HY-FOLIC® FOR INFERTILITY
Across much of the world, there exists a strong cultural belief that children enhance the well-being of their parents, particularly mothers, and this belief has reinforced prevailing norms surrounding the desire to have children. Parenthood can transform an individual’s life in both positive and negative ways, many of which are unforeseen by parents themselves. Having children may increase happiness, strengthen social bonds with family and friends (Gallagher and Gerstel, 2001; Umberson and Gove, 1989), and create new adult roles that confer rights, responsibilities, and a sense of maturity.
Individuals raised in positive home environments with stable families often aspire to create meaningful lives with one another. They seek to establish families characterized by happiness and love, where they can provide care and affection for their children.
Infertility is a multidimensional issue with social, economic, and cultural implications, posing potential threats to population growth in countries with strong demographic structures. It is a medical condition that may lead to psychological, physical, mental, and spiritual distress, as well as a decline in overall health among affected patients.
The causes of infertility are diverse: one in three infertile women experience disorders of the reproductive system; one in three infertile men face reproductive dysfunction; and one in three couples encounter combined factors or causes that remain unidentified. This unique medical condition involves not only the individual patient but also their partner.
FEMALE INFERTILITY
Infertility is a common medical condition, affecting approximately 10% of women. The likelihood of infertility increases with advancing age. The World Health Organization (WHO) has conducted multinational studies to determine the distribution by sex and the etiology of infertility.
Infertility is defined as the inability of a woman in a couple to conceive after 12 months of regular, unprotected sexual intercourse. This may occur if one partner is unable to contribute to conception, or if the woman is unable to carry a pregnancy to term. Data indicate that infertility is attributable to female factors alone in 37% of cases, to both male and female factors in 35% of cases, and to male factors alone in 8% of cases.
Signs of Infertility in Women
In women, changes in the menstrual cycle and ovulation may serve as indicators of conditions associated with infertility. The symptoms include:
There are many potential causes of infertility; however, identifying the exact cause can be challenging, and some couples are diagnosed with “unexplained infertility.” Possible female infertility factors include:
Several factors can increase the likelihood of infertility in women. General health status, genetic predisposition, lifestyle, and age all play significant roles. Specific risk factors include:
Age is one of the most significant factors influencing female infertility, particularly as many couples delay childbearing until their 30s or 40s. Women aged 35 and older face higher risks of fertility challenges due to:
MALE INFERTILITY
For conception to occur, a man’s sperm must successfully unite with a woman’s ovum. The testes are responsible for producing and storing sperm, and dysfunction of the testes is the primary cause of male infertility. Other contributing factors include hormonal imbalances and obstructions within the male reproductive tract. Approximately 50% of male infertility cases remain idiopathic (of unknown cause).
Between 10% and 15% of male infertility cases are attributable to low sperm count. Hormonal disturbances or blockages that affect sperm transport can result in reduced sperm production. In some cases, men produce significantly fewer sperm than normal. A leading cause of this condition is varicocele, an enlargement of the veins within the testes, which is observed in about 40% of men with infertility.
Common symptoms of male infertility include:
Sperm may be immature, abnormally shaped, or exhibit impaired motility. In some cases, men may produce too few sperm or no sperm at all. These problems may arise from various conditions, including:
Homocysteine is an amino acid produced during the metabolism of methionine, a process dependent on specific B vitamins, including folate. Disruptions in this pathway often lead to elevated homocysteine concentrations, a condition known as hyperhomocysteinemia. Normal plasma homocysteine levels typically range from 5 to 15 µmol/L, although levels may vary between men and women.
Insufficient folate intake has been linked to elevated homocysteine concentrations, contributing to hyperhomocysteinemia. Elevated homocysteine can impair reproductive function in both men and women by affecting sperm quality, ovulation, and embryo implantation. Significantly higher homocysteine levels have been observed in patients with infertility. Research further demonstrates that infertility and recurrent pregnancy loss are correlated with hyperhomocysteinemia. Consequently, folate deficiency is recognized as a risk factor for infertility through its role in disrupting homocysteine metabolism.
Folic acid and 5-MTHF are not the same. Folic acid is the synthetic, inactive form of folate commonly used in supplements and fortified foods. In the body, folic acid must undergo multiple metabolic steps before being converted into its biologically active form, 5-MTHF (Active Folate), as provided in products such as HY-FOLIC®.
Figure 1. Folic Acid Metabolism Process
Within the human body, not everyone metabolizes folic acid into 5-MTHF with the same efficiency. In other words, folic acid supplementation is not equally effective for all individuals. As a result, unmetabolized folic acid (UMFA) may accumulate in the bloodstream, where it has been associated with various health concerns.
This phenomenon is largely explained by genetic variations in MTHFR (methylenetetrahydrofolate reductase), the gene encoding the enzyme responsible for converting folic acid into its biologically active form, 5-MTHF. Studies indicate that approximately 25% of the global population, 42% of the Southeast Asian population and 37,1% of Indonesian population carry common MTHFR polymorphisms (C677>T and A1298>C) that impair this metabolic process, thereby reducing the optimal utilization of folic acid. Consequently, even with supplementation, individuals carrying these variants remain at elevated risk of folate deficiency.
Both men and women experiencing infertility are often found to have low folate levels, which may be linked to MTHFR mutations. Moreover, MTHFR polymorphisms are associated with elevated plasma homocysteine concentrations, which in pregnant women have been correlated with a 4–7% rate of fetal non-viability. Thus, genetic factors play an important role in infertility.
During pregnancy, when folate requirements rise substantially, women carrying MTHFR polymorphisms may fail to benefit from folic acid supplementation due to the accumulation of UMFA, even at high doses. HY-FOLIC®, by providing folate in its active form (5-MTHF), bypasses this enzymatic limitation, making it a more effective option for ensuring adequate folate intake.
Research indicates that folic acid intake exceeding 200 mcg per day can increase circulating UMFA levels, which have been detected in human plasma and linked to several health risks. Reported concerns associated with elevated UMFA include:
Given these concerns, HY-FOLIC® provides a superior alternative to folic acid supplementation, as it prevents the formation of UMFA.
HY-FOLIC® contains (6S)-5-Methyltetrahydrofolic acid glucosamine salt (active folate) 1,100 mcg, which is directly bioavailable and does not require MTHFR-mediated conversion. This makes HY-FOLIC® particularly beneficial for couples struggling with infertility, especially in cases associated with elevated homocysteine levels or MTHFR polymorphisms, both of which can compromise fertility in men and women.
A study involving 33 couples with a history of recurrent miscarriage showed that supplementation with 5-MTHF (Active Folate) have a significant positive impact on pregnancy outcomes. Administration of 5-MTHF therapy was given to 33 couples who experienced fertility problems for 4 months, resulting in spontaneous pregnancies in 13 couples and 13 other couples successfully conceived through Assisted Reproductive Technology (ART). Results showed that 26 couples (86.7%) successfully achieved pregnancy after 4 months of taking 5-MTHF (active folate).
PT. SIMEX PHARMACEUTICAL INDONESIA as one of the pharmaceutical companies in Indonesia, proudly presents HY-FOLIC®, a supplement containaining the active form of folate (5-MTHF). HY-FOLIC® as active folate does not form UMFA which occurs in folic acid administration. HY-FOLIC® has better absorption compared to folic acid; has a dose that can be used for therapy in pregnancy and infertility; and is easy to take. HY-FOLIC® contains 5-MTHF which has been approved by FDA and EFSA and HY-FOLIC® has Halal certified.
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