Efficacy of myo-inositol in the clinical management of patients with asthenozoospermia.

OBJECTIVE: The aim of this study was to analyze the effect of myo-inositol in combination with minerals and vitamin on sperm motility in patients affected by asthenozoospermia as index of Bulgarian population. PATIENTS AND METHODS: One-hundred-nine men aged between 18 and 50 years with reduced sperm motility identified by routine semen analysis were enrolled in this study. After excluding any urological problems, three months of treatment with a supplementation based on myo-inositol and other minerals and vitamins (Andrositol, MLD trading, Bulgaria) was prescribed. The sperm motility was evaluated by statistical analysis. RESULTS: A significant improvement in sperm motility was reported in 85.32% of the patients. Furthermore, the average motility was improved from 20.31% (SD ± 8.5) to 27.98 (SD ± 9.69) after the treatment. In particular, 38 of these patients restored a normal sperm motility (34.86% of the patients) while 14 patients (12.84%) didn't show any beneficial effect and, even if any side effects were reported, 2 patients (1.84%) showed a worsened the motility. CONCLUSIONS: A treatment with Andrositol significantly improved sperm motility, increasing the likelihood of achieving a spontaneous pregnancy.

[SEX HORMONE INFLUENCE ON PERIPHERAL NATURAL KILLER CELLS COUNT].

Proper evaluation of immunological factors connected with pregnancy establishment increased the possibility for exact treatment in high risk gestation cases. Hormonal changes during an ovarian cycle may affect immune response, which is crucial for the embryonic implantation. Peripheral Natural killer (pNK) cells are key components of immune systems and their activities could be regulated by sex hormones. In the present study we investigated the effects of estrogen fluctuation on the number of NK cells in vivo during the early follicular and middle luteal phase of menstrual cycle. In 63 healthy women with at least one full term pregnancy and regular menstrual cycle with duration between 24 and 32 days, blood samples have been collected twice for investigation of CD3/CD16/CD56 positive lymphocytes. The mean pNK count in follicular phase was 11.6% with 4.7% variation. The median was 10.6%. The mean pNK count in luteal phase was 12.1% with 5.1% variation, respectively median for cell number 11.8%. The two-tailed t-test comparison did not find any statistical difference despite the slight elevation of pNK cells count in luteal phase. The insignificant variation in pNK cells count objected the suggestion to evaluate immunological status in women with adverse pregnancy outcome in specific phase of menstrual cycle.

[ACTIVATION OF PERIPHERAL NATURAL KILLER CELLS IN WOMEN WITH REPEATED EARLY PREGNANCY LOSS].

The increased number of peripheral blood NK (pNK) cells has been discussed as a factor for embryo implantation failure and early pregnancy loss. However, the assessment of activated pNK cells with increased cytotoxic activity could be a distinct marker for immune dysregulation leading to pregnancy complications. CD69 membrane receptor expression has been measured by flow cytometry in different subtypes of pNK cells in 55 women with two or more pregnancy loss between six and twelve week of gestation with absence of any hormonal, anatomical or inherited cause for pregnancy loss and in 43 healthy women with at least one delivery at term and no history for reproductive failure. Increased expression of CD69 in CD56 positive pNK cells was found in the study group compared to controls (12.2% versus 6.5%, p<0.005). In addition, the subpopulation of CD56dim and CD56brightpNK cells in women with recurrent pregnancy loss showed increased percent of CD69 activation marker expression compared to controls (respectively 13.2% versus 7.2 p<0.005; and 4.6% versus 3.1% p=0.04). CD56brightCD16negative pNK cells (identical with those in uterine endometrium) in the investigated group has been found with higher CD69 expression compared to controls (3.3% versus 1.7%, p=0.03). Primary dysregulation in NK cells activity could be supposed in women with repeated early pregnancy loss without another underlined pathology. Investigation of active status of NK cells but not only NK cell count could be evaluation marker of impaired immunology regulation in early pregnancy development.

[Implication of PAI-1 4G/5G polymorphism in recurrent implantation failure after IVF].

During implantation, an accurate balance of coagulation, fibrin deposition and fibrinolysis is mandatory for trophoblastic invasion. Inhibition of fibrinolysis after increased activity of plasminogen activator inhibitors such as PAI-1 could impair properdeep trophoblastic invasion. This study investigated correlation between increased PAI-1 levels due to gene polymorphism (PL) 4G/5G and recurrent implantation failure after IVF procedure. Sixty one women with two or more unsuccessful IVF procedure after good quality embryo transfer and 97 health women with at least one normal delivery were investigated for carrier status for PL 4G/5G (genotype 4G/4G) and serum levels of anti-cardiolipin (ACA) and anti-beta2-glycoprotein antibody level (IgG and IgM type). The prevalence of genotype 4G/4G in women with RIF was about two times higher compared to controls although the difference did not rich significance (respectively 41% and 26.8%, OR 1.9, 95%CI 0.91-3.96, p=0.09). The prevalence of polymorphism was similar after exclusion of for women with elevated levels of ACA (respectively 42.1% and 26.8%, OR 1.99, 95%CI 0.94-4.21, p=0.075). PL 4G/5G could be possible risk factor forimpaired embryo implantation. The causative hypofibrinolysis due to increased PAI-1 levels should be interpreted in context of multifactor complexity of recurrent implantation failure development. A discussion remains for fraction heparin application and endometrial receptivity modulation in very early pregnancy wastage.

[Preplacentation pregnancy loss in cases of angiotensin-converting enzyme insertion/deletion polymorphism].

The balance between coagulation and fibrinolysis processes is critical for establishment and development of early pregnancy. Angiotensin-converting enzyme (ACE) is related with plasminogen activator inhibitor-1 activity which is a key regulator in embryo implantation. Therefor polymorphisms in ACE gene and variation in ACE activity could be associated with an early pregnancy wastage risk. This study investigated carrier status for insertion/deletion (I/D) polymorphism in introne 16 of ACE gene in 71 women with two or more pregnancy loss in preplacentation period (between 10 and 14 weeks of gestation) and 75 women without pregnancy complications. DD genotype for I/D polymorphism was found respectively in 31% and 24% in patients and controls. Heterozygosity of D allele was found correspondingly in 47.9% and 54.7%. The dominant genetic model was used for allele prevalence comparison. D allele in DD genotype was not significantly prevalent in women with early pregnancy wastage compared with the control subjects, OR = 1.42, 95% CI (0.64-3.15). The study found a weak association between I/D polymorphism and preplacentation pregnancy loss. The additive effect over the pregnancy loss risk of I/D polymorphism could be supposed in a presence of other inherited or acquired factors connected with endometrial receptivity and implantation process.

[A weak association of 677 C>T polymorphism in MTHFR with recurrent embryonic loss].

Early (embryonic) pregnancy loss before 10 week of gestation (wg) could also be related with endometrial receptivity as well as with gene expression regulation in developed embryo. Methylation of genome is a key process in the gene expression. Because the methylenetetrahydrofolate reductase (MTHFR) have had significant role in methionine metabolism polymorphisms into the gene could be related with early embryonic development. This study evaluated relationship between T allele in 677 C>T polymorphism in MTHFR and recurrent embryonic loss development. One hundred six women with tree or more pregnancy loss before 10 wg and 165 women without reproductive failure have been evaluated for 677 C>T carrier status. Sixteen (15.1%) of women with pregnancy loss have had TT genotype and 54 (50.9%) are heterozygous carriers for T allele. T allele frequency was higher but not significant differ from carrier status in control group (13.9% for TT genotype and 43.9% for CT OR and 95% CI respectively 1.1, 0.52-2.3 u 1.34, 0.8-2.26, p > 0.05). T allele (in homozygous and heterozygous carriers) was in higher but not significant prevalence in patients compared with controls (66% and 57.6% respectively, OR 1.43, 95% CI 0.84-2.46, p > 0.05), This study found a weak association between T allele carrier status (both in homozygous and heterozygous state) and recurrent embryonic loss development. T allele in 677 C>T polymorphism could be considered like an agent for early pregnancy wastage only in a constellation with other risk factors influencing embryonic development.

[Factor V Leiden in women with repeated IVF failures].

A plenty of factors have been connected with embryo implantation and further fetus development. Recurrent implantation failure (RIF) after assisted reproductive technology (ART) forces seeking the causes of decreased endometrial receptivity. A non-haemostatic function of thrombophilic mutations such as Factor V Leiden (FVL) was considered a factor related with endometrial receptivity. One hundred eighty eight women with two or more RIF after in vitro fertilization procedures investigated for carrier status for FVL was compared with carrier status of 97 women without reproductive failure who give a birth of at least one health child. There was no significant difference in carrier status for FVL in patients and controls (5.9% and 7.2% respectively, OR 0.80, 95% CI (0.26-2.73, p>0.05). Negligible higher prevalence of FVL was fond in health subjects compared with women with RIF A slightly positive relationship was found between FVL and embryo implantation. A preliminary determination of thrombophilic status in RIF women could specify needing or rejection of anticoagulant therapy during implantation period.

[Inherited thrombophilic factors in women with secondary infertility].

Because of the presence of additional confounding factors, such as cervical incompetence or uterine infections, the impact of inherited thrombophilia in women with second infertility has been hard to assess. The evaluation of the significance of the most common inherited thrombophilic factors - Factor V Leiden (FVL), prothrombin gene mutation 20210 G > A (FII), polymorphism (PL) 677 C > T in MTHFR, PL A1/A2 in platelet glycoprotein IIb/IIIa and PAL-1 PL 4G/5G in 35 women with two or more secondary (who have given birth to at least one child) recurrent pregnancy loss (RPL) before 14 weeks of gestation compared to 70 healthy women with no history of RPL and at least one uncomplicated full-term pregnancy, has been performed. Eight out of 35 women with secondary RPL (25.7%) and 6 out of 70 controls (8.6%) have had FVL or FII 20210 G > A (OR: 3.7, 95% CI: 1.05-13.2, p = 0.038). Five (14.3%) women with secondary infertility were carriers for FVL and four (11.4%) for FII 20210 G > A, corresponding to four (5.7%) and two (2.9%) of the women in the control group. The carrier status for MTHFR 677 C > T (TT genotype), PL A1/A2 and PL 4G/5G (4G/4G genotype) was as follows: 11.4%, 28% and 30.8% in patients and 14.3%, 17.1% and 24.3% in controls without significant difference between the groups. Despite of the presence of background factors, an appreciable role of inherited thrombophilia in secondary RPL was established, which enforces thrombophilia testing and management of women with second infertility as well as women with primary RPL.

[Platelet intregrin beta3 A1/A2 polymorphism in women with stillbirth].

Maternal thrombophilia was recently discussed as possible cause for pregnancy complication, although the roles of some coagulation factors have not been clarified. Carrier status for platelet integrin beta3 polymorphism A1/A2 (PL A1/A2) was considered as possible risk factor for pregnancy complication. Seventy women with one or more stillbirth (intrauterine fetal death after 20 week of gestation) and 100 healthy control subjects were evaluated for PL A1/A2 to assess the impact of polymorphism for late pregnancy loss. The prevalence for PL A1/A2 in women with stillbirth was higher but not significantly differs from carrier status in control subjects (respectively 28.3% and 17%, OR = 1.93; 95% CI: 0.84 - 4.45). After adjustment for carrier status for Factor V Leiden (FVL) and Prothrombin (FII) gene mutation 20210 G > A the prevalence of PL 1/A2 remains a similar (28.2% O R = 1.92; 95% Il: 0.78 - 4.75). Combined carriers status for PL A1/ A2 with FVL or III 20210 G > A have had significantly higher prevalence in investigated group comparing with control subjects (respectively 20% and 2%, p < 0.0001). An independent impact of PL A1/A2 on risk of stillbirth development is not be yet established but additive role of the polymorphism in combination with other thrombophilic factors should be considered.

[Combined thrombophilic factors among women with late recurrent spontaneous abortions].

The aim of this study was to assess the role of combined thrombophilic factors carrier status for development of late recurrent pregnancy loss (RPL). The polymorphism 4G/5G (PL 4G/5G) - genotype 4G/4G in plasminogen activator inhibitor type 1 (PAI-1), Factor V Leiden (FVL) and prothrombin (FII) gene mutation 20210 G>A in 52 women with recurrent pregnancy loss between 10 and 20 weeks of gestation and in 125 healthy women with at least one uncomplicated full-term pregnancy was investigated. Combined carrier status for thrombophilic factors was more pronounce among women with RPL (7.7%) compared to control subjects (3.2%), (OR=2.52, 95% CI (0.5- 12.62), p-ns). The most common association was between FVL and PL 4G/5G (5.8% compared to 0.8% in patients and controls, OR=7.59, 95% CI (0.68 - 191.04), p-ns). Because of relatively small size of the study, the difference in carrier status between women with RPL and control subjects did not rich statistical significance. A weak association between double carrier status for inherited thrombophilic factors and RPL was established. The strong determination in larger studies of the relation between combined inherited thrombophilic status and RPL development could better specify anticoagulant prophylaxis in further pregnancy

[Plasminogen activator inhibitor type 1 activity in women with unexplained very early recurrent pregnancy loss].

The aim of the study was to assess the independent role of polymorphism 4G/5G (PL 4G/5G)--genotype 4G/4G in plasminogen activator inhibitor type 1 (PAI-1) in the development of very early recurrent pregnancy loss (RPL)--before 10 weeks of gestation of pregnancy. The polymorphism 4G/5G as well as Factor V Leiden (FVL), prothrombin (FII) gene mutation 20210 G > A and polymorphism 677 C > T in methylentetrahydrofolat reductase (MTHFR) gene was investigated in 110 women with recurrent pregnancy loss before 10 weeks of gestation and in 97 healthy women with at least one uncomplicated full-term pregnancy. A significant prevalence of PL 4G/5G in women with RPL was found in comparison to prevalence of the polymorphism in controls (41.8% versus 26.8% respectively in patients and controls, OR: 1.96, 95% CI: 1.05 3.69, p = 0.034). The difference in prevalence of the polymorphism remains still significant after exclusion of patients and control carriers of FVL, FII 202010 G > A and 677 C > T in MTHFR (the prevalence of PL 4G/5G alone was 44.1% and 24% respectively in patients and controls, OR: 2,5, 95% CI: 1,15 5, 45, p = 0.018). The found association of PL 4G/5G in PAI-1 with early recurrent pregnancy loss encourage an extension of the list of inherited thrombophilic factors with this one. This result also could have had an implication for adjustment of further prophylactic low-molecular weight heparin implication in further pregnancy to prevent a poor foetal outcome.

[Inherited thrombophilic factors in women with unexplained intrauterine fetal deaths].

The aim of the study was to investigate a relationship between carrier status for factor V Leiden (FVL), prothrombin gene mutation 20210 G>A (PTM 20210 G>A) and development of unexplained intrauterine fetal deaths (UIFD). Thirty three women with one or more UIFD and stillbirths were investigated for carriers status for FVL and PTM 20210 G>A. Women with multiple pregnancies, congenital anomalies, intrauterine infection or chorioamnionitis were excluded from the study. Control group consisted of 79 women without reproductive failure were selected and investigated. The prevalence of FVL was significantly higher in the study group (21.1%) compared with 6.3% in the control group (OR 3.98, 95% CI 1.02- 16.14, p = 0.045). The prevalence of PTM 20210 G>A was also much higher in patients (10%) than in controls (2.5%) (OR 3.85, 95% CI 0.49-35.08, p-ns). Seven patients with UIFD and other obstetrics complications (preeclampsia, placental abruption, intrauterine growth retardation) showed high prevalence (over 40%) of FVL and PTM 20210 G>A. We found an important association between UIFD and FVL and PTM 20210 G>A, although the data on PTM 20210 G>A was non-significant because of low rate of the mutation and small group of investigated women. This data serves as a background to suggest a routine testing for inherited thrombophilia in women with UIFD aiming and individual approach of preventive use of low-molecular-weight heparin to avoid obstetric complication in future pregnancy.

[Frequency of miscarriages among pregnant women with autoimmune thyroid disorders].

AIM OF THE STUDY: To analyse the influence of antithyroid antibodies (ATA) on the frequency of spontaneous abortions (SA) by pregnant women with a normal thyroid gland function. DESIGN OF THE STUDY: Prospective clinical study on 42 selected pregnant women with a normal thyroid gland function divided into two groups: I-st group--ATA positive pregnant [n = 28] and II-end group ATA negative pregnant [n = 14]. RESULTS: Increased ATA have been found by 30 (71.4%) out of the studied 42 pregnant women. There has been no significant difference found among the values of FT3, FT4 and TSH for women with positive and negative ATA. SA have been observed at 63.3% (19/30 women) from the ATA positive ones and at 25% (4/12 women) from the ATA negative ones (P = 0.001). By the ATA positive women with SA the average values of antithyroglobulin autoantibody (Tg-Ab) (Tg-Ab positive.-189.6 +/- 49.8 IU/ml vs. Tg-Ab -negative 118.2 +/- 58.3 IU/ml, P = 0.02) and antithyroid peroxidase autoantibody (TPO-Ab) (TPO-Ab positive-176.9 +/- 57.4 IU/ml vs. TPO - negative 118.2 +/- 81.3 IU/ml, P = 0.004) are both found to be significantly higher. CONCLUSION: There is a correlation found between ATA and the increased risk of SA, where the increased concentration of ATA is combined with an increased frequency of SA.

[The study of ovarian autoimmunity and ovarian reserve in women with uncertain sterility].

UNLABELLED: Ovarian autoimmunity can be induce ovarian function, which is shown clinically with premature ovarian failure, unknown sterility and unsuccessful in vitro fertilizations. Antiovarian antibodies are directed to antigens functional zones of zona pellucida and granulose cells with important part in follicle genesis and fertilization. AIM: We have to investigate the influence of ovarian autoimmunity, antiovarian and antizona pellucida antibodies on endocrinology markers of ovarian reserve: inhibin B, FSH, LH by the women with unknown sterility. MATERIALS AND METHODS: 340 women were investigated with unknown sterility and 60 women were investigated with only one successful pregnancy at least. We investigated them for presence of antiovarian antibodies, antizona pellucida antibodies, and of course the levels of FSH, LH, inhibin B on the third day of menstrual cycle. Serological methods were used: ELISA- biochemical technique to detect the presence of antiovarian antibodies and antizona pellucida antibodies, inhibin B, FSH, LH. Statistical methods for analysis were also used. RESULTS: In investigated group was found the presence of antiovarian antibodies in 58 women (17.05%) and in control group was not found. Antizona pellucida antibodies presence was found in 43 women (12.64%) in investigated group and in control found was not found. It was not found important difference in levels of FSH, LH, inhibin B on the third day of menstrual cycle between women with and women without antiovarian antibodies. CONCLUSION: Antiovarian antibodies were observed only in women who have had laparoscopic ovarian drilling. The frequency of antiovarian antibodies among the Bulgarian women with unknown sterility is 17.05%. The presence of antiovarian antibodies is not associated with poor ovarian reserve as we investigated the levels of FSH, LH, inhibin B on the third day of the menstrual cycle.

[The importance of the presence of antisperm antibodies in serum and ejaculate of men with infertility].

UNLABELLED: There are multiple insults to the male genital tract that have been associated with an increased risk of antisperm antibodies (ASA) formation. The presence of ASA has been regarded as typical and specific for the immunological infertility. It has been suggested that the presence of agglutinated spermatozoa is suggestive of the existence of an immunological cause of infertility such as the existence of ASA. AIM: The objective of this study was to determine the clinical significance of serum and seminal plasma ASA as well as whether varying degrees of sperm agglutination can be a predictive indicator of positive serum and/or seminal plasma ASA. PATIENTS AND METHODS: 100 infertile and 30 fertile men were tested for ASA in seminal plasma and serum. The evaluation of patients included complete history, physical examination, scrotal ultrasound and semen analysis. ASA in serum and seminal plasma were tested by ELISA (Biosource, Belgium) and results were compared with the data of the semen analysis. RESULTS: 44 (44%) of the patients tested positive for ASA in seminal plasma, 9 of them had positive serum ASA. In the control group, seminal plasma ASA were not detected and two men (6.7%) tested positive for serum ASA. Correlation was established between seminal plasma ASA and two of the semen analysis markers: agglutination and increased viscosity. CONCLUSION: ASA in seminal plasma are much more predictive than ASA in serum and have major role in the pathogenesis and diagnostics of male infertility.

[High risk of recurrent spontaneous abortion during second trimester in women carriers of polymorphism A2 in platelet glycoprotein IIb/IIIa].

The aim of this study was to evaluate the role of polymorphism A2 (PLA2) in platelet glycoprotein IIb/IIIa (GP IIb/IIIa) in the development of recurrent spontaneous abortion (RSA)--miscarriages before 20th week of gestation (wg) of pregnancy. The carriage status of PLA2 in GP IIb/IIIa, single and in combination with FVL and FII G20210A was investigated in 56 women with recurrent miscarriages before 10 g, in 38 women with RSA from 10 to 20 wg and in 98 healthy women with at least one uncomplicated full-term pregnancy. The significant prevalence of carriage of PLA2 in GP IIb/IIIa in women with RSA in first 20 wg was found with high risk or miscarriage (OR = 4.32; 95% CI: 2.10-8.97, p < 0.0001). However, after adjustment for combined carriage of other thrombophilic factors (PLA2 and FVL or PLA2 with FII G20210A) the risk was still high (OR = 2.07; 95% CI: 0.98-4.40 p = 0.058), but not significant. The similar results (OR = 2.632; 95% CI: 1.140-6.104, p = 0.021) were found for women with recurrent miscarriages in the first 10 wg. The prevalence of PLA2 adjusted for combined carriage of other thrombophilic factors was also not significant. The carriage status of PLA2 in GP IIb/IIIa in women with RSA in the period from 10 to 20 wg was significantly higher as compared to controls (OR = 8.79; 95% CI: 3.477-22.605, p < 0.0001). The prevalence, adjusted for combined carriage of other thrombophilic factors (PLA2 with FVL or PLA2 with FII G20210A) was also significantly higher (OR: 2.990; 95% CI: 1.178-7.613, p = 0.018). These results confirm the impact of PLA2 polymorphism on RSA in the period of 10 to 20 wg, and its contribution to RSA in the first 10 wg in combination with other thrombophilic mutations. The results support the suggestion of testing women with miscarriages in first 20 wg for PLA2 carriage and application of appropriate prophylactic antiplatelet drug therapy for next planned pregnancy.

[Risk of thrombophilia in carriers of thrombophilic genetic factors in unsuccessful assisted reproduction].

The aim of this study was to evaluate an association of carrier status of common inherited thrombophilic genetic mutations and implantation failure after assisted reproduction (ART): IVF and ICSI. Sixty seven women with failure of embryo implantation and ninety six controls--women without obstetric complication were investigated for carriage of factor V Leiden (FVL), G20210A prothrombin gene mutation, genetic variant C677T in methylentetrahydrofolate reductase gene (MTHFR) and polymorphism A2 in platelet glycoprotein IIb/IIIa (GIPr IIb/IIIa). A significantly higher prevalence of polymorphism A2 in GIPr IIb/IIIa was found in women with implantation failure in ART compared to controls (respectively 26.1% and 12.5%; OR: 2.571, 95% CI: 1.066-6.258, p = 0.033). A higher but not significant prevalence of G20210A prothrombin gene mutation carriage was found inpatients compared to controls (respectively 5.8% and 3.13%, OR: 1.968, 95% CI 0.356-11.539). The carriage of FVL was a little but not significantly higher in controls. The carriage of genetic variant C677T in MTHFR was the same in both groups. These data suggest that polymorphism A2 in GIPr IIb/IIIa and G20210A prothrombin gene mutation could be play a role in the etiology of IVF failures and the carriers of GIPr IIb/IIIa A1/A2 and G20210A prothrombin gene mutation are at higher risk of implantation failure and not successful ART outcome. The carriage of these two genetic defects should be investigated in women undergoing IVF and the antithrombotic or anticoagulant prophylaxis should be indicated for carriers of these two factors.

[Genetic variant C677T in the MTHFR in women with recurrent early fetal loss].

The aim of this study was to evaluate correlation of carrier status for thrombophilic gene mutation--C677T in the methylenetetrahydrofolate reductase (MTHFR) and recurrent early pregnancy loss. Recently inherited thrombophilia was discussed as a predisposed factor for early recurrent fetal loss (ERFL). We investigated carrier status for C677T genetic variant in 54 women with ERFL before 10 week of gestation and 67 women with one or more successful pregnancy. It was found significant prevalence of C677T genetic variant in MTHFR in women with ERFL compared with controls (p = 0.005). The significant high prevalence of C677T genetic variant in women with ERFL suggests that thrombophilia have an increased risk of early pregnancy loss and possibly, although the definition of the magnitude of risk will require prospective longitudinal studies.

[Immunological aspects of postoperative analgesia after abdominal hysterectomy].

BACKGROUND: Prostaglandins modulate cytokine release though increases in cAMP, regulating interleukin-6 and interleukin-10. Ketoprofen inhibits cyclo-oxygenase activity and hence prostaglandin production. AIM: We hypothesized that ketoprofen would affect release of IL-6 and IL-10 and modulate the immune response. METHOD: We have evaluated 40 women, divided into four groups by the model of postoperative pain treatment: control group (only opioid) and experimental group (combination of i.v. ketoprofen and opioid). Serum IL-6 and IL-10 were measured before surgery, 24 and 72 hours after skin incision. Due to days in hospital we detected temperature and severe complications. RESULTS: IL-6 increased at 24h and normalized at 72h. In contrast IL-10 did not change significantly. CONCLUSION: The two models of postoperative analgesia have both modulated immune response after abdominal hysterectomy in same way.

[Genetic thrombophilic defects (Factor V Leiden, prothrombin G20210A, MTHFR C677T) in women with recurrent fetal loss].

Maternal thrombophilia (inherited and acquired) has recently been identified as a major cause of thrombembolism, but it may also contribute to adverse pregnancy outcomes and recurrent pregnancy loss. To determine the association of specific inherited thrombophilias and recurrent fetal loss (RFL), three gene mutations (Factor V Leiden, prothrombin G20210A, MTHFR C677T) were investigated. The prevalence of the thrombophilic markers was compared in 156 women with history of fetal loss in different trimester of pregnancy and 80 matched controls. At least one thrombophilic defect was found in 28.2% of total study group women compared with 16.2% in controls (p=0.06; OR-2.02) and in 50% of women with RFL in third trimester (p=0.008; OR-5.15). Factor V Leiden was more common in the group of women with fetal loss in third trimester (37.5%) compared to the controls (6.2%) (p=0.002; OR-9.0). Presence of FVL was associated with a significant increased risk for RFL in second and third trimester (OR-6.25; P<0.001) and significant protection for RFL in first trimester (OR-0.16; P<0.001). Mutation prothrombin G20210A or MTHFR C677T was more common in group of women with fetal loss in first trimester compared to the controls (28.3% vs. 11.2% respectively; p=0.009; OR-3.11). The presence of either of these mutations was associated with no significant increased risk for RFL in first trimester (OR-2.5). Genetic thrombophilic defects are common in women with RFL and are associated with late fetal loss. This association is manifest by FVL rather than total number of defects involved.