I. Hormone therapy 1. androgens: including low-dose androgen therapy and testosterone rebound therapy. vandekerckhove et al [3] conducted an evidence-based analysis of 11 randomized controlled trials and showed that low-dose androgens were not statistically different in semen parameters and pregnancy rates compared with placebo or no-treatment controls (OR1.10, 95% CI0.75 to 1.61); testosterone There was also no difference in rebound therapy compared with controls (OR1.10, 95% CI0.42 to 6.16) and side effects such as headache and papules, suggesting that there is insufficient evidence to support the use of androgens for idiopathic male infertility as an efficacious approach. 2. Gonadotropins: Based on the clinical finding that hCG (humanchorionic
gonadtropin) was found to be effective in the treatment of hypogonadal mechanical hypogonadism with low gonadotropins, hCG and hMG have been used since the early 1960s to treat idiopathic oligospermia. However, Schill [4] reviewed 39 uncontrolled trials using hCG/hMG and reported limited results with pregnancy rates ranging from 8% to 14%. Arango et al [5] reported one case of significant breast feminization and severe impairment of spermatogenesis after treatment with hCG/hMG, which recovered after discontinuation of the drug. Few reports of hCG/hMG for idiopathic male infertility have been published in the last decade. Recombinant FSH (follicle-stimulating
hormone) is also often used to treat idiopathic infertility, with the hope that pure FSH may provide a little better effect than hCG/hMG. A Meta-analysis [6] showed no significant change in pregnancy rates in 223 treated patients (OR 1.45, 95% CI 0.78 to 2.70). A randomized, single-blind, placebo-free study demonstrated that the use of recombinant human FSH increased sperm counts in patients with idiopathic oligospermia who had mild hypospermatogenesis with normal blood FSH levels and inhibin levels on testicular fine-needle aspiration biopsy [7]. In a randomized controlled study showed that FSH treatment significantly improved the ultramicroscopic structure of spermatozoa and increased the ICSI (intracytoplasmic
sperm injection) treatment in pregnancy rates [8]. 3. gonadotropin releasing hormone (GnRH): the use of GnRH has been shown to improve pregnancy rates with ICSI (intracytoplasmic sperm injection) [8],
GnRH: The use of GnRH is a way to increase endogenous pituitary gonadotropins by acting directly on the pituitary gland and promoting pituitary production rather than using exogenous hCG/hMG to increase pituitary gonadotropin levels. Although a controlled trial showed that GnRH was ineffective [9]; Chow et al. treated idiopathic male infertility by intranasal GnRH and found that after 30 min in a GnRH stimulation experiment, blood FSH was elevated ≥1.5-fold yielding patients with significantly increased sperm motility, while patients with an insignificant rise in FSH were ineffective [10]. 4. anti-estrogens: anti-estrogens are the most commonly used treatment for idiopathic infertility. This drug competitively binds estrogen receptors in the hypothalamus and pituitary gland, and the negative feedback effects of estrogen are effectively inhibited, leading to increased secretion of GnRH, FSH, and LH, which stimulates testosterone production by interstitial cells and facilitates spermatogenesis. The common dose of clomiphene is oral 25?/d, and the dose used to range from 12.5 to 400?/d; however, doses above going to 200?/d significantly inhibit spermatogenesis. Because high levels of testosterone may inhibit spermatogenesis, it is necessary to monitor blood gonadotropin and testosterone levels to ensure that testosterone levels are within normal limits. Tamoxifen citrate, an anti-estrogenic drug with less estrogenic effect than clomiphene, is the drug of choice in Europe for the treatment of male infertility at doses ranging from 10 to 30?/d. In a Cochrane systematic review, Vandekerckhove et al. showed a positive endocrine effect of anti-estrogenic drugs such as testosterone; the overall pregnancy rate in the treatment group was 15.4% compared to 12.5% in the control group. 12.5%, with no statistical difference between the two comparisons (OR1.26, 95% CI0.99-1.56), and there does not seem to be sufficient evidence to show that they improve productivity in patients with idiopathic oligospermia [11]. However, Dimitrios et al [12] used a combination of tamoxifen and testosterone in a prospective randomized placebo-controlled trial to treat 212 patients with idiopathic oligospermia, resulting in a pregnancy rate of 33.9% in the treatment group compared to 10.3% in the control group (95% CI 2.615 to 3.765). 5. Aromatase inhibitors: Aromatase is a cytochrome P450 enzyme found in the testes, skin, liver, brain and adipose tissue. The function of this enzyme is to convert testosterone to estradiol and estradiol to estrone. Transdermally implanted aromatase inhibitor capsules have been shown in animal studies to improve spermatogenesis, reduce seminal plasma E2 concentrations, increase T concentrations, and produce sperm in azoospermic dogs [13]. The main drugs that can be used clinically are: testosterone, anastrozole, letrozole, and exemestane, but they are expensive and have less clinical application. 6. growth hormone (growth hormone,
GH: Some studies suggest that GH may increase folliculogenesis in women, and similarly it is envisioned to increase spermatogenesis. lee [14] in a prospective, open, controlled study suggested that GH did not increase or decrease the number of sperm in patients with severe idiopathic oligospermia. While Ovesen et al [15] in a prospective open study showed that GH increased sperm motility without significant changes in sperm count. radicioni et al [16] in an open trial concluded that a short course of recombinant GH increased sperm density and motility. II. Non-hormonal treatment 1. Vasopressin: Vasopressin has been widely used to treat idiopathic male infertility in Europe and Japan. Although the vasopressin-kinin system plays a role in the inflammatory response, its role in spermatogenesis is unknown. The commonly used dose is 600 IU/d orally.
There are few side effects, except for the possibility of exacerbating chronic infections. O’Doovan et al [17] demonstrated a positive effect of vasopressin treatment in an early meta-analysis of 5 controlled trials, with an overall pregnancy rate twice as high in the treatment group as in the control group, although the results have been questioned. meta-analysis of 4 randomized placebo-controlled double-blind trials showed no significant effect of vasopressin use on pregnancy in 197 infertile couples significant effect (OR 0.92, 95% CI 0.40 to 2.08) [6]. 2. bromocriptine: bromocriptine has achieved better results in the treatment of patients with hyperproliferative vasopressors. It was envisaged that prolactin might have a direct effect on spermatogenesis, and therefore bromocriptine administration was used as an empirical treatment option for idiopathic infertility. However, the results of the related clinical reports are unfortunate, as Vandekerckhove et al [18] showed in a Cochrane systematic evaluation that bromocriptine significantly reduced blood prolactin levels (OR 0.70, 95% CI 0.15 to 3.24). 3. hapten cocaine: hapten cocaine is a phosphodiesterase inhibitor and was initially used in male infertility patients on the basis of a possible improvement in the testicular microenvironment. Maier et al [19] found no effect on sperm density, viability, etc. Merino [20] et al. treated 47 patients with idiopathic weak spermatozoa in a randomized placebo-controlled trial, and showed that ketococaine improved sperm viability, with a difference compared to placebo. 4. Canidine: Spermatozoa are produced in the testis and undergo post-gonadal adjustment in the epididymis before becoming motile and acquiring the ability to fertilize. Levocarnitine is transported from the plasma and colonizes the epididymal lumen. In several animal samples (including human), the concentration of leucanidine was 2000-fold higher in the caudal part of the epididymis than in the plasma. Levocaine enters the spermatozoa by passive diffusion and is acetylated to acetylated leucovorin. Levocannabinoids and acetylated leucocannabinoids are transported from the cytoplasm in long-chain fatty acids into the mitochondria for B-oxidation use, converting bound coenzyme A into free coenzyme A for metabolic use and providing an easily available acetyl radical for the tricarboxylic acid cycle [21]. Zopfgen [22] et al. showed that free and total carnitine was significantly lower in infertile patients with normal spermatozoa, oligospermatozoa and azoospermia compared to controls; however, carnitine levels have been increased in patients with weak spermatozoa. Animal tests have suggested that carnitine increases sperm motility in weakly spermic and oligospermic stallions, but not in normally spermic stallions [23].Andreal et al [24] observed 100 patients with unexplained male infertility in a placebo-controlled double-blind crossover trial and showed significant results in terms of sperm count and motility in the treatment group compared to the placebo group, with eight of the patients’ spouses during the trial Andreal et al [25] observed 60 patients with idiopathic oligohydromorphic spermatozoa in a randomized double-blind placebo-controlled trial using carnitine and acetylated carnitine, which resulted in a significant increase in sperm motility in the treatment group compared to the placebo group and 4 The results were significantly higher sperm motility and 4 pregnancies in the treatment group compared with the placebo group, but the seminal plasma carnitine concentration was not significant compared with placebo. 5. antioxidant therapy: excessive reactive oxygen clusters impair sperm function to the detriment of male fertility. giancarlo et al [27] treated 22 patients with weak spermatozoa with CoQ10 in an open uncontrolled study. there was a significant increase in the level of CoQ10 within the seminal plasma and sperm cells after treatment, and sperm viability was also significantly increased. mina et al [28] used the herb sairei-toz was used as an antioxidant to treat 47 patients with oligospermia or without weak spermatozoa and showed that it improved sperm quality and testicular blood supply, but SOD activity did not change significantly after treatment. 6. other treatments: Jannini et al [29] and others found that Viagra not only improved erectile dysfunction due to infertility stress, but also increased the number of spermatozoa in the cervical mucus and the total number of anterograde sperm motility. Magnesium lactate was shown to be ineffective in improving semen quality and pregnancy rates in a randomized placebo-controlled study [30]. In randomized placebo-controlled trials showed increased sperm count with folic acid and zinc sulfate combined [31]. Trinostat? mast cell blocker increased sperm count with no change in sperm viability [32]. a-blocker treatment was shown to be effective by Yamamoto et al [33] in a randomized, double-blind, placebo-controlled study. Other drugs including thyroxine, arginine, steroids, antibiotics, prostaglandin synthase inhibitors anti-inflammatory pain, vitamin A, vitamin C, vitamin E, and herbal medicines have also been used to treat idiopathic male infertility. However, most of the treatments have not been tested in true randomized comfort-controlled trials. The cause of idiopathic male infertility is unknown, and treatment theories are based on hypothesis, treatment is not targeted, the effect is limited, and the reports are inconsistent. The drug treatment of idiopathic infertility has a long way to go, and it is imperative that: firstly, because idiopathic infertility may arise from disorders in any of the many unrelated pathways in the process of spermatogenesis and maturation, basic research is needed to clarify the process of spermatogenesis and maturation and the changes in relevant test indicators when disorders occur at different stages of spermatogenesis and maturation, and gradually clarify the etiology of idiopathic infertility through basic research. Secondly, the adjustment of reproductive endocrinology is of great significance in the treatment of male infertility, therefore, we should devote ourselves to the development of new drugs with definite efficacy in spermatogenesis or sperm maturation and pituitary testicular endocrine function. infertility treatment protocols also deserve our attention. The drugs currently used for empirical treatment should be subjected to randomized double-blind controlled trials with large samples to verify the effectiveness of the drugs from the perspective of evidence-based medicine, to make scientific judgments on the efficacy of the drugs, and to discard the ineffective drugs. It is also important to note that empirical treatment, once used, should be maintained for at least 3 to 6 months with the aim of including a complete spermatogenesis cycle of 74 d. Infertility is not a fatal disease, and drugs with high toxicity or serious adverse effects should be avoided in the selection of empirical treatments into. Geng Liguo, Department of Male Medicine, Zhuhai Hospital, Guangdong Provincial Hospital of Traditional Chinese Medicine