Dose Of Human Chorionic Gonadotropin 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.

Human chorionic gonadotropin levels after ovulation triggering as predictors of clinical pregnancy after intracytoplasmic sperm injection: a prospective cohort study

ABSTRACT This study aimed to assess the correlation between human chorionic gonadotropin (HCG) levels after ovulation triggering and clinical pregnancy following intracytoplasmic sperm injection (ICSI), affected by HCG formulation and dose. The study was a prospective cohort study of 100 women who underwent ICSI and controlled ovarian stimulation (COS) using a fixed gonadotropin-releasing hormone (GnRH) antagonist protocol. Women were divided according to the type of ovulation triggering into three groups: (1) urinary HCG (uHCG) group (n = 33); (2) recombinant HCG (rHCG) group (n = 33); and (3) dual trigger group (n = 34). The three groups were compared to each other taking into consideration the HCG levels and their correlations to clinical pregnancy following ICSI. Clinical pregnancy could be predicted by serum HCG levels 34 h after ovulation triggering by uHCG, rHCG and dual trigger at cutoff levels of 73.72, 57.35 and 22.37 mIU/ml, respectively, with sensitivities of 95%, 94.7% and 87%, and specificities of 76.9%, 92.9% and 90.9%, respectively. Follicular fluid (FF) HCG levels could predict clinical pregnancy after ovulation triggering by uHCG, rHCG and dual trigger at cutoff levels of 21.58 mIU/ml, 20.82 mIU/ml and 8.66 mIU/ml, respectively, with sensitivities of 95%, 94.7% and 91.3%, and specificities of 92.3%, 92.9% and 90.9%, respectively. In conclusion, serum and FF HCG levels after ovulation triggering could predict clinical pregnancy following ICSI at variable cutoff levels according to HCG formulation and dose.

Guideline No. 315: Prevention of Ovarian Hyperstimulation Syndrome

Summary Statements1.The particular follicle-stimulating hormone formulation used for ovarian stimulation does not affect the incidence of ovarian hyperstimulation syndrome. (I)2.Coasting may reduce the incidence of severe ovarian hyperstimulation syndrome. (III)3.Coasting for longer than 3 days reduces in vitro fertilization pregnancy rates. (II-2)4.The use of either luteinizing hormone or human chorionic gonadotropin for final oocyte maturation does not influence the incidence of ovarian hyperstimulation syndrome. (I)5.There is no clear published evidence that lowering the human chorionic gonadotropin dose will result in a decrease in the rate of ovarian hyperstimulation syndrome. (III)6.Cabergoline starting from the day of human chorionic gonadotropin reduces the incidence of ovarian hyperstimulation syndrome in patients at higher risk and does not appear to lower in vitro fertilization pregnancy rates. (II-2)7.Avoiding pregnancy by freezing all embryos will prevent severe prolonged ovarian hyperstimulation syndrome in patients at high risk. (II-2)8.Pregnancy rates are not affected when using gonadotropin-releasing hormone (GnRH) agonists in GnRH antagonist protocols for final egg maturation when embryos are frozen by vitrification for later transfer. (II-2) Recommendations1.The addition of metformin should be considered in patients with polycystic ovarian syndrome who are undergoing in vitro fertilization because it may reduce the incidence of ovarian hyperstimulation syndrome. (I-A)2.Gonadotropin dosing should be carefully individualized, taking into account the patient’s age, body mass, antral follicle count, and previous response to gonadotropins. (II-3B)3.Cycle cancellation before administration of human chorionic gonadatropin is an effective strategy for the prevention of ovarian hyperstimulation syndrome, but the emotional and financial burden it imposes on patients should be considered before the cycle is cancelled. (III-C)4.Gonadotropin-releasing hormone (GnRH) antagonist stimulation protocols are recommended in patients at high risk for ovarian hyperstimulation syndrome (OHSS). The risk of severe OHSS in patients on GnRH antagonist protocols who have a very robust ovarian stimulation response can be reduced by using a GnRH agonist as a substitute for human chorionic gonadotropin to trigger final oocyte maturation. (I-B)5.A gonadotropin-releasing hormone (GnRH) antagonist protocol with a GnRH agonist trigger for final oocyte maturation is recommended for donor oocyte and fertility preservation cycles. (III-C)6.Albumin or other plasma expanders at the time of egg retrieval are not recommended for the prevention of ovarian hyperstimulation syndrome. (I-E)7.Elective single embryo transfer is recommended in patients at high risk for ovarian hyperstimulation syndrome. (III-C)8.Progesterone, rather than human chorionic gonadotropin, should be used for luteal phase support. (I-A)9.Outpatient culdocentesis should be considered for the prevention of disease progression in severe ovarian hyperstimulation syndrome. (II-2B)

Effects of Exogenous Human Chorionic Gonadotropin Administration on Plasma Testosterone and Semen Production in the Veiled Chameleon (Chamaeleo calyptratus)

Gamete collection, gamete preservation, hormone analysis, and artificial insemination have become integral parts of in situ and ex situ conservation programs for threatened and endangered species, and while these methods have been used to assist conservation in many different vertebrate groups, limited work has been done in reptiles. For example, semen collection in lizards has only recently been described and determined to be safe. The purpose of this study was to determine effective doses of human chorionic gonadotropin (hCG) for increasing plasma testosterone concentrations in the veiled chameleon (Chamaeleo calyptratus), as well as to determine whether the rise in testosterone impacts semen collection. A cross-over design was used. Chameleons were given injections of 100 IU, 200 IU, and 300 IU of hCG/animal and serial plasma testosterone measurements were collected over 24 hours. 100 IU/animal was determined to increase plasma testosterone concentrations similar to 200 IU, and 300 IU/animal. Following this, we determined weekly injections of hCG (100 IU/animal) would maintain elevated testosterone concentrations over 30 days. Additionally, we determined that elevated testosterone secondary to repeated injections of hCG decreased testicular size as determined by ultrasound. Repeated hCG injections and long-term elevation of plasma testosterone concentrations did not increase the likelihood to collect a semen sample with electroejaculation or improve ejaculate quality. Further research is needed to exogenously stimulate spermatogenesis and increase ejaculate quality to perform timed semen collections in male reptile species.

P-682 Androgen and Inhibin B levels during ovarian stimulation before and after eight weeks of low dose hCG priming in women with low ovarian reserve

Abstract Study question Does eight weeks of low dose human chorionic gonadotropin (hCG)-priming affect androgen or Inhibin B levels in serum and follicular fluid during IVF/ICSI treatment? Summary answer Inhibin B was reduced on stimulation day 1 in the IVF/ICSI cycle following hCG-priming. Androgen levels in serum and follicular fluid was not increased. What is known already In our recently published pilot study, eight weeks of low-dose hCG-priming was used to stimulate the intraovarian androgen synthesis in women with AMH <6.29 pmol/L. Priming resulted in more retrieved oocytes and more follicles sized 2-5 mm and less sized 6-10 mm at the start of stimulation. Stimulation time and FSH consumption was increased after priming. HCG priming potentially stimulate the intraovarian androgen synthesis causing upregulation of FSH receptors on granulosa cells, and therefore it was unexpected that the antral follicles were smaller and stimulation time longer following priming. This might indicate a different mechanism of action than previously thought. Study design, size, duration A prospective, paired, non-blinded, single-center study including 20 women conducted between January 2021 and July 2021 at a tertiary referral hospital. Participants underwent two identical IVF treatments: a Control cycle including elective freezing of all blastocysts and a Study cycle with fresh blastocyst transfer. The Control and Study cycles were separated by eight weeks (two menstrual cycles) of hCG-priming by daily injections of 260 IE hCG (details in our previously published paper). Participants/materials, setting, methods Women aged 18-40 years with cycle lengths of 23-35 days and AMH <6.29 pmol/L. Control and Study IVF cycles were performed in a fixed GnRH-antagonist protocol. Blood samples were taken on stimulation day 1, stimulation day 5-6, trigger day, day of oocyte pick up (OPU), and trigger day + 7 days in the Control and Study cycles. Follicular fluid was collected from the first aspirated follicle on both sides during OPU in both cycles. Main results and the role of chance Inhibin B serum levels were significantly lower on stimulation day 1 after hCG-priming, but no other significant differences in serum Inhibin B or androgen levels were seen. The concentrations of Inhibin B and androstenedione in the follicular fluid from the Study and Control cycle did not vary but testosterone was significantly lower in the Study cycle. A lower Inhibin B in the Study cycle corresponds with the antral follicles being significantly smaller after priming, and this probably led to a longer stimulation time in the Study cycle. This contradicts the theory that androgen priming causes more FSH receptors on developing (antral up to preovulatory) follicles. Instead, we hypothesize that androgen priming rescued some small antral follicles that would have otherwise undergone atresia by the end of the previous menstrual cycle. The mechanism of action was likely an increase in androgen levels and FSH receptor expression within these small follicles, however, not enough to elevate androgen levels in serum. We retrieved significantly more oocytes in the Study cycle and the production of estradiol per follicle ≥10 mm on trigger day was comparable in the Study and Control cycle, suggesting that the rescued follicles were competent in producing oocytes and steroid hormones. Limitations, reasons for caution The sample size was small, and androgen and Inhibin B levels were not the primary outcome. We have not demonstrated a higher androgen level or FSH receptor expression in small antral follicles following hCG-priming. Wider implications of the findings The results make us question the mechanism of action behind hCG-priming prior to IVF. It is important to design a study with retrieval of small antral follicles immediately after priming to investigate the proposed hypothesis and to confirm improved cycle outcomes i.e., more retrieved oocytes in a larger study population. Trial registration number NCT04643925

Puberty induction in boys with congenital isolated hypogonadotropic hypogonadism

Gonadotropin therapy in boys with congenital isolated hypogonadotropic hypogonadism helps to increase testes volume and induce spermatogenesis in comparison with testosterone therapy. However, difficulties with dose titration, partial therapy success, absence of generally accepted regimen protocols don't allow to use this therapy in order to induce puberty in adolescents with Kallmann syndrome or normosmic hypogonadotropic hypogonadism. To assess the effectiveness of combination hormonal replacement therapy via human chorionic gonadotropin and recombinant follicle stimulation hormone in adolescents with congenital isolated normosmic hypogonadotropic hypogonadism and with Kallmann syndromeMATERIALS AND METHODS: This is an open single-center prospective non-controlled study. Boys with hypogonadotropic hypogonadism were receiving hormonal replacement therapy for 12 months. Initial dose of human chorionic gonadotropin was 500 IU per week. Initial dose of recombinant follicle stimulation hormone was 37.5 IU per week. Doses were doubled in 6 months. Antropometric data, Tanner stage, testes volumes, inhibin B and anti-Mullerian hormone (AMH) levels were evaluated in all the patients before the treatment, after 6 and 12 months of the therapy. 8 boys with hypogonadotropic hypogonadism were included into the study. Median age before therapy initiation was 15.7 years [15.33; 16.41]. In 12 months after the therapy initiation puberty development, testosterone increase from 0.44 [0.34;0.62] to 4.39 [0.88;10.51] nmol/l (p=0.012), AMH decrease from 35.70 [18.00;59.00] to 14.41 [11.60;16.65] ng/ml were noted in all the patients (p=0.017). Testes volumes increase and inhibin B level increase were not statistically significant. Gonadotropin therapy is effective in order to puberty initiation in adolescents with congenital hypogonadotropic hypogonadism. In helps to achieve not only androgenization, but also to Sertoli cells maturation.

Variations in Gonadosomatic Index, Gonadal Development and Spawning Induction of Spotted Scat Scatophagus argus (Linnaeus, 1766)

This study evaluated variations in gonadosomatic index (GSI), gonadal development stages, and hormonal spawning induction of Scatophagus argus in captivity. Male and female fish were cultured separately in net cages in Tam Giang lagoon, Central Vietnam, from January to December 2020. Five fish of each sex were randomly sampled monthly. Gonads were collected, GSI determined, and subsequently prepared for histology. Gamete quality was assessed with a light microscope. Spawning was hormonally induced with different doses of human chorionic gonadotropin (hCG) and luteinizing hormone-release hormone (LHRH-A2). Gonadal development started to increase in March, peaking in July. The peak spawning period of the fish was from June to August, displaying the highest GSI value, sperm motility, and oocyte diameter. Only female GSI fluctuated significantly month-by-month (P<0.05). Histological examination indicated that S. argus is a multiple-spawner. Application of LHRH-A2 (70 µg/kg) stimulated spawning and resulted in better latency periods, fertilization, and hatching rates.

Sperm quality of artificially matured shortfinned eel is not affected by human chorionic gonadotropin dose and route of administration.

BackgroundAcquisition of high quality sperm is key to the artificial propagation of eels in captivity, but fertility drugs are expensive and repeated handling is stressful to the fish. An interrupted treatment regime (an initial hormone injection to stimulate spermatogenesis, followed several weeks later by weekly booster injections to induce sperm maturation) for acquisition of sperm in captive male eels has promise for high sperm quality on the one hand, and animal welfare benefits on the other. To further develop this approach for shortfinned eel, Anguilla australis, we evaluated the efficacy of (i) different initial doses of human chorionic gonadotropin (hCG) and (ii) route of administration.MethodsMale eels were artificially induced to mature with a single injection of 0, 250, 500 or 1,000 IU/fish of hCG, administered either intramuscularly (IM) or intraperitoneally (IP). Sperm maturation was induced with 150 IU hCG/fish from week 5 onwards and sperm collected for evaluation of quality by computer-assisted sperm analysis.ResultsControl males did not mature and hence, sperm could not be retrieved and analysed, but all other treatments were effective in inducing testicular maturation. Milt volume tended to be higher for fish injected IM compared to those injected IP, whereas hCG dose had no effect. Conversely, the concentration of spermatozoa tended to be higher for several sperm collection time points in IP-injected than in IM-injected fish. Sperm quality, represented by percent motility, percent progressive motility and curvilinear velocity, was equal in fish given an initial dose of 250 IU hCG to those given higher initial doses of hCG.ConclusionsWe recommend that an initial dose of 250 IU hCG/fish be administered to induce spermatogenesis in male A. australis, and, after a period of 4–5 weeks, weekly booster injections of ∼150 IU hCG/fish be administered in the day prior to sperm collection; both routes of administration (IM or IP) are equally effective. We contend that an interrupted treatment regime has notable benefits for induced maturation in male anguillids, as it reduces fish handling and manipulation and reduces the resources required to produce high quality sperm.

Freeze-all policy versus luteal phase support with low dose of human chorionic gonadotrophin for high-responder patients undergoing intracytoplasmic sperm injection on pregnancy outcomes: a retrospective cohort observational study

BackgroundThe literature has always controversies on the use of freeze-all policy in high-responder women performing intracytoplasmic sperm injection. In this article, we discuss the benefits of freeze-all policy on the incidence of pregnancy outcomes and the complications.The main body of abstractFreeze-all policy is applied to the intracytoplasmic sperm injection program by freezing of all embryos and delaying embryo transfer to another subsequent ovarian cycle, to decrease the incidence of ovarian hyperstimulation syndrome, especially in high-responder women. Unfortunately, freeze-all policy is correlated with an increase in the economic costs and more ICSI laboratory effort. Delayed embryo transfer (ET) is correlated with more anxiety among the patients. An alternative strategy is to perform fresh embryo transfer with more intensive luteal phase support to compensate for the negative effect of the GnRH agonist on the endometrial receptivity and luteal phase support.Short conclusionThe freeze-all policy had better pregnancy rates with less incidence of moderate to severe hyperstimulation syndrome compared with original fresh embryo transfer in high-responder women performing intracytoplasmic sperm injection.

Gonadotropin receptor polymorphisms (FSHR N680S and LHCGR N312S) are not predictive of clinical outcome and live birth in assisted reproductive technology

To study the consequences of specific genotype profiles of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone choriogonadotropin receptor (LHCGR) on assisted reproductive technology outcomes when preimplantation genetic testing for aneuploidy is used for controlling the embryo ploidy status. The most common reported single-nucleotide polymorphisms in the amino acid position for the FSHR (N680S; N: asparagine, S: serine; [rs6166]) and the LHCGR (N312S variant; N: asparagine, S:serine [rs2293275]) were chosen for this study. Retrospective cohort study. Private Fertility Clinic. All women aged 18-40 years undergoing their first assisted reproductive technology cycle with aneuploidy screening between 2006 and 2017 with body mass index of >18 and <40 kg/m2 were included. All patients received both recombinant follicle-stimulating hormone and human menopausal gonadotropin or low dose human chorionic gonadotropin. Genomic DNA was isolated from patients' blood. Genotyping of the FSHR and LHCGR polymorphisms was performed using TaqMan genotyping assays. Associations between both receptor genotypes and clinical outcomes were assessed using generalized regression and ANOVA. Live birth rate was the primary outcome. Secondary outcomes included oocyte yield, mature oocytes, blastulation rate, usable blastocyst rate, and implantation rate. A total of 1,183 patients met the inclusion criteria and generated reliable genotype results. The overall genotype frequencies in the study population for the FSHR gene were as follows: 21.7% homozygous for S in codon 680, 29.2% homozygous for N680, and 48.1% heterozygous (N680S). As for the LHCGR, 15.6% were homozygous for N312, 38.5% homozygous for S312 and 45.9% heterozygous (N312S). Our study population consisted of 53.8% non-Hispanic white; 6.1% Hispanic white; 4.1% Afro-American; 15.4% Asian; and 20.6% other or unknown. No significant association was found with any of the studied variables (oocyte yield, usable blastocyst rate, implantation rate, live birth) when genotypes were analyzed per receptor or in combination with one another. There was a statistically significant but clinically irrelevant difference in the rate of mature oocytes across different variant combinations. Our findings suggest that the presence of gonadotropin receptor polymorphisms in both FSHR N680S and LHCGR N312S are not associated with assisted reproductive technology outcomes; therefore, these variants should not be considered reproductive predictors.

Effect of elevating luteinizing hormone action using low doses of human chorionic gonadotropin on double ovulation, follicle dynamics, and circulating follicle-stimulating hormone in lactating dairy cows

Double ovulation and twin pregnancy are undesirable traits in dairy cattle. Based on previous physiological observations, we tested the hypothesis that increased LH action [low-dose human chorionic gonadotropin (hCG)] before the expected time of diameter deviation would change circulating FSH concentrations, maximum size of the second largest (F2) and third largest (F3) follicles, and frequency of multiple ovulations in lactating dairy cows with minimal progesterone (P4) concentrations. In replicate 1, multiparous, nonbred lactating Holstein dairy cows (n = 18) had ovulation synchronized. On d 5 after ovulation, all cows had their corpus luteum regressed and were submitted to follicle (≥3 mm) aspiration 24 h later to induce emergence of a new follicular wave. Cows were then randomized to NoP4 (untreated) and NoP4+hCG (100 IU of hCG every 24 h for 4 d after follicle aspiration). Ultrasound evaluations and blood sample collections were performed every 12 h for 7 d after follicle aspiration. All cows were then treated with 200 μg of GnRH to induce ovulation. In replicate 2, cows (n = 16) were resubmitted to similar procedures (i.e., corpus luteum regression, follicle aspiration, randomization, ultrasound evaluations every 12 h, GnRH 7 d after aspiration). However, cows in replicate 2 received an intravaginal P4 device that had been previously used (∼18 d). Only cows with single (n = 15) and double (n = 16) ovulations were used in the analysis. No significant differences were detected for frequency of double ovulation, follicle sizes, and FSH concentrations across replicates (NoP4 vs. LowP4 and NoP4+hCG vs. LowP4+hCG), so data were combined. Double ovulation was 40% for control cows with no hCG (CONT) and 62.5% with hCG (hCG). Double ovulation increased as the maximum size of F2 increased: <9.5 mm and 9.5-11.5 mm (7.7%) and ≥11.5 mm (94.1%). The hCG group had more cows with F2 > 11.5 (69%) than with 9.5 ≥ F2 ≤ 11.5 (25%) and F2 < 9.5 (6%). In agreement, F2 and F3 maximum size were larger in the hCG group, but FSH concentrations were lower after F1 > 8.5 mm compared with CONT. In contrast, FSH concentrations were greater before deviation (F1 closest value to 8.5 mm) in cows with double ovulations than in those with single ovulations, regardless of hCG treatment. In addition, time from aspiration to deviation was shorter in cows with double rather than single ovulation and in cows treated with hCG as a result of faster F1, F2, and F3 growth rates before diameter deviation. In conclusion, greater FSH and follicle growth before deviation seems to be a primary driver of greater frequency of double ovulation in lactating cows with low circulating P4. Moreover, the increase in follicle growth before deviation and in the maximum size of F2 during hCG treatment suggests that increased LH may also have a role in stimulating double ovulation.

Does the HCG trigger dose used for IVF impact luteal progesterone concentrations? a randomized controlled trial

Research questionIs there an association between the ovulation trigger dose of human chorionic gonadotrophin (HCG) and endogenous progesterone production during the luteal phase? DesignThis randomized controlled four-arm study, at the Fertility Clinic, Odense University Hospital, Denmark, included women undergoing gonadotrophin-releasing hormone (GnRH) antagonist IVF treatment with ≤11 follicles ≥12 mm. Group 1–3 were triggered with 5000 IU, 6500 IU or 10,000 IU HCG, respectively, receiving 17α-hydroxyprogesterone caproate intramuscularly for luteal-phase support (LPS) to measure endogenous progesterone production. Group 4 received 6500 IU HCG trigger and vaginal progesterone. During the study, the 5000 IU and 10,000 IU HCG groups were switched from urinary to recombinant HCG, as urinary HCG was removed from market. Eight blood samples were drawn during the luteal phase. ResultsNinety-four participants completed the study. There was a significant positive association between the HCG trigger dose and the progesterone at 8 days (P < 0.001), 10 days (P < 0.001) and 14 days (P < 0.001) post-oocyte retrieval. Comparing the groups individually revealed a significant difference in progesterone concentration between low and high trigger doses at 4 days (P = 0.037) and 8 days (P = 0.007) post-oocyte retrieval and between all intervention groups at oocyte retrieval + 6 days: group 1 and 2 (P = 0.011), group 2 and 3 (P = 0.042) and group 1 and 3 (P < 0.001). Higher HCG trigger dose increased the progesterone from the individual follicle. ConclusionsIncreasing HCG trigger doses significantly increased endogenous progesterone concentration during the mid–late luteal phase.

Continuous Testosterone Therapy with Recombinant FSH & HCG Improves Semen Parameters: A Pilot Study

ABSTRACT Introduction Male hypogonadism is characterized by inadequate production of Testosterone (T) and a deficiency in spermatogenesis. The main treatment of male hypogonadism is T therapy (TTh), which can disrupt normal hypothalamic-pituitary-gonadal axis function and cause oligospermia and/or azoospermia with testicular atrophy. Objective We evaluated the safety and efficacy of continuous intramuscular testosterone administration in combination with low doses of human chorionic gonadotropin (HCG) and recombinant follicle stimulating hormone (FSH) on semen parameters. Methods A total of 10 hypogonadal men on TTh, HCG, and FSH who had achieved pregnancy with their partners or had successful sperm retrievals were retrospectively identified. All of the men were maintained on continuous intramuscular testosterone therapy, HCG at 750 IU subcutaneously twice weekly and recombinant FSH 75 IU every other day. A semen analysis was performed in men who had not had vasectomy prior to or after starting therapy, and serum testosterone, estrogen, FSH, LH, hemoglobin and hematocrit levels, as well as a scrotal ultrasound for testicle size determination, were obtained. Results Of the 10 men with a mean(SD) age of 39.5(6.4) years) who underwent treatment, 7 achieved pregnancy naturally and 3 underwent sperm retrieval due to prior vasectomy, with successful sperm retrieval in all 3. Mean(SD) pretreatment T levels were 745(614) ng/dl, Estradiol 38.7(42.8) pg/ml, LH 0.18(0.24) IU/L, FSH 0.47(0.46) IU/L. Mean(SD) total motile sperm count (TMSC) was 1.43(2.99) million total motile sperm. Mean(SD) pretreatment testicular volume was 11.1(3.3)cc and post-treatment was 11(5.5) cc. Mean(SD) post-treatment T levels were 1185(482) ng/dl, Estradiol 26.0(16.9) pg/ml, LH 0.43(0.23) IU/L, FSH 1.78(0.91) IU/L, with TMSC 102.8(89.4) million. Conclusions Across a cohort of 10 men, TTh in combination with HCG and FSH resulted in resumption or increase in TMSC during treatment, resulting in either natural pregnancy or successful sperm retrieval and supporting the conclusion that TTh does not require cessation in men desiring fertility during TTh. Further prospective studies are required to validate these findings. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Vault Health

Tie1 contributes to the development of ovarian hyperstimulation syndrome under the regulation of EGR1 in granulosa cells

The expression of tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 (Tie1), a transmembrane protein expressed almost exclusively by endothelial cells, has been reported in granulosa cells. However, its significance in ovarian hyperstimulation syndrome (OHSS), which can occur after the injection of gonadotropins in infertile women undergoing controlled ovarian stimulation, is unknown. Here, we report significantly increased Tie1 and vascular endothelial growth factor (VEGF) expression in cultured granulosa cells from OHSS patients, as well as ovaries from rats with experimentally established OHSS, compared to controls, with the levels of both proteins also increasing in granulosa and SVOG cells (a nontumorigenic human granulosa-lutein cell line) treated with an acute dose of human chorionic gonadotropin (hCG). Tie1 silencing abolished the hCG-induced VEGF level in SVOG cells and attenuated the progression of OHSS in rats, as determined by histological analysis. Further studies in SVOG cells revealed that the hCG-induced upregulation of Tie1 expression involved the phosphoinositide 3-kinase/protein kinase B signaling pathway. We also report that early growth response protein 1 (EGR1), whose expression was also upregulated by hCG, bound directly to the Tie1 promoter and activated its transcription. Taken together, our results indicate that Tie1 may be a therapeutic target in cases of moderate-to-severe OHSS. Further studies are needed to address its clinical relevance.

Effect of administration two doses of Human chorionic gonadotropin and combination between human chorionic gonadotropin and flunixin meglumine on pregnancy rates in repeat breeders cross breed cows.

The aim of the current study is to treat cases of repeat breeder in crossbreed cows and to improve pregnancy rate in affected cows. The study divided the number of animals into four groups, group (10 = T1), where the first group gave human chorionic gonadotropin on the day of oestrus and repeated the same dose 1500 IU Five days postinsemination and the group (T2 = 10) where the hCG hormone was given at a dose of 1500 IU on the day of the estrus and Flunxin meglumine treatment with a dose (2ml / 50 kg b.w) each ml contain to (50mg of FM) from the fifth day post insemination for three days and the third group, which numbered 5 cows in the group (C1 = 5), were considered a control group without treatment, while the fourth group(C2=5) is considered fertile cows, the purpose of their presence in the study is to evaluate the effectiveness of the fertility of the semen straws used in the study. The study showed that the pregnancy rate in cows in the groups, respectively, is 40%, 60%, 0%, 60%. The statistical analysis showed that there were significant differences at (P˂0.01) between the treated and fertile groups and the untreated group, which means an improvement in the pregnancy rate in treated cows that were suffering from repeat breeding. Early pregnancy was diagnosed rectally using ultrasound

Adding Low Dose hCG to rFSH in GnRH Antagonist ICSI Cycles: A Randomized Controlled Trial

Inhibition of luteinizing hormone (LH) by gonadotropin releasing hormone (GnRH) antagonist may lead to suboptimal response during ovarian stimulation. In addition, several studies suggest that low level of LH is associated with lowered fertilization and implantation rate and increased early pregnancy loss rate. The aim of this study is to study the effect of adding low dose human chorionic gonadotropin (hCG - 200 IU), as an LH supplement, to recombinant follicle stimulating hormone (rFSH) in a GnRH antagonist cycles in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Sixty-three infertile women undergoing IVF were randomly divided into two groups. One group was stimulated with the conventional stimulation protocol (rFSH alone), while the second group received 200 IU hCG in addition to rFSH in the late follicular phase (hCG + rFSH). Both groups' results including pregnancy rate, total dose of rFSH required, duration of stimulation, endometrial thickness, oocytes and embryos characteristic, serum hormone levels (Testosterone, Estradiol, Progesterone, and LH) and level of epidermal growth factor (EGF) were compared. The results show that pregnancy rate among the group of women who received the low dose hCG was higher than those who did not receive hCG. However, this difference did not reach statistical significance. Furthermore, other cycle outcomes and hormonal values were comparable between the two stimulation protocols.

Dual trigger with the combination of gonadotropin-releasing hormone agonist and standard dose of human chorionic gonadotropin improves in vitro fertilisation outcomes in poor ovarian responders

The study aimed to evaluate the impact of the dual trigger with the combination of GnRH agonist and standard dose of recombinant hCG on IVF outcomes in poor ovarian responders with GnRH antagonist protocol. 1283 cycles of 1010 poor responder patients according to Bologna criteria were retrospectively analysed in terms of final oocyte maturation: dual trigger group (250 μg hCG + 0.2 mg triptorelin) or standard group (250 μg hCG). Primary outcome measures were the number of retrieved and mature oocytes. The secondary outcome measures were clinical pregnancy rates and live birth rates. The number of retrieved oocytes, mature oocytes, and the top-quality embryos transferred were significantly higher in the dual trigger group (p < .001). Fertilisation rates (73.6% vs 69.6%, p = .009), implantation rates (18.7% vs 14.6, p = .039), clinical pregnancy rate per embryo transfer (27.5% vs. 19.9%, p = .010) and live birth rate per embryo transfer (21.6% vs. 14.9%, p = .011) were also significantly higher in the dual trigger group as compared to the hCG trigger group. The usage of dual trigger with a GnRH agonist and a standard dosage of hCG could improve clinical pregnancy rates and live birth rates in poor ovarian responders undergoing GnRH antagonist IVF/ICSI cycles. IMPACT STATEMENT What is already known on this subject? Dual trigger with standard dose of hCG has been the subject of trials in normal responders to optimise IVF outcomes. The results of these studies showed significant improvements in implantation and pregnancy rates with an increase in the number of mature oocytes retrieved. As a result, dual trigger has become a popular ovulation trigger option in GnRH antagonist cycles. What do the results of this study add? There is limited data about the use of dual trigger in poor ovarian responders (PORs). According to our study, increasing the number of retrieved oocytes, mature oocytes, the number of fertilised oocytes, the number of transferred embryos and top quality embryos transferred by using dual trigger in patients with PORs have a positive impact on pregnancy outcomes. What are the implications of these findings for clinical practice and/or further research? These findings implies potential advantages of dual trigger usage for improving IVF outcomes in PORs. With large sample sized prospective randomised trials, dual trigger with combination of GnRHa and a standard dose of hCG might replace the traditional ovulation trigger with hCG in PORs.

DOES DUAL TRIGGER WITH COMBINATION OF GONADOTROPIN-RELEASING HORMONE AGONIST AND LOW DOSE HUMAN CHORIONIC GONADOTROPIN IMPROVES CLINICAL OUTCOMES IN NORMAL RESPONDERS IN GnRH ANTAGONIST IVF-ICSI CYCLES

Clinical outcomes of dual trigger containing gonadotropin-releasing hormone agonist (GnRHa) and low dose human chorionic gonadotropin (hCG) compared with the standard dose of human chorionic gonadotropin (hCG) trigger for final oocyte maturation in normal responder patients in GnRH Antagonist IVF-ICSI Cycles. A single centre prospective randomized comparative study conducted at a tertiary care infertility centre , Akanksha IVF centre, Janakpuri, New Delhi from 1st March 2020 to 28th February 2021. 80 normal responder patients defined as women in age group 21 to 37 year, with serum AMH level >1.2 ng/ml to < 4ng/ml , with AFC (3- 8) per ovary who were to undergo controlled ovarian hyperstimulation (COH) for IVF-ICSI cycles, were randomized by a computer based program into 2 groups of 40 each. All the patients underwent ovarian stimulation with a starting dose of recombinant FSH with dosage 150-225 IU on D2 and the dosage were adjusted according to follicular monitoring After at least one follicle reached a size of 14mm , antagonist Inj Cetrorelix 0.25 mg started subcutaneously daily. When > 2 follicles reached the size of 18 mm final oocyte maturation was triggered by either dual trigger of Inj Leuprolide acetate 2 mg and low dose 2000 IU highly purified Inj. hCG subcutaneously in Group 1 or by standard trigger dose 10000 IU of highly purified inj hCG in Group2. Oocyte retrievals were performed 35 to 36 hours after the trigger. IVF-ICSI was performed in all cases. Day 3 fresh embryo transfers were performed for all cases (2 x 8cell embryos).The luteal phase support was with vaginal supplementation of 800 mg micronized progesterone. Serum beta hCG was performed after14 days of embryo transfer . Primary outcome measured was clinical pregnancy rate and secondary outcomes measured were: implantation rate, miscarriage rate, number of MII oocytes picked up, number of embryos formed, and risk of OHSS. In dual trigger , group 1 the clinical pregnancy rate (52.50% vs 47.50% ) and implantation rate (29.67% vs 26.08% ) were higher than in Group 2 , and but the difference was not statistically significant. Miscarriage rate was lesser in group 1 (14.28%) than in group 2 (15.78%) and it was also not statistically significant . There were higher number of MII oocytes picked up and higher number of embryos formed in group1/ dual trigger group (10.63+5.46 and 8.2+3.4 respectively ) than in group 2 (8.10+5.74 and 6.8+3.6 respectively) and this difference was statistically significant . No OHSS was reported in group 1/ dual trigger group. Though there was increased clinical pregnancy rate, implantation rate and a lesser miscarriage rate in dual trigger group1 for but it was statistically not significant .There was significant increase in MII oocytes and number of embryos formed (p value .0064 and .0 156 respectively) in the dual trigger group. There was also no risk of OHSS in dual trigger group.

Clinical pregnancy resulting from intracytoplasmic sperm injection of prematurely ovulated oocytes retrieved from the posterior cul-de-sac

ObjectiveTo report a clinical pregnancy resulting from intracytoplasmic sperm injection of prematurely ovulated oocytes retrieved from the posterior cul-de-sac.DesignCase report.SettingAcademic center.Patient(s)A 40-year-old nulligravid woman underwent ovarian stimulation for in vitro fertilization (IVF). Daily injections of gonadotropin-releasing hormone antagonist were initiated on cycle day 8. A 10,000 IU dose of human chorionic gonadotropin was administered on cycle day 15 to trigger follicular maturation. The estradiol and luteinizing hormone levels on the trigger day were 1528 pg/mL and 2.4 mIU/mL, respectively. The patient underwent oocyte retrieval 35 hours after the trigger. Transvaginal sonography at the time of the retrieval revealed a large pocket of free fluid in the posterior cul-de-sac. Only 3 follicles measuring 10–12 mm were noted in both ovaries. No lead follicles were visualized.Intervention(s)Aspiration of free fluid from the posterior cul-de-sac.Main Outcome Measure(s)Clinical pregnancy.Result(s)The fluid in the posterior cul-de-sac was aspirated, and 3 mature oocytes were retrieved. Aspiration of the smaller ovarian follicles measuring 10–12 mm did not yield oocytes. All mature oocytes retrieved from the posterior cul-de-sac were fertilized with intracytoplasmic sperm injection. Three cleavage-stage embryos were transferred 3 days later. A single intrauterine pregnancy with cardiac activity was confirmed at a gestational age of 7 weeks.Conclusion(s)In the setting of premature ovulation, aspiration of free fluid from the posterior cul-de-sac can result in the retrieval of mature oocytes, which may result in clinical pregnancies.

Disorders of Sex Development.

Disorders of Sex Development.