Pre-treatments in IVF/ICSI cycles

In vitro fertilisation (IVF) and intra cytoplasmic sperm injection (ICSI) are important techniques for women who have trouble getting pregnant. IVF and ICSI cycles consist of a few steps. First the woman receives hormone therapy to stimulate her ovaries in producing egg cells. When a few egg cells are mature enough to be fertilized, the woman receives a single hormone injection. This triggers the ovaries to release the egg cells, so they can be gathered by the clinician. The eggs are then fertilised outside the woman's body and become embryos. At last one or two embryos are transferred into the womb.
Before the first step in IVF or ICSI cycles (hormone therapy), a pre-treatment with a combined oral contraceptive pill (OCP) can be given. A combined OCP contains both progestogen and oestrogen. Pre-treatment with a progestogen or oestrogen alone could also be used before the hormone therapy. These pre-treatments suppress the woman's own hormone production. This might improve the woman's response to the hormone therapy in IVF/ICSI cycles. In this way, adverse events such as cyst formation and the number of pregnancy losses might be reduced and pregnancy outcomes might be improved.
The aim of this review is to assess if pre-treatments with a combined OCP or a progestogen or oestrogen influence these outcomes in IVF/ICSI cycles. This is done by pooling results of more than one study, which will hopefully provide a more solid conclusion. We were able to include 23 studies: a reasonable number. However, due to the formation of subgroups, we have only pooled results of five studies maximum.

Pre-treatment with a combined OCP seems to result in fewer clinical pregnancies. More days of gonadotrophin therapy and a higher amount of gonadotrophins are needed. This is mainly important with regard to the financial aspect of the IVF/ICSI treatment. A pre-treatment with progestogen is associated with more clinical pregnancies and fewer ovarian cysts. Ovarian cysts are frequent reasons for cycle cancellation. In oestrogen pre-treated cycles more eggs are retrieved, but a higher amount of gonadotrophin therapy is needed.

A limitation of this review is that most included studies were small and of poor quality.

The need for a pre-treatment with oral contraceptives should be clearly explained to the woman undergoing IVF, because this might be hard to understand when you are trying to get pregnant.

For definitions of terminology see our Glossary.

Authors' conclusions: 

There was evidence of improved pregnancy outcomes with progestogen pre-treatment and poorer pregnancy outcomes with a combined OCP pre-treatment. However, we conclude that major changes in ART protocols should not be made at this time, since the number of overall studies in the subgroups is small and reporting of the major outcomes is inadequate.

Read the full abstract...
Background: 

For many subfertile women, assisted reproductive techniques (ART) is the only hope for a pregnancy and live birth. The combined oral contraceptive pill (OCP) given prior to the hormone therapy in an IVF cycle may result in better pregnancy outcomes of ART.

Objectives: 

To assess whether pre-treatment with combined OCPs, progestogens or estrogens in ovarian stimulation protocols affects outcomes in subfertile couples undergoing ART.

Search strategy: 

We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycINFO. Other electronic resources on the Internet, reference list of relevant articles were also searched as well as the ESHRE abstracts (2008). All these searches were conducted in November 2008.

Selection criteria: 

Randomised controlled trials of pre-treatment with combined OCP, progestogen or estrogen in subfertile women undergoing IVF/ICSI.

Data collection and analysis: 

Two authors independently extracted the data and assessed risk of bias. We calculated Peto odds ratios for dichotomous data and weighted mean difference for continuous variables. Authors of trials were contacted in case of missing data.

Main results: 

No evidence of effect was found with regard to the number of live births when using a pre-treatment. However, the combined OCP in GnRH antagonist cycles, compared to no pre-treatment, is associated with fewer clinical pregnancies (Peto OR 0.69, 95% CI 0.50 to 0.9; P = 0.03) and more days and a higher amount of gonadotrophin therapy (respectively: MD 1.44, 95% CI 1.15 to 1.72; P < 0.00001; and MD 231.14, 95% CI 161.50 to 300.78; P < 0.00001). Also compared to placebo or no pre-treatment, a progestogen pre-treatment in GnRH agonist cycles, is associated with more clinical pregnancies (Peto OR 1.95, 95% CI 1.20 to 3.17; P = 0.007) and fewer ovarian cysts (Peto OR 0.21, 95% CI 0.12 to 0.35; P < 0.00001). At last, in estrogen pre-treated GnRH antagonist cycles, compared to no pre-treatment, more oocytes are retrieved (MD 2.01, 95% CI 1.76 to2.25; P < 0.00001), but a higher amount of gonadotrophin therapy is needed (MD 207.08, 95% CI 167.77 to 246.39; P < 0.00001). For the other outcomes no evidence of effect was found or there were not enough studies available in the subgroup for pooling.

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