Patients with recurrent miscarriages – success stories

In this session, Dr Elias Tsakos, FRCOG, Medical Director at EmbryoClinic, Thessaloniki, Greece, shared his experience on how to deal with recurrent miscarriages and provided some real case studies explaining the steps that can be taken to prevent them.

Dr Tsakos started his presentation by explaining the definition of recurrent miscarriage, which is two or more miscarriages, and of course, they have to be addressed with a special team, they have to be addressed holistically, and they have to be addressed systematically so that we don’t miss anything out. If we add two more factors to recurrent miscarriages, one important factor is age. The value or the importance of a miscarriage is different if someone miscarried at 25 and if someone miscarried at 40. That reflects on the level of investigations we will probably initiate. There’s also another concept which is a recurrent IVF failure, it’s not just the miscarriages that should be investigated, but also if someone has 1,2, 3 failed IVFs that interact with some similar factors, many times with miscarriages.

If we look at female anatomy, we know there is the uterus, fallopian tubes and ovaries. There is a misconception that the ultrasound scan is the golden standard in diagnosing female anatomy, we have to be aware that this is not true. The ultrasound scan is a very significant tool, technology is getting better by the year, however, it is not the golden standard. It’s crucial to remember that female anatomy cannot be thoroughly assessed by a scan alone. The second misconception is that the tubes are not necessary, not important. If we’re doing IVF, that’s wrong, they may be significant. If the tubes are seriously affected by infection, and if the tubes suffer from a condition called hydrosalpinx, which is a big infection that’s causing fluid and toxins to accumulate within those tubes, they may affect the success of IVF, but also the outcome of pregnancy, they may cause miscarriage. The third misconception is that we don’t care about conditions like endometriosis or we don’t care so much about conditions within the uterus when we’re having IVF or when somebody is conceiving naturally, this is not true. Therefore, female anatomy is very essential and the assessment by ultrasound scan, no matter how high-tech, is not 100%.

Recurrent miscarriages – real IVF patients cases

• a woman in her mid-40s, she had lots of miscarriages and lots of failed IVFs

It turned out that the cause of the recurrent miscarriages and failed IVFs was uterine malformation. The uterine malformation is a condition that some women are born with. In the picture shown, there is a uterine malformation type 1. There are a lot of different types of malformations, but this is a fairly common one amongst infertility and patients with repeated miscarriages. It is called the uterine diaphragm, most people would call it uterine diaphragm, there are different terminologies. It means that instead of having 1 cavity, there are 2 smaller cavities, so there’s a division of the cavity into 2.

In that first case, this woman in her mid-40s was fully investigated, she had lots of scans by lots of different doctors, she had miscarriages and failed IVFs, and the problem was this diaphragm. This lady came up to the age of mid-40s without knowing that not only did she have a double uterus, but she also had a double vagina. This malformation had to be corrected surgically through hysteroscopy, and then she underwent successful IVF, and she delivered beautiful twins.

Therefore, it’s important to remember that if you do have a problem with miscarriages or IVF failures, do not rely on the scan alone and request to have further investigations to ensure that you do not suffer from a uterine malformation.

• a woman in her mid-40s with recurrent miscarriages, diagnosed with hydrosalpinx

Hydro is water, salpinx is a tube in Greek. It means that fluid accumulates in the tubes. In the picture shown, there is an X-ray, Hysterosalpingography, or HSG, and there is a lot of literature proving that it is important to exclude hydrosalpinx before doing IVF or before completing miscarriage investigations.

This particular patient underwent treatments, she had miscarriages, and she came up to her mid to late 40s before she found out that with the X-ray HSG she had hydrosalpinx. In most European clinics and most U.S. clinics, HSG is not one of the standard tests before IVF and may not even be a standard test after a miscarriage or miscarriage. It may be substituted by either a high-tech ultrasound scan or an ultrasound aided tubal assessment called HyCoSy or HyFoSy. Unfortunately, HyCoSy or HyFoSy and high definition scans are not 100% accurate in diagnosing hydrosalpinx.

Therefore, in cases of miscarriages and failed IVFs, it is significant to perform a standard X-ray HSG. If you are diagnosed with hydrosalpinx, remove it laparoscopically. The patient had a laparoscopy to remove her tubes, and then she had two beautiful children consecutively, not at the same time, through IVF.

Bear in mind the possibility of hydrosalpinx in case of miscarriages, and again some people do not quite grasp that there is a possibility of conceiving naturally even with the hydrosalpinx in place, however, there’s an increased risk of both miscarriage and ectopic pregnancy.

• a woman with recurrent miscarriages and endometrial adhesions

The miscarriage itself and perhaps the surgical evacuation, Dilation, and curettage (D&C), or even the medical evacuation may cause an additional problem, which may be the endometrial adhesion. Therefore, one of the reasons why we don’t like many miscarriages is that despite the origin and the aetiology, despite the reason a couple miscarried in the first place, the miscarriage itself may cause damage to the endometrial cavity as it did in this case. It caused this band of tissue, scar tissue, which decreases the risk of miscarriage. That was a case of endometrial adhesion, which was successfully divided and led to a spontaneous natural pregnancy.

Hydrosalpinx

• the fallopian tubes are filled with liquid that may be toxic to the embryo
• the tube is partially or totally blocked, which is causing misdiagnosis
• there’s a lower chance of pregnancy
• there’s an increased chance of miscarriage and ectopic pregnancy
• it may be unilateral, it may be on 1 tube, or it may be on both tubes
• if the height of the surface is of a high degree, the solution is removable via laparoscopy

Recurrent miscarriages – main reasons

I would like to highlight the importance of anatomy assessment. The main reasons for recurrent miscarriages or repeated IVF failures may be hormonal. We may have some thyroid defects, Polycystic ovaries may be linked with miscarriages and anatomy defects. On top of those, I would add polyps that could be in the cavity, I would add fibroids, either big fibroids or smaller ones that affect the cavity. The genetic issues may cause miscarriages, so we always suggest the karyotype testing of both couples. I feel that the patients that eventually come to an IVF clinic are not the standard patients in which karyotype disorders are uncommon. We do identify quite a few patients every month with karyotype abnormalities. Even cystic fibrosis, genetics may affect miscarriages. Serological blood testing and vaginal and cervical swabs may identify infections. Screening for medical conditions is important, diagnosing diabetes or starting phases of diabetes conditions like Lupus, etc. Other factors such as lifestyle issues may affect the fertility potential and also increase the miscarriage rate. Heavy smoking, alcohol, drug consumption and medications may also cause miscarriages. If we’ve excluded those important issues, we can always think of unexplained factors, but if we thoroughly rule out the majority of factors in the majority of situations, we may identify a reason, and we should be able to treat it accordingly.

Fibroids – myomas

Fibroids are very common, the vast majority of soft tissue tumours are benign tumours, although some of them may become malignant even in younger patients under the age of 50.

Dr Tsakos also mentioned one of his past patient’s cases. A lady had a very small fibroid, it was less than 3 cm, it wasn’t even touching the cavity, but it ended up being diagnosed as a sarcoma, which is a malignant fibroid tumour, she had to undergo a hysterectomy. She felt very lucky that it was diagnosed before IVF because she’s had lots of miscarriages before, and if that lady got pregnant through IVF, the tumour would have been undiagnosed for at least 10 months, and that would have been detrimental to her health.

Pedunculated submucosal fibroids and submucosal fibroids may affect and be associated with the miscarriage. Subserosal, intramural fibroids are not associated with miscarriages and are of no importance unless they grow fast or become bigger than perhaps 4-6 centimetres. The diagnosis is usually done by ultrasound, however, if we want to ensure that the cavity is normal we still need to do a hysteroscopy and decide if those need to be treated or not.

Male tests

• semen analysis
• semen culture
• genetic tests like Karyotype, Cystic fibrosis
• microbiology and viral tests
• hormonal tests
• more specific genetic tests like DNA fragmentation and Y microdeletion tests

Hysteroscopy

The golden standard in diagnosing the endometrial lining is hysteroscopy. It is now becoming more and more routine test on almost every who is attending a fertility clinic with a history of either miscarriage or before embarking on IVF. It’s an outpatient procedure, it’s inexpensive, and it’s highly accurate. The value of hysteroscopy has been proven and scientifically discussed.