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Biomedical subjects

M V Sauer

Publications and source records attributed to M V Sauer.

At least 19 recordsLinked to original sources

Reversing the natural decline in human fertility. An extended clinical trial of oocyte donation to women of advanced reproductive age.

OBJECTIVE: To evaluate the effect of age on pregnancy success rates in functionally agonadal women undergoing oocyte donation. DESIGN: A prospective study of 100 consecutive patients using oocyte donation for the treatment of infertility. PATIENTS: Women aged 40 years and above requesting oocyte donation (N = 104) were required to undergo medical, reproductive, and psychological screening. Suitable candidates (n = 65) were matched with an oocyte donor whose cycle was synchronized with that of the potential recipient, prior to the donor's undertaking ovarian hyperstimulation and transvaginal ultrasound-directed follicle aspiration. Outcomes were compared with those of two groups undergoing therapy at the same time: (1) women below 40 years of age undergoing oocyte donation for premature ovarian failure (n = 35) and (2) women 40 years of age and above undergoing standard in vitro fertilization and embryo transfer using their own oocytes (n = 57). MAIN OUTCOME MEASURES: Embryo implantation and pregnancy rates. SETTING: The in vitro fertilization program of the University of Southern California and the California Medical Center, Los Angeles. RESULTS: Improved outcomes were observed with regard to fertilization rates in vitro, number of embryos transferred, embryo implantation rate, clinical pregnancy rates, and ongoing or successfully completed pregnancy rates when women undergoing oocyte donation regardless of age were compared with women 40 years of age and above using their own oocytes. No age-related decline in fertility was demonstrable when oocyte donation was used, with a mean age of 44.3 +/- 3.1 years for those successfully conceiving (range, 40 to 52 years). Perinatal outcomes (n = 27) were generally uncomplicated, with a mean gestational age at delivery of 38.4 +/- 2.1 weeks (range, 34 to 42 weeks), although multiple births occurred in 24.1% of cases. CONCLUSIONS: The age-related decline in female fertility may be reversed in couples electing to use donated oocytes from a younger woman, and women of advanced reproductive age may conceive, carry, and give birth to infants with success rates similar to those of their younger counterparts using assisted reproductive methods.

Adult

Embryotoxicity of three commercially available powderless surgical gloves.

The one-cell mouse embryo bioassay was utilized to test the embryotoxicity of three brands of powerless surgical gloves; Pristine, Ansell, and BioGel. The Pristine gloves demonstrated no significant embryotoxicity, while the other two brands demonstrated a consistent inhibition of blastocyst development of one-cell mouse embryos.

Animals

Demographic differences between younger and older recipients seeking oocyte donation.

An older population of women is now increasingly seeking infertility care. The number of these patients may in fact eclipse those of younger patients for whom the method of oocyte donation was initially designed and previously offered. As a group, these older individuals appear to be energetic and demanding, with high expectations regarding the performance and the effectiveness of their fertility care. Physicians need to exercise vigilance in order to emphasize that eggs are not being bought and sold as a commodity and that guarantees of pregnancies cannot be made. Nevertheless, whereas oocyte donation requires all parties, donor, recipient, and doctor, to work together toward a common goal, it still offers women of advanced reproductive age perhaps their best chance at conception, pregnancy, and parenthood.

Abortion, Induced

Pelvic abscess complicating transcervical embryo transfer.

A severe pelvic infection resulting in a tuboovarian abscess after transcervical embryo transfer is reported. The case is unique in that the recipient was an agonadal woman who had not undergone prior transvaginal aspiration. Although rare, pelvic infection after embryo transfer may occur in spite of normal precautions.

Abscess

A prospective controlled evaluation of TEST-yolk buffer in the preparation of sperm for human in vitro fertilization in suspected cases of male infertility.

OBJECTIVE: To evaluate sperm preincubation in tes and tris (TEST)-yolk buffer as a potential enhancing agent of fertilizing capacity of sperm during human in vitro fertilization (IVF). DESIGN: Oocytes obtained during IVF were divided into two groups: one group fertilized with TEST-yolk buffer-treated sperm and the other group with standard-prepared sperm. SETTING: The University of Southern California IVF Program. PATIENTS: Thirty-nine couples with suspected male factor infertility undergoing IVF. INTERVENTIONS: Preinsemination incubation of sperm in TEST-yolk buffer for 24 hours. MAIN OUTCOME MEASURES: Fertilization rates in vitro. RESULTS: TEST-yolk buffer-treated sperm fertilized 140 of 241 oocytes (58%), whereas control sperm fertilized 108 of 251 oocytes (43%). Of four couples who had previously failed to fertilize during IVF, one fertilized with both specimens and three fertilized with TEST-yolk buffer-treated sperm only. CONCLUSIONS: TEST-yolk buffer pretreatment of sperm for 24 hours results in higher fertilization rates during IVF among suspected male factor patients.

Egg Yolk

The synergistic effects of clomiphene citrate and human menopausal gonadotrophin in the folliculogenesis of stimulated cycles as assessed by the gonadotrophin-releasing hormone antagonist Nal-Glu.

Clomiphene citrate (CC), alone or in combination with exogenous gonadotrophins, has been widely used in ovulation induction. CC promotes endogenous release of gonadotrophins, yet when used in combination with exogenous gonadotrophins, its contribution to folliculogenesis is difficult to assess. In order to determine the contribution of CC-induced endogenous gonadotrophin production to the overall ovarian stimulation in cycles treated with CC/human menopausal gonadotrophin (HMG), Nal-Glu, a gonadotrophin-releasing hormone (GnRH) antagonist was administered. Fertile women (n = 10) undergoing ovarian stimulation and oocyte aspiration for the sole purpose of gamete donation were studied. Five women received CC (100 mg daily for 5 days) in conjunction with pure follicle stimulating hormone (FSH) 150 IU daily. Five women received HMG alone. Nal-Glu (50 micrograms/kg/day) was administered intramuscularly to both groups when the leading follicles reached a mean diameter of 16 mm. Human chorionic gonadotrophin (HCG) 10,000 IU was given when the largest follicles reached a mean diameter of 20-22 mm. A significant fall in serum oestradiol levels was observed in women given CC/FSH (37.9 +/- 7.3%) within the first 24 h of Nal-Glu administration. Serum luteinizing hormone (LH) decreased greater than 20% within 24 h of Nal-Glu administration and remained low throughout the rest of the treatment. No decrease in oestradiol levels was noted in cycles receiving HMG alone. With supplemental FSH, falling oestradiol levels in CC/FSH cycles rebounded and continued to rise until the day after HCG administration. Despite a drop in oestradiol in CC/FSH cycles, the aspirated oocytes exhibited no untoward effects. The fertilization and cleavage rates were similar, and pregnancies occurred in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Clomiphene

Oocyte donors: a demographic analysis of women at the University of Southern California.

A summary is presented of 3 years' experience with donors in an oocyte donation programme. During this interval, 50 women participated as gamete donors. All proffered their services without solicitation from the programme. Most were college-educated, working mothers. The majority stated that the primary motivation for participation was concern for others' infertility. Oocytes donors generally found the required use of parenteral medication taxing but tolerable. In most cases, injections were administered to the donor by her husband or by the female recipient. The majority of donations were performed without anonymity (66%). Cycles were performed at approximately 3-month intervals. This approach as well tolerated by donors and allowed predictable scheduling of cases. All women felt their participation was of great significance and each was willing to donate oocytes again if asked.

Adult

In vitro fertilization in unstimulated cycles: the University of Southern California experience.

OBJECTIVE: To describe the clinical experience of our center with in vitro fertilization (IVF) in unstimulated cycles and to provide a comparison to stimulated cycles. DESIGN: Spontaneous ovulatory cycles were triggered with human chorionic gonadotropin in the midcycle, and 78 aspirations for IVF were performed, with the remainder of the IVF cycle proceeding in a standard manner. SETTING: The IVF program of the University of Southern California and the California Medical Center, Los Angeles, California. PATIENTS: Spontaneously ovulatory women (n = 46) with predominantly pelvic factor as their principal cause of infertility, under the age of 40, and no male factor. INTERVENTIONS: Human chorionic gonadotropin administration in midcycle, follicle aspiration, IVF, and embryo transfer. MAIN OUTCOME MEASURES: Embryo implantation and pregnancy. RESULTS: Seventy-eight follicle aspirations resulted in 11 clinical (14%) and 9 ongoing (12%) pregnancies. The per embryo implantation rate was 13% clinical and 11% ongoing. There was no decrease in per cycle pregnancy rates (PRs) for up to three unstimulated cycles. CONCLUSIONS: Unstimulated IVF is a viable alternative to stimulated cycles with PRs approximately one half those of stimulated cycles. It is reasonable to offer patients up to three cycles of unstimulated IVF without expecting a decrease in PRs.

Chorionic Gonadotropin

The effect of leuprolide acetate on steroidogenesis by granulosa and theca cells in vitro.

Enhancement of follicular response to controlled ovarian hyperstimulation for human in vitro fertilization (IVF) has been suggested following pretreatment with leuprolide acetate (LA). However, additional human menopausal gonadotropin (hMG) is required to achieve follicle maturity in the presence of LA. We studied the effect of LA on steroidogenesis of granulosa and theca cells in vitro. Human granulosa cells obtained from IVF follicular fluid aspirations were cultured for 14 days in the presence and absence of human chorionic gonadotropin (hCG). hCG significantly enhanced progesterone (P) and estradiol (E2) production by the cells, however, the addition of LA in concentrations of 10, 100, and 1000 ng/ml had no effect. Porcine granulosa cells were cultured for 48 hr in the presence and absence of follicle stimulating hormone (FSH) with the addition of LA at the same doses. LA did not affect the FSH-induced increase in P production. Porcine theca cells were cultured for 48 hr in the presence and absence of hCG. The addition of LA did not affect androstenedione (A) production by these cells. We conclude that in this dynamic model in vitro, LA does not inhibit or stimulate P or E2 production by granulosa or A production by theca cells.

Androstenedione

Comparison of intermittent and continuous use of a gonadotropin-releasing hormone antagonist (Nal-Glu) in in vitro fertilization cycles: a preliminary report.

The agonistic effect of the gonadotropin-releasing hormone agonist often necessitates an extended period of treatment, resulting in a longer treatment cycle and increased cost. We have evaluated the intermittent use of a gonadotropin-releasing hormone antagonist, Nal-Glu, and have designed a new, simplified protocol for its use in in vitro fertilization. Seven women who had previously undergone treatment with leuprolide acetate and human menopausal gonadotropins were treated with Nal-Glu. Leuprolide acetate, 1 mg/day subcutaneously, was administered in the midluteal phase until down regulation was achieved (estradiol less than 30 pg/ml). Human menopausal gonadotropins, three to four ampules per day intramuscularly, was administered in conjunction with 500 micrograms subcutaneous leuprolide acetate. In the treatment cycles Nal-Glu (50 micrograms/kg/day) was administered intramuscularly on cycle day 1 or 2 for 3 days to achieve down regulation. Human menopausal gonadotropins, three to four ampules intramuscularly, was then administered daily without the antagonist. Nal-Glu was resumed when the follicles reached 14 to 16 mm and was continued until the day of human chorionic gonadotropin administration. Compared with leuprolide acetate-human menopausal gonadotropins cycles, the days required for down-regulation with Nal-Glu were significantly shortened (20.6 +/- 4.1 vs 1.6 +/- 0.3 days, p less than 0.001), as was total cycle length (31.3 +/- 5.8 vs 11.0 +/- 1.0 days, p less than 0.01). The mean number of days of treatment with human menopausal gonadotropins, the mean number of ampules of human menopausal gonadotropins, peak estradiol levels, the number of oocytes, and the percent of oocytes fertilized were not statistically different. No luteinizing hormone surges were detected with Nal-Glu in serum or urine. Nal-Glu was well tolerated, and five pregnancies have resulted. We conclude that intermittent administration of Nal-Glu is highly effective in achieving down-regulation and blocking spontaneous luteinizing hormone surges. Compared with leuprolide acetate-human menopausal gonadotropins cycles, an equally high oocyte and embryo yield may be anticipated. This new protocol substantially decreases cycle length and increases patient convenience.

Adult

The gonadotropin-releasing hormone antagonist (Nal-Glu) acutely blocks the luteinizing hormone surge but allows for resumption of folliculogenesis in normal women.

The gonadotropin-releasing hormone antagonist offers several advantages over the use of the agonist and allows several physiologic questions to be addressed. In this study, we evaluated the ability of Nal-Glu to acutely inhibit the luteinizing hormone surge and prevent ovulation. We also assessed whether recovery of the follicle would be possible after several days of gonadotropin deprivation and estradiol decrement. Eight normal ovulatory women were randomized to control or Nal-Glu-treated cycles (50 micrograms/kg intramuscularly) for 3 to 4 days. Monitoring was carried out with daily vaginal ultrasonographic scans and serum estradiol levels and twice-daily serum luteinizing and follicle-stimulating hormone levels. Nal-Glu acutely inhibited the luteinizing hormone surge and ovulation, even when administered as late as the onset of the luteinizing hormone surge. Evidence was provided that spontaneous follicular rescue recurred in eight of 10 cycles after 3 to 4 days of Nal-Glu administration. Although an estradiol to follicular size dissociation occurred with Nal-Glu, subsequent ovulation occurred in 5.1 +/- 0.6 days after the last Nal-Glu dose. The decrement in estradiol after Nal-Glu administration correlated negatively with the days required for subsequent ovulation to occur (r = 0.77, p less than 0.05). The subsequent luteal phase also was normal in terms of length and progesterone levels. These data confirm the potency and efficacy of Nal-Glu in acutely inhibiting gonadotropins and extends our knowledge on the physiologic characteristics of the dominant follicle.

Adult

Endometrial responses to various hormone replacement regimens in ovarian failure patients preparing for embryo donation.

Various regimens are recommended for replacing sex steroids in ovarian failure patients attempting donor embryo transfer. We histologically assessed endometrial biopsies obtained on simulated cycle day 26 from functionally agonadal patients (n = 19) receiving hormone replacement according to three different regimens: Regimen 1, oral micronized estradiol (E2) 2 mg days 1-5, 4 mg days 6-9, 6 mg days 10-13, 4 mg days 14-28, with progesterone vaginal suppositories, 100 mg day 15 followed by 200 mg days 16-28; Regimen 2, oral micronized E2 1 mg days 1-5, 2 mg days 6-9, 6 mg days 10-13, 2 mg days 14-28, with progesterone vaginal suppositories, 100 mg day 15 followed by 200 mg days 16-28; Regimen 3: oral micronized E2 1 mg days 1-5, 2 mg days 6-9, 6 mg days 10-13, 2 mg days 14-28, progesterone 50 mg intramuscularly delivered day 15 followed by 100 mg intramuscularly days 16-28. Biopsies were interpreted according to Noyes criteria. While all regimens resulted in variable degrees of stromal pseudodecidualization, Regimen 1 biopsies uniformly demonstrated glandular abnormalities consistent with excessive estrogen stimulation. This included aberrant maturation, intraluminal papillary excrescences and variations in epithelium size and stratification. Regimen 2 biopsies were morphologically normal in most patients, yet many manifested minor variations in gland maturity. Only Regimen 3 biopsies were consistently normal on day 26 or slightly advanced in maturation. We conclude that endometrial morphology differs according to the hormone replacement preparation and route of administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravaginal

Oocyte and pre-embryo donation to women with ovarian failure: an extended clinical trial.

The outcome of a series of pre-embryo transfers to 31 women with ovarian failure is described. Twenty six fertile women functioned as nonanonymous donors, providing oocytes for in vitro fertilization after undergoing controlled ovarian hyperstimulation and transvaginal ultrasound directed oocyte aspiration. Recipients, 24 to 44 years of age, received hormone replacement therapy before pre-embryo transfer (ET). A mean of 13.7 +/- 1.1 oocytes were obtained per aspiration resulting in the transfer of 4.5 +/- 0.2 pre-embryos to each recipient couple. Twenty-five of 47 ET resulted in pregnancy (53.2% per ET); 5 preclinical, and 20 clinical, of which 18 are ongoing or delivered. The overall implantation rate per individual transferred fresh pre-embryo was 21.1%. We conclude that oocyte donation is a safe and highly efficient means of achieving pregnancy for women with ovarian failure.

Adult

Preovulatory follicular fluid steroid levels in stimulated and unstimulated cycles triggered with human chorionic gonadotropin.

The purpose of this study was to analyze follicular fluid (FF) samples for steroid levels from stimulated and unstimulated cycles triggered with human chorionic gonadotropin (hCG) and to assess the influence of controlled ovarian hyperstimulation and luteinizing hormone/hCG on these levels. Spontaneous ovulatory cycles were monitored with serial ultrasound examinations, and hCG 10,000 IU was given when the lead follicle was mature. Fourteen FF samples yielding fertilizable oocytes were compared with 13 FF samples from controlled ovarian hyperstimulation cycles. Progesterone (P) was higher in controlled ovarian hyperstimulation than in unstimulated cycles (9.0 +/- 1.2 micrograms/mL versus 4.4 +/- 0.6 microgram/mL; mean +/- SEM), whereas estradiol (E2) was lower (0.8 +/- 0.1 microgram/mL versus 1.3 +/- 0.2 microgram/mL), resulting in a higher P:E2 ratio (15.5 +/- 3.3 versus 4.4 +/- 0.7). Androstenedione (A), testosterone (T), and T:E2 ratios were all higher in unstimulated than controlled ovarian hyperstimulation cycles. We conclude that controlled ovarian hyperstimulation is associated with increased FF P, decreased FF E2, T, and A levels, and decreased T:E2 ratios, suggesting altered steroidogenesis and enhanced follicular aromatase activity.

Androstenedione

Pregnancy after oocyte donation to a woman with ovarian failure and classical galactosemia.

In summary, oocyte and pre-embryo donation may be used to establish pregnancy in women with galactosemia and ovarian failure. Reported is the first pregnancy after pre-embryo donation to a woman with classical galactose-1-phosphate uridyl transferase deficiency. Despite disturbances in galactose metabolism, the endometrial lining responded normally to exogenous hormone replacement and was receptive to pre-embryo implantation. Pregnancy support was provided by exogenously administered oral E2 and IM P for the initial 100 days, at which time placental hormone production solely maintained the gestation.

Adult

Utility and predictive value of a rapid measurement of urinary pregnanediol glucuronide by enzyme immunoassay in an infertility practice.

STUDY OBJECTIVE: To assess the clinical utility of measuring urinary pregnanediol glucuronide in random samples in an infertility practice. DESIGN: Samples of urine were collected from patients approximately 3 weeks from their last menstrual period to ascertain if ovulation had occurred. Each sample was tested for specific gravity before analyzing for pregnanediol glucuronide. Simultaneous venipuncture was performed to compare results from the urinary assay to quantitative measures of serum progesterone (P). SETTING: All patients were randomly sampled. PATIENTS: Three hundred ninety women undergoing pituitary down regulation with leuprolide acetate were chosen for study because they routinely initiate medication after documentation of ovulation. OUTCOME MEASURES: The performance of the urinary pregnanediol glucuronide was evaluated as to its sensitivity, specificity, predictive value, and test efficiency compared with a serum measurement of 2.5 ng/mL and 10.0 ng/mL. RESULTS: The performance characteristics of the pregnanediol glucuronide assay were directly related to the hydration status of the patient at the time of sample collection. Regardless of urine specific gravity, if pregnanediol glucuronide was qualitatively detected (greater than 3 micrograms/mL), serum P was greater than 2.5 ng/mL. However, in cases in which pregnanediol glucuronide was undetected (less than 3 micrograms/mL), results were only accurate when the specific gravity was greater than or equal to 1.020. When comparing urinary pregnanediol glucuronide values to serum greater than 10 ng/mL, both specificity and predictive value of a positive test decreased because of increased numbers of false-positive results. CONCLUSIONS: The enzyme immunoassay measurement for pregnanediol glucuronide may replace the use of serum P in documenting the ovulatory status of many patients. However, all specimens must be checked for specific gravity and if less than 1.020, a serum P should be used to ensure accuracy.

Female