Cultivable vaginal Lactobacillus is not associated with fecundability in Kenyan women attempting to conceive.

OBJECTIVE: To examine the association between cultivable vaginal Lactobacillus and fecundability in Kenyan women attempting nonmedically assisted conception. DESIGN: Prospective preconception cohort. SETTING: Nairobi and Mombasa, Kenya. PATIENT(S): Women trying to conceive who reported ≤3 months of pre-enrollment conception attempt time. INTERVENTION(S): Cultivable Lactobacillus (primary), Lactobacillus morphotypes on Gram stain (secondary). MAIN OUTCOME MEASURE(S): Participants reported the first day of their last menstrual period and recent sexual behavior, underwent pregnancy testing, and provided vaginal specimen samples for Lactobacillus culture and Gram stain at ≤6 monthly preconception visits. The outcome was fecundability-the per-menstrual cycle probability of pregnancy. Associations between cultivable Lactobacillus and Lactobacillus morphotypes on Gram stain at the visit before each pregnancy test and fecundability were estimated using proportional probabilities models to generate fecundability ratios (FRs). RESULT(S): A total of 458 women contributed 1,376 menstrual cycles. At enrollment, 65.3% (n = 299) of participants had cultivable Lactobacillus, 47.4% (n = 217) had cultivable hydrogen peroxide producing Lactobacillus, and 64.6% (n = 296) had Lactobacillus detected on Gram stain. In unadjusted analysis, there was no association between cultivable Lactobacillus at the prior visit and fecundability (FR, 0.92; 95% CI, 0.73-1.16); results were similar after adjustment for age, frequency of condomless sex, and study site (adjusted FR, 0.92; 95% CI, 0.72-1.18). Lactobacillus on Gram stain at the visit prior was associated with modestly higher fecundability (adjusted FR, 1.18; 95% CI, 0.92-1.51). CONCLUSION(S): Cultivable Lactobacillus was not associated with fecundability, although Lactobacillus morphotypes detected on Gram stain were somewhat associated with increased fecundability. The relationship between vaginal Lactobacillus and fecundity may be species-specific.

What women want: General population perspectives and access to preconception expanded carrier screening.

OBJECTIVE: Expanded carrier screening (ECS) assesses the risk of individuals and couples of having a child affected with a set of genetic conditions. Carriers have options available to optimize pregnancy outcomes based on personal values and preferences. The greatest range of options is available prior to pregnancy, therefore professional societies recommend this screening be performed preconception. This study aimed to assess awareness of, and interest in, ECS in women preconception. Additionally, it aimed to evaluate preferences for timing and location of education and availability of ECS. METHODS: A total of 260 nulliparous women from the general population were surveyed through Qualtrics, a national market research survey platform. Data were delineated using descriptive statistics. RESULTS: Of this cohort, 43.5% reported being aware of ECS prior to the survey and 77.8% indicated interest. Those previously aware were first informed by family, friends, or independent online research. Interest was primarily driven by a desire for reassurance and to make informed decisions about future pregnancies. Interested respondents indicated a willingness to request testing from providers. Participants showed a preference for education and access from a healthcare provider in person. CONCLUSION: These findings provide insight regarding when and where to best educate and reach women prior to pregnancy about ECS to maximize pregnancy outcomes.

The Impact of Preconceptional Hysterosalpingography with Oil-based Contrast on Maternal and Neonatal Iodine Status.

The objective of this study is to investigate the impact of preconceptional exposure to oil-based iodinated contrast in the hysterosalpingography (HSG) on pregnant women and their offspring's iodine status, thyroid function, and the outcomes of pregnancy. A cross-sectional evaluation of iodine status was performed on pregnant women with the preconceptional experience of ethiodized-oil HSG. For those found to have iodine excess (with serum iodine concentration (SIC) > 92 µg/L), a prospective follow-up was conducted until termination of the pregnancy or 1 week postpartum. Among 70 of 425 pregnant women with preconceptional ethiodized-oil HSG, iodine excess was initially confirmed in 38 (54.3%), with an elevated SIC (294.00 µg/L [142.00, 123.20]) and urinary iodine-to-creatinine ratio (UI/Cr) (830.00 µg/g Cr [437.50, 255.30]), both higher than the normative data (P = 0.000, P = 0.000). Subsequent follow-up in pregnancy showed a downward trend in both SIC and UI/Cr. Thirty-four women delivered healthy neonates at full term, though the other 4 cases of premature birth, abnormal fetal karyotype, spontaneous abortion, and neonatal cardiac defect were reported. After delivery, the iodine concentration in maternal breast milk and neonatal urine was 584.50 µg/L [328.50, 1507.50] and 424.00 µg/L [277.00, 657.50], respectively, both higher than normative data (P = 0.001, P = 0.015). For thyroid evaluation, 25 cases (65.79%) of clinical or subclinical hypothyroidism and 2 cases (5.26%) of thyrotoxicosis were confirmed in women with iodine excess. Neither goiter nor thyroid dysfunction was detected in any offspring. Preconceptional exposure to oil-based contrast in HSG might exert a far-reaching impact on maternal and offspring iodine status, and tend to result in increased risk of maternal thyroid dysfunction.

Factors Associated with Inflammatory Bowel Disease Flare During Pregnancy Among Women with Preconception Remission.

BACKGROUND: The factors associated with inflammatory bowel diseases (IBD) relapse throughout gestation in those with preconception remission remain unknown. AIMS: We aimed to investigate disease and pregnancy course among IBD women with quiescent disease at conception. METHODS: Women with IBD attending a multidisciplinary clinic for preconception, antenatal and postnatal treatment were prospectively recruited during 2011-2018. RESULTS: Overall, 298 women with IBD with quiescent disease at the time of conception constituted the study cohort. Of these, 112 (37.6%) women experienced disease flare during pregnancy. The risk of disease relapse was higher in those with ulcerative colitis (UC) as compared to those with Crohn's disease (CD) (48.1% vs. 31.8%, P = 0.005). The proportion of women with prior IBD-related gastrointestinal surgery was lower in those who experienced disease flare up (13.4% vs. 26.3%, P = 0.009). The use of biologic therapy at the time of conception was associated with lower rates of disease relapse (25.0% vs. 43.9%, P = 0.001). In multivariate analysis, use of conventional medications or no treatment (aOR [95% CI]: 2.0 (1.12, 3.57), P = 0.02) and lack of prior history of IBD-related surgery (aOR [95% CI]: 3.13 (1.37, 7.14), P = 0.007) were independently positively associated with disease relapse. Rates of hospitalization during pregnancy (21.4% vs. 2.2%, P < 0.001) and preterm delivery (22.3% vs. 9.1%, P = 0.002) were higher, and birthweight was lower (median 2987 vs. 3153 grams, P = 0.05) in those with disease flare as compared to those who maintained remission. CONCLUSION: Prior IBD-related surgery and biologic therapy were found as independent protective factors against relapse during pregnancy among women with quiescent disease at conception.

The Reproductive Journey in the Genomic Era: From Preconception to Childhood.

It is estimated that around 10-15% of the population have problems achieving a pregnancy. Assisted reproduction techniques implemented and enforced by personalized genomic medicine have paved the way for millions of infertile patients to become parents. Nevertheless, having a baby is just the first challenge to overcome in the reproductive journey, the most important is to obtain a healthy baby free of any genetic condition that can be prevented. Prevention of congenital anomalies throughout the lifespan of the patient must be a global health priority. Congenital disorders can be defined as structural or functional anomalies that occur during intrauterine life and can be identified prenatally, at birth, or sometimes may only be detected later during childhood. It is considered a frequent group of disorders, affecting 3-6% of the population, and one of the leading causes of morbidity and mortality. Congenital anomalies can represent up to 30-50% of infant mortality in developed countries. Genetics plays a substantial role in the pathogenesis of congenital anomalies. This becomes especially important in some ethnic communities or populations where the incidence and levels of consanguinity are higher. The impact of genetic disorders during childhood is high, representing 20-30% of all infant deaths and 11.1% of pediatric hospital admissions. With these data, obtaining a precise genetic diagnosis is one of the main aspects of a preventive medicine approach in developed countries. The field of reproductive health has changed dramatically from traditional non-molecular visual microscope-based techniques (i.e., fluorescence in situ hybridization (FISH) or G-banding karyotype), to the latest molecular high-throughput techniques such as next-generation sequencing (NGS). Genome-wide technologies are applied along the different stages of the reproductive health lifecycle from preconception carrier screening and pre-implantation genetic testing, to prenatal and postnatal testing. The aim of this paper is to assess the new horizon opened by technologies such as next-generation sequencing (NGS), in new strategies, as a genomic precision diagnostic tool to understand the mechanisms underlying genetic conditions during the "reproductive journey".

Couples' prepregnancy body mass index and time to pregnancy among those attempting to conceive their first pregnancy.

OBJECTIVE: To explore the relationship between couples' prepregnancy body mass index (BMI) and time to pregnancy (TTP) among those with no prior gravidity. DESIGN: Retrospective cohort study. SETTING: Local maternal/child health care or family-planning service institutions. PATIENT(S): A total of 2,301,782 eligible couples participating in the National Free Preconception Check-up Projects from January 1, 2015 to December 31, 2017. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Time to pregnancy. RESULT(S): Underweight, overweight, or obese status in women and underweight status in men were associated with couples' prolonged TTP. The optimal BMI levels were 20.61-23.06 kg/m2 and 22.69-27.74 kg/m2 for women and men, respectively. Compared with couples in whom both partners had a normal BMI, the pregnancy rates were reduced by 10% (fecundability odds ratio [FOR] 0.90; 95% confidence interval [CI], 0.88-0.92) and 19% (FOR 0.81; 95% CI, 0.78-0.84) for couples in whom both partners were underweight or obese, respectively. The combination of women with a normal BMI and overweight men had the greatest fertility (FOR 1.03; 95% CI, 1.02-1.03), and the combination of obese women and underweight men had the lowest fertility (FOR 0.70; 95% CI, 0.65-0.76). CONCLUSION(S): Abnormal prepregnancy BMIs in either women or men were associated with prolonged TTP among couples with no prior gravidity. Scientific management of couples' prepregnancy BMI could improve their fertility.

Parental human leukocyte antigen-C allotypes are predictive of live birth rate and risk of poor placentation in assisted reproductive treatment.

OBJECTIVE: To study the pregnancy, miscarriages, and live birth rates (LBRs) according to maternal killer cell immunoglobulin-like receptor (KIR) genes expressed by uterine natural killer cells and paternal or oocyte donor human leukocyte antigen-C (HLA-C) genes expressed by trophoblast cells in patients with recurrent reproductive failure. DESIGN: Prospective observational cohort study. SETTING: Private infertility center. PATIENT(S): Participants included 204 women with recurrent miscarriage or recurrent implantation failure. INTERVENTION(S): The KIR and HLA-C genotypes of all women and HLA-C of their partners, gamete donors, miscarriage tissue, and babies were analyzed. MAIN OUTCOME MEASURE(S): All clinical variables (pregnancy, miscarriage, and LBRs) were analyzed and categorized based on KIR, oocyte origin, and single embryo transfer (SET)/double embryo transfer (DET). RESULT(S): A higher miscarriage rate was observed after DETs in KIR AA mothers (47.8% egg donation and 37.5% in vitro fertilization [IVF]) compared with KIR AB (10.5% egg donation and 12.5% IVF) or KIR BB (6.7% egg donation and 0% IVF). A significantly decreased LBR was observed after DETs with oocyte donation in KIR AA patients (4.3%) compared with KIR AB (26.3%) or BB (46.7%). The LBR decreased significantly as the fetal HLA-C2 load increased in KIR AA women. CONCLUSION(S): Elective SET improves the reproductive outcomes compared with DET. An increased embryo HLA-C2 load has a negative impact on the LBR in KIR AA patients. The selection of HLA-C1 over HLA-C2 donors could have a positive impact on the LBR in KIR AA patients. CLINICAL TRIAL REGISTRATION NUMBER: NCT04052438.

Interconception care.

BACKGROUND: The importance of interconception care - defined as care given to women, and their partners, between one pregnancy and the next to optimise their health - is increasingly important, with rising rates of overweight, obesity, diabetes and hypertension among people of reproductive age. Women frequently visit their general practitioner (GP) in the first six months postpartum. This is an opportune time to discuss ideal interpregnancy intervals (IPIs) and advise women about contraception and healthy behaviours. OBJECTIVE: The aim of this article is to review available research and guidelines on interconception care and IPIs, and propose best-practice care for the general practice setting. DISCUSSION: GPs are uniquely placed to deliver the different aspects of interconception care including reviewing the outcomes of the previous pregnancy, advising women on optimal IPIs and providing contraception and lifestyle guidance. Studies have found that GPs may feel they lack the time and resources to provide interconception care, but support is available through online tools and easy-to-access checklists. As the prevalence of obesity and chronic diseases increases, interconception care has the potential to reduce future adverse perinatal outcomes.

Delivering family planning and preconception care to women with diabetes: Implementation challenges and promising strategies.

Diabetes is increasingly prevalent among women of reproductive age and during pregnancy. The American Diabetes Association, which has called for improvements in the patient-centeredness of care, recommends preconception counseling and care for women of reproductive age with diabetes. However, data suggests this care is not sufficiently delivered. In this article, we describe demographic shifts in the need for preconception care and outline several changes at the clinical encounter as well as the health system- and community-levels that can help improve the delivery of diabetes-specific preconception care.

Using Health Information Technology to Engage African American Women on Nutrition and Supplement Use During the Preconception Period.

Importance: Healthy nutrition and appropriate supplementation during preconception have important implications for the health of the mother and newborn. The best way to deliver preconception care to address health risks related to nutrition is unknown. Methods: We conducted a secondary analysis of data from a randomized controlled trial designed to study the impact of conversational agent technology in 13 domains of preconception care among 528 non-pregnant African American and Black women. This analysis is restricted to those 480 women who reported at least one of the ten risks related to nutrition and dietary supplement use. Interventions: An online conversational agent, called "Gabby", assesses health risks and delivers 12 months of tailored dialogue for over 100 preconception health risks, including ten nutrition and supplement risks, using behavioral change techniques like shared decision making and motivational interviewing. The control group received a letter listing their preconception risks and encouraging them to talk to a health care provider. Results: After 6 months, women using Gabby (a) reported progressing forward on the stage of change scale for, on average, 52.9% (SD, 35.1%) of nutrition and supplement risks compared to 42.9% (SD, 35.4) in the control group (IRR 1.22, 95% CI 1.03-1.45, P = 0.019); and (b) reported achieving the action and maintenance stage of change for, on average, 52.8% (SD 37.1) of the nutrition and supplement risks compared to 42.8% (SD, 37.9) in the control group (IRR 1.26, 96% CI 1.08-1.48, P = 0.004). For subjects beginning the study at the contemplation stage of change, intervention subjects reported progressing forward on the stage of change scale for 75.0% (SD, 36.3%) of their health risks compared to 52.1% (SD, 47.1%) in the control group (P = 0.006). Conclusion: The scalability of Gabby has the potential to improve women's nutritional health as an adjunct to clinical care or at the population health level. Further studies are needed to determine if improving nutrition and supplement risks can impact clinical outcomes including optimization of weight. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01827215.

Fecundability in relation to use of fertility awareness indicators in a North American preconception cohort study.

OBJECTIVE: To quantify the frequency of use of selected fertility awareness indicators and to assess their influence on fecundability. DESIGN: Web-based prospective cohort study. SETTING: Not applicable. PATIENT(S): Female pregnancy planners, aged 21-45 years, attempting conception for ≤6 cycles at study entry. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We ascertained time to pregnancy, in menstrual cycles, with bimonthly questionnaires. We estimated adjusted fecundability ratios (FRs) and confidence intervals (CIs) using proportional probabilities models, controlling for age, income, education, smoking, intercourse frequency, and other lifestyle and reproductive factors. RESULT(S): A total of 5,688 women were analyzed, with a mean age of 29.9 years and mean time trying of 2.1 cycles at baseline; 30% had ever been pregnant. At baseline, 75% were using one or more fertility indicators (counting days or charting menstrual cycles [71%], measuring basal body temperature [BBT, 21%], monitoring cervical fluid [39%], using urine LH tests [32%], or feeling for changes in position of the cervix [12%]). Women using any fertility indicator at baseline had higher subsequent fecundability (adjusted FR 1.25, 95% CI 1.16-1.35) than those not using any fertility indicators. For each individual indicator, adjusted FRs ranged from 1.28-1.36, where 1.00 would indicate no relation with fecundability. The adjusted FR for women using a combination of charting days, cervical fluid, and urine LH was 1.48 (95% CI 1.31-1.67) relative to women using no fertility indicators. CONCLUSION(S): In a North American preconception cohort study, use of fertility indicators indicating the fertile window was common, and was associated with greater fecundability.

Preconception and antenatal carrier screening for genetic conditions: The critical role of general practitioners.

BACKGROUND: General practitioners (GPs) provide advice to women and couples before and during pregnancy to optimise the health and wellbeing of couples and their child. Genetic carrier screening can identify the chance of couples having children with recessively inherited genetic conditions. The 2018 federal budget announced Mackenzie's Mission, a $20 million Medical Research Future Fund project investigating how such screening could be offered to all couples who wish to access it. OBJECTIVE: The aim of this paper is to discuss historical and current screening methodologies, options for individuals and couples identified as having a high chance of having a child with a genetic condition, screening guidelines, Mackenzie's Mission and the implications of carrier screening in general practice. DISCUSSION: GPs are crucial to any population-wide genetic carrier screening program and are often the first health professional that women and couples see for preconception and early pregnancy care. Knowledge of genetic screening will be increasingly important as such programs are developed.

Gender Stereotypes and Preconception Health: Men's and Women's Expectations of Responsibility and Intentions to Engage in Preventive Behaviors.

Introduction As mounting evidence underscores the importance of both men and women taking steps before pregnancy to improve reproductive outcomes, public health priorities are shifting toward a more gender-inclusive program of promoting preconception health (PCH). This study examined whether prescriptive gender stereotypes, defined as men's and women's beliefs about PCH behavioral norms each gender should uphold, were positively associated with intentions to engage in behaviors to protect a future child's health. Methods Data came from a June 2017 online survey of 609 U.S. men and women ages 18-44. Two six-item scales of prescriptive same- and opposite-gender stereotypes were used to predict a six-item scale of intentions to engage in six recommended PCH behaviors (i.e., avoiding smoking, secondhand smoke, drinking, exposure to bisphenol A and pesticides, and preventing Zika infection). Multiple linear regression models also adjusted for demographic, socioeconomic, and health characteristics. Results Among both male and female respondents, PCH prescriptive gender stereotypes for men were rated significantly lower than those for women. Adjusting for covariates, stronger prescriptive same-gender stereotypes were associated with increased PCH intentions (men: B = 0.496, p < 0.001; women: B = 0.486, p < 0.001). Opposite-gender stereotypes were also positively associated with PCH intentions (men: B = 0.205, p < 0.001; women: B = 0.235, p < 0.001). Current every day smoking status (men and women), being uninsured (women only), and having children (women only) were also associated with lower PCH intentions. Conclusion Prescriptive gender stereotypes may play an important, yet slightly different, role in promoting PCH behavior among men and women.

Preconception care.

BACKGROUND: Preconception care (PCC) comprises counselling and the provision of biomedical, behavioural and social health interventions to optimise the health of women and their partners prior to pregnancy and improve health related outcomes for themselves and their children. OBJECTIVE: With a focus on women, the aim of this paper is to discuss the evidence for PCC, available guidelines and strategies to increase primary care access. DISCUSSION: Each year an estimated 10% of women in Australia become pregnant. There is increasing evidence that optimising health in the preconception period is crucial to improving short-term and long-term outcomes for mothers and babies. General practitioners can have a key role in assisting women to identify modifiable and non­modifiable preconception risks and to make informed decisions about planning or avoiding pregnancy. The Royal Australian College of General Practitioners Guidelines for preventive activities in general practice includes a chapter on preventive activities prior to pregnancy, which is a useful resource. The critical first step is screening women for their pregnancy intentions by asking a simple question that can help facilitate the start of the PCC conversation.

Carrier screening for single gene disorders.

Screening for genetic disorders began in 1963 with the initiation of newborn screening for phenylketonuria. Advances in molecular technology have made both newborn screening for newborns affected with serious disorders, and carrier screening of individuals at risk for offspring with genetic disorders, more complex and more widely available. Carrier screening today can be performed secondary to family history-based screening, ethnic-based screening, and expanded carrier screening (ECS). ECS is panel-based screening, which analyzes carrier status for hundreds of genetic disorders irrespective of patient race or ethnicity. In this article, we review the historical and current aspects of carrier screening for single gene disorders, including future research directions.

Futuristic Look at Genetic and Birth Defect Diagnoses and Treatments.

One aim of prenatal care is to provide information to prospective parents. The information provided encompasses prenatal care, intrapartum and postpartum care. Learning the genetic constitution of the parents pre-conception or the ongoing pregnancy allows parents to make decisions and set expectations. Offering screening and diagnostic testing has been the main in satisfying the desire for prenatal genetic information. With rapid advances in genomics and genome sequencing, screening during an ongoing pregnancy may become obsolete. Preconception risk will be determined by whole exome sequencing and chromosomal microarray of prospective parents and a number of approaches to alter pregnancy outcome can be considered when genome variations are identified. Therapeutic approaches include mitochondrial transfer and gene editing, two technologies that are in early stages, but showing promise as tools to alter outcomes.

Care of women with diabetes before, during and after pregnancy: time for a new approach?

AIMS: This study assesses the impact of pregnancy and pre-pregnancy care on longer-term treatment goals in women with diabetes. METHODS: This retrospective study included women with Type 1 (n = 247) and Type 2 diabetes (n = 137) who were evaluated before, during and after pregnancy. RESULTS: Among women with Type 1 diabetes, average HbA1c at 12 months post-partum was similar to the preconception level [63 vs. 64 mmol/mol (7.9% vs. 8.0%), P = 0.60]. This was also the case for women with Type 2 diabetes [52 vs. 52 mmol/mol (6.9% vs. 6.9%), P = 0.79]. At 12 months post-partum, there was no improvement in other measures of diabetes control and one in five women are lost to follow-up from clinical care. In total, 44.9% of women with Type 1 diabetes and 27.7% of those with Type 2 diabetes attended pre-pregnancy care. Attendees maintained superior glycaemic control throughout the study and were more likely to be receiving specialist care post-partum. CONCLUSIONS: These findings identify a need to change our approach to the reproductive care of women with diabetes. In particular, efforts should be made to ensure all women have access to and attend pre-pregnancy care, and barriers to engagement with post-partum care should be addressed.

Changes in preconception treatment and glycemic control in women with type 1 diabetes mellitus: a 15­year single­center follow­up.

INTRODUCTION    Pregnancy in women with type 1 diabetes mellitus (T1DM) is associated with higher risk of complications. Strict glycemic control before conception reduces the risk of unfavorable outcomes. OBJECTIVES    The aim of the study was to assess changes in clinical characteristics, preconception treatment, and glycemic control of women with T1DM at the first antinatal visit. PATIENTS AND METHODS    We analyzed the records from the first antenatal visit of 524 women with T1DM in the years 1998-2012. The follow­up period was divided into 3 5­year periods. RESULTS    Differences in the age of patients between the 3 follow­up periods were observed (28.2 ±5.7 years for 1998-2002; 27.3 ±4.5 years for 2003-2007; and 29.4 ±4.8 years for 2008-2012; P <0.0001). The number of women planning pregnancy did not change and reached 32.1% in the first, 44.4% in the second, and 40.4% in the third period (P = 0.2). The use of rapid­acting insulin analogues increased from 2.6% to 46.5% and then to 95.6% (P <0.001). The rate of therapy with personal insulin pumps before pregnancy increased from 4.6% in the first, through 23.5% in the second, to 33.3% in the third period (P <0.001). Over the subsequent periods, we observed a decrease in hemoglobin A1c (HbA1c) levels at the first antenatal visit (from 7.4% ±1.6%, through 6.9% ±1.4%, to 7.0% ±1.4%; P = 0.06), as well as a decrease in HbA1c levels between the subgroups of women planning pregnancy (6.8% ±1.4%, 6.6% ±1.2%, and 6.1% ±0.8%, P = 0.015). CONCLUSIONS    In the years 1998-2012, an increase in the use of insulin analogues and personal insulin pumps by women with T1DM before conception was observed, and these changes were accompanied by a slight improvement in glycemic control, particularly among women planning pregnancy. The percentage of women planning pregnancy did not change during the follow­up.