Prevalence of Vitamin D Insufficiency and Its Determinants among Women Undergoing In Vitro Fertilization Treatment for Infertility in Sweden.

There is a lack of research on women with infertility in the northern latitudes, where vitamin D insufficiency is high. Therefore, this study aimed to assess the prevalence and determinants of vitamin D insufficiency (serum 25(OH)D concentration < 50 nmol/L) among women undergoing in vitro fertilization (IVF) treatment. Thus, 265 women scheduled for IVF/intracytoplasmic sperm injection (ICSI) between September 2020 and August 2021 at Sahlgrenska University Hospital in Gothenburg, Sweden, were included. Data on serum 25(OH)D concentration, vitamin D intake, and sun exposure were collected via questionnaires and blood samples. Approximately 27% of the women had 25(OH)D insufficiency, which was associated with longer infertility duration. The likelihood of insufficiency was higher among women from non-Nordic European countries (OR 2.92, 95% CI 1.03-8.26, adjusted p = 0.043), the Middle East (OR 9.90, 95% CI 3.32-29.41, adjusted p < 0.001), and Asia (OR 5.49, 95% CI 1.30-23.25, adjusted p = 0.020) than among women from Nordic countries. Women who did not use vitamin D supplements were more likely to have insufficiency compared with supplement users (OR 3.32, 95% CI 1.55-7.10, adjusted p = 0.002), and those who avoided sun exposure had higher odds of insufficiency compared to those who stayed "in the sun all the time" (OR 3.24, 95% CI 1.22-8.62, adjusted p = 0.018). Women with infertility in northern latitudes and those from non-Nordic countries who avoid sun exposure and do not take vitamin supplements have a higher prevalence of 25(OH)D insufficiency and longer infertility duration.

The effect of oral melatonin supplementation on MT-ATP6 gene expression and IVF outcomes in Iranian infertile couples: a nonrandomized controlled trial.

This study aims to evaluate the effect of melatonin supplementation on the outcomes of in vitro fertilization (IVF) and mitochondrial adenosine triphosphate production (MT-ATP6) gene expression in Iranian infertile couples. A single-blind nonrandomized controlled trial was conducted, recruiting 90 infertile couples who underwent IVF at an infertility center in Tehran, Iran. Patients who were assigned to the intervention group received melatonin as a supplementation to the standard controlled ovarian stimulation (COS). The control group received a COS protocol only. Primary outcome was the mRNA level of the MT-ATP6 gene in cumulus cells of ovarian follicles. Secondary outcomes were the mean number of mature oocytes retrieved, the embryo quality, and biochemical and clinical pregnancy rates. The mRNA level of the MT-ATP6 gene in cumulus cells between intervention and control groups was not statistically different (0.931 vs.1; P Ëƒ 0.05). The mean number of poor-quality embryos was significantly lower in the intervention group than that in the control group (0.27 vs. 0.80; P = 0.028). The biochemical and clinical pregnancy rates were higher in the intervention group (24% vs. 14%, P = 0.089, and 14% vs. 7%, P = 0.302, respectively); however, the difference was not significant. Melatonin supplementation did not increase the odds of clinical pregnancy and the number of mature oocytes retrieved, but significantly reduced the number of low-quality embryos. More extensive studies focusing on the level of MT-ATP6 gene expression in the oocyte or blastomere cells may further elucidate the effect of supplementation with melatonin in infertile couples who have poor clinical outcomes. Trial registration: Current Controlled Trials: IRCT2015042912307N4.

COVID-19 Pandemic and Infertility: Gynecological Dilemma from an Indian Perspective.

As the emaciated healthcare system is attempting to break the tide of the novel coronavirus pandemic across the globe, the highest cost of this fight is being borne by the third world countries. India is currently experiencing the peak incidence of COVID-19 cases. For the last 9 months, non-emergency services including OPDs have been suspended in majority of the hospitals to divert resources for combatting emergency medical care during this deadly pandemic. This temporary pause and containment could be detrimental to even patients suffering from malignancy. During this critical hour, commencement of infertility treatments including assisted reproductive technologies (ART) will add to additional burden upon the crippled medical fraternity. Fate of thousands of patients seems to hang by a fine thread now. In the resource-poor countries, it is our duty to divert maximum medical power to curtail this contagious pandemic rather than focusing on non-urgent treatment services.

Pre-Conception Interventions for Subfertile Couples Undergoing Assisted Reproductive Technology Treatment: Modeling Analysis.

BACKGROUND: Approximately 1 in 7 couples experience subfertility, many of whom have lifestyles that negatively affect fertility, such as poor nutrition, low physical activity, obesity, smoking, or alcohol consumption. Reducing lifestyle risk factors prior to pregnancy or assisted reproductive technology treatment contributes to the improvement of reproductive health, but cost-implications are unknown. OBJECTIVE: The goal of this study was to evaluate reproductive, maternal pregnancy, and birth outcomes, as well as the costs of pre-conception lifestyle intervention programs in subfertile couples and obese women undergoing assisted reproductive technology. METHODS: Using a hypothetical model based on quantitative parameters from published literature and expert opinion, we evaluated the following lifestyle intervention programs: (1) Smarter Pregnancy, an online tool; (2) LIFEstyle, which provides outpatient support for obese women; (3) concurrent use of both Smarter Pregnancy and LIFEstyle for obese women; (4) smoking cessation in men; and (5) a mindfulness mental health support program using group therapy sessions. The model population was based on data from the Netherlands. RESULTS: All model-based analyses of the lifestyle interventions showed a reduction in the number of in vitro fertilization, intracytoplasmic sperm injection, or intrauterine insemination treatments required to achieve pregnancy and successful birth for couples in the Netherlands. Smarter Pregnancy was modeled to have the largest increase in spontaneous pregnancy rate (13.0%) and the largest absolute reduction in potential assisted reproductive technology treatments. Among obese subfertile women, LIFEstyle was modeled to show a reduction in the occurrence of gestational diabetes, maternal hypertensive pregnancy complications, and preterm births by 4.4%, 3.8%, and 3.0%, respectively, per couple. Modeled cost savings per couple per year were €41 (US $48.66), €360 (US $427.23), €513 (US $608.80), €586 (US $695.43), and €1163 (US $1380.18) for smoking cessation, mindfulness, Smarter Pregnancy, combined Smarter Pregnancy AND LIFEstyle, and LIFEstyle interventions, respectively. CONCLUSIONS: Although we modeled the potential impact on reproductive outcomes and costs of fertility treatment rather than collecting real-world data, our model suggests that of the lifestyle interventions for encouraging healthier behaviors, all are likely to be cost effective and appear to have positive effects on reproductive, maternal pregnancy, and birth outcomes. Further real-world data are required to determine the cost-effectiveness of pre-conception lifestyle interventions, including mobile apps and web-based tools that help improve lifestyle, and their effects on reproductive health. We believe that further implementation of the lifestyle app Smarter Pregnancy designed for subfertile couples seeking assistance to become pregnant is likely to be cost-effective and would allow reproductive health outcomes to be collected.

First effective mHealth nutrition and lifestyle coaching program for subfertile couples undergoing in vitro fertilization treatment: a single-blinded multicenter randomized controlled trial.

OBJECTIVE: To study compliance and effectiveness of the mHealth nutrition and lifestyle coaching program Smarter Pregnancy in couples undergoing in vitro fertilization (IVF) treatment with or without intracytoplasmic sperm injection (ICSI). DESIGN: Multicenter, single-blinded, randomized controlled trial, conducted from July 2014 to March 2017. SETTING: IVF clinics. PATIENT(S): A total of 626 women undergoing IVF treatment with or without ICSI and 222 male partners. INTERVENTIONS(S): Couples were randomly assigned to the light (control group) or regular (intervention group) Smarter Pregnancy program. Both groups filled out a baseline screening questionnaire on nutrition and lifestyle behaviors, and the intervention group received coaching tailored to inadequate behaviors during the 24-week period. MAIN OUTCOME MEASURE(S): Difference in improvement of a composite dietary and lifestyle risk score for the intake of vegetables, fruits, folic acid supplements, smoking, and alcohol use after 24 weeks of the program. RESULT(S): Compared with control subjects, women and men in the intervention group showed a significantly larger improvement of inadequate nutrition behaviors after 24 weeks of coaching. At the same time, the women also showed a significantly larger improvement of inadequate lifestyle behaviors. CONCLUSION(S): The mHealth coaching program Smarter Pregnancy is effective and improves the most important nutritional and lifestyle behaviors among couples undergoing IVF/ICSI treatment. International multicenter randomized trials are recommended to study the effect of using Smarter Pregnancy on pregnancy, live birth, and neonatal outcome. NETHERLANDS TRIAL REGISTER NUMBER: NTR4150.

The Partnership and Coping Enhancement Programme for couples undergoing in vitro fertilization treatment: the development of a complex intervention in China.

PURPOSE: Couples as dyads suffer from the diagnosis of infertility and related treatment. These couples commonly experience emotional and physical pain and tension in their marital lives. The purpose of this study is to report on the process of developing a potentially feasible and effective complex intervention for couples undergoing in vitro fertilization treatment in China. METHODS: The Medical Research Council (MRC) framework for developing and evaluating the complex intervention was adopted to guide the development of the Partnership and Coping Enhancement Programme (PCEP). In developing the PCEP, three steps were taken, namely, (1) identifying evidence by conducting literature reviews, a concept analysis and a qualitative study; (2) identifying/developing a theory-in this case, a preliminary Endurance with Partnership Conceptual Framework (P-EPCF) was proposed; and (3) modelling the process and outcomes of the PCEP. RESULTS: The PCEP that was developed is targeted mainly at the domains of the partnership mediators of stress in the P-EPCF. It consists of two sections-partnership and coping-and will be delivered to infertile couples on the day of embryo transfer. The main focuses of the programme are to facilitate mutual sharing and support in infertile couples, and to improve their individual and dyadic coping strategies while undergoing IVF treatment, especially in the period when they are waiting for the results of a pregnancy test and after the disclosure of a negative treatment outcome. The programme is couple-based, consisting of experience sharing, psychoeducation, meditation exercise, skill practise and supplemental written materials. CONCLUSIONS: The Partnership and Coping Enhancement Programme (PCEP) for couples undergoing in vitro fertilization treatment was developed according to the guideline of the MRC framework. It is recommended that a pilot study be conducted to evaluate its feasibility and to model the process and outcomes of the programme.

Vitamin D in Reproductive Health and Pregnancy.

Vitamin D has been primarily known for its role in maintaining calcium and phosphorus homeostasis and promoting healthy bone mineralization. Emerging evidence suggests that vitamin D may have a plethora of other functions including cardiometabolic and immunological effects and a role in modulating human reproductive processes. Despite this, vitamin D deficiency (VDD) remains highly prevalent worldwide due to the limited availability of foods that are naturally high or fortified with vitamin D, increased sun avoidance behaviors and use of sunscreen due to fear of skin cancer, and increased sedentary indoor lifestyles, especially among those of reproductive age. This review examines current and emerging evidence for the role of vitamin D in reproductive health including in fertility, conception, and pregnancy outcomes, and outlines areas for future research. We found that existing evidence is based primarily on animal models and in vitro studies with some recent support from observational studies in humans. While these studies indicate that VDD may be a risk factor for adverse fertility and pregnancy outcomes, there is insufficient evidence to establish causality. Future efforts to clarify the benefits of vitamin D in reproductive health may bring about practical, simple, and cost-effective means of improving fertility and pregnancy outcomes.

The Assessment of Diet Quality and Its Effects on Health Outcomes Pre-pregnancy and during Pregnancy.

Overweight and obesity pre pregnancy or during pregnancy is associated with an increased risk for maternal obstetric and fetal complications. Diet is one modifiable risk factor that women may be motivated to improve. General healthy eating guidelines, micronutrient sufficiency and macronutrient quantity and quality are important nutrition considerations pre and during pregnancy. With regards to specific nutrients, health authorities have recommendations for folate and/or iodine supplementation; but not consistently for iron and omega-3 despite evidence for their association with health outcomes. There are modest additional requirements for energy and protein, but not fat or carbohydrate, in mid-late pregnancy. Diet indices and dietary pattern analysis are additional tools or methodologies used to assess diet quality. These tools have been used to determine dietary intakes and patterns and their association with pregnancy complications and birth outcomes pre or during pregnancy. Women who may unnecessarily resist foods due to fear of food contamination from listeriosis and methylmercury may limit their diet quality and a balanced approached is required. Dietary intake may also vary according to certain population characteristics. Additional support for women who are younger, less educated, overweight and obese, from socially disadvantaged areas, smokers and those who unnecessarily avoid healthy foods, is required to achieve a higher quality diet and optimal lifestyle peri conception.

Complementary Therapies and Medicines and Reproductive Medicine.

Complementary therapies and medicines are a broad and diverse range of treatments, and are frequently used by women and their partners during the preconception period to assist with infertility, and to address pregnancy-related conditions. Despite frequent use, the evidence examining the efficacy, effectiveness, and safety for many modalities is lacking, with variable study quality. In this article, we provide an overview of research evidence with the aim of examining the evidence to inform clinical practice. During the preconception period, there is mixed evidence for acupuncture to improve ovulation, or increase pregnancy rates. Acupuncture may improve sperm quality, but there is insufficient evidence to determine whether this results in improved pregnancy and live birth rates. Acupuncture can be described as a low-risk intervention. Chinese and Western herbal medicines may increase pregnancy rates; however, study quality is low. The evaluation of efficacy, effectiveness, and safety during the first trimester of pregnancy has most commonly reported on herbs, supplements, and practices such as acupuncture. There is high-quality evidence reporting the benefits of herbal medicines and acupuncture to treat nausea in pregnancy. The benefit from ginger to manage symptoms of nausea in early pregnancy is incorporated in national clinical guidelines, and vitamin B6 is recommended as a first-line treatment for nausea and vomiting in pregnancy. The safety of ginger and vitamin B6 is considered to be well established, and is based on epidemiological studies. Acupuncture has been shown to reduce back pain and improve function for women in early pregnancy. There is little evidence to support the use of cranberries in pregnancy for prevention of urinary tract infections, and chiropractic treatment for back pain. Overall the numbers of studies are small and of low quality, although the modalities appear to be low risk of harm.

Factores relacionados con el incremento de la infertilidad / Factors associated with an increase in infertility

OBJETIVOS: conocer los factores relacionados con el incremento de la infertilidad, así como las causas y criterios de derivación delas parejas estériles y revisar el proceso de las diferentes alternativas terapéuticas que se pueden proponer fruto de las nuevas tecnologías. MÉTODO: revisión narrativa en la que se realiza una búsqueda bibliográfica en las bases de datos Cochrane, Medline y Cuiden y consulta en páginas de sociedades científicas. El criterio de selección se limitó a artículos originales y revisiones en los últimos 15años, con texto disponible en abstracto a texto completo, en español y en inglés. RESULTADOS Y CONCLUSIONES: se recuperaron un total 56 referencias, de las cuales se seleccionaron 19. Del análisis de los 19artículos y documentos seleccionados se generaron tres categorías principales: factores relacionados con la infertilidad, causas de infertilidad y tratamientos de la misma. El retraso del deseo reproductivo y el estilo de vida explican un posible incremento delos problemas de infertilidad, siendo la causa única o múltiple. Para su tratamiento, la elección de una técnica u otra (inseminación artificial, fecundación in vitro y donación de ovocitos) varía en función de la etiología de la esterilidad. En España se estima que casi un 15% de las parejas tienen problemas de esterilidad. La velocidad a la que evolucionan las técnicas de reproducción humana asistida y los tratamientos de infertilidad ponen en relieve la necesidad de formación constante de los profesionales relacionados con la reproducción

OBJECTIVES: to understand those factors associated with an increase in infertility, as well as the causes and referral criteria for infertile couples and to review the process of different therapeutic alternatives which can be offered, as a result of new technologies. METHOD: narrative review involving a bibliographic research in the Cochrane, Medline and Cuiden databases, and a search in webpages by scientific societies. The selection criteria was limited to original articles and reviews within the past 15 years, with text available as abstract or full text, in Spanish and in English. RESULTS AND CONCLUSIONS: in total, 56 references were collected,and 19 of these were selected. From the analysis of these selected19 articles and documents, three main categories were generated: factors associated with infertility, causes of infertility, and treatments for this condition. The delay of the reproductive desire, as well as lifestyle, can explain a possible increase in infertility problems, which may have a single cause, or multiple causes. For treatment, the selection of a technique over another (artificial insemination, in vitro fecundation, and ovocyte donation) varies according to the etiology of sterility. It is estimated that almost15% of couples in Spain have sterility problems. The fast rate of evolution of assisted human reproduction and infertility treatments highlight the need for constant training targeting those professionals associated with reproduction

[Long term follow-up after chilhood cancer]. / Malgré la guérison, un risque accru de problèmes de santé â l'âge adulte. Suivi à long terme après un cancer chez l'enfant.

Five year survival rates among childhood cancer rose to 80%. Relapses are rare after five years of remission. Long term follow-up should also detect treatment related late adverse effects. Repeated cardiac evaluations are necessary, due to cumulative dose dependent cardiotoxicity of anthracycline. Endocrinological disorders and problems of fertility are mainly related to radiotherapy or high dose chemotherapy. Bone mineral density can be altered. Cognitive function, academic level and social outcome of irradiated patients and patients treated for cerebral tumors should be closely assessed and helped. Second neoplasms related to previous treatments may occur. One of the major on going treatment objective is to preserve the quality of life of cured patients, and to improve their information in the framework of a shared-care model involving the general practionner, the adult medicine specialists and the oncologic pediatric centre.

Psychotherapeutic intervention with hypnosis in 554 couples with reproductive failure.

The objective of this study was to establish the efficacy of psychotherapeutic intervention including hypnotherapy in couples with "unexplained" reproductive failure. The study was based on a prospective clinical model set at a Trust Hospital. The couples with reproductive failure reported for treatment. Over a period of 28 years, 554 couples without any anatomical or physiological anomaly were studied. Psychotherapeutic intervention with indirect and direct hypnosis was added to the standard protocol for investigation and therapy of infertile couples. Several stressors were identified. Stress of barrenness was seen in 100% of women. Other stressors of marital life were identified. Hypnotherapy was targeted at general stress relief initially and, towards the specific stressor/s subsequently. The results were judged as success in terms of occurrence of pregnancy. The success rate was 71.67%. There could not have been a double blind study. However, 349/554 came after failing elsewhere. They had the same success rate ie, 70%. A persistent, unprecedented high success rate establishes that "unexplained" reproductive failure is psychodynamically triggered, is reversible with psychotherapy that includes hypnosis. The study explains causation in terms of psychosomatic stress. When that is alleviated with hypnotherapy, there are remarkable results.

Lifestyle behaviors in women undergoing in vitro fertilization: a prospective study.

OBJECTIVE: To determine the lifestyle behaviors of women before and during an IVF cycle. DESIGN: Prospective survey. SETTING: Private academically affiliated infertility center. PATIENT(S): One hundred eighteen women, ages 18-44, scheduled to undergo an assisted reproductive technology (ART) cycle using their own eggs. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Lifestyle history and daily habit survey. RESULT(S): In the month before their IVF cycle, 92% exercised, 3% smoked, 73% drank alcohol, 76% drank caffeinated beverages, 14% took herbs, and 30% underwent acupuncture. During their ART cycle, 100% exercised, 2% smoked, 49% drank alcohol, 77% drank caffeine, 12% took herbs, and 47% underwent acupuncture. CONCLUSION(S): This is the first prospective assessment of numerous lifestyle habits during an ART cycle. A number of surprising observations were made. Despite physician recommendation against it, some ART patients took herbs while cycling. Patients continue to exercise regularly and drink caffeine daily, and almost half continued to drink alcohol. Lifestyle behavior counseling should be considered for patients pursuing ART. CLINICAL TRIAL REGISTRATION NUMBER: NCT01119391.

Pretreatment serum anti-müllerian hormone predicts long-term ovarian function and bone mass after chemotherapy for early breast cancer.

CONTEXT: Administration of chemotherapy to premenopausal women shortens their reproductive lifespan by depleting nonrenewable oocytes. Preservation of fertility is a priority for many such women, and identification of women at risk of infertility is therefore important. However, age is the only patient characteristic currently recognized to be predictive of long-term ovarian function after chemotherapy. OBJECTIVE: Our objective was to assess markers of ovarian reserve and age as long-term predictors of ovarian function after chemotherapy. DESIGN AND SETTING: We conducted a prospective, longitudinal study at a university hospital and research institute. PATIENTS: Patients included women who were premenopausal at the time of diagnosis of early breast cancer. MAIN OUTCOME MEASURES: Ovarian function was assessed at 5 yr follow-up in relation to pretreatment hormonal and ultrasound markers of ovarian reserve. RESULTS: Forty-two women received (neo-)adjuvant chemotherapy. Continuing menses 4-5 yr after diagnosis closely reflected ovarian activity as assessed by a range of serum markers, including estradiol, inhibin B, FSH, and anti-müllerian hormone (AMH). Pretreatment serum AMH, FSH, antral follicle count, and age predicted late ovarian activity by univariate analysis. However, only AMH was predictive in a multivariate logistic regression (odds ratio = 13.0; 95% confidence interval = 2.5-66.7); 0.71 ng/ml gave peak likelihood ratio of 7.0 with 54% sensitivity and 92% specificity. Bone mineral density fell over the 4-5 yr after diagnosis with greater loss in women with lower ovarian activity. Higher pretreatment AMH was associated with lower bone mineral density at both lumbar spine and hip at 5 yr (P < 0.02). CONCLUSION: Measurement of AMH at cancer diagnosis predicts long-term ovarian function after chemotherapy. Use of this in clinical practice may allow better prediction of chemotherapy-related risk to future fertility.

The effect of medical clowning on pregnancy rates after in vitro fertilization and embryo transfer.

This experimental prospective quasi-randomized study examining the impact of a medical clowning encounter after embryo transfer (ET) after in vitro fertilization (IVF) found that the pregnancy rate in the intervention group was 36.4%, compared with 20.2% in the control group (adjusted odds ratio, 2.67; 95% confidence interval, 1.36-5.24). Medical clowning as an adjunct to IVF-ET may have a beneficial effect on pregnancy rates and deserves further investigation.

The use of complementary and alternative fertility treatment in couples seeking fertility care: data from a prospective cohort in the United States.

OBJECTIVE: To determine the prevalence of complementary and alternative medicine (CAM) use among couples seeking fertility care and to identify the predictors of CAM use in this population. DESIGN: Prospective cohort study. SETTING: Eight community and academic infertility practices. PATIENT(S): A total of 428 couples presenting for an infertility evaluation. INTERVENTION(S): Interviews and questionnaires. MAIN OUTCOME MEASURE(S): Prevalence of complementary and alternative medicine therapy. RESULT(S): After 18 months of observation, 29% of the couples had utilized a CAM modality for treatment of infertility; 22% had tried acupuncture, 17% herbal therapy, 5% a form of body work, and 1% meditation. An annual household income of > or = $200,000 (odds ratio 2.8, relative to couples earning <$100,000), not achieving a pregnancy (odds ratio 2.3), and a positive attitude toward CAM use at baseline were independently associated with CAM use. CONCLUSION(S): A substantial minority of infertile couples use CAM treatments. CAM was chosen most commonly by wealthier couples, those not achieving a pregnancy, and those with a baseline belief in the effectiveness of CAM treatments.

When do involuntarily infertile couples choose to seek medical help?

OBJECTIVE: To estimate the probability of medical consultation for infertility during the course of a pregnancy attempt and to study its determinants. DESIGN: Pregnancy-based retrospective telephone survey analyzed with a discrete time Cox model. SETTING: Two rural counties in Brittany and Normandy, France. PATIENT(S): A random sample of 901 women from the general population aged 18-60 years reporting 1,460 pregnancy attempts resulting in a live birth between 1985 and 2000 (participation rate, 73%). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Probability of medical consultation for involuntary infertility cumulated over time. RESULT(S): The cumulative probability of medical consultation for involuntary infertility among nulligravid women was 45% after 12 months of involuntary infertility and 75% after 24 months. The probability of medical consultation at any time was half that for parous women (odds ratio 0.4, 95% confidence interval 0.2-0.6). More highly educated women were more likely to have sought medical help for infertility. Only 45% of women who had sought medical advice received infertility treatment. CONCLUSION(S): Our survival approach provides a description of infertility service use during the course of a pregnancy attempt, and confirms that parity and educational level are strong predictors of medical help-seeking behaviors.

Syndromes, disorders and maternal risk factors associated with neural tube defects (IV).

Fetuses with neural tube defects (NTDs) may be associated with maternal and fetal risk factors. This article provides a comprehensive review of maternal and fetal risk factors associated with NTDs, such as infertility, periconceptional clomiphene use and assisted reproductive technology, periconceptional folic acid deficiency and effects of folic acid supplementation and fortification on NTD rates, periconceptional vitamin B12 deficiency, single nucleotide polymorphisms and polymorphisms in genes of folate metabolism, and maternal autoantibodies to folate receptors. NTDs associated with maternal and fetal risk factors are an important cause of NTDs. Perinatal identification of NTDs should alert the clinician to the maternal and fetal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.