Recombinant follicle stimulating hormone stimulation in poor responders with normal basal concentrations of follicle stimulating hormone and oestradiol: improved reproductive outcome.

A total of 30 young infertile patients who exhibited a poor response in two previous consecutive cycles, despite having normal basal follicle stimulating hormone (FSH) and oestradiol concentrations, were invited to participate in a prospective randomized study comparing the clinical efficacy of recombinant (rFSH) and urinary (uFSH) follicle stimulating hormone. An evaluation of the total dose used (3800 IU versus 4600 IU, P < 0.05) and duration of treatment (10.2 days versus 13.2 days, P < 0.05) showed a significantly shorter treatment period as well as a significantly lower total dose of FSH required to induce ovulation successfully in the group of patients treated with rFSH. Significantly more oocytes (7.2 versus 5. 6, P < 0.05) as well as mature oocytes (5.9 versus 3.2, P < 0.01) were retrieved after rFSH treatment. In addition, significantly more good quality embryos were obtained (3.4 versus 1.8, P < 0.05) in the group of patients treated with rFSH and, as a result, higher pregnancy (33 versus 7%, P < 0.01) and implantation (16 versus 3%, P < 0.01) rates were achieved in these patients. It is concluded that rFSH is more effective than uFSH in inducing multifollicular development and achieving pregnancy in young low responders.     

The value of basal serum follicle stimulating hormone, luteinizing hormone and oestradiol concentrations following pituitary down-regulation in predicting ovarian response to stimulation with highly purified follicle stimulating hormone.

The value of gonadotrophin and oestradiol concentrations following pituitary down-regulation with leuprolide acetate in predicting ovarian response to stimulation was evaluated in three groups of women undergoing ovarian stimulation for in-vitro fertilization with highly purified follicle stimulating hormone (FSH). Leuprolide acetate was started in the midluteal phase, and either stopped at menses (IVF-SL group, n = 3), or continued throughout stimulation (IVF-LL group, n = 38; oocyte donors, n = 58). Ovarian stimulation was started on cycle day 3, after blood was drawn for down-regulated FSH, luteinizing hormone (LH) and oestradiol. Higher down-regulated LH was predictive of higher oestradiol on day 5 of stimulation in both IVF groups, and of need for fewer ampoules in the IVF-LL group, but not of oestradiol on day of human chorionic gonadotrophin (HCG) administration or number of oocytes retrieved. Higher FSH after down-regulation predicted yield of fewer oocytes in the donor and IVF-LL groups, and higher oestradiol on day 5 of stimulation, need for fewer ampoules and a shorter duration of therapy in both IVF groups. Higher oestradiol after down-regulation was associated with higher oestradiol on day 5 of stimulation and on day of HCG administration, a shorter duration of therapy and need for fewer ampoules in all groups. Whereas these results do not ascribe any predictive significance to LH, they suggest that oestradiol and FSH concentrations after down-regulation are predictive of the pattern of ovarian response to stimulation and of oocyte yield.     

Endocrinology: Nuclear maturity and oocyte morphology after stimulation with highly purified follicle stimulating hormone compared to human menopausal gonadotrophin

Several studies have shown that high concentrations of luteinizinghormone (LH) in the follicular phase of stimulation can havea negative effect on oocyte quality, pregnancy rate and incidenceof miscarriage. The aim of the present study was to examinethe effects of highly purified follicle stimulating hormone(FSH HP) on ovarian stimulation and particularly on nuclearmaturity and morphological appearance of the oocyte in intracytoplasmicsperm injection (ICSI) therapy and to compare the results withhuman menopausal gonadotrophin (HMG) stimulation. For this purpose,50 patients for ICSI (HMG: 30; FSH HP: 20) and 26 patients forin-vitro fertilization (TVF; HMG: 14, FSH HP: 12) were stimulatedwith either HMG of FSH HP using a short-term protocol. Patientswere divided into the two groups according to the first letterof their family name. No differences were observed among thegroups in relation to patient age, duration of stimulation,number of aspirated oocytes or maturity of the oocyte-cumuluscomplex. After removal of the cumulus-corona cells in the ICSIoocytes, a significantly higher proportion of oocytes in theFSH HP group were nuclear mature (metaphase II) than in theHMG group (FSH HP: 88.8%, HMG: 80.6%; P = 0.009). Furthermore,in the FSH HP group, significantly fewer oocytes with dark cytoplasmwere observed (FSH HP: 14.4%, HMG: 22.4%; P = 0.02). Fertilization,cleavage and pregnancy rates (FSH HP 38%, HMG: 34% per retrieval)were comparable in both groups. Based on the results obtained,it can be concluded that the short-term FSH HP treatment protocolsynchronizes oocyte maturation better than comparable stimulationwith HMG.     

Recombinant versus urinary follicle stimulating hormone for ovarian stimulation in assisted reproduction.

The recent availability of recombinant follicle stimulating hormone (rFSH), with its high level of purity and batch-to-batch consistency has made it an attractive alternative to urinary FSH (uFSH) for ovarian stimulation. Several trials have compared the two preparations, but none had sufficient power to detect a clinically meaningful difference in pregnancy rates. The purpose of this study was to determine the clinical pregnancy rates per started cycle by pooling data from randomized trials which compared the use of rFSH and uFSH in treatment cycles using in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). A thorough search of the literature identified 12 trials which met the inclusion criteria. In four trials, both IVF and ICSI were performed, in seven trials only IVF was performed and in one trial only ICSI was performed. Data were extracted and pooled using the principles of meta-analysis. There was no significant heterogeneity of treatment effect across the trials. The common odds ratio and the risk difference (and their 95% confidence intervals), obtained by pooling the data using a fixed effects model, were 1.20 (1.02-1.42) and 3.7% (0.5-6.9%) respectively, in favour of rFSH. The pregnancy rate with the alpha preparation of rFSH was statistically significantly higher than with uFSH in IVF cycles. The overall conclusion from this meta-analysis is that the use of rFSH in assisted reproduction is preferred over uFSH.     

Improved oocyte quality is obtained with follicle stimulating hormone alone than with follicle stimulating hormone/human menopausal gonadotrophin combination

The aim of this study was to compare the efficacy of pure follicle stimulating hormone (FSH) with that of FSH/human menopausal gonadotrophin (HMG) combination in downregulated cycles. A total of 357 patients was evaluated retrospectively. Sixty percent of patients in the FSH group and 55% in the FSH/HMG group were new; the others were repeat patients. Ovulation was suppressed with leuprolide acetate in all patients, followed by either FSH (n = 218) or FSH/HMG (n = 119). There was no difference in patients' age, infertility factors, number of ampoules used, length of stimulation, oestradiol levels on day of human chorionic gonadotrophin (HCG) administration, number of oocytes recovered or the number of embryos transferred. Also, nuclear maturity at aspiration and fertilization rates were not different between the two groups. FSH stimulation resulted in a significantly higher percentage of mature oocytes that showed the typical 'mature' morphological characteristics (P < 0.0001). The clinical pregnancy rates per transfer were 40 and 28% in patients stimulated with pure FSH and FSH/HMG respectively (P < 0.05). The significantly higher number of immature oocytes matured in vitro in the FSH/HMG group (P = 0.001) suggests a possible effect on in-vitro maturation, due to luteinizing hormone present in HMG. The difference in mature oocyte quality may be an important determinant in the higher pregnancy rates for the FSH- stimulated patients.      

Recombinant human follicle stimulating hormone versus human menopausal gonadotrophin induction: effects in mature follicle endocrinology.

To investigate follicular effects of recombinant human follicle stimulating hormone (rhFSH) induction on women with polycystic ovary syndrome (PCOS), steroid content was compared in mature follicles obtained using a long luteinizing hormone-releasing hormone agonist plus rhFSH or human menopausal gonadotrophin (HMG) in PCOS women and controls participating in an in-vitro fertilization programme. Follicular fluids (144 samples) were collected at oocyte retrieval by individual selective aspiration. Oocyte maturity and fecundability were assessed. Plasma and intrafollicular 17beta-oestradiol, progesterone, testosterone concentrations were assayed individually. No significant difference was seen in oocyte maturity and fecundability between PCOS and controls following rhFSH, or between PCOS rhFSH and HMG group. 17beta-oestradiol, testosterone and progesterone concentrations were lower in PCOS follicular fluid following rhFSH than HMG but the difference was not significant. Progesterone concentration, 17beta-oestradiol/progesterone, 17beta-oestradiol/testosterone were significantly different between the two induction groups, for PCOS fertilized oocyte follicles (P = 0.01, P < 0.05 and P < 0.05 respectively). Steroidogenic enzymatic activity seems to be regulated in healthy follicular cells in PCOS as well as in normal patients upon ovarian induction. Following rhFSH, higher PCOS follicular progesterone concentrations leading to a theoretically increased fecundability could suggest that recombinant FSH is a better inducer which needs to be confirmed.     

A randomized comparative study of highly purified follicle stimulating hormone and human menopausal gonadotrophin for ovarian hyperstimulation in an oocyte donation programme

A randomized comparative study of highly purified human follicle-stimulatinghormone (FSH-HP), administered s.c, and human menopausal gonadotrophin(HMG), administered i.m., was carried out in 41 volunteer oocytedonors. The response to ovarian hyperstimulation was similarin both groups. One cycle in both groups was cancelled. Thenumber of oocytes recovered was 16.0 ± 7.9 (mean ±SD) following stimulation with 32.8 ± 103 ampoules ofFSH-HP (n = 19) over 12.3 ± 1.7 days. Following stimulationwith 29.8 ± 10.6 ampoules of HMG over 11.5 ± 1.6days, the number of oocytes collected was 18.4 ± 12.7(n = 20). The oocyte recipients were allocated 9.2 ±3.6 oocytes in the FSH-HP group (n = 33) and 9.6 ± 4.6oocytes in the HMG group (n = 37). The fertilization rate (2PN/cell)was significantly higher in the HMG group (48%, 170/355) thanin the FSH-HP group (36%, 109/304) (P < 0.01). The numberof embryos transferred per recipient was 2.0 ± 0.4 inthe FSH-HP and 2.0 ± 03 in the HMG group. The pregnancyrate per embryo transfer was 25% in the FSH-HP (5/20) and 26%(8/31) in the HMG group. Fertile donors with body mass index£25 made up a poor responder group to s.c FSH-HP, possiblyindicating reduced absorption of the drug.     

Recombinant follicle stimulating hormone in in-vitro fertilization treatment-clinical experience with follitropin alpha and follitropin beta

The objective of this prospective study was to compare the outcome of ovarian hyperstimulation for in-vitro fertilization (IVF) using two different preparations of recombinant follicle stimulating hormone (FSH). The study was based on 296 consecutive IVF cycles in 1997, 199 performed using follitropin alpha (Gonal-F) and 97 performed using follitropin beta (Puregon). Outcome was compared regarding pregnancy rate, oestradiol and progesterone response, endometrial thickness, follicle number, number of retrieved oocytes, fertilized oocytes, sperm count and sperm motility. There was no significant difference in outcome of stimulation. Clinical pregnancy rate was similar, 29.1% for Gonal-F and 28.1% for Puregon. There was no difference in endometrial response, oestradiol response, number of smaller (12-15 mm) or larger (>15 mm) follicles, number of oocytes retrieved, fertilized, divided and replaced, in sperm counts or in sperm progressive motility. There was a lower follicle number in the Puregon group, but not statistically significant. The serum progesterone concentrations on the day of oocyte retrieval, however, were significantly lower in the Puregon group. In conclusion, it was not possible to find significant differences in the IVF programme with regard to stimulation outcome between Gonal-F and Puregon. The results of this study indicate that Gonal-F and Puregon may be equally suitable for use in ovarian stimulation for IVF.     

Ovarian sensitivity to follicle stimulating hormone is blunted in normo- ovulatory women with Down's syndrome

Ovarian sensitivity to follicle stimulating hormone (FSH) during the early follicular phase of the human menstrual cycle was studied in six post-menarchal patients with Down's syndrome and 12 normo-ovulatory women. Pure FSH (75 IU) was given i.v. to six controls and six Down's syndrome patients, while saline was administered to the remaining six controls. Plasma concentrations of luteinizing hormone (LH), FSH, oestradiol, testosterone and growth hormone (GH) in samples collected for a period of 26 h after the injection were assayed. In control patients FSH injection increased oestradiol stimulated area under the curve (AUC). This value was significantly higher than that found in Down's syndrome patients (P < 0.02), who exhibited an oestradiol- stimulated AUC equivalent to saline-treated controls. In Down's syndrome, GH plasma concentrations were significantly lower than in the control group (P < 0.05). These results indicate that the ovarian sensitivity to FSH in patients with Down's syndrome is blunted. Lower GH plasma concentrations found in this group may in part account for this biological feature.      

Recombinant hormones: Action of recombinant follicle stimulating hormone in superfused human granulosa cells in vitro

The aim of this work was to compare the action of recombinantfollicle stimulating hormone (rFSH) and urinary FSH (uFSH).Moreover we aimed to compare the secretory efficiency of continuousversus pulsatile stimulation by rFSH in superfused human lutealcells. Progesterone concentration was measured in culture mediumby radioimmunoassay. Action of rFSH and uFSH was compared instatic cultures of human granulosa cells at doses of 0.001–10IU/ml. The secretory effciency of both rFSH and uFSH was foundto be similar in a defined range of concentrations (0.001–0.3IU/ml). At concentrations of 1 and 10 IU/ml, the action of uFSHwas significantly more potent than rFSH, up to 139% (P <0.01) and 133% (P < 0.01) respectively. A concentration of0.3 IU/ml of rFSH was most potent in static cultures, and evokedprogesterone release up to 80 mg/ml. For a stimulation periodof up to 4 h, the action of rFSH and uFSH in human granulosacells was time-dependent and differences between them were notsignificant. Irregularities were observed at >4 h stimulationtime. In another experiment, in superfused human granulosa cells,we showed that the stimulatory effectiveness of pulsatile rFSHadministration (time interval 60 min, application time 10 min)was greater for progesterone release (3973 ng of progesterone/1IU rFSH) than was continuous administration (848 ng of progesterone/1IU rFSH). In conclusion, the secretory action of rFSH is similarto that of uFSH for defined times and doses. Moreover, pulsatilerFSH administration is more efficient at stimulating the releaseof progesterone than continuous administration. recombinant FSH/human granulosa cells/progesterone     

Recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (Metrodin HP): results of a randomized comparative study in women undergoing assisted reproductive techniques

A prospective, randomized, comparative, assessor-blind study was carried out in two centres to compare the efficacy and safety of recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (u-hFSH HP; Metrodin HP), both administered s.c. in women undergoing ovarian stimulation for in-vitro fertilization including intracytoplasmic sperm injection (ICSI). A total of 235 patients started a long gonadotrophin-releasing hormone agonist protocol: 119 received r-hFSH and 114 received u-hFSH HP (150 IU/day) for the first 6 days. Two patients were excluded from the study because they mistakenly received the incorrect treatment combination. Human chorionic gonadotrophin (HCG; 10000 IU, s.c.) was administered once there was at least one follicle 18 mm in diameter and two others > or = 16 mm. In all, 119 (100%) and 102 (89%) of the patients respectively in the r-hFSH and u-hFSH HP groups achieved the criteria for HCG. The mean numbers (+/- SD) of oocytes recovered (the primary endpoint) were 12.2 +/- 5.5 and 7.6 +/- 4.4 in the r-hFSH and u-hFSH HP groups respectively (P < 0.0001). However, the number of FSH treatment days (11.0 +/- 1.6 versus 13.5 +/- 3.7) and the number of 75 IU ampoules (21.9 +/- 5.1 versus 31.9 +/- 13.4) used were significantly less (P < 0.0001) in the r-hFSH group than in the u-hFSH HP group. In patients treated using ICSI (63 patients in each group), no difference in oocyte maturation was observed. The mean numbers of embryos obtained were 8.1 +/- 4.2 and 4.7 +/- 3.5 (P < 0.0001), in favour of the r-hFSH group. In the majority of patients (96 and 99% respectively) only one or two embryos were replaced (mean 2.0 +/- 0.2 and 1.9 +/- 0.1 respectively) in the r- hFSH and u-hFSH HP groups. The clinical pregnancy rates per started cycle and per embryo transfer were 45 and 36%, and 48 and 47%, respectively in the r-hFSH and u-hFSH HP groups (not significant). There were six (5.1%) and two (1.7%) cases of ovarian hyperstimulation syndrome respectively. In conclusion, it was found that r-hFSH was more effective than u-hFSH at inducing multiple follicular development. However, the high rate of low ovarian response in the u-hFSH group compared with our general experience was unexpected. The availability of a gonadotrophin with less inter-batch variation would be beneficial for clinicians. r-hFSH seems to fulfil such a requirement.      

The effect of human menopausal gonadotrophin and highly purified, urine-derived follicle stimulating hormone on the outcome of in-vitro fertilization in down-regulated normogonadotrophic women

It has been suggested that the luteinizing hormone (LH) activityof human menopausal gonadotrophin (HMG) preparations used forovarian stimulation in in-vitro fertilization (IVF) may haveadverse effects on reproductive outcome. In the present prospective,randomized trial of 218 infertile couples this notion was investigated.A total of 114 women were treated with Pergonal (HMG group)and 104 with Fertinorm HP (HP-FSH group). The two groups werecomparable with regard to duration of infertility, cause ofinfertility, age and number of previous IVF attempts and allhad normal basal gonadotrophin concentrations before treatmentwas started. A standard hormonal treatment consisting of pituitarydown-regulation with gonadotrophin-releasing hormone analogue(GnRHa) for 14 days starting on cycle day 21, followed by eitherHMG or highly purified follicle stimulating hormone (HP-FSH),three ampoules (225 IU) per day for 7 days, was used in allcases. The daily hormone dose was thereafter individualizedaccording to the ovarian response. A maximum of two pre-embryoswere transferred after 3 days of culture. Luteal support withprogesterone (300 mg per day intravaginally) was used in allcases. Serum concentrations of oestradiol, FSH and LH were measuredon days 1 and 8 of stimulation and on the day of oocyte retrieval.The mean number of days of stimulation, mean number of ampoulesof HMG or HP-FSH used, mean total motile sperm count on theday of oocyte retrieval and mean numbers of oocytes retrieved(13.4 versus 13.7) or pre-embryos transferred (1.8 versus 1.8)were similar for both groups. Significantly (P < 0.05) morecycles in the HP-FSH group (17 = 16%) were cancelled due tocomplete failure of fertilization than in the HMG group (7 =6%). The mean fertilization rate was significantly (P < 0.05)higher in the HMG group (56%) than in the HP-FSH group (50%),and significantly more transferable pre-embryos were obtainedin the HMG than in the HP-FSH group (mean: 4.0 versus 3.2; P< 0.01). Serum hormone concentrations were similar in thetwo groups on stimulation day 1, but differed significantlywith regard to FSH, LH and oestradiol on stimulation day 8.The clinical outcome was similar in the two groups, with anongoing pregnancy rate (>12 weeks of gestation) per startedcycle of 33% in the HMG group and 29% in the HP-FSH group. Theclinical abortion rates were similar(10 and 14%), and the implantationrate was 30% in each group. In conclusion, no detrimental effectof the LH activity of HMG on the clinical outcome of IVF inGnRHa down-regulated normogonadotrophic women was found. Tothe contrary, some beneficial effects of HMG on fertilizationrates and pre-embryo development as compared with HP-FSH weredemonstrated. These effects, as well as the differences in serumhormone concentrations during ovarian stimulation, may be causedby differences in LH content and/or in the composition of FSHisoforms of the HMG and HP-FSH preparations.     

Potential dangers in the customary methods of conducting meta-analyses. Recombinant versus urinary follicle stimulating hormone.

The customary method of combining success rates in meta-analyses may often result in serious biases, leading to erroneous inferences. This arises because of an inadmissible pooling of frequencies from heterogeneous sources. The fundamental statistical principle, that the magnitude of an 'effect' should always be tested against the variation in that effect over the sample, may not therefore be satisfied. A simple, but rigorous, alternative method is described.     

A prospective, randomized clinical trial comparing 150 IU recombinant follicle stimulating hormone (Puregon((R))) and 225 IU highly purified urinary follicle stimulating hormone (Metrodin-HP((R))) in a fixed-dose regimen in women undergoing ovarian stimulation.

A prospective, randomized, open, multicentre (n = 3) study was conducted to compare the efficacy and efficiency of a fixed daily dose of 150 IU (3x50 IU) recombinant follicle stimulating hormone (recFSH, Puregon((R))) and 225 IU (3x75 IU) highly purified urinary FSH (uFSH-HP, Metrodin-HP((R))) in women undergoing ovarian stimulation prior to in-vitro fertilization treatment. A total of 165 women were treated with FSH, 83 subjects with recFSH and 82 subjects with uFSH-HP. In the recFSH group a mean number of 8.8 oocytes were retrieved, compared with 9.8 in the uFSH-HP group (not statistically significant). In the recFSH group, a significantly lower total dose was required compared to the uFSH-HP group, 1479 versus 2139 IU, respectively (P < 0.0001; 95% confidence interval -747 to -572). Treatment with recFSH resulted in a significantly higher embryo development rate (69.6 versus 56.2%; P = 0.003) and more embryos accessible for the embryo freezing programme (3.3 versus 2.0; P = 0.02) compared to uFSH-HP. The vital pregnancy rate per cycle started was 30.2 versus 28.3% in the recombinant and urinary FSH group, respectively. It is concluded that treatment outcome of a fixed daily dose of 150 IU recFSH is comparable to a fixed daily dose of 225 IU uFSH-HP. However, a significantly lower total dose was needed in the recFSH group (nearly 700 IU less).     

Effect of profound suppression of luteinizing hormone during treatment with gonadotrophin-releasing hormone analogue and purified follicle stimulating hormone upon development of cryopreserved embryos

In response to previously published evidence from monkeys, this study examined the influence of the degree of luteinizing hormone (LH) suppression during the follicular phase of the stimulation cycle, upon cryopreserved embryo survival and development. The LH concentration of the mid-follicular phase was assessed in 250 in-vitro fertilization (IVF) cycles treated with gonadotrophin-releasing hormone analogue (GnRHa) and either purified follicle stimulating hormone (FSH) or human menopausal gonadotrophin (HMG), and was related to the performance of cryopreserved embryos in 351 subsequent embryo transfer cycles. Rates of embryo survival, embryo development rates, implantation rates, and pregnancy rates were examined with respect to the LH concentration recorded in the mid-follicular phase. In contrast to experimental evidence from other primates, there was no significant influence of the follicular phase LH concentration upon any of the parameters examined.      

Immunocytochemical localization of follicle stimulating hormone in normal human stomach

Immunoreactive follicle-stimulating hormone (IR-FSH) is detected in sections of formalin-fixed and paraffin-embedded gastric mucosal tissue of normal men, using the immunoperoxidase staining technique and specific antisera to hFSH (NIDDK, NIH). Positive staining for IR-FSH was detected in the parietal cells lining the gastric glands of the intermediate zone. The staining was intracytoplasmic and distributed throughout the cytoplasm. IR-FSH was also found to be present in the basal part of the foveolar epithelium. Stromal tissue and nuclei were devod of the stain. The zymogen cells in the deeper region of the mucosa did not show any detectable staining for IR-FSH. The presence of IR-FSH in gastric mucosa was also detected by radioimmunoassay. Gel chromatography of the gastric tissue extract showed a single peak of FSH immunoreactivity that coeluted with the ¹²⁵I-labled highly purified FSH preparation (NIDDK, NIH). Furthermore, the FSH in the pituitary tissue extract had a chromatographic profile similar to that of IR-FSH from gastric tissue, and ¹²⁵I-FSH labeled highly purified FSH, indicating a close resemblance in their molecular sizes. These results demonstrate that IR-FSH is present in the normal human gastric mucosa. The role of this regulatory petpide in gastric tissue, if any, needs to be investigated.     

An enhanced chemiluminescent enzyme immunoassay for follicle stimulating hormone

An enhanced chemiluminescent enzyme immunoassay for serum follicle stimulating hormone is described which involves sequential reaction of anti-follicle stimulating hormone antibody immobilised to the inside surface of an opaque microtitre plate with sample, monoclonal anti-alpha thyroid stimulating hormone antibody, and an anti-mouse IgG - horseradish peroxidase conjungate. Bound peroxidase activity was measured using a p-hydroxycinnamic acid enhanced chemiluminescent luminol-hydrogen peroxide reaction. The assay was sensitive (detection limit 0.01 mU/well) precise (intra-assay precision 2.5-8.1%, inter-assay precision 6.7-11.9%) and results obtained with this assay and a competitive radioimmunoassay were in good agreement (correlation coefficient 0.98).     

Subcutaneous self-administration of highly purified follicle stimulating hormone and human chorionic gonadotrophin for the treatment of male hypogonadotrophic hypogonadism. Spanish Collaborative Group on Male Hypogonadotropic Hypogonadism

The efficacy and safety of highly purified follicle stimulating hormone (FSH) associated with human chorionic gonadotrophin (HCG) was studied in 60 men with hypogonadotrophic hypogonadism. Of these men, 16 suffered from Kallmann's syndrome, 19 from idiopathic hypogonadotrophic hypogonadism and 25 from hypopituitarism. Basal testosterone concentrations were found to be far below the normal range. At baseline, 26 patients were able to ejaculate and all of them showed azoospermia, while the remaining patients were aspermic. All patients self-administered s.c. injections of FSH (150 IU x three/week) and HCG (2500 IU x two/week) for at least 6 months and underwent periodic assessments of testicular function. Testosterone concentrations increased rapidly during treatment and all but one patient reached normal values. Testicular volume showed a sustained increase reaching almost 3-fold its baseline value. At the end of treatment, 48 patients (80.0%) had achieved a positive sperm count. The maximum sperm concentration during treatment was 24.5 +/- 8.1 x 10(6)/ml (mean +/- SEM). The median time to induce spermatogenesis was 5 months. Eleven patients reported adverse events, generally not related to treatment. Three patients experienced gynaecomastia. No local reactions at injection site were observed. In conclusion, the s.c. self- administration of highly purified FSH + HCG was well tolerated and effective in stimulating spermatogenesis and steroidogenesis in these patients.