Sunday, February 28, 2010

Use of Ovidrel after BFP in an IVF cycle - Did It Cause My Miscarriage?



Question:
Good afternoon Dr Edward,

I'm 36yrs. I did IVF for the first time and it resulted in preg. Upon a positive pregnancy result, my doctor prescribed Ovidrel 250 iu inj to be taken immediately: This inj was given to me once a week thereafter. My dr also placed me on gestone 100mg(1 inj daily), progynova 2mg (1tab 3ce daily), folvite 5mg (1tab 2ce daily)& Ecosprin tab 75mg (1 tab daily). However, progesterone and estrogen test were not done on me.

I went for my ultrasound (U/S) on the 6th week and the sonologist said she could see a gestational sac (6x6mm), yolk sac but no embryo and no fetal heart beat. Another U/S by the 7th week revealed 2 gest sacs ( 11x11mm & 7x7mm) but no yolk sac, and embryo could not be visualised. Their prognosis was a missed abortion.

I did a search on Ovidrel and this revealed that Ovidrel is used for ovulation induction 36hrs before egg collection which was done in my case. The articles I read said women who became pregnant or think they may be pregnant after IVF treatment with Ovidrel must discontinue the use of the drug immediately because it may cause harm to an unborn baby, intrauterine death & impaired parturition!

My question is this, is it possible that Ovidrel could have caused the miscarriage I had? Secondly,under what condition should ovidrel be prescribed for a pregnant woman? I'll appreciate your honest opinion.

Thank you. O. from India.

Answer:

Hello O. from India,

I'm sorry to hear about your miscarriage. Indeed the primary indication for Ovidrel is to induce ovulation when a woman is undergoing ovulation induction with fertility medications. However, Ovidrel, which is HCG, can also be given after ovulation in order to help with implantation and support of the pregnancy. It is not used much for that indication, but some doctors will. The other medications used are also very commonly used in IVF cycles, again to support implantation and the early pregnancy. HCG has not been found to lead to birth defects or increase the risk of miscarriage. The pharmaceutical companies put that warning because of the risks of being sued in the U.S., but that is not clinically true.

At 7 weeks gestational age, the fetus should be nearly developed and will be clearly seen and with a heart beat, so your ultrasound showed that the fetus had not developed. The most common reason for this is that there was a chromosomal abnormality in the fetus, and so the fetus did not develop. At your age, you are at an increased risk of spontaneous chromosomal abnormalities because the chromosomes in eggs are more fragile in older women. This miscarriage was not due to the medications.

In the U.S., the medications you took are given as part of the IVF cycle, and many are started before or during the IVF cycle, rather than waiting until a pregnancy ensues. Most important: If they are going to help the pregnancy, and prevent a miscarriage, they need to be within the body prior to the pregnancy occurring. I don't use HCG in the manner that you were prescribed. I don't personally know any fertility specialist in the U.S. that does but I have read papers by doctors that do. HCG acts in the same way as progesterone does.

I think you just need to keep trying. The fact that you got pregnant on your first try is a very good sign and you will eventually be successful. If you don't trust the treatment or protocol that your doctor has used, then maybe you should find a different doctor to work with. Trust is of the utmost importance in a Doctor-Patient relationship.

I hope that answers your questions.
Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program

19 comments:

  1. hello dr edward,
    i'm 34yo, i had 2 failed ivf last 2006 and 2007 consecutively, i had my 3rd ivf this march 2010. my lmp was march 8, had my egg retrieval march 22 and 3blastocyst transfer march 27. after 2 weeks april 9,2010 my beta result was 55miu/ml,4/12/10 went to 111.1, 4/15/10 to 1909 and progesterone level at >60.had my first u/s 4/17 and the sac measured .4. On the 20th had little tissue spotting and had u/s again 4/21/10 and the sac measured .6 w/c the dr said, it should have grown .8 already in size. she told me not to take any progesterone medications and wait for the sac to naturally abort with menstruation. i'm perplexed as to how many weeks am i already pregnant?from my lmp till 4/21/10 is it 6weeks and 1 day?? my hcg is imncresing slowly as well as the sac, is that a good sign or should i give up?pls enlighten me as to what is your opinion on my case. thank you very much.--ani

    ReplyDelete
  2. Because IVF is programmed, we calculate the gestational age based on the day the IVF cycle starts (considered CD#2) or even more specifically, is a calculator that uses the transfer day. So if you transferred blastocysts on 3/27, you would have been 5 weeks 5 days on 4/17, 6 weks 2 days on 4/21. These are very early ultrasounds and at the 5 week scan, only a gestational sac can be seen. At the 6 wk scan, a fetal pole might be seen with or without heart motion. To confirm that the pregnancy is not viable, I would wait two weeks then repeat the scan again. At 8 weeks there should be a clear fetus with fetal heart motion. In the meantime, I would not stop the progesterone. Gestational sac and any measurements prior to 7 weeks has a very wide margin of error and are not reliable for dating or anything else.

    ReplyDelete
  3. Hello Dr. Ramirez,

    last week I came across quite a bit of informaton in just 3 days, I found out i was pregnant due to a rotune pregnancy test for another thing, my cocern is that the week before on june 2 I started my period and stopped on june 7, on june 9th i have a positive blood pregnany test. I go to my doctor and said i need to do a quantative test, the number was 467.1 and in 48 hours it went up to 1310.1 but my progesterone level is at 17. Should i be worried? I have some cramps. I see the doctor again on the 24 for an ultrasound. The doctor said I shoud be at six weeks, since my other period was on may 9th.

    thanks a lot, hope to hear from you soon

    ReplyDelete
  4. Hello. The bHCG tests were good numbers and the increase was adequate. It is not unusual to have some bleeding in the very early stages of pregnancy, as we have seen many times with IVF patients. The cramping also can go along with early pregnancy due to the uterus changing. For now, I would not worry and wait to see how things turn out. Your progesterone level is low, we prefer it to be at least 30, so you might want to ask your doc for progesterone supplementation with either Crinone or Endometrin. Other than that, the pregnancy will proceed naturally and all we can do is wait and see how things turn out. Good Luck.

    ReplyDelete
  5. hello dear edward

    im 30 years old giong thru IVF cycle,i have an ovidrel short last night at 8:45pm (monday)and my egg retrieval is tommorrow (tuesday) at 8:30am, im scared i might ovulate before the retrieval 'cos im having some cramps.

    Also i want three embryo transfer but my doctor insist on 2. and i want know if its better to do the transfer on day 2 or 5. plz i need your advise. thanx

    magana dole

    ReplyDelete
  6. Hi. There is a very very small chance that you will ovulate prior to your retrieval. The retrieval is timed to be 36hrs from the Ovidrel injection, so you don't need to worry.

    I prefer POD#3 embryo transfers in my clinic rather than POD#5. The main reason is I believe that the uterus is a better culture environment than the lab, and some potentially good embryos are lost in culturing from POD#3 to POD#5. But that is a personal preference and more and more docs are transferring on POD#5.

    At your age, the maximum number of embryos reommended to be transferred, according to SART is 1-2. Of course, ultimately it is your choice and you can choose to have 3 transferred if you want. It is not recommended, however, because of the potential risk of twins or triplets.

    Good Luck

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  7. Hi Doc Edward,

    Am currently doing medicated FET and was prescribed suprefact(0.3) on CD3 and at the same time taking progynova and cardiprin 100.

    1st scan on CD12, showed I have a cyst measuring 3.6cm on my right, felt a tiny bit of pain on the right, lining is 7.1mm and increased my progynova - from 3 tabs to 4 tabs (2mg each). Why is there a cyst out of the sudden? I do have a small fibroid - 4mm before starting my fet.

    2nd scan on CD16, cyst still remained the same. Lining increased to 7.7mm.

    3rd scan on CD19, cyst still remained the same. Lining decreased to 7.5mm. Was told to increase progynova to 6 tabs.

    4th scan on CD22, cyst has collapsed. Lining increased to 7.7mm. Took E2 bloodtest and showed that it has dropped to 700plus. Was told to increase progynova to 9 tabs and delayed my transfer.

    May I know why my lining increase so slow despite the high dosages of progynova and the drastic drop of my E2 from 2000plus to 700plus? What other ways to increase my lining?

    Today is my CD24 and another scan will be done on my CD 25. I'm still jabbing suprefact and taking cardiprin (1tab per day).

    Thank you

    ReplyDelete
  8. Hello Feb 15,

    The Suprefact is to suppress your ovarian function which allows us to control your cycle and time the transfer appropriately. The Progynova is estradiol and is used to grow and prepare your lining. the Cardiprin is aspirin to increase the blood flow to the uterine lining and reduce the immune response. I have realized that you are in a foreign country because we don't use these specific medications here in the U.S.

    An ovarian cyst can be hormonal and so usually we do a baseline ultrasound to make sure that there is no cyst present. Because it can produce estradiol, it could cause the levels to be higher than expected. This is of very little consequence in an FET cycle because the only requirement is that the endometrial lining be of adequate development (at least 9 mms thick).

    It is clear that you are not developing an adequate endometrial lining. I cannot say why that is occurring without review of your medical record. Are you taking the Progynova orally or vaginally? Oral estrogen is not as effective in the uterus and vaginally. With the vaginal form, the estrogen goes directly to the uterus instead of circulating through the liver first.

    Sorry that I cannot be of more help.

    Good Luck

    ReplyDelete
  9. Hi Doc Edward,

    Many thanks for your kind reply.

    Yes I'm from Singapore and happened to come across your blog :)

    A scan & E2 blood test on my CD 25 showed the lining still did not increase and E2 level still at 700 plus therefore I was told to paste E2 patch yesterday and proceed to do my ET on 21/02. Is this patch commonly used? I took the progynova orally, maybe it does not get absorbed properly in my body system (liver not working well?)

    I have done 2 fresh ivf and 1 natural fet. My 1st ivf (transferred 2 embryos) - BCHG BT has a reading of 40+ on D15 (after ET) and double to 100+ 2 days later.. but unfortunately it drop after a few days later. Prior to my BCHG BT on D15, I have experienced bleeding (fresh red blood) on D11 (done a pregnancy test at home - it was negative) but was told to do bed rest though I have asked for a proluton jab. On D15, I did a pregnancy test again and there was a faint line so I went down to hospital immediately for a jab but it was too late, I guessed.

    Did natural fet 5 months later, lining & E2 level was ok and proceeded to do ET without any delay. But BCHG blood test showed only 5.8 and dropped 2 days later.

    Did another fresh cycle 5 months later last year (Prior to that, I was given saizen jab for 3 months to improve my embryos' quality); aspirated over 50 follicles, retrieved 24 oocytes, retrieved matured 21 oocytes, fertilised 16 oocytes and transferred 3 embryos. But BCHG blood test showed 2.8 and dropped 2 days later.
    Is there anything that I need to do? Saizen was supposed to improve embryos quality? But I wonder why it does not get implanted? By the way, though I have over 50 follicles, I don't get ohss (I do not have pcos) My tummy does not feel very bloated. It just get a bit hard at times only.

    ReplyDelete
  10. Hello Feb 18,

    Well, in your review it shows that you do not have a problem getting pregnant with IVF, but rather, have a problem with the continuation of the pregnancy. Also, based on the number of follicles and eggs retrieved, you are clearly a PCOD patient. Since you have never gotten OHSS (despite 50 follicles), you doctor is managing that part very well.

    I'm not sure that there is an embryo quality issue. The embryo development gets alll the way to implantation so it must be adequate, but since you don't give the embryo description, I cannot say for absolute certainty. Keep in mind that IVF can only get an embryo into your uterus, thereby giving you the opportunity to become pregnant. The last two steps required to achieve the pregnancy are natural steps and since you had positive bHCG's, it is certain that those steps occurred. So what's keeping you from staying pregnant?

    The oral progesterone form is NOT recommended with IVF because the liver removes most of the active hormone. Studies have shown that inadequate levels get to the endometrial lining. For that reason, the oral tablets should be used vaginally, a vaginal formulation such as Crinone or Endometrin should be used or injectble progesterone should be used. I don't know of a progesterone patch but if that is available in your country that it would work as well.

    At this point, the losses could be due to other factors, such as an inadequate progsterone. But, there might be immune factors at work as well. If you were my patient, I would recommend adding low dose aspirin, Medrol (prednisone) and low dose heparin, in addition, to injectable plus vaginal progesterone.

    Good Luck

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  11. Dear doctor,
    i have been asked to take a HCG shot 250mg/ml after the 4th day of my embryo transfer. i was not able to take the shot due to some circumstances. what should i expect?

    ReplyDelete
    Replies
    1. Hello,

      I'm afraid I don't have an answer for your question. You don't provide enough information for me to determine exactly why type of protocol your doctor is using. I would strongly recommend that you ask your doctor this question.

      Good Luck

      Delete
  12. Hello doctor
    I am 26 years old
    I had my ivf on 20 july,on 6 augut my beta was 117
    I had scan at 21 august ,it was showing 2 empty gestational sacs ,both sacs were regular good decidual reaction was seen but showing only 4 weeks 4 days pregnancy...
    I repeat the scan after a week it was showing 7 mm growth and 5 weeks 4 days pregnancy but no yolk sac or foetal pole seen..doctor ask me to come after 7 days ....what do you think is there any hope? Or its just a blighted ovum....

    ReplyDelete
    Replies
    1. It sounds like a blighted ovum but to be sure, the ultrasound needs to be done at 8+ weeks gestational age.

      Delete
  13. Hello Dr. Ramirez,

    Myself Sri from India. My wife has PCO and undergone Laproscopy. Post Laproscopy, 2 menstrual cycles are happened. During first, 8 X 75 FSH injections were given and two follicles (one on each overy) are formed and grown upto 13 mm. Before going for IUI they got ruptured. Pregnency Test resulted -ve. During 2nd 8 X 75 FSH injections were given, then not even one follicle is formed with > 10 mm size.Hence my doc suggsted to test for AMH. AMH resulted 1.4 ng/ml. Then we met infertility specialist basis previous doc suggestion. Now we are undergoing for first IVF cycle. Till now 3 X 300 and 2 X 375 FSH and 3 X 1.0 and 2 X 0.5 Lupride are given. Today result is 2-3 follicles and each overy with 4-5 mm and one 12 mm follicles are formed. My doc suggets to go for 450 FSH from today onwards.

    May I request your opinion on overall scenario please.

    ReplyDelete
    Replies
    1. Hello,

      I do not comment on specific protocols because there are no "gold standards" or standardized protocols. Protocols can vary from country to country and clinic to clinic. None are necessarily wrong. One thing about IVF is a lot of the result has to do with the knowledge and experience of the doctor giving the treatment. PCO patients can be very difficult so you want a doctor with experience. In addition, an inexperienced doctor can cause OHSS (ovarian hyperstimulation syndrome) to occur, which is a dangerous disease resulting from fertility medications.

      That being said, PCO ovaries tend to be very sensitive to injectable fertility medications. Considering that your wife is not stimulating very well at this point, maybe that is a wrong diagnosis? PCO patients tend to form 20-30 follicles with minimal doses (75IU) of the injectable medications per day.

      Good Luck

      Delete
    2. Thank you Dr. Ramirez for your reply. My Dr said since AMH level is low w.r.to age ,follicles formation is low. As of now, FSH dosage had increased up to 525 ( total 3 x 300, 2 x 375, 4 x 450, 3 x 525) which resulted 21, 18, 17, 13 mm follicles. 4 eggs are collected. 3 got fertilized. 3 A grade embryos formed and transferred on 29th Aug. Now we are awaiting for result. Wrt PCO, multiple small follicles have formed whose growth was very very slow, only few grow. Regarding, OHSS E2 was tracked frequently whose number was always low compared to normal cycle. My question is only E2 number tracking is sufficient to avoid OHSS? And if no minimum E2 effect implantation? Thanks & Regards Sri

      Delete
    3. Yes, E2 is the main way that we monitor for OHSS, but based on your numbers, you are not at risk. OHSS is at highest risk if the E2 is above 4000 and the follicle count is >20.

      Delete
  14. Dear Dr Ramirez

    Need your help. I had my embryo transfer last Sept 27..that makes it one week today, Oct 4.

    my OB prescribed to inject 10clicks of ovidrel on Oct 1 but I missed it..

    So I did it tonight Oct 4..missed by 4 days.

    Is that okay?

    Another 10clicks is due Tom Oct 5. Do I need to space it out? Please advise...

    Due for BetaHCG test on Oct 11.

    Thanks so much in advance!

    ReplyDelete

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