Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network. Effectiveness of intrauterine insemination in subfertile couples with an isolated cervical factor: a randomized clinical trial. Intrauterine insemination with controlled ovarian hyperstimulation versus expectant management for couples with unexplained subfertility and an intermediate prognosis: a randomised clinical trial. Controlled ovarian hyperstimulation and intrauterine insemination for treating male subfertility: a controlled study. Efficacy of double intrauterine insemination in controlled ovarian hyperstimulation cycles. Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost-effectiveness analysis. A prospective trial of intrauterine insemination of motile spermatozoa versus timed intercourse. A randomized comparison of three insemination methods in an artificial insemination program using husbands' semen. Fallopian tube sperm perfusion has no advantage over intra-uterine insemination when used in combination with ovarian stimulation for the treatment of unexplained infertility.
Induction of superovulation with gonadotropins and intrauterine insemination are frequently used to treat infertility. We conducted a large, randomized, controlled clinical trial of these treatments.
                We studied 932 couples in which the woman had no identifiable infertility factor and the man had motile sperm. The couples were randomly assigned to receive intracervical insemination, intrauterine insemination, superovulation and intracervical insemination, or superovulation and intrauterine insemination. Treatment continued for four cycles unless pregnancy was achieved.
                The 231 couples in the group treated with superovulation and intrauterine insemination had a higher rate of pregnancy (33 percent) than the 234 couples in the intrauterine-insemination group (18 percent), the 234 couples in the group treated with superovulation and intracervical insemination (19 percent), or the 233 couples in the intracervical-insemination group (10 percent). Stratified, discrete-time Cox proportional-hazards analysis showed that the couples in the group treated with superovulation and intrauterine insemination were 3.2 times as likely to become pregnant as those in the intracervical-insemination group (95 percent confidence interval, 2.0 to 5.3) and 1.7 times as likely as those in the intrauterine-insemination group (95 percent confidence interval, 1.2 to 2.6). The couples in the intrauterine-insemination group and in the group treated with superovulation and intracervical insemination were nearly twice as likely to conceive as those in the intracervical-insemination group.
                Among infertile couples, treatment with induction of superovulation and intrauterine insemination is three times as likely to result in pregnancy as is intracervical insemination and twice as likely to result in pregnancy as is treatment with either superovulation and intracervical insemination or intrauterine insemination alone. After randomization of subfertile couples with an isolated cervical factor to intrauterine insemination for 6 months or expectant management for 6 months, 26 women (51%) vs. 16 women (33%) conceived, respectively. Of these pregnancies, 22 (43%) vs. 13 (27%) were ongoing (relative risk, 1.6; 95% confidence interval, 0.91 to 2.8). There was one multiple pregnancy in the group that was allocated to intrauterine insemination. This trial suggests a beneficial effect of IUI in couples with an isolated cervical factor. Intrauterine insemination with controlled ovarian hyperstimulation is commonly used as first-line treatment for couples with unexplained subfertility. Since such treatment increases the risk of multiple pregnancy, a couple's chances of achieving an ongoing pregnancy without it should be considered to identify those most likely to benefit from treatment. We aimed to assess the incremental effectiveness of intrauterine insemination with controlled ovarian hyperstimulation compared with expectant management in couples with unexplained subfertility and an intermediate prognosis of a spontaneous ongoing pregnancy.
                253 couples with unexplained subfertility and a 30-40% probability of a spontaneous ongoing pregnancy within 12 months were randomly assigned either intrauterine insemination with controlled ovarian hyperstimulation for 6 months or expectant management for 6 months. The primary endpoint of this hospital-based study was ongoing pregnancy within 6 months. Analysis was by intention to treat. This trial is registered with the Dutch Trial Register and as an International Standard Randomised Clinical Trial, number ISRCTN72675518.
                Of the 253 couples enrolled, 127 were assigned intrauterine insemination with controlled ovarian hyperstimulation and 126 expectant management. In the intervention group, 42 (33%) women conceived and 29 (23%) pregnancies were ongoing. In the expectant management group, 40 (32%) women conceived and 34 (27%) pregnancies were ongoing (relative risk 0.85, 95% CI 0.63-1.1). There was one twin pregnancy in each study group, and one woman in the intervention group conceived triplets.
                A large beneficial effect of intrauterine insemination with controlled ovarian hyperstimulation in couples with unexplained subfertility and an intermediate prognosis can be excluded. Expectant management for 6 months is therefore justified in these couples. In this randomized crossover trial we investigated whether the use of controlled ovarian hyperstimulation with low-dose human menopausal gonadotrophin in couples with male subfertility leads to a higher probability of conception when intrauterine insemination (IUI) is applied. We also investigated whether the efficacy of IUI in natural or stimulated cycles was related to the severity of male subfertility. Seventy-four couples completed 308 treatment cycles. Thirteen pregnancies occurred after IUI in a natural cycle (pregnancy rate per completed cycle: 8.4%) and 21 after IUI in a stimulated cycle (pregnancy rate per completed cycle: 13.7%). The difference between the two treatment modalities was not statistically significant. The efficacy of IUI in stimulated cycles was related to the severity of the semen defect. In couples with a total motile sperm count < 10 x 10(6), ovarian stimulation did not improve treatment outcome, while it did in couples with a total motile sperm count > or = 10 x 10(6). Compared with the expected chance of conceiving spontaneously without treatment, both natural and stimulated cycles improved the probability of conception. We conclude that, for the group as a whole, ovarian stimulation did not improve the probability of conception. However, in couples with less severe semen defects, ovarian stimulation did improve the probability of conception. To investigate the effectiveness of double IUI and to determine the optimal timing of IUI in relation to hCG administration.
                Prospective randomized study.
                Infertility Center, Department of Obstetrics and Gynecology, University of Milan.
                Patients with male factor and unexplained infertility undergoing controlled ovarian hyperstimulation (COH) and IUI.
                After COH with clomiphene citrate and gonadotropins, patients were randomly assigned to one of the following groups: group A received a single IUI 34 hours after hCG administration, group B received a double IUI 12 hours and 34 hours after hCG administration, and group C received a double IUI 34 hours and 60 hours after hCG administration.
                Number of follicles > 15 mm in diameter on the day of hCG administration, number of motile spermatozoa inseminated, clinical pregnancy rate.
                Two hundred seventy-three patients underwent 449 treatment cycles: 90 patients were treated for 156 cycles in group A, 92 patients for 144 cycles in group B, and 91 patients for 149 cycles in group C. The overall pregnancies rates for groups A, B, and C were 13 (14.4% per patient and 8.3% per cycle), 28 (30.4% per patient and 19.4% per cycle), and 10 (10.9% per patient and 6.7% per cycle), respectively. There was a statistically significant difference between group B and groups A and C.
                Our data indicate that two IUIs performed 12 hours and 34 hours after hCG administration is the most cost-effective regimen for women undergoing COH cycles with clomiphene citrate and gonadotropins. Although the second insemination adds up to a slightly higher cost, it significantly increases the chance of pregnancy. Couples affected by idiopathic subfertility or male subfertility have an estimated spontaneous conception rate of about 2% per cycle. Although various infertility treatments are available, counselling of a couple in their choice of treatment is difficult because of the lack of consistent data from good-quality comparative studies. We compared the results of treatment with intrauterine insemination (IUI) with those of in-vitro fertilisation (IVF), and did a cost-effectiveness analysis.
                In a prospective, randomised, parallel trial, 258 couples with idiopathic subfertility or male subfertility were treated for a maximum of six cycles of either IUI in the spontaneous cycle (IUI alone), IUI after mild ovarian hyperstimulation, or IVF. The primary endpoint was a pregnancy resulting in at least one livebirth after treatment. Cost-effectiveness based on real costs was studied by Markov chain analysis.
                86 couples were assigned IUI alone, 85 IUI plus ovarian hyperstimulation, and 87 IVF. Ten couples dropped out before treatment began. Although the pregnancy rate per cycle was higher in the IVF group than in the IUI groups (12.2% vs 7.4% and 8.7%, respectively; p=0.09), the cumulative pregnancy rate for IVF was not significantly better than that for IUI. Couples in the IVF group were more likely than those in the IUI groups to give up treatment before their maximum of six attempts (37 [42%] drop-outs vs 13 [15%] and 14 [16%], respectively; p<0.01). The woman's age was the only factor that influenced a couple's chance of success. IUI was a more cost-effective treatment than IVF (costs per pregnancy resulting in at least one livebirth 8423-10661 Dutch guilders [US$4511-5710] for IUI vs 27409 Dutch guilders [US$14679] for IVF).
                Couples with idiopathic or male subfertility should be counselled that IUI offers the same likelihood of successful pregnancy as IVF, and is a more cost-effective approach. IUI in the spontaneous cycle carries fewer health risks than does IUI after mild hormonal stimulation and is therefore the first-choice treatment. The efficacy of intrauterine insemination (IUI) of selected motile sperm.
                Prospective randomized sequential alternating cycle trial comparing IUI with luteinizing hormone (LH)-timed intercourse.
                Clinical infertility service.
                Couples selected included unexplained infertility (n = 73), cervical mucus hostility (n = 24), moderate semen defect (n = 110), and severe semen defect (n = 78). Two hundred eighty-five couples undertook 600 IUI cycles and 505 LH-timed intercourse.
                Overall, IUI was slightly more effective than LH-timed intercourse with a pregnancy rate of 6.2% versus 3.4% per cycle. When individual categories were considered only, IUI for severe semen defect was significantly better (5.6% versus 1.3%, P less than 0.05). The first IUI cycle was more effective when compared with both subsequent IUI cycles and the initial LH-timed cycle. Overall, 74% (27/37) of IUI pregnancies occurred in the first cycle.
                Compared with LH-timed intercourse, IUI provided little or no improved expectation of pregnancy but was beneficial in couples with severe semen defect. The occurrence of pregnancy was limited per cycle and confined essentially to the initial cycle of treatment. Continued IUI is considered to be unrewarding. To compare pregnancy rates with single intrauterine insemination (SIUI), double intrauterine insemination (DIUI) and fallopian tube sperm perfusion (FSP).
                Ninety patients undergoing a standard ovarian stimulation regimen were randomized to receive SIUI, DIUI or FSP. The end point was either pregnancy or completion of 3 treatment cycles without pregnancy.
                There were no differences in demographic data or ovarian responses. The total number of motile spermatozoa inseminated in the FSP group was significantly lower than in the SIUI group. No significant differences were found in pregnancy rate per cycle or patient, multiple pregnancy rate and outcome of pregnancy between the 3 groups.
                Similar pregnancy rates were achieved after SIUI, DIUI and FSP during stimulated cycles. In this prospective randomized study we treated 60 couples with unexplained infertility with a combination of ovarian stimulation and either intrauterine insemination (IUI) or fallopian sperm perfusion (FSP). In the IUI we used a volume of 0.5 ml of inseminate and in the FSP a volume of 4 ml. The demographic characteristics of the patients, the stimulation parameters and the sperm data were not statistically different between the two groups. The pregnancy rate per cycle was 16.2% in the IUI group and 14.5% in the FSP group and the pregnancy rate per woman was 40 and 36.7%, respectively (not statistically different). We conclude that IUI and FSP are equally effective in the treatment of couples with unexplained infertility.
Based on the results of pregnancy rate per couple in five trials, double intrauterine insemination resulted in significant benefit over single intrauterine insemination in the treatment of subfertile couples with husband semen. If advice is to be offered regarding clinical practice, further research is warranted.