Strategies for improving expression of recombinant human chorionic gonadotropin in Chinese Hamster Ovary (CHO) cells.

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.

Unusual manifestation of synovial sarcoma: A rare case report with elevated beta HCG level.

Synovial sarcoma is a rare type of soft tissue sarcoma that typically arises in the lower extremities and rarely in the upper extremities. Here, we present an unusual case of a middle-aged man who complained of dyspnea, dry cough, and chest pain and was found to have a mass-like lesion on the ulnar side of his left wrist during physical examination. The patient also exhibited gynecomastia and had elevated ß-human chorionic gonadotropin (ßHCG) levels. Subsequent imaging and histopathological analysis of the wrist mass confirmed the diagnosis of synovial sarcoma with disseminated lung metastasis. This article aims to provide a comprehensive overview of the clinical and pathological characteristics of synovial sarcoma, highlight the importance of considering synovial sarcoma as a differential diagnosis in patients with abnormal hormonal assays, and emphasize the need for clinicians to be vigilant about any pathologic lesions existing on the upper extremity to avoid late diagnosis and the development of advanced cancerous diseases.

Bilateral Tubal Ectopic Pregnancy: A Case Report and Review.

A bilateral ectopic pregnancy is a rare condition, and even more so with spontaneous conception. The known risk factors and clinical presentation are shared by both unilateral and bilateral ectopic pregnancy. This poses a risk for misdiagnosis, treatment failure, and, ultimately, maternal mortality. The current standard for diagnostics is not discernible for a bilateral ectopic pregnancy, thus, medical management tends to be sub-therapeutic. In fact, it is fairly common for the correct diagnosis and efficient treatment to be achieved by surgical intervention. As there are no established diagnostic or treatment guidelines for this rare condition, the possibility of a bilateral ectopic pregnancy should not be ruled out lightly.

Target-mediated silver deposition-based electrochemical biosensor for highly sensitive detection of human chorionic gonadotropin.

As a glycoprotein hormone, human chorionic gonadotropin (hCG) is an established marker for pregnancy test. On the basis of the target-mediated silver deposition (TSD), in this work, we report the development of an amplification-free electrochemical biosensor for the highly sensitive detection of hCG. The detection of hCG involves the use of the affinity peptide-modified electrode for hCG capture (the CGGSSPPLRINRHILTR peptide containing the hCG-binding domain of the PPLRINRHILTR sequence is used as the affinity peptide), the oxidation of the diol sites of the glycan chains on hCG hormones into aldehyde groups by NaIO4, and the deposition of silver nanoparticles (AgNPs) for the solid-state voltammetric stripping analysis. Due to the deposition of multiple AgNPs while the solid-state Ag/AgCl voltammetric process has a high signal-to-noise ratio, the TSD-based electrochemical biosensor can be applied to the highly sensitive detection of hCG without the need for signal amplification. Under optimal conditions, the stripping current increased linearly with an increasing hCG concentration over the range from 1.0 to 25 mIU/mL, with a detection limit of 0.45 mIU/mL. Owing to the high specificity of the hCG-binding peptide PPLRINRHILTR, this electrochemical hCG biosensor exhibits high selectivity. The results of the quantitative assay of hCG in urine samples at the concentrations of 25, 10, and 1.0 mIU/mL are desirable, indicating the good anti-interference capability. As the TSD-based electrochemical biosensor allows the amplification-free detection of low-abundance hCG, it is easy to use and cost-effective, showing great promise in point-of-care assay of hCG for pregnancy test.

Relationship between the effect of human chorionic gonadotropin treatment on the fifth day after artificial insemination and ovarian ultrasonographic findings and blood nutritional metabolic factors in dairy cows.

The objective of the present study was to determine the ovarian ultrasonographic findings and metabolic factors that influence the effect of human chorionic gonadotropin (hCG) treatment on the fifth day after artificial insemination (AI) in dairy cows. Thirty-seven lactating Holstein cows were assigned to two groups: the hCG group (n = 25), which received 3000 IU of hCG intramuscularly on Day 5 after AI (day of AI = Day 0), and the control group (n = 12), which received no treatment. Ovarian ultrasonography measured luteal tissue area (LTA), luteal blood flow area (LBF), relative LBF (= LBF/LTA), and dominant follicle area on Day 5. Blood tests measured plasma insulin-like growth factor-I, insulin, and metabolite concentrations on Day 5 and plasma progesterone concentrations on Days 5 and 7. LBF was greater in pregnant cows than in non-pregnant cows, and plasma Glu concentration was lesser in pregnant cows than in non-pregnant cows, but in both cases there was no interaction between group and pregnancy outcome. For plasma insulin concentration, there was an interaction between group and pregnancy outcome, with pregnant cows in the hCG group having lesser concentrations than the other groups. Logistic regression analysis showed that group and the interaction between group and plasma insulin concentration were associated with pregnancy outcome. These results suggest that the effect of hCG treatment on Day 5 after AI is related to plasma insulin concentration and is more effective in cows with lesser plasma insulin concentrations.

Diagnosis and Management of Molar Pregnancies.

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.

Increased Human Chorionic Gonadotropin Level in a Nonsexually Active Young Female.

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. CASE REPORT: 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.

Designing an Electrochemical Biosensor Based on Voltammetry for Measurement of Human Chorionic Gonadotropin.

Background: Human chorionic gonadotropin (hCG) is a polypeptide hormone synthesized during pregnancy and is also upregulated in some pathologic conditions such as certain tumors. Its measurement is essential for diagnosing pregnancy and malignancies. Despite numerous attempts to introduce an accurate method capable of detecting hCG levels, several limitations are found in previous techniques. This study aimed to address the limitations of current hCG assay methods by designing an electrochemical biosensor based on voltammetry for the rapid, selective, inexpensive, and sensitive measurement of hCG levels. Methods: A carbon paste electrode was prepared and functionalized by para-aminobenzoic acid. The primary anti-ß-hCG monoclonal antibody was immobilized on the electrode surface by activating the carboxyl groups with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide solutions. The study also involved optimizing parameters such as the time for primary antibody fixation, the time for hCG attachment, and the pH of the hydrogen peroxide solution to maximize the biosensor response. Different concentrations of hCG hormone were prepared and loaded on the electrode surface, the secondary antibody labeled with HRP enzyme was applied, thionine in phosphate-buffered saline solution was placed on the electrode surface, and the differential pulse electrical signal was recorded. Results: The linear range ranged from 5 to 100 mIU/ml, and the limit of detection was calculated as 0.11 mIU. The relative standard deviation was 3% and 2% for five repeated measurements of commercial standard samples with concentrations of 2 and 20 mIU/mL, respectively. The percent recovery was obtained from 98.3% to 101.5%. Conclusion: The sensor represents a promising advancement in hCG level measurement, offering a potential solution to overcome the existing limitations in current diagnostic strategies. Simple and inexpensive design, detecting hCG in its important clinical range during early pregnancy, and successful measurement of hCG in real serum samples are the advantages of this sensor.

The Role of hCG and Histamine in Emesis Gravidarum and Use of a Chewing Gum Containing Vitamin C as a Treatment Option: A Double-Blinded, Randomized, Controlled Trial.

Background: Nausea and vomiting in pregnancy (NVP), or emesis gravidarum, is a frequent complication of early gestation with unclear causes, suspected to involve genetic, hormonal, and gastrointestinal factors. Our study investigated the association of human chorionic gonadotropin (hCG), histamine, diamine oxidase (DAO), thyroxine and pyridoxine and the severity of NVP symptoms and assessed the efficacy of a vitamin C-containing chewing gum as a potential NVP treatment. Methods: In this prospective, double-blinded, randomized, controlled trial, 111 participants were assigned to receive vitamin C-containing chewing gum, placebo gum, or no treatment at two follow-ups during early pregnancy. Maternal serum levels of hCG, histamine, DAO, thyroxine, and pyridoxine were measured and correlated with NVP severity using the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE-24) score. Results: Elevated maternal hCG levels were significantly associated with an increased PUQE-24 score (p < 0.001), while histamine levels showed no significant correlation (p = 0.68). Maternal DAO levels negatively correlated with NVP symptoms (p < 0.001) and elevated thyroxine (p < 0.001) and pyridoxine levels (p < 0.001) were associated with increased PUQE-24 scores. The vitamin C-containing chewing gum did not demonstrate efficacy in alleviating NVP symptoms compared to placebo gum or no treatment during the first (p = 0.62) and second follow-up visits (p = 0.87). Conclusions: Our study underscores the complexity of factors contributing to NVP, highlighting the significant roles of hCG and DAO, while histamine levels appear unrelated. Maternal thyroxine and pyridoxine levels also significantly correlate with NVP symptoms. Vitamin C-containing chewing gum was not effective as a treatment for NVP. Further large-scale studies are needed to better understand these interactions and develop targeted treatments in the future.

First trimester maternal serum PAPP-A and free ß-hCG levels and risk of SGA or LGA in women with and without GDM.

BACKGROUND: Maternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fß-hCG) were associated with SGA and LGA in GDM pregnancies and controls. METHODS: Altogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fß-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking. RESULTS: In pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5-4.7) and 2.2 (95% CI 1.4-3.5) in the GDM group and 3.8 (95% CI 3.0-4.9) and 2.8 (95% CI 2.3-3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fß-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8-3.1) in the control group. In fß-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1-2.5) for LGA. CONCLUSION: Association with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fß-hCG levels are associated with SGA only in non-GDM pregnancies.

Nomogram to predict methotrexate treatment success in ectopic pregnancy.

OBJECTIVE: To evaluate clinical factors prior to methotrexate (MTX) treatment for tubal ectopic pregnancy and to apply the data to a prediction model for treatment success. METHODS: A retrospective cohort study was conducted during 2014-2022. Of the 808 patients with a tubal ectopic pregnancy, 372 with a ß-hCG level less than 5000 IU/L were treated with a single dose of MTX and were included in this study. Pretreatment factors, including patient characteristics, initial ß-hCG level, and sonographic parameters, were compared between those who achieved complete resolution and those who needed additional MTX or surgical intervention. A logistic regression model and multivariable analysis were used to predict success. A graphic nomogram was generated to represent the model. RESULTS: Complete resolution of the ectopic pregnancy was achieved in 290 (77.9%) patients after a single dose of MTX. A second dose or surgical intervention was required for 82 (22.0%): 49 (13.2%) received a second dose of MTX and 33 (8.9%) underwent laparoscopic salpingectomy. In the MTX Success group compared to the MTX Failure group, the median ß-hCG levels were lower (746 vs 1347 IU/L, P < 0.001) and the presence of a yolk sac and a fetal pole were less frequent. The predictive model, based on significant variables, includes initial ß-hCG concentration and the visibility of a yolk sac or fetal pole. Analysis with cross-validation techniques revealed that the model was both accurate and discriminative. CONCLUSION: A predictive nomogram was developed to predict the success of single-dose MTX treatment for tubal ectopic pregnancy.

Hormonal and Allosteric Regulation of the Luteinizing Hormone/Chorionic Gonadotropin Receptor.

Luteinizing hormone (LH) and human chorionic gonadotropin (CG), like follicle-stimulating hormone, are the most important regulators of the reproductive system. They exert their effect on the cell through the LH/CG receptor (LHCGR), which belongs to the family of G protein-coupled receptors. Binding to gonadotropin induces the interaction of LHCGR with various types of heterotrimeric G proteins (Gs, Gq/11, Gi) and ß-arrestins, which leads to stimulation (Gs) or inhibition (Gi) of cyclic adenosine monophosphate-dependent cascades, activation of the phospholipase pathway (Gq/11), and also to the formation of signalosomes that mediate the stimulation of mitogen-activated protein kinases (ß-arrestins). The efficiency and selectivity of activation of intracellular cascades by different gonadotropins varies, which is due to differences in their interaction with the ligand-binding site of LHCGR. Gonadotropin signaling largely depends on the status of N- and O-glycosylation of LH and CG, on the formation of homo- and heterodimeric receptor complexes, on the cell-specific microenvironment of LHCGR and the presence of autoantibodies to it, and allosteric mechanisms are important in the implementation of these influences, which is due to the multiplicity of allosteric sites in different loci of the LHCGR. The development of low-molecular-weight allosteric regulators of LHCGR with different profiles of pharmacological activity, which can be used in medicine for the correction of reproductive disorders and in assisted reproductive technologies, is promising. These and other issues regarding the hormonal and allosteric regulation of LHCGR are summarized and discussed in this review.

Analytical Investigation of the Profile of Human Chorionic Gonadotropin in Highly Purified Human Menopausal Gonadotrophin Preparations.

Highly purified human menopausal gonadotropin (HP-hMG [Menopur®, Ferring Pharmaceuticals, Saint-Prex, Switzerland]) contains a 1:1 ratio of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This analysis aimed to assess gonadotropin (FSH, LH and hCG) abundance in HP-hMG and clarify the source of hCG by assessing the presence of sulfated glycans, which are diagnostic for pituitary hCG forms due to their distinct glycosylation patterns. Additionally, the purity of each sample, their specific components, and their oxidation levels were assessed. HP-hMG samples (three of Menopur® and two of Menogon® Ferring Pharmaceuticals, Saint-Prex, Switzerland) were included in the current analyses. Brevactid® (urinary hCG; Ferring Pharmaceuticals, Saint-Prex, Switzerland) and Ovidrel® (recombinant hCG; Merck KGaA, Darmstadt, Germany) were used as control samples. Glycopeptide mapping and analysis of impurities were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oxidation was assessed through reducing peptide mapping using LC-MS/MS. The FSH and LH in the HP-hMG samples showed sulfated glycans, while no signals of sulfated glycopeptides were detected on any site of the beta subunit of hCG. HP-hMG test samples presented the same hCG glycan distribution as the control sample (placental hCG, Brevactid®) extracted from the urine of pregnant women, suggesting a non-pituitary source of hCG. Protein impurities were estimated to constitute approximately 20-30% of the entire HP-hMG protein content in the test samples. More than 200 non-gonadotropin proteins were identified in the HP-hMG test samples, of which several were involved in embryonic development or pregnancy. The alpha subunit of the tested samples was strongly oxidized, with a relative abundance of 20% of the total gonadotropin content. Without taking into account all the protein impurities, the beta subunit of LH was detected only in traces (0.9-1.2%) in all tested HP-HMG samples, confirming the data obtained by intact molecule analysis, while high levels of beta hCG (18-47%) were observed. Advanced molecular analysis of HP-hMG indicates a primarily placental origin of hCG, as evidenced by the absence of hCG sulfated glycans and the predominance of placental non-sulfated hCG in LH activity. The analysis revealed 20-30% of protein impurities and a significant presence of oxidized forms in the HP-hMG samples. These findings are critical for understanding the quality, safety, and clinical profile of HP-hMG.

PolyPyrrole based-impedimetric aptasensor for selective determination of beta-HCG from urine sample.

Herein, a conjugated conducting polymer-based impedimetric aptasensor has been developed to detect beta-human chorionic gonadotropin (bHCG), the one of the important biomarkers in gynecology, from synthetic human urine samples. In this context, gold electrodes were, firstly coated with pyrrole and pyrrole-3-carboxylic acid to obtain the poly(pyrrole-pyrrole-3-carboxylic acid) [poly(Py-PyCOOH)] conductive copolymer by cyclic voltammetry (CV). Then, bHCG-specific peptide aptamer was covalently linked onto the surface via applying a well-known carbodiimide-succinimide chemistry. The sensor developed was characterized to confirm modification steps via both electrochemical methods including CV, electrochemical impedance spectroscopy (EIS), and chronoamperometry and physico-chemically via attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), atomic force microscope (AFM), and contact angle measurements (CA). The analytical performance of the sensor was evaluated in the concentration range from 1 µg/mL to 100 µg/mL for successful detection of bHCG even in the presence of interference agents. The results have also revealed that the sensor could be classified as a promising alternative to its benchmark commercial clinical methods due its superior properties such as cost-friendliness, easy-to-prepare, stable, robust, and selectivity / sensitivity.

Paraneoplastic production of human chorionic gonadotropin by paratesticular dedifferentiated liposarcoma with rhabdomyosarcomatous differentiation.

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.

Use of hCG for luteal support in natural frozen-thawed blastocyst transfer cycles: a cohort study.

Introduction: 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. Objective: To evaluate the effect of hCG administration as LPS on reproductive outcomes in natural FET cycles. Methods: 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. Results: 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). Conclusion: 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.

Evaluation of Anti-Thyroperoxidase (A-TPO) and Anti-Thyroglobulin (A-Tg) Antibodies in Women with Previous Hashimoto's Thyroiditis during and after Pregnancy.

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.

Competence of Combined Low Dose of Human Chorionic Gonadotropin (HCG) and Clomiphene Citrate (CC) Versus Continued CC during Ovulation Induction in Women with CC-Resistant Polycystic Ovarian Syndrome: A Randomized Controlled Trial.

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.

Current landscape of fertility induction in males with congenital hypogonadotropic hypogonadism.

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.

Effect of the degree of follicular diameter ≥18mm differentiation on the day of hCG administration to the outcome of controlled ovarian hyperstimulation (COH).

Objective: To explore the impact of the level of differentiation in a minimum of two follicles with a diameter of ≥18 mm on the outcome of controlled ovarian hyperstimulation on the day of human chorionic gonadotropin (hCG) administration. Methods: Single-center data from January 2018 to December 2021 was retrospectively analyzed for 1,199 patients with fresh embryo transfer for assisted reproduction. The absolute value of the standard deviation of the follicle size of at least 2 follicles ≥18 mm in diameter in both ovaries on the day of hCG was taken as the degree of differentiation of the dominant follicle after ovulation induction, based on the standard deviation response to the degree of dispersion of the data. The degree of follicular differentiation was divided into 3 groups according to the size of the value, and the general clinical conditions, laboratory indexes, and clinical outcomes of the patients in the 3 groups were compared. Results: Among the three groups, the body mass index (BMI) of the ≤1s group was lower than that of the other two groups (P< 0.05), while the follicle-stimulating hormone (FSH) and Anti-Mullerian hormone (AMH) were higher (P< 0.05), and the implantation rate and clinical pregnancy rate were significantly higher than those of the other two groups (P< 0.01). After multifactorial logistic regression to correct for confounding factors, with the ≤1s group as the reference, the implantation rate, hCG-positive rate, clinical pregnancy rate and live birth rate of embryo transfer in the ≥2S group were significantly lower (P< 0.01). The results of curve fitting analysis showed that the live birth rate decreased gradually with the increase of the absolute standard deviation (P=0.0079). Conclusion: Differences in follicle diameters ≥18 mm on the day of hCG injection did not have an impact on embryo quality, but had an impact on pregnancy outcomes. The less the variation in follicle size, the more homogeneous the follicle development and the higher the likelihood of live births.