Laparoscopic evaluation of female genital tuberculosis in infertility: An observational study.

Background & objectives: Female genital tuberculosis (FGTB) is an important variety of extrapulmonary TB causing significant morbidity, especially infertility, in developing countries like India. The aim of this study was to evaluate the laparoscopic findings of the FGTB. Methods: This was a cross-sectional study on 374 cases of diagnostic laparoscopy performed on FGTB cases with infertility. All patients underwent history taking and clinical examination and endometrial sampling/biopsy for acid-fast bacilli, microscopy, culture, PCR, GeneXpert (only last 167 cases) and histopathological evidence of epithelioid granuloma. Diagnostic laparoscopy was performed in all the cases to evaluate the findings of FGTB. Results: Mean age, parity, body mass index and duration of infertility were 27.5 yr, 0.29, 22.6 kg/m2 and 3.78 years, respectively. Primary infertility was found in 81 per cent and secondary infertility in 18.18 per cent of cases. Endometrial biopsy was positive for AFB microscopy in 4.8 per cent, culture in 6.4 per cent and epithelioid granuloma in 15.5 per cent. Positive peritoneal biopsy granuloma was seen in 5.88 per cent, PCR in 314 (83.95%) and GeneXpert in 31 (18.56%, out of last 167 cases) cases. Definite findings of FGTB were seen in 164 (43.86%) cases with beaded tubes (12.29%), tubercles (32.88%) and caseous nodules (14.96%). Probable findings of FGTB were seen in 210 (56.14%) cases with pelvic adhesions (23.52%), perihepatic adhesions (47.86%), shaggy areas (11.7%), pelvic adhesions (11.71%), encysted ascites (10.42%) and frozen pelvis in 3.7 per cent of cases. Interpretation & conclusions: The finding of this study suggests that laparoscopy is a useful modality to diagnose FGTB with a higher pickup rate of cases. Hence it should be included as a part of composite reference standard.

Cytokine and growth factor profile in endometriosis: a multiplex analysis of peritoneal fluid to assess diagnostic utility.

We aimed to assay cytokines and growth factors in peritoneal fluid samples from women with and without endometriosis to understand the inflammatory milieu, and assess their potential diagnostic utility. This cross-sectional study conducted at a tertiary care hospital included 54 women, aged 20-45 years, with regular menstrual history and undergoing diagnostic/therapeutic laparoscopy for infertility and/or pain. Peritoneal fluid samples were collected after insertion of trocar & laparoscope but prior to other surgical intervention. A multiplex immunoassay of 27 cytokines and growth factors was performed. The concentration of FGF2 and CSF3 were significantly lower in women with endometriosis than without endometriosis (p = .043 and .003, respectively). The levels of CCL2 and IL1RN were significantly higher in moderate-severe than in minimal-mild endometriosis (p = .038 and .043, respectively). Phase-specific comparison revealed that in proliferative phase, the levels of CSF2 and CSF3 were lower in women with endometriosis than without the disease (p = .047 and .013, respectively). The ROC curve analysis provided a cutoff value 0.78 and 0.76 for FGF2 and CSF3, respectively. Cytokines and growth factors such as FGF2, CSF3, CSF2, CCL2 and IL1RN seem to contribute to the pathogenesis of endometriosis and may have a potential utility for the diagnosis of endometriosis.

An assessment of the multifactorial profile of steroid-metabolizing enzymes and steroid receptors in the eutopic endometrium during moderate to severe ovarian endometriosis.

BACKGROUND: Previous studies of expression profiles of major endometrial effectors of steroid physiology in endometriosis have yielded markedly conflicting conclusions, presumably because the relative effects of type of endometriosis, fertility history and menstrual cycle phases on the measured variables were not considered. In the present study, endometrial mRNA and protein levels of several effectors of steroid biosynthesis and action in patients with stage III-IV ovarian endometriosis (OE) with known fertility and menstrual cycle histories were compared with the levels in control endometrium to test this concept. METHODS: Endometrial samples were collected from patients without endometriosis (n = 32) or OE stages III-IV (n = 52) with known fertility and cycle histories. qRT-PCR and immunoblotting experiments were performed to measure levels of NR5A1, STAR, CYP19A1, HSD17Bs, ESRs and PGR transcripts and proteins, respectively. Tissue concentrations of steroids (P4, T, E1 and E2) were measured using ELISAs. RESULTS: The levels of expression of aromatase and ERß were lower (P < 0.0001) and 17ß-HSD1 (P < 0.0001) and PRA (P < 0.01) were higher in OE endometrium. Lower aromatase levels and higher 17ß-HSD1 levels were detected in fertile (aromatase: P < 0.05; 17ß-HSD1: P < 0.0001) and infertile (aromatase: P < 0.0001; 17ß-HSD1: P < 0.0001) OE endometrium than in the matched control tissues. Both proliferative (PP) and secretory (SP) phase OE samples expressed aromatase (P < 0.0001) and ERß (PP: P < 0.001; SP: P < 0.01) at lower levels and 17ß-HSD1 (P < 0.0001) and PRA (PP: P < 0.01; SP: P < 0.0001) at higher levels than matched controls. Higher 17ß-HSD1 (P < 0.01) and E2 (P < 0.05) levels and a lower (P < 0.01) PRB/PRA ratio was observed in infertile secretory phase OE endometrium than in control. CONCLUSIONS: We report that dysregulated expression of 17ß-HSD1 and PGR resulting in hyperestrogenism and progesterone resistance during the secretory phase of the menstrual cycle, rather than an anomaly in aromatase expression, was the hallmark of eutopic endometrium from infertile OE patients. Furthermore, the results provide proof of concept that the fertility and menstrual cycle histories exerted relatively different effects on steroid physiology in the endometrium from OE patients compared with the control subjects.

Genomic evidence of Y chromosome microchimerism in the endometrium during endometriosis and in cases of infertility.

BACKGROUND: Previous studies, which were primarily based on the fluorescent in-situ hybridisation (FISH) technique, revealed conflicting evidence regarding male foetal microchimerism in endometriosis. FISH is a relatively less sensitive technique, as it is performed on a small portion of the sample. Additionally, the probes used in the previous studies specifically detected centromeric and telomeric regions of Y chromosome, which are gene-sparse heterochromatised regions. In the present study, a panel of molecular biology tools such as qPCR, expression microarray, RNA-seq and qRT-PCR were employed to examine the Y chromosome microchimerism in the endometrium using secretory phase samples from fertile and infertile patients with severe (stage IV) ovarian endometriosis (OE) and without endometriosis. METHODS: Microarray expression analysis followed by validation using RNA-seq and qRT-PCR experiments at the RNA levels and further validation at the DNA level by qPCR of target inserts for selected targets in eutopic endometrium samples obtained from control (CON) and stage IV ovarian endometriosis (OE), either from fertile (FCON and FOE; n = 30/each) or infertile (ICON and IOE; n = 30/each) women, were performed. RESULTS: Six coding (AMELY, PCDH11, SRY, TGIF2LY, TSPY3, and USP9Y) and 10 non-coding (TTTY2, TTTY4C, TTTY5, TTTYY6, TTTY8, TTTY10, TTTY14, TTTY21, TTTY22, and TTTY23) genes exhibited a bimodal pattern of expression characterised by low expression in samples from fertile patients and high expression in samples from infertile patients. Seven coding MSY-linked genes (BAGE, CD24, EIF1AY, NLGN4Y, PRKY, VCY and ZFY) exhibited differential regulation in microarray analysis, and this change was validated by RNA-seq or qRT-PCR. DNA inserts for 7 genes in various samples were validated by qPCR. The prevalence and concentration of PCR-positive target inserts for BAGE, PRKY, TTTY9A and ZFY displayed higher values in the fertile, control (FCON) patients compared with the fertile, endometriosis patients (FOE). CONCLUSION: Several coding and non-coding MSY-linked genes displayed microchimerism as evidenced by the presence of their respective DNA inserts, along with their differential transcript expression, in the endometrium during endometriosis and in cases of infertility.

India's response to adolescent mental health: a policy review and stakeholder analysis.

PURPOSE: Mental health problems and suicide are the leading cause of mortality in young people globally. India is home to the largest number of adolescents in the world. This study was undertaken to assess the policy environment for addressing adolescent mental health in India. METHODS: We conducted a review of 6 policies and programs and 11 in-depth interviews with key stakeholders. The findings were analyzed using the policy triangle analysis framework (i.e., context, content, actors and process). RESULTS: There is no conformity of the age ranges addressed by these documents nor are vulnerable groups explicitly recognized. Stress, anxiety and depression were commonly identified as mental health concerns and diverse platforms such as community, family, school, digital and health facility were recommended to deliver preventive and treatment interventions. Some interventions specifically targeted some social determinants (like safe and supportive schools) but many others (like social norms) were not addressed. Preventive interventions were recommended for delivery through peers and other non-specialist providers while treatment interventions were recommended for delivery in healthcare facilities by specialist health professionals. There was very little engagement of young people in the development of these policies or in their implementation, except for peer educators mentioned in one policy. Stakeholders identified several major challenges in implementing these policies, notably the lack of inter-sectoral coordination and fragmentation of governance; budgetary constraints; and scanty human resources. CONCLUSIONS: Although there are now several policy instruments testifying to a comprehensive approach on adolescent mental health, there are gaps in the extent of engagement of young people and how these will be operationalized that may limit their impact on addressing the burden of mental health problems in young people in India.

Pregnancy with massive splenomegaly: A case series.

Background: Pregnancy with massive splenomegaly is a rare entity and is associated with increased risk to both mother and foetus. There is paucity of studies in the literature to guide clinicians for the management of this condition. Methods: We reviewed the course of pregnancy, maternal and foetal outcomes of 5 pregnant women with massive splenomegaly who were managed in our unit during 2015-16. Results: All 5 women had anaemia and thrombocytopenia, and had different causes for splenomegaly. One patient had chronic malaria, 2 had portal hypertension with cirrhosis and the remaining 2 had non-cirrhotic portal hypertension. Life-threatening complications were present in 2 patients; one of them had severe pre-eclampsia complicated by pulmonary oedema, cardiac arrest and the other patient developed spontaneous bacterial peritonitis. Intrauterine growth restriction and meconium-stained liquor were the most common perinatal complications. Two patients had vaginal delivery and 3 required emergency caesarean section. Postpartum haemorrhage was present in 2, and the hospital stay was prolonged in all the patients. All mothers and babies were discharged in a satisfactory condition. Conclusion: Pregnancy with massive splenomegaly poses a challenge because of diverse aetiology and potentially adverse outcomes. Multidisciplinary care in a tertiary centre can help optimize the outcome.

Frontline use of bevacizumab in ovarian cancer: Experience from India.

Background: Ovarian cancer is the second most common gynaecological malignancy in India. Despite relatively high response rates to first-line carboplatin and paclitaxel-based chemotherapy in epithelial ovarian cancer (EOC), the majority of patients experience multiple relapses and finally become resistant. Vascular endothelial growth factor (VEGF) promotes progression of ovarian cancer. Bevacizumab, a recombinant humanized monoclonal antibody directed against VEGF-A is an anti-angiogenesis agent. Data on the use of bevacizumab for EOC from India are not available. We, therefore, studied the use of bevacizumab in ovarian cancer. Methods: In this prospective, non-randomized study, 10 patients who received bevacizumab were compared with 20 age- and stage-matched controls. After maximal surgical debulking, patients in the bevacizumab arm received bevacizumab 15 mg/kg i.v. on day 1 every 3 weeks followed by paclitaxel and carboplatin from cycle 1. After 6 cycles, bevacizumab was continued for 1 year. Controls received paclitaxel 1 75 mg/m2 and carboplatin only for 4-8 cycles. The outcome measures were adverse effects and progression-free survival. Results: Haematological toxicity (i.e. neutropenia, thrombocytopenia and anaemia) was similar in both arms. Hypertension (40% v. 10%, p = 0.04) and bleeding-related complications (50% v. 0%, p = 0.002) were more in the bevacizumab arm. However, gastrointestinal (GI) perforations were not increased. The median progression-free survival was similar in both arms; 26 months versus 21 months (p = 0.57). Conclusion: In this small group of patients, addition of bevacizumab increased the toxicity of chemotherapy.

Comparative Study of Laparoscopic Abdominopelvic and Fallopian Tube Findings Before and After Antitubercular Therapy in Female Genital Tuberculosis With Infertility.

STUDY OBJECTIVE: To study the effect of antitubercular treatment (ATT) on the laparoscopic abdominopelvic and fallopian tube findings in female genital tuberculosis (FGBT). DESIGN: Prospective cohort (Canadian Task Force classification II2). SETTING: Tertiary referral center in northern India. PATIENTS: Fifty women with infertility and diagnosed with FGTB on laparoscopy, histopathology findings, or endometrial sampling (acid-fast bacilli culture, granuloma on histopathology, positive polymerase chain reaction). INTERVENTIONS: Diagnostic laparoscopy in all women diagnosed with FGTB before and after a 6-month course of ATT (2 months of rifampicin, isoniazid, pyrazinamide, and ethambutol, followed by 4 months of rifampicin and isoniazid). All procedures were performed by the same surgeon between June 2012 and May 2014. MEASUREMENTS AND MAIN RESULTS: The mean patient age was 28.7 years, mean parity was 0.9, and mean body mass index was 23.6 kg/m(2). Infertility was seen in all 50 women (66% primary infertility, 34% secondary infertility), with a mean duration of 6.06 years. Abnormal laparoscopic findings of FGTB included tubercles in the pelvic peritoneum, fallopian tube, and ovary in 27 women (54%) before ATT and in only 1 (2.04%) woman after ATT (p < .001). Caseous nodules and encysted ascites were seen in 4 women (8%) before ATT, and in no women after ATT (p < .001); however, there was no change from before ATT to after ATT in the rate of pelvic adhesions (42% vs 42.5%) and perihepatic adhesions (56% vs 58%). Laparoscopic findings in fallopian tubes included hydrosalpinx (32%), pyosalpinx (4%), beaded tubes (12%), nonvisualization of tube (20%), and tubal blockage on the right side (56%), left side (50%), and both sides (38%) before ATT. Hydrosalpinx, beaded tubes, and nonvisualized tube were seen in 33.4%, 4.1%, and 20.8% cases, respectively, after ATT; however, free spill increased to 52% on the right side and 50% on left side after ATT. CONCLUSION: ATT improves laparoscopic findings in FGTB with infertility. However, advanced fibrotic lesions (eg, pelvic and perihepatic adhesions, bilateral blocked tubes) do not improve with ATT.

Hysteroscopic septal resection using unipolar resectoscope versus bipolar resectoscope: Prospective, randomized study.

AIM: To compare the operation and reproductive outcome of hysteroscopic septal resection using unipolar resectoscope verses bipolar resectoscope. METHODS: In this prospective randomized study, 70 women underwent hysteroscopic septal resection using either unipolar resectoscope or bipolar resectoscope. Intraoperative parameters (operation time, fluid deficit and complications) and pre- and postoperative serum sodium levels were compared between the two groups. A second-look hysteroscopy was performed after 6 weeks. All pregnancies occurring during the follow-up period were recorded. RESULTS: There was no statistically significant difference between the two groups in terms of operation parameters and second-look hysteroscopy findings. Six patients in the unipolar group were found to have hyponatremia in the postoperative period compared to none in the bipolar group (P = 0.025). Regarding reproductive outcome, the difference between the two groups was not significant. CONCLUSION: The use of bipolar resectoscope is associated with lesser risk of hyponatremia compared to unipolar resectoscope. Bipolar resectoscopy is a safe alternative to unipolar resectoscopy with similar reproductive outcome.

Effectiveness of estrogen in the prevention of intrauterine adhesions after hysteroscopic septal resection: a prospective, randomized study.

AIM: The aim of this prospective randomized study was to evaluate the efficacy of estrogen in preventing intrauterine adhesions following hysteroscopic septal resection and to investigate its effect on reproductive outcome. MATERIALS AND METHODS: After hysteroscopic septal resection, 90 women received either estrogen or placebo (n=45 per group) for 30 days. A second-look hysteroscopy was performed after 2 months. All pregnancies occurring during the study period were recorded. RESULTS: Adhesions developed in three of 43 (6.9%) patients in the control group compared to none in the estrogen group. This difference was not statistically significant (P=0.24). Regarding reproductive outcome, the differences between the two groups were also not significant. CONCLUSION: Estrogen treatment was not found to prevent intrauterine adhesions or improve reproductive outcome after hysteroscopic septal resection.

Pregnancy outcome in patients with idiopathic thrombocytopenic purpura.

OBJECTIVE: To study the outcome of pregnancy in women with idiopathic thrombocytopenic purpura. MATERIALS AND METHODS: A retrospective analysis of 30 pregnancies in 26 women with idiopathic thrombocytopenic purpura was carried out at a tertiary hospital in India. The courses of the disease, maternal and perinatal outcome in these pregnancies were studied. RESULTS: Mean age of pregnant women with idiopathic thrombocytopenic purpura was 27.3 years and 61.5 % was primigravidae. Out of 26 patients with idiopathic thrombocytopenic purpura, 16 were already diagnosed while the other 10 were diagnosed during pregnancy. The incidence of bleeding episodes in antenatal period, severe thrombocytopenia and hemorrhagic complications at the time of delivery was 30, 37 and 11.1 %, respectively. Oral steroids were required in 40 % of pregnancies. Two patients received intravenous immunoglobulin therapy. Severe thrombocytopenia at the time of delivery was more commonly seen in women in whom ITP was diagnosed during pregnancy as compared to those in whom ITP was diagnosed prior to pregnancy (P = 0.04). Severe thrombocytopenia was seen in 18.5 % of neonates and intracranial hemorrhage was detected in 1 neonate. There were no still births or maternal mortality. CONCLUSION: Pregnancy outcome in patients with idiopathic thrombocytopenic purpura is generally good.

Intraperitoneal bupivacaine for pain relief after minilaparoscopy in patients with infertility.

AIM: To evaluate the efficacy of intraperitoneal bupivacaine to reduce post operative pain after diagnostic minilaparoscopy in patients with infertility. DESIGN: A prospective randomized study was performed. MATERIALS AND METHODS: The study group consisted of 104 women with infertility undergoing diagnostic minilaparoscopy. At the end of the procedure, the treatment group (Group A) was given 10 mL of intraperitoneal 0.25 % bupivacaine (100 mg) and the control group (Group B) given 10 mL of intraperitoneal saline. Post operative pain was recorded with the use of a visual analog scale with scores ranging from 1 to 10 at 2, 4, 6 and 8 h intervals after the surgery. Additional analgesics given to the patients in the post operative period and any other side effects were noted. RESULTS: The treatment group had significantly lower pain scores at 2, 4, 6 and 8 h after the procedure (P < 0.05). The need for post operative analgesics also was significantly lower in the treatment group (P = 0.007). CONCLUSION: Post operative intraperitoneal bupivacaine administration is beneficial for patients undergoing diagnostic minilaparoscopy. It can significantly decrease post operative pain for up to 8 h and reduce the need for additional analgesics.

Preliminary report on therapeutic potential of coal-derived carbon quantum dots against SARS-CoV-2 virus.

Due to the pandemic of COVID-19 and subsequent emerging of new mutant strains, there has been a worldwide hunt for therapeutic and protective agents for its inhibition. In this short communication, for the first time, we report the coal-derived carbon quantum dot (CQD) for the possible therapeutic application against SARS-CoV-2. The synthesized C1-CQD is observed to be safe towards the normal cell line at highest dose, while effectively inhibiting growth of SARS-CoV2 (>95%) with IC50 value of 5.469 µg/mL. Moreover, C1-CQD showed activity against SARS-CoV-2 infection which is comparable to known inhibitory antiviral drug i.e., Remdesivir. These novel findings indicate that coal-based CQDs have highly potent anti-viral activity and could be investigated further for developing cheap and safer alternative therapeutic strategies for inhibition of SARS-CoV-2.

"TB - Mindedness"-the only way to beat "the great mimicker": A case series with atypical presentation of female genital tuberculosis.

BACKGROUND: Incidence of Tuberculosis (TB) cases in India reported in 2019 is 193 per 1 lakh population [National Tuberculosis Elimination Plan (NTEP)]. In India, annual extra pulmonary TB burden is 20-25%, of which 4% of cases are of urogenital origin (Revised National TB Control Programme, 2019; World Health Organization, 2019). The Ministry of Health and Family Welfare has made a target of eliminating tuberculosis by 2025 under the NTEP by the process of identification, notification and treatment of cases. Tuberculosis being a leading cause of infertility in developing countries, employing best clinical practices and being "TB-minded" will also save the patient of enormous anxiety and uncertainity and also decrease the time gap between clinical presentation and diagnosis to optimize fertility outcome. METHODOLOGY: A prospective cohort study of cases presenting with unusual findings and ultimately being diagnosed as genital tuberculosis was conducted in the gynaecology OPD, AIIMS, New Delhi, from November 2020 to November 2021 (1 year). Patients were investigated judiciously, diagnosis made and followed up for their response to anti tuberculosis therapy (ATT). RESULTS: This data comprises of conglomerate of ten cases with unconventional exhibition of genital tuberculosis. 70% of the cases presented with pain lower abdomen not specifically related to menstrual cycle and often confused with IBD. Tubo ovarian mass (70%) mimicking as simple ovarian cyst, ovarian carcinoma or endometriosis was the most common clinical finding we came across.

Efficacy and safety of management of placenta accreta spectrum by transverse uterine fundal incision in a single tertiary care centre: A retrospective study.

Background We assessed the efficacy and safety of management of morbidly adherent placenta by the transfundal uterine incision approach. As a secondary outcome measure, we compared ultrasound and magnetic resonance imaging (MRI) for the diagnosis of adherent placenta. Methods We retrospectively analysed the records of 5 years of women with adherent placenta. Twenty-five women with an antenatal diagnosis of placenta increta and percreta operated by transfundal uterine incision were included. Blood loss, transfusion requirements, operative injuries, and maternal and neonatal intensive care unit (ICU) stay were compared among three different types of adherent placenta. Surgical and other outcome measures were also analysed. Results On antenatal screening with ultrasound, an accurate diagnosis could be achieved in all cases of increta and two-thirds of percreta. Antenatal diagnosis by MRI detected 93.3% of increta and all percreta cases. The mean (SD) gestation at delivery was 34 (4.9) weeks in accreta, 34.9 (2.7) weeks in increta and 31 (4.8) weeks in percreta patients. The mean blood loss encountered intraoperatively was 1012.5 (193.1) ml, 1566.67 (566.52) ml and 1591.67 (629.61) ml in accreta, increta and percreta patients, respectively. Inadvertent bladder injury occurred in 3 women who had placenta percreta invading the bladder. There was no long-term morbidity and no mortality. Conclusion Transfundal incision for delivery of baby is associated with the advantage of avoiding the placenta thereby minimizing blood loss.

Deep learning in water protection of resources, environment, and ecology: achievement and challenges.

The breathtaking economic development put a heavy toll on ecology, especially on water pollution. Efficient water resource management has a long-term influence on the sustainable development of the economy and society. Economic development and ecology preservation are tangled together, and the growth of one is not possible without the other. Deep learning (DL) is ubiquitous in autonomous driving, medical imaging, speech recognition, etc. The spectacular success of deep learning comes from its power of richer representation of data. In view of the bright prospects of DL, this review comprehensively focuses on the development of DL applications in water resources management, water environment protection, and water ecology. First, the concept and modeling steps of DL are briefly introduced, including data preparation, algorithm selection, and model evaluation. Finally, the advantages and disadvantages of commonly used algorithms are analyzed according to their structures and mechanisms, and recommendations on the selection of DL algorithms for different studies, as well as prospects for the application and development of DL in water science are proposed. This review provides references for solving a wider range of water-related problems and brings further insights into the intelligent development of water science.

Chemical and toxicological studies on black crust formed over historical monuments as a probable health hazard.

Studies to date have mostly investigated environmental factors responsible for deterioration of historical monuments. Black crusts formed on historical monuments are considered as factor for deterioration of structures or as an indicator of environmental status of the surrounding area. Black crust formed on historical monuments has never been investigated as a health hazard. Herein, for the first time, we performed in vitro and in vivo toxicology studies of black crust formed on three culturally-rich historical monuments (Rang Ghar, Kareng Ghar, and Talatal Ghar) of the Indian subcontinent to test their toxicological effect. Black crust suspension in ultrapure water was found not to be considerably toxic to the cells upon direct short-term exposure. However, the sub-acute nasal exposure of the black crust suspension in Swiss albino mice produced lung-specific pathologies and mortality. Additionally, structural formation of the black crust along with the speciation of potentially hazardous elements (PHEs), polyaromatic hydrocarbon (PAHs), and other metals were investigated. Overall, these results indicate the potential of black crust deposited on historical monuments as health hazard owing to the atmospheric pollution of the surroundings. However, it may be noted that black crust and its components have very low possibility of health implication unless they are disturbed without proper care.

Profiles of cytokines secreted by isolated human endometrial cells under the influence of chorionic gonadotropin during the window of embryo implantation.

BACKGROUND: Several studies have indicated that human pre-implantation embryo-derived chorionic gonadotropin (hCG) may influence the implantation process by its action on human endometrial epithelial and stromal cells. Despite reports indicating that hCG acts on these cells to affect the production of several cytokines and growth factors (e.g., MIF, IGF-I, VEGF, LIF, IL-11, GMCSF, CXL10 and FGF2), our understanding of the integral influence of hCG on paracrine interactions between endometrial stromal and epithelial cells during implantation is very limited. METHODS: In the present study, we examined the profile of 48 cytokines in the conditioned media of primary cell cultures of human implantation stage endometrium. Endometrial epithelial cells (group 1; n = 20), stromal cells (group 2; n = 20), and epithelial plus stromal cells (group 3; n = 20) obtained from mid-secretory stage endometrial samples (n = 60) were grown on collagen and exposed to different doses (0, 1, 10 and 100 IU/ml) of rhCG for 24 h in vitro. Immunochemical and qRT-PCR methods were used to determine cytokine profiles. Enrichment and process networks analyses were implemented using a list of cytokines showing differential secretion in response to hCG. RESULTS: Under basal conditions, endometrial epithelial and stromal cells exhibited cell type-specific profiles of secreted cytokines. Administration of hCG (100 IU) resulted in significantly (P < 0.05) different cytokine secretion profiles indicative of macropinocytic transport (HGF, MCSF) in epithelial cells, signal transduction (CCL4, FGF2, IL-1b, IL-6, IL-17, VEGF) in stromal cells, and epithelial-mesenchymal transition (FGF2, HGF, IL-1b, TNF) in mixed cells. Overall, the administration of hCG affected cytokines involved in the immune response, chemotaxis, inflammatory changes, proliferation, cell adhesion and apoptosis. CONCLUSIONS: CG can influence the function of the endometrium during blastocyst implantation via its differential action on endometrial epithelial and stromal cells. CG may also affect complex paracrine processes in the different endometrial cell types.

Successful outcome in a rare case of pregnancy with familial hypercholesterolemia and dilated cardiomyopathy.

Familial hypercholesterolemia is a rare disorder characterized by high cholesterol levels and early cardiovascular disease. Early detection and treatment with statins and other hypolipidemic agents are effective in heterozygous patients. Low-density lipoprotein apheresis and liver transplantation are treatment options in homozygous familial hypercholesterolemia. We report a case of a 27-year-old pregnant woman with familial hypercholesterolemia who presented with breathlessness and swelling in the joints. She had been taking statins previously, which were stopped and she had been put on low-lipid and low-residue diet to reduce the risk of acute coronary event and sudden intrauterine death. She was found to have dilated cardiomyopathy with 25% ejection fraction. At 36 weeks of gestation, we carried out cesarean section in view of poor biophysical profile. Familial hypercholesterolemia is a very rare disorder with only a few cases reported in the published work during pregnancy. Statins are contraindicated during pregnancy and diet modification remains the mainstay of therapy.