Use of recombinant human follicle-stimulating hormone in the treatment of male factor infertility

OBJECTIVE: To evaluate the effects of treatment with recombinant human FSH (r-hFSH) on seminal parameters and seminiferous epithelium in idiopathic patients with oligozoospermia with normal FSH plasma levels. DESIGN: Randomized single-blind study. SETTING: Academic setting. PATIENT(S): Forty-five subjects with idiopathic oligozoospermia (sperm count <10 x 10(6)/mL) and normal FSH and inhibin B plasma levels. INTERVENTION(S): Three months of treatment with r-hFSH 50 IU (15 patients) or with r-hFSH 100 IU on alternate days (15 patients) or no treatment (15 patients); bilateral testicular fine-needle aspiration (FNA) performed before and after therapy; FSH and inhibin B plasma levels evaluated during treatment. MAIN OUTCOME MEASURE(S): Seminal parameters; testicular cytological features evaluated by FNA; plasma levels of FSH, LH, T, and inhibin B. RESULT(S): Treatment with r-hFSH at a dose of 50 IU induced no increase in sperm concentration, while treatment with r-hFSH at a dose of 100 IU induced a significant increase in sperm concentration. In particular, in 11/15 patients a doubling of the pretreatment sperm concentration was observed. No significant increase in sperm parameters was observed in the control group. In both groups of patients treated with r-hFSH, the cytological analysis before treatment showed hypospermatogenesis. An increase in the percentage of spermatogonia and spermatocytes was observed only after the treatment with r-hFSH at a dose of 100 IU. CONCLUSION(S): The findings of this study demonstrate that r-hFSH at a dose of 100 IU, as previously seen with highly purified FSH, increases the spermatogonial population and sperm production in idiopathic patients with oligozoospermia with normal FSH and inhibin B plasma levels and a cytological picture of hypospermatogenesis.     

Clinical and hormonal features of selective follicle-stimulating hormone (FSH) deficiency due to FSH beta-subunit gene mutations in both sexes

OBJECTIVE: To report the clinical, hormonal, and molecular features of a female adolescent with selective FSH deficiency. In addition, a complete review of previous cases is provided, focusing on hormonal aspects. DESIGN: Clinical study. SETTING: University hospital. PATIENT(S): A 16-year-old girl with primary amenorrhea and poor breast development due to isolated FSH deficiency. INTERVENTION(S): Blood drawing before and after GnRH stimulation and pelvic ultrasound examination. MAIN OUTCOME MEASURE(S): Gonadotropin and E(2) measurements and sequencing of the FSH beta-subunit gene. RESULT(S): The patient was referred for primary amenorrhea and partial breast development (Tanner III). Her basal and GnRH-stimulated LH levels were elevated (31 IU/L and 98 IU/L, respectively), whereas her FSH levels were undetectable (<1 IU/L) in both conditions. Estradiol levels were low (<13 pg/mL). Automatic sequencing showed a nucleotide substitution of C for A in exon 3, resulting in a homozygous nonsense mutation in amino acid position 76 (Tyr76X) of the FSH beta-subunit. CONCLUSION(S): The Tyr76X mutation of the FSH beta-subunit was associated with a partial phenotype of FSH deficiency. To date, only four loss-of-function mutations of the FSH beta-subunit have been described in eight patients with undetectable serum FSH and high serum LH levels. Therefore, this unusual hormonal profile strongly suggests a defect in the FSH beta-subunit in both sexes.     

Detection of epitopes on follicle-stimulating hormone and FSH-antiserum-induced suppression of bioactivity of follicle-stimulating hormone and luteinizing hormone

There are currently two major approaches to hormonal male contraception. One relies on testosterone (analogs) either alone or in combination with gonadotropin releasing hormone (GnRH) (analogs or immunizations), the other on immunizations against follicle-stimulating hormone (FSH). Theoretically, the latter method will suppress spermatogenesis whilst not interfering with libido. An absolute requirement is, however, that an anti-FSH vaccine does not induce anti-luteinizing hormone (LH) antibodies (LH being responsible for the induction of testosterone which is necessary-to maintain libido). In this report we show that when whole FSH is used for vaccination, in most cases in addition to biological activity against FSH, anti-LH activity is also induced. By systematic analysis of the antisera raised with FSH using systematic epitope scanning (PEPSCAN) we found differences between the FSH-specific and FSH-nonspecific sera. Only the FSH-specific antiserum contained antibodies that recognized amino acid sequence 37–55 on the β-subunit in a linear manner. Because antibodies against this epitope have not been found in the cross-reactive sera this epitope forms a prime candidate for an anti-FSH contraceptive vaccine     

Mullerian duct cyst: a curable entity of male infertility. Two case reports

Purpose  

Mullerian duct cyst is a rudiment of a Mullerian duct in the fetal period which causes ejaculatory duct obstruction and male infertility.     

NovelCFAP43 andCFAP44 mutations cause male infertility with multiple morphological abnormalities of the sperm flagella (MMAF)

Research question

Multiple morphological abnormalities of the sperm flagella (MMAF) comprise a rare congenital disease that can cause primary male infertility. Several pathogenic genes (e.g. AKAP4, DNAH1, CFAP43 and CFAP44) are associated with MMAF but the pathogenic mechanisms have not been elucidated.

Azoospermia factor and male infertility

Recently, work has shown that azoospermia factor (AZF) microdeletions result from homologous recombination between almost identical blocks in this gene region. These microdeletions in the Y chromosome are a common molecular genetic cause of spermatogenetic failure leading to male infertility. After completion of the sequencing of the Y chromosome, the classical definition of AZFa, AZFb, and AZFc was modified to five regions, namely AZFa, P5/proximal-P1, P5/distal-P1, P4/distal-P1, and AZFc, as a result of the determination of Y chromosomal structure. Moreover, partial AZFc deletions have also been reported, resulting from recombination in their sub-ampliconic identical pair sequences. These deletions are also implicated in a possible association with Y chromosome haplogroups. In this review, we address Y chromosomal complexity and the modified categories of the AZF deletions. Recognition of the association of Y deletions with male infertility has implications for the diagnosis, treatment, and genetic counseling of infertile men, in particular candidates for intracytoplasmic sperm injection.     

Coenzyme Q10 and male infertility: a meta-analysis

Objective

To evaluate the effect of coenzyme Q10 treatments in male infertility, specifically in these parameters: live birth and pregnancy rates, CoQ10 seminal concentration, sperm concentration, and sperm motility.

Materials and methods

Systematic review and meta-analysis in male infertility patients with CoQ10 oral treatments. Three trials were included: 149 males in CoQ10 group and 147 males in placebo group.

Results

None of the included trials provided any data regarding live births. The results of this meta-analysis show that supplementing infertile men with CoQ10 does not increase pregnancy rates. The analysis showed, among patients receiving CoQ10 treatment, a statistically significant increase in: CoQ10 seminal concentration (RR 49.55, 95 % CI 46.44 to 52.66, I² = 17 %), sperm concentration (RR 5.33, 95 % CI 4.18 to 6.47, I² = 58 %), and sperm motility (RR 4.50, 95 % CI 3.92 to 5.08, I² = 0 %)

Conclusion

There is no evidence in the literature that CoQ10 increases either live birth or pregnancy rates, but there is a global improvement in sperm parameters. Adequately powered, robust trials of individual and combination antioxidant therapies are required to guide clinical practice.     

Isolated follicle-stimulating hormone (FSH) deficiency in a young man with normal virilization who did not have mutations in the FSHbeta gene

OBJECTIVE: To determine the cause of isolated FSH deficiency in a young infertile man. DESIGN: Case report. SETTING: Clinical and genetic studies in an academic research environment. PATIENT(S): A 19-year-old man with normal virilization, azoospermia, and isolated FSH deficiency. INTERVENTION(S): Pituitary and gonadal functions were evaluated at baseline and after repeated GnRH stimulation. FSH was tested with both immunological and biological methods. The FSHbeta gene was sequenced in the patient and in a series of 50 controls. MAIN OUTCOME MEASURE(S): Clinical, endocrine, and genetic characterization of an infertile patient with isolated FSH deficiency. RESULT(S): LH and T secretions were normal. No interference in FSH measurement was detected, and serum FSH concentrations were very low and completely unresponsive to repeated GnRH stimulation. No circulating FSH-like bioactivity was detected by means of rat Sertoli cell bioassay. Other pituitary functions were unaffected, and no lesions were seen at pituitary nuclear magnetic resonance (NMR). Inhibin B and activin levels were normal, but a progressive decrease of activin concentrations was seen during GnRH stimulation. The coding sequence of the FSHbeta gene was normal, but the patient was homozygous for a novel G/T substitution in the promoter region within a P response element. This substitution was present in heterozygosity in eight out of 50 controls and in homozygosity in one man with normal FSH levels. CONCLUSION(S): We report an infertile male with isolated FSH deficiency but no evidence of mutations in the FSHbeta gene. The G/T substitution in the FSHbeta promoter represents a novel silent polymorphism, indicating that other defects in factors involved in FSH-specific expression should be taken into account.     

The experience of infertility treatment: the male perspective

Current research surrounding infertility is focused primarily on women alone, thus removing men from the fertility equation. However, alternative research has indicated that, although men also experience infertility, there is a paucity of research on men. Therefore, very little is understood about the experiences of infertility from the male perspective. This study adopted a qualitative approach in an attempt to explore the infertility experience from the perspective of men. Fifteen men who had experienced infertility were interviewed to explore their experiences. Interpretative phenomenological analysis was used to analyse the data. Five superordinate themes were developed, and these included: (1) the influence of society on infertility; (2) feeling unacknowledged; (3) natural verses assisted conception; (4) emotional reactions; and (5) improving the infertility experience. The findings of this research indicated that men experience infertility as a mentally, physically and socially demanding condition. Comparisons to previous research have been made, and future research is proposed.     

Epigenetics and its role in male infertility

Male infertility is a common and complex problem affecting 1 in 20 men. Despite voluminous research in this field, in many cases, the underlying causes are unknown. Epigenetic factors play an important role in male infertility and these have been studied extensively. Epigenetic modifications control a number of processes within the body, but this review will concentrate on male fertility and the consequences of aberrant epigenetic regulation/modification. Many recent studies have identified altered epigenetic profiles in sperm from men with oligozoospermia and oligoasthenoteratozoospermia. During gametogenesis and germ cell maturation, germ cells undergo extensive epigenetic reprogramming that involves the establishment of sex-specific patterns in the sperm and oocytes. Increasing evidence suggests that genetic and environmental factors can have negative effects on epigenetic processes controlling implantation, placentation and fetal growth. This review provides an overview of the epigenetic processes (histone-to-protamine exchange and epigenetic reprogramming post-fertilization), aberrant epigenetic reprogramming and its association with fertility, possible risks for ART techniques, testicular cancer and the effect of environmental factors on the epigenetic processes.