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Biomedical subjects

Z Ben-Rafael

Publications and source records attributed to Z Ben-Rafael.

At least 253 records · Page 14Linked to original sources
PubMed1987

Changes in thyroid function tests and sex hormone binding globulin associated with treatment by gonadotropin.

Increasing levels of E2 in gonadotropin-treated women stimulated hepatic synthesis of SHBG and TBG, and consequently increases in T4 concentration. Nevertheless, unchanged FTI and TSH suggested that a euthyroid state was maintained. The temporal patterns for the rise in serum concentrations of TBG and SHBG during gonadotropin therapy suggest that the synthesis of these proteins by the liver has different sensitivities to E2.

Chorionic Gonadotropin↗
PubMed1987

Dose of human menopausal gonadotropin influences the outcome of an in vitro fertilization program.

This study compares outcomes of in vitro fertilization (IVF) in two groups of 57 patients when either 2 (group 1) or 3 (group 2) ampules of human menopausal gonadotropin (hMG) were administered daily. Treatment began on day 3 of the cycle and was discontinued when at least 2 follicles attained diameters greater than or equal to 1.5 cm. Human chorionic gonadotropin (hCG) was given either 24 or 48 hours after the last dose of hMG. Although serum estradiol levels were lower in group 1, the average number of oocytes retrieved (3.2 versus 2.9), fertilized (1.9 versus 2.0), and cleaved (1.7 versus 1.8) per completed cycle did not differ between groups 1 and 2. Likewise, the number of oocytes that fertilized abnormally was similar in both groups (0.5 versus 0.3/cycle). However, the number of atretic oocytes (0.03 versus 0.5/cycle) and the percent of oocytes recovered from the cul-de-sac (0 versus 7.2%) were significantly (P less than 0.05) lower in group 1. In group 1, administration of hCG 48 hours after the last dose of hMG was associated with a higher number of cleaving embryos (2.1 versus 1.5/cycle) and a higher pregnancy rate (34.8 versus 14.7%; P less than 0.05) when compared with injection at 24 hours. In group 2, the interval between hMG and hCG did not influence these results. Together, the associations between fewer oocytes that were atretic or recovered from the cul-de-sac, and a trend toward a higher pregnancy rate, suggest that follicular recruitment with 2 ampules of hMG is more appropriate than 3 ampules in an IVF program.

Chorionic Gonadotropin↗
PubMed1987

Flow cytometric analysis of deoxyribonucleic acid in human granulosa cells from in vitro fertilization cycles: relationships to oocyte maturity and fertilizability and to follicular fluid steroids.

We measured the mitotic activity of granulosa cells, sex steroid concentrations in follicular fluids, and the maturity and fertilizability of oocytes from 49 follicles. Flow cytometric measurements of DNA were used to determine the percentage of cells in G0/G1, S, and G2/M phases of the cell cycle. Mitotic index was designated as the percentage of granulosa cells in S + G2/M. The progesterone concentration and the progesterone to estradiol ratio in follicular fluids were inversely correlated to mitotic index (r = -0.506; P less than 0.001, and r = -0.320; P less than 0.02, respectively). Estradiol and androstenedione levels did not correlate with the mitotic index. The mitotic index was higher in follicles with immature oocytes [25.6 +/- 2.0% (+/- SE); n = 7] than in follicles with mature oocytes (15.6 +/- 1.2%; n = 41; P less than 0.001). The mitotic index of granulosa cells was lowest in follicles with oocytes that fertilized (15.5 +/- 1.8%), higher in follicles with oocytes that remained unfertilized (18.5 +/- 1.3%; P less than 0.03), and highest in follicles with oocytes that fertilized abnormally (24.0 +/- 2.1%; P less than 0.02). Differences in maturity or fertilizability of oocytes were not associated with variations in follicular fluid progesterone concentrations. The study supports the concept that mitotic activity is decreased when granulosa cells become luteinized. During early follicular growth it is assumed that estradiol and perhaps androstenedione may be important regulators of cell division. Our findings suggest that progesterone, perhaps acting as an antiestradiol, is more important in controlling granulosa cell division of preovulatory follicles during the late follicular phase.

Androstenedione↗
PubMed1986

Male to female ratio after gonadotropin-induced ovulation.

Two hundred fifty-six children were born in 195 births from 176 women that conceived after human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG)-induced ovulation. The secondary sex ratio was 50% male to 50% female births, which is not statistically different from the Israeli or Occidental population. The same trend was observed for single births and for twins. Thus, the data presented do not support the reports of increased numbers of female infants in those conceived after induction of ovulation. Factors that are expected to have been shown to affect sex ratio: maternal age at delivery, total number of ampules of hMG/hCG administered in the conceptional cycle, urinary estrogen levels on the day of hCG injection, degree of ovarian hyperstimulation syndrome, and time of insemination in relation to the basal body temperature rise were found to be insignificant. Thus, the hypothesis that a local hormonal environment (gonadotropin or estrogen levels) during hMG/hCG treatment possibly affects sex selection was not confirmed.

Body Temperature↗
PubMed1986

Follicular maturation parameters associated with the failure of oocyte retrieval, fertilization, and cleavage in vitro.

Follicular maturation parameters predictive of decreased success in human in vitro fertilization were evaluated in 104 gonadotropin-stimulated cycles. Falling estradiol (E2) levels correlated with decreased fertilization (1.9 oocyte/cycle) and cleavage (1.4 oocyte/cycle), when compared with cycles with increasing E2 (2.4 and 2.1 oocyte/cycle, respectively). Likewise, polyspermic fertilization was higher in the former group. Falling E2 levels after human chorionic gonadotropin (hCG) administration correlated with similar trends. Delaying hCG (24 to 96 hours) relative to the last dose of gonadotropin did not affect the total number of oocytes fertilized per cycle. However, polyspermic fertilization and cancellation rates were higher. Leading follicles growing beyond 2.3 cm (determined by ultrasound examination) were associated with decreased recovery, fertilization, and cleavage, and increased polyspermic fertilization. We conclude that ultrasonography and E2 monitoring can predict decreased fertilization and cleavage and should also be monitored after hCG administration.

Chorionic Gonadotropin↗
PubMed1986

Fertilization and cleavage after reinsemination of human oocytes in vitro.

The results of reinsemination of 150 morphologically mature oocytes that failed to fertilize within 15 to 20 hours after initial insemination were evaluated. Only 41 oocytes (27.3%) were fertilized after reinsemination, which is significantly lower than the percentage obtained after initial insemination (74%). However, the cleavage rate was not impaired significantly. Polyspermic fertilization was common (17 oocytes, 29.3%). A total of 64 oocytes were transferred. In 18 patients, all of the oocytes that were transferred had been reinseminated; none of these patients conceived. However, of 28 patients who received embryos arising from both initial insemination and reinsemination protocols, 7 conceived (25%). We suggest that the percentage of fertilization is impaired after 22 hours of incubation in vitro and that those oocytes that have fertilized after reinsemination might partly reflect a misjudgment of initial oocyte maturity. Nevertheless, reinsemination is a relatively simple procedure, with no known attributed risk. Therefore, we recommend reinsemination to increase the overall fertilization percentage. Additional studies are needed to establish better methods for assessment of oocyte maturity to evaluate properly the benefit of such reinsemination procedures.

Cleavage Stage, Ovum↗
PubMed1986

Treatment-independent pregnancy after in vitro fertilization and embryo transfer trial.

This study indicates that SP occur in a higher percentage than theoretically expected after IVE-ET treatment, but it is not conclusive as to whether the SP is independent or a result of the treatment or operative laparoscopy. Our results are in agreement with those of previous studies that have shown that SP occur with almost all kinds of infertility. We therefore reject the previous suggestion of Steptoe, who argued that to prevent ectopic pregnancy from complicating embryo replacement, preparatory electrocauterization of diseased tube should be performed. We also suggest that as long as the results of treatment are below the normal monthly spontaneous conception rate, there is justification for a prospective random study that includes all diagnoses other than BTB. Such a study might help make any future selection of patients for treatment more appropriate.

Adult↗
PubMed1986

Effects of prolactin on steroidogenesis by human luteinized granulosa cells.

The role of prolactin (PRL) in the regulation of human ovarian function is poorly understood, and reported findings are often contradictory. We have evaluated the effects of several doses of PRL on the secretion of progesterone (P) and estradiol (E2) by human granulosa cells from preovulatory follicles of gonadotropin-stimulated women. The effects of PRL were also evaluated when androstenedione (delta 4 A) was added to the cultured cells. Our findings show that the human granulosa lutein cells retain their ability to secrete large amounts of P and lesser quantities of E2 for a prolonged period in culture. E2, but not P, secretion was stimulated by the presence of delta 4 A. PRL in low doses (25 and 50 ng/ml) did not alter the secretion of either E2 or P. In contrast, high doses of PRL (100 and 1000 ng/ml) resulted in a significant suppression of E2 secretion. P secretion was inhibited only by the highest dose (1000 ng/ml) of PRL. We conclude that steroidogenesis by the granulosa lutein cells of preovulatory human follicles is probably not influenced by the quantities of PRL that are normally present in the blood or follicular fluid. Higher doses, however, may suppress production of E2 and P.

Androstenedione↗
PubMed1986

Differences in ovarian stimulation in human menopausal gonadotropin treated woman may be related to follicle-stimulating hormone accumulation.

Two groups of normal ovulatory women who displayed either a marked (high responders; HR) or a more subtle (low responders; LR) ovarian response to a fixed dose of human menopausal gonadotropins (hMG) were evaluated for differences in blood levels of hormones. Serum follicle-stimulating hormone (FSH) levels doubled during the first 3 days of treatment (to approximately 20 mIU/ml) in all patients; thereafter, the levels plateaued in LR but continued to rise steadily (to 35 mIU/ml) in HR. In the latter group, rise in estradiol (E2) and FSH was accompanied by an increase of luteinizing hormone (LH; two to five times) progesterone (P; four to eight times) testosterone (T; three to four times) and prolactin (PRL; 2 times) toward the end of the follicular phase. Positive correlation was found between FSH and E2 in HR and LR. Positive correlation was found, however, between LH, T, and P and between E2, P, and PRL only in HR. The extent of FSH accumulation in the circulation may be a principal factor in determining an individual's response to hMG therapy. Temporal changes of blood hormones indicated that the continuous rise in FSH levels in HR was associated with early luteinization of the follicles. Increased secretion of P in the follicular phase of these women (HR) probably synergized with the elevated E2 levels to elicit LH release. Similar changes in blood hormones were not found in LR.

Estradiol↗
PubMed1986

Changes in serum sex hormone-binding globulin, free estradiol, and testosterone during gonadotropin treatment.

Sex hormone-binding globulin (SHBG), estradiol (E2), percent free E2, percent of E2 bound to SHBG, and testosterone (T) were evaluated in 28 ovulatory women during human menopausal gonadotropin-stimulated cycles for in vitro fertilization. Patients were divided into two categories: low responders, in whom serum E2 concentration reached levels less than 1000 pg/ml (mean, 638 +/- 93), and high responders, with serum E2 levels greater than 1000 pg/ml (mean, 2219 +/- 330). A significant increase in SHBG can occur within a short time in high responders (from 62.8 to 103.9 nmol/l) but not in low responders. This increase is accompanied by a significant decrease in the percent free (bioavailable) E2, but the distribution of E2 between the fraction bound to SHBG or albumin did not vary. Despite the increase in the levels of SHBG, the concentration of bioavailable (free) E2 in hyperstimulated women is higher than in normal cycles. The significant increase in T in high responders, by virtue of its higher affinity for SHBG, probably contributes to the increased levels of bioavailable E2.

Estradiol↗
PubMed1986

Comparison of ultrasonographic transurethral and laparoscopic guided oocytes retrieval.

Fifty-eight patients who underwent in vitro fertilization (IVF) treatment were divided into two groups. In 28 patients, ultrasonically guided transurethral follicular aspiration was performed under light general anesthesia. In 30 patients, laparoscopic follicular aspiration was performed under general anesthesia. The mean age for both groups was similar. Follicular recruitment was achieved with human menopausal gonadotropin (hMG) or a combination of clomiphene citrate and hMG. In the ultrasonically guided aspiration group, 128 follicles were aspirated, with a 64% recovery rate (83 oocytes) and an 88.1% embryo transfer (ET) rate (67 embryos). Three (10.7%) intrauterine pregnancies were established in this group. In the laparoscopic group, 153 follicles were aspirated, with a 68.6% recovery rate (105 oocytes) and an 86.3% ET rate (82 embryos), with 4 (13.3%) intrauterine pregnancies established. Three patients had both procedures done; however, none conceived. There were no statistically significant differences between the two groups. Ultrasonically guided transurethral follicular aspiration should be considered as an alternative route for oocyte retrieval, especially when laparoscopy is contraindicated or when the ovaries are not accessible.

Female↗
PubMed1986

Total estradiol, free estradiol, sex hormone-binding globulin, and the fraction of estradiol bound to sex hormone-binding globulin in human follicular fluid.

Sex hormone-binding globulin (SHBG), percent free estradiol (E2), the fraction of E2 bound to SHBG, and total E2 were measured in the serum and follicular fluid of 12 women (25 follicles) who had received gonadotropin stimulation in an in vitro fertilization program. The women were classified as high or low responders based on peak serum E2 levels (high responders: peak E2, greater than 1500 pg/ml; low responders: peak E2, less than 1000 pg/ml). During treatment, serum levels of SHBG increased in high responders from 55 +/- 8.8 (+/- SEM) to 96 +/- 16 nM (P less than 0.01), but did not change in low responders. SHBG was more concentrated in follicular fluids from high responders (142 +/- 12.5 nM) than in those from low responders (44.4 +/- 5.8 nM). A positive correlation was found between serum and follicular fluid levels of SHBG (r = 0.873; P less than 0.01). In follicular fluid, total E2 levels, which varied from 100-2650 ng/ml, correlated (r = 0.790; P less than 0.01) closely with SHBG levels. The percent free E2 averaged 5.9% (range, 4-10.6%) in follicular fluid compared to 1.8% (range, 1.5-2.1%) in serum. An inverse correlation (r = -0.661; P less than 0.01) was found between total E2 concentrations and percent free E2 in follicular fluid. The relationship between serum and follicular fluid levels of SHBG suggests that SHBG in follicles arises from the circulation. Although SHBG is present in follicular fluid in amounts similar to those in serum, the large quantities of E2 in preovulatory follicules exceed the binding capacity for SHBG, and the majority of E2 appears to be bound to albumin. Hence, it seems unlikely that SHBG in follicular fluid regulates estrogen action in ovarian target cells.

Adult↗
PubMed1985

The diagnosis of ectopic pregnancies in cases of lower abdominal pain using beta subunit assay of human chorionic gonadotropin.

The role of beta-subunit assay of human chorionic gonadotropin (hCG) in the early and accurate diagnosis and treatment of ectopic pregnancy was evaluated prospectively in a group of 57 women who presented with lower abdominal pains. A flow scheme for diagnosis work-up based primarily on hCG beta-subunit assay resulted in no false negative result. This enabled early and conservative treatment of the condition. Ectopic pregnancy was diagnosed early in more than one third of the patients. As a result conservative treatment was performed in cases were it was required and medically possible (33% of the cases).

Abdomen↗
PubMed1983

Menarche and puberty in daughters of amenorrheic women.

Twenty-six daughters born to amenorrheic women after gonadotropin-induced ovulation were studied at 10 to 16 years of age. The aim of the study was to assess whether the mothers' condition, namely, amenorrhea and infertility followed by the pharmacologic induction of ovulation, had any effect on their female offspring in terms of endocrine disorders at puberty. The daughters were found to have normal onset of puberty as well as normal physical and mental development. The mean age at menarche, body weight, and height were similar to those of the general female population in Israel. A functioning hypothalamic-pituitary-ovarian axis was evidenced by the appearance of menarche followed by regular cycles. These data form a reassuring sample for the clinicians, the treated mothers, and their offspring.

17-Hydroxycorticosteroids↗
PubMed1983

Abortion rate in pregnancies following ovulation induced by human menopausal gonadotropin/human chorionic gonadotropin.

Despite the high incidence of fetal loss following gonadotropin therapy, the etiologic, factors that contribute to this loss remain unknown. In 203 women who conceived following gonadotropin therapy, the abortion rate was 28.5%. However, in 84 women who conceived a second time, also with gonadotropin treatment, the abortion rate was 11.9%. Second- and third-degree hyperstimulation of the ovary are accompanied by a 50% abortion rate, and the occurrence of abortion is more frequent in the first pregnancy. The contribution of multiple pregnancy, maternal age, and number of gonadotropin treatment cycles are also evaluated and discussed.

Abortion, Spontaneous↗