Four cases of fetal intra-abdominal umbilical vein varix: a single centre's approach to management.

Fetal intra-abdominal umbilical vein (FIUV) varix is a rare prenatal abnormality characterised by a focal intrahepatic or extrahepatic dilatation of the intra-abdominal portion of the umbilical vein. Usually, it is an isolated finding, but in some cases it can be associated to other fetal anomalies. Thrombosis is a possible complication of FIUV varix and it can lead to poor fetal or neonatal outcome. We describe four consecutive cases of FIUV varix diagnosed in our Unit and managed with low-dose aspirin (LDA) prophylaxis until the 35th week of gestation. None of the fetuses developed thrombosis of the varix and the neonatal outcomes were good in all the cases.

Hormonal effects of flutamide in young women with polycystic ovary syndrome.

Anovulation in women with polycystic ovary syndrome (PCOS) is the direct effect of high local androgen concentrations on the ovary. Antiandrogens are substances that prevent androgens from expressing their activity on target tissues. Flutamide is a nonsteroid antiandrogen that has been found effective in hirsute patients, although its mechanism of action is unclear. Eight girls, ranging in age from 16-19 yr, with moderate to severe hirsutism and menstrual irregularities were enrolled in this study. The basal hormonal pattern showed anovulatory cycles; increased concentrations of LH, androstenedione, and testosterone; and increased LH/FSH ratio. A baseline ultrasound scan revealed polycystic ovaries in all patients. All were given 250 mg flutamide twice a day for 6 months. LH, FSH, androstenedione, testosterone, estradiol, and progesterone were evaluated before treatment, every 4 days during the third month of treatment, and on day 24 of the sixth month of treatment. Hirsutism improved, androgen levels dropped, and ovulatory cycles were restored in all subjects. Ultrasonographic examination in follicular phase showed a significant reduction in ovarian volume and ovaries of normal appearance with one dominant follicle. The most important result of the present study was that flutamide restored ovulation in anovulatory PCOS patients. This finding supports the hypothesis that flutamide reduces androgen synthesis through restoration of ovulation, although a direct block of the steroidogenic enzymes of androgen biosynthesis in ovarian thecal cells cannot be excluded.

Increased maternal serum activin A but not follistatin levels in pregnant women with hypertensive disorders.

Activin A levels are elevated in maternal serum of pregnant women with hypertensive disturbances. Because follistatin is a circulating binding protein for activin A, the present study was designed to evaluate whether serum follistatin and activin A levels also change in patients with hypertensive disorders in the last gestational trimester. The study design was a controlled survey performed in the setting of an academic prenatal care unit. Healthy pregnant women (controls, n=38) were compared with patients suffering from pregnancy-induced hypertension (PIH, n=18) or pre-eclampsia (n=16). In addition, the study included a subset of patients with pre-eclampsia associated with intrauterine growth restriction (IUGR, n=5). Maternal blood samples were withdrawn at the time of diagnosis (patients) or in a random prenatal visit (controls), and serum was assayed for follistatin and activin A levels using specific enzyme immunoassays. Hormone concentrations were corrected for gestational age by conversion to multiples of median (MoM) of the healthy controls of the same gestational age. Follistatin levels were not different between controls and patients, while activin A levels were significantly increased in patients with PIH (1.8 MoM), pre-eclampsia (4.6 MoM), and pre-eclampsia+IUGR (3.2 MoM, P<0.01, ANOVA). The ratio between activin A and follistatin was significantly increased in patients with PIH (1.5 MoM) and was further increased in patients with pre-eclampsia (4.5 MoM) and in the group with pre-eclampsia+IUGR (2.6 MoM). Follistatin levels were positively correlated with gestational age in control subjects (r=0. 36, P<0.05) and in patients with PIH (r=0.46, P<0.05) or pre-eclampsia (r=0.61, P<0.01), while activin A correlated with gestational age only in the healthy control group (r=0.69, P<0.0001). The finding of apparently normal follistatin and high activin A levels in patients with PIH and pre-eclampsia suggests that unbound, biologically active, activin A is increased in women with these gestational diseases.

Hypothalamo-pituitary-adrenal axis and adrenal function before and after ovariectomy in premenopausal women.

The hypothalamo-pituitary-adrenal (HPA) axis is modulated by sex hormones. Few data exist on the relation between acute estrogen deficit and HPA axis response to corticotropin-releasing hormone (CRH). The effects of a sudden drop in estradiol levels on basal and CRH-stimulated levels of ACTH, cortisol, testosterone, androstenedione and 17-hydroxyprogesterone (17-OHP) were assessed in nine premenopausal women (44-48 years of age), before and after ovariectomy. The CRH test was performed before and 8 days after ovariectomy. A significant reduction in ACTH and adrenal steroids but not in cortisol response to CRH was observed after ovariectomy. The ratio of deltamax androstenedione/17-OHP after CRH stimulation was substantially the same before and after ovariectomy, whereas deltamax 17-OHP/cortisol was significantly lower in ovariectomized women showing increased 21- and 11beta-hydroxylase activity. The results show that the acute estrogen deficit induces changes in the HPA axis characterized by reduced stimulated secretion of ACTH and steroids but normal stimulated cortisol production.

Maternal serum inhibin A levels are a marker of a viable trophoblast in incomplete and complete miscarriage.

OBJECTIVE: From early gestation the human trophoblast secretes large amounts of inhibin A and activin A, and their measurement provides a value for predicting the outcome in women who become pregnant after assisted reproductive techniques. The aim of the study was to investigate the putative role of maternal serum inhibin A and activin A levels as markers of a viable trophoblast in women who miscarry. DESIGN: Controlled cross-sectional study. METHODS: One group consisted of 65 healthy pregnant women (controls), progressing to deliver a healthy singleton baby and another group consisted of 54 miscarriages (38 incomplete (27 non-viable, 11 anembryonic pregnancies) and 16 complete). Maternal blood samples were collected between 5 and 12 weeks of gestation. RESULTS: Serum human chorionic gonadotrophin concentrations in women with incomplete or complete miscarriages were significantly (both P<0.001) lower than in controls; activin A levels being lowest only in women with a complete miscarriage (P<0.001). On the other hand, inhibin A levels were significantly lower in incomplete or complete miscarriage than in controls (both P<0.0001). CONCLUSIONS: Maternal serum inhibin A, but not activin A, determination reflects the lack of a viable trophoblast in complete miscarriage.

Role of the proteasome in the regulation of fetal fibronectin secretion in human placenta.

The goal of the current study was to examine the role of the ubiquitin-proteasome system (UPS), a pathway of intracellular degradation, in the regulation of fetal fibronectin (FFN) expression in human placenta. Primary cultures of cytotrophoblasts (CTs) and placental mesenchymal cells (PMCs) were isolated from human term placentas and were maintained in serum-free medium (SFM) in the presence of inhibitors of proteasome-mediated degradation (e.g., MG132) as well as inhibitors of other proteases. Levels of secreted FFN and interleukin (IL)-8 in culture media were quantitated by enzyme-linked immunosorbent assay (ELISA), and cell viability was assessed by trypan blue exclusion. Intracellular levels of FFN and ubiquinated proteins were measured by Western blotting, and levels of fibronectin mRNA were determined following Northern blotting. We found that proteasome inhibitors (MG132, MG262, and PSI) potently suppressed levels of secreted FFN in cultures of CTs, but they not did affect levels of IL-8. Lysosomal, calpain, and serine protease inhibitors as well as the anti-inflammatory compound sulfasalazine did not markedly affect levels of secreted FFN in CT cultures. Proteasome inhibitors did not compromise cell viability during the initial 16-18 hours of treatment and did not affect intracellular levels of FFN protein or fibronectin mRNA. The efficacy of suppression of FFN in CT culture media by proteasome inhibitors reflected their effects on intracellular accumulation of ubiquinated proteins. By contrast, the presence of proteasome inhibitors did not alter levels of secreted FFN in cultures of PMCs. We conclude that inhibitors of proteasome-mediated degradation potently and specifically suppressed extracellular expression of FFN in CTs through a cell type-specific pathway that did not involve alterations in FFN synthesis. This suggests that accumulation of ubiquinated proteins in the presence of proteasome inhibitors blocks FFN secretion or promotes the extracellular degradation of FFN. This experimental paradigm will be useful for dissecting the role of the UPS in regulating CT function.

Fetal cerebral oxygenation measured by near-infrared spectroscopy shortly before birth and acid-base status at birth.

OBJECTIVE: To test the hypothesis that the mean cerebral oxygen saturation measured by near-infrared spectroscopy shortly before delivery correlates with fetal acid-base status in umbilical cord blood. METHODS: A specially designed optical probe was inserted through the dilated cervix and placed against the fetal head during labor in 41 women. Changes in cerebral oxyhemoglobin and deoxyhemoglobin concentrations were measured continuously, and the mean cerebral oxygen saturation was determined over a 10-minute period within 30 minutes of delivery. Umbilical arterial and venous blood acid-base status was assessed immediately after birth and then correlated to the values for mean cerebral saturation. RESULTS: Values for mean cerebral oxygen saturation could be determined in 33 fetuses. Umbilical cord artery and vein pH (r = 0.82 and r = 0.79, respectively) showed significant positive correlations (P < .001), whereas base deficit (r = -0.73 and r = -0.71) and carbon dioxide pressure (r = -0.68 and r = -0.63) showed significant negative correlations (P < .001) with mean cerebral oxygen saturation measured within 30 minutes before birth. There was also a significant positive correlation between umbilical vein oxygen pressure and mean cerebral oxygen saturation (r = 0.51, P < .01). CONCLUSION: Fetal umbilical blood gas and acid-base status at birth showed significant correlations with mean cerebral oxygen saturation measured shortly before delivery. Low values for saturation were related to both respiratory and metabolic acidemia.

Growth hormone secretion in premenopausal women before and after ovariectomy: effect of hormone replacement therapy.

OBJECTIVE: To evaluate the GH response to growth hormone-releasing hormone (GH-RH) stimulation in premenopausal women before and after ovariectomy and after 1 month of estrogen replacement therapy (ERT). PATIENTS: Ten women 42 to 49 years of age awaiting combined hysterectomy and ovariectomy for a variety of benign gynecological conditions. INTERVENTION: Endocrine status was determined by assay of basal levels of gonadotropins (LH, FSH), E2, P, and PRL. Stimulation with GH-RH was performed before and 8 to 10 days after ovariectomy, and after a month of ERT. RESULTS: A significant reduction in GH response to GH-RH was observed after ovariectomy. Estrogen replacement therapy restored GH response to presurgical levels. CONCLUSIONS: The results support the role of E2 in the stimulated secretion of GH and suggest that ERT increases pituitary stores of GH.

Low estrogen oral contraceptives and the hypothalamo-pituitary axis.

The hypothalamo-pituitary axis in a group of 10 women (17-25 years of age) taking low-dose-estrogen oral contraceptives (20 micrograms ethinylestradiol (EE) + 150 micrograms desogestrel) for at least 6 months was investigated. The subjects underwent the GnRH (50 micrograms) and TRH (200 micrograms) stimulation tests for the evaluation of LH, FSH, Pr1, TSH and GH secretion. In the basal blood sample, E2, P, free T, A and SHBG levels were also determined. An elevation in LH response to GnRH was found, whereas FSH was inhibited. After TRH administration, the Pr1 response was the same in the oral contraceptive cycle as in the pretreatment cycle. Similar results were observed after TSH. Significantly, GH responded to TRH stimulation in the oral contraceptive cycles, but not in the pretreatment cycles. These results show that the new combination of 20 micrograms EE and desogestrel blocks hypothalamic production of GnRH. The different response to GnRH of LH and FSH reveals a differentiated sensitivity to the oral contraceptive which seems to inhibit the pituitary FSH-secreting gonadotrope cells in particular.

Inhibition of ovulation with transdermal estradiol and oral progestogens in perimenopausal women.

The effects of 6 months of combined hormone therapy with transdermal estradiol (0.05 mg/day x 21 days) and different oral progestogens (10 mg/day medroxyprogesterone acetate [MPA] in the last 12 days, 10 mg/day dihydrogesterone in the last 12 days, and 50 mg/day cyproterone in the first 10 days), on menopausal symptoms and hypothalamo pituitary-ovarian function were studied in normal perimenopausal women. The study included 38 perimenopausal women, aged 43-49 years, with regular cycles of 26-32 days in length and menopausal symptoms. Endocrine status was determined by assay of basal levels of gonadotropins (LH, FSH), E2, and P every week until menstrual bleeding, before and during the first month of therapy. Plasma levels of LH and FSH were suppressed in the first month of therapy while E2 had a mean value of 45 +/- 12 pg/ml. Ultrasound examination and low levels of P indicated a complete block of ovulation and hypothalamo-pituitary-ovarian activity. All women reported the disappearance of vasomotor symptoms and nocturnal sweating. Transdermal estradiol and oral progestogens were well tolerated. This study shows that combined hormone therapy with low doses of transdermal estrogen patches and different oral progestogens reduces menopausal symptoms and also safeguards against unwanted pregnancies in the perimenopausal period.

Effect of nuchal cord on fetal cerebral haemodynamics and oxygenation measured by near infrared spectroscopy during labour.

OBJECTIVE: To test the hypothesis that a nuchal cord has a significant effect upon fetal cerebral haemodynamics and oxygenation during labour. STUDY DESIGN: A specially designed optical probe was inserted through the dilated cervix and placed against the scalp of 37 fetuses during labour in a teaching hospital obstetric unit. Changes in total cerebral haemoglobin concentration were measured continuously together with fetal heart rate and uterine contraction frequency during the first and second stages. RESULTS: At birth 11 fetuses (30%) were noted to have a nuchal cord (cord around the neck). For these, significantly more contractions were associated with an increase in total cerebral haemoglobin concentration when compared with the control fetuses without a nuchal cord (40.2% (S.D.19.5) vs 5.9% (S.D.7.1), P < 0.001). A significantly greater number of variable decelerations was found in the nuchal cord group (4 per 30 min vs. 2 per 30 min in the controls) (P < 0.01). There was no significant difference between mean cerebral oxygen saturation determined at the end of the first stage of labour, which was 47.0% (S.D.13.3) and 50.1% (S.D.11.8) for the nuchal cord and control groups, respectively. CONCLUSION: A nuchal cord was associated with a significant increase in cerebral blood volume during uterine contractions, without any significant effect upon cerebral oxygenation.

Fetal heart rate changes and cerebral oxygenation measured by near-infrared spectroscopy during the first stage of labour.

OBJECTIVE: To determine the relationship between contraction related changes in fetal heart rate and cerebral oxygenation measured by near-infrared spectroscopy during labour. STUDY DESIGN: A specially designed optical probe was inserted through the dilated cervix and placed against the fetal head in 30 women during labour. Alterations in fetal heart rate during the final hour of the first stage of labour were compared with changes in the cerebral haemoglobin oxygenation index (delta oxyhaemoglobin concentration - delta deoxyhaemoglobin concentration) measured before, during and after uterine contractions. RESULTS: Uterine contractions which were associated with either no alteration, accelerations or early decelerations of the fetal heart rate showed no significant changes in the haemoglobin oxygenation index. Variable, late and prolonged decelerations all showed significant decreases in the haemoglobin oxygenation index (P < 0.01) either during (variable) or after (variable, late and prolonged) the uterine contraction. CONCLUSION: The association between variable, late and prolonged FHR decelerations and significant falls in cerebral oxygenation during late labour suggests that these fetal heart rate patterns are associated with an increased risk of fetal cerebral hypoxia.

Placental and fetal pulsatility indices in gestational diabetes mellitus.

OBJECTIVE: To assess the usefulness of placental and fetal Doppler velocimetry in the surveillance of gestational diabetes mellitus (GDM). STUDY DESIGN: We studied 89 patients with GDM. All fetuses underwent umbilical, fetal descending thoracic aorta and fetal middle cerebral artery pulsatility index (PI) assessment. Doppler results were not used for management. We correlated PI with route of delivery and with the following perinatal complications: small size for gestational age, cesarean section (CS) for acute fetal distress (AFD), respiratory distress syndrome, hyperbilirubinemia, hypocalcemia, hypoglycemia, macrosomia and stay in a neonatal intensive care unit. RESULTS: Seventy-seven patients (87%) had normal Doppler measurements, while 12 (13%) showed one or more abnormal measurements. The greatest incidence of CS for AFD (42% vs. 16%, P < .001), as well as neonatal hyperbilirubinemia (25% vs. 10%, P < .001) and hypoglycemia (25% vs. 5%, P < .001) was reported among the women with abnormal Doppler measurements. CONCLUSION: Fetal placental hemodynamics are normal in most cases of GDM. In a small percentage of cases we observed abnormal fetal placental PI associated with a higher incidence of perinatal complications. Hence, the finding of abnormal PI must induce the physician to carry out more intensive obstetric care of women with GDM.

Peptidergic innervation of mesenteric lymphatics in guinea pigs: an immunocytochemical and pharmacological study.

By immunocytochemistry, substance P immunoreactive (SP-IR) and vasoactive intestinal peptide immunoreactive (VIP-IR) nerve fibers were examined in guinea pig mesenteric lymph collectors. The immunoreactive nerve fibers, located in the adventitia of lymphatics, were few and were irregularly distributed along the vessel wall. These fibers appeared to be more numerous and more evenly distributed along the corresponding artery and vein walls within the same area. SP immunoreactivity in the vascular nerves was depleted in guinea pigs injected with capsaicin but was unaffected by the injection of 6-hydroxydopamine. By contrast, VIP-IR nerve fibers were unaffected by both treatments. It is concluded that SP-IR nerve fibers in the lymphatics are likely to be of sensory origin and that VIP containing nerves in the lymph collectors are distinct from SP-containing and noradrenergic nerves. It is also suggested that lymph collectors possess a complex although limited innervation pattern not only of autonomic nerve fibers containing classic neurotransmitters but also of peptidergic nerve fibers of a different origin with a vasomotor and/or sensory action.

Activin A as a marker of intrauterine infection in women with preterm prelabour rupture of membranes.

OBJECTIVE: To assess maternal serum activin A, an early phase response protein in systemic infection, as an early marker of intrauterine infection in women with preterm prelabour rupture of membranes (PPROM). STUDY DESIGN: A prospective cohort study of women with singleton pregnancies complicated by PPROM at 24 to 34 weeks' gestation. Serum was collected for activin A and cytokine measurements. Activin A was measured using commercial enzyme-linked immunosorbent assay. Cytokines were measured using commercial multiplex assay. Pregnancy outcomes including infection were determined by case-record review. RESULT: Eighteen women with PPROM were studied, with seven developing intrauterine infection. Serum activin A in women with and without infection did not differ. Peripheral white cell count, interleukin (IL)-6 and IL-10 were higher (P=0.03, 0.05 and 0.009, respectively) and IL-7 lower (P=0.04) 72 h before delivery in women with infection. CONCLUSION: Activin A is not a clinically useful marker of intrauterine infection in women with PPROM.

Thyrotropin secretion before and after ovariectomy in premenopausal women.

Many studies have shown a physiological reduction in thyroid function with age in animals, and less clearly in humans, with an increase in the incidence of age-dependent clinical and subclinical hypothyroidism. Women are more subject to thyroid dysfunction than men. In postmenopausal women the sudden drop in estrogen levels may affect not only pituitary gonadotropins but also other pituitary hormones directly or indirectly involved in reproductive function. The response of thyrotropin to thyrotropin releasing hormone (TRH) has been shown to decrease with age and basal levels of thyrotropin have been found to be reduced in elderly subjects. In the present study we evaluated the response of thyrotropin to TRH before and after ovariectomy in premenopausal women and during estrogen therapy. The response of thyrotropin to TRH after ovariectomy was significantly less than before. Estrogen replacement therapy restored the thyrotropin response to TRH to pre-ovariectomy levels. This significant decrease in the thyrotropin response to TRH observed in surgical postmenopausal women may be explained by lower endogenous estradiol levels.

Oligomenorrhea treatment by purified FSH using a fixed protocol.

This study is designed to evaluate the effectiveness, safety and tolerability of a low dose of purified FSH administration using a fixed protocol in oligomenorrheic patients not desiring pregnancy. We used a low dose (75 IU/day for 5 days) of purified FSH (Metrodin) in 10 oligomenorrheic patients (aged 18-30) for 25 cycles. The onset of menstruation occurred in 7 patients (70%) and in 19 treatment cycles (76%), the ovulation was verified in 5 of these patients (50%) for 13 cycles (52%). One patient had spotting after the treatment, 2 patients did not have any response. The treatment did not cause side effects and it showed a good tolerability.

Danazol administration after gonadotrophin-releasing hormone analogue reduces rebound of uterine myomas.

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.