[Risk factors for the early development of septic shock in patients with severe COVID-19].

AIM: In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19. MATERIALS AND METHODS: We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure. RESULTS: We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70). CONCLUSION: The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.

Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30 mm.

OBJECTIVE: To evaluate whether the presence of cervical funneling or intra-amniotic debris identified in the second trimester is associated with a higher rate of preterm birth (PTB) in asymptomatic nulliparous pregnant women with a midtrimester cervical length (CL) less than 30 mm (i.e. below the 10th percentile). METHODS: This was a secondary cohort analysis of data from a multicenter trial in nulliparous women between 16 and 22 weeks' gestation with a singleton gestation and CL less than 30 mm on transvaginal ultrasound, randomized to treatment with either 17-alpha-hydroxyprogesterone caproate or placebo. Sonographers were centrally certified in CL measurement, as well as in identification of intra-amniotic debris and cervical funneling. Univariable and multivariable analysis was performed to assess the associations of cervical funneling and intra-amniotic debris with PTB. RESULTS: Of the 657 women randomized, 112 (17%) had cervical funneling only, 33 (5%) had intra-amniotic debris only and 45 (7%) had both on second-trimester ultrasound. Women with either of these findings had a shorter median CL than those without (21.0 mm vs 26.4 mm; P < 0.001). PTB prior to 37 weeks was more likely in women with cervical funneling (37% vs 21%; odds ratio (OR), 2.2 (95% CI, 1.5-3.3)) or intra-amniotic debris (35% vs 23%; OR, 1.7 (95% CI, 1.1-2.9)). Results were similar for PTB before 34 and before 32 weeks' gestation. After multivariable adjustment that included CL, PTB < 34 and < 32 weeks continued to be associated with the presence of intra-amniotic debris (adjusted OR (aOR), 1.85 (95% CI, 1.00-3.44) and aOR, 2.78 (95% CI, 1.42-5.45), respectively), but not cervical funneling (aOR, 1.17 (95% CI, 0.63-2.17) and aOR, 1.45 (95% CI, 0.71-2.96), respectively). CONCLUSIONS: Among asymptomatic nulliparous women with midtrimester CL less than 30 mm, the presence of intra-amniotic debris, but not cervical funneling, is associated with an increased risk for PTB before 34 and 32 weeks' gestation, independently of CL. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal vitamin C and E supplementation in smokers is associated with reduced placental abruption and preterm birth: a secondary analysis.

OBJECTIVE: Smoking and pre-eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self-reported smoking status focusing on outcomes known to be impacted by maternal smoking. DESIGN/SETTING/POPULATION: A secondary analysis of a multi-centre trial of vitamin C/E supplementation starting at 9-16 weeks in low-risk nulliparous women with singleton gestations. METHODS: We examined the effect of vitamin C/E by smoking status at randomisation using the Breslow-Day test for interaction. MAIN OUTCOME MEASURES: The trial's primary outcomes were PE and a composite outcome of pregnancy-associated hypertension (PAH) with serious adverse outcomes. Perinatal outcomes included preterm birth and abruption. RESULTS: There were no differences in baseline characteristics within subgroups (smokers versus nonsmokers) by vitamin supplementation status. The effect of prenatal vitamin C/E on the risk of PE (P = 0.66) or PAH composite outcome (P = 0.86) did not differ by smoking status. Vitamin C/E was protective for placental abruption in smokers (relative risk [RR] 0.09; 95% CI 0.00-0.87], but not in nonsmokers (RR 0.92; 95% CI 0.52-1.62) (P = 0.01), and for preterm birth in smokers (RR 0.76; 95% CI 0.58-0.99) but not in nonsmokers (RR 1.03; 95% CI 0.90-1.17) (P = 0.046). CONCLUSION: In this cohort of women, smoking was not associated with a reduction in PE or the composite outcome of PAH. Vitamin C/E supplementation appears to be associated with a reduction in placental abruption and preterm birth among smokers.

The association of beta-2 adrenoceptor genotype with short-cervix mediated preterm birth: a case-control study.

OBJECTIVE: To determine whether ß2 -adrenoceptor (ß2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester. DESIGN: A case-control ancillary study to a multicentre randomised controlled trial. SETTING: Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. POPULATION: Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. METHODS: Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. ß2 AR genotype was determined at positions encoding for amino acid residues 16 and 27. MAIN OUTCOME MEASURES: Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks. RESULTS: Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. CONCLUSIONS: ß2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with ß2 AR genotype do not appear to involve a short cervix pathway.

Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids.

OBJECTIVE: The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. STUDY DESIGN: This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. RESULTS: CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. CONCLUSION: Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population?

OBJECTIVE: To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. DESIGN: A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. SETTING: A multicentre study in 16 academic medical centres in the USA. POPULATION: Low-risk nulliparous women. METHODS: Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. MAIN OUTCOME MEASURES: Change in PlGF, sFlt-1 and sEng. RESULTS: Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. CONCLUSION: Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.

Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women.

OBJECTIVE: To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. DESIGN: A nested case-control study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. SETTING: Fourteen academic health centres in the USA. POPULATION: Women with prior spontaneous preterm birth. METHODS: In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (16-22 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. MAIN OUTCOME MEASURES: Recurrent preterm birth at <37 and <32 weeks of gestation. RESULTS: The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.48-3.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.38-1.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (-0.18, P < 0.01). CONCLUSIONS: In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth.

Clinical significance of early (< 20 weeks) vs. late (20-24 weeks) detection of sonographic short cervix in asymptomatic women in the mid-trimester.

OBJECTIVE: The aim of this study was to determine whether the risk of early spontaneous preterm delivery (PTD) in asymptomatic women with a sonographic cervical length of ≤ 15 mm in the mid-trimester changes as a function of gestational age at diagnosis. METHODS: This cohort study included 109 asymptomatic patients with a sonographic cervical length of ≤ 15 mm diagnosed at 14-24 weeks of gestation. Women with a multifetal gestation, cerclage and a cervical dilatation of > 2 cm were excluded. The study population was stratified by gestational age at diagnosis (< 20 weeks vs. 20-24 weeks) and by cervical length (≤ 10 mm vs. 11-15 mm). The primary outcome variables were PTD at < 28 and < 32 weeks of gestation and the diagnosis-to-delivery interval. RESULTS: The median gestational age at diagnosis of a short cervix before 20 weeks and at 20-24 weeks was 18.9 and 22.7 weeks, respectively. Women diagnosed before 20 weeks had a higher rate of PTD at < 28 weeks (76.9% vs. 30.9%; P < 0.001) and at < 32 weeks (80.8% vs. 48.1%; P = 0.004), and a shorter median diagnosis-to-delivery interval (21 vs. 61.5 days, P = 0.003) than those diagnosed at 20-24 weeks. The rate of amniotic fluid sludge was higher among patients diagnosed with a short cervix at < 20 weeks of gestation than in those in whom it was diagnosed between 20 and 24 weeks (92.3% vs. 48.2%; P < 0.001). CONCLUSIONS: Asymptomatic women with a sonographic cervical length of ≤ 15 mm diagnosed before 20 weeks of gestation have a dramatic and significantly higher risk of early preterm delivery than women diagnosed at 20-24 weeks. These findings can be helpful to physicians in counseling these patients, and may suggest different mechanisms of disease leading to a sonographic short cervix before or after 20 weeks of gestation.

Plasma soluble endoglin concentration in pre-eclampsia is associated with an increased impedance to flow in the maternal and fetal circulations.

OBJECTIVES: To examine the relationship between abnormalities in uterine (UtA) and/or umbilical artery (UA) Doppler velocimetry and maternal plasma concentrations of soluble endoglin (sEng) in patients with pre-eclampsia (PE). METHODS: A cross-sectional study was conducted in 135 normal pregnant women and 69 patients with PE. Patients with PE were subclassified into four groups: those who had Doppler abnormalities in both the UtA and UA, patients who had Doppler abnormalities in the UtA alone, those who had Doppler abnormalities in the UA alone, and patients without Doppler abnormalities in either vessel. Plasma concentrations of sEng were determined by enzyme-linked immunosorbent assay. RESULTS: Among patients with PE, those with abnormal UtA and UA Doppler velocimetry had the highest median plasma concentration of sEng compared with any other group (P < 0.001, Kruskal-Wallis test). Women with PE with normal Doppler velocimetry in both vessels had the lowest median plasma concentration of sEng. There was a significant relationship between plasma concentrations of sEng and mean UtA resistance index (Spearman Rho = 0.5, P < 0.001) as well as UA pulsatility index (Spearman Rho = 0.4, P = 0.002). Multiple regression analysis suggested that Doppler abnormalities in the UtA and UA as well as gestational age at blood sampling contributed to plasma sEng concentrations (P < 0.001). CONCLUSIONS: Abnormalities of impedance to blood flow in the UtA and UA are associated with an excess of sEng in the circulation of mothers with PE. These findings suggest that the 'antiangiogenic state' in PE is partially reflected in abnormalities of Doppler velocimetry.

Human fetal movement: spontaneous oscillations near one cycle per minute.

Spectral analysis of spontaneous fluctuations in human fetal movement revealed strong oscillations at frequencies between 0.24 and 0.90 cycle per minute, which are much higher than those of the cyclic alternation of quiet and active states in the fetus and neonate. Oscillations at frequencies up to 2.88 cycles per minute were also detected, but they were usually much weaker. The prominent peaks in the fetal movement spectra are in the frequency range of recently reported neonatal motor rhythms, and indicate the existence of a cyclic process controlling spontaneous motor output that oscillates near one cycle per minute and begins to function in utero.

Specific neurodevelopmental damage in mice offspring following maternal inflammation during pregnancy.

Intrauterine inflammation is a major risk for offspring neurodevelopmental brain damage and may result in cognitive limitations and poor cognitive and perceptual outcomes. Pro-inflammatory cytokines, stimulated during inflammatory response, have a pleotrophic effect on neurons and glia cells. They act in a dose-dependent manner, activate cell-death pathways and also act as trophic factors. In the present study, we have examined in mice the effect of short, systemic maternal inflammation on fetal brain development. Maternal inflammation, induced by lipopolysaccharide (LPS) at gestation day 17, did not affect morphogenic parameters and reflex development during the first month of life. However, maternal inflammation specifically increased the number of pyramidal and granular cells in the hippocampus, as well as the shrinkage of pyramidal cells, but not of the granular cells. No additional major morphological differences were observed in the cerebral cortex or cerebellum. In accordance with the morphological effects, maternal inflammation specifically impaired distinct forms of learning and memory, but not motor function or exploration in the adult offspring. The specific deficiency observed, following maternal inflammation, may suggest particular sensitivity of the hippocampus and other associated brain regions to inflammatory factors during late embryonic development.

Postmortem chorionic villus sampling: correlation of cytogenetic and ultrasound findings.

We performed chorionic villus samplings (CVS) in 795 cases in the first trimester during a 13-month period. Of these 35 were found to have a blighted ovum or missed abortion prior to the procedure. Nineteen women consented to have CVS. Ultrasonographic and cytogenetic findings in these 19 pregnancies were correlated. Expected gestational age was determined by last menstrual period. Observed gestational age was determined by crown rump length (CRL) (12 pregnancies) or gestational sac (GS) (7 pregnancies without fetal pole). The differences in days between the estimated and observed gestational ages was determined for each pregnancy. In all 19 CVS samples cytogenetic diagnosis documented aneuploidy. Ten cases had chromosome abnormalities virtually always lethal in the embryonic period (group I). Nine pregnancies had defects with moderate potential for fetal viability (group II). Gestations with low viability potential (group I) had estimated minus observed gestational age discrepancies (23.4 +/- 8.3 days) significantly greater than gestations with moderate viability potential (group II) (8.9 +/- 4.3 days) (P less than .001). The absence of a fetal pole was more common in group I. CVS in pregnancies with missed abortion or blighted ovum is feasible and has a high likelihood of documenting aneuploidy. Furthermore, the more severe the anomaly the more likely there will be very early fetal demise or intrauterine growth retardation.

Effects of induction of labor with prostaglandin E2 on fetal breathing and body movements: controlled, randomized, double-blind study.

OBJECTIVE: To evaluate the effects of prostaglandin (PG) E2, given for induction of labor at term, on fetal breathing and body movements. METHODS: Eighteen women with term pregnancies, mild gestational hypertension, intact membranes, and unripe cervices who were not in labor participated in this study. After a 60-minute baseline ultrasound examination of fetal chest and body movements, recorded on videotape, the patients were randomly assigned to either 3 mg intravaginal PGE2 tablets or controls (placebo intravaginal tablets). Following tablet insertion and a 3-hour observation time, a second 60-minute ultrasound recording of fetal movements was taped. The videotape recordings were interpreted according to the total amount of time occupied by fetal body movements and fetal breathing movements. RESULTS: There was a total of 2180 minutes of ultrasound tape recordings, with 136.2 minutes of fetal body movements (6.2%) and 207.8 minutes of fetal breathing movements (9.5%). Mean (+/- standard deviation) observation times per patient before and after tablet insertion were 60.3 +/- 1.2 and 56.4 +/- 1.2 minutes for the PGE2 group and 60.1 +/- 1.3 and 60.4 +/- 1.1 minutes for the control group. Three hours after PGE2 insertion, there were significant decreases in the percentage of time occupied by body movements (7.8 +/- 3.1 versus 3.4 +/- 2.0%; P < .003) and breathing movements (10.6 +/- 8.6 versus 3.9 +/- 2.3%; P < .007). Three hours after tablet insertion, there were statistically significant decreases in the percentage of time occupied by body movements (P < .025) and breathing movements (P < .01) between the control and study groups. CONCLUSION: Induction of labor with intravaginal PGE2 tablets inhibits fetal body and breathing movements. The effects could be due to direct action on the fetus or indirect effects of PGE2 (through uterine contraction and/or endogenous PG).

Active and quiet periods in the preterm and term fetus.

Heart rate variability and fetal movement were used to classify active and quiet fetal periods. Fetuses at 28 to 30 weeks and at 38 to 40 weeks' gestation were compared. A period of fetal movement with increased variability of heart beat was classified as active and one with the absence of movement and diminished fetal heart beat was classified as quiet. The results demonstrated significant differences both in the number of active-quiet cycles per hour and in the length of the active periods. These findings suggest that analogs of fetal behavioral states may be present before birth and have cyclic patterns, and that the time spent in each fetal period is longer in older fetuses.

Nonpharmaceutical ripening of the unfavorable cervix and induction of labor by a novel double balloon device.

Artificial ripening of the unfavorable cervix was attempted in 48 women using intracervical prostaglandin (PG) E2 gel applied by a cannula and in 70 others by a newly designed double balloon device (Atad Ripener Device). In the first group (phase A), application of PGE2 gel by intracervical cannula resulted in a mean increase of 3 points in the Bishop score and a mean instillation-to-delivery time of 34.2 hours. The study of labor induction by the double balloon device was carried out in two parts. One (phase B) consisted of a double-blind randomized controlled study in which, through the double balloon device, ten women received PGE2 gel and another ten were given placebo gel. There was no significant difference in the increase of Bishop score between the two groups (5.8 points in the treatment group and 6.0 in the placebo-controlled group). Ninety percent of women in both groups delivered vaginally with a mean of 20.8 hours after device insertion. The third phase of the study consisted of an open trial of inserting the double balloon device alone without PGE2, and inflating the balloons in 50 patients. A mean increase of 4.4 points in the Bishop score was noted in these women. These findings suggest that the use of the double balloon device for ripening of the unfavorable cervix is an effective and well-tolerated method of labor induction.

Amnioinfusion: does the choice of solution adversely affect neonatal electrolyte balance?

OBJECTIVE: To determine whether various solutions commonly used in amnioinfusion during labor affect neonatal electrolyte and blood gas values. METHODS: Amnioinfusion for thick meconium or severe variable fetal heart rate decelerations is used at our institution according to a standardized protocol. During alternating 3-week periods, the only solution made available for amnioinfusion was either normal saline or Ringer's lactate. Bolus volume, rate, and duration of infusion were determined by the individual physicians. At delivery, cord blood was collected for electrolyte and blood gas determination. These values were compared between the two solution groups and to a non-infused control group. RESULTS: Complete data on neonatal electrolytes and blood gas values were available on 53 infusion patients (20 Ringer's lactate, 33 normal saline) and 39 non-infusion patients. Comparing infusion to non-infusion patients and those infused with Ringer's lactate to those with normal saline, we found no significant difference in demographics, neonatal outcome variables, duration of labor, neonatal electrolytes, and cord blood gas values. Infusion variables (bolus volume, infusion rate, hours infused, and total volume infused) did not differ between solutions. Total volume and hours of infusion were closely correlated with each other (r = 0.93, P < .001); both were correlated with neonatal chloride (r = 0.38 and r = 0.36, respectively; P < .005). No cases of hypernatremia or hyperchloremia were found in any of the groups. The type of solution used had no effect on the neonatal chloride trend. CONCLUSION: The use of both normal saline and Ringer's lactate for indicated amnioinfusion in labor appears to have no clinically significant effect on neonatal electrolytes.

Oral contraceptive pills and follicular fluid hormones in an in vitro fertilization program.

Fluids were collected from 136 ovarian follicles of 35 women undergoing in vitro fertilization and embryo transfer (IVF-ET). Fifteen women (76 follicles) received oral contraceptive pills (OCs) prior to ovulation induction. All women received human menopausal gonadotropins (hMG) for ovulation induction and in all cases follicular aspiration was performed 32 to 34 hours after an injection of human chorionic gonadotropin (hCG). The concentrations of follicular-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and 17 beta-estradiol (E2) in the follicular fluids (FF) were measured by radioimmunoassay (RIA). FSH concentration in the FF of the OCs group (15 women, 76 follicles) was significantly lower (2.1 mIU/mL) as compared to the FSH (15.9 mIU/mL) in the FF of the control group (20 women, 60 follicles). The LH FF concentrations after hCG injection were similar in the two groups. The E2/P ratio in the OCs group (9.6) was significantly lower than the E2/P ratio in the control group (20.6). OCs given to patients before induction of ovulation with hMG results in lower E2/P ratios and lower FSH concentration in the FF.

The "forgotten" intrauterine device.

It is essential to ascertain that women who had an IUD inserted at some time have indeed had the device removed. It is also important to ensure that the whole IUD was removed and that no parts were left in the uterine cavity. This is especially true in cases of infertility and should be ascertained before invasive investigations such as hysterosalpingography or laparoscopy commence. An accurate history and ultrasonography can easily rule out a forgotten or fragmented IUD, thereby preventing considerable unnecessary suffering and expense.

PIP: This article presents 3 cases that illustrate a generally overlooked complication of IUD use: a device that is forgotten by the patient and gynecologist and remains in the uterus. The cases demonstrate the need to ensure that women who have had an IUD inserted at some point have indeed had the device removed. It is especially important to ensure that there is no IUD in utero in the following 2 situations: 1) women who claim or were told the IUD fell out or in cases where the suspected spontaneous loss of an IUD was not documented radiographically; and 2) women referred for infertility investigation, who previously had an IUD and in whom removal of an intact device is not documented by a physician's report or gross pathology report. An accurate history and ultrasonography can easily rule out a forgotten or fragmented IUD, thereby preventing considerable unnecessary testing and expense.

The effect of metoclopramide on ovarian responsiveness to gonadotropin administration in patients with severe polycystic ovarian syndrome.

Six patients with poor ovarian response to menotropin after pretreatment with a gonadotropin-releasing hormone analog exhibited improved ovarian responsiveness when metoclopramide was added on days 3, 5, and 7 of the cycle. This was evidenced by a higher number of leading follicles (4.4 versus 0.6), a higher mean of maximal serum 17 beta-estradiol levels (560 versus 178 pg/mL), a shorter duration of menotropin treatment (7 versus 11 days), and fewer ampules of menotropin used (20 versus 37 ampules/cycle) in metoclopramide-treated cycles as compared with control cycles, respectively. Serum prolactin levels reached a maximum of 172 ng/mL within 1 hour after metoclopramide administration and declined to normal range within 6 hours. These results suggest that intermittent increased prolactin secretion may augment ovarian response to gonadotropins.

Treatment of hirsutism with cimetidine: a prospective randomized controlled trial.

Cimetidine (Tagamet, Smith Klein, Brussels, Belgium) the histamine receptor type 2 blocker, has been suggested as a possible treatment of hirsutism. In a prospective randomized controlled trial, cimetidine 1.5 gm a day was given for 3 months to 12 moderately or severely hirsute women, while 8 other women were randomized to serve as a control group. There was no significant change in the hair growth rate in either group as measured by two assessment methods. This finding suggests that cimetidine, given in the recommended dose for a period of 3 months, does not have a beneficial effect on hirsutism.