What could be the cause of repeated miscarriages? Is it normal to miscarry twice in a row? How can I prevent repeated miscarriages? Is IVF treatment a solution for me? Miscarriage is more common than we might think. It affects women at any age, those under 20 and those over 30. Finding a cause of miscarriage is not always easy but… To help you get some answers to the above questions, we invited Dr Ahmet Ozyigit, Ph.D., Assistant Professor at North Cyprus IVF to speak on the topic of repeated miscarriages and their possible causes.
Dr Ahmet Ozyigit is a clinical embryologist with over a decade of experience in assisting patients with fertility treatments. Dr Ozyigit, who is also currently finishing up his MD degree, comes from an eclectic background with 2 Bachelor’s Degrees, 2 Master’s Degrees, and Ph.D. degrees in different fields. His passion for education and research is the foundation for his career as a physician, embryologist, researcher, and clinic manager. He currently holds a teaching position at the Mediterranean University of Karpasia and is the lead for clinical research at North Cyprus IVF Center. Watch the above video recording of our LIVE event with dr. Ahmet and the Q&A session with patients.
Dr Ahmet Ozyigit starts by highlighting that medicine is a very dynamic field of science. It practically changes every day. It happens that what we know one day may be refuted the next day. So even though this webinar going to cover a lot of reasons for repeated miscarriages, it is not a comprehensive list and (like any other webinar!) It should never replace a consultation with a doctor.
Dr Ozyigit goes on to explain what a miscarriage is. By definition, it is a loss of pregnancy before 20 weeks of gestation. After 20 weeks, it is called a stillbirth. Broadly speaking, there are three main types of miscarriages: complete miscarriage, incomplete miscarriage and missed miscarriage. A complete miscarriage is when all the pregnancy tissue has left the uterus. Once it happens, it is common to have vaginal bleeding, cramps and contraction pains. A complete miscarriage occurs before 12 weeks of gestation. An incomplete miscarriage, on the other hand, happens after 12 weeks of gestation. It is when some of the pregnancy tissue still remains in the cervical canal. Such type of miscarriage results in cramps and vaginal bleeding, too. When it comes to incomplete miscarriage, it is often advisable to use some medications or D&C (dilation and curettage) in cases where the pregnancy tissue does not pass on its own. Finally, the third type of pregnancy loss is called a missed pregnancy (or missed abortion). As contrary to the previous two, it is often silent – meaning there are no cramps, pain or bleeding. Although the fetal activity is stopped, the fetus does not leave the uterus and the cervix is closed. This type of miscarriage is often diagnosed at the 12- or 20-week scan.
Dr Ozyigit admits that, traditionally, the term ‘recurrent miscarriages’ was used where three or more consecutive pregnancy losses were experienced. However, the likelihood of a third pregnancy loss after a second one has been estimated as 30% while the likelihood of a fourth pregnancy loss (after a third one) has been estimated as 34%. This means that a thorough investigation is warranted after the second miscarriage – also, in order to spare a patient the devastating effects of another such stressful and traumatic experience. An investigation is not perceived as necessary in case of a single miscarriage as more than 90% of the women will go on to have a problem-free pregnancy after a first miscarriage.
When investigating pregnancy loss, doctors have to consider the time frame during pregnancy in which the pregnancy loss is experienced. Similarly, the mother’s age is very important. According to the Royal College of Obstetricians and Gynaecologists (RCOG), approximately half of all pregnancies will result in a miscarriage when the biological mother is over 40 years old.
In the case of two or more consecutive miscarriages, the possible causes may be very different. A high percentage of them (around 40-50%) are classified as unknown. It means there are still things that doctors are not able to identify. Fortunately, the rest of the causes is possible to be defined, analysed and – hopefully – successfully dealt with.
Dr. Ozyigit states that genetic causes constitute around 2-5% of all repeated miscarriages. But although it is just a small percentage, it is one of relatively less invasive and easily identifiable reasons – e.g. through a blood test or a chromosomal karyotype analysis. Chromosomal abnormalities can be classified as numerical or structural. The numerical abnormalities (meaning less or more chromosomes) are generally associated with the inability to conceive, whereas the structural ones (such as e.g. chromosomal deletions, duplications or translocations) are linked to both the inability to conceive and recurrent pregnancy losses.
Parental aneuploidy (meaning an abnormal number of chromosomes) accounts for approximately 2-5% of all miscarriages. However, up to half of the miscarriages are associated with aneuploidy in the fetus. These are the translocations (either reciprocal or Robertsonian) that are the most common cause resulting in a pregnancy loss. Translocations (and other parental chromosome abnormalities) can be revealed through a karyotype testing for both the intended mother and the father. Dr Ozyigit says that once doctors see the karyotype analysis, they follow with an IVF procedure that includes PGS (preimplantation genetic screening) on the embryos. In this way, only the chromosomally normal embryos are picked for the transfer and the chances for another miscarriage are reduced.
Dr Ozyigit then goes on to explain anatomical and structural abnormalities that have to do with either the cervix or the uterus. Cervical incompetence (or cervical insufficiency) is known as a structural cause of pregnancy loss. The cervix normally stays closed and firm throughout the course of pregnancy. Only until shortly before the onset of the labor, certain hormones cause it to soften. However, incompetent cervix will fail to remain closed. Cervical incompetence is often the cause of a miscarriage in the second trimester. Most anatomical causes, on the other hand, are congenital – it means they are present at birth but tend to go unnoticed until later in adulthood. During embryological development, most of the female reproductive tract is formed from the fusion of structures called the müllerian ducts. If they fail to fuse, they can interfere with the development of normal uterine vasculature and disrupt the blood supply to the endometrium. Another congenital transformation that can prevent a pregnancy from progressing is a septate uterus.
The third group of miscarriage causes is immunological disorders. In fact, more and more fertility issues might have to do with immunology. The human immune system is designed to defend the human body against foreign threats. Both an overactive and an underactive immune system may lead to infertility problems. Although the embryo is perceived as a foreign object, there are ten different mechanisms that are believed to prevent the mother’s immune system from being too active against it.
Dr Ozyigit differentiates between autoimmune and cell-mediated responses associated with miscarriages. The autoimmune conditions that could interfere with a successful pregnancy are organ-specific antibodies (e.g. antiphospholipid, anticardiolipin, antinuclear or anti-histone antibodies). According to dr. Ozyigit, even though you don’t show signs of autoimmune disorders, it doesn’t mean that you don’t have the antibodies for them. That’s why it makes sense to test for these antibodies. Cell-mediated immune responses (at the local and systemic level) can be identified by measuring cellular activity. Natural Killer cells can also be associated with recurrent miscarriages.
A large portion of miscarriages are also caused by thrombophilia disorders. They are relatively easier to test – the tests are less costly and more widely available than 10-15 years ago. Thrombophilia is a condition known as a blood-clotting disorder. Women with thrombophilic disorders can develop blood clots throughout the body, including at the site of embryo implantation. Blood clots can also travel into the placental circulation and stop a fetus’s heart. Inherited thrombophilic disorders are caused by a variety of mutations and deficiencies in certain genes or gene products, such as a deficiency of natural anticoagulants.
When discussing potential causes of miscarriages, one also has to take infectious diseases into account. The most common infectious agents associated with pregnancy are covered by the TORCH acronym: Toxoplasma gondii, rubella, cytomegalovirus and herpes simplex virus. However, dr. Ozyigit says that while these infections are likely to cause a single miscarriage, they’re not considered to bring about recurrent miscarriages anymore.
Finally, hormonal problems may have a serious impact on pregnancy loss. The known risk factors for miscarriages are thyroid, adrenal gland problems and diabetes. In addition, an elevated prolactin level can also disrupt the development of a normal uterine lining, thus contributing to early-term miscarriages.
Dr Ozyigit admits that although all the mentioned miscarriage causes may seem scary, doctors have different tools at their disposal that can help to reduce the likelihood of this problem. Firstly, it is important to remember that one miscarriage does not usually call for further investigation. However, after two consecutive pregnancy losses, it is advisable to begin an assessment. Dr Ozyigit says it is good to start with less invasive and less expensive tests first. Some tests, due to a number of factors (such as e.g. family history of miscarriages, relevant own medical history), may be preferred over others. The further investigation that doctors would do normally includes karyotype testing, thrombophilia testing, uterine assessment as well as autoimmune and hormonal testing.
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