Male contraception: narrative review of ongoing research.

BACKGROUND: Since the release of the combined oral contraceptive pill in 1960, women have shouldered the burden of contraception and family planning. Over 60 years later, this is still the case as the only practical, effective contraceptive options available to men are condoms and vasectomy. However, there are now a variety of promising hormonal and non-hormonal male contraceptive options being studied. The purpose of this narrative review is to provide clinicians and laypeople with focused, up-to-date descriptions of novel strategies and targets for male contraception. We include a cautiously optimistic discussion of benefits and potential drawbacks, highlighting several methods in preclinical and clinical stages of development. RESULTS: As of June 2023, two hormonal male contraceptive methods are undergoing phase II clinical trials for safety and efficacy. A large-scale, international phase IIb trial investigating efficacy of transdermal segesterone acetate (Nestorone) plus testosterone gel has enrolled over 460 couples with completion estimated for late 2024. A second hormonal method, dimethandrolone undecanoate, is in two clinical trials focusing on safety, pharmacodynamics, suppression of spermatogenesis and hormones; the first of these two is estimated for completion in December 2024. There are also several non-hormonal methods with strong potential in preclinical stages of development. CONCLUSIONS: There exist several hurdles to novel male contraception. Therapeutic development takes decades of time, meticulous work, and financial investment, but with so many strong candidates it is our hope that there will soon be several safe, effective, and reversible contraceptive options available to male patients.

RéSUMé: CONTEXTE: Depuis la sortie de la pilule contraceptive orale combinée en 1960, les femmes ont assumé le fardeau de la contraception et de la planification familiale. Plus de 60 ans plus tard, c'est toujours le cas, car les seules options contraceptives pratiques et efficaces disponibles pour les hommes sont les préservatifs et la vasectomie. Cependant, il existe maintenant une variété d'options contraceptives masculines hormonales et non hormonales prometteuses qui sont à l'étude. Le but de cette revue narrative est de fournir aux cliniciens et aux profanes des descriptions ciblées et à jour de nouvelles stratégies et cibles pour la contraception masculine. Nous incluons une discussion prudemment optimiste sur les avantages et les inconvénients potentiels, en soulignant plusieurs méthodes aux stades précliniques et cliniques du développement. RéSULTATS: En juin 2023, deux méthodes contraceptives masculines hormonales faisaient l'objet d'essais cliniques de phase II pour leur innocuité et leur efficacité. Un essai international de phase IIb à grande échelle, portant sur l'efficacité de l'acétate de ségestérone transdermique (Nestorone) et du gel de testostérone, a recruté plus de 460 couples et devrait être achevé pour la fin de 2024. Une seconde méthode hormonale, l'undécanoate de diméthandrolone, fait l'objet de deux essais cliniques axés sur l'innocuité, la pharmacodynamique, la suppression de la spermatogenèse et des hormones; le premier de ces deux essais devrait être achevé en décembre 2024. Il existe également plusieurs méthodes non hormonales à fort potentiel aux stades précliniques de développement. CONCLUSIONS: Il existe plusieurs obstacles à la nouvelle contraception masculine. Le développement thérapeutique nécessite des décennies de temps, un travail méticuleux et un investissement financier ; mais avec autant de candidats solides, nous espérons qu'il y aura bientôt plusieurs options contraceptives sûres, efficaces et réversibles, disponibles pour les hommes.

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.

Effects of alcohol use on sperm chromatin structure, a retrospective analysis.

BACKGROUND: The evaluation of the infertile couple is often complex as multiple factors in both the male and female can contribute, including social history. Previous studies have displayed that male ethanol consumption can disturb sperm motility, nuclear maturity, and deoxyribonucleic acid (DNA) integrity. The main purpose of this study is to evaluate the effects of male alcohol use on sperm chromatin structure analysis (SCSA®). This study was a retrospective chart review of 209 couples that presented to a midsize infertility clinic in the Midwest and had a semen analysis and SCSA® performed. Data extracted from the electronic medical record included demographics, tobacco use, alcohol use, occupational exposures, semen analysis results, and SCSA® results (DNA Fragmentation index (DFI) and High DNA stainability (HDS)). Statistical analysis was performed on this data set to determine significance with a p-level of 0.05, with the primary input being level of alcohol use and primary outcome being the SCSA® parameters. RESULTS: Overall, 11% of the cohort had heavy alcohol use (> 10 drinks/week), 27% moderate (3-10/week), 34% rare (0.5- < 3/week), and 28% none. 36% of the cohort had HDS > 10% (a marker of immature sperm chromatin). Level of alcohol use was not significantly associated with HDS > 10% or DFI. Heavier alcohol use was significantly associated with lower sperm count (p = 0.042). Increasing age was significantly associated with increasing DNA Fragmentation Index (p = 0.006), increased sperm count (p = 0.002), and lower semen volume (p = 0.022). Exposure to heat at work was significantly associated with lower semen volume (p = 0.042). Tobacco use was associated with lower sperm motility (p < 0.0001) and lower sperm count (p = 0.002). CONCLUSIONS: There was not a significant association between the level of alcohol use and the High DNA Stainability or DNA Fragmentation Index of sperm. Increasing age was associated with semen parameters as expected, heat exposure was associated with lower semen volume, and tobacco use was associated with lower sperm motility and density. Further studies could investigate alcohol use and reactive oxidative species in sperm.

RéSUMé: CONTEXTE: L'évaluation du couple infertile est souvent complexe car de multiples facteurs chez l'homme et la femme peuvent y contribuer, y compris l'histoire sociale. Des études antérieures ont montré que la consommation masculine d'éthanol pouvait altérer la mobilité des spermatozoïdes, la maturité nucléaire et l'intégrité de l'acide désoxyribonucléique (ADN). L'objectif principal de cette étude était d'évaluer les effets de la consommation d'alcool chez les hommes sur l'analyse de la structure de la chromatine des spermatozoïdes (SCSA®). Cette étude consistait en un examen rétrospectif des dossiers de 209 couples qui se sont présentés à une clinique d'infertilité de taille moyenne dans le Midwest et ont subi une analyse du sperme et un SCSA®. Les données extraites du dossier médical électronique comprenaient les données démographiques, le tabagisme, la consommation d'alcool, les expositions professionnelles, les résultats de l'analyse du sperme et les résultats du SCSA® (DFI et HDS). L'analyse statistique effectuée sur cet ensemble de données, pour déterminer la signification avec un niveau p de 0,05, a utilisé comme intrant principal le niveau de consommation d'alcool, le critère de jugement principal étant les paramètres du SCSA®. RéSULTATS: Dans l'ensemble, 11% de la cohorte avait une forte consommation d'alcool (> 10 verres / semaine), 27% modérée (3­10/semaine), 34% rare (0,5 à < 3/semaine) et 28% aucune. 36% de la cohorte avait HDS > 10%. Le niveau de consommation d'alcool n'était pas significativement associé à un HDS > 10% ou au DFI. Une consommation d'alcool plus importante était significativement associée à une diminution du nombre de spermatozoïdes (p = 0,042). L'augmentation de l'âge était significativement associée à une augmentation de l'indice de fragmentation de l'ADN (p = 0,006), à une augmentation du nombre de spermatozoïdes (p = 0,002) et à une diminution du volume séminal (p = 0,022). L'exposition à la chaleur au travail était significativement associée à un volume séminal plus faible (p = 0,042). La consommation de tabac était associée à une mobilité plus faible des spermatozoïdes (p < 0,0001) et à une numération plus faible des spermatozoïdes (p = 0,002). CONCLUSIONS: Il n'y avait pas d'association significative entre le niveau de consommation d'alcool et la stabilité élevée de l'ADN ou l'indice de fragmentation de l'ADN des spermatozoïdes. L'augmentation de l'âge était associée aux paramètres du sperme comme attendu, l'exposition à la chaleur à un volume de sperme plus faible, et la consommation de tabac à une mobilité et une numération plus faibles des spermatozoïdes. Des études à venir pourraient explorer les relations entre consommation d'alcool et espèces oxydatives réactives dans le sperme.

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.

The Female Athlete Triad - What it is and Why it is Important in Primary Care.

The female athlete triad (FAT) is a disorder involving greater energy expenditure than energy consumption leading to 1) low energy availability (EA) with or without disordered eating 2) menstrual irregularities or amenorrhea and 3) low bone mineral density. Consequences of FAT include osteoporosis, stress fractures, increased cardiovascular risk, infertility, and negative psychological effects. The key risk factor for FAT is inadequate caloric intake when compared to the amount and intensity of exercise. All female athletes should be screened at least annually at pre-participation physicals or with signs of disordered eating, weight loss, abnormal growth or development, menstrual dysfunction, recent injuries, decreased athletic performance, or mood changes. Presence of one of the components of the triad necessitates further investigation. Treatment involves a multidisciplinary approach with increased energy intake and decreased exercise intensity being the primary goal of treatment. Understanding FAT is important for preventative medicine, as some consequences, such as infertility and loss of bone mineral density may not be reversible.

Menstrual Migraines: Diagnosis, Evidence, and Treatment.

"Menstrual" or "catamenial" migraine (MM) is separated into two categories in the International Classification of Headache Disorders pure menstrual migraine and menstrually-related migraine. Pure menstrual migraine is defined as a migraine occurring exclusively on day 1 ± 2 of menstruation in at least two out of three menstrual cycles and at no other time in the cycle. Menstrually-related migraine is defined as the same but may occur at other times in the menstrual cycle, not just around menstruation. The withdrawal of estrogen has been correlated with the onset of MM, providing an opportunity for specific treatment with hormone therapies. Traditionally, MM has been treated with nonspecific treatments such as abortive and prophylactic non-steroidal anti-inflammatory drugs and triptans. While this is first line, evidence suggests that nonspecific treatments can be used in combination with specific hormone treatments. The hormone treatment recommended is either continuous combined hormonal contraceptives (CHCs) with no placebo pills or using just two days of placebo pills to avoid the estrogen withdrawal trigger. Although MM with aura is uncommon, when referring to using CHCs for MM with aura, the U.S. Medical Eligibility Criteria for Contraceptive Use 2016 categorizes MM with aura as "A condition that represents an unacceptable health risk if the contraceptive method is used." Therefore, the current recommendation is not to use CHCs with a history of menstrual migraine with aura, especially when other risk factors such as smoking are present. Other treatments such as GnRH agonists, selective estrogen receptor modulators, and bilateral oophorectomy have limited evidence.

Complementary and Alternative Treatments for Postpartum Depression.

Complementary and alternative treatments are commonly requested as treatment options for depression. This article provides a review of evidence for complementary and alternative therapies (doula support, saffron, yoga, aromatherapy, placentophagy, mindfulness, probiotics and wake therapy) in the treatment of postpartum depression. The included studies, mainly randomized control trials, focus on the efficacy of these interventions as compared to standard pharmacotherapy and or no treatment.

What Is New in Ovulation Induction?: Best Articles From the Past Year.

This month we focus on current research in ovulation induction. Dr. Hansen discusses five recent publications, which are concluded with a "bottom-line" that is the take-home message. A complete reference for each can be found on on this page along with direct links to abstracts.

Symptomatic Clitoromegaly: Case Report of a Clitoral Hemangioma.

BACKGROUND: Clitoromegaly is often a sign of an underlying disorder of sexual development. Isolated clitoromegaly might occur as a result of benign or malignant neoplasm. CASE: A 10-year-old girl presented with clitoral swelling and discomfort and was noted to have a 5 × 2 × 2 cm, tender, cystic mass in the left periclitoral area. Ultrasound confirmed the primarily cystic nature of the lesion. At surgery the mass was carefully excised not damaging the clitoral neurovascular bundle. Pathology showed a hemangioma. SUMMARY AND CONCLUSION: Differentiating between potential etiologies of clitoromegaly requires a careful history, physical examination, select hormone levels determination, imaging, and pathology, which allows for appropriate management. In this case the pain, tenderness, disfigurement, and imaging showing a cystic mass resulted in surgical removal of the mass.

What Is New in Recurrent Miscarriage?: Best Articles From the Past Year.

This month we focus on current research in recurrent miscarriage. Dr. Hansen discusses five recent publications, which are concluded with a "bottom line" that is a take-home message. A complete reference for each can be found on on this page along with direct links to abstracts.

So You Want To Be A Reviewer.

Peer review is a process for evaluating the quality of "work" of a scientist or professional as judged by others in the same or related field. In the context of the biomedical and health sciences, it primarily pertains to review of manuscripts submitted to journals for consideration of publication, abstracts for proposed presentations at professional meetings, and competitive research grant applications. Serving as a reviewer is a scholarly pursuit and a worthwhile endeavor, assuming it is approached in a conscientious, responsible manner. The purpose of this article is to define peer review and its various forms, suggest reasons for serving as a manuscript reviewer, discuss considerations prior to accepting a review assignment, and provide guidelines for the process.

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.

Pregnancy and Parenthood During Medical School.

PURPOSE: The stress of pregnancy and parenthood during the intense educational experience of medical school could increase the risk of student burnout. Because 9.2 percent of U.S. medical students are parents by graduation, it would seem prudent to include this topic in wellness programs and policies. The purpose of this study was to determine the effects of pregnancy and parenthood on medical students. METHOD: This was a cross-sectional, internet survey distributed to all four classes of medical students at the University of South Dakota Sanford School of Medicine during the 2016-2017 academic year. The survey determined self-reported pregnancy and parenthood information, knowledge of a medical school pregnancy policy, and policy recommendations. RESULTS: More than 85 percent of the 194 respondents recommended that the following elements be included in an institutional policy: process for arranging parental leave, how leave time might affect graduation, how missed requirements could be made up, and how to request special accommodation or leave. Twenty-nine of the respondents (15 percent) were parents or currently pregnant. Eight pregnancies during medical school were associated with complications, including three miscarriages. Of the 18 students who reported maternity or paternity leave, 13 (72 percent) and 10 (56 percent) would have extended their leave time if it did not delay graduation or only reduced their number of elective rotations, respectively. No student would choose to extend leave if it would delay graduation. CONCLUSIONS: This survey is the first of its kind investigating pregnancy and parenthood in medical students attending a U.S. medical school. Students want schools to provide clear, well-defined guidelines, scheduling flexibility and administrators who are approachable and understanding of their individual circumstances.