Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations.

OBJECTIVES: Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome-wide association studies and whole-exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants in SHH, RORA, MRPL53, ACVR1, and GDF11. MATERIALS AND METHODS: We sequenced these five genes in 1255 multi-ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools. RESULTS: Ninteen total variants of interest were found, with variant types including stop-gain, missense, synonymous, intronic, and splice-site variants. Of these, 3 novel missense variants were found, one in SHH, one in RORA, and one in GDF11. CONCLUSION: This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations.

Genomic analyses in African populations identify novel risk loci for cleft palate.

Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.

The role of sperm banking in fertility preservation.

OBJECTIVE: To investigate factors that influence sperm banking before cancer therapy and assess the use and disposal of banked sperm after cancer treatment. STUDY DESIGN: Database exploratory study combined with questionnaire survey of a cohort of 55 men who cryopreserved their sperm at an Andrology Clinic. MAIN OUTCOME MEASURE(S): Rate of use, disposal and abandonment of banked sperm, current fertility, and patient satisfaction with sperm banking. RESULTS: Using logistic regression, we analyzed the factors associated with use and disposal of banked sperm, current fertility status, reproductive outcomes and quality of life in 55 survivors of cancer therapy who cryopreserved sperm at our facility. Most (93%) of the patients undergoing sperm banking before cancer treatment did not use their samples and 33% requested sperm disposal following completion of cancer therapy. Married status and fatherhood before cancer therapy were associated with higher rates of sperm disposal. Sperm disposal was requested because the subjects remained fertile, spontaneously fathered a child, or completed their family. The families of four patients (7%) who died from their cancer also requested disposal of the stored sperm. Six (11%) patients could not be located or failed to contact the clinic and were considered to have abandoned their banked sperm. Only 7% of the patients used their cryopreserved sperm for assisted reproduction. Most of the patients that banked sperm achieved pregnancy with their partners through spontaneous conception compared to through the use of cryopreserved sperm. CONCLUSIONS: The rates of disposal and abandonment of banked sperm were high following cancer therapy. Retention of fertility appears to contribute to the low utilization of banked sperm, which emphasizes the need for appropriate consent and directives regarding disposal of unused cryopreserved sperm.

Subclinical hypothyroidism among infertile women at a tertiary hospital in South-West Nigeria.

Background: Overt thyroid dysfunction is an accepted cause of female infertility. Its milder form, subclinical hypothyroidism have also been implicated as a contributing factor to disturbed reproductive function. Objective: To determine the contribution of subclinical hypothyroidism (SCH) to the burden of infertility. Methodology: This is a cross sectional, comparative study of One hundred and twenty women with primary or secondaryinfertility who presented for evaluation at gynaecological clinic and controls which are clients that came to access Family planning services. Results: The prevalence of infertility among gynaecological patients seen in the clinic was 38.8% (192/495). The prevalence of SCH among the studied infertile women was 11.7% (7/60) compared with 3.3% (2/60) of the control group (p=0.222). The commonest type of infertility was secondary, 76.7% (46/60). All thestudied infertile women with SCH presented with secondary infertility. There was an observed statistically significant difference in the mean serum TSH (3.19±4.38mIU /L vs 1.60±1.22mIU /L) and FT3, FT4 (0.29±0.074ng/dl vs 0.95±0.16ng/dl and 0.33±0.071ng/dl vs 1.09±0.19ng/dl respectively). Conclusion: Subclinical hypothyroidism was found to be higher among infertile women but this finding was not statistically significant, therefore, the routine screening for SCH among infertile women might be unnecessary.

Fetal heart rate monitoring during nocturnal polysomnography.

STUDY OBJECTIVES: To evaluate the success rate of adding continuous electronic fetal heart rate monitoring (EFM) during full night polysomnography (PSG), in women with both gestational hypertension (GH) with uncomplicated singleton pregnancies. METHOD: As part of a larger study evaluating for the presence of sleep disordered breathing (SDB) in women with GH compared to women with uncomplicated pregnancies, continuous EFM was added to usual polysomnography. RESULTS: Forty-eight EFM studies (26 with GH and 22 with uncomplicated pregnancies) were evaluated. EFM studies were categorized by the percentage of time that interpretable tracings were obtained: < 25% of the time; 25-50% of the time; or > 50% of the time. We deemed > 50% of the time to be ideal, but under the test conditions 25-50% of the time to be acceptable. For women with GH, 71% of women had ideal or acceptable overnight EFM tracings compared to 82% for women with uncomplicated pregnancies. Of those women who were diagnosed with SDB, 77% had an acceptable or ideal EFM tracing. CONCLUSIONS: Adding EFM to conventional polysomnography is feasible and safe. It may prove an important adjunct as interest in sleep disorders of pregnancy continues to expand.

Patterns of pregnancy exposure to prescription FDA C, D and X drugs in a Canadian population.

OBJECTIVE: To examine prescription Food and Drug Administration (FDA) C, D and X drugs in general obstetric population. STUDY DESIGN: Historical cohort study. RESULT: A total of 18 575 women who gave a birth in Saskatchewan between January 1997 and December 2000 were included. Among them, 3604 (19.4%) received FDA C, D or X drugs at least once during pregnancy. The pregnancy exposure rates were 15.8, 5.2 and 3.9%, respectively, for category C, D and X drugs, and were 11.2, 7.3 and 8.2%, respectively, in the first, second and third trimesters. Salbutamol (albuterol), trimethoprim/sulfamethoxazole (co-trimoxazole), ibuprofen, naproxen and oral contraceptives were the most common C, D, X drugs used during pregnancy. CONCLUSION: About one in every five women uses FDA C, D and X drugs at least once during pregnancy, and the most common prescription drugs in pregnancy are antiasthmatic, antibiotics, nonsteroid anti-inflammation drugs, antianxiety or antidepressants and oral contraceptives.

Human papillomavirus DNA detection in sperm using polymerase chain reaction.

OBJECTIVE: To detect human papillomavirus (HPV) in semen and find if sperm washing removes HPV DNA. METHODS: Amplification by nested polymerase chain reaction (PCR) was used to detect viral DNA sequences in semen samples from 85 volunteers. Forty-five men had historical or clinical evidence of genital HPV infection (study group) and 40 were healthy, clinically HPV-negative semen donors. RESULTS: We detected HPV DNA in the sperm cells of 24 of 45 subjects (53%) with past or current HPV infections in contrast to three of 40 healthy subjects (8%) (P <.001). Overall, PCR detected HPV in 21 of 32 subjects (66%) with identifiable lesions and six of 53 (11%) without them (P <.001). Swim-up washings of all 27 prewash sperm cells with HPV reduced cellular HPV DNA below detectable levels in only two cases. CONCLUSION: HPV is present in sperm cells from infected and apparently healthy subjects, and sperm washing does not eliminate the risk of HPV transmission to recipients. We suggest that HPV DNA testing should be done on the semen of prospective donors, and those with positive tests should be excluded from donation.

Cervical cerclage operation for a dilated cervix.

Twelve pregnant women with previously undiagnosed cervical incompetence each presented with membranes bulging through a widely dilated cervix and were treated by a cerclage procedure. This emergency closure of the open cervix resulted in a high rate of fetal salvage; 10 of the 12 women were delivered of surviving infants.

Delayed interval delivery in triplet pregnancy: report of a single case and review of the literature.

A case report of delayed delivery of 99 days in a triplet pregnancy is presented. A triplet pregnancy in a single uterus resulted from Pergonal stimulation of ovulation. At 23.5 weeks' gestation, the first triplet delivered after spontaneous rupture of membranes. Ninety-nine days later, the remaining two fetuses were delivered, the second one stillborn after intrauterine death at 37 weeks of gestation, and the third fetus a normal viable female consistent with 37.5 weeks' gestation. This is the longest interval of delayed delivery discovered from a literature review, and the only such instance of triplet pregnancy in a single uterus.

Ovarian follicular development is initiated during the hormone-free interval of oral contraceptive use.

We evaluated ovarian follicular development in women during compliant use of oral contraceptives (OC). Thirty-six healthy women received: [35 microg ethinyl estradiol (21)/180 microg norgestimate (7), 215 microg norgestimate (7), 250 microg norgestimate (7)]; [30 microg ethinyl estradiol (21)/150 microg desogestrel (21)]; or [20 microg ethinyl estradiol (21)/100 microg levonorgestrel (21)] for 3 consecutive 28-day cycles. Transvaginal ultrasonography was performed every third day to monitor follicular development. If a follicle reached > or = 14 mm, ultrasonography was performed daily and blood drawn every other day to determine estradiol-17beta concentrations. Seventeen of 36 women (47%) grew follicles > or = 10 mm. Nine of the 17 women (53%) grew follicles > or = 14 mm, in association with increased serum concentrations of estradiol-17beta. Thirty-seven of 43 follicles > or = 10 mm (86%) emerged during the hormone-free interval (HFI). No ovulations were observed. Our results supported the hypothesis that follicular development to an ostensibly ovulatory diameter occurs during compliant OC use, in association with loss of endocrine suppression during the HFI.

Cesarean versus vaginal delivery in abruptio placentae associated with live fetuses.

In order to test the relative effectiveness of cesarean section and vaginal delivery in mild abruptio placentae associated with live fetuses, 23 consecutive patients were delivered vaginally and 18 by cesarean section over an 18-month period at the University of Ife Hospital in Nigeria. The perinatal mortality of the vaginal delivery group (52.2%) was significantly greater than that of those delivered by cesarean section (16.7%) (P greater than 0.02; less than 0.05; chi 2 test). The 1-min Apgar score test was also significantly greater than that of those delivered by cesarean section (P greater than 0.001). These differences have been attributed to the admission-to-delivery interval, which was significantly longer in the vaginal delivery group (12 h vs. 2 h). It is concluded that cesarean section is clearly superior to vaginal delivery in the management of abruptio placentae associated with live fetuses.

The teaching of evidence-based reproductive health in developing countries.

Evidence-based medicine is gaining increased importance in clinical practice. Unfortunately, prevailing circumstances have prevented this application of the best available evidence to clinical decision-making for reproductive health in developing countries. Poor infrastructure, inadequate personnel, gross underfunding of services for health and education as well as a conservative education system are obstacles in effecting change. By examining these impediments, we suggest strategies for clinical education and research with the aim of improving reproductive health care in developing countries. Evidence-based reproductive health will be promoted through access to appropriate information, interest from government and consumers, curriculum changes, application of research findings and finally, the judicious use of its principles in clinical practice.

Outcome of cryosurgery for cervical intraepithelial neoplasia in a developing country.

Over a 2-year period cryosurgery was used to treat 73 women who were diagnosed by colposcopy and histologic studies to have cervical intraepithelial neoplasia (CIN). Follow-up was achieved for 70% at 5 years, a significant attendance rate in a developing country. The primary cure rate was 88.5% at 1 year and 90% at 5 years (excluding those lost to follow-up) in all patients with different grades of CIN. The therapy was free of major complications and we found no adverse effect of cryosurgery on subsequent reproductive function in those desiring pregnancy. We conclude that cryosurgery has gained wide acceptance in our geographic area particularly because of its low cost, efficacy and preservation of fertility. For these reasons we would strongly recommend its use provided adequate attention is paid to meticulous pretreatment evaluation and long-term follow-up after therapy.

Ventriculoperitoneal shunt and pregnancy.

A pregnancy in a patient with ventriculoperitoneal (VP) shunt was recently managed at the authors's institution. Review of the literature showed only six previous case reports. The management of this uncommon neurosurgical condition in pregnancy is presented along with a review of the literature. We conclude that pregnancy in a patient with a VP shunt for maternal hydrocephalus, generally has a normal outcome and that the function of the shunt is unaffected by pregnancy.

Delayed interval delivery in quadruplets.

Prolonged interdelivery periods in preterm twin and triplet gestations have resulted in a good outcome for the fetus(es) remaining in utero. This is the second reported case of delayed delivery intervals in quadruplets who were born on 3 separate days. We report on a set of quadruplets following gonadotropin induction of ovulation, in which preterm delivery of the first infant occurred at 26 weeks' gestation. Active uterine contractions ceased and ultrasonography confirmed the remaining triplets to be in separate amniotic sacs with satisfactory heart rate tracings. With bed rest and tocolysis, the delivery of the second infant did not occur until 8 days later. After a further 36-h delay, placental abruption prompted cesarean delivery of the remaining twins. The first infant died of sequelae of prematurity at 7 months, while the remaining triplets survived and are neuro-developmentally normal 1 year after delivery. This report demonstrates the feasibility of prolonging the delivery interval of the fetus(es) in higher order multiple gestations, using tocolysis and watchful expectancy, after the preterm birth of one or more fetuses.

Screening for cervical neoplasia in an African population: simultaneous use of cytology and colposcopy.

In many countries cytologic screening for cervical cancer has become firmly established and accepted. This has not been the case in some developing countries because of limited financial and manpower resources. In a series of 1564 patients, simultaneous colposcopy and cytology revealed 31 women with varying degrees of cervical intraepithelial neoplasia. We feel that an initial combination of colposcopy and cytology provides a more reliable diagnosis of cervical lesions and a case is made for the establishment of mass cytologic screening in Nigeria.

Early experience with in vitro fertilization-embryo transfer and gamete intrafallopian transfer in a Nigerian hospital.

We present our early experience with in vitro fertilisation-embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT) in a Nigerian Hospital. Twenty-one patients were recruited, 11 patients for the IVF-ET program and 10 for the GIFT program. In the IVF program the oocyte recovery rate was 100%, the fertilization rate was 66% and the cleavage rate was 97% but no live pregnancies were achieved. In contrast, one live delivery was achieved with GIFT. These results suggest that both IVT-ET and GIFT are feasible in developing countries.

Emergency cerclage compared with bed rest for advanced cervical dilatation in pregnancy.

In a cohort of 43 women with viable, singleton pregnancies, cervical dilatation greater than 4 cm, and absent labor between 20 and 27 weeks gestation, 22 women who underwent emergency cerclage within six hours of admission, were compared prospectively with 15 women who elected conservative bed rest treatment. The two groups were demographically similar. Emergency cervical cerclage resulted in a longer mean gestational age at delivery compared to bed rest (p = 0.001). Women treated with cerclage required a significantly shorter period of antepartum hospitalization (p = 0.001), required less tocolysis (p = 0.005), and experienced fewer preterm membrane ruptures compared to women in the bed rest group (p = 0.01), although the latency period, following preterm rupture of membranes was shorter in the cerclage group (p = 0.005). There was no statistical difference in the frequencies of chorioamnionitis, maternal morbidity and cesarean section between the two groups. Although the perinatal mortality in the two groups was not significantly different (p = 0.3), emergency cerclage resulted in a significantly higher mean birth weight compared to conservative bed rest treatment (p = 0.02). This study demonstrates the superiority of emergency cerclage to bed rest in women with advanced cervical dilatation and absent labor in late second-trimester of pregnancy.

How important is health promotion in the lifestyle of infertile couples?

UNLABELLED: We sought to elucidate the current attitudes and practices of infertile couples concerning unhealthy lifestyle practices, and examine the extent to which the couples engaged in health promoting activities. METHODS: The study population consisted of consecutive couples who first attended an infertility clinic at a tertiary care clinic between July 1, 1995 and June 30, 1996, and voluntarily completed a questionnaire centered on knowledge, attitude and practices pertaining to unhealthy lifestyles as well as health promoting activities. RESULTS: The majority of the 106 couples 53%, reported cigarette smoking by at least one partner; 69% admitted to alcohol consumption; and 77% were using over-the-counter drugs. Only 28% of the smokers were knowledgeable about the value of smoking cessation intervention. In 11 of the 50 (22%) nonsmoking couples, both partners had stopped smoking because of their infertility. Awareness of the adverse effects of smoking on fertility was more common among nonsmokers and females. A large proportion of respondents failed to appreciate the periconceptional risks of alcohol consumption and over-the-counter drugs. Only 59 per cent of alcohol users considered its consumption to be undesirable when trying to conceive. Over-the-counter drugs were not considered to impair fertility by 71% of respondents. Compared to males, females were more conducive to health promotion practices as exemplified by smoking cessation, avoidance of second hand smoking, and regular exercising. CONCLUSIONS: Infertile couples seeking medical intervention often disregard lifestyle factors having adverse effects on fertility. Clearly, there is a need for early education on the value of health promotion and prevention in relation to the management of infertility.

A prospective study of induction of labor with prostaglandin vaginal gel: ambulatory versus in-patient administration.

BACKGROUND: Elective induction of labour is a common obstetrical practice. Dinoprostone (prostaglandin E2 in triacetin base gel) has been shown to be an effective and fairly safe agent for this purpose in inpatient settings. Currently published work does not assess the effectiveness and safety of dinoprostone in an ambulatory setting. OBJECTIVE: To assess the difference between inpatient and outpatient use of dinoprostone for elective induction of labour with regard to effectiveness, safety, length of hospital stay, and patient satisfaction. METHODS: A prospective non-randomized study, in which two groups of low risk obstetrical patients who were undergoing elective induction of labour were studied. The outpatient group was drawn from Regina Health District while the inpatient (control group) was drawn from Saskatoon. The maternal and fetal morbidity was compared in both groups as well as the efficacy, length of hospital stay and degree of patient satisfaction. RESULTS: There were statistically significant reductions in the length of hospital stay and greater patient satisfaction in the outpatient group. No difference was found in efficacy and safety of prostaglandin use. CONCLUSIONS: The findings suggest that ambulatory use of prostaglandin gel for induction of labour reduces the length of hospital stay, and leads to greater patient satisfaction. Further randomized studies with a larger number of patients are needed to evaluate the safety of this agent in an ambulatory setting.