A paradoxical decline in semen parameters in men treated with clomiphene citrate: A systematic review

Clomiphene, a selective oestrogen receptor modulator, has been utilised in managing male sub-fertility since 1967. Numerous controlled and uncontrolled studies have been published regarding the efficacy of clomiphene citrate in male sub-fertility cohorts. Although the primary intention of treating men with clomiphene citrate is to improve sperm parameters and testosterone levels, some studies have reported paradoxical decline in semen parameters. The information available on decline in sperm parameters following treatment with clomiphene is sparse. We conducted a systemic review using PubMed, Embase, Cochrane Library and Scopus databases for original studies reporting adverse effects of clomiphene citrate therapy on sperm parameters. This systematic review includes 384 men from 11 different studies that reported adverse effects of clomiphene citrate therapy. Of the men included in these studies, 19%, 21%, 17% and 24% of clomiphene-treated men demonstrated a decrease in sperm count, concentration, motility and total motile sperm count respectively. In up to 17% of patients, deterioration of semen parameters did not recover following discontinuation of therapy. In the future, more studies should report on this aspect so the magnitude of this effect can be more clearly understood.     

How defective spermatogenesis affects sperm DNA integrity

Spermatogenesis is the essential process to maintain and promote male fertility. It is extraordinarily complex with many regulatory elements and numerous steps. The process involves several cell types, regulatory molecules, repair mechanisms and epigenetic regulators. Evidence has shown that fertility can be negatively impacted by reduced sperm DNA integrity. Sources of sperm DNA damage include replication errors and causes of DNA fragmentation which include abortive apoptosis, defective maturation and oxidative stress. This review outlines the process of spermatogenesis, spermatogonial regulation and sperm differentiation; additionally, DNA damage and currently studied DNA repair mechanisms in spermatozoon are also covered.     

Elevated sperm DNA fragmentation does not predict recurrent implantation failure

In this study, we sought to determine whether sperm DNA fragmentation (DFI%) and high DNA stainability (HDS%) evaluated by sperm chromatin structure assay (SCSA) predict recurrent implantation failure (RIF) or pregnancy rate. A retrospective study was performed of consecutive cycles of ICSI treatment from 2009 to 2018. A total of 386 couples that underwent 1,216 frozen embryo transfer (FET) cycles were analysed. Mean female and male age was 34 ± 3.6 years and 37.3 ± 6.6 years, respectively, and a median total motile sperm count (TMSC) was 43.5 [9.9–105.5] million. Overall median DFI% and HDS% was 12 [7.1–18.9] and 9.6 [6.5–14.4] respectively. On multivariable analysis, DFI% and HDS% were not associated with RIF (DFI%: OR = 1.01, 95% CI: 0.98–1.04, p = .414; HDS%: OR = 0.97, 95% CI: 0.94–1.01, p = .107) or IVF success, defined as clinical pregnancy (DFI%: OR = 1.00, 95% CI: 0.99–1.01, p = .641; HDS%: OR = 1.01, 95% CI: 0.99–1.02, p = .565). We found that neither DFI% or HDS%, as assessed by SCSA, were predictive of RIF or pregnancy rate. This finding suggests that sperm DNA fragmentation does not predict RIF or pregnancy rate.     

Use of immunoadsorption columns in ABO-incompatible renal transplantation: A prospective study at a tertiary care center in India

BackgroundWe present our experience of ABO-incompatible renal transplant using immunoadsorption (IA) columns. We have compared efficacy of two commercially available columns.MethodsThis single-center prospective study was conducted at Army Hospital Research and Referral, Delhi. All consecutive ABO-incompatible renal transplants from January 2014 to February 2018 were analyzed. Of 30 patients who underwent transplantations, 28 underwent antibody depletion with immunoadsorption columns. Of them, 14 cases were in the “Glycosorb group,” while 14 in the “Adsopak group.”ResultsThe donors in the Adsopak group were older than those in the Glycosorb group (p < 0.05). Both groups had spousal donors in majority. The cutoff for the antibody titer was 1:8. The median titer in the Adsopak group was 128 (range, 1:4 to 1:2048), while that in the Glycosorb group was 24 (range, 1:8 to 1:128). All patients in the Glycosorb group had baseline titers ≤1:128, while 13 patients in the Adsopak group had baseline titers ≤1:512. Nil titer was achievable with Glycosorb® (50%,7/14) but not with Adsopak® (P < 0.01). Around 4 sessions were required for the Glycosorb group, while around 8 sessions were required for the Adsopak group before transplantation (p < 0.001). The Glycosorb group was advantageous in terms of graft failure because no rejection was noticed in these patients in their follow-up period. Three patients in the Adsopak group developed rejection (two had mixed rejection, and one had antibody-mediated rejection). Four patients died of sepsis (three in the Glycosorb and one in the Adsopak group). Lower baseline serum creatinine level was achieved in the Glycosorb group.ConclusionsResults of ABO-incompatible renal transplantation were satisfactory, and the use of immunoadsorption columns could effectively deplete antibody titers. Glycosorb columns were more efficient than Adsopak columns. Graft survival was better with Glycosorb. Posttransplant infections were a major cause of mortality.     

Fluoride in drinking water and diet: the causative factor of chronic kidney diseases in the North Central Province of Sri Lanka

A significant number of people in the North Central Province of Sri Lanka suffer from chronic kidney diseases (CKD), and the author revisits existing literature related to CKD to find its causative factor. There is a direct connection between high fluoride levels in drinking water and kidney disease, and there are unhealthy levels of fluoride in the groundwater in Sri Lanka’s CKD-affected areas. Based on the following observations, the author believes with confidence that excess fluoride in drinking water and in the locally grown food in the affected areas are the culprits of CKD in Sri Lanka.

• Fluoride excretion rate is considerably lower in children than adults, leading to renal damage of children living in areas with high fluoride.
• Adults who had renal damage due to fluoride in childhood are vulnerable to CKD with continued consumption of water from the same source.
• Patients with chronic renal insufficiency are at an increased risk of chronic fluoride toxicity.
• High content of fluoride in groundwater paves the way to excess fluoride in local food crops, consequently adding more fluoride to the systems of the consumers.
• People who work outdoors for prolonged periods consume excess water and tea, and are subjected to additional doses of fluoride in their system.
• In the mid-1980s, the increase in water table levels of the affected areas due to new irrigation projects paved the way to adding more fluorides to their system through drinking water and locally grown foods.