Fertility preservation in patients undergoing gonadotoxic treatments: a Canadian Fertility and Andrology Society clinical practice guideline.

The management of young patients with cancer presents several unique challenges. In general, these patients are ill prepared for the diagnosis and the impact on their fertility. With the improved survival for all tumour types and stages, the need for adequate fertility counselling and a multidisciplinary approach in the reproductive care of these patients is paramount. Recent advances in cryopreservation techniques allow for the banking of spermatozoa, oocytes, embryos and ovarian tissue without compromising survival. This Canadian Fertility and Andrology Society (CFAS) guideline outlines the current understanding of social and medical issues associated with oncofertility, and the medical and surgical technologies available to optimize future fertility.

The effect of gonadotrophin-releasing hormone agonist versus human chorionic gonadotrophin trigger on pregnancy and neonatal outcomes in Letrozole-HMG IUI cycles.

BACKGROUND: GnRHa and hCG are both used for oocyte maturation and ovulation triggering. However, GnRHa have a shorter half-life than hCG, which leads to luteal phase deficiency. Letrozole (LE) has been found to improve the luteal function. Thus, the choice of triggering strategy can be different in intrauterine insemination (IUI) cycles using LE and human menopausal gonadotropin (HMG). The aim of this study was to compare the pregnancy and neonatal outcomes of patients triggered with GnRHa versus hCG versus dual trigger in LE-IUI cycles. METHODS: This retrospective cohort study included 6,075 LE-HMG IUI cycles between January 2010 and May 2021 at a tertiary-care academic medical center in China. All cycles were divided into three groups according to different trigger strategies as hCG trigger group, GnRHa trigger group and dual trigger group. The primary outcome was clinical pregnancy rate. Logistic regression analysis was performed to explore other risk factors for clinical pregnancy rate. RESULTS: No significant difference was observed in clinical pregnancy rate between hCG, GnRHa and dual trigger cycles in LE-HMG IUI cycles (P = 0.964). The miscarriage rate was significantly lower in the GnRHa trigger group, and higher in the dual trigger group, compared with the hCG group (P = 0.045). Logistic analysis confirmed that triggering strategy was associated with miscarriage (aOR:0.427, 95%CI: 0.183-0.996, P = 0.049; aOR:0.298, 95%CI: 0.128-0.693, P = 0.005). No significant differences were observed regarding neonatal outcomes between the three groups. CONCLUSIONS: Our findings suggested that both GnRHa and dual trigger can be used to trigger ovulation in LE-HMG IUI cycles, but dual trigger must be used with caution.

Individualized conservative therapeutic strategies for adenomyosis with the aim of preserving fertility.

Adenomyosis is a diffuse or localized organic disease caused by benign invasion of endometrial glands and stroma into the myometrium. It is a common disease that seriously affects reproductive health of women in childbearing age. Due to the unknown etiology and pathophysiological mechanism, and the lack of unified diagnostic criteria and effective treatment methods, total or subtotal hysterectomy has become a radical treatment for adenomyosis, which will lead to the complete loss of fertility. With the continuous exploration of the treatment to adenomyotic patients who have infertility or fertility intentions, new drugs, surgical methods and treating concepts appears. Adopt individualized conservative therapeutic strategies for patients with different conditions, preserve the uterus as much as possible and protect the patient's fertility, which will play an important role on the follow-up assisted reproductive treatment and long-term management of adenomyosis.

Review of Implant Gonadotrophin-Releasing Hormone Agonist Use: Experience in a Single Academic Center.

BACKGROUND: Gonadotrophin-releasing hormone agonists (GnRHas) are used for puberty suppression in central precocious puberty (CPP) and gender dysphoria (GD). Guidelines on biochemical monitoring are not defined. OBJECTIVES: The aim of this study was to evaluate the utility of biochemical monitoring of GnRHa therapy in patients with CPP or GD. METHODS: This is a retrospective chart review of patients 18 years or younger who received GnRHa therapy from January 1, 2018, to March 20, 2021. RESULTS: A total of 103 patients were evaluated, 43 with CPP and 60 with GD. Using thresholds of basal luteinizing hormone (LH) <2 IU/L and stimulated LH <4 IU/L, biochemical pubertal suppression occurred in all but 2 patients. Basal LH frequently remained above prepubertal range. CONCLUSIONS: Laboratory assessment for puberty suppression on GnRHa therapy may be unnecessary in CPP and GD patients monitored with physical exams.

Agonist long protocol improves outcomes of vitrified-warmed embryo transfer in repeatedly thin endometrium.

RESEARCH QUESTION: Does follicular stimulation using human menopausal gonadotrophin (HMG) after pituitary down-regulation by a GnRH agonist improve endometrial thickness (EMT) and clinical outcomes of frozen-thawed embryo transfer (FET; using vitrified-warmed embryos) in women with thin endometrium after intensified oestrogen administration (IOA)? DESIGN: This was a retrospective study. A total of 627 patients attempted 683 FET cycles with at least one previous history of thin endometrium. None of the cycles reached over 7 mm EMT after using oral and vaginal oestradiol for more than 21 days (IOA protocol). A total of 129 cycles proceeded with FET, 305 cycles were cancelled, and 249 cycles involved administration of HMG following GnRH agonist pituitary down-regulation (GnRH agonist + HMG protocol) for further endometrial preparation. RESULTS: EMT became significantly greater (7.18 ± 1.14 mm versus 6.13 ± 0.63 mm, P < 0.001) using GnRH agonist + HMG compared with previous IOA cycles, but this was not related to serum oestrogen concentrations. A total of 213 cycles after the GnRH agonist + HMG protocol proceeded with FET, showing a significantly increased clinical pregnancy rate, implantation rate and live birth rate compared with those after IOA. CONCLUSIONS: The GnRH agonist + HMG protocol for endometrial preparation in FET cycles improves EMT in women with a thin endometrium after IOA and showed significantly better clinical outcomes than IOA. The authors suggest that the GnRH agonist + HMG protocol should be used for EMT that is less than 7 mm after there has been no optimal response to IOA.

Efficacy of long-term pituitary down-regulation pretreatment prior to in vitro fertilization in infertile patients with endometriosis: A meta-analysis.

Controversial conclusions have been made in previous studies regarding the influence of ultra-long gonadotropin-releasing hormone agonist (GnRH-a) in the reproductive outcomes of women with endometriosis who are undergoing in vitro fertilization/ intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). An electronic search was conducted through PubMed, Embase, Cochrane Library, Web of Science, Elsevier ScienceDirect and Medline from inception until 10 September 2022. Only randomized studies were included. After the selection process, seven articles were eventually included in the meta-analysis. The pooling of the results showed the adverse effect of ultra-long protocol in terms of live birth rate (risk ratio (RR) = 0.53, 95% confidence intervals (CI): 0.31-0.9, P=0.02) and fertilization rate (RR = 1.18, 95% CI: 1.02-1.36, P=0.02). There was no statistical significance between the ultra-long protocol and long protocol of the rest outcome Indicators. The findings of this meta-analysis suggest that ultra-long GnRH-a does not appear to improve the results of IVF/ICSI treatment outcomes in patients with endometriosis.

Effect of GnRH-a pretreatment before frozen-thawed embryo transfer on pregnancy outcome of adenomyosis-associated infertile patients with 56 cm3 ≤ uterine volume ≤100 cm3.

Background: Whether gonadotrophin-releasing hormone agonist (GnRH-a) pretreatment before transferring frozen-thawed embryos (FETs) could improve the clinical outcome of adenomyosis-associated infertile patients with 56 cm3 ≤ uterine volume ≤100 cm3 is unclear. Methods: Adenomyosis patients who underwent in vitro fertilization and frozen embryo transfers from January 2009 to December 2019 with 56 cm3 ≤ uterine volume ≤100 cm3 were included in this retrospective cohort study. The subjects were divided into two groups (GnRH-a treatment group vs. GnRH-a-free group). The effect of GnRH-a treatment before FET on pregnancy outcomes was explored by univariate and multivariate analysis. In the GnRH-a treatment group, uterine volume before and after GnRH-a pretreatment was also compared by t-tests. Results: A total of 186 patients undergoing 263 cryopreserved embryo transfer cycles were included. There was no significant difference in terms of the clinical pregnancy rate between patients in the GnRH-a treatment group (24/45, 53.3%) and the GnRH-a-free group (86/218, 39.4%) (P=0.098). The miscarriage rate in the GnRH-a treatment group (3/24, 12.5%) was significantly lower than that in the GnRH-a-free group (32/86, 37.2%) (P=0.044). The live birth rate in the GnRH-a treatment group (21/45, 46.7%) was significantly higher than that in the GnRH-a-free group (54/218, 24.8%) (P=0.009). However, the uterine volume did not change significantly before (82.0±13.4 cm3) or after GnRH-a treatment (79.3±14.0 cm3), with a P=0.123. Conclusions: GnRH-a pretreatment before FET reduced the miscarriage rate and improved the live birth rate among infertile women with adenomyosis whose uterine volume was 56-100 cm3.

HCG Trigger of GnRH Agonist-Induced Functional Ovarian Cysts Does Not Decrease Clinical Pregnancy Rate in GnRHa Pretreated Frozen Cycles: Evidence From a Retrospective Cohort Study.

Background: GnRH agonist (GnRHa) pretreatment before the frozen-thawed embryo transfer (FET) was increasingly utilized. However, the incidence of GnRHa-induced functional ovarian cysts (FC) was inevitable. The feasibility and efficacy of HCG triggering GnRHa-induced FC are unknown. Objective: The aim of the study was to investigate the effect of HCG triggering GnRHa-induced FC on FET outcomes. Methods: A total of 657 HRT-FET cycles with GnRHa pretreatment were retrospectively analyzed. Patients were divided into the FC group and the no functional cysts (NC) group according to whether the patient developed FC (follicular diameter of ≥7 mm and E2 of ≥100 pg/ml). Risk factors associated with the incidence of GnRHa-induced FC were determined by multivariate regression analysis. Pregnancy outcomes were compared between the FC group and the NC group. Propensity score matching (PSM) was performed to reduce the impact of confounding factors. Three multivariate regression models were performed to assess the association between HCG triggering GnRHa-induced FC and clinical pregnancy. Interactive analysis and subgroup analysis were also analyzed. Results: The incidence rate of GnRHa-induced FC was 9.74%. Older age (aOR 1.10, 95% CI 1.05-1.15, p-value < 0.001) and lower BMI (aOR 0.81, 95% CI 0.71-0.93, p-value=0.002) are risk factors for GnRHa-induced FC. The implantation rate, clinical pregnancy rate (CPR), and miscarriage rate were not significantly different between the FC group and the NC group before or after PSM (p-value > 0.05). Multivariate logistic models showed that HCG triggering GnRHa-induced FC does not decrease CPR in the general population (p-value > 0.05). The effect of HCG triggering GnRHa-induced FC on clinical pregnancy is interactive with age (p-value for interaction: 0.003); HCG trigger is associated with significantly higher CPR than HRT-FET cycles without FC in patients ≥35 years (aOR 4.40, 95% CI 1.57-12.3, p-value = 0.005). Conclusions: HCG triggering GnRHa-induced FC does not decrease the chance of clinical pregnancy in HRT-FET cycles pretreated with GnRHa.

Effectiveness of gonadotrophin-releasing hormone agonist therapy to improve the outcomes of intrauterine insemination in patients suffering from stage I-II endometriosis.

OBJECTIVE: To explore the role of postoperative gonadotrophin releasing hormone agonist (GnRH-a) therapy before treatment with intrauterine insemination (IUI) for infertile females with stage I-II endometriosis. MATERIAL AND METHODS: Ninety-seven patients diagnosed with stage I-II endometriosis before IUI were enrolled in this study. The clinical pregnancy rate, cumulative pregnancy rate, live birth rate and newborn conditions were compared between the two groups with and without GnRH-a therapy. RESULTS: The clinical pregnancy rate of IUI in the GnRH-a group was higher than that in the control group (15.29% vs. 11.82%, p = .035). By logistic regression analysis, patients treated with GnRH-a had a higher clinical pregnancy rate than those without (adjusted odds ratio (AOR) 23.190, 95% confidence interval (CI) 1.238-434.312). The live birth rate per IUI cycle in the GnRH-a group was also higher than in the controls (12.94% vs. 10%). However, the difference was not statistically significant (p = .311, AOR 4.844, 95% CI 0.229-102.320). The patients with GnRH-a therapy had a similar incidence of multiple pregnancy rate (0% vs. 0%), miscarriage rate (2.35% vs. 0.91%) and ectopic pregnancy rate (0% vs. 0.91%) as compared to the control group. The cumulative pregnancy rates were all higher in patients administered with GnRH-a than those without GnRH-a treatment in different cycles (one cycle: 17.07% vs 12.50%; two cycles: 29.27% vs 19.64%; three cycles: 31.71% vs 23.21%; ≥four cycles: 31.71% vs 23.21%), but the difference was not statistically significant. Notably, there was no more pregnancy after the third IUI cycle. The gestation weeks of delivery in the two groups were 39.09 ± 1.04 and 38.60 ± 1.17, respectively (p = .323). Nor was there difference in birth weight between the two groups (3236 ± 537 g vs 3435 ± 418 g, p = .360). CONCLUSIONS: The administration of GnRH-a in patients with stage I-II endometriosis could be beneficial to the outcomes of IUI. It is recommended that IUI should be discontinued after three failed attempts. KEY MESSAGESEndometriosis is a common cause of infertility, but the exact mechanism remains unclear.The administration of GnRH-a before IUI treatment is beneficial for patients suffering from stage I-II endometriosis.After three failed attempts, IUI should be stopped in patients with stage I-II endometriosis.

Cardiovascular toxicities of androgen deprivation therapy in Asian men with localized prostate cancer after curative radiotherapy: a registry-based observational study.

BACKGROUND: Androgen deprivation therapy (ADT) and radiotherapy (RT) are the mainstay treatment for localized prostate cancer and recurrence after surgery. Cardiovascular (CV) toxicity of ADT is increasingly recognized, and the risk relates to pre-existing risk factors and ADT modalities. Despite ethnic differences in the prevalence of CV risk factors and variations of CV mortality, data on ADT-related cardiotoxicities in the Asian population remain inconclusive. Our registry-based study investigated ADT-related major adverse cardiovascular events (MACE) after primary or salvage RT. METHODS: Our study combined two prospectively established registry databases from National Cancer Center Singapore and National Heart Center Singapore. The primary endpoint is time to first MACE after treatment. MACE is defined as myocardial infarction, stroke, unstable angina, or cardiovascular death. Two types of propensity score adjustments, including ADT propensity score as a covariate in the multivariable regression model and propensity score weighting, were applied to balance baseline features and CV risk factors between RT alone and RT + ADT groups. RESULTS: From 2000 to 2019, 1940 patients received either RT alone (n = 494) or RT + ADT (n = 1446) were included. After a median follow-up of 10 years (RT) and 7.2 years (RT+ ADT), the cumulative incidence of MACE at 1, 3 and 9 years was 1.2, 5 and 16.2% in RT group, and 1.1, 5.2 and 17.6% in RT + ADT group, respectively. There were no differences in the incidence of MACE between 2 groups (HR 1.01, 95% CI 0.78-1.30, p = 0.969). Pre-treatment CV risk factors were common (80%), and CV disease (15.9%) was the second leading cause of death after prostate cancer (21.1%). On univariate analysis, older age, Indians and Malays, pre-existing CV risk factors, and history of MACE were associated with higher MACE risk. After propensity score adjustments, there remained no significant differences in MACE risk between RT + ADT and RT group on multivariable analysis. CONCLUSIONS: In our registry-based study, ADT is not associated with increased risk of major cardiovascular events among Southeast Asian men with prostate cancer after curative radiotherapy.

Comparison of clinical outcomes between the depot gonadotrophin-releasing hormone agonist protocol and gonadotrophin-releasing hormone antagonist protocol in normal ovarian responders.

BACKGROUND: The gonadotrophin-releasing hormone (GnRH) antagonist protocol has some advantages, such as a simple method, short medication duration, and low incidence of ovarian hyperstimulation syndrome, but whether the GnRH antagonist protocol is suitable for normal ovarian responders has been controversial. We compared the clinical outcomes of fresh and frozen-thawed transfer cycles between the depot GnRH agonist protocol and GnRH antagonist protocol in normal ovarian responders. METHODS: Data of normal ovarian responders who underwent in vitro fertilization-embryo transfer (IVF-ET) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) between January 2017 and December 2018 in our hospital were retrospectively analysed. In this study, there were 1119 fresh transfer cycles, including 502 GnRH antagonist cycles (GnRH antagonist group) and 617 depot GnRH agonist cycles (depot GnRH agonist group), as well as 468 frozen-thawed transfer cycles, includng 191 GnRH antagonist cycles (GnRH antagonist group) and 277 depot GnRH agonist cycles (depot GnRH agonist group). The clinical outcomes were compared between the GnRH antagonist group and the depot GnRH agonist group. RESULTS: With the fresh transfer cycles, there were no statistically significant differences in the anti-Mullerian hormone level, number of transferred embryos or high-quality embryo rate between the two groups. The total dosage of gonadotropin (Gn), duration of Gn stimulation, number of oocytes retrieved, clinical pregnancy rate and incidences of moderate and severe ovarian hyperstimulation syndrome (OHSS) were significantly lower but the abortion rate was significantly higher in the GnRH antagonist group than in the depot GnRH agonist group (all P < 0.05). With the frozen-thawed transfer cycles, there were no statistically significant differences in the number of transferred embryos, clinical pregnancy rate or abortion rate between the two groups (all P > 0.05). CONCLUSIONS: With the fresh transfer cycles, the GnRH antagonist protocol had a lower clinical pregnancy rate and lower incidences of moderate and severe OHSS than the depot GnRH agonist protocol, but with the frozen-thawed transfer cycles, both protocols had similar clinical pregnancy rates. These results remain to be further confirmed through large-sample, prospective, randomized and controlled studies.

Low body mass index is associated with ectopic pregnancy following assisted reproductive techniques: a retrospective study.

OBJECTIVE: To investigate the association between body mass index (BMI) and ectopic pregnancy (EP) following embryo transfer (ET). DESIGN: Retrospective cohort study. SETTING: University-affiliated hospital. POPULATION: A total of 16 378 pregnancies derived from either fresh ET or frozen-thawed ET between January 2008 and December 2017. METHODS: We used the generalised estimating equation (GEE) to analyse the association between BMI categories and EP, as one woman may contribute to more than one pregnancy. Generalised additive models were also used to demonstrate the non-linear association. Models were adjusted for age, parity, gravidity, previous history of ectopic pregnancy, duration of infertility, polycystic ovary syndrome, endometriosis, diagnosis of tubal problems, ovarian reserve markers, ovarian stimulation parameters, insemination protocol, endometrial thickness and embryo transfer policies. MAIN OUTCOME MEASURES: Ectopic pregnancy. RESULTS: According to the WHO criteria, the number of cycles with low (<18.5 kg/m2 ), normal (18.5-24.9 kg/m2 ) and high (≥25 kg/m2 ) BMI were 2155, 13 447 and 776, respectively. In comparison with the normal BMI group, the rate of EP was significantly increased in the low BMI group (2.92% versus 2.02%, relative risk 1.45, 95% CI 1.11-1.90), but not in the high BMI group (2.84%, relative risk 1.41, 95% CI 0.92-2.20). Adjusted for confounding factors, the odds ratio for EP comparing low BMI versus normal BMI was 1.61 (95% CI 1.19-2.16) and that comparing high BMI versus normal BMI was 1.12 (95% CI 0.72-1.76). CONCLUSIONS: Low BMI is associated with an increased risk of EP. TWEETABLE ABSTRACT: The ectopic pregnancy rate after embryo transfer for lean women is higher than that for women of normal weight.

Comparison of clinical efficacy of long- versus short-acting gonadotrophin-releasing hormone agonists for pituitary down regulation in In vitro fertilisation cycles.

BACKGROUND: Gonadotrophin-Releasing Hormone agonist (GnRHa) - long and short acting - is used for pituitary down regulation prior to ovarian stimulation in in vitro fertilisation (IVF) treatment. However, there are controversies in the literature as to their effectiveness, dose of gonadotrophin needed subsequently for ovarian stimulation and the clinical outcome. OBJECTIVE: The objective of the study was to compare the efficacy of single-dose long-acting GnRHa - goserelin - and daily dose short-acting GnRHa - buserelin - for pituitary down regulation and their clinical outcome in IVF treatment. MATERIALS AND METHODS: : This prospective comparative study was undertaken at the IVF centre in National Hospital Abuja, a public tertiary hospital in Nigeria. A total of 114 IVF patients were consecutively allocated into either long-acting GnRHa - goserelin - 3.6 mg single dose (Group A) or short-acting GnRHa - buserelin - 0.5 mg daily (Group B) both starting on day 21 of the cycle preceding the IVF treatment. The effects on pituitary down regulation and treatment outcomes were compared. RESULTS: Time taken (days) to achieve down regulation (22.6 ± 4.3 vs. 26.1 ± 8.0; P = 0.084) and the mean number of human menopausal gonadotrophin (HMG) doses used (57.7 ± 13.7 vs. 54.2 ± 16.7; P = 0.222) were similar in the two groups. Although the number of oocytes retrieved (9.9 ± 6.7 vs. 7.2 ± 5.0; P = 0.02) and fertilised (6.2 ± 4.4 vs. 4.6 ± 3.5; P = 0.04) were significantly higher in Group A, there was no statistically significant difference in the number of embryos (4.4 ± 2.6 vs. 4.0 ± 3.0; P = 0.850) and clinical pregnancy rate at 6 weeks (49.2% vs. 43.6%; odds ratio 1.249; confidence interval = 0.579-2.612; P = 0.578) in both the groups. While group B had a significantly higher number of hospital visits (P = 0.0001) as well as a higher number of injections (P = 0.0001), the mean cost of GnRHa and gonadotrophin used was significantly higher in Group A (P = 0.043). CONCLUSION: Single-dose long-acting GnRHa is as effective as daily dose short-acting GnRHa for pituitary desensitisation prior to controlled ovarian stimulation in IVF cycles.

Effect of Gonadotrophin-Releasing Hormone Agonist Addition for Luteal Support on Pregnancy Outcome in vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Meta-Analysis Based on Randomized Controlled Trials.

PURPOSE: The meta-analysis aimed to evaluate the effect of gonadotrophin-releasing hormone agonist (GnRH-a) addition for luteal support on pregnancy outcome in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. METHODS: Meta-analysis. RESULTS: A total of 3,584 cycles were identified from 13 randomized controlled trials. The cumulative analysis showed that GnRH-a addition for luteal supports significantly improved live birth rate (relative risk [RR] = 1.52; 95% CI 1.20-1.94; p = 0.0006), the clinical pregnancy rate (RR 1.21; 95% CI 1.11-1.33; p < 0.0001), ongoing pregnancy rate (RR 1.18; 95% CI 1.06-1.32; p = 0.004), pregnancy rate (RR 1.36; 95% CI 1.01-1.82; p = 0.04), implantation rate (RR 1.44; 95% CI 1.17-1.77; p = 0.0007), and multiple pregnancy rate (RR 1.40; 95% CI 1.04-1.88; p = 0.03) in comparison with control, but not for the incidence of ovarian hyperstimulation syndrome (RR 0.96; 95% CI 0.32-2.89; p = 0.94). We also found that GnRH-a addition for luteal support had a tendency to decrease the abortion rate (RR 0.72; 95% CI 0.56-0.93; p = 0.01). CONCLUSIONS: Overall, the current meta-analysis showed a substantial efficacy of GnRH-a addition for luteal support on pregnancy outcomes in women undergoing IVF/ICSI and support the use of GnRH-a in luteal phase to improve the success of IVF/ICSI.

Radiotherapy Plus GnRH Analogue Versus High Dose Bicalutamide: A Case Control Study.

BACKGROUND/AIM: Radiotherapy (RT) with adjuvant hormone therapy (HT) improves prognosis in prostate cancer (PC) patients. Gonadotrophin-releasing hormone agonist (GnRHa) with luteinizing hormone-releasing hormone (LH-RH) analogues is the standard HT. High-dose antiandrogen therapy also improves survival in patients with locally advanced PC. The aim of this study was to compare the results of patients treated with RT plus GnRHa and patients treated with RT plus bicalutamide. PATIENTS AND METHODS: Our institutional PC database was used to identify patients treated with definitive or postoperative RT +/- HT which were included in this study. RESULTS: Three hundred and eighteen patients were retrospectively reviewed (median follow-up=56 months). Five-year biochemical relapse-free survival was 85.5% and 88.3% in patients treated with GnRHa and bicalutamide, respectively (p=0.712). CONCLUSION: Bicalutamide may be offered as an adjuvant treatment to RT in patients who refuse GnRHa because of related side effects. Furthermore, our study justifies randomized trials comparing RT plus GnRHa and RT plus bicalutamide.

Repeated GnRH agonist doses for luteal support: a proof of concept.

RESEARCH QUESTION: What are the safety and feasibility of repeated subcutaneous doses of gonadotrophin-releasing hormone (GnRH) agonist for luteal support in IVF cycles triggered by a GnRH agonist? DESIGN: In this prospective trial, patients exhibiting oestradiol concentrations of over 2500 pg/ml after use of a GnRH agonist for triggering ovulation were initially randomized to GnRH agonist luteal support (0.1 mg subcutaneously every other day, starting on day 3 after embryo transfer) or to a control group supported by 80 µg of recombinant human chorionic gonadotrophin (HCG) on day 3 after embryo transfer. All patients underwent a day 5 blastocyst transfer. Randomization to the HCG luteal support was stopped owing to two cases of ovarian hyperstimulation syndrome (OHSS) and the study was continued solely with GnRH agonist luteal support. RESULTS: The study included 39 women in the repeated GnRH agonist luteal support group and seven in the HCG micro dose group. There were no cases of OHSS among patients supported by a GnRH agonist, and no other adverse events were recorded. There were no cases of bleeding before the pregnancy test, and hence no cases of an insufficient luteal phase. A clinical pregnancy rate of 43.6% was achieved with GnRH agonist luteal support. Hormone dynamics during the stimulation cycle reflected rising LH and progesterone concentrations after the introduction of GnRH agonist support. CONCLUSIONS: Repeated doses of GnRH agonist every other day as a method of luteal support provided safe and effective luteal support for women who underwent GnRH agonist triggering in a GnRH antagonist IVF cycle.

Transient Arterial Hypertension Induced by Gonadotropin-Releasing Hormone Agonist Treatment for Central Precocious Puberty.

Background: Gonadotropin-releasing hormone agonists (GnRHa) are a safe and effective treatment for precocious puberty. Triptorelin is one of the long lasting GnRHa, which reversibly suppresses the pituitary-gonadal axis. Triptorelin-induced hypertension (HTN) has rarely been reported in the literature. Clinical Case/Methods: We report a 10-year-old girl with central precocious puberty who, during treatment with triptorelin, developed an asymptomatic stage II HTN. Initial workup showed no renal, thyroid, or electrolytes abnormalities. The renal ultrasound showed no parenchymal disease and no increased renal resistance index suggestive of a renal artery stenosis. Echocardiography and ocular fundoscopy were normal. HTN (stage II) was confirmed with ambulatory blood pressure monitoring (ABPM). After extensive literature review, we found 3 other cases of HTN secondary to GnRHa, improving with endocrine treatment cessation. Therefore, antihypertensive treatment was not started immediately in our patient. Indeed, after completion of her treatment with triptorelin, we observed a complete normalization of her blood pressure (confirmed with ABPM) without any medication. Conclusion: Concomitantly to GnRHa treatment, our patient developed HTN, which completely subsided after stopping triptorelin. The complete normalization of her blood pressure, together with a negative workup for HTN strongly speaks for a causal effect of her endocrine treatment. In this setting, estrogen depletion might play a role, although this remains debated.

Biological differences between focal and diffuse adenomyosis and response to hormonal treatment.

RESEARCH QUESTION: Is there any difference in ovarian steroid receptor expression and pattern of fibrosis in focal and diffuse adenomyosis and response to hormonal treatment? DESIGN: Prospective controlled study where biopsy samples were prospectively collected after surgery from 30 women with focal adenomyosis, 21 women with diffuse adenomyosis and 20 women with uterine myoma. Some of these women underwent 3-6 months of treatment with gonadotrophin-releasing hormone agonist (GnRHa) before surgery. Tissue expression of oestrogen receptor (ER) and progesterone receptor (PR) was analysed by immunohistochemistry. Distribution of tissue fibrosis was examined by Masson's trichrome staining with computer-based image analysis of fibrosis in tissues derived from women with and without adenomyosis. RESULTS: There was no difference in ER/PR expression in gland cells/stromal cells of adenomyotic lesions on the ipsilateral side of focal adenomyosis and the anterior/posterior walls of diffuse adenomyosis. Compared to myoma tissues, a relatively decreased expression of ovarian steroid receptors was observed in both focal and diffuse adenomyosis. Image analysis of tissue fibrosis indicated more fibrosis in both focal and diffuse adenomyosis compared to fibrosis in the myometrium derived from women with uterine myoma. The pattern of fibrosis was no different in tissues derived from GnRHa-treated and -untreated women with focal and diffuse adenomyosis. CONCLUSIONS: No difference was found in the expression of ER/PR and entity of fibrosis between women with focal and diffuse adenomyosis regardless of GnRHa treatment. A lower expression of ER/PR compared to myoma tissue potentially clarifies the biological rationale of non-response to hormonal therapies for adenomyosis.

Neuroticism modulates mood responses to pharmacological sex hormone manipulation in healthy women.

BACKGROUND: Women show increased risk of depressive symptoms during hormonal transition phases. The risk mechanisms may include changes in mood in response to fluctuating ovarian hormones moderated by predisposing risk factors for mood disorders, such as personality trait Neuroticism. METHODS: A pooled sample of 92 mentally healthy women (28.3 ± 7.1, mean age ± SD) from two independent cohorts run in our lab, using gonadotropin-releasing hormone agonist (GnRHa) experimentally (n = 28) compared to placebo (n = 27) and as part in vitro fertilization (n = 37), were extracted from the Center for Integrated Molecular Brain Imaging database. All women filled in questionnaires of trait Neuroticism from the NEO personality Inventory-Revised (NEO PI-R) at baseline and self-reported levels of mood disturbances with the Profile of Mood States (POMS) daily during 14 days of GnRHa intervention or placebo. Effects of intervention by trait Neuroticism on serial daily reports of mood disturbances were examined using mixed model analyses. RESULTS: Personality trait Neuroticism significantly modulated daily mood responses to GnRHa, but not placebo. Women with high and low scores on trait Neuroticism at baseline experienced more pronounced changes in mood when exposed to GnRHa, whereas women with medium trait Neuroticism scores remained relatively stable. CONCLUSIONS: The susceptibility to hormone-triggered mood changes appears to depend upon women's general tendency to experience distress and destabilization of mood, as captured by personality trait Neuroticism. This could aid clinicians evaluate hormone-related vulnerability for mood disorders in women and may guide targeted prevention in reproductive care.

Bacterial contamination hypothesis: a new concept in endometriosis.

BACKGROUND: Endometriosis is a multifactorial disease that mainly affects women of reproductive age. The exact pathogenesis of this disease is still debatable. The role of bacterial endotoxin (lipopolysaccharide, LPS) and Toll-like receptor 4 (TLR4) in endometriosis were investigated and the possible source of endotoxin in the pelvic environment was examined. METHODS: The limulus amoebocyte lysate test was used to measure the endotoxin levels in the menstrual fluid and peritoneal fluid and their potential role in the growth of endometriosis was investigated. Menstrual blood and endometrial samples were cultured for the presence of microbes. The effect of gonadotrophin-releasing hormone agonist (GnRHa) treatment on intrauterine microbial colonization (IUMC) and the occurrence of endometritis was investigated. MAIN FINDINGS RESULTS: Lipopolysaccharide regulates the pro-inflammatory response in the pelvis and growth of endometriosis via the LPS/TLR4 cascade. The menstrual blood was highly contaminated with Escherichea coli and the endometrial samples were colonized with other microbes. A cross-talk between inflammation and ovarian steroids or the stress reaction also was observed in the pelvis. Treatment with GnRHa further worsens intrauterine microbial colonization, with the consequent occurrence of endometritis in women with endometriosis. CONCLUSION: For the first time, a new concept called the "bacterial contamination hypothesis" is proposed in endometriosis. This study's findings of IUMC in women with endometriosis could hold new therapeutic potential in addition to the conventional estrogen-suppressing agent.