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Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet]. Chichester, UK: John Wiley & Sons, Ltd; 2003-.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet].

Use of clomiphene citrate in IVF treatment

This version published: 2012; Review content assessed as up-to-date: March 23, 2012.

Link to full article: [Cochrane Library]

Plain language summary

Gonadotrophin injections are commonly used in an IVF treatment to stimulate the ovaries to increase the number of available eggs, which can then be mixed with sperm in the laboratory to create embryos for transfer back into the uterus. However, the injections are expensive, inconvenient and are associated with side effects. Calls for patient friendly stimulation regimens have generated interest in using clomiphene, which is a tablet, in these treatments to reduce the burden of injections. Presently it is not known whether use of clomiphene is associated with similar pregnancy rates. The aim of this review was to compare regimens with clomiphene versus gonadotropins alone for stimulation of the ovaries during IVF treatment. A total of 12 studies, with 2536 participants, were included in the analysis. The evidence from this review suggests that use of clomiphene along with gonadotropins leads to similar pregnancy rates as those occurring after the use of gonadotropins alone. However, the evidence was limited as all studies included in this review were old. Further evidence is required to determine the clinical and cost effectiveness of stimulation regimens using clomiphene citrate with gonadotropins versus gonadotropins alone.

Abstract

Background: Gonadotropins are the most commonly used medication for controlled ovarian stimulation in in vitro fertilization (IVF). However, they are expensive, invasive and are associated with risk of ovarian hyperstimulation syndrome (OHSS). With recent calls for patient friendly IVF, there has been an interest in the use of clomiphene citrate with or without gonadotropins to reduce the burden of injections. However, it is not known whether regimens using clomiphene are at least as effective as gonadotropins alone.

Objectives: To determine whether clomiphene citrate with gonadotropins (with or without mid‐cycle antagonist) is more effective than gonadotropins with gonadotropin‐releasing hormone (GnRH) agonists for controlled ovarian stimulation in IVF or intracytoplasmic sperm injection (ICSI) treatment.

Search methods: Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched March 2012), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, first quarter), MEDLINE (1970 to March 2012), EMBASE (1985 to Mar 2012) and reference lists of articles. Relevant conference proceedings were handsearched.

Selection criteria: Randomised controlled trials (RCT) were included. Live birth rate (LBR) per woman was the primary outcome.

Data collection and analysis: Two review authors independently assessed the eligibility and quality of trials

Main results: Fourteen studies were included in the review. Meta‐analysis could be performed with the data of 12 included studies, with a total of 2536 participants. There was no evidence that clomiphene along with gonadotropins for IVF, with or without mid‐cycle GnRH antagonist, differed from gonadotropins alone in GnRH agonist protocols in terms of live births (5 RCTs, 1079 women; OR 0.93, 95% CI 0.69 to1.24) or clinical pregnancy (11 RCTs, 1864 women; OR 1.07, 95% CI 0.85 to1.33). This means that for a typical clinic with 23% LBR using a GnRH agonist regimen, switching to clomiphene protocols would be expected to result in LBRs between 16% and 26%. There was a significant reduction in the incidence of OHSS (5 RCTs, 1559 women; OR 0.23, 95% CI 0.10 to 0.52). This means that for a typical clinic with 3.5% prevalence of OHSS using a GnRH agonist regimen, switching to clomiphene citrate protocols would be expected to reduce the incidence to between 0.8% and 1.8%. The trials included in this review were very old and outcomes such as live births, multiple pregnancy, OHSS and miscarriages have not been reported by most studies.

Authors' conclusions: There was no evidence to indicate that clomiphene with gonadotropins (with or without GnRH antagonist) differed significantly from gonadotropins in GnRH agonist protocols for women undergoing IVF treatment, in terms of live births or pregnancy rates. Meanwhile, use of clomiphene led to a reduction in the incidence of OHSS. However, these results were based on data from a small number of underpowered randomised trials with few participants. Hence there was insufficient evidence to recommend use of clomiphene citrate in routine IVF practice. Larger trials with adequate power are required.

Editorial Group: Cochrane Menstrual Disorders and Subfertility Group.

Publication status: New.

Citation: Gibreel A, Maheshwari A, Bhattacharya S. Clomiphene citrate in combination with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilization. Cochrane Database of Systematic Reviews 2012, Issue 11. Art. No.: CD008528. DOI: 10.1002/14651858.CD008528.pub2. Link to Cochrane Library. [PubMed: 23152261]

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

PMID: 23152261

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