A negative second trimester triple test and absence of specific ultrasonographic markers may decrease the need for genetic amniocentesis in advanced maternal age by 60%.

OBJECTIVE: A study was conducted to evaluate the sensitivity of combining a second trimester triple test and targeted ultrasound in order to detect Down syndrome in women undergoing amniocentesis over 35 years of age. METHODS: Women over 35 years of age underwent a triple test and an ultrasound examination for chromosomal markers immediately prior to genetic amniocentesis. RESULTS: One thousand and six women were examined. Four hundred and thirty seven were triple test-positive and in 195 cases ultrasonographic abnormalities were observed. Thirteen had Down syndrome and eight had other chromosomal abnormalities. All women with Down syndrome babies were triple test-positive and seven also had ultrasonographic markers. Three of eight women who had babies with chromosomal aberrations other then Down syndrome were also triple test-positive. CONCLUSIONS: The use of the triple test as a screening tool in our population would reduce the number of amniocenteses by 60%, while no cases of Down syndrome would be missed. Ultrasonographic markers have added little to this population. Three non-Down syndrome chromosomal abnormalities and two Down syndrome mosaic cases would be missed by this approach.

Intrapartum external cephalic version of footling-breech presentation.

BACKGROUND: External cephalic version is attempted prior to the onset of labor. Women who present in labor with footling breech presentation are usually delivered by cesarean section. We present our experience of external version in women in labor. MATERIAL AND METHODS: External cephalic version was attempted in thirteen patients in labor with footling breech presentation with the breech out of the pelvis. RESULTS: The procedure was successful in twelve of the thirteen patients. Ten of them delivered vaginally. There were no maternal or neonatal complications. CONCLUSIONS: It may be reasonable to attempt external cephalic version in patients in labor prior to performing a cesarean section.

Transient cortical blindness in preeclampsia with indication of generalized vascular endothelial damage.

A 26-year-old woman with twin fetuses of 28 weeks' gestational age had symptoms of preeclampsia and was admitted to the hospital for observation. Nine days later, after reporting a severe headache, the patient experienced loss of vision in both eyes. An emergency computed tomographic brain scan was performed to rule out intracranial hemorrhage, and cesarean delivery was performed. Twelve hours after the operation, the patient's vision improved gradually and returned to normal after 24 hours. The placenta was submitted to pathologic examination, and magnetic resonance imaging was performed 4 days after birth. Recent thrombosis observed in the histologic section of the placenta, ischemic changes in the brain seen in the computed tomographic and magnetic resonance scans, and severe proteinuria manifested clinically suggest vascular endothelial damage as the underlying mechanism in this case of preeclampsia-related transient cortical blindness.

Relationship between the threshold of ovarian sensitivity to human menopausal gonadotrophin stimulation and in-vitro fertilization treatment outcome.

In a retrospective study of 813 oocyte retrieval-embryo transfer cycles in women with normal follicle stimulating hormone and luteinizing hormone concentrations, we sought to investigate the relationship between the amount of human menopausal gonadotrophin (HMG) used for ovarian stimulation and treatment outcome. Patients were divided into three groups: group A patients (495 cycles) required < 40 ampoules of HMG and had a predicted probability for pregnancy of 25% per embryo transfer; group B patients (165 cycles) required 41-77 ampoules per cycle, with a predicted probability rate for pregnancy of 5-25% per embryo transfer; and group C patients (153 cycles) required > 77 ampoules of HMG and the predicted probability for pregnancy was < 5% per embryo transfer. Groups C and A differed significantly (P < 0.005). The mean oestradiol concentration on the day of HCG administration in group C was 6412 pmol/l, and the mean number of eggs retrieved was seven. The highest success rates were found when up to 2.5 ampoules of HMG were required for each egg or 4.4 ampoules for each embryo. The lowest rates were obtained when > 4.8 ampoules of HMG were necessary for each oocyte or > 9.6 ampoules for each embryo (P < 0.005). We identified a group of infertile patients who required excessive amounts of HMG to achieve a fair degree of steroidogenesis, number of eggs and number of embryos but who had very low pregnancy rates. Although all other relevant parameters were normal, this may highlight the beginning of ovarian-gamete insufficiency before the basic hormonal status is affected. In cases of repeated failure, oocyte donation should be considered.

Induction of artificial endometrial cycles with oestradiol implants and injectable progesterone: establishment of a viable pregnancy in a woman with 17-alpha-hydroxylase deficiency.

Repeated attempts with oral oestrogens and injectable progesterone failed to induce secretory endometrium in a woman with 17-alpha-hydroxylase deficiency. The insertion of s.c. 17-beta-oestradiol implants dramatically improved the endometrial response and enabled the establishment of endometrial maturation. A viable pregnancy was achieved after the uterine transfer of in-vitro fertilized donated eggs.

Laron syndrome due to a post-receptor defect: response to IGF-I treatment.

Three siblings with Laron syndrome (LS) and normal serum growth hormone binding protein (GHBP) are described. Basal serum levels of hGH were high and IGF-1 low, and in contradistinction to the classical form of the disease serum GHBP and IGFBP-3 were normal in these patients. After 7 days of human growth hormone administration serum IGFBP-3 levels as well as the number of red blood cell IGF receptor sites increased. After short- and long-term IGF-1 administration the IGF-1 receptor binding capacity as well as the number of IGF receptor sites decreased to levels found in control subjects. One year treatment with IGF-1 increased the growth velocity by 47-96% in the two older children. It is concluded that the findings described are compatible with a normal GH receptor and normal signal transmission for IGFBP-3 synthesis but a defect exists in the post-GH receptor mechanism for the generation of IGF-1. This is the first description of this type of defect leading to a variant of Laron syndrome.

Relationship between embryo morphology and implantation rate after in vitro fertilization treatment in conception cycles.

OBJECTIVE: To investigate the relationship between the embryo number and morphology in conception cycles and the incidence of multiple pregnancies. DESIGN: The study is based on information received from a computerized data base. SETTING: In Vitro Fertilization Unit, Sapir Medical Center, Kfar Saba, Israel. PATIENTS: A total of 117 consecutive pregnancies resulted from replacement of fresh embryos in our IVF-ET program. MAIN OUTCOME MEASURES: The impact of embryo quality, as assessed by morphological parameters, on the multiple pregnancy rate (PR). RESULTS: Implantation rates positively correlated with the number and the quality of transferred embryos. However, no multiple pregnancies occurred when only two embryos were replaced. There were no multiple pregnancies when only embryos of low quality (grades 1 and 2) were transferred. Furthermore, there was no correlation between the number of replaced embryos of poor quality and the rate of implantation. The multiple PR increased from 10% when a mixture of high and low quality embryos were transferred to 30.76% when only embryos of highest quality were transferred. CONCLUSION: The implantation rate of transferred embryos is directly correlated with the morphological scoring. The results of the study suggest that the number of embryos transferred should be balanced against their morphological quality to reduce the rate of multiple pregnancies.

Insulin-like growth factor-I and follicle-stimulating hormone suppress insulin-like growth factor binding protein-1 secretion by human granulosa-luteal cells.

Local regulation of insulin-like growth factor binding protein-1 (IGFBP-1) production in the human ovarian follicle was investigated using cultured human granulosa-luteal cells. Both insulin-like growth factor-I (IGF-I) and follicle-stimulating hormone (FSH) exerted a dual effect on granulosa cells: while estradiol (E2) production was increased by both stimulants, the addition of either of the two hormones led to a reduction in IGFBP-1 secretion by more than 50%. Inhibition of IGFBP-1 production in response to IGF-I was dose-dependent,with the highest effect observed at 5 nM IGF-I. A significant correlation was found between the increase in E2 and inhibition of IGFBP-1 secretion in response to IGF-I. These observations may suggest a novel mechanism, at the follicular level, by which FSH and IGF-I amplify the IGF-I effect in the ovarian follicular cells.

Lack of correlation between hormonal blood levels and endometrial maturation in agonadal women with repeat implantation failure following embryo transfer from donated eggs.

Five women with ovarian failure who repeatedly failed to conceive following embryo transfer from donated eggs underwent endometrial development investigation. One endometrial biopsy was obtained on cycle days 19, 21, and 23 during three consecutive artificially induced cycles. All five patients had only early secretory changes on days 19 and 21. Histological evaluation on cycle day 23 revealed various developmental stages: two women had "in-phase" endometrium, two patients had adequately developed stroma but significantly retarded glandular maturation, and one women showed no progress. The histological findings were conclusive for a significant maturation delay and an impaired endometrial receptivity. There was a lack of correlation between the peripheral hormonal blood levels and the endometrial maturation.

Effect of sperm preincubation with follicular fluid on the fertilization rate in human in vitro fertilization.

The study investigates the effect of sperm preincubation with FF on the fertilization rate in an IVF program. The oocytes inseminated with FF pretreated semen showed a significantly higher rate of fertilization. The percentage of cleavage and polypronuclear occurrence did not differ from the controls.

Complete ovarian unresponsiveness to hMG stimulation after prolonged GnRH analogue administration.

GnRH agonists (GnRH-a) have recently been shown to exert an inhibitory effect on human reproductive functions, the mechanism for this effect being attributed solely to the desensitization of the pituitary gonadotropin receptors to GnRH-a. We present two cases where chronic treatment with a GnRH-a caused complete suppression of ovarian activity in vivo. The effect could not be counteracted by large hMG doses and resulted in high FSH plasma concentrations. Normal ovarian activity was restored only after withdrawal of GnRH-a.

Effect of preovulatory progesterone administration on the endometrial maturation and implantation rate after in vitro fertilization and embryo transfer.

Fifty-two women, who had 62 ovum aspiration cycles, received a progesterone (P) supplementation of 100 mg/day that was initiated 10 hours before human chorionic gonadotropin (hCG) administration and was continued over the following 6 days. Forty-eight women who had 74 ovum pick-ups, but did not get P, served as controls. Forty-four (84.6%) women of the treatment group, and 40 (83.3%) of the controls had ovum fertilization and embryo replacement. The fertilization and cleavage rates and the mean number of replaced embryos per embryo transfer (ET) cycle did not differ between the groups. Endometrial biopsies, from treatment group women with no fertilized eggs, which were taken 48 hours after ovum pick-up, mostly revealed an "advanced endometrial dating," in relation to the "day of hCG." Pregnancy rate per ET cycle for the treatment group was significantly higher than that of the controls; 41.2% versus 23.3%, respectively. It is concluded that the higher pregnancy rate resulted from an improvement in uterine receptivity.

Human follicular fluid protease and antiprotease activities: a suggested correlation with ability of oocytes to undergo in vitro fertilization.

Plasminogen activator activity was determined in human follicular fluids (FFs) obtained during in vitro fertilization procedures. The fibrinolytic activity of plasminogen activator was significantly higher in fluids from follicles that contained oocytes that were later found to fertilize in vitro (group F) as compared with fluids from follicles that contained oocytes that failed to fertilize (NF). To assess whether this difference in overt plasminogen activator activity reflects differences in conversion of an inactive, latent plasminogen activator to the active enzyme, the ability of exogenous trypsin to enhance plasminogen activation was measured. The plasminogen-dependent hydrolysis of the chromogenic substrate S-2444 in presence of trasylol (Bayer, Leverkusen, Germany) was taken as a measure of plasminogen activator activity in these experiments. No activity was found in untreated FFs, while exposure to trypsin resulted in emergence of marked plasminogen activator activity. In addition, FFs exhibited trasylol-sensitive chromogenic activity indicative of serine-protease activity. Both the plasminogen activator and serine-protease levels after tryptic activation were significantly higher in NF than in F samples. Thus, while F samples have most of their plasminogen activator in an active form, NF samples have most of their plasminogen activator in a latent, trypsin-activatable form. Follicular fluids also contain inhibitory activities toward plasmin and trypsin. The inhibition of these enzymes correlates positively with the latency of plasminogen activator. These results suggest a direct relationship between the ability of oocytes to fertilize and the overt to latent plasminogen activator activity ratios in the FFs.

Granulosa cell tumors in Israel: a study of 172 cases.

Data of an epidemiologic study of granulosa cell tumors in Israel are presented. During the 15-year period of the survey, 172 cases of granulosa cell tumors of the ovary were diagnosed. This represents a yearly incidence of 0.9/100,000 females. The incidence of occurrence was two times higher in women of European/American origin than in those of Asian/African origin. Most patients were 40 to 69 years old. The presenting symptoms were mainly those of abdominal distension and pain and changes in the menstrual pattern. Associated malignancy was relatively common. Carcinoma of the breast was present in 6.4% of patients and endometrial malignancy in 11%. Forty-five percent of patients were diagnosed at Stage I of the disease while 27% were detected at the advanced Stages, III and IV. Factors affecting the prognosis involved the clinical stage of the disease at diagnosis, the type of presenting symptoms, and to a limited extent, the age of the patient.