Use Of Gonadotropin-releasing Hormone Agonists Research Articles

Risk factors for poor oocyte yield and oocyte immaturity after GnRH agonist triggering.

What are the potential risk factors for poor oocyte recuperation rate (ORR) and oocyte immaturity after GnRH agonist (GnRHa) ovulation triggering? Lower ovarian reserve and LH levels after GnRHa triggering are risk factors of poor ORR. Higher BMI and anti-Müllerian hormone (AMH) levels are risk factors of poor oocyte maturation rate (OMR). The use of GnRHa to trigger ovulation is increasing. However, some patients may have a suboptimal response after GnRHa triggering. This suboptimal response can refer to any negative endpoint, such as suboptimal oocyte recovery, oocyte immaturity, or empty follicle syndrome. For some authors, a suboptimal response to GnRHa triggering refers to a suboptimal LH and/or progesterone level following triggering. Several studies have investigated a combination of demographic, clinical, and endocrine characteristics at different stages of the treatment process that may affect the efficacy of the GnRHa trigger and thus be involved in a poor endocrine response or efficiency but no consensus exists. Bicentric retrospective cohort study between 2015 and 2021 (N = 1747). All patients aged 18-43 years who underwent controlled ovarian hyperstimulation and ovulation triggering by GnRHa alone (triptorelin 0.2 mg) for ICSI or oocyte cryopreservation were included. The ORR was defined as the ratio of the total number of retrieved oocytes to the number of follicles >12 mm on the day of triggering. The OMR was defined as the ratio of the number of mature oocytes to the number of retrieved oocytes. A logistic regression model with a backward selection method was used for the analysis of risk factors. Odds ratios (OR) are displayed with their two-sided 95% confidence interval. In the multivariate analysis, initial antral follicular count and LH level 12-h post-triggering were negatively associated with poor ORR (i.e. below the 10th percentile) (OR: 0.61 [95% CI: 0.42-0.88]; P = 0.008 and OR: 0.86 [95% CI: 0.76-0.97]; P = 0.02, respectively). A nonlinear relationship was found between LH level 12-h post-triggering and poor ORR, but no LH threshold was found. A total of 25.3% of patients suffered from oocyte immaturity (i.e. OMR < 75%). In the multivariate analysis, BMI and AMH levels were negatively associated with an OMR < 75% (OR: 4.34 [95% CI: 1.96-9.6]; P < 0.001 and OR: 1.22 [95% CI: 1.03-1.12]; P = 0.015, respectively). Antigonadotrophic pretreatment decreased the risk of OMR < 75% compared to no pretreatment (OR: 0.72 [95% CI: 0.57-0.91]; P = 0.02). Our study is limited by its retrospective design and by the exclusion of patients who had hCG retriggers. However, this occurred in only six cycles. We were also not able to collect information on the duration of pretreatment and the duration of wash out period. In clinical practice, to avoid poor ORR, GnRHa trigger alone should not be considered in patients with higher BMI and/or low ovarian reserve, balanced by the risk of ovarian hyperstimulation syndrome. In the case of a low 12-h post-triggering LH level, practicians must be aware of the risk of poor ORR, and hCG retriggering could be considered. None. N/A.

The administration of long in-vitro fertilization protocol in adenomyosis: case series.

Adenomyosis is a gynaecological condition characterized by the infiltration of endometrial glands and stroma resulting in ectopic intramyometrial, leading to the generalized enlargement of the uterus. Various cyclical regimens are employed globally to assist infertile women with adenomyosis during in-vitro fertilization (IVF) treatment because there is no consensus regarding the best protocol for managing adenomyosis. The authors reported two cases the administration of long IVF protocol in Adenomyosis with pregnancy outcome. In both cases examined were found that the levels of anti-Mullerian hormone (AMH) were below the 25th percentile. Nevertheless, in both of these cases, the number of oocytes successfully retrieved was more than 5, which may have been influenced by the use of GnRH agonists in previous cycles of long protocol. Both of them were diagnosed with intrauterine pregnancy after transfer embryo. Although there is currently no consensus on the most suitable protocol for adenomyosis cases, the application of a long protocol in both of the aforementioned cases has yielded positive IVF outcomes.

(031) Effects of Gender Affirming Hormone Therapy vs. Puberty Blockers on Sexual Function and Desire

Abstract Introduction Many transgender and nonbinary (TGNB) individuals seek out puberty blockers (PB) to stop the progression of unwanted changes from endogenous puberty and/or gender affirming hormone therapy (GAHT) to aid in their medical transition. There has been limited research assessing the effect of these hormone therapies on sexual function and desire, especially in comparing GAHT and PB+GAHT. Objective Our aim was to compare the effect of GAHT and PB+GAHT on sexual function and desire of TGNB individuals during or following hormone therapy. Methods We performed an IRB approved two institutional study on the effect of GAHT and/or PB on sexual function and desire in adults. The GAHT group (n=12) included individuals who started GAHT (estrogen or testosterone) &amp;gt;18 years old. The PB group (n=10) included subjects with current or past history of GnRH agonist use (&amp;gt;10 years old). Enrolled subjects completed the validated Changes in Sexual Functioning Questionnaire (CSFQ). The CSFQ was validated in adults to assess medication-related changes in sexual functioning. The questionnaire is specific to sex assigned at birth with a male and female version. The answers were scored in total and separated into sexual function and sexual desire subscales. Scores in each group were compared using unpaired t-tests. Results A total of 22 TGNB (16 assigned male at birth and 6 assigned female at birth: 14 transgender women, 5 transgender men, 3 non-binary) subjects ages 18-25 completed the CSFQ about the effect hormone therapy had on sexual function and desire. There was no difference between groups in total scores (t = 0.8, p = 0.05) or in categories of sexual function (t = 0.3, p = 0.05) and desire (t = 0.8, p = 0.05). There were an equal number of participants in both groups whose results showed sexual dysfunction in total (n=2 per group) and in categories of sexual function (n=7 per group) and desire (n=3 per group). The cause of their dysfunction is unclear at this time and is to be investigated in the future. Interestingly, despite meeting quantitative criteria for sexual dysfunction, 6 participants answered that their sexual life brings them “much” or “great” enjoyment or pleasure. Conclusions Based on our results, while there were &amp;gt;70% of subjects in each group with impaired sexual function, there were no differences in effect on sexual function and desire between subjects on GAHT vs. PB+GAHT. Additionally, the scores for both groups did not differ substantially from scores of cisgender individuals (Keller, et al 2006). In fact, both the GAHT and PB+GAHT groups scored higher on average in the sexual desire category compared to cisgender individuals. Prospective data collection will help us clarify further whether starting age of pubertal blockers and hormone therapy affects sexual function and desire. Disclosure No.

(032) Experience with Gender Affirming Hormones and Puberty Blockers: A Qualitative Analysis of Sexual Function

Abstract Introduction Gender affirming hormone therapy (GAHT) is part of the transition for many transgender and nonbinary (TGNB) individuals. Additionally, it has become increasingly more common for TGNB youth to receive puberty blockers (GnRH agonist) to halt the pubertal progression. There have been few studies investigating sexual function and desire either during or after puberty blockers (PB) and/or GAHT. Objective Our aim was to qualitatively evaluate the sexual experience of TGNB individuals during or following PB and/or GAHT, and outline any potential differences between the two groups. Methods We performed an IRB approved two institutional study on the effect of PB and/or GAHT on sexual function and desire. The GAHT group (n=16): individuals who started GAHT (estrogen or testosterone) &amp;gt;18 years. The PB+GAHT group (n=10): subjects with current or past GnRH agonist use +GAHT. All 26 enrolled subjects were interviewed using an open-ended topical guide. Qualitative analysis was performed by hand coding the interview transcripts using Constructivist Grounded Theory qualitative methods. Results A total of 26 TGNB (20 assigned male at birth, 6 assigned female at birth: 18 transgender women, 5 transgender men, 3 non-binary) subjects ages 18-25y were interviewed about the effect of PB and/or GAHT on their sexual function and desire. Our analysis uncovered several themes that were consistent between groups (Table 1). Conclusions Themes were similar for both groups. Half the participants in each group reported feeling no regrets regarding hormone therapy, and the other half reported that they wished they had started hormones sooner. Two notable differences were identified between groups: those on PB+GAHT reported “less dysphoria” as a positive change in sexual desire, and the GAHT group reported more enjoyable sexual experiences since being on hormones. Interestingly, results did not reveal any significant differences between groups. The most prominent theme that arose in both groups was that the positive changes in sexual function and desire outweighed any negative changes that arose. Disclosure No.

#304 : Comparing GnRH Agonist and GnRH Antagonist Protocols for IVF-ET Outcomes in Patients with Endometriosis: A Meta-Analysis

Background and Aims: Endometriosis is known to have detrimental effects on fertility, but there is no consensus on the optimal stimulation protocol for IVF-ET in patients with endometriosis. The study aimed to compare the IVF outcomes of gonadotropin-releasing hormone (GnRH) agonist protocols versus antagonist protocols in patients diagnosed with endometriosis. Method: We performed a meta-analysis of studies that compared IVF outcomes of GnRH agonist versus antagonist protocols in patients with endometriosis. Through literature search, we retrieved 222 articles, and the last search date was April 7, 2023. Among them, six studies which met inclusion criteria were eligible for final analysis. The primary outcome was clinical pregnancy. Random effects and fixed effects models were applied according to I2 statistics. Results: The use of GnRH agonist was associated with higher clinical pregnancy rate (Odds ratio (OR) 1.61, 95% CI 1.35–1.93, 6 studies, [Formula: see text]&lt;0.00001, I2=16%), higher live birth rate (OR 1.75, 95% CI 1.32–2.33, 3 studies, [Formula: see text]&lt;0.0001, I2=12%), and similar miscarriage rate. The total dose of gonadotropin did not differ between the two methods, but the GnRH agonist protocol had a longer duration of stimulation (WMD 1.34, 95% CI 0.44–2.24, 5 studies, I2=98%), retrieved more oocytes (WMD 2.23, 95% CI 0.58–3.88, 3 studies, [Formula: see text]=0.0008, I2=97%), more MII oocytes (WMD 2.81, 95% CI 2.34–3.28, 3 studies, [Formula: see text]&lt;0.00001, I2=0), and more embryos (WMD 1.90, 95%CI 1.13–2.67, 3 studies, [Formula: see text]&lt;0.00001, I2=68%). Conclusion: Patients with endometriosis may benefit from using GnRH agonist protocol in the IVF-ET cycle, as it may be associated with a higher clinical pregnancy rate and live birth rate. Even though the stimulation duration is longer, more oocytes, mature oocytes, and embryos may be expected. Although the findings of this study may be potentially beneficial for clinicians, it is crucial to conduct additional randomized prospective trials with larger cohorts to further validate the results.

#86 : Use of Triptorelin Versus Human Chorionic Gonadotropin as Ovulation Trigger

Background and Aims: Gonadotropin releasing hormone agonist (GnRH-a) trigger has been shown to be associated with significantly lower risk of moderate or severe ovarian hyperstimulation syndrome (OHSS) when compared among women at high risk of OHSS. However, trigger failure has been shown to occur in 2% of cycles using GnRH-a as trigger. This study aims to review the use of GnRH-a as ovulation trigger. Method: Retrospective review of records in antagonist cycles from an ART unit in a tertiary hospital from 2017-2021 was performed. Follicles were considered mature when they reach [Formula: see text] 15 mm. Ovulation triggered with urinary human chorionic gonadotropin (uhCG) (5000-10000 IU), recombinant hCG (rhCG) 250 mcg, or triptorelin 0.2 mg when there were [Formula: see text] 3 mature follicles. All embryos obtained from cycles using triptorelin were cryopreserved. Outcome including the number of oocytes retrieved, the follicle to oocyte index, ovarian hyperstimulation syndrome were reviewed. Results: 1378 cycles were included. 1089 cycles had uhCG or rhCG as trigger, while 284 cycles had triptorelin as trigger. Women in the triptorelin group were significantly younger with a lower basal follicle stimulating hormone level and a higher antral follicle count (Table 1). In the triptorelin group, the total number of mature sized follicles, estrogen level at trigger, oocytes retrieved, number of blastocysts were significantly higher compared to the hCG group (Table 2). Follicle to oocyte index was significantly higher in the triptorelin group but the proportion of mature oocytes were similar in both groups. There were no cases of trigger failure and OHSS in the triptorelin group, but 30 cases of OHSS, with18 cases early onset, 12 cases late onset, amongst them 10 cases (1%) were severe OHSS) in the hCG group. Conclusion: GnRH-a trigger is a good candidate as ovulatory trigger in women at risk of OHSS without hampering the laboratory outcome.

Abstract 12107: Cardiovascular Outcomes Associated With Gonadotropin-Releasing Hormone Antagonists vs Gonadotropin-Releasing Hormone Agonists for Prostate Cancer Treatment: A Meta-Analysis of Randomized Controlled Trials

Background: Androgen deprivation therapy (ADT), comprising the administration of Gonadotropin-releasing hormone (GnRH) agonists and antagonists, is a widely utilized treatment for prostate cancer patients and has been universally accepted as the first-line treatment for symptomatic metastatic prostatic cancer. While ADT has proven effective, concerns about its impact on cardiovascular health have emerged. Conflicting results regarding the association between ADT and cardiovascular events have been reported in the most recent PRONOUNCE trial hence a meta-analysis to systematically evaluate the evidence is desired. Aim: The primary objective of this meta-analysis was to investigate and compare the effects of GnRH agonists and antagonists on cardiovascular events in patients with prostate cancer. Methods: A comprehensive search was conducted in major electronic databases to identify relevant RCTs. Studies published from inception to April 2023 were scrutinized. Results: 9 studies met the eligibility criteria and were included in the final analysis. A total of 3648 patients were randomized to receive either an agonist (n=1375) or an antagonist (n=2273). The pooled results revealed a significant reduction in the risk of adverse cardiovascular events by 48% with the use of GnRH agonists compared to GnRH antagonists (RR=0.52; 95% CI=0.39-0.71; p&lt;0.01). Furthermore, GnRH agonists also decreased the risk of all-cause mortality by 46% (RR=0.54; 95% CI= 0.33-0.88; p=0.01) and cardiovascular mortality by 78% (RR= 0.22; 95% CI= 0.07-0.76; p=0.02) compared to GnRH antagonists. Conclusion: The findings of this meta-analysis reveal the favorable cardiovascular risk profile associated with GnRH agonists, supporting their role as a preferred treatment option over GnRH antagonists.

Current status of fertility preservation in a Spanish tertiary public hospital: multidisciplinary approach and experience in over 1500 patients.

Currently, 15% of gynaecological and 9% of haematological malignancies are diagnosed before the age of 40. The increased survival rates of cancer patients who are candidates for gonadotoxic treatments, the delay in childbearing to older ages, and the optimization of in vitro fertilisation techniques have all contributed to an increased interest in fertility preservation (FP) treatments. This study reviews the experience of the Fertility Preservation Programme (FPP) of a tertiary public hospital with a multidisciplinary approach. This retrospective study included all the available (FP) treatments, performed in patients of childbearing age between 2006 and 2022. 1556 patients were referred to the FPP: 332 oocyte vitrification cycles, 115 ovarian cortex cryopreservation with 11 orthotopic autotransplantations, 175 gonadotropin-releasing hormone (GnRH) agonist treatments, 109 fertility-sparing treatments for gynaecological cancer, and 576 sperm cryopreservation were performed. Malignancy was the main indication for FP (the main indications being breast cancer in women and haematological malignancies in men), although non-oncological pathologies, such as endometriosis and autoimmune diseases, have increased in recent years. Currently, the most widely used FP technique is oocyte vitrification, the increase of which has been associated with a decrease in the use of cortex CP and GnRH agonists. The increase in FP treatment reflects the implementation of reproductive counselling in oncology programmes. A multidisciplinary approach in a tertiary public hospital allows individualised FP treatment for each patient. In recent years, there has been a change in trend with the introduction of new indications for FP and a change in techniques due to their optimisation.

Heart Failure With Preserved Ejection Fraction: An Evolving Understanding.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome in which patients have signs and symptoms of HF due to high left ventricular (LV) filling pressure despite normal or near normal LV ejection fraction. It is more common than HF with reduced ejection fraction (HFrEF), and its diagnosis and treatment are more challenging than HFrEF. Although hypertension is the primary risk factor, coronary artery disease and other comorbidities, such as atrial fibrillation (AF), diabetes, chronic kidney disease (CKD), and obesity, also play an essential role in its formation. This review summarizes current knowledge about HFpEF, its pathophysiology, clinical presentation, diagnostic challenges, current treatments, and promising novel treatments. It is essential to continue to be updated on the latest treatments for HFpEF so that patients always receive the most therapeutic treatments. The use of GnRH agonists in the management of HFpEF, infusion of Apo a-I nanoparticle, low-level transcutaneous vagal stimulation (LLTS), and estrogen only in post-menopausal women are promising strategies to prevent diastolic dysfunction and HFpEF; however, there is still no proven curative treatment for HFpEF yet.

Pretreatment with a long-acting GnRH agonist for frozen-thawed embryo transfer cycles: how to improve live birth?

BackgroundWhether pretreatment with gonadotropin-releasing hormone agonist (GnRHa) can improve the pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles is controversial. The inconsistencies in the results of different studies would be related to the characteristics of the included patients and the protocol of GnRHa use. In this study, we investigated the efficacy of pretreatment with a long-acting GnRH agonist in the early follicular phase of FET cycles and determined which population was suitable for the protocol.ResultsWe retrospectively included 630 and 1141 patients in the GnRHa FET and hormone replacement treatment (HRT) FET without GnRHa groups respectively, between October 2017 and March 2019 at a university-affiliated in vitro fertilization center. On the second or third day of menstruation, 3.75 mg of leuprorelin was administered. After 14 days, HRT was initiated for endometrial preparation. No significant differences were observed between the two groups in terms of patient characteristics. However, the GnRHa FET group showed a higher percentage of endometrium with a triple line pattern (94.8% vs 89.6%, p < 0.001) on the day of progesterone administration, with increased implantation (35.6% vs 29.8%, p = 0.005), clinical pregnancy (49.8% vs 43.3%, p = 0.008), and live birth rate (39.4% vs 33.7%, p = 0.016), than the HRT FET cycles with similar endometrial thickness, ectopic pregnancy and early miscarriage rates. Binary logistic regression analysis showed the GnRHa FET group to be associated with an increased chance of clinical pregnancy (P=0.028, odds ratio [OR] 1.32, 95% confidence interval [CI] 1.03–1.70) and live birth (P=0.013, odds ratio [OR] 1.34, 95% confidence interval [CI] 1.06–1.70) compared to the HRT FET without GnRHa group. After subgroup analysis, we found that the GnRHa FET group showed a significantly higher live birth rate in the subgroups of age < 40 years, primary infertility, with polycystic ovary syndrome (PCOS), and irregular menstruation.ConclusionsPretreatment with a long-acting GnRHa during the early follicular phase improved the live birth rate in FET cycles. Age < 40 years, primary infertility, PCOS, and irregular menstruation are effective indications for endometrial preparation with GnRHa pretreatment in FET cycles. However, further randomized controlled trials are required to verify these results.

Analysis of the benefit of gonadotropin-releasing hormone agonist treatment in premenopausal women undergoing hematopoietic cell transplantation

Gonadotropin-releasing hormone agonist (GnRHa) appears to exhibit ovarian protection during chemotherapy for malignant tumors. The purpose of this study was to analyze the benefits of GnRHa in premenopausal women undergoing hematopoietic cell transplantation (HSCT). Candidates for myeloablative chemotherapy HSCT requiring fertility preservation in the Gynecological Endocrinology Clinic of Peking University People’s Hospital from December 2011 to December 2021 were retrospectively analyzed. Patients who chose to receive GnRHa treatment were given at least 2 courses of a 3.75-mg dose of a GnRHa before myeloablative chemotherapy, and patients who chose not to receive GnRHa treatment were included in the control group. All patients were monitored for menstruation return and menopause-related symptoms, and ovarian function tests [follicle-stimulating hormone (FSH), luteinizing hormone, and estradiol] were performed 6–12 months after HSCT. In addition, we assessed the vaginal bleeding of patients in the laminar air-flow room (LAFR). A total of 234 cases were included in this study: 77 cases in the treatment group and 157 cases in the control group. The incidence of vaginal bleeding in the LAFR in the treatment group was significantly lower than that in the control group (24.68% vs. 79.62%, P < 0.001). The menopausal symptoms of the patients in the treatment group were reduced after transplantation (46.75% vs. 19.75%, P < 0.001). There was no difference in visible follicles by follow-up ultrasound in the two groups after HSCT (16.88% vs. 13.38%, P = 0.474). The level of FSH at 6–12 months after transplantation was lower (98.00 mIU/ml vs. 117.53 mIU/ml, P = 0.001). The proportion of patients with FSH < 40 mIU/ml did not differ between the two groups. One patient in the treatment group recovered spontaneous menstruation, while none recovered spontaneous menstruation in the control group (1.30% vs. 0%, P = 0.329). The use of GnRHa may relieve menopause-related symptoms and reduce vaginal bleeding in the LAFR and breakthrough bleeding after transplantation. GnRHa treatment can reduce the level of FSH after myeloablative chemotherapy, but it cannot reduce the incidence of premature ovarian failure in women of reproductive age following myeloablative HSCT.

P-680 Oocyte maturation triggering protocols in in vitro fertilisation treatment: a systematic review and network meta-analysis

Abstract Study question What is the relative effectiveness and safety of final oocyte maturation trigger protocols in women undergoing in vitro fertilisation (IVF) treatment? Summary answer OHSS rate was lowest with GnRH agonist trigger and no difference in LBR was observed comparing various trigger protocols in normal, high and poor responders. What is known already Oocyte maturation trigger prior to oocyte retrieval is a crucial component of ovarian stimulation(OS). Pituitary suppression is an important component of OS in IVF, involving the use of GnRH analogues. Currently, the GnRH antagonist regimen is predominantly used given its comparable efficacy and lower risk of OHSS compared with GnRH agonist (GnRHa) regimens. Whilst only hCG trigger can be used with GnRH agonist regimens, GnRH antagonist regimen enables use of hCG trigger, GnRH agonist trigger or combinations of both as dual or double trigger. However, there is no consensus on how these trigger protocols compare in their effectiveness and safety. Study design, size, duration The following databases were searched until August 2022: MEDLINE, EMBASE, CINAHL, CENTRAL and ClinicalTrials.gov. Randomised controlled trials (RCTs) comparing at least two trigger protocols: hCG trigger, GnRH agonist trigger, dual trigger (hCG and GnRH agonist administered at the same time) and double trigger (GnRH agonist followed by hCG after a time interval) with the antagonist regimen were included. Primary outcome was live birth (LBR) per participant. Secondary outcomes included number of oocytes and OHSS rates. Participants/materials, setting, methods Two reviewers independently screened, selected studies and extracted data. Pairwise and network meta-analyses (NMA) were conducted according to ovarian response groups (normal, high and poor response). Effect estimates were presented as weighted means difference (WMD) and risk ratio (RR) with 95% confidence interval (CI) for continuous and dichotomous outcomes respectively. Quality assessment was performed using GRADE Main results and the role of chance Initial searches identified 4225 studies, of which 54 RCTs involving 5838 women met the inclusion criteria to be included in the analysis. In normal responders, there is no difference in LBR with the GnRHa vs hCG (RR:1.11,95%CI:0.83-1.49;3 studies,430 women,I2=33%,low-certainty evidence, direct comparison(DC)),dual trigger vs hCG(RR:1.14,95%CI:0.99-1.31;4 studies,1007 women,I2=33%,low-certainty evidence, DC),double trigger vs hCG(RR:0.53, 95%CI:0.27-1.06;indirect comparison(IC)),dual vs GnRHa (RR:0.97, 95%CI:0.70-1.34, IC),double vs GnRHa (RR:2.07, 95%CI:0.98-4.38, IC),dual vs double (RR:2.14, 95%CI:1.06-4.32;IC). In high responders, there is no difference in LBR with the GnRHa vs hCG (RR:1.04, 95%CI:0.84-1.29; 3 studies,178 women, I2 = 44%, low-certainty evidence, DC, dual trigger vs hCG (RR:1.82, 95%CI:1.25-2.67; 4 studies,117 women, I2 = 37%, low-certainty evidence, DC), double trigger vs hCG (RR:2.10, 95%CI:1.29-3.43, IC), dual vs GnRHa (RR:0.57, 95%CI:0.37-0.88, IC),double vs GnRHa (RR:0.49,95%CI:0.29-0.88, IC),dual vs double (RR:0.87, 95%CI:0.64-1.18; 1 study,57 women, low-certainty evidence,DC). In poor responders, there may be a difference in LBR when comparing dual trigger to hCG (RR:1.12,95%CI:1.12-2.89 1 study,112 women,low-certainty evidence,DC). OHSS rates were lowest with the use of GnRHa in high responders (RR:0.39,95%CI:0.04-3.78;9 studies;960 women;I2 =43%, low-certainty evidence,DC) and normal responders (RR:0.88, 95%CI:0.78 to 0.99;7 studies; 2246 women; I2=0%, low-certainty evidence,DC). There was no significant difference in number of oocytes or miscarriage risks with the use of any triggers. Limitations, reasons for caution Stratifying results by predicted ovarian response resulted in disconnected networks, limiting our ability to perform NMA for certain groups and outcomes. The certainty of the evidence was limited by high risk of bias. Wider implications of the findings Our results suggest that the use of short GnRH agonist trigger results in reduced OHSS rates in women with predicted normal or high ovarian response. There is no difference in LBR and number of oocytes comparing the different trigger protocols in all response groups (normal, high, poor responders) Trial registration number Not applicable

Combined treatment of high and very high risk prostate cancer: results of neoadjuvant treatment

Purpose of the study. Assessment of safety and short‑term effectiveness of high and very high‑risk prostate cancer neoadjuvant chemo‑ hormonal treatment without distant metastases.Patients and methods. Combined hormone chemo‑ radiation treatment of 33 patients with prostate cancer of high and very high risk of progression without distant metastases was performed. Metastases to regional lymph nodes were found in 9 patients according to the examination data (MRI, MSCT), no metastases were detected in 24 patients. All patients underwent combined chemohormonal therapy in the amount of 4 courses of docetaxel intravenously at a dose of 75 mg/m2 every 3 weeks as the first stage of treatment. in combination with androgen deprivation therapy with agonists or antagonists of GnRH before performing radical radiation therapy (combined or remote). All patients underwent neoadjuvant hormone therapy: 16 patients – with the use of GnRH antagonists (Degarelix), 17 – with the use of GnRH agonists (Gozerelin/Leuprorelin/Triptorelin). The toxicity of the presented treatment regimen and its immediate effectiveness – the effect on the level of prostate‑s pecific antigen (PSA), prostate volume, and the quality of urination – were evaluated.Results. Treatment regimen was highly effective concerning PSA decrease (from initial median level 79,67 ng/ml to 1,45 ng/ml after neoadjuvant treatment), all subjects responded well, no non‑responders observed. Median prostate volume decreased from 44 cm3 to 25 cm3 after treatment, which guaranteed availability and safety of further radical radiation treatment. Urinary function was restored in all subject with initial urinary retention.Conclusion. Neoadjuvant chemo‑h ormonal treatment was highly effective in PSA level, prostate volume decrease and functional results improvement which secured further radical radiation treatment in one of its types. Toxicity was acceptable, adverse events did not exceed grade II in most cases and did not lead to treatment discontinuation in any cases, while quality of life remained high enough.

Treatment of Adolescent Endometriosis Before, During, and After Use of Gonadotropin-Releasing Hormone Agonists: A Retrospective Cohort Study

To explore the use duration of a gonadotropin-releasing hormone agonists (GnRHa) plus add-back in adolescents with laparoscopically confirmed endometriosis and the treatment course before and after GnRHa therapy. Retrospective cohort study. We identified 51 subjects with laparoscopically confirmed endometriosis who had participated in a randomized trial of a GnRHa plus add-back as adolescents between 2008 and 2012. Electronic medical records were reviewed to obtain demographic data, clinical characteristics, and treatment outcomes after trial completion. The study was deemed IRB exempt. The average age of participants during trial enrollment was 17.9±1.7 years. Thirty-three participants had stage I endometriosis (65%). The most common treatments trialed before GnRHa therapy were combined oral contraceptives (n=47, 92%) and progestin-only pills (n=23, 45%). The average duration of GnRHa use during the trial was 9.5±3.5 months; 34 subjects (67%) completed the 1-year trial. After trial completion, 23 subjects (45%) continued to use a GnRHa with add-back therapy. The mean duration of additional GnRHa use was 31.7±28.6 months, and the longest identified duration was an additional 96 months. Twenty-four subjects switched to other hormonal treatments after trial participation, most commonly oral progestins (n=15) or combined oral contraceptives (n=6). Thirteen participants (25%) returned to a therapy that had been trialed before GnRHa use. Almost half the participants in this cohort continued to use a GnRHa with add-back for treatment of endometriosis beyond the 12-month recommended duration. Treatment varied widely after discontinuation of GnRHa, with many participants returning to previously trialed medical therapies.

Efficacy of Gonadotropin-Releasing Hormone Agonist (GnRH-a) in Ovarian Preservation in Females With Systemic Lupus Erythematosus (SLE) Receiving Cyclophosphamide (CYC) [ID: 1375370]

INTRODUCTION: Systemic lupus erythematosus (SLE) female patients with severe disease manifestations are treated with cyclophosphamide (CYC), which causes ovarian cytotoxicity. Gonadotropin-releasing hormone agonist (GnRH-a) is often co-administered with CYC to preserve ovarian function and reproductive potential. However, there is a lack of evidence to support this use of GnRH-a. We conducted a retrospective study and questionnaire of SLE patients who received CYC with or without GnRH-a to evaluate its efficacy in preserving ovarian function. METHODS: This study was approved by the IRB of the National Institutes of Health (IRB#:001011). Review of medical records resulted in 50 female SLE patients treated with CYC who were less than 40 year old at the time of treatment: CYC only (n=20, group 1), CYC and GnRH-a (n=30, group 2). These patients were age/gender-matched with 50 SLE patients not treated with CYC (group 3). Data about demographics, SLE disease activity, damage accrual, cumulative CYC exposure, and pregnancy outcomes were collected by chart review. Self-reported questionnaires were used to collect data assessing menses cycles, pregnancies and their outcome, or infertility. RESULTS: There was no significant difference in SLE disease activity, baseline demographics, total damage accrual, or other clinical parameters between groups 1 and 2. The mean cumulative CYC dose was 1.2 g (group 1) and 1.5 g (group 2) (P=.16). Number of pregnancies were similar: mean (SD) group 1=2 (1.6); group 2=1.2 (1.4); group 3=1.3 (1.4) (P=.18). There were more miscarriages in group 1 compared to groups 2 and 3 (P=.015). CONCLUSION: Our data suggest use of GnRH-a improves pregnancy outcomes in SLE patients on CYC, but prospective studies are needed to establish its safety and efficacy.

Efficacy of Chinese Herbal Medicines on Pregnancy Outcomes in Patients with Endometriosis in Long-Term Management: A Multicenter Retrospective Cohort Study.

To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.

Peculiarities of the course of genital endometriosis and its recurrence in women of reproductive age

Endometriosis remains one of the most studied pathologies in modern gynecology, as it is accompanied by such complications as constant pelvic pain, menstrual cycle disorders, and infertility. These complications not only prevent the implementation of a woman’s reproductive function, but also worsen the normal life of a woman in general. The early diagnosis and the right choice of treatment is the basis of prevention of disease recurrence. Therefore, most of the efforts of scientists are directed to this.The objective: to reduce the frequency of genital endometriosis recurrence and improve the implementation of reproductive functions based on the improved approaches to its diagnosis and treatment.Materials and methods. The study included two groups of patients. The 1st group included 60 women with a diagnosis of ovarian endometriosis, whose data were analyzed retrospectively based on the results of medical histories. The 2nd group was studied prospectively and included 60 women with a diagnosis of ovarian endometriosis.All patients had general clinical and laboratory examinations, specific laboratory and ultrasound examinations. In patients of the 2nd group tumor markers were additionally determined, in particular CA-125, HE4, CA 19-9, CA 72-4, CA 15-3, REA, and the level of anti-Müllerian hormone, magnetic resonance imaging was performed. Patients of both groups were operated and histological examination of the material obtained during the operation was performed.The difference in the management of the postoperative period in the 2nd group was that, in addition to anti-inflammatory therapy all women received hormonal therapy (gonadotropin-releasing hormone agonist (GnRH agonist) with subsequent use of combined oral contraceptives (COCs) or simultaneous use of GnRH agonist and COCs with subsequent transition in both variants for dienogest for 6 months continuously). Recurrence of the pathology was detected after 3 and 6 months on the basis of a repeated diagnosis of ovarian endometriosis.Results. The obtained data showed that in the postoperative period, 3 months after treatment 5 (8.3 %) women in the 1st group had a recurrence of ovarian endometriosis and 4 (6.7 %) patients – pelvic adhesions. Whereas in the 2nd group, there were no cases of recurrence and adhesions.In 6 months after treatment in the 1st group 11 (18.3 %) patients were diagnosed with ovarian endometriosis recurrence, and 6 (10.0 %) women were diagnosed with pelvic adhesions. In the 2nd group recurrence of ovarian endometriosis was found only in 1 (1.7 %) woman, pelvic adhesions were not detected (p&lt;0.05). During the year after treatment the number of pregnant women among persons who wished to become pregnant and had a history of infertility was statistically higher in the 2nd group compared to the 1st group, in particular, 10 (16.7 %) and 2 (3.3 %) women, respectively (p&lt;0.05).Conclusions. The proposed algorithm for the diagnosis and treatment of genital endometriosis minimizes the risk of its recurrence and improves reproductive function.

Optimization of surgical treatment of uterine myoma in women with obesity and the metabolic syndrome

Objectives: to evaluate the benefits of delayed conservative myomectomy with the aim of reducing body weight and correcting hematological and metabolic parameters against the background of the use of gonadotropin-releasing hormone (GnRH) agonists and a combination of myo-inositol and D-chiro-inositol (Inofolic combi) in obese patients with metabolic syndrome by comparing this technique with immediate surgery.Materials and methods. The study included 72 patients with uterine fibroids and obesity who required conservative myomectomy. Patients were offered to postpone surgical intervention in order to correct body weight, metabolic and hematological indicators. As a preoperative preparation, patients were recommended to use GnRH agonists (goserelin), inositols, and iron preparations for anemia. Patients were divided into 2 groups: the first group (n = 31) followed all these recommendations, the second group (n = 41) refused to follow the recommendations and postponed surgical treatment. Group 1 underwent surgical treatment 3 months after the start of treatment, group 2 – after the initial consultation.Results. Patients of the first group lost an average of 7.3 ± 1.4 kg of body weight during preoperative preparation, their hemoglobin level increased by an average of 21.78%, and the volume of the largest myomatous node decreased by an average of 21.82%. The duration of the operation was significantly shorter in group 1 (75 ± 3.84 min) than in group 2 (118 ± 5.33 min). Laparotomy in the first group was not performed in any patient, in the second group it was performed in 9 patients (21.95%) (p &lt; 0.05). There was a decrease in the severity of postoperative pain in group 1, (3.4 В± 1.25 points on the visual analog scale), which was significantly lower than in group 2 (5.1 В± 3.4 points).Conclusions. Body weight reduction against the background of the use of GnRH agonists (goserelin) and inositols (Inofolic combi) due to the improvement of the technical conditions of the operation, metabolic and hematological indicators allow to reduce the duration of surgical intervention and the frequency of laparotomies in patients with uterine fibroids against the background of obesity and metabolic syndrome.

Mitigating the economic burden of GnRH agonist therapy for progestogen-resistant endometriosis: why not?

Is it possible to reduce the cost of GnRH agonist treatment for endometriosis by using non-standard dosing regimens? An extended-interval dosing regimen of a 3.75 mg depot formulation of triptorelin injected every 6 weeks instead of every 4 weeks reduces the cost by one-third without compromising the effect on pain relief. Cost constitutes a limit to prolonged GnRH agonists use. Alternative modalities to reduce the economic burden of GnRH agonist treatment have been anecdotally attempted. A systematic review was conducted to evaluate and compare the effect of three alternative modalities for GnRH use in women with endometriosis, i.e. intermittent oestrogen deprivation therapy, reduced drug dosage, and extended-interval dosing regimens of depot formulations. A PubMed and Embase search was initially conducted in October 2022 and updated in January 2023 using the following search strings: (endometriosis OR adenomyosis) AND (GnRH-agonists OR gonadotropin-releasing hormone agonists OR triptorelin OR leuprorelin OR goserelin OR buserelin OR nafarelin). Full-length articles published in English in peer-reviewed journals since 1 January 1980, and reporting original data on GnRH agonist treatment of pain symptoms associated with endometriosis were selected. Information was extracted on study design, GnRH-agonist used, dosage, total duration of therapy, side effects, treatment adherence, and pelvic pain relief. Reviews, commentaries, conference proceedings, case reports, and letters to the editor were excluded. Of the 1664 records screened, 14 studies regarding clinical outcomes associated with the 3 considered alternative modalities for GnRH agonist use were eventually included (intermittent oestrogen deprivation therapy, n = 2; low-dose or 'draw-back' therapy, n = 8; extended-interval dosing regimen, n = 4). Six studies were randomized controlled trials (RCTs) (double blind, n = 2) and eight adopted a prospective cohort design (non-comparative, n = 6; comparative, n = 2). A total of 776 women with endometriosis were recruited in the above studies (intermittent oestrogen deprivation therapy, n = 77; low-dose or 'draw-back' therapy, n = 528; extended-interval dosing regimen, n = 171). Robust data demonstrating cost saving without detrimental clinical consequences were available for the extended-interval dosing regimen only. In particular, the 3.75 mg triptorelin depot preparation inhibits ovarian function for a longer period compared with the 3.75 mg leuprorelin depot preparation, allowing injections every 6 instead of 4 weeks. Based on the cost indicated by the Italian Medicine Agency for the 3.75 mg triptorelin depot preparation, this would translate in a yearly saving of €744.60 (€2230.15-€1485.55; -33.4%). The quality of the evidence reported in the selected articles was not formally evaluated and a quantitative synthesis could not be performed. Some studies were old and the tested therapeutic approaches were apparently obsolete. Only cost containment associated with GnRH analogue use, and not cost-effectiveness, has been addressed. Consuming less resources without negatively impacting on health outcomes carries ethical and practical implications for individuals and the community, as this approach may result in overall increased healthcare access. This study was supported by the Italian Ministry of Health (Ricerca Corrente 2023, IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano). E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest. N/A.

Risk of ovarian hyperstimulation syndrome in women with malignancies undergoing treatment with long-acting gonadotropin-releasing hormone agonist after controlled ovarian hyperstimulation for fertility preservation: a systematic review.

Fertility preservation is an important quality of life issue for women of reproductive age undergoing gonadotoxic treatment. The possibility of administering an adjuvant long-acting gonadotropin-releasing hormone agonist (GnRHa) with the aim of reducing the number of follicles susceptible to the effects of chemotherapy and thus reducing the risk of ovarian damage is considered in some international society guidelines, particularly in certain cancers such as breast cancer. Nowadays, the administration of long-acting GnRHa after controlled ovarian hyperstimulation (COH) for fertility preservation by cryopreservation of oocytes or embryos is increasingly used. However, cases of ovarian hyperstimulation syndrome (OHSS) have been reported following the use of long-acting GnRHa after COH for fertility preservation, indicating that the potential adverse effects of this treatment need to be further investigated. The aim of this systematic review was to comprehensively characterize patients who developed OHSS after treatment with long-acting GnRHa following COH for fertility preservation. A comprehensive search of major electronic databases through January 2023 was performed. Studies reporting the use of long-acting GnRHa after COH for fertility preservation and the development of OHSS were included. Risk of bias was assessed using a modified version of the Newcastle-Ottawa scale. Results were synthesized qualitatively. Three studies with five patients met the eligibility criteria. The majority of patients were diagnosed with breast cancer and all patients underwent COH for oocyte cryopreservation. OHSS occurred in all patients after administration of long-acting GnRHa. The interval between ovulation induction and administration of long-acting GnRHa thereafter ranged from 3 to 5 days. All patients were treated conservatively and recovered without complications. Current evidence suggests that the use of long-acting GnRHa after COH for fertility preservation may be associated with OHSS. Healthcare providers should thoroughly discuss the benefits and risks of this intervention with their patients before making a decision. Further studies are needed to fully elucidate the causal relationship between long-acting GnRHa and OHSS in this population.