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.

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/

40 Yr Old German Woman With Great Ovarian Stim Fails IVF: Likely Abnormal Embryos, Try Again!

Question:

Dear Dr. Ramirez,

My name is A. from Germany, 40 years old, never pregnant before. I had 2 failed IVF this year (1 in March, 1 in June). My FSH=10.6, AMH=0.8. progesterone level is normal.

The 1.IVF had 6 eggs (2 embryos were transferred: 1 grade 1 and 1 grade 2) and 2.IVF had 7 eggs (3 embryos with grade 1 were transferred in July).

The 2.IVF was done in North Cyprus. Do you think the failure was caused by taking airplane back home on the 2.day after transfer? It was just about 3.5 hours flight.I will try the 3.IVF this year.

How long should I take a break before trying the 3.IVF? Because I heard that the hormone level, uterus lining and ovary need time to get back to normal. Are these correct? I have also read an answer of yours regarding implantation failure.

You wrote in March this year:

"My approach to patients with implantation failure is to add the following medications:
1. Aspirin 81 mg per day beginning at the start of the cycle.
2. Heparin 2000 units twice per day beginning at the start of the cycle.
3. Medrol 16 mg daily until transfer then 8 mg from that point until positive pregnancy, then stop.
4. Increase progesterone to 50 mg injection plus Endometrin 100 mg twice per day vaginally. The injections starts on the day of the retrieval and the suppositories start the day after the transfer. "

My questions are:

1.what for an effect is the heparin in the case of repeated failure? I did not have this in the last 2 IVF. Do I need this, even I do not have thrombosis problem?

2. Do I need to increase my progesterone level even I have a normal level?

3. I will do an autoimmune test next month. Which tests should I do in addition?Thank you very much for your time. Best Wishes. A.

Answer:

Hello A. from Germany,

I was impressed to see that your ovary stimulated well and gave you an adequate number of embryos despite your age and elevated FSH levels. One thing to keep in mind is that despite having a good IVF cycle with reasonable embryos, IVF is not a perfect technology. The last two steps, embryo hatching and attaching to the endometrium and implantation, must occur naturally. This does not always happen. Also the embryos have to be completely genetically and otherwise normal. There is a higher chance of abnormal embryos with increasing age. That is what is called the "Age factor."

What that means for older women (35 years and older) is that it may take a lot more attempts to achieve a pregnancy, but as long as the ovaries still respond and put out eggs and embryos, then you have a good chance. Also keep in mind that pregnancy rates are highly variable among clinics so the clinic you go to is very important.

With multiple failed attempts, I add the protocol that you cited. There is a saying in the U.S. called "throwing in the kitchen sink" which basically means doing everything you can possibly do. That is the reason for this protocol. These medications are mainly used in patients that have recurrent miscarriages. But in IVF failure patients, it seems to work as well.

The Heparin and aspirin are at low doses so they are mainly targeting very small clots that occur in the micro-vessels that feed the implantation site. It is not enough to prevent a large clot in your vasculature. At that level they also have an anti-immune action to prevent failure due to an increased immune response from your body. That is also the reason for the Medrol or prednisone. It is an anti-immune drug. Some women are found to have an increased immune system when an antiphospholipid antibody screen in done (21 points). Finally, the increased progesterone is to insure that adequate progesterone is reaching the endometrium because this hormone is vital to implantation and survival of the pregnancy.

Travel is not an issue. I have many patients that come to me from far away places, yet they have been successful. Studies have shown that travel has no impact on pregnancy rates. What is more important is finding a good IVF center that uses state of the art techniques and has good pregnancy rates in your age group. I have many patients that come from Europe so that is always an option as well.

Good Luck,

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

Calendar Method Vs. OPK? It's All In The Timing...

Question:

So my husband and I are trying for our first child. We've trying for about 3 months with no luck yet. i was thinking of trying the ovulation test but i'm not sure if its worth it. I've read online that they can help but i figure it would never hurt to ask. Do you know much about them and if there worth the money or should i just track my temp every morning.Thanks for the help! S. from Canada

Answer:

Hello S. from Canada,

An ovulation predictor kit (OPK) does not help any more than timing it well. I don't recommend it to my patients. Instead, I recommend the calendar timing method. It goes like this:

CD#1 The day your period starts. Mark you calendar then count each day. For instance the next day is cycle day #2, then cycle day #3 etc.

CD#10 Stop having intercourse. You can have regular intercourse until that day but you have to stop on that day.

CD#13-17 Assuming you have normal regular cycles, this is your fertile period. You should have intercourse each day, only once per day and only one ejaculation per episode. After cycle day #17 you can resume your normal frequency.

Keep in mind that 85% of women under the age of 30 take 8-12 months to achieve pregnancy so you have not yet been trying long enough. Hopefully this method will help.

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: Ok thank you so much for the advice! I'm going to try the calendar method.

Failed IVF Cycle With Drop in Estrogen & Progesterone Levels & PCO Type Response: Might Benefit From Adjustment In Protocol

Question:

HI, I have a question regarding spotting 5 days post transfer with full period bleed on 6 days post transfer. Here is our history:-I am 32 and my husband is 41. He has a daughter from a previous relationship.-I was diagnosed with diminished ovarian reserve in January, and also stage III endometriosis in June with a laparoscopy. They were able to clean out almost all of the endometriosis except for some on the colon because I did have some bowel in my colon and they didn't wan to rip it. They also found a polyp in my uterus that they removed. Also, I have a luteal phase defect as I always would spot around 9dpo and would have an 11 day luteal phase with 24-26 day cycles.

- January/February 2011 - First treatment cycle. Letrozol with monitoring and intercourse and prometrium 50mg 1x a day. Luteal phase increased to 14 days with 29 day cycle. Negative.


-February/March - An ovulatory cycle - went in on day 3 and never came down to baseline. Ovulated day 8 (which has never happened) so couldn't do meds. Prometrium again, but only 11 day luteal phase, obviously negative.


-March/April. Anther cycle on Letrozol and prometrium - same as first cycle but negative.


-April/May - Moved to injections. Follistim 150mg and then decreased to 75 due to good response and high estrogen. Ganirelex 3-4 days prior to IUI. HCG trigger with 6 follicles developed and 1 mature. IUI with crinone (prometrium was causing depression). Luteal phase 14 days with 28 day cycle - negative.-Laproscopy in June.


-IVF June/July - Long protocol - BCP, 10mg Lupron for 10 days, Follistim 150mg day's 3-6, increase to 175 day 7-9 (estrogen at 840 after this). Decrease to 150mg days 10-11(estrogen shot up to 3400) Decrease Follistim to 75mg day 11-12 (estrogen 6000). All along with 5mg Lupron. HCG shotday 13(only half dose b/c estrogen so high. Retrieval on day 15. Starteg Crinone that day. 15 eggs retrieved with 14 fertilizing without assistance (husbands sper is great quality). Day 5 transfer, 1 blastocyst very good quality. All other embryo's taken to day 6 to freeze, but all but 1 poor quality so couldn't freeze. The 1 completely hatched so couldn't freeze and they didn't want to disrupt other embryo by transferring it. I had a follow up on day 5 post transfer to just check me for OHSS and they took my levels and my progesterone was 3 and estrogen 60 (at baseline they have never seen it below 72).


I knew something was wrong b/c I started spotting that day and a full period started that night. It is very heavy bleed which I usually don't have, but not nearly as much pain as I have had int he past, most likley from the endo surgery. I am taking a little while off, but it sounds like they think I have a true luteal phase as they never see this response to IVF. I want to be as edcuated as possible when I meet with my doctor.


What would your suggestion be for a luteal phase protocol to address this? I am nervous about the shots. The nurse said possibly estrogen patch, prometrium, and crinone or something along those lines with 2 progeteron meds. I have also asked to have my levels monitored during the next luteal phase. I am taking a cycle or two off before jumping into the next cycle. I am lucky to have the flexibility b/c my insurance covers this. I appreciate your feedback on this.


Thank you! K. from New York

Answer:

Hello K. from the U.S. (New York),

You had an awkward IVF cycle to say the least, was my first impression. There were several interesting moments in your cycle. First, your response was very characteristic of a PCO-type response, very sensitive ovaries. I don't know if your doctor was expecting this or not, but hitting an estrogen level of 6000 put you at very high risk of OHSS. Despite this, your doctor continued the cycle and triggered with HCG, which further increases the risk. I think you are lucky to not have developed full blown OHSS.

Second, I found the up and down of your meds to be unusual.

Third, a PCO type response would explain the decrease in embryo quality. When the ovaries are hyperstimulated they often lead to a deficit in embryo development or quality. That would explain why there were so few embryos to freeze. If they had to culture to day#6 that means that the embryos had not reached blastocyst stage by day#5, which is not necessarily a good sign. For the one that did, I was surprised it wasn't just frozen at day#5 so there would not have been a hatching problem. Why did they wait an extra day?

Finally, the abrupt drop in estrogen and progesterone levels was sure curious. I have never seen such a precipitous drop in a patient that is receiving supplementation. Surely, the problem with serum (blood) hormone levels is that they don't accurately reflect the levels within the endometrium, but there will be some levels and there are minimum levels in the blood that we know usually mean there is adequate levels in the endometrium. Neither of your levels met these minimum levels, but there should have been hormone in the blood because of the medications you were taking. You were taking medications weren't you? I would be very surprised if they didn't supplement you. Basically the bleeding that you had was the onset of your period because the hormone levels had dropped so precipitously. That is how it works in a natural cycle.

Certainly in the next cycle, I would recommend that you take progesterone injections (50mg) per day beginning with the retrieval, then add vaginal progesterone (Crinone or Endometrin) after the embryo transfer (because it is messy and interferes with the transfer), I also would add estrogen supplementation by patch starting with the transfer as well, but in your case, your levels should have been high from the hyperstimulation. I'm still thinking of possible causes for the drop. . . did you not stop the lupron?

Protocols are highly different between centers and there is not one protocol that is necessarily better than another. These are just suggestions. Your doctor may want to do something entirely different. Also, because you had a PCO-type response, I would recommend that you not use the long protocol and instead use an antagonist protocol with Lupron 0.5 mg as the trigger instead of HCG. This will reduce your chances of developing OHSS.

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.

Inadequate Luteal Phase Support In IVF Cycle Can Cause Bleeding & Failure

Hello Dr. Edward,

Thank you in advance for your answer! I'm from Paraguay. I just went through my second IVF-ICSI and both times I started bleeding 7-8 days after day 3 transfer, just when implantation should be occurring. Do I have an implantation problem? Are there any tests I should do? What should be done to prevent this early bleeding? I'll appreciate your expert opinion on this!

Here are the details of the case:

He: 38, had testicular cancer 6 years ago (unilateral orchiectomy and radiotherapy), very low count, morphology and motility. Now healthy, treated autoinmune hypothyroidism, BMI 26.

She: 34, no known fertility concerns, healthy, BMI 27.

Went directly for IVF-ICSI due to male factor.1st IVF/ICSI: 12 eggs, 6 fertilized, 3 transfered (day 3, 2x 8 cell + 1x 7 cell, fair quality), none to freeze. Long agonist protocol: suppressed with BCP + Lupron, stimulated with Menopur + Puregon, triggered with HCG, after ER Dostinex (8 days), anti-inflammatories and antibiotics (3 days), luteal support with Prometrium. Early bleeding 8dp3dt: BFN.2nd IVF/ICSI: 14 eggs, 8 fertilized, 3 transferred (day 3, 1x 9 cell + 1x 8 cell + 1x 7 cell, good quality), 4 frozen. Same protocol, added Estrace and more Prometrium for luteal support. Early bleeding 7dp3dt: BFN. Thank you!

Answer:

Hello E. from Paraguay,

Thanks for the information. You don't mention how much Prometrium you used in your cycles but I think that may be the problem. I think you may have inadequate luteal phase support i.e not enough progesterone. Certainly prometrium should be adequate to cover the luteal phase, and many studies have shown that vaginal progesterone only is adequate, but the dosage has to be adequate as well. I think the minimum used should be 100mg three times per day. In my practice, because I don't want patients to not get pregnant or lose a pregnancy because of inadequate progesterone, I use both injectable progesterone 50mg per day and vaginal progesterone (I use Endometrin) 100 mg per day. That is what I would recommend for you. You should not be having bleeding that soon after embryo transfer.

Protocols and technique are what distinguishes IVF centers and their respective pregnancy rates. So, that is what you need to carefully evaluate.

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.

Jamaican Woman Doing 1st IVF Confused About Meds: Possible PCOS Misdiagnosis

Question:

I am about to do my first ivf with a clinic and I got a lsit of medications that I will have to use/purchase. I am a litte uncertain about one of them - menopur. The list has over 40 vials of 75iu. I am certain that this is a mistake.

I will of course be asking the clinic but I wanted to be certain. I have had two iui - failed previously. one on clomid with three follicles gretaer than 10mm and one with menopur 150 with about 4 or 5 follicles. This is why I am uncertain about the quantity of menopur on the list.This medication represents the most expensive item on the list and I wouldn't want to order this many at once.

Again, I will be clarifying but I needed additional research/opinion. I have pcos and was diagnosed with endo, had a laporoscopy, ovarian drilling, suppression after lap etc etc

Thank you. KL from Jamaica

Answer:

Hello KL from Jamaica,

I cannot tell you if this is the right dose or not because it depends on the protocol your doctor has you on. But I can make the following comments:

1. PCOS patients tend to be very sensitive to medication and therefore require less medication to stimulate. For that reason alone, I would be skeptical, as you are, of the amount of medication ordered.

2. Menopur is NOT a good medication for PCO patients (if that is a correct diagnosis) because PCO patients already tend to have an increase LH level and the additional LH in Menopur is not needed and will lead to the risk of ovarian hyperstimulation syndrome (OHSS). I will usually either use only Follistim or will use a very low dose of Menopur less than or equal to 75IU. However, given that you only had 4-5 follicles with Menopur 150IU before, I wonder if maybe the PCO diagnosis is not correct?

You definitely need to ask your doctor regarding these concerns.

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.