Pregnant women of 35 years of age or more: maternal serum markers or amniocentesis?

The aim of this prospective study was to compare triple test screening (alpha-fetoprotein, beta-chorionic gonadotrophin and unconjugated oestriol) with amniocentesis in the detection of fetuses with Down's syndrome in women of 35 years of age or more. Between 1992 and 1996, maternal serum markers were evaluated in 1406 women who had amniocentesis for prenatal diagnosis of chromosomal abnormalities related to a maternal age of 35 or more years. Sixteen fetuses with Down's syndrome were identified in the whole group by amniocentesis and karyotyping. The group with negative triple test screening consisted of 919 pregnancies and included two fetuses with trisomy-21 (false negatives). With triple test screening in the age group over 35, there was a detection rate of 87.5% for cut-off points ranging from 1:200 up to 1:350, with corresponding false positive rates ranging between 23% and 34%. In our population, if we had practiced the policy of offering amniocentesis only to women screening positive for the ages of 35 and 36 and to all pregnant women of 37 or more, we would have carried out 30% less amniocenteses. In this group of 1406 women, 33 abnormal karyotypes were detected with amniocentesis (16 Down's syndrome included) and equal number of elective abortions were carried out. Nevertheless, 19 healthy fetuses and neonates were lost after amniocentesis. Considering the high detection rates that can be achieved with triple test screening, the existing procedure related risk of amniocentesis (0.5-1.0%), and the facts that conception in women over 35 years of age is usually more difficult and the background loss usually higher than in younger women, we believe that in the future women over 35 should be offered a choice between non-invasive and invasive procedures after being thoroughly informed.

Erythromycin treatment for subclinical Ureaplasma urealyticum infection in preterm labor.

This study was undertaken to test the effects of erythromycin as an adjunct to tocolysis for preterm labor in women with vaginal cultures positive for Ureaplasma urealyticum. The study group consisted of 18 women in active preterm labor with pregnancies between 26 and 34 weeks of gestation and intact membranes who received 500 mg erythromycin orally every 8 h for 10 days. Seventeen women with similar characteristics served as controls and received no antibiotics. In all women contractions were suppressed with ritodrine. Erythromycin treatment resulted in a statistically significant greater mean delay of delivery (36.4 days) than among the control group (23.1 days). Higher proportion of term pregnancies (7 versus 3 pregnancies), higher mean birth weight (2,745 versus 2,474 g), lower neonatal morbidity (22.2 versus 42.2%) and shorter mean neonatal hospitalization time (9.6 versus 12.1 days) were observed, although these differences were not statistically significant. Adjunctive erythromycin treatment given to women treated for preterm labor with intact membranes and positive vaginal cultures for U. urealyticum appears to prolong gestation and to improve perinatal outcome.

Vimentin and alpha-fetoprotein expression in breast cancer smears: relationship with various prognostic factors.

Estrogen (ER) and progesterone (PR) receptor status, factors known to influence the prognosis and therapeutic possibilities in patients with breast cancer; alpha-fetoprotein (AFP), which is an estrogen binder; and vimentin (V) were determined in cytological imprint smears of 75 mastectomy specimens. The results were classified according to tumor type and menopausal state and analyzed to determine possible relationships among these four markers under the different circumstances. There was a positive association of ER positivity with PR positivity, AFP positivity, and V negativity using chi 2 analysis. The lobular carcinomas studied were predominantly ER+, AFP+, V-, while in the ductal carcinomas V positivity was marginally predominant and also frequently associated with ER+ or PR+ status. The small number of medullary carcinomas made statistical analysis of this group difficult. It seemed probable that the marker status of the tumors was dependent more on the tumor type than on the menopausal state of the patients, thorough follow-up, especially of V+ medullary carcinomas, may provide insight into the value of vimentin as a primary rather than a secondary prognostic factor.

Immunocytochemical localization of Cathepsin D and CA 125 in ovarian cancer.

OBJECTIVE: To study the expression of Cathepsin D (Cath D) and CA 125 antigens and ER and PR receptors on freshly obtained surgical specimens of ovarian carcinomas and their relationship with menopausal status, tumor histology, primary tumor size and lymph node invasion. METHODS: The tumors obtained from 100 women were measured and cut in half. The cut surface of one half was pressed against glass slides which were air dried and stained using the Avidin-Biotin peroxidase method for Cath D and CA 125 antigens. The slides were viewed under the light microscope for the characteristic brown granules in the cytoplasm or membrane of the malignant cells. The other half of the tumor was subjected to routine histological examination and part used for the demonstration of ER and PR receptors. The results were analyzed using chi 2 analysis. RESULTS: Cath D positivity was as common as CA 125 positivity. Cath D positivity is more frequently associated with serous carcinomas than with others. No relationship was observed between ER/PR positivity and Cath D or CA 125 positivity. CONCLUSION: The high incidence of Cath D positivity makes it a possible complementary method for following up ovarian carcinoma patients especially those who are CA 125 negative.

Expression of cathepsin-D, CA125 and epidermal growth factor receptor in imprint smears of ovarian carcinoma.

One hundred primary ovarian cancers were studied for the expression of cathepsin-D, CA125 and epidermal growth factor receptor (EGF-R) by staining of imprint smears from freshly obtained surgical specimens. Estrogen and progesterone receptors of the primary tumor, lymph node invasion, menopausal status of the patients and primary tumor size were also noted. The polymorphism of the antigenic characteristics of ovarian carcinomas was noted and significant associations of EGF-R positivity and lymph node negativity, EGF-R positivity and serous carcinomas, EGF-R positivity and cathepsin-D positivity, cathepsin-D positivity and CA125 positivity, and CA125 positivity and serous carcinomas were observed. The high incidence of cathepsin-D positivity makes it a possible complementary method to CA125 for following up patients. It is suggested that complete antigenic profiles of individual tumors are more likely to provide accurate prognostic information in individual cases.

Predictive value of amniotic fluid and fetal blood cultures in pregnancy outcome in preterm prelabour rupture of membranes.

We carried out a comprehensive prospective study of 26 pregnancies complicated by preterm rupture of the membranes. Microbiological assessment included cultures for aerobic and anaerobic bacteria, Mycoplasmas, Chlamydia, Trichomonas and fungi from: high vaginal and cervical swabs, maternal blood and urine, amniotic fluid and fetal blood on admission and finally, placenta and umbilical cord = after delivery. The group with positive cultures (n 16), was compared with the group with negative cultures = (n 10) in terms of gestational age at labour, latent phase after membrane rupture and fetal and neonatal morbidity and mortality. All patients with positive cultures delivered before 32 weeks and their neonates had evidence of infection. Three intrauterine deaths occurred in this group and 12/13 (86%) of the live neonates were admitted to the neonatal intensive care unit. The 10 (38%) patients of the group with negative cultures delivered after 32 weeks, had no perinatal deaths, and only two were admitted to neonatal intensive care. The median latent phase differed between these two groups (4.5 vs. 53.5 days, P 0.01), as did the median gestational age at labour (28 vs. 36 4 weeks, P 0.01). A positive amniotic fluid or fetal blood culture in the clinical setting of preterm rupture of the membranes indicates labour onset within a few days. Intrauterine infection with fetal sepsis is accompanied by high neonatal infectious morbidity (100%) and mortality (30%).

Percutaneous management of lymphocoeles following pelvic lymphadenectomy for cervical carcinoma.

Eighteen patients with 26 pelvic lymphocoeles following radical hysterectomy underwent percutaneous therapeutic intervention with either needle aspiration, or catheter drainage. In eight patients a percutaneous needle aspiration under sonographic control was performed. Five out of eight patients were successfully managed with needle aspiration, three of them requiring repetitive aspirations. Thirteen patients, with a total of 21 lymphocoeles underwent catheter drainage. Seventeen of the 21 lymphocoeles completely resolved. Redrainage was performed in four cases and it was successful in two of them. The duration of the catheter drainage was 8 to 34 days. Nine of the lymphocoeles were infected at initial drainage. Two patients underwent surgery because of increased volume of output. Percutaneous drainage is a safe and effective method and should be considered as the initial treatment for all patients with postoperative lymphocoeles.

Endothelin plasma levels in primary amenorrheic adolescents before and after estrogen treatment.

OBJECTIVE: We evaluated the effect of estrogen administration on endothelin (ET) secretion in primary amenorrheic (PA) adolescent girls. METHODS: Fifteen PA adolescents (ten hypergonadotropic, group A; five hypogonadotropic, group B) were treated with estrogen and progestogen tablets. A control group of ten healthy adolescents (group C) was included in the study. The ET 1-21, FSH, and LH plasma levels were tested before treatment (PrT) and immediately after the last estrogen tablet but before the progestogen administration (PoT). RESULTS: A statistically significant difference (P < .01) in ET 1-21 plasma values was found between PrT (9.66 +/- 0.80 pmol/L) and PoT (7.56 +/- 0.89 pmol/L) levels in group A cases. A similar reduction (P < .05) was recorded between PrT (8.06 +/- 0.46 pmol/L) and PoT (5.59 +/- 0.53 pmol/L) ET 1-21 plasma levels in group B cases. Endothelin 1-21 plasma PrT values were higher in both group A and B cases in comparison with controls (6.66 +/- 0.44 pmol/L; P < .01, P < .1, respectively). CONCLUSIONS: Estrogens administered to PA adolescents reduce ET 1-21 plasma levels in both hyper-and hypogonadotropism.

The in vitro development of mouse embryos beyond the blastocyst stage into the hatching and outgrowth stage using different energy sources.

PURPOSE: The purpose of this study was to investigate the effect of male and female serum supplementation on the in vitro development of mouse embryos beyond the blastocyst stage until the outgrowth stage since the latter may be related to the nidation of the embryo. We also studied the effect of EGF addition on embryo culture and blastocyst outgrowth. METHODS AND RESULTS: The blastocyst and hatching rates of two-cell mouse embryos cultured in Ham's F-10 + BSA, Ham's F-10 + male serum, or Ham's F-10 + female serum were found to be comparable (P > 0.05). The outgrowth rate of hatched blastocysts was significantly increased, though, when they were transferred to 50% male serum compared to either 50% BSA or 50% female serum (P < 0.01 and P < 0.05, respectively). In the last experiment, either 100 or 150 ng/ml EGF was added to the culture medium from the two-cell stage till blastocyst development and the latter were cultured till outgrowth in 50% BSA, male serum, or female serum. For both concentrations of EGF, the outgrowth rate was significantly higher in male serum compared to the other conditions (P < 0.01 and P < 0.05, respectively). The outgrowth rate was also higher when EGF was used compared to plain medium before transferring the blastocysts to either male or female serum (P < 0.01 for both). CONCLUSIONS: We conclude that the development of embryos to the outgrowth stage is significantly enhanced by male serum. The addition of EGF from the two-cell stage also significantly improves the outgrowth success rate for both male and female serum conditions.

Conservative treatment after miscarriage of one fetus in multifetal pregnancies. Report of three cases and review of the literature.

One triplet and two twin pregnancies, with a delayed delivery of 70, 98 and 85 days, respectively, are presented. In all cases one neonate survived. Regarding both the literature and our own cases, we can make the following management suggestions: (a) the cord should be ligated as high as possible; (b) fetal growth, cervical length and dilatation should be observed by weekly ultrasound scans, and (c) it seems that both cervical cerclage and tocolysis prolong the delivery interval, while prophylactic antibiotics have no beneficial effect. Triplet pregnancy in a single uterus and with a 70-day interval between the delivery of the first and that of the remaining 2 fetuses is a rare occurrence. Moreover the delay of 98 days, in our second case, represents the fourth longest delivery interval reported in the literature.

Corticotropin-releasing-hormone levels in pregnancy-induced hypertension.

UNLABELLED: High levels of corticotropin-releasing hormone (CRH) circulate in the plasma of pregnant women especially during the third trimester and even higher levels have been reported in abnormal pregnancies of various etiologies. One of these etiologies is pregnancy-induced hypertension (PIH). OBJECTIVE: To measure CRH blood levels with a sensitive method in a large number of pregnant women with PIH, starting from very early stages of gestation, and to compare them with those in normal controls. STUDY DESIGN: Venous blood was withdrawn from, (a) 10 healthy women aged 20-35 years, (b) 62 pregnant women with PIH (109 samples), mean age 29.1 years and (c) 75 healthy pregnant women (81 samples), mean age 28.5 years, used as matched controls. In pregnant women, blood collection started at the 10th week of gestation. In 14 women from group b and in 22 from group c blood was withdrawn during labor as well. CRH was assayed by RIA. RESULTS: Levels in non-pregnant women were between 19.0-40.6 pg/ml (28.37 +/- 2.53 pg/ml, mean +/- S.E.M.). In both groups of pregnant women there was a progressive increase in plasma CRH levels becoming quite sharp towards the end of gestation. Between 10 and 20 weeks, CRH (mean +/- S.E.M.) in PIH group was 69.3 +/- 3.2 pg/ml versus 41.6 +/- 2.4 pg/ml in matched controls, at 21-25 weeks 168.0 +/- 12.8 pg/ml versus 58.5 +/- 3.8 pg/ml, at 32-35 weeks 1378.5 +/- 61.4 pg/ml versus 298.3 +/- 16.9 pg/ml and at 38 weeks 2800.0 +/- 114.1 pg/ml versus 825.0 +/- 59.8 pg/ml. At term, CRH levels were 3784.0 +/- 197.3 pg/ml in PIH, versus 1386.0 +/- 101.8 pg/ml in normal pregnancy. Statistically, at every stage of gestation, CRH levels were highly significantly different in the PIH group (P < 0.0005). One hour postpartum there was a c. 60% decrease in plasma CRH levels in both b and c groups. In three women with pre-eclampsia who underwent premature labor due to a dead fetus around the 30th week, very high levels were noticed in sequential blood samples for 4-5 weeks prior to labor. CONCLUSIONS: (a) CRH levels in women with PIH are significantly higher compared to healthy pregnant women at any stage of gestation starting from week 10; (b) very high levels during pregnancy might be predictive of premature labor or fetal loss; and (c) CRH measurement might prove to be a helpful diagnostic tool in women with pregnancy-induced hypertension.

A flexible protocol for the induction of recipient endometrial cycles in an oocyte donation programme.

Synchronization of the availability of good quality oocytes from donors and adequate endometrial maturation of recipients are very important for the success of an oocyte donation programme. A flexible protocol for the endometrial preparation of recipients is important in timing embryo transfer between days 17 and 19 of the cycle ('window of receptivity'). The purpose of this study was to evaluate the effect of the length of oestradiol administration to recipients on pregnancy outcome. Oestrogen administration was 8 mg/day, but its length varied prospectively from 6 to 27 days, followed by the addition of progesterone (100 mg daily i.m.) for 2-4 days according to the availability of good quality oocytes. Pregnancy outcome was evaluated regardless of age, indication for oocyte donation or number of embryos transferred per patient. The pregnancy rate per cycle was comparable when oestradiol was administered from 6 to 11 days before progesterone addition, while it dropped significantly thereafter. The variation in progesterone administration did not affect pregnancy outcome. These findings provide us with a greater flexibility by allowing us to vary oestradiol administration to recipients from 6 to 11 days prior to progesterone, reducing considerably, therefore, the need to cancel embryo transfer because of oocyte unavailability. Thus we can arrange to transfer embryos between days 17 and 19 of the recipient's cycle so as to obtain the best possible clinical outcome.

Circulating levels of immunoreactive parathyroid hormone-related protein and intact parathyroid hormone in human fetuses and newborns.

Undetectable or extremely low levels of circulating immunoreactive parathyroid hormone (PTH) have been reported in human newborns while PTH bioactivity was high. This prompted the hypothesis that the fetal calcemic hormone might be PTH-related protein. The purpose of this study was to measure circulating immunoreactive PTH-related protein in human fetuses and newborns in order to investigate this hypothesis. Parathyroid hormone-related protein (PTHrP(1-86) and intact PTH were measured using two-site immunoradiometric assays in plasma obtained by cordocentesis from 23 fetuses (19-33 weeks of gestation), from 17 newborns at term (38-41 weeks), from their mothers and from 22 normal women of reproductive age. Plasma PTHrP was detectable in all but one of the fetuses and newborns and in all the mothers and the controls. The mean level was similar among fetuses (19-33 weeks) (0.43 +/- 0.18 pmol/l), newborns (0.48 +/- 0.12), mothers (0.48 +/- 0.14) and normal controls (0.46 +/- 0.09). Plasma PTH was found to be significantly higher in fetuses at midgestation (1.0 +/- 0.99 pmol/l) than in the newborns (0.22 +/- 0.21) (p < 0.0025); maternal PTH was significantly higher compared to fetal level at mid-gestation (2.1 +/- 1.0, p < 0.01) as well as at term (2.69 +/- 1.40, p < 0.001). In the control women PTH was 3.07 +/- 1.25 pmol/l. These results showed that plasma amino-terminal PTHrP-(1-86) is detectable during the second half of human fetal life and its level remains unchanged during this period of time, in contrast to changing levels of fetal plasma PTH. The relatively low PTHrP-(1-86) level that we found in the newborns is not responsible for the high PTH-like bioactivity found by some investigators in cord blood at term.

Oocyte donation to women over 40 years of age: pregnancy complications.

Recently, oocyte donation to women of advanced age has led to a considerable number of conceptions, thus increasing the age limit for becoming pregnant. A main consideration encountered by physicians, though, is the potential medical and obstetric complications of a pregnancy at an advanced age. In this study, the obstetric complications, as well as the perinatal outcome, of pregnancies of aged recipients (above 40) are presented and compared to those of younger recipients. A significantly higher incidence of gestational diabetes (P < 0.001), an increased incidence of pre-eclampsia (at the 10% level of significance) and an increased risk for thrombophlebitis (again at the 10% level) was observed in the older patients, but a careful follow-up during their pregnancy led to a highly satisfactory obstetric and perinatal outcome. A rigorous precycle medical screening (especially for cardiovascular diseases and diabetes) and a careful follow-up during pregnancy is, therefore, imperative so that oocyte donation to older women is not withheld and continues to provide fertility possibilities to otherwise sterile patients.

The value of semen characteristics and tests of sperm function in selecting couples for intra-uterine insemination.

In order to improve the selection of couples for intrauterine insemination (IUI) because of longstanding primary infertility of alleged male origin, we have performed a prospective study measuring conventional and advanced analysis of sperm characteristics, the hypoosmotic swelling test, the Shorr stain, the acidified aniline blue stain and alpha-glucosidase activity in seminal plasma, of 89 couples with no demonstrable abnormality of the female partner. Twenty-four couples attained spontaneous conception, 23 were successful within six cycles of IUI, and 42 remained without conception in spite of IUI during six unstimulated cycles. The proportion and concentration of spermatozoa with progressive motility was significantly lower (P < 0.01) in the successful IUI cases than in the couples attaining spontaneous conception, and the lower quartile value was lower in the former than in the latter. There were less pregnancies among IUI treated couples when sperm concentration and motility were within the range of normal fertile men, or when the concentration of white blood cells was elevated. More pregnancies occurred when markers of epididymal function, namely the result of the Shorr stain and alpha-glucosidase measurement, were normal. Total progressive motility and the result of the Shorr stain were the only independent variables selected by logistic regression to discriminate between successful and failed IUI cases. It is concluded that only a limited group of couples may benefit from IUI.

Conservative management of vaginal intraepithelial neoplasia (VAIN) by laser CO2.

Carbon Dioxide Laser ablation therapy was originally offered to 25 women with Vaginal Intraepithelial Neoplasia (VAIN). The disease was primary in 12 and secondary after a previous hysterectomy in 13 cases. Treatment was accomplished under local anesthesia in 22 cases and was well-tolerated by all patients. The age of the patients ranged from 19 to 68 with a mean age of 44 years. All women were followed-up by cytology and colposcopy within a time period of 35 to 82 months (mean 49 months). Eight patients relapsed resulting in a failure rate of 32%. A second Laser CO2 treatment was offered to these patients with a final cure rate of 84% (21/25). The four cases in which the disease reappeared, after the 2nd treatment, were managed by upper colpectomy (3 cases) and follow-up (1 case). Laser CO2 ablation is an acceptable treatment modality for VAIN considering the promising cure rates and the preservation of the anatomic integrity of the vagina. Close colposcopic follow-up of these patients is necessary for early detection of disease relapses.