A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotropin or clomiphene citrate. Late low-dose pure follicle stimulating hormone for ovarian stimulation in intra-uterine insemination cycles.
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. 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.
There is insufficient evidence to suggest that oral agents are inferior or superior to injectable agents in the treatment of unexplained subfertility. Information on harms is sketchy, and remains compatible with large differences in either direction. Much larger trials than have previously been undertaken are required to provide information on relative harms as well as benefits.