Dopa reaction of fetal melanocytes before and after skin transplantation on to nude mice.

We have previously demonstrated that human fetal epidermal melanocytes are dopa-negative. The present study was conducted to test the hypothesis that human fetal melanocytes can be activated to produce melanin under conditions differing from their natural in utero environment. To address this question, dopa staining activity of fetal epidermal sheets, obtained from seven aborted fetuses with estimated gestational ages of 13-20 weeks, was evaluated before and after engraftment on to nude mice. Dopa staining became positive 7 days post-engraftment. The intensity of the dopa reaction and the mean number of melanocytes increased by day 14 post-engraftment, and these changes were even greater by day 30. These observations indicate that human fetal melanocytes, potentially capable of synthesizing melanin under conditions differing from their normal in utero environment, are either inhibited, or not stimulated to do so.

Actigraphic home-monitoring of the sleep patterns of in vitro fertilization children and their matched controls.

The sleep patterns of 35 in vitro fertilization (IVF) children aged 19 to 57 months and their matched controls were evaluated by actigraphic home-monitoring for three consecutive nights. Actigraphic data were analysed by an automated scoring procedure developed in the authors' laboratory. There were no significant differences in activity levels between IVF multiple-birth subjects and their matched controls or between IVF singletons and their matched controls. In contrast, multiple-birth subjects had higher activity levels during sleep and lower sleep efficiency than singletons in both IVF and control groups. Sleep measures showed night-to-night stability in all groups.

Failure of meiotic competence in human oocytes.

The administration of hCG to women undergoing in vitro fertilization and embryo transfer (IVF/ET) results in the meiotic maturation of cumulus-oocyte complexes (COC). Sometimes oocytes being aspirated for IVF/ET fail to resume meiosis in vivo and even after a subsequent 20-h incubation in vitro and are thus defined as meiotic competence failure (MCF) oocytes. The relationship between the proportion of MCF oocytes and other IVF/ET outcomes was studied over 3 years in 703 tested cycles of 487 women. Women yielding one or more MCF oocytes in at least one menstrual cycle represented 8.6% of this population and were defined as MCF women. Cumulus state in the MCF oocyte population was characterized as mature in 57.4 +/- 6.7%, intermediate in 13.9 +/- 4.0%, immature in 24.1 +/- 8.7%, and atretic in 4.6 +/- 2.7%. These values differed significantly, by 0.6-, 2.9-, 7.1-, and 4.6-fold, respectively, as compared to the corresponding COC aspirated from women yielding only meiotically competent (MC) oocytes. In a menstrual cycle yielding both MC and MCF oocytes, the IVF/ET variables were evaluated in the MC oocytes. Thus, in such cases the incidence of fertilization or cleavage and the number of blastomeres per embryo were significantly reduced concomitant with the increase in percentage of MCF oocytes. When the percentage of MCF oocytes was 25% or more, no pregnancy was achieved. Various follicular parameters and serum 17 beta-estradiol (E2) and progesterone (P4) levels were compared in MC and MCF women over the four days preceding day of aspiration.(ABSTRACT TRUNCATED AT 250 WORDS)

Transvaginal sonography, color flow imaging, computed tomographic scanning, and CA 125 as a routine follow-up examination in women with pelvic tumor: detection of recurrent disease.

We were trying to determine whether transvaginal sonography combined with color flow imaging should be used routinely for detecting recurrent pelvic tumors in patients treated for pelvic cancer. Eighteen patients who had completed their treatment for pelvic tumor were examined every 6 months by gynecologic examination, a CT scan, serum CA 125 levels, and transvaginal sonography with color flow imaging. Laparotomy or fine-needle biopsy was performed when a recurrent pelvic mass was observed or suspected on CT scans or transvaginal sonography. In nine of 18 patients a recurrent pelvic tumor was observed or suspected on CT scans or on transvaginal sonography. A recurrent pelvic tumor was diagnosed on laparotomy in five patients. In four patients, only a fine-needle biopsy was performed and only two of them had positive results. The highest sensitivity and specificity for detecting recurrent pelvic tumors were achieved by transvaginal sonography (100 and 91%, respectively) and by color flow imaging (86 and 100%, respectively). Intratumoral blood vessels were detected in all cases with recurrent pelvic tumors, and in only one of these cases the PI was high. We recommend a routine follow-up with transvaginal sonography in women completing their treatment for pelvic tumors. When a recurrence of tumor is only suspected on transvaginal sonography, color flow imaging may be used as an additional diagnostic tool.

Injury severity scoring and length of stay in hospital of war casualties--demonstration of an association and possible selection bias.

The Injury Severity Score (ISS) is a widely used measure of anatomical injury. It is the sum of squares of the highest scores on the Abbreviated Injury Scale (AIS) in each of the three most severely injured body regions. This study was designed to describe the relationship between ISS and length of stay (LOS) in hospital. The ISS was independently determined by four physicians who studied 491 war casualties, excluding dead on arrival and non-trauma patients. The study demonstrates non-linear and non-homogeneous relationships between ISS and LOS. Exclusion of fatalities resulted in biased (higher) estimates of LOS among those with ISS scores of 25-66. The patients could be grouped into five categories according to their maximal AIS (MAIS): (1) Slight injury--i.e. those with injuries appropriate for AIS scores 1 or 2 that lead to an LOS of median 5 days; (2) Moderate injury--i.e. those with injuries appropriate to AIS scores of 3, with an expected median LOS of 10 days; (3) Severe injuries--i.e. those with injuries appropriate to AIS scores of 4, with expected median LOS of about 17 days; (4) Very severe injuries--i.e. those with one injury appropriate to an AIS score of 5; and (5) Multiple severe injuries--those who are severely wounded in two or more body regions, i.e. those with two or more injuries appropriate to AIS scores of 5 and 4, with a median LOS of 39 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Investigation in real time of the effect of gravitation on human spermatozoa and their tendency to swim-up and swim-down.

To investigate in real time if and how natural gravity affects rates of swim-up and swim-down of human spermatozoa, samples of motile or immobilized spermatozoa in a sealed mini-chamber were placed vertically on a 90 degrees tilted microscope. The mode of their sedimentation, as well as the difference in the rate of their swimming up and down, were observed directly over 30 min and analysed from photomicrographs. Under the influence of natural gravity force, most immobilized spermatozoa turned their heads down in about 5 min and then sank slowly at an average speed of 0.2 mu/s. The number of motile spermatozoa that swam down was 5-6 times more than those swimming up. It can be implied that in spite of the mild force exerted by 1 g on suspended spermatozoa in comparison to the high g force obtained by centrifugation, the overall effect of gravity on the rate of swimming up or down becomes dominant. Gravity causes the sperm heads to turn downward after which the oriented spermatozoa continue to move down by their own tail movements, causing accumulation of motile spermatozoa at the bottom. This may explain why in some recent studies swim-down was superior to the swim-up procedure during sperm separation by self-migration.

Screening for ovarian cancer in women with breast cancer with transvaginal sonography and color flow imaging.

The aim of the present study was to determine the efficacy of transvaginal color flow imaging as a screening tool for ovarian cancer. Six hundred patients with previous breast carcinoma were screened for ovarian cancer. Screening was performed using transvaginal sonography with color flow imaging. Serum CA 125 levels were measured in patients with abnormal sonographic findings. Eighty-three percent of the ovaries were detected in the premenopausal patients by ultrasonographic scanning and only 26% of the ovaries were detected in the postmenopausal patients. Intraovarian blood vessels were detected in 11% of the premenopausal women. The PI was less than 1 in 80% of these ovaries, but, on repeated examinations, the values of PI increased in all the blood vessels to greater than 1. Intraovarian blood vessels were detected in 1.8% of the normal ovaries observed in the postmenopausal women, but PI was always greater than 1. Eleven women with complex ovarian cysts (not simple) and one woman with enlarged ovaries underwent explorative laparotomy. In three women, primary malignant ovarian tumors were diagnosed and in one woman metastatic ovarian cancer was diagnosed. The specificity of sonography in detecting malignant ovarian tumors was 97.5% and the positive predictive value was 25%. The specificity of color flow imaging in detecting primary malignant ovarian tumors was 99.8% and the positive predictive value was 60%. In selected groups of women, screening for ovarian cancer with transvaginal color flow imaging may be justified.

Uterine artery flow velocity waveforms and color flow imaging in women with perimenopausal and postmenopausal bleeding. Correlation to endometrial histopathology.

We performed Doppler studies of the uterine artery in 85 women with postmenopausal and perimenopausal bleeding. Sixty-six women had non-malignant changes and 19 women had malignant changes on histologic examination of the endometrium. Uterine fibroids were detected in 30 women. When malignant changes were detected in the endometrium, uterine artery resistance index was always below 0.83. The mean uterine artery resistance index was significantly lower in the group of women with pathologic changes of the endometrium (RI = 0.77 +/- 0.03) compared to the group with non pathologic changes (RI = 0.85 +/- 0.08 p < 0.01), excluding the women with uterine fibroids. The lowest mean resistance index in the uterine artery was observed in the group of women with uterine fibroids (RI = 0.60 +/- 0.09 p < 0.001). In five of six patients with endometrial carcinoma blood vessels were detected around the myometrium by using color flow imaging. Their RI was always less than 0.5. In five patients, blood vessels were detected in uterine fibroids but their RI was always more than 0.5. All six women with endometrial carcinoma but only seven of 13 women with endometrial hyperplasia, had endometrial thickness greater than 5 mm. Doppler velocimetry of the uterine artery carries a high sensitivity (100%) in detecting pathological changes of the endometrium in patients presenting with postmenopausal or perimenopausal bleeding. The presence of high resistance in this vessel, may allow a more conservative approach in this group of patients.

Premature ovarian failure--the prognostic application of autoimmunity on conception after ovulation induction.

OBJECTIVE: To assess whether the presence of autoimmune activity in patients with premature ovarian failure (POF) can predict the response to ovulation induction and conception. DESIGN: Assessment of autoimmune activity in patients with POF, correlating the response to ovulation induction with this autoreactivity. SETTING: Tertiary care academic center. PATIENTS: Forty women with POF, 15 of them treated by ovulation induction because of infertility. INTERVENTIONS: All patients were tested for the presence of autoimmune activity, antibodies against various tissues, and 15 of them were treated with combinations of hMG/hCG, glucocorticosteroids as immunosuppressant, and some of them also with a long-acting GnRH agonist. Those patients not interested in infertility were put on hormone replacement therapy (HRT). MAIN OUTCOME MEASURES: Serum E2 and P were measured during ovulation induction as well as follicular diameter monitoring by transvaginal sonography. Achievement of gestations and their outcome were monitored in the group in which ovulation induction was accomplished. RESULTS: Antibodies against thyroglobulin, nuclear antigens, heart, tissue gluten, or increased levels of immunoglobulin (Ig)M, or decreased levels of complement C3 and C4 were significantly different in the patients with POF than in the control population. Autoreactivity of at least one class of the tested antibodies was found in 31 of 40 patients (77%). In 15 patients with autoimmune activity who have undergone ovulation induction using hMG/hCG, 14 pregnancies were achieved in 8 patients. Two of the pregnancies were spontaneous, and 12 were generated by hMG/hCG and fluocortolone, with or without pretreatment with GnRH-a. Twelve healthy babies were generated by 10 gestations, 3 ended in spontaneous abortions (23%), and 1 is ongoing. All the nonspontaneous pregnancies were achieved in the first three cycles of ovulation induction. CONCLUSIONS: Patients with POF and autoimmune activity, suggesting an autoimmune etiology to the ovarian failure, may respond to ovulation induction and have a conception rate of approximately 40% in three cycles. Those who do not conceive in three treatment cycles have a very low probability to conceive; therefore, further attempts of ovulation induction should be discouraged. However, some patients may spontaneously conceive in association with HRT.

Presence of sperm in the perivitelline space predicts fertilization rate after partial zona dissection.

OBJECTIVE: To examine the association of the number of spermatozoa present in the perivitelline space and sperm parameters with fertilization after partial zona dissection in male factor patients. DESIGN: Partial zona dissection was applied in 62 couples (84 cycles). A total of 524 oocytes underwent partial zona dissection (1/8 of the zona circumference) (partial zona dissection group) and 171 sibling oocytes were not manipulated (control group). A total of 326 manipulated oocytes were examined for the presence of spermatozoa in the perivitelline space. SETTING: University-based in vitro fertilization (IVF) program. PATIENTS: Fifty-four (87%) couples had at least one complete failure of fertilization, and 8 (13%) couples had low fertilization rate (< 10%) in previous routine IVF attempts. MAIN OUTCOME MEASURES: Fertilization rate, cleavage rate, and the number of spermatozoa present in the perivitelline space after partial zona dissection. RESULTS: Monospermic and polyspermic fertilization rates were 22.3% and 6.7% in the partial zona dissection oocytes and 8.8% and 0.6% in the nonmanipulated oocytes, respectively. The cleavage rate was similar in the partial zona dissection and control group (69.2% and 66.6%, respectively). A total of 81 partial zona dissection embryos and 10 nonmanipulated embryos were transferred to the uterus of 34 women (39 cycles), resulting in four pregnancies. In 46% (18 of 39) of the patients who had both partial zona dissection and control oocytes, only the manipulated oocytes fertilized. In only 48.8% of partial zona dissection oocytes, spermatozoa were detected in the perivitelline space; in this group of oocytes the fertilization rate was 56.6%. Sperm count and morphology were not clearly correlated with the outcome of partial zona dissection. CONCLUSIONS: The partial zona dissection technique enhances fertilization of subfertile sperm. However, the low efficiency of the procedure, apart from being associated with a high polyspermic rate, is related to the failure of sperm to traverse the slit in the zona pellucida in approximately one half of the manipulated oocytes.

Use of a sealed minichamber for direct observation and evaluation of the in vitro effect of cigarette smoke on sperm motility.

OBJECTIVE: To determine the in vitro effect of cigarette smoke on sperm motility and survival in an attempt to find a possible association with clinical studies that had pointed to the existence of such an effect in vivo. DESIGN: Laboratory experiments in which the effect of cigarette smoke on human sperm placed in a sealed minichamber was directly observed and determined by motion analysis. PATIENTS: High-quality fresh semen specimens were obtained from healthy donors and used for the experimental studies. INTERVENTIONS: Various doses of filtered and nonfiltered cigarette smoke, collected by an improvised manual smoking machine, were streamed at a rate of 2 mL/s into sealed chambers containing samples of washed spermatozoa. Evaluation of the changes in sperm motility was performed in real time by direct microscopical observation and repeated determinations by the multiple exposure photography technique until their complete immobilization. RESULTS: Streaming of 100 mL of cigarette smoke induced a dramatic drop in sperm motility, which caused sperm immobilization in about 15 minutes. This effect showed a clear dose-response relationship either with the amounts streamed or with the time during which sperm were exposed to cigarette smoke. The harmful effect was almost the same whether sperm were exposed to filtered or nonfiltered cigarette smoke. The role of carbon monoxide and hydrogen cyanide on these findings was studied separately, and it was shown that the inhibitory effect was not due to the presence of these two important components of cigarette smoke. CONCLUSIONS: The clear evidence of the in vitro harmful effect of crude cigarette smoke on sperm motility points to the possibility that in heavy smokers certain toxic agents may reach mature spermatozoa or their precursors via the blood stream and induce their harmful effect on sperm motility in vivo.

Increasing progesterone secretion in human granulosa-luteal cells induced by human follicular fluid.

Increasing evidence suggests that local ovarian agents play a central role in the regulation of follicular maturation and corpus luteum formation. In previous studies, we have shown that porcine follicular fluid induces granulosa cell luteinization in sow, human and rat. In the present study, the effect was investigated of either human follicular fluid (FF) alone, human follicle-stimulating hormone (FSH) alone, or both upon progesterone secretion of human granulosa-luteal cells. Granulosa-luteal cells were cultured in the presence of either FSH (5, 50 and 250 ng/ml), lyophilized FF (50 and 250 micrograms/ml) or both. Secretion of progesterone increased from a minimum of 2.5-fold to a maximum of 23-fold in the presence of FSH alone and, significantly less (approximately 2-fold) in the presence of FF alone, compared to cells cultured in medium alone. The co-administration of FSH and FF was significantly more effective than either alone, while addition of both FSH (250 ng/ml) and FF (250 micrograms/ml) gave maximal progesterone secretion. In granulosa-luteal cells pre-cultured with both FSH and FF, subsequent exposure to human chorionic gonadotrophin (HCG) alone increased progesterone secretion 1.6-fold to 11-fold, compared to cells pre-cultured with FSH alone. The effect of FF from individual follicles was also studied. FF from follicles yielding mature cumulus-oocyte complexes was 4.2-fold more effective, than FF obtained from follicles yielding immature cumulus-oocyte complexes in enhancing the FSH stimulation of progesterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone (GH)-binding protein regulation by estrogen, progesterone, and gonadotropins in human: the effect of ovulation induction with menopausal gonadotropins, GH, and gestation.

The recently described serum GH-binding protein (GH-BP) may reflect the GH-receptor level. To assess the serum GH-BP levels under various physiological and supraphysiological levels of sex steroids, we have evaluated its concentration in 26 patients undergoing 34 cycles of ovulation induction with either human menopausal gonadotropins (hMG)/hCG or GH/hMG/hCG. The latter ovulation induction protocol was undertaken in "Clonidine negative" patients in a prospective, randomized, crossed-over manner, between GH/hMG/hCG or hMG/hCG. The increase in GH-BP levels in patients' sera undergoing ovulation induction directly correlated with peripheral estradiol (E2) (r = 0.577; P < 0.001), and with peripheral progesterone (P4) (r = 0.542; P < 0.001; n = 174) concentrations in hMG/hCG cycles, and also in GH/hMG/hCG cycles (r = 0.669, P < 0.001 for E2, and r = 0.722, P < 0.001 for P4, n = 84). GH-BP levels did not change significantly in response to 0.15 mg Clonidine ingestion. The baseline GH-BP levels significantly correlated with the body mass index of 47 patients (r = 0.547; P < 0.001). The insulin-like growth factor-I (IGF-I) concentrations increased in correlation with increasing E2 levels up to 5500 pmol/L but decreased thereafter, at very high E2 concentrations. In gestations generated by ovulation induction with hMG/hCG or GH/hMG/hCG, longitudinal measurements of GH-BP levels showed an initial sharp increase during early gestation, followed by a gradual decrease beginning around the end of the first trimester and continuing during the mid and late trimesters. In normal spontaneous pregnancies, GH-BP levels, measured from the fifth week until term, were negatively correlated with gestational age (r = -0.581; P < 0.001; n = 84). This pattern is highly suggestive of the possibility that GH-BP is coregulated not only with E2 and P4 but also with hCG, and possibly other gonadotropins as well. Indeed, in patients with "resistant ovaries", pharmacological amounts of hMG failed to increase E2 concentrations but moderately increased GH-BP levels. These data provide good indirect evidence for coregulation of the GH-BP with both sex steroids and gonadotropins. The mid and late trimesters decrease in GH-BP levels in spite of increasing sex steroids concentrations, may be attributed to the decreasing hCG concentrations, and/or to the increasing secretion of placental lactogen (PL) and placental GH with the advancing gestation.

Pregnancy after subzonal insertion of cryopreserved spermatozoa from a patient with testicular seminoma.

The first pregnancy established after subzonal insertion of frozen-thawed sperm obtained from a patient with seminoma and severe oligoasthenospermia is reported. A total of 800,000 sperm with a poor progressive motility were recovered after thawing. Three to seven motile spermatozoa were injected into the perivitelline space of each of 10 oocytes, and seven sibling oocytes were coincubated and inseminated with 200,000 motile sperm/mL. Only 1 of the manipulated oocytes fertilized and was transferred to the uterus 65 hours after insemination at the eight-cell stage. A healthy boy weighing 3,600 g was delivered spontaneously at 38 weeks of pregnancy. This report gives hope to patients with testicular malignancy and severely impaired sperm function to maintain their reproductive potential through sperm banking and assisted fertilization techniques.

Growth and development of children conceived by in vitro fertilization.

To assess the physical and mental development of infants born after in vitro fertilization (IVF), we performed a general physical and developmental examination (Bayley and Stanford-Binet scales) on a cohort of 116 IVF children, conceived and born at our institution between February 1985 and March 1989, and on 116 non-IVF matched controls. Study and control groups were each composed of 66 singletons, 19 pairs of twins and 4 sets of triplets, whose age at examination ranged from 12 to 45 months. The developmental indices of IVF infants were within the normal range and did not differ from those of their matched controls. The indices were positively correlated to gestational age, birth weight, head circumference at birth and at examination, and mother's education. Mean birth weight, gestational age, and birth weight percentile of IVF infants were lower than the mean of the healthy population. Mean percentiles of weight and length at examination (mean age 22.4 months) were equally low but did not differ from those of the matched controls. However, mean percentiles of head circumference at birth and at examination compare well with the normal mean, both in IVF and control groups. Twins and triplets (IVF and controls) had significantly lower physical and mental indices as compared to singletons.

In vitro exposure to mercury and cadmium alters term human placental membrane fluidity.

The effect of incubation with mercury (Hg) as HgCl2 and cadmium (Cd) as CdCl2, at levels of 6 or 12 micrograms/ml of medium, on explants of term human placental microvillus membrane fluidity were studied. After incubation for 6 or 24 hr explants for each dose level were pooled and washed with fresh medium to remove any unbound metal. Placental membranes were separated by differential centrifugation and fluidity was studied by steady-state fluorescence polarization, expressed as the fluorescence anisotropy, r, with 1,6-diphenyl-1,3,5-hexatriene as a probe. The results show that membranes derived from explants incubated for 24 hr with either 6 or 12 micrograms/ml medium of either metal showed fluorescence anisotropy values (i.e., decreased fluidity) significantly higher than that of their respective controls. With 6 micrograms/ml of either metal the decrease in fluidity was highly significant for both metals and with 12 micrograms/ml a further decrease in membrane fluidity was observed with either metal. Both metals accumulated in placental membranes in proportion to their level in the medium. Membrane accumulation of Cd was higher than that of Hg. The cholesterol, phospholipid, and cholesterol-to-phospholipid mole ratios in membranes derived from metal-treated explants were unchanged, compared to their respective controls. However, no changes in membrane fluidity were observed in the samples incubated for 6 hr. In conclusion, exposure of placental cells to Hg and Cd caused accumulation of the metals in the membranes and lowered the membrane fluidity, which may affect membrane function and cause damage to the developing fetus.

Enzyme activities in the term human placenta: in vitro effect of cadmium.

The effect of cadmium (Cd) as CdCl2 on some placental enzyme activities were studied after explants had been incubated with the salt for 6 or 24 hr. The results indicated that, for both incubation periods, Cd at low doses had a stimulatory effect on aryl hydrocarbon hydroxylase (AHH) (a phase I enzyme) and on quinone reductase and catecholamine-O-methyltransferase (COMT) (both phase II enzymes). This effect was dose- and time-dependent. Only the activities of AHH and COMT showed a biphasic response, (i.e., increases at the lower dose levels and decreases with the higher ones), whereas that of quinone reductase continually increased with all the dose levels of the metal administered. Glucose-6-phosphate dehydrogenase (G-6-PD) activity was found to be inhibited at all the dose levels of Cd tested, the effect also being time- and dose-dependent. In conclusion, it appears that the use of placental explants can serve as a valuable means for studying the toxic effects of certain xenobiotics, as reflected in the activity of various important enzymes.

Transvaginal embryo aspiration--a safe method for selective reduction in multiple pregnancies.

OBJECTIVE: To evaluate pregnancy outcome after transvaginal selective embryo aspiration and to compare the results with those reported previously with other techniques for selective abortion. DESIGN: Retrospective case series. SETTING: University-based in vitro fertilization (IVF) program. PATIENTS: Nineteen women with multiple pregnancy who conceived after ovulation induction or IVF/gamete intrafallopian transfer. INTERVENTION: Transvaginal ultrasound-guided aspiration of the embryo(s) was performed at 7 to 8 weeks of gestation. MAIN OUTCOME MEASURES: Early and late complications related to the procedure, outcome of pregnancy, and birth weight. RESULTS: In 18 cases, the initial number of embryos (3 to 7) was reduced to two. In 1 case, the number of embryos was reduced from 4 to 3. None of the remaining fetuses vanished after the procedure. One patient delivered at 25 weeks and all other patients delivered healthy, viable infants (a pregnancy loss rate of 5.3%). CONCLUSIONS: Transvaginal embryo aspiration in early gestation appears to be a simple and relatively safe procedure for selective termination in patients with high-order multiple pregnancy. The cumulative loss rate of selective termination procedures previously reported by others is three times higher than the loss encountered in our series. This earlier procedure may be more acceptable to patients from emotional and religious points of view.

The influence of mercury on the secretion of human chorionic gonadotropin in superfused young placental tissue.

The effect of mercury (Hg), as HgCl2, in levels ranging from 0.75 to 12 micrograms/ml medium, on the secretion of human chorionic gonadotropin (hCG) was examined in first-trimester placental explants, after 6 or 24 hr incubation, employing both static and dynamic systems (the latter by superfusion). Later the unbound Hg was washed for 45 min. with fresh medium devoid of Hg, followed by superfusion with the latter medium for 75 min., during which time samples were collected for hCG assay. For the superfusion experiments the parameters used for evaluating the hCG secretion pattern were: mean peak amplitude, pulse frequency and the area under the hCG secretion curve (AUC). The results observed after 24 hr incubation indicate that in the dynamic system the hCG secretion increased significantly, and this increase was dose-dependent. There was also a dose-related increase in mean total hCG secreted by the explants exposed to Hg. Maximal hCG secretion was observed after 24 hr exposure of explants to 6 micrograms of the metal/ml. Both the mean peak amplitude and AUC parameters showed a statistically-significant increase for this dose level. At 12 micrograms/ml, the pulsatile secretion of hCG decreased, but the value for the mean hCG secretion was still higher than that observed for 0.75 and 3 micrograms/ml. After 6 hr incubation, however, there were no significant changes from the control, as judged by all of the above parameters. The levels of hCG secreted by the explants into the media in the static system were not significantly different from their respective controls, for both incubation periods and Hg levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Gonadotropin-releasing hormone analogues for dysfunctional bleeding in women after liver transplantation: a new application.

A new clinical indication for GnRH agonists treatment seems to exist in addition to the many indications known so far (4, 5). These previously mentioned indications include: uterine fibroids, precocious puberty, endometriosis, polycystic ovarian disease, ovulation induction for assisted fertilization (in vitro or in vivo), treatment of various tumors such as prostatic, breast, pancreatic, ovarian, and pituitary tumors, and various catamenial disorders such as premenstrual syndrome and porphyria. Women after liver transplantation, who are in the reproductive age and who experience menometrorrhagia or dysfunctional bleeding, seem to be a new indication for application of these useful GnRH analogues. This application may prevent the potential hepatotoxicity or cholestasis of E-P combinations usually used for treatment of dysfunctional bleeding. The recommended treatment is of relatively short duration (3 to 6 months), within the first 2 years of the transplantation, after which a more prolonged treatment should be considered. This treatment may also spare the need for contraception during its administration because both oral contraceptives and intrauterine device are relatively contraindicated in these patients (the latter because of the immunocompromised state). We believe this application to become more common because of increasing numbers of liver transplantations and improved survival rate. It may be looked at as a "new application of a relatively new drug for a new and enlarging situation."