Changes in vitamin E levels as a marker of female infertility

Mussarat Ashraf, Fatima Mustansir, Syed Mujtaba Baqir, Faiza Alam, Rehana Rehman

J Pak Med Assoc . 2020 Oct;70(10):1762-1766. doi: 10.5455/JPMA.40329.


Objective: To study the impact of Vitamin E (VE) levels of follicular fluid (FF) on oocyte competence, embryo development and pregnancy outcome in patients after intra cytoplasmic sperm injection (ICSI).

Methods: It was a cross-sectional study conducted in Islamabad Clinic Serving Infertile Couples in which follicular fluid of 137 females booked for ICSI, was obtained during oocyte retrieval, centrifuged and stored for analysis. VE levels in FF were analyzed by enzyme linked immune sorbent assay. Receiver Operating Curve (ROC)was used to demarcate VE levels required for acquiring pregnancy. Generalized linear model using log binomial regression was applied to see the effect of VE on pregnancy, the effect of VE on oocyte and embryo parameters was assessed by linear regression; all p-values less than 0.05 were considered statistically significant.

Results: ROC suggested 5.49 (unit) as the cutoff value of VE in the pregnancy group, with 72.9% area under the curve. Ninety-one females comprised Group I with VE > 5.49, whereas forty six females formed Group II with VE < 5.49. Follicular fluid VE levels were significantly high in 39 (28.5%) females who compromised pregnancy group. Chances of pregnancy increased to 4% with an increase in VE levels (p-value 0.01). VE gave significant positive relationship with all oocyte (retrieved, mature and fertilized) parameters, cleavage of embryo till its differentiation to blastocysts (p<0.01).

Conclusions: Adequate amount of VE in follicular fluid enhances the possibility of maturation of oocytes which resulted in better reproductive outcome after ICSI.

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Effect of Vitamin E deficiency on spermatogenesis in mice and its similarity to aging

Hirokatsu Saito, Kenshiro Hara, Satoshi Kitajima, Kentaro Tanemura

Reprod Toxicol . 2020 Oct 9;S0890-6238(20)30225-2. doi: 10.1016/j.reprotox.2020.10.003. Online ahead of print.


Vitamin E (VE) plays numerous important roles in mammals because of its antioxidant activity. As a result, VE deficiency (VED) leads to the dysfunction of central nervous, reproductive, and immune systems. However, few studies have reported the effects of VED on the male reproductive system. In this study, we investigated the effects of VED on male reproductive function and examined its relationship to involution in the male reproductive system with aging. We fed a VED or control diet to 4-week-old mice for 12 or 24 weeks. Following the histopathological analysis of reproductive organs, we found seminiferous tubules with exfoliation in the VED groups, and its frequency was significantly increased compared with the controls. Additionally, in the epididymis, a decrease in spermatozoa and an increase in apoptotic germ cells were observed in the VED groups compared with the controls. By Papanicolaou staining, we also found an increase in the proportion of sperm with abnormal morphology in the VED groups compared with the controls. These reproductive effects induced by VED were highly similar to one aspect of those observed in aged mice. Our findings demonstrate that the aging of the male reproductive system may be accelerated because of the impaired in vivo antioxidant capacity induced by VED.

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Comparison of the Effect of Ceratonia siliqua L. (Carob) Syrup and Vitamin E on Sperm Parameters, Oxidative Stress Index, and Sex Hormones in Infertile Men: a Randomized Controlled Trial

Mir Mohammad Reza Aghajani, Soleiman Mahjoub, Faraz Mojab, Mahshid Namdari, Neda Mahdinezhad Gorji, Afsaneh Dashtaki, Parvaneh Mirabi

Reprod Sci . 2020 Sep 21. doi: 10.1007/s43032-020-00314-3. Online ahead of print.


Herbal products with an antioxidant capacity can boost male reproductive functions. The empiric use of Ceratonia siliqua (carob) for its antioxidant properties is common among infertile men in Iran and Turkey. The objective of this study is to investigate the effects of C. siliqua (carob) on semen parameters, oxidative stress markers, and pregnancy rate in a parallel randomized, controlled study. A total of 60 infertile men with oligozoospermia, asthenospermia, and teratospermia were recruited from April 2018 to March 2019. Participants were divided randomly into the following two groups: carob syrup twice a day or vitamin E 100 mg twice a day for 3 months. Semen analysis was performed and hormonal levels and stress oxidative markers were measured in each treatment arm after 3 months. The quality of semen parameters improved in the carob group compared with Vit E semen count (p = 0.04 Cohen’s d = .51), morphology (p = 0.001 Cohen’s d = .93) and motility parameters (p = 0.002 Cohen’s d = .90) were significantly higher in the carob group. No significant difference can be detected in post-treatment hormonal parameters and oxidative markers between groups, except for total antioxidant capacity(TAC) which was higher after post-treatment in carob group. A significantly higher pregnancy rate was found among the carob group. The administration of carob may be an effective agent for the improvement of semen parameters, probably related both to its involvement in the changing of testosterone level and to its antioxidant properties. Nevertheless, additional studies to evaluate the optimal dose and duration of treatment are needed.

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Protective effect of vitamin E on sperm quality and in vitro fertilizing potential and testosterone concentration in polyvinyl chloride treated male rats

Abbas Sadeghi, Farah Farokhi, Ali Shalizar-Jalali, Gholamreza Najafi

Vet Res Forum . Summer 2020;11(3):257-263. doi: 10.30466/vrf.2019.91184.2206. Epub 2020 Sep 15.


Polyvinyl chloride (PVC) has toxic effects through the induction of oxidative stress in the body and testicles. Vitamin E (Vit E) is a dietary compound that functions as an antioxidant scavenging toxic free radicals. The present study aimed to probe the protective effect of Vit E against PVC-induced reprotoxicity in male rats. In this experimental study, 24 male rats were randomly divided into four groups (n=6) including control, Vit E (150 mg kg-1 per day; orally), PVC (1000 mg kg-1 per day; orally) and PVC + Vit E. After 40 days, rats were euthanized and epididymal sperms characteristics, embryo development and malondialdehyde (MDA) and testosterone levels were examined. The PVC decreased sperm count, motility and viability as well as testosterone level and increased sperms with damaged chromatin in comparison with controls. Also, the percentages of fertilization, two-cell embryos and blastocysts as well as MDA levels were decreased in PVC-treated rats. However, Vit E improved PVC-induced alterations in aforesaid parameters. The results indicated that PVC can reduce fertility potential in male rats probably through androgen and sperm quality and quantity reductions, while Vit E can exert protective effects in PVC-related reproductive toxicities.

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Vitamin E and ginseng supplementation to enhance female sexual function: a randomized, double-blind, placebo-controlled, clinical trial

Kiandokht Ghamari, Ladan Kashani, Morteza Jafarinia, Borna Tadayon Najafabadi, Kamyar Shokraee, Sophia Esalatmanesh, Shahin Akhondzadeh

Women Health . 2020 Sep 6;1-10. doi: 10.1080/03630242.2020.1803465. Online ahead of print.


Female sexual disorders (FSD) are a spectrum of disorders common among women, especially in their middle age, which can reduce the female quality of life substantially. We aimed to evaluate the effects of a combined vitamin E and ginseng supplement on amelioration of female sexual dysfunction. In a 6-week, double-blind, randomized, placebo-controlled clinical trial, participants, suffering from sexual dysfunction based on the female sexual function index (FSFI) questionnaire, were randomly allocated to receive the supplement (100 IU vitamin E, 67 mg Korean ginseng, and 40 mg Siberian ginseng) or placebo daily. The primary outcome in our trial was the change in the FSFI total score. Sixty-nine participants were enrolled, but only 31 in each group completed the trial. Changes in the FSFI total score and its domain scores were significant during the trial course within each group. However, the supplement only ameliorated desire and satisfaction domains superior to the placebo. In case of the total score and other domains, the changes were insignificantly different between the treatment groups. Although our study could not find additional benefits for the vitamin E and ginseng supplement over placebo in enhancing sexual function overall, the supplement worked better in enhancing sexual desire and satisfaction.

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Randomized controlled open-label study of the effect of vitamin E supplementation on fertility in clomiphene citrate-resistant polycystic ovary syndrome

Ahmed A Morsy, Nagwa A Sabri, Abdelrehim M Mourad, Eman M Mojahed, May A Shawki

J Obstet Gynaecol Res . 2020 Sep 3. doi: 10.1111/jog.14467. Online ahead of print.


Aim: To evaluate the effect of vitamin E on ovulation and pregnancy in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS).

Methods: A prospective, randomized, controlled, open label study was conducted on women with CC-resistant PCOS. Patients were randomized, to either control group (n = 30), who received metformin 500 mg thrice daily, in addition to 150 mg/day CC for 5 days starting from day 3 of menstruation for three menstruation cycles, or vitamin E group (n = 30) who received vitamin E 1500 IU/day for the whole study period in addition to metformin and CC with the same previous regimen. The primary outcome was cumulative ovulation rate, while secondary outcomes were pregnancy rate, serum midluteal progesterone, mean follicular diameter, number of dominant follicles and endometrial thickness.

Results: Ovulation was reported in 57 (64.8%) of 88 cycles in the control group and 63 (73.3%) of 86 cycles in the vitamin E group (P = 0.227), while pregnancy was reported in 4 (4.5%) of 88 cycles in the control group and 6 (7%) of 86 cycles in the vitamin E group (P = 0.491).There were nonsignificant differences between groups regarding serum midluteal progesterone, number of dominant follicles and mean follicular diameter. Endometrial thickness was significantly higher in the vitamin E group compared to the control group.

Conclusion: The findings of this trial do not support the hypothesis that vitamin E may increase the ovulation and pregnancy rates in women with clomiphene citrate-resistant PCOS.

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Protective effect of hypothermia and vitamin E on spermatogenic function after reduction of testicular torsion in rats

Xuejun Bo, Ping Wang, Yan Nie, Rongfen Li, Jiru Lu, Haiying Wang

Exp Ther Med . 2020 Aug;20(2):796-801. doi: 10.3892/etm.2020.8800. Epub 2020 May 27.


This study was designed to investigate the protective effect of hypothermia and vitamin E on spermatogenic function after reduction of testicular torsion in rats. Ninety-six pure inbred male SD rats were divided into group A, B, C and D according to the principle of body weight and birth similarity, with 24 rats in each group. Four groups of rats were respectively twisted on the left testis to establish unilateral testicular torsion rats. Rats in groups A, B, C, D were respectively given normal saline, hypothermia therapy, vitamin E therapy, and hypothermia and vitamin E therapy. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content of the four groups were detected, and the correlation levels of inflammatory factors IL-1β, hs-CRP and related sex hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (T) were detected by ELISA. Apoptosis of spermatogenic cells of testis in the four groups was detected by flow cytometry. SOD activity and MDA content in groups B, C and D were significantly higher than those in group A, MDA content was significantly lower than that in group A (P<0.05), SOD activity in group D was higher than that in groups B and C, while MDA content was lower than that in groups B and C (P<0.05). The levels of IL-1β and hs-CRP in group A were much higher than those in groups B, C and D (P<0.05). LH and FSH levels in group A were significantly higher than those in groups B, C and D (P<0.05), and in group D were significantly lower than those in groups B and C (P<0.05). Apoptosis rate of spermatogenic cells in group A was significantly higher than that in groups B, C and D (P<0.05). Hypothermia combined with vitamin E can reverse testicular injury in rats and reduce the apoptosis rate of spermatogenic cells.

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Primary and Secondary Markers of Doxorubicin-Induced Female Infertility and the Alleviative Properties of Quercetin and Vitamin E in a Rat Model

Mohammad Samare-Najaf, Fatemeh Zal, Solmaz Safari

Reprod Toxicol . 2020 Aug 15;96:316-326. doi: 10.1016/j.reprotox.2020.07.015. Online ahead of print.


The incidence of cancer has recently risen among the women at the reproductive age. Therefore, exposure to doxorubicin (DOX) chemotherapy has become a cause of reproductive toxicity followed by secondary destructive effects. The present study aimed to evaluate the effects of quercetin (QCT) and vitamin.E (Vit.E) on doxorubicin-induced toxicity in the ovary and uterus, and the secondary bone-related effects in a rat model. Animals were divided into six groups including control normal saline/corn oil (CON), QCT at 20 mg/Kg, Vit.E at 200 mg/Kg, DOX at accumulative 15 mg/Kg, DOX/QCT, and DOX/Vit.E. After 21 days of treatment, the alterations were analyzed in histoarchitecture, apoptosis, hormones secretion, the gene expression of aromatase and estrogen α-receptor (ER-α) in the uterine and ovarian tissues, and serum levels of bone-related factors. The results demonstrated the ameliorative effects of QCT and Vit.E on doxorubicin caused altered ovarian histology, increased apoptosis, decreased ovarian aromatase and ER-α gene expression (p-value<0.05), decreased estrogen and progesterone levels, decreased ALP (p-value<0.001), and increased osteocalcin (p-value<0.05). The findings suggested that the studied antioxidants administration could be a promising fertility preservation strategy in DOX-treated females.

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Nanotechnology in reproduction: Vitamin E nanoemulsions for reducing oxidative stress in sperm cells

F Sánchez-Rubio, P J Soria-Meneses, A Jurado-Campos, J Bartolomé-García, V Gómez-Rubio, A J Soler, M M Arroyo-Jimenez, M J Santander-Ortega, M Plaza-Oliver, M V Lozano, J J Garde, M R Fernández-Santos

Free Radic Biol Med . 2020 Aug 5;160:47-56. doi: 10.1016/j.freeradbiomed.2020.07.024. Online ahead of print.


Vitamin E is considered a powerful biological antioxidant; however, its characteristics such as high hydrophobicity and low stability limit its application. We propose to use nanotechnology as an innovative tool in spermatology, formulating nanoemulsions (NE) that accommodate vitamin E, protecting it from oxidation and promoting its release into the medium. The protective effect of the NE against oxidative stress was assessed in red deer epididymal sperm incubated at 37 °C. Cryopreserved sperm from eleven stags were thawed and extended to 400 × 106 sperm/ml in Bovine Gamete Medium (BGM). Once aliquoted, the samples were supplemented with the NE at different concentrations (0, 6 and 12 mM), with or without induced oxidative stress (100 μM Fe2+/ascorbate). The samples were evaluated after 0, 2 and 4 h of incubation at 37 °C. Motility (CASA), viability, mitochondrial membrane potential, acrosomal status, lipoperoxidation (C11 BODIPY 581/591), intracellular reactive oxygen species (ROS) production and DNA status (SCSA®) were assessed. After 2 and 4 h of incubation, the NE were able to prevent the deleterious effects of oxidative stress, thus improving total and progression motility (P ˂0.05). Moreover, the highest concentration tested (12 mM) improved almost every sperm kinematic variable (P ˂0.05) and preserved sperm viability in samples subjected to oxidative stress. In addition, 12 mM of NE protected the acrosomes integrity, maintained and protected mitochondrial activity, prevented sperm lipoperoxidation and reduced ROS production (P ˂0.05) in samples subjected to oxidative stress. This work indicates for the first time that vitamin E formulated in NE could be a new approach against sperm oxidative damage. This could be highly relevant for sperm physiology preservation in the context of assisted reproduction techniques.

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Ascorbic Acid and Alpha-Tocopherol Contribute to the Therapy of Polycystic Ovarian Syndrome in Mouse Models

Enitome E Bafor, Adaeze P Uchendu, Omorede E Osayande, Osemelomen Omoruyi, Uyi G Omogiade, Evuarherhere E Panama, Olusola O Elekofehinti, Ebube L Oragwuncha, Asanat Momodu

Reprod Sci . 2020 Jul 28. doi: 10.1007/s43032-020-00273-9. Online ahead of print.


Polycystic ovary syndrome (PCOS) affects up to 10% of women within reproductive ages and has been a cause of infertility and poor quality of life. Alteration in the oxidant-antioxidant profile occurs in PCOS. This study, therefore, investigates the contribution of ascorbic acid (AA) and alpha-tocopherol(ATE) on different PCOS parameters. The mifepristone and letrozole models were used, and young mature female mice were randomly assigned to groups of six per group. On PCOS induction with either mifepristone or letrozole, mice were administered AA and ATE at doses ranging from 10-1000mg/kg to 0.1-1000 mg/kg in the respective models. Vaginal cytology, body weights, and temperature, as well as blood glucose, testosterone, and insulin levels, were measured. Total antioxidant capacity and malondialdehyde levels were analyzed. Determination of gene expression of some reactive oxygen species and histomorphological analysis on the ovaries and uteri were performed. At the end of the experiments, AA and ATE restored reproductive cycling, with AA being more effective. AA and ATE increased fasting blood glucose but had no significant effect on serum insulin levels. AA decreased testosterone levels, but ATE caused slight increases. AA and ATE both increased total antioxidant capacity and decreased malondialdehyde levels. AA and ATE also slightly upregulated the mRNA expressions of catalase, superoxide dismutase, and heme oxygenase 1 mainly. AA and ATE also decreased ovarian weight and mostly resolved cysts in the ovaries and congestion in the uterus. This study has shown that AA and ATE are beneficial in the therapy of PCOS.

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