Randomized trial comparing luteinizing hormone supplementation timing strategies in older women undergoing ovarian stimulation

Abstract

In this open-label study, women aged 36-40 years undergoing ovarian stimulation were randomized to recombinant human FSH (rhFSH) plus recombinant human luteinizing hormone (rhLH) from stimulation day 1 (group A; n = 103), or rhFSH alone (days 1-5) followed by rhFSH plus rhLH from day 6 (group B; n = 99). The primary objective was equivalence in number of oocytes retrieved per patient. The mean (±SD) number of oocytes retrieved was 9.7 (±6.9) in group A and 10.9 (±6.5) in group B; the estimated difference between groups (-1.28 oocytes [95% confidence interval: -3.15 to 0.59]) did not reach the predefined limit of equivalence (±3 oocytes). The study's primary objective was therefore not met. In both groups, a mean (±SD) of 1.9 (±0.6) embryos were transferred per patient. Implantation rates were 24.7% in group A and 13.3% in group B. Clinical pregnancy rates per started cycle and per embryo transfer were 31.6% and 34.4% in Group A, 17.2% and 18.9% in Group B. Ovarian hyperstimulation syndrome was reported in four (group A) and five (group B) patients. The potential benefit of initiating LH supplementation earlier during ovarian stimulation in older women is of interest, warranting further exploration.

Recombinant human luteinizing hormone co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age: a systematic review and meta-analysis of randomized controlled trials

“…Thirty-two full-text papers were assessed for eligibility. Twenty studies were excluded because they did not fulfill the inclusion criteria [ 44 – 63 ]. Overall, 12 RCTs were identified [ 9 , 20 , 36 , 37 , 64 – 71 ].…”

“…Several regimens have been proposed. Some authors suggested starting LH upon the onset of OS treatment [ 9 , 63 ], others starting from the intermediate phase of OS [ 36 , 37 ]. In the first phase of folliculogenesis, LH receptors are expressed predominantly in theca cells thereby promoting ovarian androgen production, which, as mentioned above, is reduced in advanced age women [ 7 ].…”

“…In the first phase of folliculogenesis, LH receptors are expressed predominantly in theca cells thereby promoting ovarian androgen production, which, as mentioned above, is reduced in advanced age women [ 7 ]. The latter finding might explain why implantation and clinical pregnancy rates were better in advanced age women when r-hLH was prescribed with r-hFSH from the beginning of OS than when r-hLH was added to r-hFSH therapy during OS [ 9 , 63 ]. On the other hand, it is widely acknowledged that LH receptors are expressed in granulosa cells starting from the intermediate follicular phase, and that LH can support follicular growth [ 98 , 99 ].…”

Influence of human chorionic gonadotrophin during ovarian stimulation: an overview

“…As in previous studies, the number of oocytes retrieved was higher in the rFSH alfa arm than in the HP-hMG arm (22 ± 11.54 vs 15.1 ± 10.12) [ 14 , 79 ]. Interestingly, the PERSIST trial comparing a 2:1 formulation of rFSH alfa plus rLH (Pergoveris®) administered from Day 1 versus rFSH alfa (Gonal-F®) administered during Days 1–5 and supplemented with rLH from Day 6 of the stimulation cycle did not report a significant difference in terms of oocytes retrieved (9.7 vs 10.9, 95% confidence interval [CI]: − 3.15 to 0.59), therefore failing to meet its primary endpoint and yielding inconclusive evidence on the influence of rLH on oocyte yield [ 82 ].…”

Criopreserved ovarian tissue transplantation and bone restoration metabolism in castrated rats

“…However, one month after ovarian autotransplantation, we observed trabecular bone formation containing osteoblasts border, channels and large gaps containing osteocytes ( Figure 6). As demonstrated by assisted reproduction, these follicles can be saved from degeneration and continue to grow and secrete sexual hormones 32 .…”