Protocol of the Fit-For-Fertility study: a multicentre randomised controlled trial assessing a lifestyle programme targeting women with obesity and infertility.

INTRODUCTION: Women with obesity are at a higher risk of infertility as well as gestational and neonatal complications. Lifestyle changes are universally recommended for women with obesity seeking fertility treatments, but such intervention has only been assessed in very few robust studies. This study's objectives are therefore to assess the clinical outcomes and cost-effectiveness of an interdisciplinary lifestyle intervention (the Fit-For-Fertility Programme; FFFP) targeting women with obesity and subfertility in a diverse population. METHODS AND ANALYSIS: This pragmatic multicentre randomised controlled trial (RCT) will include 616 women with obesity (body mass index ≥30 kg/m2 or ≥27 kg/m2 with polycystic ovary syndrome or at-risk ethnicities) who are evaluated at a Canadian fertility clinic for subfertility. Women will be randomised either to (1) the FFFP (experimental arm) alone for 6 months, and then in combination with usual care for infertility if not pregnant; or (2) directly to usual fertility care (control arm). Women in the intervention group benefit from the programme up to 18 months or, if pregnant, up to 24 months or the end of the pregnancy (whichever comes first). Women from both groups are evaluated every 6 months for a maximum of 18 months. The primary outcome is live birth rate at 24 months. Secondary outcomes include fertility, pregnancy and neonatal outcomes; lifestyle and anthropometric measures; and cost-effectiveness. Qualitative data collected from focus groups of participants and professionals will also be analysed. ETHICS AND DISSEMINATION: This research study has been approved by the Research Ethics Board (REB) of Centre intégré universtaire de santé et des services sociaux de l'Estrie-CHUS (research coordinating centre) on 10 December 2018 and has been or will be approved successively by each participating centres' REB. This pragmatic RCT will inform decision-makers on improving care trajectories and policies regarding fertility treatments for women with obesity and subfertility. TRIAL REGISTRATION NUMBER: NCT03908099. PROTOCOL VERSION: 1.1, 13 April 2019.

Impact of an Educational Pamphlet on Knowledge About Health Risks After Hypertensive Disorders of Pregnancy: A Randomized Trial.

OBJECTIVE: To evaluate patients' knowledge, risk perception, and anxiety about future health risks after an episode of hypertensive disorder of pregnancy (HDP), as well as their satisfaction with an educational pamphlet. METHODS: From January 2016 to June 2017, participants were randomly assigned to one of 2 groups and asked to complete questionnaire #1 (demographics, knowledge, risk perception, anxiety, and satisfaction) after receiving medical counselling at the HDP postpartum clinic. Participants in the intervention group then received the educational pamphlet. One month later, both groups completed the questionnaire again (questionnaire #2). The primary outcome of this study was improvement in the global knowledge score at 1 month, reflecting improved understanding of the health risks of HDP. Secondary outcomes included retention of information, risk perception, satisfaction, and anxiety level. RESULTS: Of 137 eligible women, 57 were randomly assigned to the intervention group and 56, to the control group. Participants in both groups had similar baseline characteristics. Thirteen percent of participants did not complete questionnaire #2. The knowledge score was higher in the intervention group than the control group at 1 month, (88.2%; 95% confidence interval [CI] 26.37-28.32 and 71.3%; 95% CI 20.78-23.45, respectively [P <0.0001]). No difference was seen in anxiety level between the groups (4.0 ± 1.00 vs. 3.8 ± 0.92; P = 0.6746). The intervention group was highly satisfied with the medical counselling they received (5.5 ± 0.84 out 6) and with the pamphlet (5.6 ± 0.66 out 6). CONCLUSION: The educational pamphlet increased women's knowledge about future health risks of HDP without increasing anxiety and it may be helpful in promoting lifestyle changes necessary to modify these risks.

Self-Monitoring of Blood Glucose: A Complementary Method Beyond the Oral Glucose Tolerance Test to Identify Hyperglycemia During Pregnancy.

OBJECTIVES: To compare: 1) 75 g oral glucose tolerance test (OGTT) and self-monitoring of blood glucose (SMBG) in identifying gestational diabetes mellitus (GDM) and other hyperglycemic statuses in pregnant women; 2) pregnancy outcomes according to glycemic status; and 3) participants' opinions regarding both methods. METHODS: A prospective study in women with a 50 g glucose load test ≥7.2 mmol/L at 24 to 28 weeks' gestation and singleton pregnancy. Women underwent OGTT (blinded) at day 1, followed by 7 days of SMBG (4 daily measurements: fasting and 2 h postprandially) without modifying diet or lifestyle. GDM (OGTT+) was diagnosed using the criteria of the International Association of the Diabetes and Pregnancy Study Groups, while pregnancy hyperglycemia (SMBG+) was defined as ≥4/7 glucose values ≥5.3 after fasting or ≥6.7 mmol/L 2 h postprandially for any meal of the day. Equivalent management was provided to women with GDM and/or pregnancy-related hyperglycemia. RESULTS: We divided 103 participants (age: 29.5±5.0 years; prepregnancy body mass index: 25.3±5.4 kg/m2) into 4 groups according to test results: OGTT+/SMBG+ (n=12, 11.7%); OGTT+/SMBG- (n=14, 13.6%); OGTT-/SMBG+ (n=9, 8.7%); and OGTT-/SMBG- (n=68, 66.0%). Clinical characteristics and maternal outcomes were statistically similar between groups. Neonatal complication rates were greater in groups with hyperglycemia than in the OGTT-/SMBG- group, notably neonatal hypoglycemia (9/12, 7/14, 5/9 vs. 6/68; p<0.001). Participants reported no convenience difference between methods but would prefer OGTT for a future pregnancy. CONCLUSIONS: More than half of the women with OGTT+ were normoglycemic in daily life. Conversely, 11.7% of women with OGTT- had pregnancy hyperglycemia. OGTT+ and/or SMBG+ were equally associated with greater neonatal complications. This study suggests that alongside OGTT, SMBG could improve the care of pregnant women.

The Obesity-Fertility Protocol: a randomized controlled trial assessing clinical outcomes and costs of a transferable interdisciplinary lifestyle intervention, before and during pregnancy, in obese infertile women.

BACKGROUND: Obesity in infertile women increases the costs of fertility treatments, reduces their effectiveness and increases significantly the risks of many complications of pregnancy and for the newborn. Studies suggest that even a modest loss of 5-10 % of body weight can restore ovulation. However, there are gaps in knowledge regarding the benefits and cost-effectiveness of a lifestyle modification program targeting obese infertile women and integrated into the fertility clinics. This study will evaluate clinical outcomes and costs of a transferable interdisciplinary lifestyle intervention, before and during pregnancy, in obese infertile women. We hypothesize that the intervention will: 1) improve fertility, efficacy of fertility treatments, and health of mothers and their children; and 2) reduce the cost per live birth, including costs of fertility treatments and pregnancy outcomes. METHODS/DESIGN: Obese infertile women (age: 18-40 years; BMI ≥30 kg/m(2) or ≥27 kg/m(2) with polycystic ovary syndrome) will be randomised to either a lifestyle intervention followed by standard fertility treatments after 6 months if no conception has been achieved (intervention group) or standard fertility treatments only (control group). The intervention and/or follow-up will last for a maximum of 18 months or up to the end of pregnancy. Evaluation visits will be planned every 6 months where different outcome measures will be assessed. The primary outcome will be live-birth rates at 18 months. The secondary outcomes will be sub-divided into four categories: lifestyle and anthropometric, fertility, pregnancy complications, and neonatal outcomes. Outcomes and costs will be also compared to similar women seen in three fertility clinics across Canada. Qualitative data will also be collected from both professionals and obese infertile women. DISCUSSION: This study will generate new knowledge about the implementation, impacts and costs of a lifestyle management program in obese infertile women. This information will be relevant for decision-makers and health care professionals, and should be generalizable to North American fertility clinics. TRIAL REGISTRATION: ClinicalTrials.gov NCT01483612. Registered 25 November 2011.

Gestational diabetes mellitus identification based on self-monitoring of blood glucose.

In Sherbrooke, the gestational diabetes mellitus (GDM) Regional Committee proposed GDM screening during the first trimester for all pregnant women based on a 50 g glucose challenge test (50 g GCT) followed directly by capillary self-monitoring blood glucose (SMBG) at home. We evaluated implementation of committee's recommendations on the clinical trajectory of women receiving prenatal care at our institution. We analyzed data collected systematically by the Blood Sampling in Pregnancy clinic from 2008 to 2011. We evaluated the clinical trajectory of 7710 pregnant women to assess GDM screening/diagnoses and referral rates to the diabetes care centre (DCC) for education and treatment during both the first and second trimesters. The Canadian Diabetes Association glycemic treatment targets in women with GDM were used as diagnosis thresholds and DCC referral decisions: Fasting glucose of 5.3 mmol/L and postprandial 2 h glucose of 6.7 mmol/L. We found that pregnant women were 28.0±4.8 years old, and their body mass indexes were 24.5±5.5 kg/m(2). During the first trimester, 47% of women were screened for GDM, mostly (84%) using the 50 g GCT. Following SMBG, 5.7% were referred to the DCC. Only 32% of women with early GDM had >1 GDM risk factor. Thereafter, 67% of normoglycemic women screened during the first trimester were screened again during the second trimester. Among women screened during the second trimester, most screening was done using 50 g GCT, and 8.8% were referred to the DCC following SMBG. Implementation of 50 g GCT testing followed by direct home SMBG was well implemented in our area. The importance of early GDM screening and rescreening during the second trimester still needs to be emphasized.

The lack of effect of insulin on luteinizing hormone pulsatility in healthy male volunteers provides evidence of a sexual dimorphism in the metabolic regulation of reproductive hormones.

BACKGROUND: The activity of the neuroendocrine reproductive axis is closely related to nutritional status. This link is particularly important in healthy women, in whom insulin is a positive signal for the reproductive system. In contrast, very little is known regarding this relation in men. OBJECTIVES: This study was designed to evaluate the effect of insulin on the reproductive axis of young male volunteers and to study the effect of short-term hypercaloric feeding on this modulation. DESIGN: The activity of the neuroendocrine reproductive axis was characterized by the pattern of endogenous luteinizing hormone (LH) secretion on the basis of frequent blood sampling protocols. The effect of insulin was tested by comparing the LH secretion pattern between a baseline study and a hyperinsulinemic euglycemic clamp. These studies were performed first in subjects fed a controlled isocaloric diet for 6 d (calculated as 1.5 times their resting metabolic rate) then in the same subjects fed a controlled hypercaloric diet in which 30% extra calories were provided as fat and fructose (3 g · kg(-1) · d(-1)) before undergoing identical protocols. Serum gonadotropins, sex steroids, glucose, insulin, ghrelin, and leptin concentrations were assessed, and the HOMA-IR was calculated. RESULTS: The LH secretion pattern was not affected by insulin or by hypercaloric feeding. Insulin decreased ghrelin and increased leptin concentrations but had no additional effect of hypercaloric feeding despite significantly lower HOMA-IR indexes. CONCLUSIONS: Our data indicate that neither insulin nor short-term hypercaloric feeding has any effect on the activity of the male reproductive axis. They also further support the association between ghrelin and insulin and glucose metabolism. This trial was registered at clinicaltrials.gov as NCT01058681.

Reference ranges for total and calculated free and bioavailable testosterone in a young healthy women population with normal menstrual cycles or using oral contraception.

OBJECTIVE: Determine reference values for testosterone in women. DESIGN AND METHODS: 18-40 Year-old women with regular menses or using oral contraception were assessed by questionnaire and blood sample. RESULTS: In 155 women, reference values were different between women with and without hyperandrogenism for total testosterone (0.48-3.42 vs. 0.54-2.72 nmol/L) and calculated free (3-65 vs. 3-39 pmol/L) and bioavailable (0.06-1.35 vs. 0.06-0.81 nmol/L) testosterone. CONCLUSION: Upper reference values for testosterone in women must be established from a well-characterized population.

Clinically useful predictors of conversion to abnormal glucose tolerance in women with polycystic ovary syndrome.

OBJECTIVE: To determine clinically useful predictors of conversion from normal to abnormal glucose tolerance (AGT) in women with polycystic ovary syndrome (PCOS) during regular follow-up, considering that optimal timing for retesting with an oral glucose tolerance test (OGTT) is unknown. DESIGN: Retrospective cohort study. SETTING: Reproductive endocrinology clinic of an academic center. PATIENT(S): Glucose-tolerant PCOS women having a follow-up OGTT≥1 year later. INTERVENTION(S): Regular clinical follow-up. MAIN OUTCOME MEASURE(S): Sets of criteria associated with the lowest false negative rate and an optimal specificity. RESULT(S): Out of 83 women with PCOS, 24.1% converted to AGT during a median follow-up of 3.0 years, including 3.6% who converted to diabetes. Conversion to AGT was significantly associated with glucose excursion and 2-hour glucose during the normal OGTT, increase in fasting glucose (FG) and body mass index during follow-up, and homeostasis model-assessment insulin resistance and FG at follow-up. The best predictive set of criteria was a baseline glucose excursion of >25 mg/dL or an increase in FG of ≥5%. Using these criteria would have saved 45% of the OGTTs, without missing any conversion to AGT. CONCLUSION(S): Although our results need to be validated, we determined that using glucose excursion during the previously normal OGTT in combination with another predictor (e.g., increase in FG or glycosylated hemoglobin), could greatly reduce the number of OGTTs performed in PCOS women during their regular follow-ups, with a minimal rate of missed cases.