Caspase-3 gene expression in human luteinized granulosa cells is inversely correlated with the number of oocytes retrieved after controlled ovarian stimulation.

Granulosa cells control oocyte maturation through paracrine signalling and changes to the microenvironment around the oocyte. Apoptosis occurs as a physiological mechanism of granulosa cell renewal, but how it relates with the ovarian response to induced ovulation is still unclear. Therefore, this study evaluated apoptosis-related gene expression levels in granulosa cells of patients undergoing controlled ovarian stimulation. We enrolled prospectively 59 consecutive IVF patients referred to a tertiary academic hospital for couple infertility treatment. Luteinized granulosa cells were isolated from follicular fluid and the RNA was extracted, reverse-transcribed and the gene expression of apoptosis inducers (caspase-3, caspase-8 and bax) and inhibitor (Bcl-2) was quantified by real-time polymerase chain reaction. Caspase-3 gene expression correlated negatively with the number of pre-ovulatory follicles (Spearman's r = -0.308), the number of collected oocytes (r = -0.451), the number of mature oocytes (r = -0.526), the number of fertilized oocytes (r = -0.439) and the number of viable embryos (r = -0.443, all statistically significant at p < 0.02 level). No such associations were found with caspase-8, bax or bcl-2. These preliminary findings suggest that increased caspase-3 gene expression in granulosa cells is associated with a worse ovulatory response in humans.

Controlled delivery of a GnRH agonist by a silastic implant (Gonazon) results in long-term contraception in queens.

Many female cats are spayed to prevent problems associated with calling and unwanted pregnancies. This study describes the safety and efficacy of an alternative approach, using an azagly-nafarelin containing implant (Gonazon) inserted subcutaneously in the neck of six treated queens for 3 years. These six queens together with six controls were permanently housed with vasectomized tom cats, and changes in progesterone concentrations were used to document the contraceptive efficacy of Gonazon. All six control queens ovulated regularly throughout the treatment period (3 years), as shown by regular changes in progesterone concentration. Sixteen ovulatory cycles were observed in each control throughout the study. In Gonazon treated queens, during the week following implant placement, two queens displayed a treatment-induced rise in progesterone concentration. Later on, all treated queens continuously displayed low progesterone concentrations until 3 years post-implant insertion, with the exception of a single isolated episode (at approximately 2.5 years of treatment), of follicular luteinization in two queens. In all queens, azagly-nafarelin concentrations peaked in the week following implant insertion remained high for 1 month and later decreased slowly. After 2.5 years of treatment, azagly-nafarelin concentrations were still greater than 150 pg/ml in 3/6 queens. During a 6-month long extension of the study (36-42 months post-treatment), all queens (treated and controls) were run with intact tom cats. None of them conceived. Following autopsy, ovarian weight and diameter of the uterine horns of 3/6 treated queens were shown to be similar to those of the controls. In conclusion, this study demonstrated that Gonazon efficiently prevented ovulation in queens (100%) for 3 years. Return to fertile heat was not observed towards the end of treatment. However, in half of the treated queens, reversibility of the treatment induced effects on the genital tract was demonstrated.

Recrudescence of spermatogenesis in the dog following downregulation using a slow release GnRH agonist implant.

The present study examined the degree to which downregulation with a GnRH agonist impaired spermatogenesis and the time course of morphological and hormonal changes that occurred during recrudescence of spermatogenesis. Using a control group (group 1, n = 5) of dogs, the effect of a removable slow release GnRH-agonist implant was investigated in beagle dogs (group 2, n = 30). The implant was removed after 5 months (week 0) and three to four dogs were castrated at weeks 0, 3, 6, 9, 12, 15, 18, 21 and 24. The degree of downregulation and recrudescence of spermatogenesis was assessed by evaluation of 200 tubular cross-sections, resulting in an assigning of dogs of group 2 to testis developmental groups (DG) according to the most developed germ cell observed: DG A, spermatocytes; DG B, round spermatids; DG C, elongating spermatids and DG D, elongated spermatids. Downregulation led to an arrest of spermatogenesis at the level of spermatogonia/primary spermatocytes. The time course of recrudescence showed high individual variations and the number of dogs falling into DG A, B, C and D was 4, 3, 6 and 17 respectively. Spermatogenesis in group 2, DG D was not different from group 1 (control). In DG A, mean area of Leydig-cell nuclei was lower (p < 0.001) than in the other DG and group 1 and resembled that of juvenile dogs (group 3, n = 3); nuclei of Sertoli cells had changed from more flat/polygonal (group 1, group 2, DG C and D) to round/ovoid and had moved to a more luminal position. As indicated by basal testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations at implant removal, full downregulation had been obtained. Testosterone, LH and FSH concentrations [X(g) (DF), ng/ml] increased (p < 0.05) from implant removal to DG B [T: 0.1 (1.24) vs 2.12 (2.31); LH: 0.2 (2.15) vs 1.11 (1.7); FSH: 0.37 (3.50) vs 6.37 (1.68)] and were more or less constant thereafter indicating that onset of spermatogenesis was related to an increase of plasma T occurring in a very narrow time window. Following GnRH implantation, the size of the testes and the prostate decreased by approximately 55% (p < 0.001), they increased to sizes similar to pre-treatment values following implant removal.

Consensus statement on the use of gonadotropin-releasing hormone analogs in children.

OBJECTIVE: Gonadotropin-releasing hormone analogs revolutionized the treatment of central precocious puberty. However, questions remain regarding their optimal use in central precocious puberty and other conditions. The Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology convened a consensus conference to review the clinical use of gonadotropin-releasing hormone analogs in children and adolescents. PARTICIPANTS: When selecting the 30 participants, consideration was given to equal representation from North America (United States and Canada) and Europe, an equal male/female ratio, and a balanced spectrum of professional seniority and expertise. EVIDENCE: Preference was given to articles written in English with long-term outcome data. The US Public Health grading system was used to grade evidence and rate the strength of conclusions. When evidence was insufficient, conclusions were based on expert opinion. CONSENSUS PROCESS: Participants were put into working groups with assigned topics and specific questions. Written materials were prepared and distributed before the conference, revised on the basis of input during the meeting, and presented to the full assembly for final review. If consensus could not be reached, conclusions were based on majority vote. All participants approved the final statement. CONCLUSIONS: The efficacy of gonadotropin-releasing hormone analogs in increasing adult height is undisputed only in early-onset (girls <6 years old) central precocious puberty. Other key areas, such as the psychosocial effects of central precocious puberty and their alteration by gonadotropin-releasing hormone analogs, need additional study. Few controlled prospective studies have been performed with gonadotropin-releasing hormone analogs in children, and many conclusions rely in part on collective expert opinion. The conference did not endorse commonly voiced concerns regarding the use of gonadotropin-releasing hormone analogs, such as promotion of weight gain or long-term diminution of bone mineral density. Use of gonadotropin-releasing hormone analogs for conditions other than central precocious puberty requires additional investigation and cannot be suggested routinely.

Reversible downregulation of endocrine and germinative testicular function (hormonal castration) in the dog with the GnRH-agonist azagly-nafarelin as a removable implant "Gonazon"; a preclinical trial.

Downregulation of anterior pituitary GnRH-receptors by application of a slow release GnRH-implant offers an effective and reversible alternative to surgical castration of the male dog. Aim of the present study was to test the efficacy and the underlying mechanisms of a new non-biodegradable controlled-release device implant (Gonazon((R)), Intervet, containing 18.5mg of the GnRH-agonist Azagly-Nafarelin). Eight male beagle dogs were implanted s.c. at the para-umbilical region. In four dogs implant removal was after 180 days (group 1), in the other four dogs after 365 days (group 2). Eleven weeks after implantation availability of LH was reduced (p<0.0001) by 70%. After an initial increase lasting for about 4 days, testosterone (T) and estradiol (E2) concentrations decreased (p<0.0001) to basal levels within 17.5+/-8.4 days. Size of testes was decreased by about 82% after 17 weeks, size of prostate by about 46% after 5 weeks (p<0.0001). Five to 7 weeks after implantation all dogs were aspermic. Testosterone and estradiol concentrations, together with testicular and prostatic size remained suppressed in all dogs in group 1 and one dog of group 2 until implant removal. The other three dogs of group 2 escaped from down-regulation between 223 and 324 days. Effects on the availability of LH, T, E2 and on testicular and prostatic size were fully reversible after implant removal or escape from down-regulation. In six dogs semen quality was back to pre-treatment values after about 29 weeks, however, one dog developed oligozoospermia while another one stayed azoospermic, probably due to an obstruction within the epididymal duct.

Luteal phase characteristics following GnRH antagonist or agonist treatment - a comparative study.

Due to inherent differences between gonadotrophin-releasing hormone (GnRH) antagonists and agonists, their late effect on ovarian steroidal production during the luteal phase of IVF cycles may differ. The aim of this study was to characterize and compare the luteal phase hormonal profile after the use of GnRH antagonists or agonists in ovarian stimulation protocols for IVF, in non-conception cycles, to avoid the effect of human chorionic gonadotrophin (HCG) during the luteal phase in conception cycles. Seventy-eight normo-ovulatory patients <35 years old, undergoing IVF due to male or tubal infertility were randomly allocated either to a GnRH antagonist (study group) or GnRH agonist treatment (control group). Similar standard luteal support was given to all patients, using vaginal micronized progesterone. In non-conception cycles, no statistically significant differences were found comparing luteal phase. oestradiol or progesterone levels in the study and control groups. No statistically significant differences were found comparing the hormonal profile dynamics, the mid-luteal (HCG day +8) oestradiol/progesterone ratio and the percentage of mid-luteal oestradiol decline between the study and control groups. In conclusion, similar characteristics and dynamics of luteal phase oestradiol and progesterone were demonstrated comparing ovarian stimulation for IVF using GnRH agonist or antagonists, under similar luteal support.

Endometrial response to IVF hormonal manipulation: comparative analysis of menopausal, down regulated and natural cycles.

BACKGROUND: Uterine luminal epithelial cell response to different hormonal strategies was examined to determine commonality when an endometrium attains a receptive, stimulated, morphological profile that may lead to successful implantation. METHODS: Endometrial biopsies from 3 cohorts of patients were compared. The tissue samples taken from these patients were categorized into 8 different groups according to their baseline and the hormone regime used. RESULTS: Pre-treatment natural cycle tissue was variable in appearance. Downregulation with a GnRH analogue tissue appeared menopausal in character. HRT after downregulation resulted in tissue uniformity. HRT in menopause resulted in a 'lush' epithelial surface. HST in the natural cycle improved the morphology with significant difference in secretion between the two regimes examined. CONCLUSIONS: Down regulation plus HRT standardized surface appearance but tissue response is significantly different from the natural cycle, natural cycle plus HRT or menopause plus HRT. HRT in menopause reinstates tissue to a state similar to a natural cycle but significantly different from a natural cycle plus HST. HST with a natural cycle is similar to tissue from the natural cycle but significant differences reflect the influence of the particular hormones present (at any point) within the cycle.

[Effect of homocysteine concentration in follicular fluid on a degree of oocyte maturity]. / Wplyw stezenia homocysteiny w plynie pecherzykowym na stopien dojrzalosci komórki jajowej.

UNLABELLED: Homocysteine (HCY) is an amino acid being a methionin catabolite. The action of HCY is multi-directional and not yet fully known. Follicular fluid also contains homocysteine. Disorders of the composition of follicular fluid as an microenvironment of an oocyte may influence its development. AIM: The aim of our study was to evaluate correlation between follicular fluid homocysteine concentration and degree of maturity of egg cell. MATERIALS AND METHODS: The research concerned 40 patients qualified for IVF-ET. Ovulation was stimulated according to the long protocol. 20 of 40 patients underwent folic acid supplementation. Pituitary suppression was performed by administration of the nafarelin. The subsequent follicular development was stimulated by HMG. To all patients 10,000 IU of hCG was administered 34-36 hours before follicle puncture. The oocytes obtained were assessed in respect of a degree of Veeck scale. In all patients, fluid samples were recovered from more than one follicle, centrifugated and frozen before analysis. Both in the follicular fluid and serum, homocysteine concentration was determined with the FPIA method. Concentration of the folic was measured with the MEIA method. RESULTS: These data support that homocysteine concentration in follicular fluid and serum was significantly lower in group with folic supplementation. The purpose of the research was to determine the dependencies between the concentration of HCY in follicular fluid and the quality of oocytes. It has been shown that in a group of women with folic supplementation and lower HCY concentration the percentage of oocytes in first and second degree of maturity was higher. CONCLUSIONS: 1. Supplementation of folic acid diminish a concentration of homocysteine in both--follicular fluid and serum. 2. Oocytes exposed to low homocysteine concentration present better quality and higher degree of maturity. 3. There is a correlation between follicular fluid homocysteine concentration and oocyte maturity.

Cytogenetic analysis of uterine leiomyoma: the size, histopathology and GnRHa-response in relation to chromosome karyotype.

OBJECTIVE: The aim of this study was to elucidate the clinical characteristics of uterine leiomyomas having abnormal chromosome karyotype. STUDY DESIGN: A total of 394 myomas were obtained from 213 patients for cytogenetic analysis. The size (number of nodules=144), histopathology (n=302), and gonadotropin-releasing hormone analogue (GnRHa)-response (n=58) were investigated in relation to chromosome karyotype in myomas. RESULTS: 302 myomas from 166 patients were successfully karyotyped. A total of 21 myomas from 21 patients showed abnormal chromosome karyotype. The high frequencies of involved chromosomes 12, 14, 1, 7 were observed. The diameters of myomas with abnormal karyotype were significantly larger than those of myomas with normal karyotype. The frequency of the degeneration in myomas with abnormal karyotype was significantly higher than that with normal karyotype. The reduction rate in size of myomas by GnRHa treatments did not differ between the two types (karyotype normal versus abnormal) of nodules. CONCLUSIONS: Chromosomally abnormal myomas were larger in diameter and showed a higher frequency of degeneration, suggesting that the cytogenetic background in uterine leiomyoma affects a tumor's growth potential.

Membrane activity of biotechnological peptide drugs.

Charged Langmuir-Blodgett monolayers deposited at an immobilised liquid-liquid interface have been used as a simple model for a biological membrane to investigate the membrane activity of biotechnological oligopeptide drugs.

Chronic treatment with an agonist of gonadotropin-releasing hormone enhances luteal function in cattle.

Our hypothesis was that luteal function, as determined by plasma progesterone concentrations, and corpus luteum (CL) size is enhanced in cattle administered an agonist of GnRH when the CL is developing as compared with administration of an agonist when the CL is fully functional. Cattle were chronically administered a GnRH agonist, azagly-nafarelin, from Day 3 to Day 21 (D3) or Day 12 to Day 21 (D12) or served as untreated control females (Day 0 = behavioral estrus). Blood samples were serially collected on Days 7 and 14 to evaluate LH secretory patterns and twice daily to measure plasma progesterone. Ultrasonographic examinations were conducted daily to record the area of the CL. CL size and plasma progesterone concentrations were both enhanced in the D3 group as compared with the control group. Progesterone was increased in the D12 group on Days 16 and 17 as compared with the control females. Treatment with GnRH agonist increased basal and mean LH concentrations in both D3 and D12 groups as compared with the controls. We rejected our hypothesis because chronic administration of a GnRH agonist increased plasma progesterone when administered both when the CL was developing and when it was fully functional. The enhanced luteal function was likely due to increased basal LH.

The serum concentration of estradiol after embryo transfer and the decline from preovulatory levels may influence the success of IVF treatment.

AIM: To establish the influence that serum estradiol concentrations prior to oocyte retrieval and 3 days after embryo transfer have on the establishment of in vitro fertilization (IVF) pregnancy. METHOD: Preovulatory (day-0) and luteal-phase (day-6) estradiol concentrations were retrospectively analyzed in 310 infertile patients, undertaking 1st-cycle conventional IVF or intracytoplasmic sperm injection. RESULTS: The IVF treatment success is significantly reduced in patients with an estradiol level <600 pg/ml and also when a rapid decline in luteal-phase estradiol concentrations from preovulatory concentrations (day 0:day 6 ratio) was exhibited. CONCLUSION: A day 0:day 6 estradiol ratio >5 and a serum estradiol concentration <600 pg/ml may adversely impact on the establishment of pregnancy in IVF.

Effect of chronic treatment with the gonadotrophin-releasing hormone agonist azagly-nafarelin on basal concentrations of LH in prepubertal bulls.

Administration of GnRH agonist for an extended period inhibits pulsatile LH release but enhances testicular function of bulls. The mechanism whereby long-term administration of GnRH agonist enhances testosterone concentration in the blood of bulls has not been determined. The aim of this study was to determine whether chronic treatment with the GnRH agonist, azagly-nafarelin, increases blood concentrations of LH and FSH in prepubertal bulls. Two different doses of the GnRH agonist were administered via Alzet mini-osmotic pumps for 28 days. Blood samples were collected at 20 min intervals for 24 h at days 2, 13 and 25 of treatment. Agonist-treated groups had reduced testosterone pulse frequency (P < 0.05) and increased mean and basal concentrations of testosterone (P < 0.05) compared with untreated control bulls. Basal LH concentrations were higher in agonist-treated bulls during all three periods (P < 0.05) and overall (1 ng ml(-1) higher, compared with control bulls; P < 0.001). Frequency of LH pulses in the agonist-treated groups was reduced to less than one pulse in 24 h. Agonist-treated bulls tended to have (P < 0.10) or had (P < 0.05) a slight but significant increase in blood FSH concentration. In conclusion, the higher blood testosterone concentration in bulls after prolonged treatment with GnRH agonist may result, at least in part, from changes in the testes induced by enhanced basal concentration of LH.

Impact of six months of GnRH agonist therapy for endometriosis. Is there an age-related effect on bone mineral density?

OBJECTIVE: To determine if there is an age-related effect on bone mineral density (BMD) loss with GnRH agonist treatment of endometriosis and, in particular, whether the impact of this therapy in terms of BMD loss is different if it is used at an age prior to attainment of peak BMD than after attaining it. STUDY DESIGN: Data from a randomized, double-placebo-controlled clinical trial comparing efficacy and safety of two GnRH agonists, without add-back, for the treatment of endometriosis, were analyzed. RESULTS: No significant age-related effect was detected for either GnRH agonist on absolute BMD loss with a single, six-month course. However, in women at an age prior to peak BMD, prevention of the natural increase in BMD with these drugs may prevent women from attaining their peak BMD and thus increase their risk of osteoporosis in later life. CONCLUSION: GnRH agonists should be used with caution and perhaps only with strategies designed to minimize the impact on BMD in women prior to attainment of peak BMD.

Utero-ovarian blood flow characteristics of pituitary desensitization.

BACKGROUND: Down-regulation in assisted reproduction treatment cycles is monitored by suppression of ovarian/pituitary hormones and/or measurement of endometrial thickness. METHODS: This prospective longitudinal study reports on utero-ovarian characteristics of pituitary desensitization. A total of 75 patients were recruited; 32 had IVF treatment, 20 frozen--thawed embryo transfer cycles and 23 patients were recipients of donated oocytes. All received early follicular-phase down-regulation and had colour flow Doppler velocimetry of the utero-ovarian arteries < or =3 days before the start of menses and after 21 days of gonadotrophin-releasing hormone (GnRH) analogue treatment. Ovarian volume, endometrial thickness, pituitary and ovarian hormone concentrations were recorded at each scan. RESULTS: Significant changes (P < 0.05) were noted in these and utero-ovarian vasculature during the down-regulation period, with good correlation between resistance index and oestradiol estimations. Neither the type of GnRH analogue nor age influenced the changes in utero-ovarian blood flow. Ovarian artery resistance index was the best Doppler predictor for pituitary suppression and a mean discriminatory cut-off value of 0.867 +/- 0.025 was found to have the highest specificity and positive predictive value. CONCLUSIONS: This study has, for the first time, defined cut-off values for satisfactory pituitary suppression with high positive predictive value and specificity in an early follicular phase long protocol of GnRH analogue down-regulation using colour flow Doppler.

Prospective randomized comparison of ovarian blockade with nafarelin versus leuprolide during ovarian stimulation with recombinant FSH in an ICSI program.

PURPOSE: A prospective study was conducted to compare the efficiency of ovarian blockade with nafarelin versus leuprolide in a population whose indication for assisted reproduction was the male factor METHODS: A total of 238 patients were assigned at random to two types of treatment: Group I (119 aspirations), nafarelin (Synarel, Searle), 200 microg by the nasal route twice a day, and Group II (119 aspirations), leuprolide acetate (Lupron, Abbott), 0.5 mg by the subcutaneous route once a day. Both types of blockade were started during the 2nd phase (21st day of the menstrual cycle) and were continued until the day of HCG (5,000-10,000 IU). All patients received a fixed dose of recombinant FSH for 7 days and on the 8th day of stimulation the doses started to be adapted according to ovarian response. RESULTS: Patients' age did not differ (p = 0.93) between Group 1 (34.1 +/- 3.79) and Group II (34 +/- 4.64). The number of oocytes retrieved from Group I (10.5 +/- 5.93) was also similar (p = 0.57) to that retrieved from Group II (10.2 +/- 6.36). In addition, there was no difference (p = 0.58) in the number of oocytes retrieved at Metaphase II between Group I (8.2 +/- 4.61) and Group II (7.9 +/- 5.2). Fertilization rates and embryo scores were similar (p = 0.81 and p = 0.25, respectively) for Group I (67.5% +/- 21.3 and 34.4% +/- 14.4) and Group II (68.1% +/- 23and32.2% +/- 14.7, respectively). Inaddition, pregnancy rates per puncture and per embryo transfer and implantation rates were similar for Group I (30.2, 31.3, and 16.2%, respectively) then compared with Group 11(24.4, 25.2, and 12.6%, respectively) (p = 0.38, p = 0.37, and p = 0.22, respectively). CONCLUSIONS: Implantation and pregnancy rates per puncture and per embryo transfer are not statistically significant in the nafarelin group when compared with leuprolide group.

Effects of gonadal suppression on the regulation of parathyroid hormone and 1,25-dihydroxyvitamin D secretion in women.

Although a causal association between estrogen deficiency and bone loss has been established for many years, the mechanism by which estrogen deficiency leads to bone loss is unclear. Estrogen deficiency could induce bone loss either by a direct effect on bone cells to modify the production of bone-resorbing cytokines or by altering the production or response to calcium regulatory hormones such as PTH and 1,25-dihydroxyvitamin D. To assess the effects of ovarian hormones on calcium regulatory hormones, we evaluated the ability of calcium to suppress PTH secretion and the ability of PTH to increase serum 1,25-dihydroxyvitamin D and whole blood ionic calcium levels in women before and after GnRH analog-induced ovarian suppression. Sixteen women with endometriosis underwent i.v. infusion of calcium (1.1 mg calcium gluconate/cc in 5% dextrose) at a rate of 4 cc/kg x h (n = 7) or human PTH-(1-34) (Parathar) at a dose of 0.55 U/kg x h (n = 9) before and after 6 months of suppression of ovarian function with the GnRH analog nafarelin acetate (200 microg, intranasally, twice daily). Initial infusions were performed between days 6-10 of the menstrual cycle. Serum PTH and whole blood ionic calcium levels were measured at -20, -10, and 0 min and then every 10 min for 2 h during i.v. calcium infusions. Whole blood ionic calcium and 1,25-dihydroxyvitamin D levels were measured every 6 h for 24 h during i.v. human PTH-(1-34) infusions. Serum estradiol levels were markedly suppressed by nafarelin therapy in both groups of women. The relationship between whole blood ionic calcium and serum PTH levels was similar before and during nafarelin-induced ovarian suppression. The net change and rate of rise in serum 1,25-dihydroxyvitamin D levels in response to PTH infusion were similar before and during nafarelin therapy. Peak whole blood ionic calcium and incremental increases in ionic calcium in response to PTH were similar before and during nafarelin therapy. Our data suggest that ovarian suppression does not alter the regulation of PTH secretion in response to calcium, the ability of PTH to stimulate 1,25-dihydroxyvitamin D formation, or the skeletal sensitivity to PTH. These findings suggest that alterations in calcium regulatory hormones by estrogen deficiency are unlikely to play a major role in the pathogenesis of estrogen deficiency bone loss.

Nafarelin acetate for pituitary suppressions in in-vitro fertilisation cycles--a Singaporean experience.

AIM OF STUDY: The aim of this prospective clinical trial was to determine if intranasal nafarelin acetate (NA) is as effective as leuprolide (LA), our standard GnRHa, in IVF cycles. In addition, we believe that this may be the first report of such a trial in an Asian IVF population. METHOD: Midluteal GnRHa administration (LA = 0.5 mg/d; NA = 800 micrograms/d) was used with a standardised hMG ovarian stimulation protocol for all 88 consecutive cycles, randomised at recruitment. RESULTS: There were no significant differences between LA and NA in terms of the mean duration of agonist to reach pituitary suppression, total hMG dosage, number of embryos produced or frozen and the clinical pregnancy rate (LA = 21.4% and NA = 16.3% per cycle). CONCLUSION: Intranasal nafarelin acetate was as effective as leuprolide acetate in our series of IVF patients of Asian origin, and may be offered as an alternative choice for pituitary suppression.

Comparison of buserelin and nafarelin in IVF cycles and in subsequent frozen-thawed embryo transfer cycles.

OBJECTIVE: To compare two gonadotropin-releasing hormone agonists for down-regulation prior to superovulation in in vitro fertilization/embryo transfer treatment. METHODS: Infertility patients (n=181) were randomized to receive buserelin (1200 microg/day, n=90) or nafarelin (800 microg/day, n=91) intranasally starting in the luteal phase. Serum levels of LH, estradiol and progesterone were measured during the treatment. The cycles were compared with regard to number of oocytes, fertilization and implantation rates and achieved pregnancies. RESULTS: Serum LH was lower after two weeks on buserelin: 1.8 (1.3-2.4) IU/L (median, with lower and upper quartile in parenthesis), than after nafarelin: 2.6 (1.8-4.0) IU/L, (p=0.0001). No other differences in serum hormone levels could be detected. More oocytes were recovered in the buserelin group: 13.0 (8.0-19.0) vs 11.0 (6.8-15.0), (p=0.046), but the fertilization rate was higher in the nafarelin group (49.9%, vs 45.1%, p=0.023). Implantation rate was higher in the nafarelin group (26.28% vs 15.5%, p=0.030), but there were an equal number of deliveries in both groups (20.9% vs 15.6% per started stimulation, p=0.420). In the subsequent frozen-thawed embryo transfer cycles the implantation rate was 21.1% (nafarelin group) and 10.6% (buserelin group, p=0.067), the pregnancy rate/ET was 31.7% and 17.0% (p=0.107) and the delivery rate was 22.0% and 10.6% (p=0.148), respectively. CONCLUSIONS: Differences exist in IVF-cycles down-regulated with buserelin or nafarelin which might affect embryo quality and treatment outcome.

Doppler parameters of uterine and ovarian stromal blood flow in women with polycystic ovary syndrome and normally ovulating women undergoing controlled ovarian stimulation.

OBJECTIVE: To test the hypothesis that the increased ovarian sensitivity to gonadotropins observed in women with polycystic ovary syndrome (PCOS) may be due to changes in ovarian stromal blood flow in these patients. DESIGN: Uterine and ovarian stromal arterial blood flow (with transvaginal color Doppler ultrasound) were measured in ten women with PCOS and 12 normo-ovulatory women (control group), undergoing gonadotropin stimulation before in vitro fertilization. METHODS: A careful ovarian stimulation strategy was adopted for the study group in order to avoid ovarian hyperstimulation syndrome and achieve an ovarian response which was comparable to that of the control group. Resistance and pulsatility indices (RI and PI) of the uterine and ovarian stromal arteries were calculated before the onset of gonadotropin treatment, on cycle day 5 (after commencing treatment), day of human chorionic gonadotropin injection, day of ovum pick-up as well as on the day of embryo transfer, and 7 and 12 days later. RESULTS: No significant differences were found in RI and PI between the study and control groups throughout the treatment cycle. CONCLUSIONS: It seems that polycystic ovaries do not bear an inherent disturbance in blood flow dynamics of the uterine and ovarian arteries, as measured by color Doppler, which would explain the increased sensitivity of polycystic ovaries to stimulation with gonadotropins.