Low blastocyst formation rates in day-2 fertilized oocytes.

PURPOSE: To examine the blastocyst formation rates of day-2 fertilized oocytes. METHODS: A retrospective study of the outcomes/blastocyst formation of day-2 fertilized oocytes was undertaken. RESULTS: Fertilization rates of day-1 and -2 oocytes by intra-cytoplasmic sperm injection were similar. The development frequencies to four cells were similar. However, the blastulation rates were significantly lower from the day-2 fertilized eggs. The fertilization rates from day-2 conventional in vitro fertilization reinsemination were lower than the fertilization rates of day-1 oocytes. The blastulation rates from day-2 fertilized eggs were also lower than the rates from day-1 fertilized eggs in the in vitro fertilization group. CONCLUSIONS: Fertilization is not a good indicator to predict the viability of fertilized oocytes. Day-2 fertilized oocytes had significantly lower blastocyst formation rates than the rates from day-1 fertilized oocytes.

Optimal insemination concentration for human in vitro fertilization (IVF).

This study is looking for optimal insemination concentration to achieve optimal IVF pregnancy. Sperm lateral head displacement, total abnormal form, Kruger morphology and index, hypo-osmotic swelling test were significantly correlated with fertilization in vitro. Based on those parameters, logistic regression models were formulated. These models predict either fertilization probability provided with an insemination concentration or insemination concentration assigned with a definite fertilization percentage. These models showed that increased insemination concentration can increase fertilization percentage. The increase of fertilization didn't compensate for the significant loss of implantation by increasing insemination concentration.

Blastocyst formation is a good indicator for attainment of assisted reproduction.

Blastocyst formation is a late stage of embryogenesis before implantation. The examination for the percentage of blastocyst formation (PBF) can predict the viability/pregnancy of the assisted reproduction trials. The PBF significantly correlates with age and pregnancy. The PBF is significantly lower in the intracytoplasmic sperm injection (ICSI) treatment than the conventional IVF treatment. The zygotes from immature oocytes give less blastocyst formation than the zygotes from mature oocytes. One pronucleus "zygotes" have significantly less chance to blastocyst than the normal 2 pronuclei zygotes. A mathematical model is proposed, verified, and predicts the hatching/hatched is the rate limiting step for the outcome of pregnancy.

Short-term Lupron or danazol therapy for pelvic endometriosis.

OBJECTIVE: To compare the efficacy of a 3-month trial of leuprolide acetate (LA; Lupron; TAP Pharmaceuticals, Deerfield, IL) versus danazol (Danocrine; Scenofi Winthrup Pharmaceuticals, New York, NY) therapy on laparoscopically proven endometriosis. DESIGN: Endometriosis severity was assessed at the time of laparoscopy and patients were randomized to receive 0.1 mg SC LA (n = 22) or 800 mg danazol orally (n = 18) daily for 3 months. A second laparoscopy and/or laparotomy was performed to assess the change in the extent of endometriosis and for surgical therapy. SETTING: Private practice at a university-affiliated hospital. PATIENTS: Forty patients with mild, moderate, or severe endometriosis. Ten patients were excluded. INTERVENTION: Three-month treatment randomly assigned to either LA or danazol. MAIN OUTCOME MEASURES: Prospective measurement of American Fertility Society endometriosis scores and size of ovarian endometriomata before and after therapy via laparoscopy. RESULTS: The mean endometriosis score including adhesions decreased significantly from 36 +/- 4.9 to 29 +/- 5.0 (mean +/- SEM) with LA and from 34 +/- 6.4 to 29 +/- 6.5 with danazol. The mean laparoscopic endometriosis score not including adhesions decreased from 27 +/- 3.5 to 22 +/- 3.4 with LA and 22 +/- 3.5 to 19 +/- 3.1 with danazol. Seven of 18 (39%) endometriomata responded to LA and 6 of 15 (40%) endometriomata responded to danazol. CONCLUSION: We conclude that both danazol and LA will reduce endometriosis scores after a 3-month course of therapy. Larger clinical trials are needed to compare short courses of therapy with the more established 6-month trials. A 3-month versus a 6-month course of therapy offers obvious benefits including decreased cost and decreased side effects.

Insulin resistance improves in hyperandrogenic women treated with Lupron.

OBJECTIVE: To examine if changes in insulin sensitivity and glucose effectiveness in women with polycystic ovarian disease (PCOD) occurred after ovarian androgen suppression with a GnRH agonist, leuprolide acetate (LA, Lupron; TAP Pharmaceuticals, Deerfield, IL) using the minimal model method. DESIGN: Twelve patients with PCOD were tested in the untreated state (baseline) and after 6 weeks of LA treatment. Subjects were divided into two groups based on the degree of impairment of their baseline insulin sensitivity index (SI; (min-1) (microU/mL-1): mild insulin resistance (SI > 1) or severe insulin resistance (SI < 1). RESULTS: In all patients, serum T was significantly decreased from elevated baseline levels to normal female concentrations after 6 weeks of LA therapy. Insulin sensitivity in PCOD patients with mild insulin resistance significantly improved from baseline after 6 weeks of LA therapy, whereas no change in SI on LA therapy was seen in PCOD women with severe insulin resistance. Glucose utilization independent of increased insulin secretion did not change as a function of LA treatment in either group. CONCLUSION: These findings indicate a significant improvement in SI in mildly insulin-resistant women with PCOD after suppression of ovarian function with LA treatment.

Does estradiol treatment normalize the hypothalamic-pituitary-adrenal axis in streptozotocin-induced ovariectomized diabetic female rats?

We recently found circulating corticosterone (CS) levels to be significantly lower in diabetic female rats as compared with proestrous control animals. This reduction in CS was correlated with the hypoestrogenic state of the diabetic female. It was the purpose of this study to evaluate basal and corticotropin releasing hormone (CRH)-stimulated CS secretion in ovariectomized (OVX) control (C) and streptozotocin-induced diabetic (D) rats given blank, 5 mcg and 20 mcg estradiol (E2) implants to determine if adrenal CS secretion in the diabetic is normalized by E2 treatment. After 3 weeks of diabetes, pituitary-adrenal function was assessed in rats from each group with a CRH stimulation test. The remaining rats were sacrificed for determination of CS, E2, testosterone and fructosamine in serum. Suppressed CS secretion in OVX female diabetic rats was partially restored with E2 therapy. Basal CS levels were significantly higher in 20 mcg E2 treated C and D rats compared with OVX rats. However, C rats had significantly higher basal CS compared with D rats in similarly E2 treated groups. The CS response to CRH stimulation was not different between OVX female diabetic and control rats. Estrogen enhanced the CS response to CRH stimulation in control animals but not in diabetic animals suggesting altered estrogen action at the pituitary level in diabetic animals.

Intravenous glucose tolerance test-derived insulin sensitivity changes during the menstrual cycle.

Using glucose tolerance tests or a glucose clamp some studies report impaired insulin sensitivity during the luteal phase of the menstrual cycle, while others find no change in insulin sensitivity. Tissue sensitivity to insulin and glucose effectiveness can be estimated using the minimal model analysis of an iv glucose tolerance test (IVGTT), but this method has never been applied to evaluate the impact of the menstrual cycle on these parameters. We, therefore, studied eight cycling women using tolbutamide-modified IVGTTs during three different phases of the same menstrual cycle: early follicular, midcycle, and midluteal. Insulin sensitivity (SI) and glucose effectiveness were derived using insulin and glucose levels obtained from tolbutamide-modified IVGTTs and analyzed with the minimal model computer program. The mean SI (x10(-4)/min.microU/mL) decreased in a stepwise fashion from the follicular level of 6.20 +/- 0.91 to a midcycle level of 4.95 +/- 0.73 and was lowest in the luteal phase (3.20 +/- 0.25; P less than 0.007). No change in glucose effectiveness occurred as a function of the menstrual cycle. These findings indicate a significant decrease in insulin sensitivity in the luteal phase of the normal menstrual cycle, but no significant change at midcycle.

Androgen responses to acutely increased endogenous insulin levels in hyperandrogenic and normal cycling women.

We examined androgen responses in hyperandrogenic (polycystic ovarian disease [PCOD]) and normal women after an acute endogenous insulin elevation. Standard intravenous glucose tolerance tests (IVGTTs), modified to include a tolbutamide injection 20 minutes after IVGTTs, were performed. Polycystic ovarian disease patients were studied in the untreated state, after 6 weeks of ovarian androgen suppression with leuprolide acetate, after a 6-week rest period, and after 6 weeks of antiandrogen therapy with spironolactone. Normal menstruating women were studied during the early follicular, midcycle, and luteal phases of a single cycle. An acute rise in insulin did not alter serum testosterone or androstenedione levels in PCOD or normal women. A significant rise in dehydroepiandrosterone sulfate after modified IVGTTs was found in both hyperandrogenic and normal cycling women. Although these results are not supportive of the theory that insulin acts on the ovary to stimulate androgen production, they may be because of the short time course of insulin elevation that occurs during an IVGTT.

The hypothalamic-pituitary axis of streptozotocin-induced diabetic female rats is not normalized by estradiol replacement.

Studies in diabetic rats have found abnormalities at the hypothalamic, pituitary, and/or ovarian level but have not controlled for changes in estrogen levels induced by diabetes. The purpose of this investigation was to study the effect of diabetes on the hypothalamic-pituitary axis in ovariectomized rats treated with estradiol (E2). Ovariectomized 60 day old female rats were assigned to control (C, n = 42), diabetic (D, n = 47) or insulin-treated diabetic (DI, n = 16) groups. Diabetes was induced with an injection of streptozotocin in the D and DI groups. In the C, D, and DI groups, estrogen was replaced by implanting blank, 5 micrograms or 20 micrograms E2 pellets sc. Pituitary LH responsiveness to GnRH was assessed in C and D animals. Anterior hypothalamic and midhypothalamic concentrations of proGnRH and GnRH, pituitary LH and FSH and serum levels of LH, and E2 were measured by RIA. Anterior hypothalamic proGnRH concentrations were decreased in diabetic rats treated with 5 micrograms E2 compared to 5 micrograms E2 control animals (P less than 0.05). Midhypothalamic GnRH concentrations were also reduced in D vs. C animals despite comparable estrogen therapy (P less than 0.004). GnRH-stimulated LH levels were greater in E2-treated diabetic females than in similarly treated control rats (P less than 0.001). D and DI animals were more sensitive than controls to the inhibitory effect of estrogen on basal LH levels. Pituitary LH and FSH content was lower in 20 micrograms E2-replaced animals but was not influenced by the diabetic state. These data demonstrate a diabetes-induced decrease in hypothalamic proGnRH and GnRH concentration which is not corrected with E2 replacement. The hyper-responsiveness of the diabetic rat pituitary to GnRH also suggests a chronic lack of GnRH stimulation from the hypothalamus but a continued ability of the pituitary to respond to GnRH.

Diabetes-induced alterations of reproductive and adrenal function in the female rat.

Diabetes interferes with reproductive function in laboratory animals. Previous studies in female diabetic rats have not resolved if the reproductive abnormalities observed are at the hypothalamic, pituitary and/or ovarian level. The interaction of the gonadal and adrenal axes has not been studied in the diabetic female rat. The purpose of this study is twofold: first, to determine the level of dysfunction in the hypothalamic-pituitary axis caused by diabetes in the adult female rat controlling for stage of the estrous cycle, and, second, to evaluate basal corticosterone secretion in female diabetic rats. Sixty cycling 40-day-old female rats were randomly assigned to 3 groups; control (n = 32), diabetic (n = 14), and diabetic insulin-replaced animals (n = 14). The level of hyperglycemia in each group was documented by glycosylated hemoglobin levels and biweekly blood glucoses. Three weeks after induction of diabetes, pituitary luteinizing hormone (LH) responsiveness following an i.v. injection of gonadotropin-releasing hormone (GnRH) was assessed in representative diestrous rats from each group. All animals were sacrificed in either diestrus or proestrus for determination of GnRH concentration in the hypothalamus, LH and follicle-stimulating hormone (FSH) content in pituitary and LH, FSH, estradiol and corticosterone in serum. Uterine weight to body weight ratios (a bioassay for estrogen) were also calculated. Hypothalamic GnRH concentration was significantly lower in diabetic versus control diestrous rats. Basal pituitary and serum gonadotropin levels were not different between any groups. GnRH-stimulated serum LH levels were higher in diabetic vs. control and diabetic insulin-treated animals. LH surges occurred in the control and diabetic insulin-replaced but not the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical treatment of symptomatic colorectal endometriosis.

The approach to the treatment of bowel endometriosis has varied greatly. In this paper we present 77 consecutive patients with deep colorectal endometriosis treated with a full-thickness resection. Gynecologic procedures included conservative laparotomies for preserving fertility (39 patients); hysterectomy with bilateral salpingo-oophorectomy (29 patients); bilateral salpingo-oophorectomy (2 patients); left salpingo-oophorectomy (1 patient) and resection of pelvic endometriosis in patients with previous ablative surgery (6 patients). A low anterior bowel resection was performed in 68 patients (88.3%); a disc excision of the anterior rectal wall in 5 (6.5%); sigmoid resection in 3 (3.9%), and partial cecal resection in 1 (1.3%). The postoperative febrile morbidity was 10.4%, with no apparent anastomotic leaks. Of 33 patients who attempted to conceive postoperatively, 13 achieved a term pregnancy (39.4%). Complete relief of pelvic symptoms was obtained in 38 patients (49.4%); improvement in 30 (39%); no improvement in 8 (10.4%); and worsening of symptoms in 1 (1.2%). There has been no recurrence of symptomatic bowel endometriosis during 1 to 9 years of follow-up. Full-thickness resection of the colon for the treatment of deep bowel endometriosis is a safe procedure with low morbidity, good postoperative relief of symptoms, and favorable pregnancy rates.

The effect of ovarian function on insulin-like growth factor I plasma levels and hepatic IGF-I mRNA levels in diabetic rats treated with insulin.

When insulin was administered to streptozotocin-induced diabetic female rats, the percentage of glycohemoglobin, growth rate, ovulatory cycle, uterus to body weight ratio, and insulin-like growth factor (IGF-I) level returned to near normal. In untreated diabetic rats there were no normal estrous cycles, and hepatic IGF-I mRNA (7.94 +/- 1.02 O.D. units per micrograms total RNA) levels were significantly lower than the control or insulin-treated groups in proestrus (16.47 +/- 0.91 and 17.15 +/- 1.84, respectively). Insulin therapy restored the hypothalamic-pituitary-ovarian axis with the reinstitution of normal estrous cycles. Plasma IGF-I levels were highest in non-diabetic proestrous animals (277 +/- 36.9 ng/ml), significantly higher than IGF-I levels in insulin-treated diabetic rats in diestrus (174 +/- 23.1 ng/ml), non-diabetic diestrus rats (165 +/- 18.4 ng/ml) and untreated diabetic rats (135 +/- 19.7 ng/ml). Plasma IGF-I levels were elevated in insulin-treated diabetic rats in proestrus (221 +/- 78.3 ng/ml), however this was not significantly different from any other group. The increases observed in plasma IGF-I and hepatic IGF-I mRNA after insulin therapy correlate with the normalization of sex hormone secretion. Though this study does not prove a causal relationship between restoration of ovarian function and normalization of circulating IGF-I levels, a relationship has been established, as evidenced by higher levels of IGF-I in both the control and insulin-treated diabetic proestrous groups when compared to the diestrus groups.