Wednesday, August 31, 2011

Woman Has Lost Both Ovaries: Why Does She Still Have A Period?



Question:

Hi,

My daughter has lost both ovaries due to cysts. The doctor has put her on Progyluton. We are aware that she cannot get pregnant but the doc says she will still have a bleed. Is this so and if so, how come? S. in Barbados

Answer:

Hello S. from Barbados,

I sincerely hope that your daughter was not young because having cysts, if they are not malignant cancerous cysts, is not a reason to remove the ovaries of a young girl or young woman. That would be malpractice.

The reason you daughter has menstrual cycles is because she still has a uterus. It is the uterus that bleeds with the menstrual cycle. The ovary is what causes the uterine lining to grow in preparation for an embryo to implant, but if this does not occur then the lining is shed and cleaned out each month. Then the cycles starts over again. This cycle can be replicated with the birth control pill (progyluton is an estrogen or estradiol, used for hormone replacement therapy).

Thank you for writing,

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.

Friday, August 26, 2011

37 Year Old Fails 3 Clomid Cycles & 2 IUI's: What Should She Do Next?




Question:

Dear Dr. Ramirez: thank you for your great service!

I just turned 37 years old and have been ttc for 1 year already. My cycles all my life have been like clockwork (ovulating on day 13 in a 26day cycle). After charting and some blood tests during the early months of ttc, I realized I had low progesterone. I was put on suppositories and after another 6 months of no success, I was put on 50mg Clomid. That's when my cycle was completely thrown off. On Clomid cycle #1, I ovulated on day 19 (much later than normal), on Clomid cycle #2, I ovulated on day 14. Both cycles were followed by unsuccessful IUIs (intra uterine inseminations). On Clomid cycle #3, I ovulated on day 11, so we missed it and didn't do IUI. On cycle #4, I ovulated on day 10 and I did two back-to back IUI (again unsuccessful). My lining is fine, there are no cysts and all my blood work on all hormone levels is good within healthy normal levels. In fact my hormone levels were normal when I tested during my natural cycle before taking Clomid. Only progesterone was low and the suppositories didn't provide enough (day 21 showed 12 only), so 2 months ago I was put on PIO and that works like magic (level was 33 and 36 on day 21).

I read in on your blog that women who ovulate on their own shouldn't take clomid, which may REDUCE their chances of getting pregnant. Did we undertake the wrong treatment? Again, until I started clomid, you could set your watch by my cycle and I could check my ovulation using the monitor. After taking Clomid, my monitor cannot register any hormone changes and peak ovulation anymore. I was told that given my age the next thing to do is move to a more aggressive treatment (injectables), but if I was so regular and ovulating on my own, why do i need the injectables?

The fertility center never did an ultrasound to see how mature my follicles are during my natural cycle (they did this only when I was on Clomid), so my inclination is to get off clomid and try a natural cycle for a few more months again and ask them to see if my follicles are large enough. Would you think that's wise or shall I move to more aggressive treatments? My husband's sperm count varies from 25mil to 100mil during the IUI cycles. He also had average motility of 90%. Semen analysis also indicated 80% morphology.

Thank you kindly for any advice you may be able to offer. L. R. from Lancaster, PA

Answer:

Hello L. from the U.S. (Pennsylvania),

The main problem, and only problem that you have identified, is your age. I call this the age related egg factor. This means that the eggs have aged and have decreased in quality and viability. A study was done to look at embryos created at 37 years old and did genetic testing on those embryos and found that only 20% were normal, a reflection of egg quality. So that is the hill that you are trying to overcome.

In this case, the use of fertility medications is to achieve "superovulation" not ovulation. The main use of Clomid is to induce ovulation in women that are not ovulating but in older women, the goal is to increase the number of eggs that you ovulate to increase the chances that you will ovulate a good egg. In my patients over 35, my goal is to get them to ovulate 3-5 eggs per cycle. In my blog what I am referring to is the tendency for general docs (family practice and Ob/Gyn's) who automatically place an infertility patient on Clomid without finding out the root cause of their infertility, as if Clomid were some magic drug. They are misusing the medication.

In your case, because you stated that you are at a fertility center, I presume that you have undergone an infertility evaluation and nothing was found except for your age, so superovulation would be a reasonable first step. I also don't recommend consecutive Clomid cycles because Clomid works by blocking estrogen receptors and too much Clomid with block the estrogen receptors that are necessary for fertility, such as tubal motility, endometrial lining development and cervical mucous production. In that case repetitive Clomid cycles can lead to infertility by blocking these receptors.

Because of your age, I do believe that you need to pursue an aggressive treatment plan. I usually do not recommend more than 4 IUI cycles as part of an aggressive treatment plan because studies have shown that most patients will get pregnant within four attempts and pregnancy rates decrease dramatically after four. Keep in mind that at your age, your pregnancy rate per IUI cycle is only 12%. But if you want to continue to try IUI, then it is reasonable to try with injectables, although these meds are a lot more expensive, for two more carefully monitored and timed cycles. Then if that is not successful, I would strongly encourage you to proceed to IVF.

By carefully monitoring, I mean that ultrasound screening should begin at cycle day #9 the proceed from there depending on the size of the follicles. The closer you get to ovulatory size, the more frequent the ultrasounds will be. HCG should be given to trigger the ovulation. IUI's should be done at 24 and 48 hrs after the HCG trigger and then the progesterone is started the day following the second IUI and continued until the bHCG. Progesterone should be given as a vaginal suppository 2-3 times per day depending on the formulation.


Good Luck and thank you for reading my blog!

Dr. 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.

Thursday, August 18, 2011

Secondary Infertility Patient With Seven Miscarriages: Cannot Afford IVF


Question:

Hello-I am 33 and have a healthy 3 1/2 year old daughter who was conceived naturally. I have had 7 miscarriages (1 before my daughter and 6 consecutive since her birth). I have had 4 chemicals, 2 confirmed blighted ovums and 1 xxx69..this one had a heartbeat and all hormones were great, heart stopped at 8 weeks and did a karyotype on fetal tissue.

I've been to an RE and have had the following tests: Karyotype, HSG, Day 3 Hormone Panel, Clotting Disorder Panel, ultrasound to measure lining of uterus and to check for any abnormalities...all results are "normal". I have also supplemented with progesterone after a positive pregnancy test as well, my LP is usually 11-12 days. My hubby has only had a karyotype and he is "normal" as well. The RE said that our XXX69 was more than likely due to a mutated sperm containing an entire extra set of chromosomes. He has recommended we do IVF (in vitro fertilization) with PGD (pre genetic determination).

Our insurance doesn't cover ANY fertility, so that is really not an option for us.The RE wanted to me to try a monitored clomid cycle as a plan "B". In doing some research, I just don't think clomid will help with unknown recurrent pregnancy loss...what is your opinion? I "O" just fine without any meds. What else would you recommend? I am in excellent shape, eat organic whole foods, don't consume any alcohol or caffeine..

I take prenatals and fish oil daily. Do you think that all my miscarriages could be a sperm issue? I'm really at a loss....what do you think our chances are of having another healthy child without doing IVF/PGD? Thanks, S. from Maryland.

Answer:

Hello S. from Maryland,

I am sorry for your losses. You certainly have recurrent abortion as a diagnosis, but the exact cause is unknown. Granted that the fetal tissue from the last miscarriage showed a genetic abnormality, but if your husband's genetic testing was normal, then I would not expect that all the miscarriages were for the same reason. I would think that it is more likely to be a spontaneous genetic abnormality occurring with division of the embryo. Hopefully that is the case because that means that there is still a good chance of having a normal pregnancy. If the problem is a sperm abnormality causing a genetic problem, then there is very little that can be done to change that other than using donor sperm.

One alternative would be to try IUI (intra uterine insemination), since the sperm will be washed and the best sperm will be made available for fertilization. There is no guarantee with this but it is an option. Your RE is correct in that the only way to make sure that a normal embryo is available for implantation is to do preimplantation genetic screening with IVF. Since you cannot do IVF, then the only option is to continue to try and hope/pray for the best. I do not think you need to do Clomid either. It doesn't help with this problem. The good thing is that you are still young and have time to keep trying. Hopefully with continued trying, you will be successful.

If you were my patient, I think I would add low dose aspirin 81mg per day, PNV with folic acid, Medrol 16 mg per day, progesterone supplementation in the luteal phase (Crinone or Endometrin) and low dose heparin 2000 unit injections twice per day with each cycle. These are more to cover the immunologic causes of miscarriage, but have been shown in numerous studies to help. Since we cannot be sure exactly why the previous miscarriages occurred and can't conclude that it is ONLY a genetic problem, I would favor covering those bases.

Good Luck,

Dr. 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.

Saturday, August 13, 2011

Right After A Cancelled IVF Cycle, Try Naturally Or IUI?


Question:

Dear Dr. Ramirez,

I write to you from Los Angeles, California. I am 38 and just started an IVF (in vitro fertilization) cycle after two FETs (frozen embryo transfers) that did not take. Those embryos from the FET were from an IVF I did when I was 36 that resulted in my wonderful son. I am on Bravelle and went in for my first ultrasound and they saw only two developing maturing follicles, one on each side, that were outpacing all the rest. Previously, they had seen about five on each side. My doctor has cancelled this cycle but recommended continuing on the Bravelle for two more nights and then trigger ovulation and timed intercourse. My questions is, should I do IUI instead of just timing intercourse? I know that my chances are very low of conceiving anyway, but my feeling is that if we are paying for the meds and these ultrasounds, that perhaps we should optimize our chances, even though they are very low. The doctor was trying to minimize our costs and suggested timed intercourse instead of the IUI.

I am hoping that these two years that have passed since my son was born haven't led me to be a 'poor responder.' The doctor said that sometimes this happens and that we can try a fresh ivf cycle next month and he would increase the amount of the stimulation drugs.Any thoughts on IUI versus timed intercourse or anything else?

Answer:

Hello S. from California,

I don't recommend canceling IVF cycles normally because you never know if the perfect egg is in one of those follicles. In addition, despite the fact that two have outgrown the others, that does not mean you can't get mature eggs from the other follicles. There have been studies that have retrieved mature eggs from follicles as small as 10 mm. So even if there is only one follicle, I like to give it the best chance that we can. I know that this is a more expensive way to go, but I've had numerous pregnancies from just one follicle. Bear in mind that IVF has a significantly higher pregnancy rate, even with only one egg, than any other method at your age, per cycle. In my center it would be 70% pregnancy with 40% continuing with IVF vs 7-10% with IUI.

That is because, if you image how the natural cycle process works, it takes 10 steps for your body to accomplish a pregnancy:
(1)Brain sends FSH to stimulate the ovary to grow follicle
(2) Ovary grows follicle
(3) Follicle ruptures out of ovary (ovulation)
(4) egg is pulled into the culdesac with the fluid from the follicle and finds (or has to find) tube within 12-24 hrs
(5)Egg is picked up by the fimbria of the tube
(6) Sperm and Egg meet within the tube and fertilization occurs
(7) Egg travels down the tube and divides into blastocyst
(8) Embryo enters uterine cavity
(9)Embryo hatches and exits from its shell
(10) Inner mass attaches to the uterine lining and the lining grows around the embryo (implantation)

With IVF, steps 1-8 are accomplished for you and only two steps left up to chance/nature/God, whereas with IUI, only steps 1 and 2 are accomplished for you. The rest occurs naturally.

In any case, there are several issues you have brought up and questions that correspond. One is whether you should do IUI vs try naturally right after a cancelled IVF cycle. Statistically, IUI has a better chance of pregnancy than pregnancy (7-10% vs 5%), so for that reason alone, I would go with IUI. I would recommend following the exact same protocol as you would of with IVF except that retrieval and transfer will not occur. I would do the same progesterone supplementation.

The other issue is regarding your stimulation. It is obvious that you were not stimulated with the max protocol if you doctor commented that they are going to increase it. You may have a decrease in response but without getting maximum stimulation, you don't know that for sure. So, you may not be a poor responder. You just did not get stimulated adequately.

The good news is that you have had one successful pregnancy. It is a good thing that you are pursuing having the second at 38 yr.s, before you become much older and the rate of success drops dramatically.

Good Luck,

Dr. 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.

Saturday, August 6, 2011

Previous Ectopic, Left Salpingectomy, Painful HSG: Can I Still Get Pregnant?


Question:

Dear Dr. Ramirez,

Approximately 8 years ago, after the birth of my first child, I had an IUD (copper T) inserted. About 6 months later, I lost the thread,and went back to the medical practice for it to be removed and replaced, but was told that losing the thread wasn't a threat. Anyway, 2 more months later, I had an ectopic pregnancy which ruptured my left fallopian tube and resulted in an emergency salpingectomy...... the entire tube was removed (about 7 cm).

Fast forward 8 years, I am ready to have another child, however an HSG (hysterosalpingogram) revealed proximal blockage to my right tube. I was in an immense amount of pain during this procedure.....that I cried. I am not convinced that the results of the HSG are accurate because of the pain (similar to labor pains)that I felt. Also because the ectopic was due to a foreign object, I don't feel that there should be anything wrong with my right tube. Anyway, my questions are as follows and I really appreciate your time:

1. Since the IUD was the cause of my ectopic pregnancy, would I be considered a high risk for another ectopic (assuming my right tube is not blocked#?

2. Based on the pain that I was in, could the proximal blockage be a result of a tubal spasm? What are the stats on false hsg readings for proximal blockage?

3. Is it possible that a left salpingectomy could result in scar tissue blocking the remaining right tube?

4. And finally, my uterus and ovaries (I still have both) are healthy per the scan. There is evidence of scarring from my previous c-section. How feasible is it for my right tube to pick up an egg from my left ovary as I usually feel ovulation cramping on my left?

Thank you very much in anticipation. E. (age 35),USA

Answer:

Hello E. from the U.S.,

You cannot be sure that the IUD was the cause of the ectopic. That would be a false assumption. Certainly having an IUD in place can increase the risk of an ectopic but intrauterine pregnancies also occur with IUD's in place. The IUD does not block the tube, it creates a hostile bed for implantation of the embryo. Ectopic pregnancies mostly occur because of fine adhesions within the tube which prevent the embryo from migrating into the uterus. As a result, the embryo implants there. The most common reason for these adhesions are from some form of inflammatory event in the past, often a sub-clinical (no symptoms) infection by a bacteria. Chlamydia is the most common form but some studies also point to multiple different bacteria. In any case, this infection gets into the tube, causes the tubal lining to become inflamed thereby resulting in scar tissue formation. It is possible that this inflammation is was led to the blockage of the right tube, whereas the left tube was only partially blocked, hence the ectopic.

In terms of the pain with the HSG, yes, it could mean that you had tubal spasm but the more likely source was that because the tube is blocked, the increased pressure or pushing by the doc caused increased stretching of the uterus and hence increased pain. I would have to look up the statistics for false readings on HSG, but it is low and so HSG is the gold standard for the diagnosis of tubal blockage. I am sure there is some false positive or false negative readings, however.

If the surgery was performed without incident, a salpingectomy on the left should not cause blockage of the right tube at its entrance. Any pelvic surgery could lead to scar tissue formation within the pelvis and lead to blockage at the end of the tube, however (your previous c-section).

If the right tube is normal at the fimbriated end, and there are no adhesions within the pelvis, then there is a good chance of egg pickup even if ovulation is from the opposite side. The reason is that the egg from one side of the ovary does not necessarily go directly to the tube on that side. The opening to the tube is not that close to the ovary. In fact, the egg falls into a pool of fluid within the culdesac, a space behind the uterus, where the tube lies and through fluid motion, gets to the tube. So pregnancy can and have occurred in patients with a functioning ovary on one side and a normal tube, without an ovary, on the opposite side.

Good Luck,

Dr. 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: Dear Dr. Ramirez, Thank you very much for your response. You are very knowledgeable and I feel very enlightened. Again, many thanks, E.

Monday, August 1, 2011

New 2011 Study Questions Routine Metformin Use In All PCO Patients



Dear Readers,

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

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

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

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

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

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

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

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

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

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

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

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