Evaluation of two doses of recombinant luteinizing hormone supplementation in an unselected group of women undergoing follicular stimulation for in vitro fertilization. Comparative efficacy and safety of cetrorelix with or without mid-cycle recombinant LH and leuprolide acetate for inhibition of premature LH surges in assisted reproduction. Recombinant luteinizing hormone supplementation to recombinant follicle-stimulating hormone induced ovarian hyperstimulation in the GnRH-antagonist multiple-dose protocol. Exogenous luteinizing hormone in controlled ovarian hyperstimulation for assisted reproduction techniques. Recombinant human LH supplementation versus recombinant human FSH (rFSH) step-up protocol during controlled ovarian stimulation in normogonadotrophic women with initial inadequate ovarian response to rFSH. A multicentre, prospective, randomized controlled trial. Effects of recombinant human luteinizing hormone supplementation on ovarian stimulation and the implantation rate in down-regulated women of advanced reproductive age. The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study. Recombinant gonadotrophins associated with GnRH antagonist (cetrorelix) in ovarian stimulation for ICSI: comparison of r-FSH alone and in combination with r-LH. Randomized trial to compare the effect of recombinant human FSH (follitropin alfa) with or without recombinant human LH in women undergoing assisted reproduction treatment. The effect of exogenous luteinizing hormone (LH) on oocyte viability: evidence from a comparative study using recombinant human follicle-stimulating hormone (FSH) alone or in combination with recombinant LH for ovarian stimulation in pituitary-suppressed women undergoing assisted reproduction.
To evaluate the efficacy of two doses of recombinant (r)LH, 75 IU (recommended) or 37.5 IU, for follicular stimulation and outcomes in a randomized cohort of IVF patients.
                Randomized, prospective analysis.
                Private hospital incorporating an established IVF center.
                Women undergoing IVF who had a body mass index >18 or <35 and no abnormal karyotype, anovulation, oligomenorrhea, or any known endocrinopathy/illness.
                Pituitary desensitization was achieved with triptorelin (0.1 mg SC), and gonadotropin stimulation was performed with either rFSH alone (group A) or in combination with rLH in one of two doses: 37.5 IU (group B) or 75 IU (group C), daily.
                A range of endocrinologic, embryologic, clinical, and outcome parameters were evaluated.
                With rLH supplementation there was a significant increase in the incidence of implantation (9% for rFSH only [group A] vs. 11% and 16% with 37.5 IU rLH and 75.0 IU rLH [groups B and C], respectively) and clinical pregnancy (19% vs. 23% and 31%) (P<.01 and P<.04, respectively), whereas there was no difference in the multiple pregnancy rates. There was a significant (P<.001) increase in the total units of rFSH used in proportion to the amount of rLH supplementation (2,645 U vs. 3,475 U and 3,681 U) and in the level of peripheral E(2) on the day of hCG administration (1,049 pg/mL vs. 1,640 pg/mL and 1,226 pg/mL) (P<.001). There was no significant between difference in mean age, numbers of oocytes recovered, basal and downregulation hormone levels, or the incidence of fertilization in the absence or presence of rLH supplementation, but a higher incidence of grade 1 to 2 embryos was observed when rLH was supplemented.
                After pituitary desensitization, there was an increase in the incidence of implantation, clinical pregnancy, and delivery rates in patients stimulated with rFSH supplemented with rLH. An open label, randomized, multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH. Normo-ovulatory women (n = 74) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate (n = 25) before ovarian stimulation with recombinant human FSH (r-hFSH) or with cetrorelix 3 mg on stimulation day 7 (with (n = 25) or without (n = 24) r-hLH 150 IU on days 7-10). The main outcome measures were the number of metaphase II (MII) oocytes retrieved; secondary efficacy end-points; adverse events (AE) and other safety measures. There were no significant differences between groups for MII oocytes retrieved, duration of stimulation, total r-hFSH dose and pregnancy rates. The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups. The majority of AE were mild to moderate in severity. Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety, although cetrorelix has the advantage of typically requiring only one injection. Suppression of endogenous LH production by mid-follicular phase GnRH-antagonist administration in controlled ovarian hyperstimulation protocol using recombinant (rec) FSH preparations void of LH activity may potentially affect ovarian response and the outcome of IVF treatment. The present study prospectively assessed the effect of using a combination of recFSH and recLH on ovarian stimulation parameters and treatment outcome in a fixed GnRH-antagonist multiple dose protocol.
                127 infertile patients with an indication for IVF or ICSI were recruited and randomized (using sealed envelopes) to receive a starting dose of either 150 IU recFSH (follitropin alpha) or 150 IU recFSH plus 75 IU recLH (lutropin alpha) for ovarian hyperstimulation. GnRH-antagonist (Cetrorelix) 0.25 mg was administered daily from stimulation day 6 onwards up to and including the day of the administration of recombinant HCG (chorion gonadotropin alpha). Gonadotropin dose adjustments were allowed from stimulation day 6 onwards, HCG was administered as soon as three follicles > or =18 mm were present. The primary outcome parameter was treatment duration until administration of HCG.
                Exogenous LH did not shorten the time necessary to reach ovulation induction criteria. Serum estradiol (E(2)) and LH levels were significantly higher on the day of HCG administration in the recLH-supplemented group (1924.7 +/- 1256.4 vs 1488.3 +/- 824.0 pg/ml, P < 0.03), and 2.1 +/- 1.4 vs 1.4 +/- 1.5 IU/l, P < 0.01, respectively).
                Except for higher E(2) and LH levels on the day of HCG administration, no positive trend in favour of additional LH was found as defined by treatment outcome parameters. To investigate the role of exogenous LH in controlled ovarian hyperstimulation for assisted reproductive technologies.
                Prospective randomized study.
                SISMER fertility unit.
                Women showing a hyporesponsiveness to FSH under GnRH agonist down-regulation were randomized into three groups: group A (n = 54) received an increased dosage of FSH; group B (n = 54) was administered recombinant LH in addition to the increased dose of FSH; group C (n = 22) was given additional FSH and LH using hMG as a combined drug. Fifty-four age-matched women with no need to increase the FSH dose were included as a control group (D).
                None.
                Implantation and live birth rate per started cycles.
                In group B, the pregnancy and implantation rates were statistically higher when compared with groups A and C and did not differ from the control group for normal response. The live birth rate was similar in groups B and D but was half as high in groups A and C.
                Hyporesponsiveness to FSH could be related to iatrogenic LH deficiency that, in turn, could affect oocyte competence. Addition of a small amount of recombinant LH is able to rescue oocyte competence to produce viable embryos. In approximately 12-14% of young normogonadotrophic women treated with a depot GnRH agonist long protocol, the initial ovarian response to recombinant human FSH (rFSH) can be suboptimal. We have tested the hypothesis that these women may benefit from recombinant human LH (rLH) supplementation in a multicentre, prospective, randomized trial compared with patients treated with an rFSH step-up protocol.
                A total of 260 young normogonadotrophic women undergoing controlled ovarian stimulation with a GnRH agonist long protocol for IVF/ICSI were enrolled. The starting dose of rFSH was 225 IU. One hundred and thirty patients with serum estradiol levels <180 pg/ml and with at least six follicles with a mean diameter >5 mm but none >10 mm on both day 5 and day 8 of stimulation were randomly allocated to two groups. From the eighth day of stimulation, women in group A (n=65) received 150 IU of rLH in addition to rFSH, while those in group B (n=65) had an increase of 150 IU in the daily dose of rFSH (step-up protocol). One hundred and thirty normally responding women continued monotherapy with rFSH and served as a further control population (group C).
                The mean number of cumulus-oocyte complexes retrieved in group A (9.0+/-4.3) was significantly higher (P<0.01) compared with group B (rFSH 6.1+/-2.6) but significantly lower compared with group C (10.49+/-3.7, P<0.05). Implantation and pregnancy rates were significantly lower (P<0.05) in the rFSH step-up group (10.5 and 29.3% respectively) when compared with normal responders (18.1 and 47.3% respectively).
                rLH supplementation is more effective than increasing the dose of rFSH in terms of ovarian outcome in patients with an initial inadequate ovarian response to rFSH alone. To evaluate the effects of recombinant human luteinizing hormone (rhLH) supplementation on ovarian stimulation and implantation rate in down-regulated women of advanced reproductive age.
                Prospective randomized study.
                University teaching hospital.
                A total of 120 consecutive normogonadotropic infertile women > or = 35 years old undergoing their first cycle of IVF or intracytoplasmic sperm injection (ICSI) treatment.
                Ovarian stimulation in a long agonist protocol with a combination of recombinant human follicle-stimulating hormone (rhFSH) and rhLH (group 1, n = 60) starting on day 6 of FSH stimulation until hCG at a daily fixed dose of 150 IU of rhLH, or with rhFSH alone (group 2, n = 60).
                Ovarian stimulation characteristics, ovum retrieval, and IVF/ICSI outcome.
                The mean number of intermediate (10-14 mm) and large (> 14- < 18 mm) but not leading (> or = 18 mm) follicles was significantly lower in group 1 on the day of hCG injection. The oocyte yield and maturity as well as the number of oocytes fertilized were significantly higher in group 2 than in group 1. However, the number of patients having embryo transfer (n = 55 in both treatment groups), the number and quality of embryos replaced, the implantation rate (20.6% vs. 21.7%) and clinical pregnancy rates per embryo transfer (44% vs. 45%) were similar in groups 1 and 2.
                The rhLH supplementation does not increase ovarian response and implantation rates in patients of older reproductive age stimulated with rhFSH under pituitary suppression for assisted reproductive technologies (ARTs). The effect of recombinant human LH (r-hLH; lutropin alfa) in women undergoing controlled ovarian stimulation with recombinant human FSH (r-hFSH) prior to IVF was investigated.
                After down-regulation with the GnRH agonist, buserelin, 114 normo-ovulatory women (aged 18-37 years) received r-hFSH alone until the lead follicle reached a diameter of 14 mm. Patients were then randomized in a double-blind fashion to receive r-hFSH in addition to r-hLH, 75 IU s.c., or placebo daily for a maximum of 10 days prior to oocyte retrieval and IVF. The primary end-point was the number of metaphase II oocytes.
                There were no significant differences between treatment groups for the primary end-point. Serum estradiol concentrations on the day of HCG administration were significantly higher in the group receiving r-hLH plus r-hFSH than in the group receiving r-hFSH alone (P = 0.0001), but there were no significant differences between the groups in dose and duration of r-hFSH treatment required, oocyte maturation, fertilization rate, pregnancy rate and live birth rate.
                In this patient population, the addition of r-hLH during the late follicular phase of a long GnRH agonist and r-hFSH stimulation cycle provides no further benefit in terms of oocyte maturation or other end-points. The objective was to verify the outcome of intracytoplasmic sperm injection (ICSI) with ovulation induction performed with GnRH antagonists, comparing the use of recombinant follicle-stimulating hormone (r-FSH) alone and in combination with recombinant luteinizing hormone (r-LH) in a prospective and randomized trial.
                Forty male-factor infertile normo-ovulatory patients undergoing ovarian stimulation for ICSI took part in the study. After initiating ovarian stimulation with only r-FSH, all patients were treated with GnRH antagonist (cetrorelix). When beginning cetrorelix administration, the patients were randomized into two groups: in group I, 20 patients continued to receive r-FSH alone and in group II, 20 patients received combined r-FSH and r-LH. The number of metaphase II oocytes, estradiol concentration at the time of hCG administration, fertilization rate, grade 1 embryo rate, pregnancy rate per cycle, and implantation rate were measured. Results are expressed as mean+/-S.D.
                In group I, the women's age was 32.3+/-2.30 years, and FSH concentration was 7.8+/-1.7 IU/ml. In group II, the women's age was 32.2+/-2.46 years and FSH concentration was 7.5+/-1.7 IU/ml. The number of oocytes retrieved was 9.6+/-2.9 and the number of metaphase II oocytes was 6.7+/-2.2 in group I. In group II the number of retrieved oocytes were 9.9+/-2.6 and the number of metaphase II oocytes 6.9+/-2.1 (p>0.05). Estradiol concentration at the time of hCG was 4.6+/-1.8 nm/l in group I and 6.7+/-2.0 nm/l in group II (p<0.01). Fertilization rate was 73.0% in group I versus 78.2% in group II. In group I, we obtained 53.9% of grade 1 embryos versus 54.4% in group II (p>0.05). Pregnancy and implantation rates in group I were 30.0 and 16.7%, respectively and in group II 35.0 and 20.4%, respectively (p>0.05).
                The use of recombinant LH in addition to recombinant FSH may prevent a decrease in estradiol after GnRH antagonist administration, but does not influence positively the outcome of oocyte number, maturation, embryo quality, fertilization rate, pregnancy rate per cycle, and implantation rate. Women undergoing intracytoplasmic sperm injection (ICSI) for male factor infertility were randomly assigned to receive ovarian stimulation in a long agonist protocol with a combination of recombinant human FSH (r-hFSH; Gonal-F) and recombinant human LH (r-hLH; Luveris) (n = 212) starting on day 6 of FSH stimulation until human chorionic gonadotrophin (HCG) at a daily fixed dose of 150 IU r-hLH, or with r-hFSH alone (n = 219). There was no significant difference in the number of metaphase II oocytes retrieved (10.3 versus 10.4) in patients treated with r-hFSH and r-hLH versus r-hFSH alone; however, more embryos were transferred in the LH-supplemented group (2.9 versus 2.8, P = 0.037). Overall, the implantation rates were 22.9 versus 27.0% in patients treated with r-hFSH and r-hLH versus with r-hFSH alone respectively (NS). The respective numbers of MII oocytes retrieved in patients <35 or >or=35 years were 11 versus 8.3 (P = 0.010) for patients treated with r-hFSH alone, and 10.7 versus 9.3 (NS) for those given supplemental r-hLH (150 IU) from day 6. Implantation rates in patients <35 years treated with r-hFSH were higher (30.7%) than those receiving r-hFSH and r-hLH, (23.5%) (P = 0.068). In patients >or=35 years, the implantation rates were 21.7% for those patients supplemented with 150 IU r-hLH from day 6 of stimulation versus 15.7% when treated with FSH alone (NS). Younger patients therefore do not seem to benefit from an LH-supplemented ovarian stimulation protocol, but women >or=35 years undergoing assisted reproduction may benefit from using r-hLH in addition to r-hFSH. The purpose of this prospective, randomized study was to compare ovarian response and oocyte and embryo yields in women undergoing ovulation induction for IVF/ICSI using recombinant human FSH (rhFSH) alone or in combination with recombinant human LH (rhLH).
                Patients were randomized to receive rhFSH alone (group F; n = 13) or rhFSH + rhLH (group L; n = 15). rhFSH was administered according to a step-down protocol; patients assigned to group L received rhLH at a fixed dose of 75 IU (1 ampoule) throughout the treatment period.
                The total dose of rhFSH, number of growing follicles, and serum concentrations of estradiol (E2) on the day of hCG administration were similar in both treatment groups. However, the percentage of metaphase II oocytes and fertilization rate were significantly higher in group F than in group L. The lower fertilization rates associated with rhLH were also seen in a subgroup of patients from group L who had undergone a previous ART cycle stimulated with FSH only and thus acted as their own controls. However, when in vitro fertilization (IVF) and intracytoplasmic sperm injection cycles were considered separately, differences in fertilization rates were statistically significant only for oocytes treated by conventional IVF.
                This study shows that the addition of recombinant LH to recombinant FSH in pituitary-suppressed women undergoing ART does not improve the ovarian response and even may have a negative impact on oocyte maturation and fertilization.
There was no evidence of a statistical difference in pregnancy outcomes when rLH was used. Nevertheless, further large RCTs should be undertaken in long GnRH agonist down regulation protocols, since all pooled pregnancy estimates, although not statistically different probably due to the small numbers, point towards a beneficial effect of co-treatment with rLH, in particular with respect to pregnancy-loss and poor-responders.