Gonadotropin-releasing Hormone Administration Research Articles

Effect of transfer of one or two in vitro-produced embryos and post-transfer administration of gonadotropin releasing hormone on pregnancy rates of heat-stressed dairy cattle

Pregnancy rates following transfer of an in vitro-produced (IVP) embryo are often lower than those obtained following transfer of an embryo produced by superovulation. The purpose of the current pair of experiments was to examine two strategies for increasing pregnancy rates in heat stressed, dairy recipients receiving an IVP embryo. One method was to transfer two embryos into the uterine horn ipsilateral to the CL, whereas the other method involved injection of GnRH at Day 11 after the anticipated day of ovulation. In Experiment 1, 32 virgin crossbred heifers and 26 lactating crossbred cows were prepared for timed embryo transfer by being subjected to a timed ovulation protocol. Those having a palpable CL were randomly selected to receive one ( n = 31 recipients) or two ( n = 27 recipients) embryos on Day 7 after anticipated ovulation. At Day 64 of gestation, the pregnancy rate tended to be higher ( P = 0.07) for cows than for heifers. Heifers that received one embryo tended to have a higher pregnancy rate than those that received two embryos (41% versus 20%, respectively) while there was no difference in pregnancy rate for cows that received one or two embryos (57% versus 50%, respectively). Pregnancy loss between Day 64 and 127 only occurred for cows that received two embryos (pregnancy rate at Day 127 = 17%). Between Day 127 and term, one animal (a cow with a single embryo) lost its pregnancy. There was no difference in pregnancy rates at Day 127 or calving rates between cows and heifers, but females that received two embryos had lower Day-127 pregnancy rates and calving rates than females that received one embryo ( P < 0.03). Of the females receiving two embryos that calved, 2 of 5 gave birth to twins. For Experiment 2, 87 multiparous, late lactation, nonpregnant Holstein cows were synchronized for timed embryo transfer as in Experiment 1. Cows received a single embryo in the uterine horn ipsilateral to the ovary containing the CL and received either 100 μg GnRH or vehicle at Day 11 after anticipated ovulation (i.e. 4 days after embryo transfer). There was no difference in pregnancy rate for cows that received the GnRH or vehicle treatment (18% versus 17%, respectively). In conclusion, neither unilateral transfer of two embryos nor administration of GnRH at Day 11 after anticipated ovulation improved pregnancy rates of dairy cattle exposed to heat stress.

Effect of timing of prostaglandin administration, controlled internal drug release removal and gonadotropin releasing hormone administration on pregnancy rate in fixed-time AI protocols in crossbred Angus cows

Two experiments were conducted to investigate the effects of timing of prostaglandin F2 α (PGF2 α) administration, controlled internal drug release device (CIDR) removal and second gonodotropin releasing hormone (GnRH) administration on the pregnancy outcome in CIDR-based synchronization protocols. In Experiment 1, suckled Angus crossbred beef cows ( n = 580) were given 100 μg of GnRH + a CIDR on Day 0. Cows in Group 1 (modified Ovsynch-P) received 25 mg of dinoprost (PGF2 α) and CIDR device removal on Day 8 (AM), 100 μg of GnRH 36 h later on Day 9 (p.m.), and fixed-time AI (FTAI) 16 h later on Day 10 (47.5 ± 1.1 h after PGF2 α). Cows in Group 2 (Ovsynch-P) received 25 mg of PGF2 α and CIDR device removal on Day 7 (p.m.), 100 μg of GnRH 48 h later on Day 9 and FTAI 16 h later on Day 10 (66.6 ± 1.2 h after PGF2 α). Pregnancy rates were 56.5% (170/301) for Group 1 and 55.6% (155/279) for Group 2, respectively ( P = 0.47). In Experiment 2, beef cows ( n = 734) were synchronized with 100 μg of GnRH + CIDR on Day 0, 25 mg of PGF2 α and CIDR device removal on Day 7 and either 100 μg of GnRH 48 h later on Day 9 (Ovsynch-P) and FTAI 16 h later on Day 10 (64.9 ± 3.3 h from PGF2 α) or 100 μg of GnRH on Day 10 (CO-Synch-P) at the time of AI (63.2 ± 4.2 h from PGF2 α). Pregnancy rates were 48.8% (180/369) for Ovsynch-P and 44.7% (163/365) for CO-synch-P groups, respectively ( P = 0.11). In both experiments, there was a location × treatment interaction ( P < 0.05); pregnancy rates between locations were different ( P < 0.05) in the Ovsynch-P group. In conclusion, in a CIDR-based Ovsynch synchronization protocol, delaying administration of prostaglandin and CIDR removal by 12 h, or timing of the second GnRH by 16 h, did not affect pregnancy rates to FTAI. Therefore, there may be an opportunity to make changes in synchronization protocols with out adversely affecting FTAI pregnancy rates.

OUTCOME OF GONADOTROPIN THERAPY FOR MALE HYPOGONADOTROPIC HYPOGONADISM AT UNIVERSITY AFFILIATED MALE INFERTILITY CENTERS: A 30-YEAR RETROSPECTIVE STUDY

Hypogonadotropic hypogonadism (HH) is an uncommon cause of male infertility. Even specialized centers see small numbers of patients and have little experience in restoring fertility in these patients. To explore the phenotypic heterogeneity and treatment outcome of HH, we summarized our 30-year experience. Medical charts of 36 male patients (age range 11 to 42 years) with HH (81% primary, 19% secondary) treated at university affiliated male infertility centers were reviewed. Pubic hair stage, genital stage, testicular volume (TV), sexual function and sperm production were determined before and after human chorionic gonadotropin/human menopausal gonadotropin (hCG/hMG) treatment. Differences were analyzed statistically. The population was stratified according to initial TV into a small testis subset (TV less than 4 ml in 23) and a large testis subset (TV 4 ml or greater in 13). Comparison of these 2 subsets revealed significant differences in the incidence of cryptorchidism (39% vs 8%) and Kallmann's syndrome (22% vs 0%), pubic hair stage (1.3 +/- 0.5 vs 3.5 +/- 1.4), genital stage (1.2 +/- 0.4 vs 3.9 +/- 0.9) and TV (1.6 +/- 0.9 vs 7.5 +/- 3.5 ml). Long-term administration of hCG/hMG for 12 to 240 months (average 56 +/- 11) resulted in sperm production in only 36% of the small testis subjects but in 71% of the large testis subjects. Initial TV values provide insight into phenotypic variables such as time of onset and severity in patients with primary or secondary HH, and may predict sperm output in response to hCG/hMG therapy.

Subcutaneous administration of pulsatile gonadotropin-releasing hormone decreases serum follicle-stimulating hormone and luteinizing hormone levels in women with polycystic ovary syndrome: A preliminary study

The main objectives of this study were to investigate whether [1] subcutaneous (SC) administration of pulsatile gonadotropin-releasing hormone (GnRH) decreases the increased levels of luteinizing hormone (LH) observed in women with polycystic ovary syndrome (PCOS); and [2] GnRH administration modifies the pattern of LH secretion observed in these patients. Serum follicle-stimulating hormone (FSH) and LH levels and LH pulse amplitude and pulse interval were determined in 13 patients with PCOS during the first 3 days of the cycle following the administration of 10 mg of medroxyprogesterone acetate during 5 days. Infertility clinic. Thirteen women with PCOS. Determination of FSH and LH serum levels after SC administration of pulsatile GnRH. The FSH and LH levels in serum. Mean FSH and LH levels in serum decreased following the administration of subcutaneous pulsatile GnRH in all treated women compared with baseline values. The LH pulse amplitude and pulse interval decreased in all patients following the administration of pulsatile GnRH. The SC administration of pulsatile GnRH in women with PCOS significantly decreases FSH and LH levels in serum. A decrease in the secretion of gonadotropins, without reaching the intense suppression observed with GnRH analogues, could be of great utility in in vitro fertilization (IVF) treatments.

Relationship between follicle size at insemination and pregnancy success.

Administration of gonadotropin-releasing hormone (GnRH) induces a surge of luteinizing hormone and ovulation in a variety of species, including human beings. Our objectives were to determine the effect of follicle size at the time of ovulation on corpus luteum function and establishment and maintenance of pregnancy in cows in which ovulation was either spontaneous or induced with GnRH. GnRH-induced ovulation of follicles < or approximately = 11 mm in diameter resulted in decreased pregnancy rates and increased late embryonic mortality. This decrease in fertility was associated with lower circulating concentrations of estradiol on the day of insemination, a decreased rate of increase in progesterone after insemination, and, ultimately, decreased circulating concentrations of progesterone. In contrast, ovulatory follicle size had no apparent effect on fertility when ovulation occurred spontaneously. Follicles undergoing spontaneous ovulation do so at a wide range of sizes when they are physiologically mature. Therefore, administration of GnRH to induce ovulation likely initiates a preovulatory gonadotropin surge before some dominant follicles attain physiological maturity. GnRH-induced ovulation of follicles that are physiologically immature has a negative impact on pregnancy rates and late embryonic/fetal survival. These observations in cattle may have implications for assisted reproductive procedures in human beings.

Luteal stage dependence of pituitary response to gonadotrophin-releasing hormone in cyclic dairy ewes subjected to synchronisation of ovulation

Possible hormonal aberrations precluding conception or maintenance of pregnancy in dairy ewes subjected to ovulation synchronisation were investigated in this study. The pituitary response to exogenous gonadotrophin-releasing hormone (GnRH) was tested at different luteal stages in 36 ewes. Oestruses were synchronised by using progestagen-impregnated sponges and the animals were randomly allotted into one of three treatment groups (A, B and C; n = 12 for each). Treatments commenced on Days 4, 9 and 14 of the new cycle (oestrus was defined as Day 0). Ewes were given two GnRH injections, 5 days before and 36 h after a prostaglandin F2+/- (PGF2+/-) injection, and the animals were inseminated 12-14 h after the second GnRH injection (modified OVSYNCH). For luteinising hormone (LH) determination blood samples were withdrawn from six ewes of each group at the time of GnRH administration, and 30, 90, 180, 270 and 360 min later. Progesterone was assayed in samples taken every other day starting from oestrus and for 17 days after the second GnRH injection, and in an additional sample collected on the day of insemination. After the first GnRH injection, the LH concentration was higher in Group C than in Groups B and A (mean +/- s.d.: 64.8 +/- 10.0 ng mL(-1), 41.3 +/- 3.7 ng mL(-1) and 24.6 +/- 9.0 ng mL(-1), respectively; P < 0.05), whereas after the second GnRH injection a uniform LH release was found in all groups. PGF2+/- caused a significant decrease in progesterone (P4) concentration in all groups; however, at artificial insemination ewes that conceived had significantly lower P4 concentration in comparison with those that failed to conceive. As early as Day 5, pregnant animals had higher P4 concentrations than non-pregnant animals. Overall, 21 animals conceived (seven, nine and five ewes from Groups A, B and C, respectively). These results indicate that the proposed protocol is equally effective in inducing a preovulatory LH surge at any stage of the luteal phase, and that elevated P4 concentration along with a delayed P4 increase should be considered as a causative factor for inability to conceive.

Application of gonadotropin releasing hormone in hypogonadotropic hypogonadism--diagnostic and therapeutic aspects

Puberty is the result of reactivation of the gonadotropin releasing hormone (GnRH) pulse generator resulting in an increasing release of GnRH by the hypothalamus, which stimulates the gonadotropic cells of the pituitary to synthesize and secrete LH and FSH. Hypogonadotropic hypogonadism (HH) is often the result of GnRH deficiency. The clinical picture is characterized by the absence of pubertal development and infertility. It is difficult to differentiate HH from delayed puberty since low gonadotropin and low testosterone levels are found in both conditions. We hypothesized that long-term GnRH administration may differentiate between the two conditions by a difference in the increase of gonadotropins, the idea being that in normal delayed puberty the pituitary of the patient has been primed with GnRH during the fetal and early postnatal period. Seventeen adolescents suspected of having hypogonadotropic hypogonadism were treated with pulsatile GnRH for 7 days. At the present time, the diagnosis of these patients is known and the results of the long-term GnRH stimulation have been evaluated according to the present diagnosis. The results show that the increase in gonadotropins following GnRH treatment is similar in both conditions. Therefore, at a prepubertal age a normal delayed puberty cannot be distinguished from hypogonadotropic hypogonadism using long-term GnRH stimulation. Long-term pulsatile GnRH treatment is a physiological therapy for the induction of puberty. Unlike testosterone it has the advantage of stimulation of testicular growth and fertility, as well as virilization, in males. We have treated 68 male patients with HH with pulsatile GnRH. The results show testicular growth and virilization in all the patients and spermatogenesis in 58 patients. Wearing a portable pump is cumbersome. However, the patients were very motivated and adapted very easily to this inconvenience. When spermatogenesis had developed, GnRH treatment was changed to human chorionic gonadotropin (hCG) administration 1-2 times per week intramuscularly or subcutaneously. During hCG therapy spermatogenesis was maintained or even improved. At least ten patients fathered children. Pulsatile GnRH cannot distinguish between a normal delayed puberty and a hypothalamic defect in still prepubertal patients. Pulsatile GnRH offers an appropriate way to initiate testicular growth including virilization and fertility in males with hypogonadotropic hypogonadism.

Deslorelin on Day 8 or 12 postovulation does not luteinize follicles during an artificially maintained diestrous phase in the mare

Practical estrus synchronization schemes are needed for mares. The Ovsynch synchronization protocol for cattle involves the administration of gonadotropin-releasing hormone (GnRH) to induce ovulation or luteinization of dominant follicles during the luteal phase and prostaglandin 7 days later to cause regression of any luteal tissue and development of a preovulatory follicle. An Ovsynch-type synchronization program potentially could be developed for horses if luteinization or ovulation of diestrous follicles occurred in response to GnRH treatment. The objective of this study was to determine if administration of the GnRH agonist, deslorelin acetate, on Day 8 or 12 postovulation would induce luteinization or ovulation of diestrous follicles in the mare. The model used was cycling mares maintained in an artificial luteal phase by administration of a synthetic progestin following prostaglandin-induced luteal regression. On the day of ovulation, 21 light horse mares were randomly assigned to one of three groups: (1) no GnRH, altrenogest from Days 5 to 15 postovulation with prostaglandin on Day 15; (2) GnRH on Day 8, altrenogest from Days 5 to 15 with prostaglandin given on Day 6 to induce luteolysis of the primary corpus luteum, an implant containing 2.1 mg of deslorelin acetate inserted on Day 8 and removed on Day 10, with a second prostaglandin treatment on Day 15; (3) GnRH on Day 12, altrenogest from Days 9 to 19, prostaglandin on Day 10, a deslorelin acetate implant injected on Day 12 (subsequently removed on Day 14), and a second dose of prostaglandin administered on Day 19. Follicular development was monitored every other day from Day 5 until a 30-mm sized follicle was observed, and then daily to detection of ovulation. Serum progesterone concentrations were determined daily for 12 consecutive days. Progesterone concentrations in Group 1 remained elevated until approximately Day 12 postovulation. Prostaglandin administration on Day 15 resulted in complete luteolysis in all seven mares. In Group 2, progesterone concentrations in six of seven mares declined to baseline after prostaglandin treatment. No increase in serum progesterone was noted in any of the six mares that were given GnRH on Day 8, including three mares that had diestrous follicles ≥30 mm in diameter at the time of treatment. Similarly, progesterone concentrations in six of seven mares in Group 3 declined to baseline after prostaglandin and there was no increase in progesterone after administration of GnRH on Day 12. No ultrasound evidence of luteinization or ovulation of diestrous follicles were noted after GnRH administration in any mares of Group 2 or 3. In conclusion, administration of the GnRH agonist deslorelin acetate to mares failed to induce luteinization or ovulation of diestrous follicles. Consequently, the Ovsynch program (as used in cattle) has little efficacy for synchronization of estrus in mares.

Prostaglandin F2$alpha;-induced estrus in ewes exhibiting estrous cycles of different duration

Effects of prostaglandin F2α (PGF2α), administered during the mid-luteal phase of the estrous cycle, were examined in ewes exhibiting estrous cycles classified as short (≤16.5 days, short-cycle ewes, n=10) or long (≥18 days, long-cycle ewes, n=9) based on the durations of two estrous cycles (cycles −2 and −1) before treatment. The ewes received (i.m.) 20 mg of PGF2α on day 10 of the third estrous cycle (cycle 0) followed, 36 h later, by 25 μg of gonadotropin releasing hormone (GnRH) to time the events of ovulation. Duration of subsequent estrous cycles +1 and +2 were recorded, and then the ewes were treated with the same combination of PGF2α and GnRH beginning on day 10 of estrous cycle +3. Ovaries were recovered 6 h after GnRH administration to assess development of pre-ovulatory follicles. The proportion of ewes that exhibited estrus after PGF2α and GnRH treatment on cycle 0 was not different (P>0.05) between short- and long-cycle ewes. Onset of estrus occurred sooner (P<0.05) after PGF2α injection in short-cycle ewes than in long-cycle ewes (1.9±0.1 days and 2.3±0.1 days, duration of cycle 0 was 11.9 and 12.3 days, respectively). Duration of estrous cycle +1 was 1.2 days longer (P<0.01) than cycle −1 in short-cycle ewes. However, duration of estrous cycle +1 did not change (P>0.05) after PGF2α and GnRH administration in ewes having long cycles. Pre-ovulatory follicles did not differ (P>0.05) in numbers, diameter, layers of granulosa cells nor concentrations of progesterone and estradiol-17β in follicular fluid between short- and long-cycle ewes after PGF2α and GnRH treatment. In conclusion, ewes having short or long estrous cycles responded differently to PGF2α and GnRH treatment with respect to the interval to onset of estrus and duration of the subsequent estrous cycle.

Does the gonadotropin-releasing hormone stimulation test predict clinical outcomes after microsurgical varicocelectomy?

Objectives To examine the predictive value of the gonadotropin-releasing hormone (GnRH) stimulation test in a large cohort of infertile men undergoing varicocelectomy. Methods We examined the records of 144 consecutive infertile couples in whom the man underwent microsurgical varicocelectomy between September 1998 and December 2002. All men underwent a GnRH stimulation test before surgery. Data on the preoperative and postoperative semen parameters, pregnancy outcome, and follicle-stimulating hormone (FSH) and luteinizing hormone increase after GnRH stimulation were recorded. Results The mean (±SE) sperm concentration and motility 6 months after varicocelectomy were significantly greater than the preoperative values (25.3 ± 2.4 versus 19.7 ± 2.1 × 10 6/mL and 29.2% ± 1.4% versus 25.3% ± 1.3%, respectively, P <0.05). Overall, 28% of the couples achieved a spontaneous pregnancy at a mean of 22 months of follow-up. The median elevation in the FSH and luteinizing hormone value 60 minutes after GnRH administration was 1.8 and 5.6 times the baseline level, respectively. No statistically significant relationship was found between the FSH or LH response to GnRH stimulation and improvement in the semen parameters or positive pregnancy outcome in our population. Conclusions Our data showed that the FSH response to bolus GnRH stimulation does not predict improvement in semen parameters or unassisted pregnancy outcome in couples in whom the man undergoes varicocelectomy (for treatment of varicocele). The study was the largest of its type and sufficiently powered to validate these findings. The results indicate that the bolus GnRH stimulation test is of no clinical value in the treatment of infertile men with varicoceles.

Transrectal ultrasonic diagnosis of ovarian follicular cysts in goats and treatment with GnRH

Cystic ovarian disease is an important cause of reproductive failure. The objective of this study was to evaluate transrectal ultrasonography as a diagnostic tool and gonadotropin-releasing hormone (GnRH) as a therapeutic approach for ovarian follicular cysts in goats. Goats were considered to have a follicular cyst(s) if a non-echoic structure >10 mm in diameter was detected in the absence of corpora lutea (CL) in three ultrasonic examinations performed at 5-day intervals. After diagnosis (Day 0), goats with ovarian follicular cysts ( n=5) were treated with a single bolus injection of 10.5 μg synthetic GnRH followed by administration of 125 μg prostaglandin F2α (PGF2α) 10 days later. Five blood samples were collected at 5-day intervals for determination of progesterone and estradiol-17β. For detection of LH surge, blood samples were collected every 2 h. Ovulation rate was determined and pregnancy was confirmed by transrectal ultrasonography. The results showed that transrectal ultrasonography is reliable for diagnosis of ovarian follicular cysts and the mean diameter of the follicular cysts was 12.6±0.4 mm. Plasma concentrations of progesterone and estradiol-17β at the time of diagnosis of follicular cysts (Day 0) were 0.7±0.2 ng/ml and 12.7±0.9 pg/ml, respectively. The concentration of progesterone increased to 4.0±0.5 ng/ml 10 days after administration of GnRH indicating luteinization of the ovarian follicular cysts concomitant with a decrease in the concentration of estradiol-17β (3.5±0.4 pg/ml). Administration of GnRH to cystic goats resulted in a surge of LH within 2 h of treatment. The interval from PGF2α injection to the preovulatory LH surge was 62.8±1.4 h. All goats exhibited estrus 55.2±2.3 h after PGF2α injection and four goats out of the five ovulated. The ovulation rate was 1.5±0.3. In conclusion, results of this study suggest that transrectal ultrasonography is a reliable tool for diagnosis of ovarian follicular cysts. In addition, GnRH can be used to effectively treat ovarian follicular cysts in goats with 80% success rate.

The interrelationships between thyroid dysfunction and hypogonadism in men and boys.

Thyroid hormone deficiency affects all tissues of the body, including multiple endocrine changes that alter growth hormone, corticotrophin, glucocorticoids, and gonadal function. Primary hypothyroidism is associated with hypogonadotropic hypogonadism, which is reversible with thyroid hormone replacement therapy. In male children follicle-stimulating hormone (FSH) is elevated and associated with testicular enlargement without virilization. Men with primary hypothyroidism have subnormal responses of luteinizing hormone (LH) to gonadotropin-releasing hormone (GnRH) administration and normal response to human chorionic gonadotropin (hCG). Free testosterone concentrations are reduced in men with primary hypothyroidism and thyroid hormone replacement normalizes free testosterone concentrations. In men with primary hypothyroidism, prolactin is not consistently elevated (except in men and children with longstanding severe primary hypothyroidism), but prolactin declines following thyroid hormone replacement therapy. Thyroid hormone is known to affect sex hormone-binding hormonal globulin (SHBG) concentrations. Men with hyperthyroidism have elevated concentrations of testosterone and SHBG. Thyroid hormone therapy in normal men may also duplicate this elevation. In addition estradiol elevations are observed in men with hyperthyroidism, and gynecomastia is common in them as well. In contrast to patients with primary hypothyroidism, men with hyperthyroidism exhibit hyperresponsiveness of LH to GnRH administration and subnormal responses to hCG. Radioactive iodine therapy (RAI) of men treated for thyroid cancer produces a dose-dependent impairment of spermatogenesis and elevation of FSH up to approximately 2 years. Permanent testicular germ cell damage may occur in men treated with high doses of RAI. RAI commonly increases serum concentrations of FSH and LH while reducing inhibin B levels without affecting serum concentrations of testosterone. Thus, radioiodine therapy transiently impairs both germinal and Leydig cell function that usually recover by 18 months posttherapy.

Deslorelin on Day 8 or 12 postovulation does not luteinize follicles during an artificially maintained diestrous phase in the mare

Practical estrus synchronization schemes are needed for mares. The Ovsynch synchronization protocol for cattle involves the administration of gonadotropin-releasing hormone (GnRH) to induce ovulation or luteinization of dominant follicles during the luteal phase and prostaglandin 7 days later to cause regression of any luteal tissue and development of a preovulatory follicle. An Ovsynch-type synchronization program potentially could be developed for horses if luteinization or ovulation of diestrous follicles occurred in response to GnRH treatment. The objective of this study was to determine if administration of the GnRH agonist, deslorelin acetate, on Day 8 or 12 postovulation would induce luteinization or ovulation of diestrous follicles in the mare. The model used was cycling mares maintained in an artificial luteal phase by administration of a synthetic progestin following prostaglandin-induced luteal regression. On the day of ovulation, 21 light horse mares were randomly assigned to one of three groups: (1) no GnRH, altrenogest from Days 5 to 15 postovulation with prostaglandin on Day 15; (2) GnRH on Day 8, altrenogest from Days 5 to 15 with prostaglandin given on Day 6 to induce luteolysis of the primary corpus luteum, an implant containing 2.1 mg of deslorelin acetate inserted on Day 8 and removed on Day 10, with a second prostaglandin treatment on Day 15; (3) GnRH on Day 12, altrenogest from Days 9 to 19, prostaglandin on Day 10, a deslorelin acetate implant injected on Day 12 (subsequently removed on Day 14), and a second dose of prostaglandin administered on Day 19. Follicular development was monitored every other day from Day 5 until a 30-mm sized follicle was observed, and then daily to detection of ovulation. Serum progesterone concentrations were determined daily for 12 consecutive days. Progesterone concentrations in Group 1 remained elevated until approximately Day 12 postovulation. Prostaglandin administration on Day 15 resulted in complete luteolysis in all seven mares. In Group 2, progesterone concentrations in six of seven mares declined to baseline after prostaglandin treatment. No increase in serum progesterone was noted in any of the six mares that were given GnRH on Day 8, including three mares that had diestrous follicles ≥30 mm in diameter at the time of treatment. Similarly, progesterone concentrations in six of seven mares in Group 3 declined to baseline after prostaglandin and there was no increase in progesterone after administration of GnRH on Day 12. No ultrasound evidence of luteinization or ovulation of diestrous follicles were noted after GnRH administration in any mares of Group 2 or 3. In conclusion, administration of the GnRH agonist deslorelin acetate to mares failed to induce luteinization or ovulation of diestrous follicles. Consequently, the Ovsynch program (as used in cattle) has little efficacy for synchronization of estrus in mares.

Prostaglandin F 2α-induced estrus in ewes exhibiting estrous cycles of different duration

Effects of prostaglandin F 2α (PGF 2α), administered during the mid-luteal phase of the estrous cycle, were examined in ewes exhibiting estrous cycles classified as short (≤16.5 days, short-cycle ewes, n=10) or long (≥18 days, long-cycle ewes, n=9) based on the durations of two estrous cycles (cycles −2 and −1) before treatment. The ewes received (i.m.) 20 mg of PGF 2α on day 10 of the third estrous cycle (cycle 0) followed, 36 h later, by 25 μg of gonadotropin releasing hormone (GnRH) to time the events of ovulation. Duration of subsequent estrous cycles +1 and +2 were recorded, and then the ewes were treated with the same combination of PGF 2α and GnRH beginning on day 10 of estrous cycle +3. Ovaries were recovered 6 h after GnRH administration to assess development of pre-ovulatory follicles. The proportion of ewes that exhibited estrus after PGF 2α and GnRH treatment on cycle 0 was not different ( P>0.05) between short- and long-cycle ewes. Onset of estrus occurred sooner ( P<0.05) after PGF 2α injection in short-cycle ewes than in long-cycle ewes (1.9±0.1 days and 2.3±0.1 days, duration of cycle 0 was 11.9 and 12.3 days, respectively). Duration of estrous cycle +1 was 1.2 days longer ( P<0.01) than cycle −1 in short-cycle ewes. However, duration of estrous cycle +1 did not change ( P>0.05) after PGF 2α and GnRH administration in ewes having long cycles. Pre-ovulatory follicles did not differ ( P>0.05) in numbers, diameter, layers of granulosa cells nor concentrations of progesterone and estradiol-17β in follicular fluid between short- and long-cycle ewes after PGF 2α and GnRH treatment. In conclusion, ewes having short or long estrous cycles responded differently to PGF 2α and GnRH treatment with respect to the interval to onset of estrus and duration of the subsequent estrous cycle.

Effects of medroxyprogesterone acetate (MAP) on ovarian antral follicle development, gonadotrophin secretion and response to ovulation induction with gonadotrophin-releasing hormone (GnRH) in seasonally anoestrous ewes

When ovulation is induced with gonadotrophin-releasing hormone (GnRH) in anoestrous ewes, a proportion of animals fail to form normal (full-lifespan) corpora lutea (CL). Progesterone treatment before GnRH prevents luteal inadequacy. It remains uncertain whether a similar effect, achieved with medroxyprogesterone acetate (MAP) from intravaginal sponges, is mediated by influences on growing ovarian follicles and/or secretion of gonadotrophic hormones, before and after GnRH treatment. Two experiments were performed, on 13 and 11 anoestrous Western white-faced ewes, respectively. Seven and six ewes, respectively, received MAP-containing sponges (60 mg) for 14 days; the remaining ewes served as untreated controls. To test the effect of timing of GnRH administration after pre-treatment with MAP-releasing sponges, GnRH injections (250 ng every 2 h for 24 h followed by a bolus injection of 125 μg of GnRH i.v.) were given either immediately (Experiment 1) or 24 h after sponge removal in the treated ewes (Experiment 2). Ovarian follicular dynamics (follicles reaching ≥5 mm in size) and development of luteal structures were monitored using transrectal ultrasonography. In Experiment 1, the mean ovulation rate (0.7±0.3 and 1.0±0.4) and proportion of ovulating ewes (57 and 67%, respectively) did not vary ( P>0.05) between MAP-treated and control ewes. Normal (full-lifespan) CL were detected in 29% of treated and 67% of control ewes ( P>0.05). In Experiment 2, the mean ovulation rate (2.3±0.2 and 1.2±0.6; P<0.05) and percentage of ewes with normal (full-lifespan) CL (100 and 40%, respectively; P<0.10) were greater in the treated compared to control ewes. In Experiment 1, the mean peak concentration of the GnRH-induced LH surge was lower ( P<0.05) in MAP-treated than in control ewes. There were no significant differences between MAP-treated and control ewes in the characteristics of follicular waves, mean daily serum FSH concentrations, and secretory parameters of LH/FSH, based on intensive blood sampling conducted 1 day before sponging and 1 day before sponge removal. It is concluded that treatment with MAP has no effect on the tonic secretion of LH/FSH or follicular wave development in anoestrous ewes. However, the GnRH-stimulated LH discharge was attenuated in the ewes that received MAP-impregnated sponges for 14 days and were treated with GnRH immediately after sponge withdrawal. Ovulatory response and CL formation were increased when GnRH was administered 24 h after sponge removal.

Risk factors for male osteoporosis

Hypogonadism from long-term androgen deprivation therapy (ADT), either by bilateral orchiectomy or administration of gonadotropin-releasing hormone (GnRH) agonists, causes significant and accelerated bone loss that may increase the risk of bone fractures in men with prostate cancer. Recent reports, as well as new data from our institution, have shown a high prevalence of pre-existing osteopenia and osteoporosis in men with prostate cancer before receiving ADT, and this is of great concern because of the risk of further bone loss during ADT. Data from these studies suggest the urgent need for clinical guidelines for screening, prevention, and treatment of these cases. This article reviews the prevalence and risk factors associated with osteoporosis in men and addresses risk factors in men with prostate cancer not receiving ADT. Considerations for the patient selection and timing of bone densitometry will also be discussed.

Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intravenous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in women with polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in these women. Although ovulation and pregnancy have been achieved, the effectiveness of pulsatile GnRH in women with PCOS has not been clearly demonstrated. To assess the effectiveness of pulsatile GnRH administration in women with polycystic ovary syndrome (PCOS), in terms of ongoing pregnancy, ovulation, clinical pregnancy, ovarian hyperstimulation syndrome (OHSS), multiple pregnancy, miscarriage, and multifollicular growth. We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched 13 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, August 2001), MEDLINE (January 1966 to August 2003), EMBASE (January 1985 to August 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. All relevant published randomised clinical trials were selected for inclusion if treatment consisted of pulsatile GnRH administration versus another treatment for ovulation induction in subfertile women with PCOS. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. All trials were screened and analysed for predetermined quality criteria. 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto method. Four randomised clinical trials involving 57 women were identified comparing four different treatments: GnRH versus HMG, GnRH and FSH versus FSH, GnRH following pretreatment with GnRH agonist (GnRHa) versus GnRH only, GnRH following pretreatment with GnRHa versus clomiphene citrate. This means that there was only one trial in any one comparison. In two studies, data of pre- and post-crossover were not described separately. All trials were small and of too short duration to show any significant differences in pregnancy results. The odds ratio for ongoing pregnancy, only described in one trial, was 7.5 (95% CI 0.44 to 127) in the comparison GnRH following pretreatment with GnRHa versus GnRH only in favour of the first group. Multiple pregnancies were not seen. Ovarian hyperstimulation syndrome was seen only in women allocated to ovulation induction with HMG. The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Effect of royal jelly and GnRH on the estrus synchronization and pregnancy rate in ewes using intravaginal sponges

The influence of natural royal jelly (RJ) paste and gonadotropin releasing hormone (GnRH) on reproductive responses of Awassi ewes was evaluated. In May 1998, 20 Awassi ewes (aged 2–5 years and weighing 52 kg) were treated with 40 mg fluorogestone acetate (FGA) impregnated intravaginal sponges for a period of 12 days. Half of the ewes were administered orally a total of 3 g RJ paste in 12 equal doses of 250 mg per day starting at FGA sponge insertion while the remaining half received no RJ paste. Ewes were exposed to two fertile Awassi rams from the time of FGA sponge removal (0 h, 0 day). Blood samples were drawn on alternate days from days 0 to 19. Five ewes per group (RJ and control) were randomly selected to receive a 50 μg GnRH injection 28 h post-sponge removal. No interactions were detected between RJ and GnRH. Incidence of estrus was greater (8/10 versus 4/10) in RJ-treated than in control ewes and intervals from 0 h to detected estrus were similar (45±4.1 h versus 55±6.7 h, respectively). Progesterone concentration increased on days 5–7 in all ewes and remained elevated through day 19 in 60% of the RJ-treated and 20% of the control ewes. These ewes lambed on average 149 days later and the number of lambs born was similar between the two groups of ewes. Regardless of RJ treatment, GnRH administration decreased ( P<0.05) the interval from cessation of treatment to estrus. The first rise in plasma progesterone occurred on day 5 in GnRH-treated compared with day 7 for non-GnRH-treated ewes ( P<0.05). The results demonstrate that RJ treatment in conjunction with a source of exogenous progesterone can be used to induce estrus and increase first service conception rate in sheep. Administration of GnRH reduced the interval to estrus and advanced plasma progesterone elevation.

Influence of GnRH administration on timing of the LH surge and ovulation in dwarf goats

This study was conducted to determine whether or not exogenous gonadotropin releasing hormone (GnRH) alters the timing or improves the synchrony of estrus, the LH surge, and ovulation following estrous synchronization in dwarf goats, and to assess the effects of season on these parameters. In January and June, estrus was synchronized in 12 Pygmy and Nigerian Dwarf goats with a 10-day progestagen sponge, 125 μg cloprostenol i.m. 48 h before sponge removal, and 300 IU equine chorionic gonadotrophin (eCG) i.m. at sponge removal. Six of the 12 goats were given 50 μg GnRH i.m. 24 h after sponge removal. Onset of estrus was monitored using two males. Samples for plasma LH were collected at 2 h intervals beginning 22 h after sponge removal and ending at 48 h in January and at 58 h in June. Time of ovulation time was confirmed by laparoscopy at 36, 50, 60, and 74 h in January and at 50, 60, and 74 h in June. Administration of GnRH had no significant effect on the onset of estrus; however, it reduced the interval from sponge removal to the LH surge and improved the synchrony of the LH surge ( P<0.05). Treatment with GnRH also reduced the interval from sponge removal to ovulation and improved the synchrony of ovulation ( P<0.05). Season had a significant effect on the timing and the synchrony of estrus with and without GnRH treatment ( P<0.05). A seasonal shift was also observed in the timing of the LH surge in the absence of GnRH treatment ( P<0.05). Further research is required to determine the optimum time for GnRH administration and the minimum effective dose in dwarf goats.

Synchronisation of oestrus and reproductive performance of dairy cows following administration of oestradiol benzoate or gonadotrophin releasing hormone during a synchronised pro-oestrus.

To compare the use of gonadotrophin releasing hormone (GnRH) and oestradiol benzoate (ODB) administered following a synchronised pro-oestrus on reproductive performance of lactating dairy cows and the submission rates of non-pregnant cows following resynchronisation. Cohort study. Lactating Holstein cows enrolled in a controlled breeding program were first treated with an intravaginal progesterone releasing insert (IVP4) for 8 days, 2.0 mg of ODB intramuscular (i.m.) at device insertion (Day 0), an analogue of PGF2alpha at device removal and either 1.0 mg of ODB i.m., 24 h after device removal (ODB group, n = 242), or 0.25 mg of a GnRH agonist (GnRH group, n = 152) injected i.m. approximately 34 h after device removal. Every cow was artificially inseminated between 49 and 56 h after removal of its insert (Day 10). Cows detected in oestrus 1 day after artificial insemination (AI) that were not detected in oestrus on the previous day were re-inseminated on that day. All cows treated on Day 0 were resynchronised for reinsemination by insertion of a used IVP4 device on Day 23. Oestradiol benzoate at a dose of 1.0 mg was administered i.m. at the time of device insertion. Inserts were removed 8 days later (Day 31) and 1.0 mg of ODB was injected i.m. 24 h later. Those cows detected in oestrus between Days 31 and 35 were artificially inseminated. On Day 46 these cows were resynchronised for a third round of AI by insertion of an IVP4 device, used previously to synchronise cows for the first and second rounds of AI, and administration of 1.0 mg of ODB i.m.. Eight days later inserts were removed. Cows detected in oestrus between Days 54 and 58 were artificially inseminated. Bulls were run with the herd between rounds of AI and removed after 21 weeks of mating. Treatment with ODB or GnRH at the first synchronised pro-oestrus did not significantly alter the reproductive performance over three rounds of AI or over a 21-week breeding period. Treatment also did not alter submission rates at the second round of AI or the proportion of non-pregnant and non-return cows ('phantom' cows) detected and did not result in significant differences in concentrations of progesterone in plasma 10 and 18 days after removal of inserts at the first round of AI. Treatment with GnRH reduced the proportion of cows detected in oestrus at the first round of AI (36.2 vs 97.5%; P < 0.001). Administration of GnRH compared to ODB at a synchronised pro-oestrus results in similar reproductive performance. Treatment with GnRH reduced the proportion of cows detected in oestrus following treatment. This may offer advantages to the way AI is managed by enabling insemination at a fixed-time and removing the need for the detection of oestrus.