Pregnancy and reproduction in autoimmune rheumatic diseases

Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on children.

Thrombophilia and outcomes of assisted reproduction technologies: a systematic review and meta-analysis

Thrombophilia has been associated with pregnancy complications and recurrent miscarriage. The aim of this systematic review was to evaluate the controversial association between thrombophilia and failures of assisted reproduction technology (ART). A systematic search of the literature for studies reporting on thrombophilia in women undergoing ART up to April 2011 yielded 33 studies (23 evaluating anti-phospholipid antibodies, 5 inherited thrombophilia, and 5 both) involving 6092 patients. Overall, methodologic quality of the studies was poor. Combined results from case-control studies showed that factor V Leiden was significantly more prevalent among women with ART failure compared with fertile parous women or those achieving pregnancy after ART (odds ratio = 3.08; 95% confidence interval, 1.77-5.36). The prothrombin mutation, methylenetetrahydrofolate reductase mutation, deficiency of protein S, protein C, or anti-thrombin were all not associated with ART failure. Women with ART failure tested more frequently positive for anti-phospholipids antibodies (odds ratio = 3.33; 95% confidence interval, 1.77-6.26) with evidence of high degree of between-study heterogeneity (I(2) = 75%; P < .00001). Prospective cohort studies did not show significant associations between thrombophilia and ART outcomes. Although case-control studies suggest that women experiencing ART failures are more frequently positive for factor V Leiden and anti-phospholipid antibodies, the evidence is inconclusive and not supported by cohort studies.

Evaluation des effets de l’extrait aqueux des fleurs de Nymphaea lotus Linn. (Nymphéacées) sur la fonction de reproduction des rats normoglycémique et diabétique de type 1

In traditional medicine of Cameroon, Nymphaea lotus Linn. (Nympheaceae) is used for treatment of male sexual disorders. The aim of this study was to evaluate the effects of the N. lotus flowers aqueous extracts on general mating behavior, fertility and some androgenic parameters of normoglycemic and diabetic adult male rats. Mating behavior assessment was carried out with primiparous and with oestrus female rats. Male rats were divided into 5 groups and subjected once in a day to the following treatment: distilled water (10 mL/kg), Sildenafil citrate (5mg/kg), Testosterone enanthate (5mg/kg) and plant extract (75 mg/kg and 150 mg/kg). Treatment lasted for 8 and 55 days before sacrifice. Organ weight, epididymal sperm counts, motility, viability, histomorphometric analysis, muscular strength, seminal fructose, cholesterol level, epididymal and serum proteins testicular were determined. Results showed a dose- dependant influence of the treatment in sperm count and motility which significantly increases compared to the distilled water-administered control. An increase in some sexual performance parameters (mount and intromission frequencies) was observed in both diabetic and normal rats compared to respective controls. The latencies of mount and intromission were significantly reduced. Computed frequencies of penile licking, index of libido and sexual motivation were higher in normal and diabetic extract-treated animals; which suggest an enhancement of motivational parameters. The treatment also caused significant increases in the weight of the testis, prostate, epididymis, in serum cholesterol and epididymal protein level in normal rats compared to the distilled water-administered control. These results indicate an androgenic pro-sexual potential of N. lotus in male rats and justify the empirical use of N. lotus in the management of erectile dysfunction and fertility disorders in males. Key-words: Nymphaea lotus, prosexual, androgenic, fertility, diabetic, male rat. //Selon les tradipraticiens de l’Ouest-Cameroun, Nymphaea lotus Linn. (N. lotus), de la famille des Nymphéacées, est utilisé pour le traitement des dysfonctionnements sexuels chez les hommes. Dans cette étude, l’effet de l’extrait aqueux des fleurs de N. lotus sur la fonction de reproduction des rats mâles adultes normaux et diabétiques a été évalué. Dans le but d’évaluer les effets de l’extrait aqueux des fleurs de N. lotus sur les paramètres généraux de copulation, d’androgénicité et de fertilité, les rats normoglycémiques et diabétiques ont été divisé en 3 groupes contrôle [Groupe I- recevant de l’eau distillée, Groupe II et III recevant respectivement du citrate de sildénafil (5 mg/kg) et l’énanthate de testostérone (5 mg/kg)] et deux groupes expérimentaux traités à l’extrait aux doses 75 mg/kg (Groupe IV) et 150 mg/kg (Groupe V). L’eau distillée, l’extrait et la substance de référence était administré per os une fois par jour. Pour analyser le comportement sexuel et la fertilité, des femelles primipares et en oestrus étaient utilisées. Le traitement a duré 8 et 55 jours avant le sacrifice. Le poids relatif des organes, le nombre de spermatozoïde, la motilité, les analyses morphométriques, la force musculaire, le taux de cholestérol, le taux de protéines sériques et épididymaires étaient déterminé. Le temps de latence de monte et d’intromission a diminué significativement alors que la fréquence d’éjaculation a augmenté. L’index de libido, la fréquence de monte, d’intromission, d’éjaculation, d’orientation des mâles vis-à-vis d’eux même et l’index de motivation sexuelle a augmenté chez les animaux traités l’extrait comparés à ceux ayant reçu de l’eau distillée aussi bien chez les normaux que chez le diabétiques qui n’enregistrent d’ailleurs aucune éjaculation. Le traitement a augmenté significativement (P < 0,01) le poids des testicules, de la prostate et de l’épididyme. Il est observé une augmentation dose-dépendante du nombre et de la motilité des spermatozoïdes (P < 0,05), ainsi qu’une augmentation significative (P < 0,001) temps-dépendant du taux de cholestérol sérique et de protéines épididymaires. Ces résultats indiquent un potentiel androgénique pro-érectile de N. lotus chez les rats mâles et justifient l’utilisation empirique des fleurs de N. lotus dans le traitement des dysfonctions érectiles et des problèmes de fertilité chez les hommes. Mots-clés: Nymphaea lotus, pro-érectile, androgénique, fertilité, diabétiques, rat male

Management, feeding, production, reproduction and udder health on organic and conventional Swiss dairy farms

Organic dairy farms (OP; n=60) and conventional dairy farms (integrated production, IP; n=60), matched in size, location, and agricultural zone (altitude), were studied for possible differences in management, feeding, production, reproduction and udder health. OP and IP farms were similar in size (17.7 and 16.9 ha), milk quota (65900 and 70,000 kg/year), cow number (14 and 15), cow age (5.3 and 5.2 years), housing of cows of the Simmental x Red Holstein or Holstein breeds (87 and 75%; 45 and 60%), but differed significantly with respect to loose housing systems (18 and 7%), outside paddocks (98 and 75%), energy-corrected 305-d milk yield (5,695 and 6,059 kg), milk protein content (31.8 and 32.7 g/kg), use of bucket milking systems (73 and 33%), observance of regular (12-h) milking intervals (47 and 68%), routine application of the California-Mastitis-Test (10 and 28%), teat dipping after milking (25 and 43%) and blanket dry cow treatments (0 and 45%). Milk somatic cell counts on OP and IP farms (119 000 and 117,000/mL) and reproduction data were similar and there were no significant differences between OP and IP farms as concerns available feeds, planning and management of feeding. Alternative veterinary treatments were used more often on OP than IP farms (55 and 17%). Main causes for cow replacements on OP and IP farms were fertility disorders (both 45%), age (40 and 42%), sale (30 and 37%) and udder health (35 and 13%).Between OP and IP Swiss dairy farms thus relatively few larger differences were found.

Anti-inflammatory and immunosuppressive drugs and reproduction

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.

[Antirheumatic therapy and reproduction. The influence on fertility, pregnancy and breast feeding]

Antirheumatic drugs can have a negative effect on reproduction in both men and women. Possible negative effects are impairment of fertility, harmful effects on the fetus and adverse effects on the breastfed child. In women non-steroidal antiinflammatory drugs (NSAID) and cyclophosphamide can impair fertility. In men infertility can result from the use of salazopyrine and cyclophosphamide. A desire for children should be taken into account before the start of disease modifying drugs (DMARD). Treatment with NSAID is possible at some stages of pregnancy as well as during lactation. A limited number of DMARD is compatible with pregnancy and is presented. Cytostatic drugs and leflunomide must be prophylactically withdrawn before a planned pregnancy. TNF alpha antagonists should be discontinued at the start of pregnancy. Safe birth control must be practised during therapy with drugs that are gonadotoxic or teratogenic. Treatment with immunosuppressive drugs during lactation is limited because of insufficient documentation of safety for the breastfed child.

Interference of endocrine disrupting chemicals with aromatase CYP19 expression or activity, and consequences for reproduction of teleost fish

Many natural and synthetic compounds present in the environment exert a number of adverse effects on the exposed organisms, leading to endocrine disruption, for which they were termed endocrine disrupting chemicals (EDCs). A decrease in reproduction success is one of the most well-documented signs of endocrine disruption in fish. Estrogens are steroid hormones involved in the control of important reproduction-related processes, including sexual differentiation, maturation and a variety of others. Careful spatial and temporal balance of estrogens in the body is crucial for proper functioning. At the final step of estrogen biosynthesis, cytochrome P450 aromatase, encoded by the cyp19 gene, converts androgens into estrogens. Modulation of aromatase CYP19 expression and function can dramatically alter the rate of estrogen production, disturbing the local and systemic levels of estrogens. In the present review, the current progress in CYP19 characterization in teleost fish is summarized and the potential of several classes of EDCs to interfere with CYP19 expression and activity is discussed. Two cyp19 genes are present in most teleosts, cyp19a and cyp19b, primarily expressed in the ovary and brain, respectively. Both aromatase CYP19 isoforms are involved in the sexual differentiation and regulation of the reproductive cycle and male reproductive behavior in diverse teleost species. Alteration of aromatase CYP19 expression and/or activity, be it upregulation or downregulation, may lead to diverse disturbances of the above mentioned processes. Prediction of multiple transcriptional regulatory elements in the promoters of teleost cyp19 genes suggests the possibility for several EDC classes to affect cyp19 expression on the transcriptional level. These sites include cAMP responsive elements, a steroidogenic factor 1/adrenal 4 binding protein site, an estrogen-responsive element (ERE), half-EREs, dioxin-responsive elements, and elements related to diverse other nuclear receptors (peroxisome proliferator activated receptor, retinoid X receptor, retinoic acid receptor). Certain compounds including phytoestrogens, xenoestrogens, fungicides and organotins may modulate aromatase CYP19 activity on the post-transcriptional level. As is shown in this review, diverse EDCs may affect the expression and/or activity of aromatase cyp19 genes through a variety of mechanisms, many of which need further characterization in order to improve the prediction of risks posed by a contaminated environment to teleost fish population.