Dyslipidaemia in women with polycystic ovary syndrome referred to a teaching hospital in Cape Town, South Africa.

The polycystic ovary syndrome (PCOS) imparts health risks including dyslipidaemia, diabetes and cardiovascular disease that are amenable to lifestyle adjustment and/or medication. We describe dyslipidaemia in women referred to a gynaecological endocrine clinic. Clinical data and endocrine and lipoprotein investigations comprising fasting triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDLC) and calculated low density lipoprotein cholesterol (LDLC) were studied along with electrophoresis patterns of apolipoprotein B-containing lipoproteins. The 1721 participants comprised black, mixed ancestry, white and Indian individuals (9.8%, 83.2%, 5.8% and 1.2%, respectively). The mean ± standard deviation of the age, body mass index (BMI) and waist/hip ratio were 26.0 ± 5.9 years, 32.3 ± 8.3 kg/m2 and waist/hip ratio 0.88 ± 0.11, respectively. Overweight status (BMI 26-30 kg/m2) and obesity (BMI >30 kg/m2) involved 272 (15.8%) and 1010 (58.7%) individuals, respectively. Morbid obesity (BMI >40 kg/m2) was present in 309 (17.9%) individuals. The TG, TC, HDLC and LDLC concentrations were 1.22 ± 0.86, 4.77 ± 1.02, 1.3 ± 0.36, 2.94 ± 0.94 mmol/L, respectively. LDL hypercholesterolaemia occurred in 753 (43.7%) and exceeded 5 mmol/L in 39 (2.3%) women. Low HDLC (<0.9 mmol/L) affected 122 (7%), hypertriglyceridaemia (>1.7 mmol/L) affected 265 (15.4%) and exceeded 2.5 mmol/L in 91 (5.3%) women. Mixed hyperlipidaemia (TG >1.7, TC >5.0 mmol/L) occurred in 176 (10.2%). Electrophoresis revealed small LDL particles in 79 (4.6%) and dysbetalipoproteinaemia in 13 (0.76%) of the cohort. Small LDL associated with obesity, blood pressure, TG and glucose concentration and higher androgenic state. Many women with PCOS had unfavourable lipoprotein results: mostly moderate changes in TG, HDLC and LDLC. Small LDL is not rare, may aid risk assessment and is best determined directly. Incidental monogenic disorders of lipoprotein metabolism included dysbetalipoproteinaemia, familial hypercholesterolaemia and severe hypertriglyceridaemia. Dyslipidaemia in PCOS requires more careful diagnosis, individualised management and research.

Increased HIV-1 infection in PBMCs treated in vitro with menstrual cycle phase hormones or medroxyprogesterone acetate likely occurs via different mechanisms.

PROBLEM: Both luteal phase progesterone (P4) levels and use of the intramuscular (IM) injectable progestin-only contraceptive depo-medroxyprogesterone acetate (DMPA-IM) have been linked to increased S/HIV acquisition in animal, clinical and in vitro models. Several plausible mechanisms could explain MPA-induced HIV-1 acquisition while those for the luteal phase are underexplored. METHOD OF STUDY: Peripheral blood mononuclear cells (PBMCs) were treated with P4 and estrogen at concentrations mimicking the luteal phase, follicular phase or with levels of MPA mimicking peak serum levels in DMPA-IM users. Cells were infected with an R5-tropic infectious molecular clone and HIV-1 infection was measured. A role for the glucocorticoid receptor (GR) was investigated using the GR/PR antagonist RU486. CCR5 protein levels and activation status, assessed by levels of the activation marker CD69, were measured by flow cytometry after treatment in vitro and in PBMCs from naturally-cycling women or DMPA-IM users. RESULTS: Both MPA and luteal phase hormones significantly increased HIV-1 infection in vitro. However, MPA but not luteal phase hormones increased the CD4+/CD8+ T cell ratio, CCR5 protein expression on CD4+ T cells and increased expression of the activation marker CD69. The GR is involved in MPA-induced, but not luteal phase hormone-induced increased HIV-1 infection. In DMPA-IM users, the frequency of CCR5-expressing CD3+ and CD8+ cells was higher than for women in the luteal phase. CONCLUSIONS: MPA increases HIV-1 infection in a manner different from that of luteal phase hormones, most likely involving the GR and at least in part changes in the frequency and/or expression of CCR5 and CD69.

The FIGO ovulatory disorders classification system.

Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding, and infertility, and are frequent manifestations of polycystic ovary syndrome (PCOS). There are many potential causes and contributors to ovulatory dysfunction that challenge clinicians, trainees, educators, and those who perform basic, translational, clinical, and epidemiological research. Similarly, therapeutic approaches to ovulatory dysfunction potentially involve a spectrum of lifestyle, psychological, medical, and procedural interventions. Collaborative research, effective education, and consistent clinical care remain challenged by the absence of a consensus comprehensive system for classification of these disorders. The existing and complex system, attributed to WHO, was developed more than three decades ago and did not consider more than 30 years of research into these disorders in addition to technical advances in imaging and endocrinology. This manuscript describes the development of a new classification of ovulatory disorders performed under the aegis of the International Federation of Gynecology and Obstetrics (FIGO) and conducted using a rigorously applied Delphi process. The stakeholder organizations and individuals who participated in this process comprised specialty journals, experts at large, national, specialty obstetrical and gynecological societies, and informed lay representatives. After two face-to-face meetings and five Delphi rounds, the result is a three-level multi-tiered system. The system is applied after a preliminary assessment identifies the presence of an ovulatory disorder. The primary level of the system is based on an anatomic model (Hypothalamus, Pituitary, Ovary) that is completed with a separate category for PCOS. This core component of the system is easily remembered using the acronym HyPO-P. Each anatomic category is stratified in the second layer of the system to provide granularity for investigators, clinicians, and trainees using the "GAIN-FIT-PIE" mnemonic (Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and Vascular; Physiological, Idiopathic, Endocrine). The tertiary level allows for specific diagnostic entities. It is anticipated that, if widely adopted, this system will facilitate education, clinical care, and the design and interpretation of research in a fashion that better informs progress in this field. Integral to the deployment of this system is a periodic process of reevaluation and appropriate revision, reflecting an improved understanding of this collection of disorders.

The FIGO Ovulatory Disorders Classification System†.

Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding and infertility and are frequent manifestations of polycystic ovary syndrome (PCOS). There are many potential causes and contributors to ovulatory dysfunction that challenge clinicians, trainees, educators, and those who perform basic, translational, clinical and epidemiological research. Similarly, therapeutic approaches to ovulatory dysfunction potentially involve a spectrum of lifestyle, psychological, medical and procedural interventions. Collaborative research, effective education and consistent clinical care remain challenged by the absence of a consensus comprehensive system for classification of these disorders. The existing and complex system, attributed to the World Health Organization (WHO), was developed more than three decades ago and did not consider more than 30 years of research into these disorders in addition to technical advances in imaging and endocrinology. This article describes the development of a new classification of ovulatory disorders performed under the aegis of the International Federation of Gynecology and Obstetrics (FIGO) and conducted using a rigorously applied Delphi process. The stakeholder organizations and individuals who participated in this process comprised specialty journals, experts at large, national, specialty obstetrical and gynecological societies, and informed lay representatives. After two face-to-face meetings and five Delphi rounds, the result is a three-level multi-tiered system. The system is applied after a preliminary assessment identifies the presence of an ovulatory disorder. The primary level of the system is based on an anatomic model (Hypothalamus, Pituitary, Ovary) that is completed with a separate category for PCOS. This core component of the system is easily remembered using the acronym HyPO-P. Each anatomic category is stratified in the second layer of the system to provide granularity for investigators, clinicians and trainees using the 'GAIN-FIT-PIE' mnemonic (Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and Vascular; Physiological, Idiopathic, Endocrine). The tertiary level allows for specific diagnostic entities. It is anticipated that, if widely adopted, this system will facilitate education, clinical care and the design and interpretation of research in a fashion that better informs progress in this field. Integral to the deployment of this system is a periodic process of reevaluation and appropriate revision, reflecting an improved understanding of this collection of disorders.

The FIGO Ovulatory Disorders Classification System.

Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding, and infertility, and are frequent manifestations of polycystic ovary syndrome (PCOS). There are many potential causes and contributors to ovulatory dysfunction that challenge clinicians, trainees, educators, and those who perform basic, translational, clinical, and epidemiological research. Similarly, therapeutic approaches to ovulatory dysfunction potentially involve a spectrum of lifestyle, psychological, medical, and procedural interventions. Collaborative research, effective education, and consistent clinical care remain challenged by the absence of a consensus comprehensive system for classification of these disorders. The existing and complex system, attributed to WHO, was developed more than three decades ago and did not consider more than 30 years of research into these disorders in addition to technical advances in imaging and endocrinology. This manuscript describes the development of a new classification of ovulatory disorders performed under the aegis of the International Federation of Gynecology and Obstetrics (FIGO) and conducted using a rigorously applied Delphi process. The stakeholder organizations and individuals who participated in this process comprised specialty journals, experts at large, national, specialty obstetrical and gynecological societies, and informed lay representatives. After two face-to-face meetings and five Delphi rounds, the result is a three-level multi-tiered system. The system is applied after a preliminary assessment identifies the presence of an ovulatory disorder. The primary level of the system is based on an anatomic model (Hypothalamus, Pituitary, Ovary) that is completed with a separate category for PCOS. This core component of the system is easily remembered using the acronym HyPO-P. Each anatomic category is stratified in the second layer of the system to provide granularity for investigators, clinicians, and trainees using the "GAIN-FIT-PIE" mnemonic (Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and vascular; Physiological, Idiopathic, Endocrine). The tertiary level allows for specific diagnostic entities. It is anticipated that, if widely adopted, this system will facilitate education, clinical care, and the design and interpretation of research in a fashion that better informs progress in this field. Integral to the deployment of this system is a periodic process of reevaluation and appropriate revision, reflecting an improved understanding of this collection of disorders.

Prevention of noncommunicable diseases by interventions in the preconception period: A FIGO position paper for action by healthcare practitioners.

With the increase in obesity prevalence among women of reproductive age globally, the risks of type 2 diabetes, gestational diabetes, pre-eclampsia, and other conditions are rising, with detrimental effects on maternal and newborn health. The period before pregnancy is increasingly recognized as crucial for addressing weight management and reducing malnutrition (both under- and overnutrition) in both parents to reduce the risk of noncommunicable diseases (NCDs) in the mother as well as the passage of risk to her offspring. Healthcare practitioners, including obstetricians, gynecologists, midwives, and general practitioners, have an important role to play in supporting women in planning a pregnancy and achieving healthy nutrition and weight before pregnancy. In this position paper, the FIGO Pregnancy Obesity and Nutrition Initiative provides an overview of the evidence for preconception clinical guidelines to reduce the risk of NCDs in mothers and their offspring. It encourages healthcare practitioners to initiate a dialogue on women's health, nutrition, and weight management before conception. While acknowledging the fundamental importance of the wider social and environmental determinants of health, this paper focuses on a simple set of recommendations for clinical practice that can be used even in short consultations. The recommendations can be contextualized based on local cultural and dietary practices as part of a system-wide public health approach to influence the wider determinants as well as individual factors influencing preconception health.

Reciprocal Modulation of Antiretroviral Drug and Steroid Receptor Function In Vitro.

Millions of women are exposed simultaneously to antiretroviral drugs (ARVs) and progestin-based hormonal contraceptives. Yet the reciprocal modulation by ARVs and progestins of their intracellular functions is relatively unexplored. We investigated the effects of tenofovir disoproxil fumarate (TDF) and dapivirine (DPV), alone and in the presence of select steroids and progestins, on cell viability, steroid-regulated immunomodulatory gene expression, activation of steroid receptors, and anti-HIV-1 activity in vitro Both TDF and DPV modulated the transcriptional efficacy of a glucocorticoid agonist via the glucocorticoid receptor (GR) in the U2OS cell line. In TZM-bl cells, DPV induced the expression of the proinflammatory interleukin 8 (IL-8) gene while TDF significantly increased medroxyprogesterone acetate (MPA)-induced expression of the anti-inflammatory glucocorticoid-induced leucine zipper (GILZ) gene. However, peripheral blood mononuclear cell (PBMC) and ectocervical explant tissue viability and gene expression results, along with TZM-bl HIV-1 infection data, are reassuring and suggest that TDF and DPV, in combination with dexamethasone (DEX) or MPA, do not reciprocally modulate key biological effects in primary cells and tissue. We show for the first time that TDF induces progestogen-independent activation of the progesterone receptor (PR) in a cell line. The ability of TDF and DPV to influence GR and PR activity suggests that their use may be associated with steroid receptor-mediated off-target effects. This, together with cell line and individual donor gene expression responses in the primary models, raises concerns that reciprocal modulation may cause side effects in a cell- and donor-specific manner in vivo.

Differential metabolism of clinically-relevant progestogens in cell lines and tissue: Implications for biological mechanisms.

Steroid hormones regulate a variety of physiological processes, including reproductive function, and are widely used in hormonal therapy. Synthetic progestogens, or progestins, were designed to mimic progesterone (P4) for use in contraception and hormonal replacement therapy in women. Medroxyprogesterone acetate (MPA) and norethisterone (NET) are the most widely used injectable contraceptives in the developing world, while other progestins such as levonorgestrel (LNG), etonogestrel (ETG) and nestorone (NES) are used in or being developed for other forms of contraception. As concerns remain about the most appropriate choice of progestin and dosage, and the associated side-effects, the mechanisms and biological effects of progestins are frequently investigated in various in vitro mammalian cell line and tissue models. However, whether progestogens are differentially metabolised in different cell types in vivo or in vitro is unknown. For nine mammalian cell lines commonly used to investigate progestogen mechanisms of action, we developed and validated an ultra-high performance supercritical fluid chromatography-tandem mass spectrometry (UHPSFC-MS/MS) protocol for simultaneously quantifying the metabolism of the above-mentioned steroids. We show for the first time that, while 50-100% of P4 was metabolised within 24 h in all cell lines, the metabolism of the progestins is progestin- and cell line-specific. We also show that MPA and NET are significantly metabolised in human cervical tissue, but to a lesser extent than P4. Taken together, our findings suggest that differential progestogen metabolism may play a role in cell-specific therapeutic and side-effects. Relative affinities for binding to steroid receptors as well as potencies, efficacies and biocharacters for transcriptional activity of progestins, relative to P4, are most frequently determined using some of the cell lines investigated. Our results, however, suggest that differential metabolism of progestins and P4 may confound these results. In particular, metabolism may under-estimate the receptor-mediated intrinsic in vitro binding and dose-response values and predicted endogenous physiological effects of P4.

The contraceptive medroxyprogesterone acetate, unlike norethisterone, directly increases R5 HIV-1 infection in human cervical explant tissue at physiologically relevant concentrations.

The intramuscular progestin-only injectable contraceptive, depo-medroxyprogesterone acetate (DMPA-IM), is more widely used in Sub-Saharan Africa than another injectable contraceptive, norethisterone enanthate (NET-EN). Epidemiological data show a significant 1.4-fold increased risk of HIV-1 acquisition for DMPA-IM usage, while no such association is shown from limited data for NET-EN. We show that MPA, unlike NET, significantly increases R5-tropic but not X4-tropic HIV-1 replication ex vivo in human endocervical and ectocervical explant tissue from pre-menopausal donors, at physiologically relevant doses. Results support a mechanism whereby MPA, unlike NET, acts via the glucocorticoid receptor (GR) to increase HIV-1 replication in cervical tissue by increasing the relative frequency of CD4+ T cells and activated monocytes. We show that MPA, unlike NET, increases mRNA expression of the CD4 HIV-1 receptor and CCR5 but not CXCR4 chemokine receptors, via the GR. However, increased density of CD4 on CD3+ cells was not observed with MPA by flow cytometry of digested tissue. Results suggest that DMPA-IM may increase HIV-1 acquisition in vivo at least in part via direct effects on cervical tissue to increase founder R5-tropic HIV-1 replication. Our findings support differential biological mechanisms and disaggregation of DMPA-IM and NET-EN regarding HIV-1 acquisition risk category for use in high risk areas.

Medical conditions associated with recurrent miscarriage-Is BMI the tip of the iceberg?

BACKGROUND: In contrast to sporadic miscarriage, recurrent miscarriage (RM) is a rare entity which affects 1% of couples attempting conception. It is distressing for couples and healthcare professionals as the aetiology is unclear with limited treatment options. Apart from anti-phospholipid syndrome (APS), the strength of associations between RM and commonly investigated endocrine, autoimmune, thrombophilic and uterine structural abnormalities remains uncertain and variable. OBJECTIVES: To assess the prevalence of commonly investigated medical conditions associated with RM. STUDY DESIGN: A 9-year retrospective analysis of a prospectively collected database was conducted for 592 patients seen between 2008 and 2016, in tertiary level RM clinic in South Africa. RESULTS: In this period, 592 patients were assessed. The mean age was 29.73±5.46 (mean±SD), gravidity 4.6±1.82 and parity 0.98±1.05. The mean number of miscarriages per patient was 3.34±1.63, of which two-thirds (61.3%) were in the first trimester, a third (33%) in the second trimester and intrauterine fetal deaths (IUFDs) constituted 6% of total losses. Of the 50% of patients with no identified associated disorders, 15% were unexplained (investigations complete but no associations found), 10% became pregnant during investigation (investigations incomplete) and 25% were lost to follow-up (investigations incomplete). Nearly forty percent (38%) of patients had an associated endocrine disorder (22% PCOS, 11% IGT, 3% Diabetes Mellitus and 2% Thyroid Dysfunction) and 10% a uterine factor (4% Cervical Incompetence, 2% Fibroids, 2% Synechiae and 2% Anomalies). APS and Thrombophilias constituted 3% and 2% of patients respectively. The BMI (mean±SD) amongst patients with Unexplained RM, PCOS and IGT were 28.85±5.95, 30.86±7.79 and 33.40±6.47 respectively. Patients with IGT had significantly higher mean BMI in comparison to those with Unexplained RM (p<0.0001)*** and PCOS (p<0.001)**. CONCLUSION: PCOS, IGT and Type II Diabetes are all likely surrogates for elevated BMI and constitute 70% of those women with RM and identified associated medical disorders. In our population, BMI seems to have a substantial impact on recurrent pregnancy loss and future studies should interrogate its effect on recurrent miscarriage.

Elevated placental expression at the maternal-fetal interface but diminished maternal circulatory kisspeptin in preeclamptic pregnancies.

OBJECTIVE: To investigate the placental mRNA and protein expression of metastasis suppressor gene Kiss-1 and the transcript expression of its receptor GPR-54 across the maternal-fetal interface of healthy and preeclamptic pregnancies. To furthermore compare placental tissue kisspeptin expression to circulatory kisspeptin levels in these pregnancies. SETTING: Secondary and Tertiary Hospital Setting in Cape Town, South Africa. POPULATION: Patients with and without preeclampsia undergoing elective caesarean delivery. METHODS: The placenta, placental bed and decidua parietalis as well as maternal and cord blood in both healthy and preeclamptic pregnancies were simultaneously sampled at elective caesarean delivery. RT-PCR was utilised to determine mRNA expression while immunohistochemistry was employed to investigate protein expression in maternal-fetal tissues. Circulating maternal and cord serum kisspeptin concentrations were determined using ELISA. MAIN OUTCOME MEASURES: Maternal-fetal tissue mRNA expression of Kiss-1 and GPR-54 as well as maternal/cord serum kisspeptin concentrations in healthy and preeclamptic pregnancies. RESULTS: There was high placental kisspeptin expression but low circulating serum kisspeptin levels in pregnancies complicated by preeclampsia. Kiss-1 mRNA and protein expression was minimal in the maternal tissues (placental bed and decidua parietalis) of both healthy and preeclamptic pregnancies. No difference was found in Kiss-1 receptor (GPR-54) mRNA expression across maternal-fetal tissues of healthy and preeclamptic pregnancies. CONCLUSIONS: Increased placental kisspeptin expression is consistent with reduced trophoblast invasiveness and may represent a molecular mechanism that explains the development of preeclampsia. Decreased circulating kisspeptin concentration has the potential to be utilised as a marker for placental dysfunction.

Contraception usage and timing of pregnancy among pregnant teenagers in Cape Town, South Africa.

OBJECTIVE: To evaluate knowledge and use of contraception among pregnant teenagers in the Cape Town metropolitan area. METHODS: A cross-sectional study enrolled women aged 16 to 19 years who were pregnant and attending prenatal clinics, and prenatal and labor wards at regional hospitals and midwife-run obstetric clinics in the Cape Town area between March 1, 2011 and September 30, 2011. Data were collected using an administered questionnaire. RESULTS: The study enrolled 314 participants. Of the participants, 240 (76.4%) felt their pregnancies had occurred at the "wrong time" but only 38 (12.1%) were using contraception at the time of conception. The form of contraception that participants most commonly had knowledge of was injectable hormonal contraception (274 [87.3%]). Contraception use was low, with 126 (40.1%) participants having never used contraception. The forms of contraception used most commonly were the male condom (106 [33.8%]) and injectable contraception (98 [31.2%]). The majority of participants found it easy to get contraception (192 [61.1%]) and felt that information regarding contraception was readily available (233 [74.2%]). CONCLUSION: Contraception use is suboptimal but this may not simply be a reflection of ineffective family-planning services. Further research is needed to fully explain the lack of contraceptive use in this population.

Reproductive knowledge and use of contraception among women with diabetes.

BACKGROUND: Poorly controlled diabetes is associated with poor maternal and fetal outcomes, yet many women become pregnant before establishing control. Reducing unintended pregnancies is a vital step towards improving perinatal and maternal morbidity and mortality. OBJECTIVES: To assess the reproductive knowledge and use of contraception in women of reproductive age attending diabetes outpatient clinics. METHODS: A prospective descriptive study was conducted of women known to have diabetes, aged 18 - 45 years, attending the diabetic clinics at Groote Schuur Hospital or the local community health centres in Cape Town, South Africa. A questionnaire consisting of social, demographic and family details as well as contraceptive use and knowledge was administered. RESULTS: Some common themes emerged, namely that 44.2% of the women with previous pregnancies had had unintended pregnancies, and that this was more common among single (58.8%) and younger women. Women with type 1 diabetes had better knowledge than those with type 2 diabetes of how pregnancy affects diabetes, but better knowledge did not translate to better contraception use. Despite the fact that 102 participants (88.7%) attended diabetes clinics two or more times a year, knowledge of pregnancy- and reproductive health-related complications was limited, and only 30 participants (26.1%) had received advice on contraception at these clinics. CONCLUSION: Knowledge about the impact of diabetes on pregnancy and that of pregnancy on diabetes was suboptimal. We recommend that reproductive health services be included at the routine diabetes clinic visit.

Mutations in Exon 1 highlight the role of MED12 in uterine leiomyomas.

Mediator regulates transcription by connecting gene-specific transcription factors to the RNA polymerase II initiation complex. We recently discovered by exome sequencing that specific exon 2 mutations in mediator complex subunit 12 (MED12) are extremely common in uterine leiomyomas. Subsequent screening studies have focused on this mutational hot spot, and mutations have been detected in uterine leiomyosarcomas, extrauterine leiomyomas and leiomyosarcomas, endometrial polyps, and colorectal cancers. All mutations have been missense changes or in-frame insertions/deletions. Here, we have analyzed 611 samples representing all above-mentioned tumor types for possible exon 1 mutations. Five mutations were observed, all of which were in-frame insertion/deletions in uterine leiomyomas. Transcriptome-wide expression data revealed that MED12 exon 1 and exon 2 mutations lead to the same unique global gene expression pattern with RAD51B being the most upregulated gene. Immunoprecipitation and kinase activity assays showed that both exon 1 and exon 2 mutations disrupt the interaction between MED12 and Cyclin C and CDK8/19 and abolish the mediator-associated CDK kinase activity. These results further emphasize the role of MED12 in uterine leiomyomas, show that exon 1 and exon 2 exert their tumorigenic effect in similar manner, and stress that exon 1 should be included in subsequent MED12 screenings.

Maternal hair selenium levels as a possible long-term nutritional indicator of recurrent pregnancy loss.

BACKGROUND: Approximately 1% of all couples trying to conceive will suffer from recurrent pregnancy loss (RPL). Nutritional deficiencies have been postulated as a possible cause of RPL and in particular, selenium deficiency has been associated with reproductive failure in animal studies and more recently, in some human studies. This study was undertaken to assess the maternal hair selenium levels in women with RPL without an identified cause and to compare these results with those of women with successful reproductive histories. METHODS: Twenty four patients with RPL and twenty four control subjects with at least one successful pregnancy and no pregnancy failures, who were matched for age and ethnicity, were recruited. A questionnaire was completed, which included demographic and social information and a dietary history. Hair samples were collected and analyzed for selenium content by inductively coupled plasma mass spectrometry. RESULTS: The control subjects had a higher mean income and had completed more years of education compared with the RPL patients. There was no significant difference in the intake of selenium rich foods between the 2 groups. The patients, however, consumed significantly more fruit, cheese, potatoes and chocolate than the controls. The median (range) selenium content was 0.80 ppm (0.19-4.15) and 0.68 ppm (0.43-3.76) in patients and controls respectively (Mann Whitney U test 209.5 p = 0.74). CONCLUSIONS: While there were significant differences in the 2 groups with regard to resources, education and diet our results show that hair selenium concentrations and dietary selenium intake, were similar in the two groups. Both groups had low levels of this important element.

The differential expression of Kiss1, MMP9 and angiogenic regulators across the feto-maternal interface of healthy human pregnancies: implications for trophoblast invasion and vessel development.

Genes involved in invasion of trophoblast cells and angiogenesis are crucial in determining pregnancy outcome. We therefore studied expression profiles of these genes in both fetal and maternal tissues to enhance our understanding of feto-maternal dialogue. We investigated the expression of genes involved in trophoblast invasion, namely Kiss1, Kiss1 Receptor (Kiss1R) and MMP9 as well as the expression of angiogenic ligands Vascular Endothelial Growth Factor-A (VEGF-A) and Prokineticin-1 (PROK1) and their respective receptors (VEGFR1, VEGFR2 and PROK1R) across the feto-maternal interface of healthy human pregnancies. The placenta, placental bed and decidua parietalis were sampled at elective caesarean delivery. Real-time RT-PCR was used to investigate transcription, while immunohistochemistry and western blot analyses were utilized to study protein expression. We found that the expression of Kiss1 (p<0.001), Kiss1R (p<0.05) and MMP9 (p<0.01) were higher in the placenta compared to the placental bed and decidua parietalis. In contrast, the expression of VEGF-A was highest in the placental bed (p<0.001). While VEGFR1 expression was highest in the placenta (p<0.01), the expression of VEGFR2 was highest in the placental bed (p<0.001). Lastly, both PROK1 (p<0.001) and its receptor PROK1R (p<0.001) had highest expression in the placenta. Genes associated with trophoblast invasion were highly expressed in the placenta which could suggest that the influence on invasion capacity may largely be exercised at the fetal level. Furthermore, our findings on angiogenic gene expression profiles suggest that angiogenesis may be regulated by two distinct pathways with the PROK1/PROK1R system specifically mediating angiogenesis in the fetus and VEGFA/VEGFR2 ligand-receptor pair predominantly mediating maternal angiogenesis.

The gynaecological subspecialties: advances in women's health.

Under Professor Dennis Davey's leadership, the Department of Obstetrics and Gynaecology recognised the need for subspecialist expertise and training. Thus, the gynaecological subspecialties were developed, the first of which was gynaecological oncology. We review the research, and subsequent clinical application, which has evolved from the subspecialist units.

An audit of indications and complications associated with elective hysterectomy at a public service hospital in South Africa.

OBJECTIVE: To assess relationships between clinical indication for hysterectomy and postoperative histologic findings, and to audit complications of hysterectomy at the gynecologic surgical unit of a public-service hospital in South Africa. METHODS: Surgical indications and details, histologic findings, and postoperative course were reviewed and analyzed for 335 patients who underwent hysterectomy at Groote Schuur Hospital, Cape Town, South Africa, in 2007. RESULTS: Hysterectomy was performed abdominally in 265 patients (79.1%) and vaginally in 70 (20.9%) patients (5 of these procedures were laparoscopically assisted). The most common indication was fibroid-related menorrhagia (23%), followed by abnormal uterine bleeding (14.9%). The incidence of intraoperative complications was 6-fold greater among patients with malignant disease than among those with a benign condition (P=0.001). The incidence of postoperative complications was greater following abdominal rather than vaginal surgery, whether traditional or laparoscopic (P=0.02). CONCLUSION: Most hysterectomies were carried out abdominally rather than vaginally, in part because many patients presented with advanced cancer or other condition that warranted this approach. Because of resource constraints, patients with benign conditions were more likely to be offered surgery if they had a clearly defined condition.