Intramuscular injection of human chorionic gonadotropin prior to secretory transformation in patients undergoing frozen-thawed embryo transfer cycles

Background: The major difference between a natural cycle and an artificially prepared cycle is the lack of luteinizing hormone (LH) peak in the latter. The LH/hCG receptors were identified to express in human endometrium and evidences of experiments also suggested the beneficial role of hCG in embryo implantation, indicating that the LH peak might be of clinical significance and the activation of LH/hCG receptors in the endometrium could improve embryo implantation. Hence, we postulated that the addition of hCG prior to secretory transformation in an artificial cycle might improve pregnancy outcomes.

Methods: This retrospective cohort study was conducted at a Reproductive Medicine Center between 2016 and 2018. Patients aged ≤43 years at the (index) oocyte retrieval and undergoing artificially prepared frozen-thawed embryo transfer (FET) with at least one good-quality embryo transferred were included. The cycles were divided into two groups: The hCG group (n = 337) received an intramuscular injection of 10,000 IU hCG before secretory transformation; the control group (n = 364) performed FET without hCG administration. The primary endpoint was live birth delivery rate (LBR), secondary outcomes included implantation rate, clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR).

Results: The LBR (49.9% vs 39.6%, P < 0.01), CPR (61.4% vs 50.5%, P < 0.01) and OPR (52.8% vs 43.1%, P < 0.05) were statistically significantly higher in the hCG group than the control group. The superiority in LBR after hCG administration remained significant after adjusting for confounding factors (OR 1.613, 95% CI 1.173-2.217; P < 0.01). In the subgroup analysis, the improvement in LBR was statistically significant after hCG administration for cleavage-stage embryo transfer cycles (51.2% vs 42.3%, P < 0.05), whereas for blastocyst transfer cycles, the improvement in LBR was not (45.7% vs 31.3%, P > 0.05).

Conclusions: Intramuscular hCG injection prior to secretory transformation may benefit LBR in patients undergoing artificially prepared FET cycles. But it should be noted that nonsignificant tendency towards higher LBR was observed after hCG administration in patients undergoing blastocyst transfer. So, future prospective randomized controlled studies are required to confirm, especially for blastocyst transfer cycles.