Long-term Gonadotropin-releasing Hormone Agonist Research Articles

O-056 Can we tailor ART to endometriosis patients?

Abstract ART remains an effective treatment for endometriosis-associated infertility, although there is evidence that pregnancy rates are diminished in women with endometriosis compared with other etiologies of infertility. In this lecture, the literature relating to endometriosis-associated infertility will be evaluated and recommendations will be made on the management of patients both pre-ART and during ART in order to improve ART outcomes in women with endometriosis. Surgery as an adjuvant to ART appears to have a favorable effect in patients with minimal to mild endometriosis prior to IVF. However, this evidence is based on only one study and more research is needed. As deep endometriosis (DE) is usually accompanied by advanced intra-abdominal disease resulting in distortion of the pelvic anatomy and tubal dysfunction, it is not surprising that IVF is considered as first line treatment. Observational data are available on the outcomes of DE surgery regarding conception rates in infertile patients with endometriosis suggesting that surgery may increase natural pregnancy rates as well as improve IVF outcomes. However, randomized trials comparing IVF to DE surgery are non-existent, as DE surgery is still mainly performed for pain and reduced quality of life rather than for treating infertility. In order to improve IVF success rates in endometriosis, various pre-ART treatments have been suggested. The oldest one relates to the use of gonadotropin releasing hormone (GnRH) agonist prior to IVF. Currently there is uncertainty as to whether long-term GnRH agonist therapy is beneficial when compared to standard IVF/ICSI in endometriosis. In addition, there is no evidence to support the use of oral GnRH antagonists and oral contraceptives as pre-treatment prior to ART, but results of ongoing studies will determine further. More recent studies support defects in endometrial receptivity as a cause of IVF failure. In recent years a new marker for endometrial receptivity in endometriosis emerged: BCL6, a biomarker for endometrial inflammation as it stimulates endometrial cytokine expression. Prospective cohort data provide a proof of concept that high BCL6 expression is associated with adverse IVF outcomes in women with endometriosis and that patients with high BCL6 expression may benefit from medical and surgical treatment prior to IVF. In order to improve IVF success rates in endometriosis, various pre-ART treatments have been suggested. The oldest one relates to the use of gonadotropin releasing hormone (GnRH) agonist prior to IVF. Contrary to previous findings, there is currently uncertainty as to whether long-term GnRH agonist therapy is beneficial when compared to standard IVF in endometriosis. In addition, there is also no evidence to support the use of oral GnRH antagonists and oral contraceptives as pre-treatment prior to ART in endometriosis, but results of ongoing studies will determine further. It has been hypothesized that applying local endometrial injury might induce a beneficial effect on endometrial receptivity prior to ART. However, scratching the endometrium as well as infusing fluids (Lipiodol and ExEm gel) into the uterine cavity (uterine bathing) in endometriosis patients prior to ART did not improve IVF success. During ART, a specific protocol for ART in women with endometriosis cannot be recommended. Both GnRH agonist and antagonist protocols can be used. For ovarian stimulation, a higher dose of gonadotropins may be required in stage III-IV endometriosis due to a poorer ovarian response. There is insufficient evidence for the routine use of prophylactic antibiotics at the time of oocyte retrieval in patients with endometriosis, but their use is recommended in patients with endometrioma. Considering fertilization, there appears no added benefit in using ICSI over IVF in endometriosis unless male-factor infertility is present. Finally, there is insufficient evidence to recommend any particular luteal support in women with endometriosis undergoing ART.

Clinical Use of Long-Term GnRH Agonist in Prepubertal Bitches: Effect on P4, E2 and Melatonin Serum Concentration before and During First Estrus

Abstract The aim of this study was to determine the length of the contraceptive period after the application of deslorelin implant (4.7 mg) in juvenile, prepubertal bitches and assess the effects on the hormonal status (P4, E2 and melatonin), as well as on the occurrence of normal physiological estrus. Twelve crossbred prepubertal female dogs (4 months of age) were divided into the two groups, the treated group (DESLO) and control (placebo) group (C). Hormone assays, vaginal microbiological and cytological smears and the measurements of electrical resistance of cervical mucus were performed once in 3 weeks until the first signs of proestrus, and every day during estrus. GnRH implant significantly postponed time of onset of estrus (633 ± 30,38 days vs. 143.80 ± 52,30 days, P<0.001). In estrus, DESLO group showed statistically higher E2 (34.58 pg/mL vs. 20.59 pg/mL, P<0.001) and melatonin serum concentration (45.86 pg/mL vs. 18.85 pg/mL, P<0.001) compared to the control group. The average P4 serum concentration had no statistically significant differences between groups. In conclusion, deslorelin implants do not cause “flare up” effect in perpubertal bitches, however, increase of E2 and especially melatonin serum concentrations show the need to explore the consequences and mutual influence of melatonin and deslorelin implants in the future.

Evaluating the Impact of Long-Term GnRH Agonist Therapy on Pregnancy Outcomes in Endometriosis-Associated Implantation Failure and Pregnancy Loss

Purpose This study aimed to investigate the efficacy of long-term gonadotropin-releasing hormone (GnRH) agonist therapy in preventing endometriosis progression and relieving symptoms, particularly on pregnancy outcomes during thawed embryo transfer in patients experiencing endometriosis and recurrent implantation failure or recurrent pregnancy loss. Methods In individuals with clinical endometriosis and a history of recurrent implantation failure or recurrent pregnancy loss, we conducted a comparative analysis of clinical outcomes between those undergoing long-term GnRH agonist treatment for symptom relief, such as menstrual pain, followed by embryo transfer using Hormone Replacement Therapy (HRT) cycle, and those undergoing embryo transfer using an HRT cycle without GnRH agonist treatment. The study examined various clinical outcomes between the two groups. Results The primary outcomes included live birth rate (LBR), miscarriage rate, biochemical pregnancy rate, and perinatal complications. The GnRH agonist group showed significantly higher LBR than the control group (37.50% vs. 13.04%; p=0.02). Multivariable logistic regression analysis, adjusted for age and gravidity, showed significantly higher LBR in the GnRH agonist group compared to the control group (odds ratio: 15.3; 95% confidence interval: 2.30, 102.00; p=0.005). Conclusions The findings of this study suggested that employing a GnRH agonist in the embryo transfer protocol is effective for patients with endometriosis experiencing recurrent implantation failure or recurrent pregnancy loss.

Serum Cholesterol Level Changes during Gonadotropin-Releasing Hormone-Agonist Therapy in Premenopausal Female Patients with Breast Cancer.

To investigate the changes in cholesterol levels during medical ovarian suppression. We reviewed the medical records and blood test results of 187 female patients with breast cancer who underwent gonadotropin-releasing hormone (GnRH)-agonist therapy for > 24 weeks at our hospital between 1 January 2018 and 31 December 2020. The study excluded patients in this cohort who had previously been diagnosed with dyslipidemia, diabetes, or had recently received lipid-lowering agents, resulting in a final sample size of 152 participants. The age at diagnosis and preoperative body mass index (BMI) were included as baseline demographics. A generalized additive mixed model was applied to analyze the relationship between the duration of GnRH-agonist treatment and changes in cholesterol levels. The study participants had a mean age of 42.5 ± 5.2 years and a mean preoperative BMI of 23.0 ± 3.6 kg/m²; the mean GnRH-agonist therapy duration was 19.3 months (range: 5.6-37.7 months); and the total cholesterol level before GnRH-agonist treatment was 171 mg/dL that was significantly higher at 181 mg/dL (P = 0.03) during the most recent measurement. The total cholesterol level was unaffected by the GnRH-agonist therapy until 19.3 months after which it significantly increased by 1.28 mg/dL per month (P = 0.011). There was no significant effect of age, preoperative BMI, or the glomerular filtration rate on the total cholesterol levels. Long-term GnRH agonist therapy for > 19 months can cause a significant increase in the serum cholesterol levels. To prevent complications, patients receiving the treatment should be informed and monitored for the possible progression of dyslipidemia.

SAT403 Long-term Metabolic Effects Of Gonadotropin Releasing Hormone Agonist (GnRH) Therapy In Transgender Women Veterans

Abstract Disclosure: G. Le: None. S. Pinkson: None. J. Trejo: None. L. Gondin Hernandez: None. M. Mok: None. A. endoza: None. D. Tripathy: None. There is controversy regarding the effects of long-term GnRH agonist therapy on cardiovascular risk factors in older men with prostate cancer. GnRH agonists are used for gender affirming hormone therapy in adolescents and in adults who fail to suppress testosterone adequately. We examined the cardiometabolic effects of long-term GnRH agonist therapy in transwomen veterans. A retrospective chart review was performed on 74 transwomen veterans who were followed at the ALM VA Endocrinology clinic for at least 12 months and had detailed clinical, hormonal and biochemical profile (testosterone, estradiol, HbA1c, lipid profile) measured. Thirtytwo transwomen on GnRH agonist therapy (age 48 ± 2 yrs, BMI 28 ± 1 kg.m2) followed for 45 ± 5 months were compared with 22 transwomen (age 44 ± 3 yrs, BMI 28 ± 2 kg.m2) followed for 41 ± 7 months not on GnRH therapy. In the GnRH group, 14 were on oral E2, 12 on E2 patch and 6 were on E2 Injection. Similarly, in the non-GnRH group, the number of subjects on oral E2, E2 patch or E2 Injection were 17, 1, and 4 respectively. The average oral estrogen dose in both groups was 4 ± 0.4 mg. In the GnRH group, serum testosterone declined from 420 ± 36 ng/dl to 40 ± 5 ng/dL and serum estradiol before and after therapy was 39 ± 9 vs 89 ± 12 pg/mL. GnRH therapy led to increase in BMI (28 ± 1 vs 31 ± 2 kg.m2, p=0.006), though no difference was observed in SBP (126 ± 2 vs 120 ± 2 mmHg, p=ns), total Cholesterol (170 ± 7 vs 171 ± 8 mg/dL), HDL Cholesterol (45 ± 2 vs. 46 ± 2 mg/dL), LDL Cholesterol (98 ± 7 vs 99 ± 5 mg/dL) before and after treatment. There was no change in BMI (28 ± 2 vs 29 ± 1 kg.m2), SBP (121 ± 3 vs 125 ± 3, p=ns), total cholesterol (173 ± 5 vs. 170 ± 9 mg/dL), HDL chol (46 ± 2 vs. 49 ± 2 mg/dL), or LDL chol (97 ± 6 vs. 95 ± 7 mg/dL) in the control group. Plasma triglycerides increased in both the GnRH (134 ± 10 vs 168 ± 16 mg/dL, p<0.05) as well as in the control group (154 ± 30 vs 167 ± 20 mg/dL, p<0.05) after treatment. In conclusion, long-term estrogen therapy in transwomen increased plasma triglyceride. Concomitant GnRH agonist therapy was associated with greater weight gain, but did not affect other cardiovascular risk factors. Presentation: Saturday, June 17, 2023

The Effect of Uterine Adenomyosis on IVF Outcomes: a Systematic Review and Meta-analysis.

To investigate the impact of uterine adenomyosis on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) clinical outcomes and also to evaluate the impact of gonadotropin-releasing hormone agonist (GnRHa) and surgical treatments. Infertile women with adenomyosis undergoing conventional IVF or ICSI were compared with women without adenomyosis. Fertility outcomes were evaluated in two patients with adenomyosis untreated and treated surgically or medically therapy. The review protocol was registered in PROSPERO (CRD42020214586). We consider the live birth rate (LBR) as the primary outcome. The analysis showed that women with adenomyosis had lower LBR (OR 0.59, 95% CI 0.37-0.92, p = 0.02), clinical pregnancy rate (OR 0.66, 95% CI 0.48-0.90), and ongoing pregnancy rate (OR 0.43, 95% CI 0.21-0.88) compared to those without adenomyosis, and miscarriage rate was higher in women with adenomyosis (OR 2.11, 95% CI 1.33-3.33). Surgical treatment increases natural conception in women with adenomyosis although the paucity of data (only two studies), and conversely, treatment with GnRHa does not increase the IVF outcomes. Women with adenomyosis have decreased IVF clinical outcomes. Pretreatment with the use of long-term GnRHa could not be beneficial, even though only three studies were included in the meta-analysis. The major part of the studies has not divided focal and diffuse adenomyosis, and this represents a relevant source of bias: studies conducted with standardized diagnostic criteria for adenomyosis are still needed to determine if the different clinical presentations of such condition could compromise IVF outcomes.

GnRH receptor mediates lipid storage in female adipocytes via AMPK pathway.

Objective: Due to high levels of serum gonadotropin-releasing hormone (GnRH), perimenopausal or menopausal women, girls with central precocious puberty, women of polycystic ovary syndrome, and females receiving long-term GnRH agonist (GnRHa) treatment are at substantially higher risk of developing obesity. However, it remains poorly understood how GnRH affects body weight. Here, we explored whether the gonadotropin-releasing hormone receptor (GnRHR) was expressed in adipocytes and how GnRHR mediated lipid accumulation and the development of obesity.Methods: The samples were from 18 patients with benign tumors operated between 01/2018 and 06/2018 at the Women's Hospital School of Medicine Zhejiang University. Immunofluorescence, Western Blotting, and RT-PCR were used to detect whether the GnRH receptor was expressed in the specimens and human preadipocytes-subcutaneous (HPA-s). The GnRH receptor agonist diphereline with different concentrations was used to stimulate the HPA-s cells for 24, 48, and CCK-8 was used to detect cell proliferation. Oil red-O staining was used to detect lipid droplets in mature adipocytes. The phosphorylation of AMPK-Ser485/Thr172 was detected by Western Blotting.Results: GnRH receptor was expressed in all 18 human subcutaneous adipose tissue specimens. Cultured HPA-s expressed the GnRH receptor, and the expression increased during the process of cell maturation. The GnRH receptor agonist diphereline can stimulate the proliferation of HPA-s cells, which can advance the earliest occurrence of lipid droplets in HPA-s cells and the occurrence of lipid droplets in 50% cells by 1-2 days. Diphereline can stimulate the increase in the number of lipid droplets in mature adipocytes. The phosphorylation level of AMPK-Ser485/Thr172 in mature adipocytes was decreased by diphereline.Conclusion: The GnRH receptor was expressed in adipocytes. As adipocytes mature, GnRH receptor expression gradually increased. GnRHa stimulates the proliferation of HPA-s, promotes adipocyte maturation, increases the formation of lipid droplets in mature adipocytes, and inhibits the activation of the AMPK pathway in adipocytes. Our findings may elucidate the mechanism of obesity in these female populations and provide some evidence on how GnRH contributes to obesity. Additionally, these results provide theoretical support for further research on the mechanisms of obesity, thus enhancing our understanding of the functional diversity of GnRH and establishing a new theoretical basis for the impact of GnRH on metabolism.

Long-term GnRH agonist pretreatment before frozen embryo transfer improves pregnancy outcomes in women with adenomyosis

Research questionDo frozen embryo transfer (FET) cycles following long-term gonadotrophin-releasing hormone agonist (GnRHa) pretreatment have better pregnancy outcomes than fresh embryo transfer cycles with long or ultra-long GnRHa protocol in these patients? DesignThis study included 537 women with adenomyosis divided into three groups: (Group A) FET cycles following long-term GnRHa pretreatment (192 patients); (Group B) fresh embryo transfer cycles with the ultra-long GnRHa protocol (241 patients); (Group C) fresh embryo transfer cycles with the long GnRHa protocol (104 patients). ResultsThe total gonadotrophin dose and stimulation duration were significantly lower in Group A than in Groups B and C. The implantation and live birth rates were significantly higher in Group A than in Groups B and C. In the long-term GnRHa pretreatment and FET treatment of Group A, implantation (odds ratio [OR] 1.729, 95% confidence interval [CI] 1.073–2.788, P = 0.025), clinical pregnancy (OR 1.665, 95% CI 1.032–2.686, P = 0.037) and live birth rates (OR 1.694, 95% CI 1.045–2.746, P = 0.033) increased and miscarriage rate (OR 0.203, 95% CI 0.078–0.530, P = 0.001) decreased when compared with Group C. Comparison of Groups A and B showed that with the long-term GnRHa pretreatment, FET was a protective factor for live birth rate (OR 1.350, 95% CI 1.017–1.792, P = 0.038). ConclusionFET following long-term GnRHa pretreatment has a better IVF/intracytoplasmic sperm injection outcome, and a potential benefit in terms of a lower gonadotrophin dose, and a shorter stimulation duration than fresh embryo transfer combined with a long or ultra-long GnRHa protocol.

SUN-044 Gonadotropin Releasing Hormone (GnRH) Agonist Therapy Induces a Sustained Reduction in Plasma Testosterone Levels and Is Well Tolerated in Transwomen Veterans

Gender affirming hormone therapy (GAHT) is the mainstay of long-term management of transgender individuals. In transwomen, treatment with physiologic doses of estrogen alone is often insufficient to suppress testosterone to the desired level. Although GnRH agonist therapy is usually prescribed for puberty suppression in trans youth, in adult transwomen, GnRH agonist may be added. The durability of long-term GnRH agonist in lowering testosterone as well as the long-term safety is not clear. We examined the effect of leuprolide a GnRH agonist, on testosterone as well as clinical and metabolic features in transwomen Veterans. Out of 91 subjects with gender dysphoria followed at a VA Endocrinology clinic, 65 were transwomen (age 49 ± 3 years) who had a detailed clinical, biochemical and hormonal profile (lipid profile, HbA1C, FPG, testosterone, estradiol). We performed a retrospective cohort study of the 31 (48%) transwomen on Leuprolide (3.375mg q month) and 33 transwomen who were not on Leuprolide. Plasma testosterone, lipid profile, were analyzed before, 6 months, 1 year and at the last follow-up visit. The median follow-up of subjects on Leuprolide was 2.7 (1.7-3.8) years. Plasma testosterone concentration declined by 89% from 432±32 ng/dl to 47±9 ng/dl within 3-6 months after initiation of GnRH agonist treatment. Plasma testosterone remained persistently low 39±4ng/dl at 1 year and at the end of 2.7 yrs, most subjects on Leurprolide had plasma testosterone concentration <50ng/dl. Leuprolide therapy led to similar rapid decline in testosterone concentration in both younger (<40yrs) or relatively older (>50yr) transwomen. Leuprolide was in general well tolerated requiring discontinuation in just one patient due to severe fatigue. Three subjects (10%) experienced hot flashes which did not lead to discontinuation of medication. In the non-Leuprolide group, of 33 subjects, the follow-up was relatively inconsistent and only 12 subjects were regularly followed throughout a year with stable treatment. The decline in plasma testosterone was of a lower magnitude versus the leuprolide group (55% vs 89%, p <0.05). The testosterone levels declined from 393±42 to 180±44 ng/dl at 6 months. Body weight, and lipid profile: triglyceride, and plasma HDL concentration did not change significantly with or without GnRH agonist therapy. In conclusion, GnRH agonist therapy led to a sustained suppression of plasma testosterone levels in transwomen and was not associated with worsening lipid profile, was effective, and well tolerated in transwomen regardless of their age and may be considered an adjunct to the ant-androgen and estrogen therapy.

Autoimmune thyroiditis after long term gonadotropin- releasing hormone agonist treatment for central precocious puberty: case report

There is a small number of studies that have reported abnormalities in endocrine function after a long-term gonadotropin-releasing hormone agonist (GnRHa) treatment in girls. This treatment is considered as safe and effective by most authors. We report our second case of unusual outcome of long-term GnRHa therapy in a girl with central precocious puberty (CPP) of idiopathic or familial etiology. She has received monthly depot of injections of triptorelin for a time period of 4 years. We have examined thyroid function by measuring serum levels of thyrotropin (TSH), thyroxine (T4), thyroid antibodies and ultrasound of thyroid gland. At the age of 11 years she developed a mild goiter and presented with autoimmune thyroiditis, having elevated thyroid antibodies and ultrasound of thyroid gland typical for Hashimoto thyroiditis. Having in mind these two cases, we suggest a closer monitoring of thyroid function in girls with CPP, before and during therapy with GnRH agonist.

Combined Androgen Blockade in Localized Prostate Cancer Treated With Definitive Radiation Therapy.

The addition of androgen deprivation therapy to radiation therapy (RT) improves survival in patients with intermediate- and high-risk prostate cancer (PCa), but it is not known whether combined androgen blockade (CAB) with a gonadotropin-releasing hormone agonist (GnRH-A) and a nonsteroidal antiandrogen improves survival over GnRH-A monotherapy. This study evaluated patients with intermediate- and high-risk PCa diagnosed in 2001 through 2015 who underwent RT with either GnRH-A alone or CAB using the Veterans Affairs Informatics and Computing Infrastructure. Associations between CAB and prostate cancer-specific mortality (PCSM) and overall survival (OS) were determined using multivariable regression with Fine-Gray and multivariable Cox proportional hazards models, respectively. For a positive control, the effect of long-term versus short-term GnRH-A therapy was tested. The cohort included 8,423 men (GnRH-A, 4,529; CAB, 3,894) with a median follow-up of 5.9 years. There were 1,861 deaths, including 349 resulting from PCa. The unadjusted cumulative incidences of PCSM at 10 years were 5.9% and 6.9% for those receiving GnRH-A and CAB, respectively (P=.16). Compared with GnRH-A alone, CAB was not associated with a significant difference in covariate-adjusted PCSM (subdistribution hazard ratio [SHR], 1.05; 95% CI, 0.85-1.30) or OS (hazard ratio, 1.02; 95% CI, 0.93-1.12). For high-risk patients, long-term versus short-term GnRH-A therapy was associated with improved PCSM (SHR, 0.74; 95% CI, 0.57-0.95) and OS (SHR, 0.82; 95% CI, 0.73-0.93). In men receiving definitive RT for intermediate- or high-risk PCa, CAB was not associated with improved PCSM or OS compared with GnRH alone.

Effects of long-term release GnRH agonist “deslorelin” on testicular HSP expression, accessory sex glands and testicular functions in adult male rats

The objective of the present was to determine the effect of long-term release GnRH agonists “deslorelin” on suppression and restoration of testicular and accessory sex glands functions, and expression of HSP in testes of adult male rats. A group of twenty-eight male rats and fifty-six female rats were kept for eleven months. The male rats were subdivided into treatment (n = 18; deslorelin, an analogue of GnRH, 4.7 mg, S.C; six months) and control (n = 10; untreated), and the adult female rats were introduced with either treatment or control male rats at the 2nd, 6th and 11th months post implant insertion. At 6th month of deslorelin implants insertion, six male rats from treatment and five rats from control group were sacrificed. The remaining (twelve treatment and five control) male rats were sacrificed at 11 months. The testicular dimension were measured monthly in both treatment and control rats. The blood samples were collected for testosterone and HSP70 antibody, whereas, the testes and accessory glands were isolated for histological examination at each sacrificial time. The results showed that testicular dimension were significantly lesser in treatment group until 9 months post treatment. HSP70 protein expression was negligible at 6 months in treatment group but its intensity increased in spermatids 11 months of treatment similar to control group. Significantly lower testosterone concentrations with poor semen quality, and smaller litter size were observed in treatment group. The histological picture of accessory sex glands and seminiferous tubules shown a variable integrity in treatment group than control at 6 months implant insertion. In conclusion, the subcutaneous application of 4.7 mg of the GnRH-analogue deslorelin represents a practicable, like in the female rats, method to suppress testicular, accessory sex glands functions, testicular HSP expression and fertility in male rats. Moreover, the suppressive effects of deslorelin, continued until 11th months after removal of the implant.

Long-term GnRH agonist therapy before in vitro fertilization (IVF) for improving fertility outcomes in women with endometriosis

Long-term GnRH agonist therapy before in vitro fertilization (IVF) for improving fertility outcomes in women with endometriosis

Gonadotropin releasing hormone agonists are effective in long-term treatment of women with abnormal uterine bleeding and anticoagulant therapy: Report of 3 cases and review of the literature

To evaluate the efficacy of gonadotropin-releasing hormone agonist (GnRHa) in women with abnormal uterine bleeding (AUB) on anticoagulant therapy. Prospective observational case series (Canadian Task Force Classification II-3) at University-affiliated teaching hospital. From January 2002 through December 2019, three premenopausal women on warfarin therapy were identified from our clinical practice. After clinical assessment, including Papanicolaou smear, endometrial biopsy, and pelvic sonography, a GnRHa was used to treat their AUB. Two women were receiving warfarin therapy (5–7 mg/day) for previous venous thromboembolism and one for mechanical heart valve replacement associated with Marfan’s syndrome. All patients had additional comorbid conditions and were at high risk for traditional medical or surgical therapies. After treatment with GnRHa, all women reported menstrual reduction at 3 months and remained amenorrheic for 2 to 11 years, two of whom reached menopause. In properly assessed and selected premenopausal women with AUB receiving anticoagulant therapy and at high risk for traditional therapies, long-term GnRHa was an effective treatment in 3 patients.

The effect of intrauterine human chorionic gonadotropin flushing on live birth rate after vitrified-warmed embryo transfer in programmed cycles: a randomized clinical trial.

To assess the influence of intrauterine human chorionic gonadotropin (hCG) before embryo transfer on the clinical pregnancy and live birth rates after vitrified-warmed embryo transfer (ET) in programmed cycles. This study was a single-blind randomized clinical trial for eligible patients underwent frozen ET cycles with long-term hormonal GnRH agonist protocol for endometrial preparation. Immediately prior to ET, the women were randomly divided into three groups. In the experimental group, 7-10min before embryo transfer, 500IU of hCG with a 40μL of culture medium was injected into the uterus. In the first control (sham) group, 7-10min before ET just 40μL of culture medium intrauterine was infused. In the second control group, no intervention was done. The pregnancy outcomes were compared in the three groups using appropriate statistical tests. Finally, 180 patients allocated into three groups. There was no significant difference in terms of patients 'characteristics among three groups. No significant difference was found in terms of clinical pregnancy among three groups. The miscarriage rate in control group (0%) was significantly lower than those of in the sham and hCG groups (9.8% and P = 0.01, 6.6% and P = 0.04, respectively). In addition, live birth rate (39.3%) in control group was significantly higher than those of in the sham and hCG groups (16.4% and P = 0.005, 23% and P = 0.051, respectively). It was found that intrauterine injection of 500IU hCG before vitrified-warmed ET at cleavage stage has no beneficial effect on pregnancy outcome and is not suggested. NCT02355925.

Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis

To systematically review and summarize the existing evidence related to the effect of adenomyosis on fertility and on invitro fertilization (IVF) clinical outcomes, and to explore the effects of surgical or medical treatments. Meta-analysis. Not applicable. An electronic-based search was performed with the use of the following databases: Pubmed, Embase, Ovid Medline, Cochrane Central Register of Controlled Trials, and Google Scholar, identifying all related articles up to November 2016. We included 11 comparative studies that evaluated the clinical outcomes of IVF treatments in women with (519 patients) and without (1,535 patients) adenomyosis diagnosed with the use of magnetic resonance imaging or transvaginal ultrasound. We also separately evaluated four articles comparing fertility outcomes in two groups of infertile adenomyotic patients untreated and treated surgically or medically with the use of GnRH agonist (GnRHa). None. Primary outcome: clinical pregnancy rate after IVF. rates of implantation, ongoing pregnancy, live birth, miscarriage, and ectopic pregnancy. The summary measures were expressed as odds ratio (OR) and 95% confidence interval (CI). The rates of implantation, clinical pregnancy per cycle, clinical pregnancy per embryo transfer, ongoing pregnancy, and live birth among women with adenomyosis were significantly lower than in those without adenomyosis. The miscarriage rate in women with adenomyosis was higher than in those without adenomyosis. It appears that surgical treatment or treatment withf GnRHa increases the spontaneous pregnancy rate in women with adenomyosis. Adenomyosis has a detrimental effect on IVF clinical outcomes. Pretreatment with the use of long-term GnRHa or long protocol could be beneficial.

Does presence of adenomyosis effect reproductive outcome - a retrospective analysis of 607 patients having endometriosis, endometriosis with adenomyosis and only adenomyosis who underwent IVF/ICSI

Adenomyosis is encountered more often among infertile women undergoing IVF/ICSI programmes. There are conflicting findings of the impact of adenomyosis on assisted reproduction treatment (ART) outcomes. The objective of the present study was to evaluate the effect of adenomyosis on first IVF/ICSI cycle. All women were pretreated with long-term (2months) GnRH-agonist prior to IVF/ICSI.

Age of menarche and near adult height after long-term gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty.

PurposeGonadotropin-releasing hormone agonist (GnRHa) is known for improving final adult height in patients with central precocious puberty (CPP). This study aimed to investigate the age of menarche and near adult height in girls with CPP who had been treated with GnRHa.MethodsIn this retrospective study, we reviewed the medical records of 71 Korean girls with CPP who had started menarche or reached over 13 years of bone age after long-term GnRHa treatment. We estimated near adult height using the Bayley-Pinneau method and identified the age of menarche in girls with CPP.ResultsMean chronological and bone age at menarche were 11.9±0.7 and 12.8±0.4 years, respectively. The period between menarche and the end of treatment was 14.0±5.6 months. Posttreatment near adult height was 163.8±4.7 cm, which was significantly greater than pretreatment predicted adult height (158.7±4.1 cm).ConclusionGnRHa treatment in girls with CPP could improve final adult height and made the age of menarche close to that of the general population.

Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex biased gene expression of amygdala in sheep

The nature of hormonal involvement in pubertal brain development has attracted wide interest. Structural changes within the brain that occur during pubertal development appear mainly in regions closely linked with emotion, motivation and cognitive functions. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) receptors, results in exaggerated sex-differences in cognitive executive function and emotional control, as well as sex and hemisphere specific patterns of expression of hippocampal genes associated with synaptic plasticity and endocrine signaling. In this study, we explored effects of this treatment regime on the gene expression profile of the ovine amygdala. The study was conducted with 30 same-sex twin lambs (14 female and 16 male), half of which were treated with the GnRH agonist (GnRHa) goserelin acetate every 4th week, beginning before puberty, until approximately 50 weeks of age. Gene expression profiles of the left and right amygdala were measured using 8×15 K Agilent ovine microarrays. Differential expression of selected genes was confirmed by qRT-PCR (Quantitative real time PCR). Networking analyses and Gene Ontology (GO) Term analyses were performed with Ingenuity Pathway Analysis (IPA), version 7.5 and DAVID (Database for Annotation, Visualization and integrated Discovery) version 6.7 software packages, respectively. GnRHa treatment was associated with significant sex- and hemisphere-specific differential patterns of gene expression. GnRHa treatment was associated with differential expression of 432 (|logFC|>0.3, adj. p value <0.05) and 46 (p value <0.0.5) genes in the left and right amygdala, respectively, of female animals, relative to the reference sample which consisted of all a pooled sample from control and treated animals of both sexes. No genes were found to be differentially expressed as a result of GnRHa treatment in the male animals. The results indicated that GnRH may, directly and/or indirectly, be involved in the regulation of sex- and hemisphere-specific differential expression of genes in the amygdala. This finding should be considered when long-term peri-pubertal GnRHa treatment is used in children.

Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis

Some studies have shown that long-term gonadotropin-releasing hormone (GnRH) agonist administration before in vitro fertilization/intracytoplasmic sperm in infertile women with endometriosis or adenomyosis significantly increases the chances of pregnancy. We were interested in whether long-term GnRH agonist pretreatment could improve pregnancy outcomes in adenomyosis patients undergoing frozen embryo transfer (FET) after preparation of the endometrium with hormone replacement therapy (HRT). Totally, 339 patients with adenomyosis were included in this retrospective study, 194 received long-term GnRH agonist plus HRT (down-regulation + HRT) and 145 received HRT. There were no differences between the groups in characteristic such as age, body mass index, duration or cause of infertility, serum CA-125 level and basal hormone levels. On the day of progesterone administration, mean endometrial thickness and serum progesterone level were significantly greater in HRT patients. Mean score and number of embryos transferred showed no differences. In down regulation + HRT group, clinical pregnancy, implantation and ongoing pregnancy rates were 51.35%, 32.56% and 48.91%, respectively, significantly higher than that of HRT group (24.83%, 16.07% and 21.38%, respectively). So, we concluded that in FET, long-term GnRH agonist pretreatment significantly improved pregnancy outcomes in patients with adenomyosis.