Lubna Pal

Replete vitamin D stores predict reproductive success following in vitro fertilization

OBJECTIVE To determine whether 25OH-D levels in the follicular fluid (FF) of infertile women undergoing IVF demonstrate a relationship with IVF cycle parameters and outcome, hypothesizing that levels of 25OH-D in body fluids are reflective of vitamin repletion status. DESIGN Prospective cohort study. SETTING Academic tertiary care center. PATIENT(S) Eighty-four infertile women undergoing IVF. INTERVENTION(S) Follicular fluid from follicles>or=14 mm; serum (n = 10) and FF levels of 25OH-D. MAIN OUTCOME MEASURE(S) Clinical pregnancy (CP), defined as evidence of intrauterine gestation sac on ultrasound, following IVF; IVF cycle parameters. RESULT(S) Serum and FF levels of 25OH-D were highly correlated (r=0.94). In a predominantly Caucasian population (66%), significantly lower FF 25OH-D levels were noted in Black versus non-Black patients. Significant inverse correlations were seen between FF 25OH-D levels and body mass index (r=-0.25). Significantly higher CP and implantation rates were observed across tertiles of FF25OH-D; patients achieving CP following IVF (n=26) exhibited significantly higher FF levels of 25OH-D. Multivariable logistic regression analysis confirmed FF 25OH-D levels as an independent predictor to success of an IVF cycle; adjusting for age, body mass index, ethnicity, and number of embryos transferred, each ng/mL increase in FF 25OH-D increased the likelihood for achieving CP by 6%. CONCLUSION(S) Our findings that women with higher vitamin D level in their serum and FF are significantly more likely to achieve CP following IVF-embryo transfer are novel. A potential for benefit of vitamin D supplementation on treatment success in infertile patients undergoing IVF is suggested and merits further investigation.

Obstetric and Neonatal Outcomes of Maternal Vitamin D Supplementation: Results of an Open-Label, Randomized Controlled Trial of Antenatal Vitamin D Supplementation in Pakistani Women

OBJECTIVE The objective of the study was to determine whether vitamin D (vitD) supplementation during pregnancy affects obstetric and neonatal outcomes. SETTING The study was conducted at a university hospital in Karachi, Pakistan. METHODS The study was a single-center, open-label, randomized, controlled trial of routine care (group A, 200 mg ferrous sulfate and 600 mg calcium daily) vs vitD supplementation (group B, 4000 IU vitamin D3 daily), started at 20 weeks and continued till delivery. Maternal serum samples of 25-hydroxyvitamin D (25OHD) were collected at baseline and delivery. Neonatal vitD status was assessed in cord blood or in neonatal serum samples within 48 hours of birth. Obstetric outcomes included gestational hypertension, gestational diabetes, and preterm labor, and neonatal well-being included small for gestational age, birth weight, length, head circumference, and 1- and 5-minute Apgar scores. RESULTS Of 207 gravidae enrolled, 193 completed the trial. Maternal age, vitD status, and gestational age at enrollment were comparable between the two groups. At delivery, maternal 25OHD was increased in group B (18.3 ± 11 ng/dL vs 8.82 ± 11.84 ng/dL (P = .001) compared with group A (6.9 ± 7.0 ng/dL vs 6.32 ± 3.97 ng/dL, P = .06). The obstetric outcomes were comparable between the two groups (P > .05). Neonatal 25OHD levels were significantly higher in group B compared with group A (19.22 ± 12.19 ng/dL vs 6.27 ± 5.2 ng/dL). There was positive correlation between maternal and neonatal 25OHD levels (r = 0.83, P = .001). One- and 5-minute Apgar scores were significantly higher in group B (7.10 ± 0.66 vs 6.90 ± 0.50, P = .026, and 8.53 ± 0.68 vs 8.33 ± 0.81, P = .051, respectively). Neonatal anthropometric parameters were comparable between the two groups (P > .05). CONCLUSION Maternal vitD supplementation improved maternal and neonatal vitD status.

Therapeutic implications of vitamin D and calcium in overweight women with polycystic ovary syndrome

Objective: To assess effects of vitamin D and Calcium (Ca) on hormonal and metabolic milieu of polycystic ovary syndrome (PCOS). Design: Single arm open label trial. Methods: Twelve overweight and vitamin D deficient women with PCOS underwent a 2 hour oral glucose tolerance testing at baseline and following 3-month supplementation with vitamin D (daily dose of 3533 IU, increased to 8533 IU after the first five participants) and 530 mg elemental Ca daily. Main outcome measures: Blood pressure (BP), plasma glucose, insulin, total testosterone (T) androstenedione (A), sex hormone binding globulin, lifestyle parameters were assessed at baseline and following 3-month intervention. Insulin resistance (IR) and area under the curve for glucose and insulin were computed; paired analyses were conducted. Results: Improved serum 25OHD (p < 0.001) and reductions in total T (p = 0.036) and A (p = 0.090) levels were noted following 3-month supplementation, compared to baseline. Significant lowering in BP parameters was seen in participants with baseline BP ≥ 120/80 mmHg (n = 8) and in those with baseline serum 25OHD ≤20 ng/ml (n = 9). Parameters of glucose homeostasis and IR remained unchanged (p > 0.05). Conclusions: Androgen and BP profiles improved followed three month intervention, suggesting therapeutic implications of vitamin D and Ca in overweight and vitamin D deficient women with PCOS.

High prevalence of vitamin D deficiency in Pakistani mothers and their newborns

To determine the prevalence of vitamin D deficiency in Pakistani parturients and their newborns and to assess the correlation between maternal and newborn serum levels of the vitamin D metabolite 25‐hydroxy vitamin D3.

Knowledge, attitudes, and practices regarding conception and fertility: a population-based survey among reproductive-age United States women

OBJECTIVE To assess overall knowledge, attitudes, and practices related to conception and fertility among reproductive-age women in the United States. DESIGN Online survey of a cross-sectional sample of 1,000 women. SETTING United States, March 2013. PATIENT(S) Women aged 18-40 years. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Knowledge, attitudes, and practices regarding selected topics in reproductive health. RESULT(S) Forty percent of women across all age groups expressed concerns about their ability to conceive. Yet one-third of women were unaware of adverse implications of sexually transmitted infections, obesity, or irregular menses for procreative success, and one-fifth were unaware of the effects of aging. Approximately 40% were unfamiliar with the ovulatory cycle. Overall, younger women (18-24 years) demonstrated less knowledge regarding conception, fertility, and ovulation, whereas older women tended to believe in common myths and misconceptions. Respondents in all age groups identified womens health care providers (75%) and Web sites (40%) as top sources of reproductive health-related information; however, engagement with providers on specific factors affecting fertility is sparse. CONCLUSION(S) Knowledge regarding ovulation, fertility, and conception is limited among this sample of reproductive-age US women. Future initiatives should prioritize improved provider engagement and accurate information dissemination in Web-based venues.

Predictors of chronic disease at midlife and beyond - the health risks of obesity

A burgeoning pandemic of obesity is well characterized. 41% of U.S. adults are projected to be obese by 2015 and obesity, a potentially modifiable risk, is emerging as a leading predictor of lifetime health. The wide spectrum of morbidities related to excess body mass includes risks for diabetes, hypertension, coronary artery disease, dyslipidemia, malignancy, venous thrombosis, degenerative joint disease, pulmonary compromise, sleep apnea, cholelithiasis, depression and overall reduced quality of life. Beyond the myriad major and minor morbidities linked to obesity, increased all-cause mortality and cardiovascular mortality is recognized in the obese. Bariatric surgery literature suggests that, in the morbidly obese, increase in the lifespan is achievable with reversal of obesity, reinforcing the realization that sequelae therein are by no means inevitable. Aggressive efforts must be targeted towards population-based strategies to educate and sensitize all generations on contributors to and sequelae of excess body mass as obesity represents one of the few modifiable factors that impact on the quantity and quality of lifespan.

Endometrial thickness, Caucasian ethnicity, and age predict clinical pregnancy following fresh blastocyst embryo transfer: a retrospective cohort.

BackgroundIn-vitro fertilization (IVF) with blastocyst as opposed to cleavage stage embryos has been advocated to improve success rates. Limited information exists on which to predict which patients undergoing blastocyst embryo transfer (BET) will achieve pregnancy. This studys objective was to evaluate the predictive value of patient and cycle characteristics for clinical pregnancy following fresh BET.MethodsThis was a retrospective cohort study from 2003–2007 at an academic assisted reproductive program. 114 women with infertility underwent fresh IVF with embryo transfer. We studied patients undergoing transfer of embryos at the blastocyst stage of development. Our main outcome of interest was clinical pregnancy. Clinical pregnancy and its associations with patient characteristics (age, body mass index, FSH, ethnicity) and cycle parameters (thickness of endometrial stripe, number eggs, available cleaving embryos, number blastocysts available, transferred, and cryopreserved, and embryo quality) were examined using Students T test and Mann-Whitney-U tests as appropriate. Multivariable logistic regression models were created to determine independent predictors of CP following BET. Receiver Operating Characteristic analyses were used to determine the optimal thickness of endometrial stripe for predicting clinical pregnancy.ResultsPatients achieving clinical pregnancy demonstrated a thicker endometrial stripe and were younger preceding embryo transfer. On multivariable logistic regression analyses, Caucasian ethnicity (OR 2.641, 95% CI 1.054–6.617), thickness of endometrial stripe, (OR 1.185, 95% CI 1.006–1.396) and age (OR 0.879, 95% CI 0.789–0.980) predicted clinical pregnancy. By receiver operating characteristic analysis, endometrial stripe ≥ 9.4 mm demonstrated a sensitivity of 83% for predicting clinical pregnancy following BET.ConclusionIn a cohort of patients undergoing fresh BET, thicker endometrial stripe, Caucasian ethnicity, and younger age are positive predictors of clinical pregnancy after fresh BET. These findings may be useful in clinical management of infertile patients undergoing fresh BET cycles.

Self-reported menopausal symptoms, coronary artery calcification, and carotid intima-media thickness in recently menopausal women screened for the Kronos early estrogen prevention study (KEEPS)

OBJECTIVE To determine whether self-reported menopausal symptoms are associated with measures of subclinical atherosclerosis. DESIGN Cross-sectional analysis. SETTING Multicenter, randomized controlled trial. PATIENT(S) Recently menopausal women (n = 868) screened for the Kronos Early Estrogen Prevention Study (KEEPS). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Baseline menopausal symptoms (hot flashes, dyspareunia, vaginal dryness, night sweats, palpitations, mood swings, depression, insomnia, irritability), serum E2 levels, and measures of atherosclerosis were assessed. Atherosclerosis was quantified using coronary artery calcium (CAC) Agatston scores (n = 771) and carotid intima-media thickness (CIMT). Logistic regression model of menopausal symptoms and E2 was used to predict CAC. Linear regression model of menopausal symptoms and E2 was used to predict CIMT. Correlation between length of time in menopause with menopausal symptoms, E2, CAC, and CIMT were assessed. RESULT(S) In early menopausal women screened for KEEPS, neither E2 nor climacteric symptoms predicted the extent of subclinical atherosclerosis. Palpitations and depression approached significance as predictors of CAC. Other symptoms of insomnia, irritability, dyspareunia, hot flashes, mood swings, night sweats, and vaginal dryness were not associated with CAC. Women with significantly elevated CAC scores were excluded from further participation in KEEPS; in women meeting inclusion criteria, neither baseline menopausal symptoms nor E2 predicted CIMT. Years since menopause onset correlated with CIMT, dyspareunia, vaginal dryness, and E2. CONCLUSION(S) Self-reported symptoms in recently menopausal women are not strong predictors of subclinical atherosclerosis. Continued follow-up of this population will be performed to determine whether baseline or persistent symptoms in the early menopause are associated with progression of cardiovascular disease. CLINICAL TRIAL REGISTRATION NUMBER NCT00154180.

Implications of blood type for ovarian reserve

BACKGROUND We explored the relevance of blood type to ovarian reserve, as reflected by early follicular phase FSH levels. METHODS For this cross-sectional observational study, early follicular phase serum levels of FSH (mIU/ml) and estradiol (E2, pg/ml), and information on blood type (A, B, AB and O) and patient age were procured for female patients, ≤ 45 years age (n= 544), who were undergoing fertility evaluation at one of two tertiary care facilities. Serum FSH > 10 mIU/ml was taken to reflect diminished ovarian reserve (DOR). Data distribution for FSH and age was analyzed and non-parametric tests used for comparisons across blood groups. Multivariable logistic regression analyses determined the relationship between elevated FSH and respective blood types after adjusting for age and study site. RESULTS Prevalence of blood types according to order of frequency was: O (45%), A (35%), B (16%) and AB (5%). After adjusting for age and study site, patients with blood type O were twice as likely to exhibit FSH > 10 mIU/ml compared with those with A or AB blood types [odds ratio (OR) 2.36; 95% confidence interval (CI) 1.27-4.41; P= 0.007], and three times as likely to manifest FSH > 12 m IU/ml (OR 3.48, 95% CI 1.46-7.32, P= 0.004). The B blood group antigen failed to exhibit any relationship with ovarian reserve as reflected by baseline FSH (P> 0.05). CONCLUSIONS The A blood group antigen appears to be protective for ovarian reserve, whereas blood type O appears to be associated with DOR, in a relationship that is independent of advancing age. Further studies are needed to establish causality and identify the underlying mechanisms for the association.

Cardiovascular disease and ovarian function.

Purpose of review Coronary heart disease (CHD) is the leading cause of death in the aging female population in the developed world. Ovarian endocrinology plays an important role in modulating a womans CHD risk. We herein present an overview of our current understanding of CHD risk profile in the context of ovarian physiology and senescence. Recent findings Endogenous ovarian estrogen has long been recognized to offer cardiac benefit and vascular protection against atherosclerosis. Existing data, however, do not allow for an extrapolation of the recognized cardioprotective implications of the reproductive-age endogenous estrogenic milieu to the use of exogenous estrogen in postmenopausal women. Ongoing efforts are targeting the concept that when reintroduced proximate to onset of ovarian senescence, exogenous estrogen may retard the process of atherogenesis. Until this hypothesis is substantiated, cardioprotection must not be an indication for initiating hormone therapy in menopausal women. Summary Ovarian hormones modulate the processes of atherosclerosis and the mechanisms underlying CHD. The female reproductive hormones offer a cardioprotective milieu that is rapidly attenuated with the cessation of ovarian function (be it following natural menopause or after medical or surgical ovarian extirpation). The role of exogenous hormone therapy, and the nuances of timing and duration of exposure, are still being elucidated.