**Abstract**

The miscarriages' investigation should include a familiar history, gynecological examination and a full laboratory testing including hormonal control, as well as karyotype, maternal immune control and thrombophilia testing. If the physician suspects the cause of abortions is chromosomal due to heredity, a special blood test (karyotype) for the pair is recommended. Chromosomal abnormalities are the most common reason for first trimester abortions, and are impossible to be prevented. Based on the above data, abortion and the subsequent possible infertility should not be considered as a personal failure for the woman and the treating physician. Nowadays, medical advancement provides many options combined with psychological support can actually reduce the miscarriages' risk.

**Keywords:** spontaneous abortions, recurrent abortions, diagnosis, therapy

### **1. Introduction**

Spontaneous abortions are considered as one of the most common complications in pregnancy. Abortion is defined as the ejection of the fetus until the 20th week and is clinically classified based on ultrasound evaluation. Threatened abortion is usually accompanied by vaginal bleeding without affecting the pregnancy. Incomplete miscarriage is described as incomplete passage of conception products. Complete, when all pregnancy products are spontaneously aborted. Septic abortion when endometrial infection coexists. Finally, recurrent abortions that are defined when three consecutive abortions occur before 20th weeks of gestation [1–5].

More than 80% of miscarriages occur up to 12 weeks. The percentage of clinically recognized abortions (appeared after 6th week) is estimated to be 12–15%. More analytically, 2 miscarriages occurred in 5% of women and ≥3 miscarriages in 1–3% of women [1–5]. Recurrent miscarriages consist of a serious problem for women with physical and psychological consequences. Abortions and especially recurrent miscarriages are considered as heterogeneous groups in regard to etiology [1–5]. Two or more causes can coexist, whereas about 50% of cases are characterized as idiopathic as a result of genetic, anatomical, endocrine, genetic, anatomical, endocrine, autoimmune factors or infections exclusion [1–5].

The number of clinically recognized miscarriages to total number of pregnancies is about 10–15%, while the equivalent of early abortions based only on human chorionic gonadotropin (hCG) measurements is actually much higher (50–60%) and interestingly before and after the implantation it is 30% but are not perceived [1, 6–10].

A positive correlation has been identified between the mother's biological age and the incidence rate of spontaneous abortions. So, a progressive increase of 10-fold afterwards the age of 40 is observed compared to younger women aged <35 years [1, 6–10].

Regarding the gestational age in first trimester and the abortion risk, this counts to 4 and 2%, respectively, in 6th and 8th week of gestation [1, 6–10]. The risk of recurrence in the next pregnancy is minor except of cases diagnosed with congenital uterine abnormalities [1, 6–10].

#### **1.1 Recurrent miscarriages**

Recurrent miscarriages are defined as three or more consecutive embryos losses weighing under 500 g. According to bibliography we can find different definitions for miscarriages [1, 11, 12]: two or more miscarriages of clinical pregnancies [7]; three or more miscarriages of the first trimester or one or more miscarriages of the second trimester; three or more miscarriages <14 weeks [1, 11, 12]. Frequency appearance is of quite large (1 in every 300 pregnancies).

Recurrent miscarriages (frequency 1–3% among couples of reproductive age) usually occur during the first trimester and relative risk increases with the number of previous miscarriages [1, 11, 12]. Consequently, after the first miscarriage, this risk reaches 24%, after the second one to 26% and after the third it amounts to 32% [1, 11, 12]. About 10–15% of all clinical recognized pregnancies are aborted and the theoretical risk for three consecutive pregnancy losses is 0.34% [1, 11, 12].

Receiving history includes:


The possibility to predict the risk of recurrence depends on several factors like as maternal age, fetal parental karyotypes gestational age, presence of various maternal laboratory findings [1, 11, 12].

About 80% of abortions occur during the first trimester, 50–60% of them are based on genetic abnormalities. The risk of pregnancy loss is 2–5% after the recognition of heart function, 5% for women who report two miscarriages and finally 1% of women mentioning more than three miscarriages [1, 11, 12].

**61**

*Abortions in First Trimester Pregnancy, Management, Treatment*

Investigation of recurrent pregnancy loss (RPL) begins with personal history, followed by laboratory, genetic, hormonal, anatomic, immunologic, thrombophilic factors and infective reasons that can affect pregnancy outcome. It is quite often that 2 or more factors coexist [11–20]. In half of cases, etiology cannot be identified, so it is described as "Recurrent miscarriages of unknown etiology" [1, 11, 16].

During the clinical examination, a gynecological examination and a check for

hyperandrogenemia and hyperprolactinemia signs should be done [1, 17].

• Control of progesterone levels in the middle of the luteal phase cycle

• Check the levels of FSH,LH,PRL and testosterone (2–5th day of period)

It is of great importance in thrombophilia examinations control to include V

Anatomical abnormalities that can cause miscarriages are typically recognized using hydrosonohysterography (HSG), hysteroscopy, laparoscopy, possible in same

Congenital anomalies malformations of the female reproductive tract uterine anatomical abnormalities, such as bicornuate uterus or uterine diaphragm, polyps, heart-shaped ultrasound fibroids are results from failure completion of bilateral

Especially with regard to fibroids, they may block the development of early pregnancy, but their influence on spontaneous abortions is also affected by other factors such as age and hormonal disorders. Müllerian anomalies occurred in 8–10% of women, who had three or more consecutive spontaneous abortions. The fibromuscular tissue in septate uterus is poorly vascularized fibromuscular tissue that is associated with the highest pregnancy loss rate in some studies reporting an average of 65%. Except the above-mentioned abnormality, high frequency for pregnancy

Intrauterine adhesions (Asherman syndrome) are acquired uterine defect resulting from infection, endometritis and unsuccessful curettage, which is associated with recurrent miscarriage, oligomenorrhea and amenorrhea and bad prognosis.

cases magnetic resonance and recently three-dimensional ultrasonography.

duct elongation, fusion, septal resorption of müllerian ducts [13–15].

loss is noticed in didelphys, bicornuate and unicornuate uterus [13–15].

*DOI: http://dx.doi.org/10.5772/intechopen.86194*

**2. Clinical examination**

**3. Laboratory check**

• Karyotype in couple

• Anticardiolipins and LA

**4. Anatomical factors**

A laboratory control includes:

• Hysteroscopy or hysterosalpingography (HSG)

• TVS (transvaginal ultrasound) [1, 13–20].

Leiden factor and prothrombin 20210 mutation [1, 15–20].

*Abortions in First Trimester Pregnancy, Management, Treatment DOI: http://dx.doi.org/10.5772/intechopen.86194*

Investigation of recurrent pregnancy loss (RPL) begins with personal history, followed by laboratory, genetic, hormonal, anatomic, immunologic, thrombophilic factors and infective reasons that can affect pregnancy outcome. It is quite often that 2 or more factors coexist [11–20]. In half of cases, etiology cannot be identified, so it is described as "Recurrent miscarriages of unknown etiology" [1, 11, 16].

#### **2. Clinical examination**

*Induced Abortion and Spontaneous Early Pregnancy Loss - Focus on Management*

endocrine, autoimmune factors or infections exclusion [1–5].

appearance is of quite large (1 in every 300 pregnancies).

• the gestational age of spontaneous abortions

More than 80% of miscarriages occur up to 12 weeks. The percentage of clinically recognized abortions (appeared after 6th week) is estimated to be 12–15%. More analytically, 2 miscarriages occurred in 5% of women and ≥3 miscarriages in 1–3% of women [1–5]. Recurrent miscarriages consist of a serious problem for women with physical and psychological consequences. Abortions and especially recurrent miscarriages are considered as heterogeneous groups in regard to etiology [1–5]. Two or more causes can coexist, whereas about 50% of cases are characterized as idiopathic as a result of genetic, anatomical, endocrine, genetic, anatomical,

The number of clinically recognized miscarriages to total number of pregnancies is about 10–15%, while the equivalent of early abortions based only on human chorionic gonadotropin (hCG) measurements is actually much higher (50–60%) and interestingly before and after the implantation it is 30% but are not perceived

A positive correlation has been identified between the mother's biological age and the incidence rate of spontaneous abortions. So, a progressive increase of 10-fold afterwards the age of 40 is observed compared to younger women aged

Regarding the gestational age in first trimester and the abortion risk, this counts to 4 and 2%, respectively, in 6th and 8th week of gestation [1, 6–10]. The risk of recurrence in the next pregnancy is minor except of cases diagnosed with congeni-

Recurrent miscarriages are defined as three or more consecutive embryos losses weighing under 500 g. According to bibliography we can find different definitions for miscarriages [1, 11, 12]: two or more miscarriages of clinical pregnancies [7]; three or more miscarriages of the first trimester or one or more miscarriages of the second trimester; three or more miscarriages <14 weeks [1, 11, 12]. Frequency

Recurrent miscarriages (frequency 1–3% among couples of reproductive age) usually occur during the first trimester and relative risk increases with the number of previous miscarriages [1, 11, 12]. Consequently, after the first miscarriage, this risk reaches 24%, after the second one to 26% and after the third it amounts to 32% [1, 11, 12]. About 10–15% of all clinical recognized pregnancies are aborted and the

theoretical risk for three consecutive pregnancy losses is 0.34% [1, 11, 12].

• the certification in the presence of embryonic pole and heart function

• the symptoms related to the antiphospholipid syndrome and family history of

The possibility to predict the risk of recurrence depends on several factors like as maternal age, fetal parental karyotypes gestational age, presence of various mater-

About 80% of abortions occur during the first trimester, 50–60% of them are based on genetic abnormalities. The risk of pregnancy loss is 2–5% after the recognition of heart function, 5% for women who report two miscarriages and finally 1%

of women mentioning more than three miscarriages [1, 11, 12].

**60**

[1, 6–10].

<35 years [1, 6–10].

tal uterine abnormalities [1, 6–10].

Receiving history includes:

automatic abortions

nal laboratory findings [1, 11, 12].

**1.1 Recurrent miscarriages**

During the clinical examination, a gynecological examination and a check for hyperandrogenemia and hyperprolactinemia signs should be done [1, 17].

#### **3. Laboratory check**

A laboratory control includes:


It is of great importance in thrombophilia examinations control to include V Leiden factor and prothrombin 20210 mutation [1, 15–20].

#### **4. Anatomical factors**

Anatomical abnormalities that can cause miscarriages are typically recognized using hydrosonohysterography (HSG), hysteroscopy, laparoscopy, possible in same cases magnetic resonance and recently three-dimensional ultrasonography.

Congenital anomalies malformations of the female reproductive tract uterine anatomical abnormalities, such as bicornuate uterus or uterine diaphragm, polyps, heart-shaped ultrasound fibroids are results from failure completion of bilateral duct elongation, fusion, septal resorption of müllerian ducts [13–15].

Especially with regard to fibroids, they may block the development of early pregnancy, but their influence on spontaneous abortions is also affected by other factors such as age and hormonal disorders. Müllerian anomalies occurred in 8–10% of women, who had three or more consecutive spontaneous abortions. The fibromuscular tissue in septate uterus is poorly vascularized fibromuscular tissue that is associated with the highest pregnancy loss rate in some studies reporting an average of 65%. Except the above-mentioned abnormality, high frequency for pregnancy loss is noticed in didelphys, bicornuate and unicornuate uterus [13–15].

Intrauterine adhesions (Asherman syndrome) are acquired uterine defect resulting from infection, endometritis and unsuccessful curettage, which is associated with recurrent miscarriage, oligomenorrhea and amenorrhea and bad prognosis.

Recommended treatment in these cases includes balloon catheter, administration of estrogen and progestin medication [1, 16–18].

Uterine cavity abnormalities including submucosal, intramural >40 myomas, polyps are associated to poorly vascularization of endometrium led to failure of implantation, placenta tissue development and contribute to pregnancy loss. Cervical insufficiency is described as an acquired uterine anomaly, which is depending in painless cervical dilatation, effacement and inability of the uterine cervix to retain the amniosac is the commonest reason for abortion in the second trimester [16–18]. Exposure of the embryo in diethylstilbestrol DES and a variety of environmental factors like thalidomide, infectious agents and ionizing radiation affects the uterine morphology by triggering changes in both the location and amount of HOXA/Hoxa expression in the development of Müllerian ducts. No prospective studies exist. The HOXA genes along the Müllerian ducts, influencing the development of Müllerian ducts are: HOXA9 Oviduct, HOXA10, HOXA11 Uterus, HOXA11, HOXA13 Cervix and HOXA13 Upper vagina [1, 19–21].

## **5. Chromosomal abnormalities**

Genetics reasons of recurrent pregnancy loss be subdivided in embryo abnormalities resulting of known parental genetic pathology and embryo aneuploidy in parents to be chromosomally normal A variety of genetic factors including aneuploidy (gain or loss of a chromosomal), chromosomal imbalance resulting from harbored translocations, inversions, deletions, duplications within chromosomes, single gene mutations led to recurrent pregnancy loss (RPL) [1, 22–33]. In 3–5% of couples with RPL, the ratio of parental chromosome abnormalities in contrast to the general population is 0.7%. The most common chromosomal abnormalities leading to RPL are balanced translocations. The first chromosomally abnormal abortion was reported in 1961. Chromosomal abnormality is approximately responsible for half of the clinically diagnosed abortions in the first trimester. About 50% of them are autosomal trisomy, 20% monosomy XO, 20% polyploidy and 10% variety of other abnormalities [33–35].

#### **5.1 Karyotype examinations in aborted fetus**


About 25% of cases exist in the first trimester, in which although the embryos are normal and euploid, they cannot develop properly. The reasons include women with müllerian agenesis and other significant anatomic abnormalities. In the second trimester, the abortion incidence due to a chromosomal abnormality is <20%. Structural chromosome abnormalities (Robertson-type balancing and translocations).

X-inactivation chromosome (?)

aneuploidy of spermatozoa (?).

Recurrent abortion (RA) as well as repeated IVF failure (RIF) has a common underlying factor which is the significant increase in the rate of chromosomal abnormality [35]. The results also suggest that in women with recurrent abortions,

**63**

*Abortions in First Trimester Pregnancy, Management, Treatment*

ization and biopsy of embryo blastocyst are widely used [34–36].

the transfer of normal embryos improves the pregnancy rate and live-birth rate in both younger and older women. In these cases, preimplantation genetic diagnosis is recommended, testing for structural chromosomal aberrations like translocations, inversions, removing cells from the resultant embryo or oocyte evaluating the cells for genetic abnormalities and determine the optimal embryos for uterine transfer [35–37]. Last year, novel technologies like microarrays, fluorescence in situ hybrid-

Women with RPL have reproductive difficulties because they are concerned about various toxins and agents within the environment. It is of great importance to counseling these couples in health care institutions to have current and accurate information and to avoid exposures to these substances [37, 38]. The rate of spontaneous abortion is positively associated to cigarette smoking, alcohol consumption, obesity, body mass index (BMI, weight in kilograms divided by square of height in

In some case, a failure to activate a normal control mechanism to prevent an immune reaction against self is observed and this subsequently led to autoimmune response. Natural killer cells are attached to the cytotrophoblast of the embryo. However, the mechanism by which such cells may or may not affect the embryo is not proven. When implantation occurs, there is a slight inflammatory response. Patient with infertility and recurrent miscarriages develop less prominent reaction that may prevent the embryo from implanting [39, 40]. Autoimmune abortions are thought to be caused by the presence of autoantibodies that already exist in the woman against membrane phospholipids, thyroid antigens, nuclear antigens, syncytiotrophoblast cells or against other organelles

About 10–15% of all women have antinuclear antibodies regardless of medical history of RPL. In cases of presence of antinuclear antibodies, the possibility of successful pregnancy outcome is independent of antibodies existence [39, 40]. Autoimmune factors causing RPL are: antiphospholipid antibody syndrome, aPL antibodies (anticardiolipin antibodies and lupus anticoagulant), ß2 glycoprotein antibodies, phosphatidyl serine. Antibody hemeostasis in systemic circulation is different between men and women, just because women need to be better equipped, so that they can cope with the required immune tolerance in fetal anti-

The "thermostat" is therefore positioned higher in women, as a result, autoimmune diseases have much higher incidence in women. If autoantibodies are found in relation to a pathological condition, this means: whether they are the pathogenetic factors of the disease (autoimmune hemolytic anemia); whether it is the result of a previous pathological process (autoantibodies against cardiac muscle after its destruction) and whether they are causative agents without damaging themselves,

If the antibodies are present in the mother's serum as a result of allogeneic stimulation during pregnancy, then they are not considered to be autoantibodies unless they exist previously [40, 41]. Until now, there is no common point of

, caffeine intake (excess of 300 mg/day) and ionizing radiation

*DOI: http://dx.doi.org/10.5772/intechopen.86194*

**5.2 Lifestyle and environment**

meters) >30 kg/m2

or tissues [39, 40].

gens derived from them [39, 40].

which is the most common, as is believed [40, 41].

**6. Immunological factors**

[37, 38].

*Abortions in First Trimester Pregnancy, Management, Treatment DOI: http://dx.doi.org/10.5772/intechopen.86194*

the transfer of normal embryos improves the pregnancy rate and live-birth rate in both younger and older women. In these cases, preimplantation genetic diagnosis is recommended, testing for structural chromosomal aberrations like translocations, inversions, removing cells from the resultant embryo or oocyte evaluating the cells for genetic abnormalities and determine the optimal embryos for uterine transfer [35–37]. Last year, novel technologies like microarrays, fluorescence in situ hybridization and biopsy of embryo blastocyst are widely used [34–36].

#### **5.2 Lifestyle and environment**

*Induced Abortion and Spontaneous Early Pregnancy Loss - Focus on Management*

estrogen and progestin medication [1, 16–18].

**5. Chromosomal abnormalities**

and 10% variety of other abnormalities [33–35].

**5.1 Karyotype examinations in aborted fetus**

• No need for molecular karyotype

• No need for microdeletions control

X-inactivation chromosome (?) aneuploidy of spermatozoa (?).

• Karyotype in couple

Recommended treatment in these cases includes balloon catheter, administration of

Uterine cavity abnormalities including submucosal, intramural >40 myomas, polyps are associated to poorly vascularization of endometrium led to failure of implantation, placenta tissue development and contribute to pregnancy loss. Cervical insufficiency is described as an acquired uterine anomaly, which is depending in painless cervical dilatation, effacement and inability of the uterine cervix to retain the amniosac is the commonest reason for abortion in the second trimester [16–18]. Exposure of the embryo in diethylstilbestrol DES and a variety of environmental factors like thalidomide, infectious agents and ionizing radiation affects the uterine morphology by triggering changes in both the location and amount of HOXA/Hoxa expression in the development of Müllerian ducts. No prospective studies exist. The HOXA genes along the Müllerian ducts, influencing the development of Müllerian ducts are: HOXA9 Oviduct, HOXA10, HOXA11 Uterus, HOXA11, HOXA13 Cervix and HOXA13 Upper vagina [1, 19–21].

Genetics reasons of recurrent pregnancy loss be subdivided in embryo abnormalities resulting of known parental genetic pathology and embryo aneuploidy in parents to be chromosomally normal A variety of genetic factors including aneuploidy (gain or loss of a chromosomal), chromosomal imbalance resulting from harbored translocations, inversions, deletions, duplications within chromosomes, single gene mutations led to recurrent pregnancy loss (RPL) [1, 22–33]. In 3–5% of couples with RPL, the ratio of parental chromosome abnormalities in contrast to the general population is 0.7%. The most common chromosomal abnormalities leading to RPL are balanced translocations. The first chromosomally abnormal abortion was reported in 1961. Chromosomal abnormality is approximately responsible for half of the clinically diagnosed abortions in the first trimester. About 50% of them are autosomal trisomy, 20% monosomy XO, 20% polyploidy

About 25% of cases exist in the first trimester, in which although the embryos

Recurrent abortion (RA) as well as repeated IVF failure (RIF) has a common underlying factor which is the significant increase in the rate of chromosomal abnormality [35]. The results also suggest that in women with recurrent abortions,

are normal and euploid, they cannot develop properly. The reasons include women with müllerian agenesis and other significant anatomic abnormalities. In the second trimester, the abortion incidence due to a chromosomal abnormality is <20%. Structural chromosome abnormalities (Robertson-type balancing and

**62**

translocations).

Women with RPL have reproductive difficulties because they are concerned about various toxins and agents within the environment. It is of great importance to counseling these couples in health care institutions to have current and accurate information and to avoid exposures to these substances [37, 38]. The rate of spontaneous abortion is positively associated to cigarette smoking, alcohol consumption, obesity, body mass index (BMI, weight in kilograms divided by square of height in meters) >30 kg/m2 , caffeine intake (excess of 300 mg/day) and ionizing radiation [37, 38].

#### **6. Immunological factors**

In some case, a failure to activate a normal control mechanism to prevent an immune reaction against self is observed and this subsequently led to autoimmune response. Natural killer cells are attached to the cytotrophoblast of the embryo. However, the mechanism by which such cells may or may not affect the embryo is not proven. When implantation occurs, there is a slight inflammatory response. Patient with infertility and recurrent miscarriages develop less prominent reaction that may prevent the embryo from implanting [39, 40]. Autoimmune abortions are thought to be caused by the presence of autoantibodies that already exist in the woman against membrane phospholipids, thyroid antigens, nuclear antigens, syncytiotrophoblast cells or against other organelles or tissues [39, 40].

About 10–15% of all women have antinuclear antibodies regardless of medical history of RPL. In cases of presence of antinuclear antibodies, the possibility of successful pregnancy outcome is independent of antibodies existence [39, 40].

Autoimmune factors causing RPL are: antiphospholipid antibody syndrome, aPL antibodies (anticardiolipin antibodies and lupus anticoagulant), ß2 glycoprotein antibodies, phosphatidyl serine. Antibody hemeostasis in systemic circulation is different between men and women, just because women need to be better equipped, so that they can cope with the required immune tolerance in fetal antigens derived from them [39, 40].

The "thermostat" is therefore positioned higher in women, as a result, autoimmune diseases have much higher incidence in women. If autoantibodies are found in relation to a pathological condition, this means: whether they are the pathogenetic factors of the disease (autoimmune hemolytic anemia); whether it is the result of a previous pathological process (autoantibodies against cardiac muscle after its destruction) and whether they are causative agents without damaging themselves, which is the most common, as is believed [40, 41].

If the antibodies are present in the mother's serum as a result of allogeneic stimulation during pregnancy, then they are not considered to be autoantibodies unless they exist previously [40, 41]. Until now, there is no common point of the effect of pregnancy on the production of autoantibodies. Although no clear increase in autoantibodies has been found during normal pregnancy, an increase in some of them has been reported in pathological pregnancies, most of which have been described as antiphospholipid antibodies [40, 41]. In the group of recurrent miscarriages, 15% were certified positive findings for the lupus anticoagulant or antiphospholipid antibodies or both of them. It is important to notice that lupus anticoagulant is not synonymous with systemic lupus erythematosus (SLE), where it is found in only 5–15% [40, 41].

#### **6.1 Antiphospholipid antibodies**

Antiphospholipid antibodies (APAs) are a family of immunoglobulins which react with anions of phospholipids or anions of phospholipid-protein complexes in the cell membrane of the syncytiotrophoblast [1, 41, 42].

The finding of aPL antibodies is associated to adverse pregnancy outcomes such inducing vessel thrombosis of the surrounding placental maternal unit, placenta infarction, and fetal death. The primary mechanism in the first trimester depends on a deleterious effect directly on trophoblastic cells, inhibition of secretion of human placental chorionic gonadotropin, and the expression of trophoblast cell adhesion molecules (a1, a5 integrins, E, VE-cadherins). The most widely used are anti-cardiolipin (diphosphatidyl-glycerol) [1, 41, 42].

Others are anti-phosphatidylserine anti-phosphatidylethanolamine, antiphosphatidylcholine, anti-phosphatidylinositol, and phosphatidic acid. Large variation in APHA measurements between laboratories and in the same laboratory for the same patient and great fluctuation in the values during pregnancy are observed.

It is questionable whether the same or other substnces (anti-β2-glycoprotein I) have similar impact according to recurrent pregnancy loss [42–45].

Possible action of APAs on miscarriages:

Abnormalities in endothelial cell function of vessels (decrease in production of arachidonic acid prostacyclin and a relative increase of thromboxane which is a potent vasoconstrictor and promotes platelet aggregation).

Obstructive angiopathy (reaction with anion phospholipids exposed after vessel damage).

Platelet stimulation and/or adhesion (in damaged platelets, APAs bind phosphatidylserine to the structural element of the inner membrane of the platelets and promote platelet aggregation and thrombus formation).

Placental infarction (microscopic arterial thrombosis and necrotic fibrous deposition have been found). It also appears to be due to reduced flow in the vessels, as has been found to occur in the umbilical and maternal arteries in patients with lupus or APS. This situation resembles a destruction of the vessels through antibodies after heart transplantation, coronary bypass, or angioplasty [42–45].

Inhibition of protein C stimulation in S. These two proteins, after their activation, inactivate clotting factors Va and VIIa. Stimulating their stimulation creates an increased tendency for coagulation.

Reduction of levels of annexin V, a protein with potent antithrombotic effect on the surface between trophoblast and endothelial cells.

Effect on placental function: (ACA inhibits the secretion of gonadotropin secretion from placenta, which can act on the secretion of hormones from the placenta, negatively affecting the viability of the fetus).

Phospholipids bind to the surface of trophoblast, and this results in direct destruction of cells, inhibition of syncytia formation, decrease of hCG production and defective penetration into maternal peristalsis.

**65**

*Abortions in First Trimester Pregnancy, Management, Treatment*

Antiphospholipid syndrome: high levels of antiphospholipid antibodies and history of miscarriages and/or endometrial death and/or thrombosis—risk of autoim-

Vascular thrombosis (one or more clinical episodes of venous, arterial, or small

Gestational complications (one or more recurrent miscarriages after the 10th week of gestation, one or more preterm births and one or more recurrent miscar-

Laboratory criteria: cardiolipin antibodies (IgG or IgM anti-cardiolipins, at moderate or high levels in two or more measurements over a period of at least

Lupus anticoagulant (in two or more measurements at least 6 weeks apart)

Steroids (complications: pregnancy and prematurity) are not recommend based on current publication evidence. It is reported that the maternal and fetal complications increase without affecting the pregnancy outcome and live births [43–47].

It may prevent recycling in the circulation of cardiolipins or suspend the discharge

It appears that combining aspirin and heparin has the best results. Patients should

start taking heparin as early as possible when pregnant and continue until labor and during puerperium [42–50]. Combination of aspirin and heparin is associated with better results. Heparin subcutaneously, for example, low molecular weight heparin one injection per day may prevent recycling of circulating anti-cardiolipins or suppress the secretion of embryotoxic agents or HLA-related agents. It also reduces the percentage of NK (CD56+/CD16+) cells [46–50]. It has been associated with gestational hypertension and diabetes mellitus and mainly with premature labor and low birth weight neonates. Combination of aspirin with heparin, aspirin

of embryo toxic factors or factors associated with HLA. In addition, it lowers NK (CD56+/CD16+) cell percentage. It has been associated with pregnancy hypertension, diabetes mellitus, and mainly with premature labor and low-weight new-born babies. Aspirin should be given preconceptually. **Aspirin in low dosage** (80–100 mg daily) may suspend cyclooxygenase (COX) action on platelets, by suspending the composition of thromboxane thrombosis and thus preventing vascular thrombosis in placental blood vessels. At discontinuance after around 32 weeks, heparin (does not pass the placenta) should be started after the first positive pregnancy test and should be continued until of labor to avoid thrombosis risk: hypo-heparin, for example, **heparin of low molecular weight,** one injection daily. Anticoagulant action (reinforces the action of antithrombin III), while it may bind AFAs, thus prevents chorionic villus sampling (CVS) phospholipids from being destroyed, by assisting in the successful implantation in the early stages of pregnancy [43–47]. Thrombocytopenia and osteoporosis check-up. Discontinuation after 34 weeks of pregnancy and prior to

*DOI: http://dx.doi.org/10.5772/intechopen.86194*

mune in subsequent pregnancy ~90% [46, 47].

vessel thrombosis in any tissue or organ).

riages before the 10th week of gestation).

**7. Antiphospholipid syndrome: management**

**7.1 Prednisolone, between 10 and 20 mg daily dosage**

**6.2 Autoimmune factors**

**6.3 Clinical criteria**

6 weeks between them).

giving birth. **(Now in labor)**.

[44–47].

## **6.2 Autoimmune factors**

*Induced Abortion and Spontaneous Early Pregnancy Loss - Focus on Management*

it is found in only 5–15% [40, 41].

**6.1 Antiphospholipid antibodies**

are observed.

damage).

the cell membrane of the syncytiotrophoblast [1, 41, 42].

anti-cardiolipin (diphosphatidyl-glycerol) [1, 41, 42].

Possible action of APAs on miscarriages:

increased tendency for coagulation.

the effect of pregnancy on the production of autoantibodies. Although no clear increase in autoantibodies has been found during normal pregnancy, an increase in some of them has been reported in pathological pregnancies, most of which have been described as antiphospholipid antibodies [40, 41]. In the group of recurrent miscarriages, 15% were certified positive findings for the lupus anticoagulant or antiphospholipid antibodies or both of them. It is important to notice that lupus anticoagulant is not synonymous with systemic lupus erythematosus (SLE), where

Antiphospholipid antibodies (APAs) are a family of immunoglobulins which react with anions of phospholipids or anions of phospholipid-protein complexes in

The finding of aPL antibodies is associated to adverse pregnancy outcomes such inducing vessel thrombosis of the surrounding placental maternal unit, placenta infarction, and fetal death. The primary mechanism in the first trimester depends on a deleterious effect directly on trophoblastic cells, inhibition of secretion of human placental chorionic gonadotropin, and the expression of trophoblast cell adhesion molecules (a1, a5 integrins, E, VE-cadherins). The most widely used are

Others are anti-phosphatidylserine anti-phosphatidylethanolamine, antiphosphatidylcholine, anti-phosphatidylinositol, and phosphatidic acid. Large variation in APHA measurements between laboratories and in the same laboratory for the same patient and great fluctuation in the values during pregnancy

It is questionable whether the same or other substnces (anti-β2-glycoprotein I)

Abnormalities in endothelial cell function of vessels (decrease in production of arachidonic acid prostacyclin and a relative increase of thromboxane which is a

Platelet stimulation and/or adhesion (in damaged platelets, APAs bind phosphatidylserine to the structural element of the inner membrane of the platelets and

Placental infarction (microscopic arterial thrombosis and necrotic fibrous deposition have been found). It also appears to be due to reduced flow in the vessels, as has been found to occur in the umbilical and maternal arteries in patients with lupus or APS. This situation resembles a destruction of the vessels through antibod-

Inhibition of protein C stimulation in S. These two proteins, after their activation, inactivate clotting factors Va and VIIa. Stimulating their stimulation creates an

Reduction of levels of annexin V, a protein with potent antithrombotic effect on

Effect on placental function: (ACA inhibits the secretion of gonadotropin secretion from placenta, which can act on the secretion of hormones from the placenta,

Phospholipids bind to the surface of trophoblast, and this results in direct destruction of cells, inhibition of syncytia formation, decrease of hCG production

ies after heart transplantation, coronary bypass, or angioplasty [42–45].

Obstructive angiopathy (reaction with anion phospholipids exposed after vessel

have similar impact according to recurrent pregnancy loss [42–45].

potent vasoconstrictor and promotes platelet aggregation).

promote platelet aggregation and thrombus formation).

the surface between trophoblast and endothelial cells.

negatively affecting the viability of the fetus).

and defective penetration into maternal peristalsis.

**64**

Antiphospholipid syndrome: high levels of antiphospholipid antibodies and history of miscarriages and/or endometrial death and/or thrombosis—risk of autoimmune in subsequent pregnancy ~90% [46, 47].

## **6.3 Clinical criteria**

Vascular thrombosis (one or more clinical episodes of venous, arterial, or small vessel thrombosis in any tissue or organ).

Gestational complications (one or more recurrent miscarriages after the 10th week of gestation, one or more preterm births and one or more recurrent miscarriages before the 10th week of gestation).

Laboratory criteria: cardiolipin antibodies (IgG or IgM anti-cardiolipins, at moderate or high levels in two or more measurements over a period of at least 6 weeks between them).

Lupus anticoagulant (in two or more measurements at least 6 weeks apart) [44–47].
