[COMBINED APPLICATION OF FETAL FIBRONECTIN AND INSULIN-LIKE GROWTH FACTOR IN PRETERM DELIVERY DIAGNOSIS--OUR RESULTS].

The insulin-like growth factor IGFBP-1 is a binding protein (IBP-1), also known as placental protein (PP12), is encoded in people as IGFBP-1 gene. The IGFBP-1 is an especially vital hormone in the female reproductive physiology. The presence of it in large quantities in the amniotic fluid can be used as a biochemical marker for preterm birth and premature rupture of membranes. Fetal fibronectin is a high-molecular glycoprotein, that is produced during pregnancy and has a role as biological glue, binding the foetus membranes to the endometrium. fFN can be found in the cervicovaginal secretions until 22nd gestational week and later on during the last trimester (1 to 3 weeks before birth). fFN is usually absent between 24th and 34th gestational week. Thirty sixth (30%) of all the 120 females tested had positive fFN test results and were, therefore, at high risk for preterm delivery. Despite the implemented tocolytic therapy, 15 (12.5%) of them delivered before the 37th gestational week. The results from the investigation for the presence of pLGFBP-1 in 120 pregnant women show that 35.8% (43 women) were positive and 15(12,5%) of them delivered before the 37th gestational week despite the implemented tocolytic therapy In both tests, the average gestational age of the premature fetus was 32.5 ÷ 2.8 gestational weeks.

[A case of bilateral tubal pregnancy after IVF - ET].

The authors describe a rare case of bilateral tubal pregnancy after IVF. The patient is with secondary infertility. The preceding diagnostic laparoscopy excluded the presence of tubal factor. The results of the spermogram show average to severe form of Oligoasthenozoospermia. Short protocol with GnRH-antagonist was performed and two embryos were transferred on the third day. On the 36th day after the embryo transfer the patient was hospitalized with abdominal pain in the right hypogastric region, clinical and ultrasound indications for hemoperitoneum. Urgent laparotomy was performed followed by salpingectomy dextra due to hemoperitoneum caused by tubal abortion. The examination of the left adnexa reveals uruptured tubal pregnancy in the isthmic part of the tube and the decision for salpingectomy sinistra was taken. Histological examinations confirmed the diagnosis of ectopic pregnancy in both tubes. The frequency of some rare forms and localizations of ectopic as well as heterotopic pregnancies increase after ART.

[Life threatening postpartal haemorrhage after rupture of the vagina, uterine cervix, caesarean section or hysterectomy].

The authors discuss 10 cases--seven after vaginal and cervical rupture, 2 after Caesarean section and 1 after hysterectomy. Six of them died--5 after rupture of the vagina and cervix and one after Caesarean section. The lethal issue was avoidable in all cases because it was a result of untimely done or not done at all hysterectomy and other interventions, e.g., ligation of the hypogastric arteries, as well as of faulty surgical performance. Basic principles of surgical behavior in such cases are postulated.

[Strategies for hormonal ovarian stimulation in IVF, based on materials of the centre for assisted reproduction "varna"].

During a two years' period (2008-2009), 834 patients underwent IVF in the Centre. Long protocol was used where normal response was expected; for high risk patients was used protocol with antagonist and induction of ovulation with agonist or 5 000 IU HCG; and when poor response was expected, flare up protocol was applied. 363 clinical pregnancies were registered--50% for transfer and 43.4% for cycle. Experience shows that antagonist - agonist protocol reduces significantly but not completely the risk of OHSS. On poor responders, the standard short protocol shows better results than any of the recently suggested protocols. In future, the so called "controlled ovarian hyperstimulation" will be performed only in its soft version and when certain indications exist.

[Oocyte and embryo donation and surrogacy. Religious, medico-social, ethical, financial and legal problems].

The authors quote and discuss the postulates of the Orthodox, Jewish, Catholic and Islamic religions towards ART as well as worldwide legislations and standards and the attitude of female students of medicine in Varna. Indications of oocyte and embryo donation and surrogacy are proposed but all kinds or surrogacy should be permitted. The ART legislation and standards in Bulgaria should be thoroughly revised.

[Successful treatment of locally invasive, nonmetastatic choriocarcinoma after ectopic pregnancy by monochemotherapy].

A case of choriocarcinoma in 33-year old woman after ectopic pregnancy has been reported. CT-scan established an invasion of the vagina, posterior wall of the bladder and rectum. The patient's leading symptoms were: severe genital bleeding,haematuria, acute postbleeding anaemia, haemorrhagical shock. After treatment with Metothrexate and symptomatic therapy the patient achieved complete clinical remission and she is free of disease 18 months after the onset of the therapy.

[Ovulation induction in high risk IVF patients: GnRH-agonist, diminished dose of urinary or recombinant chorion gonadotropin].

In high risk IVF patients the ovulation triggering was done with agonist (0.2 mg), 1.gr., Pregnyl 5000 IE, 2. and 4.gr., Ovitrelle 0.250 mg, 3.gr., and Pregnyl 10000 IE in the fifth--non-risk group. The protocol of the first and fourth group included antagonist, the second and third group was with short and the fifth group with long agonist protocol. There was no grave OHSS in the first group, one case in each second, third and fourth group and 4 cases in the fifth group, as a whole 7 patients (3.3%). In all of them an abdominal drainage lasting 4 to 30 days was performed and all pregnancies were preserved. The average success rate was 50%, 71.4% in the fourth and 43.1% in the fifth group. A protocol with antagonist and ovulation triggering with agonist or reduced dose ChG in order to diminish OHSS in high risk IVF patients is recommended.

[Main principles and IVF-ET results of the centre for assisted reproduction "Varna", Bulgaria].

The authors formulate the main principles of IVF-ET, based on personal experience i.e. hormonal ovarian stimulation, ovarian puncture, fertilization and ET, prophylaxis and therapy of early complications. Clinical pregnancy was achieved in 287 of 612 patients (43.9% per cycle and 46.9% per transfer). The cancellation rate is 9.6% (42 patients), the miscarriage rate is 14.2% (41 patients). In three cases the pregnancy was ectopic. The multiple pregnancy rate is 32.7% (94 cases): 84 bigemini, 9 trigemini and 1 quadrigemini. In 2006 the multiple pregnancy rate was reduced to 28%. The mean number of transferred embryos was 3.2 and in 2006--2.8; 80.5% of the pregnant women were under 35 years of age. Severe complications occurred in 16 cases--2.6%: OHSS in 15 cases and one with massive intraabdominal hemorrhage from ruptured ovaries. In conclusion the authors stressed the necessity of undelayed resort to ART treatment. Hydrosalpinxes have to be removed preliminarily and partial resection of the ovaries should be done only in rare cases. In Bulgaria at least 6000 fully reimbursed IVF-ICSI procedures yearly ought to be done because of the considerable rate of the inflammatory female and male infertility.

[Role of intercellular adhesion molecule-1 and E-selectin in the pathogenesis of ovarian hyperstimulation syndrome].

OBJECTIVE: To explore the ICAM-1 and E-selectin in patients with OHSS and clarifying its role in pathogenesis of the syndrome. MATERIALS AND METHODS: 20 patients were included in the research and 20 control patients with stimulating ovarian cycle for the purposes of ART, during the period from 01.01.2004 till 01.01.2005 years in the center of ART-MU-Varna and Department of Obstetrics and Gynecology-IVF-ward-MU-Ben-Gurion, Israel. The patients were divided into 3 subgroups according to the degree of OHSS by the classification of Golan- mild, moderate, severe. The method of ELISA was used to record the values of the factors under research. RESULTS: Six patients with severe OHSS, showed increase in the value of the ICAM-1 and somebody of them, showed low level of E-selectin testing in serum and ascitic fluid in comparison with the control group and the rest of the patient with OHSS. CONCLUSION: OHSS is a life-threatening complication in which the main pathophysiology factor is the increased of capillary permeability. ICAM-1 are expressed on human granulosa cells and by the vascular endothelium after the stimulation by inflammatory cytokines and acts as a mediator of the cohesion with the lymphoid cells. E-selectin is produced by the endothelium after cytokine activation. The soluble forms of these molecules are found in serum, follicular fluid during the COH, as well as in ascitic fluid in severe OHSS. In our research adhesion molecules- ICAM-1 are correlated to the OHSS, especially in the severe forms of the syndrome.

[Cesarean section in modern obstetrics and methods of prophylaxis of postoperative sepsis]. / "Tsezarizm't" v s'vremennoto akusherstvo i metod za profilaktika na postoperativniia sepsis.

The author discusses the problem Caesarean section in present day obstetrics and points out that the percentage of Caesarean births has been unnecessarily increased. This justifies the term "Caesarean epidemy". In spite of discussions and recommendations it turns out impossible to cope with this problem, i.e. reducing the rate to 15% in these countries where it is higher. Methods of infections morbidity prophylaxis are discussed too, especially the peri- and intraoperative antibiotic application (PAP, IAL) as well as the inaugurated by the author in 1987 postoperative intermittent intrauterine antibiotic lavage (PIAL). PIAL should be applied in very high risk cases, e.g. severe chorionamnionitis or vulvovaginitis combined with PAP and IAL. The use of these methods renders hysterectomy as ultra ratio prophylactic measure unnecessary. It is explicitly stressed that there is no prophylactic method to compensate defective surgical skills or flaws in aseptics and antiseptics.

[The multiple pregnancy problem in the technologies of assisted reproduction]. / Problemut mnogoplodna bremennost pri tekhnologiite za asistirana reproduktsiia.

After a review of the literature the author discusses methods, results and risks of the multifetal pregnancy reduction and shares his experience. Prophylactic measures are proposed too. Embryocide in twin or triplet pregnancy is not recommended except for malformation.

[The basic problems and outlook for assisted reproductive technologies]. / Osnovni problemi i perspektivi na tekhnologiite za asistirana reproduktsiia.

In this article the authors discuss some problems in ART:COH, stimulation protocols, culture media, transfer of embryos, luteal phase support, ethical, financial, religious and legal problems etc. Tha main complications are discussed, toosyndrom and pseudosyndrom of the empty follicle, OHSS, multiple pregnancy. In these cases the prophylactic and therapeutical measures are pointed out. Finally the main perspectives and developments of ART in the new millennium are outlined.

[The ovarian hyperstimulation syndrome in pregnancy after IVF-ET]. / Ovarialen khiperstimulatsionen sindrom pri bremennost sled IVF-ET.

The authors present 3 cases of OHSS in 85 patients (3.5%), treated with long stimulation protocol. They propose an original grading of the severity of the syndrome as well as prophylactic and therapeutic measures.

[Haemostatic postpartal problems in Kasabach-Merritt syndrome. Case report]. / Problemi na khemostazata sled razhdane pri sindroma na Kazabakh-Merit. Opisanie na edin sluchai.

A recurrent postpartal haemorrhage in Kasabach-Merritt sd. which continued in spite of hysterectomy is described. The bleeding was controlled only after ligation of the hypogastric arteries.

[The results of using ICSI at the Center for Assisted Reproduction, Varna]. / Rezultati ot prilozhenieto na IKSI v Tsentura za asistirana reproduktsiia--Varna.

The authors present the results of 31 consecutive cycles of ICSI. Fertilization occurred in 251 /88%/ of 279 oocytes which resulted in 8 clinical pregnancies /27% per transfer/--3 singleton, 2 multiple uterine pregnancies, 2 abortions and 1 ectopic pregnancy.

[Indices of a threatened pregnancy in the first trimester]. / Prouchvaniia na niakoi pokazateli pri narushena bremennost v purviia trimestur.

Studies were carried out on 167 pregnant women, divided into 4 groups in accordance with the values of human chorionic gonadotropin (HCH). Fetal death was established by ultrasound in 41 of the pregnant women including all cases with HCG under 5000 IU, but it was also found in 19.18% of women with values of HCG over 10,000 IU. Pregnancy advanced unfavourably in other 16 pregnant women of altogether in 34.13%. Prognosis was unfavourable in the presence of decidual hematoma. The gestational sac was enlarged on the average. 1.3 mm per day in normal development. Treatment was made in two groups: with hormones, spasmolytics and vitamins and only with spasmolytics and vitamins. The results showed that progesterone preparations, used singly or in combination with estradiol, did not improve the results.

[Fetal shoulder girdle dystocia during labor]. / Distotsiia na ramenniia poias na ploda po vreme na razhdane.

Shoulder dystocia occurred in 98 women (0.9%) among 10,695 deliveries during the period of 1986-1988. The most frequent cause was overweight and strangulated umbilical cord. The following maneuvers were used: pressure on the uterine fundus, strong flexion of legs (maneuver of Knebel-Macroberts-Korokawa) and in 12 cases--extraction of the posterior hand. The head should be rotated to the opposite thigh of the parturient in cases with incorrect rotation of the head--the most frequent cause for low shoulder dystocia. Prophylactic measures are of special significance: cesarean section in women with large fetus, estimated by ultrasound, or with fetus with thoracic diameter larger than biparietal diameter with 1.5 sm. The delivery should be managed by the most experienced obstetricians and should not be protracted or precipitate without indications.

[Abruptio placentae in the data from the obstetrical clinics in Varna, Tolbukhin and Shumen during 1984-1987]. / Abruptio placentae vurkhu material na klinikite po akusherstvo vuv Varna, Tolbukhin i Shumen za perioda 1984--1987 g.

Abruptio placentae was established in 202 pregnancies out of 43,678 pregnancies (0.48%). Pre-eclampsia was diagnosed in 76 women as well (37.6%). Caesarean section was performed in 109 women as vital maternal indications were found in 43 of them. 139 children were born alive (67.8%), but the perinatal mortality was 43.9% (90 children). The maternal mortality was 1.98% (4 women). Caesarean section should be made only in women with alive infant, but obligatory in all cases with severe separation, if preconditions for quick management of delivery by vaginal way lack. Vaginal delivery is recommended in all milder cases and dead fetus, but the duration of delivery should not surpass 6 hours. Total hysterectomy and tamponade of the operative field and vagina should be performed in women with persistent bleedings, but in grave cases a ligature of the hypogastric arteries as well. All interventions should be done after application of intensive infusion, transfusion and other reanimation. The authors propose a scheme for medicamentous treatment.

[Diagnostic and clinical status of premature ovarian failure]. / Diagnostichno-klinichni pokazateli pri ranno nastupila iaichnikova nedostatuchnost.

Premature Ovarian Failure is a heterogeneous disorder with numerous causes. The exact prevalence of POF is unknown. In this study, we want to make Differentiate diagnosis of hypergonadotropic amenorrhea and to determine the difference between them. Retrospective, we follow up 475 women at which we perform ovarian stimulation and we observe that 6 (1.3%) have Gonadotropin resistant ovary syndrome in IVF-centre--MU--Varna.

[Some aspects of ovarian hyperstimulation syndrome]. / Niakoi aspekti na ovarialniia khiperstimulatsionen sindrom.

Ovarian hyperstimulationsyndrome (OHSS) is a serious and potentially life-threatening complication of ovarian stimulation. The clinical picture of severe OHSS, includes ovarian enlargement, ascites, pleural effusion, hypercoagulation and electrolyte disorders. In this study we describe some factors which are linked with pathogenesis of OHSS. We had a case of moderate OHSS with a twin pregnancy after IVF-ET. In this case, because of abdominal pain and discomfort from the ascites, we perform abdominal paracentesis without termination of pregnancy.