P-611 Quantity or quality? Comparative study on the effectiveness of recombinant, purified and mixed gonadotropins on the outcome of ICSI treatments from an embryologist perspective
Authors: Valera M  Á , Garg A , Carrión T , Bori L , Pérez-Albalá S , Meseguer M 
Published: July 2024

Abstract

Study question
Are oocyte retrieval and embryo development affected by the origin of the gonadotropins used for controlled ovarian stimulation (COS), when controlling fertilization and culture conditions?

Summary answer
Patients stimulated with recombinant gonadotropins obtained similar number of oocytes than those using purified hormones, but more blastocysts and better embryo morphology, needing lower doses.

What is known already
Many authors have questioned the safety of purified urinary gonadotropins used for COS prior to an IVF treatment, and have demonstrated the presence of impurities and a high heterogeneity between batches. Another strategy involves using recombinant follicle-stimulating hormone with/without luteinizing hormone (rFSH+/-rLH) synthetized in vitro. Many studies have compared the cost-effectiveness of these drugs; however, a conclusion has not been reached. These studies have varying inclusion criteria and focus on final endpoints such as pregnancy and live birth, sometimes lacking control over the many variables introduced during the fertilization and culture procedures, which affect embryo development and potential.

Study design, size, duration
Preliminary retrospective observational study performed over 453 patients subjected to COS prior to autologous ICSI treatments in a private clinic over 3 years, using Time-lapse incubator. The total dose employed, the number and maturity rate of the oocytes retrieved of patients subjected to stimulation with recombinant (RH; n = 46) or mixed hormones (MH; n = 332) were compared with those using purified hormones (PH; n = 75). After ICSI, fertilization and embryo development were also compared between the three groups.

Participants/materials, setting, methods
The stimulation protocol was adjusted for each patient following the standard protocols of the clinic. Fertilization was performed by ICSI and embryo culture was carried out in Geri time-lapse incubators using Geri Medium (Genea Biomedx). When available (1,097 embryos), Eeva-Xtend Test was applied. Statistical analysis was performed by generalized estimating equations (significance: P≤0.05). Considered confounders include age, body mass index, days of stimulation, down-regulation protocol, and other variables relevant to embryo development.

Main results and the role of chance
Proper follicle stimulation was achieved with lower doses of RH (1,606.26±1,110.52 IU) than PH (2,941.73±1,011.14 IU) and MH (3,629.68±1,080.79 IU). No association was found between the use of different gonadotropins and the number of oocytes collected (Odds ratio (OR, RH vs PH)=2.51, P=0.411; OR (MH vs PH)=1.26, P=0.754) or their maturity rate (OR (RH vs PH)=2.38, P=0.328; OR (MH vs PH)=1.01, P=0.988). No significant association was found between the odds of a correct fertilization and the type of hormone used. However, the odds of reaching blastocyst stage were statistically higher for embryos from patients treated with RH: OR (RH vs PH)=1.72, P=0.006; OR (MH vs PH)=1.45, P=0.005; blastocyst rate=68.7% RH, 61.9% MH and 54.6% PH. The mean morphological classification by ASEBIR criteria of the embryos was significantly better in the RH group than in the PH group (OR = 1.55, P=0.032), but no association was found in the MH-PH comparison (OR = 1.26, P=0.092). No association was found between the type of hormone and the distribution of the Eeva-Xtend scores. Significantly lower values of the morphokinetic parameter s2 (synchrony between the second and third cell divisions) were also associated with the use of RH (OR (RH vs PH)=0.311, P=0.004).

Limitations, reasons for caution
The reduced sample size and the heterogeneous number of patients in the three groups limit the statistical power of the comparisons. Different hormones and brands were included in each group.

Wider implications of the findings
Although not altering the number of oocytes retrieved, the use of RH may improve the chances of success of ICSI cycles by increasing the number of available blastocysts. The positive outcomes paired with the lower dose needed, could make the use of recombinant hormones a cost-effective strategy.

Trial registration number
Not applicable