"Ideas whose times have not come"?
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Ethics, Medical↗
Biomedical subjects
R J Chetkowski
Publications and source records attributed to R J Chetkowski.
Secondary donation of frozen embryos is more common after pregnancy initiation with donated eggs than after in vitro fertilization-embryo transfer and gamete intrafallopian transfer.
OBJECTIVE: To determine the availability of donated cryopreserved embryos. DESIGN: Retrospective review. SETTING: Community hospital-based donor oocyte program. PATIENT(S): Eighty-nine consecutive infertile couples and women who had 94 sets of embryos cryopreserved after pregnancy initiation with unfertilized donated eggs between January 1, 1991 and December 31, 1996. INTERVENTION(S): Cryopreservation of fertilized ova or cleaving embryos. MAIN OUTCOME MEASURE(S): Disposition of frozen embryos as of June 1, 1997. RESULT(S): Of the 94 sets of frozen embryos, 52 (55.3%) were thawed into the original recipient. At an average of 30 months since the treatment cycle, 26 (27.7%) sets of embryos remain in storage. Of the 16 sets of embryos not thawed for transfer, 11 sets (11.7%) were donated and 5 sets (5.3%) were destroyed. The fraction of spare embryos donated was much higher after pregnancy initiation with unfertilized donated eggs than after IVF-ET and GIFT (68.8% versus 19.1%, respectively). CONCLUSION(S): Couples and women who did not use their frozen embryos after pregnancy initiation with unfertilized donated eggs were twice as likely to donate them as to have them destroyed. Secondary donation of cryopreserved embryos was much more common after pregnancy initiation with unfertilized donated eggs than after standard IVF-ET and GIFT.
Adult↗
In premature luteinization, progesterone induces secretory transformation of the endometrium without impairment of embryo viability.
OBJECTIVE: To determine the effect of serum P on endometrial histology in stimulated cycles. DESIGN: Prospective clinical study. SETTING: Community hospital-based donor oocyte program. PATIENT(S): Fertile young oocyte donors and infertile donor oocyte recipients. INTERVENTION(S): Oocyte donors underwent gonadotropin stimulation after midluteal pituitary suppression. Endometrial biopsies were obtained at the time of oocyte retrieval. MAIN OUTCOME MEASURE(S): Endometrial histology and serum P levels in oocyte donors. Pregnancy and implantation rates in oocyte recipients. RESULT(S): Thirteen biopsy specimens (52.0%) showed in-phase mixed proliferative pattern (days 14 to 15), whereas 12 (48.0%) were secretory (days 16 to 17). On the day of hCG, subjects with secretory endometrium had higher P of 1.7 ng/mL (5.4 nmol/L) than women with the mixed pattern (0.8 ng/mL [2.5 nmol/L]). Progesterone > or = 0.9 ng/mL had a 78.6% positive predictive value for secretory transformation. In 75.0% of cycles with secretory endometrium, P was > or = 0.9 ng/mL, (2.9 nmol/L) as early as 2 days before hCG. Both mixed and secretory patterns were associated with similar clinical pregnancy rates (57.1% and 60.0%, respectively) and delivery rates (38.1% and 50.0%, respectively) in recipients. CONCLUSION(S): Subtle elevation of P induced secretory endometrial transformation without reduction in embryo viability.
Adult↗
Donation of frozen embryos after in vitro fertilization is uncommon.
OBJECTIVE: To determine the availability of donated cryopreserved embryos. DESIGN: Retrospective review. SETTING: Community hospital-based IVF-ET program. PATIENTS: Eighty-three consecutive infertile couples who had 98 sets of embryos cryopreserved after IVF-ET and GIFT between January 1, 1989 and December 31, 1991. INTERVENTION(S): Cryopreservation of fertilized oocytes or cleaving embryos after IVF-ET and GIFT. MAIN OUTCOME MEASURE(S): Disposition of frozen embryos as of December 31, 1995. RESULT(S): Of 98 sets of frozen embryos, 71 (72.4%) were thawed for transfer into the infertile woman. At an average of 6 years since the treatment cycle, six sets of embryos (6.1%) remain in storage. Of 21 sets of embryos not thawed for autologous transfer, the majority (17.4%) were discarded, leaving only four clutches (4.1%) available for donation. CONCLUSION(S): Couples who did not use their frozen embryos after IVF-ET and GIFT were four times more likely to destroy them than to donate them.
Cryopreservation↗
The effect of pituitary suppression and the women's age on embryo viability and uterine receptivity.
OBJECTIVE: To examine the effect of pituitary suppression and the women's age on embryo viability and uterine receptivity. DESIGN: Retrospective analysis of 394 embryo transfers (ET) after in vitro fertilization (IVF). SETTING: Community hospital IVF program from 1986 to 1990. PATIENTS: Three groups were studied: women less than 40 years with pituitary suppression (group 1) and without pituitary suppression (group 2); women 40 years of age and older with pituitary suppression (group 3). INTERVENTIONS: Pituitary suppression was achieved in groups 1 and 3 with daily leuprolide acetate starting in the luteal phase; human menopausal gonadotropin and progesterone were given intramuscularly. MAIN OUTCOME MEASURES: Ongoing and multiple ongoing pregnancy rates (PRs) were compared in the three groups. A mathematical model of implantation was used to estimate embryo viability and uterine receptivity. RESULTS: Ongoing and multiple ongoing PRs per ET in group 1 (28.6% and 12.3%) were significantly higher than the corresponding rates in group 2 (16.9% and 2.4%) and in group 3 (16.9% and 3.4%). Implantation analysis revealed higher embryo viability without change in uterine receptivity with pituitary suppression (group 1 versus 2). Decrease in both embryo viability and uterine receptivity was noted in women greater than 40 (group 1 versus 3). CONCLUSIONS: (1) Pituitary suppression improved implantation outcome by increasing embryo viability with no change in uterine receptivity and was associated with a high multiple PR in women less than 40; (2) in women greater than 40 both embryo viability and, to a lesser extent, uterine receptivity were decreased; (3) transfer of a larger number of embryos in older patients may improve IVF outcome without excessive risk of multiple pregnancy.
Adult↗
Improved pregnancy outcome with the addition of leuprolide acetate to gonadotropins for in vitro fertilization.
In vitro fertilization treatment outcomes were compared prospectively in unselected patients with and without the addition of leuprolide acetate to gonadotropins for ovarian hyperstimulation. While the leuprolide patients required greater quantities of exogenous gonadotropins to achieve ovarian stimulation, significant improvements in the fertilization, implantation, and spontaneous abortion rates were observed compared with patients not receiving leuprolide. The ongoing pregnancy ("take home baby") rates per aspiration with and without leuprolide were 29% and 12%, respectively. Furthermore, the multiple pregnancy rate was markedly increased in the leuprolide group (44% versus 8%), suggesting that the improved pregnancy outcome with pituitary suppression was due primarily to higher oocyte and embryo quality.
Adult↗
Isofluorane inhibits early mouse embryo development in vitro.
In vitro development of 2-cell mouse embryos to the blastocyst stage was used to assess the toxicity of isofluorane, nitrous oxide, fentanyl, and meperidine. Isofluorane at concentrations similar to those employed during human oocyte recovery for IVF significantly inhibited mouse embryo development. Since the other agents were without effect, balanced anesthesia with nitrous oxide and narcotics may be preferable to isofluorane for IVF and GIFT.
Animals↗
Biologic effects of transdermal estradiol.
We conducted a dose-response study in 23 postmenopausal women to compare the physiologic effects of transdermal estradiol and oral conjugated equine estrogens. The doses studied were 25, 50, 100, and 200 micrograms of transdermal estradiol per 24 hours, and 0.625 and 1.25 mg of oral conjugated estrogens. Transdermal estradiol increased circulating concentrations of estradiol and estrone. Oral conjugated estrogens also raised the levels of estrogen, particularly estrone. Both preparations lowered gonadotropin levels, decreased the percentages of vaginal parabasal cells, increased the percentage of superficial cells, and lowered urinary calcium excretion. The effects of 0.625 and 1.25 mg of oral estrogens were similar to those of 50 and 100 micrograms of transdermal estradiol per 24 hours, respectively. Oral estrogens significantly increased circulating levels of renin substrate, sex-hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin; transdermal estradiol had no effect. The higher dose of oral estrogens had favorable effects on concentrations of low-density and high-density lipoproteins, but transdermal estradiol did not. Neither preparation affected any of the four clotting factors studied. These data indicate that transdermal estradiol can elicit many of the desirable actions of estrogen while avoiding the pharmacologic effects of oral estrogens on hepatic proteins.
Administration, Oral↗
Autonomous cortisol secretion by a lipoid cell tumor of the ovary.
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Adult↗
Optimization of hydrogen-ion concentration during aspiration of oocytes and culture and transfer of embryos.
Rapid and marked shifts in pH can have deleterious effects on oocytes and embryos. Such shifts are most likely to occur during laparoscopy and examination of gametes and embryos. We studied the rate of pH change of follicular fluid and bicarbonate- and phosphate-based media during exposure to 100% CO2 with a constant surface area to volume ratio. All solutions tested developed a pH below the physiological range of 7.30-7.50 within 2 min of exposure to 100% CO2. We also examined the rate of increase in pH due to CO2 loss from media in room air within standard organ culture dishes and tubes. After exposure to ambient conditions for 2 min, the pH of modified Ham's F-10 medium in organ culture dishes rose above the physiological range. We have used a needle laparoscope to confirm intraperitoneal placement prior to the insufflation of a 5% CO2 gas mixture for laparoscopic oocyte retrieval. We have carried out all examinations of oocytes and embryos within a pediatric isolette equipped with an automatic CO2 controller to maintain a 5% CO2 environment. We have transferred embryos in 15% fetal cord serum to avoid the alkaline pH associated with a high concentration of equilibrated heat-inactivated preovulatory serum. These simple techniques can optimize the hydrogen-ion concentration of media during the entire process of in vitro fertilization and embryo transfer.
Carbon Dioxide↗
Treatment of hot flashes with transdermal estradiol administration.
A randomized prospective double blind study was performed to assess the ability of a transdermal therapeutic system (TTS) delivering estradiol (E2) to suppress hot flashes (HFs) in symptomatic postmenopausal women. Patients were given placebo or E2 in four doses for a 20-day period, and serum gonadotropin and estrogen levels and the occurrences of HFs were measured. Administration of placebo had no measurable effect on either estrogen or gonadotropin levels or the occurrence of HFs. A dose-response relationship was found between the rate of E2 administered and the circulating level of E2, with 25, 50, 100, and 200 micrograms/24 h dosages raising the mean E2 concentrations from mean baseline levels of 5-8 pg/ml to 18, 38, 73, and 100 pg/ml, respectively. Estrone levels also increased with TTS application, but to a lesser extent than did E2 levels. Dose-response reductions of FSH and LH with increasing amounts of E2 administration occurred, but gonadotropin levels were not lowered in any of the patients into the ranges found in premenopausal women. TTS application significantly suppressed the occurrence of HFs at the 50 micrograms/24 h dosage and higher. A significant negative correlation (r = 0.6045; P less than 0.001) between E2 levels and the rates of occurrence of HFs was found during hormone administration. Based on this regression, 50% and 100% reductions of HFs should occur at 61 and 122 pg/ml E2. These data indicate that the transdermal delivery of E2 with these systems significantly reduced the occurrence of HFs and allowed definition of the therapeutic range of hormone replacement in terms of lost ovarian function, as reflected by circulating E2 levels.
Administration, Topical↗
Transvaginal ultrasound scanning of ovarian follicles.
The transvaginal approach to ultrasound scanning is a practical method complementary to the transabdominal technique for the minority of cases where, regardless of technological refinements, anatomic constraints require an alternative port of access to the pelvic cavity.
Female↗
The incidence of late-onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency among hirsute women.
Late-onset congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a cause of hirsutism in adult women. Its reported frequency of occurrence in hirsute women has varied from 0-30%, but the number of patients studied was small. To establish the incidence of CAH, 83 unselected hirsute women were studied prospectively with a standard ACTH stimulation test. On the basis of an exaggerated response of serum 17 alpha-hydroxyprogesterone to ACTH, 1 patient with CAH was found, for an incidence of 1.2%. The 95% confidence limits for the incidence of CAH among hirsute women were 0% and 3.4%. Five of seven hirsute women without CAH whose serum 17 alpha-hydroxyprogesterone levels rose above 3 ng/ml in response to ACTH had simultaneous serum progesterone values consistent with recent ovulation. Since routine screening of all hirsute women by means of ACTH stimulation does not appear to be cost effective, reported cases of CAH were reviewed in order to discern potentially helpful clinical clues. Severe hirsutism, virilization, early onset of symptoms, short stature, familial occurrence, and regular menses were identified as the clinical characteristics associated with late-onset CAH.
17-alpha-Hydroxyprogesterone↗
Origin of serum progestins in polycystic ovarian disease.
The glandular origin of excess circulating steroid hormones in women with polycystic ovarian disease has been difficult to establish with previously described perturbation techniques. Recently it was demonstrated that daily administration of a potent gonadotropin-releasing hormone agonist achieves complete and reversible suppression of ovarian steroid secretion. To examine the source of C-21 steroid hormones, circulating levels were measured before and after administration of the same agonist in polycystic ovarian disease subjects and normal control subjects. Serum levels of these hormones were also determined after administration of dexamethasone and adrenocorticotropic hormone (ACTH) as well as bilateral oophorectomy. Subjects with polycystic ovarian disease exhibited significant elevations of serum pregnenolone, 17OH -pregnenolone, and 17OH -progesterone by comparison with normal control subjects. The glandular origins of the excess levels of pregnenolone and 17OH -pregnenolone were more difficult to determine and appear to be different from that of 17OH -progesterone.
17-alpha-Hydroxypregnenolone↗