Detailed Description:. The baseline blood determinations are part of the standard pre cycle screening at CHR for all patients. After signing informed consent subjects will be randomly assigned to either active testosterone cream treatment or placebo.
Active treatment will consist of a testosterone delivery system that will deliver transdermal testosterone cream 0. The cream and placebo cream will be compounded by Metro Drugs New York, NY and dispensed in calibrated pump that will deliver one gram of cream per stroke. The dose of testosterone cream will be 2 grams of cream per day applied to the left inner forearm.
The study medication will continue to be applied for 6 weeks. All patients with evidence of diminished ovarian reserve in our practice are treated with DHEA. Patients who achieve a level of serum testosterone in the desired range using DHEA alone will not be eligible for this study. FDA Resources. Arms and Interventions. Testosterone cream 2 gms per day applied transdermally to the left wrist to deliver 1.
These patients will receive the placebo cream along with her DHEA supplements. Carrier cream without added testosterone in the identical type of pump. Other Name: Carrier cream without added testosterone. Outcome Measures. Primary Outcome Measures : Clinical and Ongoing Pregnancy [ Time Frame: 8 weeks post treatment initiation ] Clinical pregnancy is defined as the presence of a viable gestational sac visible in the uterus 4 weeks after embryo transfer.
The number of oocytes retrieved at oocyte retrieval for in-vitro fertilization will be compared between the treatment group and placebo. Eligibility Criteria. Information from the National Library of Medicine Choosing to participate in a study is an important personal decision.
Inclusion Criteria: Women with 38 to 44 years old planning to undergo ovulation induction for IVF who are willing to sign an informed consent. Baseline Total Testosterone less than 30 ng per deciliter 1. You do not currently have access to this article.
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View Metrics. Email alerts Article activity alert. Advance article alerts. New issue alert. Receive exclusive offers and updates from Oxford Academic. Related articles in Web of Science Google Scholar. The IM is a part of the mesoderm, which is located between the lateral plate mesoderm and paraxial mesoderm of three germ layers and can generate the kidney, gonads, and genital tracts Fig.
Furthermore, our previous data showed that Sertoli-like cells, which have a similar origin to LCs, can be successfully generated from the IM [ 41 ]. A Diagram of developmental stages of native Leydig cells during embryogenesis. The derivation methods are presented. Lam et al. Consistent with their report, CHIRtreated cells showed epithelial to mesenchymal transition, migrating away from the margin of hESC colonies Fig.
These results suggest that ME differentiated into the IM. Because this study aimed to develop a method for the rapid generation of LLCs from hESCs, we tested various durations of treatment and evaluated the expression of LC markers on days 3, 5, and 7 of differentiation.
Therefore, the duration of the differentiation medium treatment for LLC differentiation was fixed to this intermediate period, i. Liu et al. Statistical data on the percentages of these cells are shown in Fig. Finally, we measured the levels of testosterone secreted by the LLCs from each group. Three sections per slide were counted. The life expectancy of humans has increased due to advances in medicine; thus, the desire to maintain vitality and improve the quality of life after aging is increasing.
In males, testosterone is an essential hormone that regulates the physiology of the whole body [ 44 ]. Testosterone dysfunction can occur due to aging, trauma, radiotherapy, or chemotherapy, which can result in various diseases, such as sexual dysfunction, cardiovascular disease, and osteoporosis, and is known to affect approximately Although TRT has been used to overcome testosterone dysfunction, it is not fully capable of restoring the physiological patterns of testosterone metabolism.
Therefore, it is necessary to develop an alternative method to TRT to mimic the physiological patterns of testosterone in hypogonadism. LCs, which produce a vast majority of testosterone in males, are a promising cell source for the treatment of male hypogonadism. However, it is difficult to secure enough cell count for treatment because LCs have limited proliferation capacity and are rare in the testis. Recently, SLCs, which are progenitor stem cells for LCs, have been utilized to understand LC development and for the treatment of hypogonadism [ 6 ].
Furthermore, it might be possible to use autologous SLC transplantation. In summary, in the present and previous studies, we confirmed that HTSCs have not only high proliferative ability but also differentiation ability to various cell types, such as the three germ layer lineages and LCs [ 17 ]. On induction day 9, LLCs were formed. Despite these advantages, it is still necessary to develop universally usable LCs for stable clinical applications.
In this study, we proposed a rapid and efficient system for the differentiation of hESCs into LLCs based on embryonic development in vivo. Although several studies have reported that LCs can be generated from various stem cells, most studies require the additional expression of ectopic genes and longer time [ 6 , 20 , 21 , 22 , 24 , 25 , 26 , 27 , 28 ]. To overcome these issues, we developed a direct method of inducing LCs from hESCs using a few defined molecular compounds within 9 days.
LCs and SLCs originate from the coelomic epithelium and mesonephros formed by the intermediate mesoderm. We established a three-step differentiation strategy to mimic these embryological processes in vitro. Nonetheless, this medium can generate LLCs from the hESC-derived IM within 4 days after treatment, which is very beneficial in terms of reducing the cost of preparing cells for clinical application. These findings could contribute to a safer and more cost-effective strategy for further clinical use of LC transplantation therapy for male hypogonadism.
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