Midazolam-fentanyl sedation in conjunction with local anesthesia during oocyte retrieval for in vitro fertilization.
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Drug Therapy, Combination↗
Biomedical subjects
D Levran
Publications and source records attributed to D Levran.
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↗
The incidence of combined intrauterine and extrauterine pregnancy after in vitro fertilization and embryo transfer.
Our data demonstrate the high incidence of combined pregnancy among patients who have undergone IVF. Close monitoring of pregnancies in IVF programs may prevent a possibly deleterious delay in the treatment of simultaneous ectopic and intrauterine gestation.
Embryo Transfer↗
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↗
Endocrine and biological factors influencing implantation of human embryos following cryopreservation.
Several parameters affecting survival and implantation of frozen-thawed embryos were studied. Of 386 embryos frozen in dimethylsulfoxide (DMSO) or in 1,2 propanediol (PROH), the survival rate was 63.5% (245/386). Three different methods of cycle preparation were compared prior to thawed embryo replacement. The pregnancy rate was 16.1% (9/56) in spontaneous cycles; 11.4% (5/44) in an ovarian stimulation protocol; and 9.5% (4/42) with estrogen and progesterone substitutional therapy (p = NS). There was no difference in the estradiol/progesterone ratio among the three different protocols during the early luteal phase of the cycle, which may indicate that implantation of thawed embryos could be related to their developmental potential rather than to the endometrial environment. In the spontaneous cycles, when endometrium was synchronized or advanced to embryonic stage up to 32h, implantation rate was 29.2%.
Adult↗
Pregnancy potential of human oocytes--the effect of cryopreservation.
BACKGROUND: In vitro fertilization, sometimes involving the cryopreservation of human embryos, has become a routine procedure for the treatment of infertility. Even though there are embryos available for transfer in about 85 percent of the treatment cycles, the rate of pregnancy rarely exceeds 25 percent per cycle. We designed this study to investigate two questions: Does this high rate of failure result from inadequate technique, or does it simply reflect the maximal potential of a cohort of aspirated eggs to produce a pregnancy? And to what extent does cryopreservation affect the capacity for implantation of embryos? METHODS: The study was conducted among patients enrolled in an egg-donation program. Aspirated eggs from a given cohort were distributed to the donor herself and a few recipients. The recipients were prepared by a standard protocol of hormone replacement and were assigned at random to the transfer of either fresh or frozen and thawed embryos. The donors received only fresh embryos. RESULTS: Forty cycles of donation were studied. In 25 cycles (63 percent) pregnancy was established in the donor, in the recipient (or recipients), or in both. Of the fresh embryos that were transferred to the recipients, 24 percent were successfully implanted, as compared with only 7.7 percent of the frozen and thawed embryos (P less than 0.01). A pregnancy success rate of 37 percent per recipient cycle was observed in the recipients of fresh embryos, as compared with a rate of only 16 percent in those receiving frozen and thawed embryos (P less than 0.05). CONCLUSIONS: The majority of egg cohorts evidently possess the potential to produce a pregnancy, but cryopreservation of human embryos significantly reduces their capacity for implantation.
Adult↗
Ovarian stimulation with gonadotropin-releasing hormone (GnRH) analogue improves the in vitro fertilization (IVF) pregnancy rate with both transvaginal and laparoscopic oocyte recovery.
The relative impact of ovarian stimulation protocol and oocyte retrieval technique on success rates of in vitro fertilization program was studied in 200 patients. Sixty-three patients received gonadotropin-releasing hormone analogue (GnRHa) with human menopausal gonadotropin (hMG), and 137 received hMG only. The GnRHa + hMG protocol resulted in higher pregnancy rates than the hMG-only protocol (19.0 vs 9.5%, respectively; P less than 0.01) despite a lower cleavage rate. Oocyte retrieval was performed via laparoscopy in 100 patients and transvaginally in 100 patients. The number of oocytes recovered per cycle was 6.1 +/- 3.9 with laparoscopy and 7.0 +/- 3.1 transvaginally. Pregnancy rates were similar for both retrieval techniques (13 and 12%, respectively). A breakdown of these results showed that the advantage for the GnRHa + hMG protocol was not affected by the oocyte retrieval technique. A comparison of simultaneous blood and follicular fluid pH measured every 10 min during laparoscopy and transvaginal oocyte recovery revealed a constant decline in follicular fluid pH during laparoscopy, while no changes were observed during the vaginal procedure. We conclude that the improvement in in vitro fertilization results during the period of our study is due primarily to the introduction of GnRHa + hMG protocol rather than the method of oocyte retrieval.
Biopsy, Needle↗
Anomalies of human oocytes from infertile women undergoing treatment by in vitro fertilization.
During in vitro fertilization treatment, three types of oocyte anomalies were observed in four infertile women. These anomalies were related to (1) failure of oocyte maturation from the germinal vesicle stage of meiosis, (2) failure of polar body formation and cleavage, and (3) absence of oocytes in otherwise mature follicular aspirates. These anomalies are considered to contribute to these patients' infertility.
Adult↗
Gonadotropin-releasing hormone therapy analog and migraine?
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Central Nervous System↗
The treatment of patients with polycystic ovarian syndrome by in-vitro fertilization and embryo transfer: a comparison of results with those of patients with tubal infertility.
Sixteen patients with polycystic ovarian syndrome (PCO) were treated by in-vitro fertilization (26 treatment cycles). The results were compared with 37 normo-ovulatory women with tubal disease (37 treatment cycles). The oestradiol and progesterone levels were higher during the follicular phase in the PCO patients, but were statistically significantly higher only on the day after human chorionic gonadotrophin administration. Although more oocytes were recovered per cycle from the PCO group (19.3 +/- 6.1) than from the control group (5.4 +/- 2.9) with P less than 0.004, the mean numbers of embryos per cycle were similar in both groups (3.7 +/- 2.4 versus 3.6 +/- 2.2, respectively). The pregnancy rate was also comparable in both groups (30.7 versus 29.7%, respectively). The fact that more oocytes are recovered from PCO patients, balances their lower fertilization and cleavage rates. We conclude, therefore, that IVF treatment may be a viable solution for PCO patients resistant to an in-vivo protocol treatment regimes.
Cell Count↗
Steroid secretion by granulosa cells isolated from a woman with 17 alpha-hydroxylase deficiency.
Steroid synthesis in luteal/granulosa cells harvested after follicular aspiration in a patient with 17 alpha-hydroxylase deficiency was investigated. Follicular stimulation with purified FSH after the suppression of ACTH and gonadotropin secretion by corticoid analogs and superactive GnRH agonist permitted ovum pick-up and the study of steroid synthesis in the obtained granulosa cells. Progesterone synthesis was elevated while 17 alpha-hydroxy progesterone, testosterone, androstenedione, and estrogen production was minimal. Aromatase activity was retained in these cells, as demonstrated by the 100-fold increase in estrogen levels after the addition of androgens. Progesterone levels in follicular fluids were in the normal range, while estrogen, 17 alpha-hydroxy progesterone, and androgen levels were minimal. These results provide in vitro evidence of 17 alpha-hydroxylase deficiency in the granulosa cells of this patient.
Adrenal Hyperplasia, Congenital↗