Miscarriages statistics leave no illusions. It happens more often than we think. At age 30, one in five pregnancies ends in a miscarriage. At age 42, it’s already one in two. The subject is not only depressing in its nature but also extremely difficult and complex in medical terms, it’s important to consult with the best experts in the field. Dr Natalia Szlarb is one of them. In this webinar, she tries to answer the question: MISCARRIAGES. How and where to look for solutions?
At age 30, one in five pregnancies ends in a miscarriage. At age 42, it’s already one in two.
Dr Natalia Szlarb starts with a technical definition of a miscarriage – it is when the embryo, previously adhered to the lining of the uterus, is getting detached. All miscarriages before the 20th week of gestation are called ‘early miscarriages’. Pregnancy losses that happen later are called ‘late miscarriages’. Depending on the type, they are approached and analysed differently.
First, we have to be aware that women are born with a certain amount of eggs in their ovaries. This amount diminishes as women age. Additionally, the older a woman gets, the lower number of genetically normal embryos she’s generating. A majority of miscarriages happen due to genetically abnormal embryos. Putting it simply, the immune cells of a woman’s body ‘see’ a genetically abnormal embryo as a foreign body and that’s why it is getting miscarried. So however brutal it may sound, Dr Szlarb admits that when looking from this perspective, women themselves are the cause of miscarriages.
Dr Natalia Szlarb says that every patient’s case is thoroughly analysed and decided upon. Doctors have to determine the chances of having a woman pregnant with her own eggs or – if the chances are low – make her a candidate for egg donation. The basis of such an evaluation is the patient’s ovarian reserve, meaning 3 A’s: age, AMH (Anti-Müllerian Hormone) level and AFC (Antral Follicle Count). Dr Szlarb goes on to explain all of these factors in detail.
A woman’s age is the most important of all the mentioned factors. Dr Szlarb admits that women are designed to generate healthy embryos and have children until they are 35 years old. Later, women’s fertility drops dramatically and at the age of 45 women do not generate genetically healthy embryos. According to Dr Szlarb, generating a genetically healthy embryo at that age is like winning a million dollars in the lotto. For example, the risk of Down’s Syndrome in patients who are older than 35 years old is 3.5 times greater than in somebody who is 23 years old. However, thanks to modern technology that allows for the genetic testing of embryos (PGS and PGD), doctors nowadays are able to define chromosomal abnormalities in preimplantation embryos (such as Down’s Syndrome, Edwards’ Syndrome and Patau’s syndrome).
AMH, on the other hand, allows doctors to see how many eggs they can expect from a female patient in one cycle. For example, if the AMH level is more than 2 ng/ml, it means that around 16-20 eggs can be generated at once. Of course, only the strongest eggs are going to make it through and become day 5 embryos (blastocysts). Only then is the genetic testing carried out and the number of genetically normal embryos is defined. And it is age-dependant. At the age of 20, a woman can generally generate around 80% healthy (euploid) embryos. In the case of 30-year-old patients, the euploidy rate is 50%. However, after 10 years, the euploidy rate is only 20% (in the case of 40-year-old women). With that knowledge, as well as a comprehensive embryo selection, experienced and qualified doctors are able to avoid miscarriages in IVF patients. Healthy embryos are then frozen by the vitrification method. Thanks to it, a patient can have her embryos transferred at any time in her life. Dr Szlarb admits that it is common for her to do the whole family planning for her patients in just one cycle.
Dr Szlarb recalls the statistics showing that the pregnancy rate in women, who are over 35 years old and do not undergo the genetic testing of embryos, is only 18%. It happens so because, as mentioned before, the majority of embryos at this age are genetically abnormal. At the same time, when 35-year-old women decide to test their embryos comprehensively with the PGS method, their accumulated pregnancy rate (after 3 transfers) is 91%. Of course, these statistics do not apply to patients who have only a few embryos generated or whose embryos’ quality (due to a patient’s advanced age) is low. While the latter have usually egg donation suggested, the former are sometimes offered the solution called embryo banking. Embryo banking is offered to patients who generate good-looking embryos that are graded either A (excellent) or B (good) quality, but have low AMH. Low AMH means that a patient generates only 1 or 2 genetically normal blastocysts. In such a case, cycles are repeated every 2-3 months to generate more blastocysts to find at least 20-30% of the healthy ones (determined by PGS).
Egg donation is taken into account when doctors see that there are no genetically healthy embryos left. According to Spanish law, egg donation is anonymous. Dr Szlarb ensures that when searching for a perfect egg donor for a patient, she always tries to find the one who is as physically close to the recipient as possible. The donors always undergo a thorough assessment at the clinic, involving e.g., testing for a variety of infectious and genetic diseases, as well as mental health screening.
Dr Szlarb reveals that it’s best to always perform the so-called ‘mock cycles’ prior to an actual cycle. It means that doctors mimic a patient’s natural cycle with the use of artificial hormones. They prescribe 15 days of oestrogen supplementation, scan the uterus lining afterwards to see how thick it is, and then decide whether the dose of hormones is well-adjusted to the patient’s body or not. If the results are satisfactory, the patient (as well as her donor) is put on birth control pills for a couple of days. Then the recipient takes estrogens orally and the donor takes injections to make her eggs grow. If the sperm results on the part of a male patient are good, eggs are fertilised and the embryos are grown up to the stage of blastocysts. Then the embryo transfer is conducted.
Dr Szlarb admits that the pregnancy rates in egg donation are amazing. It is possible to enable someone who is over 40 to achieve the pregnancy rate of a woman who is 20 years old. After one transfer, 70% of patients are found pregnant, after 2 transfers – 90%, and after 3 transfers – 97%.
Apart from discussing female reasons for infertility, Dr Szlarb focuses on the so-called ‘male factor’ which – according to recent research – influences around 40% of infertility cases. If there is a male factor involved, such as karyotype abnormalities or pathological FISH sperm test results, less genetically normal embryos are generated. During the first visit, a male partner undergoes an extensive sperm workup that includes WHO criteria such as volume, motility, and morphology and then also sperm DNA fragmentation testing and FertiCert™.
Finally, Dr Szlarb says that in order to assure the successful implantation of a genetically normal embryo, it is important to conduct a uterus lining biopsy. Using ErMap (Endometrial Receptivity Map) it is possible to calculate the exact moment (the so-called ‘implantation window’) for the embryo transfer. It is especially significant in cases of IVF cycles with own eggs where there is, e.g., only one genetically normal embryo generated. The uterus lining biopsy is also significant to identify and solve immunological issues. The latter, identified as one of the most common reasons for miscarriages, are dealt with through the use of individualised treatment protocols.- Questions and Answers
No. The only possibilities for aneuploid embryos are either disposal or donating them for research or education of new embryologists. The decision lies with the patients, but it must be one of these three options.