Conventional in-vitro fertilisation versus intracytoplasmic sperm injection for the treatment of non-male-factor infertility: a randomised controlled trial. Clinical pregnancy and male subfertility; the ESHRE multicentre trial on the treatment of male subfertility. European Society of Human Reproduction and Embryology. Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost-effectiveness analysis. Removal of cervical mucus: effect on pregnancy rates in IVF/ICSI. Low-dose aspirin therapy and hypertensive pregnancy complications in unselected IVF and ICSI patients: a randomized, placebo-controlled, double-blind study. A randomised control trial examining the effect of an antioxidant (Menevit) on pregnancy outcome during IVF-ICSI treatment. IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Endometrin for luteal phase support in a randomized, controlled, open-label, prospective in-vitro fertilization trial using a combination of Menopur and Bravelle for controlled ovarian hyperstimulation. Cervical dilatation has a positive impact on the outcome of IVF in randomly assigned cases having two previous difficult embryo transfers. Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilisation/intra cytoplasmic sperm injection: a randomised clinical trial.
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. 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. 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. Cervical mucus may cover the embryo transfer catheter during passage of the cervical canal, interfering with the correct placement of the embryo(s) into the uterine cavity. The effect of removal of cervical mucus prior to embryo transfer in IVF/ intracytoplasmic sperm injection (ICSI) on live birth rate was studied. The study was set up as a single blind randomized controlled trial. Couples undergoing IVF/ICSI were randomly allocated to either removal of cervical mucus prior to embryo transfer, or a mock procedure. Randomization was done with stratification for age, cycle number and method of treatment. Primary outcome was live birth rate. A total of 317 couples were included and underwent 428 cycles, of which the outcome of 3 cycles was unknown. Baseline characteristics of both groups were comparable. Live birth occurred in 52 of 220 (24%) cycles in the treatment group and 42 of 205 (21%) cycles in the control group (risk difference 3%, 95% confidence interval-5- 11%). It is unlikely that removal of cervical mucus prior to embryo transfer has a significant effect on live birth rate. A small effect, however, cannot be excluded. Low-dose aspirin therapy could improve remodelling of maternal spiral arteries during early placentation and prevent subsequent pregnancy-related hypertensive disorders. We investigated whether low-dose aspirin therapy reduces the incidence of hypertensive pregnancy complications in unselected IVF and ICSI patients when medication was started prior to pregnancy.
                A total of 487 patients who underwent IVF/ICSI were randomized to receive 100 mg aspirin (n = 242) or placebo (n = 245) daily, starting on the first day of gonadotrophin stimulation. Pregnant women continued the medication until delivery. A total of 107 patients (52 with aspirin and 55 with placebo) experienced live birth and were included in this follow-up study. The main outcome measure was the incidence of hypertensive pregnancy complications.
                Embryo transfer took place in 227 (94%) women in the aspirin group and in 229 (93%) women in the placebo group. The live birth rate between the aspirin (22.9%) and placebo (24.0%) groups did not differ significantly (P = 0.78). The overall incidence of hypertensive pregnancy complications was 15.4% (8/52) in the aspirin group and 18.2% (10/55) in the placebo group (P = 0.70, 95% confidence interval for the difference of proportions -17 to 11%). There were two cases of severe pre-eclampsia in the aspirin group and three cases in the placebo group.
                In the present study, the incidence of hypertensive pregnancy complications did not differ statistically significantly between low-dose aspirin and placebo groups in unselected IVF/ICSI patients, when medication was started concomitantly with gonadotrophin stimulation and continued until delivery. The study was registered at clinicaltrials.gov. NCT00683202. Evidence has accumulated supporting the role of reactive oxygen species (ROS) in the pathogenesis of sperm dysfunction among men with infertility. Damage to sperm DNA by ROS can lead to failure of conception, miscarriage or potentially even childhood cancer. The objective of this study was to examine the effect of male antioxidant treatment on embryo quality and pregnancy outcome during in vitro fertilisation-intracytoplasmic sperm injection (IVF-ICSI) treatment.
                Sixty couples with severe male factor infertility were enrolled in a prospective randomised double-blind placebo-controlled trial. Male participants were randomly assigned to take either one capsule per day of the Menevit antioxidant or an identical in appearance placebo for three months prior to their partner's IVF cycle. The primary outcome was cleavage stage embryo quality and the secondary outcomes were oocyte fertilisation rate, pregnancy rates and treatment side-effects. Approval by the local Human Research Ethics Committee was obtained prior to the commencement of this study.
                The antioxidant group recorded a statistically significant improvement in viable pregnancy rate (38.5% of transferred embryos resulting in a viable fetus at 13 weeks gestation) compared to the control group (16% viable pregnancy). No significant changes in oocyte fertilisation rate or embryo quality were detected between the antioxidant and the placebo groups. Side-effects on the Menevit antioxidant were rare (8%) and mild in nature.
                The Menevit antioxidant appears to be a useful ancillary treatment that significantly improves pregnancy rates in couples undergoing IVF-ICSI treatment for severe male factor infertility. To study if luteal E(2) pre-treatment before GnRH antagonist protocol improves IVF/ICSI outcomes compared with standard long GnRH agonist protocol.
                A prospective, randomized and controlled study.
                ART center of a state public hospital
                Two hundred twenty infertile women underwent IVF/ICSI treatments.
                Participants received oral Estradiol Valerate 4 mg/day preceding the IVF cycle from day 21 until day 2 of next cycle before GnRH antagonist protocol (E(2) pre-treatment group n=109) or received standard long GnRH agonist protocol as control group (n=111).
                Number of oocytes collected, MII oocytes, fertilization, implantation, live birth and early pregnancy rate, and hormone profiles.
                E(2) pre-treatment exerted a significant suppressive effect on FSH but not LH secretion compared with basal FSH and LH levels. In E(2) pre-treatment group serum LH level was significantly higher during COH and serum P was also significantly higher on the day of HCG injection compared with control group. Five patients from E(2) pre-treatment group had elevated LH at all time (>or= 10 IU/L) and also a concomitantly high P (>1 ng/mL). Two of the five women achieved pregnancy but had early pregnancy loss. Overall, IVF/ICSI outcomes such as implantation, clinical pregnancy and live birth rates were similar between E(2) pre-treatment and control groups.
                Luteal E(2) pre-treatment before GnRH antagonist protocol significantly increases serum LH level and incidence rate of premature LH but no significant effect is observed on implantation, clinical pregnancy, live birth and early pregnancy loss rates compared with long GnRH agonist protocol. However, more studies in large numbers of cycles are needed to confirm that increased serum LH level by E(2) pre-treatment during COH has no negative effect on the IVF/ICSI outcomes. To study the effects of folic acid and zinc sulfate treatment on semen variables in fertile and subfertile men.
                Double-blind, placebo-controlled interventional study.
                Two outpatient fertility clinics and nine midwifery practices in The Netherlands.
                One hundred eight fertile and 103 subfertile men.
                Both groups were randomly assigned to receive one of four treatments for 26 weeks: folic acid and placebo, zinc sulfate and placebo, zinc sulfate and folic acid, and two placebos. Folic acid was given at a daily dose of 5 mg, and zinc sulfate was given at a daily dose of 66 mg.
                Before and after treatment, standardized semen and blood samples were obtained for determinations of sperm concentration, motility, and morphology according to World Health Organization guidelines; semen morphology according to strict criteria; and blood folate and zinc concentrations. Effects of the four interventions were evaluated separately in subfertile and fertile men.
                Subfertile men demonstrated a significant 74% increase in total normal sperm count and a minor increase of 4% abnormal spermatozoa. A similar trend was observed in fertile men. Pre-intervention concentrations of folate and zinc in blood and seminal plasma did not significantly differ between fertile and subfertile men.
                Total normal sperm count increases after combined zinc sulfate and folic acid treatment in both subfertile and fertile men. Although the beneficial effect on fertility remains to be established, this finding opens avenues of future fertility research and treatment and may affect public health. To assess the efficacy and safety of a vaginal progesterone (P(4)) insert (Endometrin) for luteal support for assisted reproductive technology (ART).
                Multicenter, randomized, open-label (assessor-blinded) phase III clinical trial.
                Twenty-five U.S. ART centers.
                A total of 1,211 ART patients randomized to three groups: Endometrin 100 mg twice daily (n = 404), Endometrin 100 mg three times daily (n = 404), and P(4) 90 mg 8% gel daily (n = 403).
                In vitro fertilization and ET were performed according to site-specific protocols. The day after oocyte retrieval, Endometrin or vaginal P(4) gel was begun for luteal support and continued for up to 10 weeks of pregnancy.
                Biochemical, clinical, and ongoing pregnancy and live birth rates.
                Pregnancy rates were high and similar in all treatment groups, with biochemical rates exceeding 50%, clinical and ongoing rates >or=40%, and live birth rates at 35%-38%. The adverse event profiles were similar across groups.
                Pregnancy rates and live birth rates for Endometrin (twice daily and three times daily) were high and similar to those for P(4) gel. The adverse event profiles for both were similar to that for P(4) gel and primarily due to IVF stimulation and oocyte retrieval. Endometrin was safe and well tolerated. The difficulty of embryo transfer has been reported to affect success rates in some centres, but not in others. Cervical dilatation has been proposed as a means to overcome difficult embryo transfer, but consistent criteria for patient selection are lacking. In a prospective randomized study, we examined the influence of cervical dilatation 1-3 months before embryo transfer on the outcome of IVF in cases having difficult embryo transfer in two previously failed IVF cycles.
                Two alternative methods of embryo transfer preparation were evaluated in 283 randomly assigned women having difficult embryo transfers in two previously failed IVF attempts. Randomization was made using a computer-generated random number table. Cervical dilatation before starting any IVF treatment was used in 145 cases, and no dilatation was performed in 138 cases.
                The cervical dilatation group yielded a significantly higher pregnancy rate than the non-dilated group (40% versus 24%; P < 0.01). Likewise, the implantation rate (24.1% versus 14.9%; P < 0.01) and the live birth rate (34.48% versus 19.56%; P < 0.01) were significantly higher in the dilatation group than in the non-dilated group.
                In patients with prior difficult embryo transfer, cervical dilatation 1-3 months before embryo transfer lead to an improved pregnancy rate.
                Copyright 2004 European Society of Human Reproduction and Embryology Implantation failure is the most important cause of recurrent in vitro fertilisation (IVF)/intra cytoplasmic sperm injection (ICSI) failure. It has been reported that endometrial injury using a biopsy catheter resulted in a higher pregnancy rate in following cycle of treatment. The local endometrial trauma increases the implantation rate through the release of chemical mediators such as histamine and growth factor.
                To evaluate the influence of endometrial biopsy on increasing implantation rate in patients with recurrent implantation failures.
                In a randomised control trial study, 115 women each with at least two implantation failures were randomly assigned to two groups. In the case group, endometrial biopsy was obtained from patients in the luteal phase of previous cycle, and implantation and clinical pregnancy rates were compared with those of patients in the control group.
                The implantation rate was determined as 10.9% in the biopsy group compared to 3.38% in the controls. The clinical pregnancy rate was significantly higher in the case group than in controls (27.1% and 8.9% respectively).
                The results suggest that pregnancy outcome increases through IVF or ICSI after endometrial biopsy.
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.