A 20 year experience in the management of non-tubal ectopic pregnancies in a tertiary hospital - a retrospective review.

BACKGROUND: Non-tubal ectopic pregnancies account for < 10% of all ectopic pregnancies. Due to its rarity and wide variation in clinical practice, there is no guideline or consensus for its management. We reported our 20-year experience in the management of non-tubal ectopic pregnancies in a tertiary hospital. METHODS: This is a retrospective review of all women admitted for non-tubal ectopic pregnancies from January 2003 to December 2022 in a tertiary hospital. Women with non-tubal ectopic pregnancies diagnosed by ultrasound or operation were included for analysis. RESULTS: Within the study period, 180 women were diagnosed to have non-tubal ectopic pregnancies at a mean gestation of 6.8 weeks. 16.7% (30/180) were conceived via assisted reproduction. Medical treatment was the first-line management option for 81 women, of which 75 (92.1%) women received intralesional methotrexate administered under transvaginal ultrasound guidance. The success rate of intralesional methotrexate ranges from 76.5% to 92.3%. Intralesional methotrexate was successful even in cases with a positive fetal pulsation or with high human chorionic gonadotrophin levels up to 252605U/L. Twenty seven women were managed expectantly and 40 underwent surgery. Nine (11.1%), two (6.1%), and one (2.3%) women required surgery due to massive or recurrent bleeding following medical, expectant, or surgical treatment. Hysterotomy and uterine artery embolization were necessary to control bleeding in one Caesarean scar and one cervical pregnancy. CONCLUSIONS: Intralesional methotrexate is more effective than systemic methotrexate and should be considered as first line medical treatment for non-tubal ectopic pregnancies. It has a high success rate in the management of unruptured non-tubal ectopic pregnancies even in the presence of fetal pulsations or high human chorionic gonadotrophin levels, but patients may require a prolonged period of monitoring. Close surveillance and readily available surgery were required due to the risk of heavy post-procedural intra-abdominal bleeding.

The ovarian stimulation regimen does not affect aneuploidy or blastocyst rate.

RESEARCH QUESTION: Could the total dose (<3000 IU or ≥3000 IU) and type of exogenous gonadotrophin (i.e. recombinant FSH and/or human menopausal gonadotrophin [HMG]) influence aneuploidy and blastulation rates and produce different reproductive outcomes? DESIGN: This retrospective, observational, multicentre cohort study included a total of 8466 patients undergoing IVF using autologous oocytes and preimplantation genetic testing for aneuploidies. Participants were divided according to the dosage of total gonadotrophins and stratified by maternal age. RESULTS: The aneuploidy rates, pregnancy outcomes and cumulative live birth rates (CLBR) were similar among women who received total gonadotrophin dosages of <3000 or ≥3000 IU. No statistical differences were reported in the blastulation rate with lower or higher gonadotrophin dosages. Women receiving a higher amount of HMG during ovarian stimulation had a lower aneuploidy rate (P = 0.02); when stratified according to age, younger women with a higher HMG dosage had lower aneuploidy rates (P< 0.001), while no statistical differences were observed in older women with higher or lower HMG dosages. No significant differences were observed in IVF outcomes or CLBR. CONCLUSIONS: High doses of gonadotrophins were not associated with rate of aneuploidy. However, an increased fraction of HMG in younger women was associated with a lower aneuploidy rate. The study demonstrated that the total gonadotrophin dosage did not influence aneuploidy, reproductive outcomes or CLBR. The increased gonadotrophin and HMG dosages used for ovarian stimulation did not precede aneuploidy, and the use of HMG should be evaluated on a case-by-case basis, according to the individual's characteristics and infertility type.

The role of QRFP43 in the secretory activity of the gonadotrophic axis in female sheep.

In mammals reproduction is regulated by many factors, among others by the peptides belonging to the RFamide peptide family. However, the knowledge concerning on the impact of recently identified member of this family (QRFP43) on the modulation of the gonadotrophic axis activity is still not fully understood and current research results are ambiguous. In the present study we tested the in vivo effect of QRFP43 on the secretory activity of the gonadotrophic axis at the hypothalamic-pituitary level in Polish Merino sheep. The animals (n = 48) were randomly divided into three experimental groups: controls receiving an icv infusion of Ringer-Locke solution, group receiving icv infusion of QRFP43 at 10 µg per day and 50 µg per day. All sheep received four 50 min icv infusions at 30 min intervals, on each of three consecutive days. Hypothalamic and pituitaries were collected and secured for further immunohistochemical and molecular biological analysis. In addition, during the experiment a blood samples have been collected for subsequent RIA determinations. QRFP43 was found to downregulate Kiss mRNA expression in the MBH and reduce the level of IR material in ME. This resulted in a reduction of GnRH IR material in the ME. QRFP43 increased plasma FSH levels while decreasing LH levels. Our findings indicate that QRFP43 inhibits the activity of the gonadotropic axis in the ovine at the level of the hypothalamus and may represent another neuromodulator of reproductive processes in animals.

Puberty Suppression for Pediatric Gender Dysphoria and the Child's Right to an Open Future.

In this essay, we consider the clinical and ethical implications of puberty blockers for pediatric gender dysphoria through the lens of "the child's right to an open future," which refers to rights that children do not have the capacity to exercise as minors, but that must be protected, so they can exercise them in the future as autonomous adults. We contrast the open future principle with the beliefs underpinning the gender affirming care model and discuss implications for consent. We evaluate claims that puberty blockers are reversible, discuss the scientific uncertainty about long-term benefits and harms, summarize international developments, and examine how suicide has been used to frame puberty suppression as a medically necessary, lifesaving treatment. In discussing these issues, we include relevant empirical evidence and raise questions for clinicians and researchers. We conclude that treatment pathways that delay decisions about medical transition until the child has had the chance to grow and mature into an autonomous adulthood would be most consistent with the open future principle.

Fertility preservation in patients undergoing gonadotoxic treatments: a Canadian Fertility and Andrology Society clinical practice guideline.

The management of young patients with cancer presents several unique challenges. In general, these patients are ill prepared for the diagnosis and the impact on their fertility. With the improved survival for all tumour types and stages, the need for adequate fertility counselling and a multidisciplinary approach in the reproductive care of these patients is paramount. Recent advances in cryopreservation techniques allow for the banking of spermatozoa, oocytes, embryos and ovarian tissue without compromising survival. This Canadian Fertility and Andrology Society (CFAS) guideline outlines the current understanding of social and medical issues associated with oncofertility, and the medical and surgical technologies available to optimize future fertility.

Oncostatin M and STAT3 Signaling Pathways Support Human Trophoblast Differentiation by Inhibiting Inflammatory Stress in Response to IFNγ and GM-CSF.

Interleukin-6 (IL-6) superfamily cytokines play critical roles during human pregnancy by promoting trophoblast differentiation, invasion, and endocrine function, and maintaining embryo immunotolerance and protection. In contrast, the unbalanced activity of pro-inflammatory factors such as interferon gamma (IFNγ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) at the maternal-fetal interface have detrimental effects on trophoblast function and differentiation. This study demonstrates how the IL-6 cytokine family member oncostatin M (OSM) and STAT3 activation regulate trophoblast fusion and endocrine function in response to pro-inflammatory stress induced by IFNγ and GM-CSF. Using human cytotrophoblast-like BeWo (CT/BW) cells, differentiated in villous syncytiotrophoblast (VST/BW) cells, we show that beta-human chorionic gonadotrophin (ßhCG) production and cell fusion process are affected in response to IFNγ or GM-CSF. However, those effects are abrogated with OSM by modulating the activation of IFNγ-STAT1 and GM-CSF-STAT5 signaling pathways. OSM stimulation enhances the expression of STAT3, the phosphorylation of STAT3 and SMAD2, and the induction of negative regulators of inflammation (e.g., IL-10 and TGFß1) and cytokine signaling (e.g., SOCS1 and SOCS3). Using STAT3-deficient VST/BW cells, we show that STAT3 expression is required for OSM to regulate the effects of IFNγ in ßhCG and E-cadherin expression. In contrast, OSM retains its modulatory effect on GM-CSF-STAT5 pathway activation even in STAT3-deficient VST/BW cells, suggesting that OSM uses STAT3-dependent and -independent mechanisms to modulate the activation of pro-inflammatory pathways IFNγ-STAT1 and GM-CSF-STAT5. Moreover, STAT3 deficiency in VST/BW cells leads to the production of both a large amount of ßhCG and an enhanced expression of activated STAT5 induced by GM-CSF, independently of OSM, suggesting a key role for STAT3 in ßhCG production and trophoblast differentiation through STAT5 modulation. In conclusion, our study describes for the first time the critical role played by OSM and STAT3 signaling pathways to preserve and regulate trophoblast biological functions during inflammatory stress.

Methotrexate as the first-line treatment of unruptured tubular ectopic pregnancies with high initial human chorionic gonadotropin levels: A retrospective cohort.

Objectives: To evaluate the effectiveness of the first-line medical management with Methotrexate (MTX) in the treatment of patients with stable tubal Ectopic Pregnancies (EPs) and varying ranges of Beta-Human Chorionic Gonadotropin (ß-HCG) levels. Materials and methods: In this retrospective cohort study, we reviewed the medical records of a total of 184 patients with the diagnosis of tubal EP, who received MTX as their first-line treatment. Patients with a baseline ß-HCG< 4800 mIU/mL received single-dose MTX (n = 136) and those with an initial ß-HCG≥ 4800 mIU/mL underwent the double-dose MTX regimen (n = 48). The treatment success was determined by evaluating the reported weekly ß-HCG levels of the patients. Results: Baseline ß-HCG and mass size in the single-dose group were 1895.1 ± 1463.4 mIU/mL and 2.2 ± 1.1 cm, respectively, compared to 17,867.6 ± 31,870.5 mIU/mL and 2.3 ± 1.1 cm in the double-dose group. Treatment duration was 30.6 ± 16.9 days for single dose and 41.0 ± 27.0 days for double dose, with additional MTX in 27.2% and 12.5% in respective groups. Single dose achieved a 92.6% success rate, and double dose, 81.3%, without serious adverse effects. No significant effects were seen for either baseline ß-HCG and mass size on the treatment success rates of both groups (p-value>0.05). However, the presence of Fetal Heart Rate (FHR) was associated with poorer responses only in the single-dose group (p-value=0.034). Conclusions: Medical management with MTX shows promise as a first-line treatment for tubal EPs with ß-HCG> 2000, suggesting a potential reassessment of existing guidelines in light of this emerging evidence. However, further research seems crucial in this field.

Effects of equine chorionic gonadotropin dosage and its splitting in different days on reproductive performance of Nellore cows synchronized for timed-artificial insemination.

This study evaluated the effects of dose of equine chorionic gonadotropin (eCG) and its splitting in different days of the synchronization protocol on reproductive performance of primiparous and multiparous Nellore cows. In the present study, 2,536 Nellore cows (1,634 primiparous and 902 multiparous) were assigned to receive in a 2 × 2 factorial design 1) an intravaginal progesterone (P4) device and 2.0 mg of estradiol benzoate (EB) on day -11, 12.5 mg (i.m.) of dinoprost tromethamine (PGF), 300 IU (i.m.) of eCG, 0.6 mg (i.m.) of estradiol cypionate (ECP), and P4 device withdrawal on day -2, followed by TAI on day 0 (n = 632 cows, being 409 primiparous and 223 multiparous; 300-2), 2) 300 IU (i.m) of eCG administered on days -4 and -2 (150 IU of eCG/day; n = 637 cows, being 412 primiparous and 225 multiparous; 300-4-2), 3) 400 IU (i.m.) of eCG administered on day -2 (n = 633 cows, being 406 primiparous and 227 multiparous; 400-2), and 4) 400 IU (i.m) of eCG administered on days -4 and -2 (200 IU of eCG/day; n = 634 cows, being 407 primiparous and 227 multiparous; 400-4-2). Individual cow BCS was assessed on days -11, 0 (timed-AI), and 31 of the study. Body condition score of the animals was classified into LOW or HIGH using the threshold of 2.75 (≤2.75 = LOW; >2.75 = HIGH). For primiparous cows, an eCG splitting effect was observed on follicle size, as cows receiving eCG on days -4 and -2 of the synchronization protocol had a larger follicle than cows administered eCG only on day -2. For day 31 P/AI, primiparous cows receiving 400-4-2, regardless of BCS, had a greater P/AI than cows from other treatments. Administering 400-4-2 to LOW BCS cows also resulted in greater P/AI than all other treatments assigned to LOW BCS cows. For multiparous cows, no treatment effect was observed for follicle size, estrus expression, and day 31 P/AI (P ≥ 0.21). In summary, increasing the dose and splitting the dose of eCG positively impacted the pregnancy rates of primiparous cows under a BCS ≤2.75, but no effects were detected on multiparous cows.

Novel Finding of Micropenis Caused by Mutation of the ADGRG2 Gene: A Case Report and Literature Review.

BACKGROUND: This study reported a case of micropenis caused by a novel hemizygous mutation in the ADGRG2 gene, which aimed to expand the understanding of sexual dysplasia caused by ADGRG2 gene mutation. CASE PRESENTATION: We present the clinical data and genetic test results of a patient with micropenis admitted in September, 2022, to the Tongji Hospital. The patient was a 9-year-10- month-old male whose chief complaint was the presence of a short penis over a period of three years. In April 2016, the patient underwent corrective surgery for a clubbed penis. Upon admission to the study hospital, his height and weight were 145.0 cm (75-90th percentile) and 37.8 kg (50-75th percentile), respectively, and his BA was 12 years old. His physical characteristics included a normal face, bilateral testicle size of 2 ml, and penile length of about 3 cm. A gonadotrophin-releasing hormone-stimulating test revealed normal hypothalamic-pituitary-gonadal axis function. An HCG stimulation test indicated normal sperm production in the testis. Key abnormalities from auxiliary examinations included low testosterone and high ACTH, dehydroepiandrosterone sulfate, androstenedione, and 17-OH-P levels. Genetic testing revealed a new hemizygous mutation, a splicing mutation in intron 4 of the ADGRG2 gene (ChrX: 19040187 (NM_001079858.3): c.154 + 2T > A, inherited from the mother. CONCLUSION: This study reported a case of micropenis caused by a new hemizygous mutation in the ADGRG2 gene. This indicates the importance of genetic testing and gene-guided treatments to improve prognosis.

The association between human chorionic gonadotropin and adverse pregnancy outcomes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the association between human chorionic gonadotropin and adverse pregnancy outcomes. DATA SOURCES: Medline, Embase, PubMed, and Cochrane were searched in November 2021 using Medical Subject Headings (MeSH) and relevant key words. STUDY ELIGIBILITY CRITERIA: This analysis included published full-text studies of pregnant women with serum human chorionic gonadotropin testing between 8 and 28 weeks of gestation, investigating fetal outcomes (fetal death in utero, small for gestational age, preterm birth) or maternal factors (hypertension in pregnancy: preeclampsia, pregnancy-induced hypertension, placental abruption, HELLP syndrome, gestational diabetes mellitus). METHODS: Studies were extracted using REDCap software. The Newcastle-Ottawa scale was used to assess for risk of bias. Final meta-analyses underwent further quality assessment using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method. RESULTS: A total of 185 studies were included in the final review, including the outcomes of fetal death in utero (45), small for gestational age (79), preterm delivery (62), hypertension in pregnancy (107), gestational diabetes mellitus (29), placental abruption (17), and HELLP syndrome (2). Data were analyzed separately on the basis of categorical measurement of human chorionic gonadotropin and human chorionic gonadotropin measured on a continuous scale. Eligible studies underwent meta-analysis to generate a pooled odds ratio (categorical human chorionic gonadotropin level) or difference in medians (human chorionic gonadotropin continuous scale) between outcome groups. First-trimester low human chorionic gonadotropin levels were associated with preeclampsia and fetal death in utero, whereas high human chorionic gonadotropin levels were associated with preeclampsia. Second-trimester high human chorionic gonadotropin levels were associated with fetal death in utero and preeclampsia. CONCLUSION: Human chorionic gonadotropin levels are associated with placenta-mediated adverse pregnancy outcomes. Both high and low human chorionic gonadotropin levels in the first trimester of pregnancy can be early warning signs of adverse outcomes. Further analysis of human chorionic gonadotropin subtypes and pregnancy outcomes is required to determine the diagnostic utility of these findings in reference to specific cutoff values.

Mechanism of HCG regulating epithelial-mesenchymal transition progression in endometrial cells through the FoxO1/miR223-5p/Wnt5α pathway.

RESEARCH QUESTION: Does human chorionic gonadotrophin (HCG) influence endometrial receptivity and epithelial-mesenchymal transition (EMT) via the FoxO1/miR223-5p/Wnt5α pathway? DESIGN: This study aimed to establish the co-culture system of human embryonic trophoblast cell line (HTR-8-Svneo) cells and human endometrial epithelial cell line (HEEC) cells. The expression of Wnt5α protein and EMT-related proteins in HTR-8-Svneo and HEEC cells treated in a gradient-dependent manner using HCG and exosome inhibitor GW4869 were detected in the co-culture system. RESULTS: In the HTR-8-Svneo/HEEC co-culture system, miR223-5p in HEEC cells increased significantly with induction of HTR-8-Svneo cells by 100 IU/ml HCG for 48 h (P = 0.046), and Wnt5α protein decreased significantly in HEEC cells (P = 0.021). Pretreatment of HTR-8-Svneo cells with GW4869, and knockdown of FoxO1 in HTR-8-Svneo cells, significantly inhibited the above effects of HCG on miR223-5p and Wnt5α expression in HEEC cells in the HTR-8-Svneo/HEEC co-culture system. HTR-8-Svneo cells induced with 100 IU/ml HCG for 48 h significantly enhanced the logarithmic phase proliferation activity of HEEC cells in the co-culture system (P < 0.001), while knockdown of FoxO1 in HTR-8-Svneo cells and inhibition of miR223-5p in HEEC cells suppressed proliferation of HEEC cells in the HTR-8-Svneo/HEEC co-culture system (P < 0.001). CONCLUSIONS: HCG exposure induces HTR-8-Svneo cells to up-regulate miR223-5p expression, which enters HEEC cells in the co-culture system through the exosomal pathway, and inhibits Wnt5α expression and the progress of EMT.

A direct healthcare cost analysis of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

PURPOSE: We have previously published a retrospective matched-case control study comparing the effect of recombinant LH (r-hLH) versus highly purified human menopausal gonadotropin (hMG) supplementation on the follicle-stimulating hormone (FSH) during controlled ovarian hyperstimulation (COH) in the GnRH-antagonist protocol. The result from that study showed that the cumulative live birth rate (CLBR) was significantly higher in the r-hLH group (53% vs. 64%, p = 0.02). In this study, we aim to do a cost analysis between these two groups based on our previous study. METHODS: The analysis consisted of 425 IVF and ICSI cycles in our previous study. There were 259 cycles in the r-hFSH + hMG group and 166 cycles in the r-hFSH + r-hLH group. The total cost related to the treatment of each patient was recorded. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed and created. RESULTS: The total treatment cost per patient was significantly higher in the r-hFSH + r-hLH group than in the r-hFSH + hMG group ($4550 ± 798.86 vs. $4290 ± 734.6, p = 0.003). However, the mean cost per live birth in the r-hFSH + hMG group was higher at $8052, vs. $7059 in the r-hFSH + r-hLH group. The CEAC showed that treatment with hFSH + r-hLH proved to be more cost-effective than treatment with r-hFSH + hMG. Willingness-to-pay was evident when considering a hypothetical threshold of $18,513, with the r-hFSH + r-hLH group exhibiting a 99% probability of being considered cost-effective. CONCLUSION: The cost analysis showed that recombinant LH is more cost-effective than hMG supplementation on r-hFSH during COH in the GnRH-antagonist protocol.

Should the trigger to oocyte retrieval interval be different in progestin-primed ovarian stimulation cycles?

RESEARCH QUESTION: Does the trigger to oocyte retrieval interval (TORI) affect oocyte maturation rates differently in progestin-primed ovarian stimulation (PPOS) and gonadotrophin-releasing hormone (GnRH) antagonist cycles? DESIGN: This was a retrospective cohort study. The interaction between the stimulation protocol and TORI was assessed in a linear mixed effects multivariable regression analysis with oocyte maturation rate as the dependent variable, and stimulation protocol (GnRH antagonist or PPOS), age (continuous), gonadotrophin type (FSH or human menopausal gonadotrophin), trigger (human chorionic gonadotrophin [HCG] or GnRH agonist), TORI (continuous) and days of stimulation (continuous) as the independent variables. Oocyte maturation rate was defined as number of metaphase II oocytes/number of cumulus-oocyte complexes retrieved. The maturation rate was calculated per cycle and treated as a continuous variable. RESULTS: A total of 473 GnRH antagonist and 205 PPOS cycles (121 conventional PPOS and 84 flexible PPOS) were analysed. The median (quartiles) female age was 36 (32-40) years. Of these cycles, 493 were triggered with HCG and 185 with a GnRH agonist. The TORI ranged between 33.6 and 39.1 h, with a median (quartiles) of 36.2 (36-36.4) hours. Maturation rates were similar between fixed PPOS, flexible PPOS and antagonist cycles (median 80%, 75% and 75%, respectively, P = 0.15). There was no significant interaction between the stimulation protocols and TORI for oocyte maturation. CONCLUSIONS: PPOS cycles do not seem to require a longer TORI than GnRH antagonist cycles.

Development of an acute ovine model of polycystic ovaries to assess the effect of ovarian denervation.

Introduction: Polycystic ovary syndrome (PCOS) seems to be associated with increased ovarian sympathetic nerve activity and in rodent models of PCOS reducing the sympathetic drive to the ovary, through denervation or neuromodulation, improves ovulation rate. We hypothesised that sympathetic nerves work with gonadotropins to promote development and survival of small antral follicles to develop a polycystic ovary phenotype. Methods: Using a clinically realistic ovine model we showed a rich sympathetic innervation to the normal ovary and reinnervation after ovarian transplantation. Using needlepoint diathermy to the nerve plexus in the ovarian vascular pedicle we were able to denervate the ovary resulting in reduced intraovarian noradrenaline and tyrosine hydroxylase immunostained sympathetic nerves. We developed an acute polycystic ovary (PCO) model using gonadotrophin releasing hormone (GnRH) agonist followed infusion of follicle stimulating hormone (FSH) with increased pulsatile luteinising hormone (LH). This resulted in increased numbers of smaller antral follicles in the ovary when compared to FSH infusion suggesting a polycystic ovary. Results: Denervation had no effect of the survival or numbers of follicles in the acute PCO model and did not impact on ovulation, follicular and luteal hormone profiles in a normal cycle. Discussion: Although the ovary is richly inervated we did not find evidence for a role of sympathetic nerves in ovarian function or small follicle growth and survival.

Case Report: Complete pathological remission of human chorionic gonadotrophin-producing gallbladder carcinoma with multiple liver metastases after treatment with chemotherapy plus an immune checkpoint inhibitor.

Background: Gallbladder carcinoma (GBC) producing human chorionic gonadotrophin (HCG) is an extremely rare and highly invasive tumor with a poor prognosis. This unfavorable clinical outcome is partly due to the aggressive nature of the tumor and its insensitivity to chemotherapy. Case presentation: We herein report a case of primary GBC producing HCG with liver metastases in a 58-year-old woman. The patient presented with a markedly elevated ß-HCG level and a mass in the gallbladder with multiple liver metastases. A definitive diagnosis was obtained after a needle biopsy of the liver metastases, showing poorly differentiated carcinoma with large-scale necrosis and strong positivity of immunostaining for HCG in tumor cells. The patient received chemotherapy (gemcitabine plus capecitabine) combined with carrellizumab, an immune checkpoint inhibitor (ICI). Pathological complete response was achieved after eight courses of combined therapy, which was confirmed by pathological analysis of resected specimens. After surgery, two courses of chemotherapy plus ICIs were adopted again. Complete response remained for approximately 1 year up to the present. Tumor tissue was collected to perform immunostaining of PD-L1, whole-exome sequencing, and RNA-seq. Low-TMB (1.51 mut/Mb), MSS, and high PD-L1 expression (TPS ≥ 50%) were observed in the tumor. Besides, the dominant types of infiltrating immune cells were macrophage and CD4+ T cells. Compared to other gallbladder adenocarcinoma without HCG, the proportion of M1 macrophage was at a higher level and the gene sets of MYC targets v1 and PI3K/AKT/mTOR signaling were highly expressed in our case. To the best of our knowledge, this is the first case report of complete remission of HCG-producing gallbladder carcinoma with liver metastases after chemotherapy combined with an immune checkpoint inhibitor. Furthermore, this is also the first report that described the tumor genetic feature and tumor immune microenvironment atlas of HCG-producing GBC. Conclusion: chemotherapy plus an immune checkpoint inhibitor may provide a potentially curative option for gallbladder carcinoma with HCG production.

Metabolic Profile of Growing Immune- and Surgically Castrated Iberian Pigs Fed Diets of Different Amino Acid Concentration.

The purpose of the current study was to further characterize the performance and nitrogen retention differences previously observed between immunocastrated (IC) and surgically castrated (SC) pure Iberian pigs. Fifty-four pigs were used (three sexes: IC males, IC females and SC males), fed three isoenergetic diets (160, 140 and 120 g CP/kg DM; six pigs/treatment combination) from 40 kg BW until slaughter (105 kg BW). Plasmatic post-absorptive metabolites and hormones, and backfat tissue composition were determined. The IC males showed a trend towards higher plasmatic creatinine (p = 0.06) and IGF-1 concentrations than SC males and IC females (p < 0.001). SC males showed a higher predisposition to carcass fatness and insulin resistance compared to IC males. Plasmatic isoleucine concentration was higher in IC and SC males compared to IC females (p < 0.01), and valine was greater in IC males compared to the rest of the pigs (p < 0.001). Total branched-chain amino acids (AA) were greater in IC males than in IC females (p < 0.01). Total plasmatic essential AA concentrations tended to be greater in IC males (p = 0.09). The present results support the increased performance and nitrogen retention capacity previously observed in IC male Iberian pigs compared to SC males and IC females, which can be attributed to increased anabolic capacity related with lean growth in Iberian IC males.

Recurrent Life-Threatening Gastrointestinal Bleeding From Primary Intestinal Choriocarcinoma: A Case Report.

Choriocarcinoma is a highly aggressive, malignant tumor that arises from trophoblastic cells. Although choriocarcinomas usually arise in the genital organs, they can also originate in extragenital organs, but gastrointestinal tract lesions are rare. Gastrointestinal choriocarcinoma can be primary or metastatic. Most primary gastrointestinal choriocarcinomas are associated with adenocarcinomas. We report a case of jejunal choriocarcinoma presenting with acute abdominal pain and intestinal bleeding. The patient had a very high serum beta-human chorionic gonadotropin (ß-HCG) level with an isolated jejunal lesion on contrast-enhanced computed tomography of the abdomen and pelvis. The patient underwent emergency surgical resection of the jejunal lesion with good recovery. The histopathological analysis of the resected specimen confirmed the diagnosis of choriocarcinoma. However, the patient suffered from life-threatening rebleeding one month after surgery and succumbed to her illness.

The effect of gonadotrophin-releasing hormone agonist versus human chorionic gonadotrophin trigger on pregnancy and neonatal outcomes in Letrozole-HMG IUI cycles.

BACKGROUND: GnRHa and hCG are both used for oocyte maturation and ovulation triggering. However, GnRHa have a shorter half-life than hCG, which leads to luteal phase deficiency. Letrozole (LE) has been found to improve the luteal function. Thus, the choice of triggering strategy can be different in intrauterine insemination (IUI) cycles using LE and human menopausal gonadotropin (HMG). The aim of this study was to compare the pregnancy and neonatal outcomes of patients triggered with GnRHa versus hCG versus dual trigger in LE-IUI cycles. METHODS: This retrospective cohort study included 6,075 LE-HMG IUI cycles between January 2010 and May 2021 at a tertiary-care academic medical center in China. All cycles were divided into three groups according to different trigger strategies as hCG trigger group, GnRHa trigger group and dual trigger group. The primary outcome was clinical pregnancy rate. Logistic regression analysis was performed to explore other risk factors for clinical pregnancy rate. RESULTS: No significant difference was observed in clinical pregnancy rate between hCG, GnRHa and dual trigger cycles in LE-HMG IUI cycles (P = 0.964). The miscarriage rate was significantly lower in the GnRHa trigger group, and higher in the dual trigger group, compared with the hCG group (P = 0.045). Logistic analysis confirmed that triggering strategy was associated with miscarriage (aOR:0.427, 95%CI: 0.183-0.996, P = 0.049; aOR:0.298, 95%CI: 0.128-0.693, P = 0.005). No significant differences were observed regarding neonatal outcomes between the three groups. CONCLUSIONS: Our findings suggested that both GnRHa and dual trigger can be used to trigger ovulation in LE-HMG IUI cycles, but dual trigger must be used with caution.

Tiny Hydatidiform Mole Presenting As Pregnancy of Unknown Location.

Pregnancy of unknown location (PUL) is a condition in which a pregnancy test, such as elevation of serum or urine ß-human chorionic gonadotrophin (hCG) level, is rendered positive; however, intrauterine or extrauterine pregnancy cannot be confirmed by transvaginal sonography (TVS). Diagnostic dilation and curettage (D&C) or laparoscopy may be performed to search for the pregnancy location. We experienced a case of PUL in which D&C was performed and histological examination revealed a tiny complete hydatidiform mole within the uterine contents. A retrospective review of the clinical course of this case, such as the evaluation of serum ß-hCG levels and TVS findings, suggested that this medical entity could be explained by a tiny hydatidiform mole. In PUL, during D&C, when abnormal villi are detected, even if the lesion is tiny, a suspicion of a hydatidiform mole should be considered by the pathologists, and immunostaining and/or chromosome testing/molecular genotyping should be subsequently performed. Whether a tiny hydatidiform mole poses a risk of persistent gestational trophoblastic disease requires further study based on the accumulation of cases. D&C for PUL patients may be a useful procedure to determine such diagnoses and pick up cases.