Whole-Genome Sequencing Reveals Exonic Variation of ASIC5 Gene Results in Recurrent Pregnancy Loss.

Family trio next-generation sequencing-based variant analysis was done to identify the genomic reason on unexplained recurrent pregnancy loss (RPL). A family (dead fetus and parents) from Saudi Arabia with an earlier history of three unexplained RPLs at the ninth week of pregnancy was included in the study. Whole-genome sequencing (WGS) of a dead fetus and the parents was done to identify the pathogenic variation and confirmed through Sanger sequencing. WGS of dead fetus identifies a novel homozygous exonic variation (NM_017419.3:c.680G>T) in ASIC5 (acid-sensing ion channel subunit family member 5) gene; the parents are heterozygous. Newly designed ARMS PCR followed by direct sequencing confirms the presence of heterozygous in one subject and absence of homozygous novel mutation among randomly selected healthy Saudis. The second family with heterozygous was confirmed with three unexplained RPLs. Pathogenicity analysis of R227I amino acid substitution in ASIC5 protein through molecular docking and interaction analysis revealed that the mutations are highly pathogenic, decrease the stability of the protein, and prevent binding of amiloride, which is an activator to open the acid-sensing ion channel of ASIC5. The identified rare and novel autosomal recessive mutation, c.680G>T:p.R227I (ASIC5Saudi), in two families confirm the ASIC5 gene association with RPL and can be fatal to the fetus.

Etiology of Recurrent Pregnancy Loss in Saudi Females.

OBJECTIVE: The aim of our retrospective study was to assess the etiology of recurrent pregnancy loss (RPL) in Saudi couples attending a specialized RPL clinic at King Fahad Hospital of the University, Al-Khobar, Saudi Arabia. PATIENTS AND METHODS: A total of 59 couples attending the RPL clinic between January 2010 and December 2013 and who had completed their workup and investigations for RPL were included in the study. Data were collected from patients' charts and computer-based laboratory results. RESULTS: Protein S deficiency was found in 47% of patients, a chromosomal abnormality in 6.7%, uterine abnormality in 12%, antiphospholipid syndrome (APS) in 12%, and antithrombin III and Protein C deficiency in 1.7%. However, no patient had Factor V Leiden mutation. In 39% of the patients, there was no identifiable cause, and therefore, they had been diagnosed as unexplained RPL. CONCLUSION: The most common cause of RPL was Protein S deficiency followed by congenital uterine anomalies and APS. Almost 40% of couples with RPL remain with unknown etiology.

The effect of body mass index on the outcome of pregnancy in women with recurrent miscarriage.

BACKGROUND: Maternal obesity is associated with menstrual disorders, infertility and sporadic miscarriages. Recurrent miscarriage (RM) affects at least 1% of couples trying to conceive. In over 50% of cases, the cause of the loss of pregnancy remains unexplained. The aim of this study was to determine the relationship between maternal Body Mass Index (BMI) and future outcomes of pregnancy in couples with "unexplained" RM. METHODS AND RESULTS: All couples referred to the specialist recurrent miscarriage clinic at St. Mary's Hospital, London, were investigated for an underlying cause. Those with unexplained RM were eligible. Demographic and clinical data were retrieved from a computerised database and medical records. The World Health Organisation (WHO) classification of BMI was used. Univariate analysis demonstrated that BMI, maternal age, number of previous miscarriages and ethnicity were significantly associated with pregnancy outcome. Logistic regression demonstrated that maternal obesity (BMI ≥ 30 kg/m(2)) significantly increased the risk of miscarriage in couples with unexplained RM (OR 1.73; 95% CI 1.06 - 2.83). Asian women with a BMI similar to Caucasian women had a higher risk of a further miscarriage (OR 2.87, 95% CI, 1.52 - 5.39). CONCLUSIONS: Maternal obesity is an independent factor associated with an increased risk of miscarriage in couples with RM. All women with RM should have their BMI recorded at their first clinic visit. The potential effect of weight loss on the outcome of subsequent pregnancies should be assessed in future studies. The increased risk of miscarriage in Asian women needs to be explored further.

Recurrent hydatidiform mole: A case report of six consecutive molar pregnancies complicated by choriocarcinoma, and review of the literature.

Hydatidiform mole (HM) is the most common form of gestational trophoblastic neoplasia. Recurrence of HM is extremely rare. Here, we report the case of a patient with six consecutive partial HMs without normal pregnancy. A 42-year-old lady who was referred to us at King Fahad Hospital of the University, Al Khobar, initially as a case of 26-year-old with persistent trophoblastic disease after three recurrent molar pregnancies that were confirmed histologically in the referring hospital. She underwent evacuation and curettage and was followed up by serial ß-human chorionic gonadotropin levels, and did not require chemotherapy. She then had three more molar pregnancies in 1995, 1996, and 2004; all molar pregnancies were evacuated by suction curettage at her base hospital, but in the last event, she complained of shortness of breath and abdominal pain. Diagnostic workup in our hospital confirmed choriocarcinoma, for which she received multiple regimen chemotherapy and was cured. Unfortunately, she lately presented with symptoms suggestive of premature menopause.

Ovarian tumors in children and adolescents--a clinical study of 52 patients in a university hospital.

STUDY OBJECTIVE: To review the clinical presentation of ovarian tumors in children and adolescents treated at the University of Dammam and King Fahad University Hospital. DESIGN: Data of the patients was noted retrospectively from the hospital medical records regarding age, presentation, diagnosis, treatment, and outcome. SETTING: The study was carried out in the Ob/Gyn department at King Fahad Hospital of Dammam University, Saudi Arabia between January 1985 and December 2009. PARTICIPANTS: There were 52 patients between 6 and 20 years of age who presented with an ovarian tumor during the study period. INTERVENTION: Preoperative diagnostic approach included history, physical examination, ultrasonography, radiological examination, tumor markers, operative treatment, and histopathological examination of the tumor. Chemotherapy was given to patients where indicated. RESULTS: The main presenting symptom was abdominal pain in 30 (58%) patients. Of the neoplastic tumors, 87% were germ cell tumors, of which 73% were benign while 13% were malignant. Operative procedures included 48 (92%) exploratory laparotomies and 4 (8%) laparoscopic resections. Ovarian cystectomy was done in 23 (44%) patients and salpingoophorectomy in 28 (54%) patients. Of the 7 (13%) patients with malignant tumors, five received postoperative chemotherapy. Three patients with malignancy died in the series. CONCLUSION: Early diagnosis of ovarian masses in young girls is important. Since most of these masses are benign, operation should be designed to optimize future fertility, while the treatment of malignant tumors would involve complete staging, resection of the tumor, postoperative chemotherapy when indicated, to give the patient a chance for future childbearing.

Ovarian tumors associated with pregnancy: a 20-year experience in a teaching hospital.

OBJECTIVE: Pregnancy associated with ovarian tumors was reviewed over a 20-year period to determine the maternal and fetal outcome in patients undergoing surgery during pregnancy. METHOD: A retrospective study of 94 cases of ovarian tumors treated surgically during pregnancy was investigated for incidence, clinico-pathological features and outcome in a teaching hospital between June 1987 and May 2007. RESULTS: The overall incidence of ovarian tumor in pregnant women was 1 in 505 (0.2%) deliveries. Diagnosis of 69.2% tumors resulted in the first and second trimesters of pregnancy. Twenty-two (23.4%) patients presented as an emergency at different periods of gestation and 16 (17.1%) tumors were incidentally discovered at cesarean section which underlines the significance of examining the ovaries routinely at cesarean section. Benign teratoma (39.4%) and serous cystadenoma (24.5%) were the most common types of ovarian tumors found in the study. The incidence of malignant tumors was 5.3%. Tumors with low malignant potential comprised 40% of malignancy. The miscarriage rate after surgery was 44.4% in the first trimester compared with 16.6% in the second trimester. The preterm birth rate was 4.3% in the series. CONCLUSION: The value of clinical and ultrasound examinations in early pregnancy as a diagnostic aid is highlighted. Whenever an ovarian tumor is detected in pregnancy, malignancy should always be suspected. Treatment of an ovarian tumor in pregnancy should be tailored according to the age, parity, clinical presentation, gestational age and histopathology of the tumor. Removal of persisting or enlarging ovarian masses as soon as possible is important to obtain a final histologic diagnosis and rule out malignancy. Early diagnosis and appropriate treatment of malignant tumors offers the best prognosis for the patient.