Bleeding After Embryo Transfer

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

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Answer:

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

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

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

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

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

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

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

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

http://www.montereybayivf.com/

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