FSH therapy for idiopathic male infertility: four schemes are better than one

[madman]

ABSTRACT

Objective

The aim of this article is to propose an algorithm that aids the clinician in choosing the best therapeutic scheme of follicle-stimulating hormone (FSH) in the treatment of men with idiopathic infertility, based on testicular volume (TV) and serum total testosterone concentrations; highlighting the potential role of additional therapy with hCG in a sequential temporal scheme.


Materials and methods

We subdivided patients into four clinical groups: patients with normal TV and serum testosterone concentrations (A); patients with normal TV and reduced serum testosterone concentrations (B); patients with reduced TV and serum testosterone concentration (C); and patients with low TV e normal serum testosterone concentrations (D). Then, we administered to each group a specific therapeutic scheme. Group A: was treated with FSH alone for at least 3 months; Group B: was treated with hCG alone twice a week for 3 months and the addition of FSH for poor responders (unmodified sperm parameters); Group C: was treated ab initio with FSH and hCG until the pregnancy was reached; group D: treated with FSH alone for 3 months and addition of hCG for moderate poor responders (increased TV but unmodified sperm parameters) or second cycle of FSH for 3 months for severe poor responders (unmodified TV and sperm parameters). After 6 months we evaluated the therapeutic response in terms of sperm parameters normalization rate, spontaneous pregnancy rate, and sperm DNA fragmentation normalization rate.


Results

40% of patients became normozoospermic after treatment, while 30% achieved spontaneous pregnancy. B was the group that best responded to treatment in terms of normalization of seminal parameters; while the highest spontaneous pregnancy rate was obtained from the D group. B group also obtained the highest sperm DNA fragmentation normalization rate.


Conclusions

To date, no reliable predictors of response to treatment with FSH exist, but TV and serum testosterone concentrations can help the clinician choose the best therapeutic scheme for men with idiopathic infertility. The groups treated with a sequential temporal scheme (B and D groups) showed better clinical results compared with two groups treated with conventional schemes (A and C groups.)






Conclusion

Gonadotropin therapy may represent a good alternative to ART in couples suffering from idiopathic male infertility. But, the scheme must be customized and, in the evaluation of the patients, it is necessary to keep in mind that:


a. TV must always be measured by testicular ultrasound, since the orchidometric evaluation may be inaccurate due to overestimation [15];

b. the echotexture as well as the volume is an important indicator of testicular health. For this reason, patients with TV between 12 and 15 mL can be treated with the scheme suggested for the C or D groups (according to serum testosterone levels) if testicular echotexture is hypoechoic or altered;

c. the evaluation of the clinical response to treatment with FSH should be always carried out considering, in addition to the conventional sperm parameters, also the biofunctional ones, in particular the sperm DNA fragmentation;

d. the sperm DNA fragmentation must be evaluated with one of the following methods: TUNEL, Comet assay (single cell gel electrophoresis), SCSA (sperm chromatin structure assay);

e. in patients with TT < 350 ng/dL and gonadotropins in the low quartile of the range, secondary hypogonadism should be excluded. In these cases, the evaluation of the pituitary function and magnetic resonance imaging of the hypothalamic-pituitary region could be indicated.

 

[madman]

Figure 1. The four possible drug treatment strategies in patients with idiopathic male infertility. TV: testicular volume; TT: total testosterone; Gn: Gonadotropins

 

[Nelson Vergel]

Wow, nice algorithm. Here are others to improve fertility from Baylor University for men on TRT or who got off anabolic steroids.

Recovery of sperm production following testosterone replacement or anabolic steroids

 

[Nelson Vergel]

FSH and hCG dual therapy may result in the more rapid recovery of sperm to the ejaculate

024 Dual Therapy with rFSH and HCG Results in a Significantly Shorter Time to Return of Spermatogenesis than Combination HCG and Clomiphene (2021) K. Campbell, J. Sullivan, R. Valero Carrion, J. Kraus, B. Stocks, A. Lawrence, L. Lipshultz Introduction: The use of testosterone replacement...

www.excelmale.com

 

[Dcalicotte03]

View attachment 7184
Figure 1. The four possible drug treatment strategies in patients with idiopathic male infertility. TV: testicular volume; TT: total testosterone; Gn: Gonadotropins

Is there an advantage to pulsing 150iu of FSH 3x week over 60-70iu daily?

 

[madman]

Is there an advantage to pulsing 150iu of FSH 3x week over 60-70iu daily?

The weekly dose used may be more important as there is some limited evidence suggesting that higher doses of FSH may be more effective.

The most common dosing scheme is 3X weekly.

Many studies have been done using daily/EOD injections.

Take home point:

*no conclusive results have ever been produced about the most effective FSH regimen

FSH receptor agonists for male infertility therapy

ABSTRACT Introduction According to estimates by the World Health Organization, about 17.5% of the adult population – roughly 1 in 6 globally – experience infertility. The causes of male infertility remain poorly understood and have yet to be fully evaluated. Follicle-stimulating hormone (FSH)...

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*The most used scheme in the treatment of infertile patients is the administration of FSH at a dose of 150 IU three times a week, even if there is evidence that more prolonged therapies or at different doses may have greater efficacy. Furthermore, several parameters have been called into play to predict the response to FSH administration, and, among all, the guidelines cite testicular cytology and the presence of spermatids as predictors of treatment efficacy [83].

 

[madman]

Is there an advantage to pulsing 150iu of FSH 3x week over 60-70iu daily?

EAU Guidelines on Sexual and Reproductive Health (2023)


11.5.3 Hormonal therapy

11.5.3.1 Gonadotrophins

Follicle Stimulating Hormone is primarily involved in the initiation of spermatogenesis and testicular growth during puberty. The role of FSH post-puberty has not been clearly defined. Luteinizing hormone stimulates testosterone production in the testes, but due to its short half-life, it is not suitable for clinical use. Human chorionic Gonadotrophin acts in a similar manner to LH and can be used pharmacologically to stimulate testosterone release in men with failure of their hypothalamic-pituitary-gonadal axis. Human Chorionic Gonadotrophin can adequately stimulate spermatogenesis in men who have developed hypopituitarism after normal puberty. Therefore, the treatment of men with secondary hypogonadism depends on whether or not they developed hypothalamic-pituitary failure before or after puberty [5]




11.5.3.2.2 Post-Pubertal Onset Secondary

If secondary hypogonadism develops after puberty, hCG alone is usually required first to stimulate spermatogenesis. Doses of subcutaneous hCG required may be lower than those used in individuals with pre-pubertal onset; therefore, a starting dose of 250 IU twice weekly is suggested, and if normal testosterone levels are reached, hCG doses may be increased up to 2,000 IU twice weekly as for pre-pubertal onset. Again, semen analysis should be performed every 3 months to assess response, unless conception has taken place. If there is a failure of stimulation of spermatogenesis, then FSH can be added (75 IU three times per week, increasing to 150 IU three times per week if indicated). Similarly, combination therapy with FSH and hCG can be administered from the beginning of treatment, promoting better outcomes in men with HH [141]. No difference in outcomes was observed when urinary-derived, highly purified FSH was compared to recombinant FSH [141].

Greater baseline testicular volume is a good prognostic indicator for response to gonadotrophin treatment[2138]. Data had suggested that previous testosterone therapy can have a negative impact on gonadotropin treatment outcomes in men with HH [2138]. However, this observation has been subsequently refuted by a meta-analysis that did not confirm a real negative role of testosterone therapy in terms of future fertility in this specific setting [141].

In the presence of hyperprolactinemia, causing suppression of gonadotrophins resulting in sub-fertility the treatment independent of etiology (including a pituitary adenoma) is dopamine agonist therapy or withdrawal of the drug that causes the condition. Dopamine agonists used include bromocriptine, cabergoline andquinagolide




11.5.3.3 Primary Hypogonadism

There is no substantial evidence that gonadotrophin therapy has any beneficial effect in the presence of classical testicular failure. Likewise, there is no data to support the use of other hormonal treatments (including SERMs or AIs) in the case of primary hypogonadism to improve spermatogenesis [105, 2139].

FSH and hCG dual therapy may result in the more rapid recovery of sperm to the ejaculate

024 Dual Therapy with rFSH and HCG Results in a Significantly Shorter Time to Return of Spermatogenesis than Combination HCG and Clomiphene (2021) K. Campbell, J. Sullivan, R. Valero Carrion, J. Kraus, B. Stocks, A. Lawrence, L. Lipshultz Introduction: The use of testosterone replacement...

www.excelmale.com