Urinary FSH Research Articles

A Study Comparing the Effects of Two Follicle-Stimulating Hormones used in Assisted Reproductive Technique

To compare the efficacy of recombinant follicle-stimulating hormone (rFSH) and highly-purified urinary follicle-stimulating hormone (uFSH HP) used in in-vitro fertilization(IVF) or intracytoplasmic sperm injection (ICSI) treatment. 76 patients undergoing in-vitro fertilization(IVF) or intracytoplasmic sperm injection (ICSI) treatment were divided into rFSH group (n=38) and uFSH HP group (n=38) randomly. Two groups were used rFSH and uFSH HP respectively after the pituitaries were down regulated with Gonadotropin releasing hormone agonist (GnRH-a). Human chorionic gonadotrophin (HCG) were injected intramuscularly when the diameter of the dominant follicle were more than 18mm, and IVF/ICSI were treated after 36 hours of oocytes retrieval. The embryos were transferred 2 days later. The results were observed including the number of ampoules, follicles and oocytes retrieved, serum estradiol level, the fertilization rate, the pregnancy rates and the rate of complications. There were significant difference in the number of ampoules between rFSH group (34.50±7.87) and uFSH HP group (40.47±9.22) (P<0.05). The total doses of rFSH group was lower than those of uFSH HP group[2587.50±590.23IU vs. 3035.53±691.30IU (P<0.05)]. There were no significant difference in the number of follicles and serum estradiol level on the day of human chorionic gonadotropin administration day, and number of oocytes retrieved. The fertilization rate was higher in rFSH group(87.18%) than in uFSH HP (73.65%)(P<0.05). The pregnancy rates were 36.8% and 26.3% for each group respectively. No differences were found in the number of spontaneous abortion, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS), and the weeks and the weights of the infants(P>.05). rFSH produced higher fertilization rate and pregnancy rate than uFSH, and the total dose required was lower. It was a more efficiency and save follicle stimulating hormone, and more suitable for clinical application.

Use of follicle-stimulating hormone for the treatment of female infertility – current concepts

Ovulatory dysfunction, which is common among women of reproductive age, often results in infertility. Over the last three decades, follicle-stimulating hormone (FSH), in the form of either urinary human menopausal gonadotropin or highly purified urinary FSH (uFSH), has been the mainstay in the treatment of women with ovulatory dysfunction. However, these preparations have several disadvantages, including variable composition, contamination with urinary proteins, and the limited availability of human menopausal urine from which uFSH is extracted. Recombinant human FSH (rhFSH) demonstrates higher purity and specific activity, and is suitable for subcutaneous administration. Additionally, rhFSH has facilitated the development of additional FSH products such as FSH-carboxy terminal peptide that possess different pharmacokinetic and pharmacodynamic properties and may provide more options in the treatment of ovulatory dysfunction and infertility. This article reviews the mechanism of action of FSH in folliculogenesis and ovulation, the current use of FSH in women for the medical management of infertility, and the published clinical experience to date with different rhFSH preparations.

Use of Follicle-Stimulating Hormone for the Treatment of Female Infertility – Current Concepts

Ovulatory dysfunction, which is common among women of reproductive age, often results in infertility. Over the last three decades, follicle-stimulating hormone (FSH), in the form of either urinary human menopausal gonadotropin or highly purified urinary FSH (uFSH), has been the mainstay in the treatment of women with ovulatory dysfunction. However, these preparations have several disadvantages, including variable composition, contamination with urinary proteins, and the limited availability of human menopausal urine from which uFSH is extracted. Recombinant human FSH (rhFSH) demonstrates higher purity and specific activity, and is suitable for subcutaneous administration. Additionally, rhFSH has facilitated the development of additional FSH products such as FSH-carboxy terminal peptide that possess different pharmacokinetic and pharmacodynamic properties and may provide more options in the treatment of ovulatory dysfunction and infertility. This article reviews the mechanism of action of FSH in folliculogenesis and ovulation, the current use of FSH in women for the medical management of infertility, and the published clinical experience to date with different rhFSH preparations.

A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination

There are few data in the literature regarding the utility of metfomin before and during gonadotrophin administration in women with polycystic ovary syndrome (PCOS). The aim of the present study was to assess the effect of the pre-treatment and co-administration of metformin in infertile PCOS women treated with controlled ovarian stimulation (COS) followed by timed intercourse (TI) or intrauterine insemination (IUI). Seventy insulin-resistant primary infertile women with PCOS were randomized to receive metformin cloridrate (850 mg twice daily; group A) or placebo tablets (two tablets daily; group B) for 3 months. Three trials of COS using highly purified urinary FSH (hpFSH) plus TI/IUI were performed. Number of ampoules of gonadotrophin used, duration of the ovarian stimulation, cycle cancellation, ovulation, pregnancy, abortion, live birth, mono-ovulatory cycles, multiple pregnancies and ovarian hyperstimulation syndrome (OHSS) rates were assessed. No difference between groups was detected in ovulation, cycle cancellation, pregnancy, abortion, live birth, multiple pregnancies and OHSS rates. The mono-ovulatory cycle rates were significantly (P = 0.002) more frequent in group A than in group B, whereas the days of stimulation for non-cancelled cycles and the number of vials of gonadotrophins used were significantly (P < 0.001) higher in group A than in group B. In insulin-resistant women with PCOS, metformin pre-treatment and co-administration with hpFSH increases the mono-ovulatory cycles.

Cigarette smoking and effects on hormone function in premenopausal women.

Cigarette smoke contains compounds that are suspected to cause reproductive damage and possibly affect hormone activity; therefore, we examined hormone metabolite patterns in relation to validated smoking status. We previously conducted a prospective study of women of reproductive age (n = 403) recruited from a large health maintenance organization, who collected urine daily during an average of three to four menstrual cycles. Data on covariates and daily smoking habits were obtained from a baseline interview and daily diary, and smoking status was validated by cotinine assay. Urinary metabolite levels of estrogen and progesterone were measured daily throughout the cycles. For the present study, we measured urinary levels of the pituitary hormone follicle-stimulating hormone (FSH) in a subset of about 300 menstrual cycles, selected by smoking status, with the time of transition between two cycles being of primary interest. Compared with nonsmokers, moderate to heavy smokers (≥ 10 cigarettes/day) had baseline levels (e.g., early follicular phase) of both steroid metabolites that were 25–35% higher, and heavy smokers (≥ 20 cigarettes/day) had lower luteal-phase progesterone metabolite levels. The mean daily urinary FSH levels around the cycle transition were increased at least 30–35% with moderate smoking, even after adjustment. These patterns suggest that chemicals in tobacco smoke alter endocrine function, perhaps at the level of the ovary, which in turn effects release of the pituitary hormones. This endocrine disruption likely contributes to the reported associations of smoking with adverse reproductive outcomes, including menstrual dysfunction, infertility, and earlier menopause.

Use of Follicle-Stimulating Hormone Test to Predict Poor Response in In Vitro Fertilization

Optimized ovarian stimulation protocols are required for the success of in vitro fertilization (IVF). The purpose of this study was to estimate whether the ovarian reserve test using exogenous follicle-stimulating hormone (FSH) could predict ovarian response in IVF. This was a prospective observational study of 110 patients who underwent their first IVF cycle. The FSH test was administered as 150 IU of urinary FSH daily from day 3 to day 6 of the menstrual cycle preceding the IVF cycle for evaluation of the plasma estradiol level. Outcomes of IVF, including ovarian response, were analyzed. A negative correlation was observed between the duration of stimulation and the result of the FSH test (r = -.238, P = .014) and between the dose of FSH per retrieved mature oocyte (metaphase II oocyte) and the result of the FSH test (r = -.308, P < .001). In addition, our results showed that the result of the FSH test was significantly lower in poor responders defined by FSH of 400 IU/metaphase II oocyte or greater (207 +/- 149 compared with 293 +/- 174 pg/mL, P = .007). The FSH test can be a useful tool for determining the conditions of individualized clinical management plans and optimizing stimulation protocols in IVF.

Embryo quality based on ovulation induction: defining the differences

Patients undergoing IVF, with or without intracytoplasmic sperm injection, were treated with either recombinant human FSH or urine-derived FSH. Response to ovarian stimulation was monitored by ultrasound examinations and measurement of serum oestradiol concentrations. To define any differences in embryo quality and hence assisted reproductive technology success rates, a retrospective analysis of 811 recombinant FSH versus 555 urinary FSH cycles was undertaken. Embryo quality was assessed as embryo cell number and degree of fragmentation. Implantation and ongoing pregnancy rates were also compared. Use of recombinant FSH resulted in a higher percentage of mature oocytes, improved embryo cleavage, with more embryos available for freezing and higher implantation rates compared with urinary FSH. Oocyte and embryo quality were superior when recombinant FSH was used for ovarian stimulation compared with urinary FSH.

326 OPTIMIZING FREQUENCY OF FSH APPLICATION FOR SUPEROVULATORY TREATMENT IN CATTLE

The aim of the study was to examine the influence of the application frequency of Pluset® (Calier, Spain) and Folltropin® (Vetrepharm, London, Ontario, Canada) on the results of embryo recovery in Simmental cattle. Moreover, pulsatility of LH concentrations in plasma should be studied before and after application of Pluset. FSH was given in a treatment of eight or four injections on four consecutive days starting between Days 9 and 13 of the estrous cycle. Luteolysis was induced by application of 500 μg Estrumate® (Essex Tierarznei, Munich, Germany), applied 72 and 84 h after the first FSH injection. Embryo recovery was performed non-surgically on Day 7 of the following estrous cycle. Heifers received either a total amount of 500 IU Pluset according to the International Standard for human urine FSH and LH (P1: 8 injections, n = 20; P2: 4 injections, n = 54) or 200 mg Folltropin according to NIH bFSH-B1 (F1: 8 injections, n = 117; F2: 4 injections, n = 60). Cows received either 550 IU Pluset (P3: 8 injections, n = 54; P4: 4 injections, n = 183) or 260 mg Folltropin (F3: 8 injections, n = 36; F4: 4 injections, n = 159). Altogether 8 heifers were bled throughout 8 h every 10 min on Days 9 and 12 (before and during stimulation with FSH). The samples were analyzed for LH by ECLIA (intra-assay coefficient of variation (VK) 6.4%, inter-assay VK 8.9%). The evaluation of the data was carried out with the procedure ‘GLM’ of the statistics software package SAS (SAS Institute, Inc., Cary, NC, USA) and PULSAR analysis. As a post hoc test Student's t-test was used. Significance was set at P = 0.05. Results of embryo recovery are shown in the table. Number of LH pulses in 8 h (LSM ± SE) was 2.3 ± 0.4 on Day 9 and 0.6 ± 0.4 on Day 12 (P &lt; 0.05). We conclude that four injections of both FSH products can lead to results comparable with those reached with eight injections in a 12 hours interval. Therefore, the effort for superovulatory treatments can be reduced. However, it has to be considered that the portion of transferable embryos was reduced, partly significantly, after four FSH injections. This result was independent of the drug used. Table 1. Results of embryo recovery

Effect of urinary versus recombinant follicle-stimulating hormone on platelet function and other hemostatic variables in controlled ovarian hyperstimulation

To determine the effect of urinary versus recombinant FSH on platelet function and hemostatic variables in women undergoing controlled ovarian hyperstimulation cycles. Randomized clinical study. Major university-based infertility and in vitro fertilization unit and hemostasis laboratory. Ten healthy women (in vitro study), and 24 women undergoing routine controlled ovarian hyperstimulation cycles (in vivo study), randomly assigned to receive either urinary (u-FSH) or recombinant gonadotropin (r-FSH). In vitro study: effect of preincubation of plasma with u-FSH or r-FSH, in the presence or absence of estradiol, on platelet function and coagulation parameters. In vivo study: Changes in platelet function and coagulation parameters after treatment with u-FSH or r-FSH during controlled ovarian hyperstimulation cycles. Platelet aggregation and ATP release, activated protein C resistance ratio, free protein S. In vitro study: Platelet aggregation and ATP release were significantly inhibited by u-FSH relative to r-FSH in both the presence and absence of estradiol (P=.047). In vivo study: Platelet function was significantly inhibited after treatment with u-FSH (P=.05) but not with r-FSH. In both studies, small changes of minor clinical significance were noted in activated protein C resistance and free protein S levels. The different platelet response to u-FSH and r-FSH may have clinical implications in selected patients, especially those at risk of thromboembolic complications, in decisions regarding the appropriate medication for controlled ovarian hyperstimulation cycles.

Recombinant versus urinary follicle-stimulating hormone in intrauterine insemination cycles: A prospective, randomized analysis of cost effectiveness

To compare the clinical results and the cost effectiveness of urinary FSH and recombinant FSH in ovarian stimulation for IUI cycles. Prospective, randomized trial. University Hospital, Perugia, and A.G.UN.CO. Obstetrics and Gynaecology Centre, Rome, Italy. IUI cycles were performed in 67 infertile patients. Protocols of ovarian stimulation with urinary FSH or recombinant FSH were randomly assigned, for a total of 138 cycles performed (67 and 71, respectively). Number of mature follicles, days of stimulation, number of ampules, and IU used per cycle, biochemical/clinical pregnancy rates and cost-effectiveness ratio. Follicular development, length of stimulation, pregnancy and delivery rates were not statistically different. Although in the urinary FSH group a significantly higher number of IU of gonadotropins were used (815.5 +/- 284.9 vs. 596.0 +/- 253.8), the cost per cycle remained significantly lower (220.73 +/- 94.72 vs. 318.50 +/- 125.21). The cost-effectiveness ratio was 1,848.61 euro in the urinary FSH group and 2,512.61 euro in the recombinant FSH group. Urinary FSH and recombinant FSH are both effective in ovarian stimulation in IUI cycles. The urinary preparation is more cost effective due to the difference of its cost per IU.

Effects of recombinant FSH on the gene expressions in human endometrial cells

Human endometrial cells have FSH receptor as well as LH/hCG receptor. However, the effect of recombinant FSH on the human endometrium is not evaluated. The objective of this study was to compare the effects of recombinant FSH (rFSH) and urinary FSH (uFSH) on the expression pattern of implantation-related genes in the in vitro culture system. A prospective controlled laboratory study. Human endometrial specimens were obtained from premenopausal women undergoing hysterectomy. Endometrial stromal cells isolated, and its purity was confirmed by immunocytochemistry of vimentin. The primary stromal cells were cultured with DMEM/F-12 containing 0, 10, 100, and 1,000 mIU /ml of rFSH and uFSH for 72 hours, respectively. Total RNA was extracted from the cultured cells and converted to cDNA with reverse transcriptase. Equivalent amount of RNA were subjected to real time RT-PCR, and β-actin was used as an internal control for quantitative analysis of gene expressions. We analyzed seven implantation-related genes, such as progesterone receptor (PR), estrogen receptor-α/β (ER-α/β), cyclooxygenase-2 (Cox-2), leukemia inhibitory factor (LIF), homeobox A10-1 and -2 (HoxA10-1 and -2). Primary stromal cells showed polygonal and spindle shaped, and more than 95% of cells were vimentin positive in immunocytochemistry. The PR expression was not altered, however, the ER-α was increased to six folds by time dependent in both rFSH and uFSH treatment. The 1,000 mIU/ml of rFSH induced five folds higher expressions of ER-β and eight folds of Cox-2 than the uFSH. The LIF expression was increased to three and four folds by the 100 mIU/ml of uFSH and rFSH, respectively. On both rFSH and uFSH treatment, the HoxA10-1 and -2 expressions were slightly increased in a time dependent manner. We observed that rFSH and uFSH could differentially regulate the gene expressions in the in vitro cultured human endometrial stromal cells. This study represents several positive effects of rFSH on the expression of implantation related genes, such as increase of ER-α/β, Cox-2 and LIF. The rFSH is unlikely to adversely impact endometrial receptivity. We are currently examining the effect of rFSH on the in vivo system of human endometrium in assisted reproductive cycles.

Highly purified follicle-stimulating hormone and oocyte and embryo quality

The availability of recombinant follicle-stimulating hormone (rFSH) has introduced a valid and attractive alternative to urine-derived follicle stimulating hormone (uFSH) for ovarian stimulation regimens. However, the efficacy and efficiency of rFSH compared to uFSH is still a matter of turbulent debate. In this study, the effect of highly purified urinary FSH and recombinant FSH on oocyte and embryo quality was investigated.

An open, prospective, randomized, multicenter study to compare recombinant human follicle stimulating hormone (rec-FSH; follitropin-β; Puregon® solution) with highly purified urinary FSH (uFSH, urofollitropin (highly purified), Metrodin® HP) in Chinese women undergoing in vitro fertilization (IVF)

To compare the efficacy, efficiency and safety of rec-FSH (follitropin-β; Puregon® solution) and highly purified urinary FSH (Metrodin® HP) in Chinese women undergoing controlled ovarian stimulation (COS) for IVF.

Avantages pharmaco-économiques de la FSH d'origine recombinante par rapport à la FSH d'origine urinaire

Nowadays, the use of urinary FSH is essentially justified by a lower acquisition price compared to modern products generated by Biotechnology (recombinant FSH). However, the public price of a product is only one element of the total cost of a therapeutic regimen that must be taken into account in medical decision-making. This is the role of pharmacoeconomic studies including cost-effectiveness models, which allow proceeding to complex situational comparisons such as several attempts of Assisted Reproduction Techniques. Different models have been carried out and published in several countries and present consistently that recombinant FSH is more cost-effective that urinary derived FSH.

Reduction of dehydroepiandrosterone sulfate synthesis in women with polycystic ovary syndrome by human menopausal gonadotropin but not purified urinary follicle stimulating hormone: a comparative pilot study

We aimed to compare the effects of two different gonadotropins on steroid production in patients with polycystic ovary syndrome (PCOS). The study group comprised 20 infertile patients diagnosed with PCOS who were accepted into in vitro fertilization – embryo transfer and gamete intra-Fallopian transfer programs. Ten patients were consecutively allocated to a purified urinary follicle stimulating hormone (FSH) administration group while the other ten received human menopausal gonadotropin (hMG). All patients were pretreated with a gonadotropin releasing hormone-agonist. The patients were followed by daily vaginal ultrasonography until at least two follicles reached a diameter of 17 mm or an estradiol value of at least 100 pg/ml per follicle. To induce ovulation, human chorionic gonadotropin was given. On the 3rd day of menstruation, serum estradiol, luteinizing hormone (LH), FSH, total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I and insulin were measured. These same parameters were measured again on the day of follicle aspiration in both serum and follicular fluid. In both groups, the serum levels of estradiol and androstenedione were raised significantly, and on aspiration day the serum level of DHEAS was significantly raised in the FSH group but not in the hMG group. Our findings suggest that in PCOS patients exogenous hMG induces a different steroid synthesis pattern compared to pure FSH, hypothetically by reduction of the Δ-5 steroid synthesis pathway in the adrenals and/or in the ovary.

La fécondation in vitro en France. Approche économique et influence du choix des gonadotrophines (urinaires ou recombinantes) sur le coût

Objectives. – The objective of the study was to make an economic evaluation of in vitro fertilization and to determine the impact of some factors on its cost, particularly the choice between recombinant follicle stimulating hormone (r-FSH) and urinary FSH (u-FSH) for ovarian stimulation. Patients and methods. – Costs were calculated in a Public Health view, by studying two phases: the stimulation cycle (including down-regulation) and the pregnancy (including the neonatal period). The calculation has included the side effects and the frozen embryos transfers. Economic data came from various sources: the French nomenclature on medical treatments (NGAP), the French drugs dictionary (Vidal) and the French Information system medical plan (PMSI). FSH costs were computed according to the currently marketed products, i.e., Fostimon ® ( Laboratoires Genévrier, Sophia-Antipolis, France) for urinary FSH, and Gonal-F ® (Laboratoires Serono, Boulogne-Billancourt, France) and Puregon ® (Laboratoires Organon, Puteaux, France) for recombinant FSH. Two different ways of efficacy between u-FSH and r-FSH were considered for the calculations, those reported in Daya’s meta-analysis (3.7% in favour of r-FSH for the clinical pregnancy rate per initiated cycle) and in the only double-blind study (Frydman et al., no difference). Results. – The annual cost of ART reaches approximately 130 million euros in France, for the cycles only, and 170 million euros when including the pregnancy costs. Urinary FSH is much cheaper than recombinant FSH. Whereas the number of administered FSH units was higher in u-FSH, this results in a mean lower cost of 500 euros per cycle (2422 euros for u-FSH and 2959 euros for r-FSH). For one complete year, in France, the potential over cost of recombinant products reaches 24 million euros when considering only the cycles (128.4 vs. 104.0 million euros) and 24–31 million euros when pregnancies and babies (neonatal period) are considered (171.4 vs 140.7 and 147.0 million euros, respectively). The IVF per baby cost can be estimated at 16 463 euros for r-FSH and at 14 116 euros (in case of equivalence between the two drugs) to 15 805 euros (in case of a difference of 3.7% pregnancy per oocyte recovery) for u-FSH. Conclusion. – This gives Public Health lighting to the choices in the matter of ovulation stimulation. It shows the economic impact of the choice in the FSH type.

FSH: urinary and recombinant

Infertility affects approximately 10–15% of couples. To enhance the chances of conception, assisted reproductive techniques (ART) have been improved and, in the last 5 years, thousands of babies have been delivered after IVF or ICSI procedures. To obtain an appropriate and controlled ovarian hyperstimulation (COH), clinicians have introduced many drug protocols based on GnRH agonists or antagonists for pituitary down-regulation and FSH or HMG for ovarian stimulation. Currently FSH is the most common drug used for ovulation induction. It is a glycosylated protein with a molecular weight of 28 000–30 000 Da, normally secreted by the anterior pituitary gland. The recombinant preparations of follicle stimulation hormone (r-FSH) are characterized by a higher level of purity, reduced batch to batch variability and no risk of infection. The purpose of this review was to establish the efficacy of different trials based on the use of r-FSH and urinary FSH (u-FSH) comparing published data from randomised studies on the ovulation induction for assisted reproductive techniques. Unfortunately, we did not find any paper with sufficient power to detect a clinically significant difference in pregnancy rates, however, recent meta-analysis among homogeneous trials indicates that the use of r-FSH is to be preferred to u-FSH because more oocytes were collected in cycles with better embryo quality and with more pregnancies. Recombinant FSH has a higher cost per ampoule than urinary FSH, but also a higher effectiveness. A recent cost-effectiveness analysis on follitropin alfa compared to urinary FSH-HP, using a Markov model, confirmed other previous studies that, considering the ongoing pregnancies beyond 12 weeks gestation, r-FSH is the most effective therapy for ovulation induction in ART.

Ovulation induction with urinary FSH or recombinant FSH in polycystic ovary syndrome patients: a prospective randomized analysis of cost-effectiveness

The aim of this prospective, randomized trial was to compare the clinical results and the cost-effectiveness of urinary FSH (uFSH) and recombinant FSH (rFSH) in ovarian stimulation for intrauterine insemination (IUI) cycles in polycystic ovary syndrome (PCOS) patients. One-hundred and seventy PCOS infertile patients undergoing IUI were enrolled, and protocols of ovarian stimulation with uFSH or rFSH were randomly assigned. The total number of cycles performed was 379 (182 and 197, respectively). The main outcome measures were the number of mature follicles, the days of stimulation, the number of ampoules and IU used per cycle, the biochemical/clinical pregnancy rates, the number of multiple pregnancies and the cost-effectiveness. No statistically significant differences were found in the follicular development, length of stimulation, pregnancy rates, delivery rates and multiple pregnancies between the two groups. In the uFSH group, the cost per cycle remained significantly lower (€218.51 ± 88.69 versus €312.22 ± 118.12; P < 0.0001), even though a significantly higher number of IU of gonadotrophins were used (809.3 ± 271.9 versus 589.1 ± 244.7; P < 0.0001). The cost-effectiveness (i.e. within a group, the total cost of all cycles divided by no. of clinical pregnancies) was 1729.08 in the uFSH group and 3075.37 in the rFSH group. In conclusion, uFSH and rFSH demonstrated the same effectiveness in ovarian stimulation in IUI cycles in PCOS patients. The urinary preparation is more cost-effective due to the difference of its cost per IU.

Low-dose ovulation induction with urinary gonadotropins or recombinant follicle timulating hormone in patients with polycystic ovary syndrome

Patients with polycystic ovary syndrome (PCOS) are highly sensitive to gonadotropins. In recent years a number of publications have shown that chronic low-dose protocols are effective in reducing complications, in particular ovarian hyperstimulation syndrome (OHSS), especially if recombinant human follicle stimulating hormone (rhFSH) is used. The aim of the present study was to compare the efficacy and safety of rhFSH (Gonal-F®, Serono) versus urinary human FSH (uhFSH) (Metrodin®, Serono) in a low-dose step-up protocol for ovulation induction in clomiphene-resistent infertile PCOS patients. Twenty PCOS patients were recruited in two centers for an open randomized comparative study. A starting dose of a 75-IU ampule of rhFSH or uhFSH was used for 14 days with an increment of 37.5 IU every 7 days. Human chorionic gonadotropin (hCG) (10 000 IU, Profasi®, Serono) was administered if one to three follicles achieved a diameter of ≥ 16 mm. Sonographic and hormonal (serum estradiol and progesterone) monitoring of the cycles was performed. All the six pregnancies induced were in the rhFSH group, but two of them ended with miscarriage. There were no differences between the two groups concerning the number of ampules used, the stimulation days, the estradiol levels on the day of hCG administration, and the progesterone levels 7 days after hCG administration. Three patients had grade II, and one patient grade III OHSS. In conclusion, our results support the literature data that rhFSH is superior to uhFSH regarding pregnancy rates, not only in in vitro fertilization cycles, but also with a low-dose protocol in patients with PCOS.

A turbulent arena

Recombinant FSH has spawned many randomized controlled trials in a relatively short time span. With phase III trials under way for little more than a decade, 21 randomized controlled trials of long GnRH agonist protocols have been designed, as well as trials using other pituitary suppression protocols (1). Four trials compared recombinant FSH with hMG, 6 with a more purified urinary product (urinary FSH), and 11 with highly purified FSH. These assessments of recombinant FSH effectiveness coincided with a widespread trend to use the long pituitary suppression protocol in ART cycles and with a plateau in the upward progression of live birth rates per cycle initiated (2).