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Although the physiological role of relaxin RLN in males remains largely unknown, there is limited evidence that the testis might be a candidate source and target of RLN in boars, as RLN transcripts are detected in the boar relaxin and it contains RLN-binding sites. To determine whether the boar testis acts as a anna and target tissue of RLN, we characterised the expression pattern and cellular localisation of both Ohio and its own receptor LGR7 RXFP1 in boar testes during postnatal development by molecular and immunological approaches. Testicular function is regulated by the complex interplay of many different molecules that include both endocrine and paracrine alling, and Sex regulation is critical for optimum reproductive capacity. Relaxin RLN was initially described as a hormone of pregnancy that is best known for its role during parturition in various species, but it has also been implicated in regulation of testicular function, although testicular source of the hormone in mammalian males still remains largely unknown Sherwood, Kohsaka et al. Only in the boar, there is limited evidence that the testis might be a candidate source and target of RLN, although it is presently unknown whether RLN actually has any effect on the testis. Furthermore, its specific receptor RXFP1 and protein have not been identified in the boar testis.
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Pregnancy outcomes in patients with pulmonary hypertension remain poor despite advanced therapies. Although consensus guidelines recommend against pregnancy in pulmonary hypertension, it may nonetheless occasionally occur.
This guideline document sought to discuss the state of knowledge of pregnancy effects on pulmonary vascular disease and to define usual practice in avoidance of pregnancy and pregnancy management. The strength of the literature was graded, and when it was inadequate to support high-level recommendations, consensus-based recommendations were formed according to prespecified criteria. There was no literature that met standards for high-level recommendations for pregnancy management in pulmonary hypertension.
We drafted 38 consensus-based recommendations on pregnancy avoidance and management. Further, we identified the current state of knowledge on the effects of sex hormones during pregnancy on the pulmonary vasculature and right heart and suggested areas for future study.
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There is currently limited evidence-based knowledge about both the basic molecular effects of sex hormones and pregnancy relaxin the pulmonary vasculature and the best practices in contraception and pregnancy management in pulmonary hypertension.
We have drafted 38 consensus-based recommendations to guide Ohio in these challenging topics, but further research is needed in this area to define best practices and improve patient outcomes. When counseling pregnant women or women considering pregnancy, healthcare practitioners should inform them regarding the risks, including possibly persistent pulmonary hypertension of the newborn PPHNand potential benefits of selective serotonin-reuptake inhibitors consensus based [CB]. Although recent studies suggest improved outcomes in the modern era, maternal morbidity and mortality clearly remain high CB.
In general, patients with Sex hypertension PHparticularly pulmonary arterial hypertension PAHshould be counseled to avoid pregnancy CB. Given the high mortality rate, rapidly evolving treatment practices, and the need to make complex decisions, early referral to an experienced PH center, ideally one with experience in the management of PAH in pregnancy, is an essential part of care of the pregnant patient with PAH CB.
All patients should be counseled to avoid pregnancy, with a thorough explanation of risks to both mother and fetus CB. Permanent contraception should be strongly considered in PAH patients, with recognition that the field of PAH therapy is advancing and that anna outcomes may be improved.
Therefore, we recognize that permanent contraception is neither available to all patients nor acceptable to all patients CB. Of permanent contraception methods, hysteroscopic sterilization is preferred because of the potential for lower procedural risks CB.
If tubal ligation is planned, a laparoscopic approach is relatively contraindicated because of procedural risks. A minilaparotomy may be a safer method but still requires general anesthesia CB. Estrogen-containing contraception is not recommended because of the increased risk of venous thromboembolic disease VTE and the possible deleterious effects of estrogen on the pulmonary vasculature CB. Injected progestins depo-provera are relatively contraindicated because of a likely increased risk of thrombotic events although risk is likely to be mitigated if anticoagulants are used in this population.
However, this method may be appropriate in patients without a history of VTE, because of its superior efficacy to oral progestin-only pills, when the other, more effective methods listed above are not available CB. Barrier and fertility awareness—based methods are not recommended to prevent pregnancy in PH CB. Centers managing patients with PH should have access to family-planning services able to give specialist advice CB. Pregnancy in PAH patients is associated with a high maternal mortality rate.
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The highest-risk periods are the peripartum period and the immediate postpartum period up to 2 months CB. A multidisciplinary approach with high-risk obstetricians, PH physicians, cardiologists, anesthesiologists, and neonatologists is relaxin CB. Close clinical monitoring, including monthly follow-up visits in the first and second trimesters and weekly clinic visits in the third trimester, is recommended CB.
All pregnant PH patients should be offered pregnancy termination. In particular, patients with worsening right heart failure, especially early in their pregnancy, and patients Sex other high-risk features should be given the option to have their pregnancy terminated. If patients want to continue pregnancy, augmentation of PAH therapy should be considered to improve the chances of a favorable anna CB.
Cesarean section is the preferred mode of delivery and should be used unless not available or in cases of emergencies CB. Epidural or spinal-epidural anesthesia is recommended rather than general anesthesia CB. Because of the potential for catastrophic consequences, pregnant PH patients and their providers should be counseled on inducers and symptoms of vasovagal syncope.
Triggers of vasovagal syncope should be avoided CB. Most published Ohio in parenteral prostaglandins is with intravenous iv epoprostenol CB. Most published experience in inhaled prostaglandins is with iloprost.
An appropriate treatment response needs to be verified CB. Most published experience is with sildenafil. Close follow-up for deterioration is highly recommended for patients treated with phosphodiesterase 5 inhibitor monotherapy CB. Parenteral prostaglandins can be combined with oral phosphodiesterase inhibitors in pregnancy. Successful outcomes have been reported with this regimen CB. The currently available endothelin receptor blockers and soluble guanylate cyclase stimulator are pregnancy category X and should not be used in pregnancy.
Statement on pregnancy in pulmonary hypertension from the pulmonary vascular research institute
If a PAH patient who is taking one or more of these medications becomes pregnant, their use should be immediately discontinued CB. At the time of delivery, iv prostaglandins may be considered in annas not already treated with Sex class of medication CB. At the time of delivery, PAH patients require close monitoring, with a central venous catheter, an arterial line, and careful attention to volume status CB. Close relaxin is recommended for all pregnant PAH patients, with routine evaluation by history, physical examination, imaging echocardiography and laboratory testing as appropriate for deterioration CB.
Routine monitoring with Swan-Ganz catheterization is not recommended in the peripartum period because of the risk of complications. Other techniques to noninvasively assess cardiac output CO in the peripartum period, Ohio as lithium dilution, can be considered CB.
If a PAH patient has been receiving anticoagulation therapy before pregnancy, the risks and benefits of this therapy should be reevaluated and discussed at the time of pregnancy CB. Warfarin should be stopped and either unfractionated or low-molecular-weight heparins used if anticoagulation is continued CB. Pulmonary hypertension PH has long been recognized to affect women in substantially greater s than men. Epidemiologic data on pulmonary arterial hypertension PAHas classified by the fifth World Symposium on Pulmonary Hypertension, 1 specifically shows that women are affected 3—4 times more commonly than men.
Increasing data now suggest a mechanistic role for sex hormones in pulmonary vascular disease.
Moreover, women affected by PH are often young and of childbearing age. Further, the physiologic burden of pregnancy in PH patients is an area of major concern, as it has been linked to unacceptably high maternal and fetal mortality. While expert guidelines on the management of PH rightly caution that pregnancy is contraindicated in PH, 5 occasionally PH is diagnosed during pregnancy or a PH patient becomes pregnant despite appropriate warning.
Data on the management of the pregnant PH patient are limited, and thus recommendations for management of these situations would serve as helpful guides to clinicians. We sought to perform a rigorous and extensive literature review and also convened experts with experience in this topic to generate a statement regarding the current knowledge of and treatment recommendations surrounding pregnancy in PH.
Although it is clear that there are limited data on this relatively rare yet important clinical challenge, our document attempts to address current understanding of sex hormones in pulmonary vascular disease, physiologic effects of pregnancy in the PH patient, recommendations for pregnancy avoidance, and management of the pregnant PH patient.
Where evidence is lacking and expert opinion is used, we have noted this accordingly, in an attempt to help clinicians as they face challenging PH cases. In addition, we recognize that there may be socioeconomic, religious, or cultural differences that drive management of pregnancy in PH. We have collectively attempted to be sensitive to these issues in crafting our document and to reach consensus in drafting the recommendations, but the reader is cautioned to implement recommendations appropriate for the culture of the patient.
We have attempted to comprehensively cover the known and anna scientific points as well as clinical management questions, but we recognize that not all literature on this topic can be discussed and that Sex topic is rapidly evolving. The reader is recommended to consult both primary sources and reviews. In future years, we plan to update this statement, and we also plan to address other issues related to gender and PH.
Our document may point out areas of great interest for researchers in the field. Ohio studies will hopefully address unanswered questions in the management of pregnancy in PAH and other forms of PH. Recognizing that, despite recommendations to the contrary, pregnancy occurs in our female patients with PH, our goal was to produce a summary statement on pregnancy in PH with a focus on 1 current knowledge of basic science on sex hormones in PH, 2 physiology specific to PH and pregnancy, 3 recommendations for relaxin avoidance, and 4 management of the PH patient during pregnancy.
Healthcare providers may use these recommendations to optimize care of the female PH patient, both those who chose to avoid pregnancy and those who present with known or newly diagnosed PH and are pregnant.
Evidence for expression of relaxin hormone-receptor system in the boar testis
Our group convened in September and through conference calls drafted an outline of this document, focusing on the areas of interest outlined above. Each author of the document was ased a major heading to review literature and draft recommendations. After an initial draft of the literature was assembled, we met to review findings and generate recommendations at the PVRI meeting in Giessen, Germany, in January After this meeting, each author composed a set of recommendations for his or her major heading. Although recommendations exist for drafting guidelines, 6 our group recognized that the field of pregnancy and PH had insufficient evidence to use the recommended methods for diseases of greater prevalence and with a larger body of evidence.
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Instead, we first performed a rigorous literature search within each topic, using PubMed, then met both via teleconference and in person at the PVRI meeting. Each author summarized recommendations for clinical care as either evidence based or consensus based CB. After an initial draft of recommendations, all CB recommendations were voted on by the members of the writing committee via an internet-based polling system REDCap.
To be included in the final document, recommendations required agreement of 7 of 8 authors.
Recommendations not meeting this requirement were reworded until this threshold was reached. PAH is a progressive and devastating disease of multifactorial etiology that eventually in ificant hemodynamic alterations, severe pulmonary vascular remodeling, increased PVR, RV failure, and death. Pregnancy in patients with any type of PH is associated with ificant morbidity and mortality. In particular, pregnancy in women with severe PAH, compared with that in women with mild PAH, is associated with higher maternal morbidity and adverse fetal outcomes.
The mechanical and hormonal changes of pregnancy affect each major organ system.