The effect of chemiluminescent light exposure on the in vitro development of mouse embryos.
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Animals↗
Biomedical subjects
M V Sauer
Publications and source records attributed to M V Sauer.
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↗
Diagnosing human papillomavirus of the female lower genital tract: failure of the Pap smear as a sole screening test.
Of 197 patients referred for colposcopy who underwent repeat Pap smears and colposcopic biopsies (when indicated), histologic evidence of human papillomavirus (HPV) infection involving the endocervix, cervix, or vagina or all three sites was documented in 109 biopsies. Sixty-six (61%) had normal Pap smears at the time of colposcopy. Despite a specificity of 92% for detecting HPV, the Pap smear demonstrated a low sensitivity (39%), with a positive and negative predictive test value of 88% and 50%, respectively. In patients with biopsies revealing HPV infection without associated dysplasia, false negative Pap smears were found most often in women with strictly vaginal HPV (74%) (P less than 0.05), followed by those with coexistent cervical and vaginal HPV (65%), and then by those with solely cervical HPV (51%). We question the use of the Pap smear for the detection of lower genital tract HPV, particularly in patients with only vaginal involvement, especially when the smear is repeated at the time of colposcopy. Benefits and disadvantages of other screening tests for HPV are discussed.
Biopsy↗
Consecutive pregnancies in a menopausal woman following oocyte donation.
A second pregnancy was successfully achieved by a menopausal women who had previously conceived and delivered an infant using donated oocytes. The same nonanonymous oocyte donor provided the gametes for both procedures. Prior to embryo transfer, the functionally agonadal recipient received exogenous steroid hormone replacement therapy. Both pregnancies followed the transfer of 5 embryos which were conceived by the in vitro fertilization of the donated oocytes with the recipient husband's sperm. The first pregnancy ended with an intrauterine fetal demise at 40 weeks gestation. The second pregnancy is proceeding unremarkably.
Adult↗
Routine use of vaginal ultrasonography in the preoperative evaluation of gynecologic patients. An adjunct to resident education.
To determine the clinical utility of routine vaginal ultrasound in evaluating gynecologic patients, we prospectively studied 133 women scheduled to undergo elective surgery based upon abnormal clinical findings as determined by residents and faculty in a large, county-based teaching hospital. Patients were examined bimanually by the surgeons and then examined ultrasonographically using a 5.0-MHz vaginal probe. Surgery was scheduled within 48 hours of the clinical examinations. Vaginosonography demonstrated enhanced sensitivity, specificity and predictive value as compared to bimanual pelvic examination. The technique was quickly mastered by resident physicians, with discrepancies between preoperative ultrasound observations and actual surgical findings present in but 15 of 532 instances. Vaginal ultrasonography is an effective routine adjunct to physical examination in the preoperative evaluation of surgical patients. Furthermore, it has diagnostic capabilities superior to those of the bimanual pelvic examination and increases the accuracy of preoperative diagnoses in gynecologic patients.
Adolescent↗
Counseling the infertile couple: when enough is enough.
Therapy of infertility rarely offers a clear end point for cessation after repeated failure. Yet fertility treatment, especially if repeatedly unsuccessful, is associated with economic as well as emotional cost. Stopping treatment becomes an increasingly important option for couples whose therapy does not produce the desired result. It is the clinician's obligation to make infertile couples aware of this option early in the treatment plan and to give specific suggestions that allow these couples to stop treatment at a medically arbitrary, yet temporally well-defined point. To this end, we suggest the following for infertile couples undergoing treatment: 1) an ongoing relationship with a qualified counselor; 2) the best estimates for pregnancy rates, including the background (treatment-independent) rate, for all forms of treatment available at any point in time; 3) the option of stopping treatment from the start; 4) encouragement to seek second opinions throughout treatment; 5) time off from treatment; and 6) the opportunity to set arbitrary but relatively firm time limits. Incorporation of these suggestions into the therapeutic plan for infertile couples underscores the imperfect nature of infertility treatment and acknowledges that sometimes the most we can do for our patients is to help them stop.
Clinical Protocols↗
A preliminary report on oocyte donation extending reproductive potential to women over 40.
BACKGROUND: Fertility in women 40 years of age or older is decreased, and in those with ovarian failure it is thought to be irrevocably lost. The donation of oocytes to young (less than 35 years old) women with ovarian failure has allowed many considered infertile a chance to become pregnant. In these women gonadal hormone replacement results in an endometrium receptive to implantation. It is not known whether the endometrial response to such replacement is decreased in women over the age of 40. METHODS: To test the efficacy of oocyte donation to older women, we enrolled seven women 40 to 44 years old with ovarian failure in a trial of hormone replacement and embryo transfer, using oocytes obtained from women undergoing ovarian hyperstimulation solely for gamete donation. RESULTS: Seven stimulated cycles in the donors that were synchronized with nine cycles in the recipients resulted in eight embryo transfers. Five viable pregnancies were established, one with twins. A sixth pregnancy ended in miscarriage. Five normal infants were delivered by cesarean section, and one stillborn infant was delivered vaginally. The outcomes were compared with those in women under the age of 40 with ovarian failure who were also participating in our donor-oocyte program and in infertile ovulating women 40 or older who were undergoing standard in vitro fertilization. No significant differences in rates of implantation or ongoing pregnancy were noted in older women as compared with younger women receiving donated embryos. These rates, however, were higher than the rates in the infertile ovulating women of similar age who were undergoing standard in vitro fertilization. CONCLUSIONS: These preliminary results suggest that the endometrium retains its ability to respond to gonadal steroids and provides a receptive environment for embryo implantation and gestation even in older women.
Adult↗
Successful pre-embryo donation in ovarian failure after treatment for breast carcinoma.
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Adult↗
Reevaluation of the role of culdocentesis in the management of ectopic pregnancy.
Culdocentesis has been used routinely in the evaluation of ectopic pregnancy. To determine whether culdocentesis continues to play an important role, we reviewed the operative findings of 297 women undergoing an operative procedure because of ectopic pregnancy. Culdocentesis was performed before surgery in 252 cases. Of those, 210 (83%) had positive test results and 42 (17%) had negative results. Positive results accurately predicted a ruptured ectopic pregnancy in 50% of cases, whereas negative test results were predictive of an unruptured ectopic pregnancy in 58% of cases. Six patients without an ectopic pregnancy underwent unnecessary laparotomy because of positive culdocentesis test results, whereas 27 patients who were discharged from the emergency room after negative test results were obtained subsequently were found to have ectopic pregnancies. The results of this study imply that culdocentesis is of limited value in a clinical setting in which sensitive and rapid testing and pelvic ultrasonography are used.
False Negative Reactions↗
Human oocyte and preembryo donation: an evolving method for the treatment of infertility.
The utilization of oocyte and preembryo donation in the treatment of infertility has recently expanded. Since 1983, modifications in the retrieval of donated female gametes have enhanced both the safety and the efficacy of the procedure. Pregnancy rates in women receiving donated preembryos are remarkably high, with success occurring in 25% to 50% of transfer cycles. The technology used for preembryo donation continues to evolve, and the current and future role ovum donation in the treatment of infertility.
Adult↗
Factors affecting embryo implantation after human in vitro fertilization: a hypothesis.
In the clinical practice of human in vitro fertilization, pregnancy is dependent on embryo implantation. Pregnancy is a function of the number of embryos transferred, with multiple embryos resulting in a higher likelihood of pregnancy. We formulated a mathematic model of embryo implantation. This model describes embryo implantation as dependent on three factors--transfer efficiency, embryo quality, and endometrial receptivity. Application of existing embryo implantation data to this model allows the calculation of the approximate value of each of these factors. On the basis of historic data, data obtained from our in vitro fertilization program, and these theoretic considerations, it is our hypothesis that (1) there is an inherent inefficiency associated with the mechanical transfer of embryos into the uterine cavity, which limits the maximal embryo implantation rate; (2) the quality of embryos produced by controlled ovarian hyperstimulation, follicle aspiration, and in vitro fertilization is very high and approaches that of embryos produced in natural cycles in vivo; and (3) endometrial receptivity is markedly diminished in stimulated cycles and is the current rate-limiting step of pregnancy success of in vitro fertilization.
Embryo Implantation↗
Utility of an algorithm to diagnose ectopic pregnancy.
In recent years, algorithms have been proposed to evaluate ectopic gestations. To determine the usefulness of an algorithm for a large county hospital, a surveillance project was initiated. During 2 years, 4045 women were screened in the emergency room for pregnancy. Of these, 1648 (41%) were noted to be pregnant, initially detected by rapid enzyme immunoassay for urinary human chorionic gonadotropin, and later confirmed using quantitative radioimmunoassay for serum human chorionic gonadotropin. Within this group, 249 women were diagnosed with ectopic pregnancies. Hemoperitoneum was discovered by culdocentesis in 128 of 249 cases of ectopic gestations, all operated upon acutely. A discriminatory zone for ultrasound was diagnostic of ectopic pregnancy in only 33 cases, as the majority of women presented with human chorionic gonadotropin levels below 6500 mIU/ml. Uterine curettage performed when abnormal serial levels of chorionic gonadotropin were observed detected an additional 46 cases. Early diagnosis permitted treatment prior to tubal rupture in 147 instances with conservation of the fallopian tube in 125 (50%). We conclude: (1) even in a busy county emergency room, algorithms are useful for expediting the diagnosis of ectopic pregnancy; (2) when ectopics are diagnosed early, conservative tubal surgery is possible in many patients.
Algorithms↗