GnRH Analogue Administration Research Articles

Influence of hormonal treatments on progesterone levels to enhance embryo survival and kidding rates in goats.

This study investigated the efficiency of different estrous synchronization programs and hormonal treatments in improving reproductive outcomes in goats. Conducted on a commercial farm in southern Thailand, the study used multiparous Shami and Anglo-Nubian breed goats. In experiment 1, goats were randomly allocated to two estrous synchronization treatments: 11-day (CI11D) and 13-day (CI13D) intravaginal progesterone implants, followed by artificial insemination (AI) with frozen-thawed semen. Various hormonal treatments (human chorionic gonadotropin (hCG), GnRH analogue, progestogen) were administered on day 5 post-AI to elevate progesterone levels. Experiment 2 assessed embryo survival after transferring early- and late-stage embryos, using GnRH analogue to increase progesterone levels in the recipient goats. Results showed that GnRH analogue significantly increased pregnancy rates, kidding rates, and the number of kids born in the CI13D group. Progesterone levels were higher in treated groups, particularly with GnRH analogue, though estradiol levels varied between synchronization protocols. Late-stage embryo transfers significantly improved pregnancy rates and reduced embryonic loss compared to early-stage transfers. GnRH analogue supplementation reduced early embryonic mortality, enhancing embryo survival and overall reproductive performance. This study demonstrates the efficacy of tailored estrous synchronization and hormonal treatments in optimizing goat reproductive outcomes, with significant implications for improving fertility management in commercial goat farming. Although no significant differences were observed in progesterone levels, the administration of GnRH analogue reduced early embryonic mortality and improved reproductive outcomes, demonstrating its potential to enhance embryo survival and reproductive performance in goats.

Adherence to fertility preservation guidelines in young patients with breast cancer: A retrospective analysis.

e23255 Background: Breast cancer affects a considerable proportion of women of childbearing age making it important to provide options for fertility preservation. At Chihuahua's State Cancer Center, a state-federal-funded institution providing free oncological care, and ensuring access to fertility preservation measures is integral to the multidisciplinary approach for young cancer survivors. Recognizing chemotherapy's impact on fertility, implementing fertility preservation measures is key. Assessing adherence to these guidelines is essential for comprehensive care and holistic well-being in young breast cancer patients at our center. Methods: In this retrospective study at the Chihuahua´s State Cancer Center, we examined adherence to fertility preservation guidelines among breast cancer patients aged 18 to 40 years. The primary method used for fertility preservation was the administration of GnRH analogs, such as triptorelin and goserelin. Data on GnRH analog use, chemotherapy regimens, and patient demographics were collected from medical records. The study aimed to assess the integration of fertility preservation measures, particularly GnRH analogs, into treatment plans for young breast cancer patients. Additionally, we aimed to identify barriers to accessing fertility preservation services in this population. Results: The study findings revealed that out of the 749 registered breast cancer patients, 95 (12.6%) were 40 years old or younger. Among these, 75 (79%) received adjuvant and/or neoadjuvant chemotherapy, with 58 (77.3%) being in locally advanced clinical stages. Of the 75 patients who underwent chemotherapy, 20 (26.7%) also received GnRH analogs, while 55 (73.3%) did not. Among the 75 chemotherapy recipients, 16 (p = 0.046) were estrogen receptor-positive and received analogs. Furthermore, out of the 20 patients with triple-negative breast cancer, only 1 (1.3%) received an analog. Conclusions: The study indicates that GnRH analogs usage in breast cancer patients is significantly associated with estrogen receptor positivity. While estrogen receptor status is crucial for determining treatment suitability, GnRH analog utilization was notably low among triple-negative breast cancer patients. This suggests that triple-negative status alone should not preclude GnRH analog use. The findings underscore the need to raise awareness and improve adherence to ovarian suppression recommendations to enhance clinical outcomes and quality of life for breast cancer patients.

Effects of puberty suppression on bone, body composition, handgrip strength and glucolipid profile in early-pubertal transgender adolescents

Introduction The effects of puberty suppression for more than 2 years before the start of gender-affirming hormones (GAH) on bone mass acquisition and body composition are understudied. Materials and methods Retrospective study on 46 transgender adolescents (20 trans boys and 26 trans girls) receiving a gonadotropin-releasing hormone analogue (GnRHa) from Tanner stage 2-3, followed by GAH around the age of 16 years. At start of GnRHa and at start of GAH, dual-energy X-ray absorptiometry (DXA) at lumbar spine (LS), femoral neck (FN) and total body (TB), handgrip strength test and fasting blood sampling were performed. Z-scores were calculated using reference values for both cis girls and cis boys. Results GnRHa were administered for a median of 3.2 years (± 0.69) in trans boys and 2.7 years (± 1.05) in trans girls. Bone mineral apparent density (BMAD)-LS Z-scores decreased significantly in both trans boys and trans girls, while BMAD-FN Z-scores decreased only in trans boys. Fat% and Fat Mass Index Z-scores significantly increased in both groups, while Lean Mass Index Z-scores significantly decreased. Handgrip strength Z-scores for the sex registered at birth (SRAB) remained stable in trans boys while they decreased in trans girls. There was no significant influence of the treatment on either insulin sensitivity or lipid profile. Discussion GnRHa administration for more than two years during the physiological time of puberty decreases bone mass acquisition, mainly at the lumbar spine and induces a general increase in fat mass. Although lean mass acquisition is undermined in both groups, handgrip strength is affected mainly in trans girls compared with age-matched peers for the SRAB.

Effect of a Single Injection of GnRH Analog Alone and at the Time of AI on Reproductive Performance of Nili Ravi Buffaloes

Introduction: The gonadotropin-releasing hormone (GnRH) is a decapeptide hormone released from basal neurons of the hypothalamus. It stimulates the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the pituitary. The objective of the study was to evaluate the effect of a single injection of gonadotropin-releasing hormone (GnRH) analog at the time of artificial insemination (AI) on buffalo estrus, conception, pregnancy, and calving rate. Materials and methods: The anestrus nulliparous Nili Ravi buffalo heifers (n=80) were divided into 4 groups randomly. Group A (n=20) received only a single injection of GnRH analog at start of the experiment (Day 0), group B (n=20) received a single injection of GnRH analog at Day 0 and prostaglandine (PGF2α) at Day 7, group C (n=20) received progesterone sponge for 7 days, and group D (n=20) received progesterone sponge for 7 days and PGF2α at Day 9. In 2nd study, buffaloes (n=60) expressing first (n=20), second (n=20), and third (n=20) postpartum estrus were enrolled. Moreover, heifers (n=20), expressing estrus first time were also included. Animals (n=10) from each group, received a single injection of GnRH analog at the time of AI were named as treatment group and the control (n=10) did not receive any treatment. Pregnancy tests were performed with the help of ultrasound on days 35 and 65 post-AI. Results: The pregnancy and calving rates were lower in GnRH group compared to other treatments. Similarly, the administration of GnRH analog did not increase pregnancy rates in treatment groups. Conclusion: The single injection of GnRH analog alone at the time of AI did not improve the reproductive performance of buffaloes.

Comparative effectiveness of different methods of using the analogue of gonadotropin-releasing hormone for ovulation stimulation in rabbit does

Modern reproductive technologies require artificial insemination (AI) protocols that are safe for the health of animals and do not violate their welfare. Stress factors arising in the reproduction process of industrial rabbit breeding negatively affect the sexual function and reproductive performance of rabbits and their offspring. In recent years, researchers have focused on alternative methods of ovulation stimulation, including intravaginal introduction of hormonal means of its induction. Therefore, the aim of our study was a comparative evaluation of the effectiveness of the intramuscular method of administration of the gonadotropin-releasing control (GnRH) analogue and its addition to the sperm dose for AI on Hyplus rabbit (n = 30), which were randomly divided into three groups. For this, buserelin acetate was administered intramuscularly at a dose of 1 μg per rabbit immediately after artificial insemination (control group). Experimental animals were inseminated with sperm doses with the addition of a GnRH analogue in the amount of 25 μg (experimental group 1) and 15 μg (experimental group 2). The influence of the method of administration of GnRH analogue on reproductive function was evaluated by indicators of the effectiveness of AI, fertility, and the dynamics of the progesterone level during pregnancy. A decrease in fecundity was observed in females; for example, in experimental group 1, the effectiveness of AI in terms of the number of rabbits was 64.3 %; in animals of experimental group 2 – 41.2 %, and the number of inseminations in this group of rabbits was 41.7% higher compared to control data. The fertility of rabbits of all groups was high, reaching the maximum value in the control group (10.42 ± 0.52 heads/female). Fertility according to live newborns in experimental group 1 was the highest among all groups of rabbits and was 9.67 ± 0.49 heads/female, which showed an increasing trend compared to the control. Also, in the animals of experimental group 1, an increase in the level of progesterone in blood serum was observed (on the 7th day of pregnancy by 13.2 %, on the 14th day by 14.3 %, on the 21st day by 16.4 %). In contrast, in experimental group 2, a significant decrease in the progesterone level was noted. Thus, 25 μg of GnRH analogue added to the extender is optimal. It is worth noting that there were no advantages of intravaginal administration over intramuscular administration in terms of reproductive performance. However, the number of live births and progesterone levels were improved.

Pharmacological methods for ovarian function and fertility preservation in women with cancer: A literature review.

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality. The effect of chemotherapy can range from minimal effects to complete ovarian atrophy. Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. In this manuscript, we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data, as well as future perspectives in this field that upcoming research should focus on.

Reproductive Performance of Female Rabbits Inseminated with Extenders Supplemented with GnRH Analogue Entrapped in Chitosan-Based Nanoparticles.

Rabbit is a reflexively ovulating species. Accordingly, in the practice of artificial insemination (AI) ovulation must be induced via exogenous GnRH (Gonadotropin-Releasing Hormone) administration, which may be performed intramuscularly, subcutaneously, or intravaginally. Unfortunately, the bioavailability of the GnRH analogue when added to the extender is lower due to the proteolytic activity in the seminal plasma and the poor permeability of the vaginal mucosa. The aim of the study was to refine the practice of AI practice in rabbits by replacing parenteral GnRH analogue administration (subcutaneous, intravenous, or intramuscular injection) with intravaginal application, while reducing its concentration in the diluent. Extenders containing the buserelin acetate in chitosan-dextran sulphate and chitosan-alginate nanoparticles were designed and 356 females were inseminated. Reproductive performance of females inseminated with the two experimental extenders, receiving 4 μg of buserelin acetate intravaginally per doe, was compared with that in the control group, the does of which were inseminated with the extender without the GnRH analogue and induced to ovulate with 1 μg of buserelin acetate administered intramuscularly. The entrapment efficiency of the chitosan-dextran sulphate complex was higher than that of chitosan-alginate. However, females inseminated with both systems showed similar reproductive performance. We conclude that both nanoencapsulation systems are an efficient way of intravaginal ovulation induction, allowing a reduction in the level of the GnRH analogue normally used in seminal doses from 15-25 μg to 4 μg.

Isolated Superior Mesenteric Artery Dissection Following Gonadotropin-releasing Hormone Analog Administration

Abstract In this article, we report the case of a patient with isolated superior mesenteric artery dissection (ISMAD). The patient presented with abdominal pain, but all the routine tests were negative. ISMAD was diagnosed by computed tomography angiography. She was treated conservatively. After 2 days of fasting, the patient gradually started to eat liquid food and the abdominal pain symptoms did not recur. We then followed her for 6 months, during which there was no recurrence.

Efficiency of Bovine Embryo Transfer in JSC "Agroindustrial Firm "Nasha Zhitnitsa"

The aim of the study was to estimate the effectiveness of embryo survival rate in cows and heifers selected as recipients. Embryo transfer was carried out in JSC "Agroindustrial Firm "Nasha Zhitnitsa", Rodomanovo village, Smolensk region. The embryos were obtained from donors of the Aberdeen-Angus breed located in the Center for Reproductive Technologies LLC, Syreyka, Samara region. For the experiment, mongrel animals (n = 110) were selected and divided into two groups. The group I contained cows (n = 52) with 2-4 calves. Heifers (n = 58) of a random age were put into the group II. All the animals selected for the experiment were previously subjected to hormonal stimulation in order to synchronize their estrus cycles. The synchronization scheme included the introduction of an introvaginal Y-shaped implant "CIDR", intramuscular administration of GnRH analogues at a dose of 10 ml per animal and PgF2? cloprostenol at a dose of 500 mcg per animal. On the 7th day of the estrus cycle, all animals were transferred frozen-thawed embryos into the lateral horn of the uterus relative to the corpus luteum diagnosed on the ovary. Pregnancy diagnosis was performed on the 25th day after embryo transfer, which corresponded to the 32nd day of embryo development. During rectal examination of the cow recipients in group I, as for the result of the survival rate of transferred frozen-thawed embryos, pregnancy on the 30th day was diagnosed in 53.9% (28/52) of animals. In group II, in which heifers of random age were selected as recipients, pregnancy was diagnosed in 62.1% (36/58) of animals. Thus, the research results show that the survival rate of embryos in group II was significantly (P < 0.01) higher by 8.2% compared with the results obtained on animals in group I.

Massive haematometrosalpinx in a young girl with cloacal anomalies: Laparoscopic management

A cloacal anomaly refers to the collection of defects that occur during fetal development, where the intestinal, urinary and reproductive tracts open into a common cavity. It is imperative to address this condition since despite its fairly low incidence and limited data, it has a very high impact on the patient's quality of life, and therefore mandates further study to effectively manage these patients. This study is regarding a 13-year-old girl diagnosed to have a cloacal anomaly since birth presenting with cyclical abdominal and pelvic pain for 6 months. She had undergone multiple abdominal and pelvic corrective surgeries since birth, leading to a colostomy and Mitrofanoff channel for bowel and bladder control, respectively. Diagnostic imaging revealed bilateral haematosalpinx for which ultrasound guided aspiration followed by subcutaneous administration of GnRH analogues was given as a temporary mode of relief which eventually recurred within 4 months. Following an extensive Multidisciplinary discussion, the team proceeded with the crucial decision of a hysterectomy and bilateral salpingectomy. The surgery itself was challenging due to multiple adhesions, scarring and difficulty in port placement. Following surgery, the patient's quality of life significantly improved allowing her to attend to her activities of daily living and maintain a social life. The need for future appointments to address sexual functions and fertility wishes was explained.

The risk of menopausal symptoms in premenopausal breast cancer patients and current pharmacological prevention strategies

Introduction For young premenopausal breast cancer (BC) patients, adjuvant chemotherapy and other anti-cancer treatments can increase the risk of menopausal symptoms and may cause chemotherapy-related amenorrhea (CRA), infertility and premature ovarian insufficiency (POI). Areas covered In this report, menopausal symptoms related to anti-cancer treatment are described. Menstrual disturbances associated with the use of adjuvant chemotherapy, endocrine therapy and targeted therapy against human epidermal growth factor receptor 2 (HER2) in premenopausal women with BC are discussed. To prevent menopausal symptoms, CRA and POI, data on the efficacy of temporary ovarian suppression with gonadotropin-releasing hormone analogues (GnRHa) during chemotherapy are highlighted. Pooled analyses have confirmed that concurrent administration of GnRHa during chemotherapy could significantly reduce the risk of developing chemotherapy-induced POI in premenopausal women with early-stage BC. In addition, reports have suggested that embryo/oocyte cryopreservation may increase the chance of pregnancy after the diagnosis of BC, although such data remain limited. Expert opinion Commonly experienced by pre-menopausal women with BC, anti-cancer treatment could cause severe menopausal symptoms. Temporary ovarian suppression with GnRHa during chemotherapy provided a safe and efficient strategy to reduce the likelihood of chemotherapy-induced POI in premenopausal patients with early-stage BC undergoing (neo)-adjuvant chemotherapy.

The Impact of Ethanol Sclerotherapy on ICSI Outcomes in Infertile Patients with Endometriomas Undergoing Controlled Ovarian Stimulation

Objective: the aim of the study was to determine whether endometrioma aspiration and alcohol sclerotherapy performed prior to controlled ovarian stimulation has any beneficial effects on ICSI outcomes in patients with endometriomas.
 Methods: The cycle characteristics and pregnancy outcomes of 103 patients with endometriomas who underwent ethanol sclerotherapy on day 2 of the controlled ovarian stimulation with a gonadotropin antagonist protocol were retrospectively compared with the cycle characteristics of 405 patients with endometriomas who did not receive scleroterapy before stimulation.
 Results: No statistically significant difference was observed in the number of retrieved oocytes, metaphase II oocytes, fertilization and good quality embryo rates between the two groups. The clinical pregnancy rate, implantation rate and live birth rates were similar among the two groups. No major complications including intraperitoneal haemorrhage, peritonitis, ovarian abscess or intestinal perforation were recorded.
 Conclusion: The results of the present study indicate that ethanol sclerotherapy does not improve ICSI outcomes when performed right before ovarian stimulation and without concomittant GnRH analogue administration. Since it is a simple outpatient procedure without significant complications, ethanol sclerotherapy may be performed prior to IVF as an alternative to surgery to improve the accessibility of follicles and monitoring of follicle growth in patients with large endometriomas and for those patients with intractable pain symptoms, without decreasing the ovarian reserve.

Is Anti-Müllerian Hormone a Marker of Ovarian Reserve in Young Breast Cancer Patients Receiving a GnRH Analog during Chemotherapy?

Introduction: Anti-Müllerian hormone (AMH) is the most reliable biomarker of ovarian reserve; however, its role in predicting ovarian recovery after chemotherapy is unclear. Administration of a GnRH analog (GnRHa) during chemotherapy significantly reduces the ovarian failure rate and increases the pregnancy rate. The available data on the behavior of AMH during concurrent administration of chemotherapy and GnRHa are inconsistent. We investigated whether concurrent administration of triptorelin and adjuvant chemotherapy might reduce the expected drop of AMH. Methods: Eligible patients were premenopausal women aged <40 years, with a diagnosis of early breast cancer, and candidates to 4–8 cycles of adjuvant chemotherapy. Triptorelin (3.75 mg i.m.) was started before chemotherapy and administered every 4 weeks thereafter. The principal endpoint was the proportion of patients with an AMH percent change ≤50% between 12 months after chemotherapy and basal levels. The secondary endpoint was the proportion of patients achieving postchemotherapy AMH levels above the threshold of 0.2 ng/mL. Results: Fifty patients were enrolled, 31 of whom had blood samples available at baseline and 1 year after the end of chemotherapy. AMH decreased to nearly undetectable levels after chemotherapy and recovered after 12 months, but they did not exceed 1 tenth of the pretreatment levels. As for the secondary endpoint, 15 of the 31 patients recovered AMH levels above the threshold. Conclusions: This study did not reach its principal endpoint; however, the rate of 48% of patients who recovered AMH above threshold levels favorably compared with those in studies without concurrent GnRHa, supporting a better recovery of AMH with triptorelin.

Bone Development in Transgender Adolescents Treated With GnRH Analogues and Subsequent Gender-Affirming Hormones.

ContextHormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual.ObjectiveTo describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones.DesignObservational prospective study.Subjects51 transgirls and 70 transboys receiving GnRHa and 36 transgirls and 42 transboys receiving GnRHa and gender-affirming hormones, subdivided into early- and late-pubertal groups.Main Outcome MeasuresBone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers.ResultsAt the start of GnRHa treatment, mean areal bone mineral density (aBMD) and BMAD values were within the normal range in all groups. In transgirls, the mean z-scores were well below the population mean. During 2 years of GnRHa treatment, BMAD stabilized or showed a small decrease, whereas z-scores decreased in all groups. During 3 years of combined administration of GnRHa and gender-affirming hormones, a significant increase of BMAD was found. Z-scores normalized in transboys but remained below zero in transgirls. In transgirls and early pubertal transboys, all bone markers decreased during GnRHa treatment.ConclusionsBMAD z-scores decreased during GnRHa treatment and increased during gender-affirming hormone treatment. Transboys had normal z-scores at baseline and at the end of the study. However, transgirls had relatively low z-scores, both at baseline and after 3 years of estrogen treatment. It is currently unclear whether this results in adverse outcomes, such as increased fracture risk, in transgirls as they grow older.

GnRHa for trigger and luteal phase support in natural cycle frozen embryo transfer – A proof of concept study

We aimed to explore whether ovulation induced by a GnRH analogue (GnRHa), followed by daily GnRHa luteal support provides an efficient platform for natural cycle frozen embryo transfer (NC-FET).In this cohort study, included were normo-ovulatory women who underwent NC-FET cycles, under the age of 40, with an antral follicle count > eight. Ovulation was triggered with triptorelin (0.2 mg Decapeptyl; Ferring), and luteal support was initiated two days later, using a Nafarelin inhaler (Synarel, Pfizer), 200 μg twice daily. Main outcome measures were luteal estradiol and progesterone levels (three to five days following ovulation), implantation rate, ongoing pregnancy rate, early pregnancy loss rate, and live birth rate.Fifty-one patients treated between 2017 and 2018 were included. Mid luteal progesterone levels among study patients, were non-significantly different between patients who achieved pregnancy and those who did not, but differed significantly on day 14 following ovulation (86.0 ± 31.3 vs. 9.8 ± 9.5 nmol/L, respectively, p < 0.001). Twenty-three patients achieved a clinical pregnancy (45.1 %); interestingly, there were no chemical pregnancies. Three pregnancies ended in an early abortion at 6–7 weeks gestation, and 20 pregnancies continued as ongoing pregnancies (39.2 %). One patient had a late abortion at 16 weeks gestation, and 14 had a live birth.In conclusion, in this proof of concept study, inducing ovulation with a bolus of GnRHa in NC-FET, followed by repeated daily GnRHa administration, resulted in satisfactory luteal phase steroid levels and high ongoing pregnancy and live birth rates.

GnRHa treatments of Atlantic Salmon broodstock suppresses effects of endocrine disruptors, benefitting offspring quality

The use of synthetic hormones to regulate sexual maturity in captive fish is a common practice. With aquaculture practices, fish production is desired throughout the year, necessitating the maintenance of quality standards, mainly regarding the characteristics of the fish produced. Embryonic development may be affected by toxins in the environment and by a variety of pathologies. The aim of this study was to determine the effects of treatment with gonadotropin-releasing hormone analog (GnRHa) on captive male and female Atlantic Salmon (Salmo salar) broodstock, observing the effects on the hormonal milieu and impacts on breeding outcomes. Sexually mature fish were fertilized with and without imposing a GnRHa treatment to evaluate the development of offspring up to the fry stage. The concentrations of 17β-estradiol (E2) and testosterone (T) were determined using commercially available ELISA kits. The results indicate the administration of GnRHa had marked effects on reductions of morphological deformities in the offspring and promoted development during the larval stage by inducing sexual maturity in both treated parents. The E2/T ratio results indicate the presence of endocrine disruptors. It is concluded that the use of GnRHa at a dose of 10 ug/kg in captive male and female Atlantic salmon broodstock has an inhibitory effect on the impacts of endocrine disruptors, does not affect fertilization rate, and has positive effects on development of offspring by reducing the number of morphological deformities during the larval stage of development.

Ovarian 25OH-vitamin D production in young women affected by polycystic ovary syndrome.

Vitamin D is involved in the regulatory mechanisms of ovarian function and is frequently low in PCOS patients. Since obesity and hyperinsulinemic state negatively influenced vitamin D levels, therefore, we evaluated the production of vitamin D at the ovarian level only in lean and normoinsulinemic PCOS subjects. Basal, GnRH analogue-induced ovarian production of 25OH-vitamin D (VitD) and a direct sampling at ovarian vein level were investigated. Basal and GnRH analogue-induced hormone levels were evaluated at peripheral level in 45 subjects, aged 18-39years, and in 22 healthy women with age- and BMI-matched as controls. In 12 PCOS patients, undergoing laparoscopy, a venous sampling at both peripheral and ovarian level was further done. All subjects presented low VitD levels, appropriate to the season and with no difference between PCOS and control subjects. GnRH analogue significantly stimulated plasma LH, FSH, 17-OHP and estradiol secretion (p from < 0.05 to < 0.001 vs basal levels), whereas no effect was observed on both serum AMH and VitD concentrations in all groups. A significant difference (p < 0.006), between peripheral and ovarian veins, was observed in both AMH and estradiol levels in PCOS subjects, while no gradient of VitD was detected. All patients presented with low VitD levels. The absence of any VitD variation, both at basal and after GnRH analogue administration, or at peripheral-ovarian vein gradient, suggests no pituitary-ovarian axis involvement in VitD production or its direct ovarian production in lean and normoinsulinemic PCOS subjects.

Adjuvant treatment strategies in ovarian stimulation for poor responders undergoing IVF: a systematic review and network meta-analysis.

Despite great advances in assisted reproductive technology, poor ovarian response (POR) is still considered as one of the most challenging tasks in reproductive medicine. The aim of this systemic review is to evaluate the role of different adjuvant treatment strategies on the probability of pregnancy achievement in poor responders undergoing IVF. Randomized controlled trials (RCTs) comparing 10 adjuvant treatments [testosterone, dehydroepiandrosterone (DHEA), letrozole, recombinant LH, recombinant hCG, oestradiol, clomiphene citrate, progesterone, growth hormone (GH) and coenzyme Q10 (CoQ10)] were included. Relevant studies published in the English language were comprehensively selected using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) until 11 July 2018. We included studies that investigated various adjuvant agents, including androgen and androgen-modulating agents, oestrogen, progesterone, clomiphene citrate, GH and CoQ10, during IVF treatment and reported subsequent pregnancy outcomes. The administration of GnRH analogs and gonadotrophins without adjuvant treatment was set as the control. We measured study quality based on the methodology and categories listed in the Cochrane Collaboration Handbook. This review protocol was registered with PROSPERO (CRD42018086217). Of the 1124 studies initially identified, 46 trials reporting on 6312 women were included in this systematic review, while 19 trials defining POR using the Bologna criteria reporting 2677 women were included in the network meta-analysis. Compared with controls, DHEA and CoQ10 treatments resulted in a significantly higher chance of clinical pregnancy [odds ratio (OR) 2.46, 95% CI 1.16 to 5.23; 2.22, 1.08-4.58, respectively]. With regard to the number of retrieved oocytes, HCG, oestradiol and GH treatments had the highest number of oocytes retrieved [weighted mean difference (WMD) 2.08, 0.72 to 3.44; 2.02, 0.23 to 3.81; 1.72, 0.98 to 2.46, compared with controls, respectively]. With regard to the number of embryos transferred, testosterone and GH treatment led to the highest number of embryos transferred (WMD 0.72, 0.11 to 1.33; 0.67, 0.43 to 0.92; compared with controls, respectively). Moreover, GH resulted in the highest oestradiol level on the HCG day (WMD 797.63, 466.45 to 1128.81, compared with controls). Clomiphene citrate, letrozole and GH groups used the lowest dosages of gonadotrophins for ovarian stimulation (WMD 1760.00, -2890.55 to -629.45; -1110.17, -1753.37 to -466.96; -875.91, -1433.29 to -282.52; compared with controls, respectively). CoQ10 led to the lowest global cancelation rate (OR 0.33, 0.15 to 0.74, compared with controls). For patients with POR, controlled ovarian stimulation protocols using adjuvant treatment with DHEA, CoQ10 and GH showed better clinical outcomes in terms of achieving pregnancy, and a lower dosage of gonadotrophin required for ovulation induction. Furthermore, high-level RCT studies using uniform standards for POR need to be incorporated into future meta-analyses.

Perbandingan Skala Nyeri Pasien Kista Endometriosis Dan Adenomiosis Sebelum Operasi, Setelah Operasi Dan Setelah Pemberian GNRH Analog

Background : Endometriosis is the growth of the epithelium and endometrial glands outside the uterine cavity. In endometriosis there is a process of neurogenesis and angiogenesis. The degree of endometriosis pain depends on the depth of endometrial implant infiltration in nerve fibers and / or neurogenesis. Operative action and postoperative hormone therapy are the main choices for preventing recurrence and reducing pain complaints. Purpose : to determine the comparison of pain scales of patients with endometriosis before surgery, after surgery and after administration of GnRH analogues. Method : This study was an observational analytic with a retrospective cohort design in the Obstetrics and Gynecology Clinic of RSUP Dr. M. Djamil Padang in June 2017 to January 2018. The sample size were of 35 people with inclusion and exclusion criteria. The inclusion criteria were the diagnosis of endometriosis (endometriosis cysts and adenomyosis) from ultrasonography and anatomical pathology, had surgery and received analogue GnRH injection three times. Exclusion criteria were not proven endometriosis, hysterectomy surgery, using analgesics and not following analogue GnRH injection procedures. The pain scale is assessed by the Wong-Baker Faces Pain Rating Scale. The pain scale is assessed during menstruation before surgery, first menstruation after surgery and first menstruation after three analogues of GnRH injections. Data analysis using SPSS version 22, where univariate analysis is used to see the characteristics of respondents and bivariate analysis using Wilcoxon Test. Statistical test results were significant if p &lt;0.05. Result : Based on the Wilcoxon statistical test results obtained p value = 0.0001 (p value &lt;0.05) which can be concluded that there is a significant reduction in the pain of endometriosis of patients after surgery compared to before surgery. Conclusion : There was a significant decrease in pain in endometriosis patients before surgery . Keywords: Endometriosis, Adenomyosis, Pain Scale, GnRH anaologist

Treatment of Breast Cancer With Gonadotropin-Releasing Hormone Analogs.

Although significant progress has been made in the implementation of new breast cancer treatments over the last three decades, this neoplasm annually continues to show high worldwide rates of morbidity and mortality. In consequence, the search for novel therapies with greater effectiveness and specificity has not come to a stop. Among the alternative therapeutic targets, the human gonadotropin-releasing hormone type I and type II (hGnRH-I and hGnRH–II, respectively) and its receptor, the human gonadotropin-releasing hormone receptor type I (hGnRHR-I), have shown to be powerful therapeutic targets to decrease the adverse effects of this disease. In the present review, we describe how the administration of GnRH analogs is able to reduce circulating concentrations of estrogen in premenopausal women through their action on the hypothalamus–pituitary–ovarian axis, consequently reducing the growth of breast tumors and disease recurrence. Also, it has been mentioned that, regardless of the suppression of synthesis and secretion of ovarian steroids, GnRH agonists exert direct anticancer action, such as the reduction of tumor growth and cell invasion. In addition, we discuss the effects on breast cancer of the hGnRH-I and hGnRH-II agonist and antagonist, non-peptide GnRH antagonists, and cytotoxic analogs of GnRH and their implication as novel adjuvant therapies as antitumor agents for reducing the adverse effects of breast cancer. In conclusion, we suggest that the hGnRH/hGnRHR system is a promising target for pharmaceutical development in the treatment of breast cancer, especially for the treatment of advanced states of this disease.