Thrombophilia and Recurrent Pregnancy Loss: The Enigma Continues.

BACKGROUND Thrombophilic gene polymorphism is known to be a risk factor for recurrent pregnancy loss (RPL), but few studies have confirmed a possible role of thrombophilic genes polymorphism in RPL risk. This study was conducted to understand the relationship of the mutations of some thrombophilia-associated gene polymorphism (heterozygous/homozygous) with RPL. We compared patients with 2 abortions to patients with 3 or more abortions among Turkish women. MATERIAL AND METHODS In this study, patients previously diagnosed with habitual abortus at Obstetrics and Gynecology outpatient clinics in Turkey between 2012 and 2016 were included. In their peripheral blood, we detected factor V Leiden H1299R, prothrombin G20210A, MTHFR C677T, MTHFR A1298C, PAI-1 4G/5G, and PAI-1 4G/4G gene mutations. RESULTS In this study, we have observed statistically meaningful data (P<0.01) related to the relationship between RPL and thrombophilia-associated gene polymorphisms such as heterozygous factor V Leiden H1299R, heterozygous prothrombin G20210A, PAI-1 4G/5G, and PAI-1 4G/4G. CONCLUSIONS We found that diagnosis of thrombophilic genes polymorphism is useful to determine the causes of RPL, recognizing that this multifactorial disease can also be influenced by various acquired factors, including reproduction-associated risk factors and prolonged immobilization.

Human Papilloma Viruses and Their Genotype Distribution in Women with High Socioeconomic Status in Central Anatolia, Turkey: A Pilot Study.

BACKGROUND In the present study we retrospectively evaluated the results of outpatients who had an HPV analysis, and present objective evidence for the administration of preventive inoculation in our area. MATERIAL AND METHODS We retrospectively reviewed 532 outpatients who visited a single center between 2012 and 2016 and had an HPV infection analysis. The criteria for inclusion of patients with unhealthy cervix in the study were: erosion, chronic cervicitis, healed lacerations, hypertrophied cervix, and abnormal discharges from the cervix. RESULTS We found that 122 out of 532 patients were infected with HPV, and the rate of multiple infections was 59.0% (72/122). HR-HPV (group 1 carcinogens HPV-16 (18.9%, 23/122), HPV-18 (13.1%, 16/122), HPV- 31 (4.9%, 6/122), HPV-33 (3.3%, 4/122), HPV-35 (7.4.9%/122), HPV-39 (5.7%, 7/122), HPV-45 (5.7%, 7/122), HPV-51 (11.5%, 15/122); Group 3 LR-HPV; HPV-6 (31.1%, 38/122), HPV-11 (26.2%, 32/122), HPV-42 (9.0%, 11/122) and HPV-43 (4.9%, 6/122). In terms of linear-by-linear association test, no significant statistical difference was identified between years. The P value for HPV infection rate on year basis was P>0.05. CONCLUSIONS In this hospital-based retrospective analysis, HPV types were found to be similar to HPV types reported in developed countries. We firmly suggest that patients should be informed about the risk of HPV infection at early ages.

There is a Positive Correlation Between Socioeconomic Status and Ovarian Reserve in Women of Reproductive Age.

BACKGROUND The purpose of this study was to investigate the potential association between socioeconomic status and ovarian reserve, anti-Mullerian hormone level, antral follicle count, and follicle stimulating hormone level in women of reproductive age. MATERIAL AND METHODS A total of 101 married women between 20-35 years of age who presented to the Department of Obstetrics and Gynecology, Health Research System In Vitro Fertilization (HRS IVF) Center between October 2014 and November 2015 and met the inclusion criteria were included in this study. The participants were divided into three socioeconomic groups using Kuppuswamy's socioeconomic status scale. Thirty-one participants were assigned to the low socioeconomic status group, 37 to the middle socioeconomic status group, and 33 to the high socioeconomic status group. On days 3-6 of the menstrual cycle, 10 mL of blood was collected from the participants for follicle stimulating hormone and anti-Mullerian hormone measurements. Transvaginal ultrasonography was performed for both ovaries for the purpose of counting antral follicles measuring 2-10 mm in diameter. RESULTS Both ovarian reserve parameters, namely anti-Mullerian hormone level and antral follicle count, exhibited a significant association with socioeconomic status (p=0.000 and p=0.000, respectively). The association between follicle stimulating hormone level and socioeconomic status was also significant (p=0.000). CONCLUSIONS A low socioeconomic status aggravated by sources of stress such as undernutrition and financial hardships affects ovarian reserve, which should be remembered in approaching infertile patients.

Environmental Tobacco Smoke Exposure during Intrauterine Period, Promotes Caspase Dependent and Independent DNA Fragmentation in Sertoli-Germ Cells.

Objectives. To investigate the effect of cigarette smoke exposure during intrauterine period on neonatal rat testis. Methods. Twenty-five rats were randomized to be exposed to cigarette smoke with the Walton Smoking Machine or to room air during their pregnancies. The newborn male rats (n = 21) were grouped as group 1 (n = 15) which were exposed to cigarette smoke during intrauterine life and group 2 (n = 6) which were exposed to room air during intrauterine life. The orchiectomy materials were analyzed with TUNEL immunofluorescent staining for detection of DNA damage. To detect apoptosis, immunohistochemical analyses with caspase-3 were performed. Primary outcomes were apoptotic index and immunohistochemical scores (HSCORES); secondary outcomes were Sertoli-cell count and birth-weight of rats. Results. Sertoli cell apoptosis was increased in group 1 (HSCORE = 210.6 ± 41.9) when compared to group 2 (HSCORE = 100.0 ± 17.8) (P = 0.001). Sertoli cell count was decreased in group 1 (P = 0.043). The HSCORE for the germ cells was calculated as 214.0 ± 46.2 in group 1 and 93.3 ± 10.3 in group 2 (P = 0.001) referring to an increased germ cell apoptosis in group 1. The apoptotic indexes for group 1 were 49.6 ± 9.57 and 29.98 ± 2.34 for group 2 (P = 0.001). The immunofluorescent technique demonstrated increased DNA damage in seminiferous epithelium in group 1. Conclusions. Intrauterine exposure to cigarette smoke adversely affects neonatal testicular structuring and diminishes testicular reserve.

Factors Influencing the Preference of Regional Anaesthesia in the Obstetric Population: A Survey Study.

OBJECTIVE: Most patients in Turkey still prefer general anaesthesia (GA) and are somehow afraid of regional blocks. Receiving adequate information is likely to increase patients' awareness about regional anaesthesia (RA). We aimed to determine the current preferences of parturients, the reasons for refusal of RA techniques, and how detailed information about the type of anaesthesia affect a patient's preference for anaesthesia among obstetric cases. METHODS: One hundred fifty patients, scheduled for elective caesarean section (C/S), were surveyed before and after the C/S. The survey included three parts: the first part involved demographic features, anaesthesia preferences, prior opinions and experiences related to RA, and assessment of preoperative fears and reasons, and the second part involved persuasion of patients after reading the information sheet about RA. The final part was composed of postoperative satisfaction and complications related to the RA or GA depending on the patients' preferences. Complications were recorded on the anaesthesia chart. RESULTS: Of all patients, 42.7% (n=64) approved and 48% (n=72) refused RA at the first preoperative anaesthesia visit. The remaining patients (n=14) had no idea of which anaesthesia type to choose. After being informed about RA in detail, 48 (66.6%) of the patients who previously refused RA and all patients who had no idea approved the procedure, and all of them were satisfied with the anaesthesia following the procedure. CONCLUSION: Our study revealed exactly that particularly obstetric anaesthetists should inform their patients about the advantages and disadvantages of all alternative types of anaesthesia. Effective and correct information is the major point.

Environmental tobacco smoke exposure during intrauterine period promotes granulosa cell apoptosis: a prospective, randomized study.

OBJECTIVE: To evaluate the intrauterine effect of cigarette smoke on cell death and DNA damage in follicular cells of fetal ovarian tissue. METHODS: A prospective, randomized study was conducted with 25 female wistar-albino rats. The rats were randomized to be exposed either to cigarette smoke or to room air, initiating from proestrous period and during pregnancy. Newborn female rats were categorized as Group 1 (n = 24) that had been exposed to cigarette smoke during intrauterine life and Group 2 (n = 7) that had been exposed to room air during intrauterine life. Bilateral ooferectomies were performed on the 2nd week of their life. TUNEL (in-situ Terminal Deoxynucleotidyl-Transferase Mediated dUTP-Nick-End Labeling) immunofluorescent staining and immunohistochemical analyses with caspase-3 were used for detection of DNA damage and apoptosis. Primary outcomes were apoptotic index and immunohistochemical scores (HSCORE). Secondary outcomes were ovarian follicle counts and birth weights of newborn rats. RESULTS: There was a significant increase of HSCORE and apoptotic index in Group 1. Increased immunofluorescent staining; evaluating DNA damage, with TUNEL method was observed in granulosa cells in Group 1. CONCLUSIONS: Intrauterine exposure to cigarette smoke diminishes ovarian reserve of female offspring, raising the concern about the generational impact of maternal smoking on ovarian function in the human.

CYP17 and CYP2C19 gene polymorphisms in patients with endometriosis.

Endometriosis seems to be the result of a complex interaction between environmental factors and various genes. In this regard, the cytochrome subfamily 17 (CYP17) may play an important role by altering the biosynthesis of sex steroids. CYP2C19 is also an important member of the cytochrome P450 (CYP) family, and related mutations may result in an inability to fully metabolize environmental chemicals and cytokines, leading to several diseases. This study sought to determine whether there is a relationship between endometriosis and CYP17 T>C, CYP2C19 *2 and CYP2C19 *3 polymorphisms. When samples from 46 patients with endometriosis and 39 healthy controls were analysed, A2A2 type mutation of the CYP17 gene was observed to be more frequent in patients with endometriosis (34.8 versus 7.7%, P = 0.003). No association was found between the severity of endometriosis and CYP2C19 *2 or CYP2C19 *3 polymorphisms of the CYP2C19 gene. These results suggest that mutations related with sex steroid metabolism seem to have an important role in endometriosis. However, the relation between detoxification ability and endometriosis should be examined in further studies with larger sample sizes.

Single intramural leiomyoma with normal hysteroscopic findings does not affect ICSI-embryo transfer outcome.

Where there is no distortion of the endo-myometrial junction, the effect of an intramural leiomyoma on reproductive performance is controversial. The current study compared the performance of patients having a single leiomyoma and intact endometrium confirmed by hysteroscopy (study group) with that of controls having intact endometrium alone in intracytoplasmic sperm injection (ICSI) cycles. A total of 61 consecutive infertile patients were retrospectively enrolled into the study group from a computerized IVF database. The control group consisted of 444 age-matched patients undergoing ICSI-embryo transfer without any endocervical or intrauterine pathology confirmed by both transvaginal ultrasonography and office hysteroscopy. The baseline characteristics, performance of ovarian stimulation and embryological data were similar between the two groups. The clinical pregnancy per embryo transfer (36 versus 38%) and implantation rate (20 versus 19%) were also comparable. Although the miscarriage rate tended to be higher in the leiomyoma group (27 versus 19%), the difference did not reach statistical significance. In conclusion, in the presence of intact endometrium, a single intramural leiomyoma does not seem to have a deleterious effect on ICSI cycles. Before ICSI is attempted, hysteroscopy may be useful for ruling out distortion of the endometrium due to leiomyoma in selected cases.

Role of leukotrienes in the pathogenesis of dysmenorrhea in adolescent girls.

Although dysmenorrhea is a leading cause of gynecologic complaints among adolescents, its pathogenesis is incompletely understood. The purpose of this study was to determine the role of prostaglandins and leukotrienes in the pathogenesis of dysmenorrhea. Twenty patients with dysmenorrhea aged 16.2+/-1.2 years and 20 healthy age-matched controls with eumenorrhea (absence of pain during menstruation) were included in the study. Serial measurements of serum PGF2alpha and urinary LTE4 levels during the menstrual cycle were obtained; serum progesterone was measured and ultrasonographic evaluations were made. LTE4 and PGF2alpha levels decreased on the third day and recovered on the 10th day of the menstrual cycle in both groups. Urinary LTE4 levels were higher in the control group than in the patient group on the 1st, 3rd and 10th days of the cycle (p<0.05 for each). This study suggests that there is a distinct pattern of leukotriene production during the menstrual cycle, but the changes in the systemic level are not responsible for their role in the pathogenesis of dysmenorrhea. Further studies at the local level in the target organ are necessary to elucidate the role of the lipid mediators in the pathogenesis of dysmenorrhea.

Perinatal outcomes of spontaneous twins compared with twins conceived through intracytoplasmic sperm injection.

OBJECTIVE: To compare perinatal outcomes in spontaneous twins compared with those conceived by intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective case-control study. PATIENTS: Cases consisted of 274 intracytoplasmic sperm injection twins, controls were 348 naturally conceived twins delivered between 1999 and 2003 in a tertiary hospital. MAIN OUTCOME MEASURES: Birth weight, gestational age at birth, cesarean delivery rate, perinatal mortality and morbidity, congenital anomalies, gestational diabetes and pregnancy induced hypertension. RESULTS: Preterm deliveries (76.6% vs. 64.1% <37 weeks and 19.7% vs. 13.2% <32 weeks) and low birth weight (73% vs. 60.3% <2500 g and 19.7% vs. 12.6% <1500 g) were significantly higher in the ICSI group compared with controls. Gestational diabetes mellitus (8% vs. 2.9%) and cesarean deliveries (95.2% vs. 77.6%) were more common in cases compared with the control group. There was a significantly higher rate of perinatal morbidity (16.4% vs. 7.8%) and mortality (8% vs. 2.6%) in ICSI twins. The incidence of congenital malformations diagnosed at birth was higher in cases (4.4%) compared with controls (0.9%) but the difference was not significant when adjusted for maternal age. CONCLUSION: Perinatal outcomes of twins after ICSI treatment are less optimal than naturally conceived twins.

A successful pregnancy after intracytoplasmic sperm injection and embryo transfer in a patient with endometrial cancer who was treated conservatively.

OBJECTIVE: To describe a patient with polycystic ovary syndrome (PCOS) conceiving with intracytoplasmic sperm injection (ICSI) and embryo transfer after conservative treatment of early stage endometrial cancer. DESIGN: Case report. SETTING: Tertiary center for assisted reproductive technologies.A 32-year-old woman with PCOS, primary infertility of 4 years duration, and grade 1 endometrioid endometrial cancer. INTERVENTION(S): Assessment of myometrial invasion and extrauterine spread with magnetic resonance imaging (MRI) and explorative laparotomy. High-dose progestin treatment and ICSI and embryo transfer. MAIN OUTCOME MEASURE(S): Successful take-home baby and no residual endometrial cancer. RESULT(S): A healthy normal female infant with a birth weight of 1740 g was born by cesarean section at 30 weeks' gestation. No residual cancer was detected at the follow-up curettage performed 2 months after the delivery. CONCLUSION(S): Conservative uterus-preserving treatment may be considered in patients with early stage endometrial cancer. Assisted reproductive technologies may be used in such patients for immediate achievement of pregnancy.

Menorrhagia at menarche: a case report.

Dysfunctional uterine bleeding is defined as abnormal endometrial bleeding without any underlying disease. It is particularly a common problem for adolescents and a majority are caused by immature hypothalamic-pituitary-ovarian axis. Usually, it presents as minor alterations of the cycle flow length, but occasionally can be severe enough to require hospitalization. A 12 year-old girl with menorrhagia at menarche was admitted to our Adolescent Unit. She had heavy bleeding for 16 days causing a hemoglobin level of 5.5 gr/dl. She was first treated with blood transfusion and hemostasis was achieved rapidly through high doses of combination oral contraceptives. Whenever menorrhagia occurs at menarche, it is important to exclude an underlying hematologic disease. If there is no response to hormonal therapy in 48 hours there is a need for reevaluation of coagulopathy. In this report, we show how an acute and heavy anovulatory bleeding episode can be controlled and followed-up in an adolescent girl.

Trigeminal schwannoma mimicking magnesium intoxication in a pregnancy complicated by severe preeclampsia.

We present a case report describing a pregnancy complicated by severe preeclampsia and a trigeminal schwannoma which caused loss of consciousness, diplopia and blurred vision, which were initially thought to be signs of magnesium intoxication.