Effect of the degree of follicular diameter ≥18mm differentiation on the day of hCG administration to the outcome of controlled ovarian hyperstimulation (COH).

Objective: To explore the impact of the level of differentiation in a minimum of two follicles with a diameter of ≥18 mm on the outcome of controlled ovarian hyperstimulation on the day of human chorionic gonadotropin (hCG) administration. Methods: Single-center data from January 2018 to December 2021 was retrospectively analyzed for 1,199 patients with fresh embryo transfer for assisted reproduction. The absolute value of the standard deviation of the follicle size of at least 2 follicles ≥18 mm in diameter in both ovaries on the day of hCG was taken as the degree of differentiation of the dominant follicle after ovulation induction, based on the standard deviation response to the degree of dispersion of the data. The degree of follicular differentiation was divided into 3 groups according to the size of the value, and the general clinical conditions, laboratory indexes, and clinical outcomes of the patients in the 3 groups were compared. Results: Among the three groups, the body mass index (BMI) of the ≤1s group was lower than that of the other two groups (P< 0.05), while the follicle-stimulating hormone (FSH) and Anti-Mullerian hormone (AMH) were higher (P< 0.05), and the implantation rate and clinical pregnancy rate were significantly higher than those of the other two groups (P< 0.01). After multifactorial logistic regression to correct for confounding factors, with the ≤1s group as the reference, the implantation rate, hCG-positive rate, clinical pregnancy rate and live birth rate of embryo transfer in the ≥2S group were significantly lower (P< 0.01). The results of curve fitting analysis showed that the live birth rate decreased gradually with the increase of the absolute standard deviation (P=0.0079). Conclusion: Differences in follicle diameters ≥18 mm on the day of hCG injection did not have an impact on embryo quality, but had an impact on pregnancy outcomes. The less the variation in follicle size, the more homogeneous the follicle development and the higher the likelihood of live births.

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

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

Meta-analysis of intrauterine hCG perfusion efficacy in recurrent implantation failure as defined by ESHRE guidelines.

PURPOSE: This study evaluates the efficacy of intrauterine hCG perfusion for RIF, as defined by ESHRE 2023 guidelines, highlighting hCG as a cost-effective alternative to other immunotherapies, especially suitable for less developed regions. It aims to clarify treatment guidance amidst previous inconsistencies. METHODS: This meta-analysis, registered with PROSPERO (CRD42024443241) and adhering to PRISMA guidelines, assessed the efficacy and safety of intrauterine hCG perfusion in enhancing implantation and pregnancy outcomes in RIF. Comprehensive literature searches were conducted through December 2023 in major databases including PubMed, Web of Science, Embase, the Cochrane Library, and key Chinese databases, without language restrictions. Inclusion and exclusion criteria were strictly aligned with the 2023 ESHRE recommendations, with exclusions for studies lacking robust control, clear outcomes, or adequate data integrity. The risk of bias was evaluated using the Newcastle-Ottawa Scale, ROBINS-I, and RoB2 tools. Data analysis was performed in R using the 'meta' package, employing both fixed and random effect models to account for study variability. Subgroup analyses by dosage, volume, hCG concentration, timing of administration, and type of embryo transfer were conducted to deepen insights, enhancing the reliability and depth of the meta-analysis in elucidating the role of hCG perfusion in RIF treatments. RESULTS: Data from 13 studies, comprising six retrospective and six prospective studies from single centers, along with one multi-center RCT, totaling 2,157 participants, were synthesized to evaluate the effectiveness of intrauterine hCG perfusion in enhancing implantation and pregnancy outcomes in patients with RIF. Significant improvements were observed in clinical pregnancy and embryo implantation rates across various dosages, timing of administration, and embryo developmental stages, without impacting miscarriage rates. Notably, the most significant efficacy within subgroups occurred with a 500 IU dosage and perfusion parameters of ≤ 500µL volume and ≥ 2 IU/µL concentration. Additionally, a limited number of studies showed no significant increases in ectopic pregnancy or multiple pregnancy rates, and a modest improvement in live birth rates, although the small number of these studies precludes definitive conclusions. CONCLUSIONS: The analysis suggests that intrauterine hCG perfusion probably enhances embryo implantation, clinical pregnancy, and live birth rates slightly in RIF patients. Benefits are indicated with a dosage of 500 IU and a maximum volume of 500µL at concentrations of at least 2 IU/µL. However, substantial heterogeneity from varying study types and the limited number of studies necessitate cautious interpretation. These findings underscore the need for more rigorously designed RCTs to definitively assess the efficacy and safety.

Network meta-analysis of four common immunomodulatory therapies for the treatment of patients with thin endometrium.

OBEJECTIVE: To compare the effectiveness of endometrial receptivity and pregnancy outcomes of four common immunomodulatory therapies for patients with thin endometrium. METHOD: This systematic review and network meta-analysis using a literature search up to January 2024, to identify relevant trials comparing endometrial receptivity and pregnancy outcomes of human chorionic gonadotropin (hCG), platelet-rich plasma (PRP), infusion of granulocyte colony-stimulating factor (IG-CSF), and peripheral blood mononuclear cell (PBMC) for patients with thin endometrium. We used surface under the cumulative ranking (SUCRA) to ranked four common immunomodulatory therapies on endometrium thickness, implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR). RoB2 and ROBINS-I were used to assess the certainty of evidence. RESULTS: The pooled results of 22 studies showed that hCG (mean difference [MD]: 3.05, 95% confidence interval [CI]: 1.46-4.64) and PRP (MD: 0.98, 95% CI: 0.20-1.76) significantly increase endometrium thickness. The hCG was the best among the IG-CSF (MD = -2.56, 95% CI = -4.30 to -0.82), PBMC (MD = -2.75, 95% CI = -5.49 to -0.01), and PRP (MD = -2.07, 95% CI = -3.84 to -0.30) in increasing endometrium thickness. However, IG-CSF and PRP significantly improved IR (IG-CSF: risk ratio (RR; IG-CSF: RR = 1.33, 95% CI = 1.06-1.67; PRP: RR = 1.63, 95% CI = 1.19-2.23), and LBR (IG-CSF: RR = 1.53, 95% CI = 1.16-2.02; PRP: RR = 1.59, 95% CI = 1.08-2.36). CONCLUSIONS: Available evidence reveals that hCG and subcutaneous or intrauterine CSF (SG-CSF) may be the best treatment options for current thin endometrium patients. However, future high-quality and large-scale studies are necessary to validate our findings.

Vitamin D binding protein correlate with estrogen increase after administration of human chorionic gonadotropin but do not affect ovulation, embryo, or pregnancy outcomes.

Background: Vitamin D binding protein (DBP) might increase substantially after ovarian stimulation and hence could be associated with IVF/ICSI outcomes because it determines the fraction of free bioavailable 25(OH) vitamin D. In this study, we aim to determine whether DBP is associated with E2 level after ovarian stimulation and IVF/ICSI outcomes. Design: Post-hoc analysis of a prospective observational cohort. Setting: Single-center study. Participants: 2569 women receiving embryo transfer. Intervention: None. Main outcome measures: The main outcomes were oocyte and embryo quality as well as pregnancy outcomes. Results: DBP concentration correlates with E2 on hCG day (=day of inducing ovulation with hCG; correlation coefficient r = 0.118, P<0.001) and E2 x-fold change to baseline level (r = 0.108, P<0.001). DBP is also positively correlated with total 25(OH)D (r = 0.689, R2 = 0.475, P<0.001) and inversely with free 25(OH)D (r=-0.424, R2=0.179, P<0.001), meaning that E2-stimulated DBP synthesis results in a decrease of free 25(OH)D during ovarian stimulation. However, such alteration does not affect IVF/ICSI outcomes when considering confounding factors, such as the number and quality of oocytes nor embryo quality as well as pregnancy outcomes. Conclusion: DBP concentration correlates with the degree of E2 increase after ovarian stimulation. DBP is also positively correlated with total 25(OH)D and inversely with free 25(OH)D, suggesting that the proportion of free 25(OH)D decreases during ovarian stimulation caused by E2-stimulated DBP synthesis. However, such alteration does not affect clinical IVF/ICSI outcomes.

In vitro fertilization outcome based on the detailed early luteal phase trajectory of hormones: a prospective cohort study.

BACKGROUND: Ovarian stimulation and the use of human chorionic gonadotropin (hCG) for triggering oocyte maturation in women undergoing in vitro fertilisation (IVF) introduces several differences in luteal phase hormone levels compared with natural cycles that may negatively impact on endometrial receptivity and pregnancy rates after fresh embryo transfer. Exogenous luteal phase support is given to overcome these issues. The suitability of a pragmatic approach to luteal phase support is not known due to a lack of data on early phase luteal hormone levels and their association with fertility outcomes during IVF with fresh embryo transfer. This study determined early luteal phase profiles of serum progesterone, 17-hydroxyprogesterone and hCG, and associations between hormone levels/hormone level profile after hCG trigger and the live birth rate in women undergoing IVF with fresh embryo transfer. METHODS: This prospective single center, cohort study was conducted in Vietnam from January 2021 to December 2022. Women aged 18-38 years with normal ovarian reserve and undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol were included. Serum hormone levels were determined before trigger, at 12, 24 and 36 h after hCG, and daily from 1 to 6 days after oocyte pick-up. Serum hormone level profiles were classified as lower or upper. The primary outcome was live birth rate based on early luteal phase hormone level profile. RESULTS: Ninety-five women were enrolled. Live birth occurred in 19/69 women (27.5%) with a lower progesterone profile and 13/22 (59.1%) with an upper progesterone profile (risk ratio [RR] 2.15; 95% confidence interval [CI] 1.28-3.60), and in 6/31 (19.4%) versus 26/60 (43.3%) with a lower versus upper serum 17-hydroxyprogesterone profile (RR 2.24; 95% CI 1.03-4.86). Nearly 20% of women had peak progesterone concentration on or before day 3 after oocyte pick-up, and this was associated with significantly lower chances of having a life birth. CONCLUSIONS: These data show the importance of proper corpus luteum function with sufficient progesterone/17-hydroxyprogesterone production for achievement of pregnancy and to maximize the chance of live birth during IVF. TRIAL REGISTRATION: NCT04693624 ( www. CLINICALTRIALS: gov ).

Pulsatile gonadotropin releasing hormone therapy for spermatogenesis in congenital hypogonadotropic hypogonadism patients who had poor response to combined gonadotropin therapy.

Objective: Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). This study aimed to evaluate the effect of pulsatile GnRH therapy on spermatogenesis in male patients with CHH who had poor response to combined gonadotropin therapy. Materials and methods: Patients who had poor response to combined gonadotropin therapy ≥ 6 months were recruited and shifted to pulsatile GnRH therapy. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, testosterone, and testicular volume were used for data analysis. Results: A total of 28 CHH patients who had poor response to combined gonadotropin (HCG/HMG) therapy for 12.5 (6.0, 17.75) months were recruited and switched to pulsatile GnRH therapy for 10.0 (7.25, 16.0) months. Sperm was detected in 17/28 patients (60.7%). The mean time for the appearance of sperm in semen was 12.0 (7.5, 17.5) months. Compared to those who could not achieve spermatogenesis during pulsatile GnRH therapy, the successful group had a higher level of LH60min (4.32 vs. 1.10 IU/L, P = 0.043) and FSH60min (4.28 vs. 1.90 IU/L, P = 0.021). Testicular size increased during pulsatile GnRH therapy, compared to previous HCG/ HMG therapy (P < 0.05). Conclusion: For CHH patients with prior poor response to one year of HCG/ HMG therapy, switching to pulsatile GnRH therapy may induce spermatogenesis.

High progesterone levels on the day after HCG injection has no effect on clinical pregnancy outcomes in in vitro fertilization-embryo transfer.

Background: This study investigates the potential impact of high progesterone (P) level on the day following human chorionic gonadotropin (HCG) injection on the clinical pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET). Methods: Retrospective analysis was conducted on 6418 cycles of IVF-ET performed at Liuzhou Maternal and Child Health Hospital between August 2020 to December 2021. Excluding cycles with progesterone levels ≥1.5ng/ml on HCG injection, a total of 781 cycles were identified according to the standard, and they were divided into five groups according to the progesterone level on the day after HCG: Group A: progesterone level < 2.5 ng/ml (n = 128); Group B: 2.5 ng/ml ≤ progesterone level < 3.5 ng/ml (n = 174); Group C: 3.5 ng/ml ≤ progesterone level < 4.5 ng/ml (n = 153); Group D: 4.5 ng/ml ≤ progesterone level < 5.5 ng/ml (n = 132); Group E progesterone level ≥5.5 ng/ml(n=194). Comparative analyses of clinical data, including general clinical data, and clinical pregnancy outcomes such as clinical pregnancy rate, miscarriage rate, and live birth rate were performed among these groups. Results: There were significant differences in estradiol levels on HCG injection, but there were no differences in available embryo rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Binary logistic regression analysis showed that there was no significant correlation between P level on the day after HCG injection and the live birth rate. Conclusion: Under the condition of low P level on HCG injection, high progesterone levels on the day after HCG injection does not affect the clinical pregnancy outcomes of IVF-ET.

Analysis of use of different rFSHs during IVF/ICSI-assisted conception in elderly population and effect of double trigger on clinical outcomes.

OBJECTIVE: To compare the number of oocytes retrieved and clinical outcomes of ovulation induction in an older population treated with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) (IVF/ICSI) using different rFSH options and the effectiveness of antagonist treatment to induce ovulation using gonadotropin-releasing hormone agonists (GnRH-a) in combination with an human chorionic gonadotropin (HCG) trigger. METHODS: A total of 132 fresh cycles were selected for this study, which were treated with IVF/ICSI in our hospital from March 2022 to December 2022. Observations were made according to different subgroups and the effects of different triggering methods on the number of oocytes obtained, embryo quality, and clinical outcomes. RESULTS: The initial gonadotropin (Gn) dose, the number of oocytes, and the number of MII oocytes were higher in group A than in group B (p < .05), and the clinical pregnancy rate was 29.41% in group A. Group B had a clinical pregnancy rate of 27.5%. The double-trigger group was superior to the HCG-trigger group in terms of the number of 2PN, the number of viable embryos, and the number of high-quality embryos (p < .05). The use of a double-trigger regimen (OR = 0.667, 95%CI (0.375, 1.706), p = .024) was a protective factor for the clinical pregnancy rate, whereas AFC (OR = 0.925, 95%CI (0.867, 0.986), p = .017) was an independent factor for the clinical pregnancy rate. CONCLUSIONS: The use of a dual-trigger regimen of GnRH-a in combination with HCG using an appropriate antagonist improves pregnancy outcomes in fresh embryo transfer cycles in older patients.

Changes on corpus luteum structure and progesterone synthesis pathway after hCG or GnRH treatment during the early luteal phase in sheep.

This study investigated the effect of hCG or GnRH on structural changes of the corpora lutea (CL) and the regulation of the expression of steroidogenic enzymes involved in P4 secretion in post-ovulatory (po-CL) and accessory CL (acc-CL). Sixty-four ewes were assigned to three groups receiving: 300 IU of hCG (hCG) or 4 µg Buserelin (GnRH) or 1 mL of saline solution (Control) on Day (d) 4 post artificial insemination (FTAI). Laparoscopic ovarian were performed on d 4, 14 and, 21 post-FTAI to determine the numbers of CL. Blood samples were collected for serum LH and P4 analysis. On d 14 post-FTAI, both CL were removed from the ovary to determine large luteal cell (LLC) number and to evaluate the expression of steroidogenic enzymes (HSD3B1, STAR, CYP11A1). Only hCG and GnRH treated ewes generated acc-CL. The LLC in both po- and acc-CL were significantly greater in the hCG group compared to GnRH and Control groups (P<0.05). Overall, hCG group showed the greatest immunodetection of HSD3B1and STAR in both po- and acc-CL (P<0.05). rnRNA expression of HSD3B1, STAR and CYP11A1 in the acc-CL tended to be greater in hCG group than in GnRH group (P<0.1). The LH concentration was increased in GnRH group (P<0.05) and P4 concentration was greater in hCG group compared to the other groups (P<0.05). In conclusion, administration of hCG has a notably impact on acc-CL development and the expression of steroidogenic enzymes compared to GnRH treatment in ewes. This leads to elevated P4 concentration and improved luteal function.

Modified natural cycle allows a window of 7 days for frozen embryo transfer planning.

RESEARCH QUESTION: Should ovulation be triggered in a modified natural cycle (mNC) with recombinant human chorionic gonadotrophin (rHCG) as soon as a mean follicle diameter of 17 mm is visible, or is more flexible planning possible? DESIGN: This multicentre, retrospective, observational study of 3087 single frozen blastocyst transfers in mNC was carried out between January 2020 and September 2022. The inclusion criteria included endometrial thickness ≥7 mm and serum progesterone <1.5 ng/ml. The main outcome was ongoing pregnancy rate. Secondary end-points were pregnancy rate, implantation rate, clinical pregnancy rate and miscarriage rate. The mean follicle size at triggering was stratified into three groups (13.0-15.9, 16.0-18.9 and 19.0-22 mm). RESULTS: The baseline characteristics between the groups did not vary significantly for age, body mass index and the donor's age for egg donation. No differences were found in pregnancy rate (64.5%, 60.2% and 57.4%; P = 0.19), clinical pregnancy rate (60.5%, 52.8% and 50.6%; P = 0.10), implantation rate (62.10%, 52.9% and 51.0%; P = 0.05) or miscarriage rate (15.0%, 22.2%; and 25.0%; P = 0.11). Although ongoing pregnancy rate (54.9%, 46.8% and 43.1%; P = 0.02) varied significantly in the univariable analysis, it was no longer significant after adjustment for the use of preimplantation genetic testing for aneuploidies and egg donation. CONCLUSIONS: The findings showed rHCG could be flexibly administered with a mean follicle size between 13 and 22 mm as long as adequate endometrial characteristics are met, and serum progesterone is <1.5 ng/ml. Considering the follicular growth rate of 1-1.5 mm/day, this approach could allow a flexibility for FET scheduling of 6-7 days, simplifying mNC FET planning in clinical practice.

Using mycobacterium cell wall fraction to decrease equine chorionic gonadotropin after abortion.

BACKGROUND: Equine embryonic loss following the development of endometrial cups delays return to cyclicity due to the production of equine chorionic gonadotropin (eCG). Natural degradation of endometrial cups coincides with an influx of immune cells at 100-120 days of gestation, but therapeutic stimulation of reduced eCG production has been relatively unsuccessful. Recently, we observed an increase in pro-inflammatory cytokine production following the use of the immunostimulant mycobacterium cell wall fraction (MCWF). OBJECTIVES: To evaluate the efficacy of hysteroscopic-guided injection of MCWF on the accelerated decline of eCG secretion. STUDY DESIGN: In vivo experiment. METHODS: Mares were pharmacologically aborted at 40-45 days of gestation, and then divided into groups: MCWF-treated (6 mg MCWF suspended in 20 mL LRS; n = 10) and Control (20 mL LRS; n = 6). Five days after abortion, hysteroscopic-guided injection of endometrial cups was performed, with 1 mL of volume placed into each visible endometrial cup. This was repeated 7 days later. Trans-rectal ultrasonography was performed to monitor ovarian activity, and serum was obtained to assess eCG and cytokine concentrations. RESULTS: Concentrations of eCG decreased in the MCWF-treated group (p < 0.01) with a significant suppression noted as early as 14 days after onset of treatment and remained suppressed for the duration of the study. This coincided with an increase in peripheral IFN-γ (p < 0.01) and IL-1ß (p < 0.01) concentrations. Eight out of ten MCWF-treated mares (80%) developed pre-ovulatory follicles, in comparison to 2/6 controls (33%). A pre-ovulatory follicle was noted 23 ± 4 days after onset of treatment. MAIN LIMITATIONS: No pregnancy data was obtained following treatment. CONCLUSIONS: This is the first report of a treatment for the accelerated reduction of eCG following abortion. Stimulation of this process allowed mares to develop a pre-ovulatory follicle within a month of MCWF treatment onset, granting repeat attempts at breeding within the confines of a single breeding season.

Investigation of luteal HCG supplementation in GnRH-agonist-triggered fresh embryo transfer cycles: a randomized controlled trial.

RESEARCH QUESTION: Does splitting the human chorionic gonadotrophin (HCG) support in IVF cycles triggered by a gonadotrophin-releasing hormone agonist result in a better progesterone profile? DESIGN: Randomized controlled three-arm study, performed at the Fertility Clinic, Odense University Hospital, Denmark. Patients with 12-25 follicles ≥12 mm were randomized into three groups: Group 1 - ovulation triggered with 6500 IU HCG; Group 2 - ovulation triggered with 0.5 mg GnRH agonist, followed by 1500 IU HCG on the day of oocyte retrieval (OCR); and Group 3 - ovulation triggered with 0.5 mg GnRH agonist, followed by 1000 IU HCG on the day of OCR and 500 IU HCG on OCR + 5. All groups received 180 mg vaginal progesterone. Progesterone concentrations were analysed in eight blood samples from each patient. RESULTS: Sixty-nine patients completed the study. Baseline and laboratory data were comparable. Progesterone concentration peaked on OCR + 4 in Groups 1 and 2, and peaked on OCR + 6 in Group 3. On OCR + 6, the progesterone concentration in Group 2 was significantly lower compared with Groups 1 and 3 (P = 0.003 and P < 0.001, respectively). On OCR + 8, the progesterone concentration in Group 3 was significantly higher compared with the other groups (both P<0.001). Progesterone concentrations were significantly higher in Group 3 from OCR + 6 until OCR + 14 compared with the other groups (all P ≤ 0.003). Four patients developed ovarian hyperstimulation syndrome in Group 3. CONCLUSION: Sequential HCG support after a GnRH agonist trigger provides a better progesterone concentration in the luteal phase.

Single and multi-dose pharmacology of recombinant and urinary human chorionic gonadotrophin in men.

OBJECTIVE: Human choriogonadotrophin (hCG) treatment of gonadotrophin-deficient infertile men uses hCG of urinary (uhCG) or recombinant (rhCG) origin, but these treatments have not been compared nor are there studies defining rhCG dosing in men. DESIGN: hCG products were studied in randomized cross-over single-dose studies of standard (Study 1, 1500 IU and 62.5 µg, respectively) or high (Study 2, 5000 IU and 250 µg) dose and a multi-dose population pharmacology study of hCG use. PARTICIPANTS: Eight (Study 1) and seven (Study 2) volunteers in cross-over and 52 gonadotrophin-deficient men in the multi-dose study MEASUREMENTS: In cross-over studies, serum testosterone (T), dihydrotestosterone (DHT) and estradiol by liquid chromatography-mass spectrometry (LCMS) and serum hCG, LH, FSH, SHBG and T (observational study) by immunoassays. RESULTS: After standard and high-dose injection, serum hCG and testosterone responses had similar timing and peak concentrations except for a mildly lower early (<48 h) serum testosterone with uhCG. In the multi-dosing study, both hCGs had similar pharmacokinetics (pooled half-life 5.8 days, p < .001), while serum testosterone concentrations were stable after injection and did not differ between hCG products. Bench testing verified that 20% of pens from 4/10 individuals were used inappropriately. CONCLUSIONS: Although hCG pharmacokinetics are not formally bioequivalent, the similar pharmacodynamic effects on serum testosterone indicate that at the doses tested both hCGs provide comparable clinical effects. The starting dose of rhCG for treating gonadotrophin-deficient men should be 62.5 µg (6 clicks) of the rhCG pen.

Low-dose human chorionic gonadotropin supplementation initiated at the onset of ovarian stimulation can improve oocyte quality without impairing endometrial receptivity: Case series.

RATIONALE: Whether continuous low-dose human chorionic gonadotropin (hCG) supplementation during controlled ovarian hyperstimulation (COH) can improve oocyte and embryo quality is still controversial in clinical practice. PATIENT CONCERNS: We report the first case series of inadvertent COH in luteal-phase stimulation in the presence of endogenous or exogenous low-dose hCG. DIAGNOSES: Patients were diagnosed with infertility. OUTCOMES: The first two cases had inadvertent COH during preexisting pregnancy, and one of which produced more high-quality embryos (5 vs 1) in the presence of low hCG. Both cases had a live birth. The third case had 7 repeated failures of IVF, during which a total of 55 oocytes were obtained, but only 3 developed into transferable embryo. However, supplementation of 330 IU hCG per day from the onset of COH resulted in the recovery of one high-quality embryo and subsequent delivery of a healthy baby following fresh embryo transfer in eighth attemption. LESSONS: In conclude, supplementation with low-dose hCG from the onset of ovarian stimulation can improve oocyte quality without impairing endometrial receptivity.

Elevated serum progesterone levels on the hCG trigger day have a negative impact on the live birth rate in the first fresh IVF-ET cycle.

To investigate whether there is a relationship between elevated serum progesterone (PROG) on the hCG trigger day and the live birth rate (LBR) in IVF/ICSI cycles, the retrospective analysis was carried out from the patients undergoing the first ART cycles throughout 2016. The PROG levels were measured on the hCG trigger day. The LBR, clinical pregnancy rate (CPR), implantation rate (IR) and other parameter rate values were compared among the three different PROG elevations. A total of 2550 IVF/ICSI cycles fulfilling all the inclusion and exclusion criteria were selected. Finally, three groups [PROG <0.40 ng/mL, 0.40 ≤ PROG < 1.5 ng/mL, PROG ≥ 1.5 ng/mL] were categorised based on the serum PROG levels. LBR, CPR and IR declined as the PROG value increased, while there was no difference in the embryo utilisation rates. Serum PROG levels on the day of hCG administration were negatively associated with the LBR, even in ETs with a good prognosis.Impact StatementWhat is already known on this subject? The clinical effects of PROG are still controversial. Some studies have confirmed that there was not too much association between premature elevation of PROG and live birth, some are still convincing that there is a negative correlation and will result in ART cycles of pregnancy and LBR reduction.What do the results of this study add? Our data substantiated that the high serum PROG level had the lowest LBR, IR and CPR, but the embryo utilisation rate may not have too much to do with the elevated PROG.What are the implications of these findings for clinical practice and/or further research? This study further strengthens the negative impact of elevated PROG levels on pregnancy outcomes, and suggests that frozen thawed embryo transfer appears to be a reasonable and advantageous approach for this subset of patients.

Granulocyte colony stimulating factor versus human chorionic gonadotropin for recurrent implantation failure in intra cytoplasmic sperm injection: a randomized clinical trial.

BACKGROUND: Repeated implantation failure (RIF) is defined as the case whereby the transferred embryos fail to implant after several attempts of In vitro fertilization (IVF) which causes a profound impact on the quality of life and financial burden. Some clinical studies have confirmed that Granulocyte colony-stimulating factor (G-CSF) and human chorionic gonadotropin (HCG) can improve pregnancy outcomes and implantation rates. Hence, our study aims to compare the efficacy of G-CSF and HCG on pregnancy outcomes in RIF women who undergo intra-cytoplasmic sperm injection (ICSI). METHODS: This randomized, single-blinded study was conducted et al.-Azhar University Hospitals, Cairo, Egypt, between 10th October 2020 and 20th December 2020. The study included 100 women aged 20-43 years old undergoing ICSI cycles, with a history of RIF. Patients were divided randomly into two groups: group (1): included 50 patients injected with 500 IU of intrauterine HCG on embryo transfer day, and group (2): Included 50 patients injected with G-CSF on the embryo transfer day. RESULTS: In 100 RIF women, we found a significant improvement in pregnancy outcomes favoring G-CSF over HCG including implantation rate, chemical pregnancy, and clinical pregnancy (P < 0.0001, P = 0.0003, and P = 0.0006, respectively). CONCLUSION: For the first time, we demonstrated a significant improvement in pregnancy outcomes favoring G-CSF over HCG in terms of implantation rate, chemical pregnancy, and clinical pregnancy. TRIAL REGISTRATION: The study was registered on Pan African Clinical Trials Registry with the following number: PACTR202010482774275 and was approved on 2nd October 2020.

Impact of blood levels of progesterone on the day of ovulation onset on clinical, laboratory and reproductive parameters of young patients undergoing assisted reproduction: a cross-sectional study.

OBJECTIVE: To assess whether there is an association between the level of progesterone on the day of administration of human chorionic gonadotropin and clinical and laboratory characteristics, in addition to the results of in vitro fertilization of patients with a good prognosis. METHODS: A cross-sectional study comprising 103 women who underwent intracytoplasmic sperm injection treatment, between November 2009 and May 2015, aged ≤35 years, with no comorbidities, with fresh embryo transfer. Data were collected from patient medical records. RESULTS: There was a weak positive correlation between the level of progesterone on the day of human chorionic gonadotropin and the number of follicles larger than 14mm (ß=0.02, p=0.001), retrieved oocytes (ß=0.01, p=0.01) and oocytes in metaphase II (MII) (ß=0.02, p=0.02); that is, the increase in progesterone level has a slight association with increased values of these variables. Body mass index was inversely correlated with progesterone level on the day of human chorionic gonadotropin (ß=-0.01, p=0.02). No association was found between the level of progesterone on the day of human chorionic gonadotropin and the protocols used for controlled ovarian stimulation, quality of transferred embryos and the pregnancy rate. CONCLUSION: There is an association between the value of progesterone on the day of human chorionic gonadotropin administration with body mass index, number of follicles larger than 14mm, number of retrieved oocytes and oocytes in metaphase II. Unlike embryo quality and pregnancy rate, which do not have a statistically significant relation with this value in the population studied.

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

STUDY QUESTION: 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? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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. PARTICIPANTS/MATERIALS, SETTING, METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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). LIMITATIONS, REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Shanghai Municipal Health Commission of Science and Research Fund (20184Y0289). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: This trial was registered in the Chinese Clinical Trial Registry (ChiCTR-1800016285). TRIAL REGISTRATION DATE: 24 May 2018. DATE OF FIRST PATIENT'S ENROLMENT: 2 January 2019.

The optimal period for oocyte retrieval after the administration of recombinant human chorionic gonadotropin in in vitro fertilization.

BACKGROUND: Our objective was to investigate the existence of an optimal period for oocyte retrieval in regards to the clinical pregnancy occurrence after the administration of recombinant human chorionic gonadotropin (rhCG) (Ovitrelle®). METHODS: We studied the digital records of 3362 middle eastern couples who underwent in vitro fertilization (IVF) treatment between 2019 and 2021. RESULTS: Through statistical testing, we found that there is a significant positive correlation between the oocyte retrieval period and the clinical pregnancy occurrence up to the 37th hour, where retrieval at the 37th hour was found to provide the most optimal outcome, especially in the case of gonadotropin-releasing hormone agonist (GnRHa) long protocol. CONCLUSIONS: This cohort study recommends retrieval at hour 37 after ovulation triggering under the described conditions.