Gonadotropin-releasing hormone antagonists increase follicular fluid insulin-like growth factor-I and vascular endothelial growth factor during ovarian stimulation cycles.

The aim of the present study was to investigate the effect of gonadotropin-releasing hormone (GnRH) antagonists (GnRH-ant) on follicular fluid (FF) insulin-like growth factor-I (IGF-I) and FF vascular endothelial growth factor (VEGF) levels. Sixty women undergoing assisted reproduction were randomized and assigned to two different GnRH analog regimens: GnRH agonist (GnRH-a) and GnRH-ant. FF VEGF and FF IGF-I concentrations were significantly increased in the patients treated with GnRH-ant (p < 0.001). In the same patients we observed a statistically significant reduction in serum luteinizing hormone (LH) and estradiol (E2) levels (p < 0.001 and p < 0.05, respectively), FF E2 and FF androstenedione levels (p < 0.05 and p < 0.001, respectively), as well as a reduction in the number of pregnancies although this was not statistically significant. In the GnRH-ant group, FF VEGF levels were positively correlated with FF IGF-I levels, and both were negatively correlated with serum LH levels. The increase in FF IGF-I and FF VEGF levels in women treated with GnRH-ant could be explained by a deleterious follicular environment in response to profound suppression of LH and E2 levels.     

Gonadotropin-releasing hormone antagonists increase follicular fluid insulin-like growth factor-I and vascular endothelial growth factor during ovarian stimulation cycles

The aim of the present study was to investigate the effect of gonadotropin-releasing hormone (GnRH) antagonists (GnRH-ant) on follicular fluid (FF) insulin-like growth factor-I (IGF-I) and FF vascular endothelial growth factor (VEGF) levels. Sixty women undergoing assisted reproduction were randomized and assigned to two different GnRH analog regimens: GnRH agonist (GnRH-a) and GnRH-ant. FF VEGF and FF IGF-I concentrations were significantly increased in the patients treated with GnRH-ant (p < 0.001). In the same patients we observed a statistically significant reduction in serum luteinizing hormone (LH) and estradiol (E₂) levels (p < 0.001 and p < 0.05, respectively), FF E₂ and FF androstenedione levels (p < 0.05 and p < 0.001, respectively), as well as a reduction in the number of pregnancies although this was not statistically significant. In the GnRH-ant group, FF VEGF levels were positively correlated with FF IGF-I levels, and both were negatively correlated with serum LH levels. The increase in FF IGF-I and FF VEGF levels in women treated with GnRH-ant could be explained by a deleterious follicular environment in response to profound suppression of LH and E₂ levels.     

Pericardial fluid and serum levels of vascular endothelial growth factor and endostatin in patients with or without coronary artery disease.

BACKGROUND/PURPOSE: Vascular endothelial growth factor (VEGF) and endostatin are related to ischemic heart disease. This study investigated pericardial fluid and serum levels of VEGF and endostatin in patients with or without ischemic heart disease. METHODS: A total of 39 patients (24 patients in the CAD group with significant coronary artery disease; 15 patients in the non-CAD group without coronary artery disease) undergoing open heart surgery were enrolled. In the CAD group, patients were classified according to good coronary collateralization (Group A; n = 11) or poor coronary collateralization (Group B; n = 13). Pericardial fluid and serum samples were obtained at the time of surgery. VEGF and endostatin were measured by enzyme-linked immunosorbent assay. RESULTS: The levels of endostatin in both serum and pericardial fluid were significantly lower in the CAD group than in the non-CAD group (130.5 +/- 37.3 ng/mL vs. 172.4 +/- 37.8 ng/mL and 119.0 +/- 25.0 ng/mL vs. 143.0 +/- 23.5 ng/mL). The concentration of serum VEGF in the CAD group (92.6 +/- 18.2 pg/mL) was significantly higher than that in the non-CAD group (75.2 +/- 22.3 pg/mL). The concentration of serum VEGF in Group A (100.1 +/- 20.7 pg/mL) was significantly higher than that in Group B (84.3 +/- 12.4 pg/mL). The levels of pericardial fluid VEGF, serum and pericardial fluid endostatin were not significantly different between Groups A and B. CONCLUSION: Patients with coronary artery disease have lower serum and pericardial fluid levels of endostatin and higher serum levels of VEGF. Serum level VEGF, but not endostatin, is associated with good or poor collateralization in patients with coronary artery disease.     

Anti-annexin V antibodies in patients with early pregnancy loss or implantation failures

OBJECTIVE: To examine the impact of flare (short) vs. down-regulation (long) GnRH agonist (GnRH-a) on serum and follicular fluid (FF) LH and androgen concentrations in women undergoing IVF treatment cycles. DESIGN: Prospective observational study. SETTING: IVF clinic. PATIENT(S): One hundred sixteen ovulatory subjects undergoing IVF. INTERVENTION(S): Fifty-eight ovulatory patients undergoing a down-regulation regimen matched with 58 undergoing the flare regimen as part of an IVF cycle. MAIN OUTCOME MEASURE(S): Serum concentrations of LH, FSH, Progesterone (P4), Androstenedione (A), T, and E(2) on the day of hCG administration were compared between the two groups. In addition, the FF P4, 17OHP4, A, T, and E(2) levels were compared in the two groups. RESULT(S): Serum LH was significantly higher with the flare regimen (15.2 +/- 1.14 IU/L, P<.05) when compared with results with the down-regulation protocol (9.5 +/- 0.77 IU/L). In addition, FF A was significantly higher in the flare protocol (57.3 +/- 13.3 ng/mL, P<.05) compared with in the down-regulation protocol (27 +/- 2.44 ng/mL). Serum and FF P4, 17OH P4, T, and E(2) were not statistically significantly different between the two groups. CONCLUSION(S): Serum LH and FF A are significantly higher in the flare regimen in comparison with the down-regulation regimen. Circulating LH appears to play a role in determining FF A concentration.     

Follicular fluid levels of vascular endothelial growth factor. Are they predictive markers for ovarian hyperstimulation syndrome?

OBJECTIVE: To determine the possible predictive role of vascular endothelial growth factor (VEGF) levels in the follicular fluid (FF) at the time of oocyte retrieval in the development of ovarian hyperstimulation syndrome (OHSS) and its possible origin. STUDY DESIGN: FF was obtained from 174 high-responder patients at the time of oocyte retrieval. The study group comprised 16 high-responder patients who developed early, severe OHSS and from whom serum and peritoneal fluid (PF) were obtained during the active phase of the syndrome. These women were compared to 16 high-responder patients who did not develop OHSS. An additional control group comprised 16 low-responder patients who also did not develop OHSS. The FF, serum and PF samples were tested for VEGF by enzymelined immunosorbent assay. RESULTS: No differences in the FF VEGF levels were found among the OHSS group (1,742.3 +/- 522.4 pg/mL), the high-responder group that did not develop OHSS (1,802.0 +/- 584.3 pg/mL) and the low-responder group (1,686.7 +/- 374.2 pg/mL). In the OHSS group, no differences were found between the serum and PF VEGF levels (247.3 +/- 31.4 and 642.9 +/- 328.3 pg/mL, respectively). No correlation was found between the FF concentrations of VEGF and the mean serum 17-beta estradiol levels or number of oocytes retrieved. CONCLUSION: We conclude that preovulatory FF levels should not serve as a possible predictive factor for development of OHSS. The increased capillary permeability found in OHSS may be due to its systemic effect.     

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.     

Follicular fluid concentrations of vascular endothelial growth factor, inhibin A and inhibin B in IVF cycles: are they markers for ovarian response and pregnancy outcome?

OBJECTIVE(S): The aim of this study was to measure concentrations of vascular endothelial growth factor (VEGF), inhibin A and inhibin B in follicular fluid (FF) of women undergoing to in vitro fertilization (IVF) cycles and to determine their relationship with ovarian response and pregnancy. STUDY DESIGN: Follicular fluid was collected from 58 patients undergoing oocyte retrieval for IVF. Ovulation was induced with GnRH analogues and gonadotropins. Follicular fluids of mature follicles (>17 mm) were aspirated and pooled for each patient. Follicular fluid steroid hormone levels (E2, P) and VEGF, inhibin A, inhibin B concentrations were studied. The serum levels of E2, P and VEGF were also assessed on the day of the oocyte retrieval. These parameters and characteristics of the cycles were compared between the pregnant (group 1) and non pregnant (group 2) patients. RESULTS: The serum and FF VEGF levels were found to be significantly lower in the group in whom the pregnancy was achieved (P < 0.001). The FF inhibin A and FF inhibin B were found to be significantly higher in pregnant group (P < 0.001). However, age, day 3 FSH, dosage of gonadotropin administered, fertilization rate, sperm count, motile and morphologically normal sperm percentage were not significantly different in the two groups. There was an negative correlation between VEGF and number of follicles, number of oocytes, FF inhibin A, FF inhibin B. The number of oocytes retrieved, the fertilization rate were positively correlated with FF inhibin B and FF inhibin A. CONCLUSION: This study demonstrated that decreased FF VEGF, serum VEGF and elevated FF inhibin A and B are associated with better ovarian response and high pregnancy rate.     

Comparison of gonadotropin-releasing hormone and gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism.

OBJECTIVE: To compare pulsatile gonadotropin-releasing hormone (GnRH) therapy with gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism. DESIGN: Prospective study. Patients had free choice between the two forms of therapy. SETTING: Patients were treated on an outpatient basis in our department. PATIENTS: Eighteen patients of matched age (mean [+/- SD] age: 21.1 +/- 3.0 years and 23.6 +/- 7.3 years) and similar testicular volume were treated in each group. INTERVENTIONS: Pulsatile GnRH therapy was started with 4 micrograms GnRH subcutaneously every 2 hours using a portable pump and gonadotropin therapy with 3 x 2,500 IU human chorionic gonadotropin (hCG) weekly injected intramuscularly. After 8 to 12 weeks of hCG treatment, 150 IU human menopausal gonadotropin two to four times weekly were added. RESULTS: Testosterone (T) and estradiol (E2) levels increased significantly higher (T: P less than 0.03; E2; P less than 0.001) in the gonadotropin group than in the GnRH group (T: 22.5 +/- 8.1 versus 16.8 +/- 5.5 nmol/L; E2: 150 +/- 70 versus 88. +/- 59 pmol/L). Five patients developed gynecomastia during gonadotropin therapy. The rise of testicular volume was significantly more pronounced (P less than 0.001) in the GnRH group (delta testicular volume = 8.1 +/- 2.0 mL) than in the gonadotropin group (delta testicular volume = 4.8 +/- 1.8 mL). Ten patients of the GnRH and 8 of the gonadotropin group had positive sperm counts, ranging from 1.5 to 26 x 10(6) spermatozoa/mL. The latter was achieved more rapidly in the GnRH group (12 +/- 1.6 versus 20 +/- 2.3 months: P less than 0.02). CONCLUSIONS: Endocrine and exocrine testicular function can be normalized by both forms of therapy. Gonadotropin therapy has more side effects. Gonadotropin-releasing hormone leads to a higher testicular volume and a more rapid initiation of spermatogenesis compared with gonadotropin therapy.     

Endocrine assessment of relative reproductive age in normal eumenorrheic younger and older women across multiple cycles

OBJECTIVE: The aim of this study was to better characterize the ranges and intercycle variability for day 3 follicle-stimulating hormone, estradiol, and inhibin B levels in normal eumenorrheic women. STUDY DESIGN: Healthy eumenorrheic volunteers were recruited, of whom 27 women were 20 to 25 years old (peak reproductive age) and 36 women were 40 to 45 years old (study population). Blood samples were obtained on day 3 of two consecutive menstrual cycles. In some women, an additional blood sample on day 3 was obtained within 1 year. RESULTS: In normal women aged 20 to 25 years versus women aged 40 to 45 years, the day 3 follicle-stimulating hormone geometric mean is 5.6 IU/L (95% CI, 3.3-9.5 IU/L) versus 9.6 IU/L (95% CI, 3.8-23.8 IU/L), the day 3 estradiol geometric mean is 44.0 pg/mL (95% CI, 20.4-95.0 pg/mL) versus 52.4 pg/mL (95% CI, 22.4-122.8 pg/mL), and the day 3 inhibin B geometric mean is 100.4 pg/mL (95% CI, 51.7-195.0 pg/mL) versus 52.4 pg/mL (95% CI, 9.5-289.3 pg/mL). Furthermore, 22% of women in the older age group have a normal day 3 follicle-stimulating hormone and estradiol level in one cycle but an elevated value in a consecutive cycle (P=.008). CONCLUSION: In women of peak reproductive age, the upper limit of day 3 follicle-stimulating hormone and estradiol levels are 9.5 IU/L and 95.0 pg/mL, respectively, and the lower limit of day 3 inhibin B level is 51.7 pg/mL. If the initial day 3 follicle-stimulating hormone and estradiol levels in an older woman are normal, then a second measurement in a subsequent cycle should be obtained before counseling this woman regarding her reproductive potential.     

Correlation between maternal thyroid function tests and endothelin in preeclampsia-eclampsia.

OBJECTIVE: To investigate the relationship between results of maternal thyroid function tests and endothelin levels in preeclamptic or eclamptic women. METHODS: Thyroid hormones, TSH, and endothelin were measured in plasma or serum from 37 proteinuric, preeclamptic or eclamptic women and 20 normotensive, nonlaboring, pregnant women. Subjects were subdivided into four groups according to hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and birth weights of infants with respect to gestational age. RESULTS: A significant decrease in concentrations of total thyroxine (T4) (13.76+/-1.84 microg/dL versus 10.00+/-1.48 microg/dL, P < .05), total triiodothyronine (T3) (180.58+/-30.84 ng/dL versus 141.16+/-27.31 ng/dL, P < .01), free T4 (1.45+/-0.27 ng/dL versus 1.10+/-0.21 ng/dL, P < .01) and free T3 (3.32+/-0.56 pg/mL versus 2.41+/-0.60 pg/mL, P < .01) and a significant increase in TSH (1.55+/-0.89 microIU/mL versus 2.96 +/-1.07 microIU/mL, P < .05) and endothelin (2.31+/-0.61 pg/mL versus 6.11+/-1.41 pg/mL, P < .001) levels were observed in the preeclamptic-eclamptic group compared with the normotensive group. Also, women without HELLP syndrome and without small-for-gestational-age infants had elevated levels of thyroid hormones and decreased levels of TSH and endothelin compared with other subgroups, but stastical significance was reached only in total T4 (P < .05), TSH (P < .05), and endothelin (P < .001). Birth weights of infants born to preeclamptic or eclamptic women correlated positively with total T4 (P < .01) and total T3 (P < .01) and negatively with TSH (P < .01) levels. A more significant negative correlation was found in preeclamptic-eclamptics (P < .001) between birth weight and endothelin levels than in control subjects (P < .05). Endothelin levels in preeclamptic or eclamptic women correlated negatively with total T4 (P < .01), total T3 (P < .05), free T4 (P < .05), and free T3 (P < .05) and positively with TSH levels (P < .01) compared with control subjects. CONCLUSION: Moderate decreases in thyroid hormones with concomitant increases in TSH levels in maternal serum correlated with severity of preeclampsia or eclampsia and high levels of endothelin. Changes in results of thyroid function tests induced by preeclampsia or eclampsia might be consequences of the dysfunction in the hypothalamic-pituitary-thyroid axis, secondary to the disease itself.     

The effect of cabergoline on folicular microenviroment profile in patients with high risk of OHSS

Abstract

The aim of this study to evaluate the effect of cabergoline on follicular microenvironment by measuring follicular fluid (FF) insulin like growth hormone –I (IGF-I), antimullerian hormone (AMH), inhibin B and hepatocyte growth factor (HGF) levels in women with PCOS and high risk of ovarian hyperstimulation syndrome (OHSS). In this prospective cohort study, 41 women with PCOS undergoing controlled ovarian hyperstimulation for assisted reproduction and having the high risk factors for OHSS are included. The women in the study group (n?=?15) received cabergoline for OHSS prevention while the women in the control did not received any medications for OHSS prevention. FF samples were collected during oocyte pick-up procedure for all women were determined using commercially available ELISA kits. Concentrations of FF IGF-I, AMH, inhibin B and HGF were assessed. In the study group FF AMH (2.96?±?1.27 versus 1.91?±?0.64?ng/mL), Inhibin B (1339.47?±?198.56 versus 1200.09?±?133.64?pg/mL), HGF (5623.21?±?2411.09 versus 3787.42?±?2269.89?pg/mL) and IGF-I (298.60?±?37.80 versus 219.90?±?71.40?pg/mL) concentrations were significantly decreased compared with control group. Cabergolin prevents OHSS in high risk patients by disrupting FF hormone microenvironment.     

Gonadotropin-releasing hormone antagonist and metformin for treatment of polycystic ovary syndrome patients undergoing in vitro fertilization-embryo transfer.

AIM: The combination of gonadotropin-releasing hormone (GnRH) antagonist and gonadotropin represents a valid alternative to the classical protocol with GnRH agonist for ovulation induction in patients with polycystic ovary syndrome (PCOS). The use of metformin is of benefit to women with PCOS. The aim of the present study was to compare the stimulation characteristics and in vitro fertilization (IVF)-embryo transfer (ET) outcomes of the standard short GnRH antagonist protocol for ovarian stimulation with or without metformin. MATERIALS AND METHODS:We recruited 40 PCOS patients. The population studied was divided into two groups (A and B). Group A was pretreated for 2 months with metformin 1.5 g/day (Glucophage(R); Merck Pharm), and then stimulated with recombinant follicle-stimulating hormone (rFSH) 150 UI/day (Gonal F(R) 75 UI; Serono). GnRH antagonist, cetrorelix acetate 0.25 mg/day (Cetrotide(R); Serono), was started when the leading follicle reached 14 mm diameter on ultrasound scan. Group B was treated only with rFSH 150 UI/day and GnRH antagonist 0.25 mg/day when the leading follicle was >or=14 mm in diameter. RESULTS: In group A we found a statistically significant (p < 0.05) decrease in the number of ampoules of rFSH (A vs. B: 18+/-6 vs. 24+/-8) and estradiol levels (A vs. B: 2400+/-600 vs. 3370+/-900 pg/ml) (all values mean+/-standard deviation). Group A had significantly fewer cancelled cycles (A vs. B: 1 vs. 3; p < 0.05). The incidence of ovarian hyperstimulation syndrome was 5% in group A and 15% in group B (p < 0.05). In patients treated with metformin, the total number of follicles on the day of human chorionic gonadotropin treatment (23+/-1.2 vs. 33+/-2.6) was decreased with no change in the number of follicles >or=14 mm in diameter (A vs. B: 18+/-1.2 vs. 19+/-1.7). However, the mean number of mature oocytes (A vs. B: 8.4+/-1.5 vs. 5.0+/-1.5) was increased with metformin treatment (p < 0.05). No difference was found in the number of cleaved embryos (A vs. B: 2.5+/-0.5 vs. 2.2+/-0.3). CONCLUSIONS: The use of metformin with GnRH antagonist improves the outcome of ovarian stimulation in IVF-ET cycles in PCOS patients.     

Correlations between concentrations of interleukin-12 and interleukin-13 and lymphocyte subsets in the follicular fluid of women with and without polycystic ovary syndrome

OBJECTIVE: To investigate a possible correlation between interleukin-12 (IL-12) and IL-13 levels and lymphocyte subsets in the preovulatory follicles of patients with and without polycystic ovarian syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: University hospital. PATIENT(S): Seventy-eight infertile women undergoing IVF-embryo transfer. INTERVENTION(S): The subjects underwent blood sampling, ovum retrieval, and embryo transfer. MAIN OUTCOME MEASURES: Follicular fluid levels of T, androstenedione (A); IL-12, IL-13, activated T cells, T helper, and T-suppressor lymphocytes. RESULT(S): The level of IL-12 detected in follicular fluid (FF) was significantly lower in patients with PCOS than in normally ovulating women (mean: 1.47 +/- 0.3 pg/mL vs. 2.25 +/- 0.7 pg/mL, respectively); in contrast, FF IL-13 concentrations were significantly higher in the patients with PCOS than in the normally ovulating women (mean: 32.5 +/- 3.7 pg/mL vs. 19.6 +/- 2.5 pg/mL, respectively), as was the total number of activated T lymphocytes (11.5% +/- 1.5% vs. 4.8% +/- 0.4%). A significant correlation was observed between FF activated T-cell concentrations and FF IL-12, IL-13, T, and A levels. No significant differences were observed when these data were compared with embryological parameters. CONCLUSION(S): The present study shows significant differences in the correlation between FF IL-12 and IL-13 levels and T lymphocyte numbers in the subset of patients with PCOS as compared to normally ovulating women.     

Selective deficit of angiogenic growth factors characterises pregnancies complicated by pre-eclampsia.

OBJECTIVE: To compare serum levels of angiogenic growth factors vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and angiogenin in pre-eclamptic women and matched controls. DESIGN: Retrospective analysis of -70 degrees C stored serum of women who developed pre-eclampsia and matched controls. SETTING: Department of Gynaecology and Obstetrics, St Elisabeth Hospital, Cura?ao, Netherlands Antilles. SAMPLE: Thirty women with pre-eclampsia and 30 normotensive controls matched for age and gestation. RESULTS: VEGF and PIGF serum levels were significantly lower in pre-eclamptic pregnancies, compared with controls (VEGF 0.31 +/- 1.20 vs 18.30 +/- 24.97 pg/mL, P = 0.0004; PlGF 54.19 +/- 32.05 vs 497.95 +/- 340.51 pg/mL, P < 0.0001). Matched couple analysis showed VEGF serum concentrations to be lower in the majority of pre-eclamptic women and PlGF concentrations to be lower in all pre-eclamptic women. Angiogenin serum levels showed no statistical significant difference between pre-eclamptic pregnancies and controls (523.68 +/- 367.55 vs 670.41 +/- 251.54 ng/mL, P = 0.058), with matched couple analysis showing no clear pattern. CONCLUSIONS: Decreased serum levels of VEGF and PIGF characterise, and therefore seem to be of importance during (the development of), pre-eclampsia. This selective deficit of angiogenic growth factors might in part explain the shallow placentation found in this pregnancy complication.     

Changes in serum levels of heat shock protein 70 in preterm delivery and pre-eclampsia

AIM: The aim of this study was to investigate heat-shock protein (Hsp)70 as a novel marker to evaluate the curative effects of treatment for preterm delivery high-risk patients and pre-eclampsia. METHODS: After obtaining informed consent, serum samples were collected from 31 preterm delivery high-risk patients with a tocolysis index of three points or above (A), seven pre-eclampsia patients (P), 46 normal pregnant women (B), and seven non-pregnant women (C). Of the 31 preterm delivery high-risk patients, 15 had preterm delivery (Ap) and 16 had full-term delivery (Af). The levels of Hsp70 were measured using enzyme-linked immunosorbent assay. RESULTS: The Hsp70 levels in normal pregnant women were 8.6 +/- 1.9 ng/mL (first trimester), 5.5 +/- 1.0 ng/mL (second trimester) and 5.5 +/- 0.7 ng/mL (third trimester). There was no statistical difference in the Hsp70 levels between the three trimesters. The mean Hsp70 levels were 21.9 +/- 5.3 ng/mL (A), 35.3 +/- 9.6 ng/mL (Ap), 9.4 +/- 2.2 ng/mL (Af), 24.4 +/- 3.6 ng/mL (P), 6.1 +/- 0.6 ng/mL (B), and 2.4 +/- 0.6 ng/mL (C). Group Ap had significantly higher Hsp70 levels than group Af (P = 0.0112) and group B (P <0.0001). The duration of pregnancy after hospitalization for group Ap was significantly shorter than that for group Af (P=0.0088) and group B (P <0.0001). Group P also had significantly higher Hsp70 levels than group B (P <0.0001). CONCLUSION: Because Hsp70 levels were particularly high in treatment-resistant preterm delivery cases, Hsp70 may prove to be a useful marker for evaluating the curative effects of treatment for preterm delivery.     

Preferred treatment of infertile women older than 37 years of age who demonstrate premature luteinization in the first evaluation cycle

OBJECTIVE: To evaluate the efficacy of various treatments in abolishing premature luteinization in infertile women over 37 years old who are undergoing ovulation induction. DESIGN: Prospective, nonrandomized study. SETTING: Tertiary care medical clinic. PATIENT(S): Seventeen infertile women >37 years old in whom premature luteinization was detected during their evaluation (pretreatment) cycle. INTERVENTION(S): The patients underwent three consecutive treatment cycles with clomiphene citrate (group A), hMG (group B), and a GnRH agonist plus hMG (group C). MAIN OUTCOME MEASURE(S): Premature luteinization, defined as a progesterone/E2 ratio of >1 on the day of hCG administration. RESULT(S): Fifteen (88%) of the 17 patients in group A and 13 (76%) of the 17 patients in group B demonstrated premature luteinization. In contrast, only 1 (6%) of the 17 patients in group C had a progesterone/E2 ratio of >1 on the day of hCG administration. The mean (+/-SD) E2 level on the day of hCG administration was significantly higher in group C (1.236 +/- 772.7 pg/mL) than in group A (214.02 +/- 104.46 pg/mL) or group B (412.5 +/- 337 pg/mL). CONCLUSION(S): Pituitary desensitization with a GnRH agonist in conjunction with hMG may be of benefit for older infertile women who demonstrate early luteinization in their first evaluation cycle.     

Management of women with polycystic ovary syndrome who experienced premature luteinization during clomiphene citrate treatment

OBJECTIVE: To determine the preferred treatment modality in patients with PCOS who experienced premature luteinization during CC treatment. DESIGN: Prospective randomized study. SETTING: Tertiary medical center. PATIENTS: Twenty-two infertile women with PCOS demonstrating premature luteinization during at least two consecutive CC cycles. INTERVENTIONS: Randomized induction of ovulation either with FSH alone or with GnRH agonist combined with FSH for a single treatment cycle. MAIN OUTCOME MEASURES: Premature luteinization was defined as serum progesterone >1.5 ng/mL before hCG administration. RESULTS: Premature luteinization occurred in eight of the 10 patients (80%) in group A and in two of the 12 patients in group B (16.6%). This result corresponds to the higher mean (+/-SD) progesterone level present in group A patients as compared to those in group B (2.0 +/- 1.2 ng/mL vs. 1.2 +/- 0.6 ng/mL, P=0.03). No pregnancies were achieved in group A, whereas the pregnancy rate per cycle observed in group B was 33.3% (4/12). On the day of hCG administration, the maximum mean (+/-SD) estradiol level was significantly lower (P<0.0001) in group A (210.6 +/- 37.9 pg/mL) than in group B (600.3 +/- 253.8 pg/mL). The treatment duration and the number of FSH ampules used did not differ between the groups.Conclusions: Pituitary desensitization with GnRH analog in combination with FSH is superior to FSH-only treatment in PCOS patients who demonstrate premature luteinization during CC treatment.     

Reducing the dose of human chorionic gonadotropin in high responders does not affect the outcomes of in vitro fertilization

OBJECTIVE: The lowest effective hCG dose in high responders during IVF-embryo transfer (ET) has not been established. This study was performed to confirm that a dose of 3,300 IU is sufficient to provide adequate oocyte maturation and fertilization. DESIGN: Retrospective review of IVF clinical data. SETTING: Infertility center at a tertiary care university. PATIENT(S): Ninety-four IVF cycles were analyzed from high responders based on peak E(2) levels. Demographics were compared including age, diagnosis, and stimulation protocol. INTERVENTION(S): On the day of hCG administration, if E(2) levels were >/=2,500 but <4,000 pg/mL, patients received 5,000 IU (group A). For levels between 4,000 pg/mL and 5,500 IU pg/mL, they received 3,300 IU (group B). MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, proportion of mature oocytes, fertilization rates, chemical and clinical pregnancy rates (PR). The incidence and severity of ovarian hyperstimulation syndrome (OHSS) was also analyzed. RESULT(S): Mean ages were 35.4 +/- 0.7 and 33.2 +/- 0.7 for groups A and B, respectively. Peak E(2) levels differed significantly (2,907 +/- 76 vs. 4,260 +/- 129 pg/mL), as well as the mean number of eggs retrieved (15.9 +/- 0.9 vs. 20.3 +/- 1.2). Proportion of mature eggs (81.6% vs. 81.9%), fertilization rate (70.5% vs. 68.7%), chemical PR (58.7% vs. 58.7%), and clinical PR (50.0% vs. 43.5%) were similar. There was no difference in the incidence of mild, moderate, or severe OHSS. CONCLUSION(S): A reduced hCG dose of 3,300 IU results in a similar proportion of mature eggs, similar fertilization rates, and similar PRs compared to 5,000 IU. Reducing the dose of hCG does not eliminate the risk of OHSS in a high-risk group.     

Prostacyclin and thromboxane levels in women with severe preeclampsia undergoing magnesium sulfate therapy during antepartum and postpartum periods.

OBJECTIVE: To study effects of magnesium sulfate (MgSO(4)) on prostacyclin (PGI(2)) and thromboxane A(2) (TXA(2)) levels in women with severe preeclampsia during antepartum and postpartum periods. METHODS: Women with severe preeclampsia were randomized into two groups. Patients in Group A were continuously infused with MgSO(4) for 24 hours postpartum. In Group B, MgSO(4) administration was discontinued when urinary output was of > or =100 ml/hr for 2 consecutive hours. Patient demographic data were collected. Venous blood was drawn at time of MgSO(4) administration and 24 hours after delivery. Plasma levels of 6-keto-PGF1alpha and TXB(2), stable metabolites of PGI(2) and TXA(2), were measured by enzyme-linked immunosorbent assay (ELISA). Data are presented as mean +/- SE, and analyzed by paired t-test. RESULTS: A total of 50 patients were recruited, with 27 in Group A and 23 in Group B. There were no statistical differences for demographic data between the two groups with regards to maternal age; gestational age; systolic and diastolic blood pressures at admission, 12 hours postpartum, and 24 hours postpartum; and mode of delivery. Platelet counts were all within the normal range at the time of enrollment. MgSO(4) was administered for an average of 10 hours postpartum in Group B. Maternal blood pressures returned to normal or close to normal levels in both groups at 24 hours postpartum. 6-keto PGF1alpha levels were significantly decreased 24 hours after delivery compared with the levels at enrollment in both groups, (Group A: 98 +/- 13 vs. 180 +/- 28 pg/mL; Group B: 142 + 17 vs. 194 +/- 31 pg/mL, p < 0.05, respectively). However, there was no difference detected between the two groups. TXB(2) levels were not different between group A and Group B at the time of enrollment, 38 +/- 9 vs. 33 +/- 8 pg/mL, and 24 hours postpartum, 26 +/- 5 vs. 25 +/- 3 pg/mL, respectively. CONCLUSIONS: Administration of MgSO(4) does not affect prostacyclin and thromboxane levels in the maternal circulation in women with preeclampsia during antepartum and postpartum periods. We speculate that a higher level of prostacyclin before delivery may reflect compensatory effects of this vasodilator to offset increased maternal blood pressure during pregnancy.     

Lower levels of inhibin A and pro-alphaC during the luteal phase after triggering oocyte maturation with a gonadotropin-releasing hormone agonist versus human chorionic gonadotropin

OBJECTIVE: To investigate the effect of triggering oocyte maturation with GnRH agonist on corpus luteum function by measuring luteal phase levels of inhibin A and pro-alphaC. DESIGN: Prospective randomized trial. SETTING: In vitro fertilization (IVF) program at a university hospital. PATIENT(S): Infertile women undergoing IVF-ET treatment. INTERVENTION(S): Controlled ovarian hyperstimulation with FSH and GnRH antagonist, triggering of final oocyte maturation with either hCG (n = 8) or GnRH agonist (n = 8), IVF-ET, and collection of blood samples every 2-3 days during the luteal phase. MEASUREMENTS AND MAIN RESULTS: Luteal phase serum levels of inhibin A and pro-alphaC, P, and E(2). RESULT(S): Levels of inhibin A, pro-alphaC, estrogen, and P were significantly lower from day 4 to day 14 after triggering final oocyte maturation by GnRH agonist compared with hCG. Maximal luteal serum inhibin A and pro-alphaC levels were 91.5 +/- 23.6 and 184.1 +/- 23.5 pg/mL in the GnRH agonist-treated women compared with 464.7 +/- 209.1 and 7,351.6 +/- 934.3 pg/mL in women treated with hCG. CONCLUSION(S): Triggering final oocyte maturation with GnRH agonist instead of hCG in IVF cycles dramatically decreases luteal levels of inhibins, reflecting significant inhibition of the corpus luteum function. This effect may explain, at least in part, the mechanism of ovarian hyperstimulation syndrome prevention by the use of GnRH agonist.