This study was a randomized clinical trial conducted on 37 patients with oligoasthenospermia treated by IUI during 2016-2017. In this study, the patients were randomly divided into two groups of oligoasthenospermia treated with (Case group) and without Myo-inositol (Control group). The case group received 0.5 ml of Myo-inositol with a concentration of 2 mg/ml and incubated at 37°C incubator for 2 hr, but the control group had no interventions. The results of this study showed that there was a significant increase in sperm motility during the treatment with Myo-inositol. The therapeutic effect of this method was confirmed on induction of pregnancy in 18% of the treated patients, in such a way that was about twice greater than those who did not receive the drug. According to the results of this study, the use of Myo-inositol is efficient enough to change sperm parameters to increase the chance of fertility. Int J Reprod Biomed (Yazd). 2019 Oct; 17(10): 749–756. Published online 2019 Nov 7. doi: 10.18502/ijrm.v17i10.5296 Myo-inositol (myo-ins) represents a safe compound that proved useful in issues related to female fertility and pregnancy. In fact, myo-ins participates in several signaling processes, including the pathways of insulin and gonadotropins, and, therefore, it is likely to positively affect fertility. In particular, several clinical trials demonstrate that its administration can have therapeutic effects in infertile women, and that it can also be useful as a preventive treatment during pregnancy. Particularly, myo-ins could prevent the onset of neural tube defects and the occurrence of gestational diabetes mellitus, promoting a trouble-free gestation. Due to the safety and efficiency of myo-ins, such a treatment may also substitute several pharmaceuticals, which are contraindicated in pregnancy. Pharmaceuticals (Basel). 2021 Jun; 14(6): 504. Published online 2021 May 25. doi: 10.3390/ph14060504

Coenzyme Q10 (CoQ10)—an essential cofactor for energy production with major antioxidant properties—is commonly used to support spermatogenesis in idiopathic male infertility. This systematic review aims to elucidate the usefulness of CoQ10 supplementation in the treatment of male infertility, particularly with regard to semen quality assessed by conventional and advanced methods, and pregnancy rates. All studies report a beneficial effect of CoQ10 supplementation on semen parameters, although randomized controlled trials are a minority. Moreover, the optimal dosage of CoQ10 or how it can be combined with other antioxidant molecules to maximize its effect is unknown. However, CoQ10 is still one of the most promising molecules to treat idiopathic male infertility. Antioxidants (Basel). 2021 Jun; 10(6): 874. Published online 2021 May 30. doi: 10.3390/antiox10060874 Management of women with reduced ovarian reserve or poor ovarian response (POR) to stimulation is one of the major challenges in reproductive medicine. This prospective, randomized controlled study included 186 consecutive patients with POR stratified according to the POSEIDON classification group 3 (age < 35, poor ovarian reserve parameters). The participants were randomized to the CoQ10 pre-treatment for 60 days preceding IVF-ICSI cycle or no pre-treatment. The number of high quality embryos was a primary outcome measure. CoQ10 pretreatment resulted in significantly lower gonadotrophin requirements and higher peak E2 levels. Women in CoQ10 group had increased number of retrieved oocytes (4, IQR 2–5), higher fertilization rate (67.49%) and more high-quality embryos (1, IQR 0–2); p < 0.05. Significantly less women treated with CoQ10 had cancelled embryo transfer because of poor embryo development than controls (8.33% vs. 22.89%, p = 0.04) and more women from treatment group had available cryopreserved embryos (18.42% vs. 4.3%, p = 0.012). The clinical pregnancy and live birth rates per embryo transfer and per one complete stimulation cycle tended to be higher in CoQ10 group. Pretreatment with CoQ10 improves ovarian response to stimulation and embryological parameters in young women with poor ovarian reserve in IVF-ICSI cycles. Reprod Biol Endocrinol. 2018; 16: 29. Published online 2018 Mar 27. doi: 10.1186/s12958-018-0343-0

Daily supplementation with ALA improved total motility and progressive motility of the spermatozoa. In the ALA-treated group, sperm motility and progressive motility increased significantly, similarly, the mean percentage of sperm vitality demonstrated a significant increase among the ALA treated group (p < 0.001). Analysis revealed a statistically significant increase in semen volume and sperm concentration in the ALA supplemented group, while abnormal morphology decreased significantly (p < 0.001). ALA supplementation significantly improved sperm parameters and functional tests in group A patients. ALA supplementation in patients with idiopathic asthenozoospermic thus enhanced sperm quality and viability Human Fertility , Published online: 13 Jan 2022 https://doi.org/10.1080/14647273.2021.2025271 The available literature demonstrates the positive effects of ALA in multiple processes from oocyte maturation (0.87 ± 0.9% of oocyte in MII vs 0.81 ± 3.9%; p  < .05) to fertilization, embryo development (57.7% vs 75.7% grade 1 embryo; p  < .05) and reproductive outcomes. Its regular administration both in sub-fertile women and men shows to reduce pelvic pain in endometriosis ( p  < .05), regularize menstrual flow and metabolic disorders ( p  < .01) and improve sperm quality ( p  < .001). ALA represents a promising new molecule in the field of couple infertility. Gynecological Endocrinology Volume 37, 2021 - Issue 6, https://doi.org/10.1080/09513590.2020.1843619 This study included 101 consecutive IVF/ICSI cycles in 101 infertile patients over 37 years who were given lipoic acid at a dose of 200mg twice a day orally for 60-90 days before and during COS period (study group, n=53) or were not given lipoic acid (control group, n=48) in our center between March 2015 and June 2016. The expression of PGC-1alpha mRNA in granulosa cells was analyzed by realtime RT-PCR. The numbers of mature oocytes, fertilized oocytes and grade I or II embryos were significantly higher in the study (p < 0.001, p < 0.001, p = 0.003, respectively). Relative amount of PGC-1alpha mRNA in the ganulosa cells was significantly higher in the study group of 8.45 ± 3.84 compared with 3.04 ± 1.98 in the control group (p < 0.001). Clinical pregnancy rate seemed to be higher in the study. The supplementation of lipoic acid of 200mg twice a day for 60-90 days increases the numbers of mature oocytes and good quality embryos and PGC-1alpha gene expression in granulosa cells in aging women undergoing IVF. Fertility and Sterility, VOLUME 108, ISSUE 3, SUPPLEMENT , E228, SEPTEMBER 01, 2017 DOI: https://doi.org/10.1016/j.fertnstert.2017.07.689

After N-Acetyl-Cysteine (NAC) treatment, patients’ sperm count and motility increased significantly whereas abnormal morphology, DNA fragmentation and protamine deficiency showed significant decreases compared to pre-treatment levels (P < 0.05). Hormonal profile improvement was associated with lowered FSH and LH levels and increased amount of testosterone (P < 0.05). TAC significantly increased and MDA decreased with an inverse significant correlation between TAC and MDA (P < 0.05). NAC oral supplementation may improve sperm parameters and oxidative/antioxidant status in infertile males. Reproductive Biology and Endocrinology volume 17, Article number: 24 (2019) The objective of this study is to explore the efficacy and safety of N-acetyl-cysteine (NAC) as adjuvant therapy in female infertility. Fifteen RCTs recruiting 2330 female receiving NAC were included. The pooled estimate showed the statistically insignificant improvement in outcomes; clinical pregnancy rate 1.55 (95% CI 0.98-2.47; I2=68%; p<0.01), ovulation rate 1.77 (95% CI 0.76-4.14; I2=90%; p<0.01), multiple pregnancy rate 0.83 (95% CI 0.34-1.99; I2=10%; p=0.31) and miscarriage rate 0.76 (95% CI= 0.37, 1.53; I2=0%; p=0.69) . NAC was found less efficacious and safe than metformin in all outcomes. Overall, NAC showed statistically insignificant (OR=0.98-2.47). AC can be an effective adjuvant in PCOS related and unexplained female infertility. The effect could be more profound in women with high BMI, insulin resistance, and oxidative stress. J Basic Clin Physiol Pharmacol. 2020 Nov 19;32(5):899-910. DOI: 10.1515/jbcpp-2020-0107

According to what has been said, it is clear that the use of l-carnitine and its esters, acetyl-l-carnitine and propionyl-l-carnitine, is effective in determining an improvement in sperm parameters and in particular of the total motility and progressive motility, reduces the levels of ROS in seminal fluid, and would be able to improve the quality of the semen, also in case of cryopreservation. The administration of these molecules in the treatment of male infertility (alone or in combination) is, therefore, a rational and effective therapeutic strategy. Andrology, Volume4, Issue5 September 2016 Pages 800-807, https://doi.org/10.1111/andr.12191 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. 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. 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. Reprod Biol Endocrinol. 2018 Jan 26;16(1):5. doi: 10.1186/s12958-018-0323-4. DOI: 10.1186/s12958-018-0323-4

The clinical efficacy and acceptance of L-arginina HCL was tested in 40 infertile men. All of these men had a normal number of spermatozoa (> 20 million/ml), but a decreased motility; this decreased motility was not due to infection or to immunological disorders. The treatment consisted of 80 ml of 10% L-arginine HCL administered daily per os for 6 months. L-arginine HCL showed to be able to improve the motility of spermatozoa without any side-effects. Minerva Urol Nefrol . 1994 Dec;46(4):251-3. This small-scale randomized controlled study aimed to examine the effect of l-arginine supplementation on the human chorionic gonadotropin (hCG)-positive rate and clinical pregnancy rate (CPR) in women undergoing assisted reproductive technology (ART) treatment for 3 months. In the subgroup of women receiving ART because of male infertility, the hCG-positive rate and CPR were significantly increased in the l-arginine groups compared to those in the control group (13.42 [95% CI, 1.42-366.9] and 13.62 (95% CI, 1.42-367.6), respectively). Thus, arginine supplementation may be an option for women who desire pregnancy, especially those undergoing an ART program because of male infertility. Nutr Res . 2020 Oct;82:67-73. doi: 10.1016/j.nutres.2020.08.008. Epub 2020 Aug 22., DOI: 10.1016/j.nutres.2020.08.008