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Biomedical subjects

J Dor

Publications and source records attributed to J Dor.

At least 55 records · Page 3Linked to original sources

Glucocorticoid administration during transfer of frozen-thawed embryos: a prospective, randomized study.

OBJECTIVE: To establish whether there is any improvement in pregnancy and implantation rates after administration of "low-dose," long-acting glucocorticoids during transfer of cryopreserved-thawed embryos. SETTING: An IVF unit in a university hospital. DESIGN: Prospective, randomized study. Ninety-nine consecutive transfer cycles of frozen-thawed embryos to the uterine cavity of randomly chosen women diagnosed as having tubal factor infertility only. Fifty-two patients underwent transfer of frozen-thawed embryos and received 0.5 mg of dexamethasone; 47 women (control group) did not receive the drug during transfer. PATIENTS: Normal ovulatory patients with tubal factor infertility. INTERVENTIONS: Oral dexamethasone administration before, during and after transfer of thawed embryos. MAIN OUTCOME MEASURES: Pregnancy and implantation rates. RESULTS: The pregnancy rate was 13.5% (7/52) in patients treated with the "low-dose" regimen of dexamethasone compared with 12.8% (6/47) in the control group. The implantation rate was similar. CONCLUSION: Our results demonstrated that the use of 0.5 mg dexamethasone for an immuno-suppressive effect, administered for a short period to patients diagnosed as having "pure" tubal factor infertility, did not improve the implantation or pregnancy rates.

Adult↗

Cumulative pregnancy rate following in-vitro fertilization: the significance of age and infertility aetiology.

During the years 1984-1992, 951 couples completed 2252 in-vitro fertilization (IVF) treatment cycles at the In-Vitro Fertilization Unit of The Chaim Sheba Medical Centre. This study was conducted to evaluate the success of IVF using the cumulative pregnancy rate (CPR), with special emphasis on the optimal number of treatment cycles, the age of the patients and female infertility factors. It was found that the CPR showed a constant rise during the six initial IVF treatments (56% CPR), and plateaued in the subsequent three cycles (63% CPR). Various female infertility factors did not influence this rate. Women > or = 40 years of age have a significantly lower CPR. Thus, it was concluded that the CPR in IVF declined after the sixth initial treatment cycle, and in women > or = 40 years of age. The infertility factor did not significantly influence CPR.

Adult↗

Micromanipulation improves in-vitro fertilization results after epididymal or testicular sperm aspiration in patients with congenital absence of the vas deferens.

In all, 58 couples suffering from infertility because of congenital bilateral absence of the vas deferens underwent a total of 67 combined microsurgical epididymal aspiration or testicular sperm extraction (TESE) and in-vitro fertilization (IVF) treatments. The oocytes recovered were inseminated by either the microdroplet IVF technique (N = 20), subzonal insemination (SUZI; n = 10) or intracytoplasmic sperm injection (ICSI; n = 37). Of the ICSI cycles, 12 were performed using spermatozoa obtained by TESE. Fertilization rates for epididymal spermatozoa were significantly higher for SUZI (17.9%, 17/95) and ICSI (34.4%), 137/398) than for microdroplet IVF (5.2%, 18/343) cycles. The proportion of cycles in which fertilization was achieved was higher in the SUZI (80%) and ICSI (95%) cycles than in the IVF cycles (45%). Delivery or an ongoing pregnancy was achieved in one (5%) IVF cycle, two (20%) SUZI cycles and seven (18.95) ICSI cycles. SUZI or ICSI using epididymal or testicular spermatozoa significantly improved the oocyte fertility rate. The ICSI procedure was especially advantageous in patients for whom spermatozoa were obtained from a testicular biopsy.

Cytoplasm↗

The addition of a glucocorticoid to the protocol of programmed oocyte retrieval for in-vitro fertilization--a randomized study.

A group of 78 infertile women, diagnosed as having tubal factor infertility only, was enrolled in a prospective, randomized study conducted to determine whether the addition of different doses of glucocorticoids to the protocol of ovulation induction for in-vitro fertilization (IVF) would be beneficial. Oocyte numbers, percentage of fertilization, oestradiol, luteinizing hormone and follicle stimulating hormone serum concentrations, number of embryo transfers and pregnancy rate were evaluated. Compared to control cycles (group A; n = 24), the addition of 0.5 mg (group B; n = 27) of 1 mg dexamethasone (group C; n = 27), combined with the protocol of programmed oocyte retrieval for IVF patients in the study, demonstrated equivalent results. The mean numbers of oocytes retrieved were 10.8 +/- 3.9 in the control group, compared to 11.2 +/- 4.0 in group B and 10.5 +/- 3.6 in group C. The fertilization rates were 69 +/- 21, 66 +/- 18 and 70 +/- 15% respectively. The pregnancy rates were 20, 16 and 20.8% respectively. The addition of up to 1 mg dexamethasone daily to the protocol of ovulation induction for oocyte retrieval did not improve the overall IVF-embryo transfer outcome in patients with tubal factor infertility.

Adult↗

Parameters that influence the results of in vitro fertilization/embryo transfer: a study of an egg donation model.

A retrospective analysis was carried out after ovulation induction in donors, and treatment outcome in donors and recipients, relating to variables such as: age, protocol of ovarian stimulation, transfer of fresh or cryopreserved embryos, number of embryos transferred including quality and etiology of donor and recipient infertility. The recipients underwent 214 cycles of embryo transfer from 82 different donors. Forty-five (21%) pregnancies were recorded. The age of the recipients significantly affected the conception rate (pregnancy rate of 30% in those aged < 30 years, compared to 9.7% in those aged > 44 years) and the donors were contributed more to pregnancies were also younger. The pregnancy rate was significantly higher when fresh embryos were transferred to recipients (28%, compared to 15% when cryopreserved embryos were transferred). In addition, the number of embryos transferred affected the pregnancy rate if > or = 3 embryos were transferred and, if they were of good quality, the success was significantly higher. Ultimately, when the ovarian stimulation protocol was clomiphene citrate and human menopausal gonadotropin or gonadotropin-releasing hormone agonist/follicle-stimulating hormone/human menopausal gonadotropin, and the etiology of infertility was polycystic ovarian disease in the donors, the success rate was significantly increased in the recipients.

Abortion, Spontaneous↗

High levels of soluble p55-TNF receptors in seminal and prostatic fluids of normal and infertile men.

PURPOSE: To study the role of tumor necrosis factor (TNF) in the male reproductive systems by examining the occurrence, source, and possible functional significance of soluble TNF receptors in seminal fluids of normal and infertile men. MATERIALS AND METHODS: Concentrations of soluble TNF receptors (p55-sTNF-R and p75-sTNF-R) were measured by ELISA in human sera, seminal fluids, prostatic fluid and fluid obtained from an epididymal spermatocele. RESULTS: The level of p55-sTNF-R in seminal fluids of normospermic men was approximately equal to 20-fold higher than in normal serum (13.9 +/- 6.9 ng./ml. versus 0.7 +/- 0.2 ng./ml.). In contrast, p75-sTNF-R, which occurs in serum at amounts higher than p55-sTNF-R, was almost indiscernible in the seminal fluids (<0.18 +/- 0.28 ng./ml. versus 1.9 +/- 0.6 ng./ml. in sera). Concentrations of p55-sTNF-R in seminal fluids of oligoasthenospermic and azoospermic men were similar to those of normospermic men (15.6 +/- 8.5 ng./ml. and 14.9 +/- 6.5 ng./ml., respectively). Higher p55-sTNF-R concentrations were found in prostatic fluids and first split ejaculates (39.8 +/- 1.2 ng./ml. and 32 +/- 1.7 ng./ml., respectively), while second split ejaculates and the fluid from an epididymal spermatocele were found to contain p55-sTNF-R at lower levels (10.8 +/- 1 ng./ml. and 1 ng./ml., respectively). CONCLUSIONS: These findings suggest intense local biosynthesis of p55-sTNF-R in the prostate occurring independently of spermatogenesis. Possible functional implications are: 1) shielding of spermatozoa from the inhibitory effect of TNF in the female reproductive tract; 2) a role for TNF in the normal physiology of the prostate; and 3) blocking TNF-mediated immune response in the prostate, which may have bearings on the development of prostatic hypertrophy or cancer.

Antigens, CD↗

Two embryonal cancers after in vitro fertilization.

BACKGROUND: In vitro fertilization is not considered to be associated with an increased rate of pediatric malignancies, and only three have been reported in the literature. Two additional rare pediatric tumors in children conceived through this technique are reported. METHODS: Two children 12 and 18 months of age, developed hepatoblastoma and clear cell sarcoma of the kidney, respectively. They were both products of uneventful pregnancies induced by in vitro fertilization. No other environmental, prenatal, or family factor was found. RESULTS: The first child died after a failed remission induction with cisplatin, doxorubicin, and vincristine, whereas the second child is alive with no evidence of disease 18 months after diagnosis and treatment according to NWTS protocol. CONCLUSIONS: A possible association between in vitro fertilization and pediatric malignancies is suggested.

Antibiotics, Antineoplastic↗

Sperm capacitation in humans is transient and correlates with chemotactic responsiveness to follicular factors.

In humans, only a small fraction (2-12%) of a sperm population can respond by chemoattraction to follicular factors. This recent finding led to the hypothesis that chemotaxis provides a mechanism for selective recruitment of functionally mature spermatozoa (i.e., of capacitated spermatozoa, which possess the potential to undergo the acrosome reaction and fertilize the egg). This study aimed to examine this possibility. Capacitated spermatozoa were identified by their ability to undergo the acrosome reaction upon stimulation with phorbol 12-myristate 13-acetate. Under capacitating conditions, only a small portion (2-14%) of the spermatozoa were found to be capacitated. The spermatozoa were then separated according to their chemotactic activity, which resulted in a subpopulation enriched with chemotactically responsive spermatozoa and a subpopulation depleted of such spermatozoa. The level of capacitated spermatozoa in the former was approximately 13-fold higher than that in the latter. The capacitated state was temporary (50 min < life span < 240 min), and it was synchronous with the chemotactic activity. A continuous process of replacement of capacitated/chemotactic spermatozoa within a sperm population was observed. Spermatozoa that had stopped being capacitated did not become capacitated again, which indicates that the capacitated state is acquired only once in a sperm's lifetime. A total sperm population depleted of capacitated spermatozoa stopped being chemotactic. When capacitated spermatozoa reappeared, chemotactic activity was restored. These observations suggest that spermatozoa acquire their chemotactic responsiveness as part of the capacitation process and lose this responsiveness when the capacitated state is terminated. We suggest that the role of sperm chemotaxis in sperm-egg interaction in vivo may indeed be selective recruitment of capacitated spermatozoa for fertilizing the egg.

Acrosome↗

A randomized study of intracytoplasmic sperm injection (ICSI) versus subzonal insemination (SUZI) for the management of severe male-factor infertility.

OBJECTIVE: Our objective was to compare the fertilization rates achieved by ICSI versus SUZI in couples with severe male infertility. DESIGN: This was a randomized, prospective study. SETTING: The study took place at the In-Vitro Fertilization-Embryo Transfer Unit, Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center. MATERIALS AND METHODS: Oocytes of 12 patients were randomly allocated to either ICSI or SUZI procedures. Each woman thus served as her own control. All 12 patients had undergone at least two previous in vitro fertilization cycles with no fertilization or had a very low sperm count, i.e., a total motile sperm count of less than 0.5 x 10(6). RESULTS: A total of 117 oocytes was obtained for fertilization. Of these oocytes, 16% (10/63) were successfully fertilized by SUZI, compared to 33% (18/54) treated by ICSI. This difference was statistically significant (P < 0.05). Of the 12 cycles, ICSI provided embryos in 10 cycles (83%), while SUZI was successful in only 6 cycles (50%). Four pregnancies were achieved: 33% per attempt, or 40% per transfer.

Adult↗

Endometrial blood flow response to hormone replacement therapy in women with premature ovarian failure: a transvaginal Doppler study.

OBJECTIVE: To evaluate the endometrial blood flow response to hormone replacement therapy (HRT) in women with premature ovarian failure who plan to enter an oocyte donation program. DESIGN: Transvaginal color Doppler ultrasound examinations were performed in women with ovarian failure before and during a cycle of standard HRT and in those with normal menstrual cycles. Blood flow response was assessed by visualization of arterial wave forms in the endometrial region. The transvaginal color flow mapping system was used. Resistance indexes were calculated for analysis and correlated with plasma E2 and P concentrations. PATIENTS: Eighteen women with ovarian failure (study group), and 12 volunteers with normal ovarian cycles (control group). RESULTS: Data for resistance indexes were divided into five phases according to the day of hormonal cycle: 0, pretreatment phase; I, early follicular phase (days 5 to 7); II, late follicular phase (days 11 to 13); III, early luteal phase (days 17 to 21); and IV, late luteal phase (days 23 to 25). All women with ovarian failure demonstrated continuous forward end-diastolic flow velocities at phase I, whereas none showed this pattern during the pretreatment period (phase 0). Women with ovarian failure in the early follicular phase had a significantly higher resistance index (0.85 +/- 0.1; mean +/- SD) than that in the late follicular phase (0.57 +/- 0.1), and the resistance index in the early luteal phase (0.67 +/- 0.1) was significantly higher than that of the late follicular phase. There was no difference in the resistance index between early and late luteal phases. A similar pattern of lower resistance index around midcycle was observed in the control group. However, a comparison of the resistance indexes between ovarian failure and control patients revealed a significant difference between values in the early follicular phase only (0.85 +/- 0.1 versus 0.68 +/- 0.1). In the late follicular phase and during the entire luteal phase, the mean resistance index did not differ between the study and control groups. CONCLUSIONS: The observed data suggest that standard HRT in women with premature ovarian failure enables restoration of endometrial blood flow to normal. This may imply uterine receptivity for oocyte donation.

Diastole↗

Adjuvant growth hormone therapy in poor responders to in-vitro fertilization: a prospective randomized placebo-controlled double-blind study.

The objective of the study was to assess the effect of growth hormone (GH) supplementation to a combined gonadotrophin-releasing hormone agonist/human menopausal gonadotrophin (GnRHa/HMG) treatment protocol on ovarian response in 'poor responders' undergoing in-vitro fertilization (IVF). GH or a placebo were administered in a prospective randomized double-blind manner. A total of 14 poor-responder patients (oestradiol < 500 pg/ml, less than three oocytes retrieved in two previous IVF cycles) were randomly allocated to a combined treatment of either GnRHa/HMG/GH (18 IU on alternate days, total dose 72 IU) or GnRHa/HMG placebo. No difference was found between the study and control groups in the number of HMG ampoules used, the number of follicles (> 14 mm) and serum oestradiol concentrations on the day of administration of human chorionic gonadotrophin (HCG), the number of oocytes retrieved and fertilized, and the number of embryos transferred. The GH group (n = 7) did not show a better ovulatory response in the study cycles; mean +/- SD serum oestradiol on day of HCG 411 +/- 124 versus 493 +/- 291 pg/ml, aspirated oocytes 2.2 +/- 1.5 versus 1.9 +/- 2.0. Interestingly, when the above results for the placebo group were compared with their previous cycles (serum oestradiol 403 +/- 231 pg/ml; 0.4 +/- 0.5 aspirated oocytes), a non-specific effect was found. Follicular recruitment, oestradiol secretion by mature follicles and the number of oocytes retrieved in poor responders were not improved by GH supplementation.

Adult↗

A reappraisal of the feedback effects of oestradiol upon luteinizing hormone surge.

The objective of this study was to assess the temporal relationships of serum oestradiol and luteinizing hormone (LH) with regard to the feedback mechanism leading to the LH surge. Daily measurements of oestradiol, LH and follicle stimulating hormone were made in 65 women with ovarian failure undergoing an evaluation of endometrial response to oral cycle stimulation. Patients received incremental oral oestradiol valerate for varying durations at the in-vitro fertilization unit of the Sheba Medical Center, Tel Hashomer, Israel. The treatment protocol involved the administration of daily oestradiol valerate, starting with 1 mg/day, followed by a daily increment of 1 mg for a total of 4, 6 and 8 days. After the last day, a daily maintenance dose of 2 mg was continued. Serum oestradiol concentrations correlated with the dose of oral oestradiol valerate. Peak oestradiol concentrations (mean +/- SEM) were 572 +/- 60, 721 +/- 42 and 797 +/- 53 pg/ml for 4, 6 and 8 days of oestradiol valerate administration respectively. Serum LH, after an initial suppression, peaked 2 days after maximal oestradiol valerate dose and 1 day after peak serum oestradiol. The magnitude of the LH peak was proportional to the duration of incremental oestradiol valerate treatment. In conclusion, the LH surge is temporally related to the cessation of serum oestradiol increase. Consequently, the occurrence of this surge can be explained by a simple negative feedback inhibition of pituitary LH release rather than by a dual negative/positive mechanism.

Adult↗

A cytosolic protein tyrosine kinase activity is induced by follicle stimulating hormone and insulin like growth factor-I in human granulosa cells.

Follicle stimulating hormone (FSH) induces estradiol (E2) production in rat, porcine and human granulosa cells with a concomitant increase in cAMP. In human granulosa cells insulin like growth factor-I (IGF-I) induces E2 production without cAMP accumulation. In the current study we report that IGF-I and FSH effects on aromatase activity both involve activation of a cytosolic soluble protein tyrosine kinase (CytPTK). This FSH and IGF-I stimulated CytPTK activity was blocked by AG-82 (a tyrosine kinase inhibitor) and by staurosporine (STS) (a non specific protein kinase inhibitor) at concentrations which inhibited E2 production. These new findings strengthen the concept of fail-safe mechanism in E2 production in human granulosa cells by an involvement of tyrosine kinase(s) activity downstream of cAMP formation and protein kinase A (PKA) activation.

Alkaloids↗

Polycystic ovarian syndrome: pregnancy outcome following in vitro fertilization-embryo transfer.

A retrospective study of a series of pregnant patients with polycystic ovarian syndrome following in vitro fertilization-embryo transfer was conducted to assess the outcome after ovarian stimulation by different protocols. Forty-one pregnancies were evaluated in patients with polycystic ovarian syndrome who conceived during in vitro fertilization-embryo transfer using human menopausal gonadotropin alone (17 pregnancies), or combined with gonadotropin releasing hormone analog (24 pregnancies). The demographic data of in vitro fertilization-embryo transfer cycles and pregnancy outcome were compared with the use of Student's t-test, the Mann-Whitney U test and Fisher's exact test, where appropriate. Among the pregnancies that were initiated following treatment, the protocol of the combination of the two was not associated with a higher rate of deliveries. The rate of first-trimester abortions was not statistically different between the two groups. These results suggest that the combined use of gonadotropin releasing hormone agonist and human menopausal gonadotropin in an in vitro fertilization program may not have beneficial effects on pregnancy outcome in patients with polycystic ovarian syndrome.

Adult↗

Congenital bilateral absence of vas deferens in the absence of cystic fibrosis.

The high frequency of mutations in the cystic fibrosis gene in patients with congenital bilateral absence of vas deferens (CBAVD) has raised the question whether all of them have a genital form of cystic fibrosis. We investigated 47 CBAVD patients by ultrasonography, 10 (21%) had renal malformations and 37 (79%) did not. In the former group, no cystic fibrosis mutations were found and sweat chloride concentrations were normal. In the latter group, 18 patients (49%) carried at least one cystic fibrosis mutation and sweat chloride was high in 17 of 26 tested (65%). Our findings suggest that CBAVD patients with renal malformations do not necessarily have cystic fibrosis.

Cystic Fibrosis↗

Hormonal treatment in pregnancy: a possible risk factor for neuroblastoma.

In the last 4 years, 24 cases of neuroblastoma were treated in the Pediatric Hematology-Oncology Unit at the Chaim Sheba Medical Center, 8 of whom were under 1 year of age. Four of them were the product of a pregnancy-induced or preserved by gonadotropins, clomiphene citrate, or progestational hormones. These drugs are known to produce a higher than normal level of estradiol or progesterone in the early stages of pregnancy. Our observation led to the hypothesis that high levels of progestational hormones given during pregnancy are a risk factor for neuroblastoma in infancy.

20-alpha-Dihydroprogesterone↗