Different Doses Of hCG Research Articles

A Subovulatory Dose of Human Chorionic Gonadotropin (hCG) May Sustain Terminal Follicle Development and Reproductive Efficiency during Anestrus in Sheep.

The study tested the hypothesis that a single administration of hCG supports the LH-dependent phase of terminal follicular development in synchronized sheep during anestrus, using eCG as a functional reference. Using a clinical approach, four experiments were designed to achieve the following: (1) Identify the inhibitory influence of anestrus on reproduction efficiency; (2) Assess the potential of hCG to keep functional blood concentrations after a single dose; (3) Characterize the effect of different doses of hCG on reproductive functional markers; (4) To compare the ability of hCG to that of eCG to support follicular development and fertility based on the same markers. The results showed that anestrus seems to affect follicular and luteal function under LH dependency as FSH-dependent markers are not compromised; hCG maintains higher blood concentrations than controls for at least 48 h; hCG improves follicular development and ovulatory rates compared to controls and at standards comparable to a breeding season; and ewes treated with hCG exhibit similar performance to those treated with eCG. Our results conclude that hCG can be used to support follicular function during anestrus in sheep, aiming to perfect its regulation in assisted reproduction.

Randomized, Controlled Pilot Study of Low-Dose Human Chorionic Gonadotropin Administration Beginning From the Early Follicular Phase for Women With Polycystic Ovarian Syndrome Undergoing Ovarian Stimulation Using the Progesterone Protocol.

Purpose: To illustrate whether low-dose human chorionic gonadotropin (hCG) administration during the early follicular phase could reduce the number of large preovulatory follicles in women with polycystic ovarian syndrome (PCOS) undergoing ovarian stimulation using the progesterone protocol.Methods: We performed a randomized, controlled pilot trial at a university-affiliated tertiary hospital. A total of 40 infertile women undergoing their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment with the freeze-all strategy were included. Human menopausal gonadotropin (hMG) and progesterone soft capsule 100 mg/d were added simultaneously beginning from menstrual cycle day 3 for all participants. Low-dose hCG (200 IU) was injected every 3 days in the study group from the first day of ovarian stimulation until trigger. The primary outcome was the number of large preovulatory follicles. Secondary outcomes included the incidence of ovarian hyperstimulation syndrome (OHSS); the number of oocytes retrieved, mature oocytes, and good-quality embryos; and clinical results after frozen-thawed embryo transfer (FET) cycles.Results: The study group had slightly more large preovulatory follicles than the control group (17.75 ± 10 vs. 13.2 ± 5.34; P > 0.05). None of the participants experienced severe OHSS. There were no statistically significant differences in the number of oocytes retrieved (15.9 ± 8.46 vs. 15.75 ± 6.96), mature oocytes (13.55 ± 6.56 vs. 13.4 ± 6.34), and good-quality embryos (5.5 ± 3.41 vs. 4.9 ± 2.99) between the two groups (P > 0.05). Clinical pregnancy rates (65.52 vs. 41.94%; P = 0.067) and live birth rates (48.28 vs. 35.48%; P = 0.315) per transfer following FET of the study group were higher than those of the control group, but without statistical significance.Conclusions: Administration of low-dose hCG from the early follicular phase for PCOS patients undergoing ovarian stimulation with progesterone protocol may lead to slightly more early preovulatory follicles and marginally, but not significantly, higher clinical pregnancy rates. A continuous trial should be performed to explore the effects of supplementation with different doses of hCG from the start of ovarian stimulation in PCOS patients using the progesterone protocol.Clinical Trial Registration: Chictr.org.cn, identifier: ChiCTR-IOR-15007165

Effects of hCG on reduced numbers of hCG receptors in the prefrontal cortex and cerebellum of rat models of Alzheimer’s disease

ABSTRACTAge-associated changes in the levels of luteinizing hormone and human chorionic gonadotropin (hCG) are potential risk factors for Alzheimer’s disease (AD); hCG concentration is related to the incidence of AD. The highest density of hCG receptors is in zones of the brain that are vulnerable to AD and streptozotocin (STZ) can decrease the density of this receptor. We investigated the effects of different doses of hCG on hCG receptor density in the prefrontal cortex and cerebellum in a rat model of STZ-induced AD. AD was induced by intracerebroventricular injection of 3 mg/kg STZ. The resulting AD rats were treated for 3 days with 50, 100 or 200 IU/200 μl hCG, or with saline as a control. Sections of prefrontal cortex and cerebellum were stained immunohistochemically and hCG receptor-immunoreactive (ir) neurons were counted. STZ injected into the lateral ventricles of rat brains reduced the density of hCG receptor-ir neurons in the prefrontal cortex and cerebellum. hCG administration resulted in a significant dose-dependent increase in the number of hCG receptor-ir neurons in the prefrontal cortex and cerebellum. The maximum increase in the number of receptors occurred following the 200 IU dose of hCG. Administration of hCG ameliorated the lowered density of hCG receptor-ir neurons in the cerebellum and prefrontal cortex in STZ-induced AD rats.

Human chorionic gonadotropin attenuates amyloid-β plaques induced by streptozotocin in the rat brain by affecting cytochrome c-ir neuron density.

Objective(s):Amyloid β plaques, in Alzheimer’s disease, are deposits in different areas of the brain such as prefrontal cortex, molecular layer of the cerebellum, and the hippocampal formation. Amyloid β aggregates lead to the release of cytochrome c and finally neuronal cell death in brain tissue. hCG has critical roles in brain development, neuron differentiation, and function. Therefore, we investigated the effect of hCG on the density of the congophilic Aβ plaque and cytochrome c-ir neurons in the hippocampus, prefrontal cortex, and cerebellum of Streptozotocin (STZ)-treated rats. Materials and Methods:Alzheimer model in rats (except the control group) was induced by streptozotocin (3 mg/kg, Intracerebroventricularly (ICV)). Experimental group rats received streptozotocin and then different doses of hCG (50, 100, and 200 IU, intraperitoneally) for 3 days. 48 hr after last drug injection and after histological processing, the brain sections were stained by congo red for congophilic amyloid β plaques and cytochrome c in the hippocampus, prefrontal cortex, and cerebellum were immunohistochemically stained. Results:Density of congophilic Aβ plaques and cytochrome c-immunoreactive neurons was significantly higher in ICV STZ treated rats than controls. Treatment with three doses of hCG significantly decreased the density of congophilic Aβ plaques and cytochrome c-immunoreactive neurons in the rat hippocampus, prefrontal cortex, and cerebellum in ICV STZ-treated rats (P<0.05).Conclusion: hCG can be useful in AD patients to prevent the congophilic Aβ plaque formation and decrease cytochrome c-immunoreactive neuron density in the brain.

The Use of Power Mode Doppler Ultrasonography as a Predictive Tool of Early Pregnancy in the Mare

Human chorionic gonadotropin (hCG) has been used to induce ovulation and as a luteotrophic agent in cattle. However, the effect of hCG therapy on the functional status of the equine corpus luteum (CL) is unclear. This study aimed to characterize the hemodynamic and secretory function of early CL of mares treated with different doses of hCG at distinct stages of the estrous cycle. Mares were assigned to nine experimental groups (n = 6 mares/group) according to dose of hCG and time of treatment. A single injection of one of three different doses of hCG (750, 1,500, or 2,500 IU) was performed in one of three distinct stages of the estrous cycle: preovulatory follicle ≥35 mm, day of ovulation (D0), or 48 hours after ovulation (D2). In addition, a control group treated with NaCl 0.9% was included in the study. The end points evaluated daily from D0 to D8 were area of the CL, luteal vascularity, number of colored pixels and total pixel intensity, and concentrations of plasma progesterone (P4). No effect (P > .1) of dose or time of treatment was observed for any end point, within each day. Luteal area did not differ throughout the days (P > .1), whereas Doppler parameters and concentrations of plasma P4 presented a progressive increase (P < .05) after ovulation in all groups. Secretory function and luteal hemodynamic were not affected (P > .1) by hCG dose and time of treatment. In conclusion, hCG therapy during estrus or early diestrus, at the doses tested, did not improve P4 secretion or luteal blood flow.

Preovulatory Follicle Dynamics, and Ovulatory and Endometrial Responses to Different Doses of hCG and Prediction of Ovulation in Mares

A more precise characterization of the effects of human chorionic gonadotropin (hCG) treatment on the preovulatory follicle is needed to improve reproductive efficiency in broodmare management. The objectives of this study were (1) to study the effects of different hCG doses within and among three consecutive estrous cycles on ovulatory response, preovulatory follicle dynamics, and endometrial echotexture; (2) to study the temporal relationship among changes in preovulatory follicle diameter, endometrial echotexture, and estradiol levels; and (3) to analyze a system for prediction of ovulation. In experiment 1, mares were treated with 2,500 IU hCG, 1,500 IU hCG, 500 IU hCG, or saline (controls) and examined by ultrasonography every 6 hours across three consecutive preovulatory periods (n = 135). Similar treatment groups were utilized in experiment 2 (n = 177 preovulatory periods) with examinations performed every six, 12, or 24 hours to test the effectiveness of a prediction of ovulation system. Effective hCG doses (2,500 and 1,500 IU) led to cessation of growth rate and reduction of the preovulatory follicle diameter concurrently with a reduction in systemic estradiol concentration and endometrial echotexture score. A system of prediction of ovulation, based on preovulatory follicle ultrasonographic signs of impending ovulation, was highly accurate for the diagnosis of positive and negative outcomes in both hCG-treated and control groups. However, the effectiveness of this prediction system was reduced due to the false-negative diagnoses that were a reflection of a lack of sensitivity for the detection of nonovulation.

Human chorionic gonadotrophin priming for fertility treatment with in vitro maturation.

In vitro maturation (IVM) is a fertility treatment that involves the transvaginal retrieval of immature oocytes, and their subsequent maturation and fertilisation. Although the live birth rate is lower than conventional in vitro fertilisation (IVF) with ovarian stimulation, it is a useful treatment, as it avoids the risk of ovarian hyperstimulation syndrome (OHSS). Women with polycystic ovaries (PCO) or polycystic ovarian syndrome (PCOS) are at an increased risk of OHSS. Thus, IVM may be a more useful treatment in this patient group.Strategies to maximise the maturation rates of the immature oocytes are important. This review focuses on the administration of human chorionic gonadotrophin (hCG) prior to immature oocyte retrieval. To determine the effectiveness and safety of hCG priming in subfertile women who are undergoing IVM treatment in the context of assisted reproduction. We searched the following electronic databases up to 29 August 2016: Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL. We also searched the trial registries ClinicalTrials.gov and WHO ICTPR to identify ongoing and registered trials. We sought recently published papers not yet indexed in the major databases, and reviewed the reference lists of reviews and retrieved studies as sources of potentially relevant studies. There were no language restrictions. We included randomised controlled trials (RCTs) that compared hCG priming with placebo or no priming in women undergoing IVM. We also included RCTs that compared different doses of hCG, or the timing of oocyte retrieval. The primary outcomes were live birth rate and miscarriage rate per woman randomised. Two review authors independently selected studies for inclusion, and with a third author, assessed risk of bias and extracted data. We contacted the original authors where data were missing. For dichotomous outcomes, we used the Mantel-Haenszel method to calculate odds ratios (OR). For continuous outcomes, we calculated the mean differences (MD) between treatment groups. We assessed statistical heterogeneity using the I² statistic. We assessed the overall quality of the evidence using GRADE methods. We included four studies, with a total of 522 women, in the review. One of these studies did not report outcomes per woman randomised, and so was not included in formal analysis. Three studies investigated 10,000 units hCG priming compared to no priming. One study investigated 20,000 units hCG compared to 10,000 units hCG priming. Three studies only included women with PCOS (N = 122), while this was an exclusion criteria in the fourth study (N = 400).We rated all four studies as having an unclear risk of bias in more than one of the seven domains assessed. The quality of the evidence was low, the main limitations being lack of blinding and imprecision.When 10,000 units hCG priming was compared to no priming, we found no evidence of a difference in the live birth rates per woman randomised (OR 0.65, 95% confidence intervals (CI) 0.24 to 1.74; one RCT; N = 82; low quality evidence); miscarriage rate (OR 0.60, 95% CI 0.21 to 1.72; two RCTs; N = 282; I² statistic = 21%; low quality evidence), or clinical pregnancy rate (OR 0.52, 95% CI 0.26 to 1.03; two RCTs, N = 282, I² statistic = 0%, low quality evidence). Though inconclusive, our findings suggested that hCG may be associated with a reduction in clinical pregnancy rates; 22% of women who received no priming achieved pregnancy, while between 7% and 23% of women who received hCG priming did so.The study comparing 20,000 units hCG with 10,000 units hCG did not report sufficient data to enable us to calculate odds ratios.No studies reported on adverse events (other than miscarriage) or drug reactions. This review found no conclusive evidence that hCG priming had an effect on live birth, pregnancy, or miscarriage rates in IVM. There was low quality evidence that suggested that hCG priming may reduce clinical pregnancy rates, however, these findings were limited by the small number of data included. As no data were available on adverse events (other than miscarriage) or on drug reactions, we could not adequately assess the safety of hCG priming. We need further evidence from well-designed RCTs before we can come to definitive conclusions about the role of hCG priming, and the optimal dose and timing.

Effect of exogenous hormones on ovulation and gonadal steroid plasma levels in starry flounder, Platichthys stellatus

The present study was designed to examine the potential for inducing ovulation in starry flounder (Platichthys stellatus) using gonadotropin-releasing hormone analog (GnRHa) and human chorionic gonadotropin (hCG) to assess whether starry flounder are differentially responsive to GnRHa and hCG. Female starry flounder were injected or implanted with different doses of hCG or GnRHa pellets to examine their ovulation-inducing potential and effects on plasma levels of testosterone (T), 17β-estradiol (E2), and 17,20β-dihydroxy-4-pregnen-3-one (17,20βP). Blood samples were collected for up to 10 or 25 days post-injection or post-implantation in two separate experiments designed to mimic the early and middle stages of spawning, respectively. Fish treated with the GnRHa pellets (100 µg) showed a significant increase in the total number of stripped eggs relative to the controls. GnRHa administration had no effect on the floating rate or fertilization rate of ovulated eggs in the both experiments, whereas hCG injection affected both of these rates. Plasma T levels were not significantly different between the exogenous hormone-treated and control fish. In contrast, the plasma E2 level was elevated in those fish treated with GnRHa, regardless of injection or implantation, and was accompanied by increased numbers of stripped eggs in both experiments. Treatment with GnRHa resulted in higher 17,20βP levels compared to the controls, and there was a positive relationship between elevated plasma 17,20βP and an increase in ovulated eggs in response to GnRHa treatment. The implantation of starry flounder with GnRHa-containing pellets was effective at inducing sustained ovulation compared to hCG treatment.

Characterization of Luteal Blood Flow and Secretion of Progesterone in Mares Treated With Human Chorionic Gonadotropin for Ovulation Induction or During Early Diestrus

Human chorionic gonadotropin (hCG) has been used to induce ovulation and as a luteotrophic agent in cattle. However, the effect of hCG therapy on the functional status of the equine corpus luteum (CL) is unclear. This study aimed to characterize the hemodynamic and secretory function of early CL of mares treated with different doses of hCG at distinct stages of the estrous cycle. Mares were assigned to nine experimental groups (n = 6 mares/group) according to dose of hCG and time of treatment. A single injection of one of three different doses of hCG (750, 1,500, or 2,500 IU) was performed in one of three distinct stages of the estrous cycle: preovulatory follicle ≥35 mm, day of ovulation (D0), or 48 hours after ovulation (D2). In addition, a control group treated with NaCl 0.9% was included in the study. The end points evaluated daily from D0 to D8 were area of the CL, luteal vascularity, number of colored pixels and total pixel intensity, and concentrations of plasma progesterone (P4). No effect (P > .1) of dose or time of treatment was observed for any end point, within each day. Luteal area did not differ throughout the days (P > .1), whereas Doppler parameters and concentrations of plasma P4 presented a progressive increase (P < .05) after ovulation in all groups. Secretory function and luteal hemodynamic were not affected (P > .1) by hCG dose and time of treatment. In conclusion, hCG therapy during estrus or early diestrus, at the doses tested, did not improve P4 secretion or luteal blood flow.

Effect of different doses of hCG on diameter of the preovulatory follicle and interval to ovulation in mares

Effect of different doses of hCG on diameter of the preovulatory follicle and interval to ovulation in mares

Induction of oocyte maturation in the white croaker Micropogonias furnieri (Pisces: Sciaenidae) by human chorionic gonadotropin.

The present work aimed to identify the best doses of human chorionic gonadotropin (hCG) needed to induce oocyte maturation of Micropogonias furnieri and to characterize ovarian dynamics during the periovulatory period. Adult M. furnieri females with fully developed ovaries were injected intraperitoneally with four different doses of hCG. The gonadotropin response was succeeded by analyzing morphologically gonadal biopsies and following the postinjection changes in follicle diameter. Oocyte maturation was induced by three doses used: 100, 300, and 500 IU of hCG kg bw-1, and was reached 48 h after treatment with 300 and 500 IU of hCG kg bw-1, and 72 h after treatment with 100 IU of hCG kg bw-1. Concerning ovarian dynamics, only 100 and 300 IU of hCG kg bw-1 mimicked the natural ones which have a synchronic group maturation. In conclusion, the dose mimicking natural ovarian dynamics and inducing oocyte maturation more quickly is 300 IU of hCG kg bw-1.

Arachidonic acid release from rat Leydig cells depends on the presence of luteinizing hormone/human chorionic gonadotrophin receptors.

In this work, the involvement of arachidonic acid (AA) in the luteinizing hormone and human chorionic gonadotrophin (LH/hCG) action on Leydig cells was studied. Experiments were first designed to evaluate [14C]AA incorporation into membrane phospholipids. Subsequently, time-course, pulse-chase and dose-response studies of the effect of hCG on [14C]AA release were performed. Results indicated that 4 h was optimal for maximal incorporation of [14C]AA into membrane phospholipids of viable Leydig cells. Pulse-chase experiments and studies performed to evaluate the effect of different doses of hCG on [14C]AA release demonstrated that this hormone stimulates [14C]AA release in a dose-response and time-dependent manner. Furthermore, using a desensitised animal model, a link between the presence of LH/hCG receptors and LH/hCG-stimulated [14C]AA release in Leydig cells could be established. In fact, the amount of [14C]AA released was significantly dependent on, and directly proportional to, the concentration of LH/hCG binding sites. Thus [14C]AA released from intact rat Leydig cells decreased when animals had been previously injected with a high single dose of hCG (desensitised animals), which is known to cause a dramatic decrease in the number of LH/hCG binding sites. These results demonstrate that the mechanism of AA release in Leydig cells depends on LH/hCG-receptor interaction and also suggest that AA could act as an additional intracellular messenger associated with the hormonal action of LH/hCG.

Phospholipase C and adenylate cyclase signalling systems in the action of hCG on porcine myometrial smooth muscle cells.

Although the uterus is a target tissue for LH and its homologue hCG the second messenger system responding to LH/hCG in myometrial cells is not established. In this study we investigated the involvement of protein kinase A and protein kinase C in the action of hCG on porcine myometrial smooth muscle cells in vitro. Myometrium was obtained from ovariectomized gilts given 2.5 mg oestradiol benzoate plus 50 mg progesterone for five consecutive days. Myometrial cells were cultured for 48 h and different doses of hCG were then added. Increasing doses of hCG stimulated concentration-dependent increases in [3H]inositol phosphates (IPs) accumulation in incubations lasting 24 h. The highest dose of hCG (1000 mU/ml) increased turnover of IPs by 2.4-fold as reflected in elevations in IP1, IP2 and IP3, and similar effects were observed with noradrenaline. The time- and concentration-dependent effects of hCG on IPs accumulation occurred between 16 and 24 h of incubation. Incubation of myocytes with the lowest doses of hCG (0.1 and 1 mU/ml) caused a significant increase in cAMP accumulation but the highest doses (10-1000 mU/ml) had no effect on cAMP concentrations. This is the first demonstration that LH/hCG receptor signalling leads to increased inositol phosphate turnover in myometrial cells as well as cAMP generation and it leads to the conclusion that both protein kinase A and protein kinase C signalling mechanisms are involved in gonadotrophin action in porcine myometrial smooth muscle cells.

A physiological increase in LH may influence vascular permeability in the rat testis

Adult male rats were injected with different doses of hCG, or with 2.5 micrograms ovine LH subcutaneously, and other rats were mated with oestrous females. The animals were examined 4 h after treatments. Treatment with hCG resulted in a dose-dependent increase in leucocyte concentration in testicular blood vessels and in the number of blood vessels which could be labelled with intravenously injected carbon particles. Carbon leakage was not observed in control testes. Treatment with a low dose of ovine LH or inducing an endogenous LH peak by mating also resulted in leucocyte accumulation and vascular leakage of carbon in the testis. The magnitude of the response was considerably lower than after high doses of hCG. The physiological relevance of the discrete response observed after physiological LH stimulation is unknown but LH-induced changes in testicular microcirculation could be of interest for the understanding of the physiology and pathophysiology of the testis.

In vitro and in vivo studies on Leydig cell function in old rats.

Young adult (3 months old) and old (26-28 months old) male Wistar rats were studied. Testicular weight was 1.66 g (range: 1.33--2.86) in the younger group and 1.62 g (range: 1.04--1.90) in the older group. The total Leydig cell volume as measured by a quantitative histometric method was significantly larger in the old animals (-x = 0.153 ml vs. -x = 0.089 ml). The testicular HCG binding capacity was 2.54 ng HCG per 100 mg tissue (range: 1.88--3.77) in the younger animals and 1.83 ng HCG per 100 mg tissue (range: 0.80--3.02) in the older ones (P less than 0.01). Plasma testosterone was on an average 242 ng/100 ml (range: 72--1162) in the young adult rats and 91 ng/100 ml (range: 23--277) in the older rats. Plasma LH was only slightly (P less than 0.05) decreased and was 49 ng LH-RP-1/ml (range: 14--120) in the younger group and 40 ng LH-RP-1 ng/ml (range: 5--98) in the older. When the testicular tissue pieces were incubated with different doses of HCG or dibutyryl cAMP and testosterone production was measured, identical dose-response curves for old and young tissue were obtained. After in vitro incubation with a NADPH generating system, which under the conditions used was a much stronger stimulus for steroid biosynthesis than HCG or dibutyryl cAMP, the tissue of young rats produced about twice the amount of testosterone precursors (pregnenolone, progesterone, 17alpha-hydroxyprogesterone and androstenedione) than old tissue.