Luteinizing hormone response to gonadotrophin-releasing hormone in normal women undergoing ovulation induction with urinary or recombinant follicle stimulating hormone

Oestradiol enhances pituitary sensitivity to gonadotrophin-releasing hormone (GnRH) in normal women, while in women undergoing ovulation induction the putative factor gonadotrophin surge attenuating factor (GnSAF) attenuates the response of luteinizing hormone (LH) to GnRH. To study the relationships between oestradiol and GnSAF during ovulation induction, 15 normally ovulating women were investigated in an untreated spontaneous cycle (control, first cycle), in a cycle treated with daily i.m. injections of 225 IU urinary follicle-stimulating hormone (FSH) (Metrodin HP, uFSH cycle) and in a cycle treated with daily s.c. injections of 225 IU recombinant FSH (Gonal-F, rFSH cycle). Treatment with FSH started on cycle day 2. The women during the second and third cycle were allocated to the two treatments in an alternate way. One woman who became pregnant during the first treatment cycle (rFSH) was excluded from the study. In all cycles, an i.v. injection of 10 microg GnRH was given to the women (n = 14) daily from days 2-7 as well as from the day on which the leading follicle was 14 mm in diameter (day V) until mid-cycle (n = 7). The response of LH to GnRH at 30 min (deltaLH), representing pituitary sensitivity, was calculated. In the spontaneous (control) cycles, deltaLH values increased significantly only during the late follicular phase, i.e. from day V to mid-cycle, at which time they were correlated significantly with serum oestradiol values (r = 0.554, P < 0.01). Initially during the early follicular phase in the uFSH and the rFSH cycles, deltaLH values showed a significant decline which was not related to oestradiol (increased GnSAF bioactivity). Then, deltaLH values increased significantly on cycle day 7 and further on day v with no change thereafter up to mid-cycle. On these two days, deltaLH values were correlated significantly with serum oestradiol values (r = 0.587 and r = 0.652 respectively, P < 0.05). During the pre-ovulatory period, deltaLH values in the FSH cycles were significantly lower than in the spontaneous cycles. Significantly higher serum FSH values were achieved during treatment with uFSH than rFSH. However, serum values of oestradiol, immunoreactive inhibin, and deltaLH as well as the number of follicles > or = 12 mm in diameter did not differ significantly between the two FSH preparations. These results suggest that in women undergoing ovulation induction with FSH, oestradiol enhances pituitary sensitivity to GnRH, while GnSAF exerts antagonistic effects. The rFSH used in this study (Gonal-F) was at least as effective as the uFSH preparation (Metrodin-HP) in inducing multiple follicular maturation in normally cycling women.     

Biology of colorectal cancer in ulcerative colitis

Within the last decade, induction of ovulation with gonadotrophins, specially for patients with polycystic ovary syndrome, has been extensively revisited. On the basis of physiological concepts as the FSH threshold, the FSH window and the hypersensitivity to FSH of selected dominant follicle, news protocols have been described: step-up protocol, step-down, sequential protocol. In this article, their efficacy and safety are discussed. It is presumed that these new protocols would open a new way in the management of ovulation induction.     

Induction of single ovulation by sequential follicle-stimulating hormone and pulsatile gonadotropin-releasing hormone treatment

OBJECTIVE: To induce single follicular ovulation by sequential treatment with FSH and pulsatile GnRH. DESIGN: Prospective study. PATIENTS: Eighteen hypogonadotropic anovulatory patients. INTERVENTIONS: In sequential treatment, daily FSH injection was switched to pulsatile GnRH administration (20 micrograms/120 minutes SC) when the follicle diameter reached 11 mm. In conventional FSH treatment, daily FSH injection was continued. In both cycles, hCG was given when the diameter of the dominant follicle reached 18 mm. MAIN OUTCOME MEASURES: Developed follicle numbers and serum FSH concentrations during treatment. RESULTS: Single follicular development was achieved in 80.0% of cycles by sequential treatment but in no cycle by conventional FSH treatment. The number of developed follicles was 1.26 +/- 0.55 (mean +/- SD) on sequential treatment and 3.94 +/- 1.48 on conventional FSH treatment. Preovulatory FSH level was significantly lower on sequential treatment than on conventional FSH treatment (5.26 +/- 1.80 versus 11.55 +/- 3.43 mIU/mL [conversion factor to SI unit, 1.00]). CONCLUSION: The sequential treatment achieved single follicular development without complications. The sequential FSH-pulsatile GnRH treatment may offer a better chance for development of a single dominant follicle and ovulation.     

FFI cases from the United States, Australia, and Japan

In this study we examined the possible correlation between insulin metabolism and outcome of gonadotrophin stimulation in infertile clomiphene citrate resistant women with polycystic ovary syndrome (PCOS). The patient group comprised 42 women who were entered into the study in a consecutive fashion. Following performance of the CIGMA (continuous infusion of glucose with model assessment) test, 17 women were classified as insulin resistant and 25 women as non-insulin resistant. Each woman received up to two cycles of low-dose follicle stimulating hormone (FSH) stimulation starting with 75 IU of FSH for 1 week, giving a total of 70 cycles performed. The insulin resistant PCOS women required more gonadotrophin and a longer time to achieve follicular maturation. By multiple regression gonadotrophin consumption correlated best with CIGMA value but not with fasting insulin concentration or body mass index. In the insulin resistant PCOS women 10 out of 29 cycles were cancelled due to a multifollicular response, while only one of 41 cycles was cancelled in the non-insulin resistant PCOS women. Although ovulation rate in completed cycles was similar between the groups, the conception rate was significantly better in the non-insulin resistant PCOS women. In conclusion, in PCOS women insulin resistance seems to be an unfavourable condition resulting in an elevated cancellation rate and a low conception rate following low-dose FSH stimulation.     

Human chorionic gonadotrophin and steroid concentrations in follicular fluid: the relationship to oocyte maturity and fertilization rates in stimulated and natural in-vitro fertilization cycles

The study investigates the relationship of follicular fluid steroids and human chorionic gonadotrophin to oocyte maturity and fertilization rates in stimulated and natural cycles. Oestradiol, progesterone, testosterone and human chorionic gonadotrophin were quantified in 129 samples of follicular fluid and the progesterone:oestradiol ratio calculated. Both stimulated cycles (short and long luteinizing hormone-releasing hormone/human menopausal gonadotrophin regimens) and natural cycles were compared. A total of 60 women were studied, 20 in each group. In the natural cycles, testosterone was significantly lower in follicles with intermediate oocytes (P = 0.015). Both oestradiol and testosterone were significantly lower in stimulated cycles compared to natural cycles (P = 0.032 and P = 0.034 respectively). In the ovarian stimulation cycles, the progesterone:oestradiol ratio was significantly higher when oocytes fertilized (P = 0.052). Moreover, in the stimulated cycles, oestradiol and human chorionic gonadotrophin were singnificantly lower in the short protocol compared to the long protocol. The data demonstrate that the hormonal milieu of the follicle is altered in down-regulated stimulated cycles to varying degrees, depending partially on the type of protocol used. Furthermore, the progesterone:oestradiol ratio, rather than individual hormone concentrations, may be a useful predictor of the fertilizing capacity of the oocytes.     

Purified urinary follicle stimulating hormone induces different hormone profiles compared with menotrophins, dependent upon the route of administration and endogenous luteinizing hormone activity

The effects of treatment of patients with gonadotrophin-releasing hormone analogue (GnRHa) combined with purified follicle stimulating hormone (FSH) for in-vitro fertilization (IVF) were investigated in detail to determine the influences of different administration routes and the degree of suppression of luteinizing hormone (LH). Responses to exogenous gonadotrophins were studied in infertile women (n = 60) with normal menstrual rhythm whose endogenous gonadotrophin activity was suppressed using a GnRHa in a long protocol. They were randomized to receive i.m. administration of human menopausal gonadotrophins (HMGim, Pergonal) or purified follicle stimulating hormone (FSH, Metrodin High Purity) administered either i.m. (MHPim) or s.c. (MHPsc). Responses were assessed by measuring plasma FSH, LH, oestradiol, testosterone and progesterone. After stimulation day 4, the MHPsc group showed significantly higher circulating concentrations of FSH than either the MHPim or HMGim group. However, the HMG group showed significantly higher oestradiol concentrations after stimulation day 5 than either MHP group. The differences in circulating oestradiol concentrations in the MHP-treated patients appeared to be strongly influenced by the mean circulating concentrations of LH in the follicular phase. The patients who showed mean follicular phase LH concentrations of < 1 IU/l showed longer follicular phases, lower circulating oestradiol and testosterone concentrations and also lower follicular fluid concentrations of oestradiol and testosterone, indicating a reduction in the normal follicular metabolism of progesterone to androgens and oestrogens under these conditions. This group of patients also showed longer follicular phases, which may have consequences for future clinical management.     

Leptin concentrations in the follicular phase of spontaneous cycles and cycles superovulated with follicle stimulating hormone

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.     

Follicle stimulating hormone alone supports follicle growth and oocyte development in gonadotrophin-releasing hormone antagonist-treated monkeys

Both follicle stimulating hormone (FSH) and luteinizing hormone (LH) are proposed requirements for follicular growth and steroidogenesis; however, the role of LH in primate folliculogenesis is unclear. Follicular stimulation by recombinant human FSH (n = 5) with and without recombinant LH (1:1; n = 6) following 90 days of gonadotrophin-releasing hormone (GnRH) antagonist (Antide) treatment in macaques was evaluated. Human chorionic gonadotrophin (HCG) was administered when six follicles > or = 4 mm were observed. Oocytes were aspirated 27 h later and inseminated in vitro. Chronic Antide reduced serum oestradiol and bioactive LH to concentrations observed in hypophysectomized rhesus monkeys. Multiple follicular growth required a longer interval following recombinant FSH (12 +/- 1 days) than recombinant FSH+recombinant LH (9 +/- 0.2 days), but the total number of follicles/animal did not differ between groups. The day prior to HCG, oestradiol concentrations were 4-fold less following recombinant FSH compared to recombinant FSH+recombinant LH. With recombinant FSH, more oocytes completed meiosis to metaphase II (51%) and fertilized (89 +/- 5%) relative to recombinant FSH+recombinant LH (12 and 52 +/- 11% respectively). Follicular growth and maturation in LH-deficient macaques occurred with FSH alone. Thus, LH is not required for folliculogenesis in primates. Higher fertilization rates following follicular stimulation with FSH alone suggest that the presence of LH with FSH (1:1) during the pre-ovulatory interval impairs gametogenic events in the periovulatory period.     

Histological evaluation of endometrium on the day of oocyte retrieval after gonadotrophin-releasing hormone agonist-follicle stimulating hormone ovulation induction for in-vitro fertilization

The objective of this study was to evaluate the histopathological characteristics of endometrial biopsies taken on the day of oocyte recovery in in-vitro fertilization (IVF) cycles with a satisfactory response to ovulation induction. A group of 33 patients who went through ovulation induction for IVF, and in whom an endometrial polyp was suspected on transvaginal ultrasonography during the monitoring phase, were studied. Following oocyte recovery, hysteroscopy, polypectomy and endometrial curettage were performed. Dating of endometrial glands and stroma was carried out in the tissue not containing the polyps. The total dose of follicle stimulating hormone (FSH), duration of ovulation induction, peak oestradiol and luteinizing hormone (LH) concentrations, thickness of endometrium and number of oocytes were recorded and compared to the endometrial dating of the specimens. In 15 cycles (45.5%), the endometrium was classified as 'in phase' (group I), 'advanced' by 2-4 days in a further 15 (45.5%, group II), and in the remaining three cycles (9%) it was delayed in maturation (group III). Younger age was correlated with advanced staging of the endometrium (r = -0.42; P = 0.015). Women with 'in phase' and 'advanced' maturation were similar in their response to ovulation induction; however, there was a strong correlation between advanced dating of endometrium and number of oocytes retrieved (r = 0.49; P = 0.04). Endometrial staging on the day of oocyte retrieval varied widely in patients treated by the same gonadotrophin-releasing hormone agonist (GnRHa)/FSH protocol for ovulation induction. This difference was not predictable by parameters monitored through the cycles.     

Abnormal twenty-four hour pattern of pulsatile luteinizing hormone secretion and the response to naloxone in women with hyperprolactinaemic amenorrhoea

OBJECTIVE: Hyperprolactinaemic amenorrhoea is associated with disturbances of pulsatile gonadotrophin secretion. The underlying mechanism remains unclear and the aim of this study was to investigate the 24-hour secretory pattern of gonadotrophins in women with hyperprolactinaemic amenorrhoea. The effect of opioid blockade using naloxone infusion on LH secretory pattern was also studied. DESIGN: The secretory patterns of LH, FSH, PRL and their responses to naloxone infusion were studied by serial blood samples collected at 10-minute intervals for 24 hours. On the following day, naloxone was infused at a dose of 1.6 mg per hour for 4 hours. PATIENTS: Eight women with hyperprolactinaemic amenorrhoea, two women hyperprolactinaemic but with normal ovarian cycles, and nine control subjects in the early follicular phase of menstrual cycle. MEASUREMENTS: Concentrations of LH, FSH and PRL were measured in plasma samples obtained at 10-minute intervals for 24 hours. In one woman, concentrations of urinary oestrone glucuronide were measured daily during treatment with pulsatile GnRH. RESULTS: The number of LH pulses per 24 hours was significantly fewer in women with hyperprolactinaemic amenorrhoea than in those with hyperprolactinaemia with normal cycles or control subjects (mean +/- SEM 4.5 +/- 2.4 vs 13.5 +/- 2.5 vs 17.3 +/- 0.8, P < 0.001). The magnitude of each episode of secretion was significantly higher in the hyperprolactinaemic amenorrhoeic women (P < 0.05) so the overall mean concentrations of LH throughout the 24-hour period was similar in the three groups (5.2 +/- 1.1, 4.8 +/- 0.8 and 5.2 +/- 0.4 U/l respectively). In women with hyperprolactinaemic amenorrhoea there was no significant change in the pattern of LH secretion during sleep in contrast to the control women in whom there was a slowing in the LH pulse frequency during the night. There was no significant change in the mean concentrations of LH, FSH and PRL during the naloxone infusion. There were also no significant changes in the LH pulse frequency in response to naloxone infusion when compared with an equivalent period of time in the previous 24 hours. In one hyperprolactinaemic amenorrhoeic woman, follicular development, ovulation and pregnancy were induced when gonadotrophin releasing hormone (GnRH) was infused in a pulsatile manner at a dose of 5 micrograms every 90 minutes. CONCLUSIONS: The suppression of normal ovarian cycles in women with hyperprolactinaemic amenorrhoea is due to a significant reduction in frequency of LH (GnRH) secretion which is not due to an increase in hypothalamic opioid activity. As normal ovarian cycles can occur or be induced by exogenous GnRH in hyperprolactinaemia, it is unlikely that a high level of prolactin by itself inhibits follicular development and ovulation.     

Glycoform composition of serum gonadotrophins through the normal menstrual cycle and in the post-menopausal state

The heterogeneity of follicle stimulating hormone (FSH) and luteinizing hormone (LH) was investigated in five women aged 29.4 +/- 3.2 years (mean +/- SD) throughout their menstrual cycles and in five post-menopausal women aged 53.8 +/- 5.6 years. Chromatofocusing (pH range 7-4) revealed menstrual cycle stage- and postmenopausal-related differences in the serum gonadotrophin charge. There were differences in the proportion of FSH with an isoelectric point (pl) > 4.3 across phases of the menstrual cycle (P = 0.019): midcycle (MC) 50%; early to mid-follicular (EMF) 36%; late follicular (LF) 37%, luteal (L) 29% and following the menopause (PM) 17%. There was no significant difference in the proportion of LH with pl > 6.55 between midcycle (53%) and EMF, LF or L phases (36, 43 and 32% respectively); although all were greater than that found in the menopause (13%). Concanavalin A chromatography revealed less (P < 0.005) complex FSH and LH glycoforms at midcycle (63 and 13%) than in the EMF, LF and L phases (90 and 18; 90 and 20 and 93 and 24% respectively). Menopausal gonadotrophins were least complex (FSH 34%, LH 4%). There was a direct relationship between serum FSH and FSH pl/complexity, and less acidic FSH was associated with reduced FSH complexity. Increased oestradiol was associated with basic FSH isoforms during the menstrual cycle and reduced follicular phase FSH complexity. We conclude that changes in gonadotrophin glycoforms occur through the menstrual cycle which are related to changes in the prevailing steroid environment. Following the menopause oestrogenic loss resulted in acidic, relatively simple glycoforms.     

Endometrial stripe thickness as a predictor of ectopic pregnancy

We have examined the efficacy of highly purified follicle stimulating hormone (FSH-HP) for controlled ovarian stimulation in our in-vitro fertilization (IVF) programme, and compared the results obtained with this preparation with those using human menopausal gonadotrophin (HMG) in 15 patients who had received treatment with both FSH-HP and HMG in consecutive cycles (n = 39). No differences were found in the duration of stimulation, which was 13.9 days (HMG) as compared with 14.3 days (FSH-HP). However, in the FSH-HP-treated cycles we found a striking difference in the rise of serum oestradiol, which was significantly lower than in HMG-treated cycles (2953 +/- 938 pmol/l as compared with 6349 +/- 3683 pmol/l on the day before ovum retrieval). Number and size of follicles were similar in the two groups, as were oocyte characteristics. Increase in endometrial thickness at two days prior to ovum retrieval was slightly higher after HMG. The results indicate that in combination with a long gonadotrophin-releasing hormone agonist (GnRHa) protocol, pure FSH is sufficient for adequate follicle recruitment and growth. However, since FSH-HP resulted in markedly reduced concentrations of serum oestradiol as compared to HMG cycles, IVF programmes using repeated oestradiol measurements to decide the day of ovum retrieval must take this into consideration in order not to prolong the stimulation unnecessarily.     

The addition of a glucocorticoid to the protocol of programmed oocyte retrieval for in-vitro fertilization--a randomized study

A group of 78 infertile women, diagnosed as having tubal factor infertility only, was enrolled in a prospective, randomized study conducted to determine whether the addition of different doses of glucocorticoids to the protocol of ovulation induction for in-vitro fertilization (IVF) would be beneficial. Oocyte numbers, percentage of fertilization, oestradiol, luteinizing hormone and follicle stimulating hormone serum concentrations, number of embryo transfers and pregnancy rate were evaluated. Compared to control cycles (group A; n = 24), the addition of 0.5 mg (group B; n = 27) of 1 mg dexamethasone (group C; n = 27), combined with the protocol of programmed oocyte retrieval for IVF patients in the study, demonstrated equivalent results. The mean numbers of oocytes retrieved were 10.8 +/- 3.9 in the control group, compared to 11.2 +/- 4.0 in group B and 10.5 +/- 3.6 in group C. The fertilization rates were 69 +/- 21, 66 +/- 18 and 70 +/- 15% respectively. The pregnancy rates were 20, 16 and 20.8% respectively. The addition of up to 1 mg dexamethasone daily to the protocol of ovulation induction for oocyte retrieval did not improve the overall IVF-embryo transfer outcome in patients with tubal factor infertility.     

Effects of different test conditions on MICs of food animal growth-promoting antibacterial agents for enterococci

To examine whether luteal phase defect is, in part, causally related to insufficient gonadotrophin stimulation, we compared the relation of the increment of serum progesterone concentrations in response to human chorionic gonadotrophin (HCG) with its basal level at mid-luteal phase. Thirty-eight naturally cycling infertile women aged between 27-41 years old were evaluated for hormonal responses to HCG injection at the mid-luteal phase. We measured luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol and progesterone concentrations, before and 1, 2 and 3 h after the administration of HCG (5000 IU, i.m.) 7 days after ovulation verified by ultrasonography. Eleven out of 38 women exhibited progesterone concentrations below 10 ng/ml (low progesterone group), and those remaining showed progesterone concentrations of > or = 10 ng/ml (normal progesterone group). The basal LH, FSH and oestradiol concentrations were essentially the same in both groups. Progesterone concentrations rose significantly 1 h after the injection and levelled off thereafter. The increment of progesterone concentrations at 1 h in the normal progesterone group was 5.7 ng/ml on the average, whereas that in low progesterone group was 1.1 ng/ml. Furthermore, the percentage increase in progesterone concentrations at 1 h in the normal progesterone group was significantly greater than that in the low progesterone group. Both groups equally exhibited significant but marginal increases in oestradiol concentrations 1 h after the injection. LH and FSH concentrations at 3 h decreased significantly in both groups. In summary, HCG readily stimulates progesterone production in normally functioning corpus luteum whereas its stimulatory effect is minimal on malfunctioning corpus luteum. This suggests that luteal phase defect is not caused by inadequate gonadotrophin stimulation and, therefore, does not benefit from HCG administration.     

A comparative evaluation of two sensitive serum neutralization tests for bovine herpesvirus-1 antibodies

The need for frequent injections and monitoring, the possibility of multiple gestations, and the higher cost compared to clomiphene citrate, prevents many clinicians from using human menopausal gonadotrophin (HMG) for ovulation induction. A sequential medication regimen, in which HMG is taken after clomiphene, overcomes these problems. We retrospectively compared per cycle fecundity and birth rates in 119 cycles of clomiphene-HMG, 524 cycles of clomiphene alone, 57 cycles of HMG alone, and 79 cycles of concurrent HMG and clomiphene in patients receiving intra-uterine insemination (IUI), who were free of endometriosis or tubal disease. Per cycle fecundity for clomiphene-HMG was 22% [95% confidence interval (CI) 12-34%], double that of clomiphene alone (11%) (95% CI 8-14%) (P < 0.01), and equal to HMG alone (18%) (95% CI 7-29%) or HMG and clomiphene together (19%) (95% CI 10-28%). The multiple birth rate for clomiphene-HMG (7/21) equalled that for HMG alone (3/12) and HMG and clomiphene together (3/8). The average number of ampoules of HMG required [follicle stimulating hormone (FSH) 75 mIU, luteinizing hormone (LH) 75 mIU] was decreased by 65% from 24.5 +/- 1.0 for HMG or HMG and clomiphene together to 8.6 +/- 0.3 for clomiphene-HMG (P < 0.001). Per cycle fecundity was identical when one, two or three ampoules of HMG per day were administered after clomiphene. We conclude that ovulation induction with sequential clomiphene-HMG results in fecundity double that of clomiphene alone and equal to HMG alone or concurrent with clomiphene, thereby reducing the requirement for HMG.     

Further observations of the ovarian response of the tammar wallaby (Macropus eugenii) to exogenous gonadotrophins: an improved method for superovulation using FSH/LH

This study reports the development of an improved superovulation protocol in the monovulatory tammar wallaby, Macropus eugenii. Treatment with pregnant mare's serum gonadotrophin (PMSG; 10-20 IU) inhibited follicle development in the corpus luteum (CL)-bearing ovary and only 2-3 eggs per female could be recovered after ovulation induction with gonadotrophin releasing hormone (GnRH; 3 x 30 microg at 3-h intervals) or porcine luteinizing hormone (LH; 4, 5 or 8 mg) 3 days after PMSG priming. Treatment with porcine FSH (8 x 6 mg at 12-h intervals for four consecutive days) was found to override this inhibition and resulted in the recovery of 7-13 eggs per female after ovulation induction with porcine LH (4 mg on day 5). For these animals, there was no difference in numbers of developing follicles, ovulation sites and eggs recovered between the CL- and non-CL-bearing ovaries. This FSH/LH protocol was effective in both cycling and non-cycling females, and multiple ovulation occurred from about 36 h after LH treatment. After LH treatment, eggs were recovered from the oviduct at 36-50 h. At 51-57 h, 12-25% of eggs were recovered from the uterus, and by 75 h all eggs were recovered from the uterus. It is concluded that the described FSH/LH protocol used results in higher ovulation success than the PMSG/GnRH method.     

Follicle stimulating hormone-granulosa cell axis involvement in the antifolliculotrophic effect of low dose mifepristone (RU486)

This study was designed to assess the involvement of follicle stimulating hormone (FSH)-granulosa and luteinizing hormone (LH)-theca axes in the antifolliculotrophic effect of mifepristone. Plasma gonadotrophins, including plasma LH bioactivity and pulsatility, oestradiol, testosterone and inhibin concentrations, and follicular growth were monitored in volunteer women treated with placebo or mifepristone in two consecutive cycles. Mifepristone was given either as a single dose of 5 mg (n = 7) when the leading follicle had reached a diameter between 12 and 14 mm, or as a multiple dose of 5 mg/day for 3 days, beginning when the leading follicle had reached a diameter between 14 and 16 mm (n = 5) or between 6 and 11 mm (n = 5). Following the single dose of mifepristone, follicular growth and the accompanying increase in plasma oestradiol were arrested at 12 and 36 h respectively without changes in gonadotrophin or testosterone serum concentrations. The 3 day regimen arrested follicular growth and oestradiol rise and decreased plasma inhibin concentrations when follicles were larger than 12 mm at the onset of treatment. These results indicate that the antifolliculotrophic action of mifepristone is associated with a selective compromise of the FSH-granulosa axis of dominant follicles that have passed a critical stage of growth.     

Outcome from consecutive in-vitro fertilization/intracytoplasmic sperm injection attempts in the final group treated with urinary gonadotrophins and the first group treated with recombinant follicle stimulating hormone

In the absence of specific dose equivalency data, the aim of this study was to compare the clinical results during the cross-over from menopausal urinary products (human menopausal gonadotrophin; HMG) to recombinant follicle stimulating hormone (FSH) follitrophin beta (FSHr) in order to determine whether the manufacturer's recommendation for equivalence of ampoule to ampoule (50 IU FSHr:75 IU HMG) would prove clinically correct. A total of 353 consecutive in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment cycles was studied between 1st September 1996 and mid-February 1997. This included cycles in the last 191 women receiving HMG and the first 162 taking FSHr. All were down-regulated using a gonadotrophin releasing hormone (GnRH) agonist long protocol method from day 1 of the cycle. Greater efficacy was seen in the HMG group in terms of days of stimulation required, need to increase dosage, cycle discontinuation, number of follicles punctured, the numbers of oocytes retrieved and their quality. The hormonal response to stimulation assessed by oestradiol concentrations on days 5, 8 and day of human chorionic gonadotrophin (HCG) was significantly lower in the FSHr group. The ratio of oestradiol per follicle and per oocyte was significantly lower in the FSHr group. There was a highly significant increase in cost with FSHr therapy. Clinical pregnancy rates were 14% per cycle with FSHr and 20% per cycle with HMG.     

Hypothalamic-pituitary-ovarian response to clomiphene citrate in women with polycystic ovary syndrome

OBJECTIVE: To examine the hypothalamic-pituitary sites of clomiphene citrate (CC) action in women with polycystic ovarian syndrome (PCOS). DESIGN: Prospective controlled trial. PATIENTS, PARTICIPANTS: Seventeen women with PCOS and 9 normal-cycling women. INTERVENTIONS: Subjects with PCOS received CC, 150 mg/d for 5 days. MAIN OUTCOME MEASURES: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and LH pulse characteristics and their response to gonadotropin-releasing hormone (GnRH, 10 micrograms) were examined before and after 3 days of CC in PCOS subjects during a 12-hour frequent sampling study (n = 8). Daily urinary estrone glucuronide and pregnanediol glucuronide levels after CC were compared with concentrations in normal-cycling women through one menstrual cycle. In another nine PCOS subjects, pituitary and ovarian hormonal cyclicity was monitored by daily blood sampling. RESULTS: Thirteen of 17 treated cycles were ovulatory with normal luteal phases. In the ovulatory cycles, serum LH, FSH, estradiol (E2), and estrone levels increased after CC. Luteinizing hormone pulse frequency was unchanged, but LH pulse amplitude increased significantly after CC. Both LH and FSH response to exogenous GnRH was significantly attenuated after CC treatment. In anovulatory cycles, serum LH, FSH, and E2 increased initially and then returned to baseline and remained unchanged for the ensuring 40 days. CONCLUSIONS: Clomiphene citrate-induced ovulation in women with PCOS is accompanied by increased secretion of LH and FSH with enhanced estrogen secretion. The increased LH pulse amplitude after CC, together with decreased pituitary sensitivity to GnRH, suggests a hypothalamic effect.