GnRH Analogue Research Articles

Girls with idiopathic central precocious puberty did not display substatial changes in body mass index after treatment with gonadotropin-releasing hormone analogues.

To evaluate changes in body mass index (BMI) in girls during and after treatment for idiopathic central precocious puberty (iCPP). We studied 123 girls receiving gonadotropin-releasing hormone analogue (GnRHa)treatment for iCPP from 2009 to 2019. Pubertal and anthropometric measurements were monitored at routine clinical visits. BMI standard deviation scores (SDS) were estimated at baseline and followed in two stages from baseline to end of treatment (median 18.9 months) and from end of treatment to end of follow-up (median 18.2 months). The influence of baseline BMI SDS and the frequency and dose of treatment was evaluated using BMI trajectories and latent class mixed models. The median age at treatment initiation was 8.5 years. The median BMI SDS at baseline was 0.7, corresponding to a median BMI of 17.4 kg/m2 . Overall, no changes in BMI SDS were observed during treatment. According to baseline BMI subgroups, an increasing trend in BMI trajectories during treatment was observed for girls in the lowest BMI group. After treatment, most girls maintained stable BMI levels. Our retrospective study did not provide evidence that GnRHa treatment for iCPP had a significant impact on BMI trajectories in girls.

Histomorphology of the ovaries of rabbits does during ovulation induced by the combined use of gonadotropins

Hormonal stimulation of folliculogenesis is a general method of increasing reproductive capacity in rabbits; however, studying the safety of the developed protocols remains an urgent scientific task. The use of hormonal agents is due to the physiological characteristics of rabbits, primarily coitus-dependent mechanisms of ovulation. Applying gonadotropin-releasing analogs depends on mature follicles ready for ovulation in the ovary. It, therefore, has limited effectiveness for rabbits of the “zero” cycle that have not yet given birth. Therefore, such females are recommended to use medications based on gonadotropins obtained from the serum of foal mares (eCG) or human chorionic gonadotropin (hCG). There is limited data on the combined use of gonadotropins, especially the long-term administration in different doses. Thus, the research aimed to conduct a morphological evaluation of rabbit's ovaries with combined serum and chorionic gonadotropins to stimulate folliculogenesis before artificial insemination to assess the safety of the proposed dosages and long-term administration. Stimulation of ovulation in rabbits of experimental groups was caused by the combined use of serum and chorionic gonadotropins (eCG – 400 IU; hCG – 200 IU) for experimental groups 1 and 2 at a dose of 40 IU and 24 IU, respectively. Females of the control group were induced to ovulate by subcutaneous injection of 0.2 ml of gonadotropin-releasing hormone analog. Ovaries were collected on the seventh day of gestation after the euthanasia of the rabbit with prior premedication. After dissection and macroscopic examination, the ovaries were fixed in a 10% aqueous solution of neutral formalin. Histological slides were made according to the general method by pouring in paraffin and subsequent staining with hematoxylin and eosin. The research has established that repeated (during five reproductive cycles) combined use of serum and chorionic gonadotropins has dose-dependent effectiveness and can cause dysfunction of ovaries and blood circulation. Pathological changes may acquire a systemic character with the manifestation of critical conditions for the health and life of rabbits. The stimulating effect of the combined use of eCG and hCG was detected at a dose of 40 IU, and the inhibition of folliculogenesis was observed at 24 IU. Since the premises for the hyperandrogenism were found microscopically, it was essential to investigate the level of androgens in the blood of rabbits after using a dose of 24 IU. At the same time, both doses of gonadotropins affect the reactivity of the endothelium, which is manifested by the presence of intravascular vesicles and changes in the rheological properties of blood.

Laparoscopic medulla-sparing ovarian tissue biopsy for cryopreservation: step-by-step surgical technique

To describe a laparoscopic technique for ovarian tissue biopsy (OTB) for fertility preservation. In the last years, the demand for fertility preservation has grown because of the increasing survival rates among patients with cancer and the rising awareness of the importance of quality of life after gonadotoxic therapy. Among fertility-sparing approaches, ovarian tissue cryopreservation is a valid strategy to preserve ovarian endocrine and reproductive function in prepubertal and postpubertal women who will undergo gonadotoxic cancer treatments. Currently, there is no universal consensus regarding ovarian tissue retrieval technique for fertility preservation. Step-by-step description of the surgical technique with narrated video footage. Academic tertiary hospital. Patients with a high risk of premature ovarian insufficiency, usually due to gonadotoxic treatments, who undergo OTB for fertility preservation were included in the study. In this video, we present the clinical case of a 28-year-old patient affected by Hodgkin lymphoma who underwent laparoscopy for OTB before chemotherapy. After exposing the chosen ovary, an incision at the tubal pole of the ovary is made with scissors. Through section and dissection, a large cortical biopsy of the ovary is performed without removing and avoiding any damage to the medulla. At the end of the procedure, hemostasis was achieved with selective coagulation using bipolar coagulation. Step by step educational video. The post-operative course was uneventful and the patient was discharge 24 hours after surgery. Standardization of a step-by-step laparoscopic technique can provide an effective method to optimize ovarian tissue removal while minimizing tissue injury. Medulla-sparing ovarian biopsy allows retrieval of only the cortical part of the ovary, maximizing the number of primordial follicles obtained without damaging the vascular supply of the ovary contained within the medulla. Primordial follicles are resistant to cryoinjury owing to their relatively inactive metabolism, and they are usually found at approximately 0.8 mm below the surface of the cortex. This technique could also reduce the back-table processing time of the ovarian tissue before cryopreservation. One disadvantage could be the difficulty of the technique compared to an oophorectomy because it requires a skilled surgeon that can easily find the cleavage plane between the medulla and the cortex, even in patients submitted to previous chemoradiotherapy or during gonadotropin-releasing hormone analogue therapy.

Evaluation of the Outcome of Interventions for Thoracic Endometriosis Syndrome at a Tertiary Level Health Institution in Southern Nigeria

Background: Thoracic Endometriosis Syndrome (TES) is a clinical condition characterized by the presence of endometrial tissue within the thoracic cavity, catamenial pneumothorax, catamenial haemothorax, catamenial haemopneumothorax, catamenial haemoptysis and or endometrial nodular lung mass. The management can be challenging as treatment is fraught with recurrence.
 Aim: To evaluate the outcome of interventions for Thoracic Endometriosis Syndrome.
 Methods: This was a prospective cross-sectional study of 14 patients with thoracic endometriosis syndrome who were managed at the university of Port Harcourt Teaching Hospital between August 1, 2017, and July 31, 2023. A proforma was used to collect data on socio-demographic characteristics, clinical presentation, type of intervention and evidence of recurrence of chest symptoms and entered into a spread sheet. Data analysis was done with SPSS version 28. Results are presented as frequency tables and percentages.
 Results: The age of the patients ranged between 20 and 44 years. Of the 14 patients, 11 (78.6%) were married, and 3 (21.4%) of the patients had established abdominal endometriosis with symptoms of thoracic endometriosis, while 4 (28.6%) had a histologic diagnosis of thoracic endometriosis. Pneumothorax was observed in 9 (64.23%) patients, 3 (21.43%) had haemopneumothorax, 2 (14.29%) with cyclical haemoptysis and haemothorax, and 4 (28.57%) of the patients had thoracic endometriotic nodules, while all the married patients had primary infertility. Twelve (85.7%) of the patients had closed tube thoracostomy drainage (CTTD) with chemical pleurodesis, while 4 (28.6%) had thoracotomy, decortication, bleb, and nodules resection with chemical pleurodesis. All the patients had hormonal therapy using luteinizing hormone-releasing hormone (LHRH) analogues. There was recurrence in 2 (14.3%) of the patients after a one-to-six-year period of follow-up.
 Conclusion: The treatment of TES using CTTD with pleurodesis, thoracostomy, decortication, bleb resection and or hormonal therapy with appropriate patient selection is effective as only two cases of recurrences were recorded.

Effect of GnRH analogs in advanced male breast cancer: 10-year experience from the Henan Breast Cancer Center and literature review.

Effect of GnRH analogs in advanced male breast cancer: 10-year experience from the Henan Breast Cancer Center and literature review.

Peptide Therapeutics: Unveiling the Potential against Cancer-A Journey through 1989.

The United States Food and Drug Administration (FDA) has approved a plethora of peptide-based drugs as effective drugs in cancer therapy. Peptides possess high specificity, permeability, target engagement, and a tolerable safety profile. They exhibit selective binding with cell surface receptors and proteins, functioning as agonists or antagonists. They also serve as imaging agents for diagnostic applications or can serve a dual-purpose as both diagnostic and therapeutic (theragnostic) agents. Therefore, they have been exploited in various forms, including linkers, peptide conjugates, and payloads. In this review, the FDA-approved prostate-specific membrane antigen (PSMA) peptide antagonists, peptide receptor radionuclide therapy (PRRT), somatostatin analogs, antibody-drug conjugates (ADCs), gonadotropin-releasing hormone (GnRH) analogs, and other peptide-based anticancer drugs are analyzed in terms of their chemical structures and properties, therapeutic targets and mechanisms of action, development journey, administration routes, and side effects.

Integrin αvβ3 and LHRH Receptor Double Directed Nano-Analogue Effective Against Ovarian Cancer in Mice Model.

The high mortality rate of malignant ovarian cancer is attributed to the absence of effective early diagnosis methods. The LHRH receptor is specifically overexpressed in most ovarian cancers, and the integrin αvβ3 receptor is also overexpressed on the surface of ovarian cancer cells. In this study, we designed LHRH analogues (LHRHa)/RGD co-modified paclitaxel liposomes (LHRHa-RGD-LP-PTX) to target LHRH receptor-positive ovarian cancers more effectively and enhance the anti-ovarian cancer effects. LHRHa-RGD-LP-PTX liposomes were prepared using the thin film hydration method. The morphology, physicochemical properties, cellular uptake, and cell viability were assessed. Additionally, the cellular uptake mechanism of the modified liposomes was investigated using various endocytic inhibitors. The inhibitory effect of the formulations on tumor spheroids was observed under a microscope. The co-localization with lysosomes was visualized using confocal laser scanning microscopy (CLSM), and the in vivo tumor-targeting ability of the formulations was assessed using the IVIS fluorescent imaging system. Finally, the in vivo anti-tumor efficacy of the formulations was evaluated in the armpits of BALB/c nude mice. The results indicated that LHRHa-RGD-LP-PTX significantly enhanced cellular uptake in A2780 cells, increased cytotoxicity, and hand a more potent inhibitory effect on tumor spheroids of A2780 cells. It also showed enhanced co-localization with endosomes or lysosome in A2780 cells, improved tumor-targeting capability, and demonstrated an enhanced anti-tumor effect in LHRHR-positive ovarian cancers. The designed LHRHa-RGD-LP-PTX liposomes significantly enhanced the tumor-targeting ability and therapeutic efficacy for LHRH receptor-positive ovarian cancers.

The effect of GnRH analog treatment on BMI in children treated for precocious puberty: a systematic review and meta-analysis.

The purpose of the present meta-analysis was to systematically evaluate the effect of GnRHa treatment on the BMI of children with precocious puberty after GnRHa treatment as compared to before, and to analyze the effect of GnRHa treatment on the body composition of children with precocious puberty at different BMIs by classifying into normal body mass, overweight, and obese groups according to BMI at the time of initial diagnosis. A meta-analysis was performed using Stata 12.0 software by searching PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), and Wan fang database for relevant literature on standard deviation score of body mass index (BMI-SDS) after GnRHa treatment as compared to before in children with precocious puberty. A total of eight studies were included with a total sample size of 715 cases, and the results of meta-analysis showed that BMI-SDS increased in children with precocious puberty after GnRHa treatment as compared to before starting [(weighted mean difference (WMD)=0.23, 95 % CI: 0.14-0.33, p=0.000)] and also increased in children with normal body mass [(WMD=0.37, 95 % CI: 0.28-0.46, p=0.000)], and there was no significant change in BMI-SDS in children in the overweight or obese group [(WMD=0.01, 95 % CI:-0.08-0.10, p=0.775)]. Overall, there was an observed increase in BMI-SDS at the conclusion of GnRHa treatment in children with precocious puberty. Additionally, it was found that the effect of GnRHa treatment on body composition varied among children with different BMI status. Clinicians should emphasize the promotion of a healthy lifestyle and personalized dietary managementfor children.

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.

Progestins for pituitary suppression during ovarian stimulation in artificial reproductive technology

Background: Progestins can suppress endogenous luteinizing hormone secretion from the pituitary gland. Progestins can be used orally and are less expensive than gonadotrophin-releasing hormone (GnRH) analogs. However, early endometrial exposure to progestin precludes fresh embryo transfer (ET), but the emergence of vitrification for oocyte cryopreservation cycles allows more opportunities for using progestins for pituitary suppression.
 Objective: To assess the mechanism of pituitary suppression by progestins, the effectiveness of progestins compared with GnRH analogs, the effect of progestins on oocyte and embryo developmental potential and euploidy status, and the cost-effectiveness of progestin-primed stimulation. 
 Methods: A literature search using the keywords “multiple waves of antral ovarian follicular development, In Vitro Fertilization, Ovarian stimulation ” was performed in the PubMed database.
 Results: The duration of stimulation, gonadotrophin consumption, and oocyte yield were similar in progestins and GnRH analogs. However, progestins were associated with significantly lower gonadotrophin consumption than their analogs. Overall, live birth and clinical pregnancy rates per ET were similar to those of progestins and GnRH analogs. Studies comparing medroxyprogesterone acetate, dydrogesterone, and micronized progesterone suggest similar ovarian responses and pregnancy outcomes. The euploidy status of embryos and obstetric and neonatal outcomes from progestin-primed cycles are similar to those of embryos from conventional stimulation cycles. Despite the lower cost of progestins than GnRH analogs, the mandatory cryopreservation of all embryos followed by a deferred transfer may increase the cost per live birth with progestins compared with an artificial reproductive technology cycle culminating in a fresh ET.
 Conclusion: Progestins present an effective option for women who do not contemplate a fresh ET, e.g., fertility preservation, anticipated hyper responders, preimplantation genetic testing, oocyte donors, and double stimulation cycles.

Pharmacological therapies for height improvement in pubertal children with short stature

Short stature in puberty significantly affects the physical and mental health of adolescents. The continuous acceleration of skeletal maturation, caused by sex hormones during puberty, limits the time available for growth and poses a considerable challenge for the treatment of short stature. To date, there is still no standardized treatment protocol for this disorder. However, puberty is the last period to improve the final adult height. Currently, commonly used pharmacological treatments in clinical settings include recombinant human growth hormone, gonadotropin-releasing hormone analogs, and third-generation aromatase inhibitors. In recent years, personalized treatment aiming to improve the final adult height has become a key focus in clinical practice. This article provides a comprehensive summary of research on pharmacological therapies for height improvement in pubertal children with short stature, offering valuable insights for healthcare professionals.

The Visual Effect of a Down-Regulation With Dienogest and GnRH Analogues in Endometriosis: Lessons Learned From Two-Step Surgical Approach

ObjectiveTo evaluate the intraoperative visual effect of treatment with GnRH-analogues and Dienogest in endometriosis. DesignRetrospective observational study. SettingEvery laparoscopy from all the different disciplines in our hospital is documented on video and stored in a database. The study was approved by the local ethics committee. A total of 193 patients with histological proven endometriosis from 2007 to 2021 were included, who underwent 2-step surgical procedure. Indications were endometrioma before CO2-Laser therapy, missing consent because of emergencies or other surgeries from other disciplines, or high active and extended disease. When endometriosis was suspected in a surgery conducted by other disciplines, a gynecological surgeon was called during the surgery. Data and intraoperative videos were reviewed by 2 independent reviewers at one referral center. Only cases with available video of first and second look laparoscopy were included. We excluded patient who had prior hormonal treatment in the last 6 months. Lesions were classified according to the description of Khan et al. Statistical analysis was performed using SPSS (Version 27.0, IBM). Mann-Whitney U test (nonparametric analysis) and χ2 tests were applied. Percentages were calculated for categorical variables and mean and standard deviation were calculated for continuous variables. Significance level was set to p <.05. InterventionsSeventy-seven received GnRH-analogues and 116 Dienogest for preoperative hormone down-regulation. The median duration of down-regulation with GnRH-analogues or Dienogest was 3 months. The mean age was 32.3 (SD 6.3) years for GnRH-analogues and 32.6 (SD 6.3) years for Dienogest, p = .619 respectively. The visible intraoperative effect will be demonstrated in the video. ConclusionThe effect of a hormonal treatment can be observed macroscopically in endometriosis. This can help to understand the in vivo response to the administrated treatment. This video is showing our past experience, as performing second-look laparoscopy is not state of the art anymore.

Comparison of gonadotropin-releasing hormone and estradiol benzoate plus gonadotropin-releasing hormone to initiate a progesterone-based timed artificial insemination resynchronization protocol in lactating dairy cows

The present study compared 2 strategies to initiate a progesterone (P4)-based timed artificial insemination (TAI) protocol for lactating dairy cows: only GnRH or estradiol benzoate (EB) plus GnRH (EB+GnRH). Lactating Holstein cows (n = 487; 184 primiparous and 303 multiparous) from 2 commercial dairy herds were used for their second or greater services postpartum. Each week, cows that were nonpregnant at the pregnancy diagnosis 32 d after a previous AI were randomly assigned to 1 of 2 experimental groups that differed only in the strategy to initiate (d 0) the TAI protocol. On d 0, every cow received a 2.0-g P4 implant; in the EB+GnRH group, cows were treated with 2.0 mg i.m. of EB and 16.8 µg i.m. of the GnRH analog buserelin acetate, whereas in the GnRH group, cows received only 16.8 µg i.m. of GnRH. On d 7 after the initial treatment, 0.530 mg i.m. of cloprostenol sodium (PGF) was administered in all cows, followed by a second dose on d 8, concomitant with 1.0 mg i.m. of estradiol cypionate and P4 implant withdrawal. The TAI was performed on d 10 (48 h after P4 device withdrawal) in both experimental groups. Only conventional Holstein semen was used throughout the study. The percentage of cows with corpus luteum (CL) on d 0 (73%) and overall ovulation rate after d 0 (54%) did not differ between groups. The CL regression between d 0 and the first PGF treatment was greater in the EB+GnRH group than the GnRH group (42% vs. 31%). Consequently, the proportion of cows with CL at PGF was greater when only GnRH was used on d 0 compared with EB+GnRH (86% vs. 82%), and the mean number of CL at PGF was greater (1.23 vs. 1.11). The expression of estrus near TAI was greater in GnRH group (84% vs. 77%), and cows showing estrus had greater (44% vs. 10%) pregnancy per AI (P/AI) on d 32 for both treatments. We found no effect of the presence of CL on d 0 or at PGF, nor of ovulation after d 0 or CL regression between d 0 and d 7 on fertility. However, fertility was critically impaired when cows did not have CL at both times, d 0 and at PGF treatment. We did not observe any interaction between treatment and other variables, and the P/AI was similar in cows receiving EB+GnRH or only GnRH on d 0 (37.8% vs. 36.6%). In summary, although there was no detectable difference in P/AI between treatments, this study demonstrated potential negative physiological outcomes caused by EB treatment on d 0 (greater incidence of luteolysis after d 0 and fewer cows with CL at PGF treatment). Overall, we found no benefit of adding EB at the initiation of a P4-based TAI protocol on fertility compared with using GnRH alone, despite differences in ovarian dynamics and expression of estrus.

Central Precocious Puberty in Italian Boys: Data From a Large Nationwide Cohort.

There are only a few nationwide studies on boys with central precocious puberty (CPP) and the last Italian study is a case series of 45 boys that dates back to 2000. We aimed to evaluate the causes of CPP in boys diagnosed during the last 2 decades in Italy and the relative frequency of forms with associated central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) compared to idiopathic ones. We performed a national multicenter retrospective study collecting data from 193 otherwise normal healthy boys with a diagnosis of CPP. Based on MRI findings, the patients were divided into: Group 1, no CNS abnormalities; Group 2, mild abnormalities (incidental findings) unrelated to CPP; and Group 3, causal pathological CNS abnormalities. The MRI findings show normal findings in 86%, mild abnormalities (incidental findings) in 8.3%, and causal pathological CNS abnormalities in 5.7% of the cases. In Group 3, we found a higher proportion of patients with chronological age at diagnosis < 7 years (P = .00001) and body mass index greater than +2 SDS (P < .01). Gonadotropin-releasing hormone analogue therapy was started in 183/193 subjects. The final height appeared in the range of the target height in all groups and in 9 patients in whom the therapy was not started. In our study on a large nationwide cohort of boys referred for precocious puberty signs, the percentage of forms associated with CNS abnormalities was one of the lowest reported in the literature.

Peak serum luteinising hormone cut-off during gonadotropin-releasing hormone analogue test for diagnosing central precocious puberty was lower in girls with obesity as compared with girls with normal weight.

Serum luteinising hormone (LH) concentration has been reported to be lower in girls with overweight and obesity (OW/OB) as compared with girls with normal weight (NW). This study aimed to evaluate peak serum LH concentration during gonadotropin-releasing hormone analogue (GnRHa) test in girls with OW/OB and NW who had central precocious puberty (CPP) and to determine peak serum LH cut-off for diagnosing CPP in girls with OW/OB. Medical records of 971 girls with premature breast development who underwent subcutaneous GnRHa (100 µgof triptorelin acetate) test were reviewed. All girls were classified as either CPP or premature thelarche. All of them were further classified into two groups according to their body mass index as NW and OW/OB groups for each Tanner stage. There were 634 and 337 girls in NW and OW/OB groups, respectively. CPP was diagnosed in 600 girls (249 had Tanner stage II and 351 had Tanner stage III). There were no differences in peak serum LH concentrations between CPP girls with NW and OW/OB. Peak serum LH cut-off of 5 IU/L (the current widely used cut-off) had a sensitivity and a specificity of 75% and 90%, respectively in NW group. Peak serum LH cut-off for CPP diagnosis was lower at 4 IU/L in the OW/OB group with greater sensitivity and specificity of 86% and 93%, respectively. The results were reproducible for each Tanner stage of breasts. Lower peak serum LH cut-off to 4 IU/L for diagnosing CPP in girls with OW/OB should be considered to avoid underdiagnosis of the condition.

Unification and orificing of two functional noncommunicating uterine horns through the created neovagina using peritoneum

ObjectiveTo demonstrate the surgical approach for Müllerian agenesis with bilateral uterine remnants containing functional endometrium. DesignStepwise demonstration of the technique with narrated video footage SettingA Tertiary University Hospital, Reproductive Surgery Unit. PatientAn 18-year-old adolescent was admitted to a tertiary university hospital with complaints of primary amenorrhea and cyclic pelvic pain. Physical examination and MRI scans suggested a complex Müllerian abnormality. The patient had uterine remnants with bilateral functional endometrium and cervico-vaginal agenesis. InterventionAn operation was planned to reconstruct her anatomy by providing a neovagina and anastomosing the uterine remnants. GnRH analogs were prescribed to suppress her menstruation until the procedure. The operation was performed in the third month after the initial diagnosis. A laparoscopy was conducted, revealing approximately 5x6 cm bilateral uterine horns with healthy adnexa.As the first step, a neovagina was created using a modified peritoneal pull-down technique, a standard approach in our clinic. A vaginal incision was made, and a blind vaginal dissection was performed to reach the peritoneum vaginally. Subsequently, an acrylic vaginal mold was inserted. The vaginal orifice was laparoscopically incised using ultrasonic energy with guidance from the inserted vaginal acrylic mold. The orifice was gradually dilated with larger molds. The entire pelvic peritoneum was dissected circularly, and the distal part of the dissected peritoneum was pulled down using four 2.0 Vicryl sutures at 0, 90, 180, and 270 degrees from the opened vaginal orifice. The uterine cavities of both remnants were incised, and two separate Foley catheters were placed in both cavities. A mold with a hole was used to insert the catheters through the vagina. Both catheters were secured in the cavities with Prolene sutures pulled up from the anterior abdominal wall.The next step involved uterine anastomosis. The uterine remnants were unified through continuous suturing, resulting in the formation of a normally shaped uterus. In the final step, the created uterus and neovagina were anastomosed. The patient received instructions on how to perform mold exercises and follow-up care. Main Outcome MeasureDescription of a laparoscopic management of a rare mullerian abnormality. ResultsThe postoperative MRI scan at one month revealed healed unified uterine cavities and vagina. The patient experienced spontaneous menstruation in the second month after surgery and now maintains regular menses with an approximately 9-10 cm functional vagina. Within three months after surgery, the VAS (visual analog scale) scores for chronic pelvic pain and dysmenorrhea decreased from 9 to 2-3. ConclusionsMüllerian abnormalities are exceptionally rare, and their spectrum is broad, making it challenging to identify an exact surgical method to restore functional anatomy. Therefore, a customized surgical approach should be designed for each patient based on their unique condition.

Progestin-primed ovarian stimulation.

The use of progestins as pituitary suppressors has increased progressively, along with more detailed indications for their use, thereby consolidating an alternative approach to the personalization of ovarian stimulation. Based on the ability of progesterone to inhibit ovulation, progestins have been used in ovarian stimulation (OS) follicular protocols to prevent a luteinizing hormone surge in patients undergoing in vitro fertilization (IVF), as an alternative to gonadotropin-releasing hormone (GnRH) analogue administration. This review explores the different types of progestogen protocols and their efficacy depending on the type of population or reproductive procedure in which they are administered and in comparison with that of GnRH analogues. Their effect on oocytes and embryos and their safety and cost-effectiveness are also analyzed. Progestins have proven their effectiveness as a gonadotropin adjuvant in terms of ovarian response, reproductive outcome, and safety. In addition, they offer the convenience of oral administration and a lower cost than GnRH analogues. Whereas oocytes or embryos should be vitrified as it displaces the receptive period with the consequent asynchrony between embryo and endometrium. The evidence endorses progestins as a more friendly approach to OS, especially when frozen-thawed embryo transfer is planned.

Sex differences in the cardiovascular effects of GnRH analogues.

The integral role of the hypothalamic-pituitary-gonadal axis in reproductive processes makes it a prime therapeutic target. By inhibiting sex steroid synthesis, gonadotropin-releasing hormone (GnRH) analogues are used in the management of cancers, benign neoplasms, infertility and gender dysphoria. However, the wide application of these therapeutics raises concerns regarding the unintended effects upon the cardiovascular system. In males with prostate cancer, GnRH analogues when used as an androgen deprivation therapy appear to increase the risk of cardiovascular disease, which is the leading cause of death in this population. Therefore, due to the utilisation of GnRH analogues across the lifespan and gender spectrum, this relationship merits discussion. Existing data suggest an association between GnRH analogues and major adverse cardiovascular events in males. Conversely, females receiving GnRH analogues for breast cancer treatment appear to be at an increased risk of developing hypertension. In this narrative review, we describe the uses of GnRH analogues in adults, adolescents and children. We discuss whether sex plays a role in the cardiovascular effects of GnRH analogues and explore the significance of sex hormone receptors in the vasculature. We also consider confounding factors such as malignancy, advanced age and infertility.

The effect of gonadoliberin analog treatment in precocious puberty on polycystic ovarian syndrome prevalence in adulthood.

The study group consists of 24 women (median age 22 88 years, median BMI 23.5) treated with GnRHa for central precocious puberty in childhood. The control group includes 40 women (median age 23 years, median BMI 25.6) diagnosed with isolated premature thelarche and not using GnRHa in the childhood. Anthropometric measurements, ultrasound examination of minor pelvis and hormonal profile were performed. PCOS diagnosis was based on Rotterdam criteria. The study confirmed a higher prevalence of PCOS in the study group (50%) than in the control group (10%); p=0.0006. Significant, linear correlation between free testosterone levels and ovarian size was found in the study group (R=0.45 p= 0.03). GnRHa therapy during childhood may have a potential influence on incidence of PCOS in the adulthood. Therefore, in this group of patients long-term follow-up focused on screening for PCOS would seem beneficial.

The effect of gonadotropin-releasing hormone analog treatment on the endocrine system incentral precocious puberty patients: a meta-analysis.

Gonadotropin-releasing hormone (GnRHa) is the first choice for the treatment of patients with central precocious puberty (CPP). However, the effects of GnRHa on the endocrine system of CPP patients, including insulin sensitivity, lipid level, thyroid function, bone mineral density (BMD), and testosterone (T)level, are currently contradictory. Therefore, the long-term safety of GnRHa therapy remains controversial. A systematic literature search was performed using PubMed, Embase, Cochrane Library, and CNKI databases. The changes in HOMA-IR, TG, LDL-C, HDL-C, TSH, FT3, FT4, T, and BMD in CPP patients before and after GnRHa treatment were compared by meta-analysis. As the heterogeneity between studies, we estimated standard deviation mean differences (SMDs) and 95 % confidence intervals (CIs) using a random-effects model. Egger's test was used to assess publication bias. A total of 22 studies were included in our meta-analysis. Compared with before GnRHa treatment, there were no statistically significant differences in endocrine indicators including HOMA-IR, TG, LDL-C, HDL-C, TSH, FT4, FT3, T, and BMD of CPP patients treated with GnRHa. Treatment with GnRHa for central precocious puberty will not increase the adverse effect on the endocrine system.