Using GnRH agonists in combination with hCG in antagonist ART cycles: A SCOPING Review of recent evidences.

Assisted Reproductive technology encompasses all techniques involving ovarian stimulation to produce high-quality oocytes and manipulation of both oocytes and sperm in vitro to produce embryos for the purpose of reproduction. The final maturation of oocytes induced by a "trigger" is a crucial step with the potential to affect in vitro fertilization outcomes. Human chorionic gonadotropin has traditionally been used as a substitute for luteinizing hormone to induce final oocyte maturation and meiosis. However, this practice may cause a potentially fatal iatrogenic complication known as ovarian hyperstimulation syndrome, which can cause significant morbidity and, in rare cases, death in otherwise healthy women. Thus, gonadotropin releasing hormone agonists have been promoted as a safer alternative for inducing oocyte maturation, albeit at the expense of luteal phase defect. Since then, various combinations of gonadotropin releasing hormone agonists and human chorionic gonadotropin have been tried. This scoping review evaluates these trigger combinations in various types of responders.

Adult Height of Patients with SHOX Haploinsufficiency with or without GH Therapy: A Real-World Single-Center Study.

INTRODUCTION: Isolated SHOX haploinsufficiency is a common monogenic cause of short stature. Few studies compare untreated and rhGH-treated patients up to adult height (AH). Our study highlights a growth pattern from childhood to AH in patients with SHOX haploinsufficiency and analyzes the real-world effectiveness of rhGH alone or plus GnRH analog (GnRHa). METHODS: Forty-seven patients (18 untreated and 29 rhGH-treated) with SHOX haploinsufficiency were included in a longitudinal retrospective study. Adult height was attained in 13 untreated and 18 rhGH-treated (rhGH alone [n = 8] or plus GnRHa [n = 10]) patients. RESULTS: The untreated group decreased height SDS from baseline to AH (-0.8 [-1.1; -0.4]), with an increase in the prevalence of short stature from 31% to 77%. Conversely, the rhGH-treated group had an improvement in height SDS from baseline to AH (0.6 [0.2; 0.6]; p < 0.001), with a reduction in the prevalence of short stature (from 61% to 28%). AH in the rhGH-treated patients was 1 SD (6.3 cm) taller than in untreated ones. Regarding the use of GnRHa, the subgroups (rhGH alone or plus GnRHa) attained similar AH, despite the higher prevalence of pubertal patients and worse AH prediction at the start of rhGH treatment in patients who used combined therapy. CONCLUSION: The use of rhGH treatment improves AH in patients with SHOX haploinsufficiency, preventing the loss of height potential during puberty. In peripubertal patients, the addition of GnRHa to rhGH allows AH attainment similar to the AH of patients who start rhGH alone in the prepubertal age.

Short-term Administration of Gonadotropin-releasing Hormone Agonist (Buserelin) Induces Apoptosis in Rat Ovarian Developmental Follicles

ABSTRACT Objective: To investigate the effects of buserelin on the development of follicles, apoptosis index and steroid hormones level. Methods: Twenty-four 3-month-old female rats were randomly divided into three groups: a low-dose group, a high-dose group and a control group (n = 8). Buserelin and normal saline were injected subcutaneously for 5 days. Thirty days after the first injection, the ovaries were removed for staining. Blood samples were collected and centrifuged. Their serum was used for measuring estradiol and progesterone levels, using enzyme-linked immunosorbent assay. Results: The findings revealed a significant decrease in the mean of secondary and Graafian follicles in the high-dose group compared with the control group (p = 0.037, p = 0.034, respectively). The serum estradiol level increased significantly in the high-dose group, compared with the low-dose and control groups (p = 0.027, p = 0.047, respectively). The serum progesterone level decreased, although not significantly. In contrast to the control group, the significant increase of apoptotic cell death was found in primordial, unilaminar and multi-laminar follicles in the high-dose group (p = 0.004, p = 0.049, p = 0.047, respectively). Conclusion: The findings of this study suggest that short-term administration of high-dose buserelin increases the serum estradiol level and apoptosis in the granulosa cells but has an inhibitory effect on follicular development.

Gonadotropin-releasing hormone agonists for ovarian protection during cancer chemotherapy: systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of gonadotropin-releasing hormone agonist (GnRHa) administration before and/or during cancer chemotherapy for the protection of ovarian reserve in premenopausal women without prior diagnosis of infertility. METHODS: This was a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing administration of GnRHa before and/or during chemotherapy vs chemotherapy alone. Eligible participants were premenopausal women at any stage of cancer, without previous diagnosis of infertility. An electronic database search in MEDLINE, CENTRAL, LILACS and ClinicalTrials.gov was performed. After selecting eligible studies, the relative risk (RR) was assessed for primary ovarian insufficiency (POI)/amenorrhea and for spontaneous pregnancy after completion of treatment. RESULTS: Thirteen RCTs comparing concurrent use of GnRHa and chemotherapy (609 participants) with chemotherapy alone (599 participants) were eligible for meta-analysis. All trials were open-label and patients had been treated for breast cancer (n = 1099) or lymphoma (n = 109). GnRHa had a significant benefit on the risk of POI/amenorrhea (RR, 0.60; 95% CI, 0.45-0.79), which persisted in subgroup analysis for breast cancer (RR, 0.57; 95% CI, 0.43-0.77) but not for lymphoma patients (RR, 0.70; 95% CI, 0.20-2.47). The rate of spontaneous pregnancy after completion of treatment was higher in women receiving GnRHa plus chemotherapy compared with those receiving chemotherapy alone (RR, 1.43; 95% CI, 1.01-2.02). Overall, the quality of evidence was low due to the unclear risk of bias, short follow-up and lack of objective assessment of ovarian function and reserve. CONCLUSIONS: Evidence, albeit of low quality, supports the use of GnRHa before and/or during chemotherapy to reduce the risk of POI and increase the probability of spontaneous pregnancy in the short term. Further high quality RCTs with more accurate assessment of ovarian reserve are needed to support definitive recommendations for clinical practice. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Hormonal responses and clinical outcome are the same with three doses of gonadotropin-releasing hormone agonist used in the short stimulation protocol.

OBJECTIVE: The aim of this study was to compare 3 different doses of GnRH-a in a short protocol on ICSI outcome. METHODS: 91 ovulatory patients were randomly assigned to three groups; group A (N=34), group B (N=34) and group C (N=23). All started treatment with urinary gonadotropins, 2 ampoules per day and GnRH-a (Triptorelin) on the first day of the menstrual period and continued till the day of (hCG) administration. The daily dose of Triptorelin was 0.1 mg, 50 µg, and 25 µg in groups A, B and C respectively. RESULTS: Stimulation requirements, days of stimulation and total ampoules of gonadotropins did not differ between the three groups. The mean number of follicles aspirated and the mean number of Metaphase 2 oocytes retrieved were similar in the three groups. Fertilization and cleavage rates were similar in the three groups. The mean number of embryos available for transfer was 6.4±0.5, 9.4±0.5 and 7±0.7 in groups A, B and C, with a significant difference only between groups A and B. Pregnancy rates per cycle were 35.3%, 35.3% and 34.8 % for groups A, B and C, respectively with no significant difference. CONCLUSION: Early and late hormonal changes, stimulation requirements and final outcome were similar with the different doses of the agonist. Other factors should be considered, most importantly: treatment cost and side effects.

Time to menarche and final height after histrelin implant treatment for central precocious puberty.

OBJECTIVE: To compare final height, change in body mass index (BMI), and time from end of treatment until menarche in girls with central precocious puberty treated with the histrelin implant versus depot gonadotropin releasing hormone agonist injections. STUDY DESIGN: Chart review, interview, and final height measurements of 2 groups of girls with central precocious puberty; triptorelin depot (TD) group: 23 girls were treated from age 8.4 ± 0.3 with monthly injections of TD, for 26.7 ± 2.5 months; histrelin implant group: 11 girls were treated from age 8.7 ± 0.3 years for 28.4 ± 3.7 months, of whom 9 initially received monthly TD injections for 1.5-39 months. Final height, BMI (pretreatment vs recent), and time between either implant removal or last injection to menarche were compared. RESULTS: Time between removal of implant or last injection and menarche was 9.3 ± 1.5 (histrelin implant group) versus 16.1 ± 1.7 (TD group) months (P = .02). Predicted height at implant insertion was 156.8 ± 2.6 cm, and final height was 161.1 ± 2.0 cm (not significant [NS]). Predicted height for TD was 155.2 ± 1.9 cm and final height was 157.9 ± 1.7 cm (NS). Change from onset of treatment to final BMI-SDS for histrelin implant was -0.41 ± 0.3, and for TD was -0.03 ± 0.2 (NS). CONCLUSIONS: Menarche occurred sooner after implant removal. There was no difference in final height or BMI outcomes between the 2 treatment modalities.

Tratamento da hemorragia uterina provocada pelo uso de anticoagulantes / Treatment of uterine bleeding due to the use of anticoagulants

O uso de anticoagulantes para tratamento de doenças sistêmicas pode provocar hemorragia uterina em mulheres na fase reprodutiva. No presente artigo os autores acompanharam cinco mulheres com síndromes trombogênicas (síndrome antifosfolipídica, tromboembolismo, síndrome de Budd-Chiari, arterite de Takayasu e tromboangeíte obliterante com AVC) que apresentavam hemorragia uterina pelo uso de anticoagulantes. Devido à restrição ao uso de estrogênios e progestogênios, os autores optaram por usar os análogos agonistas do hormônio liberador das gonadotrofinas, em administrações mensais, intramusculares de 3,75 mg. Em todas as pacientes a administração do análogo não só diminuiu significativamente o sangramento uterino, como reduziu a anemia e melhorou a qualidade de vida das pacientes.