P-639 Are our advanced maternal age population being affected by the shortage of HP-hMG?
Authors: Cruz Palomino M , Vergara V , Prados N , Rubio I , Agudo D , Requena A 
Published: June 2023

Abstract

Study question
Could we stimulate patients of advanced maternal age in the face of a shortage of HP-hMG without impacting outcomes?

Summary answer
Given the current low availability of HP-hMG, it is safe to stimulate only with recombinant FSH in women of advanced maternal age without affecting results.

What is known already
. Studies on the role of luteinizing hormone (LH) supplementation in patients undergoing assisted reproductive treatments use different sources of LH bioactivity. It is well known that the addition of LH supplementation was associated with a tendency towards improved IVF outcome in specific profiles of patients undergoing Assisted Reproductive treatment. However, during the last quarter of 2022, we are facing a temporary fall in the global supply of HP-hMG, which has hCG-driven LH activity, and may impact ovarian stimulation outcomes in women of advanced maternal age undergoing a preimplantation genetic testing treatment (PGT).

Study design, size, duration
Retrospective and observational study during November-December 2022 in any of the 11 clinics belonging to the IVIRMA group in Spain. Study population included women ≥38 years undergoing PGT treatment who received monotherapy with recombinant FSH (n = 73), a combination of FSH + HMG containing an FSH: LH activity in a ratio 1:1 (n = 103), or a fertility drug with recombinant FSH + recombinant LH in a 2:1 ratio (n = 112). The study was approved by an IRB (2003-MAD-020-AR)

Participants/materials, setting, methods
All women underwent short GnRH antagonist protocol. Initial doses were adjusted based on weight and body mass index according to the clinician’s experience. Daily doses of 0.25 mg GnRH antagonist were started on day 6 of stimulation. Finally, a single dose of 0.2 mg GnRH agonist was administered to trigger final oocyte maturation. Embryo biopsy was performed on day 5 with a subsequent freeze-all. A frozen single embryo transfer was accomplished in a subsequent cycle.

Main results and the role of chance
Assuming the limitations of the study design, we observed significant differences in gonadotropin doses but not in retrieved oocytes, metaphase II oocytes or euploidy rate: the results were as follows for recombinant FSH, FHS + hMG and FSH + LH respectively: gonadotropin doses [2254 (692) vs. 2033 (680) vs. 2000 (660), p = 0.0035]; retrieved oocytes [10.1 (5.4) vs. 11.1 (8.0) vs. 9.2 (6.0), p = 0.131], metaphase II oocytes [8.7 (4.7) vs. 9.8 (7.1) vs. 8.3 (5.1), p = 0.147]; and euploidy rate (38.7% vs. 36.3% vs. 31.5%, p = 0.182). Moreover, recombinant FSH in monotherapy in this specific population could guarantee the efficiency of the cycle since there are no significant differences in the usable blastocyst rate. Finally, clinical results were analyzed in those cases in which a frozen single embryo had been performed in a subsequent artificial cycle, in which the effect of LH on the endometrium is obviated; once again, no significant differences were observed between the study groups neither for the implantation rate (50% vs. 56% vs. 45%, p = 0.780) or the clinical pregnancy rate (50% vs. 56% vs. 45%, p = 0.772).

Limitations, reasons for caution
This is a retrospective and observational study and thus possible confounders cannot be completely excluded. More data are needed to draw firm conclusions and it will be critical to increase the sample size to check if the results observed in this work remains in the general population.

Wider implications of the findings
In view of tailoring assisted reproductive protocols to meet patient needs and improve the likelihood of positive outcomes, these data suggest that it is optimal to perform an ovarian stimulation protocol only with recombinant FSH in a frozen embryo program in advanced maternal age context without clinical outcomes being affected.

Trial registration number
Not applicable