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Biomedical subjects

Z Ben-Rafael

Publications and source records attributed to Z Ben-Rafael.

At least 235 records · Page 13Linked to original sources

Pregnancy outcome after unwinding of twisted ischaemic-haemorrhagic adnexa.

Six women who became pregnant after human menopausal gonadotrophin/human chorionic gonadotrophin (hMG/hCG) treatment regimens were operated on between 6 and 21 weeks gestation with an intra-operative diagnosis of twisted ischaemic-haemorrhagic adnexa. During operation unwinding of the adnexa was performed in all patients. Monitoring of the pregnancy before and after operation by ultrasonography was normal. The postoperative period and the rest of the pregnancy were uneventful. Three women were delivered normally at term. One patient was delivered by caesarean section because of twin pregnancy with malpresentation, and two pregnancies are still ongoing beyond the first trimester. This preliminary study suggests that detorsion of ischaemic-haemorrhagic adnexa during pregnancy is an option that is not associated with subsequent complications. This approach might be adopted relatively safely when preservation of future fertility is a goal.

Adnexa Uteri↗

Suppression with gonadotropin-releasing hormone analogues prior to stimulation with gonadotropins: comparison of three protocols.

This study compared three groups of patients treated with three different protocols of suppression of the pituitary-ovarian axis prior to and during gonadotropin stimulation for in vitro fertilization with a nonsuppressed control group. Patients treated with daily injections of DTRp6 (Decapeptyl 0.5 mg) or with a single injection of Decapeptyl depot (3.2 mg CR) had a longer folicular phase than patients treated with Buserelin (1.2-1.5 mg daily) and the patients in the control group. The number of human menopausal gonadotropin ampules required to reach adequate stimulation was also significantly higher in the former two groups of patients. The number of oocytes recovered (6-7 per patient), fertilized (45-58%) and cleaved (92-100%) did not differ among the groups. Peak estradiol levels and the pregnancy rate were highest in the group treated with Buserelin. The overall picture would indicate that suppression with Buserelin was the least profound.

Adult↗

Fatal disruption of a splenorenal shunt after multiple pregnancies.

A 39-year-old woman underwent a distal splenorenal shunt operation for bleeding esophageal varices due to liver cirrhosis. Following the operation she had 7 pregnancies at almost yearly intervals. At the term of the last pregnancy a disruption of the anastomotic site caused a fatal hemorrhage. The outcome of postshunt pregnancies as reviewed in the literature is usually favorable, but numerous pregnancies in these circumstances may carry a considerable risk.

Adult↗

Repetitive ovarian response to gonadotropin stimulation in an in vitro fertilization program.

The temporal changes of estradiol levels in 19 women undergoing ovulation induction for in vitro fertilization (IVF) and embryo replacement were described by a mathematical model. The model was analyzed for differences between treatment cycles of an individual woman and between cycles of different women. This model was also used to evaluate the results of IVF treatment. The variation between cycles within individuals was found to be less than that between different women. The parameters that describe this model were found to correlate with follicular growth but not with number of oocytes retrieved, fertilized or cleaved.

Adult↗

Programmed oocyte retrieval: clinical and biological effects of oral contraceptives administered before in vitro fertilization.

We have prospectively compared two regimens of suppression of the hypothalamic-pituitary-ovarian axis by oral contraceptives (OCs) for 15 or 30 days and two ovarian stimulation protocols. The latent phase, which represents a period of ovarian insensitivity, was prolonged and directly correlated to the duration of suppression. Thirty days' suppression, compared with 15 days', resulted in the cancellation of more cycles and a lower fertilization and pregnancy percentage. No significant increase in either serum progesterone or luteinizing hormone was noted in suppressed cycles. It is concluded that if programming is desired, OCs should be used for the shortest period possible. The variation in the length of the follicular phase indicates that there is a different 'fixed' day for retrieval for each suppression-stimulation protocol and this day should be established prospectively.

Adult↗

Ovarian hyperstimulation syndrome due to exogenous gonadotropin administration.

During the last decade, 154 patients treated with human menopausal gonadotropin human chorionic gonadotropin developed hyperstimulation necessitating hospitalization in 201 cycles. Moderate ovarian hyperstimulation occurred in 116 of the patients and severe ovarian hyperstimulation in 34. Sixteen patients underwent operative procedures. Twelve patients underwent puncture of the pleura or abdomen to drain symptomatic hydrothorax or ascites, with clinical improvement of the symptoms in all of them. Three patients had coagulation abnormalities, and 1 patient had thromboembolic phenomena. Hyperstimulation seems to be associated with an increased pregnancy rate, since seventy-five pregnancies (35%) occurred in the study group. Appropriate monitoring can reduce the rate of OHSS but it should be kept in mind that death due to OHSS may occur.

Adult↗

Collagen matrix influences the morphologic features and steroid secretion of human granulosa cells.

Steroid secretion and structure of granulosa cells on floating collagen gels were compared with those of cells grown on plastic. Granulosa cells from follicles of gonadotropin-treated women were plated either onto dishes coated with type I collagen or onto plastic dishes. Medium containing serum was removed after 24 hours, defined medium was added, and the gel was floated. Medium was changed daily for 3 days, after which the granulosa cells were prepared for light and electron microscopy. Cells grown on collagen secreted significantly more estradiol and progesterone than those grown on plastic during the 3 days of culture. The round multilayered granulosa cells on collagen had abundant mitochondria and lipid droplets and they formed numerous intercellular junctions. On plastic surfaces, flat granulosa cells grew as a monolayer with few junctions and less abundant mitochondria or lipid droplets. We conclude that growth on floating collagen promotes structural changes of human granulosa cells that enhances cell interaction and secretion of steroid hormones.

Cells, Cultured↗

Secretory dynamics of bioactive and immunoreactive prolactin in polycystic ovary syndrome.

To further investigate prolactin (PRL) secretion in polycystic ovary syndrome (PCO), the authors evaluated immunoreactive (immuno) and bioactive (bio) PRL levels in the basal state and in response to provocative testing with intravenous dopamine (DA), metoclopramide (MCP), and gonadotropin-releasing hormone (GnRH), before and after disulfiram. Basal measurements of immuno-PRL, bio-PRL, and the ratio of bio/immuno-PRL were similar in PCO and controls. The immuno-PRL decrement after DA was greater than that of bio-PRL in both groups (P less than 0.05). After MCP, immuno-PRL increased more than bio-PRL in PCO (P less than 0.01), and this immuno-PRL increment was greater than that of controls (P less than 0.05). Bio-PRL and immuno-PRL increased after GnRH in PCO, but not controls, and these responses were inhibited by disulfiram. These data confirm PRL hypersecretion in some women with PCO, which is better expressed by immunoreactivity than bioactivity. Given the assay systems and patients studied, bioactivity

Adult↗

Follicular aspiration and in vitro fertilization associated with pelvic reconstructive surgery.

Between August 1982 and May 1987, 103 patients underwent in vitro fertilization-embryo transfer (IVF-ET) in association with pelvic reconstructive surgery for infertility. Follicular stimulation was induced with clomiphene citrate and laparotomy scheduled day 12 to 15 of the menstrual cycle. Ultrasound measurements of follicular diameter and number of follicles were obtained on the day of human chorionic gonadotropin (hCG) administration, and laparotomy and ovum retrieval performed 36 hours later. Embryo transfer was performed 48 to 72 hours after insemination. Patients were treated postoperatively with intramuscular progesterone. In addition to evaluating the overall pregnancy rate, the outcome of patients having one or more follicles greater than or equal to 1.4 cm in mean diameter (group A) were compared to those in group B (no follicles greater than or equal to 1.4 cm in diameter). The number of oocytes obtained and the fertilization rate and polyspermic fertilization rate were not significantly different between groups; 10.1% of patients in group A conceived but no patient conceived in group B, yielding an overall pregnancy rate of 8.7%. These data suggest that physicians having IVF-ET at their disposal offer patients IVF during pelvic reconstructive surgery.

Adult↗

An increased initial follicle-stimulating hormone/luteinizing hormone ratio does not affect ovarian responses and the outcomes of in vitro fertilization.

The tenet that a combination of human follicle-stimulating hormone (hFSH)/human menopausal gonadotropin (hMG) improves follicular recruitment was assessed by randomly treating ovulatory women either with hFSH/hMG on days 3 and 4 of the cycle followed by two ampules of hMG daily or with a constant daily dose of 2 ampules of hMG. Estradiol (E2) levels on the day of human chorionic gonadotropin (hCG) and the mean number of mature, immature and atretic oocytes per cycle did not differ between the two groups. Likewise, fertilization, cleavage, and pregnancy rates were similar for the two treatments. When daily hormone levels were compared in 11 patients during two successive treatment cycles with both stimulation protocols, the temporal pattern of FSH accumulation was repeated in both cycles, but FSH levels were significantly higher when patients received hFSH/hMG. Nevertheless, during both cycles, E2 reached similar peak levels and the mean number of follicles per cycle on the day of hCG administration was not different. We conclude that routine use of hFSH/hMG does not improve the success of an in vitro fertilization (IVF) program and that higher FSH levels do not change the individuality of ovarian response in the same woman.

Estradiol↗

Flow cytofluorometric analysis of granulosa cell proliferation in rats.

Immature rats were given PMSG followed by an ovulatory dose of hCG. Mature cyclic rats were given an ovulatory dose of hCG on the day of dioestrus, 24 h before the endogenous LH surge was expected to occur. Granulosa cells from individual follicles were subjected to flow cytometry at various times after hormone administration. Administration of PMSG to immature rats caused a marked, transient increase in 'cycling' granulosa cells (cells in S, G2, or M phases of the cell cycle). Administration of hCG to adult cyclic rats caused a slight, but significant, increase in 'cycling' granulosa cells. The results could be taken to indicate that hCG-induced luteinization is not, in fact, accompanied by cessation of cellular proliferation. However, the data lend themselves to alternative explanations. The observed phase shifts may be due to the lengthening of the duration of S and G2 phases, indicating an actual decrease in the rate of cell proliferation. Flow cytometry was found to be a rapid, inexpensive tool for the study of follicular growth in the rat, but, due to variation between follicles and the need for a minimal sample size of 2000 cells, its application is limited to large follicles.

Animals↗

Incidence of abortion in pregnancies after in vitro fertilization and embryo transfer.

Our purpose was to assess factors that are associated with an increased rate of spontaneous abortion in pregnancies initiated by in vitro fertilization. Pregnancies were diagnosed by measurement of serum human chorionic gonadotropin (hCG) 15 days after embryo transfer. Of the 64 women who conceived, 47 delivered term infants, one patient delivered a stillborn at 22 weeks, 14 aborted in the first trimester, and two had pregnancies that implanted in the tube. Abortion rates were similar for women treated with human menopausal gonadotropin (24%; 12 of 54) and those who received clomiphene citrate (12.5%; one of eight). Two patients conceived after treatment with a combination of clomiphene citrate and human menopausal gonadotropin, neither of whom aborted. In 54 patients treated with human menopausal gonadotropin, there were no significant differences in mean maternal age, number of years of infertility before the pregnancy, history of previous pregnancies, amount of human menopausal gonadotropin used to induce ovulation, serum estradiol levels on the day of hCG administration, mean number of follicles, and the mean number of transferred embryos between the group who delivered and the group who aborted. We conclude that none of these factors are associated with increased tendency for fetal loss in our in vitro fertilization program. Beta-hCG levels on day 15 after embryo transfer were significantly lower in the group who aborted than in the group who delivered, and may be predictive of implantation failure.

Abortion, Spontaneous↗

Cortisol stimulation of estradiol and progesterone secretion by human granulosa cells is independent of follicle-stimulating hormone effects.

The effects of cortisol on steroid secretion by human luteinized granulosa cells was investigated by culturing cells from mature follicles of gonadotropin-treated women. After culturing for 24 hours in medium containing 10% fetal bovine serum, the cells were washed and incubated in a chemically defined medium. Cortisol (10(-5), 10(-6), and 10(-7) M), follicle-stimulating hormone (FSH; 100 ng/ml), FSH plus cortisol (10(-6], or vehicle were added to replicate cultures. After incubating for 6 hours, medium was harvested and assayed for estradiol (E2) and progesterone (P). Cortisol (10(-5), 10(-6) but not 10(-7) M) significantly (P less than 0.05) stimulated E2 secretion when compared to controls. FSH alone did not alter E2 secretion while FSH plus cortisol had a similar effect to cortisol alone. Likewise, P secretion was significantly (P less than 0.05) increased by cortisol when compared with controls and the stimulation was dose dependent. FSH also stimulated P secretion, but the combination of FSH and cortisol did not give an additive or synergistic effect. It appears that cortisol can stimulate the secretion of E2 and P by human granulosa cells without involving FSH receptor interaction. The findings suggest that, in addition to pituitary and ovarian hormones, cortisol may also be directly involved in granulosa cell function.

Cells, Cultured↗

Ovarian response of individuals to different doses of human menopausal gonadotropin.

Hormonal profiles were compared in 14 ovulatory women who were treated with two different doses of gonadotropins in successive in vitro fertilization cycles. All patients suffered from mechanical causes of infertility. Serum estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone (P) were measured daily during the follicular phase. Women were arbitrarily classified as high responders (E2 greater than 1000 pg/ml on the day of human chorionic gonadotropin administration, n = 8) or as low responders (E2 less than 1000 pg/ml, n = 6), according to the peak E2 levels during the cycle when they received 3 ampules of human menopausal gonadotropin (hMG). When patients were treated with 3 ampules of hMG, serum FSH, LH, and P concentrations increased significantly during the follicular phase in high responders but remained unchanged in low responders. When these patients were treated with 2 ampules of hMG, the temporal profiles of the hormones were similar, but the magnitude of increases in serum levels of gonadotropins and sex steroids was significantly reduced in high responders. The authors conclude that temporal individuality of endocrine profiles cannot be altered by varying the dose of gonadotropin. Increases in hormone levels accompanying a high response to hMG can, however, be dampened by lowering the dose. In contrast, hormone concentrations are not influenced by changing the dose of hMG in low responders.

Adult↗

Ovarian response to human menopausal gonadotropin following suppression with oral contraceptives.

The main conclusion of this study is that a profound suppression of the pituitary and ovary can be associated with an inadequate response which may require a longer or different regimen of stimulation to achieve the desired outcome for IVF. We suggest that a pretreatment determination of E2 and gonadotropins can be of value to predict the nature of ovarian response in women with suppressed pituitary-ovarian function.

Contraceptives, Oral↗

Relationship of human oocyte maturity, fertilization, and cleavage to follicular fluid prolactin and steroids.

Follicular fluid (FF) levels of prolactin (PRL), estradiol (E2), progesterone (P), and androstenedione (delta 4A) were related to diversities in oocyte maturation, fertilization, and cleavage among oocytes obtained for in vitro fertilization. Follicles with mature stage I oocytes contained similar concentrations of PRL and E2, more P, and less delta 4A compared to follicles containing immature oocytes. Follicles with mature stage II oocytes had higher amounts of P and E2 but similar levels of PRL and delta 4A compared to follicles with mature stage I oocytes. Prolactin was lower and E2 higher in FF associated with fertilizable oocytes than in those with unfertilized gametes. Follicles which yielded gametes that ultimately divided to more than four cells had the highest E2 levels, while the lowest E2 concentrations were associated with fertilized, uncleaved eggs. P, delta 4A, and PRL levels in FF were not related to oocyte cleavage. We conclude that human menopausal gonadotropin (hMG) treatment does not necessarily lead to a synchrony or uniformity of preovulatory follicles, maturation of oocytes is associated with rising levels of progesterone and decreasing levels of delta 4A in FF, an increased cleavage rate in vitro is associated with higher FF levels of E2, and high levels of PRL in FF are associated with unfertilized oocytes. These findings emphasize that differences in the hormonal milieu surrounding oocytes may have profound effects on the success of in vitro fertilization.

Androstenedione↗

Relationships between polypronuclear fertilization and follicular fluid hormones in gonadotropin-treated women.

Similar incidences of congenital abnormalities in in vitro fertilization and embryo transfer (IVF-ET) pregnancies and births in the general population have not supported earlier concerns that IVF may increase chromosomal aberrations. Nevertheless, polypronuclear fertilization is a common, undesirable, and poorly understood outcome of IVF. We evaluated hormone levels in 20 follicular fluids that were associated with mature oocytes that have fertilized abnormally (greater than or equal to pronuclei) and compared them to follicles with mature oocytes that cleaved normally, fertilized but failed to cleave, or did not fertilize. Progesterone (P), androstenedione, estradiol, percent free estradiol, sex hormone-binding globulin, insulin, and prolactin were measured. P levels were significantly higher in follicular fluids associated with oocytes that fertilized abnormally than in the other groups. Levels of the other hormones were similar in all the study groups. We conclude that IVF of oocytes from highly luteinized follicles as judged by P levels may result in polypronuclear fertilization.

Body Fluids↗