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

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 fewstudies have analysed this issue in theGnRHantagonist protocol and the results of these trials obtained in older women (.35 years old) are conflicting. Study design, size, duration: AmulticentreRCTwas performed between 2004 and 2010 in 253 couples whowere 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: Therewere no demographic or clinical differences between the groups. The intentionto-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 21.5%; 95% confidence interval (CI) 29.4 to 12.7, P ¼ 0.9). Ongoing pregnancy rates were 25 (20%) versus 28 (21.9%) (mean difference 21.9%; 95% CI 28.2 to 11.9, P ¼ 0.9) and implantation rates 18.8 versus 20.7% (mean difference 21.9%; 95% CI 28.0 to 11.7, P ¼ 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. Study funding/competing interest(s): Merck Serono Netherlands, an affiliate of Merck Serono SA- Geneva, an affiliate of Merck KGaA, Darmstadt, Germany has donated the r-LH (Luverisw). No conflict of interest to declare

Vascular Problems of the Pelvis

Regardless of the gender, the human pelvis represents a complex anatomic region shared by the organs of the gastrointestinal and genitourinary tracts and the reproductive system. All these structures are included in a rigid bone case which also harbors the intricate neurovascular network that crosses over the pelvic area in direction to the lower limbs. The adequate approach of the diseases arising in the pelvic vascular network is difficult requiring precise anatomical knowledge and often the collaboration of interdisciplinary teamwork. The present chapter describes in detail the pelvic vascular anatomy and also provides a full discussion of both the tumor-related and tumor-unrelated diseases affecting these vascular structures