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Biomedical subjects

D Levran

Publications and source records attributed to D Levran.

At least 37 records · Page 2Linked to original sources

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↗

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↗

How often should infertile men have intercourse to achieve conception?

OBJECTIVE: To clarify how often infertile men should have intercourse to achieve conception, the effect of sequential ejaculation on total motile sperm counts was investigated. DESIGN: Case-control study. SETTING: Infertility and IVF unit, tertiary care center. PARTICIPANTS: Five hundred seventy-six men who produced two closely spaced sequential ejaculates. MAIN OUTCOME MEASURE: The total motile sperm counts of the second ejaculates were compared with the total motile sperm counts of the first ejaculates. RESULTS: In normospermic men (n = 359), the total motile sperm counts decreased significantly from 93 (18 to 601) (median [minimum to maximum] x 10(6)) in the first ejaculate to 42 (1.2 to 387) in the second ejaculate, produced 24 hours later. In contrast to the normospermic men, in the asthenospermic group (24 hours difference, n = 81) and in both oligospermic groups, (1 to 4 hours difference, n = 27; and 24 hours difference, n = 45), there were no significant changes in the total motile sperm counts (24 [5.9 to 229] versus 30 [0.8 to 150], 6 [0.8 to 18] versus 3.6 [0.1 to 63] and 13 [2.5 to 32] versus 10 [0.1 to 66], respectively). Moreover, in both oligoasthenospermic groups (1 to 4 hours difference, n = 23; and 24 hours difference, n = 41) the total motile sperm counts increased significantly (3.2 [0.6 to 7.9] versus 8 [0.4 to 48] and 4 [0.2 to 13] versus 4 [0.1 to 101], respectively). In all groups, pooling sequential ejaculates significantly increased the total motile sperm counts, over and above that of the first ejaculate, by 49% in the normospermic group, 95% in the asthenospermic group, 67% and 75% in the oligospermic groups (1 to 4 hours and 24 hours difference, respectively), and 233% and 139% in the oligoasthenospermic groups (1 to 4 hours and 24 hours difference, respectively). CONCLUSIONS: Sequential ejaculation may overcome the impaired sperm transport causing low total motile sperm counts observed in some oligospermic and/or asthenospermic men. Most of these infertile men may significantly increase their fertility potential, assessed by the total motile sperm counts, either by pooling sequential ejaculates for IUI, GIFT, and IVF, or by having intercourse every day or even twice a day, at the time of ovulation.

Case-Control Studies↗

Unsuccessful methotrexate treatment of a tubal pregnancy with a live embryo.

Two cases with unsuccessful local and systemic methotrexate (MTX) therapy of tubal pregnancy with fetal heart rate activity are reported. The three modes of therapy, the first with local potassium chloride solution injection, the second with local MTX injection, and the third with systemic MTX injection, failed in the resolution of viable ectopic pregnancy. Therapy of MTX in cases of tubal pregnancy with demonstrable fetal heart rate beats, should be reconsidered.

Adult↗

The prognostic importance of the number of oocytes retrieved and estradiol levels in poor and normal responders in in vitro fertilization (IVF) treatment.

A low response to ovarian stimulation in in vitro fertilization poses a unique therapeutic challenge. Gonadotropin-releasing hormone agonists (GnRHa) have been suggested as a modality for treatment of this condition. In this study, we analyzed the results of 880 in vitro fertilization treatment cycles with respect to modality of ovarian stimulation, degree of hormonal response, and number of oocytes retrieved. In patients with estradiol (E2) levels less than 501 pg/ml on the day of human chorionic gonadotropin administration, 27% pregnancy rate was achieved with clomiphene citrate (CC) combined with human menopausal gonadotropin (hMG), compared to 15.1% (P less than 0.005) with hMG alone and 20.8% (NS) with GnRHa and hMG. Pregnancy rates were not lower in these patients compared to patients with higher estradiol levels in the different stimulation protocols, but pregnancy rates were significantly lower in cycles during which three or fewer oocytes were retrieved, compared to those in which four or more oocytes were retrieved (10.8 vs 23.8%; P less than 0.0005). In low-retrieval cycles pregnancy rates actually decreased with increasing levels of estradiol. Our results indicate that the number of oocytes retrieved is a better prognostic parameter than E2 levels in predicting the outcome of in vitro fertilization treatment and that GnRHa in the long protocol do not seem to be superior to CC combined with hMG for the treatment of poor responders.

Biomarkers↗

The effect of gonadotropin-releasing hormone agonist on the ovarian response and in vitro fertilization results in polycystic ovarian syndrome: a prospective study.

OBJECTIVE: To assess the effect of gonadotropin-releasing hormone agonist (GnRH-a) on pituitary suppression, subsequent ovarian response, and results of in vitro fertilization (IVF) treatments in polycystic ovarian syndrome (PCOS) patients. DESIGN: Randomized prospective study. SETTING: In vitro fertilization program and endocrinologic institute. PATIENTS: Thirty patients with PCOS; 16 received GnRH-a, and 14 did not receive GnRH-a. INTERVENTIONS: Ovum pick-up and embryo transfer. MAIN OUTCOME MEASURES: Response to GnRH-a test, serum and follicular fluid (FF) hormonal measurements, steroid levels, and aromatse activity in granulosa cell (GC) culture, and results of IVF. RESULTS: Pituitary responsiveness was abolished in all patients 14 days after GnRH-a administration, and early luteinization was prevented. Steroid levels in FF did not differ between the two groups. In GC culture, progesterone (P) levels were higher in patients without the GnRH-a (3,704 +/- 1,232 nmol/L versus 2,117 +/- 235 nmol/L; P less than 0.05) as were androstenedione (A) levels (5.3 +/- 1.0 nmol/L versus less than 3.5 nmol/L; P less than 0.05). However, aromatase activity and IVF results were similar in the two groups. CONCLUSIONS: Administration of GnRH-a in patients with PCOS decreases P and A production by the GC cells and prevents early luteinization. It does not affect the IVF results.

Female↗

Failure to fertilize in vitro in couples with male factor infertility: what next?

OBJECTIVE: To assess the predictive value of a failure to fertilize in vitro in couples with sperm abnormalities on future fertility. DESIGN: Retrospective file review. SETTING: In vitro fertilization and embryo transfer (IVF-ET) program in the Sheba Medical Center during the years 1983 to 1990. PATIENTS: Seventy-six couples with sperm abnormalities who had at least one IVF cycle during which fertilization did not occur. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Occurrence of fertilization, percentage of fertilization, and pregnancies in additional IVF-ET cycles. RESULTS: Of 44 couples who underwent an additional IVF attempt with husband's sperm, 36 (81.2%) fertilized, with a mean fertilization rate of 47.7% +/- 26.6%. Of 17 couples who failed twice, 11 attempted IVF again with husband's sperm and 7 fertilized, with a median rate of 33%. A higher sperm concentration was found on the cycles during which fertilization occurred. Men with single parameter abnormalities did not fertilize better than those with two or three defective parameters. CONCLUSIONS: Failure to fertilize in vitro in couples with male factor infertility does not seem to predict future fertilization in IVF. At least two cycles of IVF should be tried before reverting to other options such as insemination by donor sperm or gamete micromanipulation.

Embryo Transfer↗

The relative success of gonadotropin-releasing hormone analogue, clomiphene citrate, and gonadotropin in 1,099 cycles of in vitro fertilization.

OBJECTIVES: To evaluate the effectiveness of and analyze the factors influencing the outcome of three ovarian stimulation protocols used during in vitro fertilization (IVF) in a large population. DESIGN: Retrospective file review. SETTING: In vitro fertilization program in one center during the years 1985 to 1990. PATIENTS AND PROTOCOLS: Three hundred forty-one patients received clomiphene citrate (CC) and human menopausal gonadotropin (hMG), 365 received hMG alone, and 393 received gonadotropin-releasing hormone analogue (GnRH-a) for pituitary suppression followed by hMG stimulation. MAIN OUTCOME MEASURE: Rates of cancellation, total pregnancies, and ongoing pregnancies, with breakdown by age of patients. RESULTS: The cancellation rate because of early luteinization following GnRH-a/hMG was significantly reduced compared with the other two protocols: 3.6% versus 9.4% and 13.7% for CC/hMG and hMG, respectively. However, in women over 40 years of age, GnRH-a/hMG resulted in the highest rate of poor ovarian response. Significantly more oocytes were retrieved, fertilized, and cleaved after the use of GnRH-a/hMG compared with the other two protocols. Despite this, clinical pregnancy rate (PR) was the highest with CC/hMG compared with GnRH-a/hMG and hMG:31.4% versus 16.9% and 15.7%, respectively. Ongoing PRs were 20.5%, 9.7%, and 11.6%, respectively. CONCLUSIONS: Although the use of GnRH-a for pituitary suppression before ovarian stimulation for IVF reduced the cancellation rate and increased the number of retrieved oocytes, it was not found to result in higher PRs than those achieved by stimulation with CC/hMG. This suggests that treatment by GnRH-a/hMG should be reserved mainly for the prevention of early luteinization.

Clomiphene↗

Insulin-like growth factor-I (IGF-I) may not be essential for ovarian follicular development: evidence from IGF-I deficiency.

Insulin-like growth factor-I (IGF-I) stimulates growth and differentiation in follicular granulosa cells (GC). To examine whether this effect is prerequisite to human folliculogenesis, a patient with Laron-type dwarfism (IGF-I deficiency secondary to GH receptor abnormality) was examined while undergoing in vitro fertilization treatment. Despite low levels of IGF-I in serum and follicular fluid (less than 3 and less than 2 nmol/L) and very high levels of IGF-I-binding protein, the patient developed normal ovarian follicles. After the administration of GnRH analog (GnRHa) and human menopausal gonadotropin in a dose similar to that used in normovulatory women, estradiol (E2) levels reached above 5000 pmol/L on the day of hCG administration, and mature fertilizable oocytes were retrieved during ovum pickup. The patient's GC E2 production, tested in a primary culture, did not respond to IGF-I after 4 days of incubation, while control cultures showed a significant increase. Only after a priming period of 7 days did IGF-I have a significant effect on E2 production, as observed in the patient's GC culture. This delayed response suggests that the patient's GC were not exposed in vivo to IGF-I. Our data support the view that IGF-I is not required for normal follicular development, but is, rather, a nonessential modulator of FSH action.

Adult↗

Combined gonadotropin releasing hormone agonist/human menopausal gonadotropin therapy (GnRH-a/hMG) in normal, high, and poor responders to hMG.

Patients who failed to conceive after gonadotropin stimulation in in vitro fertilization treatment were classified into normal, high, or poor responders. They were routinely offered another cycle with a combination of a gonadotropin releasing hormone agonist and gonadotropin therapy (in order to evaluate whether this combined therapy could improve their response). The gonadotropin-induced cycle was compared with the combined therapy cycle. With the combination treatment, in the normal responders the phase of ovarian stimulation was significantly (P less than 0.001) prolonged, and the number of follicles and oocytes collected (5.7 +/- 0.7 vs 3.1 +/- 0.4) was increased, without any change in serum estradiol level compared to the control cycle. In high responders the number of oocytes was not modified by the combined treatment compared with the control cycle. However, serum estradiol level was significantly (P less than 0.005) decreased. The combined therapy did not modify any parameter of response in poor responders. We conclude that the response to combined agonist/gonadotropin therapy is dependent on the patient's own basal response. No improvement in response was expected in poor responders.

Delayed-Action Preparations↗

Hysteroscopy in a program of in vitro fertilization.

Two hundred twenty-four women underwent hysteroscopic evaluation without anesthesia after at least two failed attempts of in vitro fertilization and embryo transfer. One hundred fifty-three (68%) women were diagnosed as having mechanical infertility, and abnormal hysteroscopic findings were observed in 32 (21%). Forty-one women were diagnosed as having unexplained infertility (18%) and six (15%) had abnormal findings with hysteroscopy. Of the 30 couples who entered the in vitro fertilization regimen program because of male infertility, 4 (13%) had abnormal findings. The overall rate of abnormal findings was 19%; cervical canal and intrauterine abnormalities were found in 10 and 32 patients, respectively. Ten patients were treated during hysteroscopic evaluation procedure, and four patients subsequently underwent operative hysteroscopy under general anesthesia. We suggest that diagnostic hysteroscopy should be a routine procedure before in vitro fertilization and embryo transfer therapy.

Adult↗

Failure of oocyte retrieval during in vitro fertilization: a sporadic event rather than a syndrome.

Failure to retrieve oocytes during in vitro fertilization (IVF) treatment was recently referred to as the "empty follicle syndrome." Data on the possible repetitiveness of this during previous or subsequent IVF attempts is lacking, which limits the understanding of its significance to the involved patients. Of 26 patients who had cycles during which no oocytes were retrieved, 10 were pregnant in the past and 20 had at least one other IVF cycle that yielded oocytes. There was no difference in the frequency of any stimulation protocol among the failure cycles compared with the successful ones. Hormonal response pattern and the number of large follicles observed sonographically did not differ between the two occasions. Fertilization occurred in 70% of the successful cycles and two biochemical pregnancies were recorded. In 13 patients, at least one cycle was canceled because of poor ovarian response, but 9 of these 13 had at least one other successful cycle. We conclude that the so-called empty follicle syndrome cannot be predicted by the pattern of ovarian response and does not predict a reduced fertility potential in future cycles.

Clomiphene↗

Aging of endometrium and oocytes: observations on conception and abortion rates in an egg donation model.

OBJECTIVE: To assess the comparative contribution of endometrial and oocytic aging to the decline in fertility with age. DESIGN: Retrospective analysis of conception and abortion rates in an egg donation program, with respect to donor and recipient ages. PATIENTS: All oocyte recipients had ovarian failure. Donors were women undergoing in vitro fertilization who contributed up to a third of retrieved oocytes. INTERVENTIONS: None. RESULTS: Thirty pregnancies (28 intrauterine) were recorded in 169 reception cycles originating from 91 donation cycles. Women who conceived were younger than those who did not (median age 31 versus 37; P less than 0.046), with no difference in age of donors. There was a significant difference in spontaneous abortion rate by age of donor rather than by age of recipient. Donors to successful pregnancies were younger than donors to aborted pregnancies (median age 27.5 versus 33; P less than 0.0211), but the 11 women with aborted pregnancies did not differ in age from the 17 women with successful pregnancies. CONCLUSIONS: In women, endometrial function as expressed by conception rate in the recipients declines with age, whereas it is oocyte age that primarily influences risk of abortion.

Abortion, Spontaneous↗

The effect of smoking on the outcome of in-vitro fertilization--embryo transfer.

This study investigated the influence of cigarette smoking on the outcome of in-vitro fertilization-embryo transfer. Forty-one women under the age of 37 years, suffering from mechanical infertility, were suppressed with gonadotrophin releasing analogue from day 21 of the cycle. Twenty women were smokers and 21 women were non-smokers. Gonadotrophin releasing analogue was injected daily before ovarian stimulation with gonadotrophin was begun. The follicular phase was longer and the number of human menopausal gonadotrophin ampoules required to reach adequate stimulation were higher in smokers. The peak serum oestradiol level was not significantly different in smokers compared to non-smokers. However, follicular fluid levels of oestradiol were significantly lower in smokers than in non-smokers (657 +/- 367 versus 1077 +/- 786 ng/ml) respectively. Furthermore, the fertilization rate was also lower in smokers than in non-smokers (40.9 versus 61.7%) respectively. Four pregnancies were achieved in the non-smokers group, while only one ectopic pregnancy was diagnosed in the smokers group. These findings suggest that cigarette smoking has a detrimental effect on the outcome of in-vitro fertilization and embryo transfer.

Adult↗