Effect of pre-treatment with deslorelin on the ovarian response of ewes superovulated with FSH.

This study evaluated the use of the GnRH agonist hormone, deslorelin, to control the follicular population before initiating multiple ovulation and embryo transfer (MOET) treatment. Twenty-four cross-bred Santa Inês ewes, aged between 2 and 4 years, were randomly assigned to either a control group (n = 11) or a treated group (n = 13). All ewes received an intravaginal device containing 60 mg of medroxyprogesterone acetate on day 0, and a new device on day 7, which remained in place until day 14. Additionally, the ewes were administered 125 µg of cloprostenol on day 7. The superovulatory treatment involved administering 200 mg of pFSH, divided into eight decreasing doses at 12-h intervals starting on day 12. On day 14, 300 IU of eCG was administered. In the deslorelin group, three doses of 100 µg of deslorelin were administered starting on day 3 after the insertion of the vaginal device, with subsequent doses given at 72-h and 144-h intervals. Natural mating was performed 36 h after the removal of the progesterone implant using males with proven fertility. Embryo collection took place on the 6th day after mating, and the recovered structures were quantified and evaluated for quality and developmental stage. Transrectal ultrasonography was conducted on days 12, 16 and 21 to evaluate the ovaries, specifically to assess the ovarian follicular population and the presence of the corpus luteum. Ewes in the control group had higher embryo recovery rates (p < .01) compared to the treated group (5.2 ± 0.8 vs. 1.1 ± 0.8), with differences observed primarily in the number of morulae. The number of corpus luteum observed during the laparotomy on day 21 was significantly higher (p < .01) in the control group (10.44 vs. 4.5 corpus luteum per ewe). Yet, the treated group had a significantly higher number of follicles (p < .05) on the first day of pFSH application (5.5 vs. 3.0 follicles per ewe). In conclusion, although the inclusion of deslorelin in the superovulation protocol resulted in increased synchronization of oestrus and follicle number, it did not lead to an increase in the number of corpus luteum or harvested embryos.

Elevated temperature impairs gonadal development by suppressing the expression of the genes for kisspeptin, GnRH1 and GTH subunits in Nile tilapia Oreochromis niloticus.

Temperature is a preeminent factor in the regulation of fish reproduction and hinders gonadal development beyond a specific threshold. To comprehend the molecular mechanism responsible for reproductive suppression at different temperature, expression of the genes encoding kisspeptin (kiss2), gonadotropin-releasing hormone (gnrh1) and their receptors (gpr54, gnrh1r) in the brain, and the gonadotropin (GTH) subunits (fshb and lhb) in the pituitary were studied in juvenile Nile tilapia (Oreochromis niloticus) along with gonadal histology. Fish were acclimatized to three distinct temperatures, including 31 °C, 34 °C and 37 °C for 14 days. The mRNA levels of kiss2, gpr54, gnrh1, and gnrh1r were significantly decreased at 37 °C compared to 31 °C and 34 °C in the both sexes. In parallel, the expression level of fshb in the both sexes and lhb in the female were significantly lower at 37 °C in the pituitary. Histologically, the gonads of both sexes had normal growth of gametes at control temperature (31 °C), whereas the spermatogenesis and oocyte maturation were slowed down and atretic oocytes were found in the ovary at 37 °C acclimation temperature. Taken together, the results imply that elevated temperature beyond the specific threshold may have a negative impact on reproduction by suppressing the gene expressions of kisspeptin/GnRH1/GTH system and eventually restrains normal growth and maturation of gametes in the both sexes of Nile tilapia.

Reproductive outcomes in Holstein heifers synchronized with timed-AI protocols that provide for a lengthened proestrus.

This study compared reproductive outcomes among two protocols for synchronization of ovulation that provide for a lengthened proestrus with the conventional oestradiol-based protocol currently used for timed-AI (TAI). Holstein heifers (13-15 months) at one location were assigned randomly to one of three TAI protocols. Heifers (n = 150) in the 7-day oestradiol benzoate (EB) group received a progesterone device (Cue-Mate) and 2 mg EB on Day 0; 500 µg of cloprostenol (PGF) and Cue-Mate removal on Day 7; 1 mg of EB on Day 8 and TAI on Day 9 (54 h after Cue-Mate removal). Heifers (n = 150) in the 5-day CO-Synch (CO) group received a Cue-Mate and 100 µg of gonadotropin-releasing hormone (GnRH) on Day 2; Cue-Mate removal and PGF (twice, 12 h apart) on Day 7; and GnRH along with TAI on Day 10 (72 h after Cue-Mate removal). Heifers (n = 150) in the J-Synch (JS) group received a Cue-Mate and 2 mg of EB on Day 1; PGF and Cue-Mate removal on Day 7; GnRH and TAI on Day 10 (72 h after Cue-Mate removal). Heifers were inseminated by one technician with frozen-thawed conventional semen from one of four commercially available sires. Plasma progesterone (P4) concentrations (ng/mL) were determined at Cue-Mate removal and TAI. Ovarian ultrasonography was done in a subset of 217 heifers at the initiation of protocols, at Cue-Mate removal; TAI; and 7 days after TAI. Approximately, 28 and 50 days after TAI pregnancy status was determined by ultrasonography. Mean (±SEM) plasma P4 concentration at Cue-Mate removal was greater (p < .01) in CO (6.02 ± 0.2) and JS (6.51 ± 0.2) compared to EB heifers (4.53 ± 0.2). Mean (±SEM) plasma P4 concentration at TAI was lowest in the JS (0.28 ± 0.05), intermediate in CO (0.46 ± 0.02), and greatest in EB heifers (0.66 ± 0.05, p < .01). The diameter of the ovulatory follicle (mean ± SEM) was the smallest in the JS group compared to that in the CO and EB groups (15.8 ± 0.5; 13.9 ± 0.5; and 12.7 ± 0.5 mm for EB, CO and JS, respectively). More (p < .01) heifers in the JS group had their oestrous cycle synchronized (50.0, 78.8 and 82.4% for EB, CO and JS groups), and were pregnant at 28 (40.3, 51.3 and 63.3% for EB, CO and JS groups) and 50 days after TAI (32.6, 46.0 and 60.0% for EB, CO and JS groups). In summary, heifers subjected to the J-Synch TAI protocol had lower P4 at TAI, and better overall response to hormonal treatments, which resulted in increased P/AI at 28 and 50 days after TAI compared to those heifers subjected to either a 7-day EB protocol or a 5-day CO-synch protocol.

Peripheral administration of a κ-opioid receptor agonist nalfurafine inactivates gonadotropin-releasing hormone pulse generator activity in goats.

Neurons co-expressing kisspeptin, neurokinin B, and dynorphin A (KNDy neurons), located in the arcuate nucleus (ARC) of the hypothalamus, are indicated to be the gonadotropin-releasing hormone (GnRH) pulse generator. Dynorphin A is reported to suppress GnRH pulse generator activity. Nalfurafine is a selective agonist of the κ-opioid receptor (KOR), a receptor for dynorphin A, clinically used as an anti-pruritic drug. This study aimed to evaluate the effects of nalfurafine on GnRH pulse generator activity and luteinizing hormone (LH) pulses using female goats. Nalfurafine (0, 2, 4, 8, or 16 µg/head) was intravenously injected into ovariectomized Shiba goats. The multiple unit activity (MUA) in the ARC area was recorded, and plasma LH concentrations were measured 2 and 48 h before and after injection, respectively. The MUA volley interval during 0-2 h after injection was significantly increased in the nalfurafine 8 and 16 µg groups compared with the vehicle group. In 0-2 h after injection, the number of LH pulses was significantly decreased in the nalfurafine 8 and 16 µg groups, and the mean and baseline LH were significantly decreased in all nalfurafine-treated groups (2, 4, 8, and 16 µg) compared with the vehicle group. These results suggest that nalfurafine inhibits the activity of the GnRH pulse generator in the ARC, thus suppressing pulsatile LH secretion. Therefore, nalfurafine could be used as a reproductive inhibitor in mammals.

Does the activation of sea bass GnIH receptor modulate GnRH receptor signaling?

Previous studies have revealed the stimulatory and inhibitory actions of gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH) on the control of reproduction in European sea bass (Dicentrarchus labrax) and other vertebrates, respectively. However, information on the possible interactions between GnRH and GnIH on cell signaling is sparse in vertebrates. In the current study, we investigated if activation of sea bass GnIH receptor (GnIHR) can interfere with GnRH receptor II-1a (GnRHR-II-1a) involving the PKA pathway. Our results showed that GnIH and GnRH functioned via their cognate receptors, respectively. However, it appears that neither GnIH1 nor GnIH2 can block GnRH/GnRHR-II-1a-induced PKA signaling in sea bass. This is the first study to examine the potential interactions of GnIH with GnRH receptor signaling in teleosts. Further research seems necessary to shed light on unknown interactions in other signaling pathways and other GnIH/GnRH receptors involved in the physiological functions of these two relevant neuropeptides, not only in sea bass but also in other species.

Effectiveness and safety of GnRH antagonist originator and generic in real-world clinical practice: a retrospective cohort study.

Objective: This study aims to determine whether the live birth rates were similar between GnRH antagonist original reference product Cetrotide® and generic Ferpront®, in gonadotropin-releasing hormone (GnRH) antagonist protocol for controlled ovarian stimulation (COS). Methods: This retrospective cohort study investigates COS cycles utilizing GnRH antagonist protocols. The research was conducted at a specialized reproductive medicine center within a tertiary care hospital, spanning the period from October 2019 to October 2021. Within this timeframe, a total of 924 cycles were administered utilizing the GnRH antagonist originator, Cetrotide® (Group A), whereas 1984 cycles were undertaken using the generic, Ferpront® (Group B). Results: Ovarian reserve markers, including anti-Mullerian hormone, antral follicle number, and basal follicular stimulating hormone, were lower in Group A compared to Group B. Propensity score matching (PSM) was performed to balance these markers between the groups. After PSM, baseline clinical features were similar, except for a slightly longer infertile duration in Group A versus Group B (4.43 ± 2.92 years vs. 4.14 ± 2.84 years, P = 0.029). The duration of GnRH antagonist usage was slightly longer in Group B than in Group A (6.02 ± 1.41 vs. 5.71 ± 1.48 days, P < 0.001). Group B had a slightly lower number of retrieved oocytes compared to Group A (14.17 ± 7.30 vs. 14.96 ± 7.75, P = 0.024). However, comparable numbers of usable embryos on day 3 and good-quality embryos were found between the groups. Reproductive outcomes, including biochemical pregnancy loss, clinical pregnancy, miscarriage, and live birth rate, did not differ significantly between the groups. Multivariate logistic regression analyses suggested that the type of GnRH antagonist did not independently impact the number of oocytes retrieved, usable embryos, good-quality embryos, moderate to severe OHSS rate, clinical pregnancy, miscarriage, or live birth rate. Conclusion: The retrospective analysis revealed no clinically significant differences in reproductive outcomes between Cetrotide® and Ferpront® when used in women undergoing their first and second COS cycles utilizing the GnRH antagonist protocol.

Effect of body mass index on progesterone level on trigger day in gonadotropin-releasing hormone antagonist cycles.

OBJECTIVE: To investigate the effect of body mass index (BMI) on progesterone (P) level on trigger day in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles. METHODS: This study was a retrospective cohort study. From October 2017 to April 2022, 412 in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) patients who were treated with GnRH-ant protocol for controlled ovarian hyperstimulation (COH) in the reproductive center of our hospital were selected as the research objects. Patients were divided into three groups according to BMI level: normal weight group (n = 230):18.5 kg/m2≤BMI < 24 kg/m2; overweight group (n = 122): 24 kg/m2≤BMI < 28 kg/m2; Obesity group (n = 60): BMI ≥ 28 kg/m2. Variables with p < .10 in univariate analysis (BMI, basal FSH, basal P, FSH days, Gn starting dose and E2 level on trigger day) and variables that may affect P level on trigger day (infertility factors, basal LH, total FSH, HMG days and total HMG) were included in the multivariate logistic regression model to analyze the effect of BMI on P level on trigger day of GnRH-ant protocol. RESULTS: After adjustment for confounding factors, compared with that in normal weight patients, the risk of serum P elevation on trigger day was significantly lower in overweight and obese patients (OR = 0.434 and 0.199, respectively, p < .05). CONCLUSION: The risk of P elevation on trigger day in GnRH-ant cycles decreased with the increase of BMI, and BMI could be used as one of the predictors of P level on trigger day in GnRH-ant cycles.

Genome sequencing projects reveal new insights into the mammalian Gonadotropin-releasing Hormone II system.

The type II gonadotropin-releasing hormone (GnRH-II) was first discovered in chicken (Gallus gallus) brain and then shown to be present in many vertebrates. Indeed, its structure is conserved unchanged throughout vertebrate evolution from teleost fish through to mammals suggesting a crucial function. Yet the functional significance has been largely unexplored. Studies in comparative endocrinology show that the GnRH-II system is differentially functional in mammalian species. Intact GnRH-II neuropeptide and receptor genes (GnRH2 and GnRH receptor 2 GnRHR2) occur in marmoset monkeys (Callithrix jacchus), musk shrews (Suncus murinus) and pigs (Sus scrofa). However, one or other or both of these genes are inactivated in other species, where mutations or remnants affecting GnRH2 neuropeptide and/or type II GnRHR exons are retained in conserved genomic loci. New data from DNA sequencing projects facilitate extensive analysis of species-specific variation in these genes. Here, we describe GnRH2 and GnRHR2 genes spanning a collection of 21 taxonomic orders, encompassing around 140 species from Primates, Scandentia, Eulipotyphla, Rodentia, Lagomorpha, Artiodactyla, Carnivora, Perissodactyls, Pholidota, Chiroptera, Afrotheria, Xenarthra and Marsupialia. Intact coding exons for both GnRH2 and GnRHR2 occur in monkeys, tree shrews, shrews, moles, hedgehogs, several rodents (degu, kangaroo-rat, pocket mouse), pig, pecarry and warthog, camels and alpaca, bears, Weddell seal, hyena, elephant, aardvark and marsupials. Inactivating mutations affecting GnRH2 and GnRHR2, some located at conserved sites within exons, occur in species of primates, most rodents, lagomorphs, bovidae, cetaceans, felidae, canidae and other carnivora, pangolins, most bats, armadillo, brushtail and echidna. A functional GnRH-II system appears retained within several taxonomic families of mammals, but intact retention does not extend to whole taxonomic orders. Defining how endogenous GnRH-II neuropeptide operates in different mammals may afford functional insight into its actions in the brain, especially as, unlike the type I GnRH system, it is expressed in the mid brain and not the hypothalamus.

Co-administration of GnRH-agonist and hCG (double trigger) for final oocyte maturation increases the number of top-quality embryos in patients undergoing IVF/ICSI cycles.

BACKGROUND: The utilization of a double trigger, involving the co-administration of gonadotropin-releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG) for final oocyte maturation, is emerging as a novel approach in gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during controlled ovarian hyperstimulation (COH). This protocol involves administering GnRH-a and hCG 40 and 34 h prior to ovum pick-up (OPU), respectively. This treatment modality has been implemented in patients with low/poor oocytes yield. This study aimed to determine whether the double trigger could improve the number of top-quality embryos (TQEs) in patients with fewer than three TQEs. METHODS: The stimulation characteristics of 35 in vitro fertilization (IVF) cycles were analyzed. These cycles were triggered by the combination of hCG and GnRHa (double trigger cycles) and compared to the same patients' previous IVF attempt, which utilized the hCG trigger (hCG trigger control cycles). The analysis involved cases who were admitted to our reproductive center between January 2018 and December 2022. In the hCG trigger control cycles, all 35 patients had fewer than three TQEs. RESULTS: Patients who received the double trigger cycles yielded a significantly higher number of 2PN cleavage embryos (3.54 ± 3.37 vs. 2.11 ± 2.15, P = 0.025), TQEs ( 2.23 ± 2.05 vs. 0.89 ± 0.99, P < 0.001), and a simultaneously higher proportion of the number of cleavage stage embryos (53.87% ± 31.38% vs. 39.80% ± 29.60%, P = 0.043), 2PN cleavage stage embryos (43.89% ± 33.01% vs. 27.22% ± 27.13%, P = 0.014), and TQEs (27.05% ± 26.26% vs. 14.19% ± 19.76%, P = 0.019) to the number of oocytes retrieved compared with the hCG trigger control cycles, respectively. The double trigger cycles achieved higher rates of cumulative clinical pregnancy (20.00% vs. 2.86%, P = 0.031), cumulative persistent pregnancy (14.29% vs. 0%, P < 0.001), and cumulative live birth (14.29% vs. 0%, P < 0.001) per stimulation cycle compared with the hCG trigger control cycles. CONCLUSION: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) may be suggested as a valuable new regimen for treating patients with low TQE yield in previous hCG trigger IVF/intracytoplasmic sperm injection (ICSI) cycles.

Central precocious puberty - etiology with particular consideration of neurological causes.

Central precocious puberty (CPP) is a rare disease of poorly understood etiology. The cause is mostly idiopathic. However, congenital and acquired structural changes in the central nervous system are also involved. Prevalent organic changes in the central nervous system, especially among boys, prompt imaging assessment in each case of CPP. In addition, genetic and environmental factors have been reported. Safe and effective treatment is available. The time of treatment implementation is crucial to the successful outcome. Proper diagnosis and treatment make it possible to avoid a number of complications of untreated CPP. There are only a few studies analyzing the prevalence and risk factors for the disease. The aim of this paper is to discuss the current causes of CPP with particular consideration of neurological aspects.

Treatment alternatives to induce follicular wave emergence for timed-AI in lactating dairy Cows.

Two experiments evaluated the effect of different hormonal treatments to synchronize follicle wave emergence on follicle dynamics and pregnancies per AI (P/AI) in estradiol (E2)/progesterone (P4) timed-AI (TAI) protocols in lactating dairy cows. In Experiment 1, lactating, primiparous Holstein cows (n = 36) received a P4 releasing device (Day 0) and were allocated at random to one of the following three treatment groups: Group EB received 2 mg E2 benzoate (EB) intramuscularly (i.m.), Group EB + GnRH received 2 mg EB+20 µg buserelin (GnRH) i.m., or Group EB + P4 received 2 mg EB + 100 mg of injectable P4 (iP4) in oil i.m. All cows received 0.150 mg D-Cloprostenol on Days 7 and 8 followed by P4 device removal, 400 IU eCG and 1 mg ECP on Day 8. Daily ultrasound examinations revealed that although the interval from P4 device removal to ovulation was not affected by treatment, cows that received EB + GnRH had an earlier (P < 0.05) emergence of the new follicular wave (Day 2.6 ± 0.2) than the other two treatment groups (Days 3.5 ± 0.3 and 6.1 ± 0.3, for EB and EB + P4, respectively). In Experiment 2, 808 lactating cows were assigned randomly to the three treatments evaluated in Experiment 1, and all the cows were TAI to determine P/AI. Cows in the EB + GnRH group had greater P/AI (57.4 %, P < 0.01) than those in the EB (44.6 %) or EB + P4 (45.7 %) groups. In conclusion, the administration of GnRH, but not iP4, on the day of insertion of a P4 device improves P/AI in lactating dairy cows synchronized for TAI with an estradiol/P4-based protocol.

Reproductive outcome after in vitro fertilization in endometriosis - key factors and implications.

Endometriosis is a benign chronic disease with a major impact on a woman's quality of life, mainly due to painful physical symptoms. Endometriosis is also a common cause of infertility caused by low ovarian reserve, distorted pelvic anatomy, and severe local inflammation with a direct negative impact on the quality of oocytes, embryos, and endometrium. We conducted a retrospective study between January 2019 and December 2023, including women with a history of surgery for endometriosis who underwent in vitro fertilization (IVF) to achieve pregnancy. Their reproductive outcome was compared with a group of patients with documented tubal obstruction. The aim of our study was to identify the factors associated with a positive impact on the pregnancy rate, specifically age, anti-Mullerian hormone (AMH), ovarian stimulation protocol, and types of gonadotropins used. We analyzed a group of 175 patients with endometriosis compared with 189 patients with tubal obstruction. The average age was similar between the two groups but with a difference in the average AMH value (1.63 ± 1.09 ng/mL vs. 2.55 ± 1.67 ng/mL). The most utilized ovarian stimulation protocol in both groups was the short gonadotropin-releasing hormone (GnRH) antagonist. The clinical pregnancy rate was 27.2% in the endometriosis group and 54.7% in the tubal obstruction group. Our study revealed that treatment with corifollitropin alfa in the endometriosis group was associated with a higher clinical pregnancy rate. AMH and age proved to be significant independent factors for the reproductive outcome.

Early-Life Resource Scarcity in Mice Does Not Alter Adult Corticosterone or Preovulatory Luteinizing Hormone Surge Responses to Acute Psychosocial Stress.

Early-life stressors can affect reproductive development and change responses to adult stress. We tested if resource scarcity in the form of limited bedding and nesting (LBN) from postnatal days (PND) 4 to 11 delayed sexual maturation in male and female mice and/or altered the response to an acute, layered, psychosocial stress (ALPS) in adulthood. Contrary to the hypotheses, age and mass at puberty were unaffected by the present application of LBN. Under basal conditions and after ALPS, corticosterone concentrations in males, diestrous females, and proestrous females reared in standard (STD) or LBN environments were similar. ALPS disrupts the luteinizing hormone (LH) surge in most mice when applied on the morning of proestrus; this effect was not changed by resource scarcity. In this study, the paucity of effects in the offspring may relate to a milder response of CBA dams to the paradigm. While LBN dams exited the nest more often and their offspring were smaller than STD-reared offspring on PND11, dam corticosterone concentrations were similar on PND11. To test if ALPS disrupts the LH surge by blunting the increase in excitatory GABAergic input to gonadotropin-releasing hormone (GnRH) neurons on the afternoon of proestrus, we conducted whole-cell voltage-clamp recordings. The frequency of GABAergic postsynaptic currents in GnRH neurons was not altered by LBN, ALPS, or their interaction. It remains possible that ALPS acts at afferents of GnRH neurons, changes response of GnRH neurons to input, and/or alters pituitary responsiveness to GnRH and that a more pronounced resource scarcity would affect the parameters studied.

Severe ovarian hyperstimulation syndrome in an oocyte donor despite preventive strategies.

We present a rare case of severe ovarian hyperstimulation syndrome (OHSS) in a 19-year-old woman undergoing a second donation cycle of controlled ovarian hyperstimulation. The patient developed severe OHSS despite the implementation of preventive strategies and required hospitalization for 14 days, including treatment in the intensive care unit. The underlying pathophysiology that triggers this extreme systemic response in certain patients, despite the implementation of preventive measures, remains unknown. Continued research efforts are necessary to improve our understanding and management of this condition.

Gonadotropin-Releasing Hormone (GnRH) Agonist Protocol Improves Pregnancy Outcomes During In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) Treatment in Young Infertile Women: A Retrospective Study.

Objective The objective of this study was to determine if gonadotropin-releasing hormone agonist (GnRH-a) or gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment in young infertile women improve their pregnancy outcomes. Methodology We retrospectively reviewed the records of 876 young infertile women aged 20-35 years who underwent fresh embryo transfer in IVF/ICSI cycles. The data were collected from their initial visits to the reproductive medicine center of the Second Affiliated Hospital of Zhengzhou University between January 2019 and December 2022. We divided them into two groups according to the controlled ovarian hyperstimulation (COH) protocols: GnRH-a (n = 580) and GnRH-ant (n = 296). The primary outcome assessed in this study was the live birth rate. The secondary observation indicators included the total dose and duration of gonadotropin (Gn), total embryo transfer, day three (D3) embryo transfer, total two pro-nuclei (2PN) cleavage count, number of fertilizations, and implantation rate. Results The live birth rate had no clinical significance (P > 0.05). The total dose and duration of Gn stimulation in the GnRH-ant group were lower than in the GnRH-a group (P  < 0.05). The total embryo transfer, D3 embryo transfer, total cleavage count, total 2PN cleavage count, number of fertilizations, transfer, and mature oocytes in metaphase II (MII) of D3 embryos in the GnRH-a group were higher than those in the GnRH-ant group (P  < 0.05). The clinical pregnancy rate and implantation rate of the GnRH-a group were higher than those of the control group. Conclusions The total embryo transfer, D3 embryo transfer, total cleavage count, total 2PN cleavage count, number of fertilizations, transfer and MII of D3 embryos, clinical pregnancy, and implantation rates were significantly higher in the GnRH-a protocol group. The total dosage of Gn and duration of Gn stimulation were lower in the GnRH-ant group than in the GnRH-a group. These findings provide the basis for the selection of the COH protocol in normal Chinese ovarian response patients undergoing IVF/ICSI.

High water temperature triggers early sexual maturation in the juvenile red spotted grouper Epinephelus akaara: Via regulation of reproduction-related hormones in the brain-pituitary-gonadal axis.

The red spotted grouper Epinephelus akaara is a marine species of economic importance and also at risk of extinction. This study investigated the effects of high water temperature on the growth and maturation of juvenile E. akaara females. From 160-420 days post-hatching (dph), the fish were maintained under natural water temperature (NT) and a constant high-water temperature (HT). From 240 dph, both the total length and body weight in the HT group were greater than in NT group. After 360 dph, the gonadosomatic index was also increased in the HT group compared to NT group. Mature oocytes were only observed in the HT group at 330, 360, and 390 dph. Both kiss1 and kiss2 levels increased at 240 and 270 dph in both groups; however, they were greater in the HT group at 240 dph. Similarly, gpr54 levels after 360 dph were greater in the HT group, suggesting that kisspeptin is related to maturation via its receptor gpr54. Levels of fshß and lhß were greater in the HT group after 360 dph. Estradiol-17ß (E2) levels after 160 dph (except 300 dph) were greater in the HT group than in the NT group, suggesting that the higher E2 levels trigger maturation, and is related to increased fshß and lhß. This study provides evidence that high water temperature is effective in accelerating growth and triggering early maturation of juvenile E. akaara, via regulating gpr54, fshß, lhß, and E2 levels.

Puberty suppression in adolescents with gender dysphoria: an emerging issue with multiple implications.

Controversy exists over puberty suppression (PS) in adolescents with gender dysphoria (GD). PS is preferentially achieved with GnRH analogues. By preventing the development of secondary sex characteristics, PS may improve psychological functioning, well-being, quality of life, emotional and behavioral (especially internalizing) problems and depressive symptoms, thus decreasing suicidality. PS can also extend the diagnostic period and give transgender adolescents time to explore their gender identity. GnRHa may also decrease the need for feminization/masculinization surgery. However, 2-year treatment with GnRHa may result in bone mass accrual retardation (decrease in BMD/BMAD z-scores), growth velocity deceleration (decrease in height SDS), increase in fat mass, temporary pause in oocyte/sperm maturation. The most common side effects of GnRHa are hot flashes, mood fluctuations, fatigue and headache. They are usually mild and rarely lead to GnRHa discontinuation. Based on current scientific evidence, PS could be recommended to adolescents who meet the diagnostic criteria of gender incongruence (by DSM-5 and/or ICD-11) and have long-lasting intense GD, which aggravates with puberty onset. Before initiating PS, possible mental issues should be addressed and informed consent (by the adolescent/caregiver) should be given, after counseling on probable reproductive effects of GnRHa. GnRHa can only be started after the adolescent has entered Tanner stage 2. Nevertheless, published studies are inadequate in number, small in size, uncontrolled and relatively short-term, so that it is difficult to draw safe conclusions on efficacy and safety of GnRHa. Large long-term randomized controlled trials are needed to expand knowledge on this controversial issue and elucidate the benefit and risks of PS.

Pelvic ultrasound and pubertal attainment in girls with sexual precocity: the pivotal role of uterine volume in predicting the timing of menarche.

Introduction: Among girls assessed for pubertal precocity, pelvic ultrasound (pUS) may represent a pivotal tool to predict the time expected to elapse between sonographic assessment and the onset of menarche (TUS-M). Accordingly, the present analysis is meant to define the statistical relationship between sonographic parameters and TUS-M, in order to identify the most reliable predictor of the timing of menarche. Methods: Retrospective, multicenter analysis. Girls assessed for sexual precocity and showing sonographic and clinical findings consistent with pubertal onset upon referral were considered eligible. Patients treated with GnRH analogues were excluded and only those who had subsequently achieved complete and spontaneous pubertal attainment and for whom the exact date of menarche was available were included. Overall, we enrolled 184 girls from five tertiary care Italian Centers. Results: The time elapsed (months) between baseline endocrine assessment and spontaneous achievement of menarche showed a negative statistically significant correlation (p<0.0001) with LH (r:-0.61), FSH (r:-0.59), estradiol (r:-0.52) and stimulated LH values (r:-0.58). Among pUS parameters, ovarian volume (r:-0.17 left, -0.30 right) and uterine body-to-cervix ratio (r:-0.18) poorly correlated with TUS-M, while uterine diameters (r:-0.61 longitudinal, -0.64 anteroposterior) and volume (r:-0.70) achieved a highly statistical significance (p<0.0001). Uterine volume (UV) showed a negative logarithmic relationship with TUS-M and represented the most reliable predictor of the timing of menarche in uni- and multivariable analyses (p <0.001). ROC analyses identified the UV thresholds that best predict the onset of menarche within 18, 12 and 6 months, respectively: 3.76, 6.02 and 8.80 ml. Conclusion: The logarithm of UV shows the best statistical performance in predicting the timing of menarche in girls assessed for pubertal precocity. Accordingly, we developed a user-friendly online application that provides clinicians with an estimation of the months expected to elapse before menarche, based on the UV recorded upon pUS.

Longitudinal Evaluation of Reproductive Endocrine Function in Men with ACTH-Dependent Cushing Syndrome.

CONTEXT: Hypogonadism may be caused by Cushing syndrome (CS) and may intensify its adverse consequences. OBJECTIVE: To determine the frequency of male hypogonadism before and after curative surgery for CS, and its cause. DESIGN: Post-hoc analyses of prospective cohort studies. SETTING: Clinical research center. PATIENTS: Men with ACTH-dependent CS. Cohort 1 (C1) (n=8, age 32.5±12 y; studied 1985-1989); Cohort 2 (C2) (n=44, 42.7 ± 15.1 y; studied 1989-2021). INTERVENTIONS: C1: Every 20-minute blood sampling for 24h before and 1-40 months after surgical cure. Three subjects underwent GnRH stimulation tests pre- and post-surgery. C2: Hormone measurements at baseline and 6 and 12 months (M) post-cure. MAIN OUTCOME MEASURES: C1: LH, FSH, LH pulse frequency and LH response to GnRH. C2: LH, FSH, testosterone (T), free T, fT4, T3, TSH and UFC levels and frequency of hypogonadism pre- and post-surgery. RESULTS: C1: mean LH and LH pulse frequency increased after surgery (p < 0.05) without changes in LH pulse amplitude, mean FSH, or peak gonadotropin response to GnRH. C2: 82% had baseline hypogonadism (total T 205 ± 28 ng/dL). Thyroid hormone levels varied inversely with UFC and cortisol. LH, total and free T, and SHBG increased at 6M and 12M post surgery, but hypogonadism persisted in 51% at 6M and in 26% at 12M. CONCLUSION: Hypogonadism in men with CS is widely prevalent but reversible in ∼75% of patients one year after surgical cure and appears to be mediated through suppression of hypothalamic GnRH secretion, and modulated by thyroid hormones.