History of Miscarriages, Now 9 Weeks Pregnant: Continue Progesterone Supplement (Crinone) ?

Question:

I'm from the U.S. After a long struggle with secondary infertility and 2 miscarriages, I am pregnant again, 9 weeks along. I'm on supplemental progesterone, Crinone 8% once a day. When can I feel okay about stopping the Crinone? I was supposed to see my doctor in 2 days, but he experienced a family tragedy, and I'm not sure when he'll be back. I think he had talked about stopping the Crinone at 9 or 10 weeks, but I was going to confirm that with him at my appointment, and I have no way of asking now.

Thank you for your time. M. from the U.S.

Answer:

Hello M. from the U.S.,

With your history of two miscarriages, I will usually be very conservative and continue the progesterone until 12 weeks gestational age.  However, medically, it would be okay to stop at 10 weeks.  By then, the placenta should be fully functional and providing all the hormone necessary to maintain the pregnancy.

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.

 

**For my readers who are unfamiliar with the use of progesterone to support a pregnancy, here are some additional facts: "Progesterone is essential for the normal functioning of the reproductive system. After ovulation, the corpus luteum (which is the empty follicle from which the egg was released) produces progesterone, which acts on the womb lining and causes it to thicken in preparation for a fertilized egg to implant. This is known as the luteal phase of the menstrual cycle. If an egg implants successfully into the womb, the corpus luteum continues to produce progesterone to maintain the pregnancy until the placenta develops fully. The placenta produces increasing amounts of progesterone until it is fully developed, when it then takes over the production of progesterone to continue to support the pregnancy.

In some women, insufficient progesterone is produced during the luteal phase and this causes problems with implantation of fertilized eggs into the womb lining and maintaining a pregnancy in the early stages. Crinone vaginal gel is used to treat this hormone deficiency. One applicatorful is inserted into the vagina every day, starting either one day after ovulation is known to have occurred, or on day 18 to 21 of the woman's cycle. (Day one is the first day of your period.) The gel is usually continued until the placenta is producing enough progesterone to support the pregnancy.
Crinone vaginal gel is also used to support pregnancy in women having in vitro fertilization (IVF). In this case the gel is used daily, starting after the embryo has been transferred into the womb, for the first 30 days of confirmed pregnancy." www.netdoctor.co.uk/pregnancy/medicines/crinone.html

 

Severe Allergy To Progesterone During IVF Cycles

QUESTION:

Dr. Ramirez, I have a problem with progesterone but my symptoms are not typical of an allergic reaction. My husband and I have done 3 IVF cycles, all failed. They were all chemical pregnancies

1st cycle: The day after the first progesterone in ethyl oleate injection, I developed chills, a high fever, blood pressure drop and an elevated heart rate. The doctor thought it was an infection but the lab results were negative. I was then switched to Endometrin which caused intense vaginal itching and burning. So the RE put me on Crinone which also resulted in intense burning and terrible headaches.

2nd cycle: I was put on compounded progesterone capsules. After 5 days, I developed severe redness, swelling and pain. So I was then put on compounded suppositories which looked like white bullets. These caused burning and bleeding. The RE then had me try progesterone in sesame oil injection. About an hour after the shot, I became flushed and felt like I was going to pass out. I also developed a fever, drop in blood pressure and an increase in my heart rate.

We then did a mock cycle with the compounded progesterone capsules along with Zyrtec and Singulair. When the vaginal redness, swelling and pain returned, I was put on Benadryl. Unfortunately, that didn't work either.

3rd cycle: The RE had me do daily HCG injections along with oral Prometrium 200 mg three times daily. I had no problems with that protocol but it was not successful in achieving a pregnancy.

Prior to my mock cycle, an allergist tested the various progesterones to which I had an adverse reaction. The prick test was negative for all but the intra-dermal shots induced a wheal (9 & 10) and flare (both 12).

Is there a way to either prevent symptoms from developing or are there other progesterones which will not induce a reaction in the first place? Thank you! S. from Michigan

ANSWER: Hello S. from Michigan,

I think that you should avoid compounded progesterone. Instead, you could try an injectable progesterone made with an oil other than sesame oil so that would be one option, or a pharmaceutical formulated progesterone such as Crinone 8% or Endometrin would be alternatives. I use a pharmacy called MDR who makes an progesterone in a different oil that is less viscous and more easy to inject. I presume that the injectable that was tested by your allergist was with sesame oil. It is most likely that the allergen was the "oil" and not the progesterone itself, since the oil is a protein. You might want to have him check that.

Crinone and Endometrin are both used vaginally which has been shown to be the optimal method for delivering progesterone to the endometrium. Oral progesterones have been shown to be ineffective because most of the drug is lost in the first pass through the liver. Only injectable, vaginal or dermal have been shown to be effective.

Although there are no pharmaceutical companies that sell transdermal progesterone products on the market, there are a lot available through health stores and the internet, and also can be compounded. I don't use them so can't attest to their effectiveness or dosage but have seen some studies looking at them. It is possible that MDR can compound one for you.

The alternative for luteal phase support would be low dose HCG injections, like your RE has done. That has been shown to be effective. As a last resort, a surrogate could be used. Although expensive, it is an alternative that some of my patients have used with success when they could not carry the pregnancy for whatever reason.

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.

Why Do I Need HCG Injections After Ovulation During IUI Cycle?

Question:

Dr. Ramirez,

My husband and I have been trying to start our family for a few years. I have been pregnant and miscarried 3 times, but is has been over a year and a half since my last miscarriage. I am seeing a Reproductive Endocrinologist and their diagnosis for not getting pregnant again is unexplained infertility. We have are trying the IUI process now using Letrozole and I have also been given a prescription to do HCG injections on days 3, 6, and 9 past my LH surge. I am not finding very much information about using HCG after ovulation. I know their reasoning is to supplement my progesterone... but not sure why then, they don't just use progesterone? Please help!

Thank you! G. from Colorado

Answer:

Hello G. from the U.S. (Colorado),

HCG (human chorionic gonadotropin) injections can be used to support the luteal phase in place of progesterone and there is nothing wrong with that protocol. Most don't use that method because you have to take it as injections and the medication is considerably more expensive. There are many progesterone alternatives such as Crinone, Endometrin, Prometrium that can be used vaginally as a supplement. You should ask your doctor why they don't just use a progesterone supplement.

The other question to ask is "what are they treating or trying to achieve"? Do they suspect that your miscarriages are due to a luteal phase defect i.e. decreased progesterone? In that case testing by an end of cycle endometrial biopsy for dating and/or b-integrin would have diagnosed luteal phase defect and your diagnosis would not be "unexplained infertility." I am not a strong believer in "unexplained infertility" as a real entity. I think it is more like undiagnosed infertility. The cause just has not been found because either a test has not been done to find it or doesn't exist. Often we find that many of these cases of fertilization failures or defects with the sperm (found at the time of IVF) or endometriosis found on laparoscopy. Sometimes age is the problem as well leading to poor embryo quality.

Your question is a good one and you should ask your doctor. Be sure they explain everything to you!

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: Thank you so much... for all of your information and quick response! I will follow up with my doctor.

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

Question:
Hello, I’m in California.

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

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

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

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

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

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

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

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

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

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

Answer:

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

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

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

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

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

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

Good Luck,

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

Monterey, California, U.S.A.

Alaskan Worried After First Miscarriage: Was The Cause Low Progesterone? No!

Question:

Hello, I am writing to you from a remote community in Alaska,

We have a clinic and Doctors here but, no hospital or specialists, so I am glad to have found your site and hope to receive an answer to my concern. I suffered a miscarriage on Jan 10th at 8 weeks. For the year leading up to my pregnancy I had mid cycle bleeding starting around 7 DPO. I now believe that I bled and lost my pregnancy due to low progesterone.

My MD here in town tested my levels on days 10-12-14 post ovulation and the results were 7.8 - 17.9 - 20. She says these are all normal and I can try again, but everything I see online says the numbers are in fact low and supplements should be started after I ovulate next. I also have been BBT charting and my temp drops to pre ov levels within 2 days of the ovulation spike and stays low. Do you see a low progesterone issue here and would you recommend suppositories? Please respond as I am so confused and somewhat upset that the info I am getting from my Doc. does not match the info on the web. Thank you so very much for taking the time to consider this.

I appreciate it more than you know. S. From Alaska, USA

Answer:

Hello S. from Alaska,

Thank you for writing me with your concerns. Progesterone levels measured at the mid-luteal phase do not make the diagnosis of luteal phase defect. They are mainly used to confirm ovulation. Any level above 10 confirms ovulation if the test is done in the mid-luteal phase (CD#20-22). In order to make a diagnosis of luteal phase defect, an endometrial biopsy would need to be taken at the end of the cycle to check for endometrial dating. This is usually done around CD#26-28 (before your period starts).

Progesterone is such a simple treatment with no side effects and much benefit that I do not see any harm from using it after ovulation. We certainly use it with every type of fertility treatment that we give. There are two that are made specifically for infertility treatment called Crinone and Endometrin. Another one that is used is called Prometrium but is not specifically for infertility use. You would start the supplementation on cycle day #16 and continue until a pregnancy test is done at the end of the month. Do not stop the medication until a pregnancy test is done and do not wait for a period because the progesterone will likely prevent that from occurring. If you are pregnant then you would continue it until you are 10 weeks gestational age.

Now with all that being said, a lack of progesterone is NOT the reason why you miscarried. The placenta takes over progesterone production at the 6th week so a luteal phase defect or lack of progesterone would not cause a miscarriage at that point. It is usually earlier. The most common reason for a miscarriage in the first trimester is a spontaneous chromosomal defect that occurred at the time of embryo division. This led to an abnormal embryo, which the body detected and stopped. It is most likely that you will have a successful pregnancy subsequently.

You have to take the information you find on the web with a very large grain of salt, and don't try to micro-interpret what may or may not have happened or is happening. Since you were able to get pregnant naturally before, you chances of a successful pregnancy are high. We don't worry about recurrent miscarriages until there have been at least three consecutive miscarriages. Keep trying!

Good Luck,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com

Patient With Short Luteal Phase Has Spotting With Progesterone Suppositories, Is This Normal?

QUESTION:

Dr. Ramirez, I am hoping that you can help answer some questions for me as I am feeling confused and hopeless...I am 30 years old and I am trying to concieve. I was on the birth control pill for 9 years and stopped taking it in June. I have been charting my Basal Body Temps and discovered that I have a short luteal phase--

I begin spotting 9 days after ovulation and start my period the following day making my luteal phase 9-10 days. My period is very light-- only lasting a few days. I have been taking Vitamin B6 supplements and my doctor started me on Crinone Progesterone Suppositories this month. I began 3 days after ovulation and am taking 90mg once per day.

Yesterday, 9 days into my luteal phase, I began spotting very lightly when wiping. This was very discouraging as I usually begin spotting on day 9 before starting the suppositories. I was convinced that I was starting my period as I had in previous months and that this was not implantation spotting due to the coincidence of the spotting on day 9.

However, now on day 10, I am wondering if I gave up hope too soon. The spotting is still VERY scant and does not seem to be increasing as in previous months. Also, the actual flow of the bleeding seems a little different than previous months. Upon intially wiping, there is no blood on the toilet paper. After wiping a couple of times, a very small amount of red blood appears on the toilet paper. In fact, as I continue to wipe, the bleeding seems to increase with each wipe. Also, it does not resemble my usual spotting (blood mixed with a wet discharge) but just small amounts of blood smears. The flow only appears when wiping.

Should the progesterone suppositories have increased my luteal phase count at least a little bit? It's very discouraging to think that there was no increase at all. If my period is beginning, does this mean that it is not a progesterone issue? What else could cause a Luteal Phase Defect? Can your period begin while you are taking the suppositories? I read online that your period will not begin until you stop taking the progesterone? However, I have also read conflicting info as well.

Could this be "break-through bleeding"? Is this common with suppositories? Could you explain what this is? Does this sound like implantation spotting? I called my Dr. and she said to stay on the progesterone for a few more days and see if my period does start. She has admitted that she is not too familiar with LPD isues and has referred me to a Reproductive Endocrinologist however the earliest appointment I could get is March. I am feeling really confused and discouraged. Any help, guidance or suggestions would be greatly appreciated! Also, I did take a pregnancy test today and it was negative but realize that it may have been too early. I am writing from Massachusetts.

ANSWER:

Hello D. from Massachusetts,

I have found that vaginal spotting is very common with the use of Crinone in my IVF patients, so I don't think you need to worry about it. Supplemental progesterone is the appropriate treatment for suspected luteal phase defect. A pregnancy test will be required because your natural period will not occur if you are on supplemental progesterone. The incident that causes the withdrawal bleed (your period) to occur is the abrupt drop of progesterone in your system if a pregnancy has not occurred. Therefore, I would recommend a scheduled serum bHCG at 14 days after ovulation. If it is negative, then stop the progesterone but don't stop until you have that result.

There are gynecologists out there that are well versed in infertility treatments. You don't necessarily have to see an RE for your level of care. You might want to call around and see if you can find one so you don't have to wait so long to undergo proper treatment. However, be very careful because there are many general Ob/Gyn's that say they do infertility that know very little and don't render proper care. You might want to ask them specifically how they diagnose and treat luteal phase defect. You also might want to find one that does IUI treatments, and avoid the ones that don't do this level of care.

Follow Up Question:

Thank you so much for your quick response! This was very helpful. It is encouraging to know that spotting is common when using Crinone. From your response, it sounds like my period will not start until I stop taking the progesterone. Do you feel confident that given the info that I provided that it is not my period starting and just due to the progesterone? Is this "break-through bleeding?"Also, do you think 90 mg once per day is adequate? I read about women taking the supplements 2 times per day. Again, thank you for any help you can provide and for your timely feedback. I appreciate your advice re: the RE as well. March seems like it will never get here!!

Follow Up Answer:

Hello Again,
I am confident that this bleeding is not your period, but keep in mind that there are always exceptions. It is most likely breakthrough bleeding as I explained previously. Crinone has been extensively studies for use in infertility and once per day is adequate.

I am happy to have helped clear up some of your fears. Good luck with your treatment and don't hesitate to write again!

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.

A Positive BHCG But Now Bleeding Two Weeks After Embryo Transfer: Am I Miscarrying?

Question:

Hello. I did an IVF transfer June 24th, was told it was a beautiful transfer of 3 beautiful embryos. This past Tuesday, July 6th, I got a positive result, however doc told me to be cautiously optimistic as it could be a chemical pregnancy because my level was 33. The next morning I woke up to cramps and started brown (old blood like) spotting, which is kind of weird for me to be honest. My cautious optimism diminishes to despair. Called doc, told me it was normal and had to wait. Retested 48 hrs later (yesterday) and it was 60, so it nearly doubled! Which was a big shocker...I was really expecting it to go down. But yeah, right?

This morning, July 10th, I woke up to heavier spotting and an actual clot like thing (which kind of looked like a massive amount of my Crinone gel). Mostly brown blood with a little red now, but mostly when I wipe after going to the bathroom (sorry TMI). They say it could be a number of things, irritation from the progesterone gel, passing of one of the embryos, or just normal pregnancy symptoms. I think they are miscarry symptoms. I go back for blood draw Monday and I am just beside myself. I am normally a pretty together person but this has turned me upside down as I feel like I'm on an emotional roller coaster. One day I think I am dealing with a m/c and then we get news that my hcg doubles. This bleeding after my embryo transfer worries me.

I guess what I'm asking is should I look at the doubling as good news or could it be my levels haven't caught up with what will happen? Could I be passing one or two embryos while one implants? Is a m/c imminent in your opinion? Any help would be most appreciated. Thank you in advance. D. from the U.S.

Answer:

Hello D. from the U.S.,

First, let me answer your last question. Based on your symptoms and bHCG levels, you CANNOT make a diagnosis of imminent miscarriage. It can go either way, but I tend to focus on the good side.

The bHCG levels doubled as they were supposed to. I generally follow them every 48 hrs for the first four levels, but your doctor has a different protocol. As long as they continue to rise and approximately double (they don't have to double exactly), then we wait and see how things go. There is only a limited amount of information that you can gather from this blood test. If they are going up, you are pregnant and things are looking good. If they plateau or drop then things are not good. One cannot necessarily predict the outcome based on the levels.

Second, I would totally disregard the spotting that you are having, and not worry unless it is bright red blood that flows like a period. Anything less than that can be "normal" at this point. Bleeding after embryo transfer is more common than you think. We see this very, very often. . . in almost 90% of our IVF patients using Crinone. In fact, there have been studies showing increased spotting with vaginal progesterones like Crinone. It is thought that the progesterone makes the cervix more prone to oozing from the surface. In any case, this type of spotting with Crinone is very common.

Not much can be known about the pregnancy at this very early point, except that you are pregnant! Now, despite the worry, you have to wait and see how things progress. Try to be optimistic and keep the stress level down. I would not assume that you are destined for a miscarriage or are miscarrying yet. It can still go either way. Whatever is destined to happen, will happen and we don't have the power to change that at this point. We can only hope and pray for the best. By the way, it is never "TMI" (too much information), rather, all the information you can provide is appreciated by a physician.

The very best of luck to you both, my thoughts are with you. Sincerely,

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

Prometrium Vs. Endometrim For Luteal Phase Support In IVF

Question:

Dear Dr. Ramirez,

I've written to you before about luteal phase bleeding. We've tried 3 IUI's, but my husband's morphology has been consistently 0%, so we are moving on to IVF with ICSI.

My RE has me on a long protocol (BCP, Synarel, Puregon, Repronex). My main concern is luteal phase support. My RE plans to have me on 200mg of Prometrium PV TID starting the evening of retrieval... During my last natural cycle I tried this dose of Prometrium and I still had some breakthrough bleeding (but not everyday). Do you think that this is sufficient luteal phase support for someone with a history of luteal bleeding? My RE is doing a hysteroscopy next week to rule out other causes.

Thank-you for your time, L. from Canada

29yo, secondary infertility

Answer:

Hello L. from Canada,

The dosage of prometrium that your doctor has prescribed is certainly adequate for luteal phase support but is not the mainstay with IVF treatments. The gold standard is injectable progesterone 50 mg per day starting on the day of the retrieval. The alternatives that have been studied with IVF are Endometrin 100 mg vaginally three times per day or Crinone 8%/Prochieve 8% vaginally each morning. I double up and use the progesterone injection and the Endometrin or Crinone together to make sure that I have adequate progesterone coverage. So, prometrium can be used but is not the medication of choice with IVF. It is the cheapest alternative however.

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.

Comment: Thank-you Dr. Ramirez! My RE has given me the option of using Endometrin (just recently approved in Canada) so I will use your advice.

PCOS Patient Taking Natural Progesterone Cream For Cycles: NPC Does Not Help You To Ovulate, Only Regulates Cycle

Question:

Hi,

I have long cycles and was recently diagnosed with PCOS. Prior to my diagnosis I have tried everything under the sun to regulate them and help me to ovulate. Vitex, Evening Primrose Oil, Dr John Lee's Shutdown, (in which Natural Progesterone Cream is applied for CD's 5-26, then stopped) a couple unmedicated cycles, soy isoflavones, currently on 1000mg/day of Metformin and the ONLY cycles I had "normal" cycle length with ovulation, is when I took NPC (25mg/BID) from CD's 5-26 (or til Aunt Flow) I know normally NPC should suppress ovulation, but instead for me it helps me ovulate. Why would that be? I cannot make sense of it at all, but am impressed that this is all it took.

I recently had an appointment with my dr, who actually told me that the NPC would do me no good in the beginning of my cycle and I should stop the NPC and start BCP's for a while to help get my cycles regulated again.

Thank you,

L. from Oregon

Answer:

Hello L. from Oregon,

Natural progesterone cream (NPC) will NOT get you to ovulate, but will help to keep you regular. In fact, you don't need to take it as many days as you are taking if all you want is to have a period on a regular basis. All you have to do is use it on CD#16-25 (10 days). When you withdraw the progesterone, you will have a period, because that is what happens in the luteal phase of the cycle. The progesterone is working directly on the endometrial lining and causing it to "luteinize" which is why withdrawal of the hormone causes it to breakdown and bleed. We use other forms of "natural" progesterone such as prometrium, Crinone, Procheive, Endometrin and Provera to accomplish the same task. But the progesterone does nothing to the ovary so ovulation does not occur. In large enough doses of progesterone, as that contained in birth control pills, it will cause a suppression of ovarian function.

The birth control pill is only a treatment to regulate your cycles. If a woman with PCOS is not intending to become pregnant, then the treatment of choice is to use the birth control pill. On the other hand, if your goal is to start ovulating, because you want to get pregnant, then as a woman with PCOS you need to use a medication that will induce the ovaries to ovulate such as Clomid, Femara or injectable medications.

I hope this helps to explain things,

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.

Kuwaiti Woman Asks: How To Thicken My Endometrium Lining?

Question:

Hi Dr. Ramirez,

I feel am really blessed to find someone very expert and caring like you :)

This is N. from Kuwait, I am very concerned about my endo thickness (was between 6.5 to 7.9 on CD14). On the other hand, I don’t want to take medicine that may harm me. The dr. is giving me Duphaston and Progyluton. The Norgestrel is combined with Estradiol valerate in one pill that comes in medicine call Progyluton (I don’t know if you know it). 11 white tablets each containing Estradiol valerate and 10 light brown tablets to be taken from CD16, each containing Estradiol valerate and Norgestrel). You have said previously that the Norgestrel is not used in the USA to treat endos.

What about the Duphaston which is Dydrogesterone 10 mg- Orally – 2 times a day from CD14? Should I take it Vaginally? Does it hurt? What do you suggest? Should I take natural Progesterone instead of the Duphaston? If yes, would you please give me name of the medicine?

Unfortunately it seems there are not that good doctors over here, they are RE and Gyno. This is the 3rd doc. The 2nd doc believes that clomid will increase the endo because it produces eggs; and she sees endo thickness 7 or 8 mm is not bad!!! Dr. Ramirez, If you don’t mind to give me Online Consultancy and I will PAY for it (I can call). Write me a prescription with what should I take and when and how? For example estrace from CDx to CDx, and then XXX medicine from CDxx. (I can order them online)

I know that it sounds weird, but with the globalization and the existence of internet the behaviors and habits are changing. I will go to the doctor on CD14 (or whenever you think is the best) to do the ultrasound and then will let you know about the size of eggs, endo and so on :)

Thank you!

Answer:

Hello N. from Kuwait,

The Duphaston can be used vaginally. Progesterone is important to help with implantation. I would NOT recommend the Progyluton. It is used from hormone replacement therapy and cycle control. It is not used in infertility because of the Norgestrel. Although the Estradiol component is okay, and necessary to increase the uterine lining, the Norgestrel (progesterone) will compete with the estrogen and keep the lining thin. With this combination women don't usually have periods, which is the reason why it is used for menopausal hormone replacement therapy. In fertility cycles, the first half of the cycle needs to have unopposed estrogen stimulation so that the lining will grow. Then once ovulation occurs, the progesterone is introduced to help the lining convert to a luteal phase lining so that implantation can occur.

Your proposal for an internet consultancy is interesting, I will send you an email. I'll have to think about that one. In terms of your supplementation, I use the following protocol:

1. I use the estrogen patch for estrogen supplementation such as the Climara patch. I use two 0.1 mg Climara patches beginning at the start of the cycle and continuing until the pregnancy test. If it is positive, then I continue it until you are 10 weeks pregnant.

2. For progesterone, I use a product called Endometrin 100 mg vaginal tablets. You place 1 vaginally twice per day beginning on cycle day # 16, or beginning with the HCG injection if you use an HCG trigger for ovulation. You would then continue this until the pregnancy test or 10 weeks gestational age if you get pregnant. Other forms of progesterone that you can use in the same way are Prometrium 100 mg or Crinone/Procheive 8% cream.

If you look up my blog regarding how I do Clomid ovulation inductions, it will give you directions on how I recommend doing Clomid cycles. Normally, as the follicles are stimulated and grow, they produce increasing amounts of estrogen. This then goes to the uterine lining and increases it. The problem with Clomid, however, is the way it works. It blocks estrogen receptors in the reproductive system and tricks the brain into thinking that it is not producing enough estrogen. So the brain responds by increasing the amount of stimulation of the ovary, hence ovulation is stimulated or multiple eggs are stimulated. By blocking the receptors, however, it can cause the uterine lining (endometrium) to no grow sufficiently.

Don't stress too much over all this, please take your time and copy these instructions. Take the time to discuss this thoroughly with your physician and 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.

Spotting In First Trimester Not Placenta Previa

Question:

Hi Dr. Ramirez,

I am a 35 yo with no children. I found out I am 7 weeks pregnant and went for blood work and a sonogram since I have been spotting and had sporadic cramps for a few days. My doctor discovered I have low implantation of the embryo and placenta previa from the sono, and low progesterone levels from my blood work.

My doctor said my progesterone levels are 13.5 and should be higher (around 15) so he prescribed Prochieve Vaginal Gel. Is Procheive a good thing and is it needed? Will it produce side effects in the baby?

For the placenta previa, I have read so much negative information which speaks of hemorrhaging to hysterectomy and C-section. While I am okay with the thought of a C-section as it may save my life and the baby's, is there any statistical information available which discusses the probabilities of fatalities and hysterectomies?

With that being said, I am pro-choice and would like to make an educated decision on if I should carry this pregnancy to full term. With all the obstacles in front of me, in your experience and opinion, what are the chances of having a healthy child?

Answer:

First of all, I don't think you need to consider terminating this pregnancy because there is nothing seriously wrong at this point.I think that your doctor is over-calling things. To be frank, the recommendations and diagnosis he/she has given you is inappropriate at this gestational age.

Placenta previa CANNOT be made at 7 weeks gestation. That is a third trimester (after 28 weeks) diagnosis. At your gestational age, the entire amniotic sac is filled with the placenta. The mature placenta has not even developed yet. Placenta previa is when the placenta blocks the cervical opening, which then requires a c-section. As the uterus grows, the placenta will move and 99% of the time, the placenta moves out of the way. So you don't need to worry about it.

In terms of the progesterone, he/she is mistaken about that as well, however, we use progesterone all the time with infertility patients to help support the pregnancy. It is usually started before implantation, however. It would not hurt and Endometrin is the prescription that I use. It will not harm you or the baby. The alternatives to Endometrin, which are just as good, are Crinone and Procheive.

Spotting is very common in the first trimester. We see it all the time with our IVF patients. It does not necessarily mean that anything bad is occurring. However, you are still in the miscarriage risk stage so sometimes, spotting or bleeding could mean that the pregnancy is not doing well and will eventually end in miscarriage. There is no way to know this unless the ultrasound does not show a viable fetus i.e. no heart beat or not growing.

I hope this helps. Don't worry too much.

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

Monterey, California, U.S.A.

www.montereybayivf.com

Bleeding After Embryo Transfer

In the course of my volunteering as the Infertility Expert on About.com's AllExperts site, as well as here on my own blog, I have had many questions regarding bleeding right after embryo transfer or in the Luteal phase. What follows is an attempt to answer one of the chief concerns that IVF patients have, namely, "What if I have bleeding after my embryo transfer?" 

**For those who wish to COMMENT with questions or observations, please note that the comment section is CLOSED on this post as it has exceeded the limit Blogger allows. Solution: You are welcome to choose any other blog post to comment on "bleeding after embryo transfer" and I will be able to answer you without a problem. Just return to the home page and choose a recent post. This is the most popular blog post because it is an issue that many go through while undergoing IVF, therefore do not hesitate to comment.**

Answer:

The embryo transfer is the most crucial step in the In Vitro Fertilization procedure/process. You can have the best quality embryos, but if they are not placed into the uterus correctly, then pregnancy will not occur. That is why "transfer technique" is so important. There have been studies showing that pregnancy rates can vary by Physicians within the same group, and this is all because of transfer technique. Once the disparities between transfer techniques were corrected and unified, the pregnancy rates became consistent. For this reason, you want to seek out a Physician who has a lot of experience with embryos transfers and comparable good pregnancy rates. If you go to a clinic that has multiple doctors, ask for the pregnancy rates of each Physician or your particular Physician. Although I know that newly trained REI Physicians have to get experience, most don't have a lot of embryo transfer experience from their fellowship. So, if I were paying $10,000 or more for an IVF cycle, I would ask for a more experienced doc to do the transfer. For more details regarding post embryo transfer bleeding, pain and other symptoms, see "What To Expect After Your Embryo Transfer". 

Bleeding, usually bright red blood, with the embryo transfer is an absolute no no. If blood contaminates the endometrial cavity at the time of the transfer, this will kill the embryos and pregnancy will not occur. The catheter must be placed as gently and atraumatically as possible. That is an absolute requirement. The endometrium, which is now in its fullest growth state, thickened from estrogen stimulation, can be easily scraped and cause bleeding.

At our center, we use very soft catheters, very gentle technique, ultrasound guidance and mock embryo transfers preceding the cycle, to accomplish this. The mock embryo transfer or MET is especially important so that the Physician is not learning the curves of your canal at the time of transfer but has worked it out prior. You should have the same Physician who did the MET doing your transfer. This is especially important in patients whom we consider to have a "tortuous" canal, making it more difficult to insert the catheter with care. In this type of patient I will sometimes do the MET two to three times to become well acquainted with their canal.

You should not worry if brown blood or discharge occurs at the time of transfer, it will usually manifest within the first day or so after the transfer, but not into the mid-luteal phase or later. That type of bleeding would be from a different source.

There are situations, however, when bleeding can occur but not be ominous. Sometimes a woman's cervix will bleed easily from being scraped by the speculum or irrigation or wiping. This external bleeding will not affect the endometrial cavity as long as the transfer catheter is not exposed to the blood. For example, I do not let the catheter get exposed until the introducer is well into the cervical canal, near the internal cervical os (entrance to the endometrial cavity), to begin advancing the catheter.

Bleeding that occurs later in the luteal phase, days after the transfer, is very common if vaginal progesterone is used. This has been shown in various studies using Crinone, for example. In my patients, because I use both vaginal and injectable progesterone, it is almost 90%, but the bleeding tends to occur near the time of the pregnancy test or soon thereafter. This is probably caused by some erosion occuring on the external cervix. The exact cause, however, is not clearly understood. It is usually light spotting and can be anywhere from red to brown. Red is newer blood and brown is old blood. In general I tell my patients not to worry about this. The only bleeding that I would worry about is bleeding that is red and heavy like a period. This is not good, and should not occur if the hormones progesterone and/or estrogen have not been discontinued. Some patients will experience slight spotting 3-5 days after embryo transfer and refer to this as "implantation bleeding." Whether or not this is caused by implantation is not known. Implantation should not cause bleeding. However, again, if it is not bright red blood that is heavy like a period, it should not cause worry.

I certainly hope this information will help those of you who have either queried me or who have Googled for some reassurance in this regard.

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

http://www.montereybayivf.com/

Progesterone Injections & Travel After IVF

Question:

Dear Sir,

Our first IVF (during June 2008) failed and so, we are going for the second IVF which is FET (frozen embryo transfer). I have the following questions:

a) Progesterone-in-oil shots: During the last IVF it was very difficult and stressful to have the intra-muscular shots every day. After a week, the muscle became very rigid and at some point could not even poke the needle into the muscle. Will it be okay if I do a hot water massage after every shot? I am concerned because some nurses are saying it may raise the body temperature and could cause problems.

Are there any alternatives for intra muscular injections (for progesterone)? One of the nurses is suggesting to apply directly into the vaginal area. Since we haven't done that before we are not sure how tedious is that and the possibilities it could go wrong.

b) Will it be okay to travel long distance (approx. 3 hours) in a car - three days after the transfer?

Thanks so much in advance for your valuable suggestions.

Roger

Answer:

Dear Roger,

The progesterone injections are probably the worst of all the injections because it requires a bigger needle and the fluid is thick. I have changed from a prgesterone in sesame oil to a progesterone in canola oil that my pharmacy make us (MDR). Because it flows easier, we can use a smaller bore needle to reduce the pain and it doesn't harden up. You might want to check into that formulation. MDR Pharmacy is an infertility specialty pharmacy and you can get your meds via mail. It is also less expensive.

In terms of hot packs at the injection site, that would be fine. I don't expect that will change anything at all if it stays local.

Also, make sure you are rotating the sites i.e. one buttock then the other. You can also change the specific sites in the buttocks as long as you are in the upper outer quadrant. Make sure your nurse shows you all the areas that you can use.

As an alternative to IM progesterone, you can also use vaginal progesterone. There are several formulations: Crinon 8%, Prochieve 8%, Endometrin 100mg and pharmacy formulated versions. Several very good studies have shown equal efficacy to IM progesterone. However, most RE's are trained on IM Prog and so don't want to make any drastic changes. I happen to use both. Some programs, such as USC, have switched to vaginal completely. If your wife cannot tolerate the IM Prog or has an allergic reaction to it, then you can switch to the vaginal version. Crinone and Procheive are twice per day, and Endometrin is three times a day. They are messy but they don't hurt.

In terms of travel, yes it is okay to take a three hour trip after the transfer. As long as your wife is in a resting position, such as sitting, then you can travel. I only don't recommend strenuous activities such as exercise, karate, horse back riding, running and the like.

I hope this helps!

Edward J. Ramirez, MD

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

Monterey, California, U.S.A.

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