Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline PART II.

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

Ghrelin ameliorates adhesions in a postsurgical mouse model.

BACKGROUND: Peritoneal adhesion formation is a well-recognized consequence of abdominal and pelvic surgery, causing infertility, chronic pelvic pain, and intestinal obstruction. We hypothesized that ghrelin, a 28-amino acid peptide predominantly found in the stomach, plays an important role in preventing postoperative surgical adhesions. The purpose of this study was to develop a new surgical peritoneal adhesion model to define the role that ghrelin plays in wound healing and adhesion formation. MATERIALS AND METHODS: C57BL/6 wild-type mice (n = 40) and growth hormone secretagogue receptor-knockout (GHSR KO) mice (n = 20) underwent a midline laparotomy to establish a peritoneal adhesion model characterized by the combination of two different techniques: ischemic peritoneal buttons and cecal multiple abrasion. All mice received intraperitoneal injections with ghrelin (0.16 mg/kg) or saline twice daily for 20 d after surgery. Peritoneal ischemic buttons were harvested to determine protein expression of collagen (Masson trichrome, picrosirius red stain, and Western blot). RESULTS: The novel mouse model demonstrated consistent and easily reproducible formation of intra-abdominal adhesions. Ghrelin administration significantly reduced postoperative adhesion formation (P < 0.001) in wild-type mice. The antifibrotic effect of ghrelin in wild-type mice was confirmed by measuring collagen I protein levels via Western blot analysis. The anti-adhesion effect of ghrelin seen in wild-type mice was not detected in GHSR KO mice demonstrating that this effect is mediated by the GHSR-1a receptor. CONCLUSIONS: Ghrelin administration may improve surgical outcome by reducing peritoneal adhesion formation and fibrotic response in a mouse model.

Increased expression of CYP24A1 correlates with advanced stages of prostate cancer and can cause resistance to vitamin D3-based therapies.

A major limitation of exogenous vitamin D3 administration for the treatment of prostate cancer is the marginal, if any, clinical efficacy. We dissected the basis for the resistance to the vitamin D3 antitumor properties and specifically examined the effect of its major catabolic enzyme, CYP24A1, in prostate cancer. Local CYP24A1 expression levels and the effect of selective modulation were analyzed using tissue microarrays from needle core biopsy specimens and xenograft-bearing mouse models. CYP24A1 mRNA was elevated in malignant human prostate tissues compared to benign lesions. High CYP24A1 protein levels were seen in poorly differentiated and highly advanced stages of prostate cancer and correlated with parallel increase in the tumor proliferation rate. The use of CYP24A1 RNAi enhanced the cytostatic effects of vitamin D3 in human prostate cancer cells. Remarkably, subcutaneous and orthotopic xenografts of prostate cancer cells harboring CYP24A1 shRNA resulted in a drastic reduction in tumor volume when mice were subjected to vitamin D3 supplementation. CYP24A1 may be a predictive marker of vitamin D3 clinical efficacy in patients with advanced prostate cancer. For those with up-regulated CYP24A1, combination therapy with RNAi targeting CYP24A1 could be considered to improve clinical responsiveness to vitamin D3.

Herbal/hormonal dietary supplement possibly associated with prostate cancer progression.

BACKGROUND: Patients seek herbal/hormonal dietary supplements (HHDS) to prevent and/or solve health and aging issues. After two men developed an unusual course of clinically aggressive prostate cancer within months of starting daily consumption of the same HHDS product, we investigated the effect of this product on prostate cancer progression. METHODS: We evaluated serum levels of total testosterone, luteinizing hormone, and follicle-stimulating hormone and screened prostate biopsy and metastatic specimens for androgen receptor protein expression and mutations. We did hormone analyses and capillary electrophoresis. We tested the effect of the HHDS product on androgen receptor-negative (DU-145 and PC-3) and androgen receptor-positive (LNCaP) human prostate cancer cell lines. RESULTS: Both patients had low hormone levels. The androgen receptor was expressed in all primary and metastatic prostate cancer tissues and no mutations were identified. Hormone analysis revealed that the HHDS contained testosterone and estradiol. The HHDS product was a more potent dose-dependent stimulator of cancer cell growth than testosterone both in androgen receptor-negative and receptor-positive cell lines. Blocking experiments with increasing concentrations of bicalutamide did not prevent the HHDS product-stimulated growth. We filed an adverse event report with the Food and Drug Administration who issued a warning letter. The manufacturer responded by removing this HHDS product from the market. CONCLUSIONS: The HHDS product contained one or more endocrinologically active tumor-promoting components that had cellular androgen receptor status-independent activity. The HHDS product exhibited potent prostate cancer growth stimulatory activity that was more powerful than that of testosterone, independent of the androgen-receptor status of prostate cancer cells, and resistant to antiandrogen blockade.