According to some publications, recurrent pregnancy loss is called 2 or 3 or more pregnancy loss according to some publications. Recurrent pregnancy loss (Recurrent pregnancy loss) is also divided into two definitions. Primary RPL is pregnancy loss without ever having a child before, Secondary RPL is the case of having a child once and then having pregnancy loss.
The most important problem in recurrent pregnancy loss is the patient’s anxiety and psychology. For this reason, we ask, “Why are my pregnancies falling? Will I ever be able to have children? How many times will the same situation happen to me?” Questions like this often come up.
So what are the causes of these pregnancy losses? There are many reasons for this situation:
1- Genetic Disorders
2- Thrombophilia (coagulation) disorders
3- Uterine anomalies (Anatomic causes of the uterus)
4- Endocrine (hormonal) / Metabolic causes
6- Environmental and other factors
In fact, miscarriage (abortion) is the most common complication in pregnancy. In fact, fertilization occurs in some months, but the fertilized product falls silently with menstrual bleeding before it settles in the uterus. This can only be detected in a blood pregnancy test. In other words, not every fertilization results in a healthy pregnancy. This is what we call a “chemical pregnancy”. Let’s take a look at the causes and treatments for pregnancy loss one by one.
1- Genetic (chromosomal) disorders
It is the most common cause of pregnancy loss in the first trimester. If the mother or father is a carrier, these conditions do not cause disease in the mother and father, but they can become obvious during pregnancy and result in abortions that are incompatible with life. Therefore, genetic examination helps us in recurrent miscarriages. In addition, chromosome analysis of the abortion material is useful in investigating the failure of the treatment method. Chromosomal anomaly has been detected in 90% of pregnancy losses without heartbeat. In consanguineous marriages, the frequency of single gene mutations increases.
So what to do if there is a genetic problem? This is where pre-operative genetic screening comes into play. Embryos obtained by in vitro fertilization are screened with pregestational screening methods and the genetically normal embryo or embryos are placed in the uterus. In this case, the miscarriage rate is minimized. Recent studies report that pregnancy rates and live birth rates do not increase, but because it prevents recurrent miscarriages, earlier pregnancy occurs.
2- Thrombophilia (Coagulation) disorders
There are congenital, that is, congenital and acquired coagulation disorders. Since some of the congenital coagulation disorders have a high incidence in the society, no relation with RPL was found in the studies conducted. However, FV leiden mutation and prothrombin gene mutation were found to be associated with preeclampsia and growth retardation in advanced weeks of pregnancy. MTHFR gene mutation, which has a high frequency in the community, was not found to be associated with fetal losses.
The main thing here is the acquired coagulation disorder. In the 1980s, researchers suggested that the formations caused by the stimulation of a factor that is effective in the regulation of the defense system, which is called anti-phospholipid antibody, which occurs as a result of deviation from normal in the body, may be the cause of recurrent miscarriage. Clear relationships were found between these items and fetal death. The mechanism of action of these substances is vascular disorders that lead to insufficient blood supply of the placenta. In the treatment of patients with positive antiphospholipid antibody test, low-dose aspirin and anticoagulant needles, which we call blood thinners, and sometimes steroid treatment are required.
If factor V is homozygous, it must be treated, and if lupus anticoagulant is available, all systems should be screened. Low-dose aspirin, blood thinners, and if other systems are also involved, corticosteroid therapy should be given.
As a result, antiphospholipd antibody test, which is associated with early pregnancy loss and recurrent miscarriages, should be screened. Congenital coagulation disorders should also be investigated in high-risk patients for thrombosis or pregnancy poisoning due to high blood pressure in pregnancy, which we call preeclampsia. There is no need to routinely screen for coagulation disorders in patients who cannot conceive.
3- Anatomical disorders of the uterus (uterus) and insufficiency of the cervix (cervix)
Structural disorders of the uterus, which we call congenital anomalies, are deformities such as a curtain inside the uterus (uterus septum), heart-shaped uterus (bicornuate uterus), double uterus (uterus didelphis). These congenital anomalies are more common in primary RTG.
Structural disorders of the uterus are fibroids, polyps (meat glands), intrauterine adhesions. 3D ultrasound plays an important role in diagnosis. MRI can help us make the diagnosis if we are unclear about the diagnosis. Apart from this, HSG, which we call uterine tube film, is useful in diagnosing. Imaging of the uterus by injecting fluid into the uterus (SIS) or the evaluation of the uterus and tubes under ultrasound guidance by injecting opaque material (HyCoSy) are other diagnostic methods. However, hysteroscopy is the gold standard for imaging the inside of the uterus. The frequency of structural disorders of the uterus is 10-15%. In RPL, these disorders either adversely affect vascularity or reduce and change the size of the uterine cavity, making the area where the fetus will be placed unsuitable. Surgical correction of these anomalies reduces miscarriage rates.
Cervical insufficiency is a condition that occurs when the cervix is opened without pain, especially between the 4th and 6th months of pregnancy, and the fetus is expelled by rupture of the gestational membranes. Its treatment is surgery. At the end of the third month, the cervix is sutured.
HSG is used to view intrauterine adhesions. Hysteroscopy is the gold standard for diagnosis. The treatment is to cut the adhesions with hysteroscopy.
Presence of intrauterine veil has no effect on infertility, but the number of miscarriages increases in patients with intrauterine veil. The length of the curtain does not matter. Studies show that cutting the curtain with hysteroscopy significantly reduces the risk of miscarriage. Spontaneous pregnancy rate is high after waiting two months after this surgery.
Since the width of the uterus is small in the T-shaped uterus, intrauterine expansion operation is performed with hysteroscopy.
If there is a notch in the uterus, which we call arcuate uterus, the risk of RPL is doubtful. In addition, there is no difference in terms of TGK whether this notch is cut by hysteroscopy or not.
The studies carried out reduce the miscarriage rate of polyps, which we call intrauterine meat glands, by hysteroscopy. Myomas on the outer wall of the uterus have no effect on fertility. Intramural fibroids on the uterine wall reduce pregnancy rates whether they press on the uterus or not. Therefore, if there are no other factors affecting fertility, it should be removed.
4- Endocrine (Hormonal) / Metabolic causes
The most common hormonal causes associated with RPL are as follows.
thyroid gland disease
Diabetes (diabetes) disease
polycystic ovary disease
Excessive secretion of prolactin (milk hormone)
Luteal phase failure
In studies, it is stated that goiter function tests, milk hormone, which we call prolactin, and sugar regulation should be screened in patients with RPL. If goiter function tests are impaired, thyroid autoantibodies (antiTPO, antiTg) screening should be performed. Because the relationship between thyroid dysfunction and RPL was found to be significant. Cells that facilitate the expulsion of the fetus from the uterus (TH1) are also increased in autoimmune thyroid diseases.
In those with overt diabetes, the parameter showing the regulation of blood sugar in the last three months (HbA1C) should be checked. Those with HbA1C >7 have an increased risk of miscarriage and congenital anomaly. But controlled diabetes does not increase the risk of miscarriage. Insulin resistance is especially important in patients with polycystic ovary syndrome associated with hormonal disorders. If there is insulin resistance, sensitizing drugs should be started.
Since high prolactin (milk hormone) is associated with recurrent pregnancy loss and infertility, it must be treated.
Problems related to menstrual irregularity are mostly seen in “ovulation”, that is, ovulation related problems. It is thought that disorders that cause insufficiency of the “progesterone” hormone, which is necessary for the continuation of pregnancy, may cause RPL.
The structure we call the “yellow body or corpus luteum” that remains after the egg is laid produces the hormone progesterone, which ensures the continuation of pregnancy. After three months, it transfers its duty to the placenta. However, if it is premature aging and disappears without transferring its task to the placenta, this is called “corpus luteum failure” and pregnancy results in miscarriage. While corpus luteum insufficiency was diagnosed by biopsy taken from the uterus in the past, this method has now been abandoned. In the second half of the menstrual cycle, the diagnosis is made by looking at the LH and progesterone hormone levels in the blood. Its treatment is to start progesterone treatment in the luteal phase, that is, after ovulation, and to continue this treatment for up to three months.
Vitamin D plays an important role in the reproductive system. Vitamin D is associated with thyroid functions, insulin resistance, and androgen excess. Therefore, vitamin D deficiency should be treated. There is no consensus yet on how many should be taken as the limit value here.
It is thought that infections caused by viruses and bacteria, especially those involving the genital area, may cause pregnancy loss. However, although these infections are known to cause a single abortion, there is not enough evidence that they are the cause of recurrent miscarriage.
6- Environmental and Other Factors
Pregnancy loss increases with increasing maternal age. Increasing gestational age increases chromosomal disorders called aneoploidy.
The risk of miscarriage increases in pregnant women exposed to heavy chemicals. Smoking and alcohol increase the risk of miscarriage. There is no clear information about passive smoking.
It is not clear whether psychological factors are the cause of RSI, as it is difficult to examine. Apart from this, there are also pregnancy losses, the cause of which we do not know. Progesterone support is important in pregnancy loss whose cause is unknown. There is no difference between oral or vaginal use of progesterone.
Follow-up of Patients with Recurrent Pregnancy Loss
Patients should be educated about the fact that the loss will increase with the age of the mother, even if there are no findings, and they should know that they are at an increased risk of other pregnancy complications such as preterm birth and ectopic pregnancy.
It is helpful to say that activities such as sexual intercourse and exercise that normally cause increased uterine cramps will not disrupt a healthy pregnancy.
The timing for detailed examination in patients with recurrent pregnancy loss may vary according to the patient’s age and the patient’s anxiety state.
Couples who have had a miscarriage need intensive doctor support in the first three months when they become pregnant after a complete evaluation and successful treatment. Their anxiety is high, so it is very important to support them.
Families facing recurrent pregnancy loss should believe that it is not destiny. With this belief and patience, necessary precautions should be taken in cooperation with the doctor. It should be kept in mind that successful pregnancy rates can be very high (90%) after treatment for the cause. Despite this, the successful pregnancy rate is high when the abortions of unknown cause are treated patiently in the light of the data we have. Therefore, we recommend our patients to be hopeful and patiently follow the treatment.