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Supplementation with L-Carnitine Improves Uterine Receptivity in Women with Prior Implantation Failure during frozen Embryos Transfer: A double-blinded, randomized, placebo-controlled clinical trial.
Abstract
Aim: To evaluate the impact of adding L-carnitine (LC) to usual endometrial preparation on endometrial receptivity in women with at least one prior implantation failure during intra-cytoplasmic sperm injection (ICSI)/ frozen embryo transfer (FET) cycles.
Methods: This prospective, double-blinded, placebo-controlled, randomized, parallel group, concealed allocation, superiority trial was conducted at a private specialized IVF center Benha, El-Qalubia, Egypt, between November 2015 and May 2017 .124 infertile couples with at least one prior implantation failure (PIF) in ICSI / FET cycles were allocated to receive usual endometrial preparation plus 3 gm LC /daily until transfer (62) or received placebo (62) plus usual estradiol valerate. Outcomes were endometrial thickness, implantation rate, chemical pregnancy rate, clinical pregnancy rate, ongoing implantation rate, ongoing pregnancy rate, live birth rate and live borne babies rate.
Results: infertile women with at least one prior implantation failure in ICSI/FET cycles co treated with L-Carnitine showed significantly thicker endometrium (mm) 9.8 1.2 in LC vs 8.4 0.7 in non LC with (95% CI) = 1.4 (1.74, 1.05) and higher chemical pregnancy rate 46 (74.2%) in LC vs 22 (35.4%) in non LC with PP (95% CI) = 38.8 (71.46; 52.96) and RR (95% CI) = 2.09 (1.44, 30.1) and NNT (95% CI) = 3 (2, 5). Also, higher clinical pregnancy rate (34 (54.8%)) in LC vs 14 (22.6%) in non LC with PP (95% CI) = 32.2% (15.13, 46.77) and RR (95% CI) = 2.4 (1.45, 40.5) and NNT (95% CI) = 4 (3 – 7) as well as higher live birth rate, live bone rate of singletons fetus (P < 0.05).
Conclusion: The data showed in this trial support the supplementation of LC to usual endometrial preparation in women with at least one prior implantation failure in ICSI / FET cycles as it improved endometrial receptivity indicated by improved implantation rate, clinical pregnancy rate, live birth rate.
... ALC is abundant in the hypothalamus, where it affects the neuronal activity of the hypothalamo-pituitary-gonadal (HPG) axis and plays an essential role in female reproduction [25,26]. Studies in both animals [27][28][29][30] and humans [17,[31][32][33] have shown that ALC helps in improving fertility and pregnancy rates in PCOS [17]. Recent studies have shown its implications as a novel treatment option for female infertility and improving mitochondrial functions, leading to an improved metabolic profile and reduced oxidative stress [31]. ...
IntroductionPolycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder and the main cause of infertility in women of reproductive age. Affected women suffer from insulin resistance and present with an intense stress response. Treatment with insulin sensitizers alone and in combination is used to ameliorate the signs and symptoms associated with the disease. This study was designed to compare the endocrine and metabolic parameters as well as subjective and objective measures of stress in women with PCOS before and after treatment with acetyl-l-carnitine (ALC) and metformin plus pioglitazone.MethodsA total of 147 women with PCOS were randomly assigned into two groups: the combo group (n = 72) received a combination of metformin, pioglitazone, and ALC (500 mg, 15 mg, and 1500 mg, respectively), twice daily; the Met + Pio group (n = 75) received metformin plus pioglitazone (500 mg, 15 mg, respectively) and placebo (citric acid plus calcium carbonate), twice daily for 12 weeks. Medications were discontinued when pregnancy was confirmed. The Perceived Stress Scale (PSS14) and Profile of Mood States (POMS) were employed as subjective measures of stress. The endocrine and metabolic functions of women with PCOS were assessed by measuring insulin, leutinizing hormone (LH), follicle-stimulating hormone
(FSH), testosterone, and adiponectin levels in fasting blood samples. Insulin resistance was calculated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).ResultsWomen at baseline had significantly elevated circulating concentration of insulin and low level of adiponectin. Treatment decreased insulin in both groups; however, the combo group showed a significant decrease (p = 0.001). Serum adiponectin level was raised significantly after treatment in both groups (p < 0.001). HOMA-IR also decreased in both groups (both p < 0.001). Testosterone, FSH, and LH significantly improved in both groups. LH also decreased in both groups; however, the change was significant only in the combo (metformin plus pioglitazone plus ALC) group (p = 0.013). Interestingly, there was a significant improvement in body circumference (p < 0.001) in the combo group. The PSS scores of the patients improved significantly (p < 0.001) in the combo group. Interestingly, regular menstrual cycles were found (97.2%) in the carnitine group, but in only 12.9% of the other group.Conclusion
We conclude that addition of ALC therapy is superior to metformin plus pioglitazone in ameliorating insulin resistance, polycystic ovaries, menstrual irregularities, and hypoadiponectinemia in women with PCOS. Trial RegistrationTrial registration: clinicalTrial.gov NCT04113889. Registered 3 October, 2019. https://clinicaltrials.gov/ct2/show/NCT04113889.
... The previous observation of LC favorable role in early pregnancy success through increasing the clinical pregnancy rate might be attributed to increase in endometrial receptivity which was evident through the increase in the mean endometrial thickness at the day of HCG administration throughout the study among the LC group compared to placebo ( The result of this work regarding increase in endometrial thickness and receptivity came consistent with the work of Yehia E. & Ehab B. in which infertile women with at least one prior implantation failure in ICSI/FET cycles co-treated with L-Carnitine showed significantly thicker endometrium (mm)compared to non LC (9.8±1.2 mm vs. 8.4±0.7 mm, respectively with significant p value) and higher chemical pregnancy rate 46 (74.2%) in LC vs. 22 (35.4%) in non LC with significant p value. Also, higher clinical pregnancy rate (34 (54.8%)) in LC vs 14 (22.6%) in non LC with significant p value [11]. ...
Carnitine is quaternary ammonium compound and required for the transport of fatty acids from the cytosol into the mitochondria for the generation of metabolic energy. The aims of the present study were to assess the effects of L-carnitine administration to pregnant mice on some parameters of reproductive performance and pregnancy outcome.
One hundred and five pregnant female mice Swiss albino strain mice age: 12-14 weeks were used in this study. Pregnant mice were divided randomly into three equal groups including control group (administered distilled water; DW), low dose group (T1) administered 0.5 mg/Kg L-carnitine and high dose group (T2) administered 1 mg/Kg L-carnitine. Daily administration of D.W. or L-carnitine was continued from day 1 (day post-sexual mating) until parturition. Hormone assay involving follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), litter size, percentage of female sex, weight of the reproductive system and endometrial thickness were assessed.
Assessment of levels of serum reproductive hormones appeared that the FSH and LH and E2 for both treated groups were increased significantly (P
To study ovulatory response and genital and in vitro embryo characteristics of control rabbit does (G1) compared with those treated with Coenzyme Q10 (10 mg CoQ10/kg LBW, G2) and L-Carnitine (40 mg LC kg-1 LBW, G3). Total of 15 mature NZW rabbit does (5.3 mo of age, 3.35 kg LBW) and 6 NZW bucks (7.0-9.0 mo of age and 3.85 kg LBW) were used in this study for 21 days prior to natural mating. All does were slaughtered 64-66 h post-mating to determine genital measurements and follicular and Corpora Lutea (CLs) number, Ovulation Rate (OR) and embryo Recovery Rate (RR) rates. By flushing the oviducts, embryos was counted and evaluated. Also, post-thawing Survival Rate (SR) and Viability Rate (VR) rates were determined. Results showed that dose in G2 showed greater number of follicles (18.2), CLs (13.6) and embryos (16.3) per dose and the highest OR (74.7%), RR (100%), excellent embryos (86.8%) and the lowest good and fair embryos (10.4% for each) compared with G1. Genital characteristics were not affected. Post-thawing SR was not affected, while VR was higher (p<0.05) in G2 and G3 than in G1 (88.9 and 87.5 vs. 76.9%). In vitro blastocyst production rate was higher (p<0.05) in G2 and G3 than in G1 (64.58 and 60.00 vs. 52.63%). In conclusion, pre-conception daily oral dose of rabbit does for 21 days with 10 mg CoQ10/kg LBW has impact on yield, quality, survival and viability of vitrified embryos and in vitro blastocyst production.
Background:
L-carnitine (LC), and its acetylated form, acetyl L-carnitine (ALC), have immense functional capabilities to regulate the oxidative and metabolic status of the female reproductive system. The vulnerability of this system to free radicals demand for advanced strategies to combat them. For this purpose, the ‘quasi vitamins’ LC and ALC can be used either individually, or in combination with each other or with other antioxidants.
Main body:
This review (a) summarizes the effects of carnitines on female fertility along with the findings from various in vivo and in vitro studies involving human, animal and assisted reproductive technology, and (b) proposes their mechanism of actions in improving female fertility through their integrated actions on reducing cellular stress, maintaining hormonal balance and enhancing energy production. They reportedly aid β-oxidation in oocytes, maintain its cell membrane stability by acetylation of phospholipids and amphiphilic actions, prevent free radical-induced DNA damage and also stabilize acetyl Co-A/Co-A ratio for adequate acetyl storage as energy supply to maintain the robustness of reproductive cells.
Conclusion:
While both LC and ALC have their applications in improving female fertility, ALC is preferred for its better antioxidant properties and LC for amelioration of energy supply to the cells. These beneficial effects show great promise in its application as a treatment option for women facing infertility disorders.
L-carnitine (LC) is an antioxidant with the ability to promote the growth in vitro embryo.
Objective
The goal was to evaluate the effect of LC on some indicators of embryo development and blastocyst quality including zona pellucid (ZP) thickness, the hatching of blastocysts and their cell numbers.
Materials and Methods
Mouse embryos were randomly divided into five groups and incubated with different concentrations of LC (I; 0, II; 0.5, III; 1, IV; 2 and V; 4 mg/ml) from 2-cell to hatched blastocyst. The percentage of blastocysts and hatched blastocysts was calculated. Blastocysts ZP thickness was measured and the number of blastocyst cells was counted using Hoechst and propidium iodide (PI) staining.
Results
The results showed concentration of 0.5 mg/ml of LC had an antioxidant effect as in this group, the percentage of blastocysts and hatched blactocysts (p=0.01), the ZP thickness (p=0.00) and the number of blastocyst inner cell mass were significantly more favorable than the control group (p=0.03); and concentration of 4 mg/ml of LC had a toxic effect on embryo development and blastocyst quality (p=0.00).
Conclusion
The results suggest that LC may increase the number of blastocyst cells, which probably helps to expand the blastocyst and thinning of the ZP thickness and, therefore, creating a successful hatching for implantation.
Objective: To evaluate the effectiveness of L-carnitine (LC) or L-acetyl-carnitine (LAC) or combined LC and LAC treatment in improving semen kinetic parameters and the total oxyradical scavenging capacity in semen. Design: Placebo-controlled, double-blind, randomized trial.Setting: Andrology unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.Patient(s): Sixty infertile men, ages 20 to 40 years, with the following baseline sperm selection criteria: concentration > 20 × 10 6 / mL, sperm forward motility < 50 %, and normal sperm morphology > 30 %; 59 patients completed the study.Intervention(s): Patients underwent a double-blind therapy of LC 3 g / d, LAC 3 g / d, a combination of LC 2 g / d + LAC 1 g / d, or placebo. The study design was 1 month of run in, 6 months of therapy or placebo, and 3 months of follow-up evaluation.Main Outcome Measure(s): Variations in semen parameters used for patient selection, and variations in total oxyradical scavenging capacity of the seminal fluid.Result(s): Sperm cell motility (total and forward, including kinetic features determined by computer-assisted sperm analysis) increased in patients to whom LAC was administered both alone or in combination with LC; combined LC + LAC therapy led to a significant improvement of straight progressive velocity after 3 months. The total oxyradical scavenging capacity of the semen toward hydroxyl and peroxyl radicals also increased and was positively correlated with the improvement of kinetic features. Patients with lower baseline values of motility and total oxyradical scavenging capacity of the seminal fluid had a significantly higher probability of responding to the treatment.Conclusion(s): The administration of LC and LAC is effective in increasing sperm kinetic features in patients affected by idiopathic asthenozoospemia and improves the total oxyradical scavenging capacity of the seminal fluid in the same population (Fertil Steril ® 2005;84:662–71.©2005 by American Society for Reproductive Medicine.).
Little consensus has been reached on the best protocol for endometrial preparation for frozen embryo transfer (FET). It is not known how, and to what extent, hormone supplementation in artificial cycles influences endometrial preparation for embryo implantation at a molecular level, especially in patients who have experienced recurrent implantation failure. Transcriptome analysis of 15 endometrial biopsy samples at the time of embryo implantation was used to compare two different endometrial preparation protocols, natural versus artificial cycles, for FET in women who have experienced recurrent implantation failure compared with fertile women. IPA and DAVID were used for functional analyses of differentially expressed genes. The TRANSFAC database was used to identify oestrogen and progesterone response elements upstream of differentially expressed genes. Cluster analysis demonstrated that natural cycles are associated with a better endometrial receptivity transcriptome than artificial cycles. Artificial cycles seemed to have a stronger negative effect on expression of genes and pathways crucial for endometrial receptivity, including ESR2, FSHR, LEP, and several interleukins and matrix metalloproteinases. Significant overrepresentation of oestrogen response elements among the genes with deteriorated expression in artificial cycles (P < 0.001) was found; progesterone response elements predominated in genes with amended expression with artificial cycles (P = 0.0052).
The primary limiting factor for effective IVF treatment is successful embryo implantation. Recurrent implantation failure (RIF) is a condition whereby couples fail to achieve pregnancy despite consecutive embryo transfers. Here we describe the collection of gene expression profiles from mid-luteal phase endometrial biopsies (n = 115) from women experiencing RIF and healthy controls. Using a signature discovery set (n = 81) we identify a signature containing 303 genes predictive of RIF. Independent validation in 34 samples shows that the gene signature predicts RIF with 100% positive predictive value (PPV). The strength of the RIF associated expression signature also stratifies RIF patients into distinct groups with different subsequent implantation success rates. Exploration of the expression changes suggests that RIF is primarily associated with reduced cellular proliferation. The gene signature will be of value in counselling and guiding further treatment of women who fail to conceive upon IVF and suggests new avenues for developing intervention.
In vitro maturation (IVM) is a first and crucial step to determine the success of in vitro embryo production. L-carnitine enhances lipid metabolism in cells and exerts antioxidant effects as well. Such properties are known to be beneficial for oocyte maturation. Thus, to investigate the effects of L-carnitine during IVM on maturation rate of swamp buffalo oocytes, oocytes were matured in IVM medium supplemented with 0.3, 0.6 and 1.2 mg/mL of L-carnitine (0.3, 0.6 and 1.2 L-carnitine groups, respectively). Oocytes matured in 0 mg/mL of L-carnitine were treated as a control group. After IVM, oocytes were denuded by hyaluronidase and fixed with ethanol: acetic acid (3:1) for 3 days. After that, the fixed oocytes were stained with 1% (w/v) orcein in acetic acid for 10 min. Oocytes appearing a metaphase plate and one polar body were regarded as metaphase II stage (MII). Supplementation of L-carnitine at 0.3 mg/mL (0.3 L-carnitine group) showed a significantly higher MII rate than that in control group (83/123, 67.5% vs 69/120, 57.5%); however, the rate was not significantly higher than those in 0.6 mg/mL (79/124, 63.7%) and 1.2 mg/mL (79/123, 64.2%) groups. In conclusion, supplementation of L-carnitine during IVM could improve the nuclear maturation rate to MII and 0.3 mg/mL was the optimal concentration.
Pentoxifylline (PX) is a methyl xanthine derivative that influences the sperm motion characteristics and L-carnitine (L-C) is an amino acid that is naturally produced in the body. In general, separate administration of PX and L-C has been reported to be effective on preserving sperm motility in vitro, and also when is consumed orally by the Idiopathic oligoasthenoteratozoospermia (IOAT) patients.
The aim of this study was to evaluate any possible effect of a combination of L-C and PX on sperm characteristics and improving the type of assisted reproductive techniques (ART) in a group of patients with unexplained oligoasthenoteratozoospermia.
Two hundred twelve infertile men with IOAT in a double-blind, placebo-controlled, randomized clinical trial were allocated for this study. They randomized to four groups. Group I received PX/ and L-C (each one, twice daily), group II, PX and placebo, group III, L-C with the placebo, and group IV, received placebo tablets. Finally, we compared pre and post intervention sperm parameters and ART procedures between groups.
While the use of PX and L-C are only improved sperm motility, but their combined uses improved all sperm parameters, especially the sperm count. Also the combination of PX and L-C was effective on improving the ART procedures (p<0.01).
Our results demonstrate that the combination use of PX and L-C is useful in improving of sperm parameters in IOAT patients and also, improve ART procedures in this group of patients.
The present study was designed to investigate the effect of L-carnitine treatment during IVM on nuclear and cytoplasmic maturation of immature oocytes selected by Brilliant Cresyle Blue (BCB) staining, and their subsequent developmental competence.
Compact cumulus-oocyte complexes (COCs) were collected from NMRI mice ovaries and stained with BCB staining. BCB+ (colored cytoplasm) oocytes were then cultured in tissue culture medium (TCM) 199 with 0.0, 0.3 and 0.6 mg/ml L-carnitine.
The both L-carnitine concentrations significantly increased the intracellular glutathione (P < 0.001), nuclear maturation (P < 0.01) and expression levels of cyclin-dependent kinase1 (CDK1) (P < 0.05). Moreover, treated oocytes with 0.6 mg/ml L-carnitine showed increased (P < 0.05) expression of mitogen-activated protein kinase1 (MAPK1) mRNA. Also, adding L-carnitine (0.6 mg/ml) to IVM medium significantly increased the cleavage rate (P < 0.05). The blastocyst development rate (BDR) in the both L-carnitine treated groups was significantly higher (P < 0.001) than the control group. L-carnitine had no significant effect on total blastocyst cell numbers.
These data indicated that L-carnitine supplementation during IVM of immature BCB+ oocytes improved preimplantation developmental competence of oocytes after IVF, probably by accelerating cytoplasmic and nuclear maturation of oocytes. It may provide a novel approach to improving ART outcomes in infertile couples.
STUDY QUESTION How does l-carnitine (LC) supplementation during vitrification and in vitro maturation (IVM) of germinal vesicle stage (GV)–oocytes improve the developmental competence of the resultant metaphase II
(MII) oocytes?
One hundred and Eighty hens + Eighteen cocks of 50 weeks old were randomly chosen from a large flock with insignificant differences in body weight and laying rate and were divided into 6 groups ( each of 30 birds+3 cocks ) The birds classificated into six groups of three replicates each:
1- The first group was control and fed egg production diet only.
2-The second group fed egg production diet with 0 mg L-carnitine / kg diet + 1 g ascorbic
acid / kg diet.
3-The third group fed egg production diet with 100 mg L-carnitine / kg diet + 0 g ascorbic
acid / kg diet.
4 -The fourth group fed egg production diet with 100 mg L-carnitine / kg diet + 1 g ascorbic
acid / kg diet.
5 -The fifth group fed egg production diet with 200 mg L-carnitine / kg diet + 0 g ascorbic
acid / kg diet.
6-The sixth group fed egg production diet with 200 mg L-carnitine / kg diet + 1 g ascorbic
acid / kg diet.
Birds were housed in individual wire cages during the whole experimental period (50 to 70 weeks of age).
Using 30 cocks for 6 group, 5 cocks / group and classeficated into the same six groups for determined of the semen quality parameters and plasma testosterone hormone.
Body weight, weight gains, feed intake and feed conversation of birds were recorded 4 week, egg number, egg weight and egg mass were recorded daily and calculated 4 week and egg quality, fertility, hatchability%, and semen quality were taken at the end of experimental period. The body temperature (◦C) and respiratory rate (count /min) were taken at 4 weeks intervals during the whole experimental period, and the averages were estimated. These groups were taken along the experimental period which lasted five months during summer season, the temperatures degree were over 30 º C during the experimental period .
At the end of the experimental period five laying / group were randomly chosen, weighted, slaughtered and eviscerated. Some physiological and immunological traits were determined and illustrated in this study. The results indicated that:
- Body weight and body gain were decreased and improving feed conversation in groups fed L-carnitine alone or with ascorbic acid compared with control group.
- Egg number, egg mass and egg production percentage were significantly increased by using L-carnitine alone or with ascorbic acid compared with control group, while egg weight increased by using L-carnitine with ascorbic acid compared with other groups.
- Fertility and hatchability percentages were significantly increased and improving semen quality by supplementation of L-carnitine alone and with and ascorbic acid to the layer diets as compared with control group.
- Body temperature do not affected, while respiratory rate was significantly decreased by using L-carnitine alone or with ascorbic acid compared with control group.
- Levels of plasma calcium, phosphorus, total protein and globulin were significantly increased by using L-carnitine alone or with ascorbic acid compared with control group.
-Levels of plasma T3and testosterone hormones were significantly increased, Ratio of T3/T4 and AST enzyme were significantly decreased, while T4 hormone and ALT enzyme were did not affected by using L-carnitine alone or with ascorbic acid compared with control group.
- Levels of plasma and yolk cholesterol, LDL, HDL and total lipids were reduced significantly by using L-carnitine alone or with ascorbic acid compared with control group.
-Using both L-carnitine and ascorbic acid alone or their combinations was significantly increased found in antibody titters against avian Newcastle and Influenza diseases compared with control and the relative weights of spleen and thymus were significantly increased by using either L-carnitine alone or with ascorbic acid compared with control group.
- Using both L-carnitine and ascorbic acid alone or their combinations was significantly decreased of gizzard, liver and abdominal fat relative weights and was significantly increased of kidney, ovary relative weights and oviduct length compared with control group.
It can be concluded that supplementation of 100 or 200 mg L-carnitine + 1 g ascorbic acid /kg diet, improved productive, reproductive , physiological and immunological performance and using 200 mg L-carnitine + 1 g ascorbic acid /kg diet gave the best results for old Golden Montazh laying hens at 50 - 70 week of age during summer season.
High lipid content in embryos is associated with low freezing tolerance. This study assessed the effects of exogenous l-carnitine, an enhancer of lipid metabolism, on the in vitro development and freezing survival of bovine embryos. Also, effects on metabolic activity, reactive oxygen species (ROS) and apoptosis were investigated. Supplementation of embryo culture medium with 1.518 mM or 3.030 mM l-carnitine significantly increased the rates of zygote development to the blastocyst stage and blastocyst cell numbers whereas 6.072 mM of this compound did not improve embryo development. Survival rates after slow freezing of blastocysts were significantly higher when embryos were cultured in the presence of 1.518 mM or 3.030 mM l-carnitine compared with the control. A lower density of lipid droplets was detected in l-carnitine-treated blastocysts compared with the control. l-carnitine significantly reduced ROS levels in 2-cell embryos but did not reduce ROS levels at later stages. The apoptotic cell rate was not different between control and l-carnitine-treated blastocysts. l-carnitine significantly increased ATP levels in 2-cell embryos but not at the 8-cell or blastocyst stages. l-carnitine increased the expression of metabolism-related ATP6 and COX1 genes in blastocysts. In conclusion, l-carnitine supplementation enhanced lipid metabolism in embryos resulting in improved development and cryotolerance of bovine blastocysts produced in vitro.
The objective of this study was to investigate whether medical therapy can reduce sperm aneuploidy levels and improve the results of intracytoplasmic sperm injection (ICSI) in patients with severe idiopathic oligoasthenoteratospermia (OAT). Thirty-three infertile couples requiring ICSI because of severe idiopathic OAT after at least one unsuccessful ICSI cycle were considered. Semen parameters (concentration, motility and morphology), the percentage of aneuploid sperm and the results of ICSI (the number of oocytes fertilized, embryos transferred, biochemical pregnancies, clinical pregnancies and live births) were compared before and after a 3-month course of treatment with L-carnitine 1 g given twice per day+acetyl-L-carnitine 500 mg given twice per day+one 30-mg cinnoxicam tablet every 4 days. Aneuploidy was assessed using fluorescent in situ hybridisation (FISH) performed on chromosomes X, Y, 13, 15, 16, 17, 18, 21 and 22. The results showed that 22 of the 33 patients had a reduced frequency of aneuploid sperm and improved sperm morphology after treatment (group 1), and 11 showed no change (group 2). The numbers of biochemical pregnancies, clinical pregnancies and live births were significantly higher in group 1 than in group 2. No significant difference was found between the groups regarding the numbers of oocytes fertilized and embryos transferred. The side effects were negligible. The numbers of ICSI pregnancies and live births in severe idiopathic OAT patients improved with a course of L-carnitine, acetyl-L-carnitine and cinnoxicam.
The aim of the present study was to assess the effects of L-carnitine, an enhancer of lipid metabolism and mitochondrial activity, during in vitro maturation (IVM) on nuclear maturation and in vitro fertilisation of porcine follicular oocytes and subsequent embryo development. Mitochondrial functions, intracellular lipid content and reactive oxygen species (ROS) levels in oocytes were also investigated. L-carnitine supplementation in 0.6–5 mg mL–1 concentration during IVM significantly improved (P < 0.05) the rates of metaphase-II (MII) stage oocytes compared with the control; however, fertilisation rates and monospermy were not improved. Although supplementation of IVM medium with L-carnitine significantly increased oocyte cleavage (P < 0.05), further development to the blastocyst stage was not improved. The density of active mitochondria was significantly higher and the density of lipid droplets was significantly lower (P < 0.05) in L-carnitine-treated oocytes compared with the control. Furthermore, the ROS levels in L-carnitine-treated oocytes were significantly lower than those in the control. In conclusion, enhancing mitochondrial functions by L-carnitine improved oocyte maturation and cleavage underlining the importance of lipid metabolism for nuclear and cytoplasmic maturation of porcine oocytes.
We determined the effects of L-carnitine (200 ppm), chromium nicotinate (CrNic; 200 ppb), a combination of L-carnitine and CrNic, or flushing (11 Ibid of complete diet fed for 14 d prior to breeding) on ovulation and fertilization rates in gilts. All gilts (n = 105) were administered PG600 to aid in the synchronization of estrus. After detection of estrus, gilts were assigned randomly to dietary treatments and were fed at 4 Ibid with the exception of gilts on the flushing treatment. Treatments were continued until breeding at the third estrus. Surgeries were performed on d 2 to 3 after third estrus was detected to determine ovulation rate and collect embryos and unfertilized eggs. An increase (P<.10) in ovulation rate was observed for gilts in the flushing or L-carnitine treatment. Supplemental L-carnitine decreased (P =.10) fertilization rate of embryos recovered. No differences were observed for number of empty zonae or number of unclassifiable eggs. Increased ovulation rates for L-carnitine-treated gilts warrants further evaluation to determine whether L-carnitine increases number of pigs farrowed. Swine Day, Manhattan, KS, November 19, 1998
Successful embryo implantation depends on the quality of the embryo, as well as on the receptivity of the endometrium. The aim of this study was to investigate the endometrial gene expression profile in women with unexplained infertility in comparison with fertile controls at the time of embryo implantation in order to find potential predictive markers of uterine receptivity and to identify the molecular mechanisms of infertility. High-density oligonucleotide gene arrays, comprising 44 000 gene targets, were used to define the endometrial gene expression profile in infertile (n = 4) and fertile (n = 5) women during the mid-secretory phase (day LH + 7). Microarray results were validated using real-time PCR. Analyses of expression data were carried out using non-parametric methods. Hierarchical clustering and principal component analysis showed a clear distinction in endometrial gene expression between infertile and fertile women. In total we identified 145 significantly (>3-fold change) up-regulated and 115 down-regulated genes in infertile women versus controls. Via Database for Annotation, Visualization and Integrated Discovery functional analysis we detected a substantial number of dysregulated genes in the endometria of infertile women, involved in cellular localization (21.1%) and transport (18.8%) and transporter activity (13.1%) and with major localization in extracellular regions (19.2%). Ingenuity Pathways Analysis of the gene list showed dysregulation of gene pathways involved in leukocyte extravasation signalling, lipid metabolism and detoxification in the endometria of infertile women. In conclusion, endometrial gene expression in women with unexplained infertility at the time of embryo implantation is markedly different from that in fertile women. These results provide new information on genes and pathways that may have functional significance as regards to endometrial receptivity and subsequent embryo implantation.
The effect of two dietary levels of L-carnitine and vegetable fat powder on broiler breeder fertility, hatchability, egg yolk and serum cholesterol and triglyceride was studied. Two hundred fifty female and twenty five male (Classic Hubbard parent stock) were distributed randomly in five groups of 50 with five replicate of 10 females and one male. Two levels of L-carnitine 0, 60 ppm (for females) and 0, 500 ppm (for males) and vegetable fat powder (0, 1.5%) and a diet with high lysine and methionine (0.3%) fed for both of male and female within one of treatment were used in a complete random design of treatments. The parameters as hatchability, fertility, egg weight, albumen height, Haugh unit, color of yolk, shell thickness, shell strength, yolk weights, egg yolk and serum cholesterol and triglyceride were measured. No significant differences were observed in external and internal egg quality. Supplemented diet with L-carnitine had effect on hatchability (P< 0.05) and fertility (P< 0.01). L-carnitine had no effect on egg production except on fifth and sixth weeks (P< 0.01). None of experimental diet had no effect on male serum cholesterol, serum triglyceride in both sex and total yolk cholesterol but L- carnitine had effect on female serum cholesterol (P< 0.05). L- carnitine had decreased egg yolk cholesterol (mg/gr) (P< 0.05). Yolk weight increase in response to dietary supplementation of L-carnitine(P< 0.05) and L-carnitine content of egg yolk increase with L-carnitine supplementation (P< 0.05).
Repeated implantation failure (RIF) is a severe obstacle in human assisted reproduction treatment.
Aiming to identify global gene profile in RIF patients, gene-array analyses were performed on endometrial samples collected on day 21 of the cycle from fertile women (n = 12) and from RIF patients (n = 20). Validation of cyclin E2, Slug, dickkopf homolog 1 (DKK1), lymphoid enhancer-binding factor 1 (LEF1) and secreted frizzled-related protein 1 (SFRP1) was carried out by real-time PCR.
Gene-array analysis revealed 313 genes exhibiting modified expression levels in RIF patients. Of these, 288 genes (92%) were down-regulated and only 25 genes (8%) were up-regulated. Classification of the down-regulated genes to biological pathways revealed cell cycle, Wnt signaling and cellular adhesion pathways. Real-time PCR validation of cyclin E2, SFRP1 and LEF1 showed significantly lower expression levels in RIF-IVF patients as compared with fertile women. In addition, two up-regulated genes, Slug and DKK1, were also validated. Interestingly, about 8% of the down-regulated genes were estrogen-dependent. Western blot of estrogen receptor alpha revealed low expression of this protein in the RIF group.
The evaluation of the endometrium of RIF patients by gene array analysis demonstrates that the expression of various genes is altered, including those belonging to the cell cycle, Wnt signaling and cellular adhesion pathways.
To determine the efficacy of combined l-carnitine and l-acetyl-carnitine therapy in infertile males with oligo-astheno-teratozoospermia.
Placebo-controlled double-blind randomized trial.
University tertiary referral center.
Sixty infertile patients (aged 20-40 years) with the following baseline sperm selection criteria: concentration, 10 to 40 x 10(6)/mL; forward motility, <15%; total motility, 10% to 40%; and atypical forms, <80%. Fifty-six patients completed the study.
Patients were submitted to a combined treatment of l-carnitine (2 g/d) and l-acetyl-carnitine (1 g/d) or of placebo; the study design was 2 months' wash-out, 6 months of therapy or of placebo, and 2 months' follow-up.
Variation in the semen parameters that were used for patient selection.
Even though increases were seen in all sperm parameters after combined carnitine treatment, the most significant improvement in sperm motility (both forward and total) was present in patients who had lower initial absolute values of motile sperm (<4 x 10(6) forward or <5 x 10(6) total motile spermatozoa per ejaculate).
Combined treatment with l-carnitine and l-acetyl-carnitine in a controlled study of efficacy was effective in increasing sperm motility, especially in groups with lower baseline levels.
Carnitine plays essential roles in energy production, oxidative stress and glucose metabolism. This study was planned to determine serum total L-carnitine levels in non-obese women with polycystic ovary syndrome (PCOS).
There were 27 non-obese women with PCOS and 30 healthy, age- and body mass index (BMI) matched controls were evaluated in this controlled clinical study. Serum lipid sub-fractions, fasting glucose, insulin and other hormones (gonadotrophins, androgens) and total L-carnitine levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance.
The women with PCOS had significantly higher serum dehydroepiandrosterone sulfate, total testosterone, free androgen index (FAI), luteinizing hormone (LH), low-density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, fasting insulin levels and HOMA-IR measurement and LH/FSH ratios than healthy women. However, total L-carnitine and sex hormone-binding globulin (SHBG) levels were significantly lower in women with PCOS. L-Carnitine level was negatively correlated with FAI, but positively correlated with SHBG. Multiple regression analysis revealed that SHBG was a strong predictor of serum total L-carnitine level.
Decreased total L-carnitine levels may be associated with hyperandrogenism and/or insulin resistance in non-obese women with PCOS. Long-term studies are needed to evaluate carnitine metabolism in PCOS, especially with regard to the molecular basis.
Objective:
To assess whether follicular fluid (FF) from infertile women with endometriosis in advanced stages [moderate/severe (EIII/IV) without or with endometrioma (Endometrioma)] induce more oocyte damages than in early stages (minimal/mild: EI/II); and whether supplementation with L-carnitine (LC) and omega 3 (n3) can prevent these oocyte damages.
Methods:
Experimental study using bovine oocytes (obtained of ovaries from slaughterhouse), and human FF (samples were obtained during oocyte recovery for ICSI). Bovine oocytes were submitted to in vitro maturation (IVM) divided into 9 groups: no FF(No-FF), with 1% FF from infertile women without endometriosis (FFC), with EI/II, EIII/IV and Endometrioma, and with (or not) LC+n3 addition. After IVM, oocytes were fluorescently labelled and visualized by confocal microscopy to analyze chromosomes and spindle.
Results:
FF from endometriosis decreased rate of normal MII (spindle assembly and chromosome alignment) compared to No-FF (87.2%) and FFC (87.2%). FFEIII/IV (80.7%) and FFEndometrioma (69.3%) decreased total MII rate compared to No-FF (91.9%) and FFC (89.2%), and FFEndometrioma had lower total MII rate compared to other groups. LC+n3 increased MII rate in the FFEIII/IV (80.7% vs. 90.8%) and the Endometrioma (69.3% vs. 86.4%), and it prevented damages in spindle and chromosomes in MII oocytes in the FFEI/II group (62.2% vs. 84.5%) and the FFEIII/IV group (70.2% vs. 84.1%).
Conclusions:
FF of endometriosis damaged the meiotic spindle of bovine MII oocytes. EIII/IV led to impaired nuclear maturation; FF from women with endometrioma had further negative impact in oocyte maturation. LC+n3 completely prevented the effects of FF from women with endometriosis on oocyte.
Introduction:
Limited data are available assessing the effects of oral carnitine supplementation on mental health parameters and biomarkers of oxidative stress of women with polycystic ovary syndrome (PCOS).This study was designed to determine the effects of oral carnitine supplementation on mental health parameters and biomarkers of oxidative stress in women with PCOS.
Methods:
In the current randomized, double-blind, placebo-controlled trial, 60 patients diagnosed with PCOS were randomized to take either 250 mg carnitine supplements (n = 30) or placebo (n = 30) for 12 weeks.
Results:
After 12 weeks' intervention, compared with the placebo, carnitine supplementation resulted in a significant improvement in Beck Depression Inventory total score (-2.7 ± 2.3 versus -0.2 ± 0.7, p < 0.001), General Health Questionnaire scores (-6.9 ± 4.9 versus -0.9 ± 1.5, p < 0.001) and Depression Anxiety and Stress Scale scores (-8.7 ± 5.9 versus -1.2 ± 2.9, p = 0.001). In addition, changes in plasma total antioxidant capacity (TAC) (+84.1 ± 151.8 versus +4.6 ± 64.5 mmol/L, p = 0.01), malondialdehyde (MDA) (-0.4 ± 1.0 versus +0.5 ± 1.5 μmol/L, p = 0.01) and MDA/TAC ratio (-0.0005 ± 0.0010 versus +0.0006 ± 0.0019, p = 0.003) in the supplemented group were significantly different from the changes in these indicators in the placebo group.
Conclusions:
Overall, our study demonstrated that carnitine supplementation for 12 weeks among patients with PCOS had favorable effects on parameters of mental health and biomarkers of oxidative stress.
This review explores the role of carnitine in male infertility. The structure of this review is organized into short paragraphs that address the following aspects: antiapoptotic effect of l-carnitine on germ cells, effects of l-carnitine on conventional sperm parameters, in vitro effects of l-carnitine on sperm function, and the role of l-carnitine on erectile function.
Objective:
Limited data are available evaluating the effects of oral carnitine supplementation on weight loss and metabolic profiles of women with polycystic ovary syndrome (PCOS). This study was designed to determine the effects of oral carnitine supplementation on weight loss, and glycaemic and lipid profiles in women with PCOS.
Design, patients and measurements:
In a prospective, randomized, double-blind, placebo-controlled trial, 60 overweight patients diagnosed with PCOS were randomized to receive either 250 mg carnitine supplements (n=30) or placebo (n=30) for 12 weeks. Fasting blood samples were obtained at the beginning and end of the study to quantify parameters of glucose homeostasis and lipid concentrations.
Results:
At the end of the 12 weeks, taking carnitine supplements resulted in a significant reduction in weight (-2.7±1.5 vs. +0.1±1.8 kg, P<0.001), BMI (-1.1±0.6 vs. +0.1±0.7 kg/m(2) , P<0.001), waist circumference (WC) (-2.0±1.3 vs. -0.3±2.0 cm, P<0.001) and hip circumference (HC) (-2.5±1.5 vs. -0.3±1.8 cm, P<0.001) compared with placebo. In addition, compared with placebo, carnitine administration in women with PCOS led to a significant reduction in fasting plasma glucose (-0.38±0.36 vs. +0.11±0.97 mmol/L, P=0.01), serum insulin levels (-14.39±25.80 vs. +3.01±37.25 pmol/L, P=0.04), homeostasis model of assessment-insulin resistance (-0.61±1.03 vs. +0.11±1.43, P=0.04) and dehydroepiandrosterone sulfate (-3.64±7.00 vs. -0.59±3.20 μmol/L, P=0.03).
Conclusions:
Overall, 12 weeks of carnitine administration in PCOS women resulted in reductions in weight, BMI, WC and HC, and beneficial effects on glycaemic control; however, it did not affect lipid profiles or free testosterone. This article is protected by copyright. All rights reserved.
Viable lambs can be produced after transfer of in vitro-derived embryos from oocytes harvested from prepubertal lambs. However, this occurs at a much lower efficiency than from adult ewe oocyte donors. The reduced competence of prepubertal oocytes is believed to be due, at least in part, to deficiencies in cytoplasmic maturation. Differences in the cytoplasmic ultrastructure between prepubertal and adult oocytes have been described in the sheep, pig, and cow. Prepubertal lamb oocytes have been shown to have a different distribution of mitochondria and lipid droplets, and less mitochondria and storage vesicles than their adult counterparts. L-carnitine plays a role in supplying energy to the cell by transporting long-chain fatty acids into mitochondria for β-oxidation to produce ATP. Both L-carnitine and its derivative acetyl-L-carnitine have been reported to increase the blastocyst rate of oocytes from mice, cows, and pigs, treated during IVM. L-carnitine has also been shown to increase mitochondrial biogenesis in adipose cells. Therefore, the aims of this study were to determine if treatment of oocytes from prepubertal lambs with acetyl-L-carnitine during IVM could increase the blastocyst rate and alter mitochondria, vesicle, or lipid droplet number, volume, or distribution. The blastocyst rate was doubled in prepubertal lamb oocytes treated with acetyl-L-carnitine when compared to untreated oocytes (10.0% and 4.6%, respectively; P = 0.028). Light microscopy, scanning electron microscopy, and stereology techniques were used to quantify organelles in untreated and acetyl-L-carnitine-treated lamb oocytes, and quantitative polymerase chain reaction methods were used to measure the mitochondrial DNA copy number. There were no differences in mitochondrial volume, number, or mitochondrial DNA copy number. Acetyl-L-carnitine treatment increased the cytoplasmic volume (P = 0.015) of the oocytes, and there were trends toward an increase in the vesicle volume (P = 0.089) and an altered distribution of lipid droplets (P = 0.076). In conclusion, acetyl-L-carnitine can be used to increase the in vitro blastocyst rate of juvenile oocytes and therefore to improve juvenile in vitro embryo transfer methods. These methods can be used for livestock improvement by increasing the rate of genetic gain. Further work is required to identify the contents of the vesicles and confirm the mode of action of acetyl-L-carnitine in improving oocyte competence.
Copyright © 2015 Elsevier Inc. All rights reserved.
Objective:
To evaluate the effectiveness of L-carnitine on improving the ovulation and pregnancy rates as well as adverse metabolic indices in clomiphene-resistant PCOS.
Design:
Single center, double blinded, superiority, randomized controlled clinical trial.
Setting:
Women's Health Hospital, Assiut University.
Methods:
One hundred and seventy women diagnosed with PCOS were found to be clomiphene resistant. The women were randomly allocated into two groups: Group A (n=85), where patients received 250 mg clomiphene citrate from day three until day seven of the cycle plus L-carnitine (LC) 3g daily; and Group B (n=85) received 250 mg clomiphene citrate with placebo.
Outcome:
Primary outcome is cumulative clinical pregnancy rate. Secondary outcomes are changes in serum glucose level and lipid profile.
Results:
The combination of L-carnitine and CC significantly improve both the ovulation and the cumulative pregnancy rates in clomiphene resistant PCOS (55 (64.4%) vs. 15 (17.4%) and 44 (51.5) % vs. 5 (5.8) %). The number of stimulated follicles reaching ≥17 mm diameter was significantly more in Group A to Group B (2.2 ± 0.77 vs. 0.16 ± 0.79; p<0.0001). Group A needed significantly fewer days for adequate follicular maturation, had a thicker endometrium and higher oestradiol concentration at the time of human chorionic gonadotrophin injection (10.1 ± 0.1mm vs. 6.8 ± 0.4mm; p<0.0001). The same group had a higher mean luteal-phase serum progesterone compared with the control group (13.55 ± 0.99 vs. 10.6 ± 0.98 ng; p<0.0001). A significant difference was found regarding the clinical pregnancy rates (42 (49.4%) vs. (1) 1.1% respectively p value <0.0001).
Conclusion:
Adding L-carnitine when treating clomiphene-resistant PCOS patients not only improved the quality of ovulation and the pregnancy rate with an acceptable patient tolerability, but also enhanced the patient lipid profile and body mass index.
L-carnitine is required during the oxidation of lipids for the transport of fatty acids from the cytosol into the mitochondria for generation of energy. L-carnitine exerts a substantial antioxidant, anti-cytokines and anti apoptotic actions providing multi-mechanisms protective effects for the cell. The gametes in vitro may be exposed to damaging effects from oxidative stress (OS) due to either the high oxygen tension compared to the in vivo condition or the preparation producers preceding the in vitro fertilization (e.g. sperm preparation procedures preceding the in vitro fertilization). Moreover OS can affect the gametes in vivo under certain conditions as in endometriosis or leukocytospermia. Oxidative stress and cell apoptosis may adversely impact the fertilization process and the subsequent embryo development and pregnancy outcome. This review discusses the protective effects of L-carnitine for gametes and embryos and how it may help improve the embryogenesis and the in vitro fertilization outcome.
The objective of this study was to examine the effect of L-carnitine treatment during in vitro maturation (IVM) of immature pig (Sus scrofa) oocytes. Specifically, the effects of L-carnitine treatment on nuclear maturation and oocyte intracellular glutathione (GSH) levels, embryonic development after parthenogenetic activation (PA) and somatic cell nuclear transfer (SCNT), and gene expression levels in SCNT pig embryos were determined. During IVM culture, immature oocytes were either treated or not treated with 10 mM L-carnitine. L-carnitine treatment did not improve the nuclear maturation of oocytes but significantly increased intracellular GSH levels, which led to a reduction of reactive oxygen species (ROS) levels in IVM oocytes. Oocytes treated with L-carnitine showed higher (P<0.05) rates of blastocyst formation after PA (39.4% vs. 27.1%) and SCNT (23.2% vs. 14.9%) compared with untreated oocytes. SCNT embryos that were derived from L-carnitine-treated oocytes showed increased (P<0.05) expression levels of DNMT1, PCNA, FGFR2, and POU5F1 mRNA compared with control embryos. Treatment of recipient oocytes with L-carnitine increased (P<0.05) the expression of both BAX and p-Bcl-xl mRNA in SCNT blastocysts. However, the increase was more prominent in BAX than in p-Bcl-xl mRNA. Our results demonstrate that L-carnitine treatment during IVM improves the developmental competence of SCNT embryos. This effect is probably due to increased intracellular GSH synthesis in recipient ooplasts, which reduces ROS levels, and the stimulation of nuclear reprogramming via increased expression of POU5F1 and transcription factors.
The objective was to examine if IVF/ICSI repeated implantation failures (IF) or recurrent miscarriages (RM) could be related to preconceptional endometrial deregulations. IF was defined as the absence of pregnancy despite the transfer of at least ten IVF/ICSI good quality embryos, and RM as having at least three unexplained miscarriages. Fertile controls (FC) were women who had given birth at least once. Endometrial biopsy was performed in the mild luteal phase of a non-conceptual cycle (five women were selected in each group). Affymetrix chips (GeneChip Human Genome U133 Plus2.0 Array) were used for hybridization. Data were normalized by the gcRMA method, and raw p values adjusted by the Bonferroni procedure (1%). Differential expression of selected genes was analysed using real-time PCR. Gene networks and biological functions were explored using the Ingenuity Pathways Analysis software. Endometrial gene expression profiles at the time of uterine receptivity differ dramatically in the endometrium among FC, RM, and IF patients. Compared to FC, 2126 and 2477 genes are differentially expressed in IF and RM groups, respectively, and 2363 between IF and RM. In both conditions, differential gene expression referred mainly to DNA transcription and expression. Other main cellular functions deregulated in IF conditions correspond to cell morphology, cellular development, cell cycle, and cellular assembly, while in RM conditions, deregulated cellular functions relate to cell signalling (degradation of cyclic AMP and calcium metabolism) and cellular maintenance. In both conditions, there is an over-representation of deregulations related to the haematological system. In the IF condition, cell-mediated immune response and nervous system development and function are highly deregulated, while in RM patients, main deregulations are in organ and tissue development, humoral immune response, and muscular system development and function. Extensive endometrial deregulations are present before conception in patients who experienced IF or RM with both distinct and common deregulation.
The objective was to determine whether adding L-carnitine in IVM/IVC medium enhanced maturation and developmental competence of porcine oocytes in vitro. Oocyte maturation rates did not differ significantly among groups supplemented with 0, 0.25, 0.5, or 1 mg/mL of L-carnitine added during IVM (although 2 mg/mL of L-carnitine reduced maturation rate). Compared with control oocytes, those treated with 0.5 mg/mL of L-carnitine during IVM had greater (P < 0.05) rates of blastocyst formation after parthenogenetic activation, and these blastocysts had less (P < 0.05) apoptosis. Adding 0.5 mg/mL of L-carnitine during IVM also significantly reduced intracellular reactive oxygen species (ROS), and increased glutathione (GSH) concentrations. With or without glucose supplementation, 0.5 mg/mL of L-carnitine in the IVM medium significantly hastened nuclear maturation of oocytes. Moreover, supplementing the IVM medium with either glucose or L-carnitine increased (P < 0.05) percentages of oocytes that reached the metaphase II (MII) stage, relative to a control group. Final maturation rates in IVM medium containing either glucose or L-carnitine were not significantly different. Adding L-carnitine (0 to 2 mg/mL) to IVC medium for activated porcine oocytes did not significantly affect development. However, 0.5 mg/mL of L-carnitine in IVC medium significantly reduced reactive oxygen species levels and apoptosis in activated blastocysts, although glutathione concentrations were not significantly altered. In conclusion, adding L-carnitine during IVM/IVC improved developmental potential of porcine oocytes, and also the quality of parthenogenetic embryos, probably by accelerating nuclear maturation, and preventing oxidative damage and apoptosis.
The objective of this study was to detect a therapy for idiopathic and varicocele-associated oligoasthenospermia (OAT). Idiopathic and varicocele OAT patients were randomized into 3 groups. Each group was composed of varying degrees of left varicoceles (graded into 5 grades with echo-color Doppler) and of idiopathic OATs. Group 1 used a placebo, group 2 used oral L-carnitine (2 g/d) + acetyl-L-carnitine (1 g/d), group 3 used L-carnitine/acetyl-L-carnitine + 1 x 30-mg cinnoxicam suppository every 4 days. Drugs were administered for 6 months. The groups were composed as follows: group 1, 71 varicoceles and 47 idiopathic OATs; group 2, 62 varicoceles and 39 idiopathic OATs; group 3, 62 varicoceles and 44 idiopathic OATs. Sperm concentration, motility, and morphology before during and after treatments were assessed. Pregnancy rates and side effects were recorded. Group 1 did not have modified sperm patterns during treatment. Group 2 had significantly increased sperm patterns at 3 and 6 months into therapy in idiopathic patients and in patients with grades I, II, and III varicocele, but not in grades IV and V. Group 3 had significantly increased sperm parameters in all patients, with the exception of grade V varicocele. Group 3 sperm patterns proved significantly higher during therapy than group 2. All sperm patterns fell to baseline after therapy suspension. Minor side effects occurred. Pregnancy rates were 1.7% (group 1), 21.8% (group 2), and 38.0% (group 3) (P <.01). L-carnitine/acetyl-L-carnitine + cinnoxicam suppositories proved a reliable treatment for low-grade varicoceles and idiopathic OATs.
To investigate the protective effect of L-carnitine (LC) against deleterious substances present in the peritoneal fluid (PF) of patients with endometriosis, which may affect the oocyte cytoskeleton and embryogenesis.
Experimental study.
Research embryology laboratory at an academic hospital.
Frozen metaphase II mouse oocytes and embryos.
One hundred metaphase II mouse oocytes were divided into five groups and incubated: PF from endometriosis patients; PF from endometriosis patients + LC; PF from tubal ligation patients (patient control); LC only; and human tubal fluid (HTF) alone. A total of 180 eight-cell mouse embryos were divided into: endometriosis only; tubal ligation only; endometriosis + LC; LC alone; and HTF alone.
Protective effect of LC on oocytes and embryos.
Incubation of the oocytes and the embryos with PF from patients with endometriosis statistically significantly damaged the oocyte microtubules and chromosomes and increased embryo apoptosis compared with controls. Incubation with LC (0.6 mg/mL) statistically significantly improved microtubule and chromosome structure and decreased the level of embryo apoptosis.
We propose the use of LC as a supplement in patients with endometriosis, a novel approach that may help improve in vitro fertilization outcome in these patients.
L-carnitine mediated reduction in oxidative stress and alteration in transcript level of antioxidant enzymes in sheep embryos produced in vitro
L-carnitine mediated reduction in oxidative stress
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