Do in vitro fertilization, intrauterine insemination or female infertility impact the risk of congenital anomalies in singletons? A longitudinal national French study.

STUDY QUESTION: Do IVF, IUI or female infertility (i.e. endometriosis, polycystic ovary syndrome [PCOS] and primary ovarian insufficiency [POI]) lead to an increased risk of congenital anomalies in singletons? SUMMARY ANSWER: After multivariable adjustments, the increased risks of congenital defects associated with IUI were no longer significant, but the underlying maternal infertility presented a potential emental risk, in addition to the risk associated with IVF. WHAT IS KNOWN ALREADY: Most epidemiological studies suggest that singletons born from ART have a higher risk of birth defects, specifically musculoskeletal, cardiovascular and urogenital disorders. However, most of these studies were established on data obtained at birth or in the neonatal period and from relatively small populations or several registries. Moreover, to our knowledge, female infertility, which is a potential confounder, has never been included in the risk assessment. STUDY DESIGN, SIZE, DURATION: Using data from the French National Health System database, we conducted a comparative analysis of all singleton births (deliveries ≥22 weeks of gestation and/or >500 g of birthweight) in France over a 5-year period (2013-2017) resulting from fresh embryo or frozen embryo transfer (fresh-ET or FET from IVF/ICSI cycles), IUI and natural conception (NC). Data were available for this cohort of children at least up to early childhood (2.5 years old). PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 3 501 495 singleton births were included (3 417 089 from NC, 20 218 from IUI, 45 303 from fresh-ET and 18 885 from FET). Data were extracted from national health databases and used to identify major birth defects. Malformations were classified according to the 10th revision of the International Classification of Disease. To analyse the effect of mode of conception, multivariable analyses were performed with multiple logistic regression models adjusted for maternal age, primiparity, obesity, smoking, history of high blood pressure or diabetes and female infertility. MAIN RESULTS AND THE ROLE OF CHANCE: In our cohort of children, the overall prevalence of congenital malformations was 3.78% after NC, 4.53% after fresh-ET, 4.39% after FET and 3.91% after IUI (132 646 children with major malformations). Compared with infants conceived naturally, children born after fresh-ET and after FET had a significantly higher prevalence of malformations, with an adjusted odds ratio (aOR) of 1.15 [95% CI 1.10-1.20, P < 0.0001] and aOR of 1.13 [95% CI 1.05-1.21, P = 0.001], respectively. Among the 15 relevant subgroups of malformations studied, we observed a significantly increased risk of eight malformations in the fresh-ET group compared with the NC group (i.e. musculoskeletal, cardiac, urinary, digestive, neurological, cleft lip and/or palate and respiratory). In the FET group, this increased risk was observed for digestive and facial malformations. The overall risk of congenital malformations, and the risk by subtype, was similar in the IUI group and the NC group (overall risk: aOR of 1.01 [95% CI 0.94-1.08, P = 0.81]). In addition, there was an overall independent increase in the risk of congenital defects when the mothers were diagnosed with endometriosis (1.16 aOR [95% CI 1.10-1.22], P < 0.0001), PCOS (1.20 aOR [95% CI 1.08-1.34], P = 0.001) or POI (1.52 aOR [95% CI 1.23-1.88], P = 0.0001). Chromosomal, cardiac and neurological anomalies were more common in the three maternal infertility groups. LIMITATIONS, REASONS FOR CAUTION: Male infertility, the in vitro fertilization method (i.e. in vitro fertilization without or with sperm injection: conventional IVF vs ICSI) and embryo stage at transfer could not be taken into account. Furthermore, residual confounding cannot be excluded as well as uncertainties regarding the diagnostic criteria used for the three female infertilities. Findings for specific malformations should be interpreted with caution because the number of cases was small in some sub-groups (potentially due to the Type I error or multiple testing). WIDER IMPLICATIONS OF THE FINDINGS: In this large study, after multivariable maternal adjustments, a moderately increased risk of defects subsisted after IVF, while those associated with IUI were no longer significant. In addition, our results showed that underlying maternal infertility could contribute to the increased risk of defects associated with IVF. These novel findings highlight the importance of taking into account the ART treatment methods and the type of infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Agency of Biomedicine. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: NA.

A virtual dairy herd as a tool to teach dairy production and management.

The objective of this project was to develop and test a web-based virtual dairy herd to help students understand the structure and functioning of a dairy herd, and to promote active learning. At the beginning of the course, the instructor defines the profiles of herds to be assigned to students (e.g., herd size, production, diets, fertility). Each student has a unique herd and engages in decision-making for desired management practices in the herd. Modeled events are based on cow physiology and normal dairy herd management practices. Students' activities and decisions include heat detection, insemination, pregnancy diagnosis, dry-off, diet specifications, feeding groups, colostrum and milk-replacer feeding, weaning, treatment of diseases, and milk withdrawal from the tank if antibiotics are used, among others. The daily output provides information on technical indexes, economic performance, counters of incorrect decisions as feedback for students, and score. Time in class can be devoted to discussions of dairy management issues. Additional exercises based on students' own herds (e.g., calculating required space for cows, land for forage production, manure management) can also be implemented. Students' performance in the virtual dairy farm was monitored over 3 years. The average score (n = 326) was 87.8 ± 1.1 over 100 points, suggesting that self-learning with the virtual dairy farm was highly successful. At the end of each semester, students (n = 277) responded to a survey on the experience of working with the virtual dairy herd. Most students (>87%) agreed that the virtual dairy herd was more effective and motivating than traditional lectures and helped them understand dairy production better. In an unannounced test conducted at least 2 wk before the final exam, students (n = 207) were asked 14 questions on dairy cattle and 14 similar questions on other species taught in the same class through traditional lectures. A similar test on the same students (n = 142) was conducted in their fifth semester (2 years later). Results were better in dairy compared with other species questions in the first (9.6 vs. 3.7) and fifth (8.0 vs. 3.8) semesters. The virtual dairy herd is an effective tool for teaching introductory courses in dairy production. The program can be accessed at www.virtualdairyfarm.org, and a manual and videos with instructions for instructors and students are available online.

Courtship activity, copulation & insemination success in a mosquito vector fed a herbal aphrodisiac: Implications for sterile insect technology.

BACKGROUND & OBJECTIVES: In sterile insect technology (SIT), mating competitiveness is a pre-condition for the reduction of target pest populations and a crucial parameter for judging efficacy. Still, current SIT trials are being hindered by decreased effectiveness due to reduced sexual performance of released males. Here, we explored the possible role of a herbal aphrodisiac in boosting the mating activity of Aedes aegypti. METHODS: Males were fed one of two diets in this study: experimental extract of Eurycoma longifolia (MSAs) and sugar only (MSOs). Differences in life span, courtship latency, copulation activity and mating success were examined between the two groups. RESULTS: No deaths occurred among MSA and MSO males. Life span of MSOs was similar to that of MSAs. The courtship latency of MSAs was shorter than that of MSOs (P<0.01). MSAs had greater copulation success than MSOs (P<0.001). In all female treatments, MSAs mated more than MSOs, but the differences in rate were significant only in the highest female density (P<0.05). In MSAs, mating success varied significantly with female density (P<0.01), with the 20-female group (P<0.01) having the lowest rate. Single MSA had better mating success at the two lowest female densities. In MSOs, there were no significant differences in mating success rate between the different female densities. INTERPRETATION & CONCLUSIONS: Our results suggested that the herbal aphrodisiac, E. longifolia, stimulated the sexual activity of Ae. aegypti and may be useful for improving the mating competitiveness of sterile males, thus improving SIT programmes.

Male but not female olfaction is crucial for intermolt mating in European lobsters (Homarus gammarus L.).

Chemical signals are common in most crustacean social interactions and are often perceived via chemosensory (olfactory) organs on the first antenna. Intermolt courtship behaviors and mating were investigated in size-matched pairs of intermolt European lobsters (Homarus gammarus) where the olfactory receptors of either the male or the female were lesioned with distilled water (olfactory ablation) or seawater (control). Matings or advanced male courtship behaviors (mounting and turning) were common in seawater controls and olfactory-ablated females. In contrast, when male olfaction was ablated with distilled water, there was not a single mating, and the only male courtship behaviors seen were a few very brief and unsuccessful mounting attempts. Individual females mated up to 5 times with different males, showing that previously inseminated females were still attractive to males. Thus, male but not female olfaction is crucial for intermolt mating in H. gammarus, indicating the presence of a female sex pheromone during the entire female molt cycle, not only at the time of molting. Female sex discrimination may be based on other cues from the male in combination with typical male behaviors.

Suplementación parenteral de cobre en vacas gestantes: efecto sobre postparto y terneros / Parenteral supplementation of copper in gestation cows: effect on postpartum and calves

Objetivo. Evaluar el efecto del cobre en vacas gestantes sobre el comportamiento reproductivo posparto y la salud del ternero. Materiales y métodos. Se estudiaron 80 vacas divididas en dos grupos de 40 animales cada uno. El grupo A fue tratado con 2 ml de CuSO4 (2.5%) subcutáneamente. El tratamiento se inició a los 8 meses de gestación, y se repitió a los 30 y 90 días post parto. El grupo B, se uso como control. A las vacas se les analizó el perfil hematoquímico, intervalo parto primer servicio (IPPS), intervalo parto concepción (IPC), intervalo parto-parto (IPP), índice de natalidad (IN), índice de inseminación (II) y la eficiencia en la detección de la hembra en estro (EDHE) y a los terneros los parámetros hematoquímicos. Los datos se procesaron mediante Statgraphics Plus 5.0, para las diferencias entre medias de los datos hemoquímicos y reproductivos se aplicó (ANOVA) y comparaciones de proporciones IN y EDHE. Se empleó la correlación y regresión simple para demostrar la relación del cobre con las demás parámetros estudiados. Resultados. La administración subcutánea de cobre incrementó los niveles de dicho elemento en sangre, hierro y hemoglobina (p< 0.001); así como la disminución del IPPS, IPC, IPP, IN, EDHE, e II (p< 0.05). En los terneros se aumentó la cupremia (p< 0.001), la hemoglobina (p< 0.01) y las proteínas totales (p< 0.05). Conclusiones. El tratamiento aplicado incrementó los indicadores hematoquímicos y reproductivos en los animales tratados.

Novel males' capacity to disrupt early pregnancy in mice (Mus musculus) is attenuated via a chronic reduction of males' urinary 17beta-estradiol.

Mature male mice of proven fertility were administered chronic oral doses of anastrozole, a potent aromatase inhibitor, and also given a low-phytoestrogen diet. Urine was taken non-invasively from such males and from untreated control males and assayed for 17beta-estradiol and testosterone via ELISA procedures. After 8 weeks of drug or vehicle administration, urinary 17beta-estradiol declined to significantly lower levels in anastrozole-treated males than in non-treated males, whereas testosterone levels were comparable in the two groups. Inseminated females were exposed to drug-treated, vehicle-treated, or no males during days 1-6 of gestation, around intrauterine implantation of fertilized ova. Females exposed to vehicle-treated males produced fewer litters than did those kept in isolation. Females exposed to anastrozole-treated males produced significantly more litters than did those exposed to vehicle-treated males. These data support the notion that male excretions of estrogens may in part mediate novel-male-induced pregnancy disruptions, although other influences of aromatization on behaviour and metabolism remain possibilities.

Intrauterine Insemination Using Eletroejaculation in Anejaculatory Male / 대한비뇨기과학회지

A total of 41 anejaculatory men participated in the electroejaculation study. Mean patient age was 33.2 years (range 22 to 54 years). Greater than one million motile sperm were obtained in 26 patients(63.4%). We attempted intrauterine insemination on 25 occasions in 14 subjects' spouses. Four of them(28.6%) became pregnant ;two aborted and the other two delivered fullterm healthy babies.

Social condition affects the courtship behavior of male ring doves with posterior medial hypothalamic lesions.

Following bilateral lesions to the posterior medial hypothalamus (homologue of the mammalian ventromedial nucleus), adult male ring doves regain full courtship behavior and the ability to stimulate female egg-laying when housed continuously with females. Males with PMH lesions housed singly and only tested periodically with females continue to show deficits in courtship. These findings suggest that the social environment present in adulthood itself can directly influence recovery from brain lesions. They also demonstrate the importance of PMH in the mediation of male ring dove courtship behavior.

The fertility of men with spinal injuries.

Application of a vibrator of 80 Hz and 2.5 mm amplitude to the lower surface of the glans penis caused ejaculation in less than 20 minutes (usually less than 3 minutes) in 48 of 81 men with spinal cord injuries (mostly complete) of more than 6 months duration. It failed in all the 19 of the 81 who lacked reflex hip flexion on scratching the soles of the feet, and in 14 others. It failed in 11 of 12 men with injuries of less than 6 months' duration. From 21 of 34 men for whom the vibrator failed, semen could be obtained by electroejaculation, which is just as successful within 6 months of injury as subsequently and may succeed even if reflex hip flexion is absent. Eleven pregnancies where the father had a complete or nearly complete spinal cord lesion are reported. Nine healthy children have been born.

Biochemical, hematologic, and histopathologic studies in rabbits intrarectally inseminated.

Rabbits subjected three times a week for 7 months to administrations of fresh homologous semen, colonic enemas, or semen (previously frozen at -70 degrees) preceded by enema were monitored by a battery of biochemical and hematologic tests and histopathologic examination. No biochemical, hematologic or histopathologic changes were observed. Negative blood cultures and serum endotoxin determinations excluded any possibility of systemic bacterial infection caused or induced by the treatments. Wide temporary variations in the hematologic parameters, including concentrations of T and B cells, were observed in all treated groups. The relevance of these findings to immune status is not yet certain.

Alteration of immune response induced by chronic intrarectal insemination in rabbits.

Three groups of adult male Nya:(FG) rabbits were treated intrarectally, 3 times a week for 7 months, with 1 ml of fresh homologous semen, 20 ml of colonic enema, or 20 ml of enema followed by 1 ml of previously frozen semen. A control group was untreated. The results of several in vitro tests of humoral and cellular response showed that chronic intrarectal insemination leads to an abrogation of the immune response, expressed differently in the two groups of rabbits receiving semen. A consistently depressed blastogenic stimulation in response to T-cell mitogens was observed only in the animals receiving fresh semen. Neither group produced antilymphocyte antibodies. Anti-seminal-fluid and antispermatozoa antibodies were detected after 3 months of treatment in two animals receiving enema and semen and one animal receiving fresh semen. Circulating immune complexes were detected after 2 months of treatment in animals receiving enema and semen. These immune complexes contained predominantly IgM and were specific for seminal antigens. Assay of the cellular response to a T-cell-dependent antigen showed, in the animals receiving enema and semen, a pronounced decrease in the indirect IgA and IgG plaque-forming cells response with practically no effect on the IgM response. These results, taken together with those of the preceding paper, suggest that in intrarectally inseminated rabbits the functional capabilities of the immune system may deteriorate without histologic or morphologic changes in the anorectal mucosa of relevant lymphoid tissues.