Sunday, July 19, 2009

IVF implantation failure

Questioner: Sophie
Subject: IVF implantation failure; luteal phase brown spotting, even with high progesterone levels Date

Question:
Dear Dr. Ramirez,

I have found your responses to others extremely helpful!

I am 35 years old and am writing from Hungary. My husband
and I've just finished our second, unsuccessful round of IVF
with ICSI; both were 5th-day transfers with a good quality
pair of embryos in each. My husband had had two samples
frozen before his BMT several yrs ago, which is what we used
for the IVFs--it looks like now he occasionally has a
nonmotile cell or two, but not much else.

I would very much appreciate your thoughts and advice on
luteal phase issues, including luteal phase support during
IVF, given a potentially short luteal phase and pre-cycle
brown spotting.

The first round of IVF, I got progesterone suppositories,
but my prog. level was fluctuating with that (was as low as
18.85 9 days post-transfer, and was up to 43 3 days later).
As a result, bleeding started 7 days post-transfer.

For the second IVF (with frozen embryos), I got progesterone
injections instead, which kept my prog. level up (56, 65).
Nonetheless, I still had definite brown spotting starting 4
days post transfer, gradually turning rust-colored. Both
transfers, I had mild cramps on days 2 and 3 after the
transfer.

As we were making preparations for the IVF, my fertility
doctor determined that I have a relatively short luteal
phase despite the fact that my cycles are 28-31 days long: I
ovulate on the 17th-21st day (20th is typical). In addition,
for the past three years, my period has always been preceded
by 1-4 days of brown spotting. And *including* those
spotting days, my luteal phase has been 9-12 days long
throughout 2009 (13 days when I was on Suprefact for the
ovarian stimulation).

A further detail that could be relevant: I have an
autoimmune thyrod disorder that is being monitored, no
medications for it. My anti-TPO level is 1516 and I have a
thyroid cyst about 3x2x3 cms in size, the biopsy was
negative. My thyroid levels have been normal: TSH 0.65-1.2,
T4 15.6.

Any thoughts on what might be behind the persistent pre-
cycle spotting, despite the high prog. levels with the
injections, and what can be done about it?

I would like to do all I can to exclude the possibility that
the embryos did not implant because of a luteal-phase-
related issue, especially because the number of chances
we've got are limited. Do you have any suggestions what
might be worth asking about, any variations on the protocol,
any further tests? Right now, the plan is to do the 3rd IVF
round--with potentially the last batch of frozen sperm--with
the same luteal phase support as before: ovitrelle for the
ovulation and prog injections, following a stimulation phase
consisting of suprefact and gonal-f 150. I am told that
based on my low HCG level ( 0.1) measured at 12 days post
transfer, the embryos did not even begin to implant in
either of the previous rounds. So the spotting in this
second round wasn't due to implantation then.

Also, I have read about taking vitamin B6 for luteal phase
defect, my doctor here says he doesn't know about that
helping with the short luteal phase and the spotting. What
are your thoughts on the matter?

I very much appreciate your time and help.
Yours sincerely,
Sophie

Answer:
Hello,

Thank you for all the information and the very well written letter. I can't even tell that you are from Hungary. Your English is perfect!

First of all, despite the fact that you may have had a luteal phase defect in the past, the purpose of the progesterone after retrieval is to treat for possible luteal phase defect. Therefore, you don't have a luteal phase defect with your IVF cycles, and this is NOT the reason for the implantation failure. Something else must be going on. You don't mention the quality of the embryos, but that would be one question. Also, you don't mention how many were retrieved, how many fertilized, how many did not make it to blastocyst and how many were frozen. I presume there were none to freeze since you don't mention it.

Implantation failure is a difficult problem because we are not able to distinguish all the processes required for implantation, and there are not tests to help. The only current test available, b-Integrins, don't help because the treatment is to use more progesterone. I would do that any way. Please read more on implantation failure and recurrent miscarriage here: "Recurrent Pregnancy Loss".

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.

This regimen covers most immune responses that might prevent implantation, as well as, any micro-clots that form at the site of implantation. It is used mainly in patients that have recurrent miscarriages, but has proved useful in IVF as well. You might want to suggest this to your doctors. This regimen is unproven and controversial, however. Another suggestion would be to transfer at day # 3 instead of going to blastocyst. Blastocyst culturing is not perfected, and I still believe that the uterus is a much better culture media and incubator that the lab.

Also keep in mind that pregnancy rates are very clinic dependent. There is a wide variety of pregnancy rates between clinic, and the rates can very much be influenced by the laboratory environment, the physician skill doing the transfer and the stimulation and culture protocols. One option might be to try a different clinic. I recently changed my clinic location and our pregnancy rates are much better than before because we were able to build a better facility.

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

117 comments:

  1. Dear Dr. Ramirez,

    I just completed my second failed IVF with ICSI. This last cycle we got 16 eggs of which 11 fertilized. On day 3 they called to say that 10 of them were grade 1quality and the 11th was grade 2 quality (with 1 being the best on a scale of 1-4). They waited till day five and transferred 3 very good quality blasts. They said the other 8 didn't make it to freeze.

    The first time we did IVF I had 7 fertilized eggs out of 12 and we got 2 blasts that were not nearly as good quality as this second IVF round.

    I have PCOS and Endo, but did a lap last winter and there didn't seem to be any Endo at the time. I think there's some kind of implantation failure going on because I've been actively trying for seven years and we've only been pregnant twice (1st time was empty sac, second time was Ectopic). In my twenties and thirties I didn't even ovulate because of the PCOS. I never had healthy menstruation until my mid 30's when my diet improved, which I think affected my PCOS and I started to ovulate, albeit late--on day thirty to forty.

    I only have two more IVF attempts remaining, but I have 8 IUI attempts that we could do if the IVF fails. I don't know if that's even worth consideration. I am trying to figure something out before my 2 remaining IVF's are all used up. I don't believe we can afford the nine thousand it would probably cost for donor eggs and my RE seemed to think that we had a pretty good chance with my own eggs because of all the follicles and eggs that I make. I should also mention that I just turned 44 this past January. Also, I'm well aware of the overwhelmingly dismal take-home baby rate for women who try with their own eggs who are my age.

    I've seen the advice that you've given other women in similar situations. Do you think doing a Day 3 transfer would be something to consider? My RE usually likes to do Day 5 so that they can see the quality of the blasts that make it, but so far this hasn't worked for me. Do you have any other suggestions regarding immune issues? That seems like a can of worms--something we'd never be able to get to the bottom of.

    Thank you very much for any advice,
    Elizabeth

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  2. Dear Elizabeth,

    Sorry for the delay in getting back to you. I've been searching to see how to respond and finally figured it out.

    It sounds like your two IVF cycles went very well for your age. The good thing is that your ovaries are still strong and responding.

    I think that the main issue here is inherent embryo quality, not something that you can see. I prefer day#3 transfers because we lose too many good eggs going to blasts, and blasts don't insure pregnancy. As I read your history I was thinking "why did this not work when everything looked so good?", but then I got to the age part. THAT is the problem. Despite having good looking eggs visually, that does not ensure good embryo quality inside. It is most likely that there are other problems within the embryo that is causing the problem. Going to blastocyst is a "false" test of embryo quality. I would recommend day# 3 embryos (I believe the uterus to be a better discriminator of embryos) and put back as many good ones as you can (give it your all). Bottom line, though, is you may have to use donor eggs eventually, but as long as your ovary still puts out lots of good looking embryos, I'd keep trying.

    I DO NOT recommend IUI's. It would to be a total waste of time and money.

    Sincerely,

    Edward J. Ramirez, M.D.

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  3. Dear Dr Ramirez
    Please can you advise me - I am 44 and have a healthy little boy aged 4 conceived naturally. I had a miscarriage this January (early) and then 6 months of fertility treatment. As the most eggs I could prduce with drugs was 3 and despite AIs could not concieve. Beacuse of my age we made the decision to use donor eggs and are so grateful for this incredible gift. The donor is 21 and has proven twice already. She produced 16 eggs and all ferilised, 8 Grade 5 embryos were kept and two transfereed. I felt cramping on days 3 and 4 after transfer and then very sadly they did not take. We have 5 frozen left so only two more chances to have this much longed for baby. I was on gestone injections and progynova tabs. Please can you give any advice as to how I can improve my chances for next time. Weight, fitness, supplements etc. Lining was only 7.9 but am using progesterone cream daily now to hopefully improve this, and Alpha Lipoic Acid. Please what can I do? I appreciate your advice. What are my chances of this working next time?

    ReplyDelete
  4. Hello,

    I am sorry to hear that your first cycle did not work, but that is not unusual. Even with young donor eggs, only about 50% of patients get pregnant on their first try. That is mainly because the last two steps of the process to get pregnant (hatching and implantation) are natural processes and we don't have the technology to make it happen. For that reason, you just have to keep trying. Almost 90% of patients will be pregnant by 3 attempts. It is a little reduced with frozen embryo transfers, however.

    In terms of advice to increase your chances, first of all, if your endometrial lining was inadequate (it should be at least 9 mms), you need to add estrogen, NOT progesterone. The estrogen is what makes the lining grow. I use Climara patches, but any form of estrogen can be used. With an frozen cycle, you doctor will probably take over your cycle by using a medication called Lupron to suppress the ovaries, then use some form of estrogen to thicken the lining. Then progesterone is added a few days before the scheduled transfer to convert the lining into the appropriate form for implantation.

    I also recommend low dose aspirin (81 mg) per day starting at the beginning of the cycle, and use Medrol 16 mg per day starting at the beginning of the cycle, in addition to progesterone. I also do recommend acupuncture to my patients, especially if they have failed. It is not a sure thing but it can't hurt.

    Of course, it will be important for you to be healthy, so whatever it takes to be healthy in your diet and activities is beneficial.

    You will have to ask your clinic what there frozen embryo transfer pregnancy rates are. Nationally, it is about 30% per cycle.

    Bottom line advice, don't give up. If you give up then you definitely have a low chance of getting pregnant. If you want another child, then you have to keep trying. Good Luck

    ReplyDelete
    Replies
    1. hi Dr,
      i have had 2 failed ivf.i was on aspirin,progynove6mg,clexane,predisolone,bromoprohin,doxytocin,cyclogest and progesterone inj. i have turner's syndrome so i used donor eggs.
      now my clinc is telling me that they want to test for nk to see if thats the cause for the failed implantation.they kept saying that everything was perfect and cant understand the prob. the grades of the eggs transferred was good and was a dy 5 blasto.what treatment do you think i should take tohelp my sit?
      also my first ivf they said the eggs rejected the icsi and disintegrated as soon as the needle touched it. is this possible?

      Delete
    2. Hello,

      I cannot answer your question without a complete review of your medical records. In answer to your ICSI question, I suspect that the embryologist err'd because the egg does not "disintegrate upon the needle touching it."

      Delete
  5. Dear Dr Ramirez
    Could you give me some advise. I am 36 years old and have 3 children. I was sterilised 11 years ago and then had an unsucessful sterilisation reveral 2 years ago. I was advised to try egg share / ivf.
    I have now had two failed attempts. The first attempt I produced 18 eggs thus 9 each, 6 fertilised and we had 2 grade A blastocysts which didnt implant. The second only produced 14 eggs (7 each) 2 fertilised only graded 2 & 3,I had 3 day tranfer with those. On both cycles the recipients have become pregnant.
    I have been back to the consultant and advised to have a lupus, thyroid antibody and Natural killer cells assay (CD69 & cytotoxicity)blood test. I was also told that they would like me todo another egg share as my eggs are of good quality.
    Do you recommend these blood tests as I have read conflicting evidence on these tests.
    Thank you.

    ReplyDelete
  6. Hello,

    Certainly it is perplexing that you have failed despite the recipient of your eggs getting pregnant. It is possible that you have an immunological disorder preventing implantation and that is why the doctor has recommended these tests. However, there have been many studies looking at immunological causes for IVF failure, and none have been proven. In fact, the American Society for Reproductive Medicine (ASRM.org) does not recommend immunologic testing or treatments because the data does not support this. I follow that recommendation as well.

    However, I do use a middle ground with my patients that fail implantation. I add low-dose aspiring 81 mg per day, low-dose heparin 2000 units twice per day and a steroid, Medrol 16mg twice per day, do cover possible immunologic and micro-clot causes. So as you can see, I am not totally convinced that there isn't an immunlogic cause. But, I don't waste my patient's money with extra tests. The two failed cycles is enough for me to add this regimen.

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  7. Dear Dr Ramirez,
    I apologize in advance for my question which you've undoubtedly been asked and have answered before...
    My question is centered around the protocol (meds) used post-ET and how it might be modified in my next cycle considering some of the data collBected on Day 9 post-ET.
    Recently, I had an unsuccessful IVF cycle using ICSI-PGD with assisted hatching. Two early blastocysts were transferred on Day 5 but failed to implant. I'm thinking embryo quality/maturity was the problem this time around given both males (by PGD) were characterized as 1CC's.
    Some relevant facts: I'm 37, 19 eggs were collected, 18 fertilized, 4 made it to Day 5, 2 males 1CC's were transferred, 1 female was 5CC (frozen) and 1 undetermined 1CC (frozen).
    My husband and I had 2 girls naturally and are looking to balance our family through IVF-PGD.
    We understand embryo maturation is extremely important however we can't reconcile the fact that our progesterone measured 4.6 on Day 9 post-ET while using 200 mg Prometrium vaginally 3 times a day?
    On ET day, progesterone was >40 and within 9 days it dropped an order of magnitude while on Prometrium?
    Should we consider progesterone pills or injection, immunoglobun injection, vaginal Viagra, vitamin B??? We're thinking vaginal Prometrium and daily baby aspirin was not enough to support our lut phase and implantation.
    We realize more mature blasto's would be beneficial, however we also think given the bloodwork more needs to be done for our next cycle.
    Thank you for taking the time to read and respond.

    ReplyDelete
  8. Hello,

    I have several comments regarding your cycle and recommendations for the next one.

    First, you need to keep in mind that there have been several studies showing decreased pregnancy rates with PGD. It is presumed that this is due to injury to the embryo by removal of one of the blastomeres. Therefore, it is possible that this had an effect of your pregnancy chances. I no longer recommend PGD other than for patients that require screening for inheritable genetic diseases. This is the recommendation from ASRM as well in the U.S.

    Second, certainly your post ET progesterone level was low. In the next cycle you might want to consider adding progesterone injections, 50 mg IM per day, in addition to your vaginal progesterone.

    I do not recommend viagra, vit B or immunoglobulin. However, if patients that fail, I do add heparin 2000 units SQ twice per day starting at the beginning of the cycle, to cover any low level immunologic problems and the possibility of the formation of "micro clots" at the implantation site.

    However, despite all this, I still think that the PGD may be the culprit and you will just need to keep trying.

    Good Luck,

    Edward J. Ramirez, M.D., FACOG

    ReplyDelete
  9. Hello

    I have just had my 2nd failed attempt of IVF. We are producing good quality embyros and everything looks great until we get a negative pregnancy test. Therefore I am thinking it is something to do with implantation. I am 25 so i dont think age has anything to do with it. is there anything else I can do to improve my chances of a more successful pregnancy. Maybe more tests? I heard that your immune system can effect this, is this true?

    Many Thanks
    Sharon

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  10. Dear Dr Ramirez,

    I am writing after returning home from the hospital with a descision to make.
    I am going through my third attempt of egg share at the age of 36. Previously both receiptents in egg share have been sucessful.
    I am now on day 8 of stimms and 25mg prednisolone (due to nkcells), Today I have been told that for the first time they can see a build up of fluid in my fallopian tube.
    I now have the option of continuing and donating all my eggs or have the fluid aspirated during egg collection....
    Will having the fluid aspirated increase my chances??....or should I have a my tubes clamped via a laparoscopy (as suggested by my doctor).

    Many Thanks

    ReplyDelete
  11. Hello,
    The problem with fluid in the tubes, called "hydrosalpinx" is that studies have shown a 50% decrease in prenancy rates if these are left in place. The treatment of choice is to either remove the tube or seperate the tube from the uterus by fulgeration. Aspiration of the tube is not recommended, and does carry additional risk as tubes tend to have a lot of blood flow. I would not recommend it.

    Your best option at this point would be to freeze your eggs instead of transferring, have the tube fulgerated laparoscopically, then plan the transfer for 6 weeks after the surgery (it takes 6 weeks for the inflammation caused by the surgery to resolve).

    Good Luck

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  12. Dr.Ramirez,
    I am a 32 yr old woman with no hostory of gynaec problems. My husband and I had to go in for IVF ICSI due to poor morphology, count, motility of sperm. My first IVF cycle was unsuccessful (ended last week). 21 eggs were retrieved out of which 18 were mature, 16 fertilized, single embryo transfer (blastocyt) on day 5 of grade BBB and 6 frozen. My period started on day 9 of the transfer. Due to mild OHSS, I was told not to start progesterone. Could this be a cause for implantation failure?
    I suffer from ulcerative colitis and recently had to increase my dose of prednisone to 20mg due to a mild flare up. And also my GI wanted things under control during the IVF transfer. Is there a poor chance of implantation due to UC?
    Its 11 days since the transfer and I am completely back to normal.
    We plan to try a frozen embryo transfer next time. Any advice is appreciated.
    Thanks!

    ReplyDelete
  13. I am 35 years old . Had 6 IUI failed-and 2 ivf with ICSI.Male factor infertility - low count and slow motility.I have hypothyroid but under Synthroid controlled. Recently 13 eggs retrived , 12 mature and 5 fertilized with ICSI . transfer on day 3 with 2 embryos ( 7 and 9 cell ) , rest was left to be watched but did not make it to blasto.
    I took medrol x 4 days and tetracycline ; also progesterone inj 50 mg IM.I am preparing for 3rd shot with IVF but just want to know if you do recommend any labs( immunology ) ? What else can be done to improve implantation ? How long stay on bed rest after transfer>

    ReplyDelete
  14. Hello Dorothy,

    If you have not had any immunological testing done, then it would be appropriate at this point. We check for antiphospholipid antibodies, antinuclear antibodies, antithyroid antibodies and anticardiolipin antibodies. However, you should know that this testing is no wholey accepted by all clinics and the treatment is even more controversial.

    It is possible that embryo quality is an issue with you, since you had so few embryos and none went to Blastocyst. What that means is that you just have to keep trying until you get the right embryo. Age is a factor for you, which could be causing the embryo quality issue.

    In my patients that fail an IVF cycle, I automatically add low dose aspirin (81mg) per day beginning at the start of the cycle, low dose heparin (2000units twice per day) also starting with the cycle, Medrol 16 mg per day decreasing to 8 mg after transfer, increased progesterone (50 mg injection and Endometrin 100 mg vag suppositories). The Aspirin, Heparin and Medrol are to increase uterine/endometrial blood flow and reduce the immunological response.

    Also keep in mind that pregnancy rates differ between clinics because the actual transfer technique can influence the embryos ability to implant. You can have the most perfect embryos but if it is not transferred with good technique, then implantation will be ruined at that point.

    Finally, I don't recommend bedrest, but recommend light and reduced activity for three days after transfer because this is the time it takes for the embryo and uterine lining to complete implantation.

    Good Luck

    If you produced more embryos, I would suggest culturing to blastocyst and transferring at that level, but your embryo numbers are too low for that. If there are not enoug embryos, there is to high a risk that there won't be anything to trasnfer.

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  15. Hi Dr.Ramirez,

    I'm 35 years old. I was pregnant naturally last May and miscarriaged it at 5 weeks. All my tests shows normal and my husband's sperm analysis shows a slightly low motility and 8% morphology (Kroger strict). Last week I just failed our first IVF+ICSI. I produced 17 eggs, 15 of them were mature. With ICSI, all 15 fertilized. By day 5, all of them were alive: 6 blasts and 9 morulas. We transferred 2 best BLASTS (GRADE 3AA & 3AB). However, both of them failed to implant. Given the fact that my embryos looked great, I have been trying to find what cause the failure. I notice that my last E2 was 6100 before transfer, could this be the possible reason for implantation failure? if not, what could it be? Do you have any suggestions for my next ivf cycle? Thanks a lot.

    ReplyDelete
  16. Hi,

    First of all, I think you are doing the correct treatment for the male problem.

    Secondly, it sounds, from the elevated E2 level of 61oo, that you overstimulated a bit. Did you develop hyperstimulation syndrome? Sometimes if there is overstimulation, it can lead to poorer egg quality. There have been studies that show decreased fertilization and implantation rates with hyperstimulation. It is thought that it could be due to the increased hormone effect on the endometrial lining. That could possibly be the cause of your implantation failure. This problem is usually overcome if or when the frozen embryos transfers are done.

    Thirdly, there is another possibility that you need to always keep in mind. IVF is NOT a 100% perfect technology. There is still a luck element to it because the last two stages, embryo hatching and implantation, are still natural procedures. We don't have the technology to make them happen. They have to happen on their own. Because of this, sometimes we don't get a pregnancy even if everything is done perfectly and perfectly appearing embryos are transferred. You just have to keep trying.

    Fourthly, there is an age factor involved, even-though you are only 35. That means that a good number of your eggs are not perfect eggs, and although they were cultured to blastocyst, there could still be abnormalities within that we cannot detect. That also leads to a lack of pregnancy despite perfect looking blastocysts. Keep in mind that when we rate embryos, we are using external appearance (beauty contest). We do not have the technology at this time to evaluate an embryo in detail.

    Good Luck

    ReplyDelete
  17. Dr Ramirez,

    I'm the person who wrote you on May 22, 2010. My name is Jane. First of all, I have to thank you very much for replying so fast and for taking so much time answering all my questions.

    You asked about if I developed hyperstimulation syndrome due to the high E2 level, my answer is no. Even though my E2 was high, I did not feel any discomfort - Absolutely nothing. But I realized that I might be overstimulated since my dosage had been dropped to half every two days until the very end. The night of my trigger, my RE told me that I shot only 0.75cc HCG instead of the normal 1cc. So, without any symptoms, can I still have hyperstimulation syndrome?

    Luckily, I still have three frozen embroys. My RE suggested me to do a frozen embroy transfer the very next cycle. I'm wondering without a break, if the hormone i had from last ivf cycle will still have effect on the endometrial linning and then cause a failure? (BTW: I have to mention that my last linning check during the ivf showed 14mm)

    Thank you so very much for your patience and kind replies!

    ReplyDelete
  18. Hello Jane,

    I'm glad that you did not develop the hyperstimulation syndrome. That shows that your RE managed you appropriately despite the high E2 level. Despite the fact that you did not develop the syndrome, you still hyperstimulated by definition since your E2 was over 4000. That high level could have affected your uterine lining, which led to the implantation failure. It has been shown in multiple studies that there is a decreased implantation rate in patients that develop hyperstimulation syndrome or over-stimulate.

    There is no harm to doing a frozen embryo transfer cycle right away since the ovaries are not being stimulated. It will not have any effect on your endometrial lining since the lining you formed with this cycle will shed (your period), and a new lining will develop. 14mms is an excellent lining width. The minimum is 9 mms.

    Good Luck

    ReplyDelete
  19. Dr. Ramírez.


    Leí en la página web de su clínica de Reproducción que usted habla español.

    Agradezco mucho que se tome el tiempo de leerme y contestarme.

    Soy Laura de México. Tengo 29 años y mi esposo 33.

    Lo busco pues estoy un poco desesperada... Llevo tres años en tratamientos continuos.

    Mi padecimiento es endometriosis severa que afectó a mi reserva ovarica, actualmente tengo una fsh de 15.

    También mi esposo tiene astenoterato- zoospermia.

    Mi primer IVF fue con tres embriones día 3 de calidad II con hatching,, y fue icsi. negativo.

    Mi segunda IVF fue con 1 embrión dia 3 de calidad II, con icsi, negativo.

    Mi tercer IVF fue sin estimulación ( sin medicamento alguno a diferencia de las otras dos), fue un IVF natural con un embrión que llegó a blasto día 5. negativo.


    Siempre al momento de la transferencia mi endometrio es aproximadamente de 12 mm y es trilaminar.

    No se que estudios me recomiende adicionales pues creo que el problema puede estar en la implantación... o algo que me recomiende tomar adicional a la aspirina de 100 mg y la progesterona vaginal que me dan cada 12 horas siempre.

    Agradezco de nuevo su tiempo.

    Saludos.

    Laura

    ReplyDelete
  20. Sra. Laura,
    Gracias por su pregunta y disculpame que estoy tarde con mi respuesta.

    Definitivamente, con su historia medical, fertilizacion in vitro es la unica opcion por tratamienta porque este es la unica tratamiento que puede cubrir endometriosis severa y la problema de sperma. Pero, una problema mas grave es su reserva ovarica. Porque su fsh es 15, este es un indicacion que los ovarios no estan respondando a la hormona fsh y la medicina que nosotros usamos por stimulacion es pura fsh. Por eso, el numero de huevos aspirado es bajo y los embriones formo es minimo tambien. Pero, porque usted esta joven, si la cualidad de los embriones estan bastante, la posibilidad de embarazo debe ser maximo (es 73% cada vez en mi clinica con su edad). Por eso, usted esta pensando que la problema es implantacion.

    La ultima dos partes del processo para tener un embarazo en su cuerpo es saliendo de embryo de su piel(eclosion) y implantacion junto con el endometrium. Fertilizacion in vitro no puede controlar o cambiar este dos partes. Todavia es natural. Este parte es en el mano del Dios. Pero, mucha diferente cosas pueden afectar la posibilidad de implantacion. Por ejemplo, el tecnico de su doctor es mas importante. Usted puede tener embriones perfecto pero si el tecnico para transferar los embriones es malo, el tratamiento no va a funcionar. Por este razon, un opcion que usted tiene es para cambiar su doctor o clinica. Mi profesor siempre me dijo que usted puede tener embriones perfecto pero si usted no se transfiere los embriones en la matriz perfectamente, todo es por nada. El tratamiento no va a funcionar. Este parte es la parte mas importante.

    Pienso que usted ha tenido un histeroscopia para confirmar que la cavidad de matriz y salio normal. Correcto? Si no had tenido este estudio, yo recomendo que usted tiene esta estudio para ser seguro que no tiene nada anormal adentro.

    Si usted tiene confienza en la tecnica de su doctor y el procidimiento de transferencia de embryones paso bien, esta es una problema mas dificil. En esta caso, yo recomendo usando aspirina 81mg cada dia empezando con el ciclo de tratamiento, medrol 16mg cada dia empezando con el ciclo de tratamiento y bajanda el dosis en el dia de transferencia a 8 mg, estrogeno adicional como climara 0.2 mg parche o estradiol pastillas vaginal y heparina 2000 mg dos veces al dia o lovenox 35mg por cada dia. Todos empieza con el tratameinto y continua hasta el resultado del estudio por embarazo.

    Ultimamente, si usted continua a tratar por un embarazo y tiene embriones con calidad buena, usted tendra un embarazo.

    Buena Suerte

    ReplyDelete
  21. Dr. Ramirez

    De nuevo Laura Gonzalez, agradezco mucho sus recomendaciones que tomare muy en cuenta.

    Me queda una pregunta, que marca o como se llama el medicamento de la Heparina, y que tipo de progesterona y en que dosis me recomienda tambien,,, inyectada o vaginal?

    Muchas gracias nuevamente!!


    Laura

    ReplyDelete
  22. Hola Laura,

    El nombre de Heparina es Heparina y hay mucha differente formas de progesterona que usted puede usar. No se exactamente que tipo de progesterona que usted tiene en su pais, pero en Los Estados Unidos, la forma que yo uso es Crinone 8% or Endometrin 100 mg. Este formas estan para usar vaginalmente. Si puede usar progesterona en un forma de inyeccion, pero este forma es mas dificil a usar y mas doloroso. Por eso, yo prefiero las formas vaginales.

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  23. Dr. Ramirez,

    I am 45 years old and have been pregnant 2x, the first lasting to 8 weeks and the 2nd miscarried within a week. That was 3 years ago. Having not found any challenges beyond the age of my eggs, it was suggested that we move forward with donor eggs. We ended up with 6 fertilized eggs by day 5 & 6. We have gone through 4 failed donor cycles. My lining is typically around 8mm. (They have seen some possible signs of adnomyosis.)I am hypothroid with recent tests indicating that my TSH is a low .02 and my T4 is a low .8, but normal T3. (on synthroic and cytomel). This suggests a problem with the pituary gland. Do you know if this could be contributing to the implantation failures? I can't find any information on the role of the pituitary gland beyond that of ovulation, which clearly isn't a factor here. Or perhaps its just the low t4 even though my tsh is more hyper than hypo? My doctor has had me on aspirin, trental, high dose vitamin E, plus 1mm progesterone in addition to the .02mm of estradiol. Any suggestions/insight you have on all the information shared would be much appreciated. We plan to move forward with the final 2 frozen embryos shortly and then that's it. Thank you so much for your help. - Lisa

    ReplyDelete
  24. Hello,

    I am certainly concerned that you have not gotten pregnant using donor eggs. That was definitely the right path to take considering your age. Also considering that you have been pregnant before, the donor eggs should have solved the problem and you should have been successful. It is certainly strange that this has not been the case. There could be several possible explanations: your thyroid is abnormal (hyper) and could be contributing, there is something going on with this donor's eggs that has been undiagnosed (is this a proven donor i.e. has she had pregnancies before?), you have some other underlying disorder preventing implantation such as an immune problem (has your antiphospholipids been checked?), the endometrial lining has been inadequately developed, the frozen transfers have been at the wrong time or that there is a problem with the transfer technique. I am also concerned that your clinic is only transferring one embryo at a time. I know that they are blastocysts but after the first failure, even SART recommends two blastocysts. That is what I would have done.

    I would have done some different things, such as transferring two blasts instead of only one, but also, my protocol for failed patients is to add heparin 2000 units twice per day, add vaginal progesterone (Endometrin) twice per day,and add Medrol 8-16 mg per day. Some clinics will even add anti-immune medications such as IVIG or Intralipids.

    Since you state that these next rounds of frozen transfer will be your last tries, you might want to consider moving your embryos and trying at a different clinic. I am sure that you have confidence in your clinic, but it has had plenty of tries without success. Sometimes being in different hands, especially with the embryo transfer technique, will make all the difference. Studies have shown different pregnancy rates among Physicians in the same group because of differences in transfer techniques. That is part of what makes each clinic different. I have had a similar patient that did 5 IVF cycles (both fresh and frozen) in a local university practice without success. She then transferred to me, and although she did not get pregnant on her first fresh cycle with me, she was successful with the subsequent frozen cycle.

    If doing all the above still ends in failure, you have to consider two things, if you are willing to not give up: (1) what was the quality of the embryos that were frozen? and (2) maybe it's the donor. It sounds like your donor was able to produce lots of embryos. Sometimes, that indicates that she was a PCO patient, and a high stimulation has been shown to reduce the pregnancy rate. Also, as mentioned previously, maybe there is something about the eggs from this donor and changing donors might make the difference. I have had that experience as well with a dnoor, and after she produced lousy embryos, we did not use her again. The patient used a different donor the second time and was successful. You mght want to consider that as well.

    The main deterrent to you at this point, of course, is a financial one. You have spent a lot of money thus far without success. But I am confident, because you achieved two pregnancies before, that you can get pregnant given the right circumstances. Once you move to donor, age is no longer a factor, so I would suggest that if you really want to have a child, you should re-evaluate and consider continuing your quest but using a different path this time.

    Good Luck

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  25. Dr. Ramirez, Thank you for your reply. To answer your question about immunity testing, yes I did have that checked after the 3rd failure(IgG and IgM)and everything came up normal. Would you still recommend IVIG or Intralipids knowing the immunity testing didn't indicate that as a problem? She hasn't tested me for thyroid antibodies which seems odd--no? (I'm in the process of trying to see a well known doctor experienced in thyroid and fertility--which hopefully is a worthwhile path for me to go down as he can't see me for 3 months.) As far as the donor, I don't recall if she was proven or not...agency was having trouble uncovering outcome from different agency she had donated to on East Coast. I think she produced around 10 eggs so it didn't appear that she was a PCO patient. We froze 5 which were mostly grade 1 with a few grade 2. Each thaw has been successful--only having to thaw the 1 intentended to use. The reason for the single embryo transfer was us--we didn't want to end up with twins. The clinic was open to two but never recommended it. This next, final cycle however, we will use both remaining blastocysts. It is interesting what you are saying about the clinic--as I am in San Francisco with a clinic that I believe is considered to be the best in the Bay Area. I'm not even certain who I would turn to. Finances and time (my age being 45) are both big issues at this point, so a new donor doesn't seem to be a consideration for me. Again, I so appreciate your advice.

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  26. Hi Again,

    As you know, I am very close to the Bay area and certainly my answer was not in regards to any specific clinic. I know all the clinics in the Bay area and I would not say there is one that I would call the "best in the Bay area". That is certainly open to interpretation. There are lots of clinics and most are very good. I would say that each of them, including mine, have their pros and cons. So, in consideration of your last question, there are lots of options in terms of other clinics.

    In terms of your immunity, when you say IgG and IgM, I presume you are referring to a complete (21 point) antiphospholipid antibody screen. With your thyroid history, anti-Thyroid antibodies should be checked as well. I am not a big proponent of IVIG or Intralipids, although where I trained was one of the pioneers in that treatment, because most of the studies does since then do not see benefit. Therefore, I don't recommend them. In addition, they are very very expensive, and should be reserved for other medical illnesses. Instead, I use Heparin, Aspirin and Medrol. I would add those regardless of how you tested.

    I understand your desire for a single pregnancy rather than risk a twin, and that is laudable. However, the data for single embryo transfer does show a decreased pregnancy rate per attempt, although the cumulative pregnancy rates are equivalent. That just means that it can take more tries with single embryo transfer to achieve a pregnancy, which would take only one or two attempts with multiple embryos. That is the reason I have not jumped on the bandwagon for SET.

    In any case, if you have confidence in the abilities of your doctor at the clinic that you are in, then do not feel compelled to change. It was only an observation and an opinion on my part as one thing for you to consider.

    Good Luck

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  27. Dear Dr. Ramirez,
    I just completed my second IVF cycle, which failed…
    I’ll be 34 in may, in great health and pretty active.
    Our first IVF attempt – 2 embrios were transferred on day 5 and 4 were frozen.
    My husband has a history of testicular seminoma and his right testicle was removed 10 years ago. After our first failure, he was not producing enough sperm and they had to surgically obtain it. In a way I am glad that our first try was unsuccessful, because the surgery confirmed that my husband’s cancer was back and had infected the entire testicle. They removed the remaining testicle and froze our last couple of vials of sperm.
    Our second cycle “ran by the books”, according to our doctor. I had 19 eggs, 2 embryos were transferred on day 3 and 4 were frozen. Everybody said these were first grade embryos and I was very hopeful it would work this time.
    I did feel very overstimulated, my estrogen levels were very high post retrieval…
    I wonder if try a frozen embryo instead the next time, with less or no medication, I might have a better chance of getting pregnant.
    Also, did my husband cancer have anything to do with this and my body recognized a potential problem?
    My periods are normal, with light clogging, though.
    I thank you for your time and much appreciated advice.
    Sincerely,
    P.F.

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  28. Hello P.F.,

    Let me answer the easy question first. Your husband's cancer did not have any affect on your IVF cycle or the embryos produced.

    Frozen transfer pregnancy rates tend to be lower than fresh cycles, but that is probably because the best embryos are always used first. Some previous studies have shown better implantation with the thinking that the increased hormones from a stimulation may actually adversely affect the endometrium and reduce the chances. But to put it in perspective, the pregnancy rates at your age with a fresh cycle is approximately 60-70% per cycle whereas the frozen cycle rates are 33%. However, keep in mind that in reality, each person's chance of pregnancy with any treatment is 0% or 100%. That means, you either get pregnant or you don't. Statistics is only a reflection of reality, not a premonition of it. I think it is definitely worthwhile for you to try the frozen cycles before attempting a fresh cycle, especially in light of the fact that you have limited sperm available.

    Good Luck

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  29. dear dr ramirez, i just underwent my 5th failed IVF?ICSI cycle. my husband has severe oligospermia and i was diagnosed with adenomyosis. could the adenomyosis be the cause of the implantation failure or the semen issue. thank you sir.

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  30. Hello,

    I'm afraid that I can't give you any specific information regarding your question without more specific information such as embryo quality. Because implantation is a natural process i.e. IVF does not have the technology to make it happen, there are many possible factors that would prevent it from occurring such as embryo development, embryo hatching (extrusion from its shell), attachment to the uterine lining and the uterine lining engulfing the embryo (implantation). This process can be influenced by many factors. Certainly the sperm could be an issue if it is causing poor embryo development or quality. Whether or not adenomyosis is contributing is an unknown. I would not expect that.

    One other factor if you are putting good quality embryos into the uterus and the lining is adequately developed AND you still are failing is the question of transfer technique. Studies have shown variations in pregnancy rates among Physicians in the same group due to transfer technique.

    Also, could there be immunological factors at work?

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  31. Dear Dr Ramirez,i am a 32 year old and just had a failed IVF/ICSI cycle,my fourth one. i had 4 grade one day 3 embryos transferred but i just realized that i overused my progesterone suppositories today!! instead of 1200mg in 3 divided daily doses i was inserting 2000mg daily as i didnt know the suppositories came as 400mg i thought they came as 200mg!! please sir could this have been the reason for this recent implantation failure?. please help because i can't help blaming myself!

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  32. Hello,

    There is no way to know exactly why the implantation failed. There are too many factors that are important in implantation including continued development of the embryo, embryo hatching, attachment to the uterine lining, engulfment of the embryo by the uterine lining, appropriate histology of the lining and appropriate blood flow to the implantation site. Also, there could be outside influences on this as well.

    For this reason, I don't think you should blame yourself for the failure.

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  33. Dear Dr. Ramirez

    Am 36 yrs old, I have a 6 yrs daughter conceived naturally and miscarried once before having tht daughter, since then we tried to conceive naturally 3 years but failed. We the decided to do icsi, I had my beta results its negative, my hubby had low sperm count, was put on clomid 100g, menopur injection , 6 eggs retrieved, 3 mature , 2 immature and 1 yellow. 3 were fertilized same day and 2 fertilised next day. On day 3 they transferred 3 embryos with 4, 5,6 cell.my RE said 2 were good quality but 1 is slow in terms of development, now am trying to think why failed implantation? Is anything wrong with my uterus???what else i should have done to support implantation?what should i or test t maximize the chances in my next cycle?

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  34. Hello 36yo anonymous,

    With the limited information you have given me, it is difficult to evaluate why your cycle may have failed. But, also based on the embryo data you presented, I think there was an embryo development problem. 4,5 and 6 cells embryos on day #3 are not very good development. Of course it is possible to become pregnant with these embryos, so we don't disregard them, but the best embryos are usually between 6 and 8 cells on day#3. In terms of quality, there is no technology that allows us to know exactly how good an embryo is, so we give it a grading based on how good it looks. That means that a "good quality" embryo may not necessarily be good quality internally. I tend to favor how well the embryo is developing and would probably attribute your failure to poor embryo development. This may be a reflection of your age, or the laboratory techniques such as culture media, temperature, embryo handling, etc. Certainly you did not have a good stimulation (<10 follicles and embryos retreived.)

    Based on the fact that you were able to get pregnant before, I think you still have a very good chance of getting pregnant, but you will just need to keep trying.

    Good Luck.

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  35. Hi Dr

    Angela from England here! When you say start aspirin and heparin at the beginning of your cycle, do you mean at ER?? I am doing IVF second time round in June and want to suggest this method to my clinic. Im from UK and they don't tell us anything like what the RE's do in the states. My 1st IVF failed and the embies didn't implant.......2 transferred 8 and 9 cell on day 3 high quality embies I was told, they didn't mention A's or B's just high quality. I have unexplained infertility. I was told that my fallopian tubes were scarred so I had a proceedure to have them cathetersied (paid for privately) in the hope I would be offered IUI, which I wasn't. We are trying to fall pregnant naturally even thought then next round of IVF is planned. I want to cover all avenues here. Im 36 and my husband is too, he has 2 grown up kids 14 anfd 18 from his first marriage.

    I am extremely healthy, eating a varied diet full of wholefoods and vits. I drink pleanty of fluids, mainly water and green tea. I am a personal trainer by occupation although I don't train as hard these days due to TTC and wanting to have the best chances. I do still exercise but it is light and well thought out.

    Any advice or information would be very beneficial as I feel pushed to one side by my clinic. They say I have 1% chance of natural conception, however, after I told them about my Tubal Op, they now say I have 3% chance of conception by natural methods, what does this mean.....how would the percentage be worked out?? Im confused a little. I know my post will seem a bit allover the place but in real terms that is how I feel....allover the place. Any help is gratefully taken on board at this time.

    Thank you in advance.
    Angela
    Newcastle
    United Kingdom

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  36. Hello Angela,

    First, the heparin and aspirin are started at the beginning of the cycle i.e. when you start your fertility stimulation medications. They are stopped on the day the HCG trigger shot is given and are not resumed until the day after the retrieval.

    It sounds like you had some type of tubal blockage and hence had the tubal catherization done. If the blockage was merely due to a mucous plug, then removing that plug would restore your chances of pregnancy to normal. You should have an HSG to verify that they are open. In that case, assuming a restored normal fertility rate, at 36 your chances of pregnancy would be 5-7% per month.

    On the other hand, if the tubal blockage was due to scar tissue caused by some inflammatory process or infection, then the catheterization does not restore it back to normal. The cilia in the tube would have been destroyed by the inflammation or infection and cannot be repaired. The tube is a functioning organ and not just a tube or conduit. Despite being open, then tube has to function normal for pregnancy to occur. In that case, IVF is the procedure of choice.

    I hope that answers your questions.

    Good Luck.

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  37. Thank you so much for your speedy response.

    I was told my tubes were scarred on the outside. The laparoscopy showed the supply of dye did not go through the fallopian normally. Since having my tubes catheterised the dye spillage is perfect. I have never had an infection or STI or anything that I can think of that would have meant my fallopian tubes being scarred so this is a grey area for me! I understand fully what you say and it has helped although I am still confused as to how I ended up with damaged fallopian tubes without illness. The one thing that may be significant was a termination I had when I was 19..........I had to have the termination, that decision was out of my hands! Could this procedure have caused the damage? The pregnancy was conceived naturally and it wasn't an ectopic pregnancy, suffice to say it is still raw in my mind but the pregnancy wasn't allowed to go further than 12 weeks. I'd rather not go into details. There was no medical reason to terminate. I thank you in advance once again for your help.

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  38. Hello Angela,

    Certainly a laparoscopy can see scar tissue on the outside of the Fallopian tube but it cannot see it or diagnose it on the inside. That is done by an HSG. I know that the flow became better after the tubal canalization, but again, that does not mean that the tube is completely restored to normal, as I explained in my previous response. One of the most common causes of tubal disease, and blockage, is from a bacteria called Chlamydia. The problem with this bacteria is that it can cause silent damage i.e. you would not know you had it unless a culture were done. Because you have been sexually active since a young age, it is a possibility. Now-a-days, very few patients have diagnosed PID or STD's unless they become symptomatic.

    Certainly it is possible that if you had an elective termination, that an intrauterine infection may have occurred that led to the tubal damage, but again, because it is an infection caused by some type of bacteria, it would lead to the same problem and same conclusions as to the impairment of the tube.

    I hope that clarifies things a little.

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  39. Dear Dr. Ramirez,
    Thank you for having this blog. I find your responses to be very balanced and well thought out.

    I am 36 and had bilateral ovarian dermoids removed at the age of 32. They were about 10 cm each. My cycle length went from 28 d to 25 d after that surgery. I figured my chances for natural conception was low after such a surgery. On baseline u/s, the right ovary had 15 antral follicle count and the left seemed atrophic and had maybe 4 follicles. I went to IVF about 10 m later. I had 27 eggs retrieved, 19 fertilized, and 10 went on to blastocysts. My husband's sperm count/morphology were all normal. I had one transferred and that became my beautiful son who is now 17 m. The pursuit of our 2nd child has been much more problematic. With the 9 frozen embryos, 5 day 5 and 4 day 6, I did single embryo transfers for the first two cycles and then 2 embryo transfers for the most recent cycle. None has taken. They were all done with natural cycles, using Letrazole and then just vaginal prometrium. 3 of the 4 embryos were grade 1, and one was grade 2. They were all blasts or hatching blasts. I was initially given a very good prognosis of getting pregnant within 2 cycles of FET's. After the first failure, I was given the option of trying PGD. I did not do PGD due to the cost and the possible decreased viability of the embryos. After the second failure, I was given the option of doing endometrial scraping and possibly a programmed cycle. I also did not do the endometrial scraping in fear of introducing synechiae in the uterus and also possibly forcing an unhealthy embryo to implant. I also did not do a programmed cycle because I ovulate usually around day 12-13, almost like clockwork. I also did not like the idea of injectable estrogen for 12 weeks if I did become pregnant. Of course implantation is a very mysterious process. I have several questions for you. Do you think I should have picked any of the options presented to me to enhance the implantation? Do you think it is reasonable at this point to proceed with a fresh cycle? Do you think my chances of getting pregnant would still be reasonable?

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  40. Hello August 28 Anonymous,

    I must admit that I do not do FET's with a natural cycle. The problem is that timing is critical with embryo transfer. There i only a 2 day margin in which to get the embryo into the uterus for implantation to take place. That has been shown to be cycle day 16-17. With a natural cycle, it is difficult to know exactly when that cycle day #16 or 17 is despite your regularity.

    In IVF or programmed FET, we know when that day is because we program it by determining when to start the progesterone. The progesterone starts the conversion of the endometrium into a form that allows implantation. So for example, if you are transferring day#3 embryos, you are on progesterone for four days and if you transfer day#5 embryos you are on it for 6 days. That is hard to determine in a natural cycle.

    If you have frozen embryos left, I would recommend that you continue doing FET's before moving to fresh cycles. But this time, I would recommend that you use a strict FET protocol. Not only should it be programmed, but I would recommend estrogen patches (I don't use injectable estrogen), Progesterone vaginally plus injections, low dose aspirin to help with blood flow, low dose prednisone to minimize inflammatory reaction and possibly low dose heparin to help with blood flow and prevent micro clotting since you have failed several times.

    If you do all this, considering you have been pregnant before, these are young embryos and in a good stage of development, you should have a very very good chance of success. I am surprised it has not happened already.

    Good luck.

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  41. Hi, Dr. Ramirez, thank yo so much for your speedy response. I wrote to you on Aug 28 regarding my three failed frozen cycles. My name is Ellen. Your message was very uplifting. However, after talking to my RE today, I became despondent again. He attributed the failures to the aneuploidy of the embryos. I find it hard to believe that 4 of the 5 Day 5 embryos were all aneuploidy. After all, like you said, they were young embryos and I had a lot of them, whcih I thought was a reflection of the embryo quality. The clinic I go to boasts a FET pregnancy rate for women under 35 at around 48%, which made me start to question if I'm somehow defective.

    I don't know if it's of a diminishing return to continue doing FET's if there is something wrong with this batch. My RE did say that I could try a programmed cycle but he did not think there was any added benefit. (Which makes you wonder why even recommend it in the first place?)

    I asked if I should do a fresh cycle and he said I could. He would do a day 5 PGD on all the embryos, freeze them, then wait a week for the results and then transfer the genetically normal ones. I asked if I could transfer the 2 best looking ones and then do PGD on the rest of them. He said I could do that as well. I don't get how aneuploidy all of a sudden could become such a concern. I know PGD is now employing new techniques but I still don't feel comfortable with potentially compromising the viability of the embryos. I asked if endometrial scraping would be of benefit. At first, he said it would be marginal but it would not hurt to add it. I feel like I'm being treated as someone who is in the repeated implantation failure group.

    My friend who is an RE in another city, suggested that I do a saline uterine sonogram to look for polyps which would not be readily obvious on u/s alone. Also to do an endometrial biopsy to see if I was missing some receptor for implantation. If that was the case, to stay on Lupron for 3m. I feel very confused at this point as to what the best thing to do is. I know acupuncture is a whole another topic. I don't know if you think it's worth trying even though I think my fertility problem is tubal in origin, but now I'm not so sure anymore. Thank you so much for your time. I truly appreciate the patience and professionalism you show in your blog.

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  42. Hello Ellen,

    First let me make a disclaimer. The opinions I give are generic as much as possible, meaning it is the standard methods and treatment for the infertility community. For opinions that are not standard, such as protocols etc., these are my personal recommendations and may not necessarily reflect the opinions of other RE's or IVF programs.

    The problem with RE programs is that each doctor has undergone different training and so has different protocols, standards, experience and opinions. These may not necessarily be wrong or deviant from the standard. The clinic you visit and the doctor you see is the one that you are putting your faith and trust in. You are the only one that can evaluate if that faith and trust are well placed or not.

    In terms of the failure, "aneuploidy" is the default excuse, mainly because we have no way of knowing for sure. In actuality, there are four possibilities for a failed cycle: (1) aneuploidy-meaning the embryo was abnormal and so did not continue to implantation, (2) the embryo did not achieve hatching from its shell so never attached to the uterus for implantation, (3) the embryo attached but the endometrial lining did not grow around the embryo as it should have done {This latter problem could be due to inaccurate timing, especially in your case} and (4)the embryo transfer was not done well (this has been found to influence the wide variation in pregnancy rates among Physicians). There are no tests for any of these possibilities.

    The biopsy your friend advised you of is an indirect way to see if the endometrium converts to the proper state for implantation to occur. The problem with the test is that it may not do that in the actual IVF cycle. But certainly it is an option. I do not do this test. Instead, I just increase my progesterone supplementation (the treatment if the lining is not achieving the proper state - see Beta Integrin testing).

    In terms of aneuploidy, without preimplantation genetic screening (done at day#3 or day#5) one cannot know if the embryo is genetically normal or not. Chances are, however because of your age, that this is not the problem. I would expect most of your embryos to be normal. If you were 37-40 yo, then aneuploidy would probably be the most likely explanation.

    I am surprised that your endometrial cavity was not evaluated prior to your cycles. It is an absolute requirement in my center. I don't want patients to go through a cycle and waste money without insuring that everything has been checked and is in good order. I do a hysteroscopy as an office procedure rather than a hysterosonogram because the latter test is an indirect test and the former lets you see the cavity directly. If you have not had that checked them before going any further, you should have it done.

    Good Luck.

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  43. Hello Dr Ramirez

    Thank you for taking the time to read my post.

    My name is Patricia and I am almost 41 and to date have had 3 failed iui's and 4 failed fresh icsi cycles.

    We have never had implantation and never had anything to freeze.

    Our problem we were told was my husbands low sperm count. The 3 iui's were using donor sperm and the last 2 icsi cycles were also donor sperm (different donors used each time). We are now told that perhaps there is an egg issue so we are looking into donor eggs and sperm now. We had assisted hatching done on one icsi using husbands sperm and on both icsi's using donor sperm as my eggs appeared slightly hard.

    On the 4 icsi cycles I produced between 11-15 eggs. On our best cycle (using my husbands sperm) 9 of the 15 eggs fertilised and 2 made it to blast. On day 5 we had a 9 cell and a 16 cell transferred. We had 3 day transfers on our other cycles. There was no fragmentation but also nothing to freeze. We had some fragmentation on 2 of the icsi's using my husbands sperm. My lining has always been perfect on each cycle.

    On the 2 donor sperm icsi's all the eggs fertilised, no fragmentation but by day 3 we were left with only two or three 4 cells and nothing to freeze.

    I have ulcerative colitis and wonder if this might be a reason for the implantation failures.


    When I was 24 before meeting my husband I had a termination at 7 weeks, something I regret terribly.

    I am worried that I have have an implantation problem instead of this just being an egg problem and going for donor eggs will not work.

    Would taking aspirin, heparin and medrol help and is there anything else you could suggest for me.

    I appreciate any advice you can give me

    Patricia

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  44. Hello Patricia,

    I was very surprised at your outcomes because it sounds like you were doing everything that you should have done. Your ovaries have certainly been stimulating well resulting in a lot of eggs retrieved. You also seemed to have enough embryos formed. Certainly, the main issue that could explain the failures is the age of the eggs. Because we cannot determine internal quality of the eggs, we go by external appearance. This is an imperfect method. Having older eggs means that the internal quality of the eggs are not good and could explain why you have failed implantation. If the embryos are bad or don't continue to grow to adequate levels, then implantation will not occur.

    I don't think it is a sperm issue, however, and I don't know why you switched from your husband's sperm to donor sperm. ICSI was the treatment of choice for your husband's sperm and should have covered that issue.

    I do think that maybe donor eggs is going to be the best solution for you unless you want to continue to try with your own eggs. That is a time and expense decision. I also wonder if it might now be time to seek out a different clinic. Pregnancy rates do vary greatly between clinics.

    If you have not already had a hysteroscopy (a requirement of my clinic's), then you should have one to verify that the cavity is completely normal. In addition, I definitely would add heparin, aspirin, medrol, additional progesterone and estrogen.

    Good Luck

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  45. Thank you so much for your reply Dr Ramirez.

    Just to add... We had in fact 6 icsi's not 4 as I stated earlier and of course the 3 iui's!! I have lost count at this stage. We started our first when I was 33 and our last was when I was 39.

    We were always told my eggs were fine and that it was a sperm problem but I think our clinic have given up on us at this stage so are saying 'it is probably an egg issue as well'.

    I had an Hysterosalpingogram and all was normal.
    I also had a Laparoscopy that showed mild endometriotic spots in the pouch of Douglas.
    My tubes and ovaries also appear normal.

    We are hoping to travel to Spain shortly (we live in Ireland) to see about donor eggs and sperm.

    I am so very grateful for your feedback, having another Dr look at our case is very helpful

    Thank you so much
    Patricia

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    Replies
    1. Dear Dr. Ramirez
      I just had my first ivf with donor embryo. It showed faint +ve in HPT 17 days after ET. We went to our clinic and taken two blood tests in alternate days and one urine test. After that my doctor said my hcg level is decreasing instead of doubling.In urnie test it showed negative. It is not good and will get menstruation within two days. What is the reason for this? Is it implantation failure? Is there any chance to repeat it in second trial? Now I am six days late and not started bleeding yet. Is there any chance of hope?

      Delete
    2. Hello Feb 5th,

      If you had a pregnancy test that was positive (counting the blood tests only), then implantation occurred and you don't have implantation failure. We actually call that a "chemical pregnancy" because the blood test was positive but it did not continue growing. One outcome does not predict the next one because each cycle is unique with unique eggs and embryos.

      Despite being late, the blood tests are more predictive of what is going on in this pregnancy. If the bHCG is still present, you would not have a period.

      Good Luck

      Delete
  46. Dear Dr Ramirez

    First IVF Cycle was 2006 and was sucsessfull healthy boy
    we did 3 IVF cycles after that in the last 5 years with no positive results. What can be wrong first cycle i had a Laparoscopy done befor my cycle. had 3 Emb trf back and 1 made it 2nd we had 2 good emb trf with neg outcome 3rd we had 2 emb trf with neg outcome 4th had a laparoscopy and had 3 good emb trf 2 on day 5 with neg outcome i am a health 33 year old with no health issuse other than a little endomitriouses was fond on both my Laparoscopies i really would like you help

    ReplyDelete
  47. Hello Feb 23rd,

    Without careful review of your IVF medical records, I cannot offer any advice in regards to why you have failed so many cycles. There are many reasons why IVF cycles can fail.

    Sorry

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  48. Dear Dr Ramirez

    I had my FET on March 19, 2012. On 20th morning I saw a drop of spotting. Is there anything wrong with this? Is it implantation spotting? How many days after FET implantation occurs.

    Thanks in advance

    ReplyDelete
  49. Dear Dr Ramirez
    I am Steffi from Greece. I am 38 y old with endometriosis diagnosed straight after a miscarriage of twins 2 and half years ago (palindromic). Since a laparoscopy to treat the endo (medium level with endometriomas), and 6 months with Lupron (with which I got a severe hearloss due to its ototoxicity), is was decided to use donor's eggs to increase egg quality and chances and avoid the adverse effects of the endo and the age. The use of Lupron is out of question now.
    I also had high TSH (4,7) that is corrected and I take dexamethasone to correct my level of 17-OH progesterone.
    The 1st cycle failed: 9 retrieved, 7 fertilised, 2 2day and 3 5day were transferred. Endometrium = 10,5 mm. I was on cyclacur, dermostril, folic acid, vitamin B, aspirin, progesterone 4 days prior to transfer and heparin from the transfer day.
    The 2nd cycle now failed: 7 retrieved, 5 fertilised and 4 2day transferred with a successfully proven donor. = 11 mm. Same protocol.

    The clinic reaches 70% success with donor eggs, the facility is good and there are only 2 people transferring with similar success rates. The donors cannot be bad all times ?
    Now, what is going wrong ? Is is Anti-phospholipid antibodies, Antinuclear antibodies (ANA), Antibodies to alpha-2 glycoprotein 1, Anti-Thyroid Antibodies, Natural Killer Cells, or more importantly the lack of Beta3-Integrin (due to the endometriosis) or a implantation window that is out of place.

    What would you propose and change?

    ReplyDelete
  50. Hello Dr.Ramirez,
    I started my infirtility journey when i was 29, we did 2 rounds of Timed Intercourse (BFNs), 3 iui(I chemical) and jan2011 we started our IVF journey, IVF 1-bfn (1 blast), fet 1- bfn (2 blasts),IVF-2-BFN(2 blasts), FET-2-BFP-miscarried most likely due to lovanox, IVF4-(BFN)

    i currently just had my FET transfer 3/26 and am 3dpfet, i'm hoping for the best but incase its another bust cycle, we talke about looking into PGD. i'm 31 now and still no baby when the only thing i was diagnosed with was pcos bfore starting the timed intercourse. i do trust my dr, but sometime i feel she got too aggressive too fast. i wan't go for a 2nd opinion b4 doing a pgd, but i'm praying that this fet deos the trick, we transferred 3 embyos and the meds she has had me on are del estrogen, progesteron, metformin, low dose steriod, baby aspirin, and the prenatals. what meds would you recommend for someone like me, young, produce grade A embyos, and all the bw work ups are normal? do i need the stroids? she had me on lovanox ivf 2 and fet2,when i finaly did get pregnant but started to spot at 6wks so went in for US everything looked good even saw the HB, but that evening felt something detatch in the womb, and the next morning just started bleeding like crazy, the dr thought it was lovanox, she still wanted me on lovanox IVF3, but i asked to be put on baby asprin and she was very willing to to that, my question is why not just start me with baby aspirin when i dodn't have any clotting issues. anyway i just want to know what would you recomend for a patient like me?

    ReplyDelete
  51. Hello March 19,

    Spotting may not necessarily mean anything. It can be good or bad, but for sure it occurs often with IVF.

    In terms of when implantation occurs, if it is a D#3 embryo, then it will take 4 days for implantation to occur. If it is a D#5 embryo 1-2 days.

    Good Luck

    ReplyDelete
  52. Hello March 28 Anonymous,

    the exact reason for your failure cannot be known. Certainly your doctors seem to be doing everything possible. I find it unusual that your doctors are trnasferrring so many embryos from a donor. Was the embryo quality good? Without reviewing your IVF records, I can not analyze the cycles.

    The heparin and aspirin should be covering any antibody issues. The only change I might make is to start the aspirin and heparin at the start of the cycle rather than after embryo transfer.

    Good Luck

    ReplyDelete
  53. Hello March 29 Anonymmous,

    Hopefully this message will not be required and you will be pregnant. But if not, then here are some considerations. It has been shown that in PCO patients, especially if they stimulate hard (lots of follicles and high E2), the egg and embryo quality seem to suffer a bit, even though they look good. This could possibly be the reason for your failures. The good news is that you have gotten pregnant, so you know that the IVF treatment can work. IVF cannot guarantee a pregnancy because there are still natural factors to contend with. So, it is just a matter of time before you are completely successful.

    Every docttor has their own different protocols. If you were my patient, I would use low dose aspirin, medrol, extra estrogen and extra progesterone plus either low dose heparin or lovenox. Everything except the progesterone would start with the beginning of the cycle. The progesterone starts at the designated time prior to transfer. The purpose of the aspirin, low dose heparin/lovenox and medrol is to increase blood flow to the implantation site and early embryo AND to decrease the immune response. This is a protocol that is used in recurrent miscarriage patients (which you are because you have lost three pregnancies).

    Good Luck

    ReplyDelete
  54. Hello Dr Raminez,

    I was wondering if you could help me.

    I have just had my first failed IVF attempt and wondered whether you may know why this may have failed and if there is anything more that I could do next time.

    History
    I'm 31 and have a damaged right fallopian tube due to an unknown infection years ago, my left side has a few filmy adhesions in the pouch of douglas and the left pelvic side wall between the bowel and pelvis (my only thought was that I had a grumbling appendix when I was 15 years, due to low immmune system after glandula fever where I suffered from jaundice) all STD tests, rubella and smear test have been confirmed as negative. A hycosy was done 8 months ago which showed tubes were clear, yet an ultrasound showed presence of a hydrosalpinx on right fallopian tube, a laparoscopy was conducted in March this year. A filshie clip was attached to the scarred/ blocked right tube during a laparoscopy to help IVF, as it couldn't be removed as it was stuck to my bowel, due to the scarring. They also did a endometrial scraping and a hysteroscopy at the same time.

    I normally have a 28 day cycle (bleed for around 4-6 days) and have spotting between periods for a few days and running up to periods sometimes for a day or 2 (had this for years). It has been concluded that this is hormonal.

    I have AMH levels of 38.22. I had a thyroid profile test done (TSH, FT3, FT4) all came back ok. FSH is 5, LH 4.5, oestradiol level 119 pmol/1 and progesterone was 56 on day 21 on my cycle, full blood count fine, My husbands sperm is fine; 63% motile, 59% progressively motile, forward progression rating moderate, morphology 93% abnormal, volume 2.4ml, count on lower end of normal but still falls within normal range.

    IVF procedure
    I was given synarel spray (twice a day) in down regulation, 150ml of gonalf for 9 days and ovitrelle / hCG injection before egg collection.

    They did a contrast scan as they they thought I had a polyp or a polypy type structure, it was confirmed that it may have been a polypy type structure. It was also concluded that if it was a polyp it would have been picked up in my recent laparscopy.

    I had 20 eggs collected and chose half to be IVF and the other ICSI, all the ICSI ones fertilised and 7 out of the 10 fertilised with IVF, 2 eggs were found to be immature. After 3 days, they said that 8 were developing well and they would go to blastocyst. When I went into for egg transfer (day 5), they said that only 1 had reached blastocyst and had a grade 4BC, B on the inside and grade C on the outside. The 3 others were ungraded. I asked for the best of the ungraded embryos and the blastocyst to be transferred but unfortunately it didn't work. One of the embroys on day 6 reached blastocycst grade 4BB, so I have frozen this one. I was also given vaginal progesterone pessaries called cyclogest.

    My clinic put me on tablets to stop me overstimulating for 8 days following egg collection as I collected a high number of eggs, yet I was very sore, had very bad bloating and flactulence as a result.

    Q - Do you think that as a I had mild overstimmulation and bad flactulance, this may have effected implantation? therefore, i'll have a better chance with my frozen embroyo?
    Q - Do you think the polypy type structure may have effected implantation?
    Q - They didn't measure my progesterone levels throughout, should they have?
    Q - You have suggested to other women who have failed IVF first time to try aspirin, haparin, medrol, endometrin. Apart from Aspirin, what are these other drugs? side effects? how do they help?
    Q - I'm based in the UK, just out of interest what are your success rates? how many embroys do you usually put back in?
    Q - What are your thoughts on Natural IVF?
    Q -What do you think I could try differently?
    Q - Any particular diet / lifestyle tips that can help IVF?

    Many thanks for your time

    Kind regards

    Kate

    ReplyDelete
  55. Dear Dr. Edward Ramirez,

    I have watched my sister go through the most heartbreaking ordeals to have a baby. Naturaly, IUI and now she has moved to IVF and successfully became pregnant with a 3-day transfer. transferring 5 matured eggs. she continued her progesterone shots and levels were going up nicely and at the third blood test they began to drop. Her doctor asked her to stop the progesterone injections and to prepare for a misscarriage. they mentioned a chemical pregnancy but it has been over a week and no sign of a m/c. Can she still be pregnant? I try not to ask too many questions to not upset her but i'm so concerned for her.

    Thank you,

    ReplyDelete
  56. Hello Kate,

    1. The OHSS would not impair implantation. In fact, had you become pregnant, the OHSS could have gotten worst. You will not have this risk with a frozen transfe but keep in mind that frozen embryo transfer cycles have a lower pregnancy rate than fresh cycles, probably because, in most FET's, the best embryos have already been used and the embryos being transferred are second best.

    2. I can't answer the question about the "polyp type structure" because you don't mention where it is. If it not within the endometrial cavity, in a position where it can interfere with implantation, then it is nothing to worry about.

    3. There is no need to measure progesterone levels, although I know that some clinics do. I don't but I am also providing lots of progesterone via vaginal suppositories AND injection.

    4. Aspirin, low dose Heparin and Medrol have been traditionally used for and determined to be beneficial in patients that immunological based recurrent miscarriages. They reduce the immune response and increase blood flow to the endometrium to help the implanted embryo and prevent micro-clot formation. I used it in failed patients as an adjunct if I think that there has been implantation failure due to a possible underlying immunological reason and to cover that possibility. I don't use it after only one failed cycle, however.

    5. If you look at my website, I have detailed information regarding success rates. In your age group, my cumulative pregnancy rate for under 35 years olds (2008-2012) is 76% per cycle with a 65% delivery rate. I only put in two embryos maximum in that age group. The number of 1 or 2 is dependent on what the patient chooses.

    6. I am not an advocate of "natural cycle IVF" because pregnancy rates are significantly lower and it is not cost effective. Cost is a major issue in the U.S. because insurane does not cover IVF in most cases.

    7. I think you should definitely keep trying but cannot give you specific advise without reviewing your medical records.

    8. Healthy diet and lifestyle is all that I can recommend.

    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 additional information check out my blog at http://womenshealthandfertility.blogspot.com check me out on twitter with me at @montereybayivf and facebook @montereybayivf

    ReplyDelete
    Replies
    1. Dear Dr Ramirez,

      Thanks so much for your response on this, it is really helpful.

      I'm now considering mild IVF, as I hear that egg quality may be better - do you find this?

      Also, IVM (In Vitro Maturation), which I know isn't as widely used as IVF. I know success rates are around 30%, but what is appealing is the fact that you don't need any drugs and the immature eggs taken are made to mature in the lab before fertilisation with ICSI. Do you perform IVM? What risks are there to the egg making it mature in the lab as oppose to the mothers body? I look forward to hearing from you. Many thanks Kate

      Delete
    2. Hello Kate,

      I am not a practitioner of "mild" or "minimum stimulation" IVF. On the other hand, I do believe that the stimulation has to be tempered a bit. The reason is that the goal of IVF is to find the "perfect" egg and not all the eggs in your ovary are perfect. That is, not all the ends have the potential to make a perfect embryo or lead to a successful pregnancy. So we want to get lots of eggs out in order to help us find that one good egg, which is just a matter of chance.

      Also, some studies have definitely shown that when a patient overstimulates (ovarian hyperstimulation syndrome) as with PCOD patients, the egg quality suffers and pregnancy rates decline. So too many is not good either. My goal is to get 10-15 eggs.

      I do not perform IVM and consider it to still be an experimental procedure. Because of that, I can't comment on your second question but to say that ALL maturation that occurs in the woman's body is better than the lab, including culturing to blastocyst.

      Good Luck

      Delete
    3. Thankyou again for all your help.

      Delete
  57. Hello May 23rd,

    I am suprised your sister's doctor gave up so easily. I sure wouldn't. However, if the bHCG dropped significantly, that is not a good sign and the pregnancy might be abnormal. It is likely that your sister is still pregnant and that is why the miscarriage has not occurred yet. Normal protocol would have been to continue to follow the bHCG's to plot it's course and then if possible, perform an ultrasound to rule out an ectopic (tubal pregnancy) or see what is going on within the uterus. If the bHCG plateau'd then we will usually offer to terminate the pregnancy by medical induction of a miscarriage.

    My recommendation to your sister at this point would be to have a bHCG and/or ultrsound done to see what is going on. Don't just continue to wait. An ectopic pregnancy would show an abnormal but rising bHCG until it ruptures and is a surgical emergency and could be lifethreatening. There is a 1% chance of ectopic pregnancies with IVF.

    Good Luck

    ReplyDelete
  58. Dear Dr Ramirez

    Could you help me please.

    I am 45.5. Fell pregnant naturally at the beginning of 2012 but unfortunately no heart beat at 8 week scan. Resulted in a D&C.

    Due to my age, we decided to speed things up and went straight to IVF.

    No tests were carried out - just the prescription for the medication was given to commence on day 1 of my next period.

    I used suprefact and merional for 8 days.

    2 follicles produced 2 eggs. Both fertilised and we had a 3 day transfer of Grade A 8 cell and Grade B 5 cell. ICSI and assisted hatching on both.

    I was taking:
    Cyclogest 3 x a day
    Medrol 1 x a day
    nuseals 1 x a day
    yutopar 1/2 tablet 3 x a day
    duphastone 3 x a day
    cyclacure 3 x a day

    I got a negative beta test 15 days after ER.

    As I am producing eggs, should we try another IVF cycle? and if so, what would you suggest is changed?

    Or do you think its time to go to Donor eggs?

    Your comments would be much appreciated.

    regards

    Karen

    ReplyDelete
    Replies
    1. Hello Karen,

      Thank you for your reliance on my advice. First let me say that I cannot give you specific protocol recommendations because there are many different ways to accomplish the same thing. Also, without knowing exactly what transpired in your cycle by reviewing your medical records, I don't know enough details.

      It is an amazing feat to become pregnant at 45+ years. The natural incidence is almost zero. However, the most likely cause of your miscarriage was due to chromosomal abnormalities which occurs more frequently with increasing age. There is no current technology to change the quality of eggs, and because you have become pregnant before, we know that the quality of eggs is the main problem that you are trying to overcome.

      There is only two ways to overcome this problem. You can either continue to try, but anticipate that it may take several attempts before you are successful (just as it takes most women several months of trying to get pregnant naturally), or you can move to donor eggs which will take away the age problem and your chances of success are much higher. Having a pregnancy at 45 with IVF is almost unheard of so there are no specific statitics to cite, but you can assume that it is less than 1% per attempt, whereas donor IVF cycles have up to a 74% chance per cycle depending on where you go (it is less in Europe). My advice would be to go to donor eggs if that is acceptable to you and your husband.

      Good Luck

      Delete
    2. This comment has been removed by a blog administrator.

      Delete
  59. Hi Ramirez,

    This is Rekha and I had a seven year old son conceived normally and delivered by C-section in 2005.

    i have regular periods always and will come every 28-30 days(lasts for about 3 days every month).

    After that we started trying for a second baby from 2010 October naturally but no luck.
    Then we approached Melbourne IVF in march 2012 and after 3 months careful observation with my blood tests, fallopian tube tests, left ovary, right ovary which appears everything normal,my doctor suggested my Husbands semen's analysis test twice. after two tests it was known that he had sperm morphology issue and My doctor suggested us ICSI.
    In the month of June 2012, we started ICSI , on day 13 she retrieved 5 eggs and 3 fertilised and did ET with one 4 celled embryo on day 15.
    Since then I am on Crinone 8% once per day during night
    On 13 day(today) post ET, I had my periods not very heavy flow..but started like a period, definitely not a light spotting. I informed it to nurses. she said looks like it didn't work this time but she asked me to come for blood test tomorrow(july 5 2012), the actual blood test scheduled on july 06 2012.

    what would be the causes for my failure on first attempt of icsi? Do you think its a impnatation failure? should i go for 2 icsi as i have two embryos frozen ? Also the treatment is bit expensive.

    please advise me

    Regards Rekha

    ReplyDelete
    Replies
    1. Hello Rekha,

      IVF is not a perfect technology. It still requires two natural steps to occur on their own for a pregnancy to ensue. Just like trying naturally can take several attempts, IVF can take several attempts as well, just not as many.

      In addition, your embyro quality was not good. By the 3rd day after retrieval, the good embryos will be 6-8 cells. Although 4 cells can work, the chances are much lower.

      Good Luck

      Delete
  60. Hello Dr. Ramirez,
    In 2009, I tried my first IVF cycle..I did not reach the trigger stage, for some reason my follicles disappeared. The second IVF cycle worked well. My age: 38.. Also 5 feet tall 176 pounds at the time I was on the following medication:
    Started with birth control pills
    Lupron
    Gonal F-300
    I became pregnant and had beautiful baby girl in March 2010.
    I nursed my baby for 2 years and decided to do IFV again. Now, age 41..My weight still about the same 177 pounds..Started February 2012. They following protocol was used:
    Birth Control Pills
    Lupron
    Gonal F-375 and then it went up to 450..The eggs grew slowly. They transferred 3 embryos. It did not work. My new protocol was the microflare protocol.
    Birth Control Pills
    Microdose Lupron
    Gonal-F 450
    Menopur 150
    This cycle seemed to go well. The embryos were much better quality…Though, my uterus lining was 6.7. But then when they transferred 4 embryos, it was at 9. The IFV cycle failed…Any thoughts on why it has failed…Is embryos or my uterus? Would my eggs be so bad in 2 years? I had a c-section, is there a way to see any scarring in my uterus?
    Or is it my weight affecting the IVF procedure...

    ReplyDelete
    Replies
    1. Hello July 5th Anonymous,

      Of course there is no definite way to know why the cycle failed. Implantation failure can be caused by the embryo not continuing its development, not hatching and exiting from its shell to attach to the lining and the lining not growing around the embryo. The technology does not exist to determine if these factors took place.

      However, your age makes a significant difference in the health of the eggs and resultant embryos, so that is where I would probably say is the root of the cause.

      Good Luck.

      Delete
    2. Do you think it is worth doing a 3rd IVF cycle using my own eggs? It is hard for me to believe that my eggs are not good? I had one great egg back in 2010...

      Would heparin 2000 units or increase of progestrone help?

      Delete
    3. if spooting on day 8 for few days after 5day blastocyst transfer. is this usefull to increase progestron level high as it is 45 on day 12. is implatation can occur or its failed. thanks

      Delete
  61. Dr. Ramirez, I have Adenomyodis and I am thinking of going through stimulated IVF. Can you please discuss the risks?

    ReplyDelete
    Replies
    1. Hello July 13 anonymous,

      This is a difficult question to answer because it is not know what impact adenomyosis has on implantation. There have not been definitive studies that show any decrease in implantation or pregnancy rates. Because adenomysis is within the muscle of the uterus, theoretically it should not have any impact on implantation or pregnancy. Some question whether having this heightens the immmune response because of a low grade chronic inflammation, in a similar way that pelvic endometriosis does, but that is unproven. At this point in time, IVF should not be hampered by adenomyosis.

      Good Luck

      Delete
  62. Hi,
    I am 36 yrs old (37 in Oct). TTC since I was 34. I had two miscarriages from 6 IUI's (each one after the third cycle). The first cytogenteic test of the tissue from miscarriage #1 was abnormal chromosone; the results from the second miscarriage was inconclusive. We have had full testing including genetic and autoimmune so we are in the unexpalined category.

    We just did IVF-ICSI. 19 follicles had 19 eggs. The fertilized 17 all successfully. 15 made it to day 3 and they said top quality or very good quality. 14 made it to day 5 and they transferred two. The only froze 4 of the 12 remaining as they have higher standards for freezing. At 8 days post transfer (yesterday) I got spotting all day. Today is like day one of period and I was supposed to take the bloodtest in 2 days but my RE said I can take it now. I am bracing myself that this will be a BFN although some people say a bleed can be normal, especially if one embryo doesnt make it. Is that true?

    I feel I have bad eggs, problems with my uterine lining, or some other reason they have not picked up on. What would you suggest? We will try the four remaining but we were so hopeful the IVF would work, the first trimester was the scary part.

    thanks

    ReplyDelete
  63. Hello July 17,

    Sorry for the delay in my response. By now you probably have your bHCG result. I hope it was good news as I often have patients that have spotting in the very earliest stages of pregnancy. That does not predict that the pregnancy will fail, however.

    The major reason you may have miscarried previously is not "unexplained category" but rather you have an age related risk. After 35 years old, the risk of a miscarriage goes up every year and can be as high as 40% per pregnancy. This is due to "spontaneous" chromosomal abnormalities and not something that you carry and pass from embryo to embryo. We know that because of the aged nature of the eggs, they become more deficient and debilitated in many ways, one of which is weaker chromosomes. So, in fact, you have a reason for repeated miscarriages. With that knowledge, you have to accept the fact that it just may take several attempts before you are ultimately successful. Eventually everything will come together and you will be successful!

    ReplyDelete
    Replies
    1. Hi there,
      Thank you for the reply. This is my update. On my second day of bleeding I got a hcg result at 22. My RE said that her colleague's baby started at a beta 12 so to have hope. By the fourth day of bleeding it subsided and my beta increased to 101 (2 days later so that was a great jump). I went on bed rest for the next 3 days and the next beta fell to 47. My RE said I was having an early miscarriage/chemical pregnancy so this was my third miscarriage. It is now 8 days later and my beta is now at 38.

      I understand my risk is higher but I don't know how many more attempts we should try when we are through the 4 frozen embryos. How many losses is normal for an almost 37 yr old? Is it a good sign though that I got pregnant three times in the past year? I don't think we can do more than one more IVF financially because the cost of adoption is so costly. Thank you for your optimism though, that is appreciated.

      Delete
    2. Hi Again,

      At least you know that you can get pregnant, but it is unfortunate that you have miscarried. Because of your age, you have to expect that you have an increased risk of abnormal embryos leading to miscarriages. You basically have two choice, and neither choice is to give up! Since you know you can get pregnant, it is a matter of gettin a perfect embryo in the uterus. It is possible and likely that a perfect embryo exists within your ovaries so you just need to keep trying to find that perfect embryo. The second option is to use donor eggs, which will get you the perfect embryo faster. It will then be your biologic child and your husband's genetic child, both of which are better than adoption. So, you have to decide, can you continue trying with your own eggs, knowing that there may still be miscarriages to come, just to give you the opportunity of having a genetic child, or would it be better to use a donor egg, which will most likely result in a pregnancy sooner?

      Good Luck

      Delete
  64. Dear Dr.Ramirez,

    I am 39y old, no pregnancy history. Infertility was due Q-shape cervix and pre-mature ovary failure (highest FSH 14).

    Last Sept. I had my first IVF and I only made 5 eggs and 4 out of them were fertilized. We transferred 4 embryos (3 were 8cells and 1 was 6cells). The quality of embryos was between good and average with 10% fragments. I had chemical pregnancy- 1st beta 10 (12dp3dt), 2nd beta 24 and then 56 and 72 before it dropped.

    After 3 cancelled IVF attempts due to poor response to stimulation med, we moved to donor cycle in July. The 23-year donor produced 22 eggs, 17mature, 13 fertilized, 7 got frozen were high quality. On July 30 we transferred two top-grade blasts. I had cramp on day 2-3 after the transfer. Assumingly the cramp was implantation attempt, I felt everything went well. My 9dp5dt beta was 35, and it dropped to 24 after two days. I protocol was aspirin 81mg, estrod 2mg twice per day and Crinone 8% twice per day.

    We were very shocked that the donor cycle also failed with chemical pregnancy, and really want to find reason and take proper treatment before we start a new cycle with frozen embryos.

    I am very healthy (BMI 22.56 kg/m2), good diet, exercise regularly, no med history besides the fertility treatment. I took HSN test and Hepatitis B Core Ab Total, Reflex to IgM, and no issues found. My husband had sperm analysis, HBA and Hep BCAB tested, all perfect.

    Reviewing the failed donor cycle and trying to understand the recurrent peri-implantation loss, I did some research online and strongly doubt my endometrial receptivity. My last lining check was 8.3mm and E2 was 188 on July 17th, 13 days before the transfer. With estrod 2mg twice per day, could my lining grow too thick and lose receptivity. The transfer day was Day 24 since the start of my last period. Could the MAG level be too low by the transfer time? Do you think I should take an endometrial biopsy to test MAG? Or would it be an immunological disorder preventing implantation? Please advise.

    My RE said a chemical pregnancy can enhance the possibility of pregnancy. You also commented to a post “Since you had a chemical pregnancy, I am confident that you can achieve pregnancy eventually.” Why a chemical pregnancy could be a positive indication for pregnancy? Any insight would be greatly appreciated.

    Best regards

    Victoria

    ReplyDelete
    Replies
    1. Hello Victoria,

      I think you are mixing up issues. The fact that you had a chemical pregnancy means that implantation did occur, so there is not a problem with implantation.

      A chemical pregnancy is a form of miscarriage and we know from previous studies that miscarriages can occur up to 40% of the time. Despite the young age of the donor, there could still have been developmental problems in the embryo that occurred at the time of the egg division. That is what we call a spontaneous genetic abnormality and the most common reason for miscarriages. The good news is that this is NOT a recurring problem and you will eventually be successful, most likely with one of your frozen embryo transfers. Don't give up hope.

      The only change I might suggest is to add injectable progesterone to your regimen to increase the progesterone support. This could also be a reason for a chemical pregnancy.

      Finally, recent studie show that there is an increased pregnancy rate in women that have been pregnant previously, especially within the first 6 months after a miscarriage.

      Good Luck

      Delete
  65. Saludos Dr Ramirez:

    Hace 1 ano me someti a una FIV con ICSC, mi esposo tiene oligospermia severa. Me trasfirieron 2 embriones uno en etapa de morula y otro blastosito,al dia 5 de la aspiracion. Afortunadamente fue positivo. Pero lamentablemente a las 28 semanas de embarazo me comenzaron pequenas contracciones que el ginecologo que escogi no supo tratar. Nacieron por medio de una cesarea y murrieron a los dias de nacidos.

    Voy a comenzar nuevamente tratamiento a 5 meses de mi cesarea, el Dr indica que es tiempo sufuciente. Lo que tengo duda es que el Dr solo me quiere trasferir un solo embrion esta ves.Y me da temor q no se me den. Ademas va utilizar un ciclo mas corto para sacar menos ovulos pues anterior mente utilice el follistin 900 iu y me sacaron 12 ovulos todos de excelente calidad. Ahora quiere intentar con clomid y ganirellix. Para sacar aprox 5 a 6 ovulos solamente. PAra bajar el costo de los medicamentos de la FIV.

    Estara corecto esto?
    Cual es la diferecia en cuanto efectividad del crinone y el endometrin?
    Que posibilidades con un solo embrion trasferido tengo de embarazo? Tengo 28 anos mi esposo 30, ya tengo una nena de mi anterior matrimonio.

    Gracias,

    ReplyDelete
  66. Estimado Senora,

    La probabilidad de embarazo es muy alto porque usted ha estado embarazada anteriormente. Sin embargo, las probabilidades de embarazo por ciclo con la transferencia de un solo embrión se redujo de transferencia de dos embriones, pero las posibilidades de que los gemelos se elimina. Especialistas reproductivos están tratando de reducir las posibilidades de que muchos múltiplos ahora recomiendan la transferencia de un solo embrión, pero lo dejo a la paciente para decidir

    No hay diferencia significativa entre Crinone y Endometrin excepto Crinone es más desordenado que Endometrin porque es un gel.

    No se preocupe demasiado. Sus posibilidades de éxito final es muy alta. Es sólo una cuestión de tiempo.

    Buena suerte

    ReplyDelete
  67. Hi can you play help me.? Um in my third and final IVF cycle! Ok my first cycle I produced 7 eggs but none made it to blast. But my second cycle was Great I had 13 eggs and 7 made it to blast!:) we put 4back in!! I had pain Luke thy was trying to implant but my pregnancy test came back Negative!! I'm still Heart broken. All of my eggs was excellent quality thts why we was all shocked Whn it turned out negative!! I'm 40yrs old with 2children naturally! But I had thm in my Teens! Now I'm married ans my husband had no kids!! I have one blocked tub but the other is opened! I feel like this is a implantation problem! Wht cab I do differently ths go round? I start in September 2012 I'm so SCARED!!! I HV BEEN taking supplements such as Dhea cq10, roaly jelly wheatgrass b6 fish oil prenatal vit with dha add,calcium vit d vit e vit b12 urine pulls l Larginine! For three months now. I hear u talking a lot about heparin but how about lovenox ? Can use lovenox instead of heparin? And would I use 40mg or should use the 2000mg u was talking about? Pls help this is ny last ans final try!!!!!

    ReplyDelete
    Replies
    1. Hello,

      The biggest issue you have is an AGE FACTOR. You'll find that subject discussed on this blog as well. What that means is that your eggs have declined in quality. This is not something that can be changed. When we evaluate embryos, we are looking at them through a microscope and only the external features. There is no technology available to evaluate the internal quality. We can check genetics using PGS but that is only the genetic factor. There is much more to embryos. What this means is that you need to understand that it may take several attempts at your age to achieve pregnancy. IVF is NOT a perfect technology so the hope is to eventually find the perfect egg. When that happens, you will be successful.

      In terms of other meds, these meds don't change the egg factor, but certainly are worth trying. Yes, you can use Lovenox instead of heparin.

      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 additional information check out my blog at check me out on twitter with me at @montereybayivf and facebook @montereybayivf. Skype and internet comprehensive consultations now available via my website for those who want a more extensive evaluation that this site can accommodate.

      Delete
  68. Dear Dr.Ramirez,

    Thank you so much for your response to my questions and giving us encouragement.
    Your reply is very helpful. We are looking forward to having FET soon.

    Best regards,

    Victoria

    ReplyDelete
  69. Dear. Dr. Ramirez,

    I am 36 yo and have 4 failed ICSI cycles. I am having slight polysistic ovaries but always very good response to stimulation.

    1 try – 18 eggs were collected – 16 fertilized and 2 blast very good quality put back and 4 frozen on day 5 and 2 on the next day. The cycle failed.
    2 try – 9 eggs collected – 8 fertilized and 2 3 days embryos transferred on 8 cells each and 2 frozen on day 3 each 6 cells.
    3 try – bad stimulation asynchronous growth ogf the eggs – the stimulation was only 5 days – 3 eggs collected – 2 transferred back on day 3 second quality with fragmentation and uneven cells sizes – test came negative.
    3 try – 15 eggs collected – 9 fertilized – 3 transferred back – 1 very good blast and 2 early blasts – 2 frozen on the day 6. Today I got my test it is a complete 0 this time.
    We have 2 frozen embryos which we will probably use on a FET in the next few months.

    I had all the tests done on me – everything came back normal . My husband also is having normal parameters on his.

    After transfer I am put on aspirin and PIO injections.

    My questions is as we have repeated implantation failure – is there a sense to make the FET with the embryos we have or it is worth to consider a fresh cycle.

    What do you think can I do to improve the parameters and give it best chance.

    ReplyDelete
    Replies
    1. It is very curious that you have failed four fresh cycles. You now have a lot of frozen embryos and I would recommend that you use them before trying another fresh cycle.

      Secondly, I would recommend that you change clinics. Pregnancy rates can vary between clinic to clinic and doctor to doctor. Poor transfer technique can lead to failures. You seem to have had good embryos each time, based on their appearance, so could it be something else?

      I would have to review your entire medical record of each IVF cycle to give more specific recommendations.

      Good Luck

      Delete
  70. Dear Dr. Ramirez,

    My husband and I have been trying to conceive for almost 3 years now – 2 years with the help of doctors. We have done 3 IUI (all unsuccessful) and just completed our 3rd IVF cycle (2 Fresh, 1 Frozen) with no success.

    Medical History:
    Me: I am now 37 years old. I have no known medical issues.
    Husband: He is 38 years old. He has a complicated medical history – including ulcerative colitis (had an ileostomy – 6 months ago) and primary sclerosing cholangitis (had a transplant – almost 10 years ago). Semen analysis showed compromised parameters (low count, some morphology and motility issues). Likely due to medicines needed for UC (no longer needed since ileostomy) and anti-rejection. ICSI is recommended for IVF cycles.

    IVF #1 (with ICSI) – There were 14 follicles, 10 mature eggs, 6 embryos, 1 expanded blastocyst was transferred and 2 expanded blastocysts were frozen. All were Grade A quality. Estrogen levels were 2300. Lining was triple layer 16mm (Doctor said this is great). Continued to take endometrin and estrace during 2 weeks. No pregnancy.

    IVF # 2 (FET) – Both expanded blastocysts were thawed and transferred. Lining again was great. I took baby aspirin during this cycle. No pregnancy.

    IFV # 3 (with planned PICSI/but reverted to ICSI; also assisted hatching) – There were 9 follicles, 8 mature eggs, 4 embryos, 1 expanded blastocyst and 1 compacting morula were transferred. No embryo was frozen. Blastocyst was Grade A quality; morula could not be graded but expected to reach Grade A quality by the time of transfer. Lining was great. Estrogen was 2700. I took aspirin during this cycle. I also had endometrial biopsies done (“scratching”) to help with implantation. No pregnancy. Note: Although selection of sperm through PICSI was attempted, no sperm bound to hyaluronan so sperm was selected through the ICSI process.

    Why is this not working? Embryos appear to be good quality based on all external indicators (reaches Day 5 and Grade A quality)? Two explanations are on the table: implantation failure or a genetic issue. My doctor suspects that it’s the sperm. She suggests that we try: (a) everything we did for IVF # 3 plus PGD to determine if there is a genetic defect; (b) everything we did for IVF # 3 plus steroid and blood thinner (includes PICSI/ICSI, assisted hatching, endometrial biopsies etc).

    There are no clear indicators that the implantation failure could be an autoimmune issue. In fact my thyroid levels checked out normal. Dr. Ramirez – I am looking for a second opinion - do you have any additional suggestions or insights based on the information I have provided?

    Thank you so much in advance.

    ReplyDelete
    Replies
    1. I'm sorry. This is not a comprehensive consultation site and your comment/question is too extensive to address here. If you want a comprehensive review and consultation, that can only be done through my website.

      Delete
  71. Hi Dr Ramirez

    My name is Angela, I am from England and I contacted you last year on May 10th to ask about implantation failure.

    At the time you mentioned a medication protocol that may help with implantation.

    My situation is now this, I have had 3 failed fresh IVF cycles, my first 2 the embryos were excellent and then good, my last cycle there were enough embryos of good quality (8 in total) to go to the Blastocyst stage, I am now 38 and because of my age, in England they now allow taking embryos to Blast stage for any woman over the age of 37! 1 very good expanded Blast was transferred but failed. I have 2 embryos frozen, 1 has expanded and 1 has started to hatch, the embryologist described them both as extremely good day 6 Blasts and both will be transferred when the time comes. The embryologist was very very happy with their quality and so I want to do everything I can in my FET to ensure our little embies have the best chance of implantation.

    My problem is I am going for FET on my next cycle and this will be my last attempt at IVF in England and I want to give this my best shot.

    My clinic has agreed to allow me the medications I have suggested to them, which you include in this blog.
    First my problem is that I am allergic to aspirin and so I wondered if there was an alternative that I could safely use?

    Secondly each time I read your instructions on how to take the meds, when and how much I become very confused and so I wondered if possible you could give me the protocol for meds used on a FET and be as explanative as possible so that I can understand the regimen before I present it to my clinic.

    Kind regards
    Angela from England

    ReplyDelete
    Replies
    1. Hello Angela,

      If you are allergic to aspirin, there is no alternative.

      The protocol is the same as treatment for a patient with recurrent pregnancy loss, in case your doctor's want to look it up. The medications are as follows:

      Heparin 2000U SQ twice per day starting with the beginning of the cycle and continuing until 10 weeks pregnancy if you get pregnant, otherwise stop after the pregnancy test.

      Medrol 8 mg - two tabs per day starting with the beginning of the cycle and decrease to 1 tab on the day of transfer. Continue until pregnancy test then stop.

      Progesterone in oil 50 mg to be started 5 days before the transfer (day of transfer should be the 6th day) and continue until negative pregnancy test or until 8 weeks gestational age.

      Endometrin or similar vaginal progesterone 100 mg vaginally each day starting on the day after transfer and continuing until a negative pregnancy test or until 10 weeks gestational age. If pregnant, increase to three times per day with the progesterone injections stop.

      Estrogen to be used per your doctor's FET protocol.

      Lovenox can be substituted for the Heparin and is 35 mg injections per day.

      Delete
  72. HI,

    I had a 5th day 4AA grade cell 3 embryos transferred. on day 8th we tested the beta hcg and got 8.04 and progesteron level at 34.5. now i am in 11 day post ET still i didnot get periods. do you think i can still hope for the best. please suggest.

    ReplyDelete
    Replies
    1. You had a positive bHCG so it should be followed every 48 hours to make sure it is progressing correctly and increasing. As long as this is happening, there is certainly hope.

      Delete
  73. Hi Dr. Ramirez-

    I am 32yrs old. I have had a successful natural pregnancy and birth at the age of 17 with my current husband of 16 yrs.(neither one of us has ever had any other partners) My first pregnancy was very textbook with no problems.

    We started attempting another pregnancy when we were 27 and easily got pregnant within the first month of trying that I was off of birth control pills. It ended up being a tubal pregnancy which was suprising as I don't have any risk factors for it (no hx of STD's or surgeries). My OBGYN did a salpingotomy leaving my tube intact.

    We waited for about a year to try again, well because life gets in the way, but when we did it ended up in another tubal pregnancy. This time in the opposite tube. My OBGYN then did another salpingotomy of that tube, but when she went in she saw that the first tube (left) was really scarred and was hydrosalpinx so she removed it.

    About two weeks after that procedure I ended up in the ER again because some cells from the pregnancy must have been left and regrew causing the tube to rupture and then we had to do a salpingectomy on that side (right). Leaving me with a bilateral salpingectomy.

    We have recently have had two failed IVF cycles. My husbands sperm quality is normal, my ovarian reserve is normal, and I have no other health problems.

    During both IVF cycles my E2 levels were very slow to elevate, despite the fact the we almost tripled dosage of follistim on second cycle, and I took DHEA throughout second cycle. We ended up with only 5 eggs per cylcle (all fertilized in first cycle, but only 2 made it to day 5)(2nd cycle only two fertilized, but both were grade 1 on day 3 transfer). We did not have implantation with either cycle regardless of a normal uterus and 12mm stripe and laser embryo hatching on second cycle.

    I was on 81mg of ASA, femtrace bid P.O. and progesterone intrauterine from egg retrival to negative pregnancy test.

    Do you have any advice for changes to a 3rd cycle?

    ReplyDelete
    Replies
    1. Hi,

      I would really need to review your medical records to give you any specific advice. Tere could be a lot of changes that I might suggest or medication to add, but that would depend on how you were exactly treated.

      My first worry in reading your account is the quality of the clinic you are going to. Your age and the fact that you have been pregnant before puts you in the "gold standard" category, which means we measure IVF success and compare clinics by women that are the most fertile i.e. under 35 years old. Sometimes IVF can take more than one try, even in young women, but your response to stimulation is suspicious.

      Good Luck

      Delete
  74. For my second cycle i was put on birth control for a minth prior to stim start then stsrted with 10 units of Lupron. During stim I was treated with 450 units folllistim and 2 amps of menopur with 5 units of lupron. After egg retrieval I was on femtrace bid and endometrin bid. Before and during my cycle I was on 75 Mg of DHEA and 81 Mg ASA.

    Is this helpful ?

    From anonymous on Feb 7 2013

    ReplyDelete
    Replies
    1. Hi,

      The additional information doesn't help too much but it shows that you were on the highest stimulation protocol. It shows that your ovaries are not very responsive to the stimulatory medication and we would classify you as a poor responder. Despite only having a few eggs, however, your embryos should be good quality and your chances of pregnancy should be high.

      The only think I add to my patients that fail is low dose heparin to help mute any immunological effects you might have and to increase blood flow to the implantation site. I also add a steroid called Medrol.

      But again, without a close review of your medical records, it's hard to give specific advice. I am still skeptical of your clinic as well.

      Delete
    2. One other thing to consider would be to change from the Long Lupron protocol that you have been using and trying an antagonist protocol to minimize the ovarian suppression, and possibly increase the number of follicles produced.

      Delete
  75. Dear Dr Ramirez,

    I must say i really find your articles and blog so interesting and informative. I am 30 yrs old, husband is 32 diagnosed with azoospermia . i have no family history of any medical issues so we went ahead for our first icsi last month. My AMH level was 33.5 and the doctor put me on menopur inj 150 daily and cetrotide 0.25mg daily for approx 10 days. Finally for my egg collection they were able to retrieve 14 eggs ( of which 7 fertilized) and 4 made it to 5 day blastocyst. they embrologist assured us that they were top quality and she was very pleased with the progress. prior to my transfer they had already begun hatching. i was told to take cronine vaginal 8% 1.125g at night before sleeping and 2 pessaries of viagra.seven days post transfer i started light spotting which then lead to heavy bleeding. My doctor advised me to do the beta hcg and progesterone test on day 8 post transfer .results were progesterone 1.22ml and hdc beta 0.100ml. i feel absolutely devasted but am trying to understand the cause for the negative result. My doctor is shocked to see the low progesterone level and advised that next time he will need to close monitor the progesterone level and that i was probably no absorbing the gel properly. Could this be the cause for the result? Also i am stil having bleeding , is this my period which has come 6 days early or a miscarraige? I have 2 frozen embryo's left but have been told that the success rates decline after thawing ( if they survive). i would really appreciate your advice on this .

    Thanks jada

    ReplyDelete
    Replies
    1. Hello, I cannot tell you or explain why your cycle failed. No one can know that. I also cannot explain the bleeding except that it is probably your period, not a miscarriage. Finally, there is a decrease in pregnancy rates with frozen embryos, depending on the quality of the freeze. With the new freezing techniques, pregnancy rates have actually increased and so some clinics are moving frozen embryo transfers as a standard.

      Delete
  76. Dear Dr,

    I just had my first failed ivf cycle. It was 3day transfer. Four grade B (6-8)cells were transferred . My doctor put me on
    Cap.Ultigest 300mg/TID (vaginal use)
    Inj.Naturogest 200mg(IM) once in 3 days(5)
    Cap.Co Q forte
    Tb. Rudimin
    Tb. Wingora 1\2 BD.

    We have unexplained infertility. Now my doctor says that implantation failure may be due to sperm quality. But while analysing my husbands sperm report she said it is normal.
    The report says
    Total count : 28 million per ml
    Fast progressive : 20%
    Slow progressive : 25%
    Non progressive : 5%
    pH 7.5
    MORPHOLOGY
    NORMAL :85%

    Can you please tell me what went wrong in my cycle. Does sperm qualilty is the reason as my doctor says......
    Please help
    thank you
    durga

    ReplyDelete
    Replies
    1. I'm sorry there is no way for me to know what went wrong. There are too many possibilities. For instance, after the embryo is transferred into the uterus, three more steps have to occur naturally in order for a pregnancy to occur. These steps occur naturally because we do not have the technology to make them happen. So, that means there are at least three places (steps) where an IVF cycle can fail. We also dont' have the technology to know which step did not work.

      Sorry.

      Delete
  77. I fell pregnant naturally the cycle before starting IVF treatment. My clinic had advised me to start taking cyclo progynova tablets a week after I ovulated. Once I realised that I was pregnant I contacted the clinic. They advised me to stop taking the cyclo progynova. I asked if I needed to use progesterone pessaries to support the pregnancy but was advised that I did not need to. I stopped taking the progynova on the Monday and started spotting 5 days later on the Friday. The following day (Saturday) I started bleeding and miscarried. Was I given the correct advice? Did stopping the cyclo progynova cause me to start bleeding?

    ReplyDelete
    Replies
    1. Hello. Progynova is estradiol (estrogen) and once pregnant, it not absolutely necessary to sustain the pregnancy. However, progesterone is absolutely necessary and if the pregnancy is no producing adequate amounts, a miscarriage can ensue. So in answer to your question, the clinic was correct that the progynova was not necessary. However, whether or not progesterone supplementation was required was neither "here nor there" as we say in the U.S. Meaning you could go either way. Most natural pregnancies do not need progesterone supplementation and do just fine. However, patients with recurrent miscarriages sometimes do so because of inadequate progesterone (luteal phase defect). So, my personal preference, because progesterone is easy to give, take and use, and could be important, is to give progesterone. I don't want to wait and see if you miscarry or not to decide that "oh, I probably should have given it."

      Delete
  78. Dear dr ,
    Im 28 yrs old and we have been classified unexplained infertility . Laproscopy done showed no endometriosis or anything but the dye test showed mildly slow spill on both sides fallopian tubes .but no blocks or fluid .
    Then we had one icsi and a fet both failed . I produced 11 eggs on a short antagonist protocol of which ten fertilized . For the icsi they transferred 2 blasts . The fet transferred 3 embryos on day 3 .
    Both times i was on aspirin and progynova after transfer . Gestone injections too after transfer .
    We have lost hope now as to why it has not worked and don know how to move further .,. Please advice doctor

    ReplyDelete
    Replies
    1. Hi. I can't give you specific advice without a review of your medical records to see exactly what was done. It is certainly unusual for a 28 year old to fail several times. If good embryos are available, then failure can only be due to poor transfer technique or failure of one of the last three natural steps (embryo hatching and emerging from the cell, attachment to the lining and growth of the lining around the embryo). Since there is no technology that can help these last three natural steps, all you can do is continue trying. Keep in mind that pregnancy rates are highly variable and can vary between doctors and clinics. For that reason it is important to research the quality of the doctor and clinic you go to.

      Delete
  79. Dear Dr,
    I am 31 years old, married for 3 years, tried 6 cycle time conception, 1 IUI and recentlyjust had a failed IVF with is I.
    I have only 10 eggs with 8 fertilized. Two embryo transfered ( first -grade 1 and 8cells , second -grade 2, 6 cells). My husband have good sperm count. ET is 10 mm.
    Everything seems good, but why my cycle fail?
    Is it because i have didelphis uterus? All the investigations done on uterus saying that the uterus have good size and good ET..


    thanks

    ReplyDelete
    Replies
    1. I cannot tell you why you failed. Only God knows the answer to that question. A Grade 1 8 cell embryo does not guarantee that the embryo is a good one. In fact, I am now culturing my embryos to blastocyst stage and finding that many of the embryos that I would have chosen to transfer because they were grade 1 at the 3rd day, do not make it to blastocyst. So in fact, that means that D#3 is not a good time to choose embryos to transfer. That may be the reason for the failure in this cycle.

      Delete
  80. 42 y/o F with 3 failed cycles of IUI all the while my E2 levels were <100 post treatment. However on day 8, E2 level is around 400's on 3-4 x 75IU menopur. My husband has poor morphology and sometimes poor motility. My symptoms before menstruation consist of (which usually begin on the 2nd half of my cycle), they are shivering in 100F weather, finger cuticles start to peel off, legs, back and breast cramps/tenderness which requires significant pressure such as pounding to relieve excruciating pain sensations. My eye sights become blurry. The frontal aspect of my head feels heavy like it is swollen. Sometimes I get insomnia. Before my period, my iron level is usually low, around11 and iron binding level is 3-19. I would demand hard pounding intercourse and for my partner to bite my upper back with great force to relieve those pain sensations. Then I would get my period a day or two later. Maybe I'm just not made to be pregnant. All of my symptoms resolve after my period. I'll come back on here and share about my first cycle of IVF in a week. So far, this is what is happening to me while going through IVF. I do though cant stand taking 16mg medrol. Took it once and was sweating profusely as if I just came back from a jog. I'm taking 50g DHEA bid, 200mg Coenz Q10 bid, 1200mg fish oil from Nature Made qd, 2000mg D3 bid, 1600mcg folic acid bid and Newchapter perfect prenatal multivitamin. After day 11, 5 follicles on the left ovary and 3 follicles on the right ovary. They are 14-15mm and uterus lining is 11mm. Have been taking 3x75IU menopur SQ, AM and 3vials of bravelle IM at night. 3 days ago I also included Granirelex, one per day. What's next for optimal outcome? Day 8 E2 =642. Day 11 E2 >1000. What's next for best results? I must add that so far, I've not had the urge for great pounding anywhere. Maybe this is a good sign afterall?

    ReplyDelete
    Replies
    1. Hi. You're asking me to second guess your doctor's protocol and I can't do that. There are no magic protocols and no gold standards for IVF. Each doctor uses what they feel is the best based on their knowledge and training. In your age group, the primary goal is to try to get as many eggs (<20) as possible in order to try to find a good egg. Because of your age, you have few good eggs and since we can't make egg quality better, our only option is to try to find a good one. Your doctor is using a mid-range stimulation protocol (350IU of FSH) per day, whereas the highest protocol is 600IU per day.


      I'm afraid I can't speak to the premenstrual symptoms you have. I've never heard of such symptoms before. Obviously there is hormonal involvement since it is just before your menses and better with IVF.

      Delete
  81. Dear Dr. Ramirez,
    I have a history of endometriosis on my uterus, ureter, bladder and bowel. I am 31. A laproscopic surgery was unable to remove any endometriosis. I had three months of Zoladex and then ivf which resulted in our child who is now 11 months old. It was our first ivf cycle and we transfered two 5 day blasts. We have three other 5 day blasts of excellent quality frozen. My son was delivered at 37 weeks by emergency c section due to Preeclampsia with HELLP syndrome.

    We are now starting a FET with one embryo. I just found out two weeks ago that I have now developed adenomyosis. I am very concerned this will affect a potential pregnancy and am unsure of if it can cause miscarriages and uterine rupture as I have read through Google searches.

    Is a c section necessary with adenomyosis? If pregnancy is achieved should I be concerned about increased miscarriage? Will it be possible to have more children in the future? We plan on giving all of our three embryos a chance. Is there anything I can do to increase our chances? Should we consider transferring two embryos? I'm very anxious and worried. I would appreciate your advice as my doctor is away and will not be able to meet with us until around the expected date if our embryo transfer.

    Thank you most sincerely.

    ReplyDelete
    Replies
    1. Hello,
      I apologize for not getting back to you sooner, but this blog is not really a Q&A blog. You probably have gotten answers to your questions elsewhere, but I thought I would reply and give you mine.

      Adenomyosis should have no affect on your pregnancy and will NOT necessitate a c-section. In fact, pregnancy is an excellent treatment for both endometriosis and adenomyosis. It often will put these into remission. In terms of how many embryos to transfer, that is going to depend specifically on the clinic you are working with. What is their pregnancy rates? What is their twin rates with transferring two blastocysts? In your age group and in my clinic, I have been getting a 60% twin rate in transferring two blastocysts so am considering backing off to single embryo transfers. However, I still leave it totally up to my patient. Since you have been successful previously, your chances of twins with two blastocysts would be higher. I would definitely NOT recommend three blastocysts.

      Good Luck,

      Delete
  82. Dear dr,
    I am 32 years old, diagnosed uterus didelphis. I have married 3 years and try one IUI, one fresh ivf and one FET. All fail.. My husband sperms is good. My ET is good ..my tube patent. wondering whether I am having PCOS? My BMi is 17. Had strong family hx of DM. But all my blood test doesnt show PCOS.

    ReplyDelete
    Replies
    1. Hello,

      Why would PCOS be an issue at this point? IUI and IVF negate the impact of PCOS since it is simply an ovarian or ovulation dysfunction. That is required to make the diagnosis, by the way. It is NOT just an ultrasound diagnosis. You have to have irregular menstrual cycles due to the ovarian dysfunction.

      I cannot explain why the IVF and FET failed without a close review of your medical records, but don't give up. You should still be able to get pregnant as long as you are going to a good clinic with good protocols and good pregnancy rates.

      Good Luck

      Delete
  83. Dear Dr Ramirez,
    I am 31 years old and my husband has been diagnosed with severe oligospermia (1.1M/ml & 33% progressive motility). He has bilateral varicoceles and was operated 6 months ago on the left one. This improved his sperm count slightly (it used to be 0.3M/ml with 12% prog. motility). His karyotype is normal (no Y chromosome microdeletion). On my side no issues where found although one of the gynecologists I consulted suspected a mild case of adenomyosis, my AMH is high. I also experience spotting every day in my luteal phase each month, with regular cycles and ovulation. We have now just had our 1st failed IVF ICSI cycle.
    Here was our protocol:
    Birth Control Pill for 1 month
    Follitropin beta 200IU for 8 days (combined with Orgalutran on the last 2 days)
    2 x Ovitrelle injection on day 9
    Sadly out of my 15 follicles only 3 oocytes were retrieved, all the others were empty. 2 oocytes fertilized and made it to grade 1 blastocysts on day 5 with no fragmentation. The transfer of both oocytes was done without ultrasound assistance.
    I am now 8 days post transfer and have started menstruating yesterday.
    I would be extremely grateful if you could provide your insight on any possible causes of our implantation failure and I welcome your recommendations for our next cycle.
    Many thanks

    ReplyDelete

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