Recombinant LH supplementation to a standard GnRH antagonist protocol in women of 35 years or older undergoing IVF/ICSI: a randomized controlled multicentre study.

König TE, van der Houwen LE, Overbeek A, Hendriks ML, Beutler-Beemsterboer SN, Kuchenbecker WK, Renckens CN, Bernardus RE, Schats R, Homburg R, Hompes PG, Lambalk CB.

Source

Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, VU University Medical Center (VUmc), PO Box 7057, Amsterdam 1007 MB, The Netherlands.

Abstract

STUDY QUESTION:

Does the addition of exogenous LH to an IVF/ICSI stimulation protocol with recombinant FSH (r-FSH) and a GnRH antagonist improve the ovarian response and pregnancy rates in women of 35 years and older?

SUMMARY ANSWER:

Supplementation of LH during the second half of the follicular phase has no effect on pregnancy rates, implantation rates or on ovarian response in women of 35 years and older undergoing GnRH antagonist IVF/ICSI cycles.

WHAT IS KNOWN ALREADY:

In IVF/ICSI stimulation protocols GnRH agonists or antagonists are administered to prevent a premature pituitary LH surge, which can have a detrimental effect on the IVF/ICSI procedure. In effect, GnRH analogues cause the levels of both gonadotrophins to drop. In order to allow follicle growth FSH is administered exogenously, whereas LH is usually not supplemented. Although GnRH analogues prevent LH surges, there is evidence that, particularly in older women, administration of GnRH analogues may cause endogenous LH levels to decrease excessively. Several studies have been performed to investigate whether the addition of recombinant LH (r-LH) to r-FSH improves cycle outcome. Only a few studies have analysed this issue in the GnRH antagonist protocol and the results of these trials obtained in older women (>35 years old) are conflicting.

STUDY DESIGN, SIZE, DURATION:

A multicentre RCT was performed between 2004 and 2010 in 253 couples who were undergoing IVF or ICSI. Women were 35 years or older and received ovarian stimulation in a protocol with r-FSH (Gonal-F 225 IU/day) starting from cycle day 3 and GnRH antagonist (Cetrotide 0.25 mg/day) from stimulation day 6. Randomization took place on stimulation day 6 to receive both r-FSH and r-LH (Luveris 150 IU/day) or continue with FSH alone. Randomization for r-LH supplementation was performed centrally by serially numbered, opaque, sealed envelopes, stratified by centre.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Of 253 subjects randomized, 125 received both r-FSH and r-LH and 128 received r-FSH only. Patients were recruited from the Division of Reproductive Medicine of the Obstetrics and Gynaecology department of four hospitals in the Netherlands.

MAIN RESULTS AND THE ROLE OF CHANCE:

There were no demographic or clinical differences between the groups. The intention-to-treat analysis revealed that of those receiving both r-FSH and r-LH, 35 (28.0%) had a clinical pregnancy, compared with 38 (29.7%) receiving only r-FSH (mean difference -1.5%; 95% confidence interval (CI) -9.4 to 12.7, P = 0.9). Ongoing pregnancy rates were 25 (20%) versus 28 (21.9%) (mean difference -1.9%; 95% CI -8.2 to 11.9, P = 0.9) and implantation rates 18.8 versus 20.7% (mean difference -1.9%; 95% CI -8.0 to 11.7, P = 0.6) in the 'r-FSH and r-LH' and 'r-FSH only' groups respectively.

LIMITATIONS, REASONS FOR CAUTION:

A limitation of our study is its early closure. This was done because the interim analysis after randomization of 250 patients indicated no benefit in any aspect of the experiment.

WIDER IMPLICATIONS OF THE FINDINGS:

Given previous data, including a Cochrane review, and our own results the evidence indicates that LH supplementation has no benefit on ongoing pregnancy rates in women of 35 years or older.

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2013年6月24日

35歲以上病患使用LH補充誘導排卵無明顯提高懷孕率