Use Of Gonadotropin-releasing Hormone Research Articles

Bruk av GnRH-antagonist ved in vitro-fertilisering

For many patients, the typical treatment protocol for in vitro fertilization (IVF) is both physically and psychologically demanding. An alternative approach to use of gonadotropin-releasing hormone (GnRH)-agonists traditionally used to prevent premature ovulation, is use of GnRH-antagonists. The aim of this article is to describe advantages and disadvantages of using GnRH-antagonists in IVF. The paper is based on literature identified through a non-systematic search in PubMed, and more than ten years of clinical experience with use of GnRH antagonists in IVF. To maintain a similar pregnancy rate as that with GnRH-agonists, one can use GnRH-antagonists at an earlier time-point during stimulation of the ovaries and a lower dose of follicle stimulating hormone (FSH). A less intensive stimulation implies a lower risk of complications and side effects and a shorter treatment period before egg collection (from four-five weeks to less than two weeks). The main disadvantage of the GnRH-antagonist protocol is that ovarian stimulation cannot be programmed to the same extent as that with use of a GnRH-agonist. Stimulation with a GnRH-antagonist instead of a GnRH-agonist in IVF, is less physically and psychologically demanding for the patients and maintains the same birth rate.

The Use of Gonadotropin-Releasing Hormone to Induce Ovulation

The Use of Gonadotropin-Releasing Hormone to Induce Ovulation

Is GnRH necessary at CIDR insertion using a 7-Day CIDR synchronization protocol for beef heifers?

The EAZI-BREED CIDR is commonly used in estrous synchronization protocols for both beef heifers and cows. The label calls for insertion of a progesterone-impregnated controlled internal drug release (CIDR) for 7 consecutive days with an injection of prostaglandin F2αgiven a day before CIDR removal. Animals should display estrus 1 to 3 days after CIDR removal. Modifications to this protocol include administration of gonadotropin-releasing hormone (GnRH) at the time of CIDR insertion and administration of the prostaglandin injection at the time of CIDR removal on day 7. Use of GnRH in conjunction with a CIDR may improve estrous synchronization in beef cows and fertility at fixed-time insemination but may not be necessary when synchronizing beef heifers. Our objective was to compare heat response and fertility in heifers with or without GnRH administration at the time of CIDR insertion. Our hypothesis was that heifer fertility would be similar between treatments.

Low-dose human chorionic gonadotropin versus estradiol/progesterone luteal phase support in gonadotropin-releasing hormone agonist–triggered assisted reproductive technique cycles: understanding a new approach

It remains unclear how GnRH agonist (GnRHa) triggering affects the luteal phase, so we investigated the luteal phase after GnRHa triggering, supported with conventional E(2)/P with or without low-dose hCG. E(2)/P support, compared with low-dose hCG, induced a shorter luteal phase (11.2 ± 1.1 vs. 15.0 ± 1.6 days) and fewer subjective complaints (0 vs. 42%), whereas hCG caused more free fluid accumulation and enlarged ovaries than E(2)/P alone. Steroids and low-dose hCG differentially affected corpus luteum function, ovarian size, free fluid accumulation, and patient comfort.

Partial budgeting assessment of the treatment of pyometra, follicular cysts and ovarian inactivity causing postpartum anoestrus in dairy cattle

A total of 412 multiparous German Holstein cows were screened for postpartum pyometra, follicular cysts and ovarian inactivity to assess economic and productivity losses in relation to pharmaceutical expenditures. Our results show that cows treated for pyometra with prostaglandin f2 alpha (PGF2α) and oxytetracycline had significantly ( P < 0.05) greater total and net returns than untreated cows or those treated with PGF2α + cephapirin or PGF2α alone. Milk yields from untreated cows affected by follicular cysts were significantly ( P < 0.05) lower than the yields from cows treated with gonadotrophin-releasing hormone (GnRH)− and GnRH + PGF2α. In addition, the use of GnRH to treat cows with ovarian inactivity resulted in significantly ( P < 0.05) lower costs and greater total and net return values compared to untreated controls.

Gonadotropin-releasing hormone agonist to induce final oocyte maturation prevents the development of ovarian hyperstimulation syndrome in high-risk patients and leads to improved clinical outcomes compared with coasting

Ninety-four women undergoing IVF with peak E2 level>4000 pg/mL received leuprolide acetate (LA) trigger (LA trigger group) or had gonadotropins withheld for one or more days (coasting group) followed by hCG trigger, unless cycle cancellation occurred. There were no cases of ovarian hyperstimulation syndrome in either group, and the LA trigger group had significantly more oocytes retrieved (26.9+/-9.5 vs. 17.7+/-9.3) P<0.001, more normally fertilized oocytes (15.0+/-7.8 vs. 10.3+/-6.3) P=0.01, and higher clinical and ongoing pregnancy rates than the coasting group (52.5% vs. 27.2%; 49.2% vs. 24.2%, P=0.02 for both comparisons, respectively).

Bovine embryo transfer recipient synchronisation and management in tropical environments

Numerous studies have shown that it is possible to manipulate follicular and luteal dynamics, thereby eliminating the need for oestrus detection in embryo transfer (ET) programmes. Fixed-time ET (FTET) protocols are based on the use of gonadotrophin-releasing hormone (GnRH) and prostaglandin (PG) F or progesterone/progestogen (P4)-releasing devices and oestradiol. The FTET protocols increases the proportion of recipients transferred, and therefore pregnancy rates, compared with the use of PGF followed by ET 7 days after oestrus. Furthermore, the addition of equine chorionic gonadotrophin (eCG) to the P4 and oestradiol-based FTET protocols results in an even higher proportion of recipients transferred, and thus higher pregnancy rates. The beneficial effect of eCG treatment may be related to increased growth of the dominant follicle and increased plasma P4 concentrations during the subsequent luteal phase. In Bos taurus x Bos indicus recipients, pregnancy rates were positively correlated with the diameter of the corpus luteum (CL) and the number of CL at ET. When repeat-breeder Holstein cows were used as recipients, FTET protocols increased number of recipients transferred and pregnancy rates compared with the traditional PGF-based synchronisation protocols. In conclusion, the use of FTET protocols eliminates the need for the detection of oestrus and results in a greater proportion of recipients transferred and satisfactory pregnancy rates. Thus, FTET optimises the use of recipients, reducing labour and animal handling and facilitating the use of ET.

The Use of Gonadotropin-Releasing Hormone in a Progesterone-Based Timed Artificial Insemination Protocol in Replacement Beef Heifers

The objective of this experiment was to determine the effect of supplemental gonadotropin-releasing hormone (GnRH) at the time of progesterone controlled internal drug-release (CIDR) insertion, when incorporated into a CIDR-prostaglandin F2α (PGF2α)-GnRH timed AI (TAI) protocol on pregnancy per AI of beef heifers. One hundred ninety-two beef replacement heifers in 2 locations were paired by BCS and BW and received a CIDR on d 0. At the time of CIDR insertion, heifers were assigned randomly to receive either GnRH (100 μg, i.m.) or physiological saline. On d 7, the CIDR was removed and all heifers received 25 mg PGF2α On d 9, all heifers were administered GnRH (100 μg, i.m.), followed immediately by TAI by a single inseminator. Pregnancy status was determined by ultrasound on d 35 after AI. Blood samples were collected on d −8, 0, and 9 to measure progesterone concentrations. There was no effect of location or a location × treatment interaction on pregnancy incidence (P = 0.47), and 97.8% of heifers were cyclic. Pregnancy per AI did not differ between treatments (P > 0.5). Body weight and BCS had no effect on the odds ratio of pregnancy (P > 0.5). Administration of GnRH at CIDR insertion did not improve pregnancies per AI when a 7-d CIDR-PGF2α-GnRH TAI protocol was used in cyclic beef heifers.

The efficiency of progesterone vaginal gel versus intramuscular progesterone for luteal phase supplementation in gonadotropin-releasing hormone antagonist cycles: a prospective clinical trial

We compared the efficiency of progesterone vaginal gel (PVG) with intramuscular progesterone (IMP) supplementation for luteal phase support after in vitro fertilization and embryo transfer in gonadotropin-releasing hormone (GnRH) antagonist cycles. The treatment outcomes were similar for PVG and IMP for luteal support in GnRH-antagonist protocols. With its ease of use, high tolerability by patients, and fewer side effects, PVG can be a successful alternative to IMP.

GnRH agonist versus recombinant HCG in an oocyte donation programme: a randomized, prospective, controlled, assessor-blind study

The use of gonadotrophin-releasing hormone (GnRH) agonists for triggering ovulation remains controversial. The primary objective of this study was to evaluate the incidence of ovarian hyperstimulation syndrome (OHSS) following GnRH agonist versus recombinant human chorionic gonadotrophin (HCG) as methods for triggering ovulation. A second aim was to compare the clinical outcome and embryo quality according to the two procedures. The cycle characteristics of 100 oocyte donors undergoing ovarian stimulation and IVF outcomes of their 100 oocyte recipients were analysed. Donors were prospectively randomized into two groups on the last day of ovarian stimulation: Group I received a single bolus of 0.2 mg of triptorelin and Group II received 250 microg of recombinant HCG. No differences were observed in the number of oocytes retrieved or in the proportion of metaphase II oocytes between the groups. The OHSS rate was higher in donors that received recombinant HCG ( P = 0.003). Moreover, there was no significant difference between IVF parameters and outcome in the two groups. In conclusion, a GnRH agonist effectively triggers the final oocyte maturation in oocyte donors without negatively affecting implantation, pregnancy or miscarriage rates. Moreover, this regime effectively eliminates the risk of OHSS in this group of women.

Prospective Randomized Trial Comparing Gonadotropin-Releasing Hormone Analogues With Triple Tourniquets at Open Myomectomy

The primary treatment for preservation of fertility in women with large fibroids―open myomectomy―is complicated by significant intraoperative bleeding. In a recent survey, over 85% of gynecologists in the United Kingdom reported use of gonadotropin-releasing hormone (GnRH) analogues before myomectomy to reduce operative hemorrhage at myomectomy. In contrast to pretreatment with GnRH analogues, less than 25% of gynecologists of the United Kingdom reported use of tourniquets to myomectomy-associated bleeding. Although evidence for reduction of bleeding by pretreatment with GnRH analogues has been shown in many studies, other studies have found no benefit. In a previous randomized, controlled trial, triple tourniquets (tourniquets applied to the uterine and ovarian vessels) were highly effective to temporarily occlude the uterine blood supply and reduce myomectomy-associated bleeding. This randomized, controlled trial compared the effectiveness of triple tourniquets and preoperative treatment with GnRH analogues in reducing blood loss in a population of 40 women undergoing open myomectomy for symptomatic fibroids. The study subjects were randomized to either 3 months pretreatment with a GnRH analogue or intraoperative application of triple tourniquets. To occlude the uterine blood supply, a number 1 polyglactin suture was threaded through the broad ligament incisions on each side and tied around the cervix above the level of the bladder and size 10 suction catheter tubing was also passed through the incisions and tied around the infundibulopelvic ligaments. Women randomized to tourniquets received no pretreatment. No significant differences between the 2 groups were found in the numbers of fibroids removed or in the total weight of fibroids (P = 0.13). Compared with triple tourniquets, intraoperative blood loss was significantly greater with the GnRH analogue group (GnRH analogues: median 2482 mL, 95% confidence level, 1744 to 3151 vs. tourniquets: mean 640 mL, 95% confidence level, 418 to 881, respectively, P < 0.001), and significantly more women in the GnRH analogue group required blood transfusion (70% vs. 30%, P < 0.025). The frequency of postoperative complications was similar among the 2 groups; most were minor. Two women from the tourniquet group sustained major complications that appeared to be unrelated to the use of tourniquets. There was no difference between the 2 groups in the length of the postoperative hospital stay and none of the women in either group was readmitted to hospital in the early postoperative period (<6 weeks). These data are consistent with previous findings that triple tourniquets are more effective than preoperative treatment with GnRH analogues or other available intraoperative techniques at reducing intraoperative blood loss at open myomectomy.

Use of Gonadotropin-Releasing Hormone at Fixed-Time Artificial Insemination at Eighty or Ninety-Seven Hours Post Prostaglandin F2α in Beef Cows Administered the Long-Term Melengestrol Acetate Select Synch

<h2>ABSTRACT</h2> In a 2-yr trial, the pregnancy response of 549 Angus-based cows (BCS 5.1 ± 0.56, postpartum interval 69.7 ± 19.1 d) was evaluated when estrous cycles were synchronized by feeding melengestrol acetate for 14 d with gonadotropin-releasing hormone (GnRH) given on d 26 and prostaglandin F_2α (PG) on d 33. Of all cows, those observed in estrus within 72h after PG were inseminated 9.5 ± 4.01h after estrus was first observed. The remaining cows were fixed-time inseminated (TAI) and randomly assigned to receive or not receive GnRH at TAI, and randomly assigned to be inseminated at 79.7 ± 2.26h (early) or 96.6 ± 1.94h (late) post-PG. There were no GnRH × year (<i>P</i> = 0.47) or GnRH × time of TAI (<i>P</i> = 0.96) interactions. Cows that received GnRH at TAI had a greater (<i>P</i> < 0.001) pregnancy rate than those receiving no GnRH. There was a tendency (<i>P</i> = 0.07) for a year × time of TAI interaction. In yr 1, late TAI cows had a greater (<i>P</i> = 0.01) pregnancy rate than early cows; however, in yr 2, pregnancy rate was not different (<i>P</i> > 0.10) between early and late cows. Results indicate that within the long-term melengestrol acetate Select Synch protocol, pregnancy rate of cows not observed in estrus within 72h of PG could be increased by adding a second GnRH injection at TAI, whereas the effect of delaying time of TAI until 97h post-PG on pregnancy rate was inconsistent.

Use of gonadotropin releasing hormone to improve reproductive responses of ewes introduced to rams during seasonal anestrus

Three experiments were conducted on anestrous ewes of Suffolk, Dorset, and Katahdin breeding to examine the potential value of GnRH to improve ovulation and pregnancy in response to introduction of rams. In Experiment 1, treatment with GnRH 2 d after treatment with progesterone (P 4; 25 mg i.m.) at introduction of rams was compared to treatment with P 4 alone at the time of introduction of rams. Treatment with GnRH did not increase percentages of ewes with a corpus luteum (CL) 14 d after introduction of rams, pregnant 32 d after treatment with PGF 2α 14 d after introduction of rams, or percent of treated ewes lambing to all services. In Experiment 2, treatments with GnRH on day 2, 7, or both after introduction of rams were compared. Treatments did not differ in mean estrous response, percentages of ewes with a detectable CL or number of CL present on day 11, or mean pregnancy and lambing rates. Therefore, neither one nor two injections of GnRH at these times appeared to be effective to induce anestrous ewes to breed. In Experiment 3, treatments compared included GnRH 4 d before introduction of rams, GnRH 4 d before and 1 d after introduction of rams, ram introduction alone, and treatment with P 4 (25 mg i.m.) at the time of introduction of rams. Percentages of ewes with concentrations of P 4 greater than 1 ng/mL (indicating formation of CL had occurred) 7 d after ram introduction tended to be greater ( P < 0.07) in ewes treated with GnRH or P 4 than in control ewes treated with ram introduction alone. However, there was no difference in P 4 concentrations between groups by day 11 or 12 after introduction of rams. Estrous response rates and percentages of ewes pregnant 95 d after PGF 2α was administered (on day 12 after introduction of rams) tended to be greater ( P = 0.08 and 0.06, respectively) in ewes treated with GnRH or P 4 than in ewes exposed to rams only. There was no difference in response variables between ewes treated with GnRH 4 d before introduction of rams and ewes treated with GnRH 4 d before and 1 d after introduction of rams. In conclusion, treatment with GnRH 4 d before ram introduction showed promise as an alternative to treatment with P 4 to improve the ovulatory response and reproductive performance of ewes introduced to rams during seasonal anestrus.

Vitrification is a highly efficient method to cryopreserve human embryos in in vitro fertilization patients at high risk of developing ovarian hyperstimulation syndrome

This study aimed to evaluate the efficacy of embryo vitrification as an emergency procedure for patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). A total of 69 embryos, derived from 24 patients for whom embryo transfer could not be performed because of the risk of developing OHSS, were vitrified and warmed for deferred embryo transfer. Surviving embryos were transferred, resulting in 10 clinical pregnancies, of which 4 were successfully delivered and the remaining 6 are still ongoing.

Follicular oestradiol and VEGF after GnRH antagonists or GnRH agonists in women with PCOS

The aim of this study was to determine whether follicular oestradiol and vascular endothelial growth factor (VEGF) concentrations in women with polycystic ovarian syndrome (PCOS) differ according to the use of gonadotrophin-releasing hormone (GnRH) antagonists or GnRH agonists. Furthermore, the effect of follicular oestradiol and VEGF concentrations on oocyte and embryo quality was investigated. In this prospective clinical study, 20 women with PCOS undergoing intracytoplasmic sperm injection for male factor infertility were included using a GnRH antagonist or a GnRH agonist protocol. In each follicle, oestradiol and VEGF concentrations were determined. In the GnRH antagonist group 254 follicles and in the GnRH agonist group 245 follicles, were aspirated. Fewer metaphase II (MII) and more immature and degenerative oocytes were registered in the GnRH antagonist group. Follicular oestradiol and VEGF were lower in the GnRH antagonist group ( P = 0.014 and P < 0.001, respectively). Moreover, higher oestradiol concentrations were related to embryos of higher quality ( P = 0.037). It is concluded that GnRH antagonists decrease follicular oestradiol and VEGF concentrations and the number of retrieved MII oocytes in women with PCOS.

Editorial

Editorial

Preservation of ovarian function in young women treated with neoadjuvant chemotherapy for breast cancer: A randomized trial using the GnRH agonist (triptorelin) during chemotherapy

524 Background: There is conflicting evidence on the use of gonadotropin releasing hormone (GnRH) analogues to preserve fertility in women undergoing adjuvant chemotherapy. This is the first randomized clinical trial designed to evaluate the benefit of GnRH use during chemotherapy. Methods: This prospective, randomized clinical trial explored whether the administration of the GnRH agonist (triptorelin) versus no triptorelin (control) affected the degree of chemotherapy related amenorrhea and fertility in premenopausal (age less than 44, FSH 39), ER status, and treatment type. Menstrual status, levels of FSH, Inhibin levels were monitored every 6 months. Results: Forty-nine patients (median age 39 years, range 21–43) were enrolled with 6- month follow-up data available on 44 patients, 12-month data on 42 patients, and 18 month data on 34 patients. In the triptorelin group, menses returned after...

A Comparison of Microdose Flare Protocol Versus AACEP Protocol for IVF Poor Responders

Background: There is presently no uniform consensus defining the best protocol to use for poor-responding IVF patients. At our center, we generally advocate the use of gonadotropin-releasing hormone (GnRH) agonist/antagonist conversion with estradiol valorate priming (AACEP) protocol for poor responders; we have noted much anecdotal success using AACEP even in those who have experienced repeated IVF failures. This protocol, we believe, synchronizes follicular growth while better developing the endometrium for implantation.

Complications related to ovarian stimulation and oocyte retrieval in 4052 oocyte donor cycles

A retrospective study was conducted in a private infertility centre to evaluate the rate of complications in a large oocyte donation programme. A total of 4052 oocyte retrievals were performed between January 2001 and October 2007. Altogether, 1238 cycles (30.6%) were stimulated with the use of gonadotrophin-releasing hormone (GnRH) agonists and in 2814 cycles (69.4%) the GnRH antagonist protocol was used. The GnRH antagonist treated cycles were triggered with human chorionic gonadotrophin (HCG) or a GnRH agonist in 1295 and 1519 cycles, respectively. Complications related to oocyte retrieval occurred in 17 patients (0.42%) (intra-abdominal bleeding: n = 14, severe pain: n = 2, ovarian torsion: n = 1). Fourteen of these were hospitalized (0.35%) and six donors (0.15%) required surgical intervention. Pelvic infections, injury to pelvic structures or anaesthesiological complications were not observed in this series. Moderate/severe ovarian hyperstimulation syndrome (OHSS) occurred in 22 donors; 11 required hospital admission and 11 were managed on an outpatient basis. All cases were related to HCG triggering (0.87%). Serious complications related to oocyte retrieval occurred at a low rate in healthy young donors. The risk of OHSS can be substantially reduced by specific stimulation protocols, which include GnRH agonist triggering. Prospective oocyte donors should be adequately counselled about the risks related to egg donation.

Prevention and management of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a complication of fertility treatment involving ovarian stimulation. Patient characteristics and treatment cycle parameters have a limited accuracy in predicting the risk of OHSS. In women at increased risk of OHSS, a lower starting dose of follicle stimulating hormone and use of gonadotrophin releasing hormone (GnRH) antagonist rather than GnRH agonist may lower the risk of OHSS. Cycles where ovarian response is excessive may be managed by coasting or, in severe cases, cancellation. Human chorionic gonadotrophin should be avoided for luteal support. All women at risk of OHSS should have adequate information and access to 24 h care. Mild and moderate OHSS can be managed on an outpatient basis with close monitoring, while severe OHSS merits admission. Non-steroidals and diuretics should be avoided, thromboprophylaxis provided and a close watch kept on fluid balance, allowing patients to drink to thirst. Ascites may require paracentesis. A prolonged course is expected if conception occurs, but recovery is the rule in the overwhelming majority of cases.