COVID-19 Vaccine Hesitancy in Rural Midwestern Infertility Patients: A Cross-Sectional Survey.

BACKGROUND: Pregnant patients with COVID-19 experience higher rates of maternal mortality, pregnancy loss, and other severe comorbidities. Despite these well-characterized risks, this group displayed a high level of vaccine hesitancy that contributed to their slow acceptance of the COVID-19 vaccinations and greater maternal mortality during the pandemic. The rural Midwest was no exception to this unfortunate trend, so here we sought to determine attitudes, beliefs, and perceptions in these women and their partners associated with vaccine hesitancy to better address uncertainties and improve vaccination rates. METHODS: We used a cross-sectional survey of rural Midwestern infertility patients. Study population included both women and men, ranging from 21 to 53 years old. We evaluated vaccination status, hesitancy or refusal for COVID-19 vaccination, sociodemographic factors, sources and types of medical information, employer vaccination requirements, and specific attitudes, beliefs, and perceptions towards vaccines using questions guided by the Health Belief Model. RESULTS: We surveyed 390 Midwestern patients with pre-existing clinic appointments who were being evaluated for infertility and/or trying to conceive. Vaccine-hesitant patients held significant concerns of rushed vaccine development, safety, and benefits not outweighing potential risks. Patients were significantly more likely to obtain the vaccine if it was recommended by their physician. They were also more likely to receive the vaccine if they were given written resources or if required by their employer. CONCLUSIONS: Survey results identified specific concerns and strategies that may be used to address vaccine hesitancy in this at-risk population. Addressing vaccine hesitancy may improve vaccination rates and in turn reduce maternal mortality and morbidity, particularly in rural populations.

Gestational Surrogacy and Ethical Considerations.

Gestational surrogacy provides patients with the ability to reproduce in the wake of medical contraindications to pregnancy or an inability to become pregnant. Outcomes of gestational surrogacy are overall positive and are quite similar to those of other assisted reproductive technologies. Gestational surrogacy presents several ethical considerations, including gestational carrier autonomy, procreative liberty, access to care, and cross-border surrogacy. Additionally, its legalities differ between states. Gestational surrogacy continues to be a topic that is worthy of consideration, legislation, and discussion.

Vitamin D levels and human sperm DNA fragmentation: a prospective, cohort study.

BACKGROUND: Intracytoplasmic sperm injection (ICSI) has revolutionized the treatment of couples with male factor infertility but results remain suboptimal and suggest the need for further investigation into the molecular biology of spermatozoa. Vitamin D has been implicated in spermatogenesis and sperm function. Hypovitaminosis D has been associated with abnormal testicular function, including elevated sperm DNA fragmentation in a murine model. This study's objective was to evaluate if there is a correlation between Vitamin D sufficiency and human spermatozoa DNA fragmentation index % (DFI%) in infertile couples. RESULTS: A prospective cohort study using a consecutive, convenience sample of subjects with infertility. The primary endpoint was the effect of Vitamin D sufficiency on human spermatozoa DFI%, and secondary outcomes included Vitamin D's effect on moderate DFI%, high DFI%, High DNA stainability % (HDS%), sperm density (million/mL), sperm total motility (% total) and sperm strict morphology (% total). Of the 111 participating, 9 were excluded, leaving 102subjects. The subjects were stratified by vitamin D levels: deficient (< 20 ng/mL; n = 24), insufficient (20-30 ng/mL; n = 43),, and sufficient (> 30 ng/mL; n = 35). There were no statistical difference between the categories of serum vitamin D levels and sperm DFI% as well as the secondary outcomes. An increased BMI was associated with low serum vitamin D levels (p = 0.0012). CONCLUSION: Vitamin D deficiency was not associated with sperm DFI% or routine sperm parameters. Previous animal and human studies have demonstrated conflicting results between sperm parameters and Vitamin D levels. Redundant pathways in Vitamin D and calcium homeostasis in the human male reproductive tract may maintain essential reproductive processes during Vitamin D insufficiency or deficiency. TRIAL REGISTRATION: Trial Registration Number: MOD00002311 (ClinicalTrials.gov).

RéSUMé: CONTEXTE: L'injection intracytoplasmique de spermatozoïdes (ICSI) a révolutionné le traitement des couples avec infertilité masculine, mais les résultats restent sous-optimaux et suggèrent la nécessité d'aller plus loin dans l'étude de la biologie moléculaire des spermatozoïdes. La vitamine D a été impliquée dans la spermatogenèse et les fonctions des spermatozoïdes. Dans un modèle murin, l'hypovitaminose D a été associée à une fonction testiculaire anormale, y compris une fragmentation élevée de l'ADN des spermatozoïdes. L'objectif de cette étude était d'évaluer s'il existait une corrélation entre un taux suffisant en vitamine D et l'indice de fragmentation de l'ADN (DFI) des spermatozoïdes humains chez les couples infertiles. RéSULTATS: Une étude de cohorte prospective utilisant un échantillon consécutif et approprié de sujets atteints d'infertilité. Le critère d'évaluation principal était l'effet d'un taux suffisant en vitamine D sur le DFI des spermatozoïdes humains; et les critères de jugement secondaires comprenaient l'effet de la vitamine D sur un DFI modéré, un DFI élevé, un taux élevé de coloration de l'ADN (HDS), le nombre des spermatozoïdes (millions/mL), la motilité totale des spermatozoïdes et sur la morphologie stricte des spermatozoïdes. Sur les 111 participants, 9 ont été exclus, laissant 102 sujets. Les sujets ont été stratifiés par niveau de vitamine D : déficient (<20 ng/mL ; n= 24), insuffisant (20-30 ng/mL ; n=43) et suffisant (>30 ng/mL ; n=35). Il n'y a eu aucune différence statistique entre les catégories de taux sériques de vitamine D et le pourcentage de DFI de spermatozoïdes ainsi qu'avec les critères de jugement secondaires. Une augmentation de l'indice de masse corporelle était associée à de faibles taux sériques de vitamine D (p = 0,0012). CONCLUSION: La carence en vitamine D n'est pas associée au pourcentage l'indice de fragmentation de l'ADN de spermatozoïdes ou aux paramètres de routine des spermatozoïdes. Des études antérieures chez les animaux et les humains ont montré des résultats contradictoires entre les paramètres des spermatozoïdes et les niveaux de vitamine D. Les voies redondantes dans l'homéostasie de la vitamine D et du calcium dans l'appareil reproducteur masculin humain peuvent maintenir les processus essentiels à la reproduction lors d'insuffisance ou de carence en vitamine D. MOTS-CLéS: Test de structure de la chromatine des spermatozoïdes, fragmentation de l'ADN des spermatozoïdes, vitamine D, infertilité masculine, hypovitaminose D.

Preimplantation Genetic Testing for Desired Pregnancy in Case of Parental Balanced Translocation.

There are two main types of chromosomal translocations known as reciprocal translocations and Robertsonian translocations. These chromosomal rearrangements are described as balanced when there is no significant loss of chromosomal material. Most carriers of balanced translocations are phenotypically normal and may not even know they are carriers of a balanced translocation. A parental balanced translocation may become apparent after having a child with congenital anomalies, during genetic testing, or while trying to conceive due to the increased risk of producing embryos with chromosomal imbalances. In vitro fertilization (IVF) in combination with preimplantation genetic testing (PGT) can potentially decrease the rate of miscarriages and increase the chance of a successful pregnancy. This is a case report of a 29-year-old female with a balanced translocation undergoing IVF with PGTstructural rearrangement (SR) and PGT-aneuploidy (A).

Worsening of Behcet Syndrome Symptoms During Pregnancy.

Behcet disease is a rare, chronic multisystem vasculitis of unknown etiology. It commonly causes oral and genital ulcers, eye lesions, and vascular lesions. There are limited published reports on this condition in pregnant patients and the data that does exist shows remission of the disease in most pregnant patients. Arterial and venous thrombotic events appear to be a major comorbidity in patients with Behcet disease. This is a case report of a 24-year-old pregnant woman who presented with worsening Behcet disease symptoms during her second pregnancy. Her first pregnancy was not affected by the disease. Worsening of symptoms must be considered in pregnant women with Behcet disease and treated promptly due to potential life-threatening consequences.

A Case of Uterine Arteriovenous Malformation Treated With Uterine Artery Embolization.

Uterine arteriovenous malformation (AVM) is a rare condition that is potentially life-threatening. There are limited published reports on this condition. This is a case report of a 25-year-old woman who presented with a symptomatic AVM. We review the differential diagnoses, evaluation, and treatment options. Conservative treatment with interventional radiology can be considered in select women who desire fertility preservation.

Endometriosis and Infertility.

Endometriosis is a disease that affects a significant portion of reproductive age women. It can cause chronic pelvic pain and has been associated with subfertility. Treatment options differ depending on a patient's reproductive goals; women who do not desire pregnancy are treated with hormonal medications including combined oral contraceptives, progestin only pills or intrauterine devices, gonadotropin releasing hormone agonists and antagonists, and danocrine. The treatment options for women desiring pregnancy are more limited and most often include surgery to improve pain symptoms and increase the chances of conception. However, the chance of a successful pregnancy does not increase with each concurrent endometriosis surgery, and in fact may merely delay fertility treatment using assisted reproductive technology.

Descriptive Study of Rubella Titer Status in Infertility Patients.

INTRODUCTION: There is a 6.4 percent incidence of rubella exposure during pregnancy in the U.S. Given the severe effects rubella can have on a developing fetus, vaccination of women prior to pregnancy is important. Women seeking fertility treatment therefore present a population of patients primed for the vaccination. This study collected and analyzed rubella-specific immunoglobulin G (RV-IgG) titer statuses and corresponding demographics of infertility patients to identify patients at risk of rubella nonimmunity. METHODS: The study consisted of a retrospective review of electronic medial records (EMR) of female patients, ages 18 to 50, who were new patients receiving an infertility workup at a Midwestern reproductive endocrinology clinic from Jan. 1, 2010 through Dec. 31, 2014. Of those patients who had RV-IgG titers noted in their EMR, the following demographics were collected: age, race, gravidity and parity, state of residence, and community size. RESULTS: There were 750 patients included in the study. Rubella titers were drawn on 72.7 percent of the patients. Of those drawn, 90.8 percent had a positive rubella titer. Most of the participants (92.3 percent) were identified as Caucasian/White. Caucasians/Whites, Asians, and African Americans/Blacks had the highest rates of rubella immunity, while American Indians/Alaskan Natives had the lowest rates of immunity (p=0.0006). Nulligravida participants had a positive rubella titer rate of 94.1 percent, while primigravida participants had a rate of 89.8 percent (p=0.04). Participants living in the largest sampled communities had the lowest rates of positive rubella titers, while those living in the smallest communities had the highest rates of positive rubella titers, although these findings were not statistically significant. CONCLUSIONS: Of the infertility patients, 27.3 percent did not have an RV-IgG titer drawn as part of their fertility workup. Of the 72.7 percent of patients for whom titers were checked, nearly 10 percent were not immune to rubella. While there are a couple reasons why a patient may not have a positive titer, lack of immunization is the most common reason. Data analysis identified significance in the difference in titer status only with respect to race and gravidity, and those findings, particularly race, must be viewed critically in light of the study population. While the statistical significance of the study may be limited, there is clinical significance in identifying infertility patients at highest risk of rubella nonimmunity so vaccination education and efforts can be focused accordingly.

Premature Thelarche and the PURA Syndrome.

BACKGROUND: Premature thelarche is a self-limited condition characterized by Tanner stage II-III breast development in girls younger than 8 years of age with no evidence of advancing puberty. Evaluation concentrates on excluding central or peripheral causes of precocious puberty. CASE: A girl aged 2 years 4 months with profound hypotonia and delayed developmental milestones presented with Tanner II breast development, elevated follicle-stimulating hormone levels, suppressed luteinizing hormone level, normal growth and skeletal development, and prepubertal uterine length and ovarian volume. Monitoring until 8 years of age revealed no pubertal progression. Whole exome sequencing at 8 years revealed an autosomal-dominant mutation in the purine-rich element-binding protein A (PURA) gene. Previous patients with PURA syndrome have had pituitary dysfunction and precocious puberty. CONCLUSION: Purine-rich element-binding protein A syndrome can be associated with premature thelarche.

Polycystic Ovarian Syndrome: A Primer.

Polycystic ovary syndrome (PCOS) affects 8-10 percent of reproductive-aged females, making it the most common state of endocrine dysfunction in women. Patients with PCOS are often treated for the signs and symptoms of the condition without consideration for the underlying syndrome, causing frustration for many affected patients. Abnormal uterine bleeding, endometrial hyperplasia and cancer, hirsutism and other skin changes, obesity, glucose intolerance, hypertension, and hyperlipidemia often accompany the syndrome, making it imperative to address these issues. The keys to diagnosis and treatment are understanding the diagnostic criteria of hyperandrogenism, ovulatory dysfunction, polycystic ovaries and the metabolic syndrome, while aiming treatment at controlling the symptoms and causes of the syndrome. In 2013, the Endocrine Society released its clinical guidelines, Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline. This gives clear diagnostic criteria, and treatment goals aimed at the etiology of the syndrome: to decrease hyperandrogenic symptoms, management of underlying metabolic abnormalities, prevention of endometrial hyperplasia and carcinoma, and improvement of ovulation.

Pregnancy of unknown location.

The development of highly sensitive and accurate human chorionic gonadotropin assays as well as the improvement of vaginal ultrasound have allowed for the early detection of pregnancy and have reduced the morbidity and mortality associated with ectopic gestations. One of the byproducts of this increased sensitivity is pregnancy of unknown location (PUL), a term which is used to describe pregnancy in a woman with a positive pregnancy test but no signs of intrauterine or extrauterine pregnancy. A PUL can include an early intrauterine pregnancy, a failing intrauterine/extrauterine pregnancy or ectopic pregnancy. Modern medical management has improved the diagnosis and treatment of early pregnancy and pregnancy loss. In the hemodynamically stable patient with PUL, expectant management has been shown to be safe and allows for confirmatory studies before proceeding with therapy.

A large network of interconnected signaling pathways in human ovarian follicles is supported by the gene expression activity of the granulosa cells.

Human follicular fluid (hFF), as an extra oocyte microenvironment, is essential to the biological processes of oocyte development. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 426 proteins as consistently present in hFF from different participants. According to our gene chip data, the granulosa cells in the follicle locally produce 235 of these proteins. These data suggest that the granulosa cells actively participate in the follicular development by synthesizing important molecules to support the activity of pathways that are essential to oocyte development and genomic preservation. The computational Ingenuity Pathway Analysis (IPA) suggests that the identified proteins have well-established functions in the pathways of steroidogenesis, cell-to-cell signaling and interaction, molecular transport, the antioxidative system, interleukin 1 (IL-1) and IL-6 signaling, liver X receptor/retinoid X receptor (LXR/RXR) activation, and the interconnective insulin-like growth factor and lipid metabolism networks. The hFF peptide composition is likely to serve not only the inflammatory follicular state as has been previously suggested; rather, it is a highly diverse and multifunctional environment with several interconnected pathways. These results provide us with important knowledge related to the environment in which the oocyte develops as well as the molecular basis for controlling the process independently of blood supply.

Age-related variations in follicular apolipoproteins may influence human oocyte maturation and fertility potential.

OBJECTIVE: To investigate involvement of specific apolipoproteins in the process of human oocyte maturation and age-related infertility as molecular constituents of follicular fluid. DESIGN: Laboratory-based observational study. SETTING: Basic science laboratory at a large academic institution. PATIENT(S): Follicular fluid obtained from healthy women aged 18 to 45 years undergoing in vitro fertilization for unexplained infertility, ovulatory dysfunction, tubal disease, male factor infertility, or oocyte donation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Specific concentration of apolipoproteins and content of lipoprotein particles in follicular fluid and blood plasma as related to reproductive aging. RESULT(S): We registered a decline of follicular apolipoprotein A1 (Apo A1) and apolipoprotein CII (Apo CII) and an increase of the apolipoprotein E (Apo E) with age, which parallels a lower number of retrieved mature oocytes in older women. Follicular apolipoprotein A1, apolipoprotein B (Apo B), apolipoprotein E, and apolipoprotein C II are present in diverse heterogeneous complexes including very-low-density lipoproteins (VLDL), intermediate-low-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) that vary with patient age and differ from the blood plasma lipoprotein complexes. CONCLUSION(S): Age-related variation in follicular apolipoprotein content and distribution in the cholesterol particles may be associated with the decrease in production of mature oocytes and the age-related decline in fertility potential.

Genes invoked in the ovarian transition to menopause.

Menopause and the associated declines in ovarian function are major health issues for women. Despite the widespread health impact of this process, the molecular mechanisms underlying the aging-specific decline in ovarian function are almost completely unknown. To provide the first gene-protein analysis of the ovarian transition to menopause, we have established and contrasted RNA gene expression profiles and protein localization and content patterns in healthy young and perimenopausal mouse ovaries. We report a clear distinction in specific mRNA and protein levels that are noted prior to molecular evidence of steroidogenic failure. In this model, ovarian reproductive aging displays similarities with chronic inflammation and increased sensitivity to environmental cues. Overall, our results indicate the presence of mouse climacteric genes that are likely to be major players in aging-dependent changes in ovarian function.

Headache during pregnancy.

Headache in pregnancy is a common problem but diagnosis and management can be challenging. Most headaches in pregnant women are either migraine or tension types and can be easily treated. Rarely, the headache in a pregnant patient signals a life-threatening condition. Obstetricians should be able to effectively manage the common causes of headache as well as recognize the warning signs of potentially serious conditions. Diagnosis and management should be systematic yet individualized.