Injection Of Gonadotropin-releasing Hormone Agonist Research Articles

Serum Insulin-like Factor 3, Testosterone, and LH in Experimental and Therapeutic Testicular Suppression.

Serum insulin-like factor 3 (INSL3) is a Leydig cell biomarker, but little is known about the circulating concentration of INSL3 during hypothalamus-pituitary-testicular suppression. To study the concomitant changes in serum concentrations of INSL3, testosterone, and LH during experimental and therapeutic testicular suppression. We included serum samples from 3 different cohorts comprising subjects before and after testicular suppression: (1) 6 healthy young men who were treated with androgens (Sustanon, Aspen Pharma, Dublin, Ireland); 2) 10 transgender girls (male sex assigned at birth) who were treated with 3-monthly GnRH agonist injections (Leuprorelinacetat, Abacus Medicine, Copenhagen, Denmark); and (3) 55 patients with prostate cancer who were randomized to surgical castration (bilateral subcapsular orchiectomy) or treatment with GnRH agonist (Triptorelin, Ipsen Pharma, Kista, Sweden). Serum INSL3 and testosterone concentrations were quantified in stored serum samples using validated liquid chromatography-tandem mass spectrometry methodologies, and LH was measured by an ultrasensitive immunoassay. The circulating concentrations of INSL3, testosterone, and LH decreased during experimental testicular suppression in healthy young men by Sustanon injections and subsequently returned to baseline levels after release of suppression. All 3 hormones decreased during therapeutic hormonal hypothalamus-pituitary-testicular suppression in transgender girls and in patients with prostate cancer. INSL3 resembles testosterone as a sensitive marker of testicular suppression and reflects Leydig cell function, also during exposure to exogenous testosterone. Serum INSL3 measurements may complement testosterone as a Leydig cell marker in male reproductive disorders, during therapeutic testicular suppression as well as in surveillance of illicit use of androgens.

Comparison of the effect of gonadotropin-releasing hormone agonist dosage in girls with central precocious puberty.

There are no definite guidelines on the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for treatment of central precocious puberty (CPP). We compared growth outcomes of GnRH agonist at different dosages in girls with idiopathic CPP to assess the optimal dosage. This retrospective study included 86 girls with idiopathic CPP who had been treated with GnRH agonist for at least one year and had attained their final adult height. Leuprolide was given as fixed dosage (3.75 mg every 4 weeks in body weight >20 kg, n=72) or weight-based dosage (60-85 μg/kg every 4 weeks, n=14). We compared suppression of advanced puberty and treatment response between the 2 groups. Peak estradiol and luteinizing hormone and bone age (BA)/chronological age after injection of GnRH agonist were effectively suppressed in both groups. In both groups, the height standard deviation score (SDS) for BA increased after treatment. Final adult height (FAH) (fixed dosage group,160.8±4.1 cm and weight-based dosage group, 161.2±4.4 cm) was significantly higher than the initial predicted adult height (PAH) (155.5±3.3 and 156.1±3.6 cm, respectively) (both P<0.001) and similar to midparental height (159.8±3.3 and 160.6±3.7 cm, respectively). There were no differences in gain in height SDS for BA and gain in height (FAH-PAH at the start) between the 2 groups. There were no differences in treatment outcome between fixed dosage (3.75 mg/4 wk) and weight-based dosage (60-85 μg/kg/4wk) of GnRH agonist. Therefore, a fixed dosage of GnRH agonist can be used more conveniently for CPP treatment without growth oversuppression.

Efficacy of dienogest versus gonadotropin-releasing hormone agonist combined with dienogest sequential therapy in the treatment of adenomyosis

Objective: To investigate the efficacy and safety of dienogest (DNG) alone and gonadotropin-releasing hormone agonist (GnRH-a) combined with DNG sequential treatment to adenomyosis. Methods: The clinical data of 110 patients with adenomyosis attending the First Affiliated Hospital of Nanjing Medical University from December 2019 to March 2022 were retrospectively analyzed, including 40 patients treated with DNG (2 mg/day) alone (DNG group) and 70 patients treated with sequential DNG (2 mg/day) after 3-6 injections of GnRH-a (GnRH-a+DNG group). The clinical data before and after treatment were compared between the two groups. Results: (1) The dysmenorrhea visual analogue scale (VAS) scores, cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19-9) levels at different time periods after treatment were significantly lower than before treatment in both groups (median before treatment: DNG group 70.0 mm, 68.55 kU/L, 22.45 kU/L respectively, GnRH-a+DNG group 80.0 mm, 151.50 kU/L, 20.44 kU/L respectively; all P<0.001). (2) The hemoglobin (Hb) levels of patients in both groups at different time periods after treatment were significantly higher than those before treatment (median: DNG group 102.00 g/L, GnRH-a+DNG group 94.00 g/L; all P<0.001). (3) Treatment with DNG alone did not have a significant effect on uterine volume in patients of DNG group (P>0.05), and uterine volume decreased significantly in the 15th-24th months of GnRH-a+DNG group compared with that before treatment (median: 167.76 vs 227.77 cm3; P<0.05). (4) There were no significant differences in hepatic and renal function and coagulation indexes between the two groups before and after treatment (all P>0.05), and no significant abnormal lesions were observed in breast tissue during the follow-up period. (5) The incidence of amenorrhea of GnRH-a+DNG group was higher than that of DNG group, and the incidences of irregular spotting bleeding and breakthrough hemorrhage were lower than those in DNG group. Conclusions: Whether DNG is used alone or in combination with GnRH-a in sequence, it could significantly relieve dysmenorrhea symptoms, improve the level of Hb, reduce the levels of CA125 and CA19-9 in patients with adenomyosis, with no adverse effects on coagulation and hepatic or renal function. GnRH-a sequential DNG therapy is superior to DNG alone in improving uterine bleeding patterns and controlling the growth of uterine volume in patients with adenomyosis.

Luteal phase support for women trying to conceive by intrauterine insemination or sexual intercourse.

Luteal phase support for women trying to conceive by intrauterine insemination or sexual intercourse.

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

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

Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin improves live birth rates in POSEIDON group 3 and 4 expected poor responders

Objective Aim of this study was to evaluate the effects of dual triggering with gonadotropin releasing hormone agonist and human chorionic gonadotropin (hCG) on outcomes of fresh embryo transfers following gonadotropin antagonist cycles in POSEIDON group 3 and group 4 low prognosis women and to compare the outcomes with hCG-only triggering. Methods This study was conducted by retrospective analysis of patients with expected poor ovarian response (POSEIDON group 3 and 4) that underwent fresh embryo transfers following in-vitro fertilization/intracytoplasmic sperm injection cycles with either dual triggering or hCG-only triggering between January 2010 and April 2020. A total of 1068 women that underwent dual triggering and 1931 that underwent hCG-only triggering were included in the study. Results Number of retrieved oocytes, M2 oocytes, oocyte maturation rate, fertilization rate, obtained 2PN embryos, implantation rate, clinical pregnancy rate and live birth delivery rates were found significantly higher in dual-triggering group in comparison to hCG-only group (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.02, p < 0.001 respectively). Conclusion Dual trigger with concomitant injections of GnRH agonist and hCG in GnRH antagonist cycles appears to improve IVF outcomes, increase quality of embryos, reduce miscarriage rates and consequently increase live birth delivery rates in POSEIDON groups 3/4 poor responders.

P-464 Long-acting GnRH agonist ovulation trigger to avoid ovarian hyperstimulation and to combine oocyte cryopreservation with ovarian suppression during chemotherapy

Abstract Study question Is long-acting GnRH agonist (GnRHa) trigger an efficacious and safe option in oocyte cryopreservation cycles before chemotherapy, when ovarian suppression is planned? Summary answer The flare-up effect of long-acting GnRHa is able to induce the final oocytes’ maturation and subsequently suppress ovarian function for chemotherapy What is known already When both oocyte cryopreservation and gonadal suppression during chemotherapy with long-acting GnRHa are accepted by the patient for fertility preservation (FP), the first injection of GnRHa is administered few days after oocyte retrieval in order to start oncological therapies as soon as possible. Some cases of ovarian hyperstimulation (OHSS) have been described in this setting, as a consequence of the initial flare-up effect on recently stimulated ovaries. The subsequent risks (including a possible delay in the start of chemotherapy) may discourage physicians from proposing gonadal suppression in combination with oocyte cryopreservation, denying women a FP opportunity with proven efficacy. Study design, size, duration Prospectively collected data from 75 oncological patients who underwent ovarian stimulation for oocyte cryopreservation from 2016 to 2021 were evaluated. From 2020 all patients for whom ovarian suppression after cryopreservation was planned were offered long-acting GnRHa trigger. All other patients were enrolled as controls, stratified for triggering method used (highly purified Chorionic Gonadotrophin 10000 UI or short acting GnRHa 0.2 mg). Participants/materials, setting, methods All the ovarian stimulation cycles for oocyte cryopreservation in oncological patients before chemotherapy were performed in a single tertiary level public fertility centre. Cycle outcomes were evaluated accordingly to the trigger method. Maturation rate was defined as number of cryopreserved mature oocytes/total number of oocytes retrieved. Results were compared by Mann-Whitney U test or Chi-Square test, as appropriate. When the long-acting GnRHa was used for triggering, luteal phase hormones were assessed. Main results and the role of chance After controlled ovarian stimulation (COS) with standard or random start antagonist protocol, 13 women received the long-acting GnRHa trigger (Triptorelin 3.75 mg. Group A) 36 hours before oocyte retrieval, 37 women received highly purified Chorionic Gonadotrophin 10000 UI (Group B) and 25 women the short-acting GnRHa (Triptorelin 0.2 mg. Group C). The groups were comparable in terms of demographic and clinical parameters. Median number of mature cryopreserved oocytes in group A was 11 (range 7-18) with a maturation rate of 80% (68-100), 9 (0-24) with a maturation rate of 78% (43-100) in group B, and 12 (0-34), 79% (50-100) in group C (no statistically significative difference). There was no case of OHSS in Group A. One patient in group B and one in group C developed OHSS after administration of long-acting GnRH in the luteal phase after COS (five days after oocytes retrieval). Five days after oocyte retrieval (7 days after trigger), serum FSH median level in group A was 1.29 mUI/ml (0.48-2.50) and LH median level was 1.04 mUI/ml (0.26-2.46). Limitations, reasons for caution We are aware that our data should be confirmed by more robust randomized studies and higher numbers. Wider implications of the findings We report for the first time the efficacy of long-acting GnRHa in obtaining mature oocytes and in guaranteeing complete suppression by chemotherapy initiation. The feasibility of this strategy is an important step in reducing the risk of OHSS, giving the opportunity to combine oocyte cryopreservation and ovarian suppression during chemotherapy. Trial registration number not applicable

Follicle stimulating hormone promotes production of renin through its receptor in juxtaglomerular cells of kidney

BackgroundPost-menopausal hypertension has been attributed solely to declining estrogen levels. The purpose of the research is to elucidate the mechanism by which follicle stimulating hormone(FSH) increases renin production involved in the regulation of blood pressure.MethodsThe expression of follicle stimulating hormone receptors (FSHRs) in renal juxtaglomerular cells and a As4.1 juxtaglomerular mouse cell line was evaluated. We established a mouse model by ovariectomy (OVX). Ovariectomized mice were treated with gonadotropin-releasing hormone agonist (GnRHa) (OVX + GnRHa). Ovariectomized mice initially received physiological doses of estrogen and were then injected with recombinant FSH (OVX + E + FSH).ResultsWe found that FSHR was expressed in mouse renal juxtaglomerular cells labeled by renin antibody and in As4.1 cells. FSH promoted renin synthesis via Gsα-coupled FSHRs that activated protein kinase A, cyclic adenosine monophosphate(cAMP) response element-binding protein, extracellular signal-regulated kinase (Erk1/2), Protein kinase B(AKT), and c-Jun N-terminal kinase signaling pathways in As4.1 cells. We found increased serum FSH levels in the ovariectomized mouse with concurrent increases in renin, angiotensin II, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MAP). Additionally, increases in serum renin, angiotensin II, HR, SBP, DBP, and MAP were reduced by the additional injection of GnRHa. Exogenous FSH administration completely reversed decreases in renin, angiotensin II, HR, SBP, DBP, and MAP even in mice that received physiological doses of estrogen to maintain normal estradiol levels.ConclusionsElevated FSH stimulates renin production involving a mechanism that may be relevant to the expression of FSH receptors in renal juxtaglomerular cells.

Oral Gonadotropin-Releasing Hormone Antagonist Relugolix Has the Same Effect as Gonadotropin-Releasing Hormone Agonist Injections in Terms of Preparation for Transcervical Resection Myomectomy.

For preparing the optimal condition in transcervical resection (TCR) surgery, gonadotropin-releasing hormone (GnRH) agonist has been utilized. Recently, an oral GnRH antagonist (relugolix) is available and acts directly on GnRH receptor, avoiding flare up and reducing blood E2 levels rapidly. We retrospectively compared the oral GnRH antagonist (n = 14) effect to that of subcutaneous GnRH agonist (n = 19) for the pretreatment of endometrium in TCR myomectomy. Endometrial thickening was determined by intraoperative videos. The color tone of the endometrium in the normal part was assessed by digital image processing. The median duration of the first GnRH agonist injection and the surgery was 67 days (21-136 days), which is significantly longer than that of the oral GnRH antagonist group, 18.5 days (7-157 days P < 0.01). Both the GnRH agonist and antagonist groups did not exhibit prominence in the endometrium. The GnRH antagonist group showed the same degree of whiteness in the normal endometrium as the GnRH agonist group. The oral GnRH antagonist administration could rapidly atrophy the endometrium and create an optimal surgical field for TCR in a short period.

GnRH-a-Induced Perimenopausal Rat Modeling and Black Cohosh Preparations' Effect on Rat's Reproductive Endocrine.

GnRH-a-Induced Perimenopausal Rat Modeling and Black Cohosh Preparations' Effect on Rat's Reproductive Endocrine.

O07 Managing relapsing and refractory lupus nephritis in juvenile systemic lupus erythematosus: a case report

O07 Managing relapsing and refractory lupus nephritis in juvenile systemic lupus erythematosus: a case report

Potential benefit of GnRH-agonist treatment before uterine artery embolization for large fibroids: MRI prediction of fibroid volume reduction.

Signal intensity (SI) of predominant fibroid (F1) on T2-weighted (T2W) images is useful for predicting the volume reduction response after gonadotropin-releasing hormone (GnRH)-agonist treatment. Few studies have been published regarding when and how to use GnRH agonist before UAE. To investigate magnetic resonance imaging (MRI) prediction of volume reduction rate (VRR) of large fibroids after GnRH-agonist treatment before uterine artery embolization (UAE) as well as the efficacy of UAE based on MRI. Data from 30 patients with a large fibroid and MRI results both before and after GnRH-agonist treatment were retrospectively analyzed. Indications for GnRH-agonist treatment are fibroids with a maximum diameter ≥10 cm or pedunculated submucosal fibroids ≥8 cm. GnRH agonist (3.75 mg leuprolide acetate) was administered subcutaneously once per month 2-6 times. SI of F1 on T2W imaging was measured: the SI was referenced to the SI of the rectus abdominis muscle (F/R). Mean maximum fibroid diameter was 11.1 ± 1.9 cm (range = 8.0-15.5 cm). Mean number of GnRH-agonist injections before UAE was 2.8 (range = 2-6). For predicting VRR ≥50% and <30%, the optimal cut-off values of F/R were 2.58 (sensitivity 80%, specificity 80%) and 1.69 (sensitivity 100%, specificity 70%), respectively. Of the 30 patients, fibroid infarction was complete in 29 (96.7%). SI of F1 on T2W imaging is useful for predicting the volume reduction response after GnRH-agonist treatment. After GnRH-agonist treatment for large fibroids, UAE is effective to achieve complete infarction of fibroids.

Dienogest and the Risk of Reoperation in Endometriosis.

Background: This retrospective cohort study aimed to determine whether there is a difference in reoperation rates between patients who used dienogest (DNG) and patients who did not use DNG. Methods: Using Health Insurance Review and Assessment Service (HIRA) data generated between 1 January 2010 and 30 June 2018, we identified women with an endometriosis diagnosis code who used GnRH agonists after gynecological surgery. Among them, women prescribed DNG were selected as the DNG group, and those who did not receive DNG were selected as the control group. A survival analysis of the reoperation between the two groups was performed. Results: DNG and control groups were extracted from 9735 people each. The reoperation rates were 0.4% and 0.6% in the DNG and control groups, respectively, without adjusting. In the Cox proportional risk analysis, DNG use increased the reoperation rate {hazard ratio (HR), 1.599; 95% confidence interval (CI), 1.005–2.545}. The site of endometriosis and the number of GnRH agonist injections were not associated with reoperation (HR, 1.008; 95% CI, 0.739–1.374; HR, 1.062; 95% CI, 0.690–1.635). In the subgroup survival analysis, according to the period between the last GnRH agonist injection and the first DNG dose, DNG did not increase the reoperation rates up to 9 months (~3 months: HR, 0.968; 95% CI, 0.551–1.699; 4~6 months: HR, 1.094; 95% CI, 0.58–2.063; 7~9 months: HR, 2.419; 95% CI, 0.735–7.962), but DNG increased the reoperation rate from 10 months onwards (10~12 months: HR, 3.826; 95% CI, 1.164–12.579 and ~13 months: HR, 8.436; 95% CI, 4.722–15.072). Conclusions: Women who used DNG had a higher endometriosis reoperation rate than women who did not use DNG. However, the initiation of DNG treatment within nine months after the last GnRH agonist injection did not affect the endometriosis reoperation rate.

Application of vaginoscopy in the diagnosis and treatment of occult vaginal high-grade squamous intraepithelial lesions

Objective: To investigate the application value of vaginoscopy in the diagnosis and treatment of vaginal squamous intraepithelial lesions post hysterectomy. Methods: From May 2017 to June 2020, patients with high-risk (HR)-HPV infection and (or) cytological abnormalities after hysterectomy in Obstetrics and Gynecology Hospital Affiliated to Fudan University were examined by colposcopy, and those who were not satisfied with exposure under colposcopy were further examined by vaginoscopy. The role of vaginoscopy in the detection and treatment of occult vaginal squamous intraepithelial lesions was analyzed. Results: A total of 153 patients with HR-HPV infection and (or) cytological abnormalities, and inadequate colposcopy were enrolled in this study. The average age was (49.8±8.1) years. All cases were successfully performed vaginoscopy with no vaginal perforation, no bladder and intestinal injury. During vaginoscopy, 11 (7.2%, 11/153) cases with unclear high-grade squamous intraepithelial lesion (HSIL) boundary under colposcopy were found with clear HSIL boundary, and new HSIL was found in 23 (15.0%, 23/153) cases. According to colposcopy, there were 89 cases of normal or inflammation, 45 cases of vaginal low-grade squamous intraepithelial lesion (LSIL) and 19 cases of vaginal HSIL. According to vaginoscopy, there were 56 cases of normal or chronic inflammation, 55 cases of vaginal LSIL, 40 cases of vaginal HSIL (including 2 cases of vaginal HSIL could not exclude cancer) and 2 cases of vaginal carcinoma. There were significant difference between colposcopy and vaginoscopy (P<0.01). The missed diagnosis rate of vaginal apex blind curettage under colposcopy was 54.8%. For the 40 cases with vaginal HSIL under vaginoscopy, 15 cases were completely curettaged with vaginal endoscopic claw forceps, and 22 cases were vaporized by Versapoint. Among the 37 cases of vaginal HSIL treated by vaginoscopy, 34 cases were followed up for 6 months with 31 cases of vaginal HSIL cured. The cure rate was 91.2% (31/34), the positive rate of HR-HPV decreased from 100.0% (34/34) to 79.4% (27/34). Conclusion: For patients with inadequate exposure of vaginal apex during colposcopy posthysterectomy, vaginoscopy is helpful to detect the occult lesions in the vaginal apex, and it could also be used for the treatment of vaginal squamous intraepithelial lesions.

Longitudinal study of AMH variations in 122 Adolescents and Young Adults (AYA) and non-AYA lymphoma patients to evaluate the chemo-induced ovarian toxicity to further personalise fertility preservation counselling.

What is the influence of age and chemotherapy regimen on the longitudinal blood anti-Müllerian hormone (AMH) variations in a large series of adolescents and young adult (AYA) (15-24 years old) and non-AYA (25-35 years old) lymphoma patients? In case of alkylating regimen treatment, there was a deep and sustained follicular depletion in AYA as well as non-AYA patients; however in both groups, the ovarian toxicity was extremely low in cases of non-alkylating treatments. AMH is now well-recognised to be a real-time indicator of ovarian follicular depletion and recovery in women treated by chemotherapy. Its longitudinal variations may discriminate between highly and minimally toxic protocols regarding ovarian function. It has been shown, in different cancer types, that age, type of chemotherapy regimen and pre-treatment AMH levels are the main predictors of ovarian recovery. Large studies on longitudinal AMH variations under chemotherapy in lymphoma patients are few but can provide the opportunity to assess the degree of follicle loss at a young age. This prospective cohort study was conducted in the Fertility Observatory of the Lille University Hospital. Data were collected between 2007 and 2016. Non-Hodgkin or Hodgkin lymphoma patients (n = 122) between 15 and 35 years old were prospectively recruited before commencing chemotherapy. Patients were treated either by a non-alkylating protocol (ABVD group; n = 67) or by an alkylating regimen (alkylating group; n = 55). Serial AMH measurements were performed at baseline (AMH0), 15 days after the start of chemotherapy (AMH1), 15 days before the last chemotherapy cycle (AMH2), and at time 3, 6, 9, 12, 18 and 24 months from the end of chemotherapy. The whole study population was divided into two groups according to age: AYA (15-24; n = 65) and non-AYA (25-35; n = 57). All patients received a once monthly GnRH agonist injection during the whole treatment period. A linear mixed model was used to account for the repeated measures of single patients. At baseline, non-AYA patients had higher BMI and lower AMH levels than AYA patients. All AYA and non-AYA patients having received ABVD protocols had regular cycles at 12 months of follow-up. In case of alkylating regimens, amenorrhoea was more frequent in non-AYA patients than in AYA patients at 12 months (37% vs 4%, P = 0.011) and at 24 months (24% vs 4%, P = 0.045). We distinguished a similar depletion phase from AMH0 to AMH2 between ABVD and alkylating groups but significantly different recovery phases from AMH2 to AMH + 24 months. AMH recovery was fast and complete in case of ABVD protocols whatever the age: AMH reached pre-treatment values as soon as the 6th month of follow-up in the AYA group (mean (95% CI) in log AMH M0 vs M6: 3.07 (2.86 to 3.27) vs 3.05 (2.78 to 3.31), P = 1.00) and in the non-AYA group (mean (95% CI) in log AMH M0 vs M6: 2.73 (2.40 to 3.05) vs 2.47 (2.21 to 2.74), P = 1.00). In contrast, no patients from the alkylating group returned to pre-treatment AMH values whatever the age of patients (AYA or non-AYA). Moreover, none of the AMH values post-chemotherapy in the non-AYA group were significantly different from AMH2. Conversely in the AYA group, AMH levels from 6 months (mean (95% CI) in log AMH: 1.79 (1.47 to 2.11), P < 0.001) to 24 months (mean (95% CI) in log AMH: 2.16 (1.80 to 2.52), P ≤ 0.001) were significantly higher than AMH2 (mean (95% CI) in log AMH: 1.13 (0.89 to 1.38)). Considering the whole study population (AYA and non-AYA), pre-treatment AMH levels influenced the pattern of the AMH variation both in alkylating and ABVD protocols (interaction P-value = 0.005 and 0.043, respectively). Likewise, age was significantly associated with the pattern of the recovery phase but only in the alkylating group (interaction P-value =0.001). BMI had no influence on the AMH recovery phase whatever the protocol (interaction P-value = 0.98 in alkylating group, 0.72 in ABVD group). There was a large disparity in subtypes of protocols in the alkylating group. The average duration of chemotherapy for patients treated with alkylating protocols was longer than that for patients treated with ABVD. These results make it possible to develop strategies for fertility preservation according to age and type of protocol in a large series of young lymphoma patients. In addition, it was confirmed that young age does not protect against ovarian damage caused by alkylating agents. This work was supported by Agence Régionale de Santé Hauts de France and Agence Onco Hauts-de-France who provided finances for AMH dosages (n° DOS/SDES/AR/FIR/2019/282). There are no competing interests. DC-2008-642 and CNIL DEC2015-112.

Elevated Pre-injection Basal Luteinizing Hormone Concentrations are Common in Girls Treated for Central Precocious Puberty

Objective:A consensus on how to monitor girls with central precocious puberty (CPP) during gonadotropin-releasing hormone agonist (GnRHa) treatment is lacking. Increased, unstimulated basal luteinizing hormone (LH) concentrations have been suggested to indicate lack of suppression. The aim was to evaluate pre-injection basal LH concentrations during GnRHa (leuprorelin 3.75 mg) treatment every four weeks in girls with CPP.Methods:Medical records were reviewed for girls with CPP treated at a single center from 2014-2019. Clinical characteristics and laboratory findings during treatment were systematically recorded.Results:A total of 587 GnRHa pre-injection basal LH concentrations were analyzed in 74 girls. Basal LH was pubertal (≥0.3 IU/L) in 53.5% of blood samples and 87.8% of all girls had a pubertal basal LH concentration at least once. A GnRH test (n=29) was repeated in 23 girls due to suspicion of clinical progression, elevated basal LH or recordable estradiol concentrations. None had a stimulated LH >3.1 IU/L. The predictability of treatment suppression (specificity) of basal LH concentrations was 12.0% when compared to repeated GnRH stimulation tests. Despite shortening the GnRHa injection interval to three weeks, basal LH concentrations remained pubertal in 85.7% girls. A significant reduction in height standard deviation score (p<0.001) and bone age advance (p<0.001) was observed during treatment.Conclusion:Pre-injection basal LH remains at pubertal concentrations during treatment with leuprorelin 3.75 mg in girls with CPP. Clinical monitoring of pubertal progression is preferable to routine basal LH concentrations. Repeat GnRH stimulation testing should be regarded as the gold standard.

Low sperm to egg ratio required for successful in vitro fertilization in a pair-spawning teleost, Senegalese sole (Solea senegalensis).

Cultured Senegalese sole (Solea senegalensis) breeders fail to spawn fertilized eggs. The implantation of large-scale in vitro fertilization protocols, to solve this problem, has been frustrated by low production of poor quality sperm. Cultured females were induced to ovulate with a 5 µg kg−1 single injection of gonadotropin-releasing hormone agonist (GnRHa) and viable eggs (82.6 ± 9.2% fertilization) were stripped 41:57 ± 1:46 h after the injection. Sperm was collected from cultured males, diluted in modified Leibovitz and used fresh to fertilize the eggs. Males were not treated with hormones. A nonlinear regression, an exponential rise to a maximum (R = 0.93, p < 0.0001) described the number of motile spermatozoa required to fertilize a viable egg and 1617 motile spermatozoa were sufficient to fertilize 99 ± 12% (±95% CI) of viable eggs. Similar, spermatozoa egg−1 ratios of 592 ± 611 motile spermatozoa egg−1 were used in large-scale in vitro fertilizations (190 512 ± 38 471 eggs). The sperm from a single male (145 ± 50 µl or 8.0 ± 6.8 × 108 spermatozoa) was used to fertilize the eggs. The mean hatching rate was 70 ± 14% to provide 131 540 ± 34 448 larvae per fertilization. The viability of unfertilized eggs stored at room temperature decreased gradually, and the sooner eggs were fertilized after stripping, the higher the viability of the eggs. The collection of sperm directly into a syringe containing modified Leibovitz significantly increased the percentage of motile spermatozoa (33.4 ± 12.2%) compared with other collection methods. The spz egg−1 ratios for Senegalese sole were at the lower end of ratios required for fish. Senegalese sole have a pair-spawning reproductive behaviour characterized by gamete fertilization in close proximity with no sperm competition. The provision of a large-scale in vitro fertilization protocol (200 µl of sperm per 100 ml of eggs) will enable the industry to operate sustainably and implement breeding programmes to improve production.

Fertility response of anestrous buffaloes to eCG2-Modified or Norgestomet plus eCG6- Modified-GnRH-based ovsync protocols during the breeding season.

Objective: The aim of the current study was to evaluate the fertility response of anestrous buffaloes and associated follicular growth and hormonal profiles to eCG-Modified (eCG2-ovsync) or eCG plus Norgestomet ear implant-Modified (Norgestomet-eCG6-ovsync) GnRH-Based ovsync protocols. Methods: Buffaloes (n=42) were randomly allocated into three treatment protocols: Basic-ovsync, Norgestomet-eCG6-ovsync and eCG2-ovsync (14 each). Each buffalo-cow in the Basic-ovsync protocol received two GnRH agonist injections on Days 0 (GnRHa1) and Day 9 (GnRHa2) and an injection of PGF2α on Day 7 with TAI at 16 h after GnRHa2 injection. Buffaloes in Norgestomet eCG6-ovsync (n=14) received the same treatment as Basic –ovsync plus IM injection of 250 mg of long-lasting progesterone and S/C insertion of Norgestomet ear implant in the ear Conca on Day 0 and an injection of 500 IU eCG on Day 6. Buffaloes in eCG2-ovsync received the same treatment of Basic ovsync in addition to an injection of 1000 IU eCG on Day 2. Simultaneous transrectal ultrasonography (TUS) and blood sampling were performed on Days -10, 0, 7, 9 and 10 as well as on post-TAI Days 11 and 22. Results: The largest follicle diameter (LFD) was significantly larger (p < 0.05) in eventually diagnosed pregnant (EDP) than in eventually diagnosed non-pregnant (EDnP) buffaloes in all treatment protocols on Day 9. The serum progesterone (P4) concentration was significantly higher (p < 0.05) in either EDP or EDnP buffaloes in Noegestomet eCG6-ovysync compared with other protocols on Day 7. There was a highly significant (r=0.74, P<0.01) positive correlations between corpus luteum volume (CLV) and LFD in EDP buffaloes. Conclusions: It is concluded that modifying Basic-ovsync via P4 supplementation by injection of long-lasting P4 on Day 0 and insertion of Norgestomet ear implant from day 0 to day 7 plus an injection of eCG on Day 6 improve the fertility response in true anestrus in buffaloes.

Endocrine regulation of long-term enhancement of spermiation in meagre (Argyrosomus regius) with GnRHa controlled-delivery systems

Meagre (Argyrosomus regius) undergo spermatogenesis and spermiation when reared in captivity, but often produce low milt volumes, sometimes with reduced quality and for a limited time period. In the present study we a) compared the efficiency of gonadotropin releasing hormone agonist (GnRHa) implants versus injections on testicular stimulation and spermiation enhancement, b) investigated the effect of GnRHa on the endocrine spermiation regulation (sex steroid hormones), and c) evaluated a commercial induced spawning simulation scenario. Firstly, males (n = 5) were injected with 15.0 ± 0.2 μg GnRHa kg−1 (Injections) or implanted with 51.0 ± 5.1 μg GnRHa kg−1 (Implant) and compared their sperm production response. Secondly, the best hormonal treatment (Implant) was tested treating males (n = 8) with 57.5 ± 7.5 μg GnRHa kg−1 every 3 weeks for a period of 70 days. Milt production was improved by the GnRHa implants with only minor sperm quality alterations (improved sperm motility percentage). Elevated plasma testosterone (T) and 11-ketotestosterone (11-KT) levels were recorded in response to GnRHa implants, while no significant difference for 17,20β-dihydroxy-4-pregnen-3-one (17,20β-P) was observed. In the commercial induced spawning simulation, it was shown that meagre females are capable of on-demand induction of spawning at random intervals (5–21 days) using GnRHa injections, over a period of at least 2.5 months. During this period, spermiation enhancement was achieved with GnRHa implants every 3 weeks, producing sperm with stable, in general, quality and motility parameters. Percentage of motile cells, motility duration and density fluctuated significantly, but remained within levels that are considered appropriate for high fertilization success in this species.

Priming Before In Vitro Maturation Cycles in Cancer Patients Undergoing Urgent Fertility Preservation: a Randomized Controlled Study

In vitro maturation (IVM) of oocytes retrieved at germinal vesicle stage, followed by vitrification of mature oocytes, has emerged as a fertility preservation (FP) option. This technique was first developed for patients with polycystic ovarian syndrome. In this population, providing LH activity prior to oocyte collection has been associated with better IVM outcomes. However, the benefit of this treatment in normo-ovulatory breast cancer (BC) patients undergoing IVM for FP purpose has never been investigated. To assess if the absence of therapeutic intervention prior to oocyte retrieval for IVM modifies IVM outcomes in BC patients undergoing urgent FP, we performed a non-inferiority, randomized controlled trial. The main outcome was the total number of mature oocytes obtained and cryopreserved after IVM. A total of 172 normo-ovulatory women, suffering from BC, 18 to 39years of age received no injection or a subcutaneous injection of hCG or GnRH agonist (GnRHa) 36h before oocytes retrieval according to randomized allocation. The total number of cryopreserved oocytes were 5.1 ± 3.8, 5.4 ± 3.8, and 6.0 ± 4.2 oocytes, respectively in the without, hCG and GnRHa groups. Mean differences were not significant between the three groups (- 0.5; CI 97.5% [- 2.03:1.02] and - 0.22; CI 97.5% [- 1.75:1.32], respectively). Intention to treat analyses failed to show non-inferiority in the "without injection group" in comparison with hCG or GnRHa groups. Our results are not conclusive enough to modify our practices and to stop administering hCG or GnRHa before IVM cycles for FP. The study was retrospectively registered to clinical trial (ID NCT03954197) in May 2019.