Miscarriage: Diagnosis Using Embryoscopy

Miscarriages occur frequently, perhaps as often as 20% of all pregnancies. Chromosomal abnormalities - specifically aneuploidy - are considered to cause at least 50% of all isolated miscarriages. Physicians that care for early pregnancies often diagnose miscarriages before the patients have clinical symptoms of vaginal bleeding.


When a miscarriage is diagnosed by early ultrasound with the absence of fetal cardiac activity, often the patient undergoes dilatation and curettage (D and C) . This procedure is done to remove the products of conception, sparing the patient the unpleasant physical and emotional aspects of undergoing a miscarriage with spontaneous passage of the pregnancy. In addition, the dilatation and curettagerepresents the chance to make a diagnosis of the cause of the miscarriage by ruling out the purported most common cause of pregnancy losses: aneuploidy.


However, with the D and C, maternal cells often contaminate the miscarriage specimen, yielding the false results that the pregnancy loss was normal female karyotype. This is a very common problem. Perhaps 50-80% of the 46XX (normal female karyotype) results from D and C specimens are in reality due to maternal contamination. Thus the results are erroneous, and the patient is then quite possibly falsely advised that the pregnancy loss was ‘normal’.

The physician has one chance to evaluate the cause of a miscarriage, and that opportunity comes at the time the D and C is done. If the results of a standard karyotype come back “normal 46 XX”, as it does at least 50% of the time, then unfortunately one cannot confirm that these results are indeed true. The opportunity to make a diagnosis is lost then. If the karyotype comes back showing that there is a “Y” chromosome, then one knows that there is no contamination (as the maternal cells of course have no “Y” chromosome).


Likewise, if the chromosome analysis after a D and C comes back showing an abnormal number of chromosomes (called aneuploidy) then one knows that this must indicate an embryo abnormality since the female cannot have such an aneuploidy, thus one knows that there was no contamination of the specimen. But the all too common result of 46XX from the D and C specimen remains a frustration for the patient and the physician.


Hysteroscopy is a procedure whereby a small telescopic instrument is placed into the uterus prior to the D and C. Thus ‘embryoscopy’ is simply the use of a small hysteroscope immediately prior to the D and C procedure to visualize the contents of the uterus (i.e. the embryo and the gestational sac). With this simple technique, the physician can directly sample the products of conception under visualization, preventing the problem of maternal cell contamination. In addition, one can assess the physical attributes of the embryo prior to D and C. This is helpful because 20% of the embryos that are chromosomally normal will have abnormal physical features, thus confirming a ‘genetic’ cause rather than chromosomal or other cause---like uterine defect, immune problem, etc.

If, on the other hand, the assessment with embryoscopy and chromosome analysis both look normal, then one should strongly consider further evaluation with immunology testing and hysteroscopy in the non-pregnant state to rule out uterine anomalies and endometritis. In addition, one may look at male factors that may contribute to early pregnancy loss such as DNA fragmentation and detailed morphologic assessment of sperm

A lot of work has been done with embryoscopy by Phillip et al. They recently showed a series of cases where 272 patients were assessed. These patients had a sonographically visible pregnancy that was 7-8 weeks. 232 were able to be visualized prior to D and C. 85% showed abnormal development visually, 14% looked normal. 30% of the abnormal appearing embryos had normal chromosomes. 50% of the normal appearing embryos on embryoscopy had abnormal chromosomes. Thus one can see that embryoscopy definitely helps delineate the miscarriage cause.

Ferro et al also conducted a study where they compared traditional D and C and karyotype versus that of embryoscopically directed sampling prior to D and C. Here is a summary of the results:

• 36/68 cases had karyotype results for both biopsy and curettage
• 8/36 (22%) would have been completely misdiagnosed as normal without direct biopsy via embryoscopy beforehand.
• 1/3 curettage specimens, despite precautions of rinsing the specimen to attempt to cleanse the maternal cells away, were contaminated. Embryoscopy would of course help in these instances.
• Thus the "normal" diagnosis of miscarriage specimens with karyotype 46XX was often times inaccurate.

At SIRM St Louis, we have performed many such procedures with embryoscopy prior to D and C - specifically in patients that have unfortunately miscarried after an IVF procedure.

I have also used the technique of embryoscopy to assess twin pregnancy losses, getting direct embryo samples from each sac, giving accurate analysis of the separate embryos. This is not possible to do accurately with basic D and C only.

We have found embryoscopy to be helpful in evaluation of all cases of pregnancy loss - those conceived with natural conception, IUI or IVF/ICSI. The papers that have been published to date on this process have all dealt with pregnancy loss in cases in which there was an identifiable embryo on US, i.e. those after 6 weeks estimated gestational age from the last menses (4 weeks or so after ovulation/conception). However, we have utilized the basic technique of embryoscopy to extract the entire sac in pregnancies that have arrested in development as early as 5 weeks 0 days. We have been able to obtain accurate chromosome analysis on many such pregnancy losses, providing answers to the cause of the loss in many cases where, in the past, we could only speculate the cause.

Being able to diagnose the cause of these very early pregnancy losses is extremely helpful in patient counseling, providing answers to the couple. Also, when one can rule in or out chromosome causes of pregnancy loss, one can focus further evaluation more directly. For example, if the chromosome analysis confirms normality, one can embark on immune evaluation and direct treatment in a future early pregnancy to reduce the chance of loss there.

The key to being able to diagnose pregnancy loss this early involves recognizing pregnancy early with positive tests and then simply monitoring early growth of the embryo with ultrasound starting in the early 5th week of pregnancy. If appropriate growth and developmental milestones are not achieved, then miscarriage can be diagnosed and evaluated as early as possible. These simple steps will allow intervention and an opportunity at accurate diagnosis of the loss.

Figure 5

Fig 5: This is an US picture of a pregnancy loss at 9 weeks, appears normal but there is no heart activity.

Figure 6

Fig 6: This is an embryoscopic picture of the pregnancy loss seen in Fig 5. There appears to be normal development of the embryo.

Figure 7

Fig 7: Close up of the lower extremities clearly shows abnormal development with, essentially, absent growth of the lower limbs. The chromosome analysis done on direct biopsy of the embryo revealed a normal female karyotype, 46XX. However, it is clear that there must be some other genetic or developmental phenomenon contributing to the pregnancy loss. Without embryoscopy, the loss would have been deemed ‘normal’ based upon the chromosome analysis alone.

In conclusion, current techniques of assessing the origins of miscarriage using simple D and C are insufficient. This is mainly due to the potential for inaccurate results related to contamination of the specimen by maternal endometrial tissue giving a falsely normal result. However, there can also be truly normal karyotype results but abnormal embryonic growth, suggesting a non-chromosomal cause for the loss. Therefore visualization and direct tissue sampling of the embryo prior to D and C is very helpful in assessing growth patterns of the embryo and also obtaining an uncontaminated sample for chromosome analysis. Clearly embryoscopy is helpful in such instances. However it is also helpful if the results show normal appearance and normal karyotype, then one can focus attention of other issues like immunology, uterine factors, etc that may be treatable causes of miscarriage in a future pregnancy.

Embryoscopy using the current simple techniques for basic hysteroscopy poses no additional risk to the patient and does not require elaborate equipment. Nor does the procedure add significant time to the entire process. Application of this technique to the evaluation of pregnancy losses any time there is a confirmed loss with ultrasound will advance our knowledge of early pregnancy and, of course, prove beneficial to patient counseling for future pregnancies. In addition, with this technique, one can find answers often to the cause of miscarriages—this is always helpful for patients to understand “why?” and cope with the loss.

Medical offices should evaluate pregnancies early after a positive pregnancy test. In this way, the patients can get early, serial ultrasound assessment and monitoring. Adopting this simple protocol will then lead to early diagnosis of miscarriages and hence we can evaluate them appropriately before the patient experiences bleeding and passage of the tissue. If this occurs, then the opportunity is gone for optimally assessing the pregnancy loss.