Conventional in-vitro fertilisation versus intracytoplasmic sperm injection for the treatment of non-male-factor infertility: a randomised controlled trial. Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost-effectiveness analysis. Clinical pregnancy and male subfertility; the ESHRE multicentre trial on the treatment of male subfertility. European Society of Human Reproduction and Embryology. One versus two embryo transfer after IVF and ICSI: a randomized study. A prospective, randomized trial on the effect of atmospheric versus reduced oxygen concentration on the outcome of intracytoplasmic sperm injection cycles. Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial. Effect of endometrioma cystectomy on IVF outcome: a prospective randomized study. Comparison of GnRH agonists and antagonists in normoresponder IVF/ICSI in Turkish female patients. Comparison of intracervical, intrauterine, and intratubal techniques for donor insemination.
Intracytoplasmic sperm injection (ICSI) is a more invasive option than conventional in-vitro fertilisation (IVF), which can be successful even when semen characteristics are poor. Reports of higher fertilisation rates after ICSI suggest that this technique may be better than the conventional method for all couples seeking IVF. We undertook a multicentre randomised controlled trial comparing clinical outcome after ICSI or traditional IVF in couples with non-male-factor infertility.
                415 eligible and consenting couples at four UK centres were randomly assigned IVF or ICSI (total 435 treatment cycles: IVF 224; ICSI 211). Usual clinical and laboratory protocols for the two treatment procedures were followed in each of four participating centres. The primary outcome was the implantation rate (number of gestation sacs per embryo replaced expressed as a percentage). Secondary outcomes were pregnancy and fertilisation rates associated with each treatment. Analyses were by intention to treat.
                The implantation rate was higher in the IVF group than in the ICSI group (95/318 [30%] vs 72/325 [22%]; relative risk 1.35 [95% CI 1.04-1.76]). The pregnancy rate per cycle was also higher after IVF (72 [33%] vs 53 [26%]; 1.17 [0.97-1.35]). Mean associated laboratory time was significantly shorter with IVF than with ICSI (22.9 [SD 12.1] vs 74.0 [38.1] min; 95% CI for difference 45.6-56.6).
                ICSI offers no advantage over IVF in terms of clinical outcome in cases of non-male-factor infertility. Our results support the current practice of reserving ICSI only for severe male-factor problems. 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. Ovulation induction alone, and ovulation induction in conjunction with one of four assisted procreation methods [intra-uterine insemination (IUI), intra-peritoneal insemination (IPI), gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization (IVF)] were tested as a treatment for male infertility in a prospective randomized trial. The trial when completed had generated data on 499 cycles from 346 patients. There was overwhelming evidence that some form of assisted procreation was beneficial, when compared to the spontaneous natural conception rate, which is generally assumed to be between 0.01 and 0.02 for male infertility. There was also firm evidence that IUI, GIFT or IVF (mean per cycle pregnancy rate 0.212) were superior to the remaining two treatments of IPI and ovulation induction alone (mean per cycle pregnancy rate 0.068). Duration of infertility and a diagnosis of endometriosis were the most important (adverse) pre-treatment factors detected. The main reason for adverse treatment outcome in assisted reproduction is the high rate of multiple pregnancies. The only strategy to avoid dizygotic twins is to transfer one embryo at a time.
                A total of 144 women, who had had at least four good quality embryos available after IVF/intracytoplasmic sperm injection (ICSI) and who had no more than one previous failed treatment cycle, were randomized to have either one or two embryos transferred. The treatment outcomes including those after frozen embryo transfer were compared between these groups.
                The clinical pregnancy rate per transfer was 32.4% in the one embryo transfer group and 47.1% in the two embryo transfer group, the difference being not significant. Eleven twin deliveries (n = 39) occurred in the two embryo transfer group and there was one pair of monozygotic twins in the one embryo transfer group. The cumulative pregnancy rate per patient after transfer of fresh and frozen embryos was 47.3% in the one embryo transfer group and 58.6% in the two embryo transfer group.
                Our results indicate that among women who have good quality embryos in their first IVF/ICSI, good treatment results can be achieved. They support the idea of changing embryo transfer policy towards one embryo transfer without any remarkable decrease in the success rate, while dizygotic twins can be avoided. To assess whether the embryo cultivation at different oxygen tensions had any effect on intracytoplasmic sperm injection (ICSI) outcome.
                Prospective randomized trial.
                University clinical center.
                Women undergoing ICSI (n = 647).
                Culturing of embryos, either at 6% CO(2), 5% O(2), 89% N(2), or at 6% CO(2) in air.
                The primary outcome was ongoing pregnancy rates (PR). Secondary outcomes: cumulative PRs, implantation, and embryo quality, for both treatment groups and clinical outcomes for subgroups (optimal cycles, poor responders, older women).
                Although low oxygen resulted in a higher proportion of good day 2 embryos (0.547 +/- 0.021 vs. 0.39 +/- 0.019) and optimal blastocysts (0.162 +/- 0.199 vs. 0.083 +/- 0.128), the ongoing PRs (31.6% vs. 27.1%) and implantation rates (28.8% vs. 25.2%) were similar in both oxygen groups. Low oxygen caused a higher cumulative PR (38% vs. 28.3%) in the main group and a higher PR in the poor responder subgroup (23% vs. 9.8%) with embryo transfers performed mostly on day 3.
                The use of reduced oxygen in IVF is reasonable, irrespective of the duration of embryo culture. It improves embryo development and cumulative PR and is also recommended in poor responding cycles.
                Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. A prospective randomized study comparing single embryo transfer with double embryo transfer after in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) was carried out. First, top quality embryo characteristics were delineated by retrospectively analysing embryos resulting in ongoing twins after double embryo transfer. A top quality embryo was characterized by the presence of 4 or 5 blastomeres at day 2 and at least 7 blastomeres on day 3 after insemination, the absence of multinucleated blastomeres and <20% cellular fragments on day 2 and day 3 after fertilization. Using these criteria, a prospective study was conducted in women <34 years of age, who started their first IVF/ICSI cycle. Of 194 eligible patients, 110 agreed to participate of whom 53 produced at least two top quality embryos and were prospectively randomized. In all, 26 single embryo transfers resulted in 17 conceptions, 14 clinical and 10 ongoing pregnancies [implantation rate (IR) = 42.3%; ongoing pregnancy rate (OPR) = 38.5%] with one monozygotic twin; 27 double embryo transfers resulted in 20 ongoing conceptions with six (30%) twins (IR = 48.1%; OPR = 74%). We conclude that by using single embryo transfer and strict embryo criteria, an OPR similar to that in normal fertile couples can be achieved after IVF/ICSI, while limiting the dizygotic twin pregnancy rate to its natural incidence of <1% of all ongoing pregnancies. The study was conducted to investigate the effect of conservative surgery of ovarian endometriomas before an ICSI cycle. Ninety-nine patients with endometriomas who were referred to an intracytoplasmic sperm injection (ICSI) cycle were enrolled in the study. The patients were prospectively randomized into two groups; group I (49 patients) underwent conservative ovarian surgery before the ICSI cycle and group II (50 patients) underwent the ICSI cycle directly. The stimulation was started 3 months after the operation in group I and directly in group II. In the ovarian surgery group, stimulation was significantly longer (14.0 days in group I and 10.8 days in group II; P = 0.001), total recombinant FSH dose was significantly higher (4575 IU in group I and 3675 IU in group II; P = 0.001), and mean number of mature oocytes was significantly lower (7.8 in group I and 8.6 in group II; P = 0.032). There was no difference in terms of fertilization (86% in group I and 88% in group II), implantation (16.5% in group I and 18.5% in group II) and pregnancy rates (34% in group I and 38% in group II). Ovarian surgery resulted in longer stimulation, higher FSH requirement and lower oocyte number, but fertilization, pregnancy and implantation rates did not differ between the groups. To evaluate the results of gonadotropin-releasing hormone agonist (GnRHa) and gonadotropin-releasing hormone antagonist (GnRHant) use in two demographically matched groups of normoresponder in-vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI) patients in a prospective study.
                We randomised 93 patients undergoing IVF/ICSI between May 2005 and August 2006. Patients with IVF indications were included except for those with polycystic ovary syndrome or azoospermia, women older than 38 years and those with follicle-stimulating hormone (FSH) > or =10 IU/ml. Patients were stimulated with standard 225 IU recombinant FSH. In Group I (n=45) a daily dose of GnRHant cetrorelix acetate 0.25 mg was administered when follicles reached a diameter of > or =14 mm. Group II (n=48) patients were desensitised with the GnRHa, leuprolide acetate, in a long protocol. Human chorionic gonadotropin (hCG) was administered when at least three follicles of 18 mm in diameter were observed. Oocyte retrieval was scheduled 36 hours following hCG administration and embryos were transferred on day 3 after oocyte retrieval.
                The two groups were homogenous for age, infertility duration, basal FSH and serum oestradiol (E2) (P=0.537, P=0.911, P=0.103 and P=0.733, respectively). In Group II (the GnRHa group) more antral follicles (P<0.001), a longer induction duration (P=0.017) and higher peak E2 levels (P<0.001) were observed. No differences were observed in the number of oocytes retrieved (P=0.749), embryos achieved and transferred (P=0.677), or fertilisation rates (P=0.839) between the two groups. There was no statistically significant difference between groups in clinical pregnancy rates, cycle cancellation and ovarian hyperstimulation (P=0.437, P=0.109 and P=0.415, respectively).
                GnRHant and GnRHa provide comparable results in normoresponder patients, while GnRHant allows a greater flexibility in their treatment. To compare the efficacy of intracervical insemination (ICI), intrauterine insemination (IUI), and a combination of intratubal and intrauterine insemination (ITI/IUI) for donor insemination.
                Prospective randomized clinical trial.
                The University of Michigan donor insemination program.
                Forty-one women undergoing donor insemination with cryopreserved sperm for either isolated male factor or male factor plus ovulatory dysfunction corrected by clomiphene citrate.
                Each patient was randomly assigned to receive each of the three insemination techniques in consecutive cycles until pregnancy occurred or the patient dropped from the study.
                Cycle fecundity rates were compared using the chi 2 test, and cumulative pregnancy rates (PRs) determined by life table analysis were compared using a log-rank test.
                Cycle fecundity rate was significantly higher for IUI (18.3%) than for ICI (3.9%) or ITI/IUI (7.3%). By life table analysis, the cumulative PR for IUI was significantly higher than for ICI, but the PR for ITI/IUI was not.
                For donor insemination with cryopreserved sperm, IUI increases cycle fecundity compared with ICI. The addition of ITI to IUI, however, interferes with the apparent beneficial effect of IUI alone.
Whether ICSI should be preferred to IVF for cases of non-male factor subfertility remains an open question. Further research should report live birth rates and adverse events.