pregnancy rates or live-birth rates, and the combination therapy of metformin and clomiphene citrate did not provide a significant benefit compared to clomiphene citrate alone. First-line therapy for ovulation induction in women with PCOS remains the anti-estrogen clomiphene citrate or the aromatase inhibitor letrozole. Male Treatment for oligospermia is centered around underlying causes, such as endocrine and systematic disorders that can cause hypogonadism. Typically, other assisted reproductive technologies are used. Although there is no FDA indication for use of aromatase inhibitors improving spermatogenesis, testolactone has been shown to be effective when compared to placebo. Though there is no FDA indication for the use of clomiphene in male infertility, it has been prescribed since the 1960s. As of 2013, there is not substantial evidence to suggest that clomiphene can treat male infertility. Combinations of vitamins and minerals, including selenium, co-enzyme Q10, L-carnitine, folic acid, zinc, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have been shown to improve male infertility, but due to the low amounts of studies and participants, more clinical studies are needed. Folate in combination with zinc supplementation was shown to have a statistically significant effect on sperm concentration and morphology when compared to placebo. There is evidence suggesting a significant association between vitamin D serum concentrations and the quality of sperm in men, characterized by the sperm's motility and progress motility. Because the quality of men's sperm is influenced by genetics, results should be interpreted cautiously. There is little evidence that supplementation with antioxidants, such as pentoxifylline will increase male fertility. As of September 2017, mesenchymal stem cell therapy for infertility has been studied in animals, but has not entered clinical trials. Stem cells collected from bone marrow and umbilical cord have shown the most ability to rehabilitate fertility in animals, but more studies are needed to determine efficacy. Adverse effects Cancer Since infertility increases the risk of ovarian cancer, fertility drugs have been used to combat this but the cancer risks are still not completely known. As of 2019, there have been studies that have shown the risk of developing ovarian cancer is higher when taking fertility medications. However, due to the low number of studies, lack of follow-up time and other contribution factors, the risk is unclear. Most studies conducted have shown that fertility drugs do not increase the risk of other gynecologic cancers (cervical and endometrial) or other malignant cancers (thyroid, colon, melanoma, breast). The