Drug exposure in early pregnancy might be related to the effects of increased maternal progesterone in implantation period.

AIM: This short communication aims to evaluate the relation in between drug exposure time and early pregnancy regarding gestational weeks. METHODS: The study covers the referrals made to the Department of Pharmacology for a teratogenic consultation in a 3-year period. From the recordings of pregnant women, the last menstrual period and the starting date of medication were used to determine the time of prescription with regard to gestational weeks. RESULTS: In all of the three years, potentially teratogenic medication was prescribed more frequently in the 3rd, 4th and 5th gestational weeks (in between 15-35 days of pregnancy). Approximately 75% of the pregnant women in the study were prescribed with drugs, most frequently with analgesics, antibiotics, gastrointestinal drugs and antidepressants, in these gestational weeks. CONCLUSIONS: The timing of prescriptions in early pregnancy frequently coincides with the increased levels of maternal progesterone in implantation period. Progesterone may lead to negative mood symptoms of an increased pain perception, anxiety, irritability and aggression in some of the pregnant women and therefore causes an increased stress condition which in turn may result in pain, infection and inflammation in the individual. Taking the frequently used medications into consideration, the reason for prescriptions in this period might be related to the symptoms originating from the effects of progesterone. Future studies are needed to better demonstrate this association of drug exposure and effects of maternal progesterone in early pregnancy.

Postnatal neuro-development of fetuses with absent end-diastolic flow in the umbilical artery and/or fetal descending aorta.

OBJECTIVE: To determine whether absence of end-diastolic flow in the umbilical artery and/or fetal aorta impacts postnatal neuro-development in preterm-born children. METHODS: The study group, consisting of 43 fetuses with absent end-diastolic flow in the umbilical artery and/or fetal aorta, was compared with a control group, consisting of 30 fetuses, matching for gestational age but with normal doppler-flow results. The children's neuro-developmental status was assessed using the 'Munich functional developmental diagnostics' (MFDD), between the 2nd and 3rd year of life. RESULTS: Gestational age at birth was 33 + 6 weeks in the study group and 34 + 4 weeks in the control group. A brain-sparing effect was observed in 37.3% of fetuses in the study group compared with 10.0% in the control group (p = 0.014). For all seven MFDD domains, the number of children with deficiencies was higher in the study group. For the domains perception, active speech and comprehension this effect was statistically significant (p < 0.05). Overall, 30.2% of children in the study group and 16.7% of the control group had pathologic test results (p < 0.013). CONCLUSION: Pathological doppler-flow in the umbilical artery and/or fetal descending aorta in preterm born children is associated with neuro-developmental deficiencies. Intensive pediatric care is recommended to mitigate these deficiencies during early childhood.

Letrozole vs. clomiphene citrate in patients with ovulatory infertility.

OBJECTIVE: To compare the effectiveness of letrozole and clomiphene citrate (CC) in ovulatory patients with borderline male factor infertility, early stage endometriosis, and unexplained infertility. DESIGN: Prospective quasi-randomized trial. SETTING: University infertility clinic. PATIENT(S): Forty-six consecutive patients with ovulatory infertility were recruited. Twenty-five patients (67 cycles) were given CC and 21 patients (52 cycles) were given letrozole. Both drugs were given orally on days 3-7 of menses. INTERVENTION(S): Letrozole, CC, ovulation induction, IUI, timed intercourse. MAIN OUTCOME MEASURE(S): Number of follicles, endometrial thickness, and pregnancy rates. RESULT(S): The median serum E2 concentration on the day of hCG administration in the letrozole and CC groups were 191.5 pmol/L and 476.0 pmol/L, respectively. The median endometrial thickness on the day of hCG were 8 mm in both groups. Ovulation occurred in 81% (42/52) of the letrozole-treated and 85% (57/67) of the CC-treated patients. Pregnancy rate (PR) per cycle was 9% (5/52) in the letrozole group and 12% (8/67) in the CC group. CONCLUSION(S): Letrozole and CC have comparable effectiveness in ovulatory patients with borderline male factor infertility, early stage endometriosis, and unexplained infertility.

Transabdominal pulse inversion harmonic imaging improves assessment of ovarian morphology in virgin patients with PCOS: comparison with conventional B-mode sonography.

OBJECTIVE: In virgin policystic ovary syndrome (PCOS) patients transabdominal sonography is the preferential method of the pelvic examination. The purpose of this study was to determine ovarian morphology by the transabdominal route by pulse inversion harmonic imaging (PIHI) in virgin PCOS patients and to compare the diagnostic image quality with conventional B-mode ultrasonography (CBU). METHODS: Fifty-two ovaries in 26 virgin patients were evaluated by the transabdominal approach. Each ovary was examined using both PIHI and CBU. The sharpness of the follicular cysts walls, degree of internal echo definitions of the follicle cysts and overall ovarian conspicuity was assessed subjectively, using 4 point scoring (0, being worst; 3, being best score). The number of countable follicles, the size of largest and smallest ovarian follicle and ovarian volumes were assessed quantitively by both techniques. The effect of body mass index (BMI) on qualitative and quantitative scoring was evaluated. RESULTS: The sharpness of the cyst wall and internal echo structure was significantly better with PIHI than with CBU (P < 0.001 P < 0.001 and P < 0.001, respectively). PIHI improved overall ovarian conspicuity in 41 (78.8%) of 52 examination. The number of countable follicles was significantly lower with CBU (P < 0.001). The maximum diameter of the largest follicle was larger with PIHI sonography to compared CBU (P < 0.001). Mean ovarian volume was significantly larger with CBU (P < 0.001). When data were analyzed separately according to BMI, number of non-diagnostic overall ovarian conspicuity scores with CBU was markedly high in obese patients (88% with CBU versus 3.8% with PIHI). On the other hand, mean number of countable follicles with CBU became much more lower in the obese group (P < 0.001). CONCLUSION: In virgin PCOS patients, when compared to transabdominal CBU, PIHI significantly improved the detection of ovarian follicles, especially in high BMI obese subjects, through increased contrast sensitivity for cystic structures and decreased intrafollicular artifactual echoes. Transabdominal ultrasonographic examination by PIHI mode can contribute to the evaluation of ovaries.

Doppler examinations of fetal and uteroplacental blood flow in AGA and IUGR fetuses before and after maternal physical exercise with the bicycle ergometer.

OBJECTIVE: To study changes in uteroplacental and fetal circulation after maternal exercise in appropriate-for-gestational-age fetuses (AGA) and intrauterine-growth-retarded fetuses (IUGR). MATERIALS AND METHOD: 33 women with an uncomplicated course of pregnancy and ten women with IUGR were examined. Physical stress was caused through a bicycle ergometer with 1.25 W/kg maternal weight. Doppler examinations were performed in the umbilical artery, fetal aorta, middle cerebral and in the uterine artery. Fetal heart rate was documented by monitoring. Maternal lactate and glucose levels as well as maternal blood pressure and heart rate were recorded. RESULTS: No significant changes after cycling could be observed in umbilical and uterine vessels either in the normal pregnancies or in pregnancies with IUGR. In contrast, in the fetal aorta an increase of the RI was recorded in both groups (an increase of 16% [P<0.01] and 18% [P<0.05], respectively for AGA and IUGR cases). In cerebral arteries a decrease of the RI was observed after cycling in both groups (a decrease of 24% [P<0.01] and 13% [P<0.05], respectively for AGA and IUGR cases). In AGA fetuses the RI of the aorta and middle cerebral artery returned to pre-test level by the 18th minute of examination. In IUGR fetuses the RI of the aorta and middle cerebral artery did not return to pre-test levels at the end of the test. Fetal heart rate remained unchanged in both groups. Maternal blood pressure and heart rate increased during the exertion phase but returned to initial values at the end of the test. A 21% and 24% (for AGA and IUGR groups respectively) reduction of maternal glucose values after exercise was observed (P<0.001). Lactate values doubled in both groups after exercise (P<0.001). CONCLUSION: From the results obtained we conclude that maternal exercise does not significantly alter uterine and umbilical perfusion in AGA and IUGR pregnancies, suggesting an absence of change in the uterine vascular bed resistance. However, submaximal maternal exercise was followed by fetal cerebral vasodilatation and an increase of resistance in the fetal aorta that was more evident in IUGR fetuses. This might be due to slight fetal hemoglobin desaturation in those cases.

Is pipelle biopsy really adequate for diagnosing endometrial disease?

BACKGROUND: The purpose of our research was to determine the reliability and accuracy of the Pipelle device in acquiring an adequate and representative endometrial sample and to compare it with D&C histology. MATERIAL/METHODS: A total of 127 women were prospectively included in the study. After Pipelle endometrial sampling, classic dilatation and curettage (D&C) was performed. The histological results of both techniques were compared to assess the accuracy of Pipelle sampling. Prior to endometrial sampling, transvaginal ultrasonography was performed to determine endometrial thickness and pathological lesions, and to exclude other pathologies confined to the pelvis. The outcome measures were specimen adequacy and comparability of histological diagnosis between the Pipelle specimen and the D&C specimen. RESULTS: Although no patient had a failed biopsy procedure, 13 patients had insufficient tissue in the D&C group, and 29 patients in the Pipelle group. In 100 of 127 patients (79%), the Pipelle endometrial histology results were in agreement with the D&C histology results. Pipelle biopsy was unable to diagnose 1 of 5 endometrial hyperplasia cases. CONCLUSIONS: The Pipelle device is a limited endometrial sampling technique for obtaining an adequate and representative endometrial sample. It should be reserved for those patients in whom there is only a minimal risk for endometrial carcinoma, hyperplasia and polyps. Any failure to obtain an endometrial specimen would suggest performing a full endometrial curettage, especially in anamnestically- and sonographically-determined patients at high risk for endometrial cancer.

Migration of an intrauterine contraceptive device to the ovary.

We present the case of a 37-year-old woman with a history of 2 consecutive insertions of intrauterine contraceptive devices (IUDs) 3 years before she was referred to us for sonographic evaluation of lower abdominal pain. The first of the IUDs was presumed to have been expelled spontaneously, and 3 months after insertion of the second device, the patient had begun experiencing lower abdominal pain. Medical treatment with antibiotics and spasmolytics had been unsuccessful. We performed transvaginal sonography, which revealed the presence of an IUD in the uterus and a 2-cm linear metallic echogenic area in the left ovary, believed to represent another IUD. Anteroposterior radiography confirmed that there were 2 IUDs in the pelvis, and CT demonstrated 1 IUD in the uterus and another in the left ovary. The patient underwent laparoscopic removal of the ovarian IUD and was discharged in good condition. To our knowledge, this is the first report of migration of an IUD to the ovary detected on transvaginal sonography. We recommend consideration of this possibility during evaluation of women with unexplained chronic pelvic pain.

Comparison of perinatal outcome in fetuses with reverse or absent enddiastolic flow in the umbilical artery and/or fetal descending aorta.

OBJECTIVES: To examine the differences of perinatal outcome in fetuses with absent and reversed enddiastolic flow velocity waveforms of the umbilical artery or fetal descending aorta. DESIGN: In a retrospective study, 30 pregnant women with reversed enddiastolic flow in the umbilical artery or fetal aorta (group I) were compared with 30 cases of absent enddiastolic flow (group II). Patients were included in the groups according to the last Doppler finding before delivery. Perinatal and neonatal outcome was correlated with antenatal Doppler flow findings. RESULTS: The mean gestational age at birth was 31 weeks in both groups. Fetuses with reverse flow showed higher perinatal (27% and 7% respectively) and overall mortality (53.3% and 10% respectively) compared to the absent enddiastolic flow group (p < 0.05). All the intrauterine fetal deaths occurred in the reversed flow group (n = 12). The rates of intrauterine growth retardation, oligohydramnios and hypocalcemia were different between the groups (p < 0.05). The cesarean section rate, perinatal and neonatal complications including the incidence of acidosis, the number of cases admitted to neonatal intensive care unit and mean treatment time were not different between the groups. A tendency to higher incidence of neonatal cerebral hemorrhage in reversed flow cases (28%) compared to absent enddiastolic flow cases (17%) was observed, but this was not statistically significant. CONCLUSIONS: The present study suggests that reversed flow should be seen as a particular clinical entity with higher incidences of perinatal and overall mortality, and severe intrauterine growth retardation (< 5. perc) compared to the absent enddiastolic flow group. The optimal timing of delivery in pregnancies complicated by highly pathological Doppler flow findings is only to be resolved in well-designed randomized, multicenter clinical trials.

Clinical and biophysical aspects of HELLP-syndrome.

OBJECTIVE: The maternal-perinatal outcome and the significance of biophysical parameters in HELPP syndrome patients were evaluated. METHODS: Sixty cases of HELLP syndrome were determined by retrospective analysis. Medical history, correlation of clinical, laboratory findings, records of fetomaternal Doppler studies, Nonstress test and maternal-perinatal outcome data were evaluated. Chi-square test was used for statistical analysis, and p < 0.05 was accepted as the significance level. RESULTS: The incidence of HELLP syndrome in our institution was 1.03%. Mean gestational age at birth was 33.2 weeks, mean birth weight was 1861 +/- 710 g and mean umbilical pH was 7.25 +/- 0.13. Neonatal thrombocytopenia was demonstrable in 38% of neonates. Patients with low antepartal platelets (< 60,000/microliter) had a significantly higher incidence of intrauterine growth retarded fetuses than patients with higher platelet counts (p = 0.002). Doppler flow measurements were performed in 33 patients (55%). In 16 (48.4%) a pathological Doppler flow was documented. Doppler findings demonstrated very high sensitivity (83%) and specificity (80%) in predicting adverse outcome in growth retarded fetuses. In 17 patients (27%) fetal heart rate monitoring had an obvious pathologic pattern. Respiratory distress syndrome (74.4%) was the main indication for NICU admission. Perinatal mortality rate was 8.3% and neonatal mortality rate was 11.6%. Maternal morbidity rate was 30%. The most commonly observed maternal complications were abruptio placentae (n = 8), disseminated intravascular coagulation (n = 3) and severe postpartal bleeding (n = 3). CONCLUSIONS: In HELLP syndrome patients it is very important to closely follow maternal vital signs and fluid intake and output, and to perform fetal status assessment tests. Of the biophysical parameters, Doppler flow measurement is an especially helpful predictor of poor perinatal outcome in growth retarded fetuses in HELLP patients. Patients with very low platelets have a significantly higher risk of intrauterine growth retarded fetuses.