BACKGROUND: Quantitative and qualitative human chorionic gonadotropin (hCG) tests are obtained in the emergency department (ED) to determine if a female of child-bearing age is pregnant. A positive hCG result is commonly assumed to indicate an intrauterine or other form of pregnancy. However, elevated hCG levels can also result from various other conditions, such as ovarian tumors, pituitary tumors, and thyroid disorders. Intracranial germ cell tumors, rare central nervous system tumors capable of secreting hCG, primarily affect adolescent and young adult females.
METHODS: A 16-year-old female student without significant past medical history presented to our ED with a complaint of intermittent bilateral frontal headache for two days. Last menstrual period started two days prior to presentation. The headache was associated with phonophobia, photophobia, nausea, and vomiting. Serum quantitative hCG was elevated. She denied history of sexual activity or sexual assault. Transabdominal ultrasound was negative for intrauterine pregnancy. Obstetrics and gynecology as well as pediatric oncology were consulted. Subsequent investigations, including brain imaging, revealed a 3.5 cm mass in the right caudate nucleus and corpus callosum. The patient was diagnosed with an intracranial nongerminomatous germ cell tumor, necessitating hospitalization and prompt initiation of chemotherapy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: An elevated quantitative hCG is not always indicative of pregnancy, especially in a young patient without sexual history. In the case of a nonrevealing transabdominal ultrasound, obstetrics and gynecology should be consulted for discussion of further testing and imaging. Emergency physicians should include malignancy high on their differential since prompt initiation of chemotherapy, evaluation by surgical services, and family planning will be required.

Complete and partial molar pregnancies arise from abnormal fertilization with marked proliferation of syncytiotrophoblasts. Earlier diagnosis has reduced the frequency of severe medical complications at presentation; however, the risk of progression to gestational trophoblastic neoplasia (GTN) has remained unchanged. Initial assessment should include serum hCG measurement after physical examination, laboratory testing for organ dysfunction, and Doppler ultrasound. Following uterine evacuation, pathologic assessment can distinguish complete from partial moles or non-molar gestations. Close surveillance is essential for the timely diagnosis of GTN. Cure rates and subsequent obstetrics outcomes are excellent, but all patients should be referred for psychologic support and expert level care.

Optimizations of the gene expression cassette combined with the selection of an appropriate signal peptide are important factors that must be considered to enhance heterologous protein expression in Chinese Hamster Ovary (CHO) cells. In this study, we investigated the effectiveness of different signal peptides on the production of recombinant human chorionic gonadotropin (r-hCG) in CHO-K1 cells. Four optimized expression constructs containing four promising signal peptides were stably transfected into CHO-K1 cells. The generated CHO-K1 stable pool was then evaluated for r-hCG protein production. Interestingly, human serum albumin and human interleukin-2 signal peptides exhibited relatively greater extracellular secretion of the r-hCG with an average yield of (16.59 ± 0.02 μg/ml) and (14.80 ± 0.13 μg/ml) respectively compared to the native and murine IgGκ light chain signal peptides. The stably transfected CHO pool was further used as the cell substrate to develop an optimized upstream process followed by a downstream phase of the r-hCG. Finally, the biological activity of the purified r-hCG was assessed using in vitro bioassays. The combined data highlight that the choice of signal peptide can be imperative to ensure an optimal secretion of a recombinant protein in CHO cells. In addition, the stable pool technology was a viable approach for the production of biologically active r-hCG at a research scale with acceptable bioprocess performances and consistent product quality.

A man in his 70s presented with a left inguinoscrotal mass. Testicular tumour markers showed markedly elevated human chorionic gonadotropin (hCG). The 24.5 cm mass was resected, and histology confirmed a rare diagnosis of paratesticular dedifferentiated liposarcoma (DDLPS) with rhabdomyosarcomatous differentiation. The patient expired with distant metastasis 11 months after presenting to his general practitioner.HCG-producing soft tissue sarcomas (STS) are commonly reported as high-grade, poorly differentiated and with a poor prognosis. The role of hCG in tumour angiogenesis may influence these features.Paratesticular STS treatment guidelines have been influenced by the management of retroperitoneal STS, which are relatively more common. Studies of genitourinary STS demonstrate that positive surgical margins pose the greatest risk to local recurrence and metastasis-free survival.This case demonstrates the rapid growth of DDLPS-producing hCG, the propensity to metastasise, and poor prognosis, requiring further research into the benefit of adjuvant radiotherapy for DDLPS.

UNASSIGNED: In the realm of natural frozen-thawed embryo transfer (FET) cycles, the application of luteal phase support (LPS) is a prevalent practice, primarily due to its beneficial impact on reproductive outcomes. Among the various LPS medications, human chorionic gonadotropin (hCG) is one that exerts its function on both the corpus luteum and the endometrium.
UNASSIGNED: To evaluate the effect of hCG administration as LPS on reproductive outcomes in natural FET cycles.
UNASSIGNED: This study was a retrospective cohort analysis conducted at a tertiary care hospital. It included women who underwent natural FET treatment from January 2018 to December 2022. Participants were divided into the hCG LPS group and the non-hCG LPS group on the basis of whether they used hCG as LPS after blastocyst transfer. The primary outcome was the clinical pregnancy and live birth rates. The secondary outcomes included the early miscarriage rate (before 12th gestational week) and total miscarriage rate.
UNASSIGNED: A total of 4762 women were included in the analysis, and 1910 received hCG LPS and 2852 received no hCG LPS (control group). In the general cohort, the clinical pregnancy and live birth rates in the hCG LPS group were significantly lower than those in the control group (63.82% vs 66.41%, aOR 0.872, 95% CI 0.765-0.996, P=0.046; 53.98% vs 57.15%, aOR 0.873, 95% CI 0.766-0.991, P=0.035, respectively). The early miscarriage and total miscarriage rates were similar between the two groups. In a subgroup analysis, in women who received an hCG trigger, there was no significant difference in the clinical pregnancy rate or live birth rate between the two groups. However, in women who ovulated spontaneously, the clinical pregnancy and live birth rates in the hCG LPS group were significantly lower than those in the control group (60.99% vs 67.21%, aOR 0.786, 95% CI 0.652-0.946, P=0.011; 50.56% vs 57.63%, aOR 0.743, 95% CI 0.619-0.878, P=0.001, respectively).
UNASSIGNED: Among women undergoing natural cycle frozen-thawed blastocyst transfer, hCG LPS is associated with lower clinical pregnancy and live birth rates. Additionally, the adverse effect of hCG LPS is more pronounced in women who ovulate spontaneously.

Background and Objectives: Polycystic ovarian syndrome (PCOS) is a widespread endocrine disorder affecting 5-18% of females in their childbearing age. The aim of this study is to assess the efficacy of combining a low dosage of human chorionic gonadotropin (HCG) along with clomiphene citrate (CC) for stimulating ovulation in infertile women diagnosed with CC-resistant PCOS. Materials and Methods: A randomized controlled trial was carried out on 300 infertile CC-resistant PCOS women. All participants were assigned to two groups: the CC-HCG group and the CC-Placebo group. Subjects in the CC-HCG group were given CC (150 mg/day for 5 days starting on the 2nd day of the cycle) and HCG (200 IU/day SC starting on the 7th day of the cycle). Subjects in the CC-Placebo group were given CC and a placebo. The number of ovarian follicles > 18 mm, cycle cancellation rate, endometrial thickness, ovulation rate, clinical pregnancy rate, and occurrence of early ovarian hyper-stimulation syndrome were all outcome variables in the primary research. Results: Data from 138 individuals in the CC-HCG group and 131 participants in the CC-Placebo group were subjected to final analysis. In comparison to the CC-Placebo group, the cycle cancellation rate in the CC-HCG group was considerably lower. The CC-HCG group exhibited a substantial increase in ovarian follicles reaching > 18 mm, endometrial thickness, and ovulation rate. The clinical pregnancy rate was higher in the CC-HCG group (7.2% vs. 2.3%; CC-HCG vs. CC-Placebo). Upon adjusting for BMI and age, the findings of our study revealed that individuals in the CC-HCG group who had serum prolactin levels below 20 (ng/mL), secondary infertility, infertility duration less than 4 years, baseline LH/FSH ratios below 1.5, and serum AMH levels more than 4 (ng/mL) had a higher likelihood of achieving pregnancy. In the CC-Placebo group, there was a greater prediction of clinical pregnancy for those with serum AMH (<4), primary infertility, serum prolactin ≤ 20 (ng/mL), baseline LH/FSH < 1.5, and infertility duration < 4 years. Conclusions: The use of a small dose of HCG along with CC appeared to be an effective treatment in reducing cycle cancelation, improving the clinical pregnancy rate and ovulation rate in CC-resistant PCOS patients. The trial was registered with Clinical Trials.gov, identifier NCT02436226.

Congenital hypogonadotropic hypogonadism (CHH) is a rare reproductive disorder caused by deficient secretion or action of gonadotropin-releasing hormone (GnRH) and is a hormonally treatable form of male infertility. Both pulsatile GnRH treatment and combined gonadotropin therapy effectively induce spermatogenesis in 75%-80% of males with CHH, albeit the ejaculate does not usually approach normal semen parameters by WHO criteria. This is in some contrast to the cumulative fertility outcomes in females with CHH on gonadotropin treatment that are indistinguishable from those of reproductively normal females. Emerging data provide insights into early life determinants of male fertility (i.e., minipuberty), and research has identified key predictors of outcomes for fertility-inducing treatment in men with CHH. Such developments provide mounting evidence for tailoring approaches to maximize fertility potential in CHH, although there is no clear consensus to date on the optimal approach to fertility-inducing treatment. This review provides an up-to-date review on the current evidence underpinning therapeutic approaches for inducing spermatogenesis in males with CHH. In the absence of evidence-based clinical guidelines, this synthesis of current evidence provides guidance for clinicians working with males with CHH seeking fertility.

Background/Objective: Autoimmune thyroid diseases (AITD) affect 2 to 5% of the general population. This study aimed to determine changes in activity of A-Tg and A-TPO antibodies before, during, and after pregnancy in women with previous AITD. Methods: This was a single-center study with a retrospective review of the medical records of 30 female patients aged 25-41 years who came to our endocrinology service in the city of Santo André, state of São Paulo, Brazil, to investigate thyroid diseases. The following data were reviewed: total triiodothyronine (totalT3), total thyroxine (totalT4), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and anti-TSH receptor antibodies (anti-TSH receptor or anti-thyrotropin receptor antibodies (TRAb), anti-thyroid peroxidase (A-TPO), and anti-thyroglobulin (A-Tg)). These data were reviewed for 30 patients before and during the three trimesters of pregnancy and during the three months after pregnancy. Results: During gestation, we observed a progressive decrease in the blood values of A-TPO and A-Tg, which reached their lowest values in the third trimester of pregnancy, but after birth, they returned to values statistically equivalent to those before pregnancy. Analyzing the three trimesters and the post-pregnancy period, A-TPO increased 192% between the first trimester and postpartum (p = 0.009); it increased 627% between the second trimester and postpartum (p < 0.001); and it increased >1000% between the third trimester and postpartum (p < 0.001). There was no significant difference in the A-TPO values between the pre- and post-gestational periods (p = 1.00), between the first and second trimesters (p = 0.080), or between the second and third trimesters (p = 0.247). Conclusions: According to the results presented here, we observed changes in the activities of A-Tg and A-TPO antibodies during and after pregnancy in women with previous AITD. In women who intend to become pregnant, are pregnant, or have given birth within three months, it is essential to monitor A-TPO, A-Tg, and thyroid function as well as serum thyroid hormones and TSH to identify thyroid dysfunction in a timely manner and adjust the treatment strategy to avoid the deleterious effects of hypothyroidism on both mother and baby during and after pregnancy.

UNASSIGNED: Elevated levels of tumor necrosis factor-alpha (TNF-α) have been associated with adverse pregnancy outcomes, specifically recurrent pregnancy loss (RPL). These elevated levels may be associated with the presence of autoantibodies. Although TNF-α inhibitors have shown promise in improving pregnancy rates, further research is needed to comprehend their impact and mechanisms in RPL patients.
UNASSIGNED: This study aims to investigate the association between elevated TNF-α levels and autoantibodies in RPL patients, as well as evaluate the effect of TNF-α inhibition on pregnancy outcomes.
UNASSIGNED: A total of 249 RPL patients were included in this study. Serum levels of TNF-α, autoantibodies, and complement were measured and monitored. Among these patients, 138 tested positive for TNF-α, while 111 tested negative. The medical records of these patients were retrospectively evaluated. Additionally, 102 patients with elevated TNF-α levels were treated with TNF-α inhibitors, and their pregnancy outcomes were assessed.
UNASSIGNED: TNF-α-positive RPL patients had higher levels of complement C1q, anti-cardiolipin (ACL)-IgA, ACL-IgM ,ACL-IgG, thyroglobulin antibody, and Anti-phosphatidylserine/prothrombin IgM antibody, as well as a higher positive rate of antinuclear antibodies compared to TNF-α-negative patients (23.19% vs. 12.6%, P< 0.05). Conversely, complement C3 were lower in TNF-α-positive patients (t test, P< 0.05). The use of TNF-α inhibitors led to a reduction in the early abortion rate (13.7% vs. 44.4%, P< 0.001) and an improvement in term delivery rate (52.0% vs. 27.8%, P= 0.012). Furthermore, patients who used TNF-α inhibitors before 5 weeks of pregnancy had a lower early abortion rate (7.7% vs. 24.3%, P= 0.033) and a higher term delivery rate (69.2% vs. 48.6%, P= 0.033).
UNASSIGNED: TNF-α plays a role in the occurrence and development of RPL, and its expression is closely associated with autoantibodies and complements. TNF-α inhibitors increase the term delivery rate in TNF-α-positive RPL patients, and their use before 5 weeks of pregnancy may more beneficial.

OBJECTIVE: We examined the association between progesterone (P4), estradiol (E2), and human chorionic gonadotropin (hCG) levels in early pregnancy and the development of hypertensive diseases of pregnancy among women undergoing assisted reproduction.
METHODS: Retrospective study including patients who underwent frozen embryo transfer (FET), ovarian stimulation (OS), or unassisted conception (UC) and had a live singleton birth. The primary outcome was the development of hypertensive diseases of pregnancy (gestational hypertension, preeclampsia, HELLP, or eclampsia). Secondary outcomes were the development of fetal intrauterine growth restriction (IUGR), gestational diabetes mellitus, birth weight, and pre-term birth. Hormone levels and the development of the outcomes were correlated.
RESULTS: A total of 681 patients were included; 189 had FET, 193 had OS, and 299 had UC. Patients undergoing FET or OS were not more likely to develop hypertensive diseases of pregnancy compared with UC patients. While median levels of E2 and P4 were significantly different between P-FET and NC-FET patients (E2: 252 vs 317 pg/mL, P4: 64 vs 29 ng/mL, respectively; both p < 0.01), rates of hypertensive diseases of pregnancy did not significantly differ between those two groups. In the multivariate analyses, P4, E2, and hCG were not associated with the development of hypertensive diseases of pregnancy, but progesterone levels were significantly higher among those with IUGR. This remained consistent when the analysis was limited to FET patients.
CONCLUSIONS: P4, E2, and hCG levels did not correlate with the development of hypertensive diseases of pregnancy but elevated progesterone levels did correlate with the development of IUGR.