Mild obesity does not affect perinatal outcome in gestational carrier cycles.

STUDY QUESTION: Does BMI of gestational carriers (GCs) affect perinatal outcomes after embryo transfer? SUMMARY ANSWER: Overweight and class I obesity in GCs does not affect the rate of good perinatal outcomes. WHAT IS KNOWN ALREADY: The use of GCs is increasing, but uniform guidance regarding optimal BMI for GCs is lacking. Women with obesity who conceive without fertility treatment or through autologous or donor in vitro fertilization are at higher risk of adverse maternal and fetal outcomes, but data on obesity in GCs are very limited. STUDY DESIGN, SIZE, DURATION: We performed a retrospective cohort study of 1121 GC cycles from January 2015 to December 2020 at US Fertility, the largest national partnership of fertility practices in the USA. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: All GC cycles performed at a large network of fertility practices were reviewed. Same-sex partners undergoing co-IVF were excluded. The primary outcome was good perinatal outcome from the first embryo transfer, defined as a singleton live birth at ≥37 weeks of gestation with birth weight between 2500 and 4000 g. Secondary outcome measures included frequencies of live birth, clinical pregnancy, miscarriage, full-term birth, low birth weight, large for gestational age, and cesarean delivery. A generalized linear model (log-binomial) was used for each to compare outcomes across BMI groups using normal BMI (20-24.9 kg/m2) as the reference group. Risk ratios and 95% CIs were estimated for each category group relative to normal BMI. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 1121 cycles in which GCs underwent first embryo transfer, of which 263 (23.5%) were in GCs with BMI >30. Demographics and reproductive history for GCs did not differ by BMI groups. The age of intended parents, use of frozen eggs, and fresh embryo transfers were higher with increasing BMI group. There were no statistically significant associations between BMI and good perinatal outcomes, live birth, clinical pregnancy, biochemical, spontaneous abortion, or low birth weight. However, among live births, higher BMI was significantly associated with birth by cesarean (P = 0.015) and large for gestational age infants (P = 0.023). LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study, and there may be unmeasured confounders. The number of patients with BMI <20 or ≥35 was small, limiting the power for these groups. We were not able to assess all maternal and fetal outcomes. WIDER IMPLICATIONS OF THE FINDINGS: In this study, we did not identify any significant impact of BMI on the chances of having a good perinatal outcome. Prior research studies have been inconsistent and this is the largest study to date. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this work. The authors do not have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

OBGYN screening for environmental exposures: A call for action.

BACKGROUND: Prenatal exposures have known adverse effects on maternal and neonatal outcomes. Professional societies recommend routine screening for environmental, occupational, and dietary exposures to reduce exposures and their associated sequelae. OBJECTIVE: Our objective was to determine the frequency of environmental exposure screening by obstetricians and gynecologists (OBGYNs) at initial patient visits. STUDY DESIGN: Practicing OBGYNs were approached at the University of Colorado and by social media. The survey instrument queried demographics, environmental literacy, and screening practices. Statistical analysis was performed using Chi-square and two-sample t-test. RESULTS: We received 312 online survey responses (response rate of 12%). Responding OBGYNs were predominantly female (96%), board-certified (78%), generalists (65%) with a mean age of 37.1 years. Fewer than half of physicians screened for the following factors: occupational exposures, environmental chemicals, air pollution, pesticide use, personal care products, household cleaners, water source, use of plastics for food storage, and lead and mercury exposure. Eighty five percent of respondents reported that they did not feel comfortable obtaining an environmental history and 58% respondents reported that they performed no regular screening of environmental exposures. A higher frequency of screening was associated with > 4 years of practice (p = 0.001), and having read the environmental committee opinion (p = <0.001). CONCLUSION: The majority of OBGYNs did not incorporate screening for known environmental exposures into routine practice. Reading the environmental committee opinions was strongly and significantly associated with a higher rate of screening. Improving physician comfort in counseling patients may enhance screening for exposures that affect reproductive health.

Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women.

Phthalates are known endocrine disruptors and associated with decreased fecundity, pregnancy loss, and adverse obstetrical outcomes, however the underlying mechanisms remain to be established. Environmental factors can influence gene expression and cell function by modifying epigenetic marks, impacting the developing embryo as well as future generations of offspring. The impact of phthalates on placental gene methylation and expression is largely unknown. We studied the effect of maternal phthalate exposure on the human placental DNA methylome and transcriptome. We determined epigenome-wide DNA methylation marks (Illumina Infinium Human Methylation 850k BeadChip) and gene expression (Agilent whole human genome array) associated with phthalate exposure in first trimester placenta. Integrative genomic analysis of candidate genes was performed to define gene methylation-expression relationships. We identified 39 genes with significantly altered methylation and gene expression in the high phthalate exposure group. Most of these relationships were inversely correlated. This analysis identified epidermal growth factor receptor (EGFR) as a critical candidate gene mediating the effects of phthalates on early placental function. Although additional studies are needed to determine the functional consequences of these changes, our findings are consistent with the model that phthalates impact placental function by modulating the expression of critical placental genes through epigenetic regulation.

A population-based approach to analyzing pulses in time series of hormone data.

Studies of reproductive physiology involve rapid sampling protocols that result in time series of hormone concentrations. The signature pattern in these times series is pulses of hormone release. Various statistical models for quantifying the pulsatile release features exist. Currently these models are fitted separately to each individual and the resulting estimates averaged to arrive at post hoc population-level estimates. When the signal-to-noise ratio is small or the time of observation is short (e.g., 6 h), this two-stage estimation approach can fail. This work extends the single-subject modelling framework to a population framework similar to what exists for complex pharamacokinetics data. The goal is to leverage information across subjects to more clearly identify pulse locations and improve estimation of other model parameters. This modelling extension has proven difficult because the pulse number and locations are unknown. Here, we show that simultaneously modelling a group of subjects is computationally feasible in a Bayesian framework using a birth-death Markov chain Monte Carlo estimation algorithm. Via simulation, we show that this population-based approach reduces the false positive and negative pulse detection rates and results in less biased estimates of population-level parameters of frequency, pulse size, and hormone elimination. We then apply the approach to a reproductive study in healthy women where approximately one-third of the 21 subjects in the study did not have appropriate fits using the single-subject fitting approach. Using the population model produced more precise, biologically plausible estimates of all model parameters. Copyright © 2017 John Wiley & Sons, Ltd.

Embryo quality but not pronuclear score is associated with clinical pregnancy following IVF.

PURPOSE: The association between pronuclear (PN) scoring of embryos from assisted reproductive technology (ART) and clinical pregnancy remains controversial. We hypothesized that embryos with PNs scored on the day of fertilization check offer better embryo selection on day 3 and higher CPR compared to non-PN scored embryos. METHODS: Patients (19-46 years) undergoing IVF/ICSI cycles at Montefiore's Institute for Reproductive Medicine and Health between January 2006 and December 2009 were included in our study. We analyzed fresh day 3 cycles only with autologous oocytes and partner's fresh sperm (n = 344). A total of 1,899 embryos were included. We compared CPR from non-PN scored embryos (Group 1, n = 835) with PN scored embryos (Group 2, n = 1,064). Composite scores by patient were developed based on embryo disposition. We also assessed traditional embryo grading derived from cell number, fragmentation and cell symmetry. Data analysis included chi square and t test to determine if PN scoring was associated with improved CPR, and to compare the additional variables. RESULTS: CPR between Group 1 and Group 2 were not different (p = 0.91). CPR was significantly associated with female age, number of mature oocytes retrieved, number of day 3 embryos and grade of embryos transferred on day 3 (p < 0.05). CONCLUSION: PN scoring was not associated with improved CPR in day 3 embryo transfers. Mean grade of transferred embryos continues to be a well-established, independent predictor of CPR. We conclude that further refinement of embryo grading by PN scoring is not beneficial.

Should the ketogenic diet be considered for enhancing fertility?

The ketogenic diet was first developed in the 1920s as a treatment for epilepsy in an attempt to create a prolonged physiologic starvation state. Since that time, the diet has been found to have other therapeutic effects, most of which are neurologic. Other diets, mostly based on the principals of caloric restriction, have been shown to improve fertility in certain populations. We explore the data, both clinical and laboratory, for potential fertility enhancing benefits of the ketogenic diet, beyond just caloric restriction or weight loss.

BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis.

BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. METHODS A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n = 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. RESULTS A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93-1.43) for underweight, 1.11 (1.01-1.21) for overweight, 1.28 (1.06-1.55) for obese and 2.04 (1.59-2.62) for morbidly obese men. CONCLUSIONS Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further.

The relationship between psychosocial status, acculturation and country of origin in mid-life Hispanic women: data from the Study of Women's Health Across the Nation (SWAN).

METHOD: To test the hypothesis that psychosocial symptomatology differs by country of origin and acculturation among Hispanic women, we examined 419 women, aged 42-52 years at baseline, enrolled in the New Jersey site of the Study of Women's Health Across the Nation (SWAN). Women were categorized into six groups: Central (CA, n = 29) or South American (SA, n = 106), Puerto Rican (PR, n = 56), Dominican (D, n = 42), Cuban (Cu, n = 44) and non-Hispanic Caucasian (NHC, n = 142). Acculturation, depressive symptoms, hostility/cynicism, mistreatment/discrimination, sleep quality, social support, and perceived stress were assessed at baseline. Physical functioning, trait anxiety and anger were assessed at the fourth annual follow-up. Comparisons between Hispanic and non-Hispanic Caucasians used χ², t test or non-parametric alternatives; ANOVA or Kruskal-Wallis testing examined differences among the five Hispanic sub-groups. Multivariable regression models used PR women as the reference group. RESULTS: Hispanic women were overall less educated, less acculturated (p < 0.001 for both) and reported more depressive symptoms, cynicism, perceived stress, and less mistreatment/discrimination than NHCs. Along with D women, PR women reported worse sleep than Cu women (p < 0.01) and more trait anxiety than SA and Cu women (p < 0.01). Yet, PR women were most acculturated (21.4% highly acculturated vs. CA (0.0%), D (4.8%), SA (4.8%) and Cu (2.3%) women; p < 0.001). In regression models, PR women reported depressive symptoms more frequently than D, Cu, or SA women, and reported trait anxiety more frequently than Cu or SA women. Greater acculturation was associated with more favorable psychosocial status, but PR ethnicity was negatively related to psychosocial status. CONCLUSION: Psychosocial symptomatology among Hispanic women differs by country of origin and the relatively adverse profile of Puerto Rican women is not explained by acculturation.

Menopausal symptoms within a Hispanic cohort: SWAN, the Study of Women's Health Across the Nation.

INTRODUCTION: Since the designation of people as Hispanic involves the amalgamation of a number of different cultures and languages, we sought to test the hypothesis that menopausal symptoms would differ among Hispanic women, based upon country of origin and degree of acculturation. METHODS: A total of 419 women, aged 42-52 years at baseline, were categorized as: Central American (CA, n = 29) or South American (SA, n = 106), Puerto Rican (PR, n = 56), Dominican (D, n = 42), Cuban (Cu, n = 44) and non-Hispanic Caucasian (n = 142). We assessed vasomotor symptoms, vaginal dryness and trouble in sleeping. Hispanics and non-Hispanic Caucasians were compared using the chi(2) test, t test or non-parametric alternatives; ANOVA or Kruskal-Wallis testing examined differences among the five Hispanic sub-groups. Multivariable regression models used PR women as the reference group. RESULTS: Hispanic women were overall less educated, less acculturated (p < 0.001 for both) than non-Hispanic Caucasians and more of them reported vasomotor symptoms (34.1-72.4% vs. 38.3% among non-Hispanic Caucasians; p = 0.0293) and vaginal dryness (17.9-58.6% vs. 21.1% among non-Hispanic Caucasians, p = 0.0287). Among Hispanics, more CA women reported vasomotor symptoms than D, Cu, SA, or PR women (72.4% vs. 45.2%, 34.1%, 50.9%, and 51.8%, respectively). More CA (58.6%) and D women (38.1%) reported vaginal dryness than PR (17.9%), Cu (25.0%) and SA (31.4%) women. More PR and D women reported trouble in sleeping (66.1 and 64.3%, respectively) compared to CA (51.7%), Cu (36.4%), and SA (45.3%) women. CONCLUSION: Symptoms associated with menopause among Hispanic women differed by country of origin but not acculturation. Central American women appear to be at greatest risk for both vasomotor symptoms and vaginal dryness.

Differential induction of programmed cell death in CD8+ and CD4+ T cells by the B subunit of cholera toxin.

We have recently demonstrated that a short-term treatment of parental splenocytes with the B subunit of cholera toxin (CT-B) abrogates the development of acute GVHD in F1 hybrid mice transplanted with these cells. In order to obtain better insight into the mechanism of the action of CT-B, we studied the effect of CT-B on survival of purified murine T cells and their subsets. We show that treatment with B subunit stimulates apoptosis in T cells, detectable following incubation in vitro. Although apoptosis was noticed in both CD8+ and CD4+ T cell subsets, the treatment preferentially stimulates programmed cell death (PCD) in CD8+ population. Thus, immunosuppressive action of CT-B in vivo may be in part due to its ability to eliminate CD8+ T cells.