Fourth IVF Cycle Ends In A Chemical Pregnancy: What Can Be Done?

Question:

Hi Dr. Ramirez,

I have been on a rollercoaster ride for the past week and I am hoping that you can offer me your opinion.


I received a positive beta after my 4th IVF on Monday (11dp3dt). It was 14.3 and my RE said that it was quite low. I held out hope as I am convinced that I tend to implant a little later than others. In a previous cycle I had a negative beta 12dp3dt and found out that I was pregnant a couple of weeks later. I tested 3 days later and my beta was up to 52.8. I was so excited and felt so much better about things. I am scheduled to go back on Sunday morning for another beta.

I am currently taking Crinone 2xday. For the past week, I have had dark brown Crinone gunk(sorry for TMI). Last night and this morning there was some red blood on the applicator tip. At 1st I thought it was just irritation but for the past couple of hours, when I wipe there has been more red blood. I am also getting some minor cramping.

I am freaking out and I am so worried that things are moving in the wrong direction. I called my clinic and they said that they cant know anything until Sundays beta. They said it could be start of a miscarriage given the low beta #'s or it could be irritation from the Crinone or even pregnancy spotting.

I was hoping that you could offer some advice as I remember in the past that you prescribe Crinone to your patients.

Is RED spotting normal? How much spotting is normal? Was I foolish to be hopeful after my #'s doubled? Do you think its likely that this will end in miscarriage?

Any insight would be greatly appreciated. I dont know if i can hold out until Sunday's beta.

Thank you,

D. from Boston, Mass.

Answer:

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

The advice that your doctor gave you is completely correct. It could be from the Crinone, and I have seen an increased incidence of spotting in my patients using Crinone), it could be implantation spotting or pregnancy spotting or it could be indicating an abnormal pregnancy. There is no way to know which of these is the correct diagnosis. In general, I reassure my patients not to worry about spotting. I only worry if the bleeding is bright red flow like a period with accompanying cramping. The only way to determine the fate of this pregnancy at this point is to continue to follow the bHCG's every other day. This trend will then give you a better idea of how the pregnancy is doing. AS long as the bHCG is rising, then you can be reassured. If it plateaus or drops, then that is not a good sign.

Follow-Up Question #1:

 Dr. Ramirez,


Thank you for getting back to me. Unfortunately, my beta level dropped on Saturday so it looks like I will be having another chemical pregnancy. I am devastated of course. I was hoping that you might be able to provide me with some insight as to an explanation as to why this keeps happening.

A little history:

Me: 31 years old- normal FSH but AMH is .8

Husband: Very low morphology (less than 1%)

This was our 4th IVF cycle and 3rd chemical pregnancy. I have had tons of testing... RPL work-up, HSG, genetic testing, uterine biopsy and all came back normal.

I am a low responder and in previous cycles have had poor egg quality. I just switched REs and had a better response with an Estrogen Priming Antagonist protocol. He used a low dose HCG with Gonal F. Quality and ICSI fertilization rate was much better so I was hopeful that this was it.

My RE said that it was likely a chromosomal issue with the embryo and probably because of poor egg quality and we just need to keep trying and hopefully will get that “one” good egg. I don’t know if I am comfortable with that answer. We only have 2 insurance tries left and I want to make sure we are exploring all options before proceeding again. What would you recommend for your patients at this point? Do you think that it is worth doing a Sperm DNA fragmentation test?

What could be the reason for all of these chemical pregnancies?

Any insight is greatly appreciated.

Follow-Up Answer #1 :

Hello Again,

The exact reason cannot be known, of course but the most common reason for chemical pregnancies are a genetic abnormality in the embryo. With poor morphology in the semen analysis and your young age, definitely the genetic weakness could be from the sperm. I don't recommend the sperm DNA fragmentation test because it only gives the indication for the batch of sperm that it tests and not the sperm as a whole. In addition, the treatment recommendation is to use ICSI, which I presume you are doing already. So you won't gain anything from that test. If we suspect the sperm, other than ICSI you have the choice of either using donor sperm the next time or maybe try using a supplement for three months before doing IVF again. The supplements that your husband can try, which might help with sperm quality, are either Proxeed or Fertility Blend (vitamins) and CoQ10 600 mg per day. He will have to wait three months because sperm are on a 90 day cycle #the sperm made today won't be expressed for 90 days.

The only other options I could give are what I would do with my patients who have recurrent miscarriages (which is what you have even if it is a chemical pregnancy). Studies have shown the benefit of these meds and it is standard of practice to use these with recurrent miscarriages.

I would add: aspirin 81 mg per day, Medrol 15 mg per day until transfer then decrease to 8 mg per day, Heparin 2000 units twice per day and CoQ10 600 mg per day, all starting with the start of the cycle (CD#2). The Aspirin and Heparin are withheld from the day of HCG trigger until the day after the retrieval. The only other option you might want to consider is genetic testing of the embryos prior to transfer, called preimplantation genetic screening (PGS). That way you will know if the embryos are normal genetically or not. The downside of using PGS is I have observed and some studies have shown a drop in pregnancy rates after this. Some of my colleagues say that if it is done by a very experienced embryologist who does lots of these procedures, the pregnancy rate does not drop.

You'll have to discuss these options with your doc. I'm afraid there are no exact answers to your dilemma. But, studies on patients with recurrent pregnancies have shown that eventually these patients are successful. So, hang in there, even if your insurance coverage expires.

Follow-Up Question #2:

Thank you so much for your thorough response. I really appreciate it.

I am only 31 years old but I do have a low AMH (only .8) so along with that and the fact that I am a low responder, my RE suspects that I may have a diminished ovarian reserve. So, unfortunately, both my husband and I seem to have issues.

Do you think that the low AMH and dimished ovarian reserve contribute to the repeat miscarriages? Or do you think it is likely a sperm issue?

Is there any way to tell who is main contributor to this issue? We are not ready to talk about donors at this point and will continue to try with our own eggs/sperm for now but in the event that we need to explore other options, it would be helpful to know if we would be more likely to succeed using donor egg or donor sperm.

My RE has given us the impression that it is more a egg issue but hasn't given us any explanation of why.

Any help with this would be hugely appreciated.

Follow Up Answer #2:

Hello Agian,

There is no way to know what the exact cause of the recurrent miscarriages is. It could be egg or sperm derived since the genetics of the embryo come from both. Considering that you are ONLY 31 years old, I would suspect that it is NOT an egg issue but there is no way to be sure.

It is definitely not related to AMH or low ovarian reserve. The AMH is a measure of follicle availability and low ovarian reserve is a description of ovarian response to stimulation.

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/

Can I Thicken Endometrium With Estrogen?

Question:

Dear Dr. Ramirez,

I´m 35 years old (will be 36 in Feb). I have been trying to get pregnant for 2 years (had a miscarriage a year ago). After going to a reproductive clinic, I´ve tried Clomid for 2 cycles with no success, an it really thinned up my endometrium, which usually wasn´t very thick (7-8mm). So my RE recommended to change to Menopur in the next cycle and do a IUI (My husband´s Kruger morphology is 5% - lab reference 4% all the rest is good). This current cycle (no meds) she did an sonogram on me on day 12 (my last period, which followed the Clomid treatment, was only 21 days longer and she wanted to check me for cysts). I had a 20mm follicle and several smaller ones, but my endometrium although trilaminar was only 7mm. For all I have been reading 7mm is not optimal thickness, although my doctor seems to think it´s ok and there´s no need to do anything.

So I was wondering how can I prime it before ovulation? Will taking estrogen help? Will it interfere with ovulation? What are the cycle days you normally recommend your patients to take it and what is the dosage?

Thanks for your time. I really appreciate it. C. from Brazil

Answer:

Hello C. from Brazil,

Yes, you can use estrogen in addition to the Menopur. I use it as an estrogen patch (Climara 0.2 mg per week up to 0.4 mg) or vaginal tablet (FemHRT, Estrace 1 mg up to 4 mg per day). As the follicles grow, they produce more and more estrogen so that should help as well. 7 mm is the minimum size needed, but ideally it should be 9 mms.

In terms of treatment, keep in mind that you have three problems going on. My opinion is that the more problems there are, the higher the treatment level you need to use. The problems identified are: (1) thin endometrial lining, (2) age factor (going on 36yo) and (3) severe male factor. Because of the age and SEVERE male factor, I would advise IVF with ICSI as the treatment of choice. The sperm may not have the ability to fertilize the egg naturally and so ICSI is required. This can only be done with IVF. IVF is also the only treatment that helps to increase pregnancy rates related to age, which is an egg problem, by increasing the number of eggs available to fertilize.

Follow-Up Question:

Thanks for answering my question, Dr. Ramirez.

When would I start taking the estradiol, cd1 and go up to ovulation? I´d like to know so I can talk to my doctor about it.

Also, now I am really concerned about the severe male factor. Is a 5% Kruger morphology that bad even if the sperm concentration is high (85 million/ml) and they show good motility (>70%)? For the IUI procedure, after swim up test and washes, can the doctor choose only the sperm that have good morphology? I´ve read that some doctors think that the Kruger method is really too strict and based on it, most males would be called fertile. What´s your opinion on that? Is there any treatment for sperm morphology (my husband is 37yo)?Thanks again for your valuable time and input! C. from Brazil

Follow-Up Answer:

Hello Again,

1. The estradiol patch or vaginal suppository would begin with CD#1 or 2.

2. If only 5% of the sperm are anatomically normal (morphology), even with an 85 Million count that means only 3.2 Million are available to actually fertilize the sperm (85 Million x 75% motility = 63.75 Million motile x 5% = 3.2 Million). This is inadequate for natural fertility. In addition, when there are sperm abnormalities, there is a high chance that there could be a defect in its ability to fertilize, and there is no test for that other than with IVF. For that reason ICSI is recommended. The embryologist will only take anatomically normal forward swimming sperm for the ICSI (if they are good embryologists).

3. I somewhat agree with the opinion regarding Kruger, but the decision has to be made based on the information that you have. Even 5% normal morphology is pretty low using Kruger.4. Unfortunately, other than ICSI there is no good treatment methods available to change morphology. There are two products that he can try, which are basically vitamins, called Proxeed and Fertility Blend. These can be purchased via the internet. He would need to use them for 3 months minimum. He can then repeat the semen analysis and see if this helps at all.

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.

Comment: Thank you again Dr. Ramirez. I wish I was still living in the US to go to your clinic :)

Using Holistic Medicine For Female & Male Infertility

Question:

I have had fertility issues for almost 2 years now. I want to explore a natural approach to my fertility before I use more invasive procedures. What I was wondering was if it was safe to use more than one natural herb at a time or will there be interactions. The medicines that I plan to use for myself are Chasteberry, Black Cohosh, and Siberian Ginseng. For my husband he plans to use Horny Goat Weed (which is supposed to promote potency and increase sperm production) and Gotu Cola (which is supposed to promote motility).

I have asked the sales people if these herbs are safe to use together but have never gotten clear answers. I have researched the herbs and they are supposed to be effective and like I said, I want to be as holistic as possible.
M. from the U.S.

Answer:

Hello M. from the U.S.,

I'm afraid I cannot answer this question for you as I am a traditional medicine Physician. I would recommend that you direct your question to a naturopath practitioner or herbal pharmacist. If this remedy works, please let me know. We are always looking for ways to increase pregnancy rates in our patients.

I have blogged in the past regarding improving sperm motility/morphology with supplements such as ProXeed. One ingredient in this blend, Coenzyme Q, has been shown to have a positive effect on sperm health and two other ingredients, L-Carnitine & Acetyl-L-carnitine, have been shown to affect sperm motility. The downside is that your husband needs to be on this supplement for at least three months to see results. See this link for further information: http://www.proxeed.com/ingredients.asp

On this subject, I would caution my readers to beware of false claims. Remember, if any supplement is claiming to "cure" infertility and is not backed or proven by clear clinical trials, then the claims can be considered as false. A recent undercover probe (2010) by the GAO (Government Accountability Office) found fraudulent claims for cures abound on the internet. On a recent MSNBC report it was said: "that investigators...found that labels for some supplements claim to prevent or cure ailments like diabetes or heart disease — a clear violation of U.S. law." See this link: www.msnbc.msn.com/id/37361907/ns/health-alternative_medicine

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.