Human Chorionic Gonadotropin Administration Research Articles

Evaluation of Ovarian Histomorphology and Function Following Clomiphene Citrate and Human Chorionic Gonadotropin Administration in Wistar Rats

Polycystic ovarian syndrome (PCOS), affecting 5-10% of women, is a leading cause of infertility affecting 10-15% of couples globally. Human chorionic gonadotropin (hCG) and clomiphene citrate (CC) are often utilized for the treatment of PCOS. Accordingly, this study explored the effects of CC and hCG on ovarian histomorphology and fertility parameters. Twenty adult female rats were divided into four groups as follows: Group A (control) received only feed and water; Group B received 0.7 mg/kg BW of CC twice daily for five days and was mated before sacrifice on day 19 (before litter); Group C received 0.7 mg/kg BW of CC twice daily for five days, followed by mating and allowed to litter before sacrifice; Group D received 0.7 mg/kg body weight (BW) of hCG on day one, followed by 0.7 mg/kg BW of CC twice daily for five days, and were mated before sacrifice on day 7 (before litter). Results showed that Group B rats had higher, more than other groups, Follicle-stimulating hormone (FSH), Estradiol, Testosterone and Prolactin levels when compared to the control. Similarly, rats in Group B had higher levels of Progesterone while Group D had higher levels of Luteinizing hormone (LH) when compared to the control group. Histological findings demonstrated diverse impacts on ovarian structures, ranging from congested blood vessels to haemorrhages and follicular cysts. Consequently, this study underscores the complexities of drug interactions in reproductive health and provides preliminary insights into the possible adverse effects of CC and hCG on the ovary and fertility parameters.

Risk factors of ectopic pregnancy after in vitro fertilization-embryo transfer in Chinese population: A meta-analysis.

The prevalence of ectopic pregnancy after assisted reproduction is notably high, posing a significant threat to the life safety of pregnant women. Discrepancies in published results and the lack of a comprehensive description of all risk factors have led to ongoing uncertainties concerning ectopic pregnancy after assisted reproduction. This study aimed to understand the risk factors for ectopic pregnancy after in vitro fertilization-embryo transfer in the Chinese population and provide a reference for targeted prevention and treatment. A comprehensive search of the China National Knowledge Infrastructure, Wang fang Database, China Science Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Web of Science, and Embase was conducted to identify relevant literature on the risk factors for ectopic pregnancy in Chinese women after assisted reproductive technology in Chinese women. A meta-analysis of the included studies was performed using Stata17. Overall, 34 articles were included in the analysis. The risk factors for ectopic pregnancy after in vitro fertilization-embryo transfer in the Chinese population included a thin endometrium on the day of HCG administration and embryo transplantation, a history of ectopic pregnancy, secondary infertility, a history of induced abortion, polycystic ovary syndrome, decreased ovarian reserve, tubal factor infertility, cleavage stage embryo transfer, fresh embryo transfer, artificial cycle protocols, elevated estradiol levels on the day of human chorionic gonadotropin administration, a history of tubal surgery, two or more number of embryo transfers, previous pregnancy history, and a history of pelvic surgery. This study clarified the factors influencing ectopic pregnancy after in vitro fertilization and embryo transfer in the Chinese population, focusing on high-risk groups. Targeted and personalized intervention measures should be adopted to prevent and detect the disease early to reduce its incidence and harm. The protocol for this view was registered in PROSPERO (CRD42023414710).

Intrauterine insemination: prognostic factors.

To evaluate the impact of possible maternal and paternal prognostic factors and ovarian stimulation protocols on clinical pregnancy and live birth rates in intrauterine insemination (IUI) cycles. Retrospective observational study of 341 IUI cycles performed from January 2016 to November 2020 at the Assisted Reproduction Service of the Clinics Hospital of the Ribeirão Preto Medical School, University of São Paulo. Clinical pregnancy and live birth rates and their potential prognostic factors were evaluated. Wilcoxon's non-parametric test was used to compare quantitative variables, and the chi-square test to compare qualitative variables, adopting a significance level of p<0.05. A logistic regression model was performed to verify which exploratory variables are predictive factors for pregnancy outcome. The ovulation induction protocol using gonadotropins plus letrozole (p=0.0097; OR 4.3286, CI 1.3040 - 14.3684) and post-capacitation progressive sperm ≥ 5million/mL (p=0.0253) showed a statistically significant correlation with the live birth rate. Female and male age, etiology of infertility, obesity, multifollicular growth, endometrial thickness ≥ 7 mm, and time between human chorionic gonadotropin administration and IUI performance were not associated with the primary outcomes. In the group of patients with ideal characteristics (women aged< 40 years, BMI < 30 kg/m2, antral follicle count ≥ 5, partner aged< 45 years, and post-capacitation semen with progressive spermatozoa ≥ 5 million/mL), the rate of clinical pregnancy was 14.8%, while that of live birth, 9.9%. In this study, the ovulation induction protocol with gonadotropins plus letrozole and post-capacitation progressive sperm ≥ 5 million/mL were the only variables that significantly correlated with intrauterine insemination success.

#40 : Correlation Between Pre-Trigger Estradiol Levels and the Number of Mature Oocytes in Patients Who Underwent In Vitro Fertilization

Background and Aims: Strong association between pre-trigger estradiol levels on the day of human Chorionic Gonadotropin (hCG) administration and the number of mature oocytes retrieved was widely reported. Consequently, higher estradiol levels measured might give a prediction of the higher number of mature oocytes retrieved on Ovum Pick Up (OPU) procedure. This study was done to investigate the correlation between pre-trigger estradiol levels and number of mature oocytes retrieved in patients who underwent In Vitro Fertilization (IVF) cycles in Indonesian population. Method: A cross sectional study was done at Mbrio IVF Clinic, Mitra Keluarga Hospital Kelapa Gading, Jakarta, Indonesia. Data was collected from the medical records of 77 patients who underwent IVF cycles between September 2021 and March 2023. The level of estradiol on the hCG administration day and the number of mature oocytes retrieved were analysed to find any correlation between both variables using the Spearman Test. Results: There were 77 women who underwent IVF procedures with the age range between 27 and 45-year-old (mean 35,5 ± 4,52). Most of them (83%) had primary infertility and had infertility between 1 to 14 years (mean 5,5 ± 3,48). These subjects came to the clinic mostly due to both male and female factors (49,4%), followed by male factor only (27,3%). E2 on hCG day ranged between 194 to 13.000 pg/ml with the median 2.709 pg/ml, and the mature oocytes retrieved ranged between 0 and 31 with a median of 8 oocytes. A statistically significant correlation (r = 0.827; p&lt;0.01) was found between the estradiol level and mature oocytes retrieved. Conclusion: Pre-trigger Estradiol level can be used as a predictor for the number of mature oocytes retrieved in IVF cycle as these two variables are strongly correlated to each other. A multi-centre study with larger sample size is needed to validate current data.

Effect of Elevated Progesterone Levels on hCG Trigger Day on Clinical Pregnancy Outcome in Short-Acting GnRHa Downregulated Cycles.

Previous studies suggested higher serum progesterone (P) levels were strongly associated with a lower clinical pregnancy rate (CPR) for in vitro fertilization-embryo transfer (IVF-ET). However, the effect of increased serum P levels on the day of human chorionic gonadotropin (hCG) administration on clinical outcomes in short-acting gonadotropin-releasing hormone agonist (GnRHa) downregulated IVF-ET cycles remains unclear. We conducted a retrospective cohort study from January 2017 to December 2021, which included a total of 1664 patients receiving their first short-acting GnRHa IVF-ET cycles at our reproductive medicine centre of Nanjing Drum Tower Hospital. The smooth curve fitting and interaction analysis were employed to analyse the association between the CPR and the serum P levels with different embryo types (cleavage-stage embryo or blastocyst). In addition, total cycles were grouped according to different P levels on the trigger day of hCG administration for further analysis. The CPR of patients with increased serum P level (higher than 1.5 ng/mL) on the hCG day did not decrease. A smoothing curve fitting showed that the CPR did not change obviously with the increase in serum P levels. Subgroup analysis of different types of embryos transferred showed that no correlation was observed between the CPR and serum P levels on the day of hCG administration in cleavage-stage embryo transfer cycles. However, the CPR of patients receiving blastocyst transfer showed a downward trend with the increase in serum P levels. At the same time, an interaction analysis also confirmed that the CPR of blastocyst transfer was more likely to be affected by elevated serum P levels on the hCG day. In the luteal phase short-acting GnRHa downregulated IVF-ET cycles, the elevated serum P levels on the hCG day did not affect the CPR of cleavage-stage embryo transfer but reduced the CPR of blastocyst transfer.

#290 : Does Extending the Time Interval Between hCG Trigger and Oocyte Retrieval from 36 to 37 Hours Affect the Rate of Euploid Blastocysts?

Background and Aims: Data are lacking regarding the optimal time interval between human chorionic gonadotropin (hCG) administration and ovum pick-up (hCG-OPU interval), and its impact on blastocyst euploidy. Our aim was to compare the blastocyst euploidy rate between IVF cycles with hCG-OPU interval of 36 and 37 h. Method: In this historic cohort study, we reviewed all hCG-triggered, PGT-A, IVF cycles performed in a single clinic, between 2018 and 2022. Commencing in September 2021, clinicians gradually changed the hCG-OPU interval from 37 to 36 h. We compared the outcomes of cycles with hCG-OPU interval of 36 h (35.5-36.5) to 37 h (36.6-37.5). The primary outcome was the number of euploid embryos. Cycles with oocyte donation, and cycles utilized GnRH-agonist triggers or dual-triggers were excluded. Results: The euploidy rates were similar between the 36-h group (n=2,584) and 37 h group (n=5,575; 39.7% vs. 38.8%, respectively, p=0.42). Compared to the 36-h group, patients in the 37-h group were characterized by higher numbers of total oocytes collected (15.9±8.9 vs. 17.3±9.8, respectively, p&lt;0.001), mature (MII) oocytes (8.3±8.2 vs. 9.6±9.6, respectively, p&lt;0.001) and 2PN embryos (9.8±5.5 vs. 10.3±6.4, respectively, p&lt;0.001). On multivariate logistic regression analysis, the hCG-OPU interval was not associated with euploidy (aOR 0.91, 95% CI 0.82-1.01), after controlling for female and male ages, female BMI, and number of oocytes collected. Conclusion: hCG-OPU intervals of 36 and 37 h resulted in similar blastocyst euploidy rates in IVF cycles. This finding has the potential to aid the decision-making processes when managing IVF procedures. The 37-h group was characterized by a lower female age and higher doses of gonadotropins and consequentially more eggs collected, mature eggs and 2PN embryos compared to the patients of the 36 h group. Nonetheless, the two groups had comparable rates of euploid embryos reinforcing our primary finding. Data are presented as mean ± standard deviation or n (%); hCG- Human chorionic gonadotropin; OPU- ovum pickup; BMI- BMI kg/m2, Gonadotropins- in IU; ICSI- Intra cytoplasmic sperm injection. Data are presented as mean ± standard deviation or n (%); hCG- Human chorionic gonadotropin; OPU- ovum pickup; 2PN- 2 Pronuclei.

Increased Serum Levels of Phoenixin-14, Nesfatin-1 and Dopamine Are Associated with Positive Pregnancy Rate after Ovarian Stimulation.

We study the relationship between phoenixin (PNX-14), nesfatin-1 (NES-1), dopamine (DA) and oxytocin (OT) levels together with pregnancy rates in women after ovarian stimulation (OS). In a prospective case-control study, 56 infertile women were enrolled from the Department of Gynecological Endocrinology University Hospital. Infertile women age < 40 years old, with polycystic ovary syndrome (PCOS), confirmed tubal patency and suitable sperm quality were included. Blood samples were drawn twice-before the initiation of OS and before the human chorionic gonadotropin (hCG) administration. Assessments of PNX-14, NES-1, DA and OT serum levels were performed. Pregnancy rates after OS were observed. Pregnant women showed higher baseline NES-1 and OT levels (+29.2% and +44%) but not PNX-14 and DA levels when compared to non-pregnant ones. In pregnant women, positive correlations between OT and prolactin, PRL (r = 0.47, p = 0.04), as well as between OT and NES-1 (r = 0.55, p = 0.02), were observed at baseline. At baseline, an OT level increase was associated with a positive pregnancy rate (per 100 pg/mL, OR = 1.39, 95% CI 1.04-1.74), while after OS, higher PNX-14 was a predictor of pregnancy (by 10 pg/mL, OR = 1.23, 95%CI 1.07-1.39). Post-stimulation PNX-14, NES-1 and DA concentrations were higher in pregnant women compared to non-pregnant ones (+17.4%, +26.1%, and +45.5%, respectively; all p < 0.05). In the pregnant group, OT levels were 2.7-times lower than in the remainder (p = 0.03). Moreover, in pregnant participants, a negative association between NES-1 and PNX (r = -0.53, p = 0.024) was observed. Elevated PNX-14, NES-1 and DA along with decreased OT levels were observed in women who achieved pregnancy.

Novel predictors for livebirth delivery rate in patients with idiopathic non-obstructive azoospermia based on the clinical prediction model.

To build a prediction model for live birth delivery per intracytoplasmic sperm injection (ICSI) in iNOA patients by obtaining sperm by microdissection testicular sperm extraction (mTESE). A retrospective cohort study of 377 couples with iNOA male partners treated with 519 mTESE-ICSI cycles was conducted from September 2013 to July 2021 at the Reproductive Medical Centre of Peking University Third Hospital. Following exclusions, 377 couples with iNOA male partners treated with 482 mTESE-ICSIs were included. A prediction model for live birth delivery per ICSI cycle was built by multivariable logistic regression and selected by 10-fold cross-validation. Discrimination was evaluated by c-statistics and calibration was evaluated by the calibration slope. The live birth delivery rate per mTESE-ICSI cycle was 39.21% (189/482) in these couples. The model identified that the presence of motile sperm during mTESE, bigger testes, higher endometrial thickness on the day of human chorionic gonadotrophin (hCG) administration (ET-hCG), and higher quality embryos are associated with higher live birth delivery success rates. The results of the model were exported based on 10-fold cross-validation. In addition, the area under the mean ROC curve was 0.71 ± 0.05 after 10-fold cross-validation, indicating that the prediction model had certain prediction precision. A calibration plot with an estimated intercept of -1.653 (95% CI: -13.403 to 10.096) and a slope of 1.043 (95% CI: 0.777 to 1.308) indicated that the model was well-calibrated. Our prediction model will provide valuable information about the chances of live birth delivery in couples with iNOA male partners who have a plan for mTESE-ICSI treatment. Therefore, it can improve and personalize counseling for the medical treatment of these patients.

Nature (almost) always prevails – challenging the status quo of artificial cycle frozen embryo transfers

Frozen embryo transfers (FET) have become increasingly popular in assisted reproductive technology (ART) due to advancements in cryopreservation techniques and the implementation of the ‘freeze-all’ strategy. The choice between artificial or natural cycles for FET preparation has been a subject of debate, considering factors such as endometrial receptivity, flexibility of scheduling and pregnancy outcomes. While artificial cycle protocols offer convenience and flexibility, studies have suggested potential drawbacks, including higher miscarriage rates and a greater risk of hypertensive disorders during pregnancy. In contrast, natural cycle protocols involve a frequently demanding monitoring of both endometrial proliferation and follicular growth, which may lead to increased clinic visits and scheduling issues. Multiple strategies have been proposed to enhance the usage of natural cycle FET, including addressing anovulation through minimal stimulation, reducing cycle monitoring and exploring novel FET approaches. These novel approaches, such as widening the window for human chorionic gonadotrophin administration and the natural proliferative phase protocol, offer promising outcomes and increased convenience for patients. However, further research is needed to establish the optimal timing and effectiveness of these strategies. Overall, enhancing the practicality of natural cycle FETs is crucial for expanding their utilization during ART.

Elevated estradiol levels on hCG trigger day adversely effects on the clinical pregnancy rates of blastocyst embryo transfer but not cleavage-stage embryo transfer in fresh cycles: a retrospective cohort study.

Elevated estradiol (E2) levels are an inevitable outcome of the controlled ovulation hyperstimulation. However, the effect of this change on pregnancy is still uncertain. Our study aimed to analyze the impact of increased serum E2 at the day of human chorionic gonadotropin (hCG) administration on the clinical outcomes of women with fresh embryo transfer (ET) cycles. This study included 3,009 fresh ET cycles from October 2015 to September 2021. Based on the stage of embryos transferred, these cycles were categorized into the cleavage group and blastocyst group. Both groups were then divided into four sets according to E2 levels when hCG was administered: set 1 (E2 ≤ 2,000 pg/ml), set 2 (E2 = 2,001-3,000 pg/ml), set 3 (E2 = 3,001-4,000 pg/ml), and set 4 (E2 > 4,000 pg/ml). The primary outcome was the clinical pregnancy rate (CPR). Binary logistics regression analysis was established to explore the association between CPR and E2 levels. Specifically, the threshold effect of serum E2 on CPR was revealed using the two-piecewise linear regression analyses. The multivariate regression model in the cleavage group showed that patients' CPR in set 4 was 1.59 times higher than those in reference set 1, but the statistical difference was insignificant (P=0.294). As for the blastocyst group, patients in set 4 had a lower CPR with adjusted ORs of 0.43 (P=0.039) compared to patients in set 1. The inflection point for the blastocyst group was 39.7 pg/dl according to the results of the two-piecewise linear regression model. When E2 levels were over the point, the CPR decreased by 17% with every 1 pg/dl increases in serum E2 (adjusted OR = 0.83, 95% CI [0.72-0.96], P=0.012). Elevated E2 levels (>39.7 pg/dl) on hCG trigger day were associated with decreased CPR in patients with fresh blastocyst ET. However, it had no similar effect on the CPR of patients with fresh cleavage-stage ET.

Factors influencing clinical pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection in older women.

To analyse the factors influencing clinical pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in older women, and to establish a risk prediction model. A total of 425 patients receiving IVF/ICSI from March 2018 to March 2020 were divided into pregnancy group (n=194) and non-pregnancy group (n=231). The factors affecting the outcomes of IVF/ICSI were explored by univariate and multivariate logistic regression analyses. A nomogram prediction model was constructed. The two groups had significantly different age, body mass index, dysmenorrhea, parity, times of full-term births, history of cesarean section, basal follicle stimulating hormone, basal antral follicle count (AFC), number of high-quality embryos, and basal estradiol, luteinizing hormone and endometrial thickness on the day of human chorionic gonadotropin (HCG) administration (P<0.05). Age ≥40 years old, dysmenorrhea, history of cesarean section, basal AFC<9, number of high-quality embryos <4, and endometrial thickness on the day of HCG administration <11 mm led to IVF/ICSI failure. The established model exhibited high calibration and discrimination degrees in predicting the outcome of IVF/ICSI. The risk prediction model for the pregnancy outcome of IVF/ICSI in older women helps evaluate the fertility probability and risk, providing references for formulating reasonable assisted reproduction plans.

Evaluation of serum progesterone on the day of human chorionic gonadotropin administration as a predictor of pregnancy rate in ICSI

Evaluation of serum progesterone on the day of human chorionic gonadotropin administration as a predictor of pregnancy rate in ICSI

P-606 Does trigger timing make a difference in oocyte donation?

Abstract Study question Is there optimal trigger timing in controlled ovarian stimulation (COS) for egg donors for better clinical outcome? Summary answer Different trigger timings may not affect oocyte maturity rate. 35 hour’s trigger may create optional timing for embryology to complete fertilization into a natural concept. What is known already Trigger exposure time is still a debatable clinical issue. Ovulation is triggered by administration of hCG or GnRH agonist, with retrieval taking place between 35th and 38th hour post triggering. There was a tendency to decrease post maturity risk for MII oocytes also early triggering will create optional timing for embryology laboratory for denudation, oocyte vitrification and fertilization process under oocyte cytoplasmic maturity (38 hours post trigger) and natural concept fertilization (till 40 hours post trigger) for better clinical outcome. Study design, size, duration This single center retrospective study included oocyte donors (n = 1289) with different timing of eggs retrieving. They were divided into two groups: group A, with exposure of the medicine trigger for 35 h and group B with timing which was 36 h before egg retrieval. We evaluated the concordance between the follicle-to-oocyte index (FOI), antral follicle count (AFC), number of MII oocytes, maturation rate (MR), utilization rate (UR) and the timing of triggering. Participants/materials, setting, methods The number of donors was 784 and 505 in A and B groups respectively. The mean age of the patients in this study was (SD) 26,2 (3,2) and 26,7 (3,3) years. Cycle characteristics were compared. Data was assessed using the Shapiro-Wilk test for the normality of the distribution of the variables. The association between COS cycle parameters and the differences in COS output was assessed by T-Student (parametric) or U-Mann-Whitney (non-parametric). Main results and the role of chance Donors in groups A and B had a similar mean number of oocytes retrieved (33,50±14,12 vs 30,44±13,00), in groups A and B respectively. The same tendency with no statistical difference was mentioned for values number of MII oocytes (SD): 25,16 (11,73) and 20,50 (10,19), for MR - 81% vs 80% and for AFC: 33,50 (14,18) and 30,44 (13,00) in groups A and B, respectively. Unexpectedly, values for UR and FOI (SD) were statistically significant different (p = &amp;lt;0.05): 94,1% (17,2) vs 89,1% (20,2) and 92,51 (11,43) vs 83,43 (15,63), accordingly, in group A and B respectively. Group A donor oocytes vitrified on 38 hours post trigger and fertilized on 40 hours from sibling oocytes. Group B donor oocytes vitrified on 39 hours and fertilized on 42 hours from sibling oocytes. Values for oocyte survival rate post warming were statistically non-significant different (p &amp;gt; 0.05): 96,64% (10,95) vs 95,08% (10,03). Cleavage arrest rate were statistically significant different; 8,01% vs 28,06% and used blastocysts rate were statistically significant different; 54,67% (5,02) vs 42,36% (4,08). Values for fertilization were statistically non-significant different; (p &amp;gt; 0.05): 98,64% (12,24) vs 97,08% (11.96) and used blastocysts rate were statistically significant different; 67,22% (6,18) vs 51,88%. (5,07) Limitations, reasons for caution This study is limited by its retrospective nature and the established strict time parameters of the study can be considered a limitation. Wider implications of the findings As we can see, the issue of the optimal period for oocyte retrieval after the administration of human chorionic gonadotropin should be considered very individually and in further studies it is possible to take into account wider time intervals in the design of trials. Trial registration number not applicable

Intrauterine Insemination After Human Chorionic Gonadotropin Trigger or Luteinizing Hormone Surge: A Meta-analysis.

To assess the odds of pregnancy after intrauterine insemination (IUI) timed by ultrasound monitoring and human chorionic gonadotropin (hCG) administration compared with monitoring luteinizing hormone (LH) levels. We searched PubMed (MEDLINE), EMBASE (Elsevier), Scopus (Elsevier), Web of Science (Clarivate Analytics), ClinicalTrials.gov (National Institutes of Health), and the Cochrane Library (Wiley) from the inception until October 1, 2022. No language limitations were applied. After deduplication, 3,607 unique citations were subjected to blinded independent review by three investigators. Thirteen studies (five retrospective cohort, four cross-sectional, two randomized controlled trials, and two randomized crossover studies) that enrolled women undergoing natural cycle, oral medication (clomid or letrozole), or both for IUI were included in the final random-effects model meta-analysis. Methodologic quality of included studies was assessed with the Downs and Black checklist. Data extraction was compiled by two authors, including publication information, hCG and LH monitoring guidelines, and pregnancy outcomes. No significant difference in odds of pregnancy between hCG administration and endogenous LH monitoring was observed (odds ratio [OR] 0.92, 95% CI 0.69-1.22, P=.53). Subgroup analysis of the five studies that included natural cycle IUI outcomes also showed no significant difference in odds of pregnancy between the two methods (OR 0.88, 95% CI 0.46-1.69, P=.61). Finally, a subgroup analysis of 10 studies that included women who underwent ovarian stimulation with oral medications (clomid or letrozole) did not demonstrate a difference in odds of pregnancy between ultrasonography with hCG trigger and LH-timed IUI (OR 0.88, 95% CI 0.66-1.16, P=.32). Statistically significant heterogeneity was noted between studies. This meta-analysis showed no difference between pregnancy outcomes between at-home LH monitoring and timed IUI. PROSPERO, CRD42021230520.

Impact of Accessory Corpus Luteum Induced by Gonadotropin-Releasing Hormone or Human Chorionic Gonadotropin on Pregnancy Rates of Dairy Cattle following Embryo Transfer: A META-Analysis.

The circulation of progesterone (P4) concentrations of recipients has positive correlations with embryo survival and pregnancy success of embryo transfer (ET) in dairy cows. One strategy to improve P4 concentration is the administration of gonadotropin-releasing hormone (GnRH) or human chorionic gonadotropin (hCG), thereby inducing the formation of accessory corpus luteum (CL). This study aimed at determining the efficacy of GnRH or hCG treatment regarding embryo transfer (ET) and providing a better clinical veterinary practice guidance. A meta-analysis was conducted on the data from 2048 treated recipient cows and 1546 untreated cows. By inducing the formation of accessory CL with GnRH (100 µg), GnRH analogue Buserelin (8-10 µg), or hCG (≥1500 IU) 5-11 days after synchronized ovulation, hCG alone achieved an improvement (RR = 1.39, p < 0.05), while GnRH and GnRH analogue did not result in significant changes (RR = 1.04, p = 0.26). Treatment with GnRH or hCG 5-7 days after synchronized ovulation was associated with increased chances of pregnancy compared with later treatment (11-14 days). Owing to the treatment, the pregnancy rate of cows with very poor fertility (<40%) was improved, while that of cows with good fertility (≥40%) was not affected. Treatment with GnRH or hCG greatly improved pregnancy rates of parous lactating cows (RR = 1.32, p < 0.05) compared with heifers (RR = 1.02, p > 0.05). Additionally, as indicated by pregnancy loss analysis, the treatment had no benefit on late embryo/early fetus survival at days 28-81. In conclusion, the induction of accessory CL with GnRH or hCG may benefit fertility and have important implications for the management of reproductive performance in the dairy industry.

Effectiveness of letrozole in pituitary downregulated normogonadotrophic young women with an initial poor response.

It has been reported that 10 to 15% of young normogonadotrophic women show suboptimal response to standard long protocols. Letrozole (LE), an aromatase inhibitor, was shown to improve ovarian sensitivity to follicle stimulating hormone (FSH) and follicular response to gonadotrophin treatment in poor ovarian response patients. We reasoned that it might be possible to utilize LE in young normogonadotrophic patients with unexpected hypo-response in standard gonadotropin-releasing hormone agonist long protocol. A total of 652 patients defined as normogonadotrophic patients with unexpected hypo-response were divided into 2 groups, the +LE group and the +Gn group. +LE group: A fixed daily dose of 2.5 mg of LE was added on day 8 of stimulation. +Gn group: A fixed daily dose of 75 U of human menopausal gonadotrophin was added on day 8 of stimulation. The primary outcome measures were the number of oocytes obtained, fertilization rate, days of stimulation, and total FSH dosage. The secondary outcome measures were the implantation rate and ongoing pregnancy rate. There were no significant differences in the clinical and hormonal characteristics between the 2 groups. A shorter duration of stimulation and a lower dosage of recombinant FSH consumption on the day of human chorionic gonadotropin administration were all observed in the +LE group. Patients who received LE therapy showed a higher number of oocytes obtained and significantly higher fertilization rates. The implantation rate and ongoing pregnancy rate were comparable in both groups. LE significantly improves the number of oocytes obtained in patients with suboptimal response to standard gonadotropin-releasing hormone agonist long protocol.

Correction: Clinical outcome of intrauterine administration of peripheral mononuclear cells or human chorionic gonadotropin in unexplained implantation failure

Correction: Clinical outcome of intrauterine administration of peripheral mononuclear cells or human chorionic gonadotropin in unexplained implantation failure

The importance of infertility duration and follicle size according to pregnancy success in women undergoing ovulation induction with gonadotropins and intrauterine insemination

In this study, we aimed to evaluate the effect of infertility duration and dominant follicle size measured on the day of human chorionic gonadotropin (HCG) administration on pregnancy rates in infertile women undergoing ovulation induction (OI) with gonadotropin (GND). A total of 352 patients aged 20 to 41 years who were diagnosed with unexplained infertility or polycystic ovary syndrome (PCOS) were included in this study. Patients with a history of multifollicular development or follicle stimulating hormone (FSH) value more than 12 IU/ml were excluded from the study. The demographic and clinical features of the patients were obtained from the patients’ files and hospital automation system and recorded for each woman. The demographic and clinical features of the patients were recorded. Patients were divided into two groups as live birth (group 1, n = 47) and non-live birth groups (group 2, n = 305). There were no statistically significant differences in regard to age, infertility type, follicle stimulating hormone (FSH) level, oestradiol (E2) level, antral follicle count (AFC), cycle characteristics, GND type, number of follicles, E2 level and endometrial thickness on HCG day, total GND dose, dominant follicle size (p > 0.05). Infertility duration in group 1 was 3.5 ± 2.1; in group 2, 4.7 ± 3.9 years. This difference was statistically significant (p = .014). According to this study, live birth rates after GND + IUIs(intrauterine insemination) were significantly affected by the duration of infertility. But the dominant follicle size and endometrial thickness measured on HCG day in GND and IUI cycles did not have a significant effect on pregnancy rates. IMPACT STATEMENT What is already known on the subject? It is thought that the timing of the ovarian triggering is vital for the success of intrauterine insemmination (IUI) treatment. What do the results of this study add? According to our results live birth rates after GND + IUIs were significantly affected by the duration of infertility. What are the implications of these findings for clinical practice and/or further research? It is determined that the duration of infertility is significant and patients should be encouraged to the treatment as soon as possible.

Effects of trigger-day progesterone in the preimplantation genetic testing cycle on the embryo quality and pregnancy outcomes of the subsequent first frozen-thawed blastocyst transfer.

To assess whether progesterone (P) levels on the trigger day during preimplantation genetic testing (PGT) cycles are associated with embryo quality and pregnancy outcomes in the subsequent first frozen-thawed blastocyst transfer (FET) cycle. In this retrospective analysis, 504 eligible patients who underwent ICSI followed by frozen-thawed embryo transfer (FET) with preimplantation genetic test (PGT) between December 2014 and December 2019 were recruited. All patients adopted the same protocol, namely, the midluteal, short-acting, gonadotropin-releasing hormone agonist long protocol. The cutoff P values were 0.5 and 1.5 ng/ml when serum P was measured on the day of human chorionic gonadotropin (HCG) administration, and cycles were grouped according to P level on the day of HCG administration. Furthermore, the effect of trigger-day progesterone on embryo quality and the subsequent clinical outcome of FET in this PGT population was evaluated. In total, 504 PGT cycles were analyzed. There was no significant difference in the number of euploid blastocysts, top-quality blastocysts, euploidy rate, or miscarriage rate among the three groups (P>0.05). The 2PN fertilization rate (80.32% vs. 80.17% vs. 79.07%) and the top-quality blastocyst rate (8.71% vs. 8.24% vs. 7.94%) showed a downward trend with increasing P, and the between-group comparisons showed no significant differences (P>0.05). The clinical pregnancy rate (41.25% vs. 64.79%; P<0.05) and live birth rate (35.00% vs. 54.93%; P<0.05) in subsequent FET cycles were substantially lower in the high-P group than in the P ≤ 0.5 ng/ml group. After adjustments were made for confounding variables, multivariate logistic regression analysis revealed that the high-P group had a lower clinical pregnancy rate (adjusted OR, 0.317; 95% CI, 0.145-0.692; P=0.004) and live birth rate (adjusted OR, 0.352; 95% CI, 0.160-0.773; P=0.009) than the low-P group in subsequent FET cycles, and the differences were significant. This study demonstrates that in the PGT population, elevated P on the trigger day may diminish the top-quality blastocyst rate (although there is no difference in the euploidy rate). Trigger-day P is an important factor influencing clinical outcomes in subsequent FET cycles.

Effect modification by developmental stage of embryos on the association between late follicular phase progesterone elevation and live birth in fresh transfers

BackgroundLate follicular phase progesterone elevation (LFPE) during ovarian stimulation is associated with reduced live birth rates (LBRs) after cleavage-stage embryo transfer. However, due to better synchronization with a stimulated endometrium, prior studies shown that LFPE had no effect on transferring embryos at blastocyst stage. The study aim to exam whether the developmental stage of embryos and serum progesterone levels on the day of human chorionic gonadotropin (hCG) administration jointly affect the odds of live birth in fresh fresh IVF/intracytoplasmic sperm injection (ICSI) cycles. MethodsThe single-center retrospective cohort study included a total of 4,471 fresh embryo transfer cycles with 2,342 at cleavage stage versus 2,129 at blastocyst stage. Patients underwent IVF/ICSI with ovarian stimulation in gonadotropin-releasing hormone antagonist protocol. The serum progesterone level was examined both as a continuous variable and as a categorical variable by quartiles. Analysis was performed using the generalized estimating equations framework and multivariate regression models.ResultsLBRs were inversely associated with progesterone as a continuous variable on the day of hCG in both the cleavage-stage (crude OR 0.87, 95%CI 0.73–1.03; adjusted OR 0.80, 95% CI 0.65–0.98) and the blastocyst-stage (crude OR 0.66, 95%CI 0.56–0,78; adjusted OR 0.61, 95%CI 0.50–0.73) groups. The interaction testing was highly significant (P = 0.018) indicating an effect modifying role of stage of embryos transferred on the association of pregesterone values with the LBRs in fresh cycles. A similar pattern for a greater reduction in ORs for live birth in cycles with blastocysts transfer was also observed when progesterone was analyzed by interquartile ranges. The findings remained unchanged in subgroup analysis stratified by types of ovarian response.ConclusionsIn fresh cycles, detrimental effect of late follicular phase progesterone elevation on live birth was more prominent in blastocyst-stage group compared with that in clevaged-stage group.