This study aimed to conduct computer searches in PubMed, Web of Science, Embase, the Cochrane Library, CNKI, VIP, Wanfang, and CBM databases. Literature was screened and data extracted according to the inclusion and exclusion criteria. RevMan 5.3 was used to assess the methodological quality of the included studies, while Stata 14.0 was employed to rank the efficacy and safety of the five interventions. This analysis included 20 randomised controlled trials involving a total of 2,400 patients. The cumulative probability ranking results showed that, for improving clinical pregnancy rate (CPR), leuprorelin (97.8%) ranked highest, followed by cetrorelix (70.7%), triptorelin (47.9%), buserelin (18.2%), and ganirelix (15.3%). For improving the live birth rate (LBR), leuprorelin (99.9%) ranked highest, followed by triptorelin (44.1%) and cetrorelix (5.9%). For reducing the incidence of ovarian hyperstimulation syndrome (OHSS), cetrorelix (96.9%) ranked highest, followed by buserelin (58.7%), ganirelix (57.5%), leuprorelin (21.2%), and triptorelin (15.7%). Cetrorelix demonstrated superior performance in reducing the risk of OHSS, while leuprorelin was more effective in improving CPR and LBR. For women with polycystic ovary syndrome at high risk of OHSS, cetrorelix is recommended. For patients with the primary goal of improving CPR or LBR, leuprorelin is the more appropriate choice. Key Words: Polycystic ovary syndrome, Infertility, GnRH agonist, GnRH antagonist, Assisted reproduction.

A woman in her 20s developed IgA vasculitis with nephritis (IgAVN), which started four days after oocyte donation (for in-vitro fertilisation (IVF) and transfer to another recipient). Prior to oocyte retrieval, the patient received a course of controlled ovarian stimulation (COS) with menotrophin, ganirelix acetate and choriogonadotropin alfa. Four days after COS, she developed a painful purpuric rash alongside knee pain and swelling. Prednisolone was started for presumed IgA vasculitis. Soon after, she developed de novo mononeuritis multiplex and renal dysfunction characterised by haematoproteinuria and nephrotic syndrome. A kidney biopsy confirmed the diagnosis of IgAVN. Symptoms improved over time; however, there remained questions about the possible trigger. The induced sex hormone changes associated with COS may have had an immunomodulatory effect, leading to disease development.

Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems. These characteristics qualify GnRH antagonists as revolutionary therapy for diseases such as advanced prostate cancer, endometriosis, uterine fibroids, and in vitro fertilization procedures. Key GnRH peptide antagonists authorized by the regulatory agencies include Cetrorelix, Ganirelix, Abarelix, Degarelix, and Teverelix. Assisted reproductive technologies (ART) are dominated by Cetrorelix and Ganirelix, while Degarelix and Abarelix have shown significant promise in treating advanced prostate cancer. Teverelix appears as a next-generation GnRH antagonist with an ideal mix of efficacy and safety, showing promise in a variety of reproductive and hormone-dependent illnesses. This review investigates the pharmacological role of GnRH in reproductive physiology and its consequences in disease, emphasizing structural advances in third- and fourth-generation GnRH antagonists. All GnRH peptide-based antagonists were analyzed in detail for formulation strategy, pharmacokinetics, effectiveness, and safety. This review also emphasizes GnRH antagonists' clinical promise, providing insights into their evolution and the possibility for future research in developing safer, more effective treatments for complicated hormonal diseases.

Non-obstructive azoospermia (NOA) is the most severe form of male factor infertility. It results form from either primary or secondary testicular failure. Here, we report cases of two patients with NOA due to maturation arrest and increased serum FSH, treated with GnRH agonist and gonadotrophins. The two NOA patients underwent a pharmacological treatment consisting of pituitary desensibilization using a GnRH agonist and testicular stimulation using menotropin. Testicular stimulation started one month after the beginning of GnRH agonist treatment. The female partner underwent controlled ovarian stimulation (COS) followed by intracytoplasmic sperm injection (ICSI). On the third day of the cycle, menotropin daily doses was administered. When at least one follicle ≥14 mm was visualized, pituitary blockage was performed using GnRH antagonist ganirelix. When three or more follicles attained a mean diameter of ≥17 mm, triptorelin acetate was administered to trigger final follicular maturation. Oocyte retrieval was performed 35 hours later. After treatment, male partner blood levels of the FSH, LH, decreased and total testosterone were increased. Spermatozoa was observed after semen collection in both cases. After COS, oocytes were retrieved and ICSI was performed. Embryos were biopsied for preimplantation genetic testing (PGT) and those considered euploidy were transferred resulting in positive implantation, ongoing pregnancy, and livebirth on both cases. In this report we present a successful strategy for hypergonadotropic hypogonadism AOA men, as an alternative approach to the surgical testicular sperm recovery. Nevertheless, prospective randomized trials are needed to confirm our findings.

The concept of extractables and leachable has introduced a new era for identifying potential impurities in drug products. Pharmaceutical packaging materials encompass a variety of polymers due to their appealing properties for storing the drug product. However, numerous chemical species may leach into the drug product from these polymers, posing significant health hazards in the public domain. Identifying such leachable is crucial for assessing safety and addressing toxicological concerns. Acrylic acids are commonly used materials for adhering needles to the barrel in pre-filled syringes. In this study, we identified acrylic acid leachable impurities in ganirelix drug products available in the market using mass spectrometry as an analytical technique. These impurities leached into the drug product during storage conditions. Characterization of the impurities was carried out through data obtained from HRMS and MS/MS analysis, revealing them as polyacrylic acid-ganirelix adduct impurities. This study offers valuable insights into identifying leachable and susceptible sites, providing a foundation for potential modifications in similar classes of drug products, thereby enhancing their safety and efficacy.

Luteinizing hormone (LH) is present throughout the natural follicular phase. However, the debate is still not settled on whether LH is needed during ovarian stimulation in IVF. This commentary looks at the evolution of this debate, mentioning three elephants in the room that were ignored by the Pharma industry, professional organizations, and clinicians alike: 1. The different endocrinology between the long agonist and the antagonist protocols. 2. The fixed dose of the two most widely commercially available antagonist preparations, namely cetrorelix and ganirelix. 3. The fact that most research in this area uses population-based criteria, ignoring endocrine parameters. Individual genetics of the LH receptor gene may also serve to individualize LH needs during stimulation; however, the jury is still out regarding this approach. CONCLUSIONS: Individual endocrine and genetics parameters may shed meaningful light on the question of LH supplemental during ovarian stimulation.

Ganirelix, a peptide-based drug used to treat female infertility, has been in high market demand, which attracted generic formulation. A hitherto unknown impurity of ganirelix was observed in our formulation process, which reached ~0.3% in 6 months and led to a detailed investigation of its structure. In-depth analysis of ESI-MS/MS data of this impurity coupled with an artificial intelligence prediction tool led to a highly unusual putative structure, that is, N-(2-carboxyethyl)-ganirelix ([N]CE-GA), which was authenticated by chemical synthesis from ganirelix and NMR analysis and via corroborated HPLC and MS/MS data with the formulation-derived impurity.