Poor responders to ovarian hyperstimulation may benefit from an attempt at natural-cycle oocyte retrieval.
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Adult↗
Biomedical subjects
S R Lindheim
Publications and source records attributed to S R Lindheim.
Stress and infertility: "the chicken or the egg?".
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Female↗
The utility of a midcycle follicle-stimulating hormone boost in addition to human chorionic gonadotropin for timing of follicle aspiration in unstimulated in vitro fertilization cycles.
PURPOSE: To analyze the effects and potential benefits of a single midcycle dose of follicle-stimulating hormone (FSH) prior to human chorionic gonadotropin (hCG) administration during unstimulated in vitro fertilization (IVF) cycles. METHODS: Twenty-five cycles from 20 patients receiving 150 IU of FSH 42-44 h and 10,000 IU of hCG 34-36 h prior to follicle aspiration were compared to 110 cycles triggered with hCG alone. RESULTS: Serum E2 levels were significantly lower on the day of hCG treatment in the FSH-treated group (266 vs. 297 pg/ml). On the day after hCG administration, serum E2 was similar in both groups. Maximum follicular diameters the day of and the day after hCG treatment were similar as were the number of oocytes aspirated and embryos transferred, and clinical pregnancy rates in both groups. The number of cycles dropped due to premature luteinizing-hormone (LH) surge was 8% in the FSH group compared to 20% in the group treated with hCG alone. CONCLUSIONS: A midcycle FSH boost does not increase pregnancy success of unstimulated IVF cycles but does enhance the increase in serum E2 levels after hCG, thereby potentially allowing earlier hCG administration while incurring decreased cycle cancellation rates due to premature LH surges.
Adult↗
Short-term gonadotropin suppression with oral contraceptives benefits poor responders prior to controlled ovarian hyperstimulation.
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Adult↗
Abnormal sperm morphology is highly predictive of pregnancy outcome during controlled ovarian hyperstimulation and intrauterine insemination.
PURPOSE: The purpose of this study was to assess the predictive value of a modified form of Kruger's strict criteria for sperm morphology for pregnancy outcomes after intrauterine insemination (IUI) and controlled ovarian hyperstimulation (COH) in the presence of normal sperm concentration and motility. MATERIALS AND METHODS: A retrospective review of 42 couples undergoing COH/IUI was stratified by favorable or unfavorable sperm morphology. End points were pregnancy or failure of treatment as defined by four or more cycles of COH/ IUI without pregnancy. RESULTS: An unfavorable morphology (< 4%) was highly predictive of failure during COH-IUI (94.45%; 17/18). A normal PIF was a sensitive indicator of those patients who became pregnant (93.8%; 15/16) and had a fair specificity for failure to achieve pregnancy after four cycles of treatment (65.4%; 17/26). Couples with a favorable sperm morphology were 28.3 times as likely to achieve a pregnancy within four cycles of treatment as those with unfavorable sperm morphology [95% confidence limits, 3.2 to 250.5; P < 0.001]. CONCLUSIONS: Abnormal strict morphologic assessment is both sensitive and specific for pregnancy outcomes in couples undergoing COH/IUI. Couples with persistently unfavorable sperm morphology should be counseled appropriately and would be better served by more aggressive treatment with in vitro fertilization and embryo transfer.
Adult↗
The significance of elevated early follicular-phase follicle stimulating hormone (FSH) levels: observations in unstimulated in vitro fertilization cycles.
OBJECTIVE: Our objective was to determine the effect of elevated early follicular-phase serum follicle stimulating hormone (FSH) levels on follicle growth and oocyte maturity in unstimulated in vitro fertilization (IVF) cycles. STUDY DESIGN: We compared cycles with elevated day 3 FSH levels (> 20 mIU/ml) to subsequent cycles in the same patients when day 3 FSH returned to normal and to cycles among women with normal day 3 FSH levels. PATIENTS: Seven cycles in seven patients had an elevated day 3 FSH (high-FSH group). These were compared to 11 subsequent cycles in which there was a return to a normal baseline FSH and to 13 cycles in 13 patients that entered the unstimulated protocol with a normal baseline day 3 FSH. RESULTS: The day of human chorionic gonadotropin (hCG) administration was similar in all groups as were the serum estradiol (E2) levels. Although the high-FSH group tended to have smaller maximum follicular diameters, the difference was not statistically significant. The highest FSH level on cycle day 3 in a completed cycle was 56.2 mIU/ml. The total number of oocytes aspirated and the number of embryos obtained was similar in all groups. Whereas there were no pregnancies in the high-FSH group, 2 of the subsequent 11 normal day 3 FSH cycles resulted in clinical pregnancies. Two of the 13 patients in the normal day 3 FSH values also achieved pregnancies. CONCLUSIONS: We conclude that cycle day 3 serum FSH levels as high as 56.2 mIU/ml may be associated with apparently normal follicular growth, oocyte fertilization, and embryo cleavage in unstimulated cycles. However, pregnancies are not observed. In addition, FSH levels vary widely from cycle to cycle and elevated levels in one cycle do not necessarily imply that pregnancy may not occur in a subsequent cycle when FSH levels return to normal.
Blastocyst↗
Efficacy of oocytes donated by older women in an oocyte donation programme.
Population and insemination studies indicate that women experience declining fertility with ageing. The question therefore arises whether older women are suitable oocyte donors. This study addresses this issue by examining the relationship between oocyte donor age and clinical outcome in a large oocyte donation programme. We retrospectively reviewed data from 458 consecutive oocyte donation cycles completed by 164 different designated oocyte donors. Data were divided into two groups: group A, cycles with donors aged 21-30 years at the time of follicular aspiration (193 cycles, 88 donors); and group B, cycles with donors aged 31-40 years at the time of follicular aspiration (265 cycles, 86 donors). Five donors, because of ageing during repetitive donations, contributed data to groups A and B. In a given cycle, all oocytes for a recipient came from only one designated donor. Comparing the two donor groups, there was no difference in the amount of gonadotrophin used to achieve optimal stimulation; however, more oocytes were obtained from group A than group B donors (16.8 +/- 6.9 and 15.1 +/- 8.1 respectively, P < 0.05). Similar percentages of oocytes were fertilized in each group, resulting in the transfer of comparable numbers of embryos (4.5 +/- 1.1 and 4.4 +/- 1.3 respectively). Comparable clinical pregnancy rates were achieved (group A, 36%; group B, 37%). The spontaneous abortion rates were also similar (group A, 20%; group B, 12%), resulting in comparable ongoing and delivered pregnancy rates per cycle (group A, 29%; group B, 32%) and per embryo transferred (group A, 6.4%; group B, 7.3%). In conclusion, women of proven fertility should not be excluded from donating oocytes simply because of their age. There exists a cohort of fertile women who resist the decreasing fecundity and increasing spontaneous abortion rates associated with ageing. With careful screening, many women of proven fertility can donate oocytes until the age of 40 years with an efficacy equal to that of younger women. Given the relative shortage of suitable oocyte donors, and increasing requests from recipients with previous donor oocyte babies to obtain oocytes from the same, now older, donor, the findings of this study are of practical clinical importance.
Adult↗
Basal serum follicle stimulating hormone (FSH) and estradiol levels as predictors of pregnancy in unstimulated donor insemination cycles.
PURPOSE: The purpose of this study was to evaluate the utility of basal serum follicle stimulating hormone and estradiol levels in predicting pregnancy in women undergoing artificial insemination with donor sperm for severe male factor infertility. METHOD: A retrospective chart review of 48 women who had at least 2 cycles of artificial insemination with donor sperm and who had undergone testing for basal serum follicle stimulating hormone and estradiol levels prior to or during therapy. RESULTS: There was no difference in age or mean basal serum follicle stimulating hormone between women who conceived (clinical pregnancy) and those who did not. Women who conceived had significantly lower mean serum basal estradiol levels (P = 0.02) and significantly fewer numbers of treatment cycles (P = 0.041). The highest pregnancy rate was among those women with normal basal serum follicle stimulating hormone and estradiol levels. Receiver operating characteristic curve analysis revealed basal serum estradiol to be a more reliable predictor of pregnancy than follicle stimulating hormone. CONCLUSIONS: Basal serum follicle stimulating hormone and estradiol levels may be useful in predicting success with artificial insemination with donor sperm. It may be useful to obtain basal serum follicle stimulating hormone and estradiol prior to initiating artificial insemination with donor sperm.
Adult↗
Low-dose growth hormone-releasing factor may enhance folliculogenesis in regularly menstruating women: a preliminary study.
OBJECTIVE: To evaluate the effect of low-dose GH-releasing factor (GRF) on folliculogenesis in regularly menstruating women. DESIGN: Prospective clinical trial where individual patients served as their own control. SETTING: Outpatient Reproductive Endocrine/Infertility Clinic of the Los Angeles County-University of Southern California Medical Center, Los Angeles, California. PATIENTS: Seven regularly menstruating women. INTERVENTION: During treatment cycles, subjects received 100 micrograms SC GRF on cycle days 2 to 11 and were observed during a control cycle. MAIN OUTCOME MEASURES: Follicle number and diameter, as well as endometrial thickness were all assessed by vaginal ultrasound and blood was obtained for serum FSH, LH, E2, P, GH, insulin-like growth factor 1 (IGF-1), and insulin-like growth factor binding protein-3. RESULTS: During cycles treated with GRF, GH, and IGF-1 levels were normal. However, follicular growth rates and E2 to FSH ratios were significantly higher. The day of the peak E2 to follicular diameter ratio after GRF was earlier than in control cycles. Endometrial growth rates were also greater with GRF. CONCLUSIONS: Our data, although preliminary, support the hypothesis that low doses of GRF may independently stimulate the ovary and enhance folliculogenesis.
Adult↗
Altered responses to stress in women undergoing in-vitro fertilization and recipients of oocyte donation.
Clinical impressions suggest the presence of considerable anxiety and depression in infertile couples. We utilized a psychological stress test to assess adaptations to provoked stress to improve the psychological profile of infertile women. A psychological stress test was administered to four groups: normal menstruating females (controls, n = 13); oocyte donors (n = 13); recipients of oocyte donation (n = 7); and women undergoing standard in-vitro fertilization (IVF; mean age 38.0 years; n = 8). The psychological stress test consisted of three active coping tasks: (i) serial subtraction, (ii) Stroop colour test, (iii) speech task and (iv) one passive coping task, the cold-pressor test. Haemodynamic responses (HD) were monitored before, during and after the psychological stress test, and serum samples were drawn for catecholamines and cortisol. Baseline blood pressures were similar among groups. The psychological stress test elicited different biophysical responses in controls compared with the other groups (P < 0.001). Oocyte donors had different speech task responses from baseline, although these and the other parameters of the psychological stress test were not different from either the recipient or IVF groups. Blood pressure responses from baseline were blunted in both recipients and standard IVF patients following provoked stress. Baseline cortisol and norepinephrine were similar among all groups, yet provoked stress elicited a significant increase in controls (142.0 +/- 25.2%, P < 0.001) compared with oocyte donors (17.1 +/- 19.7%), recipients and standard IVF patients (mean -15.5 +/- 17.3% respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Angiotensin-converting enzyme inhibition reverses luteal phase steroid production in oocyte donors.
OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibition would affect ovarian steroid synthesis in the oocyte donors undergoing controlled ovarian hyperstimulation (COH). SETTING: The IVF program of the University of Southern California. DESIGN: Prospective matched clinical trial. PATIENTS: Twelve oocyte donors were studied in 28 hyperstimulation cycles. INTERVENTIONS: Donors underwent a standard COH protocol. Follicle aspiration was performed 34 hours after administration of hCG. After the procedure, seven donors were administered the ACE inhibitor, captopril, 6.25 mg orally twice daily for 4 days. The remaining patients served as controls. MAIN OUTCOME MEASURES: Serum E2, P, plasma prorenin, active renin, and angiotensin II (Ang II). RESULTS: Angiotensin II increased after aspiration in both groups but was significantly lower in those receiving captopril. Peak P in the captopril group was significantly lower than controls (81.8 +/- 27.8 versus 208.5 +/- 23.9 ng/mL [conversion factor to SI unit, 3.180]). Peak E2 was significantly higher (2,222.4 +/- 875.3 versus 425.6 +/- 490.4 pg/mL [conversion factor to SI unit, 3.671]). Active renin and Ang II correlated with P. CONCLUSIONS: In stimulated cycles, inhibition of Ang II production appears to raise serum E2 and lower P levels. Angiotensin II, therefore, may have a role in the regulation of ovarian steroid synthesis.
Adolescent↗
The route of administration influences the effect of estrogen on insulin sensitivity in postmenopausal women.
OBJECTIVE: To determine the effect of transdermal estrogen on insulin sensitivity in postmenopausal women and to compare this effect with changes observed with oral conjugated equine estrogens. DESIGN: Fourteen postmenopausal women were randomized to receive a transdermal E2 patch, 0.1 mg, for 25 days each month (n = 7) or transdermal E2 with added medroxyprogesterone acetate (MPA), 10 mg, from days 16 to 25 each month (n = 7). An insulin tolerance test (ITT) was performed at baseline and between days 23 and 25 during the 2nd month of treatment to assess insulin sensitivity. Values for the disappearance of glucose (K(itt)) were calculated and compared with values obtained from women receiving 1.25 mg of oral equine estrogens (n = 8). SETTING: University Clinical Research Center. PATIENTS: Healthy postmenopausal women not receiving hormonal replacement. INTERVENTION: Insulin tolerance tests before and after treatment. MAIN OUTCOME MEASURE: Disappearance of glucose and insulin (K(itt)) before and after treatment. RESULTS: Women receiving transdermal E2 alone demonstrated improved insulin sensitivity. The K(itt) glucose values increased by 13.2%, compared with a 23.9% decrease in K(itt) values observed with 1.25 mg of conjugated equine estrogen. The group treated with transdermal E2 and MPA had a reduction in insulin sensitivity. Insulin clearance was enhanced only with transdermal estrogen and was significantly delayed (blunted clearance) with the addition of MPA to transdermal E2 and with oral estrogen. CONCLUSION: We previously demonstrated a bimodal effect of oral equine estrogens on insulin sensitivity with an improvement occurring with the lower dose of 0.625 mg but with a deterioration with the dose of 1.25 mg. Here we suggest that this effect may be related to a first-pass hepatic-portal effect in that transdermal E2 (0.1 mg), which may be equated more closely with the larger dose of oral estrogen (1.25 mg), improved insulin sensitivity. Progestin, however, appeared to attenuate the beneficial effects of transdermal estrogen and may alter the clearance of insulin.
Administration, Cutaneous↗
The independent effects of exercise and estrogen on lipids and lipoproteins in postmenopausal women.
OBJECTIVE: To assess the effects of a moderate exercise program with and without oral estrogen replacement on levels of lipids and lipoproteins in postmenopausal women. METHODS: One hundred one postmenopausal women were randomized into four groups: control or sedentary (N = 20), exercise alone (N = 25), estrogen replacement using 0.625 mg conjugated equine estrogen (N = 28), and exercise supplemented with conjugated equine estrogen (N = 28). The exercise groups were placed on a moderate exercise program. Following baseline testing, each group returned at 3 and 6 months for cardiorespiratory fitness testing and serum lipid and lipoprotein profiles. RESULTS: We found a significant decrease in systolic blood pressure (P < .05) in all treatment groups. The maximum oxygen uptake increased by 9.0 and 7.8% in the exercise and conjugated equine estrogen/exercise groups, respectively, compared to the other groups (P < .05). These responses were seen at both 3 and 6 months. Total exercise time (time spent on the treadmill until exhaustion during testing) significantly increased in the exercise group by 21% (P < .01). Exercise alone was associated with significant decreases in total cholesterol (5.2%, P < .05), triglycerides (2%, P < .05), and low-density lipoprotein (LDL) cholesterol (10%, P < .01), and a significant increase in the high-density lipoprotein (HDL) cholesterol-LDL ratio (17.2%, P < .01). Significant changes were noted in these values, as well as increases in HDL cholesterol (16 and 14.8%; P < .01) and apolipoprotein A1 (25.6 and 26.5%; P < .001) in the conjugated equine estrogen and conjugated equine estrogen/exercise groups, respectively. However, there were no differences in the changes observed in the conjugated equine estrogen groups with versus without exercise. No direct correlation was seen between measures of exercise performance and the changes seen in lipids and lipoproteins. CONCLUSIONS: Estrogen therapy alone had the greatest beneficial effect on lipids and lipoproteins. Exercise alone resulted in a significant reduction in cholesterol, triglycerides, and LDL cholesterol, and an increase in the HDL-LDL ratio. However, combined conjugated equine estrogen and exercise did not demonstrate an added improvement in lipid metabolism. Physical fitness levels increased in the exercise groups, but not in the control group or the estrogen-alone treated women.
Adult↗
Insulin sensitivity is decreased in normal women by doses of ethinyl estradiol used in oral contraceptives.
OBJECTIVE: We determined the independent effects of various doses of ethinyl estradiol used in oral contraceptives or norethindrone acetate, as well as their combination, on insulin sensitivity in normal women. STUDY DESIGN: Thirty-three normal ovulatory female volunteers were recruited for this study. Insulin tolerance tests were performed after carbohydrate loading to determine the kinetic disappearance of glucose and insulin. After initial testing the women were randomized into four groups: ethinyl estradiol 20 micrograms, 35 micrograms, and 50 micrograms and norethindrone 1 mg. Insulin tolerance tests were repeated after 1 month of treatment and again after a second month, when all ethinyl estradiol groups received the addition of norethindrone 1 mg to their doses of ethinyl estradiol. Plasma glucose and insulin were measured, and insulin sensitivity (K(itt) glucose) and the disappearance of insulin (K(itt) insulin) were calculated. RESULTS: All groups were comparable at baseline, and no significant changes in fasting glucose and insulin were evident with treatment. After ingestion of 50 micrograms ethinyl estradiol the K(itt) glucose value decreased significantly (p < 0.03) and ingestion of 20 micrograms and 35 micrograms showed individual changes, but as groups the changes were not statistically significant. All ethinyl estradiol groups combined had a significant decrease in K(itt) glucose (p < 0.01). Norethindrone 1 mg alone did not change K(itt) glucose values, and after the addition of norethindrone to ethinyl estradiol, K(itt) glucose values normalized. K(itt) insulin values were also lower with treatment but were lower with ethinyl estradiol plus norethindrone compared with ethinyl estradiol alone (p < 0.04), suggesting an attenuation of insulin clearance with the progestin. CONCLUSION: Ethinyl estradiol alone decreases insulin sensitivity, and this may occur at lower doses, but norethindrone 1 mg does not appear to do so. However, progestins may alter insulin clearance.
Adult↗
A possible bimodal effect of estrogen on insulin sensitivity in postmenopausal women and the attenuating effect of added progestin.
OBJECTIVE: To determine the effects of estrogen and of added progestin on carbohydrate tolerance in postmenopausal women. DESIGN: An insulin tolerance test (ITT) was used to assess insulin resistance in healthy post-menopausal women and to determine the effects of oral estrogen with and without added progestin on insulin sensitivity. SETTING: A menopause research clinic at a University Medical Center. PATIENTS: Fifteen healthy postmenopausal and nine premenopausal women were studied after having not received any hormone preparations for > or = 4 weeks. INTERVENTIONS: All subjects received a baseline ITT and postmenopausal women were then randomized to receive either 0.625 mg conjugated equine estrogen, 0.625 mg conjugated equine estrogen/10 mg progestin, or 1.25 mg conjugated equine estrogen for 2 months at which time a second ITT was performed. In the former two groups the women were treated for an additional 4 months to assess the long-term effects of treatment and had a third ITT performed at the end of 6 months. MAIN OUTCOME MEASURES: Fasting serum insulin and glucose were measured and K(itt) values were obtained at each visit in each group. RESULTS: Forty-four percent of nonobese healthy postmenopausal women were found to have insulin resistance. The three groups differed significantly in their K(itt) responses. Estrogen replacement improved insulin sensitivity (K(itt) increased by 25%). However, 1.25 mg of conjugated equine estrogen caused a 24.7% decrease in K(itt) values and progestins attenuated the beneficial effects of 0.625 mg conjugated equine estrogen from baseline values (K(itt) decreased by 17.0%). Two- and 6-month values did not differ. CONCLUSIONS: Insulin resistance is prevalent in healthy postmenopausal women. A moderate dose of estrogen appears to increase insulin sensitivity but higher doses may attenuate this benefit and progestins may cause a decrease in insulin sensitivity.
Adult↗
Behavioral stress responses in premenopausal and postmenopausal women and the effects of estrogen.
OBJECTIVE: Our purpose was to determine the pattern of reactivity to stress in premenopausal and postmenopausal women and to assess the effects of estrogen. STUDY DESIGN: A behavioral stress test was given to premenopausal (n = 13) and postmenopausal women (n = 36). Biophysical and neuroendocrine responses were measured during and on completion of the stress test. The postmenopausal women were then randomized to placebo or transdermal estradiol treatment for 6 weeks, at which time another behavioral stress test was given. RESULTS: Stress reactivity to math and speech tasks elicited significantly greater systolic blood pressure responses in postmenopausal women compared with premenopausal women (p < 0.05). On retesting, significant biophysical responses that were present during the initial stress testing were still present (p < 0.05) in the placebo group but were blunted with estrogen treatment. Plasma corticotropin, cortisol, androstenedione, and norepinephrine increased during testing to a similar degree in premenopausal and postmenopausal women; this response was maintained after placebo treatment. Postmenopausal women treated with estrogen had blunted responses. CONCLUSION: Significant differences in responses to psychologic stress exist in premenopausal and postmenopausal women. The lack of adaptation may account in part for the increased risk of cardiovascular disease in postmenopausal women. Estrogen appears to blunt the stress-induced response.
Aged↗
Aggressive evaluation for atypical squamous cells in Papanicolaou smears.
A retrospective study was done on women who had atypical Papanicolaou smears and were referred for immediate colposcopy. The smears were obtained during January 1985 to March 1989 at Edwards Air Force Base, California. Excluded from the evaluation were abnormal Papanicolaou smears with hyperkeratosis, parakeratosis and koilocytotic atypia suggestive of human papillomavirus (HPV) infection. The evaluation included colposcopy, colposcopically directed biopsies, endocervical curettage and repeat Papanicolaou smears. A total of 101 patients were included in the study. Cervical intraepithelial neoplasia (CIN) was seen in 29.7% (30 patients): 12.9% (13) CIN I, 12.9% (13) CIN II and 3.9% (4) CIN III. Carcinoma was seen in 3.9% (4) of the patients: 2.9% (3) was carcinoma in situ, and 0.99% (1) was invasive squamous cell carcinoma, stage IIb. HPV and dysplastic lesions were seen together in 19.8% (20) of the patients. HPV was seen alone in 45% (46). Twenty-one patients (20.8%) had no apparent lesions on colposcopy, although one developed microinvasive keratinizing squamous cell carcinoma within 36 months of colposcopy. Many significant lesions can go undetected for extended periods of time in women with atypical Papanicolaou smears, resulting in delayed management. Referral for immediate colposcopy is advocated strongly.
Adult↗
Intraoperative cholangiography. A review of indications and analysis of age-sex groups.
A retrospective review was performed of patients who had biliary tract stone formation as the primary diagnosis for hospitalization and indication for surgery. Five hundred and eighty-nine consecutive charts were reviewed of patients admitted between 1975 and 1979. Intraoperative cholangiography was performed in 166 patients of whom 22 had common duct exploration. Choledochotomy in this series was performed in 63 cases without utilizing pre-exploratory cholangiography. A normal intraoperative cholangiogram was found to be 100% accurate; however, an abnormal cholangiogram was associated with a 16% false positive rate of exploration of the common duct. The incidence of unsuspected common duct stones detected only by intraoperative cholangiography was 2.3%. Age-sex analysis confirms a 10-year mean age difference between men and women within the population of this study (p less than 0.001). This age-sex difference is maintained in patients without common duct pathology as well as in patients with sterile bile. However, the mean age difference between male and female patients with either demonstrable common duct obstruction by stones or infected bile as determined by routine intraoperative culture is not statistically significant. A review of the role of intraoperative cholangiography, and the experience at Northeastern Hospital is discussed.
Adult↗