hCG Group Research Articles

Frozen-thawed embryo transfer: does the addition of low-dose choriogonadotropin alfa to progesterone in the luteal phase of artificial cycles improve the endometrium and increase the chances of pregnancy?

Primary: To evaluate the effect of low doses of recombinant hCG (choriogonadotropin alfa) in the luteal phase of frozen-thawed embryo transfers (FET) of artificial cycles on the chances of pregnancy in patients aged ≤38years. Secondary: To assess the chances of pregnancy in the FET groups of artificial cycles using micronized vaginal progesterone (VP) versus injectable intramuscular progesterone (IMP) and the chances of pregnancy in type-1 embryo transfers (two top embryos). This retrospective cohort study included 122 cycles of FET and compared two groups of patients aged 38 years or younger, one given hCG in the luteal phase and one not administered hCG. The clinical pregnancy rates (CPR) in the control and hCG groups were 45% and 45.16%, respectively (p=0.9999). The live birth rates (LBR) were 33.33% and 32.25%, respectively, (p=0.99909). The CPR in the VP group (83 patients) was 46.89% versus 41.02% in the IMP group, (p=0.5459). The LBR was 33.73% in the VP group and 30.76% in the IMP group (39 patients), (p=0.7559). The CPR and LBR of patients undergoing FET in groups prescribed and not prescribed low doses of recombinant hCG were similar. No significant difference was found between patients given VP or IMP.

Is pregnancy loss initiated by embryonic death or luteal regression? Profiles of pregnancy-associated glycoproteins during elevated progesterone and pregnancy loss

Because progesterone (P4) is essential for pregnancy establishment and maintenance, we investigated the effect of increased concentrations of P4 on embryonic attachment and concentrations of pregnancy-associated glycoproteins (PAG). Additionally, we investigated the relationships among luteal regression, pregnancy loss, and PAG concentrations in cows undergoing pregnancy loss by d 33 of pregnancy. Lactating dairy cows were allocated into control (n = 40) and human chorionic gonadotropin (hCG; 3,300 IU on d 7 and 13 to promote greater circulating P4; GnRH = d 0; n = 46) groups. Progesterone was measured daily from d 7 to 33, and PAG was measured daily from d 17 to 33; both hormones were also measured on d 47 and 61. An increase in PAG >10% compared with d 17 was considered a marker for pregnancy. The gold standard for pregnancy diagnosis was ultrasound evaluation of embryonic heartbeat on d 33. Statistical analyses were done with PROC MIXED from SAS Institute Inc. Concentrations of P4 were greater from d 8 onward in the hCG group. Concentrations of PAG did not differ between groups from d 17 to 33, suggesting no effect of increased P4 on hastening embryonic attachment and placental development. Nevertheless, PAG was greater in the hCG group on d 47 and 61, suggesting greater placental area or PAG secretory capacity. Pregnancy loss between d 20 and 33 occurred in 24.6% of cows. About 50% of pregnancy loss was due to luteal regression and about 50% was due to conceptus failure; that is, a decrease in PAG in the absence of luteal regression. In conclusion, increased P4 does not hasten embryonic attachment or early placental development but it leads to increased PAG in the second half of the second month of gestation. Additionally, pregnancy loss seems to be initiated by either corpus luteum regression or conceptus failure.

Expression Patterns and Gonadotropin Regulation of the TGF-β II Receptor (Bmpr2) during Ovarian Development in the Ricefield Eel Monopterus albus

Bmpr2 plays a central role in the regulation of reproductive development in mammals, but its role during ovarian development in fish is still unclear. To ascertain the function of bmpr2 in ovarian development in the ricefield eel, we isolated and characterized the bmpr2 cDNA sequence; the localization of Bmpr2 protein was determined by immunohistochemical staining; and the expression patterns of bmpr2 in ovarian tissue incubated with FSH and hCG in vitro were analyzed. The full-length bmpr2 cDNA was 3311 bp, with 1061 amino acids encoded. Compared to other tissues, bmpr2 was abundantly expressed in the ovary and highly expressed in the early yolk accumulation (EV) stages of the ovary. In addition, a positive signal for Bmpr2 was detected in the cytoplasm of oocytes in primary growth (PG) and EV stages. In vitro, the expression level of gdf9, the ligand of bmpr2, in the 10 ng/mL FSH treatment group was significantly higher after incubation for 4 h than after incubation for different durations. However, bmpr2 expression in the 10 ng/mL FSH treatment group at 2 h, 4 h and 10 h was significantly lower. Importantly, the expression level of bmpr2 and gdf9 in the 100 IU/mL hCG group had similar changes that were significantly decreased at 4 h and 10 h. In summary, Bmpr2 might play a pivotal role in ovarian growth in the ricefield eel, and these results provide a better understanding of the function of bmpr2 in ovarian development and the basic data for further exploration of the regulatory mechanism of gdf9 in oocyte development.

Evaluation of hCG as gonadotropic support to timed embryo transfer protocol in beef cattle

This study compared the reproductive performance of embryo recipients treated with a timed embryo transfer (TET) protocol using human chorionic gonadotropin (hCG) or equine chorionic gonadotropin (eCG). On a random day of the estrous cycle (Day −10) indicus-taurus recipients (n = 341; 194 nulliparous and 147 multiparous cows) with a body condition score between 3.0 and 4.0, were submitted to the TET protocol consisting of an intramuscular (i.m.) injection of 2.0 mg estradiol benzoate (EB) and the insertion of intravaginal progesterone (P4) device that remained until Day −2.5. On the same day (−2.5), the recipients received i.m. 150 mg D-cloprostenol and 1 mg estradiol cypionate and were randomly divided into two groups: the eCG group (n = 179), in which females received i.m. 300 IU eCG and the hCG group (n = 162), in which females received 150 IU hCG. Then, estrus intensity and the diameter of the dominant follicle (DF) were monitored on D0 and the quality of the corpus luteum (CL) (B mode and color Doppler) was assessed on D7 to select recipients eligible for receiving the transfer of an embryo produced in vitro. Pregnancy diagnosis was assessed 23 days after the transfer. Continuous data were analyzed by ANOVA using a mixed-effects model and Tukey's test. The rates were analyzed using a logistic regression model. The diameter of the DF on day 0 of the TET protocol was influenced by the interaction between gonadotropic treatment and category (P = 0.01), and nulliparous recipients treated with hCG had the smallest diameter. Treatment with hCG and eCG resulted in a high rate of estrus expression; however, the proportion of females with a high-intensity of estrus was higher in the hCG group (79.84 vs. 68.61%, respectively; P = 0.03). The utilization rate (recipients with CL) showed a tendency (P = 0.06) to be influenced by the interaction between gonadotropic treatment and category, wherein nulliparous recipients treated with hCG exhibited a lower utilization rate than the other groups. The diameter, perimeter, and area of the CL were similar (P > 0.1) in all groups. However, the hCG group resulted in CL with a better Doppler evaluation score (P = 0.04), central blood flow (P = 0.03), and tendency towards greater peripheral blood flow (P = 0.08). The rates of conception (32.00% hCG vs. 35.10% eCG; P = 0.46) and pregnancy (24.69% hCG vs. 29.61% eCG; P = 0.20) were similar between the hCG and eCG groups. However, an interaction between the gonadotropic treatment and category revealed lower conception (P = 0.01) and pregnancy rates (P = 0.001) in nulliparous recipients treated with hCG. Treatment with hCG resulted in a greater intensity of estrus expression and CL with a higher Doppler score, which determined rates of utilization, conception, and pregnancy similar to conventional protocols using eCG. However, nulliparous recipients treated with hCG exhibited a lower overall reproductive rate.

IMPACT OF DUAL TRIGGER WITH GONADOTROPIN RELEASING HORMONE AGONIST AND HUMAN CHORIONIC GONADOTROPIN ON IN-VITRO FERTILIZATION CYCLE OUTCOMES OF POSEIDON GROUP 3 AND 4 EXPECTED POOR RESPONDER WOMEN

To compare the clinical outcomes of dual triggering with gonadotropin releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG) in POSEIDON groups 3 and 4 low prognosis women with hCG only triggering, in antagonist cycles.

Effect of Dual Trigger In Vitro Fertilization and Intracytoplasmic Sperm Injection During the Gonadotropin-releasing Hormone-Antagonist Cycle on Final Oocyte Maturation and Cumulative Live Birth Rate in Women with Diminished Ovarian Reserve.

It is well known that a dual trigger treatment can improve clinical outcomes of in vitro fertilization (IVF) in high or normal ovarian responders. However, it is not clear whether dual triggering also benefits patients with diminished ovarian reserve (DOR). The aim of this study was to investigate whether a dual trigger treatment of gonadotropin-releasing hormone (GnRH) agonist combined with human chorionic gonadotropin (hCG) for final follicular maturation improves the cumulative live birth rate (CLBR) during the GnRH-antagonist cycle in patients with DOR. This retrospective study included patients with DOR who received a GnRH-antagonist protocol during IVF and intracytoplasmic sperm injection (IVF-ICSI) cycles at Peking University People's Hospital from January 1, 2017 through December 31, 2017. Oocyte maturation was triggered by GnRH combined with hCG (n=110) or hCG alone (n=71). Embryos were transferred on the third day after oocyte retrieval or during a subsequent freeze-thaw cycle. Patients were followed up for 3 years. The dual trigger treatment did not affect CLBR, which is an overall determinant of the success rate of assisted reproductive technology (ART). Women in the dual trigger group had significantly higher rates of fertilization than those in the hCG group (90.1% vs. 83.9%, P=0.040). Dual trigger with GnRH agonist and hCG did not improve CLBR in patients with DOR, but did slightly improve fertilization rate, oocyte count, and embryo quality.

Hormonal profile in early luteal phase after triggering ovulation with gonadotropin-releasing hormone agonist in high-responder patients.

The major limitations associated with gonadotropin-releasing hormone agonist (GnRHa) triggering are inferior clinical outcomes in fresh embryo transfer cycles caused by luteal phase insufficiency following the GnRHa triggering. We included 153 high-risk patients in this study. In group I, the patients received gonadotropin-releasing hormone agonist (GnRHa) trigger + 1,500 IU human chorionic gonadotropin (hCG) support on the oocyte pick-up (OPU) day; in group II, the patients had a dual trigger (GnRHa + 1,500 IU hCG); and in group III (control), 10,000 IU hCG trigger was prescribed for the final oocyte maturation. The levels of LH, estradiol, and progesterone were evaluated in serum on the stimulation starting day, day 6 of stimulation, on the day of the trigger administration, OPU day, days 3 and 5 post-OPU, and day 14 post-ET, as well as in follicular fluid. Progesterone concentration was significantly lower in group I on OPU+5 compared to the hCG group (I vs. III, р = 0.0065). Progesterone levels were significantly lower in group II in serum on OPU+5 compared to groups I and III (I vs. II, р = 0.0068; II vs. III, р = 1.76 × 108). The progesterone levels were significantly higher in follicular fluid in group III compared to the study groups (I vs. III, р = 0.002; II vs. III, p = 0.009). However, no significant differences in clinical outcomes were found between the groups. Then, we divided all women into pregnant and non-pregnant groups and found that estradiol (p = 0.00009) and progesterone (p = 0.000036) on the day of the pregnancy test were significantly higher in the pregnant women group. Also, progesterone on OPU day was significantly higher in the non-pregnant group (p = 0.033). Two cases of moderate ovarian hyperstimulation syndrome (OHSS) late-onset occurred in group I (3.5%, 2/56), no case of moderate/severe OHSS late-onset in group II, and three cases of moderate late-onset in group III (5.7%, 3/53). The low-dose hCG supplementation improves the luteal phase insufficiency after GnRHa triggering, which is confirmed by the comparable pregnancy rates in fresh transfer cycles between the groups. However, low-dose hCG carries a similar risk of OHSS as the full dose of hCG in high-responder patients.

Intrauterine infusion of human chorionic gonadotropin improves the endometrial FoxP3+ Tregs level and pregnancy outcomes in patients with lower endometrial FoxP3+ Tregs

Intrauterine infusion of human chorionic gonadotropin (hCG) is suggested to have the capacity to recruit regulatory T cells (Tregs) in the endometrium. However, the pregnancy outcome for infertile women with a lower level of Tregs after hCG intrauterine infusion remains unknown. By examining the expression of FoxP3+ Tregs in the endometrium, this study aimed to evaluate the effectiveness of hCG intrauterine infusion in infertile women with lower endometrial Tregs in improving the Tregs level and the pregnancy outcome. This cohort study included 150 women aged 38 and younger with a lower FoxP3+ Tregs level in the mid-luteal phase. Patients were divided into the control group (n=73), and hCG group (n=77). Patients in the hCG group received three times of hCG intrauterine infusion during the follicular phase in the next biopsy and the embryo transfer cycles. The results showed that the endometrial FoxP3+ Tregs level increased significantly after hCG intrauterine infusion (P<0.001). The effective rate in rescuing the endometrial Tregs level was 77.92% (60/77). The clinical pregnancy rate was increased significantly in the hCG group than the control group (54.8% vs. 74.0%, P=0.014). The logistic regression result showed that hCG intrauterine infusion [adjusted odds ratio (aOR) (95% confidence interval (CI)) =2.347 (1.119, 4.923), P=0.024] and blastocyst transfer [aOR (CI) = 2.630 (1.090, 6.346)] are two independent factors contributing to the improved pregnancy outcome. These data highlighted the immune regulatory role of hCG intrauterine infusion and might facilitate the personal immunotherapy progress for unexplained infertility in patients with a lower endometrial Tregs level.

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.

P-584 Dual trigger with hCG plus GnRHa for final oocyte maturation in PGT-A cycles results in similar euploidy rates when compared to hCG only trigger

Abstract Study question To assess whether dual trigger alters the ploidy chance of a blastocyst in preimplantation genetic screening for aneuploidy (PGT-A) cycles Summary answer Compared to hCG triggerring, dual triggerring does not provide an additional superiority on blastocyst euploidy rate. What is known already Variables that may affect euploidy rates in various stages of an IVF cycle such as total gonadotropin dosage, stimulation regimen, ovarian response and switching to natural cycle were not shown to affect blastocyst euploidy rates. Furthermore, there is no difference when final oocyte maturation is triggered with hCG or GnRHa. On the other hand, it has been shown that dual trigger with hCG plus GnRHa may result in a higher maturation rate in oocytes, compared to hCG only trigger. There are controversial data in the literature about the effect of dual trigger on euploidy rates. Study design, size, duration This is a retrospective cohort study of 385 PGT-A cycles performed over a 7-year time period between May 2012 and April 2019 at a single tertiary center for various indications. Participants/materials, setting, methods All couples undergoing IVF/intracytoplasmic sperm injection (ICSI) with planned PGT-A were included in the study, regardless of whether an embryo transfer was performed or not. Final oocyte maturation was triggerred using human chorionic gonadotropin (hCG) or the combination of hCG and gonadotropin releasing hormone agonists (GnRHa) (Dual trigger). Participants were divided based on triggering method and all demographic and clinical characteristics of the patients were compared. Main results and the role of chance Final oocyte maturation was triggered in 143 cycles with hCG (37.1 %), and in 242 cycles with dual trigger (62.9 %). The duration of stimulation was shorter in dual trigger arm compared to hCG trigger group (10.0 ± 1.6 vs. 9.4 ± 1.4 days, p = &amp;lt;.001). Euploidy rates per blastocyst tested were 23.4 %, and 26.1 % respectively for hCG and dual trigger groups with no significant difference. When the patients were stratified according to age, euploidy rate was higher in the dual trigger group in all age groups with no significance. There was no significant difference between hCG and dual trigger groups, regarding positive pregnancy result and ongoing pregnancy rates (p = .779 vs. p = .188). Limitations, reasons for caution Retrospective design and small sample size could be accepted as the limitations. Wider implications of the findings Our study is the first study in literature exploring the ploidy status of embryos following dual trigger with hCG + GnRHa for final oocyte maturation in PGT-A cycles and, comparing it with hCG only trigger. Dual triggerring of final oocyte maturation results in similar euploidy rates in blastocysts tested. Trial registration number 2020/004

O-023 A randomized control trial on the effect of intrauterine HCG flushing on reproductive outcomes

Abstract Study question Can Intra Uterine Flushing with Human Chorionic Gonadotropin (hCG) optimize embryo implantation and reproductive outcomes in Assisted Reproductive Technique(ART) cycles? Summary answer Uterine flushing with hCG does not seem to enhance embryo implantation and optimize reproductive outcomes What is known already Human Chorionic Gonadotropin (hCG) hormone has shown to play an important role in embryo implantation. Role of hCG flushing to uterine cavity has been proposed as one of the interventions to optimize embryo implantation, but its efficiency has been debatable. Study design, size, duration This study is a Randomised Control trial (RCT) with prior approval from Institution Ethical Review Board(IEC Ref. No. ECR/1312/inst/tg/2019). Study duration between November 2020-November 2021 at a private clinic. Women undergoing In-Vitro fertilization (IVF) cycles were randomised to no hCG flush group (n = 80) and hCG flush group (n = 100). Women &amp;gt;37yrs age and BMI &amp;gt;30 or having some uterine pathology or willing for Pre-Implantation Genetic Testing (PGT) or donor gamete cycles were excluded from this study Participants/materials, setting, methods Women recruited in this study underwent ovarian stimulation as per the institutes standard operating protocols (SOP). All embryos subjected to blastocyst culture and freeze all strategy followed. In a frozen embryo replacement cycle two good grade blastocysts were transferred. In hCG flush group, 48-72hrs before anticipated embryos transfer (ET) 500IU of commercially available hCG hormone was instilled into the uterine cavity. No hCG Flush group did not have any intervention Main results and the role of chance Clinical Pregnancy rates (CPR), Implantation Rates (IR), Multiple Pregnancy rates (MPR) were compared between the groups. Means of Reproductive outcomes between hCG Vs no hCG group were as follows CPR – 71% Vs 76% (p = 0.45) IR – 59% Vs 55%(p=0.59)MPR – 18% Vs 25%(p=0.25) Data from this RCT shows that hCG flush does not seem to enhance embryo implantation. Role of hCG flush to optimize reproductive outcomes is questionable. Limitations, reasons for caution This study has not evaluated the miscarriage rates and live birth rates Wider implications of the findings Ways to enhance embryo implantation and optimising reproductive outcomes still needs further research. hCG flushing might not be a beneficial intervention to optimise embryo implantation. However, a subgroup analysis to identify efficiency of hCG in a particular group of patients like thin endometrium could be further explored. Trial registration number NA

P-705 Influence of ovulation induction strategy in oocyte meiotic maturation: hCG versus agonist

Abstract Study question What is the influence of the ovulation induction strategy on the meiotic status of collected oocytes? Summary answer Non-invasive imaging of meiotic spindles during ICSI showed that ovulation induction with a hCG improved meiotic maturation and subsequent blastocyst formation rate. What is known already Owing to the shorter half-life of GnRH, this strategy has gained attention by significantly reducing risk of ovarian hyperstimulation syndrome. Reduced exposure to LH often requires luteal support and has been associated with a lower live birth rate, a lower ongoing pregnancy rate (pregnancy beyond 12 weeks) and a higher rate of early miscarriage (less than 12 weeks) in fresh autologous cycles, nevertheless. Mid-cycle LH surge triggers molecular activity in follicle cells initiating resumption of meiosis I for competition of the first meiotic division and formation of a MII oocyte inferring competence for subsequent fertilization and further development. Study design, size, duration A retrospective observational study was carried in a cohort of 25 - &amp;gt; 36 years old women including 85 patients. Analysis was carried in two groups: 1: GnRHa trigger and 2: hCG trigger and later stratified for patient age. Participants/materials, setting, methods Women between 25 and &amp;gt; 36 years old, non PCOS, with an AMH &amp;gt; 1.2 ng/ml and stimulated under a short scheme GnRH-antagonist for downregulation, FSH and ovulation induction with GnRHa or hCG. Oocytes allocated to (intracytoplasmic sperm injection) ICSI treatment were cultured for 3-4 hours striped from cumulus cells 2 hours after retrieval and placed in G-MOPS PLUS in aglass bottom dish and with an Octax PolarAide system. Main results and the role of chance A spindle was present in 39.3% (218/554) of all morphologically mature (MII) oocytes alone. Group 1 (GnRHa trigger) and group 2 (hCG trigger) had 56% (309/554) and 44% (245/554) of oocytes at MII stage from which 38% (120/309) and 39% (96/245) showed spindles. A better meiotic maturation stage (scores 3, 4) at ICSI was found when ovulation induction was performed with hCG (group 2) (81% (98/120) versus 88% (85/96), p = 0,0031), nevertheless. Fertilization rate was no different between groups (60% and 58%, respectively), while significantly more blastocysts (at culture day 4 and 5) were generated from group 2 MII oocytes presenting a spindle and a good score (36% (35/98) versus 62% (53/85), p = 0.039). Good blastocyst quality (≥3BB) did not differ between groups. When stratifying for age, women between 25 – 30 presented no differences in presence or meiotic maturation (score 2, 3) in MII oocytes, while fertilization (42% versus 77%, p = 0.022) and blastocyst formation (32% versus 45%, p = 0.012) were better in group 2. Women between &amp;gt; 36 years old presented no differences in presence of meiotic maturation, however, fertilization (40% versus 54%, p = 0.042) and blastocyst formation (25% versus 57%, p = 0.007) were best in group 2. Limitations, reasons for caution Thorough multivariable analysis in a larger patient cohort is required to endorse these results, nevertheless. Wider implications of the findings Prediction of ovulation induction efficacy in different patient cohorts could help fine tuning cycle management. Trial registration number not applicable

Comparison of the effect of Gonadotropin-Releasing Hormone and Human Chorionic Go3nadotropin on Reproductive Performance of Romanov Ewes During the Natural Breeding Season.

Low pregnancy rate is an important issue in small ruminants. Superovulation protocols would serve as the possible techniques to increase the pregnancy rate in small ruminants due to the use of synthetic hormones. The present study aimed to assess the effect of gonadotropin-releasing hormone (GnRH) and Human chorionic gonadotropin (hCG) after artificial insemination (AI) on the pregnancy rate of Romanov ewes breed. To this end, estrus was synchronized in 140 ewes using a controlled internal drug-releasing (CIDR) device. Following CIDR removal, all ewes received 400 IU Pregnant Mare's Serum Gonadotropin (PMSG). The ewes were assigned to three groups (control, n=20; experimental groups, each of them was divided into three subgroups, n=20). The first group in each experiment was assumed as control. The second and third groups received three levels of GnRH, (400, 500, and 600 µg, n=20) and hCG (200, 300, and 400 IU) administered by the intramuscular (IM) route. As soon as the signs of estrus were observed, the ewes were isolated from the others and artificially inseminated with fresh sperm using the transcervical method. The results indicated that there were no significant differences between experimental groups in ovulation and pregnancy rates on days 33 and 90 post-AI (P>0.05). The highest twin birth rate (20%) was recorded in the hCG group (300 IU), as compared to GnRH and control groups (P<0.05). The effect of GnRH and hCG on the plasma concentration of progesterone was significant (P<0.01). The groups significantly differed in fecundity rate (Single birth, twin birth, and triple birth) (P<0.05), all of these parameters were significantly higher in the hCG 300 IU group. It can be concluded that the injection of 300 IU of hCG hormone after insemination improves pregnancy rate in ewes.

Ovulation triggering with hCG alone, GnRH agonist alone or in combination? A randomized controlled trial in advanced-age women undergoing IVF/ICSI cycles.

Is a dual ovulation trigger with a combination of GnRH agonist (GnRHa) and hCG superior to single hCG and/or single GnRHa trigger in improving treatment outcomes in advanced-age women (aged ≥ 35 years) undergoing IVF/ICSI treatment? Co-administration of GnRHa and hCG as a dual trigger increases the number of good-quality embryos but it is not associated with a higher number of oocytes retrieved, compared with single hCG or GnRHa trigger. Many studies have demonstrated that a dual trigger has positive impact on oocyte maturation, retrieval rate and pregnancy rate without increasing the risk of ovarian hyperstimulation syndrome (OHSS) in some groups of IVF patients, when compared with single hCG trigger. Few studies have however been conducted to compare a dual trigger with a single GnRHa trigger, and insufficient evidence exists to support which trigger can achieve the best outcomes in IVF patients aged ≥35 years. This was an open-label randomized controlled trial of 510 participants conducted at single reproductive medical center from January 2019 to December 2021. After a sample size calculation performed by retrospectively analyzing our previous clinical data, we planned to recruit 170 patients in each group and 510 patients in total for the study. Women aged ≥35 years undergoing IVF/ICSI treatment, receiving a non-pituitary down-regulation protocol, and with low risk of OHSS, were enrolled in this trial. On the trigger day, patients were randomized into three groups: hCG alone (who received 6000 IU of hCG), GnRHa alone (who received 0.2 mg of triptorelin) and dual trigger (who received 0.2 mg of triptorelin plus 2000 IU of hCG) groups. The primary outcome parameter was the number of retrieved oocytes. The secondary outcome parameters included, among others, the number and rates of mature oocytes, two pronuclei (2PN) embryos and good-quality embryos, as the rates of OHSS, clinical pregnancy, miscarriage and live birth. There were no significant differences in the baseline demographic characteristics among the three groups. The dual trigger was associated with a higher retrieval rate (87.9% vs 84.1% in the hCG group, P = 0.031; 87.9% vs 83.6% in the GnRHa group, P = 0.014). However, the number of retrieved oocytes in the dual trigger group was comparable with those in the hCG group (4.08 ± 2.79 vs 3.60 ± 2.71, P = 0.080) and the GnRHa group (4.08 ± 2.79 vs 3.81 ± 3.38, P = 0.101); comparable data between the groups were also found when analyzing the number of 2PN embryos and the 2PN rate. In the dual trigger group, the numbers of good-quality embryos and viable embryos were both significantly higher than in the hCG group (1.74 ± 1.90 vs 1.19 ± 1.45, P = 0.016 and 2.19 ± 2.11 vs 1.56 ± 1.66, P = 0.008, respectively) and the GnRHa group (1.74 ± 1.90 vs 1.20 ± 1.67, P = 0.003 and 2.19 ± 2.11 vs 1.45 ± 1.75, P = 0.001, respectively). Pregnancy outcomes after fresh embryo transfer (ET) were comparable between the groups. The live birth rate and ongoing pregnancy rate after frozen ET in the dual trigger group were significantly higher than those in the GnRHa group (32.6% vs 14.1%, P = 0.007 and 34.8% vs 17.6%, P = 0.013, respectively), but not superior to those in the hCG group (32.6% vs 27.9%, P = 0.537 and 34.8% vs 27.9%, P = 0.358, respectively). Women of advanced age are quite a heterogeneous population and overlap with poor ovarian responders or patients with diminished ovarian reserve. We therefore could not entirely exclude selection biases or confounding factors. This study was also not a double-blinded trial; the patients in the GnRHa and dual trigger groups could have been affected by the placebo effect. The results of this study suggest that in advanced-age women with low risk of OHSS, a dual trigger or even a single hCG trigger may be a better choice than a single GnRHa trigger. This study was supported by the Shanghai Municipal Health Commission of Science and Research Fund (20184Y0289). The authors declare no conflict of interest. This trial was registered in the Chinese Clinical Trial Registry (ChiCTR-1800016285). 24 May 2018. 2 January 2019.

Dual Trigger with hCG Plus GnRHa for Final Oocyte Maturation in PGT-A Cycles Results in Similar Euploidy Rates when Compared to hCG-Only Trigger.

Factors that may have an effect on euploidy rate of blastocysts have been investigated thoroughly in the literature. We aimed to assess whether dual trigger alters the ploidy chance of a blastocyst in preimplantation genetic screening for aneuploidy (PGT-A) cycles. This retrospective cohort study was conducted in a total of 385 PGT-A cycles at a single tertiary center for various indications. Final oocyte maturation was triggered using human chorionic gonadotropin (hCG) or the combination of hCG and gonadotropin-releasing hormone agonists (GnRHa) (dual trigger). Participants were divided based on triggering method and all demographic and clinical characteristics of the patients were compared. Final oocyte maturation was triggered in 143 cycles with hCG (37.1%), and in 242 cycles with dual trigger (62.9%). The duration of stimulation was shorter in the dual trigger arm compared to the hCG trigger group (10.0 ± 1.6 vs. 9.4 ± 1.4days, p ≤ .001). Euploidy rates per blastocyst tested were 23.4% and 26.1% respectively for hCG and dual trigger groups without significance. Similar rates of euploidy were noted, even after age stratification. There was no significant difference between the groups regarding positive pregnancy result and ongoing pregnancy rates (p = .779 vs. p = .188). Although dual triggering, compared to hCG triggering, does not provide an additional superiority on blastocyst euploidy rate, further studies in women with different infertility etiology are needed to specifically evaluate the impact of triggering method on ploidy rates.

Kontrollü Ovaryen Hiperstimulasyon Uterusta Apelin ve Apelin Reseptör Ekspresyonunu Arttırır

Objective; In this study, we investigated whether superovulation, which is frequently used in the clinic as controlled ovarian hyperstimulation, affect the expression of Apelin (APLN) and Apelin Receptor (APJ) in the uterus.&#x0D; &#x0D; Methods: Twelve female Balb-C mice 6-8 weeks old were used in this study. The groups were established as follows; virgin control female group (Knt) which did not receive any treatment, the pregnant control group (GK) which was on their pregnancy day 1, and the PMSG+hCG group (P+H) that received 5 IU/mouse/intraperitoneal (ip) PMSG and 5 IU/mouse/ip hCG . Vaginal plaque control was performed on the day after mating in the P+H and GK groups, and vaginal plaque-positive mice were accepted at day 0.5 of pregnancy. Mice in the P+H group were sacrificed 42 hours after hCG injection. Uterine tissues were obtained from all groups for immunohistochemical analysis, and paraffin sections were obtained. Adipose tissue was used as a positive control.&#x0D; &#x0D; Results: In the Knt group, APLN protein expression was present especially in the uterine glands and stromal cells that are located close to the glands. The localization of APJ protein expression was also similar to APLN. In the GK group, APLN and APJ expression levels were similar to the Knt group. However, when the localization of APJ was evaluated, it has been observed that APJ expression was intensely expressed especially in the perimetrial glands of the uterus, which was not present in the Knt group. In the P+H group, APLN expression significantly increased in the endometrial glands and stromal cells compared to the Knt and GK groups (p

Testicular haemodynamics, plasma testosterone and oestradiol concentrations, and serum nitric oxide levels in the Egyptian buffalo bull after a single administration of human chorionic gonadotropin.

This current study aimed for the first time to evaluate the effect of a single intravenous administration of human chorionic gonadotropin hormone (hCG) on the testicular artery haemodynamics measurements (resistance [RI], and pulsatility indices [PI]), plasma steroids (estradiol-17β and testosterone) and nitric oxide (NO) levels in buffalo bulls. Twelve Egyptian buffalo bulls weighted 450±20kg were randomly divided into the hCG group (n=6) and injected a single dose with Ovogest (EPIFASI; 5,000 IU, iv), whereas the others (n=6) were injected with normal saline and served as controls. Doppler evaluation and blood sampling were performed just before the administration (hour 0) and at 1, 2, 4, 6, 8, 10, 24 and 28hr after administration. Bulls in the control group did not show any alterations in hormonal levels and blood flow parameters (p>.05). In the hCG group, RI was declined (p<.05) in 6hr post-administration (0.31±0.01 versus 0.45±0.01), while PI was declined (p<.05) later in 10hr (0.74±0.01 versus 1.23±0.02). Additionally, testicular blood flow was increased (p<.05) 8hr (42.02±1.02ml/min/100g versus 31.34±0.88ml/min/100g) after administration. Testosterone and NO levels were (p<.05) increased at 4 and 6hr post-administration (3.55±0.03ng/ml versus 2.84±0.01ng/ml, and 55.32±4.25µmol/L versus 32.21±1.55µmol/L), whereas oestradiol levels were elevated (p<.05)in 6hr (31.25±0.08pg/ml) only post-administration then declined. In conclusion, the single intravenous administration of hCG triggered many alterations in the supratesticular artery vascularization and hormonal profile that could affect positively on steroidogenesis and testicular function in buffalo bull.

Comparison of GnRH and hCG effects on oestradiol, progesterone and premature luteolysis in Ovsynch-synchronized ewes.

The purpose of this study was to ascertain whether premature luteolysis can be alleviated by substituting the ovulation inducing agent hCG for GnRH. Seventy-two hours after the end of artificial insemination (AI), pluriparous Awassi ewes were randomly assigned to one of three treatment groups of 13 ewes each. First group received 37.5µg of the GnRH analog Lecirelin, the second 1000I.U hCG and the third group served as a control (received 1ml of physiological saline solution). Blood samples were collected at daily intervals after GnRH treatment and analysed for plasma oestradiol and progesterone concentrations. Ovarian follicles were monitored ultrasonically at the time of GnRH administration, 60hr and 84hr later. Pregnancy was diagnosed ultrasonically at Day 35 after AI. Number and size of ovarian follicles did not differ (p>.05) among treatment groups. Onset and duration of oestrus were not affected by treatment (p>.05). No significant differences (p>.05) were recorded in oestradiol and progesterone concentrations between the treatment groups during the inspection period. Premature luteolysis became evident in ewes with longer oestrous durations by Day 6.25 after AI and amounted to 7.69%, 18.18% and 23.07% in GnRH, hCG and Control groups respectively. Pregnancy rates increased to 92.31% and 81.82% in GnRH and hCG groups, compared to 76.92% in the Control group. The results indicate that GnRH was more effective in reducing premature luteolysis than hCG. Substituting hCG for GnRH as an ovulation inducing agent was of no avail.

Characterization of ovarian culture in vitro and sex steroids in vivo by recombinant eel gonadotropin treatments in the eel Anguilla japonica

In the present study, we investigated the effects of recombinant eel gonadotropins (rec-GTHs) on maturation induction in immature ovarian culture in vitro and sex steroid hormones in vivo in the Japanese eel Anguilla japonica. To study the in vitro effects of rec-GTHs on estradiol-17β (E2) production in immature ovarian tissues, ovarian tissues were incubated with different doses of rec-follicle-stimulating hormone (rec-FSH) or rec-luteinizing hormone (rec-LH). The results revealed that the E2 levels in the rec-FSH (0.1, 0.5, or 1 μg/mL)- and rec-LH (0.1 or 0.5 μg/mL)-treated groups were significantly higher than those in the female eels from the control group. Furthermore, to investigate the in vivo effects of rec-GTHs on the gonadosomatic index (GSI) and plasma sex steroid hormone levels, the eels were injected intraperitoneally with eel’s ringer (control), salmon pituitary extract (SPE; for female eels), human chorionic gonadotropin (hCG; for male eels), rec-FSH, rec-LH, and rec-FSH + rec-LH once a week. The results revealed that except for the SPE and the hCG groups, none of the groups exhibited a significant difference in GSI values. However, in vivo plasma E2 levels increased at the end of 4 weeks after rec-FSH treatment in female eels. Based on these results, it is suggested that rec-GTHs may have a positive effect on sexual maturation in female eels; however, further studies on complementary rec-protein production systems and additional glycosylation of rec-hormones are needed to elucidate hormone bioactivity in vivo and in vitro.

Clinical Pregnancy and Incidence of Ovarian Hyperstimulation Syndrome in High Ovarian Responders Receiving Different Doses of hCG Supplementation in a GnRH-Agonist Trigger Protocol.

Objective Ovarian hyperstimulation syndrome (OHSS) is a side effect of the exogenous human chorionic gonadotropin (hCG) hormones used to trigger oocyte maturation. High ovarian responders represent a population with a higher risk of OHSS and are characterized by an exaggerated response to gonadotropin administration. In this study, we compared clinical pregnancy and incidence of OHSS in high ovarian responders receiving different doses of hCG supplementation in a GnRH-agonist trigger protocol. Methods A total of 205 high ovarian responders who were to undergo in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were recruited and randomly assigned to receive different doses of hCG supplementation in a GnRH-agonist trigger protocol: GnRH-a (n = 42), GnRH-a + 1000 IU hCG (n = 49), GnRH-a + 2000 IU hCG (n = 54), and GnRH-a + 3000 IU hCG (n = 60) groups. Results The GnRH-a + 1000 IU hCG, GnRH-a + 2000 IU hCG, and GnRH-a + 3000 IU hCG groups had more oocytes retrieved, embryos, high-quality embryos, and a higher rate of high-quality embryos than the GnRH-a group (p < 0.05). The GnRH-a + 1000 IU hCG group demonstrated more oocytes retrieved, embryos, high-quality embryos, and a higher rate of high-quality embryos than the GnRH-a + 2000 IU hCG and GnRH-a + 3000 IU hCG groups (p < 0.05). No moderate and severe OHSS cases occurred in the GnRH-a and GnRH-a + 1000 IU hCG groups. The incidence rate of moderate and severe OHSS was remarkably lower in the GnRH-a group and GnRH-a + 1000 IU hCG groups than in the GnRH-a + 2000 IU hCG and GnRH-a + 3000 IU hCG groups (p < 0.05). The GnRH-a + 1000 IU hCG, GnRH-a + 2000 IU hCG, and GnRH-a + 3000 IU hCG groups had a higher clinical pregnancy rate than the GnRH-a group, showing no significant difference (p > 0.05). The GnRH-a + 1000 IU hCG, GnRH-a + 2000 IU hCG, and GnRH-a + 3000 IU hCG groups had a lower abortion rate than the GnRH-a group (p < 0.05). Conclusion Based on the data obtained from this prospective study, we recommend 1000 IU hCG supplementation in a GnRH-agonist trigger protocol for high ovarian responders during IVF/ICSI cycles considering a higher rate of high-quality embryos, a lower incidence rate of moderate and severe OHSS, and a lower abortion rate.