Aile Hekiminiz

Effect of pentoxifylline in reducing oxidative
stress-induced embryotoxicity1
Xiaoyan Zhang,2 Rakesh K. Sharma,2,3 Ashok Agarwal,2 and Tommaso Falcone2
Submitted May 13, 2005; accepted July 6, 2005
Purpose: To 1) evaluate the embryotoxic effects of hydrogen peroxide on mouse embryo
development and 2) examine if pentoxifylline can reverse hydrogen peroxide induced embryotoxicity.
Methods: Prospective in vitro study examining the effects of varying concentrations of hydrogen
peroxide and pentoxifylline on the blastocyst development rate alone as well as in
combination.
Results: A dose-dependent decrease in % BDR was seen with increasing concentrations
of H2O2. High concentrations of hydrogen peroxide (>60μM) were embryotoxic. Pentoxifylline
(500μM) was able to reduce the embryotoxic effect of hydrogen peroxide. Percent
blastocyst development rate increased from 44% in hydrogen peroxide alone to 85% in hydrogen
peroxide and pentoxifylline coincubation.
Conclusions: Pentoxifylline may be beneficial in reducing hydrogen peroxide induced embryo
damage and improve IVF outcome. Patients with endometriosis-associated infertility
may benefit from the use of pentoxifylline without significantly affecting embryo development.

The Impact of Reactive Oxygen Species on Early Human Embryos:
A Systematic Review of the Literature
– Sajal Gupta, Jashoman Banerjee, Ashok Agarwal
Abstract: Oocytes and embryos are constantly exposed to oxidative stress which influences
their developmental competence. But, the antioxidants present in the reproductive tissues
protect the embryos in vivo.
The effects of oxidative stress in Assisted Reproductive Technology (ART) is amplified by lack
of physiological defense by the antioxidants and also due to abundance of potential sources
that can generate Reactive Oxygen Species (ROS) in culture media. Certain levels of ROS are
necessary for sperm function,normal activity in the ovarian follicle, normal sperm-oocyte
interaction and sperm capacitation. But, excessive levels may have adverse effects on sperm
DNA, fertilization and embryo quality.
ROS not only accelerate apoptosis in the cell by direct DNA damage, but also affect the DNA
repair mechanisms along with alterations in important check points in cell cycle. In-vitro
developmental arrests are documented in mammalian embryos that are exposed to oxidative
stress. Hence blastocyst development in vitro lags behind blastocyst development in vivo.
Sperm DNA damage caused by elevated ROS levels results in embryo development arrest and
poor fertility outcomes with ART. This article reviews the literature on the sources of ROS
generation in ART setting and enumerates strategies to overcome oxidative stress.

Food intake and its relationship with semen quality:
a case-control study
Jaime Mendiola, Ph.D.,a Alberto M. Torres-Cantero, D.P.H.,b Jose M. Moreno-Grau, Ph.D.,c
Jorge Ten, Ph.D.,a Manuela Roca, M.D.,c Stella Moreno-Grau, Ph.D.,c and Rafael Bernabeu, M.D.a,d
a Department of Reproductive Biology and Medicine, Instituto Bernabeu, Alicante; d Reproductive Medicine Chair, University of
Miguel Hernandez de Elche-Instituto Bernabeu, Alicante; b Division of Preventive Medicine and Public Health, School of
Medicine, University of Murcia, Espinardo (Murcia); and c Department of Environmental and Chemical Engineering,
Technical University of Cartagena, Cartagena, Spain
Objective: To compare dietary habits in normospermic and oligoasthenoteratospermic patients attending a reproductive
assisted clinic.
Design: An observational, analytical case-control study.
Setting: Private fertility clinics.
Patient(s): Thirty men with poor semen quality (cases) and 31 normospermic control couples attending our
fertility clinics.
Intervention(s): We recorded dietary habits and food consumption using a food frequency questionnaire adapted
to meet specific study objectives. Analysis of semen parameters, hormone levels, Y microdeletions, and karyotypes
were also carried out.
Main Outcome Measure(s): Frequency of intake food items were registered in a scale with nine categories ranging
from no consumption to repeated daily consumption.
Result(s): Controls had a higher intake of skimmed milk, shellfish, tomatoes, and lettuce, and cases consumed
more yogurt, meat products, and potatoes. In the logistic regression model cases had lower intake of lettuce and
tomatoes, fruits (apricots and peaches), and significantly higher intake of dairy and meat processed products.
Conclusion(s): Frequent intake of lipophilic foods like meat products or milk may negatively affect semen quality
in humans, whereas some fruits or vegetables may maintain or improve semen quality. (Fertil Steril 2009;
91:812–8. 2009 by American Society for Reproductive Medicine.)

Food intake and its relationship with semen quality:
a case-control study
Jaime Mendiola, Ph.D.,a Alberto M. Torres-Cantero, D.P.H.,b Jose M. Moreno-Grau, Ph.D.,c
Jorge Ten, Ph.D.,a Manuela Roca, M.D.,c Stella Moreno-Grau, Ph.D.,c and Rafael Bernabeu, M.D.a,d
a Department of Reproductive Biology and Medicine, Instituto Bernabeu, Alicante; d Reproductive Medicine Chair, University of
Miguel Hernandez de Elche-Instituto Bernabeu, Alicante; b Division of Preventive Medicine and Public Health, School of
Medicine, University of Murcia, Espinardo (Murcia); and c Department of Environmental and Chemical Engineering,
Technical University of Cartagena, Cartagena, Spain
Objective: To compare dietary habits in normospermic and oligoasthenoteratospermic patients attending a reproductive
assisted clinic.
Design: An observational, analytical case-control study.
Setting: Private fertility clinics.
Patient(s): Thirty men with poor semen quality (cases) and 31 normospermic control couples attending our
fertility clinics.
Intervention(s): We recorded dietary habits and food consumption using a food frequency questionnaire adapted
to meet specific study objectives. Analysis of semen parameters, hormone levels, Y microdeletions, and karyotypes
were also carried out.
Main Outcome Measure(s): Frequency of intake food items were registered in a scale with nine categories ranging
from no consumption to repeated daily consumption.
Result(s): Controls had a higher intake of skimmed milk, shellfish, tomatoes, and lettuce, and cases consumed
more yogurt, meat products, and potatoes. In the logistic regression model cases had lower intake of lettuce and
tomatoes, fruits (apricots and peaches), and significantly higher intake of dairy and meat processed products.
Conclusion(s): Frequent intake of lipophilic foods like meat products or milk may negatively affect semen quality
in humans, whereas some fruits or vegetables may maintain or improve semen quality. (Fertil Steril 2009;
91:812–8. 2009 by American Society for Reproductive Medicine.)

Metformin as Treatment for Overweight
and Obese Adults: A Systematic Review
Kara M. Levri, MD, MPH1 Elizabeth Slaymaker, MD1,2 Allen Last, MD1 Julie Yeh, MD1 Jonathan Ference, PharmD1,3 Frank D’Amico, PhD1 Stephen A. Wilson, MD1
1University of Pittsburgh Medical Center St. Margaret, Pittsburgh, Pa 2Grace Medical Associates, Pittsburgh, Pa 3University of Oklahoma-Tulsa, Tulsa, Okla
ABSTRACT
PURPOSE We wanted to determine whether metformin is an effective medication
for treatment of overweight or obese adults who do not have diabetes mellitus or
polycystic ovary syndrome (PCOS).
METHODS We searched MEDLINE (1966–2003), EMBASE (1986–2003), Allied
and Complementary Medicine Database (1985-2003), International Pharmaceutical
Abstracts (1970-2003), the Cochrane Library, American College of Physicians
Journal Club, Database of Abstracts of Reviews of Effects, Cochrane Controlled
Trials Register, MEDLINE In-Process & Other Non-Indexed Citations, reference
lists of retrieved articles, and articles by selected authors and pharmaceutical
manufacturers. Inclusion criteria were being obese or overweight determined
by a BMI of 25 kg/m2 or greater or waist-to-hip ratio (WHR) of more than 0.8,
metformin use, and aged 18 years or older. Exclusion criteria were a diagnosis
of diabetes mellitus, polycystic ovarian syndrome or descriptors of polycystic
ovarian syndrome, human immunodefi ciency virus infection, and concomitant
antipsychotic medications. Trials were graded on an 11-point Jadad scale. Only
randomized controlled and blinded trials were accepted. Two reviewers independently
extracted data from each trial. Primary outcomes measured were changes
in BMI, WHR, and weight.
RESULTS Fifty-seven potentially relevant studies were initially identifi ed; 48 were
excluded because of lack of randomization, lack of blinding, failure to meet inclusion
or exclusion criteria, inaccessible outcomes, or improper study design. Nine
clinical trials met criteria for validity assessment. Four studies used the parameter
of waist-to-hip ratio, 3 studies included BMI, and 8 used weight. Two of the 9
studies showed a small reduction in WHR.
CONCLUSION Insuffi cient evidence exists for the use of metformin as treatment of
overweight or obese adults who do not have diabetes mellitus or polycystic ovary
syndrome. Further studies are needed to answer this clinical question.
Ann Fam Med 2005;3:457-461. DOI: 10.1370/afm.343.