Human Chorionic Gonadotropin Administration Research Articles

THE USE OF OVULATION PREDICTOR KITS FOR DONOR SPERM INSEMINATION CYCLES: THE DATA IS CLEAR

Studies have demonstrated that patient interpretation of home urinary ovulation predictor kits (OPKs) not uncommonly results in false-positive tests (McGovern PG et al., Fertil Steril 2004 Nov;82(5):1273-7). Patients undergoing donor sperm intrauterine insemination (IUI-D) typically have one opportunity for exposure to sperm during a treatment cycle, making the timing of IUI-D critical. We therefore undertook a Quality Improvement project investigating whether patients undergoing IUI-D had different success rates when IUI-D was timed 24-32 hours after positive morning OPK or 24-32 hours after clinic administration of Human Chorionic Gonadotropin (HCG).

WS-5. Proposal for a novel classification based on onset of HDP; antenatal onset, labor onset, and postpartum onset

Elevated progesterone on the day of human chorionic gonadotropin (hCG) administration is associated with decreased live birth rates in IVF cycles. The association with adverse pregnancy outcomes is unknown.Assess the association between serum progesterone on the day of hCG administration and the risk of ischemic placental disease [IPD; preeclampsia, placental abruption, and/or small for gestational age (SGA)].We conducted a retrospective cohort study of autologous fresh IVF cycles resulting in delivery between 2005 and 2018. All IVF procedures were conducted at a large, university-affiliated infertility center. Patients were divided into tertiles based on their serum progesterone level on the day of hCG administration; the lowest tertile served as the reference group. We identified pregnancies complicated by preeclampsia and placental abruption using ICD-9/10 codes and medical record review. We defined SGA as < 10th percentile using U.S. growth curves.The cohort included 166 deliveries in the lowest tertile of progesterone (0.2–0.73 ng/ml), 166 deliveries in the middle (0.64–1.05 ng/ml) and 167 deliveries in the highest tertile (1.05–5.6 ng/ml). Compared with the lowest tertile, the risk of IPD was greater in the middle (RR 1.6; 95% CI 1.1–2.5) tertile after adjustment for age, parity, number of oocytes retrieved, and estradiol. The highest tertile was also not associated with an increased risk of IPD.In an IVF population, elevated serum progesterone in the range of 0.64–1.05 ng/mL on the day of hCG administration was associated with a small increased risk of IPD.

Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Protocol and GnRH Antagonist Protocol: Effects on In-vitro Fertilization in Patients with Poor-responder Diagnosis According to Bologna Criteria

Objective: The aim of the study was to evaluate microdose flare-up Gonadotropin-Releasing Hormone (GnRH) agonist protocol and GnRH antagonist protocol with respect to their effects on in-vitro fertilization (IVF) results in patients with poor ovarian response according to the Bologna Criteria.&#x0D; Material Methods: This was a retrospective cohort study conducted in the Assisted Reproduction clinic of University of Health Sciences, Etlik Zübeyde Hanım Gynaecology Training and Research Hospital. A total of 645 patients who had been diagnosed as poor responders in our clinic, between 2007 and 2018, and received treatment with either microdose flare-up GnRH agonist protocol (n=250, 38.8%) or GnRH antagonist protocol (n=395, 61.2%), were included in the study.&#x0D; Results: The mean age of the study group was 34.5±5.5 years. Comparisons showed that IVF cycle cancellation frequency (p&lt;0.01), third day estradiol level (p=0.04) and third day follicle stimulating hormone level (p&lt;0.01) were significantly greater in patients who underwent the microdose flare-up protocol. In the GnRH antagonist group, the number of surviving children (p=0.01), antral follicle count (p&lt;0.01), follicle count on day of human chorionic gonadotropin (hCG) administration (p&lt;0.01), endometrial thickness on hCG day (p&lt;0.01), number of oocytes collected (p&lt;0.01), mature oocyte count (p&lt;0.01), embryo transfer number (p&lt;0.01) were higher compared to the microdose flare-up protocol group. The two groups were similar in terms of clinical pregnancy rate.&#x0D; Conclusions: In terms of clinical pregnancy rate, the IVF results of microdose flare-up and GnRH antagonist protocols are similar. Further studies are needed to reach more comprehensive results on the subject.

Evaluation of the relationship between serum estradiol levels on human chorionic gonadotropin administration day and intracytoplasmic sperm injection outcomes: A retrospective population-based study.

BackgroundThe correlation between high estradiol (E2) levels induced by controlled ovarian hyperstimulation (COH) and pregnancy is controversial.ObjectiveTo assess the effect of serum E2 levels on the day of human chorionic gonadotropin administration on the intracytoplasmic sperm injection (ICSI) outcome.Materials and MethodsThe current study included 551 participants who had undergone ICSI between May 2014 and May 2016. Based on E2 levels, the individuals aged 37 yr (n = 502) and 37-42 yr (n = 49) were categorized into six and three groups, respectively. ICSI outcomes including the number of retrieved oocytes (NRO), number of embryos (NE), pregnancy rate, and abortion rate were analyzed in both groups.ResultsAmong participants aged 37 yr, the NRO and NE were 8.69 3.82 and 5.24 2.32, respectively and they had a significant correlation with the E2 level on human chorionic gonadotropin administration day (p 0.001 for both). Among participants aged 37 yr, NRO and NE were 5.18 3.17 and 3.40 2.23, respectively, and the NRO (p 0.001), NE (p 0.001), pregnancy rate (p 0.001), abortion rate (p = 0.007), and the number of grade A and B embryos (p = 0.003) had a significant association with the E2 level.ConclusionCOH is a costly procedure that may have negative effects on endometrial receptivity. Thus, in order to prevent these effects and also to reduce the costs of COH, we recommend gaining optimum number of oocytes rather than maximum number during the procedure.

Ovulatory upregulation of angiotensin-converting enzyme 2, a receptor for SARS-CoV-2, in dominant follicles of the human ovary

ObjectiveTo determine the temporal expression of angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2, in dominant follicles throughout the periovulatory period in women and the regulatory mechanisms underlying ACE2 expression in human granulosa/lutein cells (hGLC).DesignExperimental prospective clinical study and laboratory-based investigation.SettingUniversity Medical Center and private in vitro fertilization center.Patient(s)Thirty premenopausal women undergoing surgery for tubal ligation and 16 premenopausal women undergoing in vitro fertilization.Intervention(s)Administration of human chorionic gonadotropin (hCG) and harvesting of preovulatory/ovulatory follicles by timed laparoscopy, and collection of granulosa/lutein cells and cumulus cells at the time of oocyte retrieval.Main Outcome Measure(s)Expression and localization of ACE2 in granulosa cells and dominant follicles collected throughout the periovulatory period of the menstrual cycle and in hGLC using quantitative polymerase chain reaction, immunoblotting, and immunohistochemistry.Result(s)ACE2 expression (mRNA and protein) is up-regulated in human ovulatory follicles after administration of hCG. ACE2 expression was higher in cumulus cells than in granulosa cells. hCG increased the expression of ACE2 in primary hGLC cultures; the increase was inhibited by RU486 (an antagonist for progesterone receptor and glucocorticoid receptor) and CORT125281 (a selective glucocorticoid receptor antagonist), but not by AG1478 (an EGF receptor tyrosine kinase inhibitor) or by dexamethasone.Conclusion(s)The hormone-regulated expression of ACE2 in granulosa cells suggests a potential role of ACE2 in the ovulatory process. These data also imply the possible impact of COVID-19 on a vital cyclic event of ovarian function and thus on women's overall reproductive health. However, SAR-CoV-2 infection in ovarian cells in vivo or in vitro has yet to be determined.

P–309 Effectiveness of intrauterine infusion of platelet-rich plasma (PRP) vs. granulocyte colony-stimulating factor (G-CSF) in women with thin endometrium undergoing assisted reproduction

Abstract Study question To compare the effect of intrauterine infusion of platelet-rich plasma (PRP) and granulocyte colony-stimulating factor (G-CSF) on endometrial thickness, clinical pregnancy rate and live-birth rate. Summary answer According to our research, PRP-therapy has more positive results in pregnancy rates. Nevertheless, there is still limited data to answer all questions completely. What is known already Thin endometrium is defined as endometrium thickness &amp;lt;7 mm or &amp;lt; 8 mm on the day of human chorionic gonadotropin (HCG) administration, which negatively affects the onset of pregnancy during natural fertilization and in assisted reproduction. Endometrial thickness may impact pregnancy and live-birth rates in fresh and frozen IVF cycles but, currently, there is minimal evidence to support any specific protocol to significantly improve pregnancy outcomes in patients with thin endometrium. Therefore, we decided to compare effects of two methods: transvaginal intrauterine perfusion of G-CSF for infertile women with thin endometrium in IVF cycles and intrauterine infusion of PRP. Study design, size, duration We conducted a systematic review and meta-analysis by PRISMA checklist. PubMed, The Cochrane Library, ClinicalTrials.gov and Google Scholar were searched electronically until 2021 using key words: “G-CSF”, “PRP”, “endometrium”. We included published and unpublished randomized clinical trials (RCT) and non-randomized clinical trials in English which include min.10 patients. Participants/materials, setting, methods Participants: female infertile patients of reproductive age with thin endometrium (≤ 7 mm) in embryo transfer cycles. Exclusion criteria: history of any chromosomal or genetic abnormalities and hematological disorders. Outcomes – endometrial thickness, pregnancy and live-birth rates.Risk of bias assessment was held using The Cochrane Handbook and The Cochrane collaboration tools. RoB 2 tool was used for randomized trials and ROBINS-I tool for non-randomized trials. For quantitative synthesis RevMan 5.4 was used to conduct meta-analysis. Main results and the role of chance Literature search resulted in 144 potentially relevant publications initially (Google Scholar: 126, PubMed: 1, Clinicaltrials: 14, Cochrane: 3). These publications were checked for titles and abstracts, duplicates were removed and 7 publications were selected. After evaluating the selection criteria, 2 articles were excluded. As a result, 5 articles remained for qualitative and quantitative synthesis, including 2 randomized controlled trials (RCT), 2 retrospective cohort studies, and 1 prospective cohort study. 403 patients participated in selected studies (the PRP group included 205 patients, and the G-CSF group - 198 patients). The primary quantitative analysis (meta-analysis) is aimed at comparison of endometrial thickness in patients receiving PRP therapy and patients receiving G-CSF. Two RCTs were included in this meta-analysis. (RR = 1.07, 95% CI: 0.81 to 1.43, P = 0.63). The heterogeneity for this comparison was 0%. Consequently, both options are equally altered by the thickness of endometrium. The secondary analysis compared clinical pregnancy rates in patients receiving PRP therapy and G-CSF. 4 studies were eligible for this synthesis. (RR = 1.36, 95% Cl: 1.06 to 1.76, P = 0.02). The heterogeneity for this comparison was 55%. PRP was significantly more effective. Limitations, reasons for caution Firstly, only 5 publications were found for the entire time. There are not enough well-conducted studies for more accurate analysis. Secondly, according to risk of bias assessment most of included studies had moderate concerns. Finally, there is no sufficient data to judge about live-birth rates after both types of treatment. Wider implications of the findings: Thin endometrium negatively affects the onset of pregnancy in assisted reproduction.Based on our meta-analysis, PRP therapy has a considerable effect on pregnancy rates in patients with thin endometrium in comparison with G-CSF.Currently, there is minimal evidence to support any specific protocol for improving IVF outcomes in women with thin endometrium. Trial registration number PROSPERO 2020 CRD42020222075

Analysis of endometrial thickness patterns and pregnancy outcomes considering 12,991 fresh IVF cycles

BackgroundDifferent endometrial patterns have an important effect on the relationship between endometrial thickness (EMT) and clinical pregnancy rate. There is a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns.MethodsThis retrospective study aimed to assess the association between EMT on human chorionic gonadotropin (HCG) administration day and the clinical outcome of fresh in vitro fertilization (IVF). The 5th, 50th, and 95th percentiles for EMT were determined as 8, 11, and 14 mm, respectively. Patients were sub-divided into four groups based on their EMT in different endometrial patterns (Group 1: < 8 mm; Group 2: ≥ 8 and ≤ 11 mm; Group 3: > 11 and ≤ 14 mm; Group 4: > 14 mm). We divided patients into three groups based on their endometrial pattern and evaluated the correlation between EMT and clinical pregnancy rate.ResultsWe found a positive correlation between pregnancy rates and EMT in all endometrial patterns. Multiple logistic regression analysis proved age, duration of infertility, cycle protocols, number of embryos transferred, progesterone on HCG day, endometrial patterns, and EMT have significant effects on clinical pregnancy rates. Meanwhile, there was a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns.ConclusionsDifferent endometrial patterns have an important effect on the relationship between EMT and clinical pregnancy rate.

Female fertility preservation: Impact of cancer on ovarian function and oocyte quality.

To evaluate the influence of cancer on ovarian response and oocyte quality in controlled ovarian hyperstimulation (COH). This prospective study conducted at the Physiopathology of Reproduction and Andrology Unit of Sandro Pertini Hospital enrolled 82 cancer patients undergoing controlled ovarian stimulation (COH) cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization for male-factor infertility from June 2016 to November 2019. The interventions performed were COH, oocyte retrieval, and quality evaluation. Main outcome measures were maximal estradiol levels on the day of human chorionic gonadotropin administration, duration of stimulation, total amount of gonadotropins administered, number of oocytes retrieved, and rates of metaphase 2 oocytes and abnormal oocytes. All data were analyzed using the Statistical Package for the Social Sciences (IBM Corp., Armonk, NY, USA) 22.0. Intergroup comparisons (82 cancer patients and 180 patients in control group) showed a significant difference in ovarian response, especially for a significant higher number of abnormal oocytes in cancer patients (P<0.0001). Regression analysis to assess the influence of the neoplastic process, regardless of the type, on ovarian response showed an effect on the main outcome measured due to cancer itself. Cancer influences the ovarian response, particularly the oocyte quality, during COH performed for fertility preservation.

Proof of concept use of progesterone/estradiol ratio to investigate late follicular progesterone in women with low number of preovulatory follicles.

The aim of this study was to investigate late follicular progesterone (P) serum levels in women with a low number of preovulatory follicles in the assisted reproductive technologies (ART) setting. Fifty-five consecutive women having four or fewer preovulatory follicles of >14 mm on the day of human chorionic gonadotropin (hCG) administration were prospectively evaluated. Spearman correlation tests were performed between serum estradiol (E<inf>2</inf>) level, serum P level, P/E<inf>2</inf> ratio, number of preovulatory follicles, oocytes and embryos. Women enrolled were further divided into two groups in accordance with the P/E<inf>2</inf> ratio on the day of hCG administration and compared. Serum E<inf>2</inf> level correlated positively with P serum level (r<inf>s</inf>=0.36, P<0.01), number of mature follicles (r<inf>s</inf>=0.50, P<0.01) and number of oocytes retrieved (r<inf>s</inf>=0.36, P<0.05), whereas negatively with P/E<inf>2</inf> ratio (r<inf>s</inf>=- 0.68, P<0.01). Likewise, number of preovulatory follicles correlated positively with E<inf>2</inf> level (r<inf>s</inf>=0.50, P<0.01), P level (r<inf>s</inf>=0.27, P<0.05) and number of oocytes retrieved (r<inf>s</inf>=0.33, P<0.05), while it correlated negatively with P/E<inf>2</inf> ratio (r<inf>s</inf>=-0.33, P<0.05). Furthermore, women with P/E<inf>2</inf> ratio >1 on the day of hCG administration received considerably higher total follicular stimulating hormone (FSH) dosage and achieved significantly lower number of oocytes and embryos as compared to controls. The reverse relationship between number of preovulatory follicles and P/E<inf>2</inf> ratio implies that P rise is not only the result of increased steroidogenic activity, but other oocyte-follicle disrupted mechanisms seem to be involved. An exaggerated FSH stimulation appears to disrupt further these mechanisms.

The value of serum progesterone level on day of human chorionic gonadotrophin administration / metaphase II oocyte ratio in predicting IVF/ICSI outcome in patients with normal ovarian reserve

BackgroundThe clinical implication of the increased serum progesterone level on the day of HCG administration in assisted reproduction treatment (ART) is still controversial. The current study aimed to compare the predictive value of serum progesterone on day of HCG administration / metaphase II oocyte (P/MII) ratio on IVF/ ICSI outcome to serum progesterone (P) level alone and the ratio of serum progesterone/estradiol level (P/E2) ratio in prediction of pregnancy rates after ART.Material & methodsTwo hundred patients admitted to the IVF/ICSI program at Minia IVF center in Egypt in the period from October 2016 to May 2018 were included in this study. Serum Progesterone (P) and Estradiol (E2) levels were estimated on the day of HCG administration. The ratio between serum P and the number of MII oocytes (P/MII ratio) was calculated and the predictive values of the three parameters (P, P/E2 ratio and P/MII ratio) in prediction of cycle outcomes were measured.ResultsP/ MII oocyte ratio was significantly lower in patients who attained clinical pregnancy (n = 97) as compared with those who couldn’t whilst there was no significant difference in P and P/E2 ratio between the two groups. Using a cut off value of 0.125, the sensitivity and specificity of progesterone/ MII ratio in prediction of no pregnancy in IVF/ICSI were 75.7 and 77.1% respectively with the area under The Receiver operating curve (ROC-AUC) = 0.808. The respective values of the ROC-AUC for the P and P/E2 ratio were 0.651 and 0.712 with sensitivity and specificity of 71.2 and 73.5%for P level and of 72.5 and 75.3% for P/E2 ratio. Implantation or clinical pregnancy rates were significantly different between patients with high and low P/MII ratio irrespective of day of embryo transfer (day 3 or 5).ConclusionsIn patients with normal ovarian response, serum progesterone on day of HCG / MII oocyte ratio can be a useful predictor of pregnancy outcomes and in deciding on freezing of all embryos for later transfer instead of high progesterone level alone.

Association between serum oestradiol level on the hCG administration day and neonatal birthweight after IVF-ET among 3659 singleton live births

Oestradiol, an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization-embryo transfer (IVF-ET) cycles. A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles. The data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 230), group 2 (serum E2 levels between 1001 and 2000 pg/mL, n = 524), group 3 (serum E2 levels between 2001 and 3000 pg/mL, n = 783), group 4 (serum E2 levels between 3001 and 4000 pg/mL, n = 721), group 5 (serum E2 levels between 4001 and 5000 pg/mL, n = 548 ), and group 6 (serum E2 levels > 5000 pg/mL, n = 852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors. The LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), 2.9% (group 5), and 2.0% (group 6) (P = 0.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET. The results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF. Although this study provides some reference, the obstetric-related factors were not included due to historical reasons. The impact of the high estrogen environment during COS on the birth weight of IVF offspring still needs future research.

A human chorionic gonadotropin (hCG) delivery platform using engineered uterine exosomes to improve endometrial receptivity

AimEndometrial exosomes carry bioactive agents to uterine epithelial cells and trophectoderm to promote implantation. On the other hand, intrauterine administration of human chorionic gonadotropin (hCG) could improve endometrial receptivity. Therefore, we investigated the delivery of hCG to the endometrial cells by uterine exosomes to increase endometrial receptivity. Main methodsExosomes were isolated from uterine fluid and characterized by dynamic light scattering, transmission electron microscopy, and western blotting. The freeze-thaw cycle and sonication methods were used to load hCG into the exosomes. The drug release pattern and uptake of exosomes into the endometrial cells were evaluated. Finally, the influence of hCG loaded-exosomes on the expression of several endometrial receptivity markers was evaluated. Key findingsThe isolated uterine fluid exosomes had a cup-shaped or spherical morphology with a mean size of 91.8 nm and zeta potential of −9.75 mV. The average loading capacity of exosomes for hCG was 710.05 ± 73.74 and 245.06 ± 95.66 IU/mg using the sonication and freeze-thaw cycle methods, respectively. The effect of hCG loaded-exosomes on the endometrial receptivity was greater than the hCG or exosomes alone. We found that hCG upregulated LIF and Trophinin and downregulated Muc-16 and IGFBP1 genes. Interestingly, the effect of hCG on the expression of LIF and Muc-16 was significantly intensified when used in the form of hCG loaded-exosomes. SignificanceThese findings strengthen our hope in using uterine fluid-derived exosome as an effective carrier for proteins or other therapeutic agents to effective delivery into endometrial cells.

The effect of embryo transfer technique on pregnancy rates in in vitro fertilization-intracytoplasmic sperm injection cycles: A prospective cohort study.

Objective:To investigate whether embryo transfer affects pregnancy rates in in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) treatment.Materials and Methods:A total of 2,257 patients who underwent IVF-ICSI treatment between 2012 and 2017 were included in this study. Subjects were categorized according to the embryo transfer technique that was required: group 1 (n=1,657) underwent easy transfer with a soft catheter; group 2 (n=548) received external guidance transfers; and group 3 (n=52) experienced difficult transfers with a stylet. Basal parameters, clinical and laboratory IVF-ICSI outcomes, and clinical pregnancy rates (CPR) were compared between the groups.Results:There were no differences between the groups in terms of age, body mass index, smoking status, duration and etiology of infertility, baseline folliclestimulating hormone, luteinizing hormone, estradiol (E2), thyroid-stimulating hormone, prolactin levels, antral follicle count, duration of stimulation, stimulation protocol, total gonadotropin dose required, peak E2 levels, progesterone levels, and endometrial thickness on human chorionic gonadotropin administration and transfer days (p>0.05). The numbers of oocytes retrieved, MII and 2PN, fertilization rate, day of embryo transfer, and CPRs were also comparable between the groups (p>0.05).Conclusion:Our data suggest that embryo transfer has no impact on pregnancy rates in patients who undergo IVF-ICSI treatment. Further studies with more participants are required to elucidate this situation.

Neurotensin: A novel mediator of ovulation?

The midcycle luteinizing hormone (LH) surge initiates a cascade of events within the ovarian follicle which culminates in ovulation. Only mural granulosa cells and theca cells express large numbers of LH receptors, and LH-stimulated paracrine mediators communicate the ovulatory signal within the follicle. Recent reports identified the neuropeptide neurotensin (NTS) as a product of granulosa cells. Here, we demonstrate that granulosa cells were the primary site of NTS expression in macaque ovulatory follicles. Granulosa cell NTS mRNA and protein increased after human chorionic gonadotropin (hCG) administration, which substitutes for the LH surge. To identify ovulatory actions of NTS, a NTS-neutralizing antibody was injected into preovulatory macaque follicles. hCG administration immediately followed, and ovaries were removed 48hours later to evaluate ovulatory events. Follicles injected with control IgG ovulated normally. In contrast, 75% of NTS antibody-injected follicles failed to ovulate, containing oocytes trapped within unruptured, hemorrhagic follicles. Serum progesterone was unchanged. Of the three NTS receptors, SORT1 was highly expressed in follicular granulosa, theca, and endothelial cells; NTSR1 and NTSR2 were expressed at lower levels. Excessive blood cells in NTS antibody-injected follicles indicated vascular anomalies, so the response of monkey ovarian endothelial cells to NTS was evaluated in vitro. NTS stimulated endothelial cell migration and capillary sprout formation, consistent with a role for NTS in vascular remodeling associated with ovulation. In summary, we identified NTS as a possible paracrine mediator of ovulation. Further investigation of the NTS synthesis/response pathway may lead to improved treatments for infertility and novel targets for contraception.

Elevated serum progesterone during in vitro fertilization treatment and the risk of ischemic placental disease.

Elevated progesterone on the day of human chorionic gonadotropin (hCG) administration is associated with decreased live birth rates in IVF cycles. The association with adverse pregnancy outcomes is unknown. Assess the association between serum progesterone on the day of hCG administration and the risk of ischemic placental disease [IPD; preeclampsia, placental abruption, and/or small for gestational age (SGA)]. We conducted a retrospective cohort study of autologous fresh IVF cycles resulting in delivery between 2005 and 2018. All IVF procedures were conducted at a large, university-affiliated infertility center. Patients were divided into tertiles based on their serum progesterone level on the day of hCG administration; the lowest tertile served as the reference group. We identified pregnancies complicated by preeclampsia and placental abruption using ICD-9/10 codes and medical record review. We defined SGA as<10th percentile using U.S. growth curves. The cohort included 166 deliveries in the lowest tertile of progesterone (0.2-0.73ng/ml), 166 deliveries in the middle (0.64-1.05ng/ml) and 167 deliveries in the highest tertile (1.05-5.6ng/ml). Compared with the lowest tertile, the risk of IPD was greater in the middle (RR 1.6; 95% CI 1.1-2.5) tertile after adjustment for age, parity, number of oocytes retrieved, and estradiol. The highest tertile was also not associated with an increased risk of IPD. In an IVF population, elevated serum progesterone in the range of 0.64-1.05ng/mL on the day of hCG administration was associated with a small increased risk of IPD.

Primary Hepatic Vascular Neoplasm in a Houston Toad (Anaxyrus houstonensis)

An 11-year-old captive, female Houston toad (Anaxyrus houstonensis) became lethargic and reluctant to move. This toad had been administered human chorionic gonadotropin (HCG) and luteinizing hormone-releasing hormone (LHRH) annually as part of a hormone-assisted captive propagation programme for 8 years. Due to poor prognosis, euthanasia was elected. At necropsy, the liver was moderately enlarged, diffusely dark red and had a nodular superficial appearance. Microscopically, the hepatic nodules consisted of poorly demarcated, non-encapsulated, paucicellular infiltrative neoplastic growths. These consisted of spindle cells, similar to sinusoidal endothelial cells, that formed irregular blood-filled vascular channels resembling sinusoids separated by thin bands of collagen and reticulin fibres. Neoplastic cells dissected through and replaced hepatic cords and bile ducts. Based on the cytohistomorphological features and analogy with vascular neoplasms in other vertebrates, a diagnosis of low-grade angiosarcoma was made. To the best of our knowledge, this is the first record of primary hepatic vascular neoplasia in an amphibian. It is not known if the long-term administration of HCG and LHRH had any oncogenic role in this animal. Vascular neoplasia should be included in the differential diagnosis of hepatomegaly and non-specific lethargy and health decline in amphibian species.

Effect of progesterone on hCG day-to-basal progesterone ratio on live birth rate in long agonist fresh IVF/ICSI cycles: a 5-year, single-center study of more than 10,000 cycles

Objective To investigate whether the ratio of the serum progesterone level on the day of human chorionic gonadotrophin (hCG) administration to the basal serum progesterone level (PhCG/Pbasal) is a predictor of pregnancy outcome during in vitro fertilization (IVF). Methods A total of 12,708 cycles were performed in 9747 patients between 19 and 36 years of age who were undergoing controlled ovarian stimulation from October 2011 to July 2016 for their first or second attempts at IVF followed by fresh embryo transfer (ET). hCG was administered 36 h before oocyte retrieval to trigger final oocyte maturation. The serum progesterone level was measured on menstrual cycle days 2-4 (basal progesterone, Pbasal) and on the day of hCG administration (PhCG). PhCG/Pbasal was calculated. Live birth rates were compared among various ordinal PhCG/Pbasal intervals (< 0.5, 0.5–1.0, 1.0–1.5, 1.5–2.0, 2.0–2.5, > 2.5). Results The average age of the patients recruited was 29.9 years. The average basal progesterone level was 0.8 ng/ml, while the average progesterone level on the day of hCG administration was 0.9 ng/ml. The live birth rates (according to the abovementioned ordinal PhCG/Pbasal intervals) were 47.3, 49.9, 47.8, 46.3, 45.5 and 44.0%, respectively. The live birth rates were significantly higher for patients with PhCG/Pbasal between 0.5–1.0 (OR = 1.14, 95% CI, 1.02–1.27, p = .02). Conclusions PhCG/Pbasal between 0.5-1.0 predicts a higher live birth rate in IVF. Both PhCG/Pbasal and P on hCG day is less predictive value for predicting live birth rate.

Progesterone levels predict pregnancy outcomes in individuals with fallopian tube associated infertility

BackgroundThis study aimed at determining the predictive value of human chorionic gonadotropin and progesterone levels on pregnancy outcomes in patients receiving in vitro fertilization due to fallopian tube associated infertility.MethodsWe retrospectively analyzed the clinical data of 854 cycles due to fallopian tube associated infertility in vitro fertilization fresh embryo transfer. The clinical data had been collected from January 2010 to December 2018 and was divided into 7 groups depending on the progesterone level on human chorionic gonadotropin administration day. Live birth rates and observation trends were calculated. The receiver operating characteristic curve was established to determine the optimal cutoff value for progesterone, which was used to further divide the data into 3 groups; Group 1 (progesterone ≦ 1.0 ng/ml), Group 2 (1.0 ng/ml ≤ progesterone ≤ 1.25 ng/ml), and Group 3 (progesterone ≥ 1.25 ng/ml). We then compared the ovulation results and clinical outcomes among the 3 groups.ResultsThere were no significant differences in age, infertility years, gonadotropin dosage, gonadotropin days, Luteinizing hormone level on human chorionic gonadotropin day, 2 pronuclear fertilization rates, clinical pregnancy rates, live birth rates, full-term birth rate, and preterm birth rates among the three groups. However body mass index (p = 0.001), basal luteinizing hormone (p = 0.034), estrogen peak (p < 0.001), number of oocytes obtained (P < 0.001) were significantly different.ConclusionsProgesterone level on human chorionic gonadotropin day does not affect the clinical pregnancy rate and live birth rates after in vitro fertilization. However, progesterone levels between 1.0 and 1.25 ng/ml may lead to good clinical pregnancy outcomes.

More is not always better-lower estradiol to mature oocyte ratio improved IVF outcomes.

AimTo find a cut-off ratio of estradiol/metaphase II oocyte (E2/M2) ratio and to evaluate the correlation with patients’ characteristics, embryo morphokinetics using EmbryoScope™ and IVF cycle outcomes.Material and methodsFor this retrospective cohort study, records of all fresh cycles that were cultured and scored by EmbryoScope™ were evaluated. The peak E2/M2 ratio was calculated on the day of human chorionic gonadotropin (hCG) administration and correlated to embryo morphokinetic quality and cycle outcomes. A receiver operating characteristics analysis was calculated for the E2/M2 ratio and clinical pregnancy rates.ResultsA total of 2461 oocytes were collected from 319 patients. Receiver operating characteristics analysis revealed a cutoff of 204 as a discriminative point to predict clinical pregnancy with a sensitivity of 69.5% and specificity of 62.1% (P < 0.001). E2/M2 > 204 group were older, had higher E2 concentration, fewer M2 oocytes despite elevated gonadotrophin doses. E2/M2 ratio ≤ 204 was correlated with higher fertilization rate, better embryo quality, higher pregnancy and live birth rates, and more frozen embryos.ConclusionE2/M2 ratio < 204 yielded the best probability to achieve good quality embryos with good morphokinetic scores and better pregnancy outcomes and may be used to predict IVF cycle outcomes. Advanced maternal age and low ovarian response received higher concentrations of gonadotrophins, which resulted in higher E2/M2 ratio. Milder stimulation to those patients may improve their cycle outcomes.

Impact of Intrauterine Administration of Human Chorionic Gonadotropin before Intrauterine Insemination in Infertile Women: A Randomized Controlled Trial.

Background:Implantation is the rate-limiting step in the success of both intrauterine Insemination (IUI) and in vitro fertilization cycles. Numerous interventions that target various local signals have been tried to improve the implantation and clinical pregnancy rate (CPR). The most significant of these signals is human chorionic gonadotropin (hCG) which acts as immunomodulator and improves implantation by decidualization of the endometrial stromal cells, trophoblast invasion, proliferation of uterine natural killer cells, stimulation of endometrial angiogenesis, and maintenance of progesterone secretion by the corpus luteum.Aim:The aim of the study is to evaluate the effect of intrauterine hCG administration before IUI on CPR.Settings and Design:A prospective parallel randomized control study was done from September 2017 to February 2019.Materials and Methods:A total of 200 eligible women planned for IUI were randomly divided just before IUI into 2 groups. A computer-generated randomization list with block size of 10 with 1:1 allocation was used to randomize the patients. Experimental group received 0.5 ml containing 500 IU hCG, on the other hand control group received 0.5 ml of normal saline 2–3 min before IUI in single sitting. The main outcomes were CPR, miscarriage rate, and ongoing pregnancy rate.Statistical Analysis:It was performed using statistical software version SPSS 17.0.Results:Patient's demographic and baseline characteristics were comparable in both the groups. CPR in experimental group was significantly high compared to control group (26% vs. 9%, P = 0.002). Ongoing pregnancy rate was also significantly higher in experimental group (23%) compared to control group (7%) (P = 0.003). No significant difference in miscarriage rate was seen between the two groups. No cases of ectopic pregnancy, ovarian hyperstimulation syndrome, or multiple pregnancy were reported.Conclusion:Intrauterine hCG administration is a simple procedure that can be used to improve pregnancy outcome in IUI cycles.