Late low-dose pure follicle stimulating hormone for ovarian stimulation in intra-uterine insemination cycles. Luteinzing hormone activity in menotropins optimizes folliculogenesis and treatment in controlled ovarian stimulation. Simplified ultralong protocol of gonadotrophin-releasing hormone agonist for ovulation induction with intrauterine insemination in patients with endometriosis. Recombinant versus urinary follicle-stimulating hormone in intrauterine insemination cycles: a prospective, randomized analysis of cost effectiveness. Use of ethinyl estradiol to reverse the antiestrogenic effects of clomiphene citrate in patients undergoing intrauterine insemination: a comparative, randomized study. A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation. Minimal stimulation protocol for use with intrauterine insemination in the treatment of infertility. Timing ovulation for intrauterine insemination with a GnRH antagonist. A randomized controlled trial of three low-dose gonadotrophin protocols for unexplained infertility. Comparison of controlled ovarian stimulation with human menopausal gonadotropin or recombinant follicle-stimulating hormone. A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotropin or clomiphene citrate. Endocrine changes and follicular development in patients during ovulation induction using Goserelin and different gonadotropin treatments. Ovulation induction with urinary FSH or recombinant FSH in polycystic ovary syndrome patients: a prospective randomized analysis of cost-effectiveness. Recombinant human FSH versus highly purified urinary FSH: a randomized study in intrauterine insemination with husbands' spermatozoa. Ovarian stimulation in intrauterine insemination with donor sperm: a randomized study comparing clomiphene citrate in fixed protocol versus highly purified urinary FSH. Clomiphene citrate versus letrozole for ovarian stimulation: a pilot study. A randomized prospective study comparing pregnancy rates after clomiphene citrate and human menopausal gonadotropin before intrauterine insemination. A randomized, multicenter study comparing the efficacy of recombinant FSH vs recombinant FSH with Ganirelix during superovulation/IUI therapy. Menotropins alone are superior to a clomiphene citrate and menotropin combination for superovulation induction among clomiphene citrate failures. High dose of phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium in patients undergoing intrauterine insemination: a randomized trial. Treatment with the GnRH antagonist ganirelix prevents premature LH rises and luteinization in stimulated intrauterine insemination: results of a double-blind, placebo-controlled, multicentre trial. The clinical efficacy of low-dose step-up follicle stimulating hormone administration for treatment of unexplained infertility. Adjunctive leuprolide therapy does not improve cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination of subfertile women. A randomized prospective study of gonadotrophin with or without gonadotrophin-releasing hormone agonist for treatment of unexplained infertility. GnRH antagonists and mild ovarian stimulation for intrauterine insemination: a randomized study comparing different gonadotrophin dosages.
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. Although the role that LH plays in folliculogenesis is still controversial, recent evidence points toward facilitatory actions of LH activity in ovulation induction. Thus, we compared the response to either highly purified FSH (75 IU FSH/ampoule; group A, 25 subjects) or human menopausal gonadotropin (75 IU FSH and 75 IU LH/ampoule; group B, 25 subjects) in normoovulatory GnRH agonist-suppressed women, candidates for intrauterine insemination. A fixed regimen of 2 daily ampoules of highly purified FSH or human menopausal gonadotropin was administered in the initial 14 days of treatment; menotropin dose adjustments were allowed thereafter. Treatment was monitored with daily blood samples for the measurement of LH, FSH, 17beta-estradiol (E(2)), progesterone, testosterone, hCG, inhibin A, and inhibin B, and transvaginal pelvic ultrasound was performed at 2-day intervals. Although preovulatory E(2) levels were similar, both the duration of treatment (16.1 +/- 0.8 vs. 12.6 +/- 0.5 days; P< 0.005) and the per cycle menotropin dose (33.6 +/- 2.4 vs. 23.6 +/- 1.1 ampoules; P < 0.005) were lower in group B. In the initial 14 treatment days the area under the curve of FSH, progesterone, testosterone, inhibin A, and inhibin B did not differ between the 2 groups, whereas LH, hCG, and E(2) areas under the curve were higher in group B. The occurrence of small follicles (<10 mm) and the inhibin B/A ratio in the late follicular phase were significantly reduced in group B. A nonsignificant trend toward a higher multiple gestation rate was present in group A (60% vs. 17%). We conclude that ovulation induction with LH activity-containing menotropins is associated with 1) shorter treatment duration, 2) lower menotropin consumption, and 3) reduced development of small ovarian follicles. These features can be exploited to develop regimens that optimize treatment outcome, lower costs, and reduce occurrence of complications such as multiple gestation and ovarian hyperstimulation. The present study was designed to assess the usefulness of the simplified ultralong protocol of gonadotrophin-releasing hormone agonist (GnRHa) for ovulation induction with intrauterine insemination (IUI) in patients with various stages of endometriosis. A prospective randomized trial was set up to compare the simplified ultralong protocol (ULP) and the long protocol (LP) of GnRHa for ovulation induction with IUI in patients with endometriosis. There was no evidence of other factors in infertility in any patient. In the ULP group (39 patients), 4 weeks after a single injection of 3.75 mg Decapeptyl had been given, daily s.c. administration of 0.1 mg Decapeptyl was initiated and continued for at least 2 weeks prior to ovarian stimulation. In the LP group (41 patients), daily s.c. administration of 0.1 mg Decapeptyl was initiated from the mid-luteal phase of the cycle preceding the stimulation cycle. After 14 days of administration, ovarian stimulation was started if pituitary desensitization had been achieved. The amount of gonadotrophins required, number of days of gonadotrophin administration, serum oestradiol response, and the number of mature follicles were comparable in both groups. The clinical pregnancy rate per cycle was significantly higher in the ULP group at 48.7% (19/39) compared with 26.8% (11/41) in the LP group. The miscarriage rates were 21.1% (4/19) in the ULP group and 18.2% (2/11) in the LP group. In patients with stage I or II endometriosis, there was no significant difference between the two groups with respect to clinical pregnancy rate per cycle (47.4 versus 35.0%). In patients with stage III or IV endometriosis, the clinical pregnancy rate per cycle was significantly higher in the ULP group at 50.0% (10/20) compared with 19.0% (4/21) in the LP group. This study suggests that a simplified ULP of GnRHa could give better chances of achieving pregnancy in endometriosis patients undergoing assisted reproductive technologies and that this protocol may be more useful in patients with an advanced stage of endometriosis. 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. To compare the effectiveness of clomiphene citrate used alone and in combination with ethinyl E2 for the induction of ovulation in patients undergoing IUI.
                Randomized, double-blind study.
                Four infertility treatment centers.
                Women aged 25-35 years with infertility of at least 2 years' duration and oligomenorrhea or amenorrhea associated with a positive menstrual response to an IM progesterone challenge.
                A total of 64 patients were randomized to treatment with CC (100 mg daily for 5 days) or CC (100 mg daily for 5 days) plus ethinyl E2 (0.05 mg daily for 5 days).
                The uterine artery pulsatility index, number of preovulatory follicles, endometrial thickness, and pregnancy rate.
                Both treatment regimens increased FSH, LH, and 17beta-E2 levels, with no statistically significant differences. There was a statistically significant difference in endometrial thickness between the two treatment groups. No statistically significant differences were noted in pulsatility index values or in the number of preovulatory follicles.
                Ethinyl E2 can reverse the deleterious effects of CC on endometrial thickness, which may contribute to higher pregnancy rates. To compare the effects of the aromatase inhibitor letrozole (7.5 mg) and clomiphene citrate (CC; 100 mg) in women undergoing superovulation and IUI.
                Prospective randomized trial.
                University teaching hospital.
                We studied a total of 238 cycles of superovulation and IUI in women with idiopathic infertility.
                Patients were randomized into treatment with 7.5 mg of letrozole daily (74 patients, 115 cycles) or 100 mg of CC daily (80 patients, 123 cycles).
                Number of follicles, endometrial thickness, pregnancy rate, and miscarriage rate.
                The mean age, parity, and duration of infertility in both groups of patients were similar. There was no significant difference between the total number of developing follicles in the letrozole (5.7 +/- 3.7) and in the CC groups (4.8 +/- 2.5). The number of follicles of > or =14 mm and of >18 mm were 2.1 +/- 1.2 and 1.4 +/- 0.7 in the letrozole group, and 1.7 +/- 0.9 and 1.1 +/- 0.5 in the CC group, respectively. No difference was found in the endometrial thickness between the two groups (7.1 +/- 0.2 mm in the letrozole group, 8.2 +/- 5.9 mm in the CC group). The pregnancy rate per cycle was 11.5% in the letrozole group and 8.9% in the CC group. Four of the 11 pregnancies in the CC group resulted in a miscarriage (36.6%).
                Superovulation and IUI with letrozole and CC are associated with similar pregnancy rates, but the miscarriage rate is higher with CC. The ideal dose of letrozole remains unknown and further study is needed. To determine whether minimal stimulation with clomiphene and one injection of 150 IU of human menopausal gonadotrophin (hMG) provides pregnancy rates comparable with those in a conventional full hMG stimulation protocol for infertile patients undergoing intrauterine insemination (IUI).
                A prospective study was carried out at the Infertility Clinic of a teaching institute and tertiary care referral center in Chandigarh, India. Two hundred couples with either unexplained infertility or ovulatory dysfunction cases who ovulated with clomiphene citrate (CC) but failed to conceive were offered ovarian stimulation with CC and hMG along with IUI for 420 cycles. Pregnancy rate, medication and monitoring cost were compared between minimal and conventional stimulation protocols.
                There was no difference in the couples of the two stimulation protocols regarding their age, duration and type of infertility as well as cause of infertility. Number of ampoules of hMG and monitoring costs were significantly higher in the full hMG stimulation cases whereas pregnancy rate was comparable in both protocols.
                Minimal stimulation appears to be an effective protocol in cases of unexplained infertility undergoing intrauterine insemination. Reduced cost and minimal monitoring is appealing to patients and the clinician. We aimed to assess the efficacy of a GnRH antagonist in intrauterine insemination (IUI) cycles to increase number of mature ovulatory follicles and pregnancy rates.
                Prospective randomized study. Women (18-38 years old) with primary/secondary infertility were included. Eighty-two patients were randomly assigned to controlled ovarian stimulation (COS) consisting of rFSH + GnRH antagonist or rFSH alone.
                A non-significant increase in the total amount of rFSH was seen in the GnRH antagonist group (707+/-240 IU) with respect to the control group (657+/-194 IU). The number of mature follicles (> or =16 mm) was significantly higher in the GnRH antagonist group than in the control group (2.4+/-1.4 versus 1.7+/-1.2, P<0.05). Pregnancy rates were significantly increased in the group of patients receiving the GnRH antagonist (38%) compared to the control group (14%). The only non-single pregnancy (triplets) occurred in the antagonist group.
                In this preliminary study, adding the GnRH antagonist to the COS protocol for IUI cycles significantly increased pregnancy rates. Nevertheless, these results may not be associated directly with the antagonist itself but with the fact that more mature ovulatory follicles are present by the day of the hCG. Finally, the risk for multiple gestations needs to be carefully evaluated. This randomized controlled trial assessed which of three low-intensity ovulation induction protocols was associated with the highest rate of cycle completion among infertile women undergoing intrauterine insemination (IUI) with their husband's spermatozoa. Sixty-three women aged < or = 42 years with normospermic partners participated in the study. The primary diagnosis of infertility was unexplained in 89% of subjects, endometriosis in 6% and tubal factor in 5%. Women were assigned to three groups according to recombinant FSH dosage: group A received two ampoules (75 IU FSH per ampoule) on cycle day 4, and one ampoule on days 6 and 8 (total four ampoules); group B received two ampoules on days 4, 6 and 8 (total six ampoules); group C received two ampoules on days 4, 6, 8 and 10 (total eight ampoules). Daily ultrasound investigations began on cycle day 9-12 and human chorionic gonadotrophin (HCG) 5000 IU was administered when one or two follicles > or = 18 mm were seen. IUI was scheduled for the next day. HCG was given and/or ovulation shown to have occurred in 88 of 109 cycles attempted (81%) with no differences among the three dose groups. Two singleton pregnancies occurred (2.3% per ovulatory cycle and 1.8% per cycle start). There were no significant differences among the three regimes in terms of cycle parameters, suggesting that an individualized and more intensive approach to ovarian stimulation is necessary for many women with unexplained infertility. To carefully examine the features of controlled ovarian stimulation performed with recombinant FSH-alpha or hMG.
                Controlled, prospective, randomized comparison of fixed gonadotropin regimens.
                Academic research institution.
                Fifty infertile patients who were candidates for IUI.
                Patients were randomized to receive a fixed regimen of recombinant FSH-alpha (150 IU/day, 25 patients) or hMG (150 IU/day, 25 patients), after GnRH-agonist suppression (long regimen).
                Daily measurements of serum LH, immunoreactive FSH, hCG, E(2), P, and T. Transvaginal pelvic ultrasound every 2 days. Pregnancy and abortion rates. Cost of medications. Two recombinant FSH-alpha-treated patients did not respond. Despite matched daily FSH dose, duration of treatment (hMG 10.8 +/- 0.4 vs. recombinant FSH-alpha 12.4 +/- 0.5 days), gonadotropin dose (21.7 +/- 0.8 vs. 25.3 +/- 1.3 ampoules), gonadotropin cost (288 +/- 10 vs. 1,299 +/- 66 /cycle), serum P levels, and small preovulatory follicle number were significantly lower, and LH, hCG, immunoreactive FSH levels, and larger follicles on day 8 were significantly higher in hMG-treated patients. The pregnancy, abortion, and twin pregnancy rates did not differ.
                The hMG administration was associated with: [1]. increased serum LH activity and immunoreactive FSH levels during treatment; [2]. reduced signs of premature luteinization; [3]. differential modulation of folliculogenesis; [4]. lower treatment duration, gonadotropin dose, and cost; and [5]. clinical outcome comparable to recombinant FSH-alpha. To determine the relative efficacy of intrauterine insemination (IUI), direct intraperitoneal insemination, and intercourse in cycles stimulated with clomiphene citrate (CC) or human menopausal gonadotropins (hMG).
                A prospective randomized trial with a 2(3) factorial design with eight different treatment alternatives. Only one cycle per couple was performed.
                The Departments of Obstetrics and Gynecology, Central Hospital, Västerås and Akademiska Hospital, Uppsala University, Uppsala, Sweden.
                Of 157 randomized couples with unexplained infertility including 51 cases with minimal or mild endometriosis, 148 were selected for comparison.
                Pregnancy rate (PR).
                Follicular stimulation with hMG gave a higher PR than with CC in the insemination cycles, 19% (10/52) and 4% (2/49), respectively, but the PRs in intercourse cycles were not significantly different for hMG and CC, 13% (3/24) and 17% (4/23), respectively. Insemination cycles and intercourse cycles had a similar overall PR, 12% (12/101) and 13% (7/47), respectively. Furthermore, IUI and direct intraperitoneal insemination did not differ in efficacy.
                Follicular stimulation with hMG is more effective than CC in insemination cycles, but insemination as such seems to have no beneficial effect on the PR in stimulated cycles for treatment of unexplained infertility. The aim of this study was to compare endocrine changes and the follicular development in patients receiving pure FSH alone or in association with LH after desensitization with an LH-RH agonist depot. Thirty four cycles were selected for this prospective randomized study. Desensitization was obtained using Goserelin the cycle before the stimulation. Induction of ovulation for IUI was carried out with 225 IU/day of pure FSH or with 225 IU/day of hMG. The number of days and ampules required for follicular maturation were equivalent in the two groups. The same number of follicles were developed, while different, but not significant, pregnancy rates were obtained. Estradiol values at the end of stimulation were significantly lower for FSH group. In conclusion the contemporary administration of LH with FSH does not exert any effect on follicular development, but it seems to facilitate E2 synthesis, probably providing more substrate for the aromatization process. 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. A randomized trial was carried out comparing recombinant FSH (rFSH) and highly purified urinary FSH (uFSH) in intrauterine insemination (IUI) with husbands' spermatozoa. A total of 45 women received rFSH (139 cycles), while 46 women received uFSH (155 cycles). The starting dose was 150 IU/day s.c., beginning on the second day, and on days 6-7 the dose was adjusted according to ovarian response, assessed by vaginal ultrasound and plasma oestradiol concentration. The pregnancy rate according to the intention to treat was 57.8% in rFSH versus 52.2% in uFSH, the corrected pregnancy rates 56.8% and 52.2%, and the cumulative pregnancy rates 69.6% and 61.0%, but the differences were not statistically significant. The per cycle pregnancy rate was 18.12% in rFSH and 15.48% in u-FSH, also not statistically significant. In the rFSH group, the consumption of FSH ampoules per cycle was significantly lower (19.20 +/- 7.02 versus 23. 80 +/- 10.78; P < 0.0001). The ratio of oestradiol/FSH ampoules was significantly higher in rFSH (56.45 +/- 31.26 versus 46.41 +/- 29. 25; P < 0.001). These data indicate that, in IUI cycles, rFSH has a higher potency than uFSH. The study was conducted to compare the results of intrauterine donor insemination (DI) under ovarian stimulation with either clomiphene citrate (CC), in a fixed protocol, or FSH, with ovarian monitoring.
                Forty-nine patients were randomized using a computer-generated list to receive highly purified urinary FSH (starting dose of 150 IU) and were subjected to periodic vaginal ultrasound and estradiol determinations. HCG was given when > or =2 follicles (> or =17 mm) were identified and estradiol reached >400 pg/ml. Intrauterine insemination (IUI) was performed 36 h later. The other 51 received CC on a fixed protocol (100 mg/day from the day 5-10 of the ovarian cycle) with HCG being administered on the day 12, and IUI performed 36 h later. Up to six IUI cycles were performed on all patients if pregnancy was not reached before. Women failing to conceive in the CC group underwent IUI with FSH. The main outcome measures were intrauterine gestational sac observed by transvaginal ultrasound, per cycle and per woman pregnancy rate (PR) and multiple PR.
                The per cycle PR was significantly higher in the FSH group, 14.4% (30/209) versus 6.1% (16/261), as well as the per woman PR, 61.2% (30/49) versus 31.4% (16/51). 12.5% (2/16) of pregnancies obtained in the CC group were multiple, compared with 20% (6/30) in the FSH group. There were no triplets or higher order pregnancies in CC versus two in FSH (6.7% of pregnancies). Patients failing to conceive with CC, who later underwent intrauterine DI with FSH, had similar results to the primary FSH group: 54.3% PR per patient (19/35) and 16.0% per cycle (19/118), with a multiple PR of 31.6% (6/19). The PR for women starting with CC cycles and, if pregnancy was not obtained, continuing with six FSH cycles, was 69.2%.
                The PR obtained with CC stimulation was approximately half that obtained with FSH. There was a trend to lower multiple PR with CC. It is recommended that each case should be considered on an individual basis and the treatment options discussed with patients. In our opinion, CC could be a reasonable approach for young women with good prognosis, whereas in the remaining cases FSH would be the preferable method. The purpose of this pilot study was to compare the endocrinological environment of cycles stimulated with clomiphene citrate (CC) or letrozole. Fifteen patients undergoing intrauterine insemination (IUI) received from day 3 to day 7 of the cycle either letrozole 2.5 mg/day (n = 7) or clomiphene citrate 100 mg/day (n = 8). IUI was performed one day after the detection of LH peak. No luteal support was administered. Significantly lower serum oestradiol concentrations were present in the follicular phase on days 9, 13 and 15 of the cycle and in the luteal phase on days 3 and 6 post-IUI in the letrozole group compared with those in the CC group. Progesterone concentrations and oestradiol concentrations were significantly lower in the letrozole group than in the CC group on the day of LH peak. Significantly more follicles developed in patients in the CC group compared with those in the letrozole group. In conclusion, significantly lower oestradiol concentrations and fewer follicles are observed in cycles stimulated with 2.5 mg letrozole compared with cycles stimulated with 100 mg CC from day 3 to day 7 of the cycle. To determine whether hMG offers an advantage over clomiphene citrate (CC) in achieving pregnancy after IUI with husband's sperm.
                Randomized prospective trial.
                Infertility patients in a university teaching hospital.
                Fifty-eight women under 39 years old undergoing ovulation induction before IUI.
                The women were assigned randomly to one of two treatment groups. Patients in group I (CCHH) received CC for the first two cycles and hMG for the last two cycles. Patients in group II (HHCC) received hMG for the first two cycles and CC for the last two cycles.
                Cycle fecundity rates for the two treatment modalities were compared statistically with use of life-table analysis.
                Of the 174 cycles studied, overall cycle fecundity rate was 11.11 (9 of 81 cycles) in the CCHH group and 10.75 (10 of 93 cycles) in the HHCC group. The difference was not statistically significant. The cycle fecundity rate was 14.44% (13 of 90 cycles) for cycles with CC and 7.14% (6 of 84) with hMG. The difference was not statistically significant.
                These data suggest that CC is an effective alternative to hMG in the population examined. The purpose of this study was to determine if use of a Gonadotropin releasing hormone (GnRH) antagonist, Ganirelix (Antagon), can improve pregnancy rates during superovulation with recombinant follicle-stimulating hormone (rFSH) followed by intrauterine insemination (IUI).
                This was a multicenter, prospective, randomized, open-label, assessor-blind, controlled trial of females (n = 54), ages 18 to 39 undergoing superovulation/IUI with up to 4 cycles of superovulation/IUI without Ganirelix (n = 66), or up to 4 cycles of superovulation/IUI with the addition of Ganirelix (n = 52).
                No statistically significant difference in clinical pregnancy rates per cycle initiated was found for patients in the treatment or control group (12% vs 7%, P =.29). Other variables assessed, including endometrial thickness, size of follicles, peak serum estradiol levels, mid-lutea progesterone levels, and total vials of rFSH used also showed no statistically significant difference.
                Superovulation/IUI cycles using Ganirelix produce similar pregnancy rates when compared with cycles not using a GnRH antagonist, although there is a trend towards better pregnancy rates in cycles with Ganirelix. To examine the difference in efficacy between two protocols of superovulation induction with IUI among infertile couples.
                A prospective randomized trial.
                Normal human volunteers in an infertility clinic.
                Consecutively treated patients attending our infertility clinic for superovulation induction with IUI who had been unsuccessfully treated by clomiphene citrate (CC).
                Infertile couples were randomized to undergo one of two controlled ovarian hyperstimulation protocols. Group A patients received daily hMG beginning on cycle day 3, whereas group B patients were administered CC days 3 through 7, followed by hMG from day 7 onward. Randomization was performed using a random numbers table. In both groups, ovulation was triggered by 5,000 IU hCG and IUI was performed by 36 hours.
                Studied cycle performance parameters included peak E2, number of dominant and intermediate-sized follicles recruited, endometrial thickness and pattern, and frequency of monitoring.
                Data analysis demonstrated no significant difference between the two groups with respect to patient age, parity, weight, indication for superovulation and IUI, number of dominant follicles recruited, peak E2, or mean number of total motile sperm inseminated. Endometrial thickness and pattern differed between treatments, however, with group A demonstrating relatively thicker and proportionately more trilaminar patterns than group B. Group A had significantly more serum E2 measurements, as well as transvaginal sonograms performed, when compared with group B. Pregnancy rates for groups A and B were 0.192 and 0.091, respectively. Of 25 pregnancies in group A, 7 (0.28) were multiples, whereas there were no multiple gestations in group B.
                For patients undergoing superovulation with IUI, a menotropin-alone protocol yields significantly higher pregnancy rates than one using a combination of menotropin with CC. These differences could not be explained by patient characteristics. Among cycle performance parameters, endometrial thickness and pattern differed significantly between the two groups. To compare the effectiveness of clomiphene citrate (CC) alone or combined with phytoestrogens (PE) in ovulation induction in patients who had intrauterine insemination in a randomized, double-blind study.
                A total of 134 women aged 25-35 years, who were infertile for at least 2 years and who had oligomenorrhea or amenorrhea associated with a positive menstrual response to the intramuscular progesterone-challenge test were enrolled. They were randomly treated with CC (100 mg daily for 5 days) and CC (100 mg daily for 5 days) in combination with PE (1500 mg daily for 10 days). We estimated the difference in uterine artery pulsatily index, number of preovulatory follicles, endometrial thickness, and pregnancy rate.
                Both treatments increased follicle-stimulating hormone, luteinizing hormone, and 17beta-estradiol plasma concentrations, but the differences were not statistically significant. However, the differences in endometrial thickness of the two groups were statistically significant. No significant differences in the pulsatility index values and in the number of preovulatory follicles were noted.
                A high dose of phytoestrogens can reverse the deleterious effects of clomiphene citrate on endometrial thickness and could contribute to higher pregnancy rates. This study was designed to assess whether the use of ganirelix in women undergoing stimulated IUI could prevent the occurrence of premature LH rises and luteinization (LH+progesterone rises).
                Women of infertile couples, diagnosed with unexplained or male factor infertility, were randomized to receive either ganirelix (n=103) or placebo (n=100) in a double-blind design. All women were treated with an individualized, low-dose rFSH regimen started on day 2-3 of cycle. Ganirelix (0.25 mg/day) was started if one or more follicles>or=14 mm were visualized. Ovulation was triggered by HCG injection when at least one follicle>or=18 mm was observed and a single IUI was performed 34-42 h later. The primary efficacy outcome was the incidence of premature LH rises (+/-progesterone rise).
                In the ganirelix group, four subjects had a premature LH rise (value>or=10 IU/l), one LH rise prior to the start of ganirelix and three LH rises during ganirelix treatment, whereas in the placebo group 28 subjects had a premature LH rise, six subjects prior to the start of placebo and 22 subjects during placebo treatment. The incidence of LH rises was significantly lower in ganirelix cycles compared to placebo cycles (3.9 versus 28.0%; P=0.003 for ITT analysis). When excluding subjects with an LH value>or=10 IU/l before the start of ganirelix/placebo the incidence of LH rises was also significantly lower in ganirelix cycles compared to placebo cycles (2.9 versus 23.4%; P=0.003 for ITT analysis). Premature luteinization (LH rise with concomitant progesterone rise>or=1 ng/ml) was observed in one subject in the ganirelix group and in 17 subjects in the placebo group of which three subjects had a premature spontaneous ovulation. Ongoing pregnancy rates per attempt were 12.6 and 12.0% for the ganirelix and placebo groups respectively.
                Treatment with ganirelix effectively prevents premature LH rises, luteinization in subjects undergoing stimulated IUI. Low-dose rFSH regimen combined with a GnRH antagonist may be an alternative treatment option for subjects with previous proven luteinization or in subjects who would otherwise require insemination when staff are not working. 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. Problems arising from controlled ovarian hyperstimulation for intrauterine insemination, such as premature luteinization and asynchronous ovarian follicular development, are identical to those encountered with controlled ovarian hyperstimulation for in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). It has been suggested that the adjunctive use of GnRH agonists for controlled ovarian hyperstimulation improves the efficiency of GIFT and IVF cycles. We hypothesized that adjunctive use of leuprolide acetate, a GnRH agonist, would have a similarly beneficial effect on cycle quality and cycle fecundity in subfertile women treated with controlled ovarian hyperstimulation and intrauterine insemination. We randomly assigned the first cycle of controlled ovarian hyperstimulation and intrauterine insemination for each of 97 subfertile women to include either human menopausal gonadotropins (hMGs) alone or hMGs following midluteal pre-treatment with leuprolide. If a pregnancy did not occur in the first cycle, the woman was given the other treatment in the second cycle. Although the cycles that included leuprolide required a larger amount of hMGs and more days of stimulation per cycle, the mean estradiol concentrations and numbers of follicles were not different. Despite prevention of premature luteinization with leuprolide, the cycle fecundity was not different between groups (0.11 with adjunctive leuprolide treatment and 0.22 with hMGs alone). We conclude that in unselected subfertile patients, the adjunctive use of leuprolide for controlled ovarian hyperstimulation and intrauterine insemination does not improve cycle fecundity compared with treatment cycles that do not include adjunctive leuprolide therapy. The use of gonadotrophin-releasing hormone agonist (GnRHa) in combination with human menopausal gonadotrophin (HMG) for ovulation induction has been advocated for the treatment, particularly by in-vitro fertilization (IVF) of various types of infertility. The present study was designed to compare the clinical efficacy of HMG alone with a short protocol of GnRHa/HMG for treatment of unexplained infertility. A total of 91 couples with unexplained infertility were randomly assigned to one of two treatments; either HMG with intra-uterine insemination (IUI) (45 patients, 62 cycles) or GnRHa/HMG with IUI (46 patients, 69 cycles) treatments. Progesterone concentrations on the day of human chorionic gonadotrophin (HCG) administration were significantly higher in HMG (1.5 +/- 0.9 ng/ml) versus GnRHa/HMG (0.8 +/- 0.6 ng/ml; P < 0.05) cycles. Furthermore, GnRHa suppressed the occurrences of premature luteinization (GnRHa/HMG 5.8% and HMG 24.2% respectively). However, there were no significant differences in HMG dose requirements, plasma oestradiol concentrations or follicular development on the day of HCG administration between the two groups. Nor were any significant differences found in the pregnancy rates between the two treatment protocols (GnRHa/HMG 13.0% and HMG 11.3% respectively). Our results suggest no beneficial effect of GnRHa/HMG compared to HMG alone for the treatment of unexplained infertility, based on pregnancy rates. The precise role of GnRH antagonists in the armamentarium of drugs for stimulation of ovulation associated with intrauterine insemination remains to be clarified. In this study, we have compared two different protocols employing GnRH antagonists in order to determine the lower effective dose of gonadotrophins to use.
                Sixty-six couples with unexplained infertility or moderate male subfertility were recruited. Starting on day 3 of the cycle, 32 patients were randomized to receive 50 IU of recombinant FSH per day, whereas 34 were treated with 50 IU of recombinant FSH on alternate days. Women received the GnRH antagonist Ganirelix at a dose of 0.25 mg per day starting on the day in which a leading follicle > or =14 mm in mean diameter was visualized, until HCG administration. Insemination was performed 34 h after HCG injection.
                The regimen with daily recombinant FSH was associated with a lower rate of mono-ovulation (53.3% versus 78.8%, P=0.06) but also with a higher clinical pregnancy rate per initiated cycle (34.4% versus 5.9%, P=0.005).
                A protocol of recombinant FSH 50 IU daily and GnRH antagonist may represent an effective and safe regimen for ovulation induction associated with intrauterine insemination.
Robust evidence is lacking but based on the available results gonadotrophins might be the most effective drugs when IUI is combined with ovarian hyperstimulation. When gonadotrophins are applied it might be done on a daily basis. When gonadotrophins are used for ovarian stimulation low dose protocols are advised since pregnancy rates do not differ from pregnancy rates which result from high dose regimen, whereas the chances to encounter negative effects from ovarian stimulation such as multiples and OHSS are limited with low dose gonadotrophins. Further research is needed for each comparison made.