Normal Serum Follicle-stimulating Hormone Research Articles

Predictive role of 17α-hydroxy-progesterone serum levels of response to follicle-stimulating hormone in patients with abnormal sperm parameters

To study the possible role of serum 17α-hydroxy-progesterone (17αOH-P) levels in predicting favorable responses to follicle-stimulating hormone (FSH) administration in patients with normal serum FSH levels and idiopathic abnormal sperm parameters. Prospective cohort study. University-affiliated fertility center. Fifty patients with oligozoospermia, asthenozoospermia, and/or teratozoospermia and normal serum levels of gonadotropins and total testosterone (TT). Treatment with exogenous FSH is administered subcutaneously at a dose of 150 IU 3 times a week for 3 consecutive months. Luteinizing hormone levels, FSH levels, TT levels, 17αOH-P levels, testicular volume, conventional sperm parameters, and seminal spermatid concentration were evaluated before and after therapy. To evaluate the predictive role of pretreatment serum 17αOH-P levels on FSH responsiveness, the doubling of sperm concentration at the end of the FSH administration was considered a positive outcome. After therapy, patients showed a significant increase in sperm concentration, total sperm count (TSC), progressive motility, percentage of normal forms, FSH levels, TT levels, and testicular volume. There was a negative correlation between pretreatment 17αOH-P levels and the posttreatment increase in sperm concentration, TSC, progressive motility, and normal morphology, and a positive correlation with the posttreatment increase in spermatids. Predictive analysis showed that 17αOH-P levels (<1.18 ng/mL) foretold a doubling of sperm concentration with a sensitivity of 90.0% and a specificity of 73.3%, and of TSC with a sensitivity of 91.3% and a specificity of 81.48%. The results of this study suggest that pretreatment serum levels of 17αOH-P, a marker of steroidogenic function, appear to be able to predict the success of subcutaneous administration of exogenous FSH in terms of spermatogenesis improvement. Receiver operating characteristic curves indicated that 17αOH-P levels (<1.18 ng/mL) predict a doubling of sperm concentration and TSC after exogenous FSH administration to patients with idiopathic abnormal sperm parameters and normal gonadotropin levels.

FSH can improve semen parameters in patients with idiopathic oligoasthenoteratozoospermia: A systematic review and meta-analysis.

Follicle-stimulating hormone (FSH) is commonly used in assisted reproductive technology to promote the development and maturation of follicles in female patients. However, there is no consensus on treating FSH in males with idiopathic oligoasthenoteratozoospermia (iOAT), especially in patients with normal serum FSH levels. To determine the role of FSH in improving semen quality in patients with iOAT, we conducted a detailed search in the commonly used database to find all studies on FSH in the treatment of iOAT. We compared the results, including semen volume, sperm count, sperm concentration, percentage of forward sperm motility, percentage of total sperm motility, percentage of normal forms and DNA fragmentation index (DFI) between the two groups treated with FSH or not. A total of 12 randomized controlled trials and one retrospective case-control study, including 924 people, were included in our meta-analysis. We found that sperm counts (MD 17.75; 95% CI 11.53-23.98 and p < 0.00001) were significantly increased in patients treated with FSH, along with improvements in sperm concentration (MD 4.52; 95% CI 1.46-7.58 and p=0.004), percentage of normal forms (MD 2.87; 95% CI 0.19-5.56 and p=0.04) and DFI (MD -12.62; 95% CI -19.27-5.97 and p=0.002). However, we found no significant differences in the two groups' changes in other semen parameters. The use of FSH can improve some semen parameters in patients with iOAT, such as sperm count, percentage of normal forms, sperm concentration and DFI.

Follicle-Stimulating Hormone Treatment and Male Idiopathic Infertility: Effects on Sperm Parameters and Oxidative Stress Indices according to FSHR c. 2039 A/G and c. -29 G/A Genotypes.

Scientific evidence shows that the administration of follicle-stimulating hormone (FSH) to infertile patients with normal serum FSH concentrations improves sperm parameters in oligozoospermic men. The aim of this study was to evaluate the effects of highly purified urofollitropin (hpFSH) on conventional and bio-functional sperm parameters and on oxidative stress indices in patients with idiopathic infertility. We also evaluated the response to hpFSH on these parameters in relationship to FSHR c. 2039 A/G and FSHR c. -29 G/A genotypes. A prospective longitudinal study was conducted on 42 patients with idiopathic male infertility, 23 of whom underwent to FSHR c. 2039 A/G and FSHR c. -29 G/A genotyping. Each patient was asked to collect two semen samples before and after administration of 150 IU hpFSH three times a week for 16 weeks. Patients were divided into responders or non-responders based on whether their total sperm count had at least doubled or was less than double at the end of treatment, respectively. Responders showed a significantly higher semen volume, sperm concentration, spermatids, and leukocytes. Non-responders had a significant decrease of the percentage of spermatozoa in early apoptosis after hpFSH administration. Oxidative stress indexes did not differ significantly after FSH administration in both groups. Conventional and bio-functional sperm parameters did not differ in patients with FSHR c. 2039 GG and AA genotypes, and FSHR c. -29 GG genotype both before and after FSH administration. The FSHR c. 2039 and FSHR -29 G/A genotypes and allelic distribution did not differ between responders and non-responders. FSH showed to be capable of ameliorating sperm parameters in about half patients treated, therefore it may be helpful in patients with idiopathic infertility.

Epigenetic Aberration of FMR1 Gene in Infertile Women with Diminished Ovarian Reserve.

Objective The diminished ovarian reserve (DOR) is a condition characterized by a reduction in the number and/or quality of oocytes. This primary infertility disorder is usually accompanied with an increase in the follicle-stimulating hormone (FSH) levels and regular menses. Although there are many factors contributing to the DOR situation, it is likely that many of idiopathic cases have genetic/epigenetic bases. The association between the FMR1 premutation (50-200 CGG repeats) and the premature ovarian failure (POF) suggests that epigenetic disorders of FMR1 can act as a risk factor for the DOR as well. The aim of this study was to analyze the mRNA expression and epigenetic alteration (histone acetylation/methylation) of the FMR1 gene in blood and granulosa cells of 20 infertile women. Materials and Methods In this case-control study, we analyzed the mRNA expression and epigenetic altration of the FMR1 gene in blood and granulosa cells of 20 infertile women. These women were referred to the Royan Institute, having been clinically diagnosed as DOR patients. Our control group consisted of 20 women with normal antral follicle numbers and serum FSH level. All these women had normal karyotype and no history of genetic disorders. The number of CGG triplet repeats in the exon 1 of the FMR1 gene was analyzed in all samples. Results Results clearly demonstrated significantly higher expression of the FMR1 gene in blood and granulosa cells of the DOR patients with the FMR1 premutation compared to the control group. In addition, epigenetic marks of histone 3 lysine 9 acetylation (H3K9ac) and di-metylation (H3K9me2) showed significantly higher incorporations in the regulatory regions of the FMR1 gene, including the promoter and the exon 1, whereas tri-metylation (H3K9me3) mark showed no significant difference between two groups. ConclusionOur data demonstrates, for the first time, the dynamicity of gene expression and histone modification pattern in regulation of FMR1 gene, and implies the key role played by epigenetics in the development of the ovarian function.

AB068. Practical diagnosis and treatment algorithm for azoospermia

A male factor is solely responsible in approximately 20% of cases of infertility and contributory in another 30-40%. Azoospermia is present in 15-20% of infertile males. Although the main goal of the evaluation of the infertile men is to identify the reversible conditions, to identify the irreversible causes that can or cannot be managed by assisted reproductive techniques (ART) is also important. Etiologies for azoospermia can be categorized as pre-testicular, testicular and post-testicular. Azoospermia is defined as the absence of sperm from at least two centrifuged semen samples. The initial evaluation of the azoospermia men includes a thorough history, physical examination, and hormonal tests. Physical examination should focus on testis size and presence of vas deferens and varicocele. Hormonal evaluation should include measurement of serum testosterone and follicle stimulating hormone (FSH) levels. When the vasa are palpable, testis size, semen volume and serum FSH are key factors in determining the etiology of the azoospermia. If the semen volume is reduced and this is not an artifact, the first laboratory test is post-ejaculatory urinalysis to exclude a retrograde ejaculation. After exclusion of retrograde ejaculation, transrectal ultrasonography (TRUS) should be considered to identify ejaculatory duct obstruction (EDO). Dilation of the seminal vesicles serves as a sign of EDO. Seminal vesicle aspiration to identify sperm at the time of TRUS can increase the diagnostic accuracy. In our center, TRUS-guided opacification of the seminal tracts with a mixture of contrast media and dye is performed to facilitate effective transurethral resection (TUR) of ejaculatory duct. Based on our experiences, patients with midline cysts who are treated by TUR are expected to have the best outcome. Testis size and level of serum FSH in azoospermic males with normal semen volume are critical factors in determining diagnostic strategies. Men with elevated FSH and bilateral small testis have non-obstructive azoospermia (NOA). Diagnostic testicular biopsy is not required in cases of NOA. Elevated FSH is indicative of a significant problem with spermatogenesis whereas a normal serum FSH does not guarantee intact spermatogenesis. Therefore, patients with normal testis size and FSH level should undergo a testicular biopsy to provide a definitive diagnosis. If the testicular biopsy is normal, most men have bilateral epididymal obstruction. Epididymal obstruction can be identified only by surgical exploration. Vasography is performed at the time of reconstructive surgery. Once sperm are found from the epididymal tubule, vasoepididymostomy is performed. The best results can be achieved by surgeons with training and on-going experience in microsurgery. There is some evidence that a small percentage of men with NOA may benefit from treatment of a clinical varicocele. Therefore, it is reasonable to offer men with NOA and clinical varicoceles a varicocelectomy. However, the most men will still need to use intracytoplasmic sperm injection (ICSI) to conceive. Testicular sperm extraction (TESE) should be offered to all men with NOA. Microsurgical TESE increases retrieval rates, and should be preferred in severe cases of NOA.

Follicle-stimulating hormone treatment in normogonadotropic infertile men

Several empirical treatments have been proposed to treat idiopathic infertility in men, including follicle-stimulating hormone (FSH). FSH administration is effective in patients with hypogonadotropic hypogonadism, which suggests it might be useful in patients with oligozoospermia who have normal FSH levels. Indeed, many studies have evaluated the efficacy of FSH administration in these patients, several of which have shown improvements in sperm parameters. By contrast, other studies have not reported any significant effect of FSH administration on conventional sperm parameters, although some of have reported the normalization of spermatozoon ultrastructural morphology, as well as reductions in DNA fragmentation, production of reactive oxygen species and aneuploidy. Contemporary studies suggest that the response to FSH treatment in oligozoospermic patients might, at least partially, reflect polymorphisms of the FSH receptor gene. Thus, FSH administration in oligozoospermic men with normal serum FSH levels might be efficacious only in selected patients. For this reason, additional studies are needed to determine the predictive factors and clinical conditions that can be used to identify patients who could benefit from FSH treatment.

Clinical Characteristics and Reproductive Outcomes in Infertile Men With Testicular Early and Late Maturation Arrest

To compare the clinical characteristics and reproductive outcomes of nonobstructive azoospermic men with uniform early and late maturation arrest. Patients with biopsy-documented uniform maturation arrest undergoing testicular sperm retrieval and complete medical records were enrolled in the present study. Their medical history, physical examination findings, testicular volume, serum hormone parameters, genetic anomalies, sperm retrieval, and reproductive outcomes were retrospectively analyzed. In a cohort of 223 nonobstructive azoospermic men, 34 men with uniform maturation arrest (21 early maturation arrest and 13 late maturation arrest) were identified. No significant differences were seen in the age distribution, testicular volume, or hormone parameters between patients with early and late maturation arrest. Only 13 patients (38.2%) had a normal serum follicle-stimulating hormone level and normal testicular volume. Patients with early maturation arrest had a greater frequency of overall genetic anomalies, and patients with late maturation arrest had a greater frequency of previous testicular insults. The sperm retrieval and impregnation rate were nonsignificantly greater in patients with late maturation arrest. Maturation arrest has a variety of causes and presents with diverse phenotypes. Not all patients with uniform maturation arrest have a normal follicle-stimulating hormone level or testicular volume. Patients with early maturation arrest have a greater incidence of genetic anomalies and are more likely to have worse reproductive outcomes than are patients with late maturation arrest.

Correlation between testicular sperm extraction outcomes and clinical, endocrine and testicular histology parameters in 120 azoospermic men with normal serum FSH levels

We retrospectively evaluated the clinical and hormonal profiles, sperm extraction outcomes and testicular histology parameters in 120 azoospermic men with normal serum follicle-stimulating hormone (FSH) level. Microsurgical epididymal sperm aspiration (MESA) and testicular sperm extraction (TESE) were performed in 33 and 87 cases, respectively. Sperm were successfully retrieved in all the MESA procedures and in 65 of the TESE procedures. The mean serum FSH and inhibin B levels and the testicular volume differed significantly according to whether or not sperm were retrieved. The threshold serum inhibin B value for predicting successful TESE was 123.5pg/mL (sensitivity: 69.7%; specificity: 66.7%). The 13 patients with Sertoli cell only syndrome (SCOS) had a higher mean serum FSH level and a lower mean serum inhibin B level than the other phenotypes. TESE was negative for 11 of the 13 SCOS men. The mean±SD inhibin B level was significantly lower in patients with 5-10IU/L of FSH than those with 2-5IU/L of FSH (108.30±53.86 vs. 175.23±70.17pg/mL, respectively). The sperm retrieval rates were 71.42% for the group with 5-10IU/L of FSH and 87.32% for the group with 2-5IU/L of FSH. Ten of the 13 SCOS men had a FSH level between 5 and 10IU/L. The clinical pregnancy rate was significantly lower (p=0.04) in the group with 5-10IU/L (50%) of FSH than in the group with 2-5IU/L (77.5%) of FSH. In conclusion, there is no FSH value below which spermatogenesis is always found. Inhibin B assays and clinical assessments are thus of particular value in men with normal serum FSH levels.

Mutation analysis of the X-chromosome linked, testis-specific TAF7L gene in spermatogenic failure

The precise temporal and spatial expressions of specific transcription regulation factors (TRF) have long been considered essential for spermatogenesis. Recently, it has been speculated that mammals have evolved more specialised TRF genes. In the human, the TAF7L gene may be essential for maintenance of spermatogenesis. In this study, we investigated the possible role of the TAF7L gene located on the X chromosome in testicular function and spermatogenic failure. In a case-controlled retrospective study, we recruited 16 infertile males with consistent, nonobstructive azoospermia and with normal serum follicle-stimulating hormone (FSH) levels. Twenty age-matched men with normal spermatogenesis with the same ethnic background (Caucasian) were recruited as controls. Their genomic DNA was screened for sequence changes in the coding regions and part of the flanking introns of the TAF7L gene by direct sequencing. Amino acid sequence was compared with the NCBI standard sequence (BC043391). Semen analysis and hormone evaluation were performed. We observed six sequence variations in four patients, consisting of two point mutations, one each in exon 9 and 13 and one six-basepair deletion in exon 13 with concomitant changes in amino acid. One additional nucleotide exchange was observed in intron 8. Most of these changes were also found in eight controls with the exception of changes in exon 13. A meta-analysis including the present study and literature data suggests a possible association of the point mutation in exon 13 with infertility. There was no association or relationship with reproductive hormones. In conclusion, the sequence variants in the cDNA sequence observed are common polymorphisms. The changes in intron 8 appear novel. We report for the first time that most of the alterations are not associated with gonadal dysfunction, while the sequence variant in exon 13 may represent a risk factor for spermatogenic failure.

Report on evaluation of the azoospermic male

Report on evaluation of the azoospermic male

Ethanol-induced alterations in Rab proteins: possible implications for pituitary dysfunction

Chronic exposure of pubertal male rats to ethanol results in a decline in serum testosterone, increased gonadotropins, pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) content, and decreased or inappropriately normal serum LH and FSH levels, suggesting impaired secretory release of gonadotropins. The molecular mechanisms behind this disorder are undefined, but a disruption of vesicle-mediated secretory processes is possible because intracellular protein trafficking pathways are involved in secretion of glycoproteins such as FSH and LH. Because small GTP-binding proteins of Rab family have been implicated as key regulators of membrane and protein trafficking in mammalian cells, this study was designed to test if ethanol-impaired pituitary FSH and LH secretion is associated with changes in Rab proteins, particularly Rab1B, Rab3B, Rab6, and Rab11. Male Sprague–Dawley rats 35 days old were pair-fed a Lieber–DeCarli diet with ethanol or without ethanol for 5 to 60 days. After ethanol exposure, serum testosterone levels decreased while LH and FSH were inappropriately unchanged. Immunohistochemical staining showed decreased Rab1B, Rab3B, and Rab11 protein levels in ethanol-treated pituitaries. Immunoblotting showed that ethanol induced a transient reduction in Rab6 after 5 days of ethanol exposure, whereas Rab3B decreased after 20 days, Rab11 after 30 days, and Rab1B after 60 days. Despite these changes in Rab proteins, mRNA levels were unaffected by ethanol exposure. We concluded that reductions in key Rab proteins may lead to altered vesicle trafficking and may play a role in disruption of pituitary FSH and LH secretion caused by ethanol.

Effect of Dihydrotestosterone on Pituitary Follicle-Stimulating Hormone Isoforms in Adult Male Rats Treated with a Gonadotropin-Releasing Hormone Antagonist

The effect of androgens on the oligosaccharide structure of follicle-stimulating hormone (FSH) isoforms was studied in adult male rats treated with a potent gonadotropin-releasing hormone (GnRH) antagonist. Animals were castrated (Cx), and 24 h later were treated with physiological doses of either testosterone propionate (T) or dihydrotestosterone propionate (DHT) (0.25 mg/rat in corn oil, daily, s.c.) for 7 days. The antiandrogen flutamide (F; 5 mg/day/rat, twice a day, s.c.) was administered to either Cx-T or Cx-DHT rats to block androgen action. The GnRH antagonist Org 30276 (Ant; 1 mg/kg/day, s.c.) was injected to both Cx- and Cx-DHT treated rats. FSH serum levels reached normal values in Cx rats treated with either T or DHT, whereas those treated with F retained Cx conditions. Both Cx-Ant and Cx-Ant-DHT treated animals presented normal serum FSH levels. Concanavalin A affinity chromatography was used to isolate pituitary FSH isoforms according to their carbohydrate inner structure. An increased proportion of FSH isoforms bearing complex-type oligosaccharides was observed in Cx rats treated with T or DHT, whereas the proportion of these isoforms was reduced in Cx and Cx-T-F or Cx-DHT-F rats. These results demonstrate that functional androgens are needed to complete the oligosaccharide processing of FSH. In addition, the proportion of the different pituitary FSH isoforms after DHT replacement was equivalent to that found when GnRH action was blocked, indicating that androgens are involved in the regulation of carbohydrate incorporation to the FSH molecule by acting mainly at the pituitary level, independently of GnRH action.

Best practice policies for male infertility

University of California, San Francisco, San Francisco, California; Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Louisville School of Medicine, Louisville, Kentucky; Baylor College of Medicine, Houston, Texas; Brown University, Providence, Rhode Island; Cleveland Clinic Foundation, Cleveland, Ohio; New York Presbyterian Hospital-Cornell, New York, New York; University of Virginia School of Medicine, Charlottesville, Virginia; Mayo Medical School, Rochester, Minnesota; University of Pennsylvania School of Medicine, York, Pennsylvania; University of California, Davis, Davis, California; and SUNY Health Science Center at Brooklyn, Brooklyn, New York

The effect of microsurgical varicocelectomy on serum follicle stimulating hormone, testosterone and free testosterone levels in infertile men with varicocele.

To analyse the effects of varicocelectomy on serum follicle-stimulating hormone (FSH), testosterone and free testosterone levels, and to investigate the interrelationships between seminal and hormonal variables. The records were retrospectively evaluated for 78 infertile patients who underwent microsurgical inguinal varicocelectomy, with documented serum FSH, testosterone, free testosterone levels, sperm concentration and sperm motility before and after surgery. Left and bilateral varicoceles were detected in 40 and 38 patients, respectively. In addition, serum hormonal values of 10 fertile men in whom physical examinations and Doppler ultrasonography revealed no evidence of varicocele were recorded and used as a control group. The mean (sd) serum FSH levels of all patients decreased from 15.21 (3.34) before surgery to 10.82 (2.93) mIU/mL afterward (P=0.01), and serum testosterone levels increased from 5.63 (1.40) to 8.37 (2.2) ng/mL (P=0.01), whereas free testosterone levels increased from 23.13 (3.19) to 32.83 (4.37) pg/mL (P<0.001). In contrast to the significant difference in sperm motility before and after surgery of all patients (P<0.01), the difference in sperm count was insignificant (P>0.05). Thirty-six patients with high serum FSH levels before surgery had significantly lower levels afterward (P=0.001). In this group, the sperm concentration and motility also increased, from 17.66 (4.35) to 20.76 (4.37) million/mL (P=0.05) and from 30.9 (4.4)% to 37.5 (4.34)%, respectively (P=0.01). In the remaining 42 patients who had normal preoperative serum FSH levels, there was a slight decrease after surgery (P=0.02). Their sperm concentration increased slightly (P=0. 04), and motility also increased (P=0.001). Sixty patients had a significantly higher testosterone level after surgery; in this group the sperm concentration and motility increased (P=0.01). Varicocelectomy promotes Sertoli and Leydig cell function. The significant increase in serum free testosterone level results in a significant improvement in sperm concentration and motility.

PRETREATMENT FOLLICLE-STIMULATING HORMONE: A PROGNOSTIC SERUM MARKER OF SPERMATOGENESIS STATUS IN PATIENTS TREATED FOR GERM CELL CANCER

Purpose We evaluate the use of pretreatment follicle-stimulating hormone (FSH) in patients with germ cell tumors as a prognostic serum marker of spermatogenesis after standard treatment. Additionally, Leydig cell function was investigated by estimation of luteinizing hormone (LH) and testosterone (T), and calculation of the T/LH ratio. Materials and Methods Serum FSH, LH and T were determined radioimmunologically associated with semen analyses in 20 patients with seminoma (pathological stages IA to IIB) after unilateral orchiectomy before and up to 24 months after infradiaphragmatic radiotherapy. Additionally, hormone analyses were performed in 18 patients with nonseminomatous germ cell tumor (pathological stages IIA to C) before and up to 36 months after standard cisplatin based chemotherapy. Results Seminoma patients undergoing radiotherapy were divided into 2 groups consisting of 12 patients with normal pretreatment serum FSH and 8 with elevated FSH reflecting spermatogenesis deficits even before treatment. Six months after irradiation a significant increase in FSH (p <0.01) associated with a decrease in sperm density was observed in both groups and 24 months after radiotherapy patients with initially normal FSH had significantly lower serum FSH (p <0.01) associated with higher sperm density than those with initially elevated FSH (p <0.01), indicating less impairment of Sertoli cell function. Comparable results were observed in chemotherapy treated germ cell tumor patients with initially normal (11) and elevated serum FSH (7), respectively, and 36 months after chemotherapy patients with initially normal FSH had significantly lower FSH concentrations than those with initially elevated FSH (p <0.01). Compensated impairment of Leydig cell function reflected by a subnormal T/LH ratio was evident before chemotherapy in 16.7% of patients increasing up to 41.2% 36 months after therapy. In contrast, 24 months after radiotherapy only 25% of seminoma patients showed a subnormal ratio reflecting less damage to the Leydig cells caused by irradiation. Conclusions Pretreatment FSH is a prognostic serum marker of spermatogenesis status of germ cell tumor patients receiving standard radiotherapy or chemotherapy. In contrast to seminoma patients after radiotherapy, impairment of Leydig cell function was evident in germ cell tumor patients after cisplatin based chemotherapy.

Non-response to ovarian stimulation in normogonadotrophic, normogonadal women: a clinical sign of impending onset of ovarian failure pre-empting the rise in basal follicle stimulating hormone levels.

The most important aspect of diminished ovarian reserve is the associated decline in reproductive potential. Assessment of ovarian reserve is mainly based on measurement of early follicular phase follicle stimulating hormone (FSH) concentration. The objective of this study was to report the identification of a group of 12 infertile women initially diagnosed as having unexplained or anovulatory infertility, who had a normal baseline hormonal profile and did not respond to repeated ovarian stimulation with gonadotrophins. All developed ovarian failure within a relatively short time span. Non-response to ovarian stimulation was defined by failure to achieve development of follicles >12 mm and failure to raise oestradiol concentration >350 pmol/l in two successive cycles of human menopausal gonadotrophin (HMG) doses of up to five ampoules per day for 5-8 days. Within a mean of 9 months following the failed attempts of ovarian stimulation the mean day 3 FSH concentrations rose from 5.4 +/- 2.7 IU/l to 53.5 +/- 19.7 IU/l. In these patients, day 3 FSH concentration failed to indicate the low ovarian reserve manifested only by lack of clinical response to treatment with gonadotrophins which was the first sign of impending ovarian failure. We conclude that women with normal early follicular phase serum FSH concentrations who do not respond to ovarian stimulation by HMG are at risk of developing ovarian failure within several months.

Prospective Study of Serum Androgen Levels Stratified by Increased or Normal Serum Follicle-Stimulating Hormone in Infertile Women with Regular Menses

Prospective Study of Serum Androgen Levels Stratified by Increased or Normal Serum Follicle-Stimulating Hormone in Infertile Women with Regular Menses

Aetiological factors involved in the low response to gonadotrophins in infertile women with normal basal serum follicle stimulating hormone levels

This study was designed to investigate possible aetiological factors involved in the low response to gonadotrophins in women with normal basal serum follicle stimulating hormone (FSH) concentrations, stimulated for assisted reproduction. Nine of these patients with normal basal serum FSH and 22 normal controls (five of whom had had a normal response to previous gonadotrophin stimulation) were prospectively subjected to: (i) transvaginal pulsed colour Doppler ultrasound evaluation of the vessels surrounding the dominant follicle for blood flow impedance analysis, (ii) the clonidine test to explore the ability of the pituitary to release growth hormone, and (iii) detection of anti-granulosa cell auto-antibodies in blood using an enzyme-linked immunosorbent assay (ELISA). The pulsatility and resistance indices (PI, RI) were significantly (P < 0.01) higher in the women with low responses as compared to the controls on days -1 and 0 (day 0 = ovulation). Seven out of the nine low responders were out of the range calculated for normal values after evaluation of the controls. A significant (P < 0.05) decrease in the secretion of growth hormone 60-90 min after clonidine ingestion was observed in the low responders as compared to five controls with previous normal response to ovarian stimulation. Six out of the nine low responders showed a negative clonidine test. No increase in anti-granulosa cell auto-antibodies was observed in the low responders as compared to the controls, including normal responders. In conclusion, an abnormal follicular blood flow impedance in the natural cycle may be related to low responses to gonadotrophins in patients with normal serum FSH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Pituitary gonadotrophin secretory capacity during the luteal phase in superovulation using GnRH-agonists and HMG in a desensitization or flare-up protocol.

Pituitary gonadotrophin reserve and basal gonadotrophin secretion were tested during the luteal phase in women superovulated with buserelin/human menopausal gonadotrophin (HMG) in a desensitization (n = 17) or flare-up protocol (n = 7). In the desensitization protocol the luteinizing hormone-releasing hormone (LHRH) stimulated serum LH and follicle stimulating hormone (FSH) concentrations remained impaired at least until day 14 after arrest of the agonist. In the flare-up protocol basal and stimulated LH secretion was still abnormal on days 14 and 15 after human chorionic gonadotrophin (HCG) injection. Normal basal serum FSH concentrations were measured at the end of the luteal phase in the flare-up protocol, but the response of FSH to LHRH injection was still subnormal. We conclude that gonadotrophin function remained impaired until the end of the luteal phase after desensitization and flare-up GnRH-agonist and HMG stimulation protocols. Corpus luteum stimulation with exogenous HCG or substitution therapy using natural progesterone are required to prevent the possible negative effects resulting from pituitary dysfunction after GnRH-agonist treatment.

The effect of mesterolone on sperm count, on serum follicle stimulating hormone, luteinizing hormone, plasma testosterone and outcome in idiopathic oligospermic men

Two hundred fifty subfertile men with idiopathic oligospermia (count less than 20 million/ml) were treated with mesterolone (100–150 mg/day) for 12 months. Seminal analysis were assayed 3 times and serum follicle stimulating hormone (FSH) luteinizing hormone (LH) and plasma testosterone were assayed once before treatment and repeated at 3, 6, 9 and 12 months after the initiation of treatment. One hundred ten patients (44%) had normal serum FSH, LH and plasma testosterone, 85 patients (34%) had low serum FSH, LH and low plasma testosterone. One hundred seventy-five patients (70%) had moderate oligospermia (count 5 to <20 million/ml) and 75 patients (30%) had severe oligospermia (count <5 million/ml). Seventy-five moderately oligospermic patients showed significant improvement in the sperm density, total sperm count and motility following mesterolone therapy whereas only 12% showed improvement in the severe oligospermic group. Mesterolone had no depressing effect on low or normal serum FSH and LH levels but had depressing effect on 25% if the levels were elevated. There was no significant adverse effect on testosterone levels or on liver function. One hundred fifteen (46%) pregnancies resulted following the treatment, 9 of 115 (7.8%) aborted and 2 (1.7%) had ectopic pregnancy. Mesterolone was found to be more useful in patients with a sperm count ranging between 5 and 20 million/ml. Those with severe oligospermia (count <5 million) do not seem to benefit from this therapy.