Association between fetal fraction of cell-free DNA and adverse pregnancy outcomes.

PURPOSE: To determine the association between fetal fraction (FF) levels in cell-free fetal DNA (cffDNA) testing and adverse pregnancy outcomes. METHODS: This retrospective cohort study, conducted at a single center, involved 2063 pregnant women with normal 1st and 2nd trimester non-invasive prenatal test (NIPT) results between 2016 and 2021. Pregnancy outcomes were examined by determining the < 4% and < 5th percentile (3.6%) cut-off values for low fetal fraction (LFF). Pregnancy outcomes were also examined by dividing the FF into population-based quartiles. Adverse pregnancy outcomes were pregnancy-induced hypertensive diseases (PIHD), gestational diabetes mellitus (GDM), spontaneous preterm birth (PTB), intrahepatic cholestasis of pregnancy (ICP), small for gestational age (SGA), large for gestational age (LGA), low birth weight (LBW), macrosomia, and 1st and 5th minutes low APGAR scores (< 7). RESULTS: PIHD was significantly higher in LFF (< 4% and < 5th percentile) cases (p = 0.015 and p < 0.001, respectively). However, in population-based quartiles of FF, PIHD did not differ significantly between groups. Composite adverse maternal outcomes were significantly higher in the FF < 4% group (p = 0.042). When analyzes were adjusted for maternal age, BMI, and gestational age at NIPT, significance was maintained at < 4%, < 5th percentile LFF for PIHD, and < 4% LFF for composite adverse maternal outcomes. However, there was no significant relationship between LFF with GDM, ICP and PTB. Additionally, there was no significant association between low APGAR scores, SGA, LGA, LBW, macrosomia, and LFF concerning neonatal outcomes. CONCLUSION: Our study showed that LFF in pregnant women with normal NIPT results may be a predictor of subsequent PIHD.

Transforming pharmaceutical education: A needs-based global analysis for policy development.

Background: A needs-based approach is desirable for the transformation of pharmaceutical education, and to link pharmaceutical education with the health needs of populations and national priorities. There are varying levels of data in the literature on the status of pharmaceutical education in all six World Health Organization (WHO) regions, especially in the context of needs identification and evidence-based policy interventions. The framework for this study was the FIP Development Goals. Objectives: The aim of the study was to develop evidence-based policies through a needs-based approach for pharmaceutical education transformation nationally, regionally and globally by addressing the following objectives: 1. Identify global and regional needs in pharmaceutical education, through a regional SWOT analysis and prioritization of FIP development goals; 2. Develop valid and credible regional roadmaps for pharmaceutical education advancement according to the identified prioritized goals and 3. Develop a global call to action as a policy intervention for advancing pharmaceutical education. Methods: This study was conducted between 2020 and 2021 using a mixed methods approach. Surveys of higher education institutions and a series of qualitative interviews were conducted with national professional leadership organizations, with further regional workshops having 284 participants recruited from the International Pharmaceutical Federation (FIP) membership base, spanning all six WHO regions. Results: Eleven out of 21 FIP DGs were identified as priorities for regional roadmaps and FIP DG 1 (Academic capacity) was identified as a priority in four regions. All regions had distinctive results with an area of commonality between them. There were common weaknesses in the adoption of competency-based education and inter-professional education. Conclusions: It is critical for every country and region to develop needs- and evidence-based policies for the transformation of pharmaceutical education, for which FIP DGs provide a systematic framework.

Liquid biopsy markers for early diagnosis of brain metastasis patients with breast cancer by metabolomics.

Introduction: Breast cancer is the most common cancer in women and is the second most common cause of cancer related mortality. Metabolomics, the identification of small metabolites, is a technique for determining the amount of these metabolites. Objectives: This study aimed to identify markers for the early diagnosis of brain metastasis by metabolomic methods in breast cancer patients. Methods: A total of 88 breast cancer patients with distant metastases were included in the study. The patients were divided into two groups according to their metastasis status: patients with brain metastases and distant metastases without any brain metastases. Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-qTOF-MS) and gas chromatography-mass spectrometry (GC-MS) analysis methods were used for metabolomic analyses. Results: 33 of them, 88 patients had brain metastasis, and 55 patients had distant metastases without brain metastasis. A total of 72 and 35 metabolites were identified by the GC-MS and LC-qTOF-MS analysis, respectively. 47 of them were found to be significantly different in patients with brain metastasis. The pathway analysis, performed with significantly altered metabolites, showed that aminoacyl tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, alanine, aspartate, and glutamate metabolism, arginine biosynthesis, glycine, serine, and threonine metabolism pathways significantly altered in patients with brain metastasis. Predictive accuracies for have identifying the brain metastasis were performed with receiver operating characteristic (ROC) analysis, and the model with fifteen metabolites has 96.9% accuracy. Conclusions: While these results should be supported by prospective studies, these data are promising for early detection of brain metastasis with markers in liquid biopsy samples.

Experiences in the molecular genetic and histopathological evaluation of calpainopathies.

Calpainopathy is mainly characterized by symmetric and progressive weakness of proximal muscles. Several reports showed that the most common LGMD subtype is LGMDR1 or calpainopathy, which had previously been defined as LGMD2A. Until now, more than 500 likely pathogenic/pathogenic variants in the CAPN3 gene have been reported. However, a clear genotype-phenotype association had not yet been established and this causes major difficulties in predicting the prognosis in asymptomatic patients and in providing genetic counseling for prenatal diagnosis. In this report, we aimed to add new data to the literature by evaluating 37 patients with likely pathogenic/pathogenic variants for the detected variants' nature, patients' phenotypes, and histopathological features. As a result, the general clinical presentation of the 23 different variants was presented, the high frequency of NM_000070.3:c.550delA mutation in Exon 4 was discussed, and some novel genotype-phenotype associations were suggested. We have underlined that calpainopathy can be misdiagnosed with inflammatory myopathies histopathologically. We have also emphasized that, in young or adult patients with mild to moderate proximal muscle weakness and elevated CK levels, calpainopathy should be the first suspected diagnosis.

JAK2V617F, CALR and MPL515L/K mutations and plateletcrit in essential thrombocythemia: A single centre's experience.

AIMS: JAK2V617F (JAK2), calreticulin (CALR) and MPL515L/K (MPL) mutations are important in essential thrombocythemia (ET) and may be associated with various clinical consequences of the disease. This study aimed to compare the clinical and haematological parameters of ET patients regarding the mentioned mutations and the role of plateletcrit (PCT). METHODS: Seventy patients who were diagnosed with ET between 2005 and 2017 in a single centre were included in this descriptive study. The initial symptoms and clinical findings were retrieved from the electronic database. JAK2 gene V617F mutations, MPL gene exon 10 mutations and CALR gene exon 9 DNA sequence analyses were performed. Forty-one healthy volunteers were included to perform ROC curve analysis for interpreting PCT value. RESULTS: The distributions of patients according to the mutations were as follows: Thirty-seven (52.9%) patients were JAK2-positive, 15 (21.4%) were CALR-positive, 2 (2.8%) patients were positive for both CALR and JAK2, and 1 (1.4%) was only MPL-positive. Fifteen (21.4%) patients were triple-negative. The ET patients with JAK2 mutation showed a higher level of haemoglobin at the time of diagnosis. The ET patients with CALR mutation presented with higher platelet and LDH levels (P = .002 and P = .001, respectively). The PCT level was higher in the CALR-positive group when compared to the others (P = .026). A sensitivity value of 97.6% and specificity value of 98.6% were determined regarding PCT% at a cut-off value of 0.37 in ET patients. In CALR-positive patients, the sensitivity and specificity values were 100% for the PCT at a cut-off value of 0.42%. CONCLUSION: We determined that the platelet count and blood LDH level was high in the ET patient group with CALR mutation. Besides, we found that the blood haemoglobin level was higher in the ET patient group with JAK2 mutation. Additionally, the PCT level was higher in the CALR group when compared to the other patient groups.

Euglycemic Diabetic Ketoacidosis Associated with Empagliflozin Use in the Course of the SARS-Cov-2 Pandemic.

Sodium glucose cotransporter 2 (SGLT2) inhibitors are among the new generation oral anti-diabetic drugs that have started to be used in the treatment of type 2 diabetes mellitus. Although these drugs are highly beneficial, life-threatening side effects such as euglycemic diabetic ketoacidosis (eDKA) are reported with their use. In eDKA, metabolic acidosis and anion gap appear in blood gases and serum glucose in less than 200 mg/dl.This can delay diagnosis and treatment. In our case, a 42-year female presented to the Emergency Room with nausea and vomiting. It was observed that the patient had been using empagliflozin for a year. Her blood gas analyses and laboratory tests showed metabolic acidosis and ketosis. The patient was initially suspected to be a case of coronavirus disease-2019 (COVID-19) complicating the course of diabetes, finally it was diagnosed as a case of eDKA due to empagliflozin use. We noticed that during the current pandemic, some other diagnoses can be missed or their diagnosis can be delayed. Key Words: Euglycemic diabetic ketoacidosis, Empagliflozin, COVID-19, Diabetes mellitus.

Impact of next-generation sequencing panels in the evaluation of limb-girdle muscular dystrophies.

INTRODUCTION: Limb-girdle muscular dystrophy (LGMD) is the fourth most common muscular dystrophy, with progressive proximal muscle weakness. However, a large number of neuromuscular conditions are similarly presented. Because of this, the use of high-throughput methods such as next-generation sequencing (NGS) is important in the evaluation of LGMD. METHODS: In this report, we applied a custom target capture-based NGS panel covering 31 LGMD-associated genes (MYOT, LMNA, CAV3, DES, DNAJB6, FLNC, CAPN3, DYSF, SGCG, SGCA, SGCB, SGCD, TCAP, TRIM32, FRKP, TTN, POMT1, ANO5, FKTN, POMT2, POMGnT1, DAG1, PLEC, GAA, GMPPB, HNRNPDL, TNPO3, LIMS2, POMK, TRAPPC11, ISPD) in 74 patients suspected of LGMD. RESULTS: In 25 (33.8%) out of 74 patients analyzed, one or more pathogenic/likely pathogenic variants in 13 different genes were detected. Six of the patients had the variants that were not found in databases and literature; thus, they were interpreted as novel pathogenic variants. DISCUSSION: The diagnosis rate achieved (33.8%) is consistent with previous literature reports and underlines the efficiency and importance of NGS technology in the molecular genetic evaluation of LGMD.

Molecular genetic evaluation of NLRP3, MVK and TNFRSF1A associated periodic fever syndromes.

Periodic fever syndromes (PFSs) are a family of clinical disorders, which are characterized by recurrent episodes of fever in the absence of microbial, autoimmune or malign conditions. Most common types of PFSs are associated with four genes: MEFV, MVK, TNFRSF1A and NLRP3. This paper aims to add new data to the genotype-phenotype association of MVK-, TNFRSF-1A- and NLRP3-associated PFSs. A total number of 211 patients were evaluated. Two different approaches were used for the molecular genetic evaluation of MVK-, TNFRSF-1A- and NLRP3-associated PFSs. For the first 147 patients, Sanger sequence analysis of selected exons of MVK, TNFRSF1A and NLRP3 genes was done. For subsequent 64 patients, targeted NGS panel analysis, covering all exons of MVK, TNFRSF1A and NLRP3 genes, was used. A total number of 48 variants were detected. The "variant detection rate in index patients" was higher in the NGS group than Sanger sequencing group (19% vs. 15,1%). For the variant positive patients, a detailed genotype-phenotype table was built. In PFSs, lack of correlation exists between genotype and phenotype in the general population and even within the families. In some cases, mutations behave differently and yield unexpected phenotypes. In this study, we discussed the clinical effects of eight different variants we have detected in the MVK, TNFRSF1A and NLRP3 genes. Four of them were previously identified in patients with PFS. The remaining four were not reported in patients with PFS. Thus, we had to interpret their clinical effects by analysing their frequencies and in silico analysis predictions. We suggest that new studies are needed to evaluate the effects of these variants more clearly. To be able to demonstrate a clearer genotype-phenotype relationship, all PFS-related genes should be analysed together and the possibility of polygenic inheritance should be considered.

Investigating KRAS/BRAF mutation in oropharyngeal squamous cell carcinomas: a preliminary study.

OBJECTIVES: This study aims to investigate the role of KRAS/BRAF gene mutation in the pathogenesis of oropharyngeal squamous cell carcinoma (OSCC). PATIENTS AND METHODS: A total of 26 OSCC patients (23 males, 3 females; mean age 60 years; range 41 to 77 years) diagnosed between January 2003 and November 2013 were included in the study. The methods used in our study were quantitative fluorescence polymerase chain reaction for KRAS/BRAF mutation analysis. RESULTS: Ten of the tumors were located at the tongue base, 12 in the tonsil and four at the floor of mouth. The mean tumor size was 3.8 cm. Six of the tumors were well differentiated, 18 were moderately differentiated and two were poorly differentiated. All cases were analyzed for KRAS and BRAF gene mutations and none of them showed gene mutations. CONCLUSION: We could not find any relation between OSCC and KRAS/BRAF gene mutations in our short case file. The role of mutations should be analyzed in larger series in OSCC to predict new targeted therapy modalities.

Determination of HER2 and p53 Mutations by Sequence Analysis Method and EGFR/Chromosome 7 Gene Status by Fluorescence in Situ Hybridization for the Predilection of Targeted Therapy Modalities in Immunohistochemically Triple Negative Breast Carcinomas in Turkish Population.

Triple negative breast cancer (TNBC), an agressive subtype accounts nearly 15 % of all breast carcinomas. Conventional chemotherapy is the only treatment modality thus new, effective targeted therapy methods have been investigated. Epidermal growth factor receptor (EGFR) inhibitors give hope according to the recent studies results. Also therapeutic agents have been tried against aberrant p53 signal activity as TNBC show high p53 mutation rates. Our aim was to detect the incidence of mutations/amplifications identified in TNBC in our population. Here we used sequence analysis to detect HER2 (exon 18-23), p53 (exon 5-8) mutations; fluorescence in situ hybridization (FISH) method to analyse EGFR/chromosome 7 centromere gene status in 82 immunohistochemically TNBC. Basaloid phenotype was identified in 49 (59.8 %) patients. EGFR amplification was noted in 5 cases (6.1 %). All EGFR amplified cases showed EGFR overexpression by immunohistochemistry (IHC). p53 mutations were identified in 33 (40.2 %) cases. Almost 60 % of the basal like breast cancer cases showed p53 mutation. Only one case showed HER2 mutation (exon 20:g.36830_3). Our results showed that gene amplification is not the unique mechanism in EGFR overexpression. IHC might be used in the decision of anti-EGFR therapy in routine practice. p53 mutation rate was lower than the rates reported in the literature probably due to ethnic differences and low sensitivity of sanger sequences in general mutation screening. We also established the rarity of HER2 mutation in TNBC. In conclusion EGFR and p53 are the major targets in TNBC also for our population.

Blastoid variant mantle cell lymphoma with complex karyotype including 11q duplication.

We describe a case of blastoid mantle cell lymphoma with a complex karyotype. The blastoid variant is a rare type of non-Hodgkin lymphoma exhibiting an aggressive clinical course. Mantle cell lymphoma is a distinct entity of mature B-cell neoplasms genetically characterized by the presence of t(11;14). In the present case, conventional analysis revealed structural abnormalities of chromosomes 2, 4, 6, 10, 13, and 19, along with 3 additional marker chromosomes. The derivative 1 chromosome determined in the case was a result of t(1p;11q). Our interesting finding was the presence of a different translocation between 11q and chromosome 1 in addition to t(11;14). Thus, the resulting 11q duplication was believed to additionally increase the enhanced expression of cyclin D1 gene, which is responsible in the pathogenesis of the disease. Fluorescence in situ hybridization method by the t(11;14) probe revealed clonal numerical abnormalities of chromosomes 11 and 14 in some cells. The detection of multiple abnormalities explains the bad prognosis in the present case. On the basis of our findings, we can easily conclude that results of cytogenetic analyses of similar mantle cell lymphoma patients would provide clues about new responsible gene regions and disease prognosis. In conclusion, it has been suggested that the presence of multiple chromosomal aberrations in addition to the specific t(11;14) may have a negative impact on clinical course and survival rate.

Presence of matrix metalloproteinase-2 and tissue inhibitor matrix metalloproteinase-2 gene polymorphisms and immunohistochemical expressions in intracranial meningiomas.

OBJECT: Meningiomas are benign extraaxial tumors with a slow progression. Some of them, in spite of being benign in nature, may show an aggressive progression pattern. To investigate the behavioral characteristics of meningiomas, researchers have studied matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), interstitial collagens, proteins, vascular endothelial growth factors (VEGF), and tumor necrosis factors. METHODS: In this study, the authors investigated MMP2 and TIMP2 gene polymorphisms in formalin-fixed paraffin-embedded tissue samples obtained from meningioma patients who had previously undergone surgery at the authors' institution. In addition, brain invasion, Ki-67 index, and MMP-2 and TIMP-2 expressions were investigated using immunohistochemical methods. MMP2 (735C>T, 1575G>A, 1306C>T) and TIMP2 (418G>C, 303C>T) gene polymorphisms were investigated from paraffin-embedded tissue sections using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: There were statistically significant differences between genotype (p = 0.001) and allele frequencies (p = 0.001 and OR 7.4 [95% CI 1.5-36.2]) in patient and control groups for MMP2 1306C>T polymorphism. The authors did not find a statistically significant difference for other polymorphisms. GA genotype was found to be more frequent when brain invasion was suspected for MMP2 1575G>A polymorphism (p = 0.006). There was not a statistically significant difference for other MMP2 or TIMP2 gene polymorphisms. CONCLUSIONS: The authors' results support the importance of MMPs and their tissue inhibitors in meningioma pathogenesis. In future studies, these gene polymorphisms, especially MMP2 1306C>T and 1575G>A, should be investigated for meningioma or brain invasion susceptibility in larger study groups.

A comparison of muscle strength and endurance, exercise capacity, fatigue perception and quality of life in patients with chronic obstructive pulmonary disease and healthy subjects: a cross-sectional study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has significant systemic effects that substantially impact quality of life and survival. The purpose of this study was to assess and compare peripheral muscle strength and endurance, exercise capacity, fatigue perception and quality of life between patients with COPD and healthy subjects. METHODS: Twenty COPD patients (mean FEV1 49.3 ± 19.2%) and 20 healthy subjects were included in the study. Pulmonary function testing and six-minute walk test (6MWT) were performed. Peripheral muscle strength was measured with a hand-held dynamometer, peripheral muscle endurance was evaluated with sit-ups, squats and modified push-ups tests. Fatigue perception was assessed using the Fatigue Impact Scale (FIS) and Fatigue Severity Scale (FSS). General quality of life was determined with the Nottingham Health Profile (NHP), and cough-specific quality of life was evaluated with the Leicester Cough Questionnaire (LCQ). RESULTS: Pulmonary functions, strength of shoulder abductor and flexor muscles, numbers of sit-ups and squats, 6MWT distance and 6MWT% were significantly lower in COPD patients than in healthy subjects (p < 0.05). FIS psychosocial sub-dimension and total scores, NHP scores for all sub-dimensions except pain sub-dimension of the COPD group were significantly higher than those of healthy subjects (p < 0.05). The LCQ physical, psychological and social sub-dimensions and total scores were significantly lower in COPD patients than in healthy subjects (p < 0.05). CONCLUSIONS: Pulmonary functions, peripheral muscle strength and endurance, exercise capacity and quality of life were adversely affected in patients with COPD. There are greater effect of fatigue on psychosocial functioning and general daily life activities and effect of cough on the quality of life in patients with COPD. This study supports the idea that COPD patients must be evaluated in a comprehensive manner for planning pulmonary rehabilitation programs.

Methylation profile analysis of DNA repair genes in hepatocellular carcinoma with MS-MLPA.

Hepatocellular carcinoma (HCC) is one of the rare tumors with well-defined risk factors. The multifactorial etiology of HCC can be explained by its complex molecular pathogenesis. In the current study, the methylation status of 7 genes involved in DNA repair mechanisms, namely MLH1, PMS2, MSH6, MSH2, MGMT, MSH3, and MLH3, was investigated in tumor samples from HCC patients, using the methylation-specific-multiplex ligated probe amplification method and the results were correlated with available clinical findings. The most common etiological factor in these cases was the presence of hepatitis B alone (47.2%). Among the 56 cases that were studied, promoter methylation was detected in at least one of the genes in 27 (48.2%) cases, only in 1 gene in 13 (23.2%) cases, and in >1 gene in 14 (25%) cases. Of the 7 genes investigated, methylation was most frequently observed in MSH3, in 14 (25%) cases. Methylation of at least 1 gene was significantly more frequent in patients with single tumors than multifocal tumors. There were significant differences regarding hepatitis B status, Child Class, tumor number, grade, and TNM stage in cases where PMS2 methylation was detected. Our results suggest that methylation of genes involved in mismatch repair may be responsible in the pathogenesis of HCC, and evaluating changes in multiple genes in these pathways simultaneously would be more informative. Despite being a robust and relatively inexpensive method, the methylation-specific-multiplex ligated probe amplification assay could be more extensively applied with improvements in the currently intricate data analysis component.

Fluorescence in situ hybridization analysis of the hTERC region in acute myeloid leukemia patients.

OBJECTIVE: The telomerase RNA component (hTERC) gene is located at 3q26. Increased hTERC gene expression has been frequently observed and amplification was shown using fluorescence in situ hybridization (FISH) in different cancers. The aim of this study was to determine whether hTERC gene amplification is detectable by FISH in acute myeloid leukemia (AML) cells. METHODS: FISH and karyotype results at the time of diagnosis of 23 adult AML patients were retrospectively evaluated. Additionally, fixed cells were hybridized with an hTERC region-specific FISH probe to determine gene amplification. RESULTS: Ten of the 23 patients had a normal karyotype and 6 had an abnormal karyotype. hTERC region amplification was not observed in any of the patients. CONCLUSION: Although it was reported that hTERC gene amplification may partially contribute to increased telomerase expression and activity in leukemic cells, it is not possible to make such a conclusion based on the results of the this study, as hTERC amplification was not observed in the study group. This suggests that increased telomerase activity via gene amplification in the development of AML may not be as important a factor as it is in solid tumors.

First-trimester ultrasonography revealed a gestational sac featuring cystic spaces and no visible embryo: a case of trisomy 7.

Ultrasound examination in early pregnancy has steadily gained importance and is now routine for most women in the first trimester. The sonographic features of early trisomy 7 pregnancies are not well characterized. We present a case of trisomy 7 in which early pregnancy ultrasound revealed a gestational sac featuring cystic spaces and no visible embryo. Based on comparison with a previously reported case of trisomy 7 featuring a multicystic anembryonic gestational sac we suggest that this ultrasonographic finding may be a sign of trisomy 7.

Her-2/neu gene amplification in paraffin-embedded tissue sections of meningioma patients.

AIM: Meningiomas arise from the meningoendothelial cells and are one of the most common tumors of the central nervous system. The HER-2/neu gene is located on the 17q11.2-q12 chromosome region and encodes an epidermal growth factor receptor. HER- 2/neu gene amplification and/or over expression have been studied most widely in breast carcinomas. Previous studies have shown the importance of HER-2/neu gene amplification on the prognosis of meningioma cases. In this study, we aimed to detect HER-2/neu gene copy number in archive materials of 55 meningioma patients by fluorescent in situ hybridization (FISH). MATERIAL AND METHODS: The patients included in the study had undergone surgery in the neurosurgery department of our hospital between 1999 and 2002. Tissue samples were classified histologically according to WHO 2007 guidelines. Interphase FISH was performed on 3 to 4microm thick paraffin embedded tissue sections for the detection of HER- 2/neu gene amplification status. RESULTS: We found HER-2/neu gene amplification in 7 (12.73%) patients. Another 2 patients had only one signal for the HER-2/neu region. We confirmed this finding by a second hybridization with the chromosome 17p13.1 (p53) probe. CONCLUSION: According to our results, HER-2/neu amplification could be regarded as an additional genetic factor playing role in meningioma pathogenesis together with known chromosomal abnormalities.

Chromosome heteromorphisms: an impact on infertility.

INTRODUCTION: Cytogenetic heteromorphisms are described as heritable variations at specific chromosomal regions without a proven impact on phenotype. MATERIALS AND METHODS: We compared the presence of chromosome heteromorphisms in the karyotypes of two patient groups. The first group of patients consisted of 276 individuals of 138 infertile couples. The second group, consisted of 1,130 amniocentesis samples. This group was considered to be a sample of the fertile population, as the fetus being karyotyped is the result of a spontaneous pregnancy. Fetal karyotyping was made due to the standard indications for prenatal diagnosis, such as abnormal maternal serum screening results. RESULTS AND DISCUSSION: Eighteen infertile patients (6.52%) and twenty fetuses (1.77%) were found to have chromosome heteromorphisms. The difference between the two groups was statistically significant (p < 0.0001). CONCLUSION: These results are consistent with other similar studies that suggest the yet undefined relationship between chromosome heteromorphisms and infertility.