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.

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.

Adult neurogenesis in the four-striped mice (Rhabdomys pumilio).

In this study, we investigated non-captive four-striped mice (Rhabdomys pumilio) for evidence that adult neurogenesis occurs in the adult brain of animal models in natural environment. Ki-67 (a marker for cell proliferation) and doublecortin (a marker for immature neurons) immunostaining confirmed that adult neurogenesis occurs in the active sites of subventricular zone of the lateral ventricle with the migratory stream to the olfactory bulb, and the subgranular zone of the dentate gyrus of the hippocampus. No Ki-67 proliferating cells were observed in the striatum substantia nigra, amygdala, cerebral cortex or dorsal vagal complex. Doublecortin-immunoreactive cells were observed in the striatum, third ventricle, cerebral cortex, amygdala, olfactory bulb and along the rostral migratory stream but absent in the substantia nigra and dorsal vagal complex. The potential neurogenic sites in the four-striped mouse species could invariably lead to increased neural plasticity.

The association between sex hormone-binding globulin and type 2 diabetes in Nigerian men.

BACKGROUND: Epidemiological studies have shown that sex hormone-binding globulin (SHBG) has a role in glucose homeostasis in both men and women. However, a prospective study on Japanese-American subjects concluded that SHBG was not a significant risk factor in either men or women, suggesting ethnic differences. We were not aware of any evaluation of SHBG in subjects of African ancestry. OBJECTIVES: We investigated the association between SHBG and insulin resistance in type 2 diabetic diabetic men in a hospital in Nigeria. METHOD: Forty-eight male subjects with type 2 diabetes and 20 non-diabetic male subjects were recruited in this cross-sectional hospital-based study by the convenient sampling method. Height and circumferences around the waist and hip were measured to the nearest 0.5 cm and the waist-hip ratio was calculated from this measurement. Weight was measured and body mass index was calculated. Fasting plasma glucose concentration was measured by the glucose oxidase method with a between-run coefficient of variation of 3%. Insulin and SHBG were measured by means of enzyme-linked immunosorbent assay (ELISA). RESULTS: There was a statistically-significant difference between test results for the diabetic and non-diabetic patients. The mean SHBG concentration was higher in the non-diabetic group (42.2 nmol/L) than the diabetic group (30.5 nmol/L). A significant inverse association between insulin resistance and SHBG was observed (r = 0.353, p < 0.015). CONCLUSION: This study supported earlier observations that a significant inverse correlation exists between SHBG and insulin resistance and provides evidence that the relationship may extend to type 2 diabetic men of African ancestry in Nigeria.

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.

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.

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.

New insights into the pathophysiology of ovarian hyperstimulation syndrome. What makes the difference between spontaneous and iatrogenic syndrome?

The recent identification of mutations in the FSH receptor gene, which display an increased sensitivity to hCG and are responsible for the development of spontaneous ovarian hyperstimulation syndrome (OHSS), provides for the first time the molecular basis for the physiopathology of spontaneous OHSS. Based on these recent findings, this paper underlines the differences between spontaneous and iatrogenic OHSS and proposes a model to account for the different chronology between the two forms of the syndrome. In the iatrogenic form, the follicular recruitment and enlargement occur during ovarian stimulation with exogenous FSH, while in the spontaneous form, the follicular recruitment occurs later through the stimulation of the FSH receptor by pregnancy-derived hCG. In both forms, massive luteinization of enlarged stimulated ovaries ensues, inducing the release of vasoactive mediators, leading to the development of the symptoms of OHSS.

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.

Sexual and reproductive rights: statements, rhetoric and responsibilities.

The current international movement for the promotion of reproductive health has great potential for improving sexual and reproductive rights. Health professionals should play a major role in applying international human rights instruments at the country level. Being at the front line of service delivery, health professionals have a duty to ensure that those rights are articulated in routine care by empowering individuals, lobbying for legislation, promoting policies and reporting violations of human rights treaties.

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.

Screening of potential semen donors for sexual transmitted diseases.

BACKGROUND AND OBJECTIVES: The risk of infection with sexually transmitted diseases (STDs) is of great concern to couples undergoing therapeutic donor insemination. GOAL OF STUDY: We sought to determine the prevalence of STDs in potential semen donors and assess the rate of acquisition of new infection during the follow-up period. STUDY DESIGN: 29 potential semen donors were screened for common STDs. RESULTS: The study population had a prevalence of the following STDs: 27.5% ureaplasma, 13.8% mycoplasma, 6.9% cytomegalovirus 6.9% group B streptococcus, and 3.4% human papillomavirus infection. No participant tested positive for gonoccoccal or HIV infection. Over all, evidence of STD was present in 10 of 29 (34.5%) prospective donors. A follow-up infection rate of 22.2% (6 of 27 enrolled donors) was found and 3 (11.1%) of these were excluded from semen donation. CONCLUSION: A high prevalence of sexually transmissible infections is present in potential semen donors. New infections are also common during the follow-up period.

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.

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.

Spontaneous ovarian hyperstimulation syndrome in four consecutive pregnancies.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is almost exclusively associated with ovulation induction with gonadotropins or occasionally, clomiphene citrate. Severe ovarian hyperstimulation associated with a spontaneously conceived pregnancy is rare with only two previous reports. Misdiagnosis as a neoplastic process may result in inappropriate intervention. CASE: A patient with polycystic ovarian disease experienced severe spontaneous OHSS in four consecutive singleton pregnancies. Serial color and pulsed Doppler ultrasonographic imaging facilitated adequate evaluation of the patient and permitted conservative therapy. She achieved live births in two of the pregnancies. This is the third reported case of spontaneous OHSS associated with pregnancy and the first to result in live births. In one previous report, misdiagnosis resulted in inadvertent castration. CONCLUSIONS: Spontaneous ovarian hyperstimulation syndrome and pregnancy may occur in patients with polycystic ovarian disease. Color Doppler ultrasonography is a useful aid in the diagnosis and management of this rare complication, and in avoiding inappropriate intervention.

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.