Young Woman With Endometriosis & PCOS Fails Five Clomid Cycles: Next Step?

Question:

Dear Doctor,

Hi, I'm from Minnesota. My husband and I have been trying to conceive since August of 2011. I have endometriosis and PCOS (polycystic ovarian syndrome) since finding out when I was around 17 years old, I'm 25 now. I have had five cycles of Clomid that didn't work. I had laparoscopy surgery for this post December, blocked tubes, suck ovaries, scar tissue, cysts and endometriosis. I'm on metformin because that's supposed to help with infertility and PCOS.

I started femara this month. Had 4 follicle on left and 1 on right from ultrasound. I usually ovulated on the 15th day, this time I didn't ovulate so I took the ovidrel shot and had a positive test. Started estrogen and progesterone day 3po. Currently on day 10po. I have cramps on and off.  I was just wondering what my chances of conceiving are and what is the next step if this didn't work this cycle. Any information or insight would be great! K. from Minnesota

Answer:

Hello K. from the U.S. (Minnesota),

Your statistical chances of pregnancy with Stage Four Endometriosis (endometriosis with extensive adhesive disease) and PCOD is probably less than 1% using any natural treatment method (Clomid, Femara or Injectables with intercourse or IUI).  That is because you have an abnormal pelvis and this location is critical for passage of the egg from the ovary to the tube.  Scar tissue, which is like spider webs, can block the egg from entering or reaching the tube.  Endometriosis causes a chronic inflammation of the pelvis which leads to the inflammatory cells attacking and destroying the egg as it exits the ovary to reach the tube. Polycystic ovarian disease is an ovarian dysfunction where the ovaries don't function properly and so there is a resultant hormone imbalance and lack of ovulation.  All of these put together significantly reduces your chances.

See my website for more extensive information and explanation of the options available for both Endometriosis and PCOS. I am convinced that with the proper information patients become empowered to make the right decision about their healthcare and can ascertain if they are receiving the best care.

It is my humble opinion that you are probably not seeing an infertility specialist because a good infertility subspecialist would have told you all this and not done all the treatments you have done.  The treatment of choice is to proceed to IVF so that you can bypass the pelvis completely.

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.

Secondary Infertility: Decreased Ovarian Reserve And Low Morphology May Be The Culprits

Hello,

I just turned 33 and I have one beautiful 18 mo little girl who is the love of my life. She was conceived on our 3rd iui using 5mg of Femara. My husband has low morphology (6%) and I have no regular periods. We both exercise / eat as we should and have no other health issues. We are considered unexplained infertility.

For the past 6mos we have been trying to conceive. I just had a large polyp removed and my fsh levels were tested. 2 1/2 years ago they were 7.0. 6 weeks ago they were 12.1. We are trying to figure out what to do next. We definitely want another child (And we would be open to 3). My questions are:

1) What do you recommend for medication? Is Femera a good starting point? Should we use the same dosage or higher?

2) Should we try an IUI or go straight to IVF?

3) Are there any "rules of thumb" for why FSH increases and how quickly it increases? I've heard stress can impact it. Thanks in advance for your help. C. from Washington State

Answer:

Hello C. from the U.S.,

Congratulations on achieving your first baby relatively easily. You do not have "unexplained" infertility as you have two reasons: sperm abnormality/low motility and irregular periods (ovulation dysfunction). Those are reasons enough to prevent spontaneous pregnancies.

In terms of your FSH level, I have to presume that it was drawn on cycle day #2 or 3, because that is the proper time to do this test and the only way that it an be interpreted. If it was, the elevated FSh level of 12.1 is not a good finding. This is called "decreased ovarian reserve", which basically means that your ovaries will be more resistant and less productive if stimulated with fertility medications. It is not an indication of ovarian function, but is somewhat of a time clock. Once the FSH level reaches 15, most IVF clinics will require you to use donor eggs. When it reaches 20, it means you are in menopause, which in your young age would be classified as premature ovarian failure. So from a time perspective, that means you don't have a lot of time to waste.

Certainly IUI is an option for you, and somewhat reasonable since it worked before. The FSH level will have no bearing on its chances of success. Chances of success depends on age and the sperm problem. If you wanted to do IUI first, I would limit it to no more than 4 attempts. You can use Femara, Clomid or injectables for these attempts and even alternate them, but don't waste a lot of time. Keep in mind that the chances of pregnancy with IUI in your age group is 20% per attempt. By four attempts you should be pregnant, otherwise the statistical chances drop dramatically after that.

If the IUI's fail, then you need to progress aggressively and quickly, especially if you want to have more than one more child. In that case I would recommend proceeding to IVF with ICSI. This will give you a 74% chance of pregnancy per attempt in my clinic (and is the treatment level that most infertility specialists would recommend with an FSH level above 10. Most would recommend not even to try the IUI).

I can't tell you why the fSH is elevated. That is an unknown.

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.

UAE Patient Tested For Infertility: Clomid or Tamoxifen?

QUESTION:

Hi Doctor,

This is S. from UAE. I would like to have your expert opinion in my case. My infertility workup showed multiple cysts in both ovaries but my hormonal work up was all within range. In addition, I have never missed a period ever in life, my cycles are pretty regular. In spite of this, my gynecologist started a Clomid induction cycle with me and monitored me. I was given Clomid in consecutive months. After reading your blog post about Clomid, I came to a conclusion that my doctor isn't doing right in giving me Clomid, and also, giving it consecutively. I switched doctors, only to recieve Tamoxifen in the subsequent cycle. I am worried. Do I need any kind of ovulation induction at all? Considering my cycles are regular and I had a normal LH/FSH ratio. Can Tamoxifen be followed immediately after Clomid?

ANSWER:

Dear Saman from the U.A.E.,

Glad to see that my blog has been helpful to you all the way in United Arab Emirates! Clomid is not indicated if you are ovulating on your own, but many many doctors use it to boost ovulation thinking that it is a "miracle" fertility drug. If you have been unable to become pregnant, and have had regular cycles, then there is something else, besides ovulation, that is causing the problem. That needs to be found. I am always skeptical when patients tell me "all my fertility tests were normal" without telling me what tests were done. That is because in most of these cases, all the fertility tests were not done, and therefore, the problem has not yet been found.

Tamoxifen has the same mechanism of action as Clomid, namely, it is an estrogen receptor blocker. Your new doctor obviously does not understand these medications. Just like I would not recommend taking Clomid in consecutive cycles because of the estrogen receptor blockage, I would not do that with ANY estrogen receptor blockers, except maybe Femara since it has less effect on the endometrial estrogen receptors. So I alternate cycles with Clomid and Femara. However, again, your new doctor is doing the same mistake and not treating anything specific. He/She needs to find out what the problem is! Ovulation induction is not the answer.

FOLLOW UP QUESTION:

Dear Dr, Thanks a whole lot for your response. It means a lot to me!I need one final querry answered. I have had the following tests:

FSH, LH, TSH, Prolactin, HSG, Fasting Insulin, Testosterone, DHEA Sulphate

All these tests and HSG have come out normal, and HSG shows Bilateral peritoneal spillage. Husband's semen analysis shows 58million/ml and 70% motility. In addition, I have never had any surgery and menstruate regularly every 28days. As I told u before, Clomid induction was done in 2 cycles which just resulted in a single ovum ripening, and was thus abandoned.

I have been adviced to have IUI. Should I go ahead with it? Because I have not had laproscopy, hysteroscopy or endometrial biopsy yet, and there might be reasons for infertility hidden there.....Isn't it better to go straight to IVF? Thank you!

FOLLOW UP ANSWER:

Hello again,

Indeed, based on the tests you have cited we know the following:

1. Your hypothalamic-ovarian pathway is normal (i.e. the ovary is being stimulated properly)
2. Your thyroid, testosterone and adrenal functions are normal.
3. Your fallopian tubes are open.
4. The sperm is normal and has the ability to get to the tube in order to fertilize your egg.

What we don't know is:

1. Is the uterine cavity normal (endometrial cavity) (hysteroscopy)
2. Is the peritoneum normal (where the egg goes through after ovulation) or is there scar tissue or endometriosis (laparoscopy)
3. Are you forming an adequate endometrial lining (endometrial biopsy).

If you wanted to pursue a natural method of getting pregnant (intercourse or IUI), then you will need to do these tests. If you would rather go directly to IVF (which bypasses almost all the steps), then the laparoscopy and endometrial biopsy are not necessary. The hysteroscopy is still needed. Some of my patients do choose to go directly to IVF because it gives you the highest chances of pregnancy. For example, the highest chance of pregnancy with each IUI cycle is 24% (under 35 year old patients), whereas IVF is 76% (at least in my clinic). So ultimately that is your decision. If you want to do things conservatively, that is, be as natural as possible, then IUI would be a reasonable step (it also costs less).

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.

Comment: Dr Ramirez's responses are ALWAYS accurate, and prompt....I can't thank him enough for the help he has given this way....IVF at his clinic is definitely on my cards, but hoping I wont need it though :)

Young Canadian With Endometriosis: Will Have Six Month Window For TTC Post Surgery

Question:

Hi, I’m from Calgary, Alberta in Canada. I am 33 and my husband is 30, we are both healthy and we’ve been TTC unsuccessfully for 19 cycles. I have never been pregnant. We have been tested at the fertility clinic and told that there is no obvious reason why we shouldn't’t be able to conceive. I had blood work to check my hormone levels, an ultrasound to check my follicles and an HSG to make sure my tubes were open, my husband had a SA done and it showed good numbers and motility. He does have some antibodies, but less than 50%.

All that being said, I contracted chlamydia about 14 years ago, but it was treated quickly (I believe within 1-2 months). I have also been experiencing some symptoms of endo since going off the BC pill so I am a candidate for the laparoscopic surgery. The doctor said I could also try clomid or clomid with assisted insemination. I’m looking for additional guidance on how to proceed. Given that I have symptoms of endo, would you recommend that I proceed with the surgery before trying clomid or even IVF?

Thanks. J. from Canada

Answer:

Hello J from Canada,

You pose an interesting question and the answer will be based on personal desires.

Given that your infertility evaluation has been negative thus far, and you are only 33 years old, if you want to attempt pregnancy by natural means (intercourse or IUI), then you should proceed with the laparoscopy. This is the only method that can diagnose endometriosis. It can be treated at the time surgically and then followed with a 3 month course of medication (Lupron depot) to eradicate any microscopic endometriosis. You will then be free to try on your own or with IUI for the next six months. That is the window of opportunity. If the laparoscopy shows that the endometriosis is stage 3 or 4, then IVF would be indicated.

Certainly if you decide to proceed with trying by natural mean after the laparoscopy, I would recommend an aggressive treatment plan because you need to try to get pregnant within six months. After six months there is a high chance that the endometriosis will return and you will be back to square one. By aggressive natural means, I mean ovulation induction with Clomid, Femara or injectables and either timed intercourse or IUI.

If you don't want to do the laparoscopy, then the best option would be to proceed with IVF. That is the decision that my wife and I made when we faced a similar point in our infertility evaluation and treatment. This is because IVF will bypass any endometriosis and you won't have to undertake the pain or risks of surgery. But, it is the most expensive way to go.

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.

UK Patient Has PCOS, On Clomid For Ovulation: After First Miscarriage, Should She Continue With Clomid Or Start Injectables?

QUESTION:

I was put on 50mg Clomid due to pcos and long cycles (42-43 days). Right away, my cycles reduced to between 26-32 days. I got pregnant on my 3rd cycle of Clomid, then miscarried.

My RE recommends that I go back on Clomid, and would like me to increase my Clomid dose to 100mg so that we can recruit more than 1 egg (since I was only ovulating one egg on the 50mg dose). I will also be taking progesterone this time.

1) Do you recommend that I increase my dose of Clomid to 100mg to recruit more than one egg (even though I was ovulating normally on the 50mg dose)?

2) If the next 3 months of Clomid are unsuccessful, my doctor recommends that I try FSH injections (since I will have been on clomid for a total of 6 consecutive months, including the 3 months before my miscarriage). Do you recommend moving to FSH injections, or staying on the Clomid since it was successful previously?

3) If I cannot get pregnant again during the next 3 months on Clomid, my doctor recommended getting a laparoscopy. Just wondering if you would recommend I proceed with a laparoscopy if I fail to get pregnant again? I feel like I just got pregnant after 3 months of Clomid, so that the procedure seems unnecessary to me. (I have also had bloodwork, SA, and HSG all come back as normal).

Thank you for your advice. Sincerely,S. from the U.K.

ANSWER:

Hello S. from the U.K.,

I am sorry for your miscarriage. Considering your treatment plan, because you responded to 50mg of Clomid previously, you certainly don't need to increase the amount. However, your doctor's strategy is to get you to ovulate more than one egg at a time to increase your chances of pregnancy with each attempt. We call that super-ovulation. With increasing the number of eggs, you certainly will be increasing the chances of a multiple pregnancy. If that is not acceptable then stay with just 50mg.

I do not recommend moving to FSH injections yet. They certainly have a place but since you have gotten pregnant with Clomid before, I would just increase the Clomid dose. You can go up to 250 mg of Clomid. 3 months also seems like a short time frame for the trial unless you are over 35 years old. Then you might want to proceed more aggressively.

If you move up to the injections then I would also recommend that you add IUI in order to increase your chances even more. I don't recommend a laparoscopy at this time because I don't see a reason for it. I keep in mind that you were successful already with Clomid which shows that everything your body needs to do in order to achieve pregnancy can occur. The pregnancy re-sets the time frame. Now you just need to go back to the same plan and keep trying!

Follow Up Question:

Dr. Ramirez,

Thank you for your prompt reply. It is extremely helpful. I just have a few follow-up questions:

I mentioned previously that I was on Clomid for 3 months and got pregnant on the 3rd month (and miscarried). I have now been on Clomid for another 2 months since the miscarriage and not gotten pregnant yet. So I will be starting my 6th consecutive month of Clomid this month.

You recommended I continue with Clomid at a higher dose (rather than move straight to the FSH injections), since Clomid worked for me before.

1) Could please tell me what is the longest period that I can safely be on Clomid for? [I keep reading that one is only supposed to be on Clomid for a limit of 6 consecutive months. I am going to be starting my 6th consecutive month of Clomid this month]

2) I also keep reading about two negative effects that can occur with continuous use of Clomid. One is thinned lining (my lining has been fine so far). The second effect I have read about is hostile cervical mucus.

My RE said she is willing to do a post-coital test to check on cervical mucus if I want one, but that she does not consider it a reliable test. So my question is - how am I supposed to know if my cervical mucus is being affected by the Clomid? Also, since I am now entering my 6th month of Clomid use, should I consider taking an estrogen supplement which can possibly improve cervical mucus? Thank you very much for your advice. Regards,S.

Follow Up Answer:

Hello Again, When I answered your previous question, I was not implying that I agreed with continuous Clomid cycles. I do not. Because of the "antiestrogenic" effects of Clomid, I do not use Clomid on a continuous monthly basis. I alternate with Femara, but if that is not used, then Clomid should be used on an every-other month basis so as not to block the estrogen receptors, for exactly the reasons you indicated. Yet, as I stated above, your pregnancy reset the time frame.

In terms of the maximum number of months to use Clomid, there is no rule that says that Clomid needs to be stopped after a certain number of months. However, if pregnancy does not occur, then you should move on to the next level of treatment after six months. In your case, since you became pregnant, that reset the count. Because fertility treatments cannot control the pregnancy, and can only give you the opportunity to become pregnant, that is where treatment success ends. So you are now on your second cycle of Clomid, not your 5th.

Certainly if you want to move to the higher level of treatments such as Follistim, there is no reason that you should not. I only suggested the Clomid because it is less expensive, easier to use and worked for you before.

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.

PCOS Challenge Radio Show Summary: Everything You Wanted To Know About PCOS, Fertility, Menopause, Pregnancy & More!

Dear Readers,
On September 29th I was interviewed by Sasha Ottey of PCOS Challenge on her BlogTalkRadio program, for an episode titled: "Ask The Fertility Specialist About PCOS And Your Fertility". I was pleasantly surprised at how quickly the one-hour interview went. It was basically a question/answer format (like my blog ). It was interesting to see how many questions I received from Sasha and her listeners that not only covered PCOS but many, many other issues that relate to women's reproductive health. For more in depth information on PCOS and infertility please see: Polycystic Ovarian Syndrome.

I will attempt to give you some idea of the many different issues that were brought up during this very enlightening hour! I can't list them all, but if any of the topics that I list below interest you, please listen to the radio show through the widget below!

Listen to internet radio with PCOSChallenge com on Blog Talk Radio

• "What is the difference between a normal menstrual cycle and one that is PCOS?" With an abnormal menstrual cycle you can develop abnormalities in your endometrial lining.
• "What are the top reasons for infertility?" Probably PCOS is the number one cause for infertility that I see, with tubal factors and age factors coming in close seconds.
• "While overweight PCOS patients are told to lose weight, lean PCOS patients are at a loss as to what to do?" I go in depth on Clomid, Femara and the injectables that might be the treatment path for "lean" PCO patients.
• "What is the difference between ovarian reserve and ovarian resistance?" With ovarian reserve you need to evaluate your FSH levels and AMH and tends to come with age, but ovarian resistance has to do with how the ovary responds to fertility medications.
• "How long do you need to wait to try for pregnancy again after you have a miscarriage?" Surprisingly, recent studies have shown that trying as soon as possible will actually increase your chances of pregnancy. You must wait until you resume your normal menstrual cycle, though.
• "What about patients that are insulin resistance and overweight, will changing their diet and losing weight help with their fertility?" This will work in a majority of patients, but some of these patients will have to go on Metformin, and possibly ovulation inducing medication.
• "I am a very heavy-bleeder during my period and are there any options besides a hysterectomy?" You need to establish first whether you want to get pregnant in the future, in which case you want to preserve your uterus. You should find out why you have the bleeding. It could be an ovarian disfunction or perhaps caused by fibroids or polyps which can be removed. Otherwise, if you don't want to get pregnant you can opt to have a D&C, bcp, Mirena, endometrial ablation, or a hysterectomy.
• "When can I expect to see or hear the heartbeat in early pregnancy?" By the seventh week you should expect to see something.
• "Can you have menopause and PCO?" Once you become menopausal PCO is not an issue anymore, you have a hormonal imbalance because your ovaries are not functioning anymore. There are treatments for menopause, including estrogen replacement therapy for the first five years.
• "What is Metformin and Spironolactone?" Metformin is an insulin blocker, while Spironolactone is a diuretic used with PCO patients that have hirsuitism as well.
• "How do you treat nausea in pregnancy?" There is a great drug out there now that I use with all my patients, including those who have just had surgery, called "Zofran". It is safe for pregnant patients.
  
  Not all the topics we covered are listed above...so tune in if you want to hear me discuss these issues and more in depth! Thank you, Sasha, for the opportunity to share this knowledge with your listeners!
  
  Edward Ramirez, MD, FACOG
  Monterey Bay IVF
  www.montereybayivf.com

American In The UK Taking Clomid & Has Thin Uterine Lining: Needs A Specialist

Question:

Hi Dr. Ramirez,

I will try to keep this as concise as possible. I am very healthy, slim and 29 years old, and have never had issues with my periods. My husband (29 years also) and I conceived on our first try last year, but unfortunately had a missed M/C at 12 wks (fetus stopped growing at 8 wks). Tests confirmed non-recurring genetic abnormality. After the D&C I had only spotting, until 5 days after when I had a very heavy bleed with large clots lasting only one day. Then I got my first period 6 weeks later. The 3 subsequent cycles were 42-45 days.

Pelvic ultrasound revealed PCOS, hormone levels were all normal, including thyroid. Lining on this ultrasound was only 5.5 on day 40, just before I started my period. I have just completed one round of 50 mg Clomid unmonitored due to travel, and BBT shows clear ovulation on day 18 with 12 day luteal phase. This cycle I have had my first follicle tracking on day 11 which showed dominant follicle at 15 mm, but lining of only 4 mm. My questions are:

1. Could the thin lining be due to problems from the D&C?

2. My gyn prescribed Progesterone pessaries for the second half of this cycle to help thicken the lining- is this the appropriate treatment?

3. When should I consider seeing a fertility specialist?

Thank you for your time- I am writing from London. M.

Answer:

Hello M. from the U.K.,

A thin lining could certainly be due to an over-vigorous D&C, leading to scarring in the uterus. This is called Asherman's syndrome. A procedure called hysteroscopy can be done to evaluate the uterus cavity for this. However, that being said, it is not very common to develop this with D&Cs. The more common possibility is a thin lining due to the use of Clomid.

Clomid is an estrogen receptor blocker and so blocks estrogen receptors at the endometrium (uterine lining). For that reason, many patients have to use extra estrogen given vaginally in order to overcome the blockage from the Clomid, or they use a different medication such as Femara or injectables.

Progesterone is NOT the hormone that thickens the uterine lining. Endometrial thickening and priming is dependent on ESTROGEN in the first half of the cycle. The fact that your doc told you the wrong info makes me skeptical that he/she clearly understands the physiology of this treatment. So, I think you should go see a fertility specialist instead. Without proper estrogen priming, the uterine lining will not be ready for implantation. The progesterone, which is given after ovulation, is to convert the endometrial lining to develop the "pinopodes" that are necessary for implantation. (See diagram up above, the "pinopodes" are small finger-like protrusions in the endometrium) Without the proper priming, the pinopodes will not develop.

Good Luck and keep trying, you should succeed with the right treatment path,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

http://www.montereybayivf.com/

Monterey, California, U.S.A.

Comment: Thank you Dr. Ramirez! I am very grateful to have your opinion, which confirmed to me that I need to see a specialist. As an American living abroad, it can be daunting to find the same quality of health care that we take for granted in the US. Again, I really appreciate your help.

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!

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.

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

Oral vs. Injectable Fertility Drugs

Question:

What's the difference between oral and injectable fertility drugs?

Answer:

They are completely different classes of drugs. The oral fertility drugs are called Clomid and Femara. Both of these are Estrogen receptor blockers. The brain modulates ovarian function by checking the estrogen levels. By blocking the estrogen receptors, the brain is fooled into thinking that there is inadequate estrogen production, so it increases the amount of FSH and LH hormone to stimulate the ovary. In this way, the ovary is stimulated to ovulation, in non-ovulatory patients, or to incerase the number of eggs ovulated, in ovulatory patients.

The injectable fertility drugs are FSH and LH. Previously, these were purified, human hormones, but now they have been able to be synthesized. They are the same hormones that the brain sends to stimulate the ovary, so they stimulate the ovary directly, instead of indirectly like the oral drugs. They are stronger and work better because of the direct stimulation. That is why we use these preferentially with IVF. They are more expensive.

I hope this answers your question!

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

for additional information check me out on Facebook and Twitter with me at @montereybayivf