Associations between follicular fluid high density lipoprotein particle components and embryo quality among in vitro fertilization patients.

PURPOSE: Follicular redox balance is likely to be important for embryo quality during in vitro fertilization (IVF), and the anti-oxidative high desity lipoprotein (HDL) particle is the sole lipoprotein measured in follicular fluid (FF). Therefore, we investigated FF HDL particle components as predictors of embryo quality during IVF. METHODS: Two research follicles collected from each participant were individually tracked, and 103 women having at least one developed embryo were included in the analysis. Concentrations of 15 non-cholesterol HDL particle components and 26 HDL-cholesterol (HDL-C) particle size subfractions were determined. Embryo quality was assessed for embryo cell number, embryo fragmentation, and embryo symmetry. Multivariable Poisson regression with a sandwich variance estimator was used to evaluate associations between HDL particle components and embryo quality, adjusted for covariates. RESULTS: Higher γ-tocopherol concentration was associated with less embryo fragmentation (relative risk [RR] = 4.43; 95 % confidence interval [CI] 1.78, 11.06), and higher apolipoprotein A-1 concentration was associated with full embryo symmetry (RR = 3.92; 95 % CI 1.56, 9.90). Higher concentrations of HDL-C subfractions in the large and medium particle size ranges were associated with poorer embryo quality. CONCLUSIONS: FF HDL lipophilic micronutrients and protein components, as well as HDL-C particle size, may be important predictors of embryo quality during IVF.

Distributions of high-density lipoprotein particle components in human follicular fluid and sera and their associations with embryo morphology parameters during IVF.

BACKGROUND: High-density lipoprotein (HDL) is the sole lipoprotein present in follicular fluid (FF). The objectives of this study were to examine HDL lipid composition and associated enzyme activities in FF and serum and to relate these levels to embryo morphology parameters in women undergoing in vitro fertilization (IVF). METHODS: Serum and FF were prospectively obtained from 60 women undergoing IVF. HDL lipids, apolipoprotein AI (ApoAI), paraoxonase 1 (PON1) and paraoxonase 3 (PON3) activities were determined. Bivariate analysis and ordinal logistic regression models were employed to examine the associations between biochemical measures and embryo morphology parameters [embryo cell number (ECN) and embryo fragmentation score (EFS)] as surrogate markers of oocyte health. RESULTS: All biochemical parameters were significantly (P < 0.05) lower in FF than serum except PON3 levels which were significantly higher. FF-HDL cholesterol (OR 0.66, 95%CI 0.46-0.96) and ApoAI (OR 0.13, 95%CI 0.03-0.97) levels were negative predictors for EFS; however, their effects were not independent and the level of one moderated the effect of the other. Limited to Day 3 embryo transfers, FF-PON1-arylesterase activity was a significant positive predictor for ECN (OR 1.09, 95%CI 1.01-1.17). CONCLUSIONS: In this pilot study, our data suggests that HDL and its component proteins within FF may play protective roles in the health of the human oocyte and subsequent early embryo development. We describe for the first time the activities of PON1 and PON3 in FF. We suspect that PON3 activity may be locally generated due to higher activities in FF compared with serum.

Follistatin antagonizes the effects of activin-A on steroidogenesis in human luteinizing granulosa cells.

Activin-A decreases progesterone secretion and aromatase activity in cultured human luteinizing granulosa cells. Follistatin is a binding protein for activin and inhibin produced by granulosa cells and present in follicular fluid. The present study examines the hypothesis that follistatin reverses the actions of activin-A on human granulosa cells. Granulosa cells from women undergoing ovarian stimulation for in vitro fertilization were cultured in defined medium with recombinant human (rh) activin-A and purified porcine follistatin. Follistatin completely reversed the inhibition of basal progesterone production by rh-activin-A, but only when added in a greater than 2:1 molar ratio to activin-A. Although variable effects of activin-A on aromatase activity were observed in these studies, follistatin also antagonized these effects. Follistatin had no effect in the absence of added activin-A. rh-Inhibin-A did not alter steroidogenesis by granulosa cells either with or without added activin-A. Even when added in a 45-fold molar excess, inhibin-A did not displace sufficient activin-A from follistatin to inhibit progesterone secretion. This suggests that the affinity of inhibin-A for follistatin is much lower than that of activin-A, and/or that activin-A bound to follistatin dissociates slowly. alpha 2-Macroglobulin, another activin-binding protein, did not alter the inhibition of progesterone production by activin-A. We conclude that in human granulosa cells, follistatin, but not alpha 2-macroglobulin or inhibin-A, acts to modulate the actions of activin-A. Follistatin and activin may be viewed as components of an autocrine/paracrine system within the human follicle that regulate the differentiated functions of granulosa cells.

Interferon-gamma and activin A promote insulin-like growth factor-binding protein-2 and -4 accumulation by human luteinizing granulosa cells, and interferon-gamma promotes their apoptosis.

Insulin-like growth factor (IGF)-binding proteins (IGFBPs) antagonize IGF and gonadotropin actions on granulosa cells. Human atretic follicles express IGFBP-2 in granulosa cells more strongly and contain higher levels of IGFBP-2 and IGFBP-4 than healthy follicles. We studied the effects of interferon-gamma (IFN gamma) and activin A, which decrease progesterone accumulation, on granulosa cell IGFBP production and apoptosis. Conditioned media from luteinizing granulosa cells cultured with IFN gamma or activin A and/or LH were subjected to ligand blotting; northern blots of total ribonucleic acid (RNA) from these cells were probed for IGFBP-2 and -4. Apoptosis was measured by in situ DNA end labeling. LH decreased medium IGFBP-2 to 21% of the control value. Although IFN gamma did not alter basal medium IGFBP-2, in the presence of LH it increased IGFBP-2 3.4-fold, with parallel changes in messenger RNA levels. Activin A also tended to increase medium IGFBP-2 in LH-treated cultures. In conditioned medium, IGFBP-4 was consistently decreased by LH, whereas both IFN gamma and activin A increased IGFBP-4 and decreased IGFBP-4 protease activity. Both LH and IFN gamma modestly stimulated IGFBP-4 messenger RNA levels. Follistatin antagonized the action of activin A, but not that of IFN gamma. IFN gamma, but not activin A, increased granulosa cell apoptosis. In conclusion, IFN gamma produced by activated lymphocytes may decrease endogenous IGF activity through stimulation of IGFBPs and may promote apoptosis of granulosa-lutein cells in vivo and, thus, luteal regression. Activin A similarly promotes IGFBP accumulation, but it does not promote apoptosis.

Reproductive aging: accelerated ovarian follicular development associated with a monotropic follicle-stimulating hormone rise in normal older women.

Women experience a decline in fertility that precedes the menopause by several years. Previous studies have demonstrated a monotropic rise in FSH associated with reproductive aging: however, the mechanism of this rise and its role in the aging process are poorly understood. The purpose of this study was to characterize ovarian follicular development and ovarian hormone secretion in older reproductive age women. Sixteen women, aged 40-45 yr, with regular ovulatory cycles were studied. The control group consisted of 12 ovulatory women, aged 20-25 yr. Serum obtained by daily blood sampling was analyzed for FSH, LH, estradiol (E), progesterone, and inhibin (Monash polyclonal assay). Follicle growth and ovulation were documented by transvaginal ultrasound. Older women had significantly higher levels of FSH throughout the menstrual cycle. E, progesterone, LH, and inhibin levels did not differ between the two age groups when compared relative to the day of the LH surge. Ultrasound revealed normal growth, size, and collapse of a dominant follicle in all subjects. Older women had significantly shorter follicular phase length associated with an early acute rise in follicular phase E, reflecting accelerated development of a dominant follicle. We conclude that older reproductive age women have accelerated development of a dominant follicle in the presence of the monotropic FSH rise. This is manifested as a shortened follicular phase and elevated follicular phase E. The fact that ovarian steroid and inhibin secretion were similar to those in the younger women suggests that elevated FSH in women of advanced reproductive age may represent a primary neuroendocrine change associated with reproductive aging.

Localization and regulation of corticotropin receptor expression in the midgestation human fetal adrenal cortex: implications for in utero homeostasis.

Developmental changes in the responsiveness of the fetal adrenals to corticotropin (ACTH) play an important role in the regulation of the fetal hypothalamic-pituitary-adrenal axis. Responsiveness of adrenal cortical cells to ACTH is dependent on the extent of ACTH receptor expression. Therefore, we examined the localization and regulation of ACTH receptor expression in the midgestation (16-24 weeks) human fetal adrenal cortex. In situ hybridization analysis was used to localize messenger RNA (mRNA) encoding the ACTH receptor in sections of human fetal adrenal glands. Messenger RNA encoding the ACTH receptor was localized in cells from all cortical zones; abundance was higher in definitive zone than in fetal zone cells and was least abundant in the more central portions of the cortex. Regulation of ACTH receptor expression was studied using Northern blot analysis of total RNA extracted from primary cultures of fetal and definitive zone cells. Two major (1.5 and 3.5 kilobases) and, upon stimulation with ACTH, 3 minor (4.0, 6.0 and 10.0 kb) ACTH receptor mRNA transcripts were detected in RNA from fetal and definitive zone cells. In both cell types, ACTH-(1-24) increased the abundance of mRNA encoding the ACTH receptor 10- to 20-fold compared with untreated cells. The effects of ACTH-(1-24) on ACTH receptor expression in fetal zone cells were time- and dose-dependent. The ED50 for the stimulation of ACTH receptor expression by ACTH-(1-24) was 1-10 pM, and maximal response to 0.1 nm ACTH-(1-24) was detected after 12-16 h. Eight-bromoadenosine cAMP and forskolin also stimulated ACTH receptor expression in fetal zone cells and closely mimicked the effects of ACTH-(1-24). In contrast, stimulation of protein kinase C with 12-O-tetradecanoyl phorbol 13-acetate had no effect on ACTH receptor expression. Changes in ACTH receptor expression in response to ACTH-(1-24), cAMP and forskolin were paralleled by changes in expression of the P450 cholesterol side chain cleavage (P450scc) enzyme. These data demonstrate that expression of the ACTH receptor by the human fetal adrenal cortex is up-regulated by its own ligand and that this effect is mediated by a cAMP-dependent mechanism. In addition, the coordinate stimulation of ACTH receptor and P450scc expression by ACTH indicates that the gene for the ACTH receptor is one of a specific cohort of genes regulated by ACTH that are required to facilitate fetal adrenal cortical response to ACTH. ACTH regulation of its own receptor may represent a mechanism by which fetal adrenal responsiveness to ACTH is maintained and possibly enhanced during fetal development.

Variability of serum prolactin and progesterone levels in normal women: the relevance of single hormone measurements in the clinical setting.

In order to delineate factors contributing to variation in hormone levels, progesterone and prolactin (PRL) levels from 28 normal women, obtained daily during one menstrual cycle and every 20 minutes during a midluteal 24-hour admission in a subgroup of five subjects, provided a data base for analysis of these variables. Pulsatile analysis of the 24-hour data was conducted using an adaptive-threshold algorithm, and normal reference ranges were generated from randomly selected daily hormone values. Our data verify that inherent variation can significantly alter single random serum levels of reproductive hormones. These variations included menstrual cycle day, circadian influence, pulsatile secretion, assay error, and biologic heterogeneity. Besides the expected day-to-day change in progesterone levels during the luteal phase, seven of ten women exhibited a significant circadian variation in progesterone; however, the time of day of the peak level was not consistent among women. Prolactin levels did not demonstrate any clinically relevant change over the menstrual cycle, but did have a consistent circadian pattern (nocturnal rise) over the 24-hour study period. Pulsatile variation occurred in both progesterone and PRL levels during the 24-hour admission. Five different reference ranges were generated from randomly selected single daily values from the 28 normal menstrual cycles. Although the mean levels calculated for each reference range were similar, the reference ranges demonstrated considerable variation due to the random sampling. In the five progesterone reference ranges, the lower limit of the range varied from 2.7-6.1 ng/mL, whereas the upper limit varied from 24.2-42.1 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of follicular phase pituitary-gonadal function by a potent new gonadotropin-releasing hormone antagonist with reduced histamine-releasing properties (ganirelix).

OBJECTIVE: To determine if daily subcutaneous doses of ganirelix will suppress and maintain E2 < or = 30 pg/mL (conversion factor to SI unit, 3.671), the serum profiles of LH and FSH during and after cessation of treatment, the time-course of the resumption of normal ovarian function after ganirelix cessation, and to identify side effects of daily treatment. DESIGN: Open-label nonrandomized clinical study. SETTING: Normal human volunteers in an academic research center. PATIENTS: Women 21 to 45 years of age, with documented ovulatory menstrual cycles. INTERVENTIONS: Ganirelix was administered subcutaneously daily for 8 days. Blood samples were obtained during dosing as well as before and after cessation of dosing. MAIN OUTCOME MEASURES: Changes in serum E2, LH, FSH, P, and ganirelix. RESULTS: Ganirelix treatment rapidly decreased serum levels of gonadotropins and E2 after both 1 and 2 mg administration. Twenty-four hours after the first dose of ganirelix, E2 decreased from a mean +/- SEM of 50 +/- 8 and 67 +/- 11 pg/mL at baseline to 25 +/- 4 and 20 +/- 3 in the 1 mg and 2 mg groups, respectively. Estradiol remained suppressed (mean levels < 26 pg/mL) on all subsequent 7 days of ganirelix dosing in both groups. After the final dose of ganirelix, there was a rapid return of ovarian function in all volunteers. All women had P levels indicative of ovulation in the subsequent cycle, and the mean number of days from the final ganirelix dose to the next menses was 25.8 +/- 2.1 and 27.3 +/- 1.6 in the 1 and 2 mg groups, respectively. CONCLUSIONS: Daily ganirelix administration is effective in suppressing the pituitary-gonadal axis and has a side effect profile that should be well tolerated.

Dose-related suppression of serum luteinizing hormone in women by a potent new gonadotropin-releasing hormone antagonist (Ganirelix) administered by intranasal spray.

OBJECTIVE: To determine if the GnRH antagonist (GnRH-a) Ganirelix (Syntex Research, Palo Alto, CA), administered by intranasal (IN) spray to normal women, is absorbed into the systemic circulation and suppresses LH secretion. DESIGN: A single center, open label, nonrandomized, dose-escalation study. SETTING: Academic research environment. PATIENT(S): Normal female volunteers ages 23 to 43 years. INTERVENTION(S): Ganirelix was administered as a single dose by IN spray. The administered doses and the number of women receiving each of them were 0.1 mg (n = 1), 0.3 mg (n = 1), 1 mg (n = 2), 3 mg (n = 5), and 6 mg (n = 5). Blood samples were collected from -15 minutes to 24 hours after dosing. MAIN OUTCOME MEASURE(S): Serum concentrations of Ganirelix and LH. RESULT(S): Ganirelix was absorbed rapidly. The mean time to maximal serum levels in the 3- and 6-mg groups was 0.67 and 0.53 hour, respectively. Mean serum LH levels were suppressed by > or = 35% relative to baseline from 2 to 12 hours after dosing in both groups. The mean maximal percent decrease in serum LH was -62% (at 8 hours after dosing) and -74% (at 6 hours after dosing) in the 3- and 6-mg groups, respectively. CONCLUSION(S): Single dose IN administration of 3 or 6 mg of Ganirelix suppressed serum LH levels in women, further enhancing the potential clinical utility of this potent GnRH-a. This is the first clinical report of a GnRH-a reducing the secretion of a pituitary gonadotropin when administered by an IN delivery system. Based on the duration and extent of LH suppression observed in this study, Ganirelix, administered by twice daily IN spray, may be effective for the treatment of gonadal hormone-dependent disorders in women.

The anterior pituitary response to a gonadotropin-releasing hormone challenge test in normal older reproductive-age women.

OBJECTIVE: To assess the pituitary responsiveness to GnRH stimulation of premenopausal women relative to age. DESIGN: Older and younger reproductive-age women underwent the GnRH stimulation test in the early follicular phase of the menstrual cycle. SETTING: Female subjects in an academic research environment. PATIENTS: Women aged 21 to 44 years consisting of normal volunteers and infertility patients. INTERVENTIONS: Gonadotropin-releasing hormone was administered intravenously between days 2 and 4 of the menstrual cycle. Blood samples were collected from -20 minutes before to 120 minutes after administration. MAIN OUTCOME MEASURE: Luteinizing hormone, FSH, inhibin, and E2 levels. RESULTS: No significant difference in baseline values existed between older and younger women with regard to LH, inhibin, and E2, but basal FSH levels were higher in older women. A significantly diminished percent of LH and percent FSH change above baseline occurred 30 minutes after GnRH administration in the older women compared with younger women. No change in inhibin or E2 levels could be detected during the sampling period. CONCLUSIONS: The present study demonstrates marked attenuation of the acute pituitary LH response (sensitivity) to GnRH stimulation in older women when compared with a younger cohort.

The effect of deglycosylated human chorionic gonadotropin on corpora luteal function in healthy women.

Fourteen healthy young women were studied through a control and a treatment menstrual cycle in two series of experiments. In the first series, they were given one of four doses of deglycosylated human chorionic gonadotropin (hCG) as a 24-hour infusion during the mid-luteal phase of the cycle. In these studies, there were no significant alterations of the length of the luteal phase of the treatment cycle, and there was no decrease in serum progesterone (P) during the infusion. In fact, serum P increased during the infusion. In the second series of studies, five subjects were given a 48-hour infusion of normal saline during the control cycle, and a 48-hour infusion of deglycosylated alpha-intact beta-hCG during the treatment cycle, both being administered during the mid-luteal phase. Treatment did not alter luteal phase duration and, again, increased serum P. It is concluded that deglycosylated preparations of hCG are not clinically useful as luteinizing hormone antagonists, probably because of residual agonist activity.

Bacteria in the transfer catheter tip influence the live-birth rate after in vitro fertilization.

OBJECTIVE: To assess the impact of individual bacteria isolated from the vagina and tip of the embryo transfer catheter on live-birth rates. DESIGN: Prospective clinical study. SETTING: Infertility outpatient clinic of a university hospital. PATIENT(S): Ninety-one women undergoing IVF-ET. INTERVENTION(S): Cultures were obtained from the vagina for aerobic and anaerobic bacteria at the time of both sonographic egg retrieval and embryo transfer and from the tip of the embryo transfer catheter. Doxycycline treatment was started after egg retrieval. MAIN OUTCOME MEASURE(S): The live birth of one or more neonates. RESULT(S): Doxycycline had no substantial impact on the recovery of individual vaginal bacteria or on bacterial vaginosis. An increase in live-birth rate was associated with the recovery of hydrogen peroxide-producing Lactobacillus from the vagina (P=0.01) and from the embryo transfer catheter (P=0.01). In contrast, a reduction in live-birth rate was associated with recovery of Streptococcus viridans (S. viridans) from the embryo transfer catheter tip (P=0.04). CONCLUSION(S): In the setting of IVF-ET, prophylactic doxycycline had little effect on vaginal bacteria. Specific bacteria recovered from the embryo transfer catheter appear associated with a detrimental or beneficial effect or with no effect on live-birth rates.

Late-onset hematometra and hematosalpinx in a woman with a noncommunicating uterine horn. A case report.

BACKGROUND: Noncommunicating uterine horns are rare, occasionally presenting with functional endometrial cavities. Surgical removal of the noncommunicating horn is commonly performed to prevent endometriosis in these patients. CASE: A 41-year-old woman with a unicornuate uterus and noncommunicating uterine horn presented with a three-month history of right-sided pelvic pain. She had previously undergone multiple assisted reproductive technique attempts with superovulation and supraphysiologic serum estradiol levels and no apparent symptomatology or evidence of hematosalpinx during laparoscopy. Shortly after completing a donor oocyte recipient cycle, she developed acute right-sided pelvic pain. Diagnostic laparoscopy and subsequent laparotomy confirmed a right hematosalpinx and hematometra of the noncommunicating horn, with stage III endometriosis. CONCLUSION: Consideration of prophylactic resection of a noncommunicating uterine horn with a cavity should be considered in an asymptomatic, reproductive-age patient with this rare müllerian anomaly.

The effect of fibroids without cavity involvement on ART outcomes independent of ovarian age.

BACKGROUND: The effect of fibroids that do not distort the endometrial cavity on pregnancy rate (PR) and implantation rate (IR) is controversial. Use of oocyte donor-derived embryos offers an ideal patient population to study the effect of fibroids in patients utilizing assisted reproductive technologies (ARTs). METHODS: We conducted a retrospective cohort study of patients undergoing oocyte donor recipient (ODR) IVF cycles at two tertiary care fertility centres. We examined medical records for the presence of non-cavity-distorting fibroids and evaluated subsequent PR and IR. RESULTS: Three hundred and sixty-nine patients, 94 with fibroids, underwent oocyte donor recipient transfer cycles with fresh embryos. There was no statistical difference in IR (36 versus 38%) or clinical PR (47 versus 54%) between patients with or without fibroids. Neither the location (subserosal versus intramural) and the presence of multiple myomas nor the size of the myomas affected outcomes. Fibroids were more likely to be present in patients with increasing recipient age. CONCLUSIONS: Clinical PR and IR are not affected by the presence of non-cavity-distorting leiomyomata. This evidence does not support myomectomy before ART in patients with asymptomatic fibroids that do not significantly distort the endometrial cavity or cause abnormal uterine bleeding.

Congenital cervical atresia: report of seven cases and review of the literature.

OBJECTIVE: Our aim was to evaluate the clinical course and management of congenital cervical atresia. STUDY DESIGN: This retrospective analysis included 7 patients referred to our clinic and a review of the medical literature. RESULTS: Including this case series, 58 cases of congenital cervical atresia have been reported in the literature. Forty-eight percent of patients had isolated congenital cervical atresia with a normal vagina whereas the remainder had either complete or partial vaginal atresia ("shortened blind vaginal pouches"). Surgical management has included abdominal hysterectomy or uterovaginal cannulation with or without vaginoplasty. In 59% of patients who underwent uterovaginal canalization procedures (23/39), normal menstrual bleeding was achieved. Four of these patients subsequently became pregnant and were delivered at term. CONCLUSION: Surgical canalization in selected patients with congenital cervical atresia can be successfully performed to provide patients an opportunity for conservative management, resulting in normal menstrual bleeding, resolution of cyclic pelvic pain, and some potential (albeit limited) for fertility.

Endogenous catecholamines augment the inhibitory effect of opioids on luteinizing hormone secretion during the midluteal phase.

OBJECTIVE: Our purpose was to test the hypothesis that endogenous catecholamines may interact with endogenous opioid peptides to influence gonadotropin secretion during the midluteal phase in normal women. STUDY DESIGN: Normal cycling women studied during the midluteal phase were randomized to one of four treatment groups: (1) alpha-methyl-para-tyrosine, (2) naloxone, (3) alpha-methyl-para-tyrosine and naloxone, and (4) control. Mean treatment luteinizing hormone levels were compared by analysis of variance. Pulse frequency, amplitude, and integrated area under the curve were assessed by CLUSTER analysis and compared by means of nonparametric analyses. RESULTS: Mean luteinizing hormone levels were significantly higher in the naloxone and alpha-methyl-para-tyrosine plus naloxone groups compared with alpha-methyl-para-tyrosine or placebo. Coadministration of alpha-methyl-para-tyrosine and naloxone caused a significant increase in large-burst luteinizing hormone pulses compared with the group receiving naloxone only. CONCLUSION: Endogenous catecholamines augment the inhibitory effect of opioids on luteinizing hormone secretion during the midluteal phase in normal cycling women.

Increased adrenocortical responsiveness to exogenous ACTH in oral contraceptive users.

To evaluate the effects of changing steroid milieu on adrenocortical function, basal levels and responses of cortisol, 17-hydroxyprogesterone (17PO), androstenedione (A), dehydroepiandrosterone (DHEA), and testosterone to exogenous synthetic ACTH were investigated in six normal women during the early follicular (EF) and midluteal (ML) phases of the menstrual cycle and in five women on an oral contraceptive (OC) agent (35 micrograms ethinyl estradiol and 1 mg ethynodiol diacetate, Demulen). Baseline serum steroid and cortisol binding globulin (CBG) levels were measured on days 3-7 and 21-23 of the menstrual cycle in the normal subjects and on days 3-7 of OC treatment cycles. ACTH stimulation (10 micrograms m-2 i.v. bolus) was performed following dexamethasone suppression (0.5 mg p.o. q 6 h X 4). Basal levels of cortisol and CBG as well as cortisol responses to ACTH were increased in OC users relative to normal women tested during both the EF and ML phases of the cycle. In addition, 17PO levels were increased during the ML phase both before and following dexamethasone suppression compared to levels present in the EF phase and in OC users, no doubt because of increased ovarian steroidogenesis.

Utility of follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and FSH:LH ratio in predicting reproductive age in normal women.

The relative efficacy of follicle stimulating hormone (FSH), luteinizing hormone (LH), FSH:LH ratio and oestradiol is evaluated as a predictor of ovarian reserve (reproductive age) in normal women. Serum levels of FSH, LH, oestradiol and FSH:LH ratios were measured during menstrual cycle days 1-4 in younger (20-25 years; n = 23) and older (40-45 years; n = 32) reproductive age women with regular menstruation and normal reproductive function. On days 1-4, mean levels of FSH, oestradiol and FSH:LH ratios were significantly higher in older compared with younger women. FSH increased in concentration across cycle days in both age groups. A significantly lower LH value in younger versus older women was found only on day 1. Oestradiol showed no change across days in the younger group, but increased significantly from day 1 to day 4 in the older group. FSH values on days 1 or 2 were the best single predictor of age differences. However, the best prediction of age differences was obtained by using the combination of FSH and LH (as opposed to the FSH:LH ratio) on day 1 of the menstrual cycle.

Treatment of uterine fibroid tumors in a nude mouse model using high-intensity focused ultrasound.

OBJECTIVE: The purpose of this study was to investigate the potential efficacy of high-intensity focused ultrasound for the treatment of uterine fibroid tumors in a nude mouse model. STUDY DESIGN: A total of 60 female athymic nude mice were inoculated subcutaneously with 3 to 5 x 10(6) ELT-3 cells, a uterine fibroid tumor cell line. Tumor size was monitored with transcutaneous caliper measurements. The high-intensity focused ultrasound probe was a concave, single-element, high-power transducer that operated at a frequency of 3.5 MHz. The tumors were treated for 30 to 60 seconds using a high-intensity focused ultrasonic intensity of 2000 W/cm(2), depending on the tumor size. RESULTS: A single high-intensity focused ultrasonic treatment resulted in an average reduction in tumor volume of 91% within 1 month of the treatment. Histologic analysis of tumors treated with high-intensity focused ultrasound showed coagulation necrosis and nuclear fragmentation of tumor cells. CONCLUSION: High-intensity focused ultrasound effectively reduced uterine fibroid tumor size in a nude mouse model. Further studies are needed to assess the in situ response of uterine fibroids to high-intensity focused ultrasonic treatment.

Attenuation coefficient and sound speed in human myometrium and uterine fibroid tumors.

OBJECTIVE: To develop a noninvasive method for treatment of uterine fibroid tumors using high-intensity focused ultrasound. Optimal high-intensity focused ultrasound treatment would be dependent on quantitative information about ultrasonic tissue characteristics. METHODS: Ultrasonic attenuation and the sound speed of fresh human fibroid tumors and myometrium were measured as a function of frequency (1-3 MHz) by using a pulse transmission technique before and after in vitro high-intensity focused ultrasound treatment (3.5 MHz at an intensity of 2,000 W/cm2). RESULTS: The ranges of the attenuation coefficients, before and after high-intensity focused ultrasound treatment, were 0.9 to 2.2 and 1.8 to 3.9 dB/cm2, respectively, for fibroid tumors and 0.5 to 1.6 and 1.7 to 3.3 dB/cm2, respectively, for myometrium. Although the sound speed appeared to be independent of frequency (1,611 to 1,616 m/s at 1 to 3 MHz) in both types of tissues, a slight increase of approximately 4 to 14 m/s was observed after high-intensity focused ultrasound treatment. CONCLUSIONS: The results of this study represent our first reported values of the attenuation coefficient and sound speed in fibroid tumors and myometrium before and after high-intensity focused ultrasound treatment.