Fertility preservation in Turkey: a global look for nationwide strategy development

As the reproductive technology advanced along with the improved outcome in cancer treatment demands implementing new fertility preservation, developing algorithms on fertility preservation requires tailoring for each society. Here, the authors attempt to modify the current medical literature on fertility preservation for the Turkish population. A PubMed search was conducted using the search term fertility preservation. Initially, 280 items of literature were accessed. In the second evaluation, 126 articles were examined and 154 items were discarded due to the low quality of the literature. In the final round, only 68 publications that were the most relevant were found eligible for inclusion in this review article. In order to develop a more systematic national guideline, forming a multidisciplinary approach to create a web-based network would be the first step. Both physicians and patients will have open access to the information. This database should be linked to an international consortium to stay integrated and open for updating. The aim of this review was to evaluate the relationship between the current situation in our country and the developments in the world in light of the literature, and to establish infrastructure for the development of future approaches in our country.

Effect of the Dexamethasone-Ondansetron Combination Versus Dexamethasone-Aprepitant Combination to Prevent Postoperative Nausea and Vomiting.

OBJECTIVE: Postoperative nausea and vomiting (PONV) is a common problem associated with general anaesthesia. The incidence can be as high as 80% in high-risk patients. Our primary objective was to compare the efficacy of the combination of dexamethasone-ondansetron and dexamethasone-aprepitant in patients undergoing laparoscopic surgery. METHODS: Seventy 18 to 60 years old patients scheduled for laparoscopic surgery were included in the study. Sixty-seven patients completed the study. Patients in the dexamethasone-aprepitant group (group DA, n=35) received 40 mg of aprepitant orally 1-2 hours before the induction of anaesthesia and 2 mL saline intravenously (iv) within the last 30 minutes of surgery; patients in the dexamethasone-ondansetron group (group DO, n=35) received oral placebo identical to aprepitant 1-2 hours before the induction of anaesthesia and 4 mg ondansetron iv within the last 30 minutes of surgery. All patients received 8 mg dexamethasone iv after the induction of anaesthesia. The primary outcome was a complete response (no postoperative nausea, retching and vomiting and no need for rescue antiemetic); the secondary outcomes were the incidence of nausea, retching, vomiting, the need of rescue antiemetic and opioid consumption within 24 hours after surgery. RESULTS: A complete response was not significantly different between the groups (group DO: 67%, DA: 69%) at 24 hours (p=0.93). The incidence of PONV and postoperative opioid consumption was similar between the groups. CONCLUSION: The study was designed to evaluate whether the combination of dexamethasone-aprepitant is better than the combination of dexamethasone-ondansetron regarding the complete response for PONV in patients undergoing laparoscopic surgery. The results however showed that dexamethasone-aprepitant has not improved the complete response for PONV compared to dexamethasone-ondansetron.

Association between fok1 polymorphism of vitamin D receptor gene with uterine leiomyoma in Turkish populations

Objective: The aim of this research was to determine the association between the fok1 polymorphism and uterine leiomyomas. Material and Methods: For genotyping the fok1 polymorphism of the vitamin D receptor, real-time polymerase chain reaction was performed on blood samples of uterine leiomyoma (n=27) and control (n=33) groups. For statistical analyses, SPSS v.23 software (SPSS Inc., Chicago, IL, USA) was used. Results: A statistically significant difference was observed for the frequency of the CC genotype between the uterine leiomyoma and control groups, and the frequencies of the T allele in the uterine leiomyoma groups were significantly higher than in the control group. CONCLUSION: The presence of the fok1 CC genotype may be a risk-reducing factor and the T allele may be a potential risk factor for developing uterine leiomyoma.

Association of CCR2 (+190 G/A) Gene Variants and Ovarian Cancer Severity.

AIM: Chemokines and their receptors play an important role in tumor progression. In the current study, we aimed to determine the association between the CCR2 gene (+190 G/A) polymorphism and ovarian cancer severity. METHODS: CCR2 (+190 G/A) genotyping was performed using real-time polymerase chain reaction for DNA isolated from blood samples from a cohort of patients with ovarian cancer (n = 44) and a control group (n = 45). RESULTS: The CCR2 (+190 G/A) GG genotype frequencies for patients were significantly higher in the stage III-IV cancer group (p = 0.036), and A allele carriers were significantly higher in the stage I-II ovarian cancer group. CONCLUSION: The CCR2 (+190 G/A) GG genotype may be a potential risk factor for the severe forms of ovarian cancer and the A allele may be a risk-reducing factor for severe ovarian cancer.

Protective Effect of Platelet Rich Plasma on Experimental Ischemia/Reperfusion Injury in Rat Ovary.

BACKGROUND/AIMS: Ovarian torsion is a common cause of local ischemic damage, reduced follicular activity and infertility. Platelet-rich plasma (PRP) contains growth factors with demonstrated cytoprotective properties; so we evaluated PRP efficacy in a rat ischemia/reperfusion (I/R) model. METHODS: Sixty adult female Sprague-Dawley albino rats were randomly assigned to 6 groups of 8 animals each: Sham, Ischemia, I/R, Sham + PRP, I + PRP and I/R + PRP; and the remaining 12 used to prepare PRP. Ischemia groups were subjected to bilateral adnexal torsion for 3 h, while I/R and I/R + PRP groups received subsequent detorsion for 3 h. Intraperitoneal PRP was administered 30 min prior to ischemia (Ischemia + PRP) or reperfusion (I/R + PRP). RESULTS: Total oxidant status (TOS), oxidative stress index (OSI) and total ovarian histopathological scores were higher in Ischemia and I/R groups than in the Sham group (p < 0.05). PRP decreased mean TOS, OSI and histopathological scores in I + PRP and I/R + PRP groups compared to the corresponding Ischemia and I/R groups (p < 0.001). There was a strong correlation between total histopathological score and OSI (r = 0.877, p < 0.001). Peritoneal vascular endothelial growth factor was significantly higher in PRP-treated groups than corresponding untreated groups (p < 0.05). CONCLUSION: PRP is effective for the prevention of ischemia and reperfusion damage in rat ovary.

The protective effect of G-CSF on experimental ischemia/reperfusion injury in rat ovary.

OBJECTIVE: This experimental study was designed to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) in ovarian ischemia and ischemia/reperfusion (I/R) injury. STUDY DESIGN: Forty-eight female adult Sprague-Dawley albino rats were divided into six groups as Group 1: sham, Group 2: torsion, Group 3: detorsion, Group 4: sham + G-CSF, Group 5: torsion + G-CSF, and Group 6: detorsion + G-CSF. Except for Groups 1 and 4, all groups underwent a dnexal torsion bilaterally for 3 h. Adnexal detorsion was applied to Groups 3 and 6 for 3 h after a 3-h torsion period. The intraperitoneal injection of G-CSF (100 IU/kg) was administered 30 min previously in Group 4, 5 and 6. At the end of the study process the animals were euthanized and their ovaries were removed for histopathological and biochemical analysis. Total oxidant status (TOS), total antioxidative status and oxidative stress index (OSI) concentrations were determined and compared. Histopathological examination of ovaries was performed for the presence of interstitial edema, congestion, hemorrhage and loss of cohesion to determine tissue damage. RESULTS: In Group 3, 4, 5 and 6, TOS, OSI and total histopathological scores of ovarian tissue were higher than in the sham group (p < 0.05). G-CSF administration decreased mean TOS and OSI levels significantly when compared with the controls (p < 0.001, p < 0.001, respectively). There was a strong correlation between the total histopathological scores of I/R injury and OSI (r = 0.862, p < 0.001). The total histopathological scores for the rats conservatively treated with G-CSF were lower than those of the control groups. CONCLUSION: G-CSF is effective for the prevention of ischemia and ischemia/reperfusion-induced damage in rat ovary.

The effects of electromagnetic fields on the number of ovarian primordial follicles: An experimental study.

The aim of this study was to evaluate the effect of an electromagnetic field (EMF), generated close to the ovaries, on primordial follicles. A total of 16 rats were used in this study. The study group consisted of rats exposed to an EMF in the abdominal region for 15 min/d for 15 days. Both the study and control group were composed of eight rats. After the treatment period of 15 days, the ovaries of the rats were extracted, and sections of ovarian tissue were taken for histological evaluation. The independent samples t test was used to compare the two groups. In the study group, the means of the right and left ovarian follicle numbers were 34.00 ± 10.20 and 36.00 ± 10.53, respectively. The average total ovarian follicle number was 70.00 ± 19.03. In the control group, the means of the right and left ovarian follicle numbers were 78.50 ± 25.98 and 71.75 ± 29.66, respectively, and the average total ovarian follicle number was 150.25 ± 49.53. The comparisons of the means of the right and left ovarian follicle numbers and the means of the total ovarian follicle numbers between the study and control groups indicated that the study group had significantly fewer follicles (p < 0.001, p = 0.011, and p = 0.002, respectively). This study found a significant decrease in the number of ovarian follicles in rats exposed to an EMF. Further clinical studies are needed to reveal the effects of EMFs on ovarian reserve and infertility.

The effects of PON1 gene Q192R variant on the development of uterine leiomyoma in Turkish patients.

AIM: This study aimed to analyze the relation between uterine leiomyoma (ULM) patients and p.Q192R polymorphism. MATERIALS AND METHODS: ULM patients (n=76) and healthy women (n=103) were recruited from the Yeditepe University, Department of Gynecology and Obstetrics. The genotype and allele distribution of p.Q192R was analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. Genotype and allele frequencies between study groups were calculated by the chi-square (χ(2)) and Fischer's exact test. RESULTS: The frequency of the B allele was lower in patients (p<0.001) and the AB genotype showed a decreased risk for ULM development (p<0.001). The variation was unrelated to ULM size and number. There was no significant difference between p.Q192R genotype frequencies and fibroid size and number. CONCLUSION: The heterogeneous AB genotype of PON1 p.Q192R variation could be recognized as a low-risk parameter for the development of ULM in Turkish women.

The effects of different doses of melatonin treatment on endometrial implants in an oophorectomized rat endometriosis model.

AIMS: To determine the effects of different doses of melatonin treatment on endometrial implants, the activity of antioxidant enzyme superoxide dismutase (SOD), the angiogenesis factor, the vascular endothelial growth factor (VEGF) and the waste metabolite product of lipid peroxidation malondialdehyde (MDA) in an oophorectomized rat endometriosis model. METHODS: Thirty-two, female, non-pregnant, nulligravid Sprague-Dawley, albino rats were used in this prospective, randomized, controlled and experimental study. Endometriosis was surgically induced in oophorectomized rats, and estradiol treatment was started after the first operation and continued till the end of the study. Second look, third look and necropsy operations were performed in the 2nd, 4th and 6th weeks. Mean volumes, histological scores and biochemical parameters were evaluated throughout the study. RESULTS: The mean volumes of endometriotic foci were 98.8 mm(3) ± 17.2 vs. 108.2 mm(3) ± 17.5, 54.1 mm(3) ± 15.6 vs. 25.8 mm(3) ± 3.6, 42.8 mm(3) ± 10.5 vs. 32.7 mm(3) ± 6.0 and histopathological scores were 2.2 ± 0.2 vs. 1.7 ± 0.1, 2.6 ± 0.2 vs. 2.2 ± 0.2, 2.6 ± 0.1 vs. 2.7 ± 0.2 in the 10 vs. 20-mg/kg/day melatonin group at the end of the second, fourth and sixth weeks, respectively. When the groups were compared, no significant differences were seen in the histopathologic scores, SOD and VEGF levels between the groups. However, the endometriotic foci volumes were significantly decreased in both melatonin treatment groups with respect to the control group at the end of the fourth and sixth weeks. Moreover, the mean MDA levels were significantly lower in the control group than in the 10-mg/kg/day melatonin group at the end of the fourth and sixth weeks. CONCLUSION: Melatonin treatment resulted in the regression of endometriotic lesions in oophorectomized rats. Higher doses of melatonin treatment might be more effective in the regression of implants and improvement of histologic scores as well as in the precise evaluation of SOD, MDA and VEGF distributions in the rat experimental models.

Ovarian cystectomy in endometriomas: Combined approach.

Endometrioma is one of the most frequent adnexal masses in the premenopausal population, but the recommended treatment is still a subject of debate. Medical therapy is inefficient and can not be recommended in the management of ovarian endometriomas. The general consensus is that ovarian endometriomas larger than 4 cm should be removed, both to reduce pain and to improve spontaneous conception rates. The removal of ovarian endometriomas can be difficult, as the capsule is often densely adherent. While the surgical treatment of choice is surgical laparoscopy, for conservative treatment, the preferred method is modified combined cystectomy. Cystectomy can be destructive for the ovary, whereas ablation may be incomplete, with a greater risk of recurrence. To the best of our knowledge, the modified combined technique seems to be more efficient in the treatment of endometriomas.

The role of TWIST, SERPINB5, and SERPIN1 genes in uterine leiomyomas.

OBJECTIVE: The aim of this study is investigate the role of the Twist homolog 1 (TWIST), serine peptidase inhibitor (SERPINB5), and plasminogen activator inhibitor 1 (SERPIN1) genes in uterine leiomyoma etiopathogenesis. MATERIAL AND METHODS: Twelve patients, aged between 39 and 58, and had a hysterectomy, were included in the study. The size of the leiomyomas was between 20 and 130 mm based on gross pathology after hysterectomy. Tissue samples were obtained from normal myometrium and leiomyoma (1 cm(3)) tissue of the uterus of the patients and stored at -86°C. Samples were divided to two groups after histopathological evaluation of the uterus: normal myometrial tissues as control group (Group 1) and leiomyoma tissue as the study group (Group 2). The TWIST, SERPINB5, and SERPIN1 genes were studied for uterine leiomyoma etiopathogenesis. RESULTS: TWIST gene expression was significantly higher in the uterine leiomyoma tissue (p<0.001). SERPINB5 and SERPIN1 gene expression was decreased in the uterine leiomyoma tissue, but the differences were not statistically significant. CONCLUSION: TWIST gene activity is significantly increased in leiomyoma tissue when compared to normal myometrium. In spite of the fact that the development of uterine leiomyomas is estrogen- and progesterone-dependent, myometrial cells could be triggered by the TWIST gene for uterine leiomyoma development.

Which cut-off value of serum anti-Müllerian hormone level can predict poor ovarian reserve, poor ovarian response to stimulation and in vitro fertilization success? A prospective data analysis.

The aim of our study is to demonstrate which cut-off value of serum anti-Müllerian hormone (AMH) level can predict poor ovarian reserve, poor ovarian response to stimulation and IVF outcomes. About 311 of 520 women enrolled IVF treatment cycle that meets inclusion criteria were recruited for this prospective data analysis. Data were collected for: age, duration of infertility, basal FSH and AMH level, total dosage of gonadotropins, maximum estradiol levels, duration of stimulations, total number of oocytes retrieved and clinical PR. Mean AMH was 1.76 ± 1.4 ng/ml and mean age was 33.25 ± 5.5 years. Clinical PR was 39.8% (n = 124). AMH was inversely correlated to total dosage of gonadotropins and age, AMH positively had a significant correlation with maximum estradiol levels, duration of stimulations and total number of oocytes retrieved. The patients in both categories of AMH levels, ≤0.5 and ≤1 ng/ml responded poorly to ovarian stimulation, had significantly higher total dosage of gonadotropins used and FSH levels on cycle day 3, lower maximum E2 levels and clinical PR. AMH could be an acceptable screening test in prediction of ovarian reserve, response to ovarian stimulation and PRs. AMH cut-off value ≤1 ng/ml may predict poor ovarian reserve, poor ovarian response to stimulation and IVF outcomes.

Hysteroscopic findings in women with recurrent IVF failures and the effect of correction of hysteroscopic findings on subsequent pregnancy rates.

INTRODUCTION: Our aim is to evaluate the incidence of unrecognized uterine abnormalities in cases with recurrent IVF failure by screening office hysteroscopy (OH), and impacts of treatment of hysteroscopic findings on the success rate of IVF. MATERIALS AND METHODS: The retrospective and descriptive study was conducted at assisted reproduction unit in a tertiary medical center. One hundred and fifty-seven patients with a history of recurrent IVF failures underwent hysteroscopy between May 2009 and March 2012. Hysteroscopy (diagnostic or operative, as appropriate) was performed to evaluate the endometrial cavity in patients with two or more IVF failures and Incidence of abnormal hysteroscopic findings and the clinical pregnancy rate (CPR) in subsequent IVF cycles were assessed. RESULTS: In all, 44.9 % of the patients included in this study had abnormal hysteroscopic findings and 75 women (48.1 %) became pregnant following hysteroscopy. Of these pregnancies, 36 occurred in women with corrected endometrial pathology, the majority of which was identified as endometrial polyps. Implantation rate and clinical pregnancy rate were statistically significant increased after polipectomy. CONCLUSION: Abnormal findings on hysteroscopy are significantly higher in patients with previous ART failure and hysteroscopy could be seen as a positive prognostic factor for achieving pregnancy in subsequent IVF procedure in women with a history of RIF.

Medicine in stamps-Ignaz Semmelweis and Puerperal Fever.

Puerperal fever was common in mid-19(th)-century hospitals and often fatal, with mortality at 10%-35%. Ignaz Philipp Semmelweis was a Hungarian gynecologist who is known as a pioneer of antiseptic procedures. Semmelweis discovered that the incidence of puerperal fever could be drastically cut by the use of hand disinfection in obstetrical clinics. He is also described as the "savior of mothers" and "father of infection control". This paper provides an overview on the process of preventing puerperal fever and the life story of the physician behind this attempt, Ignaz Semmelweis, through philately.

Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model.

OBJECTIVE: We aimed to determine the effects of melatonin treatment on endometrial implants in an oopherectomized rat endometriosis model. MATERIAL AND METHODS: This study is a prospective, randomised, controlled experimental study. It was carried out at the Experimental Research Center of Yeditepe University (YUDETAM). Twenty-two, female, non-pregnant, nulligravid Spraque-Dawley albino rats were included in our study. Endometriosis was surgically induced in oopherectomized rats. Rats were randomised into two groups: control group and melatonin group. In the melatonin group, rats were treated with melatonin (20 mg/kg/day) for two weeks. After the operations were performed to assess the regression of the endometriotic lesions, melatonin treatment was stopped. At the end of the sixth week necropsies were performed to assess the rate of recurrence. The volume and histopathological scores of endometriotic foci were examined. RESULTS: Volumes of the endometriotic lesions significantly decreased in the melatonin group. Also, when the melatonin group was analysed within itself, endometriotic lesion volumes decreased and histopathological scores increased significantly. CONCLUSION: Melatonin causes regression of the endometriotic lesions in rats and improvement in their histopathological scores.

Uterus didelphys with an obstructed unilateral vagina and ipsilateral renal agenesis: A rare cause of dysmenorrhoea.

Didelphic uterus with obstructed hemivagina and ipsilateral renal agenesis is a rare condition. It usually presents with pelvic pain following the menarche, dysmenorrhoea, and an increase in abdominal volume or a palpable mass due to unilateral haematocolpos. We present the case of a 13-year-old girl who referred with recurrent pelvic pain, mainly at the time of menses, and irregular menstrual cycle complaints in this report. The patient underwent ultrasonography and magnetic resonance (MR) imaging of the pelvis was performed. The diagnosis was uterus didelphys with obstructed hemivagina and ipsilateral renal agenesia. Laparotomy was performed for diagnosis and treatment purposes. Two separated hemiuteri and two cervices with hematometra and hematocolpos on the right side and ipsilateral renal agenesis were detected. The vaginal septum was excised completely and Strassman metroplasty was performed. Her complaints were resolved and she was absolutely asymptomatic after surgery. Diagnosis and management of this congenital anomaly is challenging due to the complexity of the anatomic structures, nonspecific complaints, and heterogenic presentation. These anomalies must always be considered while working-up female patients presenting with episodic abdominal pain and abdominopelvic mass.

Medicine in stamps: history of Down syndrome through philately.

Down syndrome (DS) is one of the most common chromosomal disorders with mental retardation and some spesific physical and physiological defects. Recently, many advances have been made in pre-natal screening and detection; and the hope is that identification of more genes will lead to a better understanding of the molecular mechanisms underlying the pathologies, and hence to more effective therapy. This paper provides an overview on the discovery of Down syndrome through philately.

Efficacy of melatonin and hyaluronate/carboxymethylcellulose membrane in preventing adhesion reformation following adhesiolysis in a rat uterine model.

AIM: To evaluate the efficacy of hyaluronate/carboxymethylcellulose (HA/CMC) membrane and melatonin separately and in combination in reducing adhesion reformation following adhesiolysis of surgically induced adhesions in a rat uterine horn adhesion model. METHODS: A randomized, prospective study was carried out in a university animal laboratory. Ninety-eight female Sprague-Dawley albino rats were operated on. Following infliction of standard lesions, all the animals underwent second operations after one week. In all the animals, there were dense and vascular adhesions only between the uterine horns. These adhesions were lysed. Following the completion of adhesiolysis, the animals were randomized before closure of the abdomen to one of four groups (melatonin, HA/CMC membrane, combination of melatonin and HA/CMC membrane, control group). Seven days after the second surgery, the third operations were carried out and adhesions were scored. The main outcome measures were type, tenacity, and extent of adhesions. Total adhesion scores were determined. RESULTS: Adhesion scores in the melatonin and HA/CMC membrane groups were similar, and significantly lower than those in the control group (P < 0.001). Adhesion scores in the combination group were lower than those in the other three groups (P < 0.001). CONCLUSION: Melatonin and HA/CMC membrane are both effective separately in preventing adhesion reformation following adhesiolysis, but in combination they are significantly more beneficial.

Etanercept causes regression of endometriotic implants in a rat model.

OBJECTIVE: To determine the effects of etanercept (anti-TNF-α) on surgically induced endometriosis in a rat model. MATERIALS AND METHODS: This is a prospective, randomized, controlled, experimental study that was carried out at the Experimental Research Center of Yeditepe University (YUDETAM). Thirty female nonpregnant, nulligravid Wistar-Hannover albino rats were used. The summary of the technique: surgical induction of endometriosis, administration of estrogen for 2 weeks, and laparotomy; administration of etanercept for 2 weeks following the induction of endometriosis and laparotomy; administration of estrogen for 2 weeks and necropsy. The volume and histopathological scores of the endometriotic foci were evaluated. RESULTS: One-hundred twenty uterine horns were implanted in 30 rats. Endometriosis was completely formatted in 112 lesions (93.3%). No rats were lost. In the etanercept group, the lesions' volumes were 83.9 ± 13.1, 47.2 ± 8.4, and 96.7 ± 34.8 mm(3) at the end of the second week (pretreatment stage), at the end of the fourth week (post-treatment stage), and at the end of the sixth week, respectively (P = 0.007). Histopathologic scores were 2.3 ± 0.2, 1.7 ± 0.2, and 1.9 ± 0.1, respectively (P = 0.08). The changes in the other groups were not statistically significant. CONCLUSIONS: Etanercept, a fusion protein consisting of human recombinant soluble TNF receptor-2, neutralizes TNF activity. Anti-TNF therapy could be a new non-hormonal therapeutic option for the treatment of endometriosis in humans.