hCG In Combination Research Articles

P-676 Comparison of hCG triggering versus hCG in combination with a GnRH agonist: a prospective randomized controlled trial

Abstract Study question Does co-administration of GnRH agonist and Human chorionic gonadotropin(dual trigger) in PGT cycles improve the number of usable blastocysts per patient compared to hCG alone? Summary answer Using the dual trigger has no effect on the number of usable blastocysts undergoing the GnRH-ant protocol for PGT compared to triggering with hCG alone. What is known already HCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, based on retrospective studies, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome and pregnancy rates. Study design, size, duration A prospective, randomized, open-label controlled clinical trial (ChiCTR-ICR-2000031342), enrolled patients attending our university affiliated Infertility and IVF center (the Reproductive and Genetic Hospital of CITIC-Xiangya, China) between August 2020 and June 2021. This sample size achieves with a power of 80%, at a significance level(α) of 0.05. A sample size of 160 patients, 80 randomized to each group, was chosen to allow for those 10% dropped out. Participants/materials, setting, methods The inclusion criteria for participating were: women age 20–35years, AMH≥1.2ng/ml and /or AFC ≥5, Couples with PGT-SR preimplantation genetic testing for chromosomal structural rearrangements (patients with abnormal chromosomal structure only in male or female), undergoing one of their first PGT cycle attempts. Patients fulfilled the criteria on the trigger day were randomly assigned to receive hCG or the dual trigger for final oocyte maturation. The primary outcome was the number of usable blastocysts per patient. Main results and the role of chance 160 patients were included in the study. The age (29.1 years versus 29.4 years), BMI (22.1 kg/m2 versus 21.9 kg/m2) and the AMH (5.3 ng/ml versus 5.3 ng/ml) were comparable between the two groups. Based on PP analysis, there were no statistical difference in the number of eggs retrieved (17.1 versus 15.9), the MII oocytes (13.3 versus 12.5), the number of usable blastocysts per patient (5.0 versus 4.6) and top-quality blastocysts per patient (3.4 versus 3.2) between the two groups. Limitations, reasons for caution None Wider implications of the findings The enhanced response observed with the dual trigger might lead to better IVF outcomes were it used more widely. Trial registration number ChiCTR-ICR-2000031342

The effect of prostaglandin and gonadotrophins (GnRH and hCG) injection combined with the ram effect on progesterone concentrations and reproductive performance of Karakul ewes during the non-breeding season.

The effect of prostaglandin and gonadotrophins (GnRH and hCG) combined with the ram effect on the progesterone (P4) concentrations and reproductive performance of Karakul ewes was investigated during non‐breeding season. Ewes (n = 93) received a male effect and were divided into two treatment groups including GnRH ‐ hCG (hCG, n = 32), GnRH ‐ GnRH (GnRH, n = 30) and a control (n = 31) group. This study was carried out from April (hormonal injection) to October (lambing). The first doses of GnRH (4.2 μg, Buserelin) were injected at the beginning of the study in treatment groups. These ewes were treated with hCG (250 IU) or the second GnRH dose five days later. All animals received two injections (ten days apart) of 150 μg PGF2α five days after the hCG or the second GnRH injection. Mating was initiated two days after the second prostaglandin injection and lasted for 34 days. Blood samples were collected by jugular venipuncture on days −10, −5, 0 (first PGF2α injection), 17 and 30 during the study. Pregnancy diagnosis was performed through transabdominal ultrasonography on day 40 after the removing of ram. Conception rate was 93.8, 90 and 87.1% in the hCG, GnRH and control groups, respectively. Lambing rate tended to increase in the hCG group compared with the control group (87.1 versus 58.1%; p < .1). There was no significant difference in P4 concentrations among studied groups in identical sampling times (p > .05). In conclusion, the administration of prostaglandin and hCG in combination with the ram effect tended to decrease lambing period. In other words this protocol tended to increase lambing rate at the first cycle. Treatment with hCG or GnRH did not increase serum P4 concentrations of treated Karakul ewes during the non‐breeding season.

SUN-092 Effect of Pubertal Induction with Gonadotropins and GnRH Therapy in Male Hypogonadotropic Hypogonadism: Meta-Analysis

Background: The use of gonadotropins is a recent strategy for inducing puberty in adolescent males with hypogonadotropic hypogonadism (HH). Testosterone use has been discouraged in patients who desire to preserve fertility. Human chorionic gonadotropin (hCG) has been recommended for inducing puberty in HH; however, several clinicians administer hCG in combination with other gonadotropins. The benefits of using combination gonadotropin therapies (hCG+) over hCG monotherapy in pre-pubertal adolescent males with HH has not been clearly established. We performed a meta-analysis to assess the outcomes of hCG compared to hCG+ in terms of virilizing effects and testicular growth in peripubertal boys with HH. Methods: We evaluated for heterogeneity among studies. We calculated pooled means for the post-treatment mean testicular volume (MTV), testosterone (T) level, and penile length for the hCG monotherapy and hCG+ treatment groups. We performed a meta-regression analysis to examine the contribution of various factors to post-treatment outcomes including baseline T level, age, treatment duration, and study quality. Results: The meta-analysis included seven studies. All participants were prepubertal (age range: 13.3–25.9 years), with weighted mean treatment durations of 10.95 months for hCG monotherapy and 28.2 months for hCG. There was significant heterogeneity in baseline age (Q = 121.71; df = 1; P < 0.001) and T levels (Q = 436.74; df = 1; P < 0.001) between the two treatment groups. The hCG+ group had a larger post-treatment MTV, but it was not significantly different between the two groups (6.60 mL [95% CI, 3.18–10.02] for hCG monotherapy vs. 10.02 mL [95% CI, 8.30–11.75] for hCG+; P = 0.079). Post-treatment T levels differed significantly between the two groups (101.89 ng/dL [95% CI, 50.7–153.08] for hCG monotherapy vs. 424.10 ng/dL [95% CI, 304.59–543.62] for hCG+; P < 0.0001). A meta-regression analysis of post-treatment T levels showed that baseline age, baseline T level, and study grade did not contribute significantly to the difference between treatment groups. Treatment duration explained 3.04% of the difference between the two groups (P < 0.0001). After adjusting for treatment duration, the post-treatment T level remained significantly higher in the hCG+ group compared to the hCG monotherapy group. The hCG+ was also associated with better outcomes for post-treatment penile length, although these findings relied on data from only three studies. Conclusion: Our study indicates that hCG+ therapies provide potential benefits over hCG monotherapy for pubertal induction in males with HH, regarding T levels and penile growth, with no difference in testicular growth between treatments. Prospective pediatric studies are needed to assess the benefits of these therapies in patients with HH and, ultimately, to establish guidelines for gonadotropin therapy in the adolescent population.

Combining several interventions to reduce the incidence of OHSS: A prospective cohort study

ObjectiveTo assess the outcome of using low-dose aspirin, dopamine agonist and triggering ovulation by low dose of HCG in combination with GnRH agonist in fixed GnRH antagonist protocol in patients at risk of OHSS. Study designThis prospective cohort study was conducted on 50 infertile women who were at high risk of OHSS. They received low dose aspirin from first day of stimulation, cabergoline 0.5mg daily from the day of HCG for 8days and low dose of HCG (2500 IU) in combination with GnRH agonist for final oocyte maturation in fixed GnRH antagonist protocol. ResultsThe study was conducted on 50 cases and all of them completed the study protocol. The clinical pregnancy rate was 40% (20 cases of 50) and no cases developed severe or critical OHSS. Only 8% (4 cases) developed moderate OHSS. ConclusionCombining aspirin, cabergoline, and triggering with low dose of HCG in combination with GnRH agonist produced excellent clinical pregnancy rate, and decreased hospital admissions with severe or critical OHSS.

Stimulation of a spermatogenesis at men gonadotrophins and an antiestrogen at a pathospermia and infertility

Aim — to investigate the methods of treatment, directed on increase in quantity of spermatozoa in an ejaculate.Material and methods. In investigation was used: chorionic gonadotrophin, anti-estrogen, recombinant preparations FSH, and also their combinations.Results. The worst efficiency (10%) was noted when using monotherapy by preparation HCG. Efficiency of monotherapy by a preparation of clomiphene was higher and made 20% concerning conception, and 63% concerning an oligoteratozoospermiya. Efficiency of the combined therapy of HCG in combination with recombinant FSH was 40% concerning conception, and 87% concerning an oligoteratozoospermiya.Conclusion. At the same time the studied types of the stimulating therapy are effective, safe and don’t lead to development of side effects.

The interplay of human chorionic gonadotropin (hCG) with basic fibroblast growth factor and adipokines on angiogenesis in vitro

IntroductionHuman chorionic gonadotropin (hCG) is suggested to regulate placental angiogenesis, however, its role is incompletely understood. hCG may directly stimulate angiogenesis or influence the effect of other angiogenic factors. We examined the effect of hCG and the interplay of hCG with basic fibroblast growth factor (bFGF) and with various adipokines on proliferation of vascular endothelial cells in vitro. MethodsHuman umbilical vein endothelial cells (HUVEC) were incubated for 2 days with combinations of hCG, bFGF, leptin, resistin, adiponectin, IL6 and TNFα. Incorporation of radiolabelled thymidine was used to assess cell proliferation. Immunofluorescence and flow cytometry were used to examine activation of p44/42 mitogen-activated kinase (MAPK). ResultshCG induced proliferation of HUVEC alone and in combination with bFGF. Cells exposed to both hCG and bFGF displayed increased activation of p44/42 MAPK as compared to hCG or bFGF alone. Increased HUVEC proliferation was observed in the presence of increasing concentrations of leptin, resistin, adiponectin, and IL6, whereas HUVEC proliferation decreased in the presence of TNFα. hCG in combination with leptin, resistin, adiponectin or IL6 stimulated HUVEC proliferation beyond the effect of hCG alone. DiscussionAn interplay of hCG with adipose tissue-derived factors with angiogenic properties is plausible. Thus, maternal obesity may affect placental angiogenesis in pregnancy. ConclusionshCG may directly stimulate angiogenesis. Also, hCG may indirectly stimulate angiogenesis through interplay with bFGF and adipokines.

Gene expression differences induced by equimolar low doses of LH or hCG in combination with FSH in cultured mouse antral follicles

In a natural cycle, follicle growth is coordinated by FSH and LH. Follicle growth stimulation in Assisted Reproductive Technologies (ART) requires antral follicles to be exposed to both FSH and LH bioactivity, especially after GNRH analog pretreatment. The main aim was to detect possible differences in gene expression in granulosa cells after exposing the follicle during antral growth to LH or hCG, as LH and hCG are different molecules acting on the same receptor. Effects of five gonadotropin treatments were investigated for 16 genes using a mouse follicle culture model. Early (day 6) antral follicles were exposed to high recombinant FSH combined or not with equimolar concentrations of recombinant LH (rLH) or recombinant hCG (rhCG) and to highly purified human menopausal gonadotropin (HP-hMG) for 6 h, 12 h, or 3 days. Expression differences were tested for genes involved in steroidogenesis: Mvk, Lss, Cyp11a1, Hsd3b1, Cyp19a1, Nr4a1, and Timp1; final granulosa differentiation: Lhcgr, Oxtr, Pgr, Egfr, Hif1a, and Vegfa; and cytokines: Cxcl12, Cxcr4, and Sdc4. Lhcgr was present and upregulated by gonadotropins. Nr4a1, Cxcl12, and Cxcr4 showed a different expression pattern if LH bioactivity was added to high FSH in the first hours after exposure. However, no signs of premature luteinization were present even after a 3-day treatment as shown by Cyp19a1, Oxtr, Pgr, and Egfr and by estrogen and progesterone measurements. The downstream signaling by rhCG or rLH through the LHCGR was not different for this gene selection. Granulosa cells from follicles exposed to HP-hMG showed an enhanced expression level for several genes compared with recombinant gonadotropin exposure, possibly pointing to enhanced cellular activity.

A randomized controlled dose–response pilot study of addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization

Is it possible to define an optimal dose of hCG in combination with rFSH from the first day of stimulation in the GnRH agonist protocol applied to IVF? Supplementation with hCG from the first day of stimulation may increase the number of top-quality embryos per patient. Daily doses of hCG up to 150 IU are compatible with good live birth rates. A ceiling level of estradiol (E(2)) was reached with hCG doses above 100 IU/day. A positive dose-response was seen for pre-ovulatory progesterone, but concentrations remained below values for which an impairment of endometrial receptivity has been previously reported. We suggest a large clinical trial to be proceeded with a group given 100 IU hCG daily versus a control group. Prospective multicentre studies have indicated increased live birth rates and increased number of top-quality embryos when low doses of hCG were associated with FSH. We analysed the clinical, embryological and endocrine aspects of adding increasing doses of hCG to rFSH from the first day of stimulation for IVF. A prospective randomized, controlled, open-label dose-response pilot study was conducted between February 2009 and June 2010 at Copenhagen University Hospital, Rigshospitalet, Denmark. Adequate allocation concealment was assured from sequentially numbered, opaque, sealed envelopes prepared from a computer-generated list. Scoring of the embryos was done in an assessor-blinded way. Endocrinologically normal IVF patients aged 25-37 years, BMI 18-30 kg/m(2), regular cycles and FSH <12 IU/l, were treated with a fixed dose of rFSH 150 IU/day and randomized to daily hCG dose of 0, 50, 100 or 150 IU from Day 1 of stimulation. Primary end-point was the total number of top-quality embryos on Day 3. Data were analysed by analysis of variance, Kruskal-Wallis test, chi-squared test or Poisson distribution count. A total of 62 patients were randomized into four hCG dose groups: Dose 0 (D0; n= 16), Dose 50 (D50; n= 15), Dose 100 (D100; n= 16) and Dose 150 (D150; n= 15). Two patients in D150 were withdrawn after randomization because of major (10- to 30-fold) hCG dosing errors, leaving 13 patients in this group. Thus, the results are based on the per protocol population. The mean numbers of top-quality embryos per patient were D0: 0.8 ± 1.2, D50: 0.5 ± 0.7, D100: 1.2 ± 1.7 and D150: 1.5 ± 1.7 (P= 0.04). All pregnancies were singleton gestations, and the live birth rates per started cycle were D0: 25%, D50: 27%, D100: 25% and D150: 31% (P= 0.98). Steady state level of serum (s)-hCG was reached on Day 6 of stimulation. S-hCG levels (IU/l) on the day of hCG administration were D0: <0.1, D50: 3.1 (2.6-3.6), D100: 5.5 (4.1-7.4) and D150: 11.0 (8.9-13.6) (P< 0.01). The patients receiving hCG supplementation were stratified by 33 and 66% percentiles into three groups according to the concentration of s-hCG on Day 6 of stimulation: 0.5-3.5 IU/l (n= 16), 3.5-8.0 IU/l (n= 14) and 8.0-21.1 IU/l (n= 14). The mean numbers of top-quality embryos in the three groups were 0.5 ± 0.9, 1.1 ± 1.8 and 1.5 ± 1.5, respectively (P= 0.03). The progesterone increments from stimulation Day 1 to the day of hCG triggering were D0 = 49%, D50 = 79%, D100 = 110% and D150 = 160% (P= 0.02). S-androstenedione level was highest in D150 (P< 0.01). S-E(2) was 2-fold higher in the D100 and D 150 compared with D0 (P= 0.09). BIAS, LIMITATION, GENERALISABILITY: Our study has a limited sample size. Supplementation with daily hCG dose up to 150 IU throughout stimulation has never been used before. Hence, this had to be tested in a small study before conducting a larger trial. Ferring Pharmaceuticals, Research and Development, provided funds for the endocrine measurements. CLINICALTRIAL.GOV REGISTRATION: NCT00844311.

Prospective, randomized study to evaluate the success rates using hCG, vaginal progesterone or a combination of both for luteal phase support

A prospective study was done to compare the efficacy of luteal phase support (LPS) using either three times hCG (group I, n=77), hCG on the day of embryo transfer (ET) in combination with daily vaginal progesterone (group II, n=62) or vaginal progesterone only (group III, n=70). All patients were treated using the long luteal protocol for controlled ovarian stimulation in an IVF (in vitro fertilization) cycle. Patients were randomized to one of these groups when estradiol was <2500 pg/ml and less than 12 oocytes were retrieved (low risk groups). If estradiol was > or = 2500 pg/ml and/or at least 12 oocytes were retrieved (high risk groups), patients were randomized to receive either hCG in combination with daily vaginal progesterone (group IV, n=83) or progesterone only (group V, n=121). For vaginal progesterone Utrogest was used (three times daily two capsules containing 100 mg progesterone, 600 mg/d). Demographic data were comparable within the high risk and low risk groups. However, for unknown reasons the fertilization rate was significantly higher in group V (48%) compared to group IV (40%) (p<0.05), leading to a significantly higher cumulative embryo score. There were no statistically significant differences with regard to the main outcome parameter, the clinical ongoing pregnancy rate in the low risk groups (14.3%, 14.5%, 11.4%) and the high risk groups (21.0%, 21.5%), respectively. Using a standardized discomfort scale, there were more complaints towards the end of the luteal phase in the groups receiving hCG only or an additional injection of hCG, when compared to the progesterone only groups. Progesterone only for luteal phase support leads to the same clinical ongoing pregnancy rate as hCG, but has no impact on the comfort of the patient.

First trimester screening for Down's syndrome using maternal serum PAPP-A and free beta-hCG in combination with fetal nuchal translucency thickness.

The aim of this study was to evaluate the potential effectiveness of maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta-hCG in combination with nuchal translucency thickness in first trimester screening for Down's syndrome. Maternal serum levels of PAPP-A and free beta-hCG were assayed in stored sera from 32 Down's syndrome and 200 unaffected pregnancies. Fetal nuchal translucency was measured by ultrasound at the time of blood sampling. Screening of Down's syndrome using a combination of maternal age, PAPP-A, free beta-hCG and nuchal translucency would achieve a detection rate of 75.8% for a false positive rate of 5%.

HCG and the free β-subunit as screening tests for Down syndrome

Published studies have reached varying conclusions as to the benefit of replacing human chorionic gonadotropin (hCG) measurements with the free beta-subunit of hCG (the free beta-subunit) for Down syndrome screening. One study reports 14 per cent higher detection for the free beta-subunit, while another finds an actual loss in detection. To explore this issue further, we directly compared the screening performance of hCG and the free beta-subunit, alone and in combination with other serum markers, using banked sera obtained prior to amniocentesis and karyotyping. Altogether, 52 Down syndrome and 5065 unaffected pregnancies were studied. Sera were thawed and assayed for hCG and the free beta-subunit over 1 year. At a 5 per cent false-positive rate, the detection rate for hCG in combination with maternal age and alpha-fetoprotein was higher than when the free beta-subunit was substituted (62 versus 57 per cent). Ultrasound dating and adding unconjugated oestriol both increased detection. The present findings, along with those from six case control studies (our re-analysis), indicate that the screening performances of hCG and the free beta-subunit are similar (median change in detection 0, range -8 to +3 per cent). Under optimal sample collection and transportation conditions, laboratories can expect to achieve similar screening performance using either hCG or the free beta-subunit measurements.

HCG and the free β‐subunit as screening tests for Down syndrome

Published studies have reached varying conclusions as to the benefit of replacing human chorionic gonadotropin (hCG) measurements with the free β-subunit of hCG (the free β-subunit) for Down syndrome screening. One study reports 14 per cent higher detection for the free β-subunit, while another finds an actual loss in detection. To explore this issue further, we directly compared the screening performance of hCG and the free β-subunit, alone and in combination with other serum markers, using banked sera obtained prior to amniocentesis and karyotyping. Altogether, 52 Down syndrome and 5065 unaffected pregnancies were studied. Sera were thawed and assayed for hCG and the free β-subunit over 1 year. At a 5 per cent false-positive rate, the detection rate for hCG in combination with maternal age and alpha-fetoprotein was higher than when the free β-subunit was substituted (62 versus 57 per cent). Ultrasound dating and adding unconjugated oestriol both increased detection. The present findings, along with those from six case–control studies (our re-analysis), indicate that the screening performances of hCG and the free β-subunit are similar (median change in detection 0, range −8 to +3 per cent). Under optimal sample collection and transportation conditions, laboratories can expect to achieve similar screening performance using either hCG or the free β-subunit measurements. © 1998 John Wiley & Sons, Ltd.

Detection of pregnancies with trisomy 18 in screening programmes for Down's syndrome.

It is possible to identify pregnancies with trisomy 18 as part of screening programmes for Down's syndrome that use maternal age, IX fetoprotein (AFP), unconjugated oestriol (uE3), and either total human chorionic gonadotrophin (total hCG) or its subunit, free ~-hCG. While the detection rates and false positive rates using risk as the test variable have been published for maternal age with (a) AFP, uE3, and hCG 2 and with (b) AFP and free ~-hCG3 this has not been done for maternal age with AFP, uE3,and free ~-hCG. Here we summarise the parameters of the distributions of the markers in affected and unaffected pregnancies, and in affected pregnancies we calculate the' standard deviation for the free ~-hCG and the correlation between free i3-hCG and AFP and between free ~-hCG and uE3.We then estimate the detection rates and false positive rates. The parameters of the distribution of all four markers in unaffected pregnancies have been published. In trisomy 18 pregnancies: (a) the parameters for AFP, uE3, and total hCG were taken from reference 2; (b) the median free ~-hCG was taken from reference 3; (c) the standard deviation for free ~-hCG was calculated by taking the difference in variance between trisomy 18 and unaffected pregnancies from reference 3 and adding this to the unaffected variance from reference 4; (d) the correlation between AFP and free ~-hCG was calculated by taking the difference in covariance between trisomy 18 and unaffected pregnancies obtained from reference 3, adding this to the unaffected covariance from reference 4 and then dividing by the standard deviations in (a) and (c); (e) there is no available correlation between uE3 and free ~-hCG and so it is assumed to be the same as in unaffected pregnancies. The truncation limits (that is, the range over which the distributions are Gaussian) for AFP, uE3, and total hCG were taken from reference 2. The limits for free i3-hCG are not yet known and are therefore assumed to be the same as for total hCG because of the high correlation between these two markers. Table 1 shows the parameters for the serum markers in the detection of trisomy 18. As in Down's syndrome pregnancies, trisomy 18 pregnancies tend to have low values for AFP and uE3, but unlike Down's pregnancies they have low levels of total hCG and free ~-hCG. Table 2 shows the detection rates, false positive rates, and odds of being affected given a positive result (OAPR) when using maternal age (England and Wales, 1984-88), AFP, uE3, and either total hCG or free ~-hCG. The birth prevalence of trisomy 18 is taken as one tenth that of Down's syndrome' with a spontaneous fetal loss rate of 70% between 16 weeks and term. A mid-trimester risk cut off of 1 in 100 with AFP, uE3, and total hCG in combination with maternal age yields a detection rate of 59% and a false positive rate of 0·19%. The OAPR at term is 1:23. With a 1% fetal loss rate due to amniocentesis there would be 0·23 unaffected fetal losses for every term pregnancy

LH and estradiol secretion after HCG and GNRH treatments in gilts.

Two different mechanisms have been proposed to regulate luteinizing hormone (LH) secretion patterns: a long-loop feedback of estradiol-17 β (E) from the ovaries (Brinkley, 1981) and(or) a short-loop or internal feedback of pituitary hormones themselves (Motta et al., 1969; Docke and Glaser, 1971). In some species the increase in circulating estrogen to a critical level in late follicular phase elicits a surge release of LH by a positive feedback mechanism (Miyake et al., 1977). Results presented by Concannon et al. (1979) suggested that the preovulatory surge of LH in the female dog may be a response to withdrawal of the negative feedback effect of estrogens. Also, this withdrawal might be facilitated by a preovulatory increase in progesterone. Previous work in our laboratory (Ziecik et al., 1987) demonstrated that 1000 and 1500 IU of hCG blocked the post-synchronization preovulatory LH surge in 33% and 50%, respectively, of gilts previously treated with altrenogest and PMSG. The objective of the following study was to investigate the effect of higher doses of hCG in combination with bolus injections of GnRH on the secretion of E and LH.