Daily or alternate-day FSH therapy in patients with polycystic ovarian disease resistant to clomiphene citrate treatment. The clinical efficacy of low-dose step-up follicle stimulating hormone administration for treatment of unexplained infertility. Treatment of clomiphene citrate-resistant polycystic ovarian syndrome with pure follicle-stimulating hormone or human menopausal gonadotropin. Efficacy of low dose purified FSH in ovulation induction following pituitary desensitization in polycystic ovarian syndrome. Late low-dose pure follicle stimulating hormone for ovarian stimulation in intra-uterine insemination cycles. Ovulation induction in polycystic ovarian disease by pure FSH (Metrodin). A comparison between chronic low-dose pulsatile administration and i.m. injections. Induction of multiple follicular development by a single dose of long-acting recombinant follicle-Stimulating hormone (FSH-CTP, corifollitropin alfa) for controlled ovarian stimulation before in vitro fertilization. Urinary follicle-stimulating hormone (FSH) versus recombinant FSH in clomiphene citrate-resistant, normogonadotropic,chronic anovulation: a prospective randomized study. Urinary follicle-stimulating hormone (FSH) is more effective than recombinant FSH in older women in a controlled randomized study.
The effectiveness of intramuscular follicle stimulating hormone (FSH) administered as daily or alternate-day injections to patients with polycystic ovarian disease (PCOD) who previously failed to ovulate on clomiphene citrate was compared. The study comprised 20 treatment cycles of daily FSH and 19 of alternate-day FSH in 12 patients. The overall ovulation rate per cycle was 78% and was similar for both groups. Nine out of 12 patients achieved a pregnancy, with twice as many occurring in the alternate-day group. It is concluded that alternate-day FSH therapy is as effective as daily FSH in achieving ovulation and pregnancies in patients with PCOD resistant to treatment with clomiphene citrate. The present study was designed to compare the clinical efficacy of low-dose step-up follicle stimulating hormone (FSH) administration with conventional FSH protocol (FSH was injected daily starting with a dose of 150 IU), both combined with intrauterine insemination (IUI), for the treatment of unexplained infertility. A total of 97 unexplained infertility couples was randomly assigned to one or other of the two treatment groups, either conventional FSH with IUI (48 patients) or low-dose step-up FSH with IUI (49 patients), and only the first treatment cycle was evaluated in each protocol. The difference in pregnancy rates per cycle was not statistically significant between the low-dose FSH group and the conventional group [seven of 49 (14.3%) and seven of 48 (14.6%) respectively]. A significant reduction in the incidence of ovarian hyperstimulation syndrome (OHSS) was observed in the low-dose group (8.3% versus 27.1%, P < 0.05). The incidence of moderate OHSS requiring hospitalization was reduced significantly in the low-dose group (low-dose 0% versus conventional 16.7%, P < 0.01). However, the low-dose protocol did not completely prevent multiple pregnancies. Our results suggest that the low-dose step-up FSH treatment appeared to be useful for the treatment of unexplained infertility because of the high pregnancy rates and the significant decrease in the incidence of OHSS. Two hundred ten treatment cycles of follicle-stimulating hormone (FSH) or human menopausal gonadotropin (hMG) were completed in 49 patients with clomiphene citrate-resistant polycystic ovarian syndrome. The results from 68 cycles of daily intramuscular (IM) FSH and 41 cycles of IM hMG were compared. The ovulation rate, maximum serum estradiol (E2) levels achieved, and pregnancy rate were similar in both groups, but FSH resulted in significantly fewer follicles developing and hyperstimulation. The 68 cycles of daily IM FSH were further compared with the outcome of administering the FSH as an alternate-day IM injection in 70 cycles, and by subcutaneous pulsatile injection in 31 cycles. There were no differences in any of the parameters measured between daily and alternate-day FSH. Pulsatile FSH required a greater total dose over a longer period of time to achieve stimulation. It also produced fewer follicles, a lower maximum serum E2 level, and the lowest incidence of hyperstimulation. Twenty pregnancies resulted, of which 6 aborted in the first trimester; there was 1 set of twins and 13 singleton pregnancies. The cumulative pregnancy rate after 6 treatment cycles was 62%. We evaluated the efficacy of ovulation induction using purified FSH in either low dose or conventional dosage in patients with polycystic ovarian syndrome. We assessed whether gonadotrophin measurement by radioimmunoassay or immunoradiometric assay is a better indicator of whether pituitary desensitization with a GnRH agonist (Zoladex) has occurred.
                Two different protocols were used. Pituitary desensitization was carried out with a GnRH agonist (Zoladex, ICI Pharmaceuticals UK). The patients were then randomized into one of two treatment groups. Conventional dose protocol: Patients commenced with a daily FSH (Metrodin, Serono Laboratories Ltd, UK) dose of 75 units for at least 7 days. The FSH dose was then increased, if necessary, based on ultrasound scans and plasma oestradiol (E2) levels in 75-unit increments. Low dose protocol: The same protocol was used except that the starting dose of FSH was 37.5 units daily with increments of 37.5 units.
                Low dose protocol (six patients, six cycles). There was a high incidence of multiple follicular development (10.3 +/- 5.6 (+/- SD) follicles, 5.0 +/- 3.8 follicles > 14 mm in diameter). Three cycles resulted in ovulation, one was anovulatory and two patients underwent gamete intrafallopian transfer due to multiple follicular development. Conventional dose protocol (seven patients, eight cycles). Again there was multiple follicular development (10.1 +/- 8.6 follicles, 2.0 +/- 2.3 > 14 mm). Three cycles were ovulatory, one anovulatory, three abandoned due to multiple follicular development and one underwent gamete intrafallopian transfer with the development of severe hyperstimulation necessitating steroid therapy. There was no difference between the two protocols in the number of days of FSH administration (low dose protocol 26 +/- 6.5, conventional dose protocol 23 +/- 8.1 days), the total number of units of FSH given per patient was 2844 +/- 1816 vs 2635 +/- 1726. The peak E2 level (pmol/l) during FSH treatment was 3193 +/- 662 vs 2389 +/- 3099 and the rate of increase in the FSH dose in ampoules of Metrodin per day was 0.058 +/- 0.03 vs 0.057 +/- 0.03. All patients were 'downregulated' (E2 < 70 pmol/l) prior to ovulation induction. However, gonadotrophin levels (IU/l) were 4.3 +/- 1.5 (LH) and 2.8 +/- 1.2 (FSH) by radioimmunoassay and LH was unchanged throughout FSH treatment whereas LH measured by immunoradiometric assay was < 1.0 IU/l prior to ovulation induction and remained so throughout. The mean LH radioimmunoassay to immunoradiometric assay ratio was 6.2 +/- 2.1.
                We conclude that regardless of the starting dose the use of pure FSH in patients with polycystic ovarian syndrome whose LH has been completely down regulated may be associated with multiple follicular development and a poor outcome. LH measured by radioimmunoassay is not a good indicator of whether pituitary densensitization has occurred but LH measured by immunoradiometric assay appears to be. These results strongly suggest that a basic minimum amount of LH is necessary for normal ovulatory development. At present, there is general agreement that ovarian stimulation improves pregnancy rates after intra-uterine insemination (IUI). Also, ovulation induction with gonadotrophins is associated with higher success rates than clomiphene citrate in IUI cycles. However, the drawbacks to the use of gonadotrophin stimulation before IUI include the risks of ovarian hyperstimulation and multiple gestation, and the relative cost of a treatment cycle in a view of the medication costs and the need for increased monitoring by hormone assays and ultrasonographic measurements. In the present prospective randomized trial, the efficacy and safety of ovarian stimulation with clomiphene citrate (50 mg/day for 5 days) and IUI (clomiphene/IUI group) were compared with those of late low-dose pure follicle stimulating hormone (FSH, 75 IU/day from day cycle 7 until the leading follicle reached > 17 mm in diameter) and IUI (FSH/IUI group) in ovulatory women who were infertile because of unexplained infertility (n = 40) or male subfertility (n = 60). The mean length of treatment in the FSH group was 6.4 +/- 2.5 days. Multiple follicular development was seen in 25% of clomiphene-stimulated cycles but only in 8% of those treated with FSH. Pregnancy rate per cycle in clomiphene/IUI and FSH/IUI groups was 4% (4/98) and 13% (12/94) respectively (P = 0.02). All pregnancies obtained were singleton. There were two and one clinical abortions in the clomiphene/IUI (50%) and FSH/IUI (8%) groups respectively. No patient developed ovarian hyperstimulation syndrome. Use of our therapeutic scheme, which proved to be efficacious, safe and economic for ovarian stimulation in IUI cycles, is advocated before the institution of in-vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT) therapy in infertile patients with patient Fallopian tubes. This late low-dose technique of administering pure FSH is suitable for use in offices without immediate access to oestradiol results. A randomized cross-over study was performed to assess the value of pulsatile versus i.m. administration of pure FSH in polycystic ovarian disease. All patients admitted to the study had failed to respond to treatment with clomiphene citrate, while four had also been unsuccessfully treated with i.m. Pergonal. Sixteen cycles with i.m. FSH and 15 cycles with pulsatile s.c. FSH were analysed. The results showed no statistically significant differences in the dosage, the rate of ovulation or pregnancy rate. Hyperstimulation occurred in 30% of both the treatment groups. It is concluded that chronic low-dose pulsatile administration of pure FSH (Metrodin, Serono) has no advantage over chronic low-dose i.m. administration. In a first feasibility study, the efficacy and safety of a single dose of recombinant long-acting FSH (FSH-CTP) were investigated in in vitro fertilization (IVF) patients undergoing controlled ovarian stimulation with a flexible GnRH antagonist protocol. Eligible subjects were randomized to receive a single dose of 120 micro g (n = 25), 180 microg (n = 24), or 240 microg (n = 25) corifollitropin alfa (FSH-CTP) or to start daily fixed doses of 150 IU recombinant FSH (rFSH) (n = 24, reference). Subjects who received a single dose of FSH-CTP continued 1 wk after injection (treatment d 8) with fixed daily doses of 150 IU rFSH (Puregon/Follistim) until the day of triggering final oocyte maturation. The terminal half-life of FSH-CTP was, on average, 65 h and dose independent. Cycle cancellation before human chorionic gonadotropin (hCG) administration occurred in only three subjects treated with FSH-CTP. The median duration of stimulation was 10.0 d in each FSH-CTP group and 9.0 d in the daily rFSH group. The total number of follicles at least 11 mm at stimulation d 8 and at the day of hCG administration tended to increase with dose of FSH-CTP, although a significant dose-response relationship was revealed only for the number of follicles at least 15 mm on the day of hCG (P = 0.03). Serum estradiol levels and inhibin-B levels were not significantly different between the four groups on d 8 and on the day of hCG. In total, 12 subjects (17.6%) in the FSH-CTP groups and two subjects (8.3%) in the rFSH group experienced a premature LH rise (defined as LH >or= 10 IU/liter) before the start of the GnRH antagonist (P value not significant between groups). This relatively high incidence of women demonstrating an early LH rise in the FSH-CTP groups may be related to the higher initial rises of serum estradiol and the use of a flexible GnRH antagonist protocol. The mean number of oocytes recovered per started cycle was higher in FSH-CTP-treated subjects compared with rFSH-treated subjects (significant at P = 0.03 for the 240- microg FSH-CTP group), but no difference could be noted between the number of good quality embryos (range of means, 3.8-4.8 per attempt), and equal numbers of embryos were available for embryo transfer. In summary, FSH-CTP appeared to be a potent inducer of multiple follicular growth; additional research will be needed to select the optimal FSH-CTP dose and treatment time interval. To compare the efficacy and safety of urinary FSH and recombinant FSH for ovulation induction in patients with clomiphene citrate-resistant, normogonadotropic, chronic anovulation.
                Prospective, randomized trial.
                University-based infertility clinic.
                Fifty-one women.
                Subjects were randomized to receive either urinary FSH (35 patients, 64 cycles) or recombinant FSH (16 patients, 32 cycles). A maximum of three cycles using the low-dose step-up protocol with the same gonadotropin were undertaken.
                Cumulative ovulation and pregnancy rates after three cycles, total gonadotropin dose, duration of stimulation, and single follicle development rate.
                Cumulative ovulation rates were 89.3% and 93.1% for the urinary FSH and recombinant FSH groups, respectively. The threshold and total doses of FSH and the duration of stimulation were similar between the two groups. Significantly more single follicle development was noted in the recombinant FSH group. The respective clinical pregnancy rates per noncanceled cycles in the urinary FSH and recombinant FSH groups were 23.2% and 27.6%. There were three sets of twins in the urinary FSH group. No case of ovarian hyperstimulation syndrome was encountered.
                Urinary FSH and recombinant FSH are both efficient and safe for inducing ovulation with the low-dose step-up protocol. The following study was conducted to determine which FSH, recombinant or urinary, works better in older women.
                We conducted a controlled randomized study in a single university IVF center.
                University IVF center.
                Women (N = 257) over 39 years old undergoing IVF.
                The patients were randomized into two study groups at their first IVF cycle: 121 patients were treated with recombinant FSH, and 120 patients were treated with urinary FSH. Both groups were suppressed with a long GnRH analog protocol.
                Days of stimulation, E2 at the day of hCG, total amount of FSH administered, number of oocytes collected, amount of FSH per oocyte, and number of embryos obtained.
                Patients treated with urinary FSH required a significantly lower total amount of FSH, and a lower amount of FSH per oocyte than women treated with recombinant FSH. The other measures evaluated did not show any statistically significant differences.
                Our study showed that urinary FSH performed better in older women than recombinant FSH when associated with the long protocol.
The use of a medium dose of long-acting FSH is a safe treatment option and equally effective compared to daily FSH. Further research is needed to determine if long-acting FSH is safe and effective for use in hyper- or poor responders and in women with all causes of subfertility.