Dose Of Gonadotropin-releasing Hormone Agonist Research Articles

Effects of pretreatment with long-acting gonadotropin-releasing hormone agonists on pregnancy outcomes in patients with minimal and mild peritoneal endometriosis: A retrospective study of 274 frozen-thawed embryo transfer cycles.

To investigate the effects of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) before frozen-thawed embryo transfer (FET) on pregnancy outcomes in patients after minimal-mild (stages I-II) peritoneal endometriosis surgery. A retrospective cohort study was performed from March 2018 to May 2019. Overall, 274 patients met inclusion criteria of undergoing FET after minimal/mild peritoneal endometriosis surgery. For the FET protocol, patients were divided into 2 groups: GnRH-a plus hormone replacement therapy (HRT) (group A, n = 154) and HRT-only (group B, n = 120), with the former divided into 2 subgroups receiving 1 (group A1, n = 80) or 2 doses (group A2, n = 74) of GnRH-a. Basic characteristics and pregnancy outcomes of groups A and B and groups A1 and A2 were compared. Clinical pregnancy rate (CPR) and live birth rate (LBR) were the primary outcomes and logistic regression was used to analyze independent correlation factors. The CPR and LBR in group A were 58.4% and 50.0%, respectively, and were not significantly higher than in group B (49.2% and 40.0%; respectively, χ2 = 2.339, P = .126 and χ2 = 2.719, P = .099, respectively). CPR and LBR in group A1 were not significantly lower than those in group A2 (52.5% and 45.0% vs 64.9% and 55.4%, respectively; χ2 = 2.420, P = .120 and χ2 = 1.665, P = .197, respectively). However, group A2's CPR and LBR were significantly higher than group B's (64.9% and 55.4% vs 49.2% and 40.0%, respectively; χ2 = 4.560, P = .023 and χ2 = 4.375, P = .026, respectively). Logistic regression analysis showed that GnRH-a pretreatment (1 or 2 doses) had no significant effect on CPR and LBR compared with the HRT-only group. Patients with minimal-mild (stages I-II) peritoneal endometriosis surgery may not require GnRH-a pretreatment before FET.

Can We Harvest More Mature Oocytes by Repeating Gonadotropin-Releasing Hormone Agonist Doses in Polycystic Ovarian Syndrome Patients at Risk of OHSS in Antagonist Cycles? A Randomised Clinical Trial.

There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for oocyte triggering in polycystic ovarian syndrome (PCOS) patients at risk for ovarian hyperstimulation syndrome (OHSS). In this study, we intend to ascertain whether the use of repeated doses of a GnRH agonist for oocyte triggering in these patients can enhance the outcomes of controlled ovarian stimulation (COS) for in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. This randomised clinical trial enrolled 70 PCOS women candidates for IVF/ICSI with the standard antagonist protocol at Royan Institute (Tehran, Iran) from May 2020 to June 2022. Patients at risk of OHSS with oestradiol (E2) levels >3000 pg/ml on the day of trigger were randomly assigned to a control or experimental group. Group A (control group) patients received 0.2 mg triptorelin (Decapeptyl®) for final oocyte maturation. Group B (experimental group) patients received a second dose of 0.1 mg Decapeptyl®12 hours after their first dose, for a total dose of 0.3 mg. IVF/ICSI outcomes were compared between the groups. Ultimately, 35 women from the study group and 33 from the control group completed the treatment cycle. Both groups were comparable in terms of demographic characteristics, baseline hormonal profiles, and PCOS phenotypes. The dosage of gonadotropin, stimulation duration, number of retrieved oocytes, oocyte maturation rate, and oocyte recovery ratio did not significantly differ between the groups. No significant differences were found in terms of the number of blastocyst and cleavage embryos, nor the quality of obtained embryos between the groups. The mild to moderate OHSS rate was significantly lower in the study group (P=0.038). A second dose of GnRH agonist 12 hours after the first dose did not improve the number and maturity of oocytes, or pregnancy outcomes in PCOS patients (registration number: NCT04600986).

Pretreatment with long-acting gonadotropin-releasing hormone agonists improved pregnancy outcomes after hysteroscopic multiple polypectomies: A retrospective study of 660 frozen–thawed embryo transfer cycles

ObjectiveTo compare the reproductive pregnancy outcomes of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) plus hormone replacement therapy (HRT) with HRT-only cycles, and investigate differences between single polypectomy and multiple polypectomies, and between one or two doses of GnRH-a. Materials and methodsThis was a retrospective cohort study on patients undergoing polypectomy who underwent frozen–thawed embryo transfer (FET) from March 2018 to May 2019. They were divided into GnRH-a pretreatment and HRT-only groups. Each group was divided into single polypectomy or multiple polypectomies (in a single hysteroscopic session) subgroups. Clinical pregnancy rate and live birth rate (LBR) were the main outcomes. The effect of GnRH-a dosage was further analysed. ResultsThere were 212 GnRH-a pretreatment cases (45 single and 167 multiple polyps) and 448 HRT-only cases (228 single and 220 multiple polyps). The LBR of the GnRH-a pretreatment group (53.3%) was significantly higher than the HRT group (43.3%; P = 0.016). Logistic regression analysis showed that GnRH-a pretreatment significantly affected the LBR (odds ratio, OR 1.470, 95% confidence interval, Cl 1.046–2.065; P = 0.026). In the multiple polypectomy subgroup, the LBR with GnRH-a pretreatment was higher than with HRT-only (54.5% vs 43.6%; P = 0.034). However, the LBR was not different between the respective single polypectomy subgroups (48.9% vs 43.0%; P = 0.466). For patients with multiple polyps, two GnRH-a pretreatments produced a higher LBR than a single GnRH-a pretreatment (62.7% vs 47.8%), but without significant difference (P = 0.055). ConclusionGnRH-a pretreatment improved the LBR for FET cycles after hysteroscopic multiple polypectomies, independent of dose.

The effect of single dose of gonadotropin-releasing hormone agonist injection in frozen-thawed embryo transfer on pregnancy outcomes: A systematic review and meta-analysis.

This systematic review and meta-analysis of randomized controlled trials aimed to evaluate the effect of a single-dose gonadotropin-releasing hormone agonist administration in the frozen-thawed embryo transfer cycle on pregnancy outcomes. A literature search was strategically conducted using PubMed, EMBASE, and the Cochrane Controlled Trials Register. The primary outcome was the clinical pregnancy rate. The secondary outcomes combined chemical pregnancy rate, implantation rate, ongoing pregnancy rate, live birth rate, miscarriage rate, and extrauterine pregnancy rate. Out of the 1594 citations that were found, only six met the criteria for being included in the meta-analysis. The clinical pregnancy rate was higher in the treatment group than in the control group (52.05% vs. 47.29%; p=0.04; RR=1.09; 95% CI=1.00-1.18). According to subgroup analysis based on the natural cycle, the clinical pregnancy rate with the agonist administration is significantly higher (43.75% vs. 27.35%; p=0.01; RR=1.6; 95% CI=1.10-2.32). However, there was no difference between the groups in terms of artificial cycles (p=0.80; 95% CI=0.96-1.20). The secondary outcomes did not show significant differences. We concluded that supplementing with a single dose of gonadotrophin-releasing hormone agonist can marginally increase the clinical pregnancy rate, particularly in the natural cycle. Other pregnancy outcomes do not improve with the treatment.

SAT621 Hemorrhage After Treatment: A Case Of Pituitary Apoplexy In Metastatic Prostate Cancer After Leuprolide

Abstract Disclosure: M. Dillon: None. S. Shteyman: None. W. Rashid: None. B.P. Ramchandani: None. A.G. Samat: None. Introduction: Hormone-sensitive cancers, including prostate and breast cancer, and some gynecological conditions can be treated with GnRH agonists, including leuprolide. However, pituitary apoplexy is a rare potential complication after administration. Case Description: 71-year-old gentleman with metastatic hormone-sensitive prostate cancer presented with an acute headache after receiving a dose of leuprolide. This was his first GnRH agonist dose after prior Degarelix treatment. After two hours, the patient developed a constant throbbing headache, palpitations, left eye tearing and non-bilious non-bloody vomiting. Vitals were within normal ranges, and initial lab work showed low serum cortisol of 4.6. CT scan of the head showed exophthalmos and a mildly enlarged sella. Subsequent MRI demonstrated pituitary hemorrhage and optic chiasm impingement from resulting swelling. Hormone levels remained normal. Since the patient did not develop visual field defects or other ocular complaints, the decision was to manage the patient medically rather than with surgery. The day after admission, he developed hypotension requiring high dose steroids. After discharge, outpatient repeat MRI showed interval resolution of hemorrhage into a predominantly cystic pituitary macroadenoma. Discussion: With continued stimulation, GnRH agonists desensitize the pituitary and cause a downregulation of hormonal induced cancer growth. However, there is an initial transient burst of stimulation that can induce pituitary apoplexy in patients who already have a large adenoma. The hemorrhage and subsequent swelling cause a sudden severe headache and possible visual loss or hypopituitarism. This is life-threatening due to hypotension from catecholamine insensitive blood vessels in the absence of cortisol. Treatment involves high dose steroids, frequent sodium checks and possible emergency neurosurgery for decompression. It is important with GnRH agonists to watch out for this rare complication, whether the hormonal axis is being suppressed for metastatic cancer treatment or for hormonally driven gynecological conditions. Sources: Briet C, Salenave S, Bonneville JF, Laws ER, Chanson P. Pituitary Apoplexy. Endocr Rev. 2015 Dec;36(6):622-45. doi: 10.1210/er.2015-1042. Epub 2015 Sep 28. PMID: 26414232. Tanios G, Mungo NA, Kapila A, Bajaj K. Pituitary apoplexy: a rare complication of leuprolide therapy in prostate cancer treatment. BMJ Case Rep. 2017 Jul 14; 2017:bcr2016218514. doi: 10.1136/bcr-2016-218514. PMID: 28710301; PMCID: PMC5534692. Presentation: Saturday, June 17, 2023

Pregnancy outcomes following supplementation of single dose GnRH agonist to sustain the luteal phase in antagonist fresh embryo transfer cycles: A multicentric prospective cohort study

Objective: To determine whether a single dose of gonadotropin-releasing hormone (GnRH) agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in antagonist protocol fresh embryo transfer cycles. Methods: This prospective, multicentric, cohort study included total 140 women, 70 in each group. Controlled ovarian stimulation was carried out as per fixed GnRH antagonist protocol. The trigger was given with hCG. In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) was performed and day-3 embryos were transferred. Patients were divided into groups 1 and 2 based on computer generated randomization sheet. Six days following oocyte retrieval, group 1 received 0.2 mg decapeptyl subcutaneously in addition to regular progesterone support while group 2 received progesterone only. Luteal support was given for 14 days to both groups; if pregnancy was confirmed luteal support was continued till 12 weeks of gestation. The clinical pregnancy rate was the primary outcome. The implantation rate, miscarriage rate, live birth delivery rate, and multiple pregnancy rates were the secondary outcomes. Results: A total of 140 patients were analysed, 70 in each group. Clinical pregnancy rates (47.1% vs. 35.7%; P=0.17), implantation rates (23.4% vs. 18.1%, P=0.24), live birth delivery rates (41.4% vs. 27.1%, P=0.08), and multiple pregnancy rates (21.2% vs. 16.0%, P=0.74) were higher in group 1 than in group 2. Group 1 had a lower miscarriage rate than group 2 (5.7% vs. 8.6%; P=0.75). However, these differences were not statistically significant between the two groups. Conclusions: Administration of a single dose of GnRH agonist in addition to regular natural micronized vaginal progesterone as luteal support in GnRH antagonist protocol cycles marginally improves implantation rates, clinical pregnancy rates, and live birth delivery rates. However, more studies with higher sample sizes are needed before any conclusive statements about GnRH agonist as luteal phase support can be made.

Additional single dose GnRH agonist during luteal phase support may improve live birth rate in GnRHa-HRT frozen–thawed embryo transfer cycle: a retrospective cohort study

BackgroundGnRH agonist (GnRHa) has been reported to have direct effects and functional roles in the endometrium and embryos. Several meta-analyses have shown that GnRHa administration in the luteal phase improved the live birth rate or pregnancy rate in both fresh and frozen embryo transfer (FET) cycles. The aim of this study was to investigate whether luteal GnRHa administration could also improve in vitro fertilization (IVF) outcomes in patients undergoing hormone replacement therapy (HRT) cycles with GnRHa suppression.MethodsThe retrospective cohort study included a total of 350 patients undergoing GnRHa-HRT FET cycles. The study group included 179 patients receiving an additional single dose of GnRHa in the luteal phase following embryo transfer. A total of 171 patients in the control group did not receive luteal GnRHa. The baseline and cycle characteristics and reproductive outcomes were compared between the two groups.ResultsBaseline and cycle characteristics were similar between the two groups, except lower AMH levels were found in the luteal GnRHa group than in the control group. The luteal GnRHa group had a significantly higher ongoing pregnancy rate and live birth rate than the control group. The multivariate analysis revealed that luteal GnRHa administration was positively associated with ongoing pregnancy (OR 2.04, 95% CI 1.20–3.47, P = 0.008) and live birth (OR 2.03, 95% CI 1.20–3.45, P = 0.009). When the subgroup of patients with recurrent implantation failure was analyzed, the multivariate analysis also showed that luteal GnRHa administration had beneficial effects on ongoing pregnancy (OR 4.55, 95% CI 1.69–12.30, P = 0.003) and live birth (OR 4.30, 95% CI 1.59–11.65, P = 0.004).ConclusionsOur data suggest that the addition of one luteal dose of GnRHa may improve the live birth rate in patients undergoing the GnRHa-HRT protocol.

GnRH agonist administration as luteal support on the transfer day of single blastocyst in dual-triggered cycles.

Luteal phase support with gonadotropin-releasing hormone agonist (GnRH-a) has been considered in terms of its potential beneficial effects on in vitro fertilisation (IVF) cycles. In our study, we assessed the effectiveness of single-dose GnRH-a administration in dual-triggered cycles on pregnancy outcomes. Eighty women who underwent intra cytoplasmic sperm injection (ICSI) cycle and had fresh blastocyst transfer were divided into two groups in terms of luteal phase support. The study group (Group A) consisted of patients (n = 40) who received a single-dose GnRH-a injection (0.1 mg of triptorelin acetate) subcutaneously 6 days after oocyte retrieval in addition to 600 mg daily of micronised progesterone, and the control group (Group B) comprised of patients (n = 40) taking 600 mg micronised progesterone daily from the first day after oocyte retrieval. GnRH-a and human chorionic gonadotropin (hCG; dual trigger) were administered to all patients. Comparison of the clinical pregnancy and live birth rates was our main goal. There was no significant difference between the two groups in terms of β-hCG positivity rates, clinical pregnancy rates and live birth rates (p value for beta-hCG = 0.25, clinical pregnancy = 0.80, live birth = 0.45). Our study demonstrated that in dual triggered cycles administration of a single dose of GnRH-a on the transfer day of a single blastocyst in addition to routine luteal phase support with progesterone does not statistically increase implantation, clinical pregnancy or live birth rates.

P-673 GnRH Agonist Early Follicular Challenge Test as a Predictor of Ovarian Response in Short Antagonist Cycles for Fertility Preservation

Abstract Study question Does the response to GnRH agonist can be used to predict ovarian function in short GnRH antagonist cycles in women undergoing oocyte cryopreservation IVF cycles? Summary answer Response to a single GnRH agonist dose at the beginning of stimulation during short antagonist cycle can predict the outcome of the fertility preservation cycle What is known already There is a need for a reliable test for ovarian reserve. Gonadotrophin agonist stimulation test (GAST) is considered a valid marker for ovarian reserve but the test was never validated for short antagonist protocol. The reported dose for this test was 0.1 mg, however, from the vast experience with GnRH agonist triggering, it is now agreed that the optimal dose for GnRH agonist flare effect is 0.2 mg. Study design, size, duration A prospective observational study of fertility preservation cycles patient in an academic hospital setting. Seventy-four Short GnRH antagonist cycles that underwent an oocyte retrieval between 1 December 2020 and 1 January 2022. Participants/materials, setting, methods On day 2, blood was sampled for basal FSH, LH, and E2 measurements, followed by a subcutaneous injection of 0.2mg GnRH agonist as part of the initial ovarian stimulation. Twelve hours later blood sampling was repeated. E2 response was used as test parameter. The major outcome was the number of cryopreserved oocytes. Main results and the role of chance Participants were divided to groups according to Day 3 E2 to Day 2 E2 response (E3/E2 ratio) to lower and upper third percentiles (<3.32, n = 24 and >5.41, n = 25). Age (32.68 vs. 32.79, p = 0.965), total gonadotropin dose injected 3216.67 vs. 2773.42 IU p = 0.16) and day 3 FSH levels (7.39 vs. 7.16, p = 0.768) were not significantly different between groups. Ovarian response as measured by E2 levels on ovulation trigger (7879.72 vs. 17572.54 pmol/ml, p = 0.001) and number of M2 oocytes retrieved were significantly different (17.92 vs. 6.24, p < 0.001). Linear correlation between E3/E2 ratio and number of M2 oocytes was calculated (R = 0.48, p < 0.001). ROC curve analysis of E3/E2 ratio for more than fifteen M2 oocytes indicate AUC value of 0.82 (cutoff value of 4.22, p < 0.001, 84.6% sensitivity, 70.8% specificity) and for less than five M2 oocytes AUC value of 0.84 (cutoff value of 3.34, p < 0.001, 76.3% sensitivity, 73.3% specificity). The results suggest that the testing response to 0.2mg GnRH agonist positively correlates with treatment outcome of the current cycle. Limitations, reasons for caution Although all patients were tested for FSH levels for ovarian reserve, they were not tested for AMH levels. Wider implications of the findings The response to single GnRH agonist dose during short antagonist cycle can be used as another biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict accurately the outcome of the specific cycle, and potentially used to adjust the treatment dose. Trial registration number NCT04973969

Aggressive (deep) angiomyxoma of the vulva: a case report\xa0

BackgroundAggressive angiomyxoma of the vulva is a benign, slow-growing tumor originating from myxoid cells of connective tissue. The tumor is known for multiple local recurrences with a low tendency to metastasize. Only around 350 cases have been documented in the scientific literature so far.Case presentationWe report a case of a 40-year-old North Indian, unmarried woman with a swelling on the left labium majora for 7 years, along with surface ulceration over the mass. Local examination showed a well-circumscribed, 8 × 8 cm pedunculated mass arising from the left labium majora with an overlying ulcer measuring 6 cm × 4 cm. After taking informed written consent, wide local excision of the mass and surrounding margins was done under anesthesia. Histopathology was suggestive of aggressive angiomyxoma. Immunohistochemistry was done, which was positive for estrogen and progesterone receptors. Her postoperative recovery was uneventful. The patient was given three doses of gonadotropin-releasing hormone agonist (injection, leuprolide 3.75 mg) once a month. No recurrence has been reported so far on follow-up visits for 1 year.ConclusionAggressive angiomyxoma is one of the differential diagnoses for vulvovaginal growth in a female. As the tumor is well known for local recurrences, correct diagnosis and appropriate management using a multidisciplinary approach are crucial to managing such patients.

Association between different dual trigger dosages and in vitro fertilization results in patients with patient-oriented strategies encompassing individualized oocyte number group IV

ObjectiveDual trigger is used to induce final oocyte maturation during the process of controlled ovarian hyperstimulation, yet yielding controversial results. Also, there are yet no data regarding the effect of the dosage of the dual trigger on clinical outcomes. Based on the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria, this study aimed to determine the clinical difference of a single bolus versus two boluses of gonadotropin-releasing hormone agonist (GnRHa) in POSEIDON group IV patients using dual trigger.MethodsWe screened a total of 1,256 patients who underwent in vitro fertilization (IVF) cycles who met the POSEIDON group IV criteria. Six hundred and twenty-nine patients received one bolus of GnRHa, and 627 patients were given two boluses. All patients received the same dose of recombinant human chorionic gonadotropin during the dual trigger cycle.ResultsMetaphase II oocyte retrieval rate, fertilization rate and clinical pregnancy rate did not differ between the two groups. However, a lower percentage of at least one top-quality embryo transfer (34.3% vs. 26.0%, P=0.001) in the two bolus-GnRHa group was noted.ConclusionA double bolus of GnRHa did not show superior clinical results compared to a single bolus of GnRHa in the dual trigger IVF cycle. Therefore, GnRHa doses for use should be decided based on individual clinical situations considering cost-effectiveness and patient compliance, but further investigation will be needed.

Effect of Administration of Single Dose GnRH Agonist in Luteal Phase on Implantation Rate of Fresh ICSI Cycles

The luteal phase (LP) in the fresh ICSI cycle is insufficient, adequate LP support is one of the approved treatments for improving implantation and pregnancy rates. It is generally known that the LP is inadequate after ovarian stimulation due to negative from supra-physiological blood levels of steroids released by numerous corporal luteal, LH concentrations are low during the luteal phase. In this study, patients were divided into two groups: (40) patients as study group; those who received GnRHa (Decapeptil 0.1 mg), three days after embryo transfer, in addition to conventional luteal phase support (LPS) in the LP to increase the implantation and pregnancy rate in IVF; and their control group (40) received standard LPS only. On the second day of stimulation, blood samples for FSH, LH, TSH, E2, and prolactin were taken. On the day of ovulation induction, measure E2, progesterone, and LH; and on the day of embryo transfers, measure progesterone and LH. The overall characteristics of the patients in both groups were not significantly different. There was also no significant change in the number of total oocytes, mean of metaphase II oocytes percent, cleavage rate, grade I embryo percent, or serum hormones level between the study and control groups (p > 0.05). GnRH agonist treatment in the luteal phase improves clinical pregnancy and implantation rate in fresh ICSI cycles but is not statistically significant.

Effect of Administration of Single Dose GnRH Agonist in Luteal Phase on Implantation Rate of Fresh ICSI Cycles

The luteal phase (LP) in the fresh ICSI cycle is insufficient, adequate LP support is one of the approved treatments for improving implantation and pregnancy rates. It is generally known that the LP is inadequate after ovarian stimulation due to negative from supra-physiological blood levels of steroids released by numerous corporal luteal, LH concentrations are low during the luteal phase. In this study, patients were divided into two groups: (40) patients as study group; those who received GnRHa (Decapeptil 0.1 mg), three days after embryo transfer, in addition to conventional luteal phase support (LPS) in the LP to increase the implantation and pregnancy rate in IVF; and their control group (40) received standard LPS only. On the second day of stimulation, blood samples for FSH, LH, TSH, E2, and prolactin were taken. On the day of ovulation induction, measure E2, progesterone, and LH; and on the day of embryo transfers, measure progesterone and LH. The overall characteristics of the patients in both groups were not significantly different. There was also no significant change in the number of total oocytes, mean of metaphase II oocytes percent, cleavage rate, grade I embryo percent, or serum hormones level between the study and control groups (p > 0.05). GnRH agonist treatment in the luteal phase improves clinical pregnancy and implantation rate in fresh ICSI cycles but is not statistically significant.

Prolonged pituitary downregulation with gonadotropin-releasing hormone agonist improves the live-birth rate: a retrospective cohort study comparing 3 different protocols.

The long protocol has been recognized as the gold standard in controlled ovarian hyperstimulation (COH). However, the full dose of gonadotropin-releasing hormone agonist (GnRH-a) under the prolonged protocol has become increasingly popular in China. This study sought to compare pregnancy outcomes among the following 3 groups: a long protocol group, and 2 types of improved prolonged protocol groups. A retrospective cohort study was conducted of 550 patients undergoing fresh embryo transfer (ET). Patients were treated either with the improved prolonged protocol in the follicular phase (Group 1; n=288) or the mid-luteal phase (Group 2; n=143), or the long protocol (Group 3; n=119). The clinical and laboratory outcomes of the 3 groups were compared. The general characteristics of the women in the 3 groups were comparable. On the day on which gonadotropin (Gn) was first administered and on the day on which human chorionic gonadotropin (hCG) was administered, the luteinizing hormone (LH) levels of patients in both Groups 1 and 2 were lower than those of patients in Group 3. The number of oocytes retrieved, fertilized, and cleaved, and the number of high-quality embryos in the 3 procedures were similar. However, the number of transferred embryos, the rate of blastocyst progression, and the rate of implantation differed. The clinical pregnancy rates (CPRs)were significantly higher in the prolonged protocol groups (62.5% and 61.5%) than the long protocol group (48.7%). Further, statistically significant differences in the live-birth rates (LBRs) (56.9% vs. 57.3% vs. 42.9%) were observed. However, no differences in early abortion rates were found. As a result of pituitary downregulation with GnRH-a, the prolonged groups had better CPRs and LBRs than the long protocol group. The prolonged protocol in the mid-luteal phase was equally effective as that in the early follicular phase in fresh in-vitro fertilization (IVF)/intracytoplasmic sperm injection-embryo transfer (ICSI-ET) cycles. High LH levels on the day of hCG may be a predictor of adverse clinical outcomes.

Effects of multiple doses of gonadotropin-releasing hormone agonist on the luteal-phase support in assisted reproductive cycles: A clinical trial study.

BackgroundThe effect of adding gonadotropin-releasing hormone (GnRH) agonist on the luteal phase support in assisted reproductive technique (ART) cycles is controversial.ObjectiveTo determine the effects of adding multiple doses of GnRH agonist to the routine luteal phase support on ART cycle outcomes.Materials and MethodsThis clinical trial study included 200 participants who underwent the antagonist protocol at the Research and Clinical Center for Infertility, Yazd, Iran, between January and March 2020. Of the 200, 168 cases who met the inclusion criteria were equally divided into two groups – the case and the control groups. Both groups received progesterone in the luteal phase, following which the case group received GnRH agonist subcutaneously (0/1 mg triptorelin) zero, three, and six days after the fresh embryo transfer, while the control group did not receive anything. Finally, chemical and clinical pregnancy rates, number of mature oocytes, fertilization rate, total dose of gonadotropin, and the estradiol level were determined.ResultsThe baseline characteristics were similar in both groups. No significant difference was observed between embryo transfer cycles. Clinical results showed that differences between the fertilization rate, chemical and clinical pregnancies were not significant.Conclusion The results showed that receiving multiple doses of GnRH agonist in the luteal phase of ART cycles neither improves embryo implantation nor the pregnancy rates; therefore, further studies are required.

Does the repeat dose of gonadotropin-releasing hormone agonist trigger in polycystic ovarian syndrome improve in vitro fertilization cycles outcome? A clinical trial study.

Background A repeat dose of Gonadotropin-releasing Hormone (GnRH) agonist could provide long duration of luteinizing hormone (LH) surge and amplitude appropriately.Objective Improvement in oocyte maturity could be obtained by a repeat dose of GnRH agonist.Materials and MethodsIn this randomized double-blinded study, 120 women with polycystic ovarian syndrome and serum estradiol level (E2) 3000 who were candidate for in vitro fertilization with Antagonist protocol were enrolled between July 2018 and July 2019. Participants were randomized in two groups - and final oocyte maturation was triggered with two doses: In group A, a repeat dose of 0.1 mg, 12 hr. after the first dose and in group B, 0.2 mg SC triptorelin (decapeptyl) 35 hr. prior to oocyte retrieval. Serum Estradiol, LH, and progesterone concentration were measured on the trigger day. Serum LH measurement was done three times in both groups. The outcomes were oocyte yield, meiosis (M) I, MII, Maturity rate, germinal vesicle (GV) rate, 2 pronuclear, embryo yield, ovarian hyper stimulation syndrome rates.ResultsMaturity rate (p = 0.89), MI (p = 0.38), MII (p = 0.89), and GV oocytes (p = 0.38) were not statistically different between the two study groups. LH levels measured at 12 hr post-trigger did not relate statistically significant with maturity rate in our participants (p = 0.96). No empty follicular syndrome was reported.ConclusionAlthough, the second dose of GnRH agonist after 12 hr since the first dose could provide duration of LH surge and amplitude and as a result no empty follicular syndrome was seen, the maturity rate, MI, MII, and GV oocytes were not different between the two study groups.

Administration of nerve growth factor-β to heifers with a pre-ovulatory follicle enhanced luteal formation and function and promoted LH release

The objective of this study was to determine the effects of bovine nerve growth factor-β (NGF) on pre-ovulatory follicle vascular area, LH release, ovulation, and luteal function when administered systemically to heifers. Post-pubertal Holstein heifers (n = 12) received an intravaginal progesterone-releasing device (CIDR) and GnRH agonist (100 μg IM). The CIDR was removed 5 d later, and heifers were given dinoprost (25 mg IM) at CIDR removal and 24 h later, followed by a second dose of GnRH agonist 48 h later. Heifers were randomly assigned to treatments using a cross-over design. For example, heifers assigned to NGF (250 μg reconstituted in 12 mL PBS IM) in replicate 1 were assigned to control (12 mL PBS IM) in replicate 2. Transrectal ultrasonography was performed before treatment and repeated every 4 h up to 32 h to determine the pre-ovulatory follicle diameter, vascular area, and ovulation. Serum samples were obtained to assess LH concentrations during the periovulatory period and every 2 d post-ovulation for measuring progesterone concentrations. A subset of heifers had luteal biopsies performed on days 9 (n = 6 per treatment) and 14 (n = 6 per treatment) post-ovulation to count luteal cell numbers and measure relative mRNA abundance for steroidogenic and angiogenic enzymes and LH receptor. Treatment with NGF increased pre-ovulatory follicle diameter (P = 0.02) and serum LH concentrations (P = 0.03) but did not affect time to ovulation (P = 0.42). Heifers treated with NGF had increased serum progesterone concentrations in the subsequent luteal phase (P = 0.03), but no change in vascular area of the follicle (P = 0.16) or CL (P = 0.20). Heifers treated with NGF had a greater number of small luteal cells (P < 0.01) and a tendency for increased LH receptor (LHR) mRNA abundance in the CL (P = 0.10). There was also increased steroidogenic acute regulatory protein (STAR; P = 0.05) and a tendency for increased cytochrome P450 family 11 (CYP11A1; P = 0.10) mRNA abundance in the CL of NGF-treated heifers. There was decreased prostaglandin E2 synthase (PGES; P = 0.03) and its receptor (PGER; P = 0.05) mRNA abundance and a tendency for decreased cytochrome P450 family 17 subfamily A member 1 (CYP17A1; P = 0.08) and hydroxysteroid 17-beta dehydrogenase (HSD17B; P = 0.06) mRNA abundance in the CL of NGF-treated heifers. Administration of NGF improved CL function in heifers potentially as a result of increased LH release.

A Second Dose of GnRHa in Combination with Luteal GnRH Antagonist May Eliminate Ovarian Hyperstimulation Syndrome in Women with ≥30 Follicles Measuring ≥11 mm in Diameter on Trigger Day and/or Pre-trigger Peak Estradiol Exceeding 10 000 pg/mL.

This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome (OHSS), characterized by more than 30 follicles measuring ≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL, which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist (GnRHa) trigger and freeze-all policy that previously have been reported. All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards. The in vitro fertilization (IVF) outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS. Moreover, patients' symptoms, reproductive hormone levels and ultrasound findings were improved significantly. This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS, especially for the patients characterized by ≤30 follicles measuring ≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL. Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.

MTHFR C677T polymorphism is associated with follicle-stimulating hormone levels and controlled ovarian hyperstimulation response: a retrospective study from the clinical database

To evaluate the impact of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with clinical data analysis in controlled ovarian hyperstimulation (COH) of infertile women in the Intravenous Infusion Safety Evaluation Center of Hunan Province, People's Republic of China. Genetic Association Study. Reproductive medicine clinical. This genetic association study included 722 infertile women who received the standard long treatment protocol with accessible and complete electronic medical records. None. The clinical parameters were obtained from the Intravenous Infusion Safety Evaluation center. Basal FSH levels in the TT group were significantly higher than those of the CC group. The FSH levels after down-regulation in the TT group were higher than those of CC/CT genotypes. The TT genotype patients received significantly higher total doses of GnRH agonist and FSH compared with CC/CT genotypes, whereas the total dose of hCG was higher in the CT genotypes compared with the CC/TT genotypes. Further association analysis between hormone levels and COH outcomes indicated significantly negative correlation of basal FSH levels with antral follicle count and number of oocytes as well as the down-regulation FSH levels with the number of metaphase II oocytes and oocytes. The MTHFR C677T polymorphism was associated with high doses of ovarian stimulation medications, as well as higher FSH levels. The negative correlation between FSH levels and the number of oocytes suggested that C677T polymorphism may play a role in the poor prognosis of COH oocytes. This needs to be studied in future prospective studies with longer follow-up.

Thermal manipulation and GnRHa therapy applied to the reproduction of lambari-do-rabo-amarelo, Astyanax altiparanae females (Characiformes: Characidae) during the non-breeding season

Lambari-do-rabo-amarelo Astyanax altiparanae in the wild reproduce during spring and summer, but females undergo vitellogenesis throughout the year, including the non-spawning winter period when water temperatures are low. The present study investigated the physiological role of temperature modulation on the hypothalamus-pituitary-gonads axis of lambari during winter, as well as the effects of gonadotropin releasing hormone agonist (GnRHa) therapy. Captive females were exposed to two different temperatures (20 °C and 27 °C) and were injected weekly with GnRHa for 21 days during winter (Control, CTR; Low dose; LD and high dose of GnRHa, HD). At the end of the 21-days period gonadosomatic index (GSI), oocyte stage of development and theoretical fecundity were evaluated, together with plasma levels of 17β-estradiol (E2). Gene expression of the two pituitary gonadotropins follicle-stimulating hormone (fshβ) and luteinizing hormone (lhβ), as well as hepatic vitellogenin-A (vtgA) expression were also analyzed. At the end of the experimental period, females from the six different experimental conditions were induced to spawn using human chorionic gonadotropin (hCG). Spawning performance parameters and plasma levels of the maturation inducing steroid (MIS) were analyzed. Gene expression of fshβ did not change with temperature manipulation, but females exposed to 27 °C and supplemented with a HD of GnRHa exhibited an increased fshβ gene expression, associated with higher E2 levels. The higher water temperature alone was able to increase E2 levels. At both water temperatures GnRHa injections induced a decrease in E2 levels. GnRHa injected females had a lower vtgA gene expression levels at 20 °C. Even with differences in the gene expression of gonadotropins among the various temperature/GnRHa treatments, GSI and oocyte diameter did not change, but GnRHa enhanced the number of vitellogenic oocytes at 20 °C. The reproductive performance of lambari induced to spawn with hCG was better after the combined treatment with GnRHa and summer temperature.