Liječenje infertiliteta uzrokovanog HLA-D statusom roditelja

Habitual abortion or recurrent spontaneous abortion is defined as a sequence of three or more pregnancies ending as miscarriage; if such a series has been preceded by a normal, successful pregnancy, it is called “secondary habitual abortion“, if not, the term “primary habitual abortion“ is used. In approximately 40% of the habitual abortions no causative factor can be determined, in this group of patients an immunological rejection reaction is suspected, although at present no distinctive pathognomonic clinical or laboratory criteria are available to characterize this subgroup of habitual abortion. Forty primary aborters enrolled in study to receive infusion humane intravenous immunoglobuline (IVIG) or didrogesteron tablet à 10 mg starting as soon as pregnancy test was positive. The aim of this study was to present the results of the treatment and eventually evidence for therapeutic effect IVIG/didrogesteron in women who had suffered at least three recurrent miscarriage. IVIG was first produced at the Institute of Immunology in Zagreb, Croatia. In this study, partners with histocompatbility in HLA-D loci were included. Tissue typing was carried out at the Tissue Typing Center, University Hospital Center Rebro, Zagreb. Before treatment at our hospital all the patients with the possibility of the chromosomal aberrations, genopaties, anatomic, microbiological, endocrinological, environmental factors or autoimmunization as a cause of abortion were excluded. Treatment (IVIG/didrogesteron, bed rest) started after confirmation of pregnancy on the fifth week of pregnancy. First infusion contained 30 grams of IVIG. Further five/six doses of 20 grams were infused every third week. Total dose of IVIG was 130/150 grams per case. All pregnancies, except one, were treated at our hospital, but five women were gave birth out of our hospital. Success was defined as pregnancy beyond gestational week 24 and/or delivery. In IVIG group: Twenty women parcipitated in study. Their average age was 31,8 years (range 24-40). Seventeen out of twenty pregnant women delivered 19 babies (one triplets). One pre-term at 28 weeks born baby died 3 hour after birth. Three abortions occurred after the first or second infusion. Due to obstetrics reasons ten deliveries were terminated by caesarean section (58,82%). Three pregnancies were (17,64%) terminated before 37 gestation weeks. Two babies were born small for gestational age. Three patients developed H-gestosis. Three women had pre-term labor pain and were treated with infusion of ritodrin. Due to incompetence of cervix in 5 cases in second trimester of pregnancy cervical cerclage were done (29,41%) In control group (bed rest, didrogesteron tablet à 10 mg until 12th weeks) the average age of women receiving didrogesteron was 27,9 years (range 22-36). Out of twenty, 18 pregnant women gave birth to 19 babies (one twins). Success rate was 90% (18/20). Twins were born at 26 weeks pre-term, and died several hours later. Three women had pre-term delivery (16,66%), in one of them caesarean section was done in 34th weeks of gestation due to worsening universal fetal hydrops. Baby was died 12 hours after delivery due to hydrops unknown etiology. Due to pre-term uterine contractions we treated five pregnant women with infusion of ritodrin. Due to incompetence of cervix in 6 cases in second trimester of pregnancy cervical cerclage was done (33,33%). Due to obstetrics reasons 5 deliveries were terminated by caesarean section (27,77%). The average weight of the newborns was 2863,2g (range 400g-3650g) in the IVIG group and 2925,8g (range 480g-4350g) in didrogesteron group. The average gestational ages were 38,11 weeks (range 29-41) in the IVIG group and 36,16 weeks (range 26-41 weeks) in control groups. No congenital malformations were observed in the newborns. In all, with no significant differences in the pregnancy course or perinatal outcome between those two-treatment group (IVIG/didrogesteron) were found. May be due to imunomodulatory effects of progesterone or emotional care associated with administration of placebo can indirectly facilitating the progression of pregnancy. Serum levels of TNF and IL2 were not significantly associated with pregnancy outcome. We did not found statistical significant differentiation in serum concentration of TNF and IL2 between IVIG group and control group. We found statistical significant elevation of serum concentration TNF in first trimester pregnancy of women with history of at least 3 consecutive spontaneous abortions, in addition first trimester normal pregnancy Only six patients in IVIG group had side effects at the time of the first infusion and they were: headache, nausea, chills, and elevated body temperature under 38 C, hot flushing, and chill. Side effects disappeared after reducing the speed of infusion