Evidence for the Oocyte Mosaicism Selection model on the origin of Patau syndrome (trisomy 13).

INTRODUCTION: In 2008, Hultén et al hypothesized that maternal ovarian trisomy 21 mosaicism might be the primary causative factor for fetal Down syndrome. We hypothesize that this theory can be extended to trisomy 13. MATERIAL AND METHODS: We collected fetal ovarian tissue from seven female fetuses between 16 and 23 gestational weeks, following the termination of the pregnancy for non-genetic reasons. All procedures were performed with informed consent and ethical approval from the local ethics committee. We used touch preparation techniques from fetal ovarian tissues and an anti-stromal antigen 3 antibody against the meiosis-specific stromal antigen 3 protein to differentiate between germ cells, ovarian stromal cells and the cells entering their first meiotic prophase. We used fluorescence in situ hybridization analysis to determine chromosome 13 numbers in each cell. RESULTS: We were able to detect a proportion of trisomy 13 cells in all cases. The average incidence of trisomy 13 cells was 2.04% in stromal antigen 3-positive and 0.91% in the stromal antigen 3-negative cells. The number of the trisomic cells increased significantly with gestational age (for stromal antigen 3-positive cells r = 0.93, P = 0.0038, for stromal antigen 3-negative cells r = 0.85, P = 0.0071). CONCLUSIONS: This study indicates that besides trisomy 21, the Oocyte Mosaicism Selection model could be extended to trisomy 13 as well. The crucial factor for trisomy 13 seems to be the pre-meiotic/mitotic trisomy 13 mosaicism, leading to a so-called secondary meiotic nondisjunction of those oocytes having three copies of chromosome 13.

[Longer oral contraception history as a possible preventive factor against fetal trisomy 21 in advanced maternal age pregnancies]. / A terhességet megelozoen alkalmazott hosszabb távú orális fogamzásgátlás mint a magzati 21-es triszómia lehetséges kockázatcsökkento tényezoje idos anyai életkorban vállalt terhességben.

Down syndrome is the most common autosomal chromosomal abnormality. According to the classical interpretation, it is the result of meiotic nondisjunction. Its occurrence is more common in advanced maternal age. Despite intensive research, pathophysiology of this genetic disorder is not fully understood. According to recent studies, a different kind of mechanism may be found in the background of trisomy 21 than was previously considered. Based on the ovarian mosaicism model, the cause of trisomy 21 (or any common trisomy) is a segregation error of a chromosome in premeiotic mitosis. The cell entering meiosis will be an oocyte with preexisting trisomy, where its (so-called "secondary") nondisjunction is essential. Maturation of the trisomic oocytes appears to fall behind the disomic oocytes, resulting in their relative accumulation in the ovaries as time progresses. The ratio of trisomic/disomic cells becomes less favorable in maternal maturity. If ovulation is inhibited - although the number of oocytes will continue to decline due to apoptosis - it can be assumed that the trisomic/disomic oocyte ratio remains more favorable with the progression of age. In our summary report, presenting and updating our previous data, we would like to propose that - according to ovarian mosaicism model - long-term oral contraception in the anamnesis may be beneficial in pregnancies with advanced maternal age. Orv Hetil. 2018; 159(28): 1146-1152.

[Diverticulosis and diverticulitis of the vermiform appendix. Report of a case and review of the literature]. / A féregnyúlvány diverticulosisa, diverticulitise. Esetismertetés és irodalmi áttekintés.

Diverticulitis of the vermiform appendix is a rare disease with clinical features often similar to conventional acute appendicitis. The importance of appendiceal diverticulosis is the fact that it can lead to an early and a higher incidence of perforation and therefore a higher mortality rate, in contrast to acute appendicitis alone. In this study we present the clinicopathology, diagnosis and therapy of the disease with a review of the literature. A 65-year-old woman presented to the emergency department with a 48-hour history of intermittent pain in the right iliac fossa. Abdominal ultrasound raised the possibility of acute appendicitis but because of the relative asymptomatic state of the patient, the lack of fever and rebound tenderness we started observation. After 2 days with episodic abdominal pain, the patient was taken to the operating theatre for laparoscopic exploration. Intraoperatively, multiple diverticula were noted on the appendix and appendectomy was performed. Histopathological examination revealed diverticulosis and inflammation of the appendiceal wall. Due to the possible complications, the difficult preoperative diagnosis and its frequent association with appendiceal neoplasm, appendiceal diverticulosis requires special attention. For asymptomatic cases, incidentally diagnosed intraoperatively or discovered by radiology prophylactic appendectomy is recommended. Orv Hetil. 2018; 159(19): 768-772.

Effect of extended oral contraception use on the prevalence of fetal trisomy 21 in women aged at least 35 years.

OBJECTIVE: To study factors influencing the number of ovulations in reproductive life as risk factors for common trisomies. METHODS: The present observational study examined data from genetic counseling sessions performed at the 1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary, between September 1, 2013, and September 1, 2015, and retrieved data on patients of advanced maternal age (≥35 years) who had fetal trisomy 21, 18, or 13 confirmed. Consecutive patients of advanced maternal age with genetic amniocentesis-confirmed healthy fetal karyotypes were also included as a control group. Medical record details were confirmed through telephone interviews with patients; the estimated ovulation number was calculated and compared among patients, as were factors contributing to the number of ovulations each patient had. RESULTS: Data from 12 776 genetic counseling situations were examined; 35 patients with fetal trisomies and 100 patients in the control group were interviewed. Shorter mean length of oral contraceptive pill use before trisomic pregnancy (P<0.001) and a higher estimated ovulation number (P=0.012) were identified among patients with pregnancies with fetal trisomies. CONCLUSION: Fewer ovulatory cycles, potentially resulting from longer oral contraceptive pill use, was associated with healthy fetal karyotypes among patients of advanced reproductive age.

[Rare case of a pregnancy in a woman with paroxysmal nocturnal hemoglobinuria. Case report]. / Paroxysmalis nocturnalis haemoglobinuriával szövodött várandósság ritka esete.

Paroxysmal nocturnal hemoglobinuria is a rare hematological disease. It is associated with increased maternal and fetal complications to such an extent that pregnancy has been considered relatively contraindicated in woman with paroxysmal nocturnal haemoglobinuria. Recently, eculizumab, a monoclonal antibody, has been shown to decrease complications during pregnancies. The highest risk is thromboembolic complication and, therefore, anticoagulant is a standard therapy during pregnancy. In the presented case, a 29-year-old woman with a 5-year history of paroxysmal nocturnal haemoglobinuria had a pregnancy. It was her first pregnancy and was complicated by a sinus thrombosis at the 11th gestational week. After the introduction of eculizumab treatment, the remaining period of pregnancy and delivery were uncomplicated. There are only a few cases in the literature about pregnancy in woman with paroxysmal nocturnal hemoglobinuria who are treated with eculizumab. This monoclonal antibody seems to be safe and it likely prevents many of the complications otherwise observed.

[Next generation sequencing and its applications in non-invasive prenatal testing of aneuploidies]. / Új generációs szekvenálás és használata az aneuploidiák nem invazív praenatalis vizsgálatában.

The development of the new generation sequencing techniques brought a new era in the field of DNA sequencing, that also revolutionized the prenatal screening for aneuploidy. In order to provide a more complete view, the authors describe some first generation methods as well as the theoretical and technical background of the next generation methods. In the second part of this review, the authors focuse on non-invasive prenatal testing, which is a fetal cell-free DNA based method requiring advanced sequencing procedures. After discussing the theoretical and technical background, the authors review current application and utility of non-invasive prenatal testing. They conclude that non-invasive prenatal testing is the most effective screening test in high risk pregnancies and its efficiency can be justified in studies involving low risk pregnancies as well.

Surgical treatment of lymph node metastases in stage IB cervical cancer. The laterally extended parametrectomy (LEP) procedure: experience with a 5 year follow-up.

INTRODUCTION: In 2003, we published our preliminary experience with the use of an operative technique (laterally extended parametrectomy, the LEP procedure) without adjuvant therapy, in the treatment of 29 stage IB, cervical cancer patients with pelvic lymph node metastases. In our present paper, by an extended recruiting period, with a completed 5 year follow up, we studied the outcome of LEP operations, used with the same indications. METHODS: In 70 out of 106 LEP-Wertheim operated patients, no adjuvant treatment was used. In 36 patients, where histology suggested tumor spread beyond the threshold of our surgery, adjuvant chemo-radiotherapy was advised. 5 year follow up was completed (without any patient lost for follow up) for the whole cohort of patients. RESULTS: In 70 patients treated by LEP procedure alone, the overall 5-year survival was 91.4%. For those 36 patients, who were excluded due to disease spread above study criteria, 5 year survival was 44%. Complications in 10% of the cases necessitated a second operation. Apart from transient hyper continence and one case of permanent incontinence, no severe quality of life consequence of the operation was observed. CONCLUSIONS: Our results suggest that in two-thirds of pelvic lymph node positive, stage IB cervical cancer cases surgery alone could provide equal or better survival (without the toxicity of chemo-radiotherapy), than any kind of multimodality treatment alternatives. LEP procedure should be considered a treatment option for stage IB cervical cancer patients with pelvic lymph node metastases.