Emergency cerclage using double-level versus single-level suture in the management of cervical insufficiency (Cervical Occlusion double-level Stitch Application, COSA): study protocol for a multicentre, non-blinded, randomised controlled trial.

INTRODUCTION: Cervical insufficiency accounts for 15% of recurrent pregnancy losses between 16 and 28 weeks of gestation. The aim of the study is to verify the effectiveness of emergency double-level cerclage with vaginal progesterone in cervical insufficiency treatment in terms of the prevention of preterm delivery before 34 weeks of gestation. METHODS AND ANALYSIS: This trial is a multicentre, non-blinded, randomised study with 1:1 allocation ratio. The study is conducted at tertiary perinatal care departments in Poland. It will include patients with cervical insufficiency with the fetal membranes visible in the open cervical canal or protruding into the vagina between 16+0 and 23+6 weeks of pregnancy. They will be randomised into two arms: emergency single-level cerclage with vaginal progesterone or double-level cerclage with vaginal progesterone. All will be administered antibiotics and indomethacin. The primary outcome is the rate of deliveries below 34+0 weeks of gestation, while secondary outcomes include gestational age at delivery, neonatal outcomes, maternal outcomes according to the Core Outcome Set for Evaluation of Interventions to Prevent Preterm Birth and cerclage procedure complications. The planned number of participants according to the power analysis is 78. ETHICS AND DISSEMINATION: The study protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials statement. It was created according to the requirements of the Declaration of Helsinki for Medical Research involving Human Subject. Ethical approval was obtained from the Ethics Committee of the Centre of Postgraduate Medical Education (no. 1/2022). The study protocol was approved and published by ClinicalTrials.gov (posted on 24 February 2022). All participants gave a written informed consent. After completion of the study its results will be published in a peer-reviewed English language journal. TRIAL REGISTRATION: NCT05268640.

Anti-Müllerian hormone as a marker of abortion in the first trimester of spontaneous pregnancy.

OBJECTIVE: To assess anti-Müllerian hormone (AMH) levels as a marker of early abortion in the first trimester among women younger than 35 years. METHODS: Prospective study of women aged 18-34 years with a spontaneous pregnancy at less than 12.6 gestational weeks in Lódz, Poland, between January 2017 and November 2018. Cases of anembryonic abortion and assisted conception were excluded. Blood samples were collected and assayed for serum AMH levels. Data were compared between women with an embryo with no cardiac activity by ultrasound (n=30) and those with a normal embryo (n=33) by using Statistica12 software. RESULTS: The 10th and 90th percentiles of serum AMH concentration among control women were used to identify a reference AMH range (1.1-4.5 ng/mL). Risk of pregnancy loss in the first trimester was found to be higher for both low AMH (<1.1 ng/mL; relative risk [RR], 3.66; 95% confidence interval [CI], 2.1-6.4; P<0.001) and high AMH (>4.5 ng/mL; RR, 3.0; 95% CI, 1.61-5.59; P<0.001). CONCLUSIONS: Both very low and very high AMH concentrations were found to significantly increase the risk of abortion in the first trimester of pregnancy. Serum AMH might be a valuable marker to predict the risk of early abortion.

One-year follow-up of ovarian reserve by three methods in women after laparoscopic cystectomy for endometrioma and benign ovarian cysts.

OBJECTIVE: To determine the long-term impact of laparoscopic cystectomy for endometriomas and benign cysts on ovarian reserve and selection of the most effective method of assessment. METHODS: The present study was carried out between November 2013 and December 2016. Participants were assigned to laparoscopic cystectomy for diagnosed unilateral benign ovarian cysts and divided into groups: the endometrioma group (EG) (n=35) and the other benign ovarian tumor group (OG) (n=35). Before and at 3 and 12 months after the procedure, transvaginal ultrasonography was performed to assess antral follicle count (AFC) and ovarian volume (OvVol); laboratory tests were ordered for anti-Mullerian hormone (AMH) serum concentration assays. Pregnancy rates were counted in a 12-month follow-up. Statistica12 software was used for analysis. RESULTS: The present study included 70 women aged 18-40 years. AMH serum concentration decreased significantly 3 months after laparoscopic cystectomy (4.89 ± 3.66 ng/mL to 3.45 ± 3.37 ng/mL; P<0.001). A greater decrease of AMH concentrations was observed in the EG (45.39% vs 14.87%; P=0.021). Twelve months of observation revealed a suppression in the drop of the AMH concentration, while AFC and OvVol remained unaffected. The likelihood of spontaneous pregnancy was three times higher in the OG (hazard ratio [HR] 3.57, 95% confidence interval [CI] 1.08-12.5). CONCLUSION: There was a significant decline in AMH levels in the EG 3 months after cystectomy. No further fall in AMH concentration was observed in the 12-month follow-up. The serum AMH concentration could be considered a valuable marker for ovarian reserve assessment after laparoscopic cystectomy.

The significance of markers in the diagnosis of endometrial cancer.

Endometrial cancer is one of the most common cancers experienced by women throughout the world. It is also the most common malignancy within the female reproductive system, representing 37.7% of all disorders. The incidence increases with age, and is diagnosed most frequently in women between 45 and 65 years old. In the last few years, numerous studies have been performed to identify tumour biomarkers. Biomarkers include not only protein routinely used as tumour markers but also genes and chromosomes. The limiting factor in the use of markers in the diagnosis of endometrial cancer is their lack of specificity. However, specific markers for endometrial cancer are the subject of much research attention. Although moderately elevated levels of markers are present in a number of inflammatory or non-malignant diseases, significantly increased levels of markers indicate the development of cancer. Recently, research has been focused on the identification of molecular changes leading to different histological subtypes of endometrial cancer. In this paper the authors reviewed several currently investigated markers. Progress in these investigations is very important in the diagnostics and treatment of endometrial cancer. In particular, the identification of novel mutations and molecular profiles should enhance our ability to personalise adjuvant treatment with genome-guided targeted therapy.

Women's fertility after laparoscopic cystectomy of endometrioma and other benign ovarian tumors - a 24-month follow-up retrospective study.

OBJECTIVES: The golden standard in treatment benign ovarian cysts is laparoscopic cystectomy, but it may also influence women's fertility. The aim of the study was to compare women's fertility after laparoscopic cystectomy of endometrioma versus other benign ovarian tumors. MATERIALS AND METHODS: Out of the 123 patients operated because of benign ovarian tumor (OT), 66 underwent laparoscopic cystectomy of endometrioma (endometrioma group) and 57 underwent laparoscopic cystectomy of other benign ovarian tumor like: functional cyst, hemorrhagic cyst, yellow body cyst or mature teratoma (reference group). OT-related data were obtained from medical documentation (diagnostic tests, medical reproductive and surgical history, clinical status during OT surgery). Follow-up data were collected by means of a telephone interview. The survey included questions focused on women's fertility during a 24-month period following the surgical treatment of OT (conception, subsequent pregnancies, recurrence of OT). RESULTS: A 24-month follow-up period revealed that the cumulative pregnancy rate was significantly higher in reference group (RG) as compared to endometrioma group (EG), i.e. 52.6% vs. 32.3%. Lower pregnancy risk was demonstrated in a EG group vs. other benign ovarian tumors, HR=0.57 (CI 0.33-0.99; p=0.049), log-rank test p=0.045. Benign OT returned in 19.3% vs. EG 36.3%, HR= 2.5 (CI 1.16-5.55 ; p=0.019) log-rank test: p=0.0136. The EG was divided on two subgroups: women with solitary endometrioma and women with endometrioma and coexistent peritoneal endometriosis. The study showed insignificantly lower risk of pregnancy in a group of advanced endometriosis vs. solitary endometrioma group (HR= 0.79 (CI 0.34-1.83; log-rank test p=0.57; pregnancy rate 29.3% vs. 40.0%). Statistically nonsignificant higher pregnancy rate occurred in a group of women with tumor ≤50mm in size among patients with benign ovarian tumor and solitary endometrioma vs. group of women with tumor >50mm (30% vs. 61%; p=0.09). CONCLUSIONS: There is a low pregnancy rate after laparoscopic cystectomy of benign OT. Moreover, pregnancy rate after cystectomy of endometrioma is significantly lower and the percentage of reccurence of endometrioma is significantly higher. That is why, the decision about surgical treatment among childbearing women must be well-considered because of the risk of subsequent surgery in the future.

Removal of uterine fibroids by mini-laparotomy technique in women who wish to preserve their uterus and fertility.

INTRODUCTION: The minilaparotomy is considered to be a safe and effective alternative to laparoscopy and abdominal laparotomy in myomectomy cases. AIM: To perform a retrospective analysis of pre-surgical assessment, surgical course and post-operational parameters in women wishing to preserve their uterus and fertility who underwent myomectomy by minilaparotomy in the Department of Gynecology and Gynecological Oncology at the Polish Mother's Memorial Hospital - Research Institute in Lodz in the years 2008-2014. MATERIAL AND METHODS: A total of 76 patients were qualified for minilaparotomy due to a benign gynecological pathology. Only 21 patients with uterine fibroids who wanted to preserve their uterus and fertility were appropriate for this study. Patients' records were analyzed in terms of: epidemiological history, surgical course, postoperative stay and pathological data. All studied patients were asked in 2014 about conception and pregnancy after minilaparotomy. RESULTS: The median age was 35.7 years. The median patient body mass index (BMI) was 24 kg/m(2). The average decrease of hemoglobin was 1.5 g/dl. The size of the myoma was between 1.5 and 15 cm. There were no serious post-surgical complications. The size of the myoma did not correlate significantly with operation time, BMI or blood loss. There was no statistically significant dependence between operation time and average hematocrit and hemoglobin decrease. In our group 7 patients who had undergone myomectomy tried to achieve conception. Four of them succeeded in pregnancy and gave birth to healthy infants. CONCLUSIONS: Myomectomy performed via minilaparotomy is a safe procedure for patients willing to preserve their uterus and fertility, and it combines some advantages of both laparotomy and laparoscopy.

Pregnancy and Delivery in Women with Uterine Malformations.

BACKGROUND: Uterine defects are the most common malformations of the female reproductive system. They can lead to many obstetric complications, e.g. preterm delivery, intrauterine growth restriction, oligohydramnios and operational delivery. OBJECTIVES: Our aim was to analyze the impact of different types of uterine defects on pregnancy outcomes. MATERIAL AND METHODS: The study involved 94 pregnant women with different types of uterine defects hospitalized at the Department of Fetal--Maternal Medicine and Gynecology, RIPMMH in Lódz, between 1994 and 2012. The patients were divided into 5 groups on the basis of diagnosed defects: arcuate (n=6), bicornuate (n=50), duplex (n=29), septate (n=5) and unicornuate uterus (n=4). In order to avoid correlated data in statistical analysis, our research did not consider the total number of pregnancies and births but the number of patients. The first pregnancy of each patient, if completed after 22-week gestation, was studied and analyzed. RESULTS: Preterm delivery was the most common complication in pregnancy (55 women, 58.5%). The caesarean section was performed in 73 (78%) women. IUGR was diagnosed in 16% of cases. Placental abruption occurred in 13 (14%) and cervical insufficiency in 10 cases (11%), respectively. Prenatal diagnostic showed abnormalities in 12 fetuses (13%). The Apgar score from 0 to 4 points was assigned to 9 newborns (9.6%), 5-7 to 20 children (21.3%) and 8-10 points to 75 cases (69.1%). Normal birth weight (>2500 g) was determined in 51 newborns (54.3%). CONCLUSIONS: Women with uterine defects are subject to an increased risk of complications in pregnancy and delivery, including premature births, low birth weights, births by cesarean section.

Leiomyomatosis peritonealis disseminata of unusual course with malignant transformation: case report.

Leiomyomatosis peritonealis disseminata is a very rare, benign entity of unknown pathogenesis, characterized by the presence of multiple subperitoneal or peritoneal smooth muscle nodules throughout the peritoneal surface. Mostly the course is asymptomatic and it is found incidentally during laparotomy, laparoscopy or cesarean section. Non-specific symptoms such as abdominal pain, vaginal bleeding, abdominal mass or gastrointestinal signs are described. Rare cases of malignant transformation have been reported. We present a case of disseminated peritoneal leiomyomatosis with an unusual course and transformation to endometrial sarcoma in a 26-year-old previously healthy woman, where the appearance of peritoneal nodules was preceded by multiple incidents of fast fibroid growth and delivery of myomatous growth into the cervical canal.

The use of panniculectomy in morbidly obese patients undergoing gynecological surgery.

Panniculectomy is a surgical procedure that involves removal of the skin and fat excess which facilitates access to the peritoneal cavity. In the paper we present three cases of morbidly obese women (BMI: 46.3-59.5) who were treated in the Department of Gynecology and Oncological Gynecology in Lodz. One of the patients underwent an operation due to the presence of a large cervical myoma. Two another women were treated for endometrial cancer. During all of the three procedures panniculectomy was the first stage of the operation.

The role of angiogenic factors in endometrial cancer.

Endometrial cancer is the most common malignancy within the female reproductive system (37.7%). The incidence increases with age. Frequently this type of cancer is diagnosed in peri- and post-menopausal women. 60-70% of cancers occur in women over 60 years of age, and less than 5% in women below 40 years of age. Angiogenesis is a process of formation of new microvessels from existing capillaries. There are four different mechanisms of new vessel growth: sprouting, intussusception, vessel elongation and incorporation of endothelial progenitor cells into new microvessels. Angiogenesis plays important roles in growth of endometrial cancers. This process is controlled by many angiogenic factors, for example vascular endothelial growth factor (VEGF). VEGF is the most powerful and most specific endothelial cell growth factor. It plays a crucial role in the initiation of physiological and pathological angiogenesis, lymphangiogenesis, and vasculogenesis. The VEGF family consists of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F and PLGF (placental growth factor). The effects of VEGF are mediated through binding to the two specific and homologous receptors VEGFR-1 (FLT-1) and VEGFR-2 (KDR). Placental growth factor (PLGF) belongs to the VEGF family and it is also a very important growth factor. So far four isoforms of PLGF have been identified: PLGF-1 (PLGF131), PLGF-2 (PLGF152), PLGF-3 (PLGF203) and PLGF-4 (PLGF224).

Mitochondrial dysfunction in cancer.

Mitochondria are semi-autonomous organelles of eukaryotic cells. They perform crucial functions such as generating most of the cellular energy through the oxidative phosphorylation (OXPHOS) system and some other metabolic processes. In addition, mitochondria are involved in regulation of cell death and reactive oxygen species (ROS) generation. Also, mitochondria play important roles in carcinogenesis via altering energy metabolism, resistance to apoptosis, increase of production of ROS and mtDNA (mitochondrial genome) changes. Studies have suggested that aerobic glycolysis is high in malignant tumors. Probably, it correlates with high glucose intake of cancerous tissues. This observation is contrary to Warburg's theory that the main way of energy generation in cancer cells is non-oxidative glycolysis. Further studies have suggested that in tumor cells both oxidative phosphorylation and glycolysis were active at various rates. An increase of intracellular oxidative stress induces damage of cellular structure and somatic mutations. Further studies confirmed that permanent activity of oxidative stress and the influence of chronic inflammation damage the healthy neighboring epithelium and may lead to carcinogenesis. For instance, chronic inflammatory bowel disease could be related to high risk of colon adenocarcinoma. The data have shown a role of ROS generation, mtDNA or nDNA alterations and abnormal apoptotic machinery in endometrial cancer progress. Recent studies suggest that mtDNA mutations might play a potential role in endometrial cancer progress and indicate an increase of mitochondrial biogenesis in this cancer. The investigators suggested that MtCOI and MtND6 alteration has an influence on assembly of respiratory complexes in endometrial cancer. In many human cancers, there is a deregulation of the balance between cell growth and death. The tumor cells can avoid apoptosis through a loss of balance between anti- and pro-apoptotic proteins, reduced caspase function and impaired death receptor signaling. Over-expression of the anti-apoptotic BCL-2 gene has also been identified in numerous cancers including colon, thyroid, breast and endometrial cancer. Most studies have found low BCL-2 family gene expression, which could be a sign of blocking apoptosis in breast and endometrial cancer. Moreover, BCL-2 gene expression is correlated with the degree of aggressiveness and differentiation in endometrial cancer. As a result, it could be a valuable predictor of disease progression.

[Salpingotomy vs salpingectomy--a comparison of women's fertility after surgical treatment of tubal ectopic pregnancy during a 24-month follow-up study]. / Salpingotomia vs salpingektomia--porównanie plodnosci kobiet po operacyjnym leczeniu jajowodowej ciazy ektopowej, 24-miesieczne badanie obserwacyjne.

INTRODUCTION: Ectopic pregnancy (EP) is usually located in the Fallopian tube and it has a significant adverse effect on womens fertility Three types of EP treatment include: expectant, medical, and surgical radical (salpingectomy) or conservative (salpingotomy) management. OBJECTIVES: The aim of the study was to compare women's fertility after surgical radical or conservative treatment of tubal ectopic pregnancy MATERIALS AND METHODS: Out of the 58 patients operated because of tubal EP pregnancy 22 underwent laparoscopic salpingotomy (group 1) and 36 laparoscopic salpingectomy (group 2). EP-related data were obtained from medical documentation (the symptoms, diagnostic tests, EP risk factors, medical reproductive and surgical history clinical status during EP surgery). Follow-up data were collected by means of a telephone interview. The survey included questions focused on women's fertility during a 24-month period following the surgical treatment of EP (conception, subsequent intrauterine pregnancies and ectopic pregnancy). RESULTS: A 24-month follow-up period revealed that the cumulative intrauterine pregnancy rate was higher in group 1 (salpingotomy) as compared to group 2 (salpingectomy), i.e. 50% vs. 41.5%, respectively. Tubal EP returned in 13.6% cases (group 1) vs. 19.4% (group 2). All submitted results are statistically insignificant. CONCLUSIONS: Our findings are consistent with the literature which reports a trend of higher odds for intrauterine pregnancy after salpingotomy for surgical treatment of EP as compared to salpingectomy Moreover the risk for recurrent tubal EP is comparable for both methods. Regardless, the decision about the operating range in case of EP always depends on the actual clinical state of the patient.