The role of NADPH-derived reactive oxygen species production in the pathogenesis of endometriosis: a novel mechanistic approach.

Endometriosis is defined as endometriotic tissue growing outside the uterine cavity. It is a common gynecological disorder in women of reproductive age and is associated with chronic pelvic pain and infertility. Despite several studies and theories to explain its cause, the exact pathogenesis of endometriosis remains unclear. Retrograde menstruation is the most plausible theory, however, it is not exclusive. The disparity between the actual prevalence of retrograde menstruation and the prevalence of endometriosis suggests that other factors may determine the susceptibility to endometriosis development. Oxidative stress has been associated with endometriosis. This study aimed to explore the role of NADPH oxidase family in the production of reactive oxygen species (ROS) and to determine whether ROS induce the proliferation of endometriotic implants via mammalian target of rapamycin (mTOR) signaling. Anonymous endometriotic tissue samples were collected from women undergoing laparoscopy for endometriosis. The samples were stained with dihydroethidium and fluorescent images of the slides were taken to detect ROS production. After extraction of RNA from the samples and c-DNA generation, quantitative real-time PCR, protein extraction and Western blot were performed to study gene and protein expression of NADPH oxidase 1 (NOX 1), mTOR and fibronectin. The results showed an increase in ROS levels and NOX 1 gene and protein expression in the endometriotic tissues compared to the normal surrounding tissue control. Also, mTOR and fibronectin, gene expression was found to be increased. Up regulation of NOX at gene and protein level leads to increased production of ROS in the endometriotic tissue, which in turn causes proliferation of the ectopic tissue via alteration of the mTOR signaling pathway. Increased fibronectin gene expression points towards tissue injury in endometriosis as compared to the normal surrounding tissue. This manuscript adds a new insight into the pathogenesis of endometriosis and serves as a background for development of new treatments for the disease-associated pain and infertility.

Endometriosis and cancer: what do we know?

Endometriosis is the presence of endometriotic tissue outside of the uterus, composed of endometriotic glands and stroma. It affects between 10% to 12% of women in reproductive age. It presents with dysmenorrhea, dyspareunia, chronic pelvic pain, infertility, urinary or digestive symptoms. Diagnosis is based on clinical suspicion, clinical exam, pelvic ultrasound or pelvic magnetic resonance, and confirmed by laparoscopy with pathology studies. Its management is better understood nowadays. However, its association with neoplasia has been questioned for many years. It probably plays a role in the etiology of gynecological cancers, mainly ovarian neoplasia. In our review, we separately compared endometriosis and endometrioma to cancer, in terms of mutual causality, common risk factors, distinction based on histological findings, in addition to molecular and genetic pathways behind this association. This article reviews the English literature for studies on the association between endometriosis and gynecological cancers. Additional reports were collected by systematically reviewing all references from retrieved papers.

In vitro fertilization in a patient with ovarian cancer (stage IC) following conservative surgery and chemotherapy: a case report.

A 30-year-old female underwent left salpingo-oophorectomy followed by chemotherapy for Stage IC adenocarcinoma of the ovary. Three years later she had ovarian hyperstimulation and in vitro fertilization (OH-IVF) resulting in a singleton pregnancy. During cesarean section peritoneal washings and biopsies were negative for recurrence. Seven years after the initial diagnosis, the patient is still free of any disease. In conclusion, OH-IVF may be considered in young patients with early ovarian cancer treated with conservative surgery and chemotherapy.

A randomised comparison of patient satisfaction with vaginal and sublingual misoprostol for induction of labour at term.

OBJECTIVE: To compare patient satisfaction with two routes of misoprostol for term labour induction. DESIGN: Prospective randomised trial. SETTING: Tertiary care hospital. POPULATION: A total of 170 women admitted at > or = 37 weeks of gestation for induction of labour. METHODS: Women were randomised to receive 50 micrograms of either sublingual or vaginal misoprostol. MAIN OUTCOME MEASURES: Patient satisfaction with the route of administration. RESULTS: Despite a similar proportion reporting the labour induction as more painful than expected in both groups, a significantly lower proportion mentioned that the pelvic examinations were very painful in the sublingual group (19.7 versus 36.1%, relative risk [RR] 0.5, 95% CI 0.3-0.9). Request for analgesia was similar in both groups. More women in the sublingual group thought that the labour experience was better than expected (RR 2.0, 95% CI 1.2-3.3), had a positive attitude towards induction in subsequent pregnancies (RR 1.6, 95% CI 1.1-2.3) and preferred the same route in subsequent pregnancies (RR 3.1, 95% CI 2.2-4.5). Mean number of misoprostol doses, oxytocin augmentation, tachysystole and hyperstimulation, induction to vaginal delivery interval, vaginal delivery after a single dose, vaginal birth within 12 and 24 hours, and caesarean delivery rates were similar in both groups. CONCLUSION: Sublingual misoprostol (50 micrograms) is associated with a significantly higher patient satisfaction rate compared with a similar dose of vaginal misoprostol. Sublingual administration offers additional choice to women, in particular those wishing to avoid vaginal administration.

Two consecutive ectopic pregnancies after in-vitro fertilization and embryo transfer. Case report.

Ectopic pregnancy is a known complication of in vitro fertilization and embryo transfer (IVF/ET). The overall incidence of ectopic pregnancy after IVF is 4.4-5.8% of clinical pregnancies. The risk factors associated with ectopic pregnancies are complex. We present a patient with two consecutive ectopic pregnancies after IVF/ET.

Synchronous vulvar and breast cancer.

Synchronous vulvar and breast cancer is rare. A 44-year-old women presented with a lesion in the right labia majora and right upper quadrant breast lump. After work-up, she underwent radical wide local vulvar excision and modified radical mastectomy with axillary lymph node dissection. The pathology of the vulva revealed moderately-differentiated squamous cell carcinoma and that of the breast infiltrating ductal carcinoma. Only two such cases have been previously reported: one was an elderly patient and the second a young patient with HIV infection. Our patient is a young and healthy woman making her presentation a unique and rare case.

Laparoscopic unwinding and cystectomy of twisted dermoid cyst during second trimester of pregnancy.

A woman in the sixteenth week of pregnancy experienced acute abdominal pain, and magnetic resonance imaging suggested a dermoid cyst. Laparoscopic unwinding and cystectomy of the twisted cyst was performed successfully.

Rupture of an unscarred uterus with misoprostol induction: case report and review of the literature.

Uterine rupture is a serious and often tragic complication that is life threatening to both mother and child. It occurs at a frequency of around 1% in patients with a previously scarred uterus. Rupture of an unscarred uterus is an unexpected and devastating complication of pregnancy. With the increased use of misoprostol as a labor-inducing agent, cases of rupture of an unscarred uterus following its use have been published in the literature. We report a case of uterine rupture in a multigravid woman with an intrauterine fetal death at 29 weeks' gestation whose labor was induced with misoprostol. A review of all cases of uterine rupture with misoprostol induction is also included. Excessive doses of misoprostol should be used with extreme caution in multiparous women and in patients with a previously scarred uterus even in the context of intrauterine fetal death or termination of pregnancy.

Effect of human follicular fluid on sperm survival.

OBJECTIVE: To study the effect of follicular fluid (FF) on sperm survival. METHOD: Swim-up sperm suspensions obtained from 20 men with normal semen analysis were incubated with Ham's F-10 only and Ham's F-10 supplemented with 20% FF or 20% serum. Sperm motility was recorded every 12 hours for 72 hours. RESULTS: Sperm motility was maintained in all media for 48 hours. However, significantly more sperm samples remained motile at 72 hours in medium supplemented with FF and serum as compared to Ham's F-10 only. CONCLUSION: FF has a positive effect on conserving sperm motility as a function of time.

The placenta in meconium staining: lesions and early neonatal outcome.

PURPOSE: To evaluate the immediate neonatal outcome and the presence of various placental lesions in 96 pregnancies with meconium-stained amniotic fluid. MATERIALS AND METHODS: The patients were divided into a group with acute (N = 41) and subacute and chronic (N = 55) meconium staining of the placenta. Apgar scores, arterial cord pH and admission to the neonatal intensive care unit (NICU) were determined in addition to the findings on gross and microscopic examination of the placentas. RESULTS: Of the 53 live births with subacute and chronic meconium staining, 13% had Apgar Scores < or = 7 at 5 minutes compared to 7% with acute meconium staining. Similarly, a significantly lower umbilical artery pH was determined in the former group [(32%) versus (7%)], (p < 0.01). When 9 different pathologic lesions of the placenta were evaluated microscopically, the frequency of villous vascular thrombosis (25.4%), infarcts (38%), acute chorioamnionitis (20%), villous edema (9.1%) and villitis (14.5%) was significantly higher in the group with longer meconium exposure compared to the other group (2.4%), (9.7%), (7.3%), (0%), and 1 (2.4%), respectively. In addition, when tested for 4 different lesions, cases with acute meconium were less likely to have one or more lesions. When one or more placental lesions were found, NICU admission rate was significantly higher in the patients with subacute and chronic meconium. CONCLUSION: Subacute and chronic meconium discharge is associated with significant placental lesions and an increased risk of adverse pregnancy outcome in the immediate neonatal period.

Failure of fertilization after intracytoplasmic sperm injection in a patient with Kartagener's syndrome and totally immotile spermatozoa: case report.

Patients with Kartagener's syndrome (KS) are invariably infertile with totally immotile spermatozoa. Intracytoplasmic sperm injection (ICSI) is considered to be the treatment of choice for patients with immotile spermatozoa. We report the second KS case in the literature from whom immotile spermatozoa from the ejaculate failed to fertilize mature oocytes after ICSI. The role of micromanipulation in the treatment of KS patients is discussed.

Artificial endometrial preparation for oocyte donation using synthetic estrogen and progestogen.

OBJECTIVE: To evaluate the outcome of an oocyte donation program using synthetic estrogen and progestational agents for uterine preparation. METHODS: Conjugated estrogen, 1.25 mg per day at increasing doses and dydrogesterone, a synthetic progestogen, 30 mg per day were used for uterine priming. All embryo transfers were done on day 2 of progestogen supplementation. RESULTS: The pregnancy rates were 38% per embryo transfer. The ongoing pregnancy rate was 31% with an abortion rate of 20%. CONCLUSION: Endometrial preparation in an oocyte donation program using orally administered synthetic estrogen and progestogen gives pregnancy rates comparable to those reported with natural products.

Successful pregnancy outcome following Tompkins metroplasty done early in pregnancy.

A hysterosalpingogram revealed a septate uterus in a 29 year old nulliparous woman with a history of recurrent pregnancy loss. The patient underwent Tompkins metroplasty in the proliferative phase of the menstrual cycle. One month after the operation she presented with a delay in her menses and a positive pregnancy test. Ultrasound revealed a viable fetus commensurate with 10 weeks gestation, making the gestation period 5 weeks at the time of surgery. After reviewing the patient's menstrual history it was found that the period the patient had before surgery was on time but with unusually minimal bleeding. A repeat ultrasound scan for anomaly done 7 weeks later was commensurate with 17 weeks gestation. The patient carried her pregnancy for the first time until approximately 37 weeks when she delivered by Caesarean section a healthy female baby weighing 3700 g.

Intrauterine insemination IUI: the effect of ovarian stimulation and infertility diagnosis on pregnancy outcome.

We determined the intrauterine insemination (IUI) pregnancy outcome in the same group of patients when applying different methods of ovulation induction. A group of patients with unexplained (no. 46) and male factor infertility (no. 101) consented to have the following treatment protocol at the American University of Beirut-Infertility Center: IUI to be performed in three natural ovulatory cycles in all patients, then in three clomiphene citrate (CC) stimulated cycles in the remaining non-pregnant patients, and then three cycles with controlled ovarian hyperstimulation (COH) in the remaining group. Of the total 147 patients 130, 138 and 123 underwent 273 natural, 278 CC and 266 COH IUI cycles, respectively. Semen processing for IUI was done by washing the sperm twice and using the swim-up technique. The chi-square test was used for statistical analysis. Pregnancy rate per cycle of IUI with COH (9.8%) was significantly higher than that of IUI in natural cycles (3.3%) but approached significance when compared to IUI with CC cycles (5.4%). Also unexplained infertility cases had a significantly higher pregnancy rate (58.7%) when compared to that of male factor cases (22.8%). IUI still has a place in the treatment of infertility due to selective causes. Combined with COH, IUI gives the best pregnancy rate although its benefit with natural or CC cycles remains obvious.

Clomiphene citrate challenge test: cycle to cycle variability of cycle day 10 follicle stimulating hormone level.

The clomiphene citrate challenge test (CCCT), a means of assessing ovarian reserve, was shown by several studies to have an excellent predictive value for achieving conception in natural cycles, during ovulation induction and in-vitro fertilization cycles. Accordingly we elected to study the cycle to cycle variability of CCCT so as to determine the reliability of a single CCCT result. Two groups of patients were studied, the first (n = 40) were those patients who were performing the test because it was indicated, and the second (n = 24) were those who were receiving clomiphene citrate for ovulation induction. In both groups CCCT intercycle variability was significant in 75% of the cases, but this variability altered the prognostic values of the test in only 40% of the first group. In conclusion, our study showed a high percentage of intercycle variability of CCCT but further studies are needed to evaluate the influence of this variability on potential conception.

Effect of serum from fertile and infertile patients with endometriosis on the development of mouse embryos.

OBJECTIVE: To evaluate the effect of serum from infertile and fertile patients with endometriosis on the development of 2-cell mouse embryos. PATIENTS: Serum was obtained from 26 infertile patients and 8 fertile patients with endometriosis. Mouse embryo development in serum samples was compared using chi 2 analysis. RESULTS: In the infertile group 23% of the embryos reached blastocyst stage, whereas 22 of the 26 samples were embryo toxic. In the fertile group significantly more embryos (45%) developed to blastocysts and only one serum samples was embryo toxic. CONCLUSION: The embryo toxicity of serum samples from patients with endometriosis is related to the infertility associated with the disease and not with the disease per se.