GnRH Analogue Research Articles

Patient diagnosed with acromegaly and pituitary apoplexy after breast carcinoma treatment: challenges in diagnosis and management

The clinical case presented describes a 44-year-old woman with a history of mucinous carcinoma in the right breast, who is diagnosed with a pituitary adenoma. Physical examination revealed signs of acromegaly, such as macroglossia and palmar hyperhidrosis. Hormonal tests were performed and showed elevated levels of insulin-like growth factor type 1 (IGF-1). The patient received GnRH analogues for breast cancer; and started medical treatment with somatostatin analogues for acromegaly, which provided improvement in symptoms. Pituitary bleeding was detected during hormone treatment, which caused the growth of the adenoma, causing it to contact the optic chiasm, although no symptoms of pituitary apoplexy were present. Transsphenoidal endoscopic surgery was performed to remove the adenoma, and the diagnosis of pituitary adenoma was confirmed by pathology. The importance of the evaluation of comorbidities in patients with acromegaly is discussed. Pituitary apoplexy as an uncommon complication of pituitary adenomas, which may be associated with the use of GnRH analogues, is addressed. Pre-surgical medical treatment in acromegaly is also discussed, highlighting the importance of a comprehensive assessment of prognostic factors and appropriate treatment selection to improve clinical outcomes. In conclusion, the importance of a multidisciplinary and personalized approach in the management of patients with GH-producing pituitary adenomas to improve quality of life and clinical outcomes is highlighted.

Dienogest versus gonadotropin-releasing hormone analogues for the clinical treatment of endometriosis: an updated meta-analysis

Endometriosis is a chronic gynecological condition where endometrial-like tissue grows outside the uterus, leading to persistent pelvic pain, dysmenorrhea, dyspareunia, and infertility. The objective of the systematic review was to examine the efficacy and safety of Dienogest, which is a synthetic, orally active 19-nortestosterone derivative, in the treatment of women with endometriosis compared to GnRH-a, which is commonly used to treat conditions like endometriosis. We conducted a search of PubMed, Google Scholar, and Cochrane Library databases from inception until August 2024 for clinical studies, using the following keywords: ("Dienogest") and ("gonadotropin-releasing hormone analogue" or GnRH Analogues OR GnRH agonist) and (Endometriosis). Relevant randomized control trials were identified. Pooled effect estimates were calculated using a random effect model. This meta-analysis included eight randomized controlled trials (RCTs) with 1,219 patients, 602 in the dienogest group and 617 in the GnRH analogue group. Both treatments were equally effective in controlling pain, dysmenorrhea, and dyspareunia, but dienogest offered advantages. Dienogest significantly reduced the recurrence rate (RR: 0.37, 95% CI [0.15, 0.91]; p=0.03) and hot flushes (RR: 0.24, 95% CI [0.10, 0.59]; p=0.002) and protected against bone mineral density (BMD) loss. However, it increased the risk of irregular vaginal bleeding (RR: 3.61, 95% CI [1.09, 11.97]; p=0.04). Other side effects, such as headache, vaginal dryness, spotting, and alopecia, were not statistically significant. It concluded that Dienogest has comparatively fewer side effects than GnRH analogue, making it a considerably safer option for treating endometriosis.

Adult Height in Girls with Central Precocious Puberty with Onset after 6 Years: Effects of Gonadotropin-releasing Hormone Analog Therapy.

Precocious puberty (PP), which is sometimes divided into gonadotropin-dependent or gonadotropin-independent precocious puberty, is a pathological condition characterized by premature secretion of gonadal steroids resulting in the early development of secondary sexual characteristics. Girls younger than 6 years with idiopathic gonadotropin-dependent precocious puberty (referred to as central PP or CPP) who receive gonadotropin-releasing hormone analog (GnRHa) therapy experience an increase in their adult height (AH) in contrast to girls who are aged 6 years or more, who show no consistent pattern of increase even with GnRHa therapy. In total, 133 girls aged 6 years or more who visited any one of the seven study centers between April 2000 and March 2020 and who met the diagnostic criteria for PP in Japan were retrospectively examined. The participants were divided into a treatment (n=56) and no-treatment group (n=77). The AH and target height (TH) were compared between the groups, and the factors influencing the AH were examined. The patients receiving GnRHa therapy achieved significantly greater increase in their AH, AHTH, and predicted adult height at the age of 6, 7, and 8 years (6 ≦ years < 9) than those without the treatment. The TH and height at the start and end of treatment influenced the AH of the former group. GnRHa therapy was effective in improving the AH in girls with CPP onset at the age of 6, 7, or 8 years. The TH was a strong determinant of the AH.

Hormonal suppression in premenopausal patients with estrogen receptor-positive breast cancer: a randomized trial comparing monthly versus trimonthly GnRH analogs

Background: Currently the standard of care for premenopausal women with estrogen receptor-positive breast cancer is the combined use of a gonadotropin-releasing hormone (GnRH) analog with either tamoxifen or an aromatase inhibitor in patients at high risk for relapse or when it is deemed necessary to optimize ovarian function suppression. Monthly GnRH analogs have been used for years but, recently, longer-acting formulations have been gaining approval. Yet, there is still a gap of evidence regarding the use of longer-acting formulations; only a few studies exist that examine their efficacy in breast cancer and compare them to the monthly formulations. It is the investigators’ hypothesis that trimonthly injections, which are more convenient for the patient and ensure better compliance, are better suited for use in breast cancer patients and may induce equally effective estrogen suppression as the monthly injections. Aim: A comparison of trimonthly versus monthly GnRH analogs in eliciting ovarian function suppression in premenopausal patients with estrogen receptor-positive breast cancer. Methodology: This is a prospective randomized open-label trial involving 25 premenopausal patients that were randomized to receive either a monthly or a trimonthly GnRH analog. Estrogen (E2) levels, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured on day 0 and on week 12. Patients, also, completed a questionnaire regarding exhibiting amenorrhea and other side-effects of the analogs. Results: All patients (N=25; 100%) from both groups achieved ovarian function suppression according to the criteria set by the researchers, which are E2 levels &lt;30 pg/mL and amenorrhea. Both groups exhibited a statistically significant decrease (almost by 50%) in E2 levels by week 12 (monthly group: E2 levels’ decrease equal to -18.5 pg/mL, p=0.00293; trimonthly group: E2 levels’ decrease equal to -13.9 pg/mL, p=0.0002441). On the contrary, FSH and LH levels did not show a statistically significant difference in either group. Moreover, when the two groups were compared, there was no statistically significant difference in the variation of all hormone levels between day 0 and week 12. All patients developed amenorrhea. There were no statistically significant differences in the number of side-effects between the two groups, even though the trimonthly group had fewer (in absolute number) side-effects than the monthly. Conclusion: This study demonstrates that the trimonthly formulations of GnRH analogs are equally effective in eliciting ovarian function suppression and present a similar percentage of side-effects as the monthly formulations, with the added benefit that patients need not undergo monthly injections.

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.

Clinical and Genetic Mechanisms in Patients with MC2R Deficiency Presenting with Early Puberty.

Melanocortin receptor 2 (MC2R) in the adrenal cortex controls the hypothalamic-pituitary-adrenal axis. The melanocortin system, influenced by leptin, regulates GnRH neurons, crucial for puberty onset and fertility. This study evaluates early puberty in primary adrenal insufficiency (PAI) patients due to MC2R gene alterations. Seven patients with PAI (P1-P7) from five unrelated families, all presenting with early or precocious puberty, were included. MC2R deficiency diagnosis ranged from 1 day to 11 months. MKRN3, DLK1, KISS1, and KISS1R genes were analyzed using Sanger sequencing in four cases (P2,P4,P6 and P7). All clinical data were obtained retrospectively. Puberty onset mean age was 8.6 years (7.4-9.5) in boys (P1, P2, P3, P7) and 8.5 years (7.4-9.5) in girls (P4, P5, P6). Tumor markers were negative; no adrenal rest or tumors were found. GnRH analogs were used for rapid puberty in P2, P3, P6. Final height in P1 and P2 was below target (-2.6 SDS, -0.7 SDS). Menarche occurred at 11 and 11.3 years in P4 and P5. No pathogenic variants were found. Genetic causes of early puberty were not identified. Elevated ACTH may stimulate kisspeptin neurons, triggering puberty. Close monitoring of these patients for pubertal development is recommended.

Current and future medical treatment for endometriosis

Endometriosis is a chronic, progressive inflammatory disease that occurs in approximately 10% of women of reproductive age, resulting in a decreased quality of life due to dysmenorrhea, chronic pain, and other problems. The primary treatment is pain control and fertility preservation, and while preserving ovarian function through drug therapy and surgery, assisted reproductive technology (ART), including in vitro fertilization (IVF), is also utilized. Hormonal therapies such as low-dose estrogen/progestin (LEP), progestins, and GnRH analogs are often the drug of choice. We presented that IAP (inhibitor of apoptotic protein) inhibitors can potentially be novel agents for treating endometriosis. Our studies using cultured cells derived from human endometriotic lesions and mouse models have revealed that inflammatory cytokines and antiapoptotic factors (IAPs) produced by peritoneal macrophages or endometriosis cells are crucial and that NF-κB (nuclear factor-kappa B) plays a central role in the pathogenesis of endometriosis. The high expression of IAPs in human endometriotic tissues, its facilitative role in ectopic survival, and the effect of IAPs on drug-resistant apoptosis of human endometriotic cells indicate its potential as a novel drug for IAP inhibitors. We found that the medicinal herb parthenolide and selective estrogen receptor modulators (SERM) can reduce lesions through NF-κB inhibition. Recently, new findings were obtained by non-invasive observation of early lesions using bioluminescence technology and by applying knockout mouse models. We will show the possibility of new therapeutic agents for endometriosis.

Factores que influyen en la inseminación artificial con semen fresco en alpacas (&lt;i&gt;Vicugna pacos&lt;/i&gt;)

The aim of the study was to evaluate factors that affect the fertility of artificial insemination (AI) with fresh diluted semen in alpacas. In Exp. 1, females with preovulatory follicles with diameters ≥7-≤ 9 or ≥10-≤12 mm were inseminated; in Exp. 2 the females were inseminated at 24, 26, 28 and 30 h after ovulation induction; In Exp. 3, alpacas were inseminated with semen at four concentrations: 15, 25, 35 and 45x106 sperm/ml; and in Exp. 4, using the best results from the previous experiments, 350 alpacas were inseminated in two peasant communities. Semen was collected by the post-copulatory method, using ejaculates with motility ≥60%, diluted in Tris-glucose-citric acid and egg yolk. Alpacas with preovulatory follicles ≥7 mm were selected for AI. Ovulation induction was done with a GnRH analogue and pregnancy diagnosis was made 30 days after service. Pregnancy rate was not affected by follicular size. AI 24 to 26 h after ovulation induction obtained a higher pregnancy rate (50 and 55%, respectively; p&lt;0.05) compared to those inseminated at 28 and 30 h (35 and 30%). AI with 15x106 sperm/ml resulted in low pregnancy rates (30%) compared to 35 and 45x106 sperm/ml (50 and 55%, respectively). In the peasant communities, 55% pregnancy rate was obtained. The results suggest that the success of AI with fresh semen in alpacas is highly dependent on sperm dose and timing of insemination.

Are gonadotropin-releasing hormone analogues effective for treatment of pain due to endometriosis?

Are gonadotropin-releasing hormone analogues effective for treatment of pain due to endometriosis?

Vaginal cytology during the estrous cycle and early pregnancy of ewes

Changes in vaginal epithelial cells and blood progesterone and estrogen concentrations were compared between estrous cycle and early pregnancy in multiparous Sanjabee ewes. Twenty non-pregnant ewes were synchronized with intravaginal insertion of a controlled internal drug release (CIDR) device which was in place for 7 days, intramuscular administration of a GnRH analog (Alarelin acetate; 12.5 µg) at the time of CIDR insertion (Day -7), a PGF2α analog (D-cloprostenol sodium; 125 µg) and 500 I.U. of human chorionic gonadotropin (hCG) at the time of CIDR removal (Day 0). At Day 0, all ewes were introduced to four fertile rams and observed for estrous signs. Ewes exhibiting estrous signs were divided into two groups: MATED (confirmed pregnant with transrectal ultrasound scanning at Day 35) and NOT-MATED (confirmed non-pregnant with transrectal ultrasound scanning at Day 35). Vaginal smears and blood samples were taken daily and every other day, respectively, from the beginning of estrus for 20 days for cytology and hormone assay. Based on the results, during days 0 and 1 of the estrous cycle, only the percentages of intermediate cells differed between the groups (P &lt; 0.05). During days 2 to 4, there was no difference in the cell populations between the groups (P ≥ 0.05). During days 5 to 16, the percentages of all cell types except the parabasal cells differed between the groups (P &lt; 0.05). During days 17 to 20, the percentages of all types of vaginal epithelial cells differed between the groups (P &lt; 0.05). Progesterone concentrations increased gradually from days 0 to 14 of the estrous cycle in both groups, however, they decreased significantly afterward in the NOT-MATED group. Estrogen concentrations changes showed an opposite pattern to that of progesterone in the study groups. Collectively, vaginal cytology can be used as a useful tool in assessing hormonal and physiological characteristics of the female reproductive system and thus provides a more accurate understanding of the physiology of estrous cycle and early pregnancy in ewes, which can be used to improve reproductive management.

Comparative evaluation of the efficacy of three GnRH analogues in induced breeding of stinging catfish, Heteropneustes fossilis under hatchery conditions

Evaluating the breeding performance of cultivable fish using gonadotropin-releasing hormone (GnRH) analogues is crucial for optimizing reproductive efficiency and enhancing the sustainability of aquaculture practices. However, there is a lack of understanding regarding which GnRH analogue performs best under hatchery conditions for stinging catfish. Therefore, this study was conducted to assess the breeding performance of stinging catfish (Heteropneustes fossilis) using three commercially available GnRH analogs: Wova-FH, Ovaprim, and Easy-spawn. For this purpose, an experiment was set up in a commercial hatchery by dividing the samples into three groups, each treated with one of the analogs: Wova-FH, Ovaprim, or Easy-spawn. In the experiment, a ratio of 1.5:1 male to female was maintained, and 1 mL syringes were used to inject the analogs. The results showed that the spawning induction efficiency differed among the three inducing agents. Compared to Ovaprim and Easy-spawn, Wova-FH-treated H. fossilis exhibited higher breeding success in all measured aspects. Specifically, Wova-FH achieved a latency period of 8 h, an ovulation rate of 87.25%, a fertilization rate of 89.33%, a hatching rate of 88.85%, and an incubation period of 16 h. In comparison, Ovaprim and Easy-spawn had incubation periods of 18 h and 24 h, respectively. In Ovaprim-induced individuals, the latency period was approximately 8.30 h, with an ovulation rate of 82.08%, a fertilization rate of 86.75%, and a hatching rate of 85.97%. In contrast, the Easy-spawn-induced individuals had a latency period of 9 h, an ovulation rate of 27.50%, a fertilization rate of 27.10%, and a hatching rate of 26.15%. Significant differences (p &amp;lt; 0.05) were observed among the treatments in both the ovulation rate, fertilization rate, latency period incubation period, and hatching rate. The findings suggest that Wova-FH is a superior alternative to Ovaprim and Easy-spawn for GnRH analogs in the induced breeding programs of H. fossilis, offering optimal yield.

Progestin-primed ovarian stimulation outcomes in in-vitro fertilization (IVF) – A systematic review of the literature

Background: Progestin-primed ovarian stimulation (PPOS) stimulates ovaries to block the premature surge of luteinizing hormone (LH) by using micronized progesterone or a progestin during the follicular phase instead of the conventional gonadotropin-releasing hormone (GnRH) analogues or GnRH antagonists downregulating LH to obtain multi-follicle engagement. Current work aims to assess the influence of progestogen treatment on ovarian stimulation and the ability to control LH surge, its efficacy and suitability in retrieving oocytes, without affecting the embryo quality and its benefit among infertile women long-term outcomes on children compared to standard stimulation protocols. Materials and Methods: The literature review used the randomized control trials published in the Pubmed database from January 2015 to April 2021. To generate the citation list, the following keywords were used: ‘progestin-primed ovarian stimulation’, ‘PPOS’, ‘micronized progesterone’, ‘medroxyprogesterone’, and/or ‘dydrogesterone’. The selected articles analyzed the cohort, intervention, and scheme of the progestin-primed ovarian stimulation protocol in controlled ovarian stimulation (COS) for in-vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI) used in Assisted Reproductive Technologies (ART). Results: Overall we concluded that PPOS for IVF/ICSI in ART results in a higher number of obtained embryos, lower incidence of OHSS, equal duration of stimulation, number of retrieved oocytes, and number of MII oocytes. It is also suggested that long-term safety in children shows no significant difference between the study and control groups. Conclusions: Despite the outcomes of progestin stimulation cycles among all cohorts, we concluded that poor ovarian responders, patients with PCOS, women of advanced age and oocyte donors benefit the most from using PPOS.

Embryonic and larval development of black jewfish, Protonibea diacanthus: A new candidate for aquaculture in northern Australia

Black jewfish Protonibea diacanthus is a large, commercially important fish distributed across the tropical Indo-Pacific. In Australia, there is an established commercial wild fishery for the species but it’s aquaculture potential has not been investigated. This research presents hatchery production of native P. diacanthus in Darwin, Australia and documents ontogeny of early life stages of this species over three trial runs. Wild P. diacanthus were induced to spawn with luteinizing hormone-releasing hormone analog (LHRHa) and eggs were released approximately 25–28 h after injection (0.88 ± 0.01 mm in diameter with oil globule 0.24 ± 0.01 mm). Larvae hatched 12 h after spawning. At one day post hatch (dph) larvae were 2.68 ± 0.01 mm standard length with 0.15 ± 0.01 mm oil globule diameter. Larvae mouths opened at 31 h post hatch (hph) and first feeding was seen at 57 hph. Swim bladder inflation (92 %) occurred between 40 and 62 hph. Larvae were progressively fed rotifers, Artemia and Otohime microdiet, and metamorphosis occurred between 20 and 25 dph, completing as they reached over 13 mm standard length. Tail biting cannibalism began with the onset of metamorphosis and caused significant mortality until approximately 24 dph when metamorphosed juveniles could be handled and moved to low stocking density systems. This study demonstrates that northern Australian P. diacanthus is amenable to hatchery production and provides important foundational knowledge for this emerging aquaculture species.

Revising LH cut-off for the diagnosis of central precocious puberty via triptorelin stimulation assay.

Precocious puberty (PP) in girls is defined by thelarche before age 8. The diagnostic gold standard is an increased LH level following gonadotropin-releasing hormone (GnRH) stimulation. Alternatively, GnRH analogues like triptorelin can be used, though their interpretation varies. Since 2000, we have used a triptorelin-induced LH cut-off of 15 IU/L, 4 h post-stimulus. However, many girls showed LH values below this threshold despite evident pubertal progression. To establish a new LH threshold post-triptorelin stimulation for earlier diagnosis of central precocious puberty (CPP) in girls showing pubertal progression and to evaluate additional parameters for diagnostic accuracy. We enrolled 186 girls with thelarche onset between ages 1-8 and a GnRH analogue assay performed between 2015-2019 without signs of axis activation. Within this cohort, 62 patients repeated the triptorelin test due to rapid pubertal progression. The assay involved administering 100 mcg/m² of triptorelin and measuring LH, FSH, and estradiol levels before and four hours post-injection. Patients with axis activation at the second test had significantly higher post-stimulus LH levels at the first test compared to those below 15 IU/L. They also had higher basal LH levels, elevated LH/FSH ratio, and increased growth velocity. Statistical analysis identified a new post-stimulus LH threshold of 5 IU/L. We propose a LH value of 5 IU/L after triptorelin administration as a new threshold for early CPP diagnosis. While the LH/FSH ratio and growth velocity are associated with axis activation, they did not significantly enhance diagnostic accuracy when combined with the LH value.

6480 Variability in Breast Development in Response to Exogenous Estrogen in Girls

Abstract Disclosure: T.M. Kurman: None. E.A. Eugster: None. Intro: Adolescents requiring treatment with exogenous estrogen (E2) include girls with primary and secondary hypogonadism and transfeminine youth. While 17B-estradiol is standard of care, the starting dose and escalation schedule are individualized. To what degree the response to E2 as assessed by breast Tanner stage is correlated with the dose is unknown. Similarly, whether the response to E2 varies depending on the underlying diagnosis has not been systematically analyzed. We aimed to investigate relationships between diagnosis, E2 dose, and breast Tanner staging in adolescent girls. Methods: We conducted a chart review of girls treated with E2 followed at our Pediatric Endocrine clinic between 2008-2022. Inclusion criteria included girls who were prepubertal at baseline and on a single increment of a 25 mcg E2 patch changed 2X/week from initiation of treatment to the first follow up visit. Only transgender girls being treated with a GnRH analog were included. Within each group of patients on the same starting dose, a Kruskal-Wallis test was conducted to evaluate differences in Tanner stage between diagnostic groups. Spearman’s correlation was used to evaluate the relationship between starting dose and Tanner stage. Finally, we evaluated differences within the Turner syndrome (TS) group for girls with monosomy X vs a mosaic karyotype. Results: Of 1,899 medical records, 70 eligible patients were identified. Of these, 33 (47.2%) had TS, 17 (24.3%) had primary ovarian insufficiency (POI), 15 (21.4%) had hypogonadotropic hypogonadism (HH), and 5 (7.1%) were transgender (TG). Twenty-three (32.9%) started on 1/4 patch (6.25 mcg), 29 (41.4%) on 1/2 patch (12.5 mcg) and 18 (25.7%) on a full patch (25 mcg). Girls on other regimens (e.g., 1/8 patch worn only at night) were excluded from analysis. The first f/u visit occurred at a median of 6 months (range 3-12 months). All TG girls were started on 25 mcg E2, which was significantly different compared to the other groups (p=0.002, p=0.005, and p=0.005 for TS, POI, and HH respectively). Breast Tanner stage at the first f/u visit ranged from 1-4 with no significant difference within each dose group based on diagnosis. However, a significant correlation between E2 dose and breast Tanner stage at f/u was seen in girls with HH (r=0.601, p=0.018). No effect of karyotype (monosomy X vs mosaic) on response to E2 in girls with TS was seen. Conclusion: There was striking variability in the starting dose of E2 in the vast majority of patients, highlighting the lack of standardization in clinical management. Interestingly, we found significant individual variability in terms of breast development in response to the initial dose of E2, regardless of diagnosis. Factors responsible for the unpredictable nature of the response to exogenous E2 are unexplored. Our findings provide important and novel prognostic information for patients and providers. Presentation: 6/1/2024

Evaluation of Synthetic GnRH-Analog Peforelin with Regard to Oocyte Differentiation and Follicular Development in C57BL/6J Mice.

In biomedical research, ovulation induction is a critical step in the reproductive biology of laboratory animals. This study evaluates the efficacy of peforelin, a synthetic gonadotropin-releasing hormone (GnRH) analog, in comparison to pregnant mare serum gonadotropin (PMSG, synonym: eCG), traditionally used for ovulation induction in mice. PMSG is derived from the serum of pregnant horses, and its production is becoming increasingly problematic due to animal welfare concerns and regulatory restrictions. The aim of this study was, therefore, to evaluate an ethically acceptable and less invasive alternative to PMSG. Female C57BL/6J mice, aged 3-4 weeks, were divided into two groups to receive either peforelin at three different concentrations or PMSG, followed by an injection of human chorionic gonadotropin (hCG) to induce ovulation. Key outcomes included the number and quality of oocytes collected, fertilization rates, ovary morphology, and follicular differentiation. Although the number of oocytes was significantly lower in the peforelin cohort, the fertilization rate was high. Ovarian morphology was not significantly altered compared to the PMSG cohort. This study showed that peforelin is suitable for superovulation in mice. These results suggest that peforelin could be an ethically acceptable alternative to PMSG stimulation for inducing superovulation in mice.

Comparison of highly purified human menopausal gonadotropin and recombinant follicle stimulating hormone use in patients undergoing in vitro fertilization with progestin-primed ovarian stimulation protocol: a single center retrospective analysis.

Recently, progesterone has been used to prevent LH surge instead of GnRH analogues during ART treatments, which is known as progesterone-primed ovarian stimulation (PPOS) protocol. During ART treatment, highly purified human menopausal gonadotropin (HP-hMG) and recombinant follicle stimulating hormone (rFSH) are two of the agents used for stimulation of antral follicles. The aim of this study is to compare the efficacy and success of HP-hMG and rFSH agents in the ovarian stimulation step of the PPOS protocol, which has not been previously reported in the literature. This retrospective study was conducted at a university hospital with patients who underwent IVF treatment using PPOS protocols in between January 2019 and July 2021. For ovarian stimulation, rFSH was used in group I and HP-hMG was used in group II. Mature oocyte ratio was the primary outcome, and live birth rate was the secondary outcome. Mann-Whitney and Chi-square tests were used for statistical analysis. All p values below 0.05 were considered significant. Total numbers of follicles, oocytes, MII, and 2PN numbers obtained were similar between the two groups. The fertilization rates were 66.7% in the rFSH group and 64.3% in the HP-hMG group (p > 0.05). The pregnancy rates were 53.5% and 46.7% in the rFSH and HP-hMG groups, respectively. There was no statistically significant difference between pregnancy, abortus, and live birth rates. In this study, it is demonstrated that stimulation of oocytes with either rFSH or hMG in the PPOS protocol, which has been added to IVF treatment protocols in recent years, had no statistical difference regarding mature oocyte numbers and live birth rates between the two groups. These results are consistent with the previous literature which compared rFSH and hMG in GnRH agonist and antagonist protocols.

Progestin-primed ovarian stimulation

The use of progestins for the prevention of premature ovulation during ovarian stimulation is called progestin-primed ovarian stimulation (PPOS). Response to ovarian stimulation with PPOS and gonadotropin-releasing hormone (GnRH) analogs seem to be similar with the clinically insignificant differences being explained by endocrine characteristics as expected. PPOS has the advantage of oral administration and lower medication cost than GnRH analogs, but the mandatory cancellation of an otherwise possible fresh embryo transfer can render PPOS less cost-effective if a fresh transfer would have been possible. Oocytes collected in PPOS cycles have similar developmental potential, including blastocyst euploidy rates. Frozen embryo transfer outcomes of PPOS and GnRH analog cycles seem similar both in terms of ongoing pregnancy/live birth rates and obstetric and perinatal outcomes. While some studies reported lower cumulative live birth rates with PPOS, they suffer from methodological issues, including arbitrary definitions of cumulative live birth rates. PPOS has been used in all patient types with consistent results and seems a patient-friendly and cost-effective choice when a fresh embryo transfer is not intended.

Potency evaluation of different GNRH analogues on ovulation induction and reproductive performance of doe rabbit.

Gonadotropin-releasing hormone (GnRH) -supplemented extenders have emerged as a welfare-orientated method to induce ovulation in the artificial insemination (AI) of rabbits. The main factor that limits the bioavailability of GnRH analogue on intravaginal administration is the proteolytic activity of enzymes present in rabbit seminal plasma. The use of GnRH analogues with higher biological potency would allow us to decrease their concentration in the seminal dose without compromising effectiveness. The current study was designed to assess the efficacy of various GnRH analogues concerning their ability to induce ovulation in rabbit AI. The base solution used for experimental extenders contained an aminopeptidase inhibitor. Four experimental groups were used, females from the Control group were induced to ovulate with an intramuscular administration of 1 μg of buserelin, while in the other three groups females received an intravaginal administration of 3.5 μg of buserelin (BUS), deslorelin (DES) or fertirelin (FER) within the seminal dose. Results showed that the ovulation frequency was similar in all groups studied. A concentration of 3.5 μg of the different GnRH analogues tested in this study showed similar potency in inducing ovulation in non-lactating females, yielding comparable results in terms of pregnancy rate at birth and prolificacy.

Importance of PSA Kinetics as a Prognostic Factor in Locally Advanced/Metastatic Prostate Cancer Patients with Prior Androgen Deprivation Therapy

Abstract Background Prostatic cancer ranks 2nd amongst men in worldwide while 4th in Egypt. Many factors are used to predict patients’ survival. PSA kinetics are one of the main prognostic factors used for treatment response in advanced or relapsed cases. However, its application as prognostic marker is lacking in Egyptian clinical settings and research. Aim of Study In this retrospective study, we aimed to assess correlation between PSA kinetics among locally advanced and metastatic prostatic cancer patients and their survival status for prognostic aspects. Methods We conducted a retrospective cohort study at Clinical Oncology department, Ain Shams University hospitals from January 2013 till December 2022 (10 years). All prostate cancer patients who were initially hormonal sensitive locally advanced or metastatic that later developed biochemical failure during follow up period were included in our study. Results Our study included 77 patients with a mean age of 66.4±7.4 years. Three cases were locally advanced while 74 cases were metastatic. The most frequent mode of ADT monotherapy prior biochemical failure was GnRH analogue in 55 cases. Upon disease progression, most of the cases were shifted to abiraterone acetate. The initial median PSA value was 100 (49.1-193.9) ng/ml. It took about 9 (6-14) months (median TTN) with a median declining rate of 10.5 (3.75-35.1) % for their PSA values to reach nadir level of median 1.2 (0.21-5.27) ng/dl. When ADT failed, PSA levels increased again reaching a median value of 8.9 (3.75-35.2) ng/ml. The median PSA velocity after progression was 35.2 (2.8-208) ng/dl/yr while median PSA DT was 3.6 (1.3-7.25) months. Univariate analysis revealed PSA nadir &amp;lt;0.76 ng/dl level (P value= 0.003) and TTN &amp;gt;11 m (p value = 0) significantly associated with longer PFS and improved survival. However, PSA DT &amp;lt; 3.1 (p value=0.017) predicts higher mortality. Meanwhile, multivariate results showed that PSA declining rate (P value= 0.047) and age &amp;gt; 67 years (P value 0.016) were statistically significant as independent factors when associated to PFS. Conclusion TTN &amp;gt; 11 months and PSA nadir &amp;lt;0.76 during initial treatment was associated with prolonged PFS and OS. They were associated with better clinical response to treatment in castration resistant prostate cancer patients. Thus, it could be helpful for decision making of early treatment strategy in castration resistant cases.