Intrauterine Therapy Research Articles

Amenorrhoea Traumatica following Therapeutic Abortion: an Approach to Management

“Amenorrhoea Traumatica” or Asherman's Syndrome follows vigorous curettage of the endometrium, thus producing adhesion of the uterine walls and secondary amenorrhoea. This condition is especially easily produced in curettage of a soft pregnant uterus where the basal endometrium can readily be denuded. Intrauterine infection probably also plays a part in the aetiology. Diagnosis of the condition should be based on the clinical history and confirmed by hysteroscopic examination, which is both diagnostic and therapeutic. Administration of sex hormones as a diagnostic test is probably not advisable. After lysis of the adhesions, insertion of intrauterine contraceptive device and sequential hormonal therapy are useful in preventing further adhesion formation. Future fertility in these women is as yet unknown.

Distribution of CPP-Protein Complexes in Freshly Resected Human Tissue Material.

Interest in cell-penetrating peptides (CPPs) as delivery agents has fuelled a large number of studies conducted on cultured cells and in mice. However, only a few studies have been devoted to the behaviour of CPPs in human tissues. Therefore, we performed ex vivo tissue-dipping experiments where we studied the distribution of CPP-protein complexes in samples of freshly harvested human tissue material. We used the carcinoma or hyperplasia-containing specimens of the uterus and the cervix, obtained as surgical waste from nine hysterectomies. Our aim was to evaluate the tissue of preference (epithelial versus muscular/connective tissue, carcinoma versus adjacent histologically normal tissue) for two well-studied CPPs, the transportan and the TAT-peptide. We complexed biotinylated CPPs with avidin-β-galactosidase (ABG), which enabled us to apply whole-mount X-gal staining as a robust detection method. Our results demonstrate that both peptides enhanced the tissue distribution of ABG. The enhancing effect of the tested CPPs was more obvious in the normal tissue and in some specimens we detected a striking selectivity of CPP-ABG complexes for the normal tissue. This unexpected finding encourages the evaluation of CPPs as local delivery agents in non-malignant situations, for example in the intrauterine gene therapy of benign gynaecological diseases.

Aloinmunización RH: manejo anteparto. Revisión de la literatura

Introducción: la aloinmunización Rh es una enfermedad frecuente en Colombia pese al uso de inmunoglobulina anti-D(Rho) en los embarazos de alto riesgo. Asimismo, es una condición que requiere la identificación temprana de los factores de riesgo, así como el adecuado tamizaje con el fin de lograr una remisión oportuna a una unidad materno-fetal con experiencia para disminuir las complicaciones fetales y brindar la terapia indicada en caso de ser necesario.Objetivo: revisar la exactitud de los métodos de tamizaje y de diagnóstico temprano, así como también la efectividad de los métodos no invasivos e invasivos de tratamiento.Metodología: se realizó una revisión de la literatura existente de acuerdo con las bases de datos PubMed, EBSCO, Ovid y ProQuest desde el año 2000 hasta el 2008, la cual incluyó artículos de revisión e investigaciones originales.Resultados: la titulación de anticuerpos y el pico de velocidad máximo sistólico de la arteria cerebral media son las herramientas que permiten realizar la evaluación y la identificación de las pacientes en riesgo. El tratamiento incluye transfusión intrauterina y parto oportuno mientras que la prevención con la inmunoglobulina anti-D (Rho) continúa indicada.Conclusión: la aloinmunización Rh aún es una patología de interés en el control de las pacientes obstétricas de bajo y alto riesgo. El conocimiento que se obtenga de la enfermedad permitirá realizar el diagnóstico oportuno y, de esta manera, identificar los fetos en riesgo que son susceptibles de terapia intrauterina.

OP22.07: Lung function at school age of 60 children after intrauterine laser therapy for twin-twin transfusion syndrome (TTTS)

OP22.07: Lung function at school age of 60 children after intrauterine laser therapy for twin-twin transfusion syndrome (TTTS)

OC02.03: Neurodevelopmental outcome at six years of age after intrauterine laser therapy for twin-twin transfusion syndrome (TTTS)

Objective: To compare an animal model of growth restriction by selective ligature of uteroplacental vessels with a model of severe hyponutrition. Methods: 16 New Zealand pregnant rabbits were included in the placental insufficiency (PI) model, in which a 40–50% of uteroplacental vessels were ligated at 25d of gestation. Contralateral horn were considered as control. After surgery, dams were allowed free access to water and standard chow. 2 New Zealand pregnant rabbits were included in the hyponutrition (HN) model, in which a sham-surgery was performed at 25d. After surgery, hyponutrition was induced by restricting up to 70% of the normal diet. Pulsed Doppler assessment was performed before Cesarean delivery. Results: Mortality rate showed significant differences between experimental groups (14,3% control; 5.0% HN; and 54.2% PI (p<0.001)). Among survivors, all biometric parameters showed a consistent and significant gradient across the experimental groups. Doppler assessment demonstrated a significant linear increase of ductus venosus and a linear decrease of umbilical vein blood flow across study groups. Additionally, umbilical artery and aortic isthmus showed a non-significant trend to increase through experimental groups. Conclusion: Selective ligature of uteroplacental vessels results in an animal model of fetal growth restriction with biometric and hemodynamic changes that closely resembles the clinical condition. This surgical model could be useful to investigate effects of hypoxic condition on different key organs, such as brain and heart.

Fetal Hydrops, Hyperechogenic Arteries and Pathological Doppler Findings at 29 Weeks: Prenatal Presentation of Generalized Arterial Calcification of Infancy – A Novel Mutation in ENPP1

Prenatal diagnosis of generalized arterial calcification of infancy (GACI) (OMIM #208000) is difficult and rare. There are various known gene mutations in ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) locus 6q22-q23. We present a case of suspected intrauterine diagnosis at 29 weeks of gestation in a consanguineous couple. The sonographic findings were fetal hydrops (hydrothorax, skin edema, ascites, pericardial effusion and polyhydramnion), echogenic great arteries and pathological Doppler findings. An intrauterine therapy with bisphosphonates was considered, but delayed due to rapid deterioration in fetal Doppler flows with suspected fetal asphyxia. The couple was informed about the most unfavorable prognosis in fetal hydrops, however, they opted for elective delivery. A cesarean section was performed. Early neonatal death occurred due to primary intracranial hemorrhage. Postmortem and genetic testing confirmed a novel mutation in the ENPP1 gene.

Laser application in obstetrics and gynecology – A short introduction to therapeutic options

Abstract For the last 20 years, laser technology has evolved as an important tool in surgical treatment and it is widely used in gynecology and obstetrics. Especially in the treatment of vulvar and benign and premalignant cervical dysplasias it can be considered as the gold standard. In prenatal medicine, laser coagulation of placenta vessels has been shown to be superior to any other intrauterine therapy of twin-to-twin transfusion syndrome in monochorionic twin pregnancies. However, not all expectations in laser technology have been fulfilled. In laparoscopy, for instance, the use of the laser has been abandoned in favor of high-frequency electric surgery. This manuscript gives a short introduction to current therapeutic applications and limits of laser technology in gynecology and obstetrics.

Current Concepts on Prenatal Diagnosis and Management of Fetal Tachyarrythmias

Sustained or recurrent tachyarrhythmias are an important cause of fetal morbidity and mortality. The most common type of fetal tachycardia is supraventricular tachycardia, followed by atrial flutter. Other tachyarrhythmias such as atrial ectopic tachycardia, junctional reciprocating tachycardia and ventricular tachycardia are rare in fetal life. Appropriate management depends on accurate diagnosis. Ultrasound is essential for a precise knowledge of the electrophysiologic mechanism underlying the arrhythmia, and to examine the hemodynamic impact of the tachycardia both before and after the antiarrhythmic therapy. The information concerning the type of fetal tachyarrhythmia is usually inferred from the fetal heart rate, and the relationship between atrial and ventricular events as demonstrated by M-mode echocardiogram and Doppler flow signals. The decision to initiate pharmacological intervention depends on several factors and must be weighed against possible maternal and fetal adverse effects of the antiarrhythmic drugs. Several options are available when facing with a fetus with a tachycardia, ranging from close observation without therapy to direct administration of antiarrhythmic drugs into the fetal circulation. Although there are many series in the medical literature reporting that fetal tachycardias can be suppressed successfully using antiarrhythmic drugs given to the mother, currently there is no global consensus concerning the precise management of these fetuses. Certainly, the ultimate decision on the management of fetal tachycardias will vary from center to center. In this paper we will analyze our experience in the diagnosis and management of fetal tachyarrhythmias together with a review of modern literature in this topic. Keywords: Fetal tachyarrhythmias, prenatal diagnosis, doppler, M-mode, supraventricular tachycardia, intrauterine therapy

Intrauterine therapy with cytomegalovirus hyperimmunoglobulin for a fetus congenitally infected with cytomegalovirus

Reported herein is a case of hydrops fetalis in which the cord blood expressed cytomegalovirus (CMV) antigen. Fetal ascites was removed from an infected fetus with hydrops in utero and 2.5 g CMV hyperimmunoglobulin was administered into the fetal abdominal cavity at 28 weeks gestation. After immunoglobulin administration, fetal ascites vanished, preload index of the inferior vena cava decreased and platelet count of the infant increased. However, despite intrauterine therapy and intensive neonatal care, the infant died soon after birth. The expression of CMV antigen in the nucleus of polymorphonuclear leukocytes in fetal cord blood indicated that the fetal hydrops was caused by CMV infection. When symptomatic CMV infection of a fetus is suspected from serological and ultrasound findings, further examinations should be performed for the diagnosis. Intrauterine immunoglobulin therapy could be one of the therapeutic options for the affected fetus.

Outcome of intensive care of homozygous alpha‐thalassaemia without prior intra‐uterine therapy

To review the outcome of homozygous alpha-thalassaemia without prior intra-uterine therapy treated in neonatal intensive care unit and identify the factors associated with survival. The hospital records of all patients with homozygous alpha-thalassaemia treated in our neonatal intensive care unit in the last 15 years were reviewed. A literature search beginning in the year 1980 was done to identify homozygous alpha-thalassaemia actively treated in neonatal intensive care units. Those receiving prior intra-uterine therapy were excluded. The following information was collected: the severity of hydrops, sizes of liver and spleen, haemoglobin level, Apgar score at 5 min, ventilator settings, timing and forms of red blood cell transfusion and presence of persistent hypoxaemia. The survivors and the non-survivors were compared. In our centre, in the last 15 years there were six infants born with homozygous alpha-thalassaemia who did not receive intra-uterine therapy; one survived and five succumbed despite aggressive respiratory therapy. In our literature search there were more reports of survivors (10) than non-survivors (six) for these infants, suggesting a reporting bias towards selection of rare cases of survival. Apgar score of four or above occurred in seven of the eight survivors with data available in the reports, whereas this occurred in four of the 11 non-survivors (P = 0.035, Fisher Exact test). Five of the 11 survivors had abnormal neurological outcome including developmental delay and spastic quadriplegia. Without prior intra-uterine therapy, homozygous alpha-thalassaemia has grave outlook in terms of mortality and morbidity despite aggressive respiratory therapy.

Parvovirus-B 19-Infektion in der Schwangerschaft

The parvovirus B 19 is part of the family of the parvoviridae and shows a distinctive tropism for erythropoid precursor cells. The virus causes in children the erythema infectiosum (German measles). Meanwhile, parvovirus B 19 infections can be associated with a wide spectrum of hematological and non-hematological complications (e.g. liver failure, hepatitis, aplastic crises primarily in association with chronic hemolytic anaemias, chronic arthritis, arthralgia/arthritis, transient/persistent anaemias, vasculitis, glomerulonephritis). Intrauterine infections can lead to specific or permanent organ defects (e.g. heart anomalies, eye diseases, micrognathy, chronic anaemia, myocarditis, hepatitis, mekonium peritonitis and central nervous system anomalies). Parvovirus B 19 infections are also associated with hydrops fetalis and intrauterine death during pregnancy. A definite relation between fetal malformations and B 19 infection has not been accomplished yet. Pregnancies complicated by parvovirus B 19 infection should be followed for further exclusion of any teratogenic effect. Although congenital malformations after a parvovirus infection are possible, this phenomenon seems to be rare. An intrauterine therapy with packed red cells could be performed for hydrops fetalis and low haemoglobin concentration. Investigation for the development and clinical testing of an efficient vaccine against parvovirus B 19 is currently in progress.

Acute Intrapartum Twin-to-Twin Transfusion Following Successful Fetoscopic Laser Ablation

Fetoscopic laser ablation of placental vascular anastomoses is an intrauterine therapy targeting the source of twin-to-twin transfusion syndrome (TTTS). Our patient had successful laser treatment, with resolution of stage II TTTS, suggesting closure of all significant anastomoses. After an uneventful pregnancy course, she elected a trial of labor. Following spontaneous onset of labor, acute intrapartum twin-to-twin transfusion was suspected, suggested by sinusoidal heart rate changes, confirmed postdelivery by twins' complete blood counts. The potential risks of labor with prior fetoscopic laser ablation are reviewed in the context of current knowledge about placental architecture in TTTS.

Successful Intrauterine Therapy for Fetal Goitrous Hypothyroidism during Late Gestation

We experienced a case of fetal goitrous hypothyroidism in an infant delivered by a 33-year-old woman receiving 300 mg/day of propylthiouracil (PTU) for hyperthyroidism due to Graves' disease. A large fetal goiter (maximum diameter, 60 mm) was detected by magnetic resonance imaging (MRI) at 36 weeks of gestation. Initial fetal blood sampling revealed hypothyroidism with a serum thyroid-stimulating hormone (TSH) of 99 microIU/mL, free triiodothyronine (T(3)) of 1.97 pg/mL, and free thyroxine (T(4)) of 0.29 ng/dL. Consequently, a diagnosis of fetal goitrous hypothyroidism due to transplacental passage of maternal PTU was made. To reduce the risk of perinatal complications, 300 microg of levothyroxine sodium (L-T(4)) was administered into the maternal amniotic fluid twice between 37 and 38 weeks of gestation. Subsequent fetal MRI showed that the size of goiter had decreased. At 38 weeks and 5 days of gestation, a 3042-g male infant was born by cesarean section. There were no severe complications at delivery, although mild tachypnea was observed and the infant's thyroid gland was slightly enlarged. He was treated with L-T(4) for two weeks. At present, his growth and neurological development are normal. This case indicates that intrauterine therapy by the intraamniotic administration of L-T(4) can be effective in treating fetal goitrous hypothyroidism even during late gestation.

OP04.25: Current aspects of intrauterine therapy of fetal tachyarrhythmia

OP04.25: Current aspects of intrauterine therapy of fetal tachyarrhythmia

Intrauterine intravenous transfusion therapy for hydrops fetalis due to anemia of uncertain causes

The treatment and prognosis of hydrops fetalis depend on the etiology or underlying fetal conditions. Intrauterine transfusions for fetal anemia can be effective in the selected cases [1,2]. Theoretically, anemia of unknown cause, after excluding common lethal problems such as Hb Bart’s disease, is probably justified for intrauterine transfusion. The purpose of the study was to demonstrate the possibility to reverse hydrops fetalis due to fetal anemia of unknown causes with intrauterine intravascular transfusion.

Evaluation of intrauterine therapies in repeat Breeder dairy cattle

A total of 160 repeat breeder dairy cows suffering from endometritis were used in this study. The cows were divided into six groups and were subjected to different intrauterine therapy, the first group was treated with 1% of Lugol's solution, the second and third group were treated with 2 gm of Oxytetracycline and chloramphenicol respectively, while the cows in the groups four and five were subjected to an intrauterine therapy with one million units of crystalline penicillin and one tube of metrijet respectively, mean while the group six was untreated and used as a control. The animals in all groups (except the group four) were inseminated on the subsequent estrous period following therapy, while the group four was subjected to post -service treatment within 24 hours after insemination. The cows were inseminated twice with 8 hours a part between them and they were injected intravenously with 1500 I.U of hCG ( chorulon ) when delayed ovulation was suspected . Pregnancy examination by rectal palpation 50 days after the second insemination revealed pregnancy rates ( %74.28 , %72 , %68 , %60 , %40 ) for the six group respectively . The results of the present study showed no significant differences (p> 0.05) among the different treated groups, and when each of the first four treated groups compared with the control one. There was a significant differences between treated and control group (p<0.05). It was concluded that the intrauterine therapies and the injection of hCG at the time of insemination are useful in the treatment of repeat breeder cows.

Strategies to Improve the Therapy of Retained Fetal Membranes in Dairy Cows

In this field trial, a protocol for the treatment of retained fetal membranes (RFM) without any intrauterine therapy was compared with 3 protocols based on the intrauterine use of antibiotic pills (AP), the manual removal (MR) of the fetal membranes, or the combination of both (PR). The study was conducted on 5 commercial dairy farms in Germany. Cows with RFM for at least 24h after calving were assigned to 1 of 4 treatment groups. Cows of all groups with a rectal temperature≥39.5°C received a systemic antibiotic treatment with ceftiofur (1mg/kg per d) for 3 to 5 consecutive days. In case of continued fever after 5 treatments, cows received a different antibiotic as an escape therapy. In the reference group (REF; n=131), cows did not receive any additional treatment. All cows in group AP (n=119) received intrauterine treatment with antibiotic pills consisting of 1,000mg of ampicillin and 1,000mg of cloxacillin for 3 consecutive days. In group MR (n=121), an attempt was made to remove the fetal membranes manually, but uterine pills were not administered. In group PR (n=130), an attempt was made to remove the fetal membranes manually and all cows received a local antibiotic treatment as in group AP. All cows received 2 doses of 25mg of PGF2α: one dose between 18 and 24 d and another between 32 and 38 d postpartum. Statistical analyses were performed using binary logistic regression models and survival analyses with group REF as reference. Of all animals, 79.8% had a body temperature of≥39.5°C at least once within 10 d postpartum and were treated with ceftiofur. Occurrence of fever within 10 d postpartum was significantly lower in groups AP and PR compared with reference group REF, but was not different between groups MR and REF. Risk of receiving an escape therapy in case of fever after 5 treatments with ceftiofur did not differ among groups. Reproductive performance measures did not differ significantly between group REF and any of the comparison groups. Compared with a treatment protocol based only on systemic treatment with antibiotics for cows with a fever, neither intrauterine antibiotics nor manual removal of fetal membranes alone or in combination reduced proportions of cows needing an escape therapy nor did those treatments improve reproductive measures in the current lactation. Systemic treatment alone based on elevated rectal temperature was effective and reduced use of antibiotics compared with therapies that included intrauterine antibiotics.

Intrauterine therapy of goitrous hypothyroidism in a boy with a new compound heterozygous mutation (Y453D and C800R) in the thyroid peroxidase gene. A long-term follow-up

We report the results of intrauterine L-thyroxine therapy, and the long-term follow-up in a fetus who presented at 32 weeks' gestation with goitrous hypothyroidism, hyperextension of the neck, and polyhydramnios. Spontaneous delivery was possible and hypothyroidism improved. Molecular analysis revealed a new compound heterozygous mutation (Y453D/C800R) in the TPO gene.

Is phototherapy a risk factor for ileus in high-risk neonates?

Background. Abdominal distension and bile stained aspirates are common in high-risk neonates under phototherapy (PT).Objective. To compare the incidence of ileus and related risk factors in extremely low birth weight (ELBW) neonates who did/did not receive PT.Design/methods. Retrospective detailed analysis of data on 52 consecutive ELBW neonatal admissions (1997–1999) including demographic characteristics, outcomes to discharge and common risk factors for ileus such as intrauterine growth retardation, PDA, indomethacin therapy, sepsis and enteral feeds. Ileus was defined as presence of abdominal distension and bile stained aspirate/s with/without dilated bowel loops on X-rays.Results. A significantly (p = 0.001) higher proportion (63.4%, 26/41) of neonates under PT developed ileus than those (1/11) who did not receive PT. The outcomes and risk factors for ileus were comparable between the two groups. Mean (±SD) gestational age and birth weight of those who did and did not receive PT [26 (±2.2) weeks and 803 (±133) grams vs. 27 (±3.2) weeks and 664 (±114.2) grams], and those who did and did not develop ileus [26.5 (±2.3) weeks and 797 (±102) grams vs. 28.0 (±1.2) weeks and 750 (±105) grams] were not significantly different.Conclusion. Phototherapy may be an independent risk factor for ileus in ELBW neonates.

Hydrops fetalis and neonatal death from human parvovirus B19: an unusual complication

A case of prenatally diagnosed human parvovirus B19 (HPVB19) infection is reported. The neonate died after intrauterine therapy and premature delivery. The fetus was diagnosed with oedema, cardiomegaly, poor myocardial contractility and a pericardial effusion at 24/40 weeks' gestation. Ultrasound using colour flow Doppler showed a midcerebral artery peak systolic velocity (MCA PSV) raised at 45 cm/s, suggesting fetal anaemia. This was confirmed on fetal blood sampling, but recovery was suggested with a reticulocyte count of 16.8%. The fetal karyotype was normal, 46,XY. Fetal IgM was positive for Parvovirus. A week later, severe fetal anaemia was suspected and intrauterine transfusion carried out. Altogether three transfusions were given. At 31/40 weeks, the mother presented to her local hospital with suspected preterm labour, a caesarean section was carried out because of fetal compromise on cardiotocography. The baby was in poor condition at birth and resuscitation was stopped at 45 min of age. The post-mortem examination confirmed the hydrops and proved persistent Parvovirus infection, cardiac involvement and severe liver fibrosis.HPVB19 generally follows a benign course with intrauterine therapy; however, in this case, the fetus died despite successful transfusions. The reasons for this are discussed.