Dr. Szlarb, what is a biochemical pregnancy? And how is it different to a miscarriage?
A biochemical pregnancy is a pregnancy that is only detected by the HCG hormone levels, before it becomes large enough to see it with ultrasound.
It is the first stage of a pregnancy, between a positive pregnancy test and the clinical pregnancy stage that starts around week 6-7 when the heartbeat and gestational sac are detected with the first ultrasound. It is important to remember this definition. We know that people use the term biochemical pregnancy to talk about pregnancies that don’t develop to the next stage. But we sometimes forget that a biochemical pregnancy is, first of all, the stage before a clinical and an ongoing pregnancy. During this time women usually do not experience any clinical symptoms. In other words, women do not feel if they are pregnant or not. Some women may even be biochemically pregnant without being aware of it.
So to be clear, the term “biochemical pregnancy” is used in reference to a pregnancy that is only detected by the HCG hormone levels. On the other hand, a miscarriage is when the pregnancy development stops after the first ultrasound.
Why a positive pregnancy test only to then suffer a chemical pregnancy?
To answer this question we have to understand what is going on during the embryo implantation. This process is a “dialog” between the embryo and the endometrium: a successful dialog between both would be a positive pregnancy or biochemical pregnancy. The embryo surface, especially when talking about good quality embryos or blastocysts, is formed by a hairy structure which has to attach to the hairy structure of the endometrium. The endometrium, of course, has to be thick enough (which can be achieved with progesterone); and the endometrium has to be in its window of implantation (WOI) for the blastocyst to implant successfully.
Once the embryo successfully attaches to the endometrial lining it starts to produce the HCG hormone. At this stage the only way to confirm a successful implantation is by means of an HCG blood test 10 days after the blastocyst transfer. But if patients do not want to carry out a blood test, whether because it is not available in their countries or it’s too expensive, it can be tested in the urine 15 days after the transfer.
Why is it happening? Should I alter my treatment to ensure it doesn’t happen again?
The main causes for biochemical pregnancy or miscarriage are genetically abnormal embryos, as well as high number of uterine immune cells that see the transferred embryo as a foreign body. This causes a disconnection between the embryo and the endometrium – as a result the embryo detaches from the uterus lining, ultimately ending the pregnancy. In reproductive medicine, however, especially in egg donation cycles where we transfer embryos from young and healthy donors, the biochemical pregnancy rate lowers to 10 – 15% (as 85% – 90% develop to clinical and ongoing pregnancies). So, to speak about a successful implantation we first of all need a euploid or “genetically healthy” blastocyst, as genetically abnormal embryos will not succeed to implant or only for a very short period of time like in biochemical pregnancies cases.
The second key factor is the endometrium – also known as uterus lining. The endometrium must be thick enough for the transferred embryo to implant, and this can only be achieved by administering progesterone to the body.
This leads us to another key factor: the window of implantation or WOI. Most patients have a so called “open” window of implantation after 5 days of intake of progesterone; 30% of women, however, need verification thereof. The patient’s WOI can only be verified by means of a biopsy of the uterus lining or ER-Map, which can be performed at our clinic. In some cases, patients may need 6, 7 or even up to 8 days of progesterone for an open WOI.
Some women, on the other hand, have an overexpressed immunological response, which means that they have too many Natural Killers cells – or NK cells. This can also be detected through a biopsy of the uterus. If an abnormally high number of NK cells is confirmed we apply our immunological protocol, which consists in administering intralipid and prednisone as a support for the implantation of the embryo.
In some cases we treat immunologically demanding patients. These patients were unable to achieve a pregnancy after 3 transfers with good quality embryos, after verifying their receptivity and immunology, their progesterone levels. If this is truly the case, we will have to look for a different donor and match her HLA to the HLA of the patient (as in transplantology) to increase the implantation rate.
What is the difference between implantation bleeding and a chemical pregnancy?
In some occasions, after a successful implantation, patients may experience implantation bleeding. This occurs whenever the embryo gets deeper into the uterus lining and the patient’s blood is thin. This usually is a very short bleeding, but we have to differentiate this type of bleeding from a possible biochemical pregnancy or miscarriage, which lasts for a longer period of time. If a patient is experiencing bleedings during longer periods of time, chances of suffering a miscarriage will be quite high.
To avoid these situations we recommend our patients to inform the clinic and stay in bed; we remove clexane and aspirin from their treatment plan, as it makes blood thinner, and perform ultrasound scans and HCG blood tests. In fact, we ask patients that suffer from such long-term bleedings to come to the clinic every 2 – 3 days to repeat the ultrasound scans and blood tests. If the HCG hormone doubles every 2 days, then the pregnancy will probably go on; if it stays on the same level or lowers we will be looking at a pathological error pregnancy, and only upon the pathology we might detect on the ultrasound scans we will decide further steps.
How long should I wait before I have treatment again?
In case of a biochemical pregnancy or early miscarriage we usually wait one or two cycles before starting a new treatment. This new treatment will not follow the same protocol, as we’ll study the possible causes for the implantation failure. So before transferring another embryo to the patient we will be looking at the uterus lining, the receptivity, immunological expression, progesterone levels, etc. and correct any of these if necessary.