Similar IVF Protocol But Different Results: Why?

Question:

Hi Dr. Ramirez,

I'm back again with a question about my recent IVF (second one). This IVF (in vitro fertilization) cycle we did the same protocol as last time (antagonist) but started off at a higher dose of Gonal-f based on my response last cycle. This cycle we started off at 300iu gonal-f and 75iu menopur whereas last cycle we started with 225iu gonal f and 75 IU menopur but had to increase to 300 IU gonal f after day 4 showed an E2 of only 90. Both cycles I started out with similar AFCs of 10 and 12 at suppression check. My usual AFC is between 16-20. Last cycle it seemed that I recruited more follies along the way and ended up with an E2 of 3030 and 23 eggs retrieved (17 of which were mature based on icsi and conventional fert rates as we did 50/50 split fertilization). This cycle my E2 was 2100 at trigger and they retrieved 12 eggs (still waiting on fert report today but we are doing all conventional fertilization).

My question is why did I have such a different response this cycle given that we started off at a higher dose this cycle compared to last? Last cycle we went up from 225iu gonal to 300 IU gonal at day 4 and stayed there until trigger. this cycle we started at 300iu gonal and stayed there until we added ganirelex on day 7. At that point my E2 stalled and do they increased my gonal f to 375iu gonal f and kept me there until trigger.

As always thanks for your advice/insight. S. from the U.S.A.

Answer:

Hello S. from the U.S. (Virginia).

The human body is not a consistent nor predictable structure so I can't explain why your response is different.  I have always explained to patients that have low response to stims that the ovaries can react differently each cycle and your experience is a case in point.  That being said, I would not have increased your dosage since your stimulation was so good the previous time and you bordered on entering OHSS territory.  In any case, IVF is not a contest where the person with the highest number of follicles or eggs wins the prize.  The goal is to find 1 or 2 perfect eggs that will lead to perfect embryos and a successful pregnancy.  So despite the fact that you stimulated less, that might be a better thing.  Bottom line is you only need one good one.  Also, there have been some studies showing that when a patient stimulates hard with lots of follicles, sometimes the egg quality suffers and the pregnancy rate drops.  This is especially true in PCO patients.  In those patients, our preference is to stimulate less and get fewer follicles.

So, in any case, as the saying goes: "I don't think you should sweat the nitty gritty" i.e the fine details.  Hope for the one perfect one.  That is the goal.

Good Luck!

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

Monterey, California, U.S.A.

New 2011 Study Questions Routine Metformin Use In All PCO Patients

Dear Readers,

A recent study published in the medical journal "Clinical Endocrinology" Frans S., Clinical Endocrinology. [Oxf], 2011; 74:148-151, brings into question the routine use of Metformin in PCO (polycystic ovary) patients. The study showed a small improvement for ovulation but not clearly better than weight loss. It also showed no improvement in pregnancy outcomes, except in patients with diabetes. It showed no benefit or improvement in hirsuitism, acne or hair loss resulting from PCO (polycystic ovary). Alone, it showed no improvement in pregnancy rates but did show some improvement in combination with Clomiphene (Clomid), yet there was no increase in the live birth rate. The authors therefore concluded that there was no real evidence to draw any conclusions regarding Metformin’s treatment in PCO, and that its only benefits may be in patients with diabetes or impaired glucose tolerance.

As you have seen through reading my blog, PCO (polycystic ovaries) is a very common problem among infertility patients. I have participated in numerous posts, have had several on-line, television and radio discussions regarding this problem, and I have given my opinion regarding the diagnosis, management and treatment options associated with this problem. One of the main problems that I face, almost on a daily basis within the medical community, is the mistreatment of PCO patients with Metformin. I see this commonly done by second tier providers such as Nurse practitioners and Physician Assistants, as well as, Physician providers such as Family Medicine practitioners and general Ob/Gyns. Many of these providers have mistakenly latched onto Metformin as the ultimate drug for the treatment of PCO, much the same as they have latched unto Clomid is the ultimate treatment for infertility. As a result, they automatically treat all suspected PCO patients with Metformin. This practice is unfounded and this recent study shows that treating all PCO patients with Metformin may be misguided. In fact, it brings into question whether there is any benefit at all.

I would not say or conclude that there is no benefit, but there is selective benefit. There are certainly studies that show benefit in a sub-population of PCO patients, just as this study shows benefit in patients with impaired glucose tolerance. These are patients that have been found to have an elevated insulin level or diabetes from insulin resistance. Not diabetics who do not produce insulin. Decreasing this level, either through weight loss or Metformin, will often return the ovary to normal function in these patients, or make their ovaries more responsive to fertility medications.

But clearly, it does not benefit all PCO patients and therefore should be selectively used, not, as many of these aforementioned providers do, used for all PCO patients. There is not a good way to know exactly which patients will respond or not respond to this medication, but here are three requirements that I abide by.\:

*First, a fasting insulin level should be taken to see if it is elevated. If not, then skip the Metformin.

*Secondly, if Metformin is going to work, it can take several months, some authors state 6-8 months, to see if there is any effect. The effect should be noticed by resumption of normal ovarian function i.e. regular menstrual cycles or decrease of the fasting insulin levels.

*Thirdly, a minimum dosage of 1500 mg per day is required. I have seen some patients taking only 500 mg. That is a total waste. If you are going to use this medication then you have to use it in the clinically effective dose.

The exact cause of PCOS is not understood. Some thought it was elevated insulin, but that clearly is not the case in all patients. Some thought it was increased weight, but that also is not the cause. It is clearly some inherent pathway within the ovary that is dyfunctioning, and it is clear that there are many forms of this disorder. It may be a multi-factorial condition where there is not one presentation or one treatment. In is imperative that patients and Physicians understand this and not latch onto one treatment modality for all. Treatments have to be specific to the patient.

Which brings me to my final point regarding the patient-doctor relationship:

This is exactly why Medicine can never be dictated by a cookbook method. People are all different, present differently and must be treated differently. We call that the art of medicine, and this is what makes some doctors better or worse than others, makes some doctors decide to specialize, an option which, unfortunately, is quickly disappearing from medicine as we look to less trained and less costly practitioners.

Edward J. Ramirez, MD, FACOG
Medical Director
The Fertility & Gynecology Center
Monterey Bay IVF
http://www.montereybayivf.com/

Norwegian Patient With Arcuate Uterus & PCOS Wants To Know: Is IUI A Good Option?

Question:

Hi, I wrote before. I have an arcuate uterus and polycystic ovaries. My hormonal results were fine as well as my test for cervical cancer. My husband and I have decided to go for artificial insemination since we have been trying to have a baby for 4 years. I have never gotten pregnant. My question will I qualify for that and what does the whole process involve? Is it less expensive than in-vitro? Thank you, N. from Norway

Answer:

Hello N. from Norway,

IUI (intrauterine insemination) is certainly an option for you, especially if you have been found to be completely normal except for ovulation, the polycystic ovarian syndrome. (As far as the "arcuate" configuration to your uterus, this is generally considered a normal variant and does NOT cause infertility, do not be concerned with that.) Because IUI is a "natural" treatment method, meaning your body has to go through all its natural steps to achieve pregnancy, each of these natural steps have to work properly to get pregnant. Therefore, it can take several IUI attempts to achieve pregnancy, just as it would take several months of trying normally for a regular couple. The pregnancy rates are age dependent and range from 3%-24%. The maximum pregnancy rate is 24% in a woman under the age of 30. It decreases from there due to age factors.

The basic problem with PCOS (polycystic ovarian syndrome) is that the ovary does not function correctly and therefore does not ovulate on a regular basis. Therefore, any infertility treatment that you do will require that you take fertility medications in order to induce the ovaries to ovulate. With IUI the goal is to get you to ovulate three eggs per month (that is what increases the pregnancy chances). Ultrasound is then used to gauge your progess and time when the insemination should be performed. Basically, when the ovulatory follicles reach appropriate ovulatory size (18-24 mms), then a trigger such as HCG is given to trigger ovulation. I do two IUI's at 24 and 48 hrs from trigger but some clinics will only do 1 IUI at 32-26 hrs. There are pros and cons of each and I believe that two IUI's are better despite the fact that studies have shown that they are equivalent (I'm not sure that the studies were good enought to show a difference). IUI cost tends to be much much less than IVF because there is less technology used. If you don't achieve pregnancy by four attempts, then the pregnancy rates decrease dramatically so it is recommended to proceed to IVF from there.

One of the difficulties with PCOS patients is that there ovaries are very difficult to stimulate, so that many (80-85%) end up proceeding to IVF. With the simple meds such as Clomiphene or Letrozole, many PCOS patients do not stimulate at all despite the highest dosages, whereas, with the injectables (gonal-f, Follistim, Bravelle, Menopur), they tend to stimulate too much and produce too many eggs necessitating cancellation of the cycle. With natural treatments like IUI we don't allow more than three ovulatory sized follicles because we cannot control how many get to the uterus, which would increase the risk of a super-multiple such as 5, 6 or 8 implanting. This is a situation you most certainly would want to avoid!

I hope this gives you the information that you desired. Thank you for writing me from Norway!

Good Luck,

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.

"Ask The Fertility Specialist About PCOS & Your Fertility" on PCOS Challenge BlogTalk Radio Show

I will be interviewed by Sasha Ottey next week on her hour-long internet radio show and I cordially invite you to tune in to what will be an interesting discussion on PCOS and how it affects women who are trying to conceive. To quote the show's host, Sasha Ottey: "It is estimated that more than 1 in 10 women are afflicted with Polycystic Ovarian Syndrome (PCOS), yet most people are uninformed about it and have no idea that such a condition exists. Women with PCOS experience a combination of symptoms that can lead to serious conditions such as heart disease, diabetes, and infertility. In fact, PCOS is a leading cause of infertility in women." Ms. Ottey is the founder of PCOS Challenge, with a very popular website as well as a television series on PCOS that will be airing this fall. PCOSChallenge.com has a wealth of information as well as forums for support...well worth visiting!

The show will air on Wednesday, September 29th at 3 pm PST, 6pm EST on BlogTalkRadio.com . You can access the internet radio show's main page by clicking here: PCOS Challenge BlogTalkRadio.com's main page . You can sign up to attend, send in your questions or simply call in when the show is in progress with any questions you may have and I will try to answer them!

Looking forward to hearing from some of you!

Edward J. Ramirez, MD
MontereyBayIVF
www.montereybayivf.com

"What FET Protocol Do You Use For Difficult PCOS Patients?" UK Patient Asks

Dear Dr Ramirez,

Firstly, thank you so much in advance for taking the time to read my question.

Brief History: Dx with PCOS at 17 y/o. HSG clear. My husband has severe m/f, so our only chance of conceiving is through IVF with ICSI. On my fresh cycle in 2008, I had 30 eggs retrieved and due to OHSS, couldn't have an Embryo Transfer. We had 13 embryos, all of which were frozen at the 2PN stage. I have gone through six FET cycles since, but only got to transfer three times, b/c the drugs used to suppress my ovaries (ProstapSR, Buserelin, Synarel) have actually stimulated my ovaries, leading to OHSS a further three times!

My treatment is in the UK and I cannot switch clinics b/c a) my treatment is free and b) since it's free I can't choose where to have my IVF/FET's. The Drs at my clinic have put their heads together to try to come up with an individualized protocol for me, since I keep suffering these rare responses to the suppression meds. I am naturally frightened and sceptical about this new protocol since it hasn't been tried and tested in the UK as yet (but apparently it has in other countries with good success for challenging PCOS patients).

The new protocol would not involve the usual suppression medications. On day 3 of my period, I would inject a long acting Cetrotide shot (sub-q) and also commence 6mg Progynova (estradiol valerate). On Day 5, I would commence daily Cetrotide shots, whilst continuing daily with the Progynova. All in all, this protocol should only take around 13days, then I would commence Progesterone, 3-4days before Embryo Transfer. I am terrified of hyperstimulating again. Is this likely to happen with the Cetrotide at all? Have you had any PCOS patients who have ever responded like I have to suppression medications?

If you were my Dr (I wish you were :D ), what protocol would you suggest for a FET? It may be helpful to add that I have always been a slim PCOSer (BMI 21) and have an AMH of 98.5. I also got pg on our first FET with twins, which I sadly miscarried at 8 weeks. My subsequent two transfers resulted in a negative beta. Thank you so much for reading and for any input you may be able to give! G. from the U.K.

Answer:

Hello G. from the U.K.,

I have never heard of such as thing as OHSS with an FET cycle. I'll have to do some research on that and see if that actually happens. If not, your docs might want to write your case up as an unusual case. Since you have been using GnRH "agonists (stimulators)" in your previous cycles, it sounds like maybe the dosages were not high enough to suppress the hypothalamus (which is what they are supposed to do and prevent ovarian function), but instead stimulated FSH production and ovarian stimulation leading to the OHSS.

I think the change to an "antagonist" is certainly the best way to go. I converted to using the antagonist, Cetrotide and now Ganerelix, over 5 years ago (mainly because it is less injections). I have not used it with an FET cycle (because it is more expensive), but it can work just as well with the protocol you have outlined. The antagonist will definitely suppress any ovarian function, so you should not be able to mount an OHSS response. This is definitely a good plan.

I thank you for the compliment :) and wish that you could be my patient as well. For many reasons, such as the fact that some like you can get IVF for free where they live, patients feel that they are stuck in the clinic near their home. This cannot be further from the truth. I have a patient from Serbia and South Korea in my IVF cycle this month. I have patients come from out-of-state, one from as far as Montana, which is like the difference between the UK and Poland. You can travel to the best center to do your IVF, thereby saving you years of frustration & grief. I had one patient who failed five times at a Los Angeles center only to succeed the first time with us. It is not that difficult to do or arrange IVF afar. There are additional costs involved, which is the biggest factor, but heck, you could plan a vacation at the same time. The IF community calls this "Reproductive Tourism" or "Cross-Border IVF", I believe.

An IVF cycle can be done so that you only have to come here for the minimum necessary time, which for an FET cycle would be 1 week or less or 10 days for a fresh cycle. Also, remember the old adage, "you get what you pay for." Free cycles are all well and good, but as you mentioned above, you are stuck with one center, one protocol, one embryology lab (and there quality can differ greatly), governmental restrictions and that is unfortunate. In the U.S., particularly in California, we have few restrictions and can do embryo donation, donor egg, donor sperm, frozen eggs, surrogacy, and are given leeway on the number of embryos we can implant. I wish that I could just outfit a 747 jet with an IVF clinic and jet all over the world where patients want to see me. I think that would be fun as well :D !!!

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.

Possible PCO Patient Adjusting IVF Antagonist Protocol For Fear Of OHSS: Decrease Gonal-F Dosage?

Question:

I am about to start my first IVF protocol (today is CD2). I am concerned about the recombinant FSH dosage prescribed and would like your opinion regarding appropriate dosage. I believe I am at higher risk for OHSS for several reasons (described below), however my recent ultrasounds are not showing definitive signs of PCO. Here is the protocol prescribed by my doc:

No pre-cycle BCPs (they make me very ill)
CD2: gonal-f 225
CD3: gonal-f 225
CD4: gonal-f 150
CD5: gonal-f 150
ultrasound on day 6
addition dosing determined following this ultrasound
Gonarilex to prevent premature ovulation

I called the doctor today because I was nervous about taking the first two days of 225IU gonal because of the risk of OHSS. After very little discussion, he switched me to 150IU for 4 days.

The difference between 225 and 150 is a big change. I wonder if I will get good results with a dosage that is this low. What is your opinion? I feel like there might be some sort of middle ground that is more appropriate? I would appreciate any thoughts. I would like to get the "best" results without complications of OHSS.

I believe I am at higher risk for OHSS than the normal woman for many reasons:

1) my ultrasound yesterday (on CD1) shows 9 follicles on right and 16 on left

2) I responded well to low doses of gonadotropins (6 IUI cycles some with letrozol/femera at 5mg/day?, others with clomid at 25mg/day all cycles gave 3-5 mature follicles on CD12),

3)I am petite (5'2", 100 lb.s)

4) in 2006 a doctor told me I had PCOS based on ultrasound results, a history of severe PMS, and moderate acne(two additional doctors I consulted with gave no diagnosis - I am not hairy or pear-shaped)

5) cancelled IUI due to elevated estrogen associated with a small complex cyst on cd2 (and another very uncomfotable IUI cycle when a different OBGYN proceeded with an IUI when I had a cyst at the start of my cycle).

6) grandma had type 2 diabetes

7)early male baldness runs in my family.

Answer:

Hello J. from the U.S.,

First of all, I have to caution you about trying to second guess your doctor. Sometimes that may not be good. I would presume that your doctor had a logical reason for selecting your protocol.

You were originally scheduled to be on a 3 down protocol (75IU x 3 for two days then decrease). That is a standard protocol and is on the low side. Because of your concern, your doc decreased you to 150IU and will make adjustments based on the response. The only down side to the lower protocol is that you may not recruit as many follicles as the higher dose, but there is no way to know this when it is the very first cycle. In most cases we determine the protocol based on an educated guess. The adjustment at CD#6 is still early enough to increase the dosage and recruit more follicles if necessary, and if you are indeed a PCO, then you will already have an increased number of follicles and the decreased dosage will be safer for you.

I am glad to see that your doc is using the "antagonist" protocol with ganerelix. I am a firm believer in this medication and its ability to decrease the risks of OHSS. With the antagonist, instead of using HCG to trigger ovulation, Lupron can be used to trigger and because of its shorter half-life, the risk of OHSS is dramatically reduced. This is the protocol I use with my PCOD patients to reduce their risk, in addition to careful monitoring, lowered FSH dosage, Drifting (if necessary) and Coasting (if necessary). My goal is to keep the Estradiol level less than 4000 at the time of trigger. With this protocol, I have had no incidence of OHSS in my center for the past 5 years. Most the reasons that you gave for being PCOD are not valid criteria, but my concern would be the same as yours based on the high number of antral follicles seen on ultrasound. I treat patients as a PCO patient if they have PCO-appearing ovaries even if they don't meet the strict criteria for PCO. And, I find that they do stimulate like a PCO ie have a high number of follicles (>25).

In your case, I think that being safe is better than being sorry and the lower dose is probably the way to go. I call your new protocol a 2up protocol and it is a standard protocol that I use with my PCO patients. I check estradiols at CD#5, however, and adjust from there.

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.

The Fertility Chase: PCOS - Polycystic Ovarian Syndrome and Fertility

Back in May 2010, we were privileged to make a movie with The Fertility Chase which aired on the We Network. This short, 7 minute movie is an intimate look at how PCOS, polycystic ovarian syndrome, has affected two women who happen to be patients of our center. They frankly discuss their frustrations and pain over their struggle with infertility. We are grateful to them for having the courage to step forward to talk about this distressing syndrome with the hope of letting others know that they are not alone and that there is hope. In addition, you will have the opportunity to meet me! Perhaps my brief overview of this syndrome will clear up some misconceptions and pave the way for those of you who are struggling with this disorder to begin to formulate a treatment path that will aid in bringing resolution to your problem.

One moving quote from the movie by our patient, Brandi: "...Being a family doesn't mean you have to have children. You're a family when you're a daughter, you're a family when you're a wife, and you don't have to have children to be a family. It's been comforting to know that, hey, I'm not the only one..."

September is PCOS Awareness Month. Other worthwhile sites to look at for more information include: PCOS Challenge, founded by Sasha Ottey (http://www.pcoschallenge.com/) and the PCOS Association, founded by Christine DeZarn (http://www.pcosupport.com/).

Very Confused Woman With PCOS & Endo, Who Is Anovulatory: TTC & Not Getting The Right Treatment

Question:

I was recently diagnosed with PCOS, (after many years of suffering with endo also) and we've been TTC for 2 years. I have been taking 1,000mg/day of Metformin to help control the insulin resistance. I have long anovulatory cycles and was recently seen by my doctor who wants to put me on Ortho-tri-cyclen to help get my cycles back under control. She said that women with PCOS have too little of estrogen and that is why I am anovulatory.

I have always learned that women with PCOS are estrogen dominant, so now I'm very confused. Which is it? Also, will I see ANY benefit from the birth control pills, after I stop taking them? Will it help to make me ovulate? I have not ovulated since November, which of course makes it difficult to TTC without that important factor.

Thank you in advance. L. from the U.S.A.

Answer:

Hi L. from the U.S.,

First, you are taking an inadequate dose of Metformin, if you have been found to have insulin resistance. The recommended dose is 1500 mg per day.

Secondly, your current doctor is incorrect in that OCP's (birth control pill) is only a treatment to regulate the cycles. If a woman with PCOS is not intending to become pregnant, then the treatment of choice is to use the birth control pill. This is the recommendation that medical doctors in my field will give you. That is mainly because the pill/patch/ring are made of estrogen and progesterone and override your ovaries. It will do nothing for your fertility. Also, the reason why you are anovulatory is because PCOS (polycystic ovarian syndrome) is an ovarian dysfunction that leads to low estrogen, high testosterone levels. It is NOT the other way around.

Once you stop the OCP's you will go back to your normal anovulatory cycles. If you want to get pregnant with PCOS, you need to use a medication that will induce the ovaries to ovulate such as Clomid, Femara or injectable medications. I would recommend that you see a fertility specialist, who understands this problem better and won't waste your time, so that you can get pregnant in the shortest period of time. 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 such as the ones mentioned above 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.

Also, keep in mind that endometriosis is also a cause for infertility so in essence, you have two problems that are preventing you from getting pregnant.

Please read further on PCOS in some of my earlier blog posts. There is one in particular with a link to a radio interview that I did on the subject. See the February blog post: http://womenshealthandfertility.blogspot.com/2010/02/interview-on-pcos-challenge-talk-radio.html

Good luck,

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.

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!

Three Miscarriages and HSG Shows Blocked Tubes

Question:

Dear Dr. Ramirez,

I have had three miscarriages in the last couple years and have been to two fertility clinics. I have had $8,500 dollars worth of tests done and all the male testing. I was told that my tubes are blocked by one doctor and the other one says that there is no way that they can just one day unblock. I was but on meformin and told that I have pcos. I read on pcos and it said that with Clomid a pregnancy is possible. What is your opinion on this?

Answer:

Thank you for your questions. You've thrown quite a lot of different things at me.

There are several issues that you have brought up. Let me see if I can answer them one at a time and give you the information that you are requesting:

1. Three miscarriages-There is an almost 40% chance of miscarriage with every pregnancy. Most are caused by a spontaneous chromosomal abnormality that occurs when the egg is dividing into an embryo. These usually lead to miscarriage within the first 8 weeks of the pregnancy. These patients will eventually be successful. A small percentage of recurrent miscarriages occur because of uterine abnormalities, hormonal abnormalities, immunological abnormalities, infectious diseases and health events like diabetes.

2. Blocked tube - Blocked tubes are evaluated by a test called an HSG (hysterosalopingogram). It is an x-ray test whereby a dye is injected into the tubes and xrays are taken as the dye flows through. If it doesn't flow through one or both tubes then that shows that the tubes are blocked. Once blocked, it is always blocked but there is an exception. Sometimes, the tube will be blocked by a mucus plug at the opening of the tube. In general, it is one side only. With increased pressure at the time of the HSG, this mucus plug can be pushed out and the tube opened. If this is the case, the HSG "helps" in clearing the tube and allowing for a natural pregnancy to occur. If pregnancy does not occur then this could not be done and that tube is probably blocked by scar tissue. The problem with one tube blocked is that the incident that caused the blockage was probably an inflammation or infection in the past, usually caused by a bacteria. These usually pass through both tubes but it affected one tube more than the other, so that one tube is blocked. That does not preclude damage in the other tube, however. As you know, it takes a very small hole to allow fluid, like the dye, to flow through. I usually counsel my patients to assume that the other tube is damaged. The inner structure can be damaged and render the tube non-functional even without it being blocked. Therefore, with any blockage, I counseled that IVF (In Vitro Fertilization) is probably the best option.

3. PCOS - I have explained this pretty extensively in past questions. Please refer to some of my previous blog posts. But to summarize for you, PCO is a disorder of the ovaries whereby ovulation does not occur. For this reason, fertility medications are required to stimulate the ovary to ovulate. Clomid is one of those medications that is used but does not work on all PCO patients. Metformin only is useful in PCO patients that have an elevated insulin level. So it does not work in over 50% of PCO patients.

I hope this answers your questions.

Follow-up Question:

If you don't mind, I was also told that when I had the HSG done that because I was in a lot of pain that my tubes could have contracted and acted like they were blocked. Is the possible? I have been pregnant 3 times and 2 of them were on Clomid alone. Is it possible that Clomid together with metformin would work?

Follow-up Answer:

Hello Again,

HSG's are generally painful, especially if the tubes are blocked. That is because they are increasing the pressure to see if the dye will flow through. Increased pain does not indicate tubal spasm, however, tubal spasm can prevent the dye from flowing through. We see this most often when injecting dye at the time of a laparoscopy. It is uncommon to see tubal spasm in both tubes, however. If you are concerned that you may have had tubal spams, then you should have the test repeated to confirm.

If the tubes are blocked, legitimately and not due to tubal spasm, then Clomid and/or metformin will not help. If the sperm and egg cannot get together, then fertilization cannot occur, and hence, pregnancy will not ensue. If the HSG result was due to tubal spasm, then it is possible they could help, so the tubes are the key element in this. Try to clear these issues with your specialist and proceed according to his/her recommendations. Good luck!

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.

19 Year Old With Very Irregular Periods May Have PCOD

Question:

I am a 19 year old female (obviously). I had my first period when I was approximately 11 years old and for the first three to four months I had a regular cycle. After that period of time my cycle became irregular (which is in no way odd for someone of that age), being that I would menstruate every other month rather than every single month. After approximately 4 to 5 months of this my menstruation stopped completely. Over the course of the next 3 years I would have a period perhaps once every 5 to 6 months, and there would never be any mood swings, cramping, bloating, or overly heavy flow. The intervals between menstruation began to increase from there, lengthening to 8 months between periods (give or take two months).

This month and last month, however, I have had my period. Two months in a row after almost 13 months without anything. This past month, however, I have experienced severe cramping and moodiness. I know that it is not uncommon for cramping to occur after a prolonged period of time without menstruation, but the fact that I was incapacitated and in bed for two days was unbelievable to me.

I have had no problem developing secondary sexual characteristics, which would probably be signals of a pituitary or other glandular disorder. I am not obese, nor am I incredibly tall or short, which, from what I have gathered, excludes most thyroid issues.

I have no health insurance at current. During the course of my teenage years I would occasionally see an MD for various checkups, and I would bring up the matter of my irregularity. Every doctor I has ever seen has sloughed off the issue as probably having to do with "stress". This answer does nothing to satisfy me, as it seems like a knee-jerk reaction because they were either at a loss or because I could not afford whatever tests might actually tell me.

My worry, for quite some time now, has been the question of fertility. I have no actual plans to have children at any point in the near future, and I am not (nor have I ever been) sexually active. However, I need to know if I even CAN have children, for my own piece of mind. I know that without an examination, there's only so much you can tell me, but any information on what you might think is amiss would be greatly appreciated.

Answer:

Thank you for your question. For a 19 year old, your writing is incredibly sophisticated and impressive. You seem to be well educated. Most women do not know about "secondary sexual characteristics" or how the "pituitary or other glands" affect their cycles. Bravo to you for this knowledge.

Your irregular period is far from normal. There is a very common disorder, which you seem to be alluding to, called polycystic ovarian syndrome or PCOS. This is an ovarian dysfunction disorder caused by the ovary not processing the pituitary hormones correctly, leading to the lack of ovulation. Without ovulation, there is no subsequent menses, assuming you are not pregnant. We know that this disorder begins in the teen years in many women. So the doctor's previous explanations of "this is normal for your age group", is incorrect. There are problems that occur from PCOD in the long term such as increased weight gain, diabetes, increased facial and body hair growth, excessive bleeding episodes, irregular bleeding, endometrial cancer and infertility. Because of this, we DO NOT recommend continuing with the irregular cycles.

In women that are not attempting pregnancy, we use the birth control pill protocol to over-ride the ovaries and keep a normal cycle. This gives the essential female hormones, estrogen and progesterone, that your ovaries are not producing, and that you are lacking, because of the lack of ovulatory cycles. When you decide to become pregnant, this has to be substituted with ovulation inducing fertility drugs. PCOD is a clinical diagnosis, and although we do hormone testing to check the thyroid, pituitary and other hormones, it is not a diagnosis made by these lab tests. From your description of your symptoms, you probably suffer from it. If you do further internet searching, you will come upon a description of patients that have this disorder, that you do not fit. However, keep in mind that there are variations on this theme and even normal appearing females can have a milder form of the disorder. Not all patients are hairy and obese :).

In terms of your future pregnancy, bravo for getting through your teen years without having had a sexual experience. When you do contemplate getting pregnant, I do not see any reason that you would be unable to become pregnant, except for your ovulatory disorder. Assuming that this is corrected with fertility drugs, you should have a pregnancy rate commensurate with your age group. I have had many PCOS patients that get pregnant with the proper protocol , though sometimes they need more than one try before they get their cycle exactly right.

I would advise you to seek another opinion with this information in hand, preferably a good OB/Gyn.

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 and Infertility

Question:

Dear Dr. Ramirez,

I have been married 17 years, we have had unprotected intercourse for that long. About 10 years ago I went through a year of testing to find out that because of higher than normal testoterone levels my cycle is off kilter and I would not conceive. I went on three rounds of Clomid and still my cycle never evened out and no eggs. Now at 37, for the last year my cycle has started and is becoming actually fairly regular monthly. Without sounding completely brainless, is there a chance my body would be starting to regulate itself enough that I might ovulate, and at this point do you think clomid may help my chances of pregnancy? Is there something I can do to maybe help it along, or am I destined never to ovulate?

Answer:

Hello Shari,

You have or had a disorder called "polycystic ovarian disease". This is an ovulatory dysfunction whereby the ovary does not ovulate on a regular basis. Because the ovary is dysfunctioning, it does not produce the appropriate levels of female hormone so that the male hormone, testosterone, becomes elevated. Most of the patients with this disorder do not respond to Clomid. The appropriate next step would have been to use injectable medications and/or proceed to IVF.

Based on your age, and history, I would recommend that you go directly to IVF. You still have a good chance of pregnancy at your current age, but the chances are decreasing significantly each year. Right now, you have a 40 - 50% chance of pregnancy with each IVF cycle. At age 40, that reduces to 27%.

Certainly, if your cycles have become more regular, then that indicates that you are ovulating. Clomid would help in that case to increase the number of eggs that you ovulate, which is what you want to overcome the age factor. You want to ovulate 3-5 eggs per cycle. If your cycles are not regular, that is 28-30 days each month, then forget the Clomid and proceed to IVF. You have been married a long time to not have had children. Now you are running out of time. You need to be more aggressive if you want to have a child from your own eggs.

Sincerely,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

Monterey, California, U.S.A.

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