• Pregnancy loss before the twentieth gestational week is defined as abortion. Abortions can be spontaneous or induced.
Spontaneous Abortions
• Spontaneous pregnancy loss occurs before the 20th week of pregnancy and the most common complication of pregnancies is spontaneous pregnancy loss. Up to 30% of pregnancies are lost after implantation. About 2/3 of them are clinically silent (preclinical abortion, biochemical pregnancy).
• More than 80% of spontaneous abortions occur in the first 12 weeks. The risk of spontaneous abortions doubles as the age of the mother and father progresses.
etiology
Fetal Causes
About half of pregnancy losses are anembryonic. Therefore, there are no embryonic elements. The remaining miscarriages (50%) are embryonic losses, and usually anomalies of the zygote, embryo, fetus or placenta are observed. Half of the embryonic losses (25% of all miscarriages) have chromosomal abnormalities (aneuploid abortions). The rest of the cases are euploid abortions (normal chromosome structure).
Aneuploid Abortions: Both the abortion rate and the chromosomal abnormality rate decrease as the gestational age progresses. Most common first trimester abortion
The most common cause of first trimester abortions is fetal aneuploidy. 55% of 1st trimester losses, 35% of 2nd trimester losses and 5% of 3rd trimester losses are chromosomally abnormal. Aneuploid miscarriages tend to happen in the early weeks of pregnancy. 75% of aneuploid abortions occur in the first 8 weeks of pregnancy and while 95% of them have errors in maternal gametogenesis; Errors in paternal gametogenesis are observed in only 5% of them.
Euploid Miscarriages: They mostly occur after the 13th week of pregnancy and their incidence increases rapidly when the maternal age passes 35.
Chromosomal distribution in embryonic abortion materials
Medicine -------------------------------------------------------------- Incidence (%)
Euploid (46,XY or 46,XX) -----------------------------------------45-55
Aneuploidy:
- Autosomal trisomy -------------------------------------------------22-32
Trisomy 16 (most common trisomy) ----------------------------- 7-8
trisomy 22
trisomy 21
trisomy 18
trisomy 13
- Monosomy X (45,X) (most common alone) ---------5-20
- Triploidy-------------------------- 6-8
- Tetraploidy ----------------2-4
- Structural anomalies --------------2
Double or triple trisomy-----------------0.7-2
The only autosomal trisomy not identified in abortions is Trisomy 1.
Maternal Causes
Personal factors
0 History of spontaneous abortion
0 Advanced maternal age
0 increased gravida
0 Use of cigarettes, alcohol, and amphetamines
0 Uterine anomalies
0 Excessive maternal weight
0 Serious maternal trauma
0 Placental anomalies
Infections
0 Brucella abortus, Campylobacter fetus and Toxoplasma gondii
Its effects on pregnancy are not fully known.
0 It is thought that Listeria monocytogenes, Parvovirus, CMV and HSV do not have abortion-producing effects.
0 Detection of Chlamydia trachomatis in 4% of abortions (normally it should be below 1%) suggests that it has a low-preventing effect.
0 Periodontal polymicrobial infections have also been shown to increase the risk of miscarriage 2-4 times.
0 Bacterial vaginosis has been shown to cause miscarriages, especially in the second trimester.
0 Mycoplasma genitalium infections are associated with spontaneous abortions.
Medical diseases
0 diabetes mellitus
0 Thyroid diseases
0 Celiac disease
0 Cyanotic heart diseases
0 Inflammatory bowel diseases
0 SLE
Abortion Types
abortion imminens
► Low threat. Bleeding before the 20th week of pregnancy, but the cervix is closed. There is fetal cardiac activity.
► Bleeding is the most important predictive factor of pregnancy loss. 50% of cases usually end in miscarriage. However, if there is fetal cardiac activity, the risk is significantly reduced.
► Although there is no pregnancy loss in most cases of abortion imminens, poor obstetric outcomes may occur in the later stages of pregnancy. Increased complications in pregnant women with bleeding in the 1st trimester; The risk of preterm birth, IUGR, preterm premature rupture of membranes, abruptio placentae, placenta previa, fetal neonatal deaths, increased cesarean rates, low birth weight and manual removal of the placenta increases.
► There is no definitive treatment. Bed rest may be recommended.
Ectopic pregnancy should be investigated in the differential diagnosis of the threat of miscarriage.
incipient abortion
► Inevitable (unstoppable) low. Before the 20th week, these pregnant women have cramp-like pain in the groin, abundant vaginal bleeding, and an opening-wiping of the cervix.
► In these cases, miscarriage cannot be prevented and curettage is performed.
Missed abortion
► These are the cases where there is a pregnancy without intrauterine fetal cardiac activity before the 20th gestational week and the dead tissue is not excreted. The cervix is closed, with little or no cramping or bleeding.
► In this case, tissue thromboplastins may mix into the circulation and cause disseminated intravascular coagulation (DIC). Its treatment is rapid evacuation of pregnancy. The DIC panel must be checked before evacuation.
Incomplete abortion
► It is the situation where some of the embryo-fetus and its appendages are thrown out of the uterus cavity and some of them remain in the cavity.
► On ultrasonographic examination, the endometrium appears irregular and thick. On vaginal examination, the cervix is dilated and feto-placental fragments from the cervix can be seen protruding into the vagina (Åž-19).
► The only approach is rest curettage.
Complete abortion
► Embryo-fetus and its appendages are completely thrown out of the uterine cavity. No intervention is required.
anembryonic pregnancy
► · Although it is over the seventh and eighth weeks of pregnancy, the embryo has not developed and the structures of the embryo cannot be seen in the ultrasonography. Diagnosis is made if the gestational sac diameter is > 25 mm and the embryo cannot be observed in transvaginal ultrasonography. It is especially common in monosomy-X..
► Curettage is done.
Septic abortion
► Endomyometritis is the most common clinical picture. Clinically, there is fever, foul-smelling discharge, severe tenderness in the abdomen and cervical examination, and DIC may develop in neglected cases.
► In case of septic abortion, the cavity is cleaned by curettage and broad-spectrum antibiotics are given. If there are signs of sepsis and the desire to reproduce is completed, hysterectomy can be applied. Even if there is a desire to reproduce, hysterectomy may be required if clinical improvement cannot be achieved by curettage.
Anti-D immunoglobulin should be administered in Rh (-) cases following abortions.
REPEAT PREGNANCY LOSSES (RPL)
• RSO; Two or more clinically defined pregnancy losses occurring before the 20th week of pregnancy. Its incidence is 1/100 pairs.
etiology
• In more than half of the cases (50-60%), the cause cannot be found (idiopathic). Apart from this, genetic, anatomical, immunological, endocrinological, thrombophilic and infectious causes are held responsible.
Situations where the cause can be determined
1. Embryonic genetic anomalies ------------------------------------------------ 60-80%
2. Endocrine Causes -------------------------------------------------------------- 17-20%
3. Anatomical Causes ------------------------------------------------------------- 12-16%
4. Antiphospholipid antibody syndrome---------------------------------------- 12-15%
5. Infectious Causes ---------------------------------------------------------------- % 7 -56
6. Parental Genetic Causes--------------------------------------------------------- 2-5%
7. Immunological (other than AFAS) and thrombotic (thrombophilia) causes-► Undetected
• Gives clues about the cause in the week of pregnancy loss. Losses due to genetics are usually in the early stages of pregnancy (5-8th weeks); Losses due to autoimmune and uterine anomalies usually occur later in pregnancy (12-20 weeks).
Immunological Causes and Thrombophilia r
antiphospholipid antibody syndrome AFAS
It is a disease characterized by the development of antibodies against phospholipids. The incidence in women with recurrent pregnancy loss is 3-5%.
0 The main risk factor for poor pregnancy outcomes is the positivity of anticardiolipin antibodies, lupus anticoagulant and anti 132-glycoprotein-1 antibodies. Pregnancy loss is seen in 20% of patients with SLE. Antiphospholipid antibodies are the cause of almost all lost pregnancies in these patients.
0 The main pathology of AFAS leading to pregnancy loss is placental thrombosis. The fetus is lost due to the disruption of uteroplacental circulation that develops as a result of intervillous thrombi, intravillous infarcts and decidual vasculopathy, and fetal hypoxia resulting from this.
0 In the early weeks of pregnancy, anti-FL antibodies directly target FL in trophoblastic cells, inhibiting trophoblastic cell division or trophoblastic invasion and trophoblastic fusion as well, leading to early pregnancy loss. In the later weeks of pregnancy, anti-FL antibodies target the trophoblastic cells of the placenta and activate complement there. Depending on the extent of the damage in the placenta, either intrauterine fetal death occurs or IUGR occurs.
Conditions caused by anti-FL antibodies in pregnancy
1. Spontaneous abortion
2. Recurrent pregnancy losses (early and late)
3.Preterm birth (<34 weeks)
4. Gestational hypertension
5. Preeclampsia
6. Intrauterine growth retardation
7. stillbirth
AFAS Diagnostic Criteria
clinical diagnostic criteria
1. Presence of one or more vascular thrombosis of any type (arterial, venous, small vessels)
2. Pregnancy complications
- 3 or more spontaneous abortions occurring before the 10th gestational week (maternal anatomical, hormonal and parental chromosomal anomalies should be excluded)
- One or more unexplained fetal deaths in the presence of a morphologically normal fetus after 10 weeks of gestation
- Preterm birth caused by severe preeclampsia and placental insufficiency before 34 weeks
Laboratory diagnostic criteria: Two or more measurements at 12-week intervals should be positive.
1. High level of IgG and/or IgM type anti-cardiolipin antibodies
2. Positive lupus anticoagulant (prolongation in phospholipid dependent coagulation tests - aPTT etc.)
3. Anti-bita 2-glycoprotein-1 antibodies (IgG and/or M) titer > 99th percentile
Treatment: Preconceptional low-dose salicylic acid (aspirin) is started in all cases that cause thrombosis in placental vessels. After conception, in addition to daily aspirin intake, heparin or low molecular weight heparin is continued until delivery. With this treatment, 70-80% of live births are obtained.
Thrombophilias
As in AFAS, which can also be considered as an acquired thrombophilia, loss of pregnancy occurs with the same mechanism, namely placental thrombosis and infarction, in genetic thrombophilias.
0 As a result of some genetic mutations, predisposition to thrombosis increases. The most common among these are factor V Leiden mutation and prothrombin gene mutation. Mutation of methylene tetrahydrofolate reductase (MTHFR) enzyme is seen in the third frequency. A homozygous mutation of this enzyme results in hyperhomocystinemia, which is a factor that increases the risk of thrombosis. Other genetic thrombophilias include antithrombin, protein-C, protein-S and factor XIII deficiencies.
Thrombophilias; They can cause spontaneous or recurrent pregnancy loss, preeclampsia, ablatio placenta, IUGR and intrauterine dead fetus. Almost all of the pregnancy losses are in the II. and III. trimester occur.
0 There is no evidence-based method for the treatment of recurrent abortion in thrombophilias.
Anatomical Causes
► Abortions due to anatomical reasons are mostly in II. They occur at the beginning of the third trimester and the cause of abortion is usually insufficient intrauterine cavity and blood supply.
Congenital malformations
0 The most common uterine anomaly in women with the highest abortion rate and recurrent pregnancy loss is the uterine septum.
0 Along with the uterine septum, the anomaly that worst affects the course of pregnancy is the unicorn uterus.
Acquired lesions
0 Myoma uteri: Among uterine fibroids, especially submucous ones cause abortion, there is no such risk in intramural and subserous fibroids with dimensions less than 5-7 cm. Locations of fibroids are more important than their size. It is unnecessary to intervene in fibroids that do not disrupt the cavity.
0 Asherman syndrome (intrauterine adhesions): It causes 40-80% abortion and 25% preterm birth. As a result of hysteroscopic adhesiolysis, 50-90% term pregnancy can be achieved.
Cervical insufficiency: It can be congenital (with bicornuate uterus) or acquired (delivery, curettage, conization, exposure to DES). II. The immature fetus is exaggerated as a result of painless cervical dilation in the third trimester. Treatment in the weeks 12-16 . Cervical cerclage (Shirodkar or Mc Donald suture) is applied and tocolytic treatment (indomethacin) is given to the case for 48 hours following the intervention. Cerclage is contraindicated in cases of uterine bleeding, premature rupture of membranes, infection, fetus with anomalies, active labor.
0 Adenomyosis
0 Endometrial polyp
Endocrine Causes
hypothyroidism
0 Pregnancy may occur in mild-moderate hypothyroidism; however, RSC is frequently encountered due to ovulatory dysfunction and luteal phase defect. The risk of miscarriage is directly proportional to the TSH level. The limit for TSH is <2.5 mIU/ml.
Diabetes
Recurrent pregnancy loss in cases has increased 2-3 times compared to the normal population and the risk of miscarriage is directly proportional to the HbA1C level..
PCOS
0 There is an increased risk of abortion in PCOS cases. Hyperinsulinemia and insulin resistance are mainly responsible for the increase in this risk.
Luteal phase defect (LFD) and Hyperprolactinemia
0 It is the insufficient secretion of progesterone by the corpus luteum.
0 It accounts for less than 10% of recurrent pregnancy losses. The orpus luteum-placenta exchange occurs between the 7th and 9th weeks of pregnancy. In this case, hyperprolactinemia should be ruled out first.
0 The treatment is progesterone and it is the 7th-9th day of pregnancy. continues until next week.
Genetic Causes
► Recurrent pregnancy losses due to aneuploidy increase especially over 35 years of age and in women over 35 years of age with a history of recurrent pregnancy loss, the majority of the losses are due to spontaneous fetal chromosomal anomalies.
► Most of the preclinical and early clinical pregnancy losses are due to fetal aneuploidies. Pregnancy losses due to genetic reasons are usually in the first 4-6th week.
► Structural anomalies are seen in most of the cases, unlike spontaneous abortions, and the most common parental chromosomal anomaly accompanying recurrent pregnancy loss is balanced reciprocal translocation (50%). This is followed by Robertsonian translocations (25%). X chromosome mosaicism (47,XXY Kleinfelter syndrome) is in the third place (12%).
► Diagnosis of chromosomal anomalies is made by parental karyotyping. Preimplantation genetic diagnosis (PGD) is used in its treatment.
Infectious Causes
► The relationship of infections with recurrent pregnancies is controversial. It is thought that the detection of chronic endometritis in endometrial biopsy (histological demonstration of plasma cells) may be associated with recurrent pregnancy losses.
► In case of suspected infection in recurrent pregnancy loss, empirical antibiotic therapy is a more appropriate approach (azithromycin, erythromycin or doxycycline) instead of culture.
Other Reasons(10%)
► Impairment of uterine receptivity
► Environmental factors:
0 Toxin
0 Cigarettes: 10 pcs/day; Increases it by 2 times
0 Caffeine: 5 cups/day (500 mg/day); Increases it by 2 times
0 Drugs
► Placental anomalies: Circumvallate placenta and placenta with marginal insertion
► Medical diseases (cardiac, renal, hematological)
► Anesthesia gases, radiation, organic solvents, heavy metals
► Exercise: There is no relationship with moderate exercise.
► Male factor: Y chromosome microdeletions, sex chromosome abnormalities, MTHFR mutation and hyperhomocysteinemia may be associated with recurrent pregnancy loss.
There is no relationship between coitus and abortion in patients without cervical insufficiency.
Approach in Recurrent Pregnancy Loss
Tests with proven diagnostic value
► Chromosomal analysis of the product of conception
► Parental peripheral karyotype analysis
► Imaging of the intrauterine cavity (hysterosalpingography, hysteroscopy, sonohysterography, 3D transvaginal ultrasonography)
► Thyroid function tests
► Anticardiolipin antibodies, lupus anticoagulant and anti beta 2-glycoprotein-1 antibodies
► HbAlc
► Prolactin
Tests with UNPROVED diagnostic value
► Thrombophilia tests (Factor V Leiden mutation, prothrombin gene defect, protein S/C activity, homocysteine level, antithrombin defect)
► Ovarian reserve tests (3rd day FSH value, clomiphene citrate loading test, antimullerian hormone)
► Screening for PCOS (LH, androgen levels)
► Testing for THJTH2 cytokine dysregulation
► Preconceptional investigation of peripheral NK cells
► Antithyroid antibody measurements
► Measurement of other autoantibodies (rheumatoid factor, etc.)
► Obtaining cervical cultures for Mycoplasma, Ureaplasma and chlamydia
► Taking endometrial biopsy for the diagnosis of luteal phase defect (Noyes criteria)
Tests with NO diagnostic value
► Antinuclear antibodies
► Antipaternal cytotoxic antibodies
► Parental HLA profile
► Lymphocyte culture
► Measurement of cytokines, oncogenes, growth factors
PROGNOSIS
• Successful pregnancy is achieved in most of those with recurrent pregnancy loss. The prognosis for obtaining a live birth in subsequent pregnancies depends on the underlying cause and the number of previous miscarriages. Observation of fetal cardiac activity may be prognostic; but the underlying cause is very important. The probability of live birth is 77% in those with fetal cardiac activity.
Causes -------------------------- Possibility of Live Birth
Endocrine reasons---------------------------------------------► > 90 %
AFAS----------------------------------------------------------- ► 70-90%
Anatomical causes-------------------------------------------- ► 60% -90
Genetic causes------------------------------------------------- ► 20-80%
The risk of ectopic pregnancy and complete mole increases in those with recurrent pregnancy loss.
induced abortions
• Therapeutic abortion can also be applied in maternal situations where the mother cannot maintain the pregnancy (cardiac decompensated heart diseases, severe hypertensive vascular diseases, serious diabetes, invasive cancer of the cervix, post-rape pregnancies) or in severe anomalies of the fetus.
Surgical Methods
• Menstrual regulation (MR): It is the aspiration of the endometrium through a cannula connected to a vacuum device.
• Dilatation and curettage (D&C)
► Vacuum curettage: It is the safest and most effective method for terminating pregnancies younger than 14 weeks.
surgical curettage (definite curettage): 14-15 if there is no vacuum curette. It is used for termination of pregnancy less than 14-15 week. There is a high risk of blood loss, procedure time, and damage to the cervix or uterus. In addition, the risk of Asherman syndrome is high.
• Dilution and vacuation (D&E) is applied in pregnancies older than 16 weeks. It is the form of sharp curettage applied to large pregnancies. The complication rate is quite high.
• Hysterotomy or Hysterectomy. Both should never be used as a first method.
MEDICAL METHODS
• Medical abortion· The 3 most commonly used agents for this purpose are mifepristone, an antiprogesterone, misoprostol, a prostaglandin E, and methotrexate, an antimetabolite. The abortion effect of all three agents is to increase the contractility of the uterus. Since these agents are teratogenic, pregnancy must be terminated surgically unless medically terminated. It can be used in oxytocin in second trimester abortions.
• Intra-amniotic fluid: It is an old method used in second trimester abortions.