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It has been reported that oestradiol may play a role in the production of leptin from adipocytes. To investigate this relationship further, nine normally ovulating women were studied during two menstrual cycles, i.e. an untreated spontaneous cycle and a cycle treated with follicle stimulating hormone (FSH) from cycle day 2 until the day of human chorionic gonadotrophin (HCG) injection. Serum leptin values on cycle day 2 did not differ significantly between the spontaneous and the FSH cycles. In the spontaneous cycles, leptin values declined gradually and significantly up to day 7 and then increased progressively up to the day of luteinizing hormone (LH) surge onset, at which point they achieved the highest values. In the FSH cycles, serum leptin values increased gradually and significantly up to day 6, remaining stable thereafter, and were in the midfollicular phase significantly higher than in the spontaneous cycles. Significant positive correlations were found between mean values of leptin and mean values of oestradiol during the second half of the follicular phase in the spontaneous cycles and during the first half in the FSH cycles. A significant negative correlation was found between these two parameters in the spontaneous cycles during the first half of the follicular phase. Serum leptin levels were significantly higher in the midluteal than in the follicular phase in both cycles. These results demonstrate for the first time significant changes in leptin values during the follicular phase of the human menstrual cycle and a significant increase during superovulation induction with FSH. It is suggested that oestradiol may be involved in the regulation of leptin production in women. Hum Reprod

Mature mammalian spermatozoa have a compact and stable nuclear structure conferred by protamines instead of histones, which are present in all other cellular types. Chromomycin A3 (CMA3) is a useful tool for the detection of protamine deficiency in sperm chromatin. The purpose of this study was to correlate the percentage of spermatozoa staining positively for CMA3 with sperm parameters and in-vitro fertilization of human oocytes. Spermatozoa were collected from 56 fertile and 18 infertile men, and washed twice in PBS, fixed in two changes of methanol : acetic acid (3 : 1 v : v) spread on rinsed slides treated with APES and dried. Twenty-four of the semen samples were subjected to both Percoll and swim-up, and were stained subsequently with CMA3. CMA3-stained spermatozoa were expressed as a percentage in a count of 200 spermatozoa. A substantial variation in the percentage of CMA3-stained cells was observed in ejaculated human spermatozoa, varying between 8% and 77%. A strong negative correlation (r = -0.64, p < 0.001) was found between sperm count and the percentage of CMA3-stained spermatozoa. No correlation was found between CMA3-stained spermatozoa and their motility, while excessive sperm morphological abnormalities were related positively to CMA3-staining. Spermatozoa in samples exhibiting low (8-62%) CMA3-staining had significantly higher fertilizing rates in vitro than did samples exhibiting high (49-77%) CMA3-staining. The mean percentage of CMA3-stained spermatozoa after swim-up or Percoll preparation (26% vs 31%) did not differ significantly. These results demonstrate a close relationship between CMA3-staining, fertilization and sperm count, and suggest potential application of this marker for the prediction of sperm quality and fertilizing capacity.

Gonadotrophin-surge-attenuating factor (GnSAF) is a putative nonsteroidal ovarian factor that is produced by FSH and that attenuates the LH surge in superovulated women. To study further the role of FSH in the production of GnSAF, 12 normally ovulating women were divided into two groups and investigated during two cycles: a cycle treated with placebo (control) and a cycle treated with FSH. In group 1 (n = 6), placebo (2 ml 0.9% normal saline) or FSH (450 iu) was injected i.m. on day 2 of the cycle (09:00 h). In group 2 (n = 6), placebo (2 ml 0.9% normal saline) or FSH (225 iu) was injected on the day (09:00 h) on which the dominant follicle was 14-15 mm in diameter, as measured by ultrasound (i.e. after the pituitary had been primed by endogenous oestrogen for several days). The response of LH over 30 min (delta LH) to an injection of 10 micrograms LHRH i.v. (bioassay for GnSAF in vivo) was investigated once a day in group 1, and 4, 8, 12 and 24 h after the injection of placebo or FSH in group 2. In group 1, delta LH was significantly attenuated 12 h after treatment with FSH compared with the control cycles, while serum oestradiol concentrations increased 24 h after the injection of FSH. The decrease in delta LH lasted for the period when the FSH concentration was increased (3 days). A significant decrease in the basal concentration of LH was correlated with the increase in the oestradiol concentration.(ABSTRACT TRUNCATED AT 250 WORDS) J Reprod Fertil

Gonadotrophin surge-attenuating factor (GnSAF) is a putative non-steroidal ovarian factor which attenuates the luteinizing hormone (LH) surge in superovulated women through the reduction of the pituitary response to gonadotrophin-releasing hormone (GnRH). The mechanism of action of GnSAF on gonadotrophin secretion was further studied by investigating six normally ovulating women in two cycles--a spontaneous and a follicle-stimulating hormone (FSH)-treated cycle. The response of the pituitary to five consecutive pulses of GnRH was investigated in late follicular phase (follicle size 15 mm) of both cycles. GnRH pulses, 10 micrograms each, were injected i.v. every 2 h and LH was measured in blood samples taken before and 30, 60 and 120 min after each pulse. FSH was injected daily at the fixed dose of 225 IU starting on cycle day 2. Peak values of LH increment occurred 30 min after each pulse. However, maximal LH increment occurred in both cycles after the second GnRH dose. In the FSH cycles the response of LH to the first three pulses was significantly attenuated compared with the spontaneous cycles, while the response to the fourth and fifth pulses was similar in the two cycles. In both cycles, LH increment 30 min post GnRH (net increase above the previous value) was similar after the fourth and fifth pulses. Serum concentrations of oestradiol and immunoreactive inhibin, although higher in the FSH cycles, remained stable throughout the GnRH experimental period in both cycles. These results demonstrate that multiple submaximal doses of GnRH can override the attenuating effect of GnSAF on LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS) Hum Reprod

Int J Gynaecol Obstet

To investigate the mechanism of blockage of the luteinizing hormone (LH) surge in superovulated women, six normally ovulating women were studied in three cycles: a spontaneous cycle treated with exogenous oestrogen (oestradiol benzoate cycle), a cycle treated with follicle stimulating hormone (FSH; 225 IU/day; FSH cycle) and a cycle treated with FSH plus exogenous oestrogen (FSH + oestradiol benzoate cycle). Oestradiol benzoate was injected i.m. on cycle days 4 (0800 and 2000 h), 5 (0800 h) and 6 (0800 h) at doses of 0.5, 1.0, 2.0 and 2.5 mg respectively to achieve supraphysiological levels of serum oestradiol. Exogenous oestrogen (supraphysiological oestradiol levels) induced an LH surge in all six women in the oestradiol benzoate cycles, but failed to stimulate an LH surge in three of the six patients during treatment with FSH. In three patients treated with FSH, an LH surge was stimulated both by supraphysiological (FSH + oestradiol benzoate cycles) and 'high normal' oestradiol levels (FSH cycles), while in three patients treated with FSH only, the LH surge was blocked, although the threshold level for the positive feedback effect had been exceeded by cycle day 9. We conclude that in women, supraphysiological concentrations of oestradiol exert a positive feedback effect on LH secretion. It is suggested that the occurrence of an LH surge in cycles superovulated with FSH is not dependent on serum oestradiol concentrations, but mainly on the strength of ovarian inhibitory substances. Hum Reprod

The objective of this randomized prospective study was to compare the efficacy of 50 mcg vaginal misoprostol and 3 mg dinoprostone, administered every nine hours for a maximum of three doses, for elective induction of labor in a specific cohort of nulliparous women with an unfavorable cervix and more than 40 weeks of gestation. One hundred and sixty-three pregnant women with more than 285 days of gestation were recruited and analyzed. The main outcome measures were time from induction to delivery and incidence of vaginal delivery within 12 and 24 hours. Admission rate to the neonatal intensive care unit within 24 hours post delivery was a secondary outcome. The induction-delivery interval was significantly lower in the misoprostol group than in the dinoprostone group (11.9 h vs. 15.5 h, p 0.05) but with the disadvantage of higher abnormal fetal heart rate (FHR) tracings (22.5% vs. 12%, p > 0.05). From the misoprostol group more neonates were admitted to the intensive neonatal unit, than from the dinoprostone group (13.5% vs. 4.8%, p > 0.05). One woman had an unexplained stillbirth following the administration of one dose of dinoprostone. Vaginal misoprostol, compared with dinoprostone in the regimens used, is more effective in elective inductions of labor beyond 40 weeks of gestation. Nevertheless, this is at the expense of more abnormal FHR tracings and more admissions to the neonatal unit, indicating that the faster approach is not necessarily the better approach to childbirth.

BACKGROUND: To investigate the natural history of HPV infection of the uterine cervix following a 10-year prospective observational study. PATIENTS AND METHODS: Three hundred and thirty women with cytological and colposcopic features of HPV infection +/- CIN 1 were recruited into the study. These women were followed up for a period of 10 years, during which time they had repeated colposcopic assessments and cytological monitoring Those women with evidence of high-grade disease at any stage of follow-up were treated by Large Loop excision of the transformation zone (LLETZ) and excluded from the study. At the end of the surveillance period, 179 women with evidence of persistent HPV infection alone or in conjunction with low-grade disease underwent a shallow diagnostic LLETZ. In total, 51 women defaulted from follow-up. RESULTS: Thirty-three per cent of the women with cytological and colposcopic features suggestive of persistent HPV infection alone during the 10-year follow-up period had histological evidence of CIN at the end of the study. Two thirds of this disease was graded as CIN 2 or 3. Nineteen per cent of the women with cytological and colposcopic features suggestive of persistent HPV infection and CIN 1 actually had high-grade CIN at histology (CIN 2 and 3). Only 6.1% of the study population had normal histological findings. CONCLUSION: The finding that a relatively large percentage of high-grade lesions might have been masked for anything up to a decade by a low-grade phenotype, coupled with the worrying percentage of defaulters from follow-up, indicate that an early decision for intervention (diagnostic and/or therapeutic) may be appropriate if a low-grade abnormality persists after a short surveillance period. Anticancer Research