Anthropometric, metabolic, and reproductive outcomes of patients with central precocious puberty treated with leuprorelin acetate 3-month depot (11.25 mg)

Objectives Longer-acting gonadotropin-releasing hormone analogs (GnRHa) have been widely used for central precocious puberty (CPP) treatment. However, the follow-up of patients after this treatment are still scarce. Our aim was to describe anthropometric, metabolic, and reproductive follow-up of CPP patients after treatment with leuprorelin acetate 3-month depot (11.25 mg). Methods Twenty-two female patients with idiopathic CPP were treated with leuprorelin acetate 3-month depot (11.25 mg). Their medical records were retrospectively evaluated regarding clinical, hormonal, and imaging aspects before, during, and after GnRHa treatment until adult height (AH). Results At the diagnosis of CPP, the mean chronological age (CA) was 8.2 ± 1.13 year, and mean bone age (BA) was 10.4 ± 1.4 year. Mean height SDS at the start and the end of GnRHa treatment was 1.6 ± 0.8 and 1.3 ± 0.9, respectively. The mean duration of GnRHa treatment was 2.8 ± 0.8 year. Mean predicted adult heights (PAH) at the start and the end of GnRH treatment was 153.2 ± 8.6 and 164.4 ± 7.3 cm, respectively (p<0.05). The mean AH was 163.2 ± 6.2 cm (mean SDS: 0.1 ± 1). All patients were within their target height (TH) range. There was a decrease in the percentage of overweight and obesity from the diagnosis until AH (39–19% p>0.05). At the AH, the insulin resistance and high LDL levels were identified in 3/17 patients (17.6%) and 2/21 patients (9.5%), respectively. The mean CA of menarche was 12.2 ± 0.5 years. At the AH, PCOS was diagnosed in one patient (4.8%). Conclusions Long-term anthropometric, metabolic, and reproductive follow-up of patients with CPP treated with longer-acting GnRHa revealed effectivity, safety, and favorable outcomes.

P–611 Innovative controlled ovarian stimulation (COS) for polycystic ovary syndrome (PCOS) produces high-quality oocytes and no ovarian hyper stimulation syndrome (OHSS)

Study question How can we find an ovarian stimulation method that does not cause hyper stimulation syndrome but can produce a high pregnancy rate at one cycle? Summary answer This newly developed method for PCOS has a higher accumulative clinical outcome for one trial and no OHSS. What is known already Almost all conventional treatments for PCOS have managed to avoid OHSS by reducing the number of growing follicles, which are associated with high Estradiol levels and stimulate the production of vessel endothelial growth hormone (VEGF), leading to increased vessel permeability. Low dose FSH administration, In vitro maturation (IVM), Ovarian Drilling and Coasting have been performed to achieve this. However, their actual clinical outcome is still unsatisfactory. Study design, size, duration Evaluation of the efficiency of this method was conducted retrospectively at St. Mother Clinic. The embryonic development and the clinical outcome were studied for 34 PCOS patients during the period between November 2018 and December 2019. Participants/materials, setting, methods We started injections of FSH (150iu/ml), then we did ultrasound follicle monitoring. GnRH antagonist shots were started when the leading follicle reached 18mm and continued until the largest follicle was 22–24mm and the E2 value was over 4000pg/ml. Letrozole (2.5mg) and leuprorelin acetate (1.88mg) was injected as trigger. Two tablets each of Letrozole, Cabergoline and GnRH antagonist were given for 5 consecutive days after the oocyte retrieval. All embryos were cryopreserved. Main results and the role of chance Number of patients and cycles were 34 and 59. Average number of cryopreserved blastocysts was 6.12 (1–16). The frequencies of OHSS (mild, moderate, severe) were 29.4% (10/34), 0% (0/34), 0% (0/34). Average days between oocyte collection and withdrawal hemorrhage was 5.44(5–7). Cryopreservation rate was 100.0% (34/34). Clinical pregnancy rate and miscarriage rate was 42.3% (25/59) and 16.0% (4/25). The cumulative pregnancy rate was 73.7% (25/34). The four remaining unsuccessful cases still have 10,6,3 and 7 frozen embryos. So, there is a high possibility that they become successful, that would bring the cumulative pregnancy rate up to 82.3% (28/34). Limitations, reasons for caution This COS for PCOS seems promising, however it is premature to conclude that this method is established. This method requires caution monitoring for hormone level, follicle size and number and coagulant function. It also accompanied with the risk of ovarian hemorrhage on aspiration of a great number of oocytes. Wider implications of the findings: This COS seems viable for PCOS cases. It could control the cohort of antral follicles with different doses of Letrozole to find the optimal COH method and it could become the first option for COS of PCOS. Trial registration number N/A

Effectiveness and Distribution of Testosterone Levels within First Year of Androgen Deprivation Therapy in a Real-World Setting: Results from the Non-Interventional German Cohort LEAN Study

Background: Observational studies generate information on real-world therapy and complement data from prospective randomized trials. LEAN is an open-label, non-interventional, multi-centre, German cohort study on leuprorelin in routine clinical practice. Objectives: To extend knowledge on the use, effectiveness, and tolerability of HEXAL/Sandoz leuprorelin (in this article, the term Leuprone® HEXAL® covers Leuprorelin Sandoz® as well) solid implant in patients with prostate cancer (PCa) in a real-world setting. Methods: 959 PCa patients scheduled for androgen deprivation therapy (ADT) received leuprorelin acetate implant. Metabolism, serum prostate-specific antigen (PSA), and testosterone data, if available, were collected at baseline and follow-up visits for ≥12 months. Results: Of 694 patients in the modified full analysis set, 26.4% received GnRH analogues ≤6 months before enrolment. Fifty-one percent of patients were treated for locally advanced or metastatic PCa. In 19.6% of patients, ADT was used in neoadjuvant or adjuvant settings and in 28.5% with rising PSA after definite therapy. Testosterone levels <0.5 ng/mL were achieved in >90% of patients. Safety profile was in line with the summary of product characteristics. Therapy was well tolerated, with patient-triggered therapy discontinuation in 3.6%. Conclusions: This interim analysis confirmed previous efficacy findings for leuprorelin implant in a real-world setting. This contemporary cohort showed a shift in the use of ADT to non-metastatic PCa stages.

MON-069 Uncontrolled Central Precocious Puberty Patient Against GnRH Agonist, After Showing Granuloma Formation and Sterile Abscess to Both Leuprorelin Acetate and Triptorelin Actate

For more than 30 years, Gonadotropin-releasing hormone (GnRH) agonist has been the treatment of choice for central precocious puberty (CPP) to expect regression of secondary sexual characteristics, delayed menarche, and maximization of linear growth. There are several kinds of GnRH agonists such as leuprorelin, triptorelin, goserelin and histrelin, etc. In Korea, leuprolide acetate and triptorelin acetate are most common used drugs, and a monthly depot preparation is typically used for suppression of the HPG axis. Local complications related to GnRH agonists, including erythematous macules, granulomas, subcutaneous nodules, and sterile abscesses, occur in 10~15% of patients, and sterile abscesses have been known to occur in less than 2~3% of patients. In present case, we would like to introduce a case of CPP patient who was treated with GnRH agonist, but not suppressed and experienced recurrent vaginal bleeding, after showing granuloma formation and sterile abscess to both leuprorelin acetate and triptoreline actate. A 8.9 year-old girl visited our clinic with breast development and vaginal bleeding. On physical examination, she had enlarged breasts (Tanner stage 4) with pigmentation of the areola. Her height and weight was measured as 144.4cm (98th percentile) and 44.2kg (98th percentile) respectively. Her bone age was advanced as 12~12.6 years of age by TW3 method. Therefore, Leuprolide acetate (Lorelin depot®, Dongkook pharm) 3.75mg was administered to the patient every 4 weeks, and until the 6th injection, she exhibited no other complications. However, after 7th injection, the patient presented with granuloma and subcutaneous nodule at the left injection site and elevated hormone levels. Although that we switched to triptorelin acetate from 8th injection, the patient also showed a sterile abscess at the injection site. We switched from triptorelin acetate to leuprolide acetate again, however, after 2 months of the switch, the patient showed abrupt vaginal bleeding and elevated hormone levels. Therefore, after assumption of unsuppression of HPG axis, leuprolide acetate 3.75mg was administered every 2 weeks for 2 months. However, her vaginal bleeding occurred monthly and hormonal level was still unsuppressed, and also, the granuloma appeared again at the injection site. So, we discussed with her parents about her uncontrolled symptoms, and we discontinued the treatment. There are many theories about the cause of local complications of GnRH agonist, but the mechanism has still not been revealed. Further studies are required to identify the mechanism and the relationship between treatment effect and local complications, which could induce uncontrolled CPP.

Endometriosis in a case with Fraser Syndrome

Introduction: Fraser Syndrome is a rare genetic disorder characterized by urogenital defects, cutaneous syndactyly and cryptophthalmos commonly diagnosed during foetal autopsy. Vaginal atresia is one of the major diagnostic criteria of Fraser Syndrome and could be a contributing factor of endometriosis following the development of hematocolpos. Imperforate hymen, often misdiagnosed as vaginal atresia, is a rare diagnosis in patients with Müllerian anomalies. Here, we report a case of Fraser Syndrome with chronic pelvic pain as a result of delayed hymenotomy and the extensive management of endometriosis. Case Report: A 15-year-old girl with Fraser Syndrome presented with pelvic pain. Examination revealed a large hematocolpos caused by an imperforate hymen. Due to the lack of paediatric intensive care locally, she had a delayed hymenotomy. She continued to suffer from chronic pelvic non-cyclical pain post-hymenotomy. Preliminary laparoscopy and biopsy showed endometriosis. Despite excision and clearance of endometriosis, she experienced persistent pain while taking morphine and was trialled with several hormonal therapies such as leuprorelin acetate, progestogen and combined hormonal therapy. She received medical therapy for 10 years until she re-presented with erratic bleeding and pain. Laparoscopy again identified endometriosis. Conclusion: Early recognition and treatment minimize risk of endometriosis especially in premenarcheal adolescent girls with obstructive Müllerian anomalies presenting with pelvic pain. Adequate pain control and medical management permit a delay in surgical intervention facilitating further investigations and thorough counselling with the patient and family about the implications of endometriosis on fertility and quality of life.