IVF Patient Has False Negative On Pregnancy Test: Late Implantation? What Went Wrong?

Question:

Dr.Ramirez,

I have written to you in the past and you have always been such a great sounding board. I need help and closure and I am hoping that you can help.

In September I went through IVF (in vitro fertilization). On 9/7 I transferred 2 embryos- 1 7cell grade AF and a 4cell grade BF. On 9/16 I had some light spotting and cramping. My beta was on 9/19 (12dp3dt)was negative & my RE instructed me to stop taking the PIO & Estrace. A few days later, what I thought was my period arrived. It was a medium flow w/some small clotting & lasted about 4 days & stopped. A couple of days later, I started bleeding very heavily & passing large clots. I went in to see my RE. She conducted an Ultrasound & some blood work to make sure I wasn't anemic. At that time I asked her to run a pregnancy test. She said that there was no way that I could have been pregnant but did it anyway. The next day she called to tell me my beta was 512!

I am absolutely devastated. I can't believe that I was pregnant the whole time. My RE is calling it a biochemical pregnancy and is saying that it probably wasn’t a healthy pregnancy but I am getting the feeling that they are trying to place blame elsewhere. I feel like I need some questions answered by a neutral party. I am having a hard time moving on so maybe you may be able to offer me some closure.

1.Should something have shown up on the beta 12dp3dt? If not, do you think it was a lab error?

2.Could it have shown as negative because of late implantation? If the cramping/spotting on the evening of the 16th was implantation, would HCG have shown up on the morning of the 19th?

3.I have a luteal phase defect. What effect/impact would stopping the PIO and Estrace have on the pregnancy? Do you think that stopping meds was the reason for the miscarriage?

4.My beta was 512 after bleeding for over a week (heavily). I would think it was much higher to start. Do you think that this would have been a healthy pregnancy?

5.Should the clinic have done a 2nd beta?

6.Any suggestions on where to go from here? Any help would be greatly appreciated.

D. from Boston, MA

Answer:

Hello D. from the U.S. (Boston),

Certainly what you have gone through is very unusual and unfortunate. It shows that late implantation exists. I usually do my first bHCG at 8-9 days post embryo transfer. I do two bHCG's, one at that time and another 48 hrs after. I have had a successful pregnancy case where the first bHCG was negative (<1) and the second positive (14) that went on to deliver a beautiful baby. Keep in mind, however, that there are no specific protocols regarding how many bHCG's to do and it is totally up to the medical director of your clinic.
I cannot answer the question about the cramping and spotting on the 16th. If you have a luteal phase defect, then yes, stopping the supplemental hormones can lead to a miscarriage. There is no way to know if this was the reason for your loss because there are many other possibilities as well, such as an abnormal embryo. I cannot answer your question about whether or not this pregnancy would have been healthy. The number was certainly a good and high number.

What is important to keep in mind at this point: This experience showed that you can achieve pregnancy. IVF only has the capability of giving you the opportunity to become pregnant. It cannot force a pregnancy on you. Keep in mind that the last two steps required to achieve pregnancy, embryo hatching and exiting the shell and implantation are natural steps. We don't have the technology to make these happen. That is why I say that IVF can only give you the opportunity. The last steps are in God's hands. The fact that implantation occurred (positive bHCG) shows that the last two steps took place and you can do it again.

Now you just have to maintain your hope, diligence and savvy. You've gotten this close. After all that you have been through, why would you not keep trying? Hopefully, the next one will be a "home run" or "touchdown" depending on which sport you prefer. If you don't try, you certainly won't be any closer to success, so don't give up!

Good Luck,
Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
http://www.montereybayivf.com/
Monterey, California, U.S.A.

How To Interpret Positive BHCG Levels After IVF: When Will You Know For Sure?

Question:

My question is about beta levels, and how to interpret what they indicate.This is my first IVF / first pregnancy, so this is a constant learning process.

1st Beta at 14 dpo (11 days past 3 day transfer) was 158.
2nd Beta at 18 dpo was 704.
3rd Beta at 21 dpo was only 1537.

My beta levels started off doubling, but then slowed considerably.I have an ultrasound upcoming next week, but not sure what to expect at this point. I am feeling very concerned about this change, and not sure if it still falls into normal range or is a valid cause for concern. Should I request a 4th beta? Can an ultrasound at 5 1/2 weeks provide a definitive answer to the viability of a pregnancy?

Thank you so much for your answer! C. from New York

Answer:

Hello C. from the U.S.,

Absolute values of the bHCG cannot be interpreted (although many people try to). bHCG's are evaluated based on their trend i.e. up/down and double every other day (actually it only needs to increase by 80%). I would caution you on trying to interpret how things are going by your bHCG levels unless they drop precipitously. The ultrasound will give you a better idea of how things are proceeding.

Viability cannot be established at 5-1/2 weeks. It is too early. That ultrasound is mainly to rule out an ectopic (tubal) pregnancy. Viability is established at 7-8 weeks gestational age.

You have a positive pregnancy test, which is a good thing! Now all you can do is wait and see how it progresses.

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.

Four Weeks Post First IVF & Positive BHCG: Not Rising Adequately & Possible Ectopic

Question:

Hi Dr. R. -

I am 39 years old and we have male factor infertility. In our first completed IVF cycle we had 27 eggs retrieved, 20 good, 14 fertilized, and 3 - day 5 blasts transferred. I had a very light implantation bleed and a positive Hcg at day 14 post retrieval.

1st Hcg 132 14 days post retrieval (this was 2 days early as I had to go out of town)

2nd Hcg 183 19 days post (this was a few days late since I was out of town)

3rd Hcg 278 21 days post (also requested a progest test which was 119 or so, can't remember exact #).

4th Hcg 479 23 days post

Had a u/s 23 days post which showed nothing other than very large ovaries. I understand the data on Hcg doubling but am curious about the 10-20% of women who do not have doubling - not a lot of literature on these patients. My RE said there is zero chance of the pregnancy progressing and said it was a chemical pregnancy and would monitor for an eptopic, I was advised to stop progesterone supps. Also, I had preg symptoms day 12-18 post but they have become less this past week. I have had no bleeding or cramping during the entire process. Any thoughts on my prognosis would be appreciated. Are my levels just too low and too slow?

One other question, my ovaries are "as big as grapefruits", is the only option to wait until they resolve and how long can that expect to take? Again, I am 4.5 wks post retrieval.

Thank you! J. from the U.S.A.

Answer:

Hello J. from the U.S.,

The minimum requirement for HCG rising in a normal pregnancy is an 80% rise, not 100% (doubling). However, your bHCG's have not been rising adequately. For example, the first bhCG at 132 should have risen to 238. The fact that your bHCG's are not rising adequately means that it is unlikely to be a normal progressing pregnancy, but you are still pregnant. In addition, an ectopic (tubal) pregnancy cannot be ruled out yet because the level is not high enough to see a pregnancy in the uterus. The level generally has to be above 2500. It is wise to keep a close eye on your situation.

The ovarian size is due to the increased stimulation you received. It will take up to two weeks to resolve in size from the cessation of the pregnancy. Remember, even though your first cycle has not been successful, you and your husband were able to go through all the steps needed to accomplish IVF, with some good embryos to transfer. I hope that you will consider trying again.

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.

A Positive BHCG But Now Bleeding Two Weeks After Embryo Transfer: Am I Miscarrying?

Question:

Hello. I did an IVF transfer June 24th, was told it was a beautiful transfer of 3 beautiful embryos. This past Tuesday, July 6th, I got a positive result, however doc told me to be cautiously optimistic as it could be a chemical pregnancy because my level was 33. The next morning I woke up to cramps and started brown (old blood like) spotting, which is kind of weird for me to be honest. My cautious optimism diminishes to despair. Called doc, told me it was normal and had to wait. Retested 48 hrs later (yesterday) and it was 60, so it nearly doubled! Which was a big shocker...I was really expecting it to go down. But yeah, right?

This morning, July 10th, I woke up to heavier spotting and an actual clot like thing (which kind of looked like a massive amount of my Crinone gel). Mostly brown blood with a little red now, but mostly when I wipe after going to the bathroom (sorry TMI). They say it could be a number of things, irritation from the progesterone gel, passing of one of the embryos, or just normal pregnancy symptoms. I think they are miscarry symptoms. I go back for blood draw Monday and I am just beside myself. I am normally a pretty together person but this has turned me upside down as I feel like I'm on an emotional roller coaster. One day I think I am dealing with a m/c and then we get news that my hcg doubles. This bleeding after my embryo transfer worries me.

I guess what I'm asking is should I look at the doubling as good news or could it be my levels haven't caught up with what will happen? Could I be passing one or two embryos while one implants? Is a m/c imminent in your opinion? Any help would be most appreciated. Thank you in advance. D. from the U.S.

Answer:

Hello D. from the U.S.,

First, let me answer your last question. Based on your symptoms and bHCG levels, you CANNOT make a diagnosis of imminent miscarriage. It can go either way, but I tend to focus on the good side.

The bHCG levels doubled as they were supposed to. I generally follow them every 48 hrs for the first four levels, but your doctor has a different protocol. As long as they continue to rise and approximately double (they don't have to double exactly), then we wait and see how things go. There is only a limited amount of information that you can gather from this blood test. If they are going up, you are pregnant and things are looking good. If they plateau or drop then things are not good. One cannot necessarily predict the outcome based on the levels.

Second, I would totally disregard the spotting that you are having, and not worry unless it is bright red blood that flows like a period. Anything less than that can be "normal" at this point. Bleeding after embryo transfer is more common than you think. We see this very, very often. . . in almost 90% of our IVF patients using Crinone. In fact, there have been studies showing increased spotting with vaginal progesterones like Crinone. It is thought that the progesterone makes the cervix more prone to oozing from the surface. In any case, this type of spotting with Crinone is very common.

Not much can be known about the pregnancy at this very early point, except that you are pregnant! Now, despite the worry, you have to wait and see how things progress. Try to be optimistic and keep the stress level down. I would not assume that you are destined for a miscarriage or are miscarrying yet. It can still go either way. Whatever is destined to happen, will happen and we don't have the power to change that at this point. We can only hope and pray for the best. By the way, it is never "TMI" (too much information), rather, all the information you can provide is appreciated by a physician.

The very best of luck to you both, my thoughts are with you. Sincerely,

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

IVF Patient With Positive Beta On Immunoglobulins (IVIG) & Has Questions

Question:

Good day Dr Ramirez,

I wrote to you a while ago. We just completed our 3rd IVF (in vitro fertilization cycle) and 2 , 5-day frozen blastocysts were transferred.

I had a blood test on day 10 post transfer and the result was positive. I suffer from rheumatoid arthritis. My doctor gave me 5ml immunoglobulin (integram) on day 2 of my cycle and 5ml again 10 days post transfer. I am also on 600mg cyclogest as well as folic acid , baby asprin, omega 3 & 6 and staminogro.

I am still concerned about the arthritis and worry about the anti bodies - is the immunoglobulin sufficient - what is the protocol, what do you suggest?

My second question is. From the day of the FET I felt this twitch on my left side of my uterus . From 7 days post transfer I have lower back and stomach pains.

Should I worry? I have heard that it is normal for FET patients to get pains and cramps and it is good pains. I have no spotting though. My first beta on day 10 was 198 and my second beta on day 12 was 416 .Can you please advise. Thank you. V.

Answer:

Hello V.,

I believe the immunoglobulin is sufficient from a fertility point of view, but I don't know in regards to the arthritis. You would need to consult a rheumatologist to get the answer to that question.

The pains you are having are probably normal. Many women experience some uterine cramping or pains in the early pregnancy. We call these "growing" pains. Your bHCG levels are good so things look good. At this point, you just have to hope for the best. Congratulations and stay positive!

Follow-Up Question:

Thank you so much for your reply. Do I understand correctly that the dosage of the immunoglobulin that I got is sufficient for the duration of the whole pregnancy and I don't need to get additional imunoglobulin again? The reason why I ask is that I had a miscarriage 7 years ago ( a natural cycle without any meds)- due to the antibodies of the athritis and I am concerned that it might happen again.

Follow-Answer:

Hello Again,

Because the use of Immunoglobulin in IVF is controversial, there are no set protocols or dosages. Therefore, I cannot comment on the dosage or times of delivery. In my experience, however, it is given at the beginning of the cycle, after the transfer and if pregnant again at that time. I would recommend that you look up the Reproductive Immunology Associates website (www.rialab.com/ivf_immunotherapy.php). They are immunologists that have geared their practice specifically to reproductive issues. They will have more specific information regarding the use of immunoglobulins. They will also answer email questions.

Good Luck,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Programwww.montereybayivf.com

Monterey, California, U.S.A.

Twitter with me at @montereybayivf and follow me on Facebook at http://bit.ly/9Iw9oV

Seventh IVF Cycle Brings Success But Patient Worried About Progesterone Levels

Question:

Hi Doctor!

I have recently become pregnant after my 7th IVF, and am currently 6 weeks. I had 2 very good quality blastocysts transferred and am awaiting my 7 weeks scan next week to see the heartbeat and hopefully tell if it's twins. I have been going in for blood tests to monitor my progesterone levels and initially I was taking 2 cyclogest (400mgs) a day, it then increased to 3 and now 4 a day. This was because my prog levels were fluctuating from 80 and 150 and my FS feels 150 is a good level. My last test showed it at 200. From doing my research, I realise that normal prog levels can be anything above 30 and less than 100. Are mine too high? IS there any danger of having prog at 150-200?

My Bhcg has also been monitored every 2-3 days and they have been climbing nicely, from 193,447,1863, 4990 and now 13900. Are those indicative of a viable pregnancy?Many thanks for your help and advice.

Regards, N. from the U.K.

Answer:

Hello N. from the U.K.,

Congratulations! I'm glad you persevered because most patients would not try IVF 7 times. All your levels are fine. Your progesterone is not too high and there is no danger with a level of 200. I'm surprised your doc is chasing the levels. Your bHCG levels are great. With a level of 13,900, the gestational sac should already be visible within the uterus, so your doc should go ahead and do a scan this week rather than wait until next week. At this point it is important to confirm the uterine pregnancy because there is a 2-5% risk of ectopic pregnancy with IVF (tubal pregnancy). If it were in the tube, this would be the time to treat it as medication can be used instead of surgery.

I don't mention this to scare you, but I normally do my first ultrasound at 6 weeks gestational age for this reason. You might want to ask your doctor to do so as well. More than likely everything will be fine. Again congratulations!

Follow-Up Question:

Hi Doctor,

Thanks so much for your advice, I really appreciate it. I took your advice and scheduled a scan for today, which confirmed a single uterine pregnancy and we saw the heartbeat. So it is a relief! I am currently 6 weeks and 4 days. Is there any chance of things going wrong after seeing a heartbeat? I haven't had any bleeding or haven't had any major cramping. I also haven't been experiencing nausea and morning sickness, but I have had lower back pain, fatigue, and strangely enough throbbing ankle or feet pain now and then. Thank you for your time and help. Regards, N.

Follow-Up Answer:

Hello N.,

Congratulations! At 6 weeks with the findings of a fetus of appropriate size and a good heartbeat, those are good signs for the pregnancy. There is still a risk of miscarriage that runs about 40% until 8 weeks gestational age. Your doctor should probably repeat the ultrasound in two weeks. If everything looks fine at the next ultrasound (8+weeks), then the risk of miscarriage drops to 5% until 12 weeks gestational age.

Of course there are lots of problems that can occur in pregnancy. Everyone has the same risks. But if you worried about every possible risk, you would go crazy and not enjoy your pregnancy. For now, I would recommend that you take things in stride and day to day. Don't worry about the future because you don't necessarily have control over it. Hope for the best because that is the most likely outcome. And as the sailors of olde used to say, pray for good winds!

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.

Twitter with me at @montereybayivf, and follow me on Facebook at http://bit.ly/9Iw9oV

Post IVF Transfer Pain: Implantation Pain or Ectopic?

Question:

My wife says that she was experiencing sharp pain yesterday (10 days after FET) on the area near right side of her stomach. She experienced the pain only yesterday and that was during a 3 mile walk. Today she says she feels some pressure near the right ovaries.

I'm concerned. Could you please let me know your suggestions? Thank you.

Answer:

Thank you for your question. This could be normal, but the main concern would be an implantation that occurs in the tubes called an ectopic pregnancy. I wouldn't jump to this conclusion but it is a possibility. This could also be what we typically call "implantation" pain. Please see my overview of what happens after the IVF transfer including pain and bleeding here: "After Your IVF Procedure".

Let me go into more detail regarding both possibilities.

All patients with infertility are at increased risk for an ectopic, even with IVF. The incidence is low but it occurs. At 10 days post transfer I usually have done my pregnancy test. This can give a better idea of how the pregnancy is doing and whether or not an ultrasound will show anything. Generally, the BHCG level has to be over 3000 to see a pregnancy in the uterus and if it is not there with that level, then an ectopic pregnancy as to be assumed. At only 10 days post transfer, it is unlikely to be an ectopic, however. These usually do not become symptomatic until 6-8 weeks of the pregnancy. At this point, it is probably not anything serious.

Pregnancy can also induce other kinds of pains and discomforts. We call them implantation pain or growing pain. Sometimes women tell us that they "feel" a sharp pain within a week or two post transfer. I cannot discount that sometimes the women who complain of this pain (and I have IUI patients who tell me the same) do have a positive pregnancy test. Another possibility on the right side, of course, would be appendicitis. You can still get other illnesses despite trying for pregnancy. However, appendicitis, is progressive and does not come and go. Once the pain started it would progressively get worst. That doesn't fit your wife's scenario. Without further evaluation it is hard to know what is going on. You should probably bring this up with your doctor.

As a side note, if your wife is actively trying to get pregnant using IVF or FET, then I would not recommend a 3 mile walk right now. She should limit her activity to more sedate activities. A short normal walk would be fine, but power walks are not recommended as are heavy exercises like aerobics, karate, gymnastics, running, etc.

Good luck with your cycle and I hope that this will be a success!

Sincerely,

Edward J. Ramirez, M.D.
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF program
http://www.montereybayivf.com/
Monterey, California, U.S.A.

IVF Patient's Early BetaHCG Levels Show Drop In Estrogen

Question:

On January 12th, I discovered I was pregnant following IVF. My HCG numbers have been excellent. However, on January 21st I learned that my estrogen levels had dropped to 259 (from 400 on Jan 15). My progesterone and HCG continued to do well (HCG 569 on Jan 15, 3616 on Jan 21st). My Doctor has indicated that I should plan a D&C imminently as the pregnancy is unlikely to be viable.

Would you share this view? How significant is an estrogen drop? Thank you.

Answer:

Thank you for your question.

In the early pregnancy, less than 6 weeks gestational age, estrogen is derived almost completely from the ovary. Placental estrogen production has not started. Based on your first BHCG, I estimated that you are less than 6 weeks gestational age (assuming your BHCG was drawn at 8-10 weeks post transfer). If that is the case, and you are not taking exogenous estrogen (from another source), then the drop is concerning because it is an essential hormone of pregnancy.

Your doctor might want to consider adding estrogen in some form. Estrogen alone is not sufficient to diagnose an impending miscarriage. If all three hormones are dropping, then that would be significant. I would continue to follow the BHCG levels, which is the most sensitive to make that diagnosis.

In such an early pregnancy, a D&C is generally not required. Good luck and hang in there!

Sincerely,

Edward J. Ramirez, M.D.

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com