An animal model of effects of nicotine exposure on endometrial receptivity and embryo implantation in pregnancy.

OBJECTIVE: This study aims at evaluating the endometrial receptivity in uterus of pregnant rats exposed to nicotine via examination of integrin expression by immunohistochemical effect. METHODS: In this study, 16 healthy pregnant rats were divided into two groups of control and study groups each comprising eight rats. The rats randomised to study group were given a certain amount of nicotine before and during the pregnancy. Integrin expression was detected in uterus of all rats by immunohistochemical staining. The effect of nicotine exposure on embryo implantation and the endometrial receptivity were immunohistochemically and pathologically evaluated. RESULTS: Comparison of both groups revealed no difference in living, viable foetuses. Intensity and universality of immunohistochemical staining of Integrin ß3 for endometrial epithelium and endometrial stroma were detected to be identical between the groups. CONCLUSION: No immunochemical effect was observed on integrin expression, which is a very important part of receptivity in an animal model created with pregnant rats that were transdermally exposed to nicotine. Our study demonstrated that the harmful effect of nicotine use before and pregnancy on implantation is limited at the level of integrin expression, in a dose-dependent manner and also by considering the method of administration.

Effect of IVF failure on quality of life and emotional status in infertile couples.

OBJECTIVE: To investigate the effect of a previous IVF failure on the quality of life and emotional distress, in couples undergoing IVF treatment. Experiencing IVF failure might cause differences on the anxiety-depression and quality of life scores of the couples, compared to the ones who were undergoing IVF treatment for the first time. STUDY DESIGN: This study included 64 couples who had previously experienced at least one IVF failure (Group 1) and 56 couples without history of IVF failure (Group 2) in a private Assisted Reproductive Center, Istanbul, Turkey. A sociodemographic data form, the FertiQoL International and Hospital Anxiety (HAD-A) and Depression scale (HAD-D) for evaluating the status of distress, were administered for the study. RESULT(S): FertiQoL scores were compared between the groups, the environment scale of the quality of life in treatment section was found to be significantly higher in Group 1 compared with Group 2 (p=0.009). The HAD-A and HAD-D scores did not differ significantly between the groups. Group-variables were investigated using multilevel analysis, the infertility duration and income level were found to have an effect on the subscales of quality of life (p=0.009 and p=0.001 respectively) in Group 2. Depression scores were higher in couples with infertility duration of below five years in Group 1 and Group 2 compared to couples with infertility duration of five years or above (MANOVA analysis). The level of education was found to affect the scores of HAD-D in Group 2, but not in Group 1 (p=0.011). The score of HAD-D was significantly affected by the family type only in Group 2 (p=0.009); the depression score of the couples living with a nuclear family was found to be higher compared with the couples living in a traditional family (p=0.021). CONCLUSION(S): Fertility-specific quality of life scores reveals better results regarding the orientation to the treatment environment in the couples with a previous IVF failure, compared to first IVF cycle couples. Treatment failure does not elevate the level of anxiety, while the effect on depression scores changes according to duration of infertility.

Kisspeptin levels in idiopathic hypogonadotropic hypogonadism diagnosed male patients and its relation with glucose-insulin dynamic.

Male hypogonadism is defined as the deficiency of testosterone or sperm production synthesized by testicles or the deficiency of both. The reasons for hypogonadism may be primary, meaning testicular or secondary, meaning hypothalamohypophyseal. In hypogonadotropic hypogonadism (HH), there is indeficiency in gonadotropic hormones due to hypothalamic or hypophyseal reasons. Gonadotropin-releasing hormone (GnRH) is an important stimulant in releasing follicular stimulant hormone (FSH), mainly luteinizing hormone (LH). GnRH omitted is under the effect of many hormonal or stimulating factors. Kisspeptin is present in many places of the body, mostly in hypothalamic anteroventral periventricular nucleus and arcuate nucleus. Kisspeptin has a suppressor effect on the metastasis of many tumors such as breast cancer and malign melanoma metastases, and is called "metastin" for this reason. Kisspeptin is a strong stimulant of GnRH. In idiopathic hypogonadotropic hypogonadism (IHH) etiology, there is gonadotropic hormone release indeficiency which cannot be clearly described. A total of 30 male hypogonatropic hypogonadism diagnosed patients over 30 years of age who have applied to Haydarpasa Education Hospital Endocrinology and Metabolic Diseases Service were included in the study. Compared to the control group, the effect of kisspeptin on male patients with hypogonatropic hypogonadism and on insulin resistance developing in hypogonadism patients was investigated in our study. A statistically significant difference was detected between average kisspeptin measurements of the groups (p < 0.01). Kisspeptin measurement of the cases in the patient group were detected significantly high. No statistically significant relation was detected among kisspeptin and LH/FSH levels. Although a positive low relation was detected between kisspeptin measurements of patient group cases and homeostasis model assessment of insulin resistance (HOMA-IR) measurements, this relation was statistically insignificant. When the patient and control groups were compared for HOMA-IR, no statistically significant difference was detected. The reason for high kisspeptin levels in the patient group compared to the control group makes us consider that there may be a GPR54 resistance or GnRH neuronal transfer pathway defect. When patients and control groups were compared for HOMA-IR, the difference was not statistically significant. It is considered that kisspeptin is one of the reasons for hypogonatropic hypogonadism and has less effect on insulin resistance.

The effects of polycystic ovary syndrome on gestational diabetes mellitus.

The aim of this study was to explore the inter-relationship between polycystic ovary syndrome and gestational diabetes mellitus, and demonstrate maternal and fetal outcomes. This was a case-control study in 1360 pregnant women who received a diagnosis of gestational diabetes mellitus between 24 and 28 weeks of gestational age. Among all diagnosed with gestational diabetes mellitus, 150 pregnant women had received a polycystic ovary syndrome, and 160 women who did not have polycystic ovary syndrome were designated as controls. The incidence of pregnancy-induced hypertension was 26.3% and 12% in the case and control groups, respectively. Preeclampsia was seen at an incidence of 12% and 6% in case and in control groups, respectively. The difference in neonatal hypoglycemia between the two groups was statistically significant, with an incidence of 17% and 5% in the case and in control groups, respectively. This study demonstrated that the presence of polycystic ovary syndrome along with gestational diabetes mellitus increases the risk of pregnancy induced hypertension by 2.4 fold, preeclampsia by 2 fold and neonatal hypoglycemia by 3.2 fold, compared to gestational diabetes mellitus alone.

Differences in clinical characteristics for the determination of adenomyosis coexisting with leiomyomas.

AIM: The objective of the analysis was to determine the characteristics that distinguish women with adenomyosis and leiomyomas from those with leiomyoma only from a sample who underwent hysterectomy for benign uterine diseases. METHODS: This retrospective study was based on the analysis of medical records of 75 women with both adenomyosis and uterine leiomyomas and 218 women with leiomyomas only, diagnosed by histologic analysis of uterine specimens. RESULTS: Results of multivariate logistic regression analyses showed that women with both adenomyosis and leiomyomas had a higher gravity (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.01-1.33) and more frequent pelvic pain (OR 0.38, 95% CI 0.21-0.7) compared with women with leiomyomas only. Postmenopausal bleeding was commonly reported in women with adenomyosis and leiomyomas. No significant difference was observed between the two groups in terms of menorrhagia and metrorrhagia and the preoperative diagnosis of prolapse. CONCLUSIONS: The presence of concomitant adenomyosis may cause different clinical symptomatology.

Predictive Risk Factors in the Treatment of Gestational Diabetes Mellitus.

OBJECTIVE: This study aims to investigate predictive risk factors in the treatment of gestational diabetes mellitus (GDM). PATIENTS AND METHODS: A total of 256 pregnant women who underwent 75 g oral glucose tolerance test (OGTT) during 24-28 weeks of pregnancy were included according to the World Health Organization criteria. Demographic characteristics of the patients, including age, parity, family history of diabetes, body weight before pregnancy, and body weight at the diagnosis of GDM, were recorded. Fasting insulin and hemoglobin A1c (HbA1c) values at the time of diagnosis were evaluated. The patients were divided into two groups: those requiring insulin treatment (insulin group, n = 89) and those receiving diet therapy (diet group, n = 167) during pregnancy according to the American Diabetes Association recommendations. RESULTS: A total of 34.76% of the pregnant women with GDM required insulin treatment. The mean age of these patients was significantly higher compared to the diet group (34.9 ± 0.6 years vs. 31.9 ± 0.6 years; P = 0.004). Body mass index before pregnancy was also significantly higher in the insulin group than that in the diet group (32 ± 0.9 kg/m(2) vs. 29 ± 0.7 kg/m(2); P = 0.004). Fasting blood glucose (FBG) during OGTT was 105.6 ± 2.1 mg/dL and 96.7 ± 1.1 mg/dL in the insulin group and diet group, respectively (P < 0.001). There was no significant difference in fasting plasma glucose during OGTT between the groups (P = 0.069), while plasma glucose at two hours was 161.1 ± 6.8 mg/dL in the insulin group and 145.1 ± 3.7 mg/dL in the diet group (P = 0.027). At the time of diagnosis, HbA1c values were significantly higher in the insulin group compared to the diet group (5.3 ± 0.1 vs. 4.9 ± 0.1; P = 0.001). There was no significant difference in FBG and homeostasis model assessment-insulin resistance values between the groups (P = 0.908, P = 0.073). CONCLUSION: Our study results suggest that age, family history of diabetes, body weight before pregnancy, FBG, and HbA1c values are predictors for the necessity of insulin treatment.

Is there any relationship between unrecognized Celiac disease and unexplained infertile couples?

BACKGROUND/AIMS: Celiac Disease (CD) is a chronic autoimmune disease characterized by small intestinal malabsorbtion and diarrhea, triggered by the ingestion of food products containing gluten. There are studies reporting that some nutritional deficiencies and some factors related to immunity may cause a decrease in fertility as well as some problems in sperm parameters. The prevalence of CD in unexplained infertility (UEI) couples is not as high as that mentioned in some reports. There is no accurate knowledge about the prevalence of CD in a UEI couple. MATERIALS AND METHODS: A total of 68 couples with UEI who were admitted at Türk Diyanet Vakfi 29 Mayis Hospital Center of in vitro fertilization (IVF) between January and June 2014 were included in this prospective pilot study. The diagnosis of UEI was made with basic infertility tests. A history of CD was questioned in the initial evaluation. Anti-gliadin, anti-endomysial, and tissue transglutaminase antibodies as well as total IgA were tested. Gastroscopy was performed in patients with positive serologic tests. Histopathological CD diagnosis was made according to Marsh criteria. RESULTS: The mean age of the study population was 33.40±4.59 years. Out of the 65 couples who were included into the study group, one of the five couples was positive for the autoantibodies (7.69%). Out of these 65 couples, none of them had autoantibody positivity at the same time in both partners. Anti-gliadin antibodies were found to be positive for two females out of five couples and in three male partners of the same group. Out of these five couples, only one male partner had all the antibodies as positive (1.5%). In the histopathological examination of patients with positive autoantibodies, only the patient in whom all autoantibodies were positive had findings compatible with Marsh IIIa gluten enteropathy. Only one couple had a diagnosis of CD (1.5%). CONCLUSION: In many studies, CD was shown to affect the reproductive system of women. CD may also cause a decrease in fertility in men by affecting sperm motility and androgen levels. Our study is based on a limited sample size. Our data should be confirmed in a larger cohort of subjects. These results suggest that investigation of both couples with a diagnosis of UEI may be more beneficial in clarifying the etiology.

Gastrointestinal Stromal Tumor: May Mimic Adnexal Mass.

Gastrointestinal stromal tumors (GISTs) are rare tumor of the gastrointestinal tract. GISTs occur in the entire gastrointestinal tract and may also arise from the retroperitoneum, omentum and mesenteries. They are originated from gastrointestinal pacemaker cells (Cajal's interstitial cells) and range from benign tumors to sarcomas at all sites of occurrence. Diagnosis of GIST could be deceptive because of their similarity in appearance to gynecological neoplasms. We would like to present a case of a woman with GIST in the small intestine giving a imprint of an adnexal mass was diagnosed correctly during surgery. The diagnosis and treatment of GIST has been reformed over the past years. It is crucial to separate GISTs from possible misdiagnosis because their prognosis and treatment could be unlike clearly. The purpose of this case is to evaluate this rarely seen clinical entity, and thus, make some contribution to the literature.

A successful healthy childbirth in a case of total globozoospermia with oocyte activation by calcium ionophore.

BACKGROUND: Globozoospermia is a rare (incidence of 0.1% among andrological patients) and poorly understood condition, but a severe disorder in male infertility. This case report detailed the course of treatment and protocol of a patient with type 1 globozoospermia using Intracytoplasmic Sperm Injection (ICSI) and oocyte activation by calcium ionophore, which yielded conception and birth of a healthy baby after six previous unsuccessful attempts, using ICSI alone. CASE PRESENTATION: A 39-year-old male with normal findings on routine examination presented to TDV 29 Mayis Hospital, Assisted Reproduction Unit (ART) with his 37-year-old wife. Her examination was also within normal limits and ovulatory cycle was regular. The male's diagnostic screening revealed normal karyotype (46, XY) and no Y-microdeletion. However, the spermogram was abnormal; sperm count of 14 million/ml with 35% active motility and 100% morphologically abnormal sperm, indicating globozoospermia. Ovarian stimulation was provided using classic long down-regulation protocol and 13 MII oocytes were collected. Next, calcium ionophore was applied following the ICSI procedure to improve the chances for fertilization. The case report compared quantitative procedural and diagnostic screening data, and fertilization rates. On day 5, two grade 1 blastocysts out of 5 embryos were transferred, yielding positive beta-human chorionic gonadotropin (beta hCG), and ultimately a healthy delivery. CONCLUSION: ICSI with assisted oocyte activation by calcium ionophore may overcome male infertility where there is total globozoospermia.

Female sexual distress in infertile Turkish women.

OBJECTIVE: To evaluate the effect of infertility on sexual distress in women attending the infertility clinic. MATERIALS AND METHODS: In a cross-sectional study we evaluated sexual distress among 88 women who attended the infertility clinic in our institute between January and June 2015. All women who were experiencing primary or secondary infertility during the study sampling were included in the sudy. Sexual distress was measured using the Female sexual distress scale-revised (FSDS-R), a cross-validated patient-reported outcomes measure. Correlations of FSDS-R with patient characteristics and laboratory measurements were calculated using Spearman's rank correlation tests. RESULTS: With the exceptions of the age of couples and serum anti-mullerian hormone (AMH) levels, no predictor of high sexual distress was found in the univariate analysis when comparing groups with regard to the FSDS-R cut-off score. The mean age of the sexually distressed women (33.6±5.8 years vs. 29.3±5.1 years) and their partners (35.4±4.8 years vs. 31.6±4.2 years) was significantly higher than those of the non distressed women, according to a FSDS-R score over 11 (p<0.05). The serum level of AMH was significantly lower in infertile women with high total sexual distress scores (1.4 vs. 7.6 ng/mL (p<0.001)). CONCLUSION: In infertile women, age of woman, age of partner, and serum AMH levels are related with the hope of women to have a child despite an association with sexual distress. Serum AMH, which is perceived as necessary for fertility, had a significant inverse correlation with levels of sexual stress.

Cornual heterotopic pregnancy after bilateral salpingectomy and uterine septum resection resulting in term delivery of a healthy infant.

Heterotopic pregnancy is the simultaneous occurrence of two or more implantation sites. A 25-year-old infertile patient with a history of bilateral salpingectomy, uterine septum resection, and left cornual resection was diagnosed with heterotopic pregnancy in her second in vitro fertilization trial. She attended our clinic when she was 7-week pregnant, complaining initially of severe abdominal pain. Findings associated with peritoneal irritation were positive during the physical examination. Transvaginal ultrasound revealed right cornual ectopic pregnancy with a live fetus in the middle of the uterine cavity. Also free fluid was noted in the pelvis. A diagnosis of heterotopic pregnancy with rupture of the cornual pregnancy was made. She underwent emergency laparoscopy with aspiration of the ruptured ectopic pregnancy, suturing to the entire visible cornual margins, and assurance of good haemostasis. Her recovery was uneventful and she continued receiving care in our obstetric unit. She delivered a healthy newborn by cesarean section at term.

First successful pregnancy in a globozoospermic patient having homozygous mutation in SPATA16.

OBJECTIVE: To report the first case of a successful pregnancy obtained with an infertile 29-year-old man with a homozygous mutation in the spermatogenesis-specific gene SPATA16 after intracytoplasmic sperm injection (ICSI). DESIGN: Case report. SETTING: Assisted reproductive technology (ART) center. PATIENT(S): A couple who suffered from infertility of whom the husband was globozoospermic and carrying a homozygous mutation in the spermatogenesis-specific gene SPATA16. INTERVENTION(S): Clinical and histopathological evaluation, transmission electron microscopy, stimulation with fixed antagonist protocol, ICSI, activation of fertilization. MAIN OUTCOME MEASURE(S): In vitro fertilization and pregnancy. RESULT(S): Oligoasthenoteratozoospermia was revealed in semen analysis. Total globozoospermia was detected. Chromatin condensation pattern was detected abnormal in 88% of spermatozoa with aniline blue staining. During the ART cycle 12 oocytes were collected. Eleven oocytes were at the metaphase II and one was at the germinal vesicle stage. After the injection, one oocyte fertilized on the following day; the 4-cell stage embryo was transferred. Pregnancy occurred and a healthy boy was delivered after 42 weeks of gestation. CONCLUSION(S): This is the first report of a pregnancy obtained in a man with homozygous SPATA16 mutated globozoospermia.

Day 3 embryo shape as a morphologic selection parameter in in vitro fertilization.

PURPOSE: To investigate whether embryo shape is a useful morphologic predictor of developmental competence in IVF cycles. METHODS: Two hundred eighteen day 3 single embryo transfer (SET) cycles and 225 day 3 double embryo transfer (DET) cycles in which only 8-cell non-fragmented embryos with symmetric blastomeres were transferred and in which the developmental fate of each embryo was known were analyzed for IVF outcomes with respect to embryo shape. Embryo shape was quantitatively calculated after digitizing embryo images using MATLAB, where a score of 1.0 represented a perfectly circular embryo. RESULTS: The SET data did not reveal a significant impact of embryo shape on embryo developmental fate. The DET data revealed a trend toward the best outcomes in cycles where both embryos exhibited "roundness" scores in the highest tertiles (T3) for embryo shape. However only one subgroup (T2/T1-one embryo in the middle shape tertile (T2) and one in the lowest shape tertile (T1)) was associated with significantly lower odds of live-birth as compared to the referent group (T3/T3). When SET and DET data were combined, embryo shape was not found to be a predictor of IVF outcome. CONCLUSIONS: Based on this retrospective analysis, the weak association of day 3 embryo shape with implantation potential suggests that this morphological characteristic is unlikely to be a useful additional marker for embryo selection after cell number, fragmentation, and blastomere symmetry. Further studies are planned to assess applicability of these conclusions to embryos of varying stages and grades.

Ovarian reserve status in young women is associated with altered gene expression in membrana granulosa cells.

Diminished ovarian reserve (DOR) is a challenging diagnosis of infertility, as there are currently no tests to predict who may become affected with this condition, or at what age. We designed the present study to compare the gene expression profile of membrana granulosa cells from young women affected with DOR with those from egg donors of similar age and to determine if distinct genetic patterns could be identified to provide insight into the etiology of DOR. Young women with DOR were identified based on FSH level in conjunction with poor follicular development during an IVF cycle (n = 13). Egg donors with normal ovarian reserve (NOR) comprised the control group (n = 13). Granulosa cells were collected following retrieval, RNA was extracted and microarray analysis was conducted to evaluate genetic differences between the groups. Confirmatory studies were undertaken with quantitative RT-PCR (qRT-PCR). Multiple significant differences in gene expression were observed between the DOR patients and egg donors. Two genes linked with ovarian function, anti-Mullerian hormone (AMH) and luteinizing hormone receptor (LHCGR), were further analyzed with qRT-PCR in all patients. The average expression of AMH was significantly higher in egg donors (adjusted P-value = 0.01), and the average expression of LHCGR was significantly higher in DOR patients (adjusted P-value = 0.005). Expression levels for four additional genes, progesterone receptor membrane component 2 (PGRMC2), prostaglandin E receptor 3 (subtype EP3) (PTGER3), steroidogenic acute regulatory protein (StAR), and StAR-related lipid transfer domain containing 4 (StarD4), were validated in a group consisting of five NOR and five DOR patients. We conclude that gene expression analysis has substantial potential to determine which young women may be affected with DOR. More importantly, our analysis suggests that DOR patients fall into two distinct subgroups based on gene expression profiles, indicating that different mechanisms may be involved during development of this pathology.

Prenatal diagnosis of Wolf-Hirschhorn syndrome (4p-) in association with congenital hypospadias and foot deformity.

BACKGROUND: Wolf-Hirschhorn syndrome is caused by distal deletion of the short arm of chromosome 4 (4p-). We report a case in which intrauterine growth restriction, hypospadias and foot deformity were detected by prenatal ultrasound examination at 29 weeks of gestation. CASE PRESENTATION: A 31-year-old gravida 2 partus 1 woman was referred at 29 weeks' gestation with suspicion of intrauterine growth restriction. Sonographic examination revealed deformity of the right lower limb and undescended testes with an irregular distal penis. A cordocentesis was performed and chromosome analysis revealed a 46,XY,del(4)(p14) karyotype. CONCLUSION: The prenatal detection of intrauterine growth restriction, hypospadias and foot deformity should lead doctors to suspect the presence of Wolf-Hirschhorn syndrome.