**7. Antiphospholipid syndrome: management**

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].

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

It may prevent recycling in the circulation of cardiolipins or suspend the discharge 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 giving birth. **(Now in labor)**.

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

with prednisolone, or all three is associated to satisfactory results. It seems that the combination of aspirin and heparin works best. Heparin should be started as soon as possible in pregnancy and should be maintained until the labor and postpartum especially when the risk of thrombosis is high [42–50]. Intravenous immunoglobulin therapy IVIG (no superior to the combination of aspirin and heparin) Intravenous injection of high doses of gamma globulin (300–500 mg/kg body weight). An increase inT-immunosuppressive cells, decreases the activity of natural killer cells, inhibition of transport by the mother's placenta of IgG, inhibition of Fc receptors in macrophages and, especially, multivalent immunosuppression. To avoid the adverse reactions of heparin therapy, it is recommended to add calcium 600 mg twice daily and vitamin D supplementation 400 IU daily to decrease the osteoporosis risk. The platelet count should be weekly examined in the first two weeks after treatment with heparin because bleeding could occur due to heparin induced thrombocytopenia [42–50].

### **8. Endocrine factors**

Mentioned here are polycystic ovary syndrome (PCOS) due to high levels of luteinizing hormone (LH), corpus luteum (CL) deficiency, nonregulated diabetes mellitus during conception period, thyroid malfunction, thrombophilic factors, alloimmunological factors: PCOS, menstrual complications, hypertrichosis, polycystic ovaries, and resistance to insulin. The contribution of endocrinological factor as reasons of RPL including luteal phase deficiency, untreated hypothyroidism, abnormal glucose metabolism hyperprolactinemia, and diminished ovarian reserve is average by 8–12% [51–54].

#### **8.1 Corpus luteum deficiency**

Corpus luteum malfunction association with RPLs still remains a hypothesis, despite the fact that there are studies that reveal that it is responsible for 12–28% of cases. Luteal phase deficiency is defined as an inability of the corpus luteum to secrete progesterone either in increased satisfactory amounts or for too short duration. This inability to function is established by alteration of preovulatory estrogen stimulation, which led to poor oocyte quality and a poorly functioning corpus luteum. The diagnosis should be confirmed either with endometrial biopsy which is not recommended as diagnostic modality or if serum progesterone levels are <10 ng/ml [51–54]. Strategy of treatments of corpus luteum malfunction has a wide variation and includes administration of progesterone or human chorionic gonadotropin induction or a combination of these. Progesterone administration either as intravaginal suppositories 50–100 mg or as intramuscular injections 50 mg IM is considered necessary only within RCTs [51–54].

#### **8.2 Hyperprolactinemia**

Hyperprolactinemia is an endocrinopathy which led to infertility and abortions due to anovulation. It is not clear whether it is associated with RPLs. Increased prolactin levels interact with the hypothalamic pituitary ovarian axis, reducing the folliculogenesis or leading to a small duration of luteal phase. Studies reveal that it affects progesterone discharge at luteal stage; however, this situation has not been confirmed in humans. A randomized control trial including 64 hyperprolactinemic women with RPL treated with bromocriptine was associated with a higher rate of successful pregnancy, whereas PRL levels were significantly higher in women that miscarried (85.7 vs. 52.4%) [55–58].

**67**

**8.8 PCOS**

*Abortions in First Trimester Pregnancy, Management, Treatment*

tinemia and a history of recurrent miscarriage [55–57].

outcome and is it safe in the first trimester [55–57].

Currently, there is no sufficient evidence for effectiveness of dopamine agonist evaluation in preventing future miscarriage in women with idiopathic hyperprolac-

Women with nonregulated DM I: diabetes mellitus (DM) in women with RPLs is associated with a higher incidence of spontaneous abortions in relation to women with euglycemic metabolism preconceptually. A well controlled diabetes mellitus decreases the rates of recurrent pregnancy loss. Testing for fasting insulin and glucose and hemoglobin A1c usually have an increased modality for the evaluation of insulin resistance. The metformin administration seems to improve pregnancy

It is well known that hypothyroidism without therapy increases the risk of abortion. Treatment before attempting a pregnancy is clearly recommend as well as keeping a TSH level between 1.0–2.5 UIU/ml in the first trimester. In cases with TSH levels higher than 2.5 MIU/ml, levothyroxine should be started at a minimum

Anti-thyroid Abs is associated with RPLs when detected before the start of

• Increased NK cell levels in the secretory phase of endometrium

• Higher levels in NK cells during the endometrium secretory phase. Strong association between maternal type Th2-cell immunity and successful pregnancy outcome. Recurrent abortions: associated with immunity type Th1 (lF-γ,

Increased levels of FSH in the early follicular phase of menstrual cycle are significant for diminished ovarian reserve. In the least years, another marker antimüllerian hormone is better to identify the number of follicular units for recruitment. It is recommended that women with RPL visit healthcare services to have appropriate

Polycystic ovary syndrome (PCOS) is associated with increased frequency of RPL and has an uncertain prevalence, because factors associated with PCOS such as obesity, insulin resistance, LH rise, and hyperandrogenemia may be the

Hypothyroidism is involved with obstetric complications like infertility, abortions, anemia, preeclampsia, placental abruption, fetal death, preterm birth, and

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

**8.3 Dopamine agonists**

**8.4 Diabetes mellitus**

**8.5 Thyroid gland disorders**

pregnancy or at an early stage.

**8.6 Alloimmune dysfunction**

• Elevated CD56+ lymphocyte levels

low birth weight [55–58].

TNF, lL-12, 58)

**8.7 Diminished ovarian reserve**

counselling to treat endocrinological disorders [59].

dose of 50 μg/d.

## **8.3 Dopamine agonists**

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

**8. Endocrine factors**

is average by 8–12% [51–54].

**8.1 Corpus luteum deficiency**

**8.2 Hyperprolactinemia**

miscarried (85.7 vs. 52.4%) [55–58].

IM is considered necessary only within RCTs [51–54].

with prednisolone, or all three is associated to satisfactory results. It seems that the combination of aspirin and heparin works best. Heparin should be started as soon as possible in pregnancy and should be maintained until the labor and postpartum especially when the risk of thrombosis is high [42–50]. Intravenous immunoglobulin therapy IVIG (no superior to the combination of aspirin and heparin) Intravenous injection of high doses of gamma globulin (300–500 mg/kg body weight). An increase inT-immunosuppressive cells, decreases the activity of natural killer cells, inhibition of transport by the mother's placenta of IgG, inhibition of Fc receptors in macrophages and, especially, multivalent immunosuppression. To avoid the adverse reactions of heparin therapy, it is recommended to add calcium 600 mg twice daily and vitamin D supplementation 400 IU daily to decrease the osteoporosis risk. The platelet count should be weekly examined in the first two weeks after treatment with heparin because bleeding could occur due to heparin induced thrombocytopenia [42–50].

Mentioned here are polycystic ovary syndrome (PCOS) due to high levels of luteinizing hormone (LH), corpus luteum (CL) deficiency, nonregulated diabetes mellitus during conception period, thyroid malfunction, thrombophilic factors, alloimmunological factors: PCOS, menstrual complications, hypertrichosis, polycystic ovaries, and resistance to insulin. The contribution of endocrinological factor as reasons of RPL including luteal phase deficiency, untreated hypothyroidism, abnormal glucose metabolism hyperprolactinemia, and diminished ovarian reserve

Corpus luteum malfunction association with RPLs still remains a hypothesis, despite the fact that there are studies that reveal that it is responsible for 12–28% of cases. Luteal phase deficiency is defined as an inability of the corpus luteum to secrete progesterone either in increased satisfactory amounts or for too short duration. This inability to function is established by alteration of preovulatory estrogen stimulation, which led to poor oocyte quality and a poorly functioning corpus luteum. The diagnosis should be confirmed either with endometrial biopsy which is not recommended as diagnostic modality or if serum progesterone levels are <10 ng/ml [51–54]. Strategy of treatments of corpus luteum malfunction has a wide variation and includes administration of progesterone or human chorionic gonadotropin induction or a combination of these. Progesterone administration either as intravaginal suppositories 50–100 mg or as intramuscular injections 50 mg

Hyperprolactinemia is an endocrinopathy which led to infertility and abortions

due to anovulation. It is not clear whether it is associated with RPLs. Increased prolactin levels interact with the hypothalamic pituitary ovarian axis, reducing the folliculogenesis or leading to a small duration of luteal phase. Studies reveal that it affects progesterone discharge at luteal stage; however, this situation has not been confirmed in humans. A randomized control trial including 64 hyperprolactinemic women with RPL treated with bromocriptine was associated with a higher rate of successful pregnancy, whereas PRL levels were significantly higher in women that

**66**

Currently, there is no sufficient evidence for effectiveness of dopamine agonist evaluation in preventing future miscarriage in women with idiopathic hyperprolactinemia and a history of recurrent miscarriage [55–57].

## **8.4 Diabetes mellitus**

Women with nonregulated DM I: diabetes mellitus (DM) in women with RPLs is associated with a higher incidence of spontaneous abortions in relation to women with euglycemic metabolism preconceptually. A well controlled diabetes mellitus decreases the rates of recurrent pregnancy loss. Testing for fasting insulin and glucose and hemoglobin A1c usually have an increased modality for the evaluation of insulin resistance. The metformin administration seems to improve pregnancy outcome and is it safe in the first trimester [55–57].
