also I feel like I need to have an ultrasound before doing anything else to check my ovaries, look for blockage in my tubes, etc. Should I request an ultrasound to check for those things or is that something that the specialist will do anyway before starting injections? I just don't want to do the injections unless they are absolutely neccessary. BTW-My doc has finally referred me to an infertility specialist.

Answer:

Your story is one that I don't like to hear because I think you have been mismanaged. You should have undergone a infertility evaluation before starting any medications/treatment, but I know that a LOT of general Ob/Gyn's and Family Practicioners like to go straight to a trial of treatment. A basic infertility evaluation is:

1. Cycle day#2/3 hormone panel

2. Hysterosalpingogram - check tubes

3. Hysteroscopy or Hysterosonogram - check uterine cavity

4. Laparoscopy - check pelvis (optional at the beginning#5. cycle day#21 progesterone level

6. Cycle day#26 endometrial biopsy - check endometrial development

7. Semen analysis

8. Pelvic ultrasound

9. Cervical cultures

Before moving further into treatment, especially injectables, I would recommend that you have the above testing done.

However, if you are going to go directly to treatment, you might want to try high dose Clomid #150-250 mg# first before injectables. Many patients will not respond to Femara but will respond to Clomid. Also, a proper ovulation induction cycle with Clomid, Femara or injectables will use the ultrasound at the beginning of the cycle, before starting medication, to make sure there are no ovarian cysts and get a baseline, then starting from day# 9 or 10, to evaluate the ovaries for #1# response to medication, #2# how many follicles are growing and #3) when to give HCG to stimulate ovulation. This also will help to know when to have intercourse or insemination.

Hopefully, your infertility specialist will advise you better than your previous doc.

Follow-Up Question:

Thank you so much for your response! You confirmed what I was thinking. I plan to request everything you listed in your steps 1-9 when I see the specialist. So I know what I'm talking about when I see the doctor, what is the reason for the pelvic ultrasound, cervical cultures, and checking the uterine cavity?

Also, I failed to mention in my first question that when I went off the pill I had normal periods for 2-4 months and then it started getting longer and longer in between periods (30-50 days). Then this past July 6 I had my last period and haven't had one since (except when taking povera for that purpose). I first started having my period at 13 and from age 13-19 had perfectly normal periods. I went on bc at 19 and stayed on them until right before my 29th birthday, and of course had very regular periods during that time. So I know that it looks like basically I'm just not ovulating, but any ideas on what else might be going on? I know it could be lots of things, but I'm just worried and seeking as many answers as I can before seeing the specialist next week.

Thanks so much

Follow-Up Answer:

Without the right tests I cannot comment on your irregular periods. I'm sure the infertility specialist will do a proper evaluation. Each test evaluates for the specific steps in the process your body goes through in order to get pregnant.

1. Ultrasound - to look for ovarian cysts, tumors, uterine fibroids, enlarged tubes or other structural abnormalities in the pelvis.

2. Cervical cultures - check to make sure you don't have any STD's or bacteria that might affect/kill the sperm.

3. Hysteroscopy - the uterine cavity is the critical place where implantation takes place. It needs to be completely normal.

You have to undergo the testing I mentioned previously to find out why your ovaries may not be working properly, hence probably, the irregular periods. It could be an ovarian problem, pituitary problem, thryoid problem, hypothalamic problem, etc. Your specialist will work with you to figure things out.

Good Luck and be sure to always take a pad of paper along for your question & answers while you progress with your evaluation.

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com

100 POSTS!!! And More To Come!

Dear, faithful readers and new visitors!

Since I started blogging about Women's Health & Fertility back in 2008, I didn't realize how much I would enjoy communicating through the huge network that we call the internet! Back then, I thought it would be enough to post general articles regarding infertility and gynecology. At about the same time, I decided to become a volunteer expert on About.com's All Experts Infertility site. There, I began receiving questions from all over the world regarding women's and men's infertility as well as gynecological issues. I had to limit my questions there to five a day because they were coming in too fast, and those who know me know that I like take my time with some questions and be thorough with my answers. To date, I have answered 1,685 questions from around the world.

I soon realized that this may be the way to go with my blog format. I saw that the same problem that plagued a reader in Copenhagen was also relevant to a reader in Australia or here, in the United States. I decided to change my format and began to post Q & A's from my blog readers as well as some of the more interesting ones that I receive on the All Expert's site (always with the person's permission, of course). It is always a pleasure to see where the people who ask me questions come from but more surprising to me, with over 8ooo page views in the last few months alone, where all my visitors come from! Now I am on Twitter, Facebook, and Networked Blogs as well, meeting more people who are involved in the ART field as well as gaining new followers, all of which makes me feel more connected and proud of what I do as an infertility specialist.

Since I added the visitor statistics widget to the blog a few months ago, it's been amazing to see how many people actually visit the blog. (Prior to installing the widget, I thought no one did!) Here are some statistics that might interest you:

My top ten popular blog entries to date:

"Bleeding After Embryo Transfer"

"Secondary Amenorrhea...Low Estrogen?"

"PCOS Patient Beginning IVF Treatment.What Questions Should She Ask Her Doctor?"

"Empty Follicle Syndrome"

"Post IVF Transfer Pain:Implantation Pain or Ectopic?"

"Three Miscarriages and HSG Shows Blocked Tubes"

"Estrogen Supplement For Thin Lining"

"No Period, Low BMI Can Equal Hypoganodotropic Hypogonadism"

"Prolactin Level and Clomid for 30 Year Old TTC'r"

"ELONVA, A New Sustained Follicle Stimulant Just Approved In Europe!"

Recent Visitors From Far & Wide:

Mumbai, India

Perth, Australia

Parma, Italy

Pound Ridge, New York

Gdansk, Poland

Sofia, Bulgaria

Cairo, Egypt

Zagreb, Croatia

Krefeld, Germany

Kamloops, Canada

Rotterdam, Netherlands

Exeter, United Kingdom

Budapest, Hungary

Bursa, Turkey

Sligo, Ireland

Kritianstad, Sweden

Rehovot, Israel

.....To name a few!!! Thank you to all of you for following my blog. I want to commend each and every one of you for taking action with your health issues and for seeking out the right kind of information that will possibly make a difference in your lives and the lives of those whom you love. It is my personal pleasure and privilege to assist you in whatever way I can, given the limits of the written word and the distance from which you communicate.

I am always available to give general responses via this blog & the All Experts Site. I am also available as a Personal Physician Email Consultant for more complicated, in depth responses to your concerns.

Regards to you all,

Edward J. Ramirez, MD, FACOG

The Fertility & Gynecology Center

Monterey Bay IVF

ejrmd@montereybayivf.com

Patient From India With 2 Ovarian Cysts For 5 Years: Cystectomy or Ovarian Wedge Resection

Question:

Hi, doc.

I have 2 cysts of size 2-3 cm on my rt ovary since last 5-6 years. My gynae has advised for analysis and removal of the cysts laparoscopically. I would like to know which is the best procedure for the same and wedge recesection is good or any other procedures are now available for this.

I am 26 years old , and I'm writing from India. Thanks for ur help. Regards.

Answer:

Hello and thank you for your question.

Certainly if these cysts have been there for the past 5-6 years, they should be removed! I would have done that years ago. It is most likely that these are benign tumors of some form.

However, the only way to be sure is to remove them and analyze them pathologically. Laparoscopy is the best way for removal if done by a doctor with experience. I would only recommend removing the cysts (cystectomy), not wedge resection or removal of the ovaries. The latter two will affect your ability to become pregnant in the future by increasing the chances of scar tissue formation. The benefit of laparoscopy, as opposed to laparotomy (open procedure) is that there is much less scar tissue formation.

I hope this answers your questions.

Sincerely,

Edward J. Ramirez, M.D.

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com

Post IVF Transfer Pain: Implantation Pain or Ectopic?

Question:

My wife says that she was experiencing sharp pain yesterday (10 days after FET) on the area near right side of her stomach. She experienced the pain only yesterday and that was during a 3 mile walk. Today she says she feels some pressure near the right ovaries.

I'm concerned. Could you please let me know your suggestions? Thank you.

Answer:

Thank you for your question. This could be normal, but the main concern would be an implantation that occurs in the tubes called an ectopic pregnancy. I wouldn't jump to this conclusion but it is a possibility. This could also be what we typically call "implantation" pain. Please see my overview of what happens after the IVF transfer including pain and bleeding here: "After Your IVF Procedure".

Let me go into more detail regarding both possibilities.

All patients with infertility are at increased risk for an ectopic, even with IVF. The incidence is low but it occurs. At 10 days post transfer I usually have done my pregnancy test. This can give a better idea of how the pregnancy is doing and whether or not an ultrasound will show anything. Generally, the BHCG level has to be over 3000 to see a pregnancy in the uterus and if it is not there with that level, then an ectopic pregnancy as to be assumed. At only 10 days post transfer, it is unlikely to be an ectopic, however. These usually do not become symptomatic until 6-8 weeks of the pregnancy. At this point, it is probably not anything serious.

Pregnancy can also induce other kinds of pains and discomforts. We call them implantation pain or growing pain. Sometimes women tell us that they "feel" a sharp pain within a week or two post transfer. I cannot discount that sometimes the women who complain of this pain (and I have IUI patients who tell me the same) do have a positive pregnancy test. Another possibility on the right side, of course, would be appendicitis. You can still get other illnesses despite trying for pregnancy. However, appendicitis, is progressive and does not come and go. Once the pain started it would progressively get worst. That doesn't fit your wife's scenario. Without further evaluation it is hard to know what is going on. You should probably bring this up with your doctor.

As a side note, if your wife is actively trying to get pregnant using IVF or FET, then I would not recommend a 3 mile walk right now. She should limit her activity to more sedate activities. A short normal walk would be fine, but power walks are not recommended as are heavy exercises like aerobics, karate, gymnastics, running, etc.

Good luck with your cycle and I hope that this will be a success!

Sincerely,

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

PCOS Patient Beginning IVF Treatment, What Questions Should She Ask Her Doctor?

Question:

I have PCOS and I've started IVF (in vitro fertilization). I have concerns because I don't really understand what is going on. They say they want my estrogen level up and that it is going in the right direction but they keep increasing my medication. Why? How can I tell if it is working?

I have started since January 22nd. Is it normal to continue and what questions do I ask my doctor to see if my chances remain good?

Answer:

Thank you for your question, it's always good to know exactly what is going on so don't hesitate to ask your doctor as many questions as you can. Take a pad of paper with you and write down the answers if you need to.

Let me begin with our protocol at our clinic for patients such as yourself. With PCOS patients we have to be very careful because if you over-respond, you could develop and illness called ovarian hyperstimulation syndrome (OHSS). Many IVF programs use a protocol called a "step-up" protocol whereby you start on a lower dose and it is slowly increased based on your estradiol levels and ovarian response. They should be doing ultrasounds at the same time to see how many follicles are growing and what size the are. Once it looks like you are stimulating, the dose is usually kept constant until the follicles reach the appropriate size for retrieval (18-24 mms).

If you started on the 22nd of January, your cycle is definitely going kind of slow. Most patients will respond within 10-16 days. I would presume you are getting closer.

If your doctor is not explaining these things, then you need to be more insistant that you want an explanation at each visit. Most doctors, or their respective nurses, will then explain how things are going and what the goal and timeline is. We can usually predict, within a day or two, when you will be ready to retrieve.

What you should ask is:

1. How am I doing?

2. Am I responding to this dose or protocol? Are my follicles increasing?

3. How many growing follicles do I have?

4. When are you expecting me to be ready to retrieve? Transfer? Explain that you need to plan the date.

5. What if I have too many follicles? Will you cancel me? Do you Coast? Will you trigger with HCG or Lupron? (Lupron is what I use because it has a shorter duration of action and has been shown to decrease the incidence of OHSS if there are too many follicles and the estradiol is too high (over 4000).

6. What is my estradiol level? (the goal is to have a level of 2000-4000 at the point that the follicles are ready for retrieval. If the estradiol level is over 4000, then the risk for OHSS is higher).

I hope this gives you enough questions to ask for now. Keep informed and stay in touch! Good luck!

Sincerely,

Edward J. Ramirez, M.D.

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF program

http://www.montereybayivf.com/

Monterey, California, U.S.A.

44 Yr. Old Has Clomid Challenge Test

Question:

Hi Dr. Ramirez,

I'm 44 yrs. old and recently had a clomiphene citrate challenge test with two ultrasounds. I took 100 mg. of Clomiphene Citrate from days 5-9.

The results are as follows: Before Clomiphene Citrate: FSH 5.5, Estradiol 131, with a baseline vaginal ultrasound showing one follicular at 4.2mm in right ovary(I believe) and endometrial lining 4.39, could not locate left ovary. Then, after taking last cc pill another blood test on 11/14 showing FSH of 27.6 and Estradiol of 90. Then, another ultrasound on 11/16 showing two follicles, 10.0 mm, 10.2 mm, in right ovary and 6mm in left ovary, with endometrial lining of 8.2 mm.

What are my options? Should I pursue taking HCG shots or other fertility drugs using my own eggs? Should I pursue donor eggs? My sister is willing to donate her eggs, she recently had a normal, healthy baby boy 10 months ago and she is 41 years old. Thank you in advance for your answers.

Answer:

Thank you for your question.

The purpose of the Clomid challenge test is to evaluate if the ovaries will respond well to stimulation. The Clomid is used for stimulation. A "positive" test is when there is an elevation of the FSH level on cycle day# 11. This shows that there is significant resistance to stimulation and the ovary will probably not stimulate well. The only way to overcome the "age" factor is to get lots of eggs from the ovary. If only a few eggs are retrieved, then the chances for success decrease significantly. Your ovaries are still working, which means that you can be stimulated to get a few (1-3) eggs, but the chances for pregnancy are not good. I do have patients try this but it is with this clear understanding. Most patients do want to try at least once on their own. As I tell them, there are always exceptions to the rule and you only need one good egg, so from an emotional and psychological point of view, it might be worth the try. Expect the worst, however.

Donor eggs is probably your best chance for pregnancy from a statistical point of view. Although your sister was recently successful, she is not the best donor candidate. IVF pregnancy rates are very dependent on the eggs retrieved. If you are going to use a donor, you want the best eggs that you can get. For that reason, we recommend donors that are under the age of 35 years old. The other problem with older eggs is the risk of genetic abnormalities, such as Down's syndrome. You would have a risk of 1:50 for this syndrome with your sister's eggs. I am sure that both you and she would be crushed if that happened. Therefore, I would recommend that you consider an anonymous donor under the age of 35.

I hope this helps,

Sincerely,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com