A long-acting gonadotropin-releasing hormone agonist inhibits the growth of a human ovarian epithelial carcinoma (BG-1) heterotransplanted in the nude mouse

Human ovarian epithelial carcinoma (BG-1) was heterotransplanted in female nude athymic mice and growth was evaluated in intact, surgically castrated, and gonadotropin-releasing hormone (GnRH) agonist (Lupron-SR)-treated mice. Tumor volume was represented as percent of tumor volume on day 0 and measured every other day from the administration of drug and/or the attainment of a minimum tumor volume of 0.5 cm3 on each side of the animal. Tumors in surgically castrated mice had significantly accelerated growth compared with control tumors grown in intact mice (1810 +/- 247.2 versus 1253.6 +/- 44.6%, respectively; P less than .05). Treatment with GnRH agonist significantly reduced tumor growth in intact mice at days 16, 18, and 20 compared with normal control tumors and placebo-treated tumors in intact mice (P less than .02). Gonadotropin levels in pooled serum of mice were reduced from normal levels with GnRH agonist treatment (control: mLH 16.9 +/- 2.2 ng/mL, mFSH 6.6 +/- 0.3 ng/mL; GnRH agonist-treated: mLH 9.3 +/- 1.8 ng/mL, mFSH 4.9 +/- 0.7 ng/mL; surgically castrated: mLH 32.2 +/- 2.7 ng/mL, mFSH 19.4 +/- 0.5 ng/mL). This human tumor model appears responsive to gonadotropins as evidenced by the ability of a GnRH agonist to inhibit growth of BG-1. These results suggest that GnRH agonist therapy may be a useful adjuvant in the treatment of human ovarian epithelial carcinoma.     

Rapid reduction of leiomyoma volume during treatment with the GnRH antagonist ganirelix

OBJECTIVE: To assess maximal volume reduction of leiomyomas and uterus and the duration of treatment required to reach these reductions with daily GnRH antagonist treatment. DESIGN: Prospective, open-label study. SETTING: Large teaching hospital in The Netherlands. POPULATION: Premenopausal women with symptomatic fibroids, who were scheduled for surgery. METHODS: Twenty women were treated with daily 2 mg of subcutaneous ganirelix. Prior to the first injection and weekly during treatment, the volume of leiomyomas and the uterus were assessed by ultrasound (USS) and serum hormones were measured. Prior to treatment and when maximal size reduction was observed by USS, the volume of the leiomyomas and the uterus were also assessed by magnetic resonance imaging (MRI). MAIN OUTCOME MEASURES: Leiomyoma and uterine size reduction, time to maximal reduction. RESULTS: One woman was excluded from the study due to incorrect administration dose of ganirelix. Data on the remaining 19 women (average age 39 years) with subserosal (n= 9), submucosal (n= 7), intramural (n= 10) and transmural (n= 1) leiomyomas were evaluated. Baseline leiomyoma volumes ranged from small (3-4 mL) to large (>1000 mL). The median duration of treatment up to maximal leiomyoma size reduction was 19 days (range 1-65 days). The maximal size reduction in leiomyomas measured by USS was -42.7% (-77.0% to 14.1%) and -29.2% (-62.2% to 35.6%) by MRI. Comparable uterine size reductions of -46.6% (-78.6% to -6.1%) and -25.2% (-63.6% to 28.9%) were observed by USS and MRI. During the first three weeks of treatment, 8 out of 19 women reported adverse events related to the induced hypoestrogenic state. Most of these events resolved within one week after treatment was discontinued. CONCLUSION: Daily treatment with 2 mg of ganirelix results in rapid reduction of leiomyoma and uterine volume in premenopausal women with minor side effects. If longer-acting GnRH antagonists become available, pretreatment with GnRH antagonist should be preferred over GnRH agonists prior to surgery.     

Effects of varicocele treatment in adolescents: a randomized study.

OBJECTIVE: To study the effects of varicocele treatment on testicular function in adolescents. DESIGN: A prospective controlled study in 88 randomly selected adolescents. SETTING: All participants were referred to the fertility outpatient clinic of our university hospital. PARTICIPANTS: All participants with a varicocele were randomly assigned into two groups. Group 1 (n = 33) was not treated, whereas group 2 (n = 34) was treated. A similar group of healthy volunteers without a varicocele served as a control group (group 3, n = 21). INTERVENTIONS: Testes volumes were measured at intake and during follow-up using an orchiometer. Semen analysis was performed according to standard procedures both at intake and after 1 year of follow-up. Serum hormone levels were determined at intake using a radioimmunoassay. Treatment was performed by means of transcatheter embolization of the left testicular vein. MAIN OUTCOME MEASURES: Testes volumes and semen quality at intake and after 1 year of follow-up were compared within and between the three groups. Hormonal parameters were determined at intake only. RESULTS: Before treatment, the mean left testis volume in groups 1 (n = 26) and 2 (n = 27) (20.0 mL; 95% confidence interval [CI]: 18.2 to 21.8 and 21.6 mL; 95% CI: 19.4 to 23.8, respectively) were significantly smaller than those in the control group (n = 19) (24.5 mL; 95% CI: 22.7 to 26.4). During follow-up, left testis volumes of the treated group were comparable with those in the control group (24.2 mL; 95% CI: 22.2 to 26.1 and 24.8 mL; 95% CI: 23.0 to 26.7 respectively) and significantly (P < 0.001) different from the untreated group (20.3 mL; 95% CI: 18.8 to 21.8). A significant increase in left (P < 0.01) as well as right (P < 0.05) testis volume was observed after treatment. Semen parameters before treatment were not significantly different between the three groups. Sperm concentration increased significantly (P < 0.01) from 47.4 x 10(6)/mL (95% CI: 42.5 to 53.3) to 68.9 x 10(6)/mL (95% CI: 50.6 to 87.2) in the treated group, whereas semen quality in the untreated and control groups did not change. Although both testes volumes and sperm concentration improved in the treated group, these phenomena were not consistently correlated to each other. CONCLUSIONS: Although not apparent in all adolescents, varicocele correction resulted in an increase in left testis volume and sperm concentration. At this moment, it is not clear if early preventive treatment of varicocele in adolescents, in time, will have a positive effect on testicular function.     

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.     

Follicular fluid vascular endothelial growth factor concentrations are increased during GnRH antagonist/FSH ovarian stimulation cycles

BACKGROUND: The aim of this study was to investigate the effect of GnRH antagonists (GnRH-ant) on follicular fluid vascular endothelial growth factor (FF VEGF). METHODS: Sixty women undergoing assisted reproduction were randomised (computer-generated randomisation list) and assigned to two different GnRH analogue regimens: GnRH agonist (GnRH-a) (Group A; n = 30) and GnRH-ant (Group B; n = 30). RESULTS: Mean (+/-S.D.) FF VEGF concentrations were 1598+/-612 pg/mL and 2906+/-1558 pg/mL for Groups A and B, respectively (p < 0.001). In the women treated with GnRH-ant, we found a statistically significant reduction in serum LH levels (1.72+/-0.74 IU/L in Group A versus 0.93+/-0.43 IU/L in Group B, p < 0.001), in serum oestradiol (E2) levels (1562.1+/-410.7 pg/mL in Group A versus 1214.67+/-779.9 pg/mL in Group B, p < 0.05), in FF E2 levels (1146+/-593 ng/mL in Group A versus 621+/-435 ng/mL in Group B, p < 0.05), and in FF androstenedione levels (136+/-55 ng/mL in Group A versus 78+/-31 ng/mL in Group B, p < 0.001), as well as a reduction in the number of pregnancies, though not statistically significant (23.3% in Group A versus 16.6% in Group B). CONCLUSION: The increase in FF VEGF levels in women treated with GnRH-ant might be explained by a suppression of LH and E2 levels.     

Depot GnRH agonist versus the single dose GnRH antagonist regimen (cetrorelix, 3 mg) in patients undergoing assisted reproduction treatment

The objective of this study was to compare, in a centre with previous experience of gonadotrophin-releasing hormone (GnRH) antagonist use, single administration of a GnRH antagonist [cetrorelix (Cetrotide) 3 mg] with a single administration of a GnRH agonist [Decapeptyl Retard 3.75 mg] in patients undergoing assisted reproduction treatment (n = 307 and 364 respectively). GnRH agonist was administered on the first day of menses, while cetrorelix was administered when the largest follicle reached 14 mm. Ovarian stimulation was performed with recombinant human FSH (r-hFSH; 150-225 IU/day). Human chorionic gonadotrophin (HCG, 10,000 IU) was administered when at least two follicles reached a mean diameter > or =18 mm. Over 90% of patients in both groups reached the criteria for HCG administration and underwent oocyte retrieval and embryo transfer. Duration of FSH therapy (9.95 versus 11.25 days) and cumulative dose of r-hFSH (1604 versus 1980 IU) were significantly reduced (P < 0.01) in the cetrorelix 3 mg group. The number of oocytes retrieved was lower (8.5 versus 11.2; P < 0.01) with cetrorelix, but the number of embryos replaced was similar (2.2 versus 2.3; NS). The pregnancy rates per oocyte retrieval were the same, 24.5%, in the antagonist and agonist groups. This study indicates that although fewer oocytes are recovered, similar pregnancy rates can be achieved with a GnRH antagonist compared with a GnRH agonist. Additionally, a single dose of 3 mg cetrorelix was administered in 84% of patients, thus being simpler and more convenient for patients. Cetrorelix 3 mg may thus be proposed as a first choice for preventing both a premature LH surge and detrimental rises in LH during ovarian stimulation prior to assisted reproduction treatment.     

Effects of cadmium chloride on the testis and sex accessory glands of the Indian palm squirrel, Funambulus pennanti (Wroughthon).

A single subcutaneous injection of cadmium chloride caused reversible destruction in the testis of palm, squirrel, Funambulus pennanti. Marked regression in testicular weight and seminiferous tubule diameter associated with complete necrosis of germinal epithelium was observed after 1, 2, 3, 5 and 7 days of cadmium administration. A significant increase in the concentration of testicular cholesterol was observed after 5 days treatment. Decrease in the citric acid concentration of prostate gland was associated with the degenerative changes of the spermatogenic elements. Reduced fructose concentration in the seminal vesicle and prostate of cadmium treated animals indicate an inhibition of androgen production. Decreased androgen production was also reflected by the atrophic seminal vesicles, prostate and epididymides. These effects were reversible and about 70% seminiferous tubules showed normal spermatogenesis. The cholesterol, fructose and citric acid concentration of testis and sex accessory glands returned to subnormal levels after 45 days of cadmium chloride treatment. It is suggested that the degenerative effects of cadmium chloride are dose, time and species dependent.     

The role of ovarian volume in an in vitro fertilization programme as assessed by 3D ultrasound

The study was designed to investigate the role of ovarian volume, as assessed by three-dimensional (3D) sonography, in predicting conception in an in-vitro fertilization-embryo transfer (IVF-ET) programme. Transvaginal 3D sonography was performed in 152 cycles before initiation of ovarian stimulation (day 1) and on the day of oocyte retrieval. Ovarian volume showed no significant correlation with IVF outcome. On the contrary, all ovarian measurements were lower, albeit non-significantly, in the conception group. Fifteen patients (15/152, 9.9%) had a minimum unilateral ovarian volume of ≤3 mL (1 SD below the mean) on day 1 of the stimulation cycle. In this subgroup, the likelihood of conception was 6.7% (1/15) versus 21.9% (30/137) in patients with an initial minimum ovarian volume of >3 mL. This difference did not reach statistical significance. In both groups, cancellation rates due to poor ovarian response or lack of fertilization were similar. In conclusion, ovarian volumetry as assessed by three-dimensional ultrasound failed to predict conception in women undergoing IVF treatment. Received: 5 August 2000 / Accepted: 11 September 2000     

On the maintenance of male fertility in the absence of native testosterone secretion: site-directed hormonal therapy in the rat

A method of direct percutaneous injection of testosterone (T)-laden microspheres directly into the testis was used in an attempt to achieve the maintenance of normal intratesticular T concentrations, spermatogenesis, and fertility. Rats were divided into three groups: (1) sham operated/injection controls; (2) animals receiving 250 micrograms/d gonadotropin-releasing hormone (GnRH)-antagonist; and (3) animals receiving GnRH-antagonist as in group 1 plus 20 mg T-laden microspheres/testis. Treatment periods were 45 and 90 days. Serum T, testicular interstitial fluid T, testis weights, epididymal weights, daily sperm production (sperm x 10(6)/g/d), cauda sperm motility, and fertility were assessed in all animals. Gonadotropin-releasing hormone antagonist treatment reduced serum and testicular interstitial fluid to below detectable levels at day 45 and to similar levels at day 90. Supplementation with T-laden microspheres maintained testicular interstitial fluid T at concentrations not different from controls without elevation of serum T concentrations. All other values, including fertility were suppressed by GnRH-antagonist treatment and maintained by supplementation with T-laden microspheres.     

Cryopreserved embryo transfer in an artificial cycle: is GnRH agonist down-regulation necessary?

The use of GnRH agonist downregulation in artificial endometrium priming cycles for cryopreserved embryo transfer was retrospectively investigated to establish whether higher live birth rates resulted. Six hundred and ninety-nine patients underwent 1129 artificial endometrium priming cycles for the transfer of cryopreserved embryos between 1 July 2009 and 1 June 2012. Hormonal supplementation with (group A, n = 280 cycles) or without (group B, n = 849 cycles) GnRH agonist co-treatment was given. Live birth rates were comparable between the two groups per started cycle (14.9% [41/275] in group A versus 15.1% [127/839] in group B) or per embryo transfer (17.5% [41/234] in group A versus 17.6% [127/723] in group B). After logistic regression analysis, the only variables that were significantly associated with live birth rates were day of embryo transfer (OR 0.69; 95% CI 0.48 to 0.98) for day 3 versus day 5 embryos, the number of embryos transferred (OR 2.13; 95% CI 1.58 to 2.86) for two embryos versus one embryo transferred and the endometrial thickness on the day of embryo transfer (OR 1.15; 95% CI 1.05 to 1.25). Live birth rates after cryopreserved embryo transfer in artificial cycles did not increase when a GnRH agonist was administered.     

Effect of cyproterone acetate on testis and accessory sex organs of male rat

A significant reduction in testis, epididymis, seminal vesicles, prostate, and adrenal weight of adult rats was observed after CA treatment (10 mg/animal/day) for 13, 26 and 39 days. Biochemical assay on the epididymis showed a fall in the activities of acid and alkaline phosphatase. A significant fall in citric acid content of seminal vesicle and prostate in experimental animals was noted after CA treatment. Histoarchitecture of accessory sex organs was severely impaired.     

Gonadotrophin-releasing hormone and magnetic-resonance-guided ultrasound surgery for uterine leiomyomata

OBJECTIVE: Magnetic-resonance-guided focused ultrasound is a novel, noninvasive technique of thermoablation for uterine leiomyomata. The hypothesis of this study was that pretreatment of leiomyomata with gonadotrophin-releasing hormone (GnRH) agonists would allow effective treatment of larger uterine leiomyomata, increasing the number of women who could benefit from this technique. METHODS: We report a prospective study of women with leiomyomata in excess of 10 cm in diameter who received GnRH agonist before magnetic-resonance-guided focused ultrasound treatment. Eligible participants were recruited from the gynecology outpatient clinics. Entry criteria were a minimal leiomyoma symptom severity score and confirmation of uterine dimensions based on screening magnetic resonance imaging. These women received a 3-month course of GnRH agonists followed by magnetic-resonance-guided focused ultrasound treatment. The primary outcome measurement was reported change in symptom severity score as judged by the Uterine Fibroid Symptom and Quality of Life questionnaire. Comparison was made at enrollment, treatment, and at 3, 6, and 12 months posttreatment. A secondary outcome was the measured change in target leiomyoma volume. RESULTS: Forty-nine women were enrolled in the study. There was a 45% reduction in median symptom severity score at 6 months and 48% at 12 months posttreatment, with 83% of women achieving at least a 10-point reduction in symptom scoring at 6 months and 89% at 12 months (P < .001). There was an average reduction in target leiomyoma volume of 21% overall at 6 months (P < .001) and 37% at 12 months (P < .001). No serious infective complications or emergency operative interventions were recorded. CONCLUSION: The use of GnRH agonist therapy before magnetic-resonance-guided focused ultrasound improves the thermoablative treatment effect. LEVEL OF EVIDENCE: II-3.     

GnRH antagonist in IVF poor-responder patients: results of a randomized trial

The aim of this prospective study was to evaluate the efficacy of gonadotrophin-releasing hormone antagonist (GnRH) in comparison with the standard long protocol in poor-responder patients. Sixty patients with poor ovarian response in previous treatment cycles were randomized into two groups: group A (n = 30) was stimulated with a standard long protocol, and group B (n = 30) received GnRH antagonist. Vaginal ultrasound was performed to evaluate ovarian response. There was a significantly reduced duration of ovarian stimulation (9.8 +/- 0.8 versus 14.6 +/- 1.2, P = 0.001) in group B in comparison with group A, and a reduced number of ampoules was used in group B (49.3 +/- 4.3 versus 72.6 +/- 6.8, P = 0.0001). In group B, the number of oocytes retrieved was significantly higher than in group A (5.6 +/- 1.6 versus 4.3 +/- 2.2, P = 0.02) and there was an increased number of follicles with a diameter >15 mm at human chorionic gonadotrophin administration in group B (P = 0.0001). Fewer cycles were cancelled with the use of an antagonist protocol. Five pregnancies (17% for embryo transfer) were obtained with GnRH antagonist protocol and two (7% for embryo transfer) with GnRH agonist protocol.     

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.     

Endometrial thickness and volume by three-dimensional ultrasound one week after embryo transfer to detect pregnancy

Purpose: Determine if the evaluation of endometrium one week after embryo transfer can predict pregnancy. Methods: Endometrial volume and thickness were evaluated by three-dimensional ultrasound in 40 patients one week after embryo transfer. These results were compared to serum pregnancy test performed one week later. Results: Eighteen patients have achieved pregnancy. A significant difference was found for endometrial volume: 6.49±1.97 mL versus 3.40±1.11 mL (pregnant versus not pregnant); and thickness: 11.15±2.75 mm versus 9.77±1.85 mm. The ROC curve was used to detect the best cutoff values: endometrial volume of 3.48 mL (sensitivity-100%, specificity-68.2%) and endometrial thickness of 10.3 mm (sensitivity-72.2%, specificity-77.3%). The area under curve was significant higher for endometrial volume (0.909 versus 0.745, p=0.027). No pregnancy was achieved in women who had an endometrial volume <3.8 mL (15 patients) or thickness <7.9 mm (3 patients). Conclusions: The endometrial volume and thickness were significant higher in pregnant women and this difference was more prominent for endometrial volume.     

Low-dose GnRH agonist therapy for the management of endometriosis.

OBJECTIVE: In order to examine whether treatment with a GnRH agonist alone can maintain estrogen levels within the "estrogen window" that inhibits endometriosis without influencing bone-mineral density, we studied the effects of GnRH agonist therapy and changes in bone-mineral density. METHODS: Buserelin acetate nasal spray was administered 3 times a day for 8 weeks (daily dose, 900 micrograms) to 21 women with endometriosis. The drug was then given twice a day for 16 weeks (daily dose, 600 micrograms). The total duration of treatment was 24 weeks. The bone-mineral density of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry before treatment (baseline), at the end of treatment, and 24 weeks after the end of treatment. RESULTS: The bone-mineral density of the lumbar vertebrae at the end of treatment was 2.44% +/- 0.46% (mean +/- standard error) lower than the baseline value. The value at 24 weeks after the end of treatment was 1.10% +/- 0.64% lower than the baseline value. More than 80% of the patients had serum-estradiol levels of 45 pg/ml or less. During treatment, more than 90% of the patients had serum-estradiol levels of 60 pg/ml or less. Genital bleeding was inhibited in 90% of the patients. After 8 weeks of treatment, the clinical symptoms improved in 75% of the patients; such improvement persisted for the duration of the treatment. CONCLUSION: Decreasing the dose of GnRH agonist during treatment can minimize the loss of bone-mineral density without lessening the beneficial effects on endometriosis. This technique might be useful in the management of endometriosis.     

65Zn incorporation in the male reproductive organs following gossypol treatment

Male hamsters and rats were administered gossypol 10 mg/kg/day for 45 and 56 days respectively. Twenty four hours before the last dose, animals were administered 65Zn (specific activity 0.258 uci/mg) subcutaneously. A marked decrease in 65Zn incorporation was observed in testis, epididymis, seminal vesicles and prostate following drug administration. A significant increase in 65Zn uptake was however observed in vas deferens in both rat and hamster following drug administration. Our results suggest that whatever the mechanism of gossypol action on testis-epididymis complex may be, the marked decrease in 65Zn uptake by testis--epididymis complex following gossypol treatment may be related to the antispermatogenic effect of gossypol.     

GnRH antagonist rescue in high responders at risk for OHSS results in excellent assisted reproduction outcomes

Gonadotrophin-releasing hormone (GnRH) antagonist rescue is performed by replacing a GnRH agonist with a GnRH antagonist in patients with rapidly rising serum oestradiol who are at risk of ovarian hyperstimulation syndrome (OHSS) during stimulation. It results in a rapid reduction in serum oestradiol, allowing for the avoidance of cycle cancellation and the continuation of exogenous gonadotrophin administration. A total of 387 patients who underwent GnRH antagonist rescue for ovarian hyperresponse were compared with 271 patients who did not receive GnRH antagonist rescue and had oestradiol concentrations >4000 pg/ml on the day of human chorionic gonadotrophin (HCG) administration. GnRH antagonist rescue decreased the mean oestradiol concentration by 35% on the first day of use. There was no difference in oocyte maturity (82% versus 83%) or fertilization rate (69% versus 67%) between the antagonist rescue and comparison groups, respectively. The percentage of high-grade embryos on day 3 and the blastocyst development rate were also similar between groups. The live-birth rate was 41.9% in the antagonist rescue group and 36.9% in the comparison group. GnRH antagonist rescue enabled cycle completion with high live-birth rates in patients at risk for OHSS. GnRH antagonist was associated with high oocyte quality, blastocyst development and pregnancy.Gonadotrophin-releasing hormone (GnRH) antagonist rescue is a protocol to reduce the risk of ovarian hyperstimulation syndrome (OHSS) in assisted reproduction treatment. Patients who have a hyperresponse to medication during their treatment cycle have their GnRH agonist discontinued and a GnRH antagonist started in its place. This causes a rapid reduction in oestrogen concentrations and allows for the continuation of stimulation medication. We evaluated the effectiveness of this protocol by comparing patients who had GnRH antagonist rescue against high-responding patients who did not receive GnRH antagonist rescue. GnRH antagonist rescue resulted in a 35% reduction in oestrogen concentration and only a 1.5% cycle cancellation rate. There were no differences in oocyte maturity or fertilization between the two groups. There were no differences in the quality of day-3 and day-5 embryos between the two groups. The live birth rate was 41.9% in the antagonist rescue group and 36.9% in the comparison group. GnRH antagonist rescue reduced serum oestradiol concentrations and enabled cycle completion with high live-birth rates in patients at risk for OHSS. GnRH antagonist was associated with high oocyte quality, blastocyst development and pregnancy.     

Induction of ovulation with pulsatile GnRH: comparison between subcutaneous and intravenous administration in the same patients

In this study we compared the results obtained during GnRH pulsatile therapy for ovulation induction in the same patients receiving successively GnRH by subcutaneous (10 mcg/90') and intravenous route (2.5 or 5 mcg/90'). Our data suggest that intravenous administration is the most effective procedure for restoring fertility, either in terms of hormonal levels (oestradiol and gonadotropin peaks) or ovulation rate (100% of ovulatory cycles on GnRH treatment versus 25% on subcutaneous administration). With regard to intravenous GnRH therapy, the dose of 2.5 mcg/90' may be more advisable and safe from ovarian overstimulation.     

Premenstrual administration of gonadotropin-releasing hormone antagonist coordinates early antral follicle sizes and sets up the basis for an innovative concept of controlled ovarian hyperstimulation

OBJECTIVE: To investigate whether premenstrual administration of a GnRH antagonist coordinates early antral follicle sizes during the subsequent follicular phase. DESIGN: Prospective, longitudinal study. SETTING: University Hospital in France PATIENT(S): Twenty-five women, 50 cycles. INTERVENTION(S): On cycle day 2 (control/day 2), women underwent measurements of early antral follicles by ultrasound and serum FSH and ovarian hormones. On day 25, they received a single cetrorelix acetate administration, 3 mg. On the subsequent day 2 (premenstrual GnRH antagonist/day 2), participants were re-evaluated as on control/day 2. MAIN OUTCOME MEASURE(S): Magnitude of follicular size discrepancies. RESULT(S): Follicular diameters (4.1 +/- 0.9 vs. 5.5 +/- 1.0 mm) and follicle-to-follicle size differences decreased on premenstrual GnRH antagonist/day 2 as compared with control/day 2. Consistently, FSH (4.5 +/- 1.9 vs. 6.7 +/- 2.4 mIU/mL), E(2) (23 +/- 13 vs. 46 +/- 26 pg/mL), and inhibin B (52 +/- 30 vs. 76 +/- 33 pg/mL) were lower on GnRH antagonist/day 2 than on control/day 2. CONCLUSION(S): Premenstrual GnRH antagonist administration reduces diameters and size disparities of early antral follicles on day 2, likely through the prevention of luteal FSH elevation and early follicular development. This simple, original approach may be used to coordinate multifollicular development in controlled ovarian hyperstimulation.