The effect of prolongation of luteal support with progesterone following in-vitro fertilisation treatments on pregnancy outcome

Russell, Richard
The effect of prolongation of luteal support with progesterone following in-vitro fertilisation treatments on pregnancy outcome. Doctor of Philosophy thesis, University of Liverpool.

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Over 5 million babies have been born as a result of IVF procedures. Worldwide, over 1 million cycles of IVF are performed annually. The IVF procedure involves ovarian stimulation with the purpose of developing multiple follicles and maximising the potential oocyte yield. As a consequence of high oestradiol levels produced during treatment and the use of GnRH agonists or antagonists, a luteal phase deficiency results. This phenomenon is associated with reduced implantation potential and suboptimal conditions for maintenance of early pregnancy. Luteal support in the form of progesterone or HCG has been demonstrated to improve pregnancy rates after IVF. A number of luteal support protocols have been investigated with progesterone the most commonly used drug. The optimum duration of luteal support has yet to be defined. With no agreement in clinical practice evident, the reported use of progesterone ranges from withdrawing luteal support at confirmation of biochemical pregnancy to continuation beyond 12 weeks gestation. Whilst luteal support is considered a very important aspect of IVF treatment, there is very little evidence to support an optimum duration of use. The DOLS trial is a prospective randomised double blind placebo controlled trial investigating the effect of additional luteal support beyond confirmation of pregnancy test after assisted conception. Four hundred and sixty seven patients were randomised after confirmation of biochemical pregnancy to receive a further 8 weeks of vaginal progesterone or 8 weeks of placebo. Summary results were to include a primary outcome defined as viable pregnancy at 12 weeks gestation, whilst secondary outcomes were to report on live birth rates, pregnancy associated complications, neonatal outcomes, effect on first trimester serum screening and effect on uterine artery Doppler velocity. The DOLS trial reported no difference in pregnancy outcome at 12 weeks gestation, with 167/228 (73.3%) women randomised to the extended luteal support treatment arm having a confirmed viable intrauterine pregnancy compared with 167/233 (71.7%) women randomised to the placebo arm of the trial; adjusted risk ratio 0.97 (95%CI 0.87 to 1.09). Similarly live birth rates were not different between the treatment groups; 71.1% versus 70.4% respectively. No effect of extending luteal support beyond positive pregnancy test was observed in reference to complications of pregnancy, neonatal outcome, uterine artery Doppler velocity or antenatal screening outcome. In conclusion, we have confirmed that continuing luteal support using progesterone beyond confirmation of biochemical pregnancy offers no benefit in terms of pregnancy outcomes. However the extended use of progesterone until 12 weeks gestation does not confer harm. We suggest that all clinics worldwide should consider offering luteal support no further than positive pregnancy test, at which point it can be safely withdrawn without compromising live birth rates and reducing treatment burden.

Item Type: Thesis (Doctor of Philosophy)
Additional Information: Date: 2014-03 (completed)
Subjects: ?? RG ??
Divisions: Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 20 Aug 2014 08:46
Last Modified: 17 Dec 2022 00:12
DOI: 10.17638/00016493
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