Dados do Trabalho

Title

DOES ATOSIBAN ADMINISTRATION IN EMBRYO TRANSFER CONTEXT IMPROVE PREGNANCY RATE?

Objective

The primary endpoint is to determine if the administration of oxytocin antagonist (Atosiban) before embryo transfer (ET) may improve reproductive outcomes, and who are the patients eligible.

Methods

Searched electronic databases Pubmed, LILACS, Cochrane using MeSH terms (Keywords): embryo transfer, Atosiban. A total number of 32 articles were found and 8 were included. All randomized controlled trials (RCTs) that evaluated use of Atosiban before ET in women undergoing in vitro fertilization (IVF) cycles.
Atosiban dose administered varied in studies, most of them applied an initial bolus of 6.75 mg, and the infusion was continued with 18 mg/h for 1 hour, but in some studies, it was maintained for the second hour at 6 mg/h until complete 37.5 mg.

Results

Atosiban is a uterine-especific oxitocine antagonist, used primarily for preterm labor. Some studies demonstrate that Atosiban may decrease uterine contractions and promote uterine receptivity. The main theory about improvement in pregnancy rate would be decrease in uterine hyperreactivity. Embryo implantation requires moderate uterine contractions and adequate endometrium blood supply. Excessive uterine contractions can reduce implantation rate in IVF cycles and even push the embryo to be expelled from uterine cavity.
Ye He et al. observed higher uterine waves per minute in endometriotic patients. Clinical pregnancy rate per cycle and implantation rate per transfer were 58.3% and 41.0%, respectively, in the atosiban group, significantly higher than in control group (38.3% and 23.4%, respectively) (95% IC 1.08–4.68; P0,044).
Yuan, C et al studied patients with previous difficult tranfer using Atosiban and only cryopreserved embryos. Clinical pregnancy rate per cycle and implantation rate per transfer in atosiban group (45.1% and 26.5%) were significantly higher than those of placebo group (15.6% and 9.7%, respectively; P < 0.05).
A multicentric randomized double blind study with 800 subfertile women undergoing IVF treatment using a general population, didn’t found significant difference on live birth rate between atosiban and placebo groups (Ng, EH et al; Li et al)
Tang CL et al compared atosiban in patients with recurrent implantation failure undergoing IVF treatment with fresh embryo and there wasn’t significant difference on live birth rate between atosiban and placebo groups (42.3% vs 35.1%, p=0.302, RR=1.206 (0.844-1.723). There weren’t significant differences between both groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy, and implantation rates.
Moraloglu, O et al on a randomized, placebo-controlled clinical study with 180 woman shown that clinical pregnancy rate (PR) per cycle and implantation rate per transfer were 46.7% and 20.4% in the atosiban-treated group, which were significantly higher than control group (28.9% and 12.6%, respectively, P = 0.01). Miscarriage rates of groups 1 and 2 were 16.7% and 24.4%, respectively (P = 0.01).
Craciunas L et al compaired the use of others oxitocine antagonists as nolasiban (oral), barusiban (subcutaneous) and atosiban (intravenous): none of them could increase live birth rate or decrease miscarriage rates.

Conclusion

Good quality embryos and ideal intrauterine environment are basic determinants of IVF outcomes, but ET is the final and crucial physician-guided step.
Use of Atosiban seems to increase pregnancy outcomes in assisted reproduction cycles in some specific patients: woman with endometriosis, previous difficult transfer (defined when intrauterine manipulation was required, transfer catheter was curved back, greater resistance was met, multiple attempts were necessary, the procedure was time consuming (>30 seconds), force was needed, or trauma occurred, even rarely, dilation was carried out) or in the context of frozen cycles. However, use of this strategy increases cycle value, length of hospital stay. Therefore, larger randomized studies are needed for better evaluation.

Keywords

embryo tranfer; atosiban; in vitro fertilization