Chorionic Gonadotropin Research Articles

Clinician's guide to the management of azoospermia induced by exogenous testosterone or anabolic-androgenic steroids.

Azoospermia, defined as the absence of sperm in the ejaculate, is a well-documented consequence of exogenous testosterone (ET) and anabolic-androgenic steroid (AAS) use. These agents suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced intratesticular testosterone levels and impaired spermatogenesis. This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery. Azoospermia is categorized into pretesticular, testicular, and post-testicular types, with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function. Key strategies include discontinuing ET and monitoring for spontaneous recovery, particularly in patients with shorter durations of ET use. For cases of persistent azoospermia, gonadotropins (human chorionic gonadotropin [hCG] and follicle-stimulating hormone [FSH]) and selective estrogen receptor modulators (SERMs), such as clomiphene citrate, are recommended, either alone or in combination. The global increase in exogenous testosterone use, including testosterone replacement therapy and AAS, underscores the need for improved management of associated azoospermia, which can be temporary or permanent depending on individual factors and the type of testosterone used. Additionally, the manuscript discusses preventive strategies, such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy. While guidelines for managing testosterone-related azoospermia remain limited, emerging research indicates the potential efficacy of hormonal stimulation therapies. However, there is a notable lack of well-structured, controlled, and long-term studies addressing the management of azoospermia related to exogenous testosterone use, highlighting the need for such studies to inform evidence-based recommendations.

Dual Trigger in IVF—A SWOT Analysis

The typical agent used for final oocyte maturation and resumption of meiosis in in-vitro fertilisation (IVF) has been human chorionic gonadotropin (hCG). This acts as a surrogate for the physiological spontaneous luteinising hormone (LH) surge. Gonadotropin-releasing hormone agonist (GnRH-a) has been used as an alternative trigger in cycles where endogenous LH control is achieved using GnRH-antagonist and has been shown to be an effective method of reducing the risk of OHSS. However, GnRHa trigger is associated with poor corpus luteum function, leading to impaired endometrial receptivity. A combination of a GnRHa and hCG (dual trigger) was proposed to improve IVF cycle outcomes, especially in poor and normo-responder patients. Dual trigger aims to provide a more physiological alternative to HCG-only trigger while obviating some of the problems associated with GnRHa alone. Clinical evidence now supports the value of dual trigger where there has been a previous low proportion of mature eggs or where there is a suboptimal LH response to GnRHa alone. In poor responders, dual triggers could be considered as an effective first line. Dual trigger allows for comparable outcomes in normal and high responders, allowing the possibility of fresh embryo transfer with good clinical pregnancy and live birth rates while minimising OHSS risk.

A comparative study to estimate three commercial products of human chorionic gonadotropin (hCG) on blood biochemistry, sexual hormones concentrations, reproductive indices, and larvae production of African catfish Clarias gariepinus brood-stock

Currently, almost all hatcheries that produce catfish seeds depend on hormone stimulations, application of human chorionic gonadotropin hormone (hCG) is considered the common method for commercial spawning of African catfish Clarias gariepinus, regardless of whether they use an artificial or semi-industrial hatching approach. Therefore, to maximise profit, the best type must be selected based on cost and effectiveness. The present study compared three common products of hCG on blood sexual hormone, reproductive performance, and fry production per kg female. Four groups were designed to be: Group1: Untreated group to (control), Group2, Group3, and Group4, the brood-stock was hormonally induced with Choriomon®, Chorionic Gonadotropin, and Epifasi®, respectively. Both males and females received the same single dose of hCG (1500 IU)/kg of biomass. 80 brood-stock (40 female + 40 male) were used and distributed in two replicates in 8 square concrete ponds (water volume: 2.4 m3) each tank was randomly stocked at a rate of (5 males + 5 females). A single dose of hCG was injected intramuscularly at an angle of 45 degrees above the lateral line towards the tail. 24 hr after the injection blood sampling was drawn and samples of testes and ovaries were collected to measure reproductive indices and analyse chemical composition. Results showed superiority in all indicators of reproductive physiology that related to reproductive between hCG-treated brood-stock and untreated group. Besides, brood-stock injected with Choriomon® was the best in fry production (34587 larvae/kg brood stock) followed by Chorionic Gonadotropin and Epifasi®, respectively, while the Chorionic Gonadotropin group had the highest dose cost for producing 1000 fry.

Impact of follicular size categories on oocyte quality at trigger day undergoing luteal phase stimulation protocol.

To investigate an optimal strategy by assessing the effectiveness of varying follicular sizes on trigger day during luteal phase stimulation protocol and provide evidence for personalized protocol adjustment. This was a retrospective study including a total of 661 patients who had started their in vitro fertilization cycle with a luteal phase stimulation (LPS) protocol during 2015-2023. We classified patients into groups according to the size of the dominant proportion of follicles on the human chorionic gonadotropin (hCG) trigger day: large, medium, and small. The metaphase II (MII) oocyte rate, immature oocyte rate, two pronuclei (2PN) fertilization rate, and available embryo rate were compared between groups. General linear model (GLM) analysis was performed for inter-group comparison of the oocyte and embryo quality. There was a statistically significant difference in the immature oocyte rate between the three groups (p = 0.005), with the Large group having the lowest immature oocyte rate and the Small group having the highest immature oocyte rate, and there was no difference in MII oocyte rate among the three groups. As for the 2PN fertilization rate, there was a statistical difference among the three groups, with the highest 2PN fertilization rate in the Large group and the lowest in the Small group. However, there was no statistically significant difference in the available embryo rate among the three groups. The GLM analysis suggested that different follicle sizes on the trigger day influenced the immature oocyte rate and the 2PN fertilization rate. But among the young women, applying different follicle sizes on the trigger day of the LPS regimen did not influence the oocyte and embryo quality, while in older women it affected the 2PN fertilization rate. Triggering when there is a high proportion of large follicles results in lower immature oocyte rate and higher 2PN fertilization rate when applying LPS protocol. However, age is a factor to be considered and the timing of triggering needs to be decided in clinical application with consideration of age and the actual situation.

Retroperitoneal ectopic pregnancy from a tertiary obstetrics hospital in Vietnam: A case series and literature review.

Retroperitoneal ectopic pregnancy is an uncommon condition in clinical practice, often associated with misdiagnosis and unconventional treatment. Delayed interventions can lead to poor prognosis and sometimes catastrophic situations. Due to the limited number of reported cases in the literature, an established treatment protocol has yet to be introduced. This case series presents three instances at a tertiary women's hospital in Vietnam. In cases 1 and 2, a single approach-either surgery or a chemo-regimen-was applied. However, the third patient was treated with a combination of both therapies. This series highlights an evolution in management, progressing from incomplete removal of the gestation to a comprehensive combination of surgery and chemotherapy. Additionally, high serum beta-human chorionic gonadotropin (β-hCG) levels and suspicious ultrasound and magnetic resonance imaging (MRI) findings are crucial for establishing the diagnosis.

18F]FDG PET/CT in Metastatic Extragonadal Choriocarcinoma.

Extragonadal choriocarcinoma in men is an extremely rare and highly aggressive malignancy. Inconclusive biopsies due to a high necrotic component often delay diagnosis. Here is such a case, in which suggestive imaging findings on [18F]FDG PET/CT, a raised level of serum β-human chorionic gonadotropin, and gynecomastia clinched the diagnosis.

Effect of administration of nanoparticles of human chorionic gonadotropin on testicular hemodynamics, testicular volume, testicular echotexture, and circulating testosterone and nitric oxide in pubescent goat bucks under heat stress conditions

The current study investigated the effect of a single administration of human chorionic gonadotropin hormone (hCG) and its nanoparticles (NPs) on testicular hemodynamics using Doppler ultrasonography, testicular volume, testicular echotexture (PIX), and circulating testosterone and nitric oxide (NO) in pubescent goat bucks during summer months. Fifteen Baladi goats were divided into three groups (5 in each) and subjected to a single intramuscular administration of one ml of physiological saline ( control group), one ml containing 500 IU of hCG (hCG group) or one ml containing 125 IU of hCG NPs (hCG NPs group). Testicular hemodynamics assessment was done just before administration (0 h), and at 2, 4, 6, 24, and daily till 7 days after administration. Testicular volume and PIX were measured and analyzed by B-mode ultrasonography and computer analysis software. Testosterone and NO concentrations were measured using commercial kits. Results revealed significant decreases (P ˂0.05) in Doppler indices values (resistance index and pulsatility index) especially at 24 h in the hCG group (0.314 ± 0.01, 0.382 ± 0.01, respectively) compared with the hCG NPs group (0.428 ± 0.01, 0.567 ± 0.02, respectively), and the control group (0.464 ± 0.006, 0.64 ± 0.01, respectively). There were significant increases (P < 0.001) in testicular volume, PIX, testosterone, and NO concentrations in hCG NPs and hCG groups compared to the control group. There were no significant differences between the hCG NPs and hCG groups (P ˃ 0.05) in testicular volume and PIX, while testosterone significantly increased in the hCG group compared to the hCG NPs group and NO was significantly increased in the hCG NPs group compared to the hCG group. In conclusion, a single administration of hCG or its NPs improved testicular vascularization, testicular volume, and circulating testosterone and NO in pubescent goat bucks. So, hCG NPs could be recommended for improving the reproductive performance of goat bucks under heat-stress conditions.

Methotrexate fixed dosing protocol for ambulatory treatment of ectopic pregnancy.

The primary objective of this study was to review a methotrexate 90-mg fixed-dose protocol for treatment of ectopic pregnancy, and to evaluate if any characteristics were associated with ectopic pregnancy treatment failure. This was a single arm retrospective cohort study conducted at Kaiser Permanente Colorado. The primary outcome was to describe rates of ectopic pregnancy treatment failure among patients who received fixed dose(s) of methotrexate for ectopic pregnancy between January 1, 2007 and August 31, 2017. Women were eligible for inclusion if they received outpatient treatment with methotrexate for an ectopic pregnancy during this time frame. Electronic administrative databases were queried to identify eligible patients and gather patient data, then patients were categorized based on success or failure of treatment. Ectopic pregnancy treatment failure was defined as the requirement for any additional intervention to terminate the pregnancy. A total of 259 patients were included in the final analysis. Overall, 210 (81.1%) ectopic pregnancies were successfully treated with methotrexate alone, and 49 (18.9%) required additional intervention. Baseline human chorionic gonadotropin (hCG) of less than 1000 mIU/ml was associated with treatment success (odds ratio for ectopic pregnancy treatment failure = 0.07 (95% confidence interval: 0.03-0.19)). Treatment of ectopic pregnancy with this fixed-dose methotrexate protocol is a reasonable alternative to weight-based dosing. Consistent with previously published studies, baseline hCG less than 1000 mIU/ml was associated with a high rate of treatment success.

Risk factors associated with the failure of local methotrexate combined with minimally invasive surgery for late cesarean scar pregnancy

BackgroundThis study aimed to investigate the risk factors related to the failure of initial combined local methotrexate (MTX) treatment and minimally invasive surgery for late cesarean scar pregnancy (CSP).MethodsThis retrospective case-control study was conducted between January 2016 and December 2023, involving patients with late CSP (≥ 8 weeks) who received local MTX injection combined with either hysteroscopic or laparoscopic surgery. Cesarean scar pregnancy was classified as type I, II, or III based on the direction of growth of the gestational sac and the residual myometrial thickness as assessed by ultrasound. Binary logistic regression analysis was utilized to identify the risk factors associated with the failure of the initial combined treatment.ResultsOverall, 574 patients with late CSP were included in our study. Among them, 29 patients (5.1%) experienced treatment failure with the initial local MTX combined with minimally invasive surgery, while 545 patients (94.9%) achieved successful treatment outcomes. In the univariate analysis, several potential risk factors associated with the initial combined treatment failure were identified, including baseline serum β-human chorionic gonadotropin (β-hCG) levels, type of CSP, time interval between MTX and surgery, and positive fetal heart activity before surgery. Subsequent binary logistic regression analysis revealed the following independent risk factors linked to the failure of the initial combined treatment: baseline serum β-hCG levels exceeding 94,000 IU/L [odds ratio (OR) 3.060, 95% confidence interval (CI) 1.387–6.749, P = 0.006], type III CSP (OR 3.574, 95% CI 1.147–11.135, P = 0.028), a time interval greater than seven days between MTX and surgery (OR 3.847, 95% CI 1.725–8.581, P = 0.001), and the presence of a fetal heartbeat before surgery (OR 4.405, 95% CI 1.014–19.128, P = 0.048).ConclusionThe findings indicate that higher baseline serum β-hCG levels, an extended time interval between MTX and surgery, type III CSP and a positive preoperative fetal heartbeat are significant risk factors for the failure of initial local MTX combined with minimally invasive surgery in patients with late CSP. Individualized treatment strategies are recommended for these high-risk patients with late CSP.

Association of First-Trimester Low PAPP-A Levels (&lt;0.2 MoM) with Maternal and Fetal Outcomes

Background and Aim: First-trimester screening is routinely performed globally to detect chromosomal abnormalities using non-invasive methods such as nuchal translucency (NT) measurements, pregnancy-associated plasma protein A (PAPP-A), and β-human chorionic gonadotropin (β-hCG). Recent studies have highlighted that low PAPP-A levels may be associated with adverse pregnancy outcomes, including pre-eclampsia, intrauterine growth restriction (IUGR), and pre-term delivery. Generally, low PAPP-A is defined as below 0.4 multiples of the median (MoM) or under the 5th percentile. However, extremely low PAPP-A, defined as levels below 0.2 MoM or under the 1st percentile, significantly increases the risk of adverse outcomes. This category has received less attention in research. Our study aims to investigate the correlation between PAPP-A levels below 0.2 MoM and adverse pregnancy outcomes. Materials and Methods: A retrospective cross-sectional study was conducted on 10,256 pregnant women who underwent first-trimester screening at Imam Khomeini Hospital in Ahvaz between January 2010 and April 2024. PAPP-A and β-hCG levels were measured, and factors such as maternal age, weight, parity, and abortion history were assessed. Data were obtained using the Fetal Medicine Foundation (FMF) software and medical records. Statistical analysis was performed using SPSS version 26. Results: Out of 10,256 pregnancies, 6,040 (6.4%) had PAPP-A levels below the 5th percentile, while 45 women had PAPP-A levels below 0.2 MoM. The average age of these women was 30.4 ± 4.812 years. Among those with PAPP-A &lt; 0.2 MoM, 2.2% had trisomy 21, 6.7% had IUGR, 26.7% experienced gestational hypertension, and 15.6% developed pre-eclampsia. Trisomies 13 and 18 were not observed in the study population. Conclusions: Pregnant women with PAPP-A levels below 0.2 MoM showed increased incidences of trisomy 21, pre-eclampsia, gestational hypertension, and IUGR. Although low PAPP-A appears to contribute to both maternal and fetal complications, it cannot be used independently to predict adverse pregnancy outcomes. Further large-scale studies are required to better understand the implications of extremely low PAPP-A on pregnancy outcomes.

In vitro effect of hCG on cryptorchid patients’ gubernacular cells: a predictive model for adjuvant personalized therapy

BackgroundCryptorchidism is the absence of one or both testicles in the scrotum at birth, being a risk factor for testis cancer and infertility. The most effective method to treat cryptorchidism is orchiopexy, followed by human chorionic gonadotropin (hCG) therapy; however, a portion of treated patients do not show a significant improvement in testis volume and vascularization after adjuvant therapy.MethodsIn this study, we generated an in vitro model to predict the patient response to hCG by cultivating and treating primary cells derived from five cryptorchid patients’ biopsies of gubernaculum testis, the ligament that connects the testicle to the scrotum. On these in vitro cultured cells, we analyzed the effect of hCG on cell proliferation, tubular structure formation, cellular respiration, reactive oxygen species content, and proteome.ResultsWe demonstrate that in vitro hCG stimulates gubernacular cells to proliferate and form vessel-like structures to a different extent among the five cryptorchid patients’ cells, with a decrease in oxygen consumption and reactive oxygen species generation. Furthermore, from the proteomic analysis, we show that hCG regulates the intra- and extra-cellular organization of gubernacular cells together with a massive regulation of the antioxidant response.ConclusionsHereby, we characterized the cellular and molecular effects of hCG, demonstrating that the diverse patient response to hCG may be ascribable to their age since young patients better respond in vitro to the hormone, supporting a prompt surgical procedure and subsequent therapy.Trial registrationThe study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee of “Azienda Ospedaliera Universitaria Integrata” (AOUI) of Verona, Italy (“ANDRO-PRO”, protocol code N. 4206 CESC of 26 April 2023).

Placental biomarkers in second trimester maternal serum are associated with postpartum hemorrhage: a secondary analysis of the NuMoM2b dataset.

Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide, which is often attributed to retained placenta (RP) after delivery. There are no biomarkers currently used to predict a risk of developing RP/PPH prior to labor. The objective of this study was to determine relationships between placental biomarkers measured in the first and second trimesters and proxy measures of postpartum blood loss relative to preeclampsia status in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) dataset. 2,192 participants had placental analytes drawn during the first and second trimesters (9-13 and 16-22 weeks gestation, respectively); the outcome was a composite of retained placenta and/or PPH requiring blood transfusion (RP/PPH). Using Kruskal-Wallis tests, median differences in levels of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), sFlt-1/PlGF ratio, soluble endoglin (sEng), beta subunit of human chorionic gonadotropin (β-hCG), inhibin A (INHA), and pregnancy-associated protein-A (PAPP-A) were assessed between women with (n=67) and without (n=2125) RP/PPH overall and stratified by preeclampsia status. Women with RP/PPH had significantly higher median levels of sEng, β-hCG, INHA, PAPP-A in the second trimester and sFlt-1was higher in both first and second trimesters, which was observed again when stratifying by preeclampsia status. Our findings indicate that biomarkers associated with angiogenesis, particularly when measured in the second trimester, are important targets for further study of RP and/or PPH pathophysiology and potential risk screening development.

Acupuncture Increased the Number of Retrieved Oocytes in a Mouse Model of POR: The Involvement of DNA Methylation in the Oocytes

Background: Poor ovarian response (POR) reduces the success rate of in vitro fertilization mainly because of fewer oocytes retrieved. Acupuncture (Ac) therapy can improve the number of retrieved oocytes in the controlled ovarian stimulation program. The role of Ac in the corresponding epigenetic mechanism of POR has not been studied. Objective: This study was conducted to determine the effect of Ac on the number of retrieved oocytes and its role in DNA methylation in a mouse model of POR. Methods:: Forty C57BL/6N female mice with normal estrous cycles were randomly classified into 4 groups of 10 each: control (Con) group, Ac-Con group, POR group, and Ac-POR group. Mice in POR and Ac-POR groups received a gastric gavage of Tripterygium wilfordii polyglycoside suspension of 50 mg/kg-1 once a day for 14 consecutive days. Ac was applied at “Shenting” (DU 24), “Guanyuan” (CV 4), “Zusanli” (ST 36), and “Shenshu” (BL 23) in the Ac-POR group for 10 min per session, once a day for 14 consecutive days. All four groups were stimulated with pregnant mare serum gonadotropin and human chorionic gonadotropin, and the number of retrieved oocytes and proportion of mature oocytes were recorded. The DNA methylation level in a single mouse oocyte in each group was analyzed using single-cell genome-wide bisulfite sequencing (scBSseq), and key pathways were identified using GO and KEGG enrichment analyses. Results: A dissecting microscope revealed that the Ac therapy improved the number of retrieved oocytes compared with the POR group (p &lt; 0.05). ScBS-seq showed that there was no significant change in global DNA methylation levels between the POR model and control group mice. However, differences were primarily observed in the differentially methylated regions (DMRs) of each chromosome, and Ac decreased global DNA methylation. DMR analysis identified 13 genes that may be associated with Ac treatment. Cdk5rap2 and Igf1r, which mediate germ cell apoptosis, growth, and development, maybe most closely related to the Ac treatment of POR. KEGG analysis revealed that differentially expressed genes were mainly enriched in Wnt, GnRH, and calcium signaling pathways. The genes were closely related to the regulation of POR via Ac. Conclusion: The results suggest that DNA methylation in oocytes is related to the development of POR and that the role of Ac in affecting DNA methylation in oocytes is associated with the Wnt, GnRH, and calcium signaling pathways as well as Cdk5rap2 and Igf1r in POR mice.

The association between the amount of fetal fraction in cell-free DNA testing and adverse pregnancy outcomes: A cohort study

Background: Noninvasive perinatal testing is a new method of screening for aneuploidy called cell-free DNA (cfDNA). Fetal fraction (FF) plays a crucial role in assessing the reliability of aneuploidy detection through noninvasive perinatal testing. Objective: We aimed to investigate the association between the amount of FF in cfDNA testing and adverse pregnancy outcomes. Materials and Methods: This cohort study was conducted on 619 singleton pregnant women who were candidates for cfDNA testing and were referred to the perinatology clinics of Shariati hospital and Arash Women’s hospital, both affiliated with Tehran University of Medical Sciences, Tehran, Iran from March 2019 to June 2020. The FF was extracted from the cfDNA test results, and the participants were followed until delivery. Results: A total of 619 singleton pregnant women with a mean ± SD age and FF of 34.4 ± 4.85 and 8.39 ± 3.95, respectively, participated in the study. A significant association between maternal age and FF was not found (p = 0.12). A lower FF was associated with a rise in the incidence of gestational diabetes mellitus (p = 0.02) and a higher FF was associated with a rise in the incidence of fetal growth restriction (p &lt; 0.001). However, high or low FF was not associated with pre-eclampsia, premature rupture of membranes, birth weight, or delivery time. No significant association was found between FF and multiple of the median of pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin. Conclusion: The amount of FF may be considered a predictor of certain adverse pregnancy outcomes. Therefore, maternity care should be performed more carefully for women with high or low FF.

Serum human chorionic gonadotropin and ultrasound criteria in women with successful expectant management of tubal ectopic pregnancies: a retrospective cohort study

Serum human chorionic gonadotropin and ultrasound criteria in women with successful expectant management of tubal ectopic pregnancies: a retrospective cohort study

Risk factors for methotrexate treatment failure in tubal ectopic pregnancy: a retrospective cohort study

BackgroundEctopic pregnancy (EP) accounts for approximately 2% of all pregnancies, with tubal ectopic pregnancies (TEPs) being the most common type. Methotrexate (MTX) is a noninvasive and effective medical management option for TEP, but failure rates range from 10 to 36%, posing challenges in clinical practice. Identifying risk factors for MTX treatment failure is crucial to improve patient outcomes and guide clinical decision-making. This study aimed to determine the risk factors associated with MTX failure in TEP patients and support personalized treatment strategies.MethodsThis retrospective study included female patients who were diagnosed with TEP at Peking Union Medical College Hospital (PUMCH) between January 2016 and December 2022. Patients received MTX treatment initially, with dosing intervals and protocols varying according to clinical practice. MTX treatment failure was defined as the need for surgery after MTX administration. The study included two groups: patients who failed MTX treatment (n = 91) and those who succeeded in treatment (n = 268). Univariate and multivariate logistic regression analyses were performed to identify significant predictors of MTX treatment failure. A nomogram was developed to visualize the predictive factors.ResultsA total of 359 patients were included, with 268 (74.7%) succeeding with MTX and 91 (25.3%) required surgery. Specifically, 282 patients (78.6%) received 1-dose MTX, whereas 77 (21.4%) received 2-dose MTX. Univariate analysis revealed that gravidity, previous EP, gestational age, pretreatment β-human chorionic gonadotropin (β-hCG) level, number of MTX treatments, and presence of a visible yolk sac in ultrasound were significant predictors (all P < 0.05). Multivariate analysis confirmed that higher gravidity (odds ratio (OR) = 1.2487, 95% confidence interval (CI): 1.0103 – 1.5433, P = 0.040) and elevated pretreatment β-hCG levels (OR = 1.0006, 95% CI: 1.0004 – 1.0008, P < 0.001) were independent risk factors. Number of MTX treatments was a significant protective factor (OR = 0.4409, 95% CI: 0.2153 – 0.9025, P = 0.025). The nomogram incorporating these six risk factors was developed.ConclusionHigher gravidity and elevated β-hCG levels were significant predictors of MTX failure, while more MTX doses provided a protective effect. These findings underscore the importance of personalized MTX treatment strategies to improve outcomes in TEP. However, the limitations of this study, including its retrospective and single-center design, suggest that further prospective multicenter studies are needed to validate these results.Trial registrationThe trial is registered at http://www.chictr.org.cn. [registration number: ChiCTR2400081314; registration date: 2024–02-28 (prospectively registered)].

Efficacy and Safety of Three Cycles of TIP and Sequential High Dose Chemotherapy in Patients with Testicular Non-Seminomatous Germ Cell Tumors

Background: Salvage treatment options have not been validated in relapsed or refractory germ cell tumors. Moreover, the study populations including these patients have different heterogeneities. This study aimed to evaluate the efficacy and safety of three cycles of TIP sequential high-dose chemotherapy in patients with testicular non-seminomatous germ cell tumors who relapsed or had a refractory course after first-line platinum-based chemotherapy. Methods: Data of 141 patients who underwent three cycles of TIP followed by HDCT due to relapsed/refractory gonadal NSGCTs after first-line cisplatin-based chemotherapy (BEP/EP) at Gulhane School of Medicine Hospital Medical Oncology Department between January 2017 and May 2024 were evaluated retrospectively. Patients underwent a treatment regimen consisting of two phases. Initially, they received three cycles of induction therapy using a combination known as TIP, which includes paclitaxel, ifosfomide, and cisplatin. Following this, they were given a single cycle of high-dose chemotherapy. Demographic and clinicopathological features of patients and treatment-related complications and survival outcomes were recorded. Results: Median follow-up for all patients was 35.2 (95% CI, 29.45 to 41.07) months. Complete Response (CR) or marker negative Partial Response (PR) after HDCT was achieved in 84 (59.6%) patients. Median time for PFS not reached (NR) (95% CI, NR) in the entire group. The 2-year PFS rate was 51.8%. Median time for OS not reached (95% CI, NR) and the 2-year OS rate was 72.3%. The most common myelotoxicity observed after HDCT until engraftment was grade 4 neutropenia (100%) and grade 4 thrombocytopenia (96.5%). Transplantation-related mortality occurred in 7.1% of patients. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis for overall survival were platinum refractory disease and AFP and/or beta HCG elevation. Conclusions: Significant survival can be achieved after three cycles of TIP consecutive HDCT, while treatment-related mortality was found to be low.

Abortion in evolution, caesarean scar pregnancy, and cervical ectopic: discerning the triplets on ultrasound.

On the second day of my clinical observership in the Obgyn Department of the Vienna University Hospital, I saw a suspected case of caesarean scar pregnancy on follow-up, with one of my very senior professors, in the gynaecology outpatient clinic. The 29-year-old multigravida with a previous caesarean section had earlier presented to the emergency room with vaginal bleeding at 7 weeks of gestation. Ultrasound scan revealed a non-viable low-lying gestational sac located near the caesarean section scar, with a myometrial thickness of 0.96 cm. There was minimal vascular flow during the Doppler interrogation. Her quantitative serum beta-human chorionic gonadotropin was 687 IU/l at presentation. This had dropped to 344 IU/l after 48 h, with a further drop to 39 IU/l after a week. Repeat ultrasound scan 1 week after revealed an empty uterus with no visible gestational sac, and vaginal bleeding had resolved. My professor made a final diagnosis of a spontaneous complete abortion. On reflection, this experience further reinforced the diagnostic dilemma that many clinical conditions can present, the need for a high index of suspicion in diagnosing and differentiating clinical conditions that present similar features, as well as the need for younger clinicians to leverage the better knowledge and experience of more senior colleagues to unknot knotty clinical dilemmas.

First-trimester screening and small for gestational age in twin pregnancies: a single center cohort study.

This study aimed to investigate the association between maternal factors and first-trimester biophysical and biochemical markers with small for gestational age (SGA) neonates in twin pregnancies (TwPs). Single-center retrospective cohort study of TwPs followed from January 2010 to December 2022 at a tertiary perinatal center, Portugal. Maternal and pregnancy characteristics, mean arterial pressure, pregnancy-associated plasma protein-A (PAPP-A), β-human chorionic gonadotropin (β-HCG), and uterine artery pulsatility index (UtA-PI) were analyzed. Univariable, multivariable logistic regression (LR) and receiver-operating characteristic curve analyses were performed. The main outcome measures considered were: SGA < 3rd, < 5th and < 10th percentile, the composite outcome of SGA combined with preterm birth (PTB) (< 32, < 34, and < 36weeks). 572 TwPs were included, 450 (78.7%) DC and 122 (21.3%) MC. TwPs affected with SGA < 3rd, < 5th or < 10th percentiles were 120/572 (20.9%), 157/572 (27.4%) and 190/572 (33.2%), respectively. SGA < 3rd percentile was associated with a higher rate of PTB, 59.0% of cases < 32weeks, OR 6.4 (95% CI: 3.2-12.7, p < 0.001). Shorter maternal height, UtA-PI ≥ 95th percentile, and low PAPP-A were identified as significant independent risk factors associated with SGA and SGA combined with PTB. The best LR model was obtained for the composite outcome SGA < 3rd percentile and PTB < 32weeks, with an AUC of 0.834, a sensitivity rate of 77%, and a false positive rate of 17%. The majority of pregnancies at risk for SGA combined with prematurity can be detected in the first trimester. However, larger datasets are necessary to develop robust predictive models.

Navigating obstetric enigma: Placenta accreta spectrum masquerading as gestational trophoblastic neoplasia.

Placenta accreta spectrum (PAS) represents a complex obstetric condition characterised by the abnormal invasion of anchoring villi and trophoblast into the myometrium. This case report explores two instances where the diagnosis of PAS was overlooked during antenatal care leading to significant complications during conservative management. Both patients presented with heavy menstrual bleeding and raised beta human chorionic gonadotrophin (β-hCG), mimicking gestational trophoblastic disease. The report delves into the clinical presentations, diagnostic challenges, and outcomes of two cases, shedding light on the importance of effective communication and follow-up in the management of PAS.