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Highly purified human menopausal gonadotropin (HP-hMG [Menopur ® , Ferring Pharmaceuticals, Saint-Prex, Switzerland]) contains a 1:1 ratio of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This analysis aimed to assess gonadotropin (FSH, LH and hCG) abundance in HP-hMG and clarify the source of hCG by assessing the presence of sulfated glycans, which are diagnostic for pituitary hCG forms due to their distinct glycosylation patterns. Additionally, the purity of each sample, their specific components, and their oxidation levels were assessed. HP-hMG samples (three of Menopur ® and two of Menogon ® Ferring Pharmaceuticals, Saint-Prex, Switzerland) were included in the current analyses. Brevactid ® (urinary hCG; Ferring Pharmaceuticals, Saint-Prex, Switzerland) and Ovidrel ® (recombinant hCG; Merck KGaA, Darmstadt, Germany) were used as control samples. Glycopeptide mapping and analysis of impurities were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oxidation was assessed through reducing peptide mapping using LC-MS/MS. The FSH and LH in the HP-hMG samples showed sulfated glycans, while no signals of sulfated glycopeptides were detected on any site of the beta subunit of hCG. HP-hMG test samples presented the same hCG glycan distribution as the control sample (placental hCG, Brevactid ® ) extracted from the urine of pregnant women, suggesting a non-pituitary source of hCG. Protein impurities were estimated to constitute approximately 20-30% of the entire HP-hMG protein content in the test samples. More than 200 non-gonadotropin proteins were identified in the HP-hMG test samples, of which several were involved in embryonic development or pregnancy. The alpha subunit of the tested samples was strongly oxidized, with a relative abundance of 20% of the total gonadotropin content. Without taking into account all the protein impurities, the beta subunit of LH was detected only in traces (0.9-1.2%) in all tested HP-HMG samples, confirming the data obtained by intact molecule analysis, while high levels of beta hCG (18-47%) were observed. Advanced molecular analysis of HP-hMG indicates a primarily placental origin of hCG, as evidenced by the absence of hCG sulfated glycans and the predominance of placental non-sulfated hCG in LH activity. The analysis revealed 20-30% of protein impurities and a significant presence of oxidized forms in the HP-hMG samples. These findings are critical for understanding the quality, safety, and clinical profile of HP-hMG.

Background: This study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f ® ) with urinary highly purified human menopausal gonadotropin (hMG HP; Menogon HP ® ), during assisted reproductive technology (ART) treatments in Germany., Methods: Data were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012, for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC). Secondary outcomes were pregnancy loss (analysed per clinical pregnancy), cancelled cycles (analysed pCC), total drug usage per oocyte retrieved and time-to-live birth (TTLB; per calendar week and per cycle)., Results: Twenty-eight thousand six hundred forty-one women initiated a first treatment cycle (r-hFSH-alfa: 17,725 [61.9%]; hMG HP: 10,916 [38.1%]). After adjustment for confounding variables, treatment with r-hFSH-alfa versus hMG HP was associated with a significantly higher probability of live birth (hazard ratio [HR]-pP [95% confidence interval (CI)]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; relative risk [RR]-pFC [95% CI]: 1.09 [1.05, 1.15], ongoing pregnancy (HR-pP [95% CI]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; RR-pFC [95% CI]: 1.10 [1.05, 1.15]) and clinical pregnancy (HR-pP [95% CI]: 1.10 [1.05, 1.14]; HR-pCC [95% CI]: 1.14 [1.10, 1.19]; RR-pFC [95% CI]: 1.10 [1.06, 1.14]). Women treated with r-hFSH-alfa versus hMG HP had no statistically significant difference in pregnancy loss (HR [95% CI]: 1.07 [0.98, 1.17], were less likely to have a cycle cancellation (HR [95% CI]: 0.91 [0.84, 0.99]) and had no statistically significant difference in TTLB when measured in weeks (HR [95% CI]: 1.02 [0.97, 1.07]; p = 0.548); however, r-hFSH-alfa was associated with a significantly shorter TTLB when measured in cycles versus hMG HP (HR [95% CI]: 1.07 [1.02, 1.13]; p = 0.003). There was an average of 47% less drug used per oocyte retrieved with r-hFSH-alfa versus hMG HP., Conclusions: This large (> 28,000 women), real-world study demonstrated significantly higher rates of cumulative live birth, cumulative ongoing pregnancy and cumulative clinical pregnancy with r-hFSH-alfa versus hMG HP.

Menopur ® is a highly purified, urine-derived, human menopausal gonadotropin containing both follicle stimulating hormone (FSH) and luteinizing hormone (LH) activity. It is an effective option for controlled ovarian stimulation (COS) in assisted reproductive technology protocols and for ovulation induction (OI) in anovulatory infertility, and is associated with a different endocrine profile from that of recombinant (r) FSH in these settings (in terms of serum levels of FSH, androgens and/or estradiol). When used for COS in women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), Menopur ® was as good as rFSH in terms of pregnancy rates (despite being associated with a lower oocyte yield) and was found to improve some aspects of embryo quality in the IVF (but not ICSI) setting; using Menopur ® in combination with highly purified urinary FSH resulted in similar reproductive outcomes as Menopur ® alone. Data for Menopur ® in OI are limited, but suggest ovulation rates may be as good as those with rFSH + rLH (in type 1 anovulation) and rFSH (in type 2 anovulation). Moreover, compared with rFSH, Menopur ® appeared to be associated with a less pronounced follicular response and a lower risk of ovarian overstimulation.

The potencies of therapeutic preparations of gonadotrophins of human, urinary origin, which comprise a heterogenous mix of isoforms with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) bioactivities, are standardized by WHO International Standards (IS). We report here, the evaluation, through an international collaborative study, of a candidate preparation, coded 10/286, to replace the 4th IS, 98/704, for human, urinary FSH and LH (Menotrophin) which has been used for many years for the potency assignment of therapeutic preparations using bioassays. The mean FSH and LH bioactivities of 10/286, determined by in vivo bioassays in terms of 98/704, were 183 IU per ampoule (95% confidence limits 165-202) and 177 IU per ampoule (95% confidence limits 159-197), respectively., (Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.)

Gonadotropins including follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play a crucial role in human-assisted reproduction techniques. Despite wide use of recombinant gonadotropins in clinical practice, the efficacy of urinary gonadotropins and the dosage of LH component have not yet been elucidated. This study was designed to investigate the difference of follicle culture outcomes according to various compositions of gonadotropins during in vitro culture of mouse preantral follicles. Ovaries were obtained from the 14-day-old C57BL/6 mice, and preantral follicles were isolated and cultured in culture media supplemented with human menopausal gonadotropin (hMG) 200 mIU/mL (group 1), recombinant FSH and LH (rFSH + rLH) 200 mIU/mL each (group 2), rFSH 200 mIU/mL + rLH 100 mIU/mL (group 3), or rFSH 200 mIU/mL + rLH 20 mIU/mL (group 4). Follicle survival rate was significantly lower in group 4. Antral follicles in lower doses of LH (groups 3, 4) showed a statistically significant larger diameter and tended to have a higher antral formation rate. However, follicles in group 1 tended to have a higher oocyte maturation rate. Estradiol concentration from conditioned media from 2:1 FSH/LH (group 3) was significantly higher than those from 1:1 FSH/LH (group 2) or 10:1 FSH/LH (group 4). Half dose of rLH to rFSH facilitated upregulation of growth differentiation factor 9 (Gdf9) expression in granulosa cells when compared to 1:1 FSH/LH or 10:1 FSH/LH. Conclusively, recombinant gonadotropins provided a comparable condition to hMG, and half dose of rLH to rFSH seems to be more suitable for follicular development during in vitro culture.

Background: Iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing. Risk of carrier status of variant CJD (vCJD), a disease associated with decades-long peripheral incubation, is estimated to be on the order of 100 per million population in the United Kingdom. Studies showing infectious prions in the urine of experimental animals with and without renal disease suggest that prions could be present in asymptomatic urine donors. Several human fertility products are derived from donated urine; recently prion protein has been detected in preparations of human menopausal gonadotropin (hMG)., Methodology/principal Findings: Using a classical proteomic approach, 33 and 34 non-gonadotropin proteins were identified in urinary human chorionic gonadotropin (u-hCG) and highly-purified urinary human menopausal gonadotropin (hMG-HP) products, respectively. Prion protein was identified as a major contaminant in u-hCG preparations for the first time. An advanced prion protein targeted proteomic approach was subsequently used to conduct a survey of gonadotropin products; this approach detected human prion protein peptides in urine-derived injectable fertility products containing hCG, hMG and hMG-HP, but not in recombinant products., Conclusions/significance: The presence of protease-sensitive prion protein in urinary-derived injectable fertility products containing hCG, hMG, and hMG-HP suggests that prions may co-purify in these products. Intramuscular injection is a relatively efficient route of transmission of human prion disease, and young women exposed to prions can be expected to survive an incubation period associated with a minimal inoculum. The risks of urine-derived fertility products could now outweigh their benefits, particularly considering the availability of recombinant products.

Advances in proteomic technology have enabled contaminant proteins to be identified from complex protein mixtures. The purity of two purified urinary gonadotrophin products, human menopausal gonadotrophin (u-HMG) and human FSH (u-hFSH), was compared with a preparation of recombinant human FSH (r-hFSH). After separation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), western blot analysis showed that the recombinant preparation contained only FSH, whereas the urine-derived preparations exhibited several non-FSH or LH-related bands. These urinary components were further investigated by a proteomic approach using two-dimensional SDS-PAGE followed by mass spectrometric identification. The proteomic approach detected a total of 23 non-gonadotrophin-related proteins, at variable levels in different batches of the urine-derived preparations. Of these, 16 co-purified proteins have not been previously reported to be present in urine-derived gonadotrophins. These results indicate that the process used to purify urinary gonadotrophins may not remove all non-gonadotrophin proteins. By using a comprehensive proteomic approach, it has been shown that the recombinant FSH preparation has greater purity than either of the urine-derived preparations.

Recently, a highly purified human menopausal gonadotrophin preparation (HMG) was launched. The composition and purity of this HMG (Menopur); Ferring Pharmaceuticals) with a claimed 1:1 ratio of FSH and LH was determined. Three gonadotrophins were observed: FSH, LH and human chorionic gonadotrophin (HCG). The immunoactivity for HCG was three-fold higher than the immunoactivity for LH. Because of the longer half-life of HCG as compared with LH, about 95% of the in-vivo LH-receptor-mediated bioactivity is attributable to the presence of HCG. This is substantiated by biochemical analyses. To the best of the authors' knowledge, this relatively high amount of HCG can only be explained by assuming the addition of HCG from external sources, which is a well established practice for standardization purposes. In addition to gonadotrophins, a number of other proteins were detected. The amount of these impurities, as determined by reversed-phase high-performance liquid chromatography on a peak-area basis, is at least 30%. Therefore, it is concluded that this HMG preparation contains at most 70% gonadotrophins. Via a proteomics approach three major impurities were identified: leukocyte elastase inhibitor, protein C inhibitor, and zinc-alpha(2)-glycoprotein. On the basis of the results obtained in this study, a comparison is made with recombinant FSH.

Evidence is emerging that suggests that the protease-resistant isoform (PrP(sc)) of the normal cellular prion protein (PrP(c)) can be detected in the blood and urine of animals and humans with transmissible spongiform encephalopathies (TSEs). The production of the human menopausal and recombinant gonadotrophin preparations for use in ovarian stimulation protocols in fertility treatment is one area where the pharmaceutical industry needs to be vigilant and take appropriate steps to ensure that the safety of such drugs remains as high as ever. The recombinant preparations utilize fetal calf serum or other animal sera or proteins as part of a culture medium during production. Human urinary-derived menotrophin preparations are exposed to the theoretical risk of infection from menopausal donors of urine. Nevertheless, the failure to demonstrate irrefutably infectivity following intracerebral inoculation with urine from TSE-infected hosts suggests that the risk associated with products derived from urine is merely theoretical. Despite the paucity of evidence to date and its relevance to the infectious spread of TSEs, it is important that robust measures are implemented to either remove or inactivate PrP(sc) in order to minimize contamination. Validation of each production process is required to assess the likelihood of contamination.

Objective: To study the correlation between stimulation duration of IVF cycles, with and without GnRH agonist (GnRH-a), and cycle outcome., Design: Retrospective analysis of data., Setting: University-affiliated IVF clinic., Patient(s): 998 IVF cycles in which long GnRH-a protocol was used, and 155 cycles with hMG only., Intervention(s): IVF cycles., Main Outcome Measure(s): Cycle outcome in number of oocytes and embryos, and pregnancy rate., Result(s): The mean stimulation duration (+/-SD) was 9.6+/-1.7 and 6.7+/-1.0 for the GnRH-a and the hMG-only cycles, respectively (P<0.01). In the GnRH-a group, no statistically significant correlation between cycle duration and pregnancy rate was found. Interestingly, the patients treated for 9 days had the highest number of oocytes retrieved and the highest pregnancy rate. Stimulation duration was not affected by age in either protocol. GnRH-a cycles yielded a significantly higher number of oocytes and embryos compared to cycles without GnRH-a. The pregnancy rate was similar in both groups., Conclusion(s): Stimulation duration in the long GnRH-a protocol group was significantly longer than in the hMG-only group. Stimulation duration was not affected by age. No statistically significant correlation was found between stimulation duration and cycle outcome in the long protocol group.

Objective: To study the influence of an LHRH (luteinizing hormone releasing hormone) antagonist protocol (Cetrorelix) and the use of recombinant follicle-stimulating hormone (FSH) on the development of leukocytosis, compared to the use of urinary HMG (human menopausal gonadotrophin)., Design: Prospective, randomized phase III clinical trial., Setting: Infertility day clinic, Department of Gynecology and Obstetrics., Patients: Thirty patients undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment following controlled ovarian stimulation using a multiple dose protocol and the LHRH antagonist Cetrorelix., Main Outcome Measure: Differences in white blood cell (WBC) count before stimulation, during the follicular phase and in the midluteal phase., Results: Statistically significant increase in WBC count in the HMG group from the start of stimulation to the midluteal phase. No statistically significant increase in the recFSH group, but only a trend towards higher values was observed., Conclusion: The development of a leukocytosis in controlled ovarian stimulation does not depend on the protocol used. Urinary gonadotrophins seem to have a greater potential to increase WBC count compared to recombinant gonadotrophins.

Objective: To compare the incidence and severity of local side effects of urinary-derived gonadotropins administered s.c. and i.m.., Design: Prospective randomized study of women undergoing IVF treatment., Setting: Tertiary referral center for assisted reproduction., Patient(s): A total of 71 patients were randomized to receive gonadotropins by the s.c. (n = 41) or i.m. (n = 30) route., Intervention(s): One cycle of IVF with gonadotropins administered either s.c. or i.m. for ovarian stimulation., Main Outcome Measure(s): Incidence and severity of local side effects, such as redness, itching, swelling, pain, and bruising., Result(s): Pain was the most common side effect, with 55.3% and 70.1% of i.m. and s.c. injections, respectively, resulting in pain. There were no statistically significant differences in the incidence of itching or bruising after i.m. and s.c. injections. Although there was a higher incidence of redness and swelling in the s.c. group compared with the i.m. group, most cases were classified as mild., Conclusion(s): There was a significantly higher incidence of some local side effects after s.c. gonadotropin administration but most of these were mild and well tolerated by patients.

Objective: To assess the pharmacokinetics after i.v. administration of a recombinant human LH and to compare them to those of a reference hMG preparation containing urinary human LH., Design: Prospective, dose-escalating, cross-over study., Setting: Phase I clinical research environment., Patient(s): Twelve healthy pituitary down-regulated females., Intervention(s): Subjects received single i.v. doses of 300, 10,000, and 40,000 IU of recombinant human LH, followed by a single i.v. dose of 300 IU of hMG, all separated by 1 week., Main Outcome Measure(s): Pharmacokinetic parameters., Results: For both preparations, LH serum levels were well described by similar biexponential models. The pharmacokinetics of recombinant human LH were linear over the 300 to 40,000 IU range. After a rapid distribution phase with an initial half-life of 1 hour, both recombinant human LH and urinary human LH were eliminated with a terminal half-life of 10-12 hours. Total serum clearance was 1.7 L/h with < 4% and 30% of the dose being eliminated in the urine for recombinant human LH and urinary human LH, respectively. The volume of distribution at steady-state was approximately 10 L. Irrespective of the dose, recombinant human LH was well tolerated., Conclusion(s): The pharmacokinetics of recombinant human LH are linear with dose and similar to those of urinary human LH.

Aims: To characterize the pharmacokinetics of recombinant-human follicle stimulating hormone (r-hFSH) and urinary-human follicle stimulating hormone (u-hFSH) using population pharmacokinetic analysis and deconvolution techniques., Methods: Sparse data were available from 62 female patients who received u-hFSH intramuscularly (i.m.) and 60 female patients who received r-hFSH subcutaneously (s.c.) as part of an in vitro fertilisation and embryo transfer (IVF-ET) procedure. The dose of u-hFSH and r-hFSH was 225 International Units (IU) FSH/day for the first 5 days of treatment. The dose of u-hFSH/r-hFSH on subsequent days depended upon the ovarian response. Intensively sampled data were also available from 12 female volunteers who received r-hFSH, 150 IU, on three occasions: intravenously (i.v.), i.m. and s.c., each separated by 1 week of wash-out. The volunteers then received multiple r-hFSH doses by the s.c. route: 150 IU once daily for 7 days. Intensively sampled data were available from a further 12 female volunteers who received u-hFSH, 150 IU, given by the i.v. and i.m. routes., Results: Analysis of the intensively sampled r-hFSH and u-hFSH data sets found that disposition could be described using a two-compartment model and that absorption was rate limiting and essentially a first order process, for both compounds. The population estimate of clearance (CL) after i.v. administration was 0.60 and 0.44 l h(-1) for r-hFSH and u-hFSH respectively. The calculated mean residence times (MRT) for r-hFSH and u-hFSH were 16 and 18 h, respectively. The different bioavailabilities (F) and mean absorption times (MAT) determined after i.m. and s.c. administration ranged from 0.60 to 0.77 and from 27 h to 48 h, depending on compound, administration route, data type and method of analysis. Population analysis of the sparse patient data found that a one compartment model with first order absorption was adequate to describe the r-hFSH and u-hFSH data. The population estimates of apparent clearance (CL/F) were 0.71 and 0.33 l h(-1) for r-hFSH and u-hFSH respectively. Urinary-hFSH CL/F increased linearly with weight and was 0.33 l h(-1) at the average weight of 58.5 kg. No other covariates (age, weight, height, creatinine clearance, body mass index, race) were found to influence the FSH disposition parameters. The sparse data population estimates of intersubject variability in CL/F for r-hFSH and u-hFSH were essentially the same, 26% and 25%, respectively., Conclusions: The population analysis indicates that the variability in CL/F is moderate, consequently, so would be the variability in exposure, given a fixed dosage regimen.

The within- and between-batch variation in the immunoreactive and in-vitro bioactive FSH content of Pergonal, Metrodin and Metrodin-HP was investigated. Three batches of Pergonal and Metrodin, consisting of three ampoules in each batch, and three batches of Metrodin-HP, consisting of between one and three ampoules per batch, were selected at random. The follicle stimulating hormone (FSH) content of Pergonal, Metrodin and Metrodin-HP was determined by radioimmunoassay (R-FSH) and the in-vitro rat Sertoli cell bioassay (B-FSH) using the international urinary standard 70/45. The variability in the FSH content of the preparations was evaluated within and between batches by analysis of variance. Within-batch variability of B-FSH was not observed in Pergonal or Metrodin-HP but was seen in two batches of Metrodin in which the potency varied by up to 2.4 fold (P = 0.03). The between-batch R-FSH potencies of Pergonal (P1-P3) varied, with P2 (59.8 +/- 0.6) and P3 (61.7 +/- 0.9) being higher than P1 (47.1 +/- 1.5 mean +/- SEM IU/ampoule, P < 0.01). A similar pattern of variability was observed for B-FSH. For Metrodin, each of the batch R-FSH potencies was dissimilar (P < 0.02), with estimates ranging from 34.9 +/- 1.2 to 64.3 +/- 1.8 IU/ampoule. Furthermore, the extensive within-batch B-FSH variation from two batches confounded any meaningful comparison of between-batch variability. For Metrodin-HP, there was no between-batch B-FSH variation (29.0 +/- 6.1 to 33.0 +/- 0.3 IU/ampoule) and the R-FSH content was also well controlled (41.2 +/- 0.5 to 46.9 +/- 1.1 IU/ampoule).(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized, double-blind, crossover study was carried out to compare purified urinary follicle-stimulating hormone (FSH) and human menopausal gonadotropin (hMG) for ovarian stimulation in polycystic ovarian syndrome (PCOS). Twelve patients were stimulated with FSH and hMG in three alternate cycles. FSH, luteinizing hormone (LH), estradiol, dihydroepiandrosterone sulphate, free and total testosterone, delta 5-androstenedione, sex hormone binding globulin, and ovarian volume were monitored during the stimulation. There was no difference between the dose of FSH and hMG necessary to induce preovulatory follicles in the individual patients. The mean increase of ovarian volume during stimulation with FSH and hMG was 120% and 129% respectively (no significant difference). Two patients became pregnant in the first cycle. Two other patients had delayed bleeding and positive serum-human chorionic gonadotropin. No significant difference was found in the endocrine changes during the two different stimulation methods. The LH/FSH ratio was normalized after a few days of treatment regardless of the type of stimulation. The size of the material does not permit a comparison of the efficacy of the two treatment schedules. Our clinical and ultrasonic observations do not support the theory that treatment of infertility in PCOS with FSH is more safe than with hMG.

The success of IVF is related to the number and quality of embryos transferred. In our IVF program we have used two different protocols for superovulation induction. In this study a group of 35 patients was randomized into two groups; the first group (15 patients) was treated with pure FSH and hMG, in the other (20 patients) the normal pituitary function was inhibited with Buserelin before the stimulation with hMG. Ovarian stimulation was monitored by ultrasound examination and endocrine parameters. The RIA determination of 17-beta estradiol (17-E2) plasmatic levels is one of the most widely used techniques in IVF cycle monitoring; however many serious disadvantages are connected with the use of RIA (short half-life of the reagents; hazard of handling radioactive materials; frequent venipunctures for the patients). For these reasons, we propose a chemiluminescence immuno assay (LIA) method for the measurement of glucuronometabolites of 17-E2 and progesterone in early morning urine samples: this technique allows to follow hormonal levels for all the cycle, avoiding patient discomfort. We have found a highly significant correlation between serum and urinary hormonal values. We noted a marked variability in the individual estrogenic response and a significant difference in the response of the two groups. The mean peak on hCG administration day was 6.4 +/- 3.5 micrograms/h for urinary E1-3G and 1270 +/- 678 pg/ml for 17-E2 in Buserelin-hMG group: these hormonal levels appear lower than without ovarian desensitization; (in FSH-hMG group we have, on the same day, 9.7 +/- 3.2 micrograms/h for E1-3G and 1630 +/- 730 pg/ml for serum 17-E2).(ABSTRACT TRUNCATED AT 250 WORDS)

Human urinary FSH (HU-FSH) was administered during 25 treatment cycles to 21 infertile women with polycystic ovary syndrome (PCO) who had failed to conceive in response to clomiphene citrate. HCG was also given in 23 of the cycles. Twenty-two (88%) ovulations occurred, and eight (38.1%) conceptions resulted, two (25%) of which terminated in abortion and six (75.0%) in normal deliveries. No multiple pregnancies occurred. Ten instances (40%) of mild-moderate hyperstimulation also resulted. A spontaneous LH surge was observed in 12 treatment cycles. Ultrasound scanning revealed multiple ovarian follicles developing at various rates. We conclude that HU-FSH is an effective form of treatment for women with PCO. However, the response to exogenous FSH is unpredictable and depends on the stage of development and the number of follicles present prior to stimulation.

This report compares the effects of human menopausal gonadotropin (hMG) and purified urinary human follicle-stimulating hormone (hFSH) protocols in patients with irreparable tubal disease as the sole indication for in vitro fertilization-embryo transfer (IVF-ET). The hFSH protocol was associated with significantly more uniform folliculogenesis and more effective steroidogenesis than the one using hMG. In addition, the hFSH protocol showed a trend toward more oocytes per laparoscopy and more embryos per transfer than the hMG group, although the difference was not statistically significant. More oocytes in the hMG group were classified as immature when compared with the hFSH group (P less than 0.05). Pregnancy rates in both groups were not significantly different. An allergic drug reaction that occurred in one patient on the hFSH protocol is the first such reaction reported with hFSH in the literature. The hFSH protocol is associated with a trend toward parameters that correlate with improved success rates in the IVF-ET program.