The ESHRE multicentre trial on the treatment of unexplained infertility: a preliminary report. European Society of Human Reproduction and Embryology. Intrauterine insemination with controlled ovarian hyperstimulation versus expectant management for couples with unexplained subfertility and an intermediate prognosis: a randomised clinical trial. Randomized comparison of ovulation induction with and without intrauterine insemination in the treatment of unexplained infertility. A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotropin or clomiphene citrate. Superovulation and intrauterine insemination vs. superovulation alone in the treatment of unexplained infertility. A randomized study. Gamete intrafallopian transfer (GIFT) compared with intrauterine insemination in the treatment of unexplained infertility. Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: a prospective, randomized, crossover study during intrauterine insemination cycles. Ovulation induction with gonadotropins as sole treatment in infertile couples with open tubes: a randomized prospective comparison between intrauterine insemination and timed vaginal intercourse. A randomised prospective trial of intrauterine insemination versus timed intercourse in superovulated cycles with clomiphene. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network. A randomized, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis. Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost-effectiveness analysis.
Nineteen European fertility centres participated in a controlled randomized trial aimed at comparing the effectiveness of five methods for the treatment of unexplained infertility. Each centre was invited to employ two of the five treatments being investigated, and the treatment allocated to individual patients was then decided by randomization. The treatments were superovulation alone, and superovulation together with one of the following procedures: intra-uterine insemination (IUI), intra-peritoneal insemination (IPI), gamete intra-Fallopian transfer (GIFT), in-vitro fertilization (IVF). All the patients admitted to the study had experienced greater than 36 months infertility prior to the start of the trial, and only patients less than 38 years of age were included in the investigation. Further, the study was confined to patients with normal Fallopian tubes, and where there was evidence of spontaneous ovulation. Yet another prerequisite for inclusion in the study was that the male partner was 'normal' as regards fertility. Due to unavoidable practical difficulties, the experimental design eventually obtained was severely unbalanced. Nevertheless, objective statistical comparisons were possible among the five treatments, using non-orthogonal analyses of variance. By the completion of the trial 444 patients had been treated in a total of 649 cycles. There was some statistical evidence that the pregnancy rate obtained from superovulation alone was inferior to that obtained by using superovulation together with one of the methods of assisted conception.(ABSTRACT TRUNCATED AT 250 WORDS) 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. The aim of this prospective randomized controlled study was to determine the possible role of ovulation induction with intrauterine insemination (IUI) in the treatment of unexplained infertility. A total of 100 patients were randomized to receive ovulation induction with or without IUI. All patients were treated with long-course gonadotrophin-releasing hormone analogue (GnRHa), starting in the luteal phase, and exogenous follicle stimulating hormone (FSH) to induce follicular growth. Ovulation was induced using human chorionic gonadotrophin and timed intercourse (TI) was advised 24-48 h later or IUI was effected 36-48 h later. Both the cycle fecundities (21.8 and 8.5%) and the cumulative ongoing pregnancy rates after three cycles (42 and 20%) were significantly higher (P < 0.03) in the IUI group than in the TI group respectively. This is a clear indication that ovulation induction with IUI is an effective treatment method for unexplained infertility, but ovulation induction with TI has a negligible impact in this large group of patients. 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. To assess whether intrauterine insemination (IUI) improves the fertility rates in women with unexplained infertility.
                We recruited 68 women with unexplained infertility and allocated them randomly to treatment with three to five cycles of superovulation plus IUI (36 patients) or superovulation alone (32 patients). Superovulation was obtained with clomiphene citrate, human menopausal gonadotropins and human chorionic gonadotropins.
                The cycle fecundity rate was 10% in patients who underwent superovulation alone and 19% in those treated with superovulation plus IUI (P < .05).
                Our results demonstrate that superovulation plus IUI is more effective than superovulation alone in the treatment of unexplained infertility. To compare GIFT, intrauterine insemination (IUI) with, and without, ovarian hyperstimulation in the treatment of unexplained infertility.
                Women randomly allocated to one of three treatment protocols.
                Northern Regional Fertility Centre.
                59 couples with unexplained infertility of more than 3 years duration.
                Three cycles of either GIFT, IUI after ovarian hyperstimulation or IUI in a spontaneous cycle.
                Pregnancy resulting in a live birth.
                Fecundabilities were 0.12 after GIFT, 0.018 after ovarian hyperstimulation and IUI, and 0.018 after IUI in a spontaneous cycle. The fecundability after IUI was no different from that which would be expected without treatment in these couples but fecundability was significantly better (P greater than 0.02) after GIFT.
                This trial does not support the use of IUI in the treatment of unexplained infertility but confirms the value of GIFT. To test the hypothesis that in couples undergoing IUI, actively managed cycles using clomiphene citrate (CC) stimulation, ultrasound monitoring, and hCG timing will result in increased pregnancy rate (PR) per cycle compared with unstimulated urinary LH-timed cycles.
                Fifty-six couples with unexplained infertility (n = 26) or male factor infertility (n = 30) participated in the study.
                Tertiary academic medical center.
                Prospective, randomized, crossover. Couples were randomized initially to one of the two study groups (treatment A: LH-timed IUI; treatment B: CC-stimulated, hCG-timed IUI). If no pregnancy occurred, each couple alternated between the two regimens during subsequent cycles, up to a total of four cycles.
                Twenty-nine couples completed the study and the analysis of 95 cycles revealed that among the male factor infertility group, one pregnancy occurred during the 26 cycles of each treatment group (PR per cycle of 3.9% for both treatment groups). In contrast, among the unexplained infertility group, there was a marked difference in the effect of treatments. During treatment A only one pregnancy occurred in 20 cycles (PR of 5% per cycle) whereas during treatment B, six pregnancies occurred in 23 cycles (PR of 26.1% per cycle).
                If IUI is chosen as the treatment modality in unexplained infertility, the addition of active ovulation management that includes CC stimulation, ultrasound monitoring of folliculogenesis, and hCG timing of ovulation increases the PR per cycle. In couples with male infertility, PR per cycle is low and is apparently not affected by the addition of active ovulation management. To assess if ovulation induction with gonadotropins alone is an appropriate treatment in couples affected by unexplained and mild male factor-related infertility and if the concomitant IUI improves the pregnancy rate (PR).
                Prospective and randomized trial.
                Infertility Centre of Department of Obstetrics and Gynecology of the University of Cagliari, Cagliari, Italy.
                Two hundred couples affected by unexplained or mild male factor-related infertility were assigned randomly to one of two treatment groups: group A (n = 100), treated with three consecutive cycles of ovulation induction with gonadotropins associated with timed vaginal intercourse; group B (n = 100), treated with three consecutive cycles of ovulation induction with gonadotropins associated with IUI.
                Pregnancy rate.
                The PRs obtained with ovulation induction with gonadotropins associated with IUI were similar to those obtained with ovulation induction with gonadotropins associated with timed vaginal intercourse.
                Ovulation induction with gonadotropins alone may be as effective as ovulation induction with gonadotropins associated with IUI in couples with unexplained and mild male factor infertility and can represent the initial treatment option for its minimal invasivity and reduced cost and organizational problems. Despite its wide use, the benefits of intrauterine insemination (IUI), its over timed intercourse (TI) in couples with unexplained infertility is a matter of debate. Studies in Indian couples with unexplained infertility showing benefit of IUI over TI are not available. The present study was done with the objective of comparing TI and IUI with husband's sperm in couples with unexplained infertility undergoing superovulation with clomiphene.
                A total of 140 couples with unexplained infertility were subjected to controlled ovarian hyperstimulation (COH) with clomiphene and prospectively randomized to receive either TI (group A) or IUI (group B). Complete follow up was available for 113 couples only.
                The pregnancy rate and cycle fecundity rate after COH/TI was 41 and 8.8 per cent and after COH/IUI 18 and 3.4 per cent respectively. The difference was statistically not significant.
                The findings of the present study showed that in women with unexplained infertility addition of IUI to ovulation induction does not improve conception rates. COH/TI can help to achieve good results and save the expense and discomfort due to a invasive procedure. 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. This study was initiated to test the hypothesis that treatment with clomiphene citrate (CC) and intrauterine insemination (IUI) results in increased fecundity when compared with periovulatory intercourse in couples with either unexplained infertility or surgically corrected endometriosis. Sixty-seven couples entered a randomized, prospective trial comparing CC/IUI with observation. During the study, there were 14 pregnancies in 148 treated cycles (fecundity = 0.095) compared with 5 pregnancies in 150 untreated cycles (fecundity = 0.033). Using life-table analysis and the log-rank test, the difference in fecundities was statistically significant. Pregnancy outcome was not significantly different between the two groups. When comparing conception with nonconception cycles during treatment, no differences between the size of the lead follicle or the number of dominant follicles was detected. We conclude that treatment with CC/IUI improves fecundity in couples with unexplained infertility or surgically corrected endometriosis. 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.
There is evidence that IUI with OH increases the live birth rate compared to IUI alone. The likelihood of pregnancy was also increased for treatment with IUI compared to TI in stimulated cycles. One adequately powered multicentre trial showed no evidence of effect of IUI in natural cycles compared with expectant management. There is insufficient data on multiple pregnancies and other adverse events for treatment with OH. Therefore couples should be fully informed about the risks of IUI and OH as well as alternative treatment options.