Insulin is a pancreatic hormone that stimulates the uptake of glucose into the cells so to make it available for the production of energy within the cellular mitochondria. A defect of insulin activity causes accumulation of glucose in the blood (hyperglycaemia). Insulin resistance is a condition characterized by low sensitivity of the insulin receptors. When insulin resistance affects the whole body, including muclular tissues, it is responsible for Diabetes Mellitus type 2, when affecting mainly the ovarian follicles in fertile women it sustains the development of the Polycystic Ovary Syndrome (PCOS). This study is registered in the American registry for clinical studies and trials ( https://clinicaltrials.gov) and the Dutch Trial registry ( www.trialregister.nl). The investigator obtains written informed consent before study participation from all participants.

Standard sperm tests focus on quantity, motility and morphology but do not test for DNA fragmentation. AEs are defined as any undesirable experience occurring to a subject during the study, whether or not considered related to Impryl. All AEs reported by the subject or observed by the investigator or his staff will be recorded. Time to pregnancy defined as (1) the time between randomisation and reaching ongoing pregnancy (confirmed by ultrasound) and (2) the time between start of fertility treatment during the study (EM, IUI and IVF/ICSI) and reaching ongoing pregnancy. Patients who are lost to follow-up right after achieving a pregnancy of less than 8 weeks of gestation are considered not to have achieved an ongoing pregnancy.

The sponsor will report expedited the following SUSARs through the web portal ToetsingOnline to the METC: PCOS (polycystic ovary syndrome) affects 1 in 10 women in the UK. It can have a significant effect on women’s fertility, through irregular or absent periods, impacting ovulation, with only 20% of PCOS women ovulating each month, even if some have seemingly regular periods. Women with PCOS are more likely to have poorer egg quality, which may be a result of overexposure to male hormones such as testosterone. Inofolic ® Alpha is a supplement that could help you – with little or no side effects. Impryl contains riboflavin (Vitamin B2), niacin (Vitamin B3), pyridoxine (Vitamin B6), 5-methyltetrahydrofolate (activated Vitamin B9), methylcobalamin (activated Vitamin B12), zinc, betaine and L-cystine. These ingredients are either essential (must be consumed in the diet) or semi-essential (can be made in the body, but typically not in sufficient quantities) and several are in their activated forms (don’t require processing by the body).

Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. However, it may happen that multiple genetic variants on the same pathway converge on the same subject generating a critical assembly. In these cases any increased demand or toxic load may generate a metabolic collapse. Such collapse is predicted to occur at time of increased demand, which in the case of the one carbon metabolism is at time to reproduce. How is IMPRYL® manufactured? Its formula contains all the substances required for the activation of antioxidant defenses in the absence of any substance with direct antioxidant activity. Moreover, it supplies the substances capable of compensating for the possible presence of the most common pathological variants of metabolic enzymes, in particular: Impryl is the first antioxidant dietary supplement based on a well defined mechanism of action: indirect antioxidant activity by means of the modulation of the enzyme CBS that regulates the synthesis of glutathione (GSH), the primary cellular antioxidant.

Time to ongoing pregnancy will be evaluated by the Kaplan-Meier approach; differences between the two arms will be tested with the log-rank test. Similar analyses will be conducted per stratum (EM, IUI or IVF/ICSI). The other secondary outcomes (overall pregnancy number, number of miscarriages, live birth rate, fertilisation rate and EUR) will be evaluated similarly to the primary outcome. Changes in semen analysis, leading to different fertility treatment categorisations, will be calculated with descriptive statistics. Furthermore, AEs will be summarised. Sensitivity analyses will be performed to evaluate possible effects in case of protocol amendments. A recent Cochrane review suggested that antioxidant supplementation in male infertility might improve the outcomes in assisted reproductive technologies. 18 However, the evidence was rated as low, and clinical studies showed contradictory results with sometimes even a negative effect of high doses of antioxidants due to reductive stress as a rebound effect. 19 Alternatives were therefore explored, to support the natural antioxidant defences that are predicted to act within the modulation of the natural cellular homeostasis without generating rebound effects. For example, the use of nutritional supplements supporting DNA methylation and the homocysteine pathway. Homocysteine is the end product of the 1-carbon cycle, feeding DNA methylation,and the starting substrate for the thiol GSH (l-γ-glutamyl-l-cysteinyl-glycine) de novo biosynthesis. GSH is the most important endogenous antioxidant, involved in maintaining the antioxidant balance in human tissues and directly involved in the elimination of ROS. 20 Homocysteine is an inhibitor of the methylation process and a powerful pro-oxidant. It has a negative effect on spermatogenesis, and its concentration in the ejaculate is inversely correlated with fertility outcome. 21 22 Dattilo et al stated that the ideal supplement should work by favouring homocysteine recycling by restoring the efficiency of the 1-carbon cycle, therefore ensuring the availability of activated methyl groups for DNA methylation and feeding the intracellular antioxidant system by supporting GSH synthesis. 23 In non-randomised pilot studies with such a 1-carbon cycle supporting nutritional supplement Condensyl, the precursor of Impryl, there was a significant decline of DNA fragmentation index leading to an improvement of the clinical pregnancy rate. However, the quality of these studies for the impact on pregnancy rate is rather low due to the non-randomised nature and having no control group. 21 24 25 Furthermore, the ideal parameters to measure DNA damage might not be DNA fragmentation but sperm-oxidation level which indirectly affects DNA damages. 26 27 The study is designed as a superiority trial. Based on the above mentioned data, we expect a 7.3% increase in ongoing pregnancy number when men are treated with Impryl compared with placebo. However, after randomisation, patients can directly start with both intervention and achieving a pregnancy, either spontaneously or with fertility treatment. In these first months, the effect of the intervention is expected to be suboptimal due to the duration of the spermatogenesis (72 days before whole renewal). Therefore, we adjusted the expected increase of 7.3% to a more realistic effect of 6.5%. We assume an equal increase in all fertility groups (meaning EM, IUI and IVF/ICSI) from 20% to 26.5%.

He did cut down on caffeine a lot but probably actually drunk more and put on a bit of weight. I 100% think this is due to Impryl.

Driving biology to support fertility

Regarding your appetite, we are not aware of any reason why Impryl would have this affect and can confirm that we have not had any other reports of this nature. We will analyse all data on an intention-to-treat basis. Data of patients who are lost to follow-up will be included in their randomised group: The present invention relates to pharmaceutical, dietary and/or food compositions, preferably dietary supplements, exerting the ability to activate the endogenous antioxidant system by feeding essential micronutrients to both the one carbon cycle and the trans-sulfuration pathway so to achieve effective oxy-redox homeostasis together with an improved energy balance and healthy processes of cell growth and differentiation including DNA methylation and epigenetic regulation. Glutathione (GSH) is the main antioxidant in the human body. It diffuses everywhere and continuously re-charges with antioxidant power all the other physiologic antioxidants. Important, GSH is not a dietary substance and is not provided by the diet neither can be assumed as a supplement. Glutathione is synthesized by the transsulfuration pathway of One Carbon Metabolism (OCM) using homocysteine/cysteine as the main substrate.

Aitken RJ, Clarkson JS, Hargreave TB, et al. . Analysis of the relationship between defective sperm function and the generation of reactive oxygen species in cases of oligozoospermia. J Androl 1989;10:214–20. 10.1002/j.1939-4640.1989.tb00091.x We aimed to recruit 1200 male participants as a part of an infertile couple, based on the following data and power calculation. A methyl group is a single carbon atom bonded with three hydrogen atoms. The methionine pathway of One Carbon Metabolism (OCM) produces S-adenosylmethionine (SAMe), the universal activated methyl donor in the human body. Methyl groups can be dynamically transferred to and from biological macromolecules such as DNA, RNA and proteins in a process called methylation to influence structure and function. What is homocysteine (HCY)? All couples will receive our standard care for infertility according to the guidelines of the Dutch Society of Obstetrics and Gynaecology. After diagnostic workup, couples will either start with EM (6 months), IUI, IVF or ICSI. Participants will take study supplement for a maximum of 6 months, even if the fertility intervention (6× IUI of 1× IVF/ICSI cycles) is not completed.

Competing interests The study is conducted by the department of gynaecology and obstetrics of the Radboudumc. As stated above in the funding section, an unrestricted grant from Goodlife Pharma B.V. was provided for the conduct of the trial. Everyone will have advice to give to you on how to get pregnant. ‘Have you tried…?’, ‘why don’t you just…?’ But ultimately, conception starts with the quality of the sperm and the egg. The best way to support your sperm (smallest cell in the body) and egg (largest cell in the body) is by creating a balanced metabolism at a cellular level – and this is exactly how Impryl ®works. The activated micronutrients in Impryl ® bring your body into a fine metabolic balance, allowing your body’s own natural antioxidant, glutathione, to optimise both egg and sperm quality as they develop. There aren’t many fertility supplements that provide this unique type of support. In fact, most fertility supplements provide unbalanced support: in other words, they focus on the benefit of one ingredient over others. Many contain strong antioxidants that can upset this important metabolic balance, damaging sperm and egg quality. But Imrpyl ®is different. Find out more about how Impryl ®can help you. Do you have PCOS? Live birth rate (beyond 24 weeks, defined as the birth of a living child) within study period of 15 months.